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Cited by 5,082Sepsis Diagnosis and TreatmentAbdominal Surgery and ComplicationsAntibiotics Pharmacokinetics and Efficacy

Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021

Open access
Evans, Laura, Rhodes, Andrew, Alhazzani, Waleed, Antonelli, Massimo, Coopersmith, Craig M., French, Craig, Machado, Flávia R., Mcintyre, Lauralyn +52 more·2021·Intensive Care Medicine
DOI 10.1007/s00134-021-06506-yPMC PMC8486643
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Integrity signals

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Crossref · 10.1007/s00134-021-06506-y

Cites

645 of 645 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 714 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    An updated meta-analysis of empiric antifungal therapy versus no antifungal therapy in adult critically ill patients found no difference in short-term mortality.

    “In an updated meta-analysis of empiric antifungal therapy versus no antifungal therapy in adult critically ill patients, no difference in short-term mortality was observed.”
    Quote in the paperSubstantial claim
  • Findingown data

    In our meta-analysis of 13 studies (1968 patients), de-escalation was associated with improved short-term mortality (RR 0.72; 95% CI 0.57-0.91).

    “We identified direct evidence from 13 studies (1968 patients) [277], including 1 RCT [278]. In our meta-analysis, we observed improved short-term mortality in patients who were de-escalated (RR 0.72; 95% CI 0.57–0.91) (Supplementary Appendix 2).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [277] Tabah A, Bassetti M, Kollef MH et al (2020) Antimicrobial de-escalation in critically ill patients: a position statement from a task force of the European Society of Intensive Care Medicine (ESICM) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Critically Ill Patients Study Group (ESGCIP). Intensive Care Med 46(2):245–265 source

      Not checked in the free run.

    • cites [278] Leone M, Bechis C, Baumstarck K et al (2014) De-escalation versus continuation of empirical antimicrobial treatment in severe sepsis: a multicenter non-blinded randomized noninferiority trial. Intensive Care Med 40(10):1399–1408 source

      Not checked in the free run.

  • Findingnone given

    No cost-effectiveness studies have compared balanced and unbalanced crystalloid solutions.

    “No cost-effectiveness studies compared balanced and unbalanced crystalloid solutions.”
    Quote in the paperSubstantial claim
  • Findingreasoning

    Limited data preclude a cutoff value for crystalloid infusion above which albumin might be considered.

    “Limited data precludes a cutoff value for crystalloid infusion above which albumin might be considered as part of resuscitation.”
    Quote in the paperSubstantial claim
  • Findingreasoning

    There is a lack of powered well-designed studies supporting gelatin administration in sepsis and septic shock.

    “Gelatin is a synthetic colloid used as a resuscitation fluid; there is a lack of powered well-designed studies supporting its administration in sepsis and septic shock.”
    Quote in the paperSubstantial claim
  • May combine two claims. 234
  • The quote only partly states this claim. 6
  • Classified as probably not a substantial claim. 64

  • May combine two claims.

    Findingown data

    In identified studies of intravascular device removal, there was no evidence of a difference in mortality, but studies had significant limitations including confounding by indication and imprecision.

    “There was no evidence of a difference in mortality, however, the studies were hampered by significant limitations, including risk of confounding by indication (the observational studies) and imprecision (the RCT), which is why the results should be interpreted cautiously.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    De-escalation was associated with shorter hospital length of stay (MD −5.56 days; 95% CI −7.68 to −3.44) but not ICU length of stay (MD −2.6 days; 95% CI −5.91 to 0.72).

    “De-escalation was associated with shorter length of stay in the hospital (MD −5.56 days; 95% CI −7.68 to −3.44), but not in the ICU (MD −2.6 days; 95% CI −5.91 to 0.72).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Long-term mortality was evaluated in one study only and did not show a difference (RR 0.99; 95% CI 0.64-1.52).

    “Long-term mortality was evaluated in one study only and did not demonstrate a difference (RR 0.99; 95% CI 0.64–1.52).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Antibiotic exposure was consistently lower in patients managed with procalcitonin and clinical evaluation, but in many trials total therapy duration remained 7 days or longer in the intervention group.

    “Antibiotic exposure was consistently lower in patients who were managed with procalcitonin and clinical evaluation, however, in many trials the total duration of therapy was still 7 days or longer in the intervention group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingnone given

    Included gelatin studies are generally small and mostly involve post-operative, non-critically ill patients.

    “Included studies are generally small and include mostly post-operative, non-critically ill patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In a systematic review of 10 RCTs, vasopressin plus norepinephrine reduced mortality compared with norepinephrine alone but did not reduce need for renal replacement therapy.

    “In our systematic review of 10 RCTs, vasopressin with norepinephrine reduced mortality as compared to norepinephrine alone (RR 0.91; 95% CI 0.83–0.99) but did not reduce the need for RRT (RR 0.79; 95% CI 0.57–1.10).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The systematic review found no difference in risks of digital ischaemia or arrhythmias.

    “There was no difference in the risks of digital ischaemia (RR 1.01; 95% CI 0.33–9.84) or arrhythmias (RR 0.88; 95% CI 0.63–1.23).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A meta-analysis of terlipressin studies found no difference in mortality but an increase in adverse events.

    “Our meta-analysis showed no difference in mortality (terlipressin: 42.9% vs 49.0%; RR 0.89 (95% CI 0.70–1.13); low quality) but an increase in adverse events.”
    Quote in the paperSubstantial claim

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    Findingown data

    Our analysis of three RCTs (1129 patients) showed no difference in mortality with low Vt ventilation (RR 1.07; 95% CI 0.91-1.26), with a trend towards lower risk of developing ARDs (RR 0.59; 95% CI 0.34-1.02).

    “Our analysis of three RCTs (1129 patients) showed no difference in mortality with low Vt ventilation (RR 1.07; 95% CI 0.91–1.26), with a trend towards lower risk of developing ARDs (RR 0.59; 95% CI 0.34–1.02) (Supplementary Appendix 4).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    When the incremental PEEP recruitment studies are analysed separately from studies utilizing traditional recruitment maneuvers, recruitment with incremental PEEP is associated with increased 28-day mortality (RR 1.12; 95% CI 1.00-1.25), which justifies the strong recommendation against using incremental PEEP titration for recruitment.

    “When the incremental PEEP recruitment studies are analysed separately from studies utilizing traditional recruitment maneuvers, recruitment with incremental PEEP is associated with increased 28-day mortality RR 1.12; 95% CI 1.00–1.25), which justifies the strong recommendation against using incremental PEEP titration for recruitment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Among patients with ARDS receiving lower VTs, we did not identify a significant benefit for use of a higher PEEP versus lower PEEP strategy for improving mortality (RR = 0.93; 95% CI 0.83-1.03), days on mechanical ventilation (RR = 0.00; 95% CI −1.02 to 1.02), or ventilator-free days (RR = 1.48; 95% CI 0.19-2.76); and there was no increase in the risk of barotrauma (RR = 1.49; 95% CI 0.99-2.23).

    “Among patients with ARDS receiving lower VTs, we did not identify a significant benefit for use of a higher PEEP versus lower PEEP strategy for improving mortality (RR = 0.93; 95% CI 0.83–1.03), days on mechanical ventilation (RR = 0.00; 95% CI −1.02 to 1.02), or ventilator-free days (RR = 1.48; 95% CI 0.19–2.76); and there was no increase in the risk of barotrauma (RR = 1.49; 95% CI 0.99–2.23).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Overall, continuous NMBA infusion reduced the risk of barotrauma (RR 0.55; 95% CI 0.35-0.85), but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was unclear.

    “Overall, continuous NMBA infusion reduced the risk of barotrauma (RR 0.55; 95% CI 0.35–0.85), but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was unclear [472, 473].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [472] Alhazzani W, Belley-Cote E, Moller MH, et al (2020) Neuromuscular blockade in patients with ARDS: a rapid practice guideline. Intensive Care Med source

      Not checked in the free run.

    • cites [473] Tarazan N, Alshehri M, Sharif S et al (2020) Neuromuscular blocking agents in acute respiratory distress syndrome: updated systematic review and meta-analysis of randomized trials. Intensive Care Med Exp 8(1):61 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A meta-analysis conducted for this guideline revision found an increase in vasopressor-free days (MD 1.5 days; 95% CI 0.8-3.11 days); however, corticosteroid use increased neuromuscular weakness (RR 1.21; 95% CI 1.01-1.45), without a clear effect on short- or long-term mortality.

    “A meta-analysis conducted for this guideline revision (Supplementary Appendix 5) found an increase vasopressor-free days (MD 1.5 days; 95% CI 0.8–3.11 days); however, corticosteroid use increased neuromuscular weakness (RR 1.21; 95% CI 1.01–1.45), without a clear effect on short- or long-term mortality.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    An updated meta-analysis of all available RCTs demonstrated a possible reduction in mortality (RR 0.87; 95% CI 0.77-0.98, low quality), however this finding was challenged by sensitivity analyses: after excluding high risk of bias trials the risk ratio is 1.14 (95% CI 0.96-1.36); and after excluding trials published prior to 2010 we observed higher mortality with haemoperfusion (RR 1.23; 95% CI 1.

    “An updated meta-analysis of all available RCTs (Supplementary Appendix 5) demonstrated a possible reduction in mortality (RR 0.87; 95% CI 0.77–0.98, low quality), however this finding was challenged by sensitivity analyses: after excluding high risk of bias trials the risk ratio is 1.14 (95% CI 0.96–1.36); and after excluding trials published prior to 2010 we observed higher mortality with haemope”
    Quote in the paperSubstantial claim

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    Findingcitation

    The IDEAL-ICU trial did not report central venous access device (CVAD) infections, and results for this outcome are unchanged from 2016.

    “The IDEAL-ICU trial [507] did not report central venous access device (CVAD) infections: the results for this outcome are unchanged from 2016.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [507] Barbar SD, Clere-Jehl R, Bourredjem A et al (2018) Timing of renal-replacement therapy in patients with acute kidney injury and sepsis. N Engl J Med 379(15):1431–1442 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The updated literature search identified no new RCTs but two meta-analyses comparing continuous and intermittent renal replacement therapies.

    “Our updated literature search identified no new RCTs but two meta-analysis comparing continuous and intermittent renal replacement therapies [503, 504].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [503] Zha J, Li C, Cheng G et al (2019) The efficacy of renal replacement therapy strategies for septic-acute kidney injury: a PRISMA-compliant network meta-analysis. Medicine (Baltimore) 98(16):e15257 source

      Not checked in the free run.

    • cites [504] Zhao Y, Chen Y (2020) Effect of renal replacement therapy modalities on renal recovery and mortality for acute kidney injury: A PRISMA-compliant systematic review and meta-analysis. Semin Dial 33(2):127–132 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    No difference in rates of clinically significant bleeding, mortality, or PE were observed between LMWH and UFH.

    “No difference in the rates of clinically significant bleeding, mortality or PE were observed.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingcitation

    No significant differences existed between the two insulin initiation blood glucose levels evaluated (> 180 vs > 150 mg/dl).

    “No significant differences existed between the two-insulin initiation blood glucose levels evaluated.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The previous meta-analysis demonstrated a significant reduction in both DVT and PE and no increase in bleeding complications with pharmacologic VTE prophylaxis.

    “Our previous meta-analysis demonstrated a significant reduction in both DVT and PE and no increase in bleeding complications.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Reductions in ICU and ventilator days in intervention patients who died before hospital discharge were found in two studies, and the third study found overall shorter ICU and hospital stay in the ethics consultation group.

    “Reductions in ICU and ventilator days in intervention patients who died before hospital discharge were found in two studies [539, 540], and the third study found overall shorter ICU and hospital stay in the ethics consultation group [541].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [539] Schneiderman LJ, Gilmer T, Teetzel HD (2000) Impact of ethics consultations in the intensive care setting: a randomized, controlled trial. Crit Care Med 28(12):3920–3924 source

      Not checked in the free run.

    • cites [540] Schneiderman LJ, Gilmer T, Teetzel HD et al (2003) Effect of ethics consultations on nonbeneficial life-sustaining treatments in the intensive care setting: a randomized controlled trial. JAMA 290(9):1166–1172 source

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    • cites [541] Chen C, Michaels J, Meeker MA (2019) Family outcomes and perceptions of end-of-life care in the intensive care unit: a mixed-methods review. J Palliat Care 35(3):143–153. https://doi.org/10.1177/0825859719874767 source

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  • May combine two claims.

    Findingcitation

    There are limited available data on undesirable effects of vitamin C; the point estimate of the HR for 90-day mortality in the largest RCT was 1.18 (95% CI 0.69-2.00), favouring the control group.

    “There are limited available data of any undesirable effects: it was noted that the point estimate of the HR for 90-day mortality in the largest RCT [524] was 1.18 (95% CI 0.69–2.00) i.e. favouring the control group.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [524] Fujii T, Luethi N, Young PJ et al (2020) Effect of vitamin C, hydrocortisone, and thiamine vs hydrocortisone alone on time alive and free of vasopressor support among patients with septic shock: the VITAMINS Randomized Clinical Trial. JAMA 323(5):423–431 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Palliative care meetings failed to show benefit in decreasing anxiety and depression in surrogate decision makers in the intervention group but did increase post-traumatic stress disorder (PTSD) symptoms.

    “Palliative care meetings failed to show benefit in decreasing anxiety and depression in surrogate decision makers in the intervention group but did increase post-traumatic stress disorder (PTSD) symptoms.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [543] Carson SS, Cox CE, Wallenstein S et al (2016) Effect of palliative care-led meetings for families of patients with chronic critical illness: a randomized clinical trial. JAMA 316(1):51–62 source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    We identified several studies exploring the use of specific criteria to trigger a goals of care discussion in critically ill patients, though none report the proportion of patients with sepsis or septic shock.

    “We identified several studies exploring the use of specific criteria to trigger a goals of care discussion in critically ill patients, though none report the proportion of patients with sepsis or septic shock.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    The support intervention did not affect family psychological outcomes but did improve perceived quality of communication and perception of patient- and family-centeredness of care.

    “The support intervention did not affect family psychological outcomes but did improve perceived quality of communication and perception of patient- and family-centeredness of care.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [538] White DB, Angus DC, Shields AM et al (2018) A randomized trial of a family-support intervention in intensive care units. N Engl J Med 378(25):2365–2375 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The outcomes of patients with both sepsis and AKI were not reported.

    “The outcomes of patients with both sepsis and AKI were not reported.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Palliative care interventions had no significant impact on family satisfaction, ICU length of stay, hospital length of stay, or mortality.

    “Palliative care interventions had no significant impact on family satisfaction with care, ICU length of stay [543, 545–548], hospital length of stay [543, 545, 548], or mortality [543, 545, 548].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [543] Carson SS, Cox CE, Wallenstein S et al (2016) Effect of palliative care-led meetings for families of patients with chronic critical illness: a randomized clinical trial. JAMA 316(1):51–62 source

      Not checked in the free run.

    • cites [545] Cheung W, Aggarwal G, Fugaccia E et al (2010) Palliative care teams in the intensive care unit: a randomised, controlled, feasibility study. Crit Care Resusc 12(1):28–35

      Not checked in the free run.

    • cites [546] Curtis JR, Nielsen EL, Treece PD et al (2011) Effect of a quality-improvement intervention on end-of-life care in the intensive care unit: a randomized trial. Am J Respir Crit Care Med 183(3):348–355 source

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    • cites [547] Lautrette A, Darmon M, Megarbane B et al (2007) A communication strategy and brochure for relatives of patients dying in the ICU. N Engl J Med 356(5):469–478 source

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    • cites [548] Ma J, Chi S, Buettner B et al (2019) Early palliative care consultation in the medical ICU: a cluster randomized crossover trial. Crit Care Med 47(12):1707–1715 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Palliative care interventions have been studied in ICU patients, but not specifically in patients with sepsis.

    “Studies have evaluated palliative care interventions in the ICU but not specifically in patients with sepsis [543, 545–548].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [543] Carson SS, Cox CE, Wallenstein S et al (2016) Effect of palliative care-led meetings for families of patients with chronic critical illness: a randomized clinical trial. JAMA 316(1):51–62 source

      Not checked in the free run.

    • cites [545] Cheung W, Aggarwal G, Fugaccia E et al (2010) Palliative care teams in the intensive care unit: a randomised, controlled, feasibility study. Crit Care Resusc 12(1):28–35

      Not checked in the free run.

    • cites [546] Curtis JR, Nielsen EL, Treece PD et al (2011) Effect of a quality-improvement intervention on end-of-life care in the intensive care unit: a randomized trial. Am J Respir Crit Care Med 183(3):348–355 source

      Not checked in the free run.

    • cites [547] Lautrette A, Darmon M, Megarbane B et al (2007) A communication strategy and brochure for relatives of patients dying in the ICU. N Engl J Med 356(5):469–478 source

      Not checked in the free run.

    • cites [548] Ma J, Chi S, Buettner B et al (2019) Early palliative care consultation in the medical ICU: a cluster randomized crossover trial. Crit Care Med 47(12):1707–1715 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The early warning system did not impact hospital mortality or hospital length of stay, but did reduce ICU transfers and ICU length of stay and increased documentation of advance directives and resuscitation status compared to the usual care group.

    “The early warning system did not impact hospital mortality or hospital length of stay, but did reduce ICU transfers and ICU length of stay and increased documentation of advance directives and resuscitation status compared to the usual care group.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [544] Picker D, Dans M, Heard K et al (2017) A randomized trial of palliative care discussions linked to an automated early warning system alert. Crit Care Med 45(2):234–240 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Ethics consultation did not result in a reduction in ICU stay, hospital stay, or life-sustaining treatments in patients who did not survive to discharge.

    “Ethics consultation did not result in a reduction in ICU stay, hospital stay, or life-sustaining treatments in patients who did not survive to discharge.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [542] Andereck WS, McGaughey JW, Schneiderman LJ et al (2014) Seeking to reduce nonbeneficial treatment in the ICU: an exploratory trial of proactive ethics intervention. Crit Care Med 42(4):824–830 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    No benefit was demonstrated on family satisfaction, ICU days, or hospital days.

    “No benefit was demonstrated on family satisfaction, ICU days, or hospital days.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [543] Carson SS, Cox CE, Wallenstein S et al (2016) Effect of palliative care-led meetings for families of patients with chronic critical illness: a randomized clinical trial. JAMA 316(1):51–62 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A reduction in ICU length of stay was noted, yet it is unknown if the reduction is due to increased mortality.

    “A reduction in ICU length of stay was noted, yet it is unknown if the reduction is due to increased mortality.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [538] White DB, Angus DC, Shields AM et al (2018) A randomized trial of a family-support intervention in intensive care units. N Engl J Med 378(25):2365–2375 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Findingreasoning

    Generating a robust evidence base for concrete recommendations about changes in the care paradigm for sepsis survivors has proven extraordinarily difficult.

    “However, generating a robust evidence base upon which to make concrete recommendations about changes in the care paradigm has proven to be extraordinarily difficult.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Observational studies suggest low SES, substance abuse, and poor nutritional status lead to poor outcomes, and critical illness itself results in lower SES post-illness.

    “Many observational studies describe the relationship between various socioeconomic supports and patient outcomes that suggest that low SES, substance abuse and poor nutritional status lead to poor outcomes, and that critical illness itself results in lower SES post-illness.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    ICU education did not appear to impact patients' anxiety and depression but did improve families' satisfaction with care.

    “ICU education did not appear to impact patients’ anxiety and depression [584, 586, 588], but did improve families’ satisfaction with care [583].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [583] Azoulay E, Pochard F, Chevret S et al (2002) Impact of a family information leaflet on effectiveness of information provided to family members of intensive care unit patients: a multicenter, prospective, randomized, controlled trial. Am J Respir Crit Care Med 165(4):438–442 source

      Not checked in the free run.

    • cites [584] Bench S, Day T, Heelas K et al (2015) Evaluating the feasibility and effectiveness of a critical care discharge information pack for patients and their families: a pilot cluster randomised controlled trial. BMJ Open 5(11):e006852 source

      Not checked in the free run.

    • cites [586] Fleischer S, Berg A, Behrens J et al (2014) Does an additional structured information program during the intensive care unit stay reduce anxiety in ICU patients?: a multicenter randomized controlled trial. BMC Anesthesiol 14:48 source

      Not checked in the free run.

    • cites [588] Schmidt K, Worrack S, Von Korff M et al (2016) Effect of a primary care management intervention on mental health-related quality of life among survivors of sepsis: a randomized clinical trial. JAMA 315(24):2703–2711 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The majority of handoff studies are observational pre-post studies and report process measures rather than clinical outcomes.

    “The majority are observational pre-post studies and report process measures such as completeness and accuracy of communication rather than clinical outcomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In an international survey of sepsis survivors from 41 countries, 45% reported dissatisfaction with sepsis education at the acute phase and 63% at the post-acute phase.

    “In an international survey of sepsis survivors from 41 countries, 45% and 63% reported dissatisfaction with sepsis education at the acute and post-acute phase, respectively [582].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [582] Huang CY, Daniels R, Lembo A et al (2019) Life after sepsis: an international survey of survivors to understand the post-sepsis syndrome. Int J Qual Health Care 31(3):191–198 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Living in low-SES neighborhoods is associated with increased risk of sepsis, community-acquired bacteremia, death from bacteremia, and worse outcomes.

    “Additionally, living in neighborhoods with low SES is associated with an increased risk of sepsis [575], community-acquired bacteremia [575] and death from bacteremia [576] and worse outcomes [577].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [575] Donnelly JP, Lakkur S, Judd SE et al (2018) Association of neighborhood socioeconomic status with risk of infection and sepsis. Clin Infect Dis 66(12):1940–1947 source

      Not checked in the free run.

    • cites [576] Koch K, Norgaard M, Schonheyder HC et al (2013) Effect of socioeconomic status on mortality after bacteremia in working-age patients A Danish population-based cohort study. PLoS One 8(7):e70082 source

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    • cites [577] Ho KM, Dobb GJ, Knuiman M et al (2008) The effect of socioeconomic status on outcomes for seriously ill patients: a linked data cohort study. Med J Aust 189(1):26–30 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Almost 40% of sepsis survivors are re-hospitalised within 3 months, often for preventable conditions, contributing to increased healthcare costs.

    “Almost 40% of sepsis survivors are re-hospitalised within 3 months, often for preventable conditions [580], contributing to increased healthcare costs [581].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [580] Prescott HC, Angus DC (2018) Enhancing recovery from sepsis: a review. JAMA 319(1):62–75 source

      Not checked in the free run.

    • cites [581] Gruther W, Pieber K, Steiner I et al (2017) Can early rehabilitation on the general ward after an intensive care unit stay reduce hospital length of stay in survivors of critical illness?: A randomized controlled trial. Am J Phys Med Rehabil 96(9):607–615 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Four observational studies examined peer support groups in ICU patients, though they were not specific to sepsis patients.

    “Four observational studies examined the impact of peer support groups on ICU patients, though they were not specific to sepsis patients.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [554] Halm MA (1990) Effects of support groups on anxiety of family members during critical illness. Heart Lung 19(1):62–71

      Not checked in the free run.

    • cites [555] Fridlund B, Stener-Bengtsson A, Wannman AL (1993) Social support and social network after acute myocardial infarction; the critically ill male patient’s needs, choice and motives. Intensive Crit Care Nurs 9(2):88–94 source

      Not checked in the free run.

    • cites [556] McPeake J, Shaw M, Iwashyna TJ et al (2017) Intensive care syndrome: promoting independence and return to employment (InS:PIRE). Early evaluation of a complex intervention. PLoS One 12(11):e0188028 source

      Not checked in the free run.

    • cites [557] Sabo KA, Kraay C, Rudy E et al (1989) ICU family support group sessions: family members’ perceived benefits. Appl Nurs Res 2(2):82–89 source

      Not checked in the free run.

    • cites [558] Parent N, Fortin F (2000) A randomized, controlled trial of vicarious experience through peer support for male first-time cardiac surgery patients: impact on anxiety, self-efficacy expectation, and self-reported activity. Heart Lung 29(6):389–400 source

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    Overall evidence for routine formal palliative care interventions in ICU patients is of low quality and shows mixed benefit.

    “Overall evidence for routine formal palliative care interventions in ICU patients is of low quality and provides mixed evidence of benefit.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    A family care conference with nursing staff at ICU discharge resulted in lower anxiety scores for family members compared to control, though it is unclear families participated in shared decision making.

    “A family care conference with nursing staff at the time of discharge from the ICU resulted in lower anxiety scores for family members compared to a control group although it is not clear that families participated in SDM [592].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [592] Bokinskie JC (1992) Family conferences: a method to diminish transfer anxiety. J Neurosci Nurs 24(3):129–133 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Family caregivers of critically ill patients discharged home felt overwhelmed, unprepared, and had difficulty managing expectations.

    “Family caregivers of critically ill patients discharged home felt overwhelmed and unprepared and had difficulty managing expectations [593].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [593] Choi J, Lingler JH, Donahoe MP et al (2018) Home discharge following critical illness: a qualitative analysis of family caregiver experience. Heart Lung 47(4):401–407 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Only one of the six RCTs specifically studied patients with sepsis, evaluating a complex intervention including education, primary care follow-up, and post-discharge monitoring.

    “Only one specifically studied patients with sepsis [588], evaluating a complex intervention, which included education along with primary care follow-up and post-discharge monitoring.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [588] Schmidt K, Worrack S, Von Korff M et al (2016) Effect of a primary care management intervention on mental health-related quality of life among survivors of sepsis: a randomized clinical trial. JAMA 315(24):2703–2711 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Medication reconciliation has been associated with fewer medication errors and may help reduce hospital readmission.

    “Medication reconciliation has been associated with fewer medication errors [598, 612] and may help reduce hospital readmission [613, 614].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [598] Mekonnen AB, McLachlan AJ, Brien JA (2016) Pharmacy-led medication reconciliation programmes at hospital transitions: a systematic review and meta-analysis. J Clin Pharm Ther 41(2):128–144 source

      Not checked in the free run.

    • cites [612] Pronovost P, Weast B, Schwarz M et al (2003) Medication reconciliation: a practical tool to reduce the risk of medication errors. J Crit Care 18(4):201–205 source

      Not checked in the free run.

    • cites [613] Ravn-Nielsen LV, Duckert ML, Lund ML et al (2018) Effect of an in-hospital multifaceted clinical pharmacist intervention on the risk of readmission: a randomized clinical trial. JAMA Intern Med 178(3):375–382 source

      Not checked in the free run.

    • cites [614] Taylor SP, Chou SH, Sierra MF et al (2020) Association between Adherence to Recommended Care and Outcomes for Adult Survivors of Sepsis. Ann Am Thorac Soc 17(1):89–97 source

      Not checked in the free run.

    • Rests on an assumption: Medication reconciliation is broadly recognised to be important during patient transitions.

  • May combine two claims.

    Findingcitation

    Hospital readmission within 90 days of discharge occurs in approximately 40% of sepsis survivors and is associated with high costs.

    “Hospital readmission within 90 days of discharge occurs in approximately 40% of sepsis survivors and is associated with high costs [624].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [624] Mayr FB, Talisa VB, Balakumar V et al (2017) Proportion and cost of unplanned 30-day readmissions after sepsis compared with other medical conditions. JAMA 317(5):530–531 source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    There are insufficient data to suggest any specific tool to assess for physical, cognitive, and emotional problems after discharge, and the optimal approach will vary by patient and setting.

    “There are insufficient data to suggest any specific tool to assess for these problems, and the optimal approach will vary by patient and setting.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    There were insufficient studies to allow meta-analysis and the limited evidence is of very low quality.

    “There were insufficient studies to allow meta-analysis and the limited evidence is of very low quality.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Post-critical illness programmes are consistently well-liked by patients and offer an environment to learn about challenges sepsis survivors face and to pilot and test interventions for enhancing recovery.

    “While efficacy data are equivocal, these programmes are consistently well-liked by patients and offer an environment to learn about challenges sepsis survivors face, as well as to pilot and test interventions for enhancing recovery [637, 643].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [637] Teixeira C, Rosa RG (2018) Post-intensive care outpatient clinic: is it feasible and effective? A literature review. Rev Bras Ter Intensiva 30(1):98–111 source

      Not checked in the free run.

    • cites [643] Prescott HC, Iwashyna TJ, Blackwood B et al (2019) Understanding and enhancing sepsis survivorship. Priorities for research and practice. Am J Respir Crit Care Med 200(8):972–981 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Few randomised studies have assessed post-critical illness clinics, and meta-analysis found no differences from usual care in mortality, quality of life, physical function, or cognition, with possible small improvements in psychological symptoms.

    “Few randomised studies have assessed post-critical illness clinics [588, 628, 638, 639], and—consistent with a recent Cochrane review [640]—our meta-analysis found no differences from usual care in terms of mortality, QoL, physical function, or cognition, with possible small improvements in psychological symptoms (anxiety, depression, PTSD).”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [588] Schmidt K, Worrack S, Von Korff M et al (2016) Effect of a primary care management intervention on mental health-related quality of life among survivors of sepsis: a randomized clinical trial. JAMA 315(24):2703–2711 source

      Not checked in the free run.

    • cites [628] Douglas SL, Daly BJ, Kelley CG et al (2007) Chronically critically ill patients: health-related quality of life and resource use after a disease management intervention. Am J Crit Care 16(5):447–457 source

      Not checked in the free run.

    • cites [638] Cuthbertson BH, Rattray J, Campbell MK et al (2009) The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving long term outcomes from critical illness: a pragmatic randomised controlled trial. BMJ 339:b3723 source

      Not checked in the free run.

    • cites [639] Jensen JF, Egerod I, Bestle MH et al (2016) A recovery program to improve quality of life, sense of coherence and psychological health in ICU survivors: a multicenter randomized controlled trial, the RAPIT study. Intensive Care Med 42(11):1733–1743 source

      Not checked in the free run.

    • cites [640] Schofield-Robinson OJ, Lewis SR, Smith AF et al (2018) Follow-up services for improving long-term outcomes in intensive care unit (ICU) survivors. Cochrane Database Syst Rev 11:CD012701

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    None of the three studies specifically evaluated a sepsis population or reported the proportion of sepsis patients.

    “None of the three studies specifically evaluated a sepsis population or reported the proportion of sepsis patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Sepsis survivors are at increased risk for recurrent infection, AKI, and new cardiovascular events compared to patients hospitalised for other diagnoses.

    “In addition, sepsis survivors are at increased risk for recurrent infection, AKI and new cardiovascular events compared to patients hospitalised for other diagnoses [580].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [580] Prescott HC, Angus DC (2018) Enhancing recovery from sepsis: a review. JAMA 319(1):62–75 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A prospective cohort study of cognitive training from ICU up to 2 months found overall minimal clinical relevance, with some meaningful results in younger patients but not middle-aged or older patients.

    “In addition, a prospective cohort study testing a series of cognitive training sessions starting in the ICU and continued for up to 2 months, found overall minimal clinical relevance as Minimum Clinically Important Difference (MID) of Montreal Cognitive Assessment (MOCA) was small, with some meaningful results in younger patients, but not in the middle-aged or older population [635, 636].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [635] Zhao J, Yao L, Li M et al (2019) Effects of early intervention training on cognitive impairment in critical patients. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 31(3):298–302

      Not checked in the free run.

    • cites [636] Wong GKC, Mak JSY, Wong A et al (2017) Minimum clinically important difference of Montreal Cognitive Assessment in aneurysmal subarachnoid hemorrhage patients. J Clin Neurosci 46:41–44 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    A proof-of-concept single-centre pilot study found the multi-faceted early cognitive intervention feasible and safe, but underpowered and inconclusive regarding clinical effects on cognitive function and health-related quality of life at 3 months.

    “The results demonstrated that the intervention was feasible and safe, but the study was underpowered and therefore inconclusive regarding its clinical effects on cognitive function and health-related QoL outcomes at 3-month follow-up.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [634] Brummel NE, Girard TD, Ely EW et al (2014) Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the Activity and Cognitive Therapy in ICU (ACT-ICU) trial. Intensive Care Med 40(3):370–379 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Meta-analysis suggests critical care transition programmes reduce risk of in-hospital mortality and potentially reduce risk of ICU readmission.

    “Meta-analysis of these studies suggests that critical care transition programmes reduce risk of in-hospital mortality and potentially reduce risk of ICU readmission.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    There are a growing number of online resources and informational brochures regarding post intensive care and post-sepsis syndrome.

    “There are a growing number of online resources and informational brochures regarding “post intensive care” / “post-sepsis syndrome”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [580] Prescott HC, Angus DC (2018) Enhancing recovery from sepsis: a review. JAMA 319(1):62–75 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    More studies of post-sepsis follow-up programmes are in process.

    “More studies of post-sepsis follow-up programmes are in process [641, 642].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [641] Kowalkowski M, Chou SH, McWilliams A et al (2019) Structured, proactive care coordination versus usual care for Improving Morbidity during Post-Acute Care Transitions for Sepsis (IMPACTS): a pragmatic, randomized controlled trial. Trials 20(1):660 source

      Not checked in the free run.

    • cites [642] Paratz JD, Kenardy J, Mitchell G et al (2014) IMPOSE (IMProving Outcomes after Sepsis)-the effect of a multidisciplinary follow-up service on health-related quality of life in patients postsepsis syndromes-a double-blinded randomised controlled trial: protocol. BMJ Open 4(5):e004966 source

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    The interventions and quality of life measures varied among the three studies, each with severe limitations.

    “The interventions and QoL measures varied among the three studies each with severe limitations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Sepsis survivors are at risk for hospital readmission, which has been associated with increased mortality or discharge to hospice.

    “Sepsis survivors are at risk for hospital readmission, which has been associated with increased mortality or discharge to hospice [622, 623].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [622] Dietz BW, Jones TK, Small DS et al (2017) The relationship between index hospitalizations, sepsis, and death or transition to hospice care during 30-day hospital readmissions. Med Care 55(4):362–370 source

      Not checked in the free run.

    • cites [623] Ortego A, Gaieski DF, Fuchs BD et al (2015) Hospital-based acute care use in survivors of septic shock. Crit Care Med 43(4):729–737 source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Post-critical illness programmes vary in structure and are not consistently available worldwide.

    “These programmes vary in their structure, and are not consistently available worldwide [637].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [637] Teixeira C, Rosa RG (2018) Post-intensive care outpatient clinic: is it feasible and effective? A literature review. Rev Bras Ter Intensiva 30(1):98–111 source

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    These physical rehabilitation studies focused on critically ill patients, generally defined by days in ICU or days with mechanical ventilation, and begin on the floor or post-hospital setting.

    “These studies focused on critically ill patients, generally defined by days in ICU or days with mechanical ventilation and begin on the floor or post-hospital setting.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Meta-analysis suggests possible small improvements in quality of life and depressive symptoms from physical rehabilitation, but no difference in mortality, physical function, or anxiety.

    “Meta-analysis suggests possible small improvements in QoL and depressive symptoms, but no difference in mortality, physical function, or anxiety.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    This suggestion is consistent with the guidance of several expert panels.

    “This suggestion is consistent with the guidance of several expert panels [646, 652, 653].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [646] Connolly B, Thompson A, Douiri A et al (2015) Exercise-based rehabilitation after hospital discharge for survivors of critical illness with intensive care unit-acquired weakness: a pilot feasibility trial. J Crit Care 30(3):589–598 source

      Not checked in the free run.

    • cites [652] Health NIf, Excellence C (2014) Rehabilitation after critical illness in adults: NICE Reino Unido; 2014. https://www.nice.org.uk/guidance/qs158/resources/rehabilitation-after-critical-illness-in-adults-pdf-75545546693317. Accessed 17 Mar 2021

      Not checked in the free run.

    • cites [653] Major ME, Kwakman R, Kho ME et al (2016) Surviving critical illness: what is next? An expert consensus statement on physical rehabilitation after hospital discharge. Crit Care 2016 20:354

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The analysis supporting the 3rd International Consensus Conference identified qSOFA as a predictor of poor outcome in patients with known or suspected infection, but no analysis supported its use as a screening tool.

    “Data analysis used to support the recommendations of the 3rd International Consensus Conference on the Definitions of Sepsis identified qSOFA as a predictor of poor outcome in patients with known or suspected infection, but no analysis was performed to support its use as a screening tool [5].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Seymour CW, Liu VX, Iwashyna TJ et al (2016) Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315(8):762–774 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sepsis performance improvement programmes are associated with better adherence to sepsis bundles and reduced mortality in patients with sepsis and septic shock (OR 0.66; 95% CI 0.61-0.72).

    “a meta-analysis of 50 observational studies on the effect of performance improvement programmes showed that these programmes were associated with better adherence to sepsis bundles along with a reduction in mortality (OR 0.66; 95% CI 0.61–0.72) in patients with sepsis and septic shock [27].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Damiani E, Donati A, Serafini G et al (2015) Effect of performance improvement programs on compliance with sepsis bundles and mortality: a systematic review and meta-analysis of observational studies. PLoS One 10(5):e0125827 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sepsis screening tools vary widely in diagnostic accuracy, with most having poor predictive values, although use of some is associated with improvements in care processes.

    “There is wide variation in diagnostic accuracy of these tools with most having poor predictive values, although the use of some was associated with improvements in care processes [28–31].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [28] Alberto L, Marshall AP, Walker R et al (2017) Screening for sepsis in general hospitalized patients: a systematic review. J Hosp Infect 96(4):305–315 source

      Not checked in the free run.

    • cites [29] Bhattacharjee P, Edelson DP, Churpek MM (2017) Identifying patients with sepsis on the hospital wards. Chest 151(4):898–907 source

      Not checked in the free run.

    • cites [30] Makam AN, Nguyen OK, Auerbach AD (2015) Diagnostic accuracy and effectiveness of automated electronic sepsis alert systems: a systematic review. J Hosp Med 10(6):396–402 source

      Not checked in the free run.

    • cites [31] Warttig S, Alderson P, Evans DJ et al (2018) Automated monitoring compared to standard care for the early detection of sepsis in critically ill patients. Cochrane Database oSyste Rev. 6(6):CD012404-CD

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While some tissues such as brain and kidneys auto-regulate blood flow, MAPs below a threshold usually understood as approximately 60 mm Hg are associated with decreased organ perfusion, which tracks linearly with MAP.

    “While some tissues, such as the brain and kidneys have the ability to auto-regulate blood flow, MAPs below a threshold, usually understood to be approximately 60 mm Hg, are associated with decreased organ perfusion, which tracks linearly with MAP [79].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [79] LeDoux D, Astiz ME, Carpati CM et al (2000) Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med 28(8):2729–2732 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Lactate cutoffs for an elevated level ranged from 1.6 to 2.5 mmol/L, with similar diagnostic characteristics regardless of cutoff.

    “The lactate cutoffs determining an elevated level ranged from 1.6 to 2.5 mmol/L, although diagnostic characteristics were similar regardless of the cutoff.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [50] Contenti J, Corraze H, Lemoel F et al (2015) Effectiveness of arterial, venous, and capillary blood lactate as a sepsis triage tool in ED patients. Am J Emerg Med 33(2):167–172 source

      Not checked in the free run.

    • cites [51] Karon BS, Tolan NV, Wockenfus AM et al (2017) Evaluation of lactate, white blood cell count, neutrophil count, procalcitonin and immature granulocyte count as biomarkers for sepsis in emergency department patients. Clin Biochem 50(16–17):956–958 source

      Not checked in the free run.

    • cites [52] Ljungstrom L, Pernestig AK, Jacobsson G et al (2017) Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis. PLoS One 12(7):e0181704 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a systematic review and meta-analysis, dynamic assessment to guide fluid therapy was associated with reduced mortality (RR 0.59; 95% CI 0.42-0.83), ICU length of stay (MD −1.16 days; 95% CI −1.97 to −0.36), and duration of mechanical ventilation (−2.98 h; 95% CI −5.08 to −0.89).

    “In a systematic review and meta-analysis, dynamic assessment to guide fluid therapy was associated with reduced mortality (RR 0.59; 95% CI 0.42–0.83), ICU length of stay (MD −1.16 days; 95% CI −1.97 to −0.36), and duration of mechanical ventilation (−2.98 h; 95% CI −5.08 to −0.89) [3].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Fleischmann-Struzek C, Mellhammar L, Rose N et al (2020) Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Intensive Care Med 46(8):1552–1562 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    qSOFA is more specific but less sensitive than two of four SIRS criteria for early identification of infection-induced organ dysfunction.

    “Studies have shown that qSOFA is more specific but less sensitive than having two of four SIRS criteria for early identification of infection induced organ dysfunction [40–43].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [40] Fernando SM, Tran A, Taljaard M et al (2018) Prognostic accuracy of the quick sequential organ failure assessment for mortality in patients with suspected infection: a systematic review and meta-analysis. Ann Intern Med 168(4):266–275 source

      Not checked in the free run.

    • cites [41] Herwanto V, Shetty A, Nalos M et al (2019) Accuracy of quick sequential organ failure assessment score to predict sepsis mortality in 121 studies including 1,716,017 individuals: a systematic review and meta-analysis. Crit Care Explor. 1(9):e0043 source

      Not checked in the free run.

    • cites [42] Serafim R, Gomes JA, Salluh J et al (2018) A comparison of the Quick-SOFA and systemic inflammatory response syndrome criteria for the diagnosis of sepsis and prediction of mortality: a systematic review and meta-analysis. Chest 153(3):646–655 source

      Not checked in the free run.

    • cites [43] Cinel I, Kasapoglu US, Gul F et al (2020) The initial resuscitation of septic shock. J Crit Care 57:108–117 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Serum lactate is an important biomarker of tissue hypoxia and dysfunction but is not a direct measure of tissue perfusion.

    “Serum lactate is an important biomarker of tissue hypoxia and dysfunction, but is not a direct measure of tissue perfusion [73].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] Levy B (2006) Lactate and shock state: the metabolic view. Curr Opin Crit Care 12(4):315–321 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Failure to receive 30 ml/kg crystalloid within 3 h was associated with delayed resolution of hypotension and increased ICU length of stay.

    “failure to receive 30 ml/kg of crystalloid fluid therapy within 3 h of sepsis onset was associated with increased odds of in-hospital mortality, delayed resolution of hypotension and increased length of stay in ICU”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [63] Kuttab HI, Lykins JD, Hughes MD et al (2019) Evaluation and predictors of fluid resuscitation in patients with severe sepsis and septic shock. Crit Care Med 47(11):1582–1590 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Temperature of the extremities, skin mottling, and capillary refill time have been validated and shown to be reproducible signs of tissue perfusion.

    “Temperature of the extremities, skin mottling and capillary refill time (CRT) have been validated and shown to be reproducible signs of tissue perfusion [76, 77].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [76] Cecconi M, Hernandez G, Dunser M et al (2019) Fluid administration for acute circulatory dysfunction using basic monitoring: narrative review and expert panel recommendations from an ESICM task force. Intensive Care Med 45(1):21–32 source

      Not checked in the free run.

    • cites [77] Lara B, Enberg L, Ortega M et al (2017) Capillary refill time during fluid resuscitation in patients with sepsis-related hyperlactatemia at the emergency department is related to mortality. PLoS One 12(11):e0188548 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    For lactate as a sepsis screen, sensitivities range from 66 to 83% and specificities from 80 to 85%.

    “Sensitivities range from 66 to 83%, with specificities ranging from 80 to 85%.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [50] Contenti J, Corraze H, Lemoel F et al (2015) Effectiveness of arterial, venous, and capillary blood lactate as a sepsis triage tool in ED patients. Am J Emerg Med 33(2):167–172 source

      Not checked in the free run.

    • cites [51] Karon BS, Tolan NV, Wockenfus AM et al (2017) Evaluation of lactate, white blood cell count, neutrophil count, procalcitonin and immature granulocyte count as biomarkers for sepsis in emergency department patients. Clin Biochem 50(16–17):956–958 source

      Not checked in the free run.

    • cites [52] Ljungstrom L, Pernestig AK, Jacobsson G et al (2017) Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis. PLoS One 12(7):e0181704 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the PROCESS, ARISE, and PROMISE trials, the average volume of fluid received pre-randomisation was in the range of 30 ml/kg, suggesting this fluid volume has been adopted in routine clinical practice.

    “In the PROCESS [64], ARISE [65] and PROMISE [66] trials, the average volume of fluid received pre-randomisation was also in the range of 30 ml/kg, suggesting that this fluid volume has been adopted in routine clinical practice [67].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] Rowan KM, Angus DC, Bailey M et al (2017) Early, goal-directed therapy for septic shock—a patient-level meta-analysis. N Engl J Med 376(23):2223–2234 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In ANDROMEDA-SHOCK, 28-day mortality was 34.9% in the peripheral perfusion group and 43.4% in the lactate group, but the difference did not reach statistical significance (HR 0.75; 95% CI 0.55-1.02).

    “28-day mortality was 34.9% in the peripheral perfusion group and 43.4% in the lactate group, but this difference did not reach statistical significance (HR 0.75; 95% CI 0.55–1.02).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] Hernandez G, Ospina-Tascon GA, Damiani LP et al (2019) Effect of a resuscitation strategy targeting peripheral perfusion status vs serum lactate levels on 28-day mortality among patients with septic shock: the ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA 321(7):654–664 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A recent RCT in patients aged 65 years and older with septic shock compared permissive hypotension (MAP 60-65 mm Hg) with usual care; the intervention group achieved a mean MAP of 66.7 mm Hg versus 72.6 mm Hg in usual care.

    “A recent RCT, monitored to ensure protocol and MAP target compliance, compared a “permissive hypotension” (MAP 60–65 mm Hg) group with a “usual care” group that received vasopressors and MAP targets set by the treating physician in patients aged 65 years and older with septic shock [82, 83]. The intervention group in this study achieved a mean MAP of 66.7 mm Hg, compared with 72.6 mm Hg in the”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [82] Lamontagne F, Meade MO, Hebert PC et al (2016) Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial. Intensive Care Med 42(4):542–550 source

      Not checked in the free run.

    • cites [83] Lamontagne F, Richards-Belle A, Thomas K et al (2020) Effect of reduced exposure to vasopressors on 90-day mortality in older critically ill patients with vasodilatory hypotension: a randomized clinical trial. JAMA 323(10):938–949 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    An elevated lactate level increases and a normal lactate level decreases the likelihood of a final diagnosis of sepsis in patients with suspected sepsis.

    “In summary, the presence of an elevated or normal lactate level significantly increases or decreases, respectively, the likelihood of a final diagnosis of sepsis in patients with suspected sepsis.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [50] Contenti J, Corraze H, Lemoel F et al (2015) Effectiveness of arterial, venous, and capillary blood lactate as a sepsis triage tool in ED patients. Am J Emerg Med 33(2):167–172 source

      Not checked in the free run.

    • cites [51] Karon BS, Tolan NV, Wockenfus AM et al (2017) Evaluation of lactate, white blood cell count, neutrophil count, procalcitonin and immature granulocyte count as biomarkers for sepsis in emergency department patients. Clin Biochem 50(16–17):956–958 source

      Not checked in the free run.

    • cites [52] Ljungstrom L, Pernestig AK, Jacobsson G et al (2017) Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis. PLoS One 12(7):e0181704 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Studies show an association between point-of-care lactate measurement at presentation and reduced mortality, but results are inconsistent.

    “Studies showed an association between the use of point-of-care lactate measurements at presentation and reduced mortality; however, the results are inconsistent [53].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [53] Morris E, McCartney D, Lasserson D et al (2017) Point-of-care lactate testing for sepsis at presentation to health care: a systematic review of patient outcomes. Br J Gen Pract 67(665):e859–e870 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Normal serum lactate levels are not achievable in all patients with septic shock, but studies support resuscitative strategies that decrease lactate toward normal.

    “The panel recognises that normal serum lactate levels are not achievable in all patients with septic shock, but these studies support resuscitative strategies that decrease lactate toward normal.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [74] Gu WJ, Zhang Z, Bakker J (2015) Early lactate clearance-guided therapy in patients with sepsis: a meta-analysis with trial sequential analysis of randomized controlled trials. Intensive Care Med 41(10):1862–1863 source

      Not checked in the free run.

    • cites [75] Simpson SQ, Gaines M, Hussein Y et al (2016) Early goal-directed therapy for severe sepsis and septic shock: a living systematic review. J Crit Care 36:43–48 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the original qSOFA derivation study, only 24% of infected patients had a qSOFA score of 2 or 3, but these patients accounted for 70% of poor outcomes.

    “In the original derivation study, authors found that only 24% of infected patients had a qSOFA score 2 or 3, but these patients accounted for 70% of poor outcomes [5].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Seymour CW, Liu VX, Iwashyna TJ et al (2016) Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315(8):762–774 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Neither SIRS nor qSOFA are ideal sepsis screening tools.

    “Neither SIRS nor qSOFA are ideal screening tools for sepsis and the bedside clinician needs to understand the limitations of each.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [40] Fernando SM, Tran A, Taljaard M et al (2018) Prognostic accuracy of the quick sequential organ failure assessment for mortality in patients with suspected infection: a systematic review and meta-analysis. Ann Intern Med 168(4):266–275 source

      Not checked in the free run.

    • cites [41] Herwanto V, Shetty A, Nalos M et al (2019) Accuracy of quick sequential organ failure assessment score to predict sepsis mortality in 121 studies including 1,716,017 individuals: a systematic review and meta-analysis. Crit Care Explor. 1(9):e0043 source

      Not checked in the free run.

    • cites [42] Serafim R, Gomes JA, Salluh J et al (2018) A comparison of the Quick-SOFA and systemic inflammatory response syndrome criteria for the diagnosis of sepsis and prediction of mortality: a systematic review and meta-analysis. Chest 153(3):646–655 source

      Not checked in the free run.

    • cites [43] Cinel I, Kasapoglu US, Gul F et al (2020) The initial resuscitation of septic shock. J Crit Care 57:108–117 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A study of 12,380 ward patients in 48 UK hospitals showed that delayed admission to ICU led to higher 90-day mortality and further physiological deterioration.

    “Similarly, another study of 12,380 ward patients in 48 UK hospitals showed that [88] delayed admission to ICU led to higher 90-day mortality and further physiological deterioration.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [88] Harris S, Singer M, Sanderson C et al (2018) Impact on mortality of prompt admission to critical care for deteriorating ward patients: an instrumental variable analysis using critical care bed strain. Intensive Care Med 44(5):606–615 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There is evidence of improved patient satisfaction, increased patient safety, better patient flow, and improved staff morale with timely ICU admission.

    “There is also evidence of improved patient satisfaction, increased patient safety, better patient flow and improved staff morale [89].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [89] Montgomery A, Panagopoulou E, Kehoe I et al (2011) Connecting organisational culture and quality of care in the hospital: is job burnout the missing link? J Health Organ Manag 25(1):108–123 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Procalcitonin is undetectable in healthy states but rises rapidly in response to pro-inflammatory stimuli, especially bacterial infections.

    “Procalcitonin is undetectable in healthy states, but rises rapidly in response to pro-inflammatory stimuli, especially bacterial infections [127].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [127] Peng F, Chang W, Xie JF et al (2019) Ineffectiveness of procalcitonin-guided antibiotic therapy in severely critically ill patients: a meta-analysis. Int J Infect Dis 85:158–166 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    All the aforementioned studies on antimicrobial timing were observational analyses and hence at risk of bias due to insufficient sample size, inadequate risk-adjustment, blending together effects of large delays with short delays, or other study design issues.

    “It should be noted that all the aforementioned studies were observational analyses and hence at risk of bias due to insufficient sample size, inadequate risk-adjustment, blending together the effects of large delays until antibiotics with short delays, or other study design issues [118].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] Weinberger J, Rhee C, Klompas M (2020) A critical analysis of the literature on time-to-antibiotics in suspected sepsis. J Infect Dis 222(Supplement_2):S110–S118 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Delayed admissions of critically ill patients from the emergency department are associated with decreased sepsis bundle compliance and increased mortality, ventilator duration, and ICU and hospital length of stay.

    “Delayed admissions of critically ill patients from ED are associated with decreased sepsis bundle compliance and increased mortality, ventilator duration, and ICU and hospital length of stay [84].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [84] Mohr NM, Wessman BT, Bassin B et al (2020) Boarding of critically ill patients in the emergency department. Crit Care Med 48(8):1180–1187 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The signs and symptoms of sepsis are nonspecific and often mimic multiple other diseases.

    “The signs and symptoms of sepsis are nonspecific and often mimic multiple other diseases [90–92].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [90] Klein Klouwenberg PM, Cremer OL, van Vught LA et al (2015) Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care 19:319 source

      Not checked in the free run.

    • cites [91] Levin PD, Idrees S, Sprung CL et al (2012) Antimicrobial use in the ICU: indications and accuracy—an observational trial. J Hosp Med 7(9):672–678 source

      Not checked in the free run.

    • cites [92] Minderhoud TC, Spruyt C, Huisman S et al (2017) Microbiological outcomes and antibiotic overuse in Emergency Department patients with suspected sepsis. Neth J Med 75(5):196–203

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    In a study of 10,811 patients treated in four Utah hospitals, each hour delay from ED arrival to antimicrobial administration was associated with 1.16 increased odds of in-hospital mortality and 1.10 increased odds of 1-year mortality (1.13 in patients with hypotension vs 1.09 in patients without hypotension).

    “Finally, in a study of 10,811 patients treated in four Utah hospitals, each hour delay in time from ED arrival to administration of antimicrobials was associated with 1.16 increased odds of in-hospital and 1.10 increased odds of 1-year mortality (1.13 in patients with”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [111] Peltan ID, Brown SM, Bledsoe JR et al (2019) ED door-to-antibiotic time and long-term mortality in sepsis. Chest 155(5):938–946 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Potential harms of unnecessary antimicrobials include allergic or hypersensitivity reactions, kidney injury, thrombocytopenia, Clostridioides difficile infection, and antimicrobial resistance.

    “These include a range of adverse events such as allergic or hypersensitivity reactions, kidney injury, thrombocytopenia, Clostridioides difficile infection, and antimicrobial resistance [101–106].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [101] Baggs J, Jernigan JA, Halpin AL et al (2018) Risk of subsequent sepsis within 90 days after a hospital stay by type of antibiotic exposure. Clin Infect Dis 66(7):1004–1012 source

      Not checked in the free run.

    • cites [102] Branch-Elliman W, O’Brien W, Strymish J et al (2019) Association of duration and type of surgical prophylaxis with antimicrobial-associated adverse events. JAMA Surg 154(7):590–598 source

      Not checked in the free run.

    • cites [103] Hranjec T, Rosenberger LH, Swenson B et al (2012) Aggressive versus conservative initiation of antimicrobial treatment in critically ill surgical patients with suspected intensive-care-unit-acquired infection: a quasi-experimental, before and after observational cohort study. Lancet Infect Dis 12(10):774–780 source

      Not checked in the free run.

    • cites [104] Ong DSY, Frencken JF, Klein Klouwenberg PMC et al (2017) Short-course adjunctive gentamicin as empirical therapy in patients with severe sepsis and septic shock: a prospective observational cohort study. Clin Infect Dis 64(12):1731–1736 source

      Not checked in the free run.

    • cites [105] Tamma PD, Avdic E, Li DX et al (2017) Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med 177(9):1308–1315 source

      Not checked in the free run.

    • cites [106] Teshome BF, Vouri SM, Hampton N et al (2019) Duration of exposure to antipseudomonal beta-lactam antibiotics in the critically ill and development of new resistance. Pharmacotherapy 39(3):261–270 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The imperative to provide antimicrobials as early as possible must be balanced against potential harms associated with administering unnecessary antimicrobials to patients without infection.

    “The imperative to provide antimicrobials as early as possible, however, must be balanced against the potential harms associated with administering unnecessary antimicrobials to patients without infection [99, 100].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [99] Klompas M, Calandra T, Singer M (2018) Antibiotics for sepsis-finding the equilibrium. JAMA 320(14):1433–1434 source

      Not checked in the free run.

    • cites [100] Prescott HC, Iwashyna TJ (2019) Improving sepsis treatment by embracing diagnostic uncertainty. Ann Am Thorac Soc 16(4):426–429 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Accurately diagnosing sepsis is challenging because sepsis can present subtly, and some presentations that first appear to be sepsis turn out to be non-infectious conditions.

    “Accurately diagnosing sepsis is challenging as sepsis can present in subtle ways, and some presentations that first appear to be sepsis turn out to be non-infectious conditions [90, 93, 107, 108].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [90] Klein Klouwenberg PM, Cremer OL, van Vught LA et al (2015) Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care 19:319 source

      Not checked in the free run.

    • cites [93] Heffner AC, Horton JM, Marchick MR et al (2010) Etiology of illness in patients with severe sepsis admitted to the hospital from the emergency department. Clin Infect Dis 50(6):814–820 source

      Not checked in the free run.

    • cites [107] Contou D, Roux D, Jochmans S et al (2016) Septic shock with no diagnosis at 24 hours: a pragmatic multicenter prospective cohort study. Crit Care 20(1):360 source

      Not checked in the free run.

    • cites [108] Rhee C, Kadri SS, Danner RL et al (2016) Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes. Crit Care 20:89 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Among hospital survivors in that study, the delayed admission group had a longer hospital stay, higher mortality, and higher rates of mechanical ventilation and central venous catheterisation.

    “Among hospital survivors, the delayed admission group had a longer hospital stay, higher mortality, and higher rates of mechanical ventilation and central venous catherisation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [87] Chalfin DB, Trzeciak S, Likourezos A et al (2007) Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit. Crit Care Med 35(6):1477–1483 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The mortality reduction associated with early antimicrobials appears strongest in patients with septic shock, with weaker associations in patients without septic shock.

    “The mortality reduction associated with early antimicrobials appears strongest in patients with septic shock, where a number of studies have reported a strong association between time-to-antibiotics and death in patients with septic shock but weaker associations in patients without septic shock [98, 109, 110].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [98] Seymour CW, Gesten F, Prescott HC et al (2017) Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 376(23):2235–2244 source

      Not checked in the free run.

    • cites [109] Kumar A, Roberts D, Wood KE et al (2006) Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 34(6):1589–1596 source

      Not checked in the free run.

    • cites [110] Liu VX, Fielding-Singh V, Greene JD et al (2017) The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 196(7):856–863 source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    In a study of 35,000 patients at Kaiser Permanente Northern California, each additional hour from ER arrival to antimicrobial administration was associated with 1.09 increased odds of in-hospital mortality (1.07 for severe sepsis and 1.14 for septic shock), equating to a 0.4% absolute mortality increase for severe sepsis and 1.8% for septic shock.

    “In a study of 35,000 patients treated at Kaiser Permanente Northern California, each additional hour of time from ER arrival to administration of antimicrobials was associated with 1.09 increased odds of in-hospital mortality (1.07 for patients with “severe” sepsis (lactate ≥ 2, at least one episode of hypotension, required non-invasive or invasive mechanical ventilation or has organ dysfunction)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [110] Liu VX, Fielding-Singh V, Greene JD et al (2017) The timing of early antibiotics and hospital mortality in sepsis. Am J Respir Crit Care Med 196(7):856–863 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a study of 49,331 patients treated at 149 New York hospitals, each additional hour from ED arrival to antimicrobial administration was associated with 1.04 increased odds of in-hospital mortality (p < 0.001), with 1.07 for patients receiving vasopressors and 1.01 for patients not on vasopressors.

    “In a study of 49,331 patients treated at 149 New York hospitals, each additional hour of time from ED arrival to administration of antimicrobials was associated with 1.04 increased odds of in-hospital mortality, p < 0.001 (1.07 (95% CI 1.05–1.09) for patients receiving vasopressors vs. 1.01 (95% CI 0.99–1.04) for patients not on vasopressors) [98].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [98] Seymour CW, Gesten F, Prescott HC et al (2017) Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med 376(23):2235–2244 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Limited data from resource-limited settings suggest that timely administration of antimicrobials in patients with sepsis and septic shock is beneficial and potentially feasible.

    “Limited data from resource-limited settings suggest that timely administration of antimicrobials in patients with sepsis and septic shock is beneficial and potentially feasible [121–126].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [121] Chalya PL, Mabula JB, Koy M et al (2012) Typhoid intestinal perforations at a University teaching hospital in Northwestern Tanzania: a surgical experience of 104 cases in a resource-limited setting. World J Emerg Surg 7:4 source

      Not checked in the free run.

    • cites [122] Phua J, Koh Y, Du B et al (2011) Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. BMJ 342:d3245 source

      Not checked in the free run.

    • cites [123] Thwaites CL, Lundeg G, Dondorp AM et al (2016) Recommendations for infection management in patients with sepsis and septic shock in resource-limited settings. Intensive Care Med 42(12):2040–2042 source

      Not checked in the free run.

    • cites [124] Urayeneza O, Mujyarugamba P, Rukemba Z et al (2018) Increasing evidence-based interventions in patients with acute infections in a resource-limited setting: a before-and-after feasibility trial in Gitwe, Rwanda. Crit Care Med 46(8):1357–1366 source

      Not checked in the free run.

    • cites [125] Urayeneza O, Mujyarugamba P, Rukemba Z et al (2018) Increasing evidence-based interventions in patients with acute infections in a resource-limited setting: a before-and-after feasibility trial in Gitwe, Rwanda. Intensive Care Med 44(9):1436–1446 source

      Not checked in the free run.

    • cites [126] Yokota PK, Marra AR, Martino MD et al (2014) Impact of appropriate antimicrobial therapy for patients with severe sepsis and septic shock—a quality improvement study. PLoS One 9(11):e104475 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In patients at low risk for MDR organisms, there are no apparent benefits of using two gram-negative agents and there is risk of antimicrobial-associated undesirable effects including direct toxicity, C. difficile infection, and development of antibiotic resistance.

    “while in patients with a low risk for MDR organisms, we suggest using a single agents for empiric treatment, as there are no apparent benefits of using two agents and the a risk of antimicrobial-associated undesirable effects, including direct toxicity, Clostridioides difficile infection and development of antibiotic resistance [165].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [165] Arulkumaran N, Routledge M, Schlebusch S et al (2020) Antimicrobial-associated harm in critical care: a narrative review. Intensive Care Med 46(2):225–235 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The desirable effects of empiric antiviral therapy are unknown, and there is a risk of undesirable effects.

    “The desirable effects of empiric antiviral therapy are unknown, and as for other antimicrobial agents there is a risk of undesirable effects [165].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [165] Arulkumaran N, Routledge M, Schlebusch S et al (2020) Antimicrobial-associated harm in critical care: a narrative review. Intensive Care Med 46(2):225–235 source

      Not checked in the free run.

    • Rests on an assumption: Effective therapies are lacking for most zoonotic viruses that can manifest with clinical signs of sepsis.

  • May combine two claims.

    Premisecitation

    In documented MRSA infections, delays of more than 24-48 hours before antibiotic administration are associated with increased mortality in some studies but not in others.

    “Among patients with documented MRSA infections, delays of > 24–48 h until antibiotic administration are associated with increased mortality in some studies [143–147], but not in others [148–154].”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [143] Gasch O, Camoez M, Dominguez MA et al (2013) Predictive factors for early mortality among patients with methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother 68(6):1423–1430 source

      Not checked in the free run.

    • cites [144] Gasch O, Camoez M, Dominguez MA et al (2013) Predictive factors for mortality in patients with methicillin-resistant Staphylococcus aureus bloodstream infection: impact on outcome of host, microorganism and therapy. Clin Microbiol Infect 19(11):1049–1057 source

      Not checked in the free run.

    • cites [145] Lodise TP, McKinnon PS, Swiderski L et al (2003) Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia. Clin Infect Dis 36(11):1418–1423 source

      Not checked in the free run.

    • cites [146] Paul M, Kariv G, Goldberg E et al (2010) Importance of appropriate empirical antibiotic therapy for methicillin-resistant Staphylococcus aureus bacteraemia. J Antimicrob Chemother 65(12):2658–2665 source

      Not checked in the free run.

    • cites [147] Schramm GE, Johnson JA, Doherty JA et al (2006) Methicillin-resistant Staphylococcus aureus sterile-site infection: the importance of appropriate initial antimicrobial treatment. Crit Care Med 34(8):2069–2074 source

      Not checked in the free run.

    • cites [148] Fang CT, Shau WY, Hsueh PR et al (2006) Early empirical glycopeptide therapy for patients with methicillin-resistant Staphylococcus aureus bacteraemia: impact on the outcome. J Antimicrob Chemother 57(3):511–519 source

      Not checked in the free run.

    • cites [149] Gomez J, Garcia-Vazquez E, Banos R et al (2007) Predictors of mortality in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia: the role of empiric antibiotic therapy. Eur J Clin Microbiol Infect Dis 26(4):239–245 source

      Not checked in the free run.

    • cites [150] Griffin AT, Peyrani P, Wiemken TL et al (2013) Empiric therapy directed against MRSA in patients admitted to the intensive care unit does not improve outcomes in community-acquired pneumonia. Infection 41(2):517–523 source

      Not checked in the free run.

    • cites [151] Kett DH, Cano E, Quartin AA et al (2011) Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study. Lancet Infect Dis 11(3):181–189 source

      Not checked in the free run.

    • cites [152] Khatib R, Saeed S, Sharma M et al (2006) Impact of initial antibiotic choice and delayed appropriate treatment on the outcome of Staphylococcus aureus bacteremia. Eur J Clin Microbiol Infect Dis 25(3):181–185 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Immunocompromised patients, including those with neutropenia, HIV, haematological malignancies, stem cell or solid organ transplants, are particularly vulnerable to viral infections, and certain viruses can cause severe disease.

    “Immunocompromised patients are particularly vulnerable to viral infections, including patients with neutropenia, human immunodeficiency virus (HIV) infection, haematological malignancies and haematopoietic stem cell transplantation or solid organ transplants”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [229] Lin GL, McGinley JP, Drysdale SB et al (2018) Epidemiology and immune pathogenesis of viral sepsis. Front Immunol 9:2147 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patient-related risk factors for MRSA include prior MRSA infection or colonisation, recent IV antibiotics, recurrent skin infections or chronic wounds, invasive devices, haemodialysis, recent hospital admissions, and severity of illness.

    “Patient-related risk factors for MRSA include prior history of MRSA infection or colonisation, recent IV antibiotics, history of recurrent skin infections or chronic wounds, presence of invasive devices, haemodialysis, recent hospital admissions and severity of illness [136, 138–142].”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [136] Aliberti S, Reyes LF, Faverio P et al (2016) Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study. Lancet Infect Dis 16(12):1364–1376 source

      Not checked in the free run.

    • cites [138] Callejo-Torre F, Eiros Bouza JM, Olaechea Astigarraga P et al (2016) Risk factors for methicillin-resistant Staphylococcus aureus colonisation or infection in intensive care units and their reliability for predicting MRSA on ICU admission. Infez Med 24(3):201–209

      Not checked in the free run.

    • cites [139] Epstein L, Mu Y, Belflower R et al (2016) Risk factors for invasive methicillin-resistant Staphylococcus aureus infection after recent discharge from an acute-care hospitalization, 2011–2013. Clin Infect Dis 62(1):45–52 source

      Not checked in the free run.

    • cites [140] Shorr AF, Myers DE, Huang DB et al (2013) A risk score for identifying methicillin-resistant Staphylococcus aureus in patients presenting to the hospital with pneumonia. BMC Infect Dis 13:268 source

      Not checked in the free run.

    • cites [141] Torre-Cisneros J, Natera C, Mesa F et al (2018) Clinical predictors of methicillin-resistant Staphylococcus aureus in nosocomial and healthcare-associated pneumonia: a multicenter, matched case-control study. Eur J Clin Microbiol Infect Dis 37(1):51–56 source

      Not checked in the free run.

    • cites [142] Wooten DA, Winston LG (2013) Risk factors for methicillin-resistant Staphylococcus aureus in patients with community-onset and hospital-onset pneumonia. Respir Med 107(8):1266–1270 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The decision to start empiric antifungal therapy depends on the type and number of risk factors and local epidemiology of fungal infections.

    “Importantly, the decision to start empiric antifungal therapy depends on the type and number of risk factors, along with the local epidemiology of fungal infections.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The risk of Candida sepsis or septic shock in immunosuppressed populations other than febrile neutropenia is highly disease- and therapy-specific.

  • May combine two claims.

    Premisecitation

    Some observational studies suggested prompt appropriate empiric antifungal therapy may be associated with reduced mortality, but these do not prove causality or clarify timing, and other studies failed to show the association.

    “Some observational studies suggested that prompt initiation of appropriate empiric antifungal therapy may be associated with a reduction in mortality, however these studies do not prove a causal relationship between antifungal therapy and outcome, nor do they clarify the role of timing of treatment, and some other studies have failed to show this association [167, 171–173].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [167] Kollef M, Micek S, Hampton N et al (2012) Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 54(12):1739–1746 source

      Not checked in the free run.

    • cites [171] Garey KW, Rege M, Pai MP et al (2006) Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 43(1):25–31 source

      Not checked in the free run.

    • cites [172] Marriott DJ, Playford EG, Chen S et al (2009) Determinants of mortality in non-neutropenic ICU patients with candidaemia. Crit Care 13(4):R115 source

      Not checked in the free run.

    • cites [173] Morrell M, Fraser VJ, Kollef MH (2005) Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 49(9):3640–3645 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Failure to cover MRSA in a patient with MRSA may be harmful, and unnecessary MRSA coverage in a patient without MRSA may also be harmful.

    “Failure to cover for MRSA in a patient with MRSA may be harmful, but unnecessary MRSA coverage in a patient without MRSA may also be harmful.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Sepsis and septic shock due to fungi are most commonly observed in ICUs and are associated with poor outcomes.

    “Sepsis and septic shock due to fungi are most commonly observed in ICUs and are associated with poor outcomes [166–170].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [166] Bassetti M, Righi E, Ansaldi F et al (2014) A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med 40(6):839–845 source

      Not checked in the free run.

    • cites [167] Kollef M, Micek S, Hampton N et al (2012) Septic shock attributed to Candida infection: importance of empiric therapy and source control. Clin Infect Dis 54(12):1739–1746 source

      Not checked in the free run.

    • cites [168] Magill SS, Edwards JR, Bamberg W et al (2014) Multistate point-prevalence survey of health care-associated infections. N Engl J Med 370(13):1198–1208 source

      Not checked in the free run.

    • cites [169] Mean M, Marchetti O, Calandra T (2008) Bench-to-bedside review: Candida infections in the intensive care unit. Crit Care 12(1):204 source

      Not checked in the free run.

    • cites [170] Pappas PG, Kauffman CA, Andes DR et al (2016) Clinical practice guideline for the management of candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 62(4):e1-50 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Empiric double coverage of gram-negative bacilli is most important in patients at high risk for resistant organisms with severe illness, particularly septic shock.

    “Empiric double coverage of gram-negative bacilli is most important in patients at high risk for resistant organisms with severe illness, particularly septic shock.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Factors guiding double gram-negative coverage include proven infection or colonisation with resistant organisms in the prior year, local prevalence, hospital-acquired/healthcare-associated infection, broad-spectrum antibiotics in prior 90 days, concurrent SDD, travel to a highly endemic country in prior 90 days, and hospitalisation abroad in prior 90 days.

    “Factors to guide this decision include: proven infection or colonisation with antibiotic-resistant organisms within the preceding year, local prevalence of antibiotic-resistant organisms, hospital-acquired/healthcare associated (versus community-acquired infection), broad-spectrum antibiotic use within the preceding 90 days”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [162] Alevizakos M, Karanika S, Detsis M et al (2016) Colonisation with extended-spectrum beta-lactamase-producing Enterobacteriaceae and risk for infection among patients with solid or haematological malignancy: a systematic review and meta-analysis. Int J Antimicrob Agents 48(6):647–654 source

      Not checked in the free run.

    • cites [163] Rottier WC, Bamberg YR, Dorigo-Zetsma JW et al (2015) Predictive value of prior colonization and antibiotic use for third-generation cephalosporin-resistant enterobacteriaceae bacteremia in patients with sepsis. Clin Infect Dis 60(11):1622–1630 source

      Not checked in the free run.

    • cites [164] Rottier WC, van Werkhoven CH, Bamberg YRP et al (2018) Development of diagnostic prediction tools for bacteraemia caused by third-generation cephalosporin-resistant enterobacteria in suspected bacterial infections: a nested case-control study. Clin Microbiol Infect 24(12):1315–1321 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    MRSA incidence may be decreasing according to some reports.

    “and may be decreasing according to some reports [134, 135]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [134] Jernigan JA, Hatfield KM, Wolford H et al (2020) Multidrug-resistant bacterial infections in U.S. hospitalized patients, 2012–2017. N Engl J Med 382(14):1309–1319 source

      Not checked in the free run.

    • cites [135] Jones M, Jernigan JA, Evans ME et al (2019) Vital Signs: trends in Staphylococcus aureus infections in veterans affairs medical centers—United States, 2005–2017. MMWR Morb Mortal Wkly Rep 68(9):220–224 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MRSA incidence varies by region, from about 2% in Western Europe to 10% in North America, and by patient-related characteristics.

    “The incidence of MRSA varies, however, by region (ranging from ~ 2% in Western Europe to 10% in North America) and by patient-related characteristics [133, 136, 137].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [133] Vincent JL, Sakr Y, Singer M, et al (2020) Prevalence and outcomes of infection among patients in intensive care units in 2017. JAMA 323(15):1478–1487 source

      Not checked in the free run.

    • cites [136] Aliberti S, Reyes LF, Faverio P et al (2016) Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study. Lancet Infect Dis 16(12):1364–1376 source

      Not checked in the free run.

    • cites [137] Rhee C, Kadri SS, Dekker JP et al (2020) Prevalence of antibiotic-resistant pathogens in culture-proven sepsis and outcomes associated with inadequate and broad-spectrum empiric antibiotic use. JAMA Netw Open 3(4):e202899 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There appears to be no overall effect of neuraminidase inhibitors on mortality in patients with influenza-related pneumonia, but there may be an effect when administered early.

    “While there appears to be no overall effect of neuraminidase inhibitors on mortality in patients with influenza-related pneumonia, there may be an effect when administered early in the course of the disease [225].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [225] Muthuri SG, Venkatesan S, Myles PR et al (2014) Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med 2(5):395–404 source

      Not checked in the free run.

  • May combine two claims.

    Premiseown data

    Long-term mortality, readmission rates, and hospital-free days were not reported in any of the procalcitonin trials, and no relevant studies on costs were found.

    “Long-term mortality, readmission rates and hospital-free days were not reported in any of the trials, and no relevant studies on the costs associated with use of procalcitonin were found.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [129] Jensen JU, Hein L, Lundgren B et al (2011) Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med 39(9):2048–2058 source

      Not checked in the free run.

    • cites [130] Layios N, Lambermont B, Canivet JL et al (2012) Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients. Crit Care Med 40(8):2304–2309 source

      Not checked in the free run.

    • cites [131] Najafi A, Khodadadian A, Sanatkar M et al (2015) The comparison of procalcitonin guidance administer antibiotics with empiric antibiotic therapy in critically ill patients admitted in intensive care unit. Acta Med Iran 53(9):562–567

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Applying a PK/PD approach to antibiotic dosing requires support from knowledgeable clinicians, a population-specific guideline, therapeutic drug monitoring, and/or dosing software.

    “Applying a PK/PD approach to antibiotic dosing requires support from knowledgeable clinician team members [254], use of a patient population-specific guideline document [255], use of therapeutic drug monitoring [256], and/or use of dosing software [238, 248].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [254] Fleuren LM, Roggeveen LF, Guo T et al (2019) Clinically relevant pharmacokinetic knowledge on antibiotic dosing among intensive care professionals is insufficient: a cross-sectional study. Crit Care 23(1):185 source

      Not checked in the free run.

    • cites [255] Ehmann L, Zoller M, Minichmayr IK et al (2019) Development of a dosing algorithm for meropenem in critically ill patients based on a population pharmacokinetic/pharmacodynamic analysis. Int J Antimicrob Agents 54(3):309–317 source

      Not checked in the free run.

    • cites [256] Wong G, Briscoe S, McWhinney B et al (2018) Therapeutic drug monitoring of beta-lactam antibiotics in the critically ill: direct measurement of unbound drug concentrations to achieve appropriate drug exposures. J Antimicrob Chemother 73(11):3087–3094 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Smaller studies suggest that source control within 6-12 hours is advantageous, and studies generally show reduced survival beyond that point.

    “smaller studies suggest that source control within 6–12 h is advantageous [265–271]. Studies generally show reduced survival beyond that point.”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [265] Azuhata T, Kinoshita K, Kawano D et al (2014) Time from admission to initiation of surgery for source control is a critical determinant of survival in patients with gastrointestinal perforation with associated septic shock. Crit Care 18(3):R87 source

      Not checked in the free run.

    • cites [266] Bloos F, Thomas-Ruddel D, Ruddel H et al (2014) Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study. Crit Care 18(2):R42 source

      Not checked in the free run.

    • cites [267] Buck DL, Vester-Andersen M, Moller MH (2013) Surgical delay is a critical determinant of survival in perforated peptic ulcer. Br J Surg 100(8):1045–1049 source

      Not checked in the free run.

    • cites [268] Chao WN, Tsai CF, Chang HR et al (2013) Impact of timing of surgery on outcome of Vibrio vulnificus-related necrotizing fasciitis. Am J Surg 206(1):32–39 source

      Not checked in the free run.

    • cites [269] Karvellas CJ, Abraldes JG, Zepeda-Gomez S et al (2016) The impact of delayed biliary decompression and anti-microbial therapy in 260 patients with cholangitis-associated septic shock. Aliment Pharmacol Ther 44(7):755–766 source

      Not checked in the free run.

    • cites [270] Moss RL, Musemeche CA, Kosloske AM (1996) Necrotizing fasciitis in children: prompt recognition and aggressive therapy improve survival. J Pediatr Surg 31(8):1142–1146 source

      Not checked in the free run.

    • cites [271] Wong CH, Chang HC, Pasupathy S et al (2003) Necrotizing fasciitis: clinical presentation, microbiology, and determinants of mortality. J Bone Joint Surg Am 85(8):1454–1460 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Antibiotics undergo changes in PK/PD parameters in sepsis and septic shock, with concentrations that may be too low risking clinical failure or too high causing toxicity.

    “Antibiotics are subject to changes in PK/PD parameters in sepsis and septic shock where resultant concentrations may be too low risking clinical failure, or too high leading to toxicity (Table 3) [237–239].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [237] Roberts JA, Abdul-Aziz MH, Lipman J et al (2014) Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 14(6):498–509 source

      Not checked in the free run.

    • cites [238] Roberts JA, Paul SK, Akova M et al (2014) DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis 58(8):1072–1083 source

      Not checked in the free run.

    • cites [239] Veiga RP, Paiva JA (2018) Pharmacokinetics-pharmacodynamics issues relevant for the clinical use of beta-lactam antibiotics in critically ill patients. Crit Care 22(1):233 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Extended and continuous infusions occupy a venous catheter/lumen more than intermittent infusion, and drug-stability and drug-drug compatibility considerations are important for effectiveness.

    “Over the course of therapy, both extended and continuous infusions will occupy a venous catheter/lumen more than an intermittent infusion and drug-stability and drug-drug compatibility considerations are important to ensure effectiveness of antibiotic and other IV drug therapies [235].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [235] Roberts JA, Paratz J, Paratz E et al (2007) Continuous infusion of beta-lactam antibiotics in severe infections: a review of its role. Int J Antimicrob Agents 30(1):11–18 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    It is possible that reducing duration of unnecessary therapy accounts for at least part of the benefit of specialist consultation.

    “However, it is also possible that reducing the duration of unnecessary therapy may account for at least part of the benefit.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In many RCTs of shorter versus longer antimicrobial courses for specific conditions, the shorter course was as effective as the longer course but associated with fewer adverse consequences.

    “In many of the trials, the shorter course was just as effective as the longer course but associated with fewer adverse consequences.”
    Quote in the paperSubstantial claim0 of 8 sources checked
    • cites [286] Chastre J, Wolff M, Fagon JY et al (2003) Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 290(19):2588–2598 source

      Not checked in the free run.

    • cites [287] Choudhury G, Mandal P, Singanayagam A et al (2011) Seven-day antibiotic courses have similar efficacy to prolonged courses in severe community-acquired pneumonia—a propensity-adjusted analysis. Clin Microbiol Infect 17(12):1852–1858 source

      Not checked in the free run.

    • cites [288] Kalil AC, Metersky ML, Klompas M et al (2016) Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the infectious diseases society of America and the American Thoracic Society. Clin Infect Dis 63(5):e61–e111 source

      Not checked in the free run.

    • cites [289] Vaughn VM, Flanders SA, Snyder A et al (2019) Excess antibiotic treatment duration and adverse events in patients hospitalized with pneumonia: a multihospital cohort study. Ann Intern Med 171(3):153–163 source

      Not checked in the free run.

    • cites [290] Eliakim-Raz N, Yahav D, Paul M et al (2013) Duration of antibiotic treatment for acute pyelonephritis and septic urinary tract infection—7 days or less versus longer treatment: systematic review and meta-analysis of randomized controlled trials. J Antimicrob Chemother 68(10):2183–2191 source

      Not checked in the free run.

    • cites [291] Runyon BA, McHutchison JG, Antillon MR et al (1991) Short-course versus long-course antibiotic treatment of spontaneous bacterial peritonitis. A randomized controlled study of 100 patients. Gastroenterology 100(6):1737–1742 source

      Not checked in the free run.

    • cites [292] Yahav D, Franceschini E, Koppel F et al (2019) Seven versus 14 days of antibiotic therapy for uncomplicated gram-negative bacteremia: a noninferiority randomized controlled Trial. Clin Infect Dis 69(7):1091–1098 source

      Not checked in the free run.

    • cites [293] Sawyer RG, Claridge JA, Nathens AB et al (2015) Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med 372(21):1996–2005 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    Most studies of de-escalation were observational, and concerns exist that de-escalation is used primarily in patients who are improving, so the improved short-term mortality should be interpreted cautiously.

    “Most studies were observational, and there are concerns that de-escalation is used primarily in patients who are getting better, which is why the reported improved short-term mortality should be interpreted with caution [277, 279].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [277] Tabah A, Bassetti M, Kollef MH et al (2020) Antimicrobial de-escalation in critically ill patients: a position statement from a task force of the European Society of Intensive Care Medicine (ESICM) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Critically Ill Patients Study Group (ESGCIP). Intensive Care Med 46(2):245–265 source

      Not checked in the free run.

    • cites [279] Tabah A, Cotta MO, Garnacho-Montero J et al (2016) A systematic review of the definitions, determinants, and clinical outcomes of antimicrobial de-escalation in the intensive care unit. Clin Infect Dis 62(8):1009–1017 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The reduction in short-term mortality from prolonged beta-lactam infusion is significant, the intervention is feasible with negligible cost implications, and no data suggest inferior outcomes.

    “The reduction in short-term mortality from prolonged infusion of beta-lactams is significant with the intervention being feasible with negligible cost implications and no data suggesting inferior outcomes with prolonged infusion.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    De-escalation is generally safe, may offer cost savings, and may reduce antimicrobial resistance, toxicity, and side-effects.

    “De-escalation is in generally safe, may offer cost savings when unnecessary antibiotics are discontinued, and reduced risk of antimicrobial resistance and reduced toxicity and side-effects may be important [280].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [280] De Bus L, Depuydt P, Steen J, et al (2020) Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study. Intensive Care Med 46(7):1404–1417 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Restricting antimicrobial therapy to the shortest course associated with better outcomes is an important part of antimicrobial stewardship.

    “Restricting antimicrobial therapy to the shortest course associated with better outcomes is an important part of antimicrobial stewardship [281–285].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [281] Fernandez-Lazaro CI, Brown KA, Langford BJ et al (2019) Late-career physicians prescribe longer courses of antibiotics. Clin Infect Dis 69(9):1467–1475 source

      Not checked in the free run.

    • cites [282] Hanretty AM, Gallagher JC (2018) Shortened courses of antibiotics for bacterial infections: a systematic review of randomized controlled trials. Pharmacotherapy 38(6):674–687 source

      Not checked in the free run.

    • cites [283] Royer S, DeMerle KM, Dickson RP et al (2018) shorter versus longer courses of antibiotics for infection in hospitalized patients: a systematic review and meta-analysis. J Hosp Med 13(5):336–342 source

      Not checked in the free run.

    • cites [284] Spellberg B (2016) The new antibiotic mantra-"Shorter Is Better". JAMA Intern Med 176(9):1254–1255 source

      Not checked in the free run.

    • cites [285] Wald-Dickler N, Spellberg B (2019) Short-course antibiotic therapy-replacing constantine units with “Shorter Is Better.” Clin Infect Dis 69(9):1476–1479 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    Very few trials focused exclusively on critically ill patients with sepsis or septic shock, and the overall quality of evidence was very low.

    “Very few trials, however, focussed exclusively on critically ill patients with sepsis or septic shock, and the overall quality of evidence was very low.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Catheter removal with adequate antimicrobial therapy is definitive and preferred in most cases.

    “However, catheter removal with adequate antimicrobial therapy is definitive and is the preferred treatment in most cases.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Antimicrobial exposure is linked to development of antimicrobial resistance, and reducing the number and spectrum of antibiotics is an important strategy in sepsis and septic shock.

    “Antimicrobial exposure is linked to the development of antimicrobial resistance and efforts to reduce both the number of antibiotics administered and their spectrum of therapy are therefore important strategies in patients with sepsis and septic shock [165].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [165] Arulkumaran N, Routledge M, Schlebusch S et al (2020) Antimicrobial-associated harm in critical care: a narrative review. Intensive Care Med 46(2):225–235 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Algorithms for antimicrobial therapy, frequency of procalcitonin monitoring, and thresholds for discontinuation differed across trials.

    “Also, the algorithms for antimicrobial therapy, frequency of procalcitonin monitoring and the thresholds (or percentage change in procalcitonin concentration) for discontinuation differed across the trials.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The SMART trial had limitations including single-centre design, no individual patient randomisation, no blinded assignment, moderate fluid volume, sepsis subgroup identification by ICD-10 codes, and a composite outcome that may not be patient-centered.

    “The SMART trial was a single-centre study without individual patient randomisation and no blinded assignment of the intervention, it exposed participants to moderate amount of fluid volume, identification of sepsis subgroups was based on ICD-10 codes, and it used a composite outcome which may not be as relevant as a patient-centered outcome [336].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [336] Myburgh J (2018) Patient-Centered Outcomes and Resuscitation Fluids. N Engl J Med 378(9):862–863 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Normal saline may cause hyperchloremic metabolic acidosis, renal vasoconstriction, increased cytokine secretion, and concern for acute kidney injury.

    “potential adverse effects that include hyperchloremic metabolic acidosis, renal vasoconstriction, increased cytokine secretion and concern about acute kidney injury (AKI) have led to increased interest in chloride-restrictive solutions, known as balanced or buffered solutions [326–330].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [326] Chowdhury AH, Cox EF, Francis ST et al (2012) A randomized, controlled, double-blind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyte(R) 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Ann Surg 256(1):18–24 source

      Not checked in the free run.

    • cites [327] Kellum JA (2002) Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: improved short-term survival and acid-base balance with Hextend compared with saline. Crit Care Med 30(2):300–305 source

      Not checked in the free run.

    • cites [328] Kellum JA, Song M, Almasri E (2006) Hyperchloremic acidosis increases circulating inflammatory molecules in experimental sepsis. Chest 130(4):962–967 source

      Not checked in the free run.

    • cites [329] Waters JH, Gottlieb A, Schoenwald P et al (2001) Normal saline versus lactated Ringer’s solution for intraoperative fluid management in patients undergoing abdominal aortic aneurysm repair: an outcome study. Anesth Analg 93(4):817–822 source

      Not checked in the free run.

    • cites [330] Williams EL, Hildebrand KL, McCormick SA et al (1999) The effect of intravenous lactated Ringer’s solution versus 0.9% sodium chloride solution on serum osmolality in human volunteers. Anesth Analg 88(5):999–1003

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The VANISH trial found no difference in kidney injury but vasopressin reduced risk of renal replacement therapy.

    “Although there was no difference with respect to kidney injury (RR 0.89; 95% CI 0.72–1.11), vasopressin use reduced the risk of RRT (RR 0.71; 95% CI 0.53–0.97) [354].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [354] Gordon AC, Mason AJ, Thirunavukkarasu N et al (2016) Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA 316(5):509–518 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A meta-analysis of septic patients found no significant mortality difference and no difference in new organ failures, ventilator-free days, or vasopressor-free days.

    “A meta-analysis of studies including septic patients did not show a significant difference in mortality (RR 0.98; 95% CI 0.89–1.08). In addition, the risk of new organ failures (RR 1.02; 95% CI 0.93–1.11), ventilator-free days or vasopressor-free days did not differ.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Evidence shows higher blood pressure at early and later time points, higher static filling pressures, and lower net fluid balance with albumin.

    “The suggestion to consider albumin in patients who received large volumes of crystalloids is informed by evidence showing higher blood pressure at early and later time points [339], higher static filling pressures [340], and lower net fluid balance [339] with albumin.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [339] Caironi P, Tognoni G, Gattinoni L (2014) Albumin replacement in severe sepsis or septic shock. N Engl J Med 371(1):84 source

      Not checked in the free run.

    • cites [340] Martin GS, Bassett P (2019) Crystalloids vs. colloids for fluid resuscitation in the Intensive Care Unit: a systematic review and meta-analysis. J Crit Care 50:144–154 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Undesirable effects of using procalcitonin with clinical evaluation to decide when to discontinue antimicrobials are considered minimal and do not outweigh potential benefits.

    “The undesirable effects of using procalcitonin along with clinical evaluation to decide when to discontinue antimicrobials are considered minimal, and do not outweigh the potential benefits [322].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [322] Arulkumaran N, Khpal M, Tam K et al (2020) Effect of antibiotic discontinuation strategies on mortality and infectious complications in critically ill septic patients: a meta-analysis and trial sequential analysis. Crit Care Med 48(5):757–764 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Albumin is theoretically more likely to maintain oncotic pressure than crystalloids.

    “Although albumin is theoretically more likely to maintain oncotic pressure than crystalloids [339]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [339] Caironi P, Tognoni G, Gattinoni L (2014) Albumin replacement in severe sepsis or septic shock. N Engl J Med 371(1):84 source

      Not checked in the free run.

  • May combine two claims.

    Premiseown data

    Albumin had a larger treatment effect in the septic shock subgroup than in the sepsis subgroup, but the subgroup analysis did not detect a subgroup effect.

    “Although albumin use resulted in a larger treatment effect in the septic shock subgroup (RR 0.88; 95% CI 0.77–0.99) than in the sepsis subgroup (RR 1.03; 95% CI 0.91–1.17), the subgroup analysis did not detect a subgroup effect (P-interaction = 0.19).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premiseown data

    Gelatins may affect haemostasis and the effect on blood transfusions was unclear.

    “Furthermore, gelatins may affect haemostasis and the effect on blood transfusions was unclear (RR 1.10; 95% CI 0.86–1.41).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    An individual patient data meta-analysis of 4 RCTs in septic shock found vasopressin alone or with norepinephrine led to higher risk of digital ischaemia but lower risk of arrhythmia compared with norepinephrine alone.

    “a recent individual patient data meta-analysis of patients with septic shock from 4 RCTs showed that vasopressin alone or in combination with norepinephrine led to higher risk of digital ischaemia (risk difference [RD] 1.7%; 95% CI 0.3–3.2) but lower risk of arrhythmia (RD −2.8%; 95% CI −0.2 to −5.3) compared to norepinephrine alone [359].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [359] Nagendran M, Russell JA, Walley KR et al (2019) Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials. Intensive Care Med 45(6):844–855 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A systematic review and meta-analysis of 11 RCTs found norepinephrine resulted in lower mortality and lower risk of arrhythmias compared with dopamine.

    “In a systematic review and meta-analysis of 11 RCTs, norepinephrine resulted in a lower mortality (RR 0.89; 95% CI 0.81–0.98) and lower risk of arrhythmias (RR 0.48; 95% CI 0.40–0.58) compared with dopamine [347].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [347] Avni T, Lador A, Lev S et al (2015) Vasopressors for the treatment of septic shock: systematic review and meta-analysis. PLoS One 10(8):e0129305 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A second meta-analysis found crystalloid use associated with lower static filling pressures and lower mean arterial pressure, but no difference in 28-day or 90-day mortality.

    “A second meta-analysis, which also included critically ill patients, found lower static filling pressures (MD −2.3 cm H2O; 95% CI 3.02–1.05) and mean arterial pressure (MAP) (MD −3.53 mmHg; 95% CI −6.71 to −0.36) with crystalloid use, but no difference in mortality at 28 days (RR 1.0; 95% CI 0.92–1.10) or 90 days (RR 1.32; 95% CI 0.76–2.29) [340].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [340] Martin GS, Bassett P (2019) Crystalloids vs. colloids for fluid resuscitation in the Intensive Care Unit: a systematic review and meta-analysis. J Crit Care 50:144–154 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A Cochrane review of 12,492 patients found no difference between albumin and crystalloids in 30-day mortality, 90-day mortality, or need for renal replacement therapy.

    “A Cochrane review including RCTs with 12,492 patients comparing albumin versus crystalloids found no difference in 30-day (RR 0.98; 95% CI 0.92–1.04) or 90-day mortality (RR 0.98; 95% CI 0.92–1.04) or need for RRT between groups (RR 1.11; 95% CI 0.96–1.27) [324].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [324] Lewis SR, Pritchard MW, Evans DJ et al (2018) Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev 8:CD000567

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    For adults with an initial diagnosis of sepsis or septic shock and adequate source control, a shorter course of antibiotics is less costly and has fewer undesirable effects without adversely impacting outcomes.

    “Thus, for adults with an initial diagnosis of sepsis or septic shock and adequate source control, we suggest a shorter course of antibiotics, as this is less costly, has fewer undesirable effects without impacting adversely on outcomes (see Table 4).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Study design and conductreasoning

    The overall quality of evidence for procalcitonin-guided discontinuation was judged low.

    “Therefore, the overall quality of evidence was judged to be low.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A phase IIb/III selepressin trial was stopped for futility after 828 patients with no significant differences in key endpoints including ventilator- and vasopressor-free days, 90-day mortality, RRT-free days, and ICU-free days.

    “The study was stopped for futility after enrolment of 828 patients, with no significant differences between any of the key endpoints [ventilator- and vasopressor-free days, 15.0 (selepressin) versus 14.5 (placebo), p = 0.30; 90-day all-cause mortality, 40.6% vs 39.4%, p = 0.77; 30-day RRT-free days, 18.5 vs 18.2, p = 0.85; 30-day ICU-free days, 12.6 vs 12.2, p = 0.41]; adverse event rates were als”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [364] Laterre PF, Berry SM, Blemings A, et al (2019) Effect of selepressin vs placebo on ventilator- and vasopressor-free days in patients with septic shock: the SEPSIS-ACT randomized clinical trial. JAMA 322(15):1476–1485 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A randomized blinded study comparing epinephrine with norepinephrine in shock found no difference in 90-day mortality and vasopressor-free days.

    “A randomised blinded study comparing epinephrine with norepinephrine in patients with shock showed no difference in 90-day mortality (HR 0.88; 95% CI 0.63–1.25) and vasopressor-free days [351].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [351] Myburgh JA, Higgins A, Jovanovska A et al (2008) A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 34(12):2226–2234 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vasopressin concentration is elevated in early septic shock but decreases to normal range in most patients between 24 and 48 hours as shock continues.

    “Studies show that vasopressin concentration is elevated in early septic shock but decreases to normal range in the majority of patients between 24 and 48 h as shock continues [352, 353].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [352] Holmes CL, Patel BM, Russell JA et al (2001) Physiology of vasopressin relevant to management of septic shock. Chest 120(3):989–1002 source

      Not checked in the free run.

    • cites [353] Landry DW, Levin HR, Gallant EM et al (1997) Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 95(5):1122–1125 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A small pilot in 20 patients with vasodilatory septic shock showed physiological efficacy without obvious safety issues for angiotensin II.

    “After a small, short-term pilot of 20 patients with vasodilatory (septic) shock 10 patients in each group which showed physiological efficacy without obvious safety issues [365]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [365] Chawla LS, Busse L, Brasha-Mitchell E et al (2014) Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study. Crit Care 18(5):534 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A previous meta-analysis of RCTs in septic patients showed higher risk of renal replacement therapy with HES 130/0.38-0.45 and higher risk of death in low risk of bias trials.

    “A previous meta-analysis of RCTs in septic patients showed a higher risk of RRT with the use of HES 130/0.38–0.45 (RR 1.36; 95% CI 1.08–1.72) and a higher risk of death in a pre-defined analysis of low risk of bias trials (RR 1.11; 95% CI 1.0–1.2) [343].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [343] Haase N, Perner A, Hennings LI et al (2013) Hydroxyethyl starch 130/0.38–0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis. BMJ 346:f839 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Sepsis-induced myocardial dysfunction is recognized as a major contributor to haemodynamic instability and is associated with worse outcomes in septic shock.

    “Sepsis-induced myocardial dysfunction is recognised as a major contributor to the haemodynamic instability and is associated with worse outcomes of patients with septic shock [368].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [368] Walley KR (2018) Sepsis-induced myocardial dysfunction. Curr Opin Crit Care 24(4):292–299 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Recent data from Africa showed that higher volume fluid resuscitation in adults was associated with increased mortality, but the generalizability of these data is limited due to high prevalence of HIV/AIDS and malnutrition and resource-scarce conditions with limited ICU access.

    “Recent data emerging from Africa showed that higher volume fluid resuscitation in adults was associated with increased mortality, but the generalizability of these data is limited due to the high prevalence of HIV/AIDS and malnutrition in the patients enrolled and the resource-scarce conditions with limited access to ICUs [69].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] Andrews B, Semler MW, Muchemwa L et al (2017) Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial. JAMA 318(13):1233–1240 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Arterial catheter insertion permits safe, reliable, continuous arterial pressure measurement and real-time analysis for therapeutic decisions.

    “Insertion of an arterial catheter permits safe, reliable and continuous measurement of arterial pressure and allows real time analysis so that therapeutic decisions can be based on immediate and accurate blood pressure information [380].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [380] Vincent J (2019) Arterial, central venous, and pulmonary artery catheters. In: JE P (ed) Critical care medicine: principles and diagnosis and management in the adult, 5th edn. Elsevier, Philadelphia, pp 40–49

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The LeoPARDS trial found levosimendan compared with no inotropic agents was associated with lower likelihood of successful weaning from mechanical ventilation and higher risk of supraventricular tachyarrhythmia.

    “Data from the LeoPARDS trial (n = 515) showed that levosimendan versus no inotropic agents was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrythmia [373].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [373] Gordon AC, Perkins GD, Singer M et al (2016) Levosimendan for the prevention of acute organ dysfunction in sepsis. N Engl J Med 375(17):1638–1648 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ultrasound guidance may increase first attempt success rate and decrease complication rate.

    “Ultrasound guidance may increase the first attempt success rate and decrease the complication rate [382, 383].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [382] Bhattacharjee S, Maitra S, Baidya DK (2018) Comparison between ultrasound guided technique and digital palpation technique for radial artery cannulation in adult patients: an updated meta-analysis of randomized controlled trials. J Clin Anesth 47:54–59 source

      Not checked in the free run.

    • cites [383] Gu WJ, Wu XD, Wang F et al (2016) Ultrasound guidance facilitates radial artery catheterization: a meta-analysis with trial sequential analysis of randomized controlled trials. Chest 149(1):166–179 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The largest terlipressin study in 617 septic shock patients found 28-day mortality of 40% with terlipressin versus 38% with norepinephrine and no differences in SOFA score at day 7 or vasopressor-free days.

    “The 28-day mortality in the two groups was 40% for terlipressin and 38% for norepinephrine (OR 0.93; 95% CI 0.55–1.56, p = 0.80), and there were no differences in SOFA score at day 7 or vasopressor free days.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [367] Liu ZM, Chen J, Kou Q et al (2018) Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial. Intensive Care Med 44(11):1816–1825 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most studies reported no need for active treatment of extravasation, and a systematic review concluded most patients with extravasation have no long-term sequelae.

    “Most of the studies reported no need for active treatment of the extravasation, and a systematic review concluded that most patients who experience extravasation events have no long-term sequelae [389].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [389] Loubani OM, Green RS (2015) A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters. J Crit Care 30(3):653e9-17 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the largest terlipressin study, more patients receiving terlipressin had serious adverse events, including digital ischaemia and diarrhea.

    “More patients who received terlipressin had serious adverse events; 33 of 260 (12%) patients experienced digital ischaemia after receiving terlipressin, versus only one patient who received norepinephrine (p < 0.0001); diarrhea was also more common in the terlipressin group (2.7% versus 0.35%, p = 0.037).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [367] Liu ZM, Chen J, Kou Q et al (2018) Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial. Intensive Care Med 44(11):1816–1825 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the ProCESS, ARISE, and ProMISe trials, approximately 7-8 L of fluids were administered in the usual care groups, with a reported low mortality rate.

    “ProCESS[64], ARISE [65] and ProMISe [66] administered approximately 7–8 L in the usual care groups with a reported low mortality rate.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [64] Investigators P, Yealy DM, Kellum JA et al (2014) A randomized trial of protocol-based care for early septic shock. N Engl J Med 370(18):1683–1693 source

      Not checked in the free run.

    • cites [65] Peake SL, Delaney A, Bellomo R et al (2015) Goal-directed resuscitation in septic shock. N Engl J Med 372(2):190–191

      Not checked in the free run.

    • cites [66] Mouncey PR, Osborn TM, Power GS et al (2015) Trial of early, goal-directed resuscitation for septic shock. N Engl J Med 372(14):1301–1311 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A systematic review of observational studies found risk of limb ischaemia and bleeding less than 1% for radial catheters, and less than 1% and 1.58% for femoral catheters, with localised haematoma the most common complication.

    “A systematic review of observational studies showed that the risk of limb ischaemia and bleeding was less than 1% for radial catheters, and the risk of limb ischaemia and bleeding was less than 1% and 1.58%, respectively, for femoral catheters. The most common complication was localised haematoma, 14% for radial and 6% for femoral catheters [381].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [381] Scheer B, Perel A, Pfeiffer UJ (2002) Clinical review: complications and risk factors of peripheral arterial catheters used for haemodynamic monitoring in anaesthesia and intensive care medicine. Crit Care 6(3):199–204 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Recent evidence suggests that IV fluids used to restore organ perfusion may damage vascular integrity and lead to organ dysfunction.

    “recent evidence suggests that IV fluids used to restore organ perfusion may damage vascular integrity and lead to organ dysfunction [394].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [394] Alphonsus CS, Rodseth RN (2014) The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia 69(7):777–784 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Dobutamine infusion may produce severe vasodilation and lower mean arterial pressure.

    “Dobutamine infusion may produce severe vasodilation and result in lower MAP.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Non-invasive cuff blood pressure estimation tends to be inaccurate, with discrepancy more pronounced in shock states.

    “Estimation of blood pressure using a non-invasive cuff tends to be inaccurate and the discrepancy more pronounced in shock states [375–379].”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [375] Araghi A, Bander JJ, Guzman JA (2006) Arterial blood pressure monitoring in overweight critically ill patients: invasive or noninvasive? Crit Care 10(2):R64 source

      Not checked in the free run.

    • cites [376] Bur A, Hirschl MM, Herkner H et al (2000) Accuracy of oscillometric blood pressure measurement according to the relation between cuff size and upper-arm circumference in critically ill patients. Crit Care Med 28(2):371–376 source

      Not checked in the free run.

    • cites [377] Kaur B, Kaur S, Yaddanapudi LN et al (2019) Comparison between invasive and noninvasive blood pressure measurements in critically ill patients receiving inotropes. Blood Press Monit 24(1):24–29 source

      Not checked in the free run.

    • cites [378] Lehman LW, Saeed M, Talmor D et al (2013) Methods of blood pressure measurement in the ICU. Crit Care Med 41(1):34–40 source

      Not checked in the free run.

    • cites [379] Riley LE, Chen GJ, Latham HE (2017) Comparison of noninvasive blood pressure monitoring with invasive arterial pressure monitoring in medical ICU patients with septic shock. Blood Press Monit 22(4):202–207 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Observational studies have shown an association between high-volume fluid resuscitation and increased mortality, but these studies are likely affected by unmeasured variables such as administering higher amounts of fluids to sicker patients.

    “Data from observational studies have shown an association of high-volume fluid resuscitation and increased mortality, but these studies are likely affected by unmeasured variables (i.e. the administration of higher amounts of fluids to sicker patients) [395, 396].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [395] Boyd JH, Forbes J, Nakada TA et al (2011) Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med 39(2):259–265 source

      Not checked in the free run.

    • cites [396] Marik PE, Linde-Zwirble WT, Bittner EA et al (2017) Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med 43(5):625–632 source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    A small study randomizing peripheral versus central access found major catheter-related complications were higher with peripheral lines, no significant difference in minor complications, difficulty in placement was the most common peripheral complication, and almost half of the peripheral group did not need a central line during ICU stay.

    “A small study (n = 263) randomly allocated patients to receive peripheral vascular access or a central access [386]. The need for vasopressor was the indication for venous access in 70% of the patients. The incidence of major catheter-related complications was higher in those randomised to peripheral venous lines with no significant difference in the incidence of minor catheter-related complicatio”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [386] Ricard JD, Salomon L, Boyer A et al (2013) Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial. Crit Care Med 41(9):2108–2115 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A post-hoc analysis of the ARISE trial found 42% of patients had vasopressors initiated via peripheral catheter with shorter time to initiation.

    “A post-hoc analysis of the ARISE trial showed that 42% of patients had vasopressors initiated via a peripheral catheter with a shorter time to initiation of vasopressors (2.4 [1.3–3.9] vs. 4.9 h [3.5–6.6], p < 0.001) [385].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [385] Delaney A, Finnis M, Bellomo R et al (2020) Initiation of vasopressor infusions via peripheral versus central access in patients with early septic shock: a retrospective cohort study. Emerg Med Australas 32(2):210–219 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A systematic review found higher risk of infections with femoral compared with radial arterial catheters, and pooled incidence of bloodstream infection was 0.96 per 1000 catheter days.

    “A systematic review showed higher risk of infections when femoral arterial catheters were used compared to radial artery catheters (RR 1.93; 95% CI 1.32–2.84), and the overall pooled incidence of bloodstream infection was 0.96 per 1000 catheter days [384].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [384] O’Horo JC, Maki DG, Krupp AE et al (2014) Arterial catheters as a source of bloodstream infection: a systematic review and meta-analysis. Crit Care Med 42(6):1334–1339 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The observational analysis adjusted only for baseline characteristics and did not account for time-varying confounders such as patient condition at initiation of inotropes, which may explain the mortality association.

    “However, the analysis adjusted only to baseline characteristics, without accounting for time-varying confounders including the patient condition at the time of initiating inotropes which may explain the association with mortality.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Extravasation may occur more frequently if vasopressors are infused distal to the antecubital fossa; a meta-analysis found 85% of reported extravasation events occurred with a catheter distal to the antecubital fossa.

    “Extravasation may occur more frequently if vasopressors are infused distally to the antecubital fossa; a meta-analysis showed that 85% of reported extravasation events occurred when vasopressors were infused by a catheter that was located distal to the antecubital fossa [389].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [389] Loubani OM, Green RS (2015) A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters. J Crit Care 30(3):653e9-17 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dobutamine increases cardiac output and oxygen transport, increases splanchnic perfusion and tissue oxygenation, and improves intramucosal acidosis and hyperlactatemia.

    “Physiologic studies demonstrate that dobutamine increases CO and oxygen transport, increases splanchnic perfusion and tissue oxygenation, improves intramucosal acidosis and hyperlactatemia [369].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [369] Cunha-Goncalves D, Perez-de-Sa V, Larsson A et al (2009) Inotropic support during experimental endotoxemic shock: part II. A comparison of levosimendan with dobutamine. Anesth Analg 109(5):1576–1583 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The 3 RCTs that guide the plateau pressure recommendation enrolled patients using the American-European Consensus Criteria Definition for Acute Lung Injury and ARDS, whereas the current document uses the 2012 Berlin definition.

    “Of note, the 3 RCTs that guide this recommendation [424, 426, 427] enrolled patients using the criteria from the American-European Consensus Criteria Definition for Acute Lung Injury and ARDS [422] whereas the current document use the 2012 Berlin definition and the terms mild, moderate, and severe ARDS (PaO2/FiO2 ≤ 300, ≤ 200, and ≤ 100 mm Hg, respectively) [423].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [424] Brower RG, Matthay MA, Acute Respiratory Distress Syndrome N et al (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342(18):1301–1308 source

      Not checked in the free run.

    • cites [426] Brochard L, Roudot-Thoraval F, Roupie E et al (1998) Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Am J Respir Crit Care Med 158(6):1831–1838 source

      Not checked in the free run.

    • cites [427] Brower RG, Shanholtz CB, Fessler HE et al (1999) Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 27(8):1492–1498 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The plateau pressure is only truly valuable if the patient is passive during the inspiratory hold.

    “The plateau pressure is only truly valuable if the patient is passive during the inspiratory hold.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    These three RCTs compared a strategy of low tidal volume and limited plateau pressure with a strategy using higher tidal volume and plateau pressure; pooled data suggest reduced mortality (RR 0.83; 95% CI 0.70-0.97) and more ventilator-free days (MD 1.8 days; 95% CI 0.35-3.25) in patients managed with low plateau pressures.

    “These three RCTS compared a strategy of low tidal volume and limited plateau pressure with a strategy using higher tidal volume and plateau pressure; pooled data suggest reduced mortality (RR 0.83; 95% CI 0.70–0.97) and more ventilator-free days (MD 1.8 days; 95% CI 0.35–3.25) in patients managed with low plateau pressures.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [424] Brower RG, Matthay MA, Acute Respiratory Distress Syndrome N et al (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342(18):1301–1308 source

      Not checked in the free run.

    • cites [426] Brochard L, Roudot-Thoraval F, Roupie E et al (1998) Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Am J Respir Crit Care Med 158(6):1831–1838 source

      Not checked in the free run.

    • cites [427] Brower RG, Shanholtz CB, Fessler HE et al (1999) Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 27(8):1492–1498 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Volume- and pressure-limited ventilation may lead to hypercapnia even with maximum-tolerated set respiratory rates; this appears to be tolerated and safe in the absence of contraindications.

    “Volume- and pressure-limited ventilation may lead to hypercapnia even with these maximum-tolerated set respiratory rates; this appears to be tolerated and safe in the absence of contraindications (e.g., high intracranial pressure, sickle cell crisis).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The use of NIV for the rescue of patients with exclusively acute hypoxic respiratory failure ("de novo respiratory failure") is less well studied, but not uncommon.

    “Patients with sepsis-induced hypoxemic respiratory failure may or may not have a competing chronic respiratory disease (ex. COPD, obesity) and the use of NIV for the rescue of patients with exclusively acute hypoxic respiratory failure (“de novo respiratory failure”) is less well studied, but not uncommon.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    In the comparison of NIV versus HFNC, the NIV technique was not standardised and the experience of the centers varied.

    “However, the NIV technique was not standardised and the experience of the centers varied.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A retrospective study suggested that tidal volumes should be lowered even with plateau pressures ≤ 30 cm H2O because lower plateau pressures were associated with reduced hospital mortality.

    “A retrospective study suggested that tidal volumes should be lowered even with plateau pressures ≤ 30 cm H2O [431] because lower plateau pressures were associated with reduced hospital mortality [432].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [431] Hager DN, Krishnan JA, Hayden DL et al (2005) Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med 172(10):1241–1245 source

      Not checked in the free run.

    • cites [432] Checkley W, Brower R, Korpak A et al (2008) Effects of a clinical trial on mechanical ventilation practices in patients with acute lung injury. Am J Respir Crit Care Med 177(11):1215–1222 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that trial, the primary outcome of intubation rate at 28 days was not different between HFNC and NIV, but 90-day survival was improved with HFNC (OR 0.42; 95% CI 0.21-0.85) and HFNC patients had significantly more days free of mechanical ventilation during a 28-day study period.

    “Although the primary outcome of intubation rate at 28 days was not different, this study demonstrated improved 90-day survival with HFNC compared with NIV (OR 0.42; 95% CI 0.21–0.85) and HFNC patients experienced significantly more days free of mechanical ventilation during a 28-day study period [411].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [411] Frat JP, Thille AW, Mercat A et al (2015) High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 372(23):2185–2196 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisenone given

    Acute hypoxemic respiratory failure can result from causes of sepsis such as pneumonia or non-pulmonary infections resulting in ARDS.

    “Acute hypoxemic respiratory failure can result from causes of sepsis such as pneumonia or non-pulmonary infections resulting in ARDS.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    In studies of restrictive IV fluid strategies, primary outcomes were mostly related to IV fluid volumes administered, and given small sample sizes, they were not powered to identify differences in patient-centered outcomes.

    “Moreover, the primary outcomes were mostly related to IV fluid volumes administered during the study period and given the small sample sizes, they were not powered to identify differences in patient-centered outcomes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    In addition to improving gas exchange, NIV may help to reduce work of breathing in select patients.

    “In addition to improving gas exchange, NIV may help to reduce work of breathing in select patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Complications with HFNC are possible; however, they are usually self-limited and do not require discontinuing therapy.

    “Complications with HFNC are possible; however, they are usually self-limited and do not require discontinuing therapy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    NIV can cause mask-related discomfort, unrecognised patient-ventilator asynchrony due to leaks, and gastric insufflation.

    “In contrast, NIV can cause mask-related discomfort, unrecognised patient-ventilator asynchrony due to leaks, and gastric insufflation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    When directly compared to invasive positive pressure ventilation, NIV may achieve similar physiologic benefits including improved gas exchange and reduced work of breathing in select patients, while avoiding complications associated with intubation, invasive ventilation, and accompanying sedation.

    “When directly compared to invasive positive pressure ventilation, NIV may be able to achieve similar physiologic benefits including improved gas exchange and reduced work of breathing in select patients, while avoiding complications associated with intubation, invasive ventilation, and accompanying sedation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Studies have suggested that NIV failure is an independent risk factor for mortality specifically in this population, although careful patient selection may reduce this risk.

    “Studies have suggested that NIV failure is an independent risk factor for mortality specifically in this population, although careful patient selection may reduce this risk [415, 416].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [415] Demoule A, Chevret S, Carlucci A et al (2016) Changing use of noninvasive ventilation in critically ill patients: trends over 15 years in francophone countries. Intensive Care Med 42(1):82–92 source

      Not checked in the free run.

    • cites [416] Demoule A, Girou E, Richard JC et al (2006) Benefits and risks of success or failure of noninvasive ventilation. Intensive Care Med 32(11):1756–1765 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    LUNGSAFE, a large international observational study, reported that plateau pressure correlated with mortality; however, the relationship was not evident when plateau pressure was below 20 cm H2O.

    “LUNGSAFE, a large international observational study, which reported that plateau pressure correlated with mortality; however, the relationship between the two was not evident when plateau pressure was below 20 cm H2O [435].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [435] Laffey JG, Bellani G, Pham T et al (2016) Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome: the LUNG SAFE study. Intensive Care Med 42(12):1865–1876 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The conservative use of oxygen may reduce oxygen exposure and diminish lung and systemic oxidative injury.

    “The conservative use of oxygen may reduce oxygen exposure and diminish lung and systemic oxidative injury.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Patients undergoing mechanical ventilation in the ICU often receive a high fraction of inspired oxygen and have a high arterial oxygen tension.

    “Patients who are undergoing mechanical ventilation in the ICU often receive a high fraction of inspired oxygen and have a high arterial oxygen tension.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    The main risk of NIV for acute respiratory failure is the potential for delaying needed intubation and increasing the risk of interval aspiration events.

    “The main risk of NIV for the indication of acute respiratory failure is the potential for delaying needed intubation and increasing the risk of an interval aspiration events.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisenone given

    High flow nasal cannula (HFNC) is a non-invasive, high concentration oxygen delivery interface that confers warming and humidification of secretions, high flow rates to better match patient demand, washout of nasopharyngeal dead space, and modest positive airway pressure effect.

    “High flow nasal cannula (HFNC) is a non-invasive, high concentration oxygen delivery interface that confers warming and humidification of secretions, high flow rates to better match patient demand, washout of nasopharyngeal dead space, and modest positive airway pressure effect.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    These studies showed differing results, which may have been caused by differences in airway pressures in the treatment and control groups.

    “These studies showed differing results, which may have been caused by differences in airway pressures in the treatment and control groups [423, 424, 428].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [423] Force ADT, Ranieri VM, Rubenfeld GD et al (2012) Acute respiratory distress syndrome: the Berlin Definition. JAMA 307(23):2526–2533

      Not checked in the free run.

    • cites [424] Brower RG, Matthay MA, Acute Respiratory Distress Syndrome N et al (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342(18):1301–1308 source

      Not checked in the free run.

    • cites [428] Eichacker PQ, Gerstenberger EP, Banks SM et al (2002) Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 166(11):1510–1514 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The LOCO-2 study was terminated early by the data safety and monitoring board and reported no difference in 28-day survival in ARDS patients managed with a conservative oxygenation strategy.

    “The LOCO-2 study was terminated early by the data safety and monitoring board and reported no difference in 28-day survival in ARDS patients managed with a conservative oxygenation strategy [409].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [409] Barrot L, Asfar P, Mauny F et al (2020) Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Engl J Med 382(11):999–1008 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Due to small number of patients studied, low quality of evidence, uncertainty regarding whether clinicians can identify hypoxic patients in respiratory failure in whom NIV might be beneficial, and observational data suggesting potential harm with NIV in this setting, no clear recommendation can be made.

    “Due to small number of patients studied, low quality of evidence, uncertainty regarding whether clinicians can identify hypoxic patients in respiratory failure in whom NIV might be beneficial, and observational data that suggest the potential for harm with NIV in this setting, no clear recommendation can be made.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    The single inspiratory limb of HFNC allows for airflows as high as 60 L per minute to achieve inspired oxygen fractions (FiO2) as high as 95-100%.

    “The single inspiratory limb of HFNC allows for airflows as high as 60 L per minute to achieve inspired oxygen fractions (FiO2) as high as 95–100%.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In the ICU-ROX trial, mortality at 90 and 180 days did not differ between conservative and liberal oxygen therapy.

    “Mortality at 90 and 180 days did not differ.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [405] Investigators I-R, the A, New Zealand Intensive Care Society Clinical Trials G et al (2020) Conservative Oxygen Therapy during Mechanical Ventilation in the ICU. N Engl J Med 382(11):989–998 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A systematic review and meta-analysis of nine RCTs showed that HFNC reduces intubation compared with conventional oxygen (RR 0.85; 95% CI 0.74-0.99) but does not affect the risk of death or ICU length of stay.

    “A systematic review and meta-analysis of nine RCTs [2] showed that HFNC reduces intubation compared with conventional oxygen (RR 0.85; 95% CI 0.74–0.99) but does not affect the risk of death or ICU length of stay [412–414].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [2] Fleischmann C, Scherag A, Adhikari NK et al (2016) Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med 193(3):259–272 source

      Not checked in the free run.

    • cites [412] Ni YN, Luo J, Yu H et al (2018) The effect of high-flow nasal cannula in reducing the mortality and the rate of endotracheal intubation when used before mechanical ventilation compared with conventional oxygen therapy and noninvasive positive pressure ventilation. A systematic review and meta-analysis. Am J Emerg Med 36(2):226–233 source

      Not checked in the free run.

    • cites [413] Ou X, Hua Y, Liu J et al (2017) Effect of high-flow nasal cannula oxygen therapy in adults with acute hypoxemic respiratory failure: a meta-analysis of randomized controlled trials. CMAJ 189(7):E260–E267 source

      Not checked in the free run.

    • cites [414] Rochwerg B, Granton D, Wang DX et al (2019) High-flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: author’s reply. Intensive Care Med 45(8):1171 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Patients with profound metabolic acidosis, high minute ventilation, or short stature may require additional manipulation of tidal volumes.

    “Patients with profound metabolic acidosis, high minute ventilation, or short stature may require additional manipulation of tidal volumes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    NIV use can be associated with complications including increased risk of gastric insufflation and aspiration, facial skin breakdown, excessively high tidal volumes, and patient discomfort related to inability to eat or effectively phonate during therapy.

    “However, NIV use can be associated with development of complications including increased risk of gastric insufflation and aspiration, facial skin breakdown, excessively high tidal volumes as well as patient discomfort related to inability to eat or effectively phonate during therapy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Very low tidal volumes may result in significant patient-ventilatory dyssynchrony and patient discomfort.

    “The clinician should keep in mind that very low tidal volumes may result in significant patient-ventilatory dyssynchrony and patient discomfort.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Both NIV and high flow oxygen avoid the complications of intubation and invasive mechanical ventilation and promote patient interaction.

    “Both therapies avoid the complications of intubation and invasive mechanical ventilation and promote patient interaction.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Sepsis is an independent risk factor for the development of ARDS, and delays in diagnosing ARDS may result in delayed use of low tidal volumes.

    “However, sepsis is an independent risk factor for the development of ARDS, and delays in diagnosing ARDS may result in delayed use of low tidal volumes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many strategies exist for treating refractory hypoxemia in patients with severe ARDS.

    “Many strategies exist for treating refractory hypoxemia in patients with severe ARDS [451].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [451] Pipeling MR, Fan E (2010) Therapies for refractory hypoxemia in acute respiratory distress syndrome. JAMA 304(22):2521–2527 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Selected patients with severe hypoxemia may benefit from recruitment maneuvers in conjunction with higher levels of PEEP, but little evidence supports the routine use in all ARDS patients, so recommendations are focused to patients with moderate-to-severe ARDS.

    “Selected patients with severe hypoxemia may benefit from recruitment maneuvers in conjunction with higher levels of PEEP, but little evidence supports the routine use in all ARDS patients, so we have focused our recommendations to patients with moderate-to-severe ARDS [453].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [453] Fan E, Wilcox ME, Brower RG et al (2008) Recruitment maneuvers for acute lung injury a systematic review. Am J Respir Crit Care Med 178(11):1156–1163 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This recommendation was based on a meta-analysis of 3 trials that examined the role of NMBAs in ARDS, showing reduced risks of death (RR 0.72; 95% CI 0.58-0.91) and barotrauma (RR 0.43; 95% CI 0.20-0.90) with the use of cisatracurium infusion.

    “This recommendation was based on a meta-analysis of 3 trials that examined the role of NMBAs in ARDS [465–467], showing reduced risks of death (RR 0.72; 95% CI 0.58–0.91) and barotrauma (RR 0.43; 95% CI 0.20–0.90) with the use of cisatracurium infusion [468].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [465] Forel JM, Roch A, Marin V et al (2006) Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome. Crit Care Med 34(11):2749–2757 source

      Not checked in the free run.

    • cites [466] Gainnier M, Roch A, Forel JM et al (2004) Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome. Crit Care Med 32(1):113–119 source

      Not checked in the free run.

    • cites [467] Papazian L, Forel JM, Gacouin A et al (2010) Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 363(12):1107–1116 source

      Not checked in the free run.

    • cites [468] Alhazzani W, Alshahrani M, Jaeschke R et al (2013) Neuromuscular blocking agents in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials. Crit Care 17(2):R43 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The most common indication for neuromuscular blocking agents (NMBAs) use in the ICU is to facilitate mechanical ventilation.

    “The most common indication for neuromuscular blocking agents (NMBAs) use in the ICU is to facilitate mechanical ventilation [462].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [462] Klessig HT, Geiger HJ, Murray MJ et al (1992) A National Survey on the practice patterns of anesthesiologist intensivists in the use of muscle-relaxants. Crit Care Med 20(9):1341–1345 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A patient-level analysis of two of the randomised PEEP trials suggested that patients with ARDS who respond to increased PEEP with improved oxygenation have a lower risk of death; this association was stronger in patients with more severe ARDS (PaO2/FiO2 < 150 mmHg) compared with patients with less severe ARDS.

    “A patient-level analysis of two of the randomised PEEP trials [440, 441] suggested that patients with ARDS who respond to increased PEEP with improved oxygenation have a lower risk of death; this association was stronger in patients with more severe ARDS (PaO2/FiO2 < 150 mmHg) compared with patients with less severe ARDS [444].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [440] Meade MO, Cook DJ, Guyatt GH et al (2008) Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 299(6):637–645 source

      Not checked in the free run.

    • cites [441] Mercat A, Richard JC, Vielle B et al (2008) Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 299(6):646–655 source

      Not checked in the free run.

    • cites [444] Goligher EC, Kavanagh BP, Rubenfeld GD et al (2014) Oxygenation response to positive end-expiratory pressure predicts mortality in acute respiratory distress syndrome. A secondary analysis of the LOVS and ExPress trials. Am J Respir Crit Care Med 190(1):70–76 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    One option for selecting higher PEEP is to titrate PEEP according to bedside measurements of thoracopulmonary compliance with the objective of obtaining the best compliance or lowest driving pressure, reflecting a favourable balance of lung recruitment and overdistension.

    “One option is to titrate PEEP according to bedside measurements of thoracopulmonary compliance with the objective of obtaining the best compliance or lowest driving pressure, reflecting a favourable balance of lung recruitment and overdistension [445].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [445] Amato MB, Barbas CS, Medeiros DM et al (1995) Beneficial effects of the “open lung approach” with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med 152(6 Pt 1):1835–1846 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most patients respond to the prone position with improved oxygenation and may also have improved lung compliance.

    “Most patients respond to the prone position with improved oxygenation and may also have improved lung compliance [457–459].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [457] Jolliet P, Bulpa P, Chevrolet JC (1998) Effects of the prone position on gas exchange and hemodynamics in severe acute respiratory distress syndrome. Crit Care Med 26(12):1977–1985 source

      Not checked in the free run.

    • cites [458] Lamm WJ, Graham MM, Albert RK (1994) Mechanism by which the prone position improves oxygenation in acute lung injury. Am J Respir Crit Care Med 150(1):184–193 source

      Not checked in the free run.

    • cites [459] Stocker R, Neff T, Stein S et al (1997) Prone postioning and low-volume pressure-limited ventilation improve survival in patients with severe ARDS. Chest 111(4):1008–1017 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Applying higher PEEP in patients with ARDS may open lung units to participate in gas exchange and may increase PaO2.

    “Applying higher PEEP in patients with ARDS may open lung units to participate in gas exchange and may increase PaO2.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A third option is to use a PEEP/FiO2 titration table that titrates PEEP based on the combination of FiO2 and PEEP required to maintain adequate oxygenation.

    “A third option is to use a PEEP/FiO2 titration table that titrates PEEP based on the combination of FiO2 and PEEP required to maintain adequate oxygenation [439–441].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [439] Brower RG, Lanken PN, MacIntyre N et al (2004) Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 351(4):327–336 source

      Not checked in the free run.

    • cites [440] Meade MO, Cook DJ, Guyatt GH et al (2008) Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 299(6):637–645 source

      Not checked in the free run.

    • cites [441] Mercat A, Richard JC, Vielle B et al (2008) Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 299(6):646–655 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Since then, several RCTs have been published, the largest of which is the ROSE Trial.

    “Since then, several RCTs have been published [469–471], the largest of which is the ROSE Trial [471].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [469] Guervilly C, Bisbal M, Forel JM et al (2017) Effects of neuromuscular blockers on transpulmonary pressures in moderate to severe acute respiratory distress syndrome. Intensive Care Med 43(3):408–418 source

      Not checked in the free run.

    • cites [470] Lyu G, Wang X, Jiang W et al (2014) Clinical study of early use of neuromuscular blocking agents in patients with severe sepsis and acute respiratory distress syndrome. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 26(5):325–329

      Not checked in the free run.

    • cites [471] National Heart L, Blood Institute PCTN, Moss M et al (2019) Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med 380(21):1997–2008 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The optimal method of selecting a higher PEEP level is not clear.

    “The optimal method of selecting a higher PEEP level is not clear.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    While the pilot study suggested benefit, the subsequent 200 patient multicentre RCT that compared PEEP titration guided by esophageal (PES) measurement versus empirical high PEEP-FiO2 titration, showed no significant difference in a composite outcome of death and days free from mechanical ventilation through day 28.

    “While the pilot study suggested benefit [448], the subsequent 200 patient multicentre RCT that compared PEEP titration guided by esophageal (PES) measurement versus empirical high PEEP-FiO2 titration, showed no significant difference in a composite outcome of death and days free from mechanical ventilation through day 28 [449].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [448] Talmor D, Sarge T, Malhotra A et al (2008) Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med 359(20):2095–2104 source

      Not checked in the free run.

    • cites [449] Turbil E, Galerneau LM, Terzi N et al (2019) Positive-end expiratory pressure titration and transpulmonary pressure: the EPVENT 2 trial. J Thorac Dis 11(Suppl 15):S2012–S2017 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    Two RCTs were published since the 2016 Guidelines, but they were not included in the meta-analyses because both studies applied recruitment maneuvers to titrate PEEP levels.

    “Two RCTs [437, 438] were published since the 2016 Guidelines [12, 13], but we did not include these trials in the meta-analyses because both studies applied recruitment maneuvers to titrate PEEP levels.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [437] Hodgson CL, Cooper DJ, Arabi Y et al (2019) Maximal recruitment open lung ventilation in acute respiratory distress syndrome (PHARLAP). A phase II, multicenter randomized controlled clinical trial. Am J Respir Crit Care Med 200(11):1363–1372 source

      Not checked in the free run.

    • cites [438] Cavalcanti AB, Suzumura EA, Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial I et al (2017) Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA 318(14):1335–1345 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While prone position may be associated with potentially life-threatening complications including accidental removal of the endotracheal tube, this was not evident in pooled analysis (RR 1.09; 95% CI 0.85-1.39).

    “While prone position may be associated with potentially life-threatening complications including accidental removal of the endotracheal tube, this was not evident in pooled analysis (RR 1.09; 95% CI 0.85–1.39).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [454] Munshi L, Del Sorbo L, Adhikari NKJ et al (2017) Prone position for acute respiratory distress syndrome. A systematic review and meta-analysis. Ann Am Thorac Soc 14(Supplement_4):S280-s8 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although the effects of recruitment maneuvers improve oxygenation initially, the effects can be transient.

    “Although the effects of recruitment maneuvers improve oxygenation initially, the effects can be transient [453].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [453] Fan E, Wilcox ME, Brower RG et al (2008) Recruitment maneuvers for acute lung injury a systematic review. Am J Respir Crit Care Med 178(11):1156–1163 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Meta-analysis including this study demonstrated reduced mortality in severe ARDS patients treated with prone compared with supine position (RR 0.74; 95% CI 0.56-0.99) as well as improved oxygenation as measured by change in PaO2/FiO2 ratio (median 23.5 higher; 95% CI 12.4-34.5 higher).

    “Meta-analysis including this study demonstrated reduced mortality in severe ARDS patients treated with prone compared with supine position (RR 0.74; 95% CI 0.56–0.99) as well as improved oxygenation as measured by change in PaO2/FiO2 ratio (median 23.5 higher; 95% CI 12.4–34.5 higher) [454].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [454] Munshi L, Del Sorbo L, Adhikari NKJ et al (2017) Prone position for acute respiratory distress syndrome. A systematic review and meta-analysis. Ann Am Thorac Soc 14(Supplement_4):S280-s8 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    In the SSC 2016 guidelines, a weak recommendation was issued for using NMBA infusion for 48 h in sepsis-induced moderate to severe ARDS.

    “In the SSC 2016 guidelines, we issued a weak recommendation for using NMBA infusion for 48 h in sepsis-induced moderate to severe ARDS [12, 13].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] Rhodes A, Evans LE, Alhazzani W et al (2017) Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med 45(3):486–552 source

      Not checked in the free run.

    • cites [13] Rhodes A, Evans LE, Alhazzani W et al (2017) surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 43(3):304–377 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Prone position was associated with an increase in pressure sores (RR 1.22; 95% CI 1.05-1.41), and some patients have contraindications to the prone position.

    “However, prone position was associated with an increase in pressure sores (RR 1.22; 95% CI 1.05–1.41) [460, 461], and some patients have contraindications to the prone position [460, 461].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [460] Gattinoni L, Tognoni G, Pesenti A et al (2001) Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 345(8):568–573 source

      Not checked in the free run.

    • cites [461] Guerin C, Gaillard S, Lemasson S et al (2004) Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial. JAMA 292(19):2379–2387 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Temporarily raising transpulmonary pressure may facilitate opening atelectatic alveoli to permit gas exchange, but could also over distend aerated lung units leading to ventilator-induced lung injury and transient hypotension.

    “Temporarily raising transpulmonary pressure may facilitate opening atelectatic alveoli to permit gas exchange [446], but could also over distend aerated lung units leading to ventilator-induced lung injury and transient hypotension.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [446] Gattinoni L, Caironi P, Cressoni M et al (2006) Lung recruitment in patients with the acute respiratory distress syndrome. N Engl J Med 354(17):1775–1786 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These drugs may improve chest wall compliance, prevent respiratory dyssynchrony, and reduce peak airway pressures.

    “These drugs may improve chest wall compliance, prevent respiratory dyssynchrony, and reduce peak airway pressures [463].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [463] Murray MJ, Cowen J, DeBlock H et al (2002) Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 30(1):142–156 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    A second option is to titrate PEEP upward while the patient is receiving a tidal volume of 6 mL/kg PBW, until the plateau airway pressure is 28 cm H2O.

    “The second option is to titrate PEEP upward while the patient is receiving a tidal volume of 6 mL/kg PBW, until the plateau airway pressure is 28 cm H2O [441].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [441] Mercat A, Richard JC, Vielle B et al (2008) Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. JAMA 299(6):646–655 source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Since the publication of the previous SSC Guidelines, two important RCTs were published both of which utilised a "non-traditional" approach to recruitment maneuvers.

    “Since the publication of the previous SSC Guidelines, two important RCTs were published both of which utilised a “non-traditional” approach to recruitment maneuvers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In 2017, a meta-analysis was published that was updated from a previous meta-analysis published in 2010, to which only 1 study, the PROSEVA trial, published in 2013 was added.

    “In 2017, a meta-analysis was published [454] that was updated from a previous meta-analysis published in 2010 [455], to which only 1 study, the PROSEVA trial, published in 2013 [456] was added.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [454] Munshi L, Del Sorbo L, Adhikari NKJ et al (2017) Prone position for acute respiratory distress syndrome. A systematic review and meta-analysis. Ann Am Thorac Soc 14(Supplement_4):S280-s8 source

      Not checked in the free run.

    • cites [455] Sud S, Friedrich JO, Taccone P et al (2010) Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis. Intensive Care Med 36(4):585–599 source

      Not checked in the free run.

    • cites [456] Guérin C, Reignier J, Richard JC et al (2013) Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 368(23):2159–2168 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A patient-level meta-analysis showed no benefit of higher PEEP in all patients with ARDS; however, patients with moderate or severe ARDS (PaO2/FiO2 ≤ 200 mmHg) had decreased mortality with the use of higher PEEP, whereas those with mild ARDS did not.

    “A patient-level meta-analysis showed no benefit of higher PEEP in all patients with ARDS; however, patients with moderate or severe ARDS (PaO2/FiO2 ≤ 200 mmHg) had decreased mortality with the use of higher PEEP, whereas those with mild ARDS did not [443].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [443] Briel M, Meade M, Mercat A et al (2010) Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 303(9):865–873 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The overall balance of effects for restrictive versus liberal transfusion is uncertain and does not favour either strategy.

    “The overall balance of effects is uncertain and does not favour either the intervention or comparator.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Polymyxin B haemoperfusion is expensive, resource intensive, potentially reduces health equity, and is infeasible in low-income economies.

    “Polymyxin B haemoperfusion is expensive, resource intensive, potentially reduces health equity, and is infeasible in low-income economies.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    In APROCCHSS, the dose of vasopressor was ≥ 0.25 μg/kg/min or ≥ 1 mg/h of norepinephrine or epinephrine, or any other vasopressor for at least 6 h to maintain a MAP ≥ 65 mmHg.

    “In APROCCHSS [478] the dose of vasopressor was ≥ 0.25 µg/kg/min or ≥ 1 mg/h of norepinephrine or epinephrine, or any other vasopressor for at least 6 h to maintain a MAP ≥ 65 mmHg.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [478] Annane D, Renault A, Brun-Buisson C et al (2018) Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med 378(9):809–818 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The three trials used different inclusion criteria: in ADRENAL, eligible patients were those on any dose of vasopressor or inotrope for ≥ 4 h to maintain a MAP > 60 mmHg, and present at the time of randomisation.

    “The three trials [354, 478, 479] also used different inclusion criteria: in ADRENAL [479] eligible patients were those on any dose of vasopressor or inotrope for ≥ 4 h to maintain a MAP > 60 mmHg, and present at the time of randomisation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [479] Venkatesh B, Finfer S, Cohen J et al (2018) Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med 378(9):797–808 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Randomised trials of this technique have been previously summarised in a systematic review and meta-analysis.

    “Randomised trials of this technique have been previously summarised in a systematic review and meta-analysis [482].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [482] Zhou F, Peng Z, Murugan R et al (2013) Blood purification and mortality in sepsis: a meta-analysis of randomized trials. Crit Care Med 41(9):2209–2220 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    In clinical practice, patient selection is important and usually discussed prior to initiation of ECMO at an ECMO centre.

    “In clinical practice, patient selection is important and usually discussed prior to initiation of ECMO at an ECMO centre.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Cost and equity are substantial issues; and registry data will be very important to document longer-term outcomes in these patients outside of the clinical trial context.

    “Cost and equity are substantial issues; and registry data will be very important to document longer-term outcomes in these patients outside of the clinical trial context.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The evidence for the use of VV-ECMO in sepsis-induced ARDS is limited, with two RCTs completed in the last 10 years to assess the potential efficacy of VV ECMO for severe ARDS.

    “The evidence for the use of VV-ECMO in sepsis-induced ARDS is limited, with two RCTs completed in the last 10 years to assess the potential efficacy of VV ECMO for severe ARDS [476, 477].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [476] Combes A, Hajage D, Capellier G et al (2018) Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med 378(21):1965–1975 source

      Not checked in the free run.

    • cites [477] Peek GJ, Mugford M, Tiruvoipati R et al (2009) Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 374(9698):1351–1363 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The previous guidelines made no recommendation regarding the use of blood purification techniques.

    “The previous guidelines made no recommendation regarding the use of blood purification techniques [12, 13].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [12] Rhodes A, Evans LE, Alhazzani W et al (2017) Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med 45(3):486–552 source

      Not checked in the free run.

    • cites [13] Rhodes A, Evans LE, Alhazzani W et al (2017) surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 43(3):304–377 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The updated literature search for guideline identified one new relevant RCT.

    “The updated literature search for guideline identified one new relevant RCT [481].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [481] Dellinger RP, Bagshaw SM, Antonelli M et al (2018) Effect of targeted polymyxin B hemoperfusion on 28-day mortality in patients with septic shock and elevated endotoxin level: the EUPHRATES Randomized Clinical Trial. JAMA 320(14):1455–1463 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    In one trial, all intervention participants were treated at one centre, which may have inflated the effect size because the centre specialised in ECMO management.

    “In one trial, all intervention participants were treated at one centre, which may have inflated the effect size because the centre specialised in ECMO management [477].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [477] Peek GJ, Mugford M, Tiruvoipati R et al (2009) Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 374(9698):1351–1363 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the TRISS trial, a transfusion threshold of 70 g/L versus 90 g/L in 1000 septic shock patients after ICU admission resulted in similar 90-day mortality, ischaemic events, and use of life support, with fewer transfusions in the lower-threshold group.

    “The results showed similar 90-day mortality, ischaemic events, and use of life support in the two treatment groups with fewer transfusions in the lower-threshold group.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [484] Hébert PC, Wells G, Blajchman MA et al (1999) a multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 340(6):409–417 source

      Not checked in the free run.

    • cites [485] Holst LB, Haase N, Wetterslev J et al (2014) Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med 371(15):1381–1391 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The optimal dose, timing of initiation, and duration of corticosteroids remain uncertain; recent RCTs used 200 mg per day of IV hydrocortisone in divided doses.

    “The optimal dose, timing of initiation, and duration of corticosteroids remain uncertain; recent RCTs used 200 mg per day of IV hydrocortisone in divided doses [354, 479].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [354] Gordon AC, Mason AJ, Thirunavukkarasu N et al (2016) Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA 316(5):509–518 source

      Not checked in the free run.

    • cites [479] Venkatesh B, Finfer S, Cohen J et al (2018) Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med 378(9):797–808 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The dose of hydrocortisone is typically 200 mg/day.

    “The dose of hydrocortisone is typically 200 mg/day.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Intravenous immunoglobulin is relatively expensive, possibly not cost-effective, and may reduce health equity.

    “Intravenous immunoglobulin is also relatively expensive, possibly not cost-effective and may reduce health equity.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    A restrictive transfusion strategy was determined likely beneficial with regards to resources required, cost effectiveness, and health equity considerations.

    “However, a restrictive strategy was determined likely beneficial with regards to resources required, cost effectiveness, and health equity considerations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Stress ulcers develop in the gastrointestinal tract of critically ill patients and can be associated with significant morbidity and mortality.

    “Stress ulcers develop in the gastrointestinal (GI) tract of critically ill patients and can be associated with significant morbidity and mortality [493].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [493] Cook DJ, Fuller HD, Guyatt GH et al (1994) Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 330(6):377–381 source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Substantial uncertainty as to any beneficial effect exists and the frequency of undesirable effects is reported in few trials.

    “Substantial uncertainty as to any beneficial effect exists and the frequency of undesirable effects is reported in few trials.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The quality of evidence for IVIG and IVIGM is low, with many included studies at high risk of bias due to single-centre design, small sample size, undefined randomisation, allocation and blinding, different dosing regimens and durations, different controls, and few reporting adverse events.

    “however the quality of evidence is low with many of the included studies at high risks of bias including single-centre trials with small sample size, undefined randomisation, allocation and blinding procedures, different dosing regimens and durations of treatment, different controls and few studies reported adverse events.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The most recent and largest RCT did not demonstrate any effect of pantoprazole versus placebo on 90-day mortality or a composite outcome of clinically important events.

    “However, it was noted that the most recent (and largest) RCT did not demonstrate any effect of pantoprazole versus placebo on 90-day mortality and a composite outcome of clinically important events [494].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [494] Krag M, Marker S, Perner A et al (2018) Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. N Engl J Med 379(23):2199–2208 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the TRICOP trial, at 28 days, mortality was 45% in the liberal group versus 56% in the restrictive group (HR 0.74; 95% CI 0.53-1.04; p = 0.08), with no differences in ICU and hospital length of stay.

    “At 28 days after randomisation, the mortality rate in the liberal group was 45% 67 patients versus 56% 84 patients in the restrictive group (HR 0.74; 95% CI 0.53–1.04; p = 0.08) with no differences in ICU and hospital length of stay.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [487] Bergamin FS, Almeida JP, Landoni G et al (2017) Liberal versus restrictive transfusion strategy in critically ill oncologic patients: the transfusion requirements in critically ill oncologic patients randomized controlled trial. Crit Care Med 45(5):766–773 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the ADRENAL study, hydrocortisone was administered for a maximum of seven days or until ICU discharge or death; in APROCCHSS hydrocortisone was administered for seven days; in VANISH 200 mg of hydrocortisone was administered daily for 5 days and then tapered over further 6 days.

    “In the ADRENAL [479] study, hydrocortisone was administered for a maximum of seven days or until ICU discharge or death; in APROCCHSS [478] hydrocortisone was administered for seven days; in VANISH [354] 200 mg of hydrocortisone was administered daily for 5 days and then tapered over further 6 days.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [479] Venkatesh B, Finfer S, Cohen J et al (2018) Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med 378(9):797–808 source

      Not checked in the free run.

    • cites [478] Annane D, Renault A, Brun-Buisson C et al (2018) Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med 378(9):809–818 source

      Not checked in the free run.

    • cites [354] Gordon AC, Mason AJ, Thirunavukkarasu N et al (2016) Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA 316(5):509–518 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductnone given

    While no adverse effects were observed, the quality of evidence for these outcomes was low.

    “While no adverse effects were observed, the quality of evidence for these outcomes was low.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The STARRT-AKI trial randomised 3000 participants and demonstrated no difference in mortality between accelerated and standard RRT strategies.

    “The trial, which randomised 3000 participants, demonstrated no difference in mortality in those allocated to an accelerated strategy of RRT compared to those allocated to a “standard” strategy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [508] Investigators S-A, Canadian Critical Care Trials G, Australian et al (2020) Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med 383(3):240–251 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    The resources required for continuous and intermittent RRT vary.

    “It was acknowledged that the resources required for the interventions vary.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    In some patients with sepsis and septic shock, pharmacologic prophylaxis may be contraindicated.

    “It is acknowledged that in some patents with sepsis and septic shock pharmacologic prophylaxis may be contraindicated.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Vitamin C is known to have anti-inflammatory properties.

    “Vitamin C is known to have anti-inflammatory properties [520].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [520] Kuhn SO, Meissner K, Mayes LM et al (2018) Vitamin C in sepsis. Curr Opin Anaesthesiol 31(1):55–60 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    In low- and middle-income economies, the specialised equipment, expertise, and personnel required for continuous modalities may not be available.

    “In low- and middle-income economies, the specialised equipment, expertise and personal required for continuous modalities may not be available.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    LMWH may have greater consumer acceptance as it requires only one subcutaneous injection daily.

    “Further, LMWH may have greater consumer acceptance as it requires only one subcutaneous injection daily.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The judgment favouring stress ulcer prophylaxis is driven by a modest reduction in gastrointestinal haemorrhage, for which there is moderate quality of evidence.

    “This is driven by a modest reduction in gastrointestinal haemorrhage for which there is moderate quality of evidence (Supplementary Appendix 5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In 2017, a single centre before and after study reported shorter duration of vasopressor therapy and lower mortality following administration of high dose vitamin C, hydrocortisone, and thiamine to patients with sepsis and septic shock.

    “In 2017, a single centre before and after study reported shorter duration of vasopressor therapy and lower mortality following the administration of combination of high dose vitamin C, hydrocortisone, and thiamine to patients with sepsis and septic shock [521].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [521] Marik PE, Khangoora V, Rivera R et al (2017) Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest 151(6):1229–1238 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The cost of pharmacologic VTE prophylaxis is not large, and it is likely feasible in countries with low- and middle-income economies.

    “The cost of intervention is not large, and it is likely feasible in countries with low- and middle-income economies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In a single centre study, targeting blood glucose to 80-110 mg/dL reduced ICU mortality, but this finding was not reproduced in subsequent multi-centre RCTs.

    “In a single centre study, targeting blood glucose to 80-110 mg/dL reduced ICU mortality [513], however this finding was not reproduced in subsequent multi-centre RCTs [514, 515].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [513] van den Berghe G, Wouters P, Weekers F et al (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345(19):1359–1367 source

      Not checked in the free run.

    • cites [514] Brunkhorst FM, Engel C, Bloos F et al (2008) Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 358(2):125–139 source

      Not checked in the free run.

    • cites [515] Preiser JC, Devos P, Ruiz-Santana S et al (2009) A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med 35(10):1738–1748 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The American Diabetes Association recommends initiating insulin therapy for persistent hyperglycemia > 180 mg/dL and targeting a glucose range of 140-180 mg/dL.

    “The American Diabetes Association, in its most recent recommendations for glycemic control of critically ill patients, recommended the initiation of insulin therapy for persistent hyperglycemia > 180 mg/dL and thereafter a target glucose range of 140–180 mg/dL [512].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [512] Diabetes Care in the Hospital (2018) Standards of Medical Care in Diabetes—2018. Diabetes Care 41(Supplement 1):S144–S151

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Prior research has suggested both benefit and harm for early versus delayed initiation of RRT.

    “Prior research has suggested benefit [505] or harm [506] for “early” versus “delayed” initiation of RRT.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [505] Zarbock A, Kellum JA, Schmidt C et al (2016) Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN Randomized Clinical Trial. JAMA 315(20):2190–2199 source

      Not checked in the free run.

    • cites [506] Gaudry S, Hajage D, Schortgen F et al (2016) Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med 375(2):122–133 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    The certainty of evidence for mortality, renal recovery, and CVAD infection was at least moderate and was only downgraded for imprecision.

    “The certainty of evidence for the key outcomes of mortality, renal recovery and CVAD infection was a least moderate and was only downgraded for imprecision (Supplementary Appendix 5).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    These patients may benefit from mechanical VTE prophylaxis.

    “These patients may benefit from mechanical VTE prophylaxis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The incidence of DVT acquired in the ICU may be as high as 10%, and the incidence of acquired PE may be 2-4%.

    “The incidence of DVT acquired in the ICU may be as high as 10% [497], the incidence of acquired PE may be 2–4% [498, 499].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [497] Cook D, Crowther M, Meade M et al (2005) Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors. Crit Care Med 33(7):1565–1571 source

      Not checked in the free run.

    • cites [498] Alhazzani W, Lim W, Jaeschke RZ et al (2013) Heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care Med 41(9):2088–2098 source

      Not checked in the free run.

    • cites [499] Kahn SR, Lim W, Dunn AS et al (2012) Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141(2 Suppl):e195S-e226S source

      Not checked in the free run.

  • The quote only partly states this claim.

    Study design and conductcitation

    The overall quality of evidence for glucose control was rated moderate.

    “The overall quality of evidence was rated as moderate (Supplementary Appendix 5).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Hyperglycemia (> 180 mg/dL), hypoglycemia, and increased glycemic variability are associated with increased mortality in critically ill patients.

    “Hyperglycemia (> 180 mg/dL), hypoglycemia and increased glycemic variability are associated with increased mortality in critically ill patients [509–511].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [509] Badawi O, Waite MD, Fuhrman SA et al (2012) Association between intensive care unit-acquired dysglycemia and in-hospital mortality. Crit Care Med 40(12):3180–3188 source

      Not checked in the free run.

    • cites [510] Krinsley JS (2008) Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med 36(11):3008–3013 source

      Not checked in the free run.

    • cites [511] Siegelaar SE, Hermanides J, Oudemans-van Straaten HM et al (2010) Mean glucose during ICU admission is related to mortality by a U-shaped curve in surgical and medical patients: a retrospective cohort study. Crit Care 14(6):R224 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    There are resource implications and costs associated with the use of mechanical VTE prophylaxis.

    “However, there are resource implications and costs associated with the use of mechanical VTE prophylaxis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The PREVENT study was downgraded during quality assessment for imprecision; for mortality, quality was moderate, and for other outcomes it was further downgraded for risk of bias.

    “The study was downgraded during the quality assessment for imprecision. For the outcome of mortality, the quality was assessed as moderate; for other outcomes it was further downgraded for risk of bias.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Any difference in resources required between LMWH and UFH was considered negligible, and LMWH administration was feasible and applicable in countries with low- and middle-income economies.

    “Any difference in resources required between the two interventions was considered to be negligible, and LMWH administration was feasible and applicable in countries with low- and middle-income economies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Interpretationnone given

    Stress ulcer prophylaxis is relatively inexpensive, requires limited resources, and is applicable to countries with low-income economies.

    “Stress ulcer prophylaxis is relatively inexpensive, requires limited resources and is applicable to countries with low-income economies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In the PREVENT study, no difference in mortality (RR 0.98; 95% CI 0.84-1.13) or rates of DVT and PE were observed between combination mechanical and pharmacological prophylaxis and pharmacological prophylaxis alone.

    “No difference in mortality (RR 0.98 95% CI 0.84–1.13), or the rates of DVT and PE were observed.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [500] Arabi YM, Al-Hameed F, Burns KEA et al (2019) Adjunctive intermittent pneumatic compression for venous thromboprophylaxis. N Engl J Med 380(14):1305–1315 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    There is broad consensus that the current healthcare system is likely falling short of optimal care during the recovery period for sepsis survivors.

    “There is broad consensus that the current healthcare system is likely falling short of what optimal care during the recovery period might look like for this patient population.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Given the variety of triggers used in these studies and the lack of superiority of any single trigger, no recommendation can be made for specific criteria to initiate a goals of care discussion.

    “Given the variety of triggers used in these studies and the lack of superiority of any single trigger, no recommendation can be made for specific criteria to initiate a goals of care discussion.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    A discussion of goals of care and prognosis is essential to determine which treatments are acceptable and which are not desired.

    “A discussion of goals of care and prognosis is essential to determine which treatments are acceptable and those interventions that are not desired [536].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [536] Ely EW (2017) The ABCDEF Bundle: science and philosophy of how ICU liberation serves patients and families. Crit Care Med 45(2):321–330 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The previous guidance was based on two small, blinded crossover RCTs that compared equimolar saline vs sodium bicarbonate in patients with lactic acidosis and failed to reveal any difference in haemodynamic variables or vasopressor requirements.

    “The previous guidance was based on two small, blinded crossover RCTs that compared equimolar saline vs sodium bicarbonate in patients with lactic acidosis and failed to reveal any difference in haemodynamic variables or vasopressor requirements [526, 527].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [526] Cooper DJ, Walley KR, Wiggs BR et al (1990) Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study. Ann Intern Med 112(7):492–498 source

      Not checked in the free run.

    • cites [527] Mathieu D, Neviere R, Billard V et al (1991) Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study. Crit Care Med 19(11):1352–1356 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Despite lack of evidence, the panel recognised that discussion of prognosis and exploration of goals of care with patients and/or family is a necessary precondition to determine patient treatment preferences and provide value-concordant care.

    “Despite lack of evidence, the panel recognised that discussion of prognosis and exploration of goals of care with patients and/or family is a necessary precondition to determine patient treatment preferences and providing value-concordant care.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisenone given

    Some patients may accept any and all treatment for their condition, but others may consider limitations depending on prognosis, invasiveness of interventions, and predicted quality of life.

    “Some patients may accept any and all treatment for their condition, but others may consider limitations depending on prognosis, invasiveness of interventions, and predicted quality of life (QoL).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Patients with sepsis or septic shock are at high risk of multi-organ failure, long-term functional sequelae, and death.

    “Patients with sepsis or septic shock are at high risk of multi-organ failure, long-term functional sequelae, and death.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Patients who survive a protracted period of ICU care for sepsis typically face a long and complicated road to recovery.

    “Patients who survive a protracted period of ICU care for sepsis typically face a long and complicated road to recovery.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Advance care planning in patients with life-limiting illness may reduce use of life-sustaining treatments, may increase use of hospice and palliative care, and may improve concordance between treatment and patient values.

    “While advance care planning in patients with life-limiting illness may reduce use of life-sustaining treatments, it may also increase use of hospice and palliative care, and improve concordance between treatment and patient values [537].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [537] Brinkman-Stoppelenburg A, Rietjens JA, van der Heide A (2014) The effects of advance care planning on end-of-life care: a systematic review. Palliat Med 28(8):1000–1025 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    The intervention of vitamin C requires limited resources and is feasible in low- and middle-income economies.

    “The intervention itself requires limited resources and is feasible in low- and middle-income economies.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The relevance of advance care planning for future health needs to goals of care discussions at the time of a critical illness is unclear.

    “The relevance of advance care planning for future health needs to goals of care discussions at the time of a critical illness is unclear.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Transitions of care are prone to communication errors, which have been identified as a barrier to timely detection and management of sepsis.

    “Transitions of care are prone to communication errors, which have been identified as a barrier to the timely detection and management of sepsis [567].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [567] Matthaeus-Kraemer CT, Thomas-Rueddel DO, Schwarzkopf D et al (2016) Crossing the handover chasm: Clinicians’ perceptions of barriers to the early detection and timely management of severe sepsis and septic shock. J Crit Care 36:85–91 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Screening for economic and social support may help reduce inequities.

    “Screening for economic and social support may help reduce these inequities.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Non-medical social needs and modifiable factors such as economic and social support largely influence health outcomes.
    • Rests on an assumption: Long-term health requires survivors to have the resources to recover and thrive.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    It is unlikely that many research studies would be conducted on screening because locally available social needs and supports vary.

    “Furthermore, it is unlikely that many research studies would be conducted, since locally available social needs and supports vary.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Transfer from ICU to general floor and hospital discharge are vulnerable periods with high frequency of medication errors and information loss.

    “Transfer from ICU to general floor and discharge from the hospital are both vulnerable periods for patients, with high frequency of medication errors and information loss [596–602].”
    Quote in the paperSubstantial claim0 of 7 sources checked
    • cites [596] Bell CM, Brener SS, Gunraj N et al (2011) Association of ICU or hospital admission with unintentional discontinuation of medications for chronic diseases. JAMA 306:840–847 source

      Not checked in the free run.

    • cites [597] Fabes J, Seligman W, Barrett C et al (2017) Does the implementation of a novel intensive care discharge risk score and nurse-led inpatient review tool improve outcome? A prospective cohort study in two intensive care units in the UK. BMJ Open 7(12):e018322 source

      Not checked in the free run.

    • cites [598] Mekonnen AB, McLachlan AJ, Brien JA (2016) Pharmacy-led medication reconciliation programmes at hospital transitions: a systematic review and meta-analysis. J Clin Pharm Ther 41(2):128–144 source

      Not checked in the free run.

    • cites [599] Morandi A, Vasilevskis E, Pandharipande PP et al (2013) Inappropriate medication prescriptions in elderly adults surviving an intensive care unit hospitalization. J Am Geriatr Soc 61:1128–1134 source

      Not checked in the free run.

    • cites [600] Scales DC, Fischer HD, Li P et al (2016) Unintentional continuation of medications intended for acute illness after hospital discharge: A population-based cohort study. J Gen Intern Med 31:196–202 source

      Not checked in the free run.

    • cites [601] Stelfox HT, Bastos J, Niven DJ et al (2016) Critical care transition programs and the risk of readmission or death after discharge from ICU. Intensive Care Med 42(3):401–410 source

      Not checked in the free run.

    • cites [602] Tomichek JE, Stollings JL, Pandharipande PP et al (2016) Antipsychotic prescribing patterns during and after critical illness: a prospective cohort study. Crit Care 20:378 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Peer support groups have been used to enhance recovery from illness with long-lasting disability but have only recently been used in critical care and sepsis.

    “Peer support groups have been used to enhance recovery from illness when survivors have long-lasting disability but have only recently been used in critical care and sepsis [549–551].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [549] Clark E, MacCrosain A, Ward NS et al (2020) The key features and role of peer support within group self-management interventions for stroke? A systematic review. Disabil Rehabil 42(3):307–316 source

      Not checked in the free run.

    • cites [550] Govindan S, Iwashyna TJ, Watson SR et al (2014) Issues of survivorship are rarely addressed during intensive care unit stays. Baseline results from a statewide quality improvement collaborative. Ann Am Thorac Soc 11(4):587–591 source

      Not checked in the free run.

    • cites [551] Wobma R, Nijland RH, Ket JC et al (2016) Evidence for peer support in rehabilitation for individuals with acquired brain injury: a systematic review. J Rehabil Med 48(10):837–840 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    Lessons learned in post-critical care clinics could be adapted to other, more-scalable interventions such as telehealth.

    “Lessons learned in post-critical care clinics could be adapted to other, more-scalable interventions such as telehealth.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Follow-up with a provider after hospital discharge is one step in the recovery process.

    “Follow-up with a provider after hospital discharge is one-step in the recovery process.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    In centers where cognitive therapy is used, it could reasonably be continued as it is likely acceptable and feasible, but there is insufficient evidence to change practice in centers without such therapy.

    “In centers where cognitive therapy is used, it could reasonably be continued as it is likely acceptable and feasible, but there is insufficient evidence to change practice in centers without such therapy.”
    Quote in the paperSubstantial claim
284 of 284

  • The paper relies on this without support.

    Early identification and appropriate management in the initial hours after sepsis onset improve outcomes.

    “Early identification and appropriate management in the initial hours after the development of sepsis improve outcomes.”

  • The paper relies on this without support.

    Timely, effective fluid resuscitation is crucial for stabilisation of sepsis-induced tissue hypoperfusion in sepsis and septic shock.

    “Timely, effective fluid resuscitation is crucial for the stabilisation of sepsis-induced tissue hypoperfusion in sepsis and septic shock.”

  • The paper relies on this without support.

    Most patients require continued fluid administration following initial resuscitation.

    “Most patients require continued fluid administration following initial resuscitation.”

  • The paper relies on this without support.

    Fluid administration beyond initial resuscitation must be balanced against risk of fluid accumulation and potential harm, including prolonged ventilation, progression of acute kidney injury, and increased mortality.

    “Such administration needs to be balanced with the risk of fluid accumulation and potential harm associated with fluid overload, in particular, prolonged ventilation, progression of acute kidney injury (AKI) and increased mortality.”

  • The paper relies on this without support.

    Heart rate, central venous pressure, and systolic blood pressure alone are poor indicators of fluid status.

    “Heart rate, central venous pressure (CVP) and systolic blood pressure alone are poor indicators of fluid status.”

  • The paper relies on this without support.

    Dynamic measures have better diagnostic accuracy at predicting fluid responsiveness than static techniques.

    “Dynamic measures have demonstrated better diagnostic accuracy at predicting fluid responsiveness compared with static techniques.”

  • The paper relies on this without support.

    Most data on fluid resuscitation arise from high-income settings, and evidence is scarce in resource-limited settings to guide optimal titration and safety endpoints.

    “Most data arise from high income settings and a paucity of evidence exists in resource-limited settings to guide optimal titration of fluid resuscitation as well as the appropriate safety end- points.”

  • The paper relies on this without support.

    MAP is a key determinant of mean systemic filling pressure, which is the major driver of venous return and cardiac output.

    “MAP is a key determinant of mean systemic filling pressure, which in turn, is the major driver of venous return and CO.”

  • The paper relies on this without support.

    Increasing MAP usually results in increased tissue blood flow and augments the supply side of tissue perfusion.

    “Increasing MAP therefore usually results in increased tissue blood flow and augments the supply side of tissue perfusion.”

  • The paper relies on this without support.

    The outcome of critically ill patients depends on timely application of critical care interventions in an appropriate environment.

    “The outcome of critically ill patients depends on timely application of critical care interventions in an appropriate environment.”

  • The paper relies on this without support.

    The availability and turn-around time for laboratory testing, rapid infectious diagnostic, imaging, etc. varies widely by regions and settings.

    “The availability and turn-around time for laboratory testing, rapid infectious diagnostic, imaging, etc. varies widely by regions and settings.”

  • The paper relies on this without support.

    The risk of Candida sepsis or septic shock in immunosuppressed populations other than febrile neutropenia is highly disease- and therapy-specific.

    “The risk of Candida sepsis or septic shock for other immunosuppressed populations is highly disease- and therapy-specific.”

  • The paper relies on this without support.

    Effective therapies are lacking for most zoonotic viruses that can manifest with clinical signs of sepsis.

    “Unfortunately, effective therapies are lacking for most of these viruses.”

  • The paper relies on this without support.

    Procalcitonin testing may not be available in all countries and healthcare settings, including LMICs.

    “Procalcitonin testing may not be available in all countries and healthcare settings, including LMICs.”

  • The paper relies on this without support.

    The direct costs of antibiotics can increase with routine use of multiple agents, particularly in resource-limited settings.

    “The overall quality of evidence was very low, and the direct costs of antibiotics can increase with the routine use of multiple agents for treatment. This may specifically have an impact in resource-limited settings.”

  • The paper relies on this without support.

    Treatment with empiric antifungals may be associated with increased costs.

    “The overall quality of evidence was low, and treatment with empiric antifungals may be associated with increased costs.”

  • The paper relies on this without support.

    Clinical experience indicates that without adequate source control, many severe presentations will not stabilise or improve despite rapid resuscitation and appropriate antimicrobials.

    “Clinical experience suggests that without adequate source control, many severe presentations will not stabilise or improve despite rapid resuscitation and provision of appropriate antimicrobials.”

  • The paper relies on this without support.

    Crystalloids are inexpensive and widely available.

    “Crystalloids have the advantage of being inexpensive and widely available.”

  • The paper relies on this without support.

    Albumin is more costly than crystalloids.

    “it is more costly and there is no clear benefit with its routine use.”

  • The paper relies on this without support.

    Norepinephrine is more potent than dopamine as a vasoconstrictor.

    “Norepinephrine is more potent than dopamine as a vasoconstrictor.”

  • The paper relies on this without support.

    Dopamine's beta-1 adrenergic receptor activity can lead to dose-limiting arrhythmias.

    “its β-1 adrenergic receptor activity can lead to dose-limiting arrhythmias.”

  • The paper relies on this without support.

    Availability of and experience with norepinephrine may vary.

    “The panel also recognised that availability of, and experience with, norepinephrine may vary.”

  • The paper relies on this without support.

    The results of clinical trials conducted in general critically ill or ARDS populations are applicable to patients with sepsis-induced ARDS.

    “Of note, the studies that guide the recommendations in this section enrolled patients using criteria from the American-European Consensus Criteria Definition for Acute Lung Injury and ARDS [422].”

  • The paper relies on this without support.

    The 2012 Berlin definition of ARDS does not materially alter the applicability of trial results that used the older American-European Consensus Criteria.

    “For the current document, we used the 2012 Berlin definition and the terms mild, moderate, and severe ARDS (PaO2/FiO2 ≤ 300, ≤ 200, and ≤ 100 mm Hg, respectively) [423].”

  • The paper relies on this without support.

    Non-medical social needs and modifiable factors such as economic and social support largely influence health outcomes.

    “Non-medical social needs and potentially modifiable factors such as economic and social support largely influence health outcomes.”

  • The paper relies on this without support.

    Long-term health requires survivors to have the resources to recover and thrive.

    “While survival from sepsis is improving, long-term health requires survivors to have the resources to recover and thrive.”

  • The paper relies on this without support.

    Socioeconomic screening is considered part of standard clinical practice.

    “Although socioeconomic screening is considered part of standard clinical practice, all clinical teams in many settings may not do it.”

  • The paper relies on this without support.

    Shared decision making is less routinely used in post-ICU and hospital discharge planning than in other aspects of acute patient care.

    “This patient-centered approach may be less routinely used in post-ICU and hospital discharge planning than in other aspects of acute patient care.”

  • The paper relies on this without support.

    Medication reconciliation is broadly recognised to be important during patient transitions.

    “Medication reconciliation is broadly recognised to be important during patient transitions.”

  • The paper relies on this without support.

    Individuals who receive referral to peer support have the choice to participate or not.

    “As individuals who receive referral to peer support have the choice to participate or not (based on personal preference, timing, location, functional status, and resources required) a weak recommendation provides an opportunity to access support for sepsis survivors who otherwise may not know where to turn [552].”

  • The paper relies on this without support.

    Many sepsis interventions and tests are time-dependent, and communication failures may increase the chances of critical medical errors.

    “While it is unclear whether structured handoffs impact important patient outcomes, many sepsis interventions and tests are time-dependent and communication failures may increase the chances of critical medical errors.”
31 of 31

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Early and effective inhibition or killing of pathogens is essential for the prevention and treatment of sepsis.

    “Early and effective inhibition or killing of pathogens is essential for the prevention and treatment of sepsis.12”

    From Identification of heptapeptides targeting a lethal bacterial strain in septic mice through an integrative approach (2022) · cites this paper as [12]

    The Infection rationale (page not provided) says early, appropriate antimicrobials reduce mortality in patients with sepsis, supporting the treatment portion. It does not establish that inhibiting or killing pathogens prevents sepsis; its recommendations concern patients with suspected or established sepsis. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Vitamin C vasopressor result is described in the opposite direction

    Minor

    The text calls the result reduced vasopressor use, but a larger proportion of vitamin C recipients than controls remained on vasopressors at the stated time point.

  • Fluid-pressure estimate falls outside its confidence interval

    Minor

    The reported mean difference is negative, but both stated confidence-interval endpoints are positive. The point estimate cannot lie within that interval.

  • Review date conflicts with its cited reference

    Minor

    The rationale dates the cited systematic review to 2015, while reference 450 lists it as published in 2012.

  • Negative confidence limit is incompatible with a risk ratio

    Minor

    The result labels its effect measure a risk ratio, but gives a confidence interval extending below zero; a risk ratio cannot be negative.

  • Digital-ischaemia percentage rounds incorrectly

    Minor

    Thirty-three of 260 patients is 12.69%, which rounds to 13%, not the reported 12%.

    Reported 12 · recomputed 12.692308

  • VTE trial control group is described two different ways

    Minor

    The trial is first described as comparing combined mechanical and drug prophylaxis with drug prophylaxis alone. The later description instead says its comparison group received mechanical prophylaxis alone, changing the comparison used to support the recommendation.

6 of 6

Cites

Flagged first, then by citations

Research works printed but not linked: 6

  1. Liu G, An Y, Yi X et al (2017) Early lactate levels for prediction of mortality in patients with sepsis or septic shock: a meta-analysis. Int J Exp Med 10:37–47
  2. Vincent J (2019) Arterial, central venous, and pulmonary artery catheters. In: JE P (ed) Critical care medicine: principles and diagnosis and management in the adult, 5th edn. Elsevier, Philadelphia, pp 40–49
  3. Belenguer-Muncharaz A, Cubedo-Bort M, Blasco-Asensio D et al (2017) Non-invasive ventilation versus invasive mechanical ventilation in patients with hypoxemic acute respiratory failure in an Intensive Care Unit. A randomized controlled study. Minerva Pneumologica 56:1–10
  4. Force ADT, Ranieri VM, Rubenfeld GD et al (2012) Acute respiratory distress syndrome: the Berlin Definition. JAMA 307(23):2526–2533
  5. Cavalcanti AB, Suzumura ÉA, Laranjeira LN et al (2017) Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA 318(14):1335–1345 · DOI · Paper page
  6. Diabetes Care in the Hospital (2018) Standards of Medical Care in Diabetes—2018. Diabetes Care 41(Supplement 1):S144–S151

Cited by

Sorted by citations

Authors
Evans, L., Rhodes, A., Alhazzani, W., Antonelli, M., Coopersmith, C. M., French, C., Machado, F. R., Mcintyre, L., Ostermann, M., Prescott, H. C., Schorr, C., Simpson, S., Wiersinga, W. J., Alshamsi, F., Angus, D. C., Arabi, Y., Azevedo, L., Beale, R., Beilman, G., Belley-Cote, E., Burry, L., Cecconi, M., Centofanti, J., Coz Yataco, A., De Waele, J., Dellinger, R. P., Doi, K., Du, B., Estenssoro, E., Ferrer, R., Gomersall, C., Hodgson, C., Møller, M. H., Iwashyna, T., Jacob, S., Kleinpell, R., Klompas, M., Koh, Y., Kumar, A., Kwizera, A., Lobo, S., Masur, H., McGloughlin, S., Mehta, S., Mehta, Y., Mer, M., Nunnally, M., Oczkowski, S., Osborn, T., Papathanassoglou, E., Perner, A., Puskarich, M., Roberts, J., Schweickert, W., Seckel, M., Sevransky, J., Sprung, C. L., Welte, T., Zimmerman, J., & Levy, M.
Affiliations
  • University of Washington (US)
  • St George's, University of London (GB)
  • McMaster University (CA)
  • Agostino Gemelli University Polyclinic (IT)
  • Emory University (US)
  • Western Health (AU)
  • Hospital São Paulo (BR)
  • Ottawa Hospital (CA)
  • Guy's Hospital (GB)
  • University of Michigan (US)
  • Cooper Norcross Health (US)
  • University of Kansas Medical Center (US)
  • Amsterdam University Medical Centers (NL)
  • United Arab Emirates University (AE)
  • University of Pittsburgh (US)
  • King Saud bin Abdulaziz University for Health Sciences (SA)
  • Universidade de São Paulo (BR)
  • University of Minnesota (US)
  • Mount Sinai Hospital (CA)
  • Humanitas University (IT)
  • The University of Tokyo (JP)
  • Peking Union Medical College Hospital (CN)
  • Vall d'Hebron Institut de Recerca (ES)
  • Prince of Wales Hospital (CN)
  • Monash University (AU)
  • Copenhagen University Hospital (DK)
  • Michigan Medicine (US)
  • Liverpool School of Tropical Medicine (GB)
  • Vanderbilt University (US)
  • Brigham and Women's Hospital (US)
  • Asan Medical Center (KR)
  • University of Manitoba (CA)
  • Makerere University (UG)
  • Faculdade de Medicina de São José do Rio Preto (BR)
  • National Institutes of Health (US)
  • Alfred Health (AU)
  • Medanta The Medicity (IN)
  • University of the Witwatersrand (ZA)
  • New York University (US)
  • Washington University in St. Louis (US)
  • University of Alberta (CA)
  • Rigshospitalet (DK)
  • The University of Queensland (AU)
  • University of Pennsylvania (US)
  • Hebrew University of Jerusalem (IL)
  • Medizinische Hochschule Hannover (DE)
  • Brown University (US)
Corresponding author
Evans, Laura
ORCID
Venue
Intensive Care Medicine
Publisher
Springer Science and Business Media LLC
Published
2021-10-02
Volume
47
Issue
11
Pages
1181-1247
ISSN
  • 0342-4642 (ISSN-L)
  • 1432-1238
DOI
10.1007/s00134-021-06506-y
PMC
PMC8486643
OpenAlex
W3202964273
Cited by
5,082
References
645
Citations by year
2026: 903 · 2025: 1227 · 2024: 1203 · 2023: 1080 · 2022: 614 · 2021: 44 · 2020: 5 · 2012: 1
FWCI
532.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Intensive Care Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (acceptedVersion, cc-by)
  • LSTM Online Archive (Liverpool School of Tropical Medicine) (acceptedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion)
Funders
  • American Thoracic Society
  • Society for Academic Emergency Medicine
  • European Respiratory Society
  • American Association of Critical-Care Nurses
  • National Institute for Health and Care Research (17/63/42)
  • Intensive Care Society
  • European Society of Clinical Microbiology and Infectious Diseases
  • European Society of Intensive Care Medicine
Topics
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Abdominal Surgery and Complications
  • Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
Keywords
sepsis, septic shock, Surviving Sepsis Campaign, sepsis screening, early sepsis treatment, fluid resuscitation, vasoactive drugs, antimicrobial therapy, mechanical ventilation, goals of care, long-term outcomes, adults
MeSH terms
Critical Care, Humans, Shock, Septic, Sepsis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-01.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-01.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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