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

In the paper

“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].”

What the sources say

• Partly supported

  Table 1 (p. 5) reports pooled median pre-randomisation fluid volumes of 27.5 and 27.7 ml/kg across ProCESS, ARISE and ProMISe, consistent with a volume near 30 ml/kg. It does not report an average for each trial or establish that 30 ml/kg had been adopted in routine clinical practice; that broader conclusion remains an inference from the trial data. (LLM, conf=0.84)

  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 sourceExperimental — accuracy not yet measured

In the paper

“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”

What the sources say

• Not checked yetcites [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
• Partly supported

  The Abstract and Trial Interventions describe a randomized comparison in patients aged 65 or older, with a 60–65 mm Hg MAP target versus clinician-directed usual care. The baseline table in the Conclusions section reports the cited 66.7 and 72.6 mm Hg values, but they are medians of patients’ mean MAP while receiving vasopressors, not group means. It also shows that about 48% of patients had septic shock; the trial enrolled patients with vasodilatory hypotension more broadly. (LLM, conf=0.91)

  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 sourceExperimental — accuracy not yet measured

In the paper

“These include a range of adverse events such as allergic or hypersensitivity reactions, kidney injury, thrombocytopenia, Clostridioides difficile infection, and antimicrobial resistance [101–106].”

What the sources say

• Partly supported

  The Discussion (page unavailable) identifies allergic reactions, renal toxicity, and C. difficile infection as harms of antibiotics; its conclusion also names antimicrobial resistance as an outcome stewardship may prevent. The paper does not mention thrombocytopenia, so it supports most, but not all, of the attributed list. (LLM, conf=0.88)

  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 sourceExperimental — accuracy not yet measured
• Not checked yetcites [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
• Partly supported

  The Introduction (page not provided) identifies resistance as a harm of excessive antimicrobial use, and the Methods list C. difficile infection among the outcomes tracked. The paper does not identify allergic or hypersensitivity reactions, kidney injury, or thrombocytopenia as harms of unnecessary antimicrobials. (LLM, conf=0.86)

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  The Association With Clinical Outcomes section (p. 5) reports that gentamicin exposure was associated with more renal-failure days, supporting kidney injury as a potential harm. The paper does not address allergic or hypersensitivity reactions, thrombocytopenia, or C. difficile infection; its resistance data (pp. 4–5) describe bacteria carried by patients, not resistance caused by unnecessary antimicrobial use. (LLM, conf=0.88)

  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 sourceExperimental — accuracy not yet measured
• Not checked yetcites [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
• Partly supported

  The Conclusions report that, among patients with severe sepsis or septic shock, each additional day of antipseudomonal β-lactam exposure was associated with increased risk of new resistance. The cited passages do not support the other listed harms—allergic or hypersensitivity reactions, kidney injury, thrombocytopenia, or Clostridioides difficile infection. Page numbers are not provided in our copy. (LLM, conf=0.88)

  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 sourceExperimental — accuracy not yet measured

In the paper

“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].”

What the sources say

• Partly supported

  The Prevalence and Characteristics of Infections section reports MRSA in 2% of patients with positive cultures in Western Europe and 10% in North America. These are proportions in a point-prevalence study, not incidence rates. The section associates patient characteristics with infection overall, but does not establish that MRSA specifically varies by those characteristics. (LLM, conf=0.88)

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (pp. 8–9) support regional variation in MRSA pneumonia prevalence and variation by patient risk factors. But the reported MRSA prevalence is 2.4% in Europe and 4.8% in North America, not about 2% in Western Europe and 10% in North America; the paper studies community-dwelling adults hospitalised with pneumonia, not MRSA incidence generally. (LLM, conf=0.90)

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (Patient Characteristics and Pathogen Epidemiology; page not provided) show that MRSA prevalence differed by patient condition: 14.0% among patients with septic shock versus 10.7% among those without it. The paper does not provide the claimed comparison of approximately 2% in Western Europe and 10% in North America; its reported measures are prevalence in a sepsis cohort, not regional incidence. (LLM, conf=0.86)

  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 sourceExperimental — accuracy not yet measured

In the paper

“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].”

What the sources say

• Supported

  Citation [254] is attached to support from knowledgeable clinician team members, not to the later claims about guidelines, monitoring, or software. The Background says pharmacokinetic knowledge is pivotal to optimizing bedside antibiotic dosing, and the Discussion identifies support from clinical pharmacists and microbiologists as a potential solution. (LLM, conf=0.91)

  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 yetcites [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 yetcites [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

In the paper

“smaller studies suggest that source control within 6–12 h is advantageous [265–271]. Studies generally show reduced survival beyond that point.”

What the sources say

• Supported

  The Results report that 60-day survival decreased as surgery was delayed and was 0% when surgery began more than 6 hours after admission. The Discussion recommends initiating surgical source control in less than 6 hours for patients with gastrointestinal perforation and septic shock, supporting the early-control point at the lower end of the cited 6–12-hour window. (LLM, conf=0.88)

  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
• Partly supported

  The Results (Time and adequacy to source control) report higher 28-day mortality when surgical source control was delayed beyond 6 hours, supporting the early-control part of the claim. The Discussion says the 12-hour window is a guideline recommendation and that evidence is insufficient to determine an optimal time point; this paper does not establish reduced survival specifically beyond 12 hours. (LLM, conf=0.85)

  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 sourceExperimental — accuracy not yet measured
• Not checked yetcites [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 yetcites [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
• Supported

  The Conclusions report that biliary decompression more than 12 hours after shock onset was associated with adverse hospital outcomes in patients with cholangitis-associated septic shock. They suggest that decompression within 12 hours could improve outcomes. The paper supports the cited point for this high-risk population, without establishing a separate 6-hour cutoff. (LLM, conf=0.90)

  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 yetcites [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 yetcites [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

In the paper

“In many of the trials, the shorter course was just as effective as the longer course but associated with fewer adverse consequences.”

What the sources say

• Not checked yetcites [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 yetcites [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
• Partly supported

  The Summary of the Evidence (pp. 39–40) reports that, in trials involving ventilator-associated pneumonia, shorter courses generally had similar clinical outcomes and reduced antibiotic exposure and recurrent pneumonia due to multidrug-resistant organisms. The Rationale (p. 40) says fewer side effects are an expected consequence of reduced exposure, not that many trials across different conditions found fewer adverse consequences. The claim extends the guideline’s VAP-specific evidence beyond what this source establishes. (LLM, conf=0.84)

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page not provided) says randomized trials show that most patients with community-acquired pneumonia can be treated for five days. The Results > Patient Outcomes (page not provided) associate each excess treatment day with higher odds of patient-reported adverse events, without improved measured outcomes. But this paper is an observational pneumonia study; it does not report that many shorter-versus-longer RCTs found both equal effectiveness and fewer adverse consequences. (LLM, conf=0.86)

  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 sourceExperimental — accuracy not yet measured
• Not checked yetcites [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 yetcites [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
• Partly supported

  The introduction (p. 1) says several RCTs found no significant difference between short and long antibiotic courses, and this trial found seven days noninferior to 14 days. But the Results (p. 1) report no significant difference in adverse events, and the discussion (p. 7) says fewer antibiotic days were not reflected in those outcomes. This source therefore does not support the claim that shorter courses in those trials were associated with fewer adverse consequences. (LLM, conf=0.88)

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion reports similar outcomes with a four-day course and fewer days of antibiotic exposure, but this paper reports one randomized trial, not many. The Results (Primary and Major Secondary Outcomes) found no significant difference in measured adverse outcomes, including C. difficile infection and infections with resistant pathogens; fewer adverse consequences were not demonstrated. (LLM, conf=0.88)

  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 sourceExperimental — accuracy not yet measured

In the paper

“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].”

What the sources say

• Supported

  The Abstract describes a retrospective before-after study comparing patients treated with intravenous vitamin C, hydrocortisone, and thiamine with an earlier control group in the same ICU. It reports lower hospital mortality (8.5% versus 40.4%) and shorter vasopressor use in the treatment group; the Results likewise report vasopressor weaning after a mean of 18.3 hours versus 54.9 hours of use in controls. The manuscript (p. 5) specifies a vitamin C dose of 6 g per day. (LLM, conf=0.93)

  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

In the paper

“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].”

What the sources say

• Not checked yetcites [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
• Partly supported

  The Background describes patients as vulnerable after ICU discharge, and the Results (Retrospective study population; page unavailable) report readmissions and ward deaths soon after transfer. The paper does not address hospital discharge or establish a high frequency of medication errors or information loss at either transition; searches for those terms and medication reconciliation found no supporting passage. (LLM, conf=0.86)

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  The paper’s “What Is Known and Objective” section (p. 1) says patients are vulnerable at hospital discharge and that poor information communication at care transitions can lead to medication errors. Its results also report discharge medication errors (p. 6). Our copy does not establish the same claim specifically for transfer from ICU to a general floor. (LLM, conf=0.88)

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  The Discussion (page not available) identifies ICU discharge and hospital discharge as points for reviewing medication appropriateness, and the Introduction reports frequent inappropriate medications at hospital discharge among elderly ICU survivors. The paper does not report a high frequency of medication errors at both transitions or address information loss. (LLM, conf=0.85)

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (p. 1) identifies ICU-to-ward transfers as occasions for errors and communication failures, and the Background (p. 1) describes medication-related vulnerability at discharge. The paper does not establish a high frequency of medication errors and information loss at both transitions; its measured post-discharge outcome is continuation of selected medications without a documented indication. (LLM, conf=0.84)

  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 sourceExperimental — accuracy not yet measured
• Not checked yetcites [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
• Partly supported

  The Discussion describes hospital discharge as a transition with high risk of medication errors and reports frequent medication discrepancies. The Background discusses antipsychotics being continued upon transfer out of the ICU, but does not establish a high frequency of medication errors at that transfer. Neither passage addresses information loss at either transition. (LLM, conf=0.88)

  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 sourceExperimental — accuracy not yet measured

In the paper

“Hospital readmission within 90 days of discharge occurs in approximately 40% of sepsis survivors and is associated with high costs [624].”

What the sources say

• Partly supported

  The Results report high costs for unplanned readmissions following sepsis hospitalization: an estimated mean of $10,070 per readmission. The Methods specify a 30-day follow-up, and the Results do not report that approximately 40% of sepsis survivors were readmitted within 90 days. The reported 12.2% is the share of readmitted medical admissions that had a sepsis diagnosis, not a readmission rate among sepsis survivors. (LLM, conf=0.90)

  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 sourceExperimental — accuracy not yet measured

In the paper

“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).”

What the sources say

• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  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 sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  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 sourceExperimental — accuracy not yet measured
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  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 yetcites [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 yetcites [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

In the paper

“In addition, sepsis survivors are at increased risk for recurrent infection, AKI and new cardiovascular events compared to patients hospitalised for other diagnoses [580].”

What the sources say

• Supported

  The Abstract (Observations) explicitly compares sepsis survivors with patients hospitalized for other diagnoses and reports increased recurrent infection, acute renal failure, and new cardiovascular events. The Clinical Sequelae sections provide supporting comparisons with matched patients or hospitalized controls; acute renal failure corresponds to AKI in the claim. (LLM, conf=0.95)

  cites [580] Prescott HC, Angus DC (2018) Enhancing recovery from sepsis: a review. JAMA 319(1):62–75 source

In the paper

“Sepsis survivors are at risk for hospital readmission, which has been associated with increased mortality or discharge to hospice [622, 623].”

What the sources say

• Not checked yetcites [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
• Supported

  The Discussion reports that 23% of at-risk septic shock survivors were readmitted within 30 days, and nearly one in six readmissions resulted in death or a transition to hospice. This supports the cited statement about readmission risk and serious outcomes, though the study specifically examined septic shock survivors. (LLM, conf=0.90)

  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

In the paper

“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.”

In the paper

“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).”

In the paper

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

In the paper

“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.”

In the paper

“Included studies are generally small and include mostly post-operative, non-critically ill patients.”

In the paper

“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).”

In the paper

“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).”

In the paper

“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.”

In the paper

“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).”

In the paper

“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.”

In the paper

“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).”

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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.”

In the paper

“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”

In the paper

“The IDEAL-ICU trial [507] did not report central venous access device (CVAD) infections: the results for this outcome are unchanged from 2016.”

What the sources say

• Not checked yetcites [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

In the paper

“Our updated literature search identified no new RCTs but two meta-analysis comparing continuous and intermittent renal replacement therapies [503, 504].”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

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

In the paper

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

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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
• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

“Studies have evaluated palliative care interventions in the ICU but not specifically in patients with sepsis [543, 545–548].”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

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

What the sources say

• Not checked yetcites [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

In the paper

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

What the sources say

• Not checked yetcites [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

In the paper

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

In the paper

“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.”

In the paper

“ICU education did not appear to impact patients’ anxiety and depression [584, 586, 588], but did improve families’ satisfaction with care [583].”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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
• Not checked yetcites [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

In the paper

“Almost 40% of sepsis survivors are re-hospitalised within 3 months, often for preventable conditions [580], contributing to increased healthcare costs [581].”

What the sources say

• Not checked yetcites [580] Prescott HC, Angus DC (2018) Enhancing recovery from sepsis: a review. JAMA 319(1):62–75 source
• Not checked yetcites [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

In the paper

“Four observational studies examined the impact of peer support groups on ICU patients, though they were not specific to sepsis patients.”

What the sources say

• Not checked yetcites [554] Halm MA (1990) Effects of support groups on anxiety of family members during critical illness. Heart Lung 19(1):62–71
• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [592] Bokinskie JC (1992) Family conferences: a method to diminish transfer anxiety. J Neurosci Nurs 24(3):129–133 source

In the paper

“Family caregivers of critically ill patients discharged home felt overwhelmed and unprepared and had difficulty managing expectations [593].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“Medication reconciliation has been associated with fewer medication errors [598, 612] and may help reduce hospital readmission [613, 614].”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

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

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

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

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

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

In the paper

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

What the sources say

• Not checked yetcites [580] Prescott HC, Angus DC (2018) Enhancing recovery from sepsis: a review. JAMA 319(1):62–75 source

In the paper

“More studies of post-sepsis follow-up programmes are in process [641, 642].”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

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

In the paper

“These programmes vary in their structure, and are not consistently available worldwide [637].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

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

In the paper

“This suggestion is consistent with the guidance of several expert panels [646, 652, 653].”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [29] Bhattacharjee P, Edelson DP, Churpek MM (2017) Identifying patients with sepsis on the hospital wards. Chest 151(4):898–907 source
• Not checked yetcites [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 yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [43] Cinel I, Kasapoglu US, Gul F et al (2020) The initial resuscitation of septic shock. J Crit Care 57:108–117 source

In the paper

“Serum lactate is an important biomarker of tissue hypoxia and dysfunction, but is not a direct measure of tissue perfusion [73].”

What the sources say

• Not checked yetcites [73] Levy B (2006) Lactate and shock state: the metabolic view. Curr Opin Crit Care 12(4):315–321 source

In the paper

“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”

What the sources say

• Not checked yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“Sensitivities range from 66 to 83%, with specificities ranging from 80 to 85%.”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“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).”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“Studies showed an association between the use of point-of-care lactate measurements at presentation and reduced mortality; however, the results are inconsistent [53].”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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].”

What the sources say

• Not checked yetcites [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

In the paper

“Neither SIRS nor qSOFA are ideal screening tools for sepsis and the bedside clinician needs to understand the limitations of each.”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [43] Cinel I, Kasapoglu US, Gul F et al (2020) The initial resuscitation of septic shock. J Crit Care 57:108–117 source

In the paper

“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.”

What the sources say

• Not checked yetcites [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