The effect of vasoactive drugs on mortality in patients with severe sepsis and septic shock. A network meta-analysis of randomized trials
Open accessAbstract
Purpose Inotropes and vasopressors are cornerstone of therapy in septic shock, but search for the best agent is ongoing. We aimed to determine which vasoactive drug is associated with the best survival.Materials and methods PubMed, BioMedCentral, Embase, and the Cochrane Central Register were searched. Randomized trials performed in septic patients with at least 1 group allocated to an inotrope/vasopressor were included. Network meta-analysis with a frequentist approach was performed.Results The 33 included studies randomized 3470 patients to 16 different comparators. As compared with placebo, levosimendan (odds ratio [OR], 0.17, 95%; confidence interval [CI], 0.05-0.60), dobutamine (OR, 0.30; 95% CI, 0.09-0.99), epinephrine (OR, 0.35; 95% CI, 0.13-0.96), vasopressin (OR, 0.37; 95% CI, 0.16-0.89), and norepinephrine plus dobutamine (OR, 0.4; 95% CI, 0.11-0.96) were significantly associated with survival. Norepinephrine improved survival compared with dopamine (OR, 0.81; 95% CI, 0.66-1.00). Rank analysis showed that levosimendan had the highest probability of being the best treatment.Conclusions Among several regimens for pharmacological cardiovascular support in septic patients, regimens based on inodilators have the highest probability of improve survival.
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There are data from RCTs on short versus long courses in specific conditions such as pneumonia, urinary tract infections, bacteremia, and intraabdominal infections.
“There are data from RCTs in specific conditions such as pneumonia (286-289), urinary tract infections (290), bacteremia (291, 292), and intraabdominal infections (293).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [287]
The Study Selection section describes RCTs comparing vasopressors or inotropes in patients with sepsis. Searches for short versus long treatment courses and antibiotic duration in pneumonia, urinary tract infections, bacteremia, and intraabdominal infections found no passage addressing those comparisons. The paper’s discussion of RCTs therefore does not verify the attributed claim. (LLM, conf=0.78)
Experimental — accuracy not yet measuredA network meta-analysis found no significant difference between epinephrine and vasopressin in mortality.
“In an indirect comparison, a network meta-analysis did not find any significant difference between epinephrine and vasopressin in terms of mortality (RR 0.94; 95% CI 0.47–1.88) [362].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [362]
A network meta-analysis found dobutamine with norepinephrine had no clear impact on mortality compared with no inotropic agents.
“Indirect comparison from network meta-analysis showed that dobutamine with norepinephrine had no clear impact on mortality when compared to no inotropic agents (OR 0.69; 95% CI 0.32–1.47) [362].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [362]
A network meta-analysis found no clear effect on mortality for dobutamine compared with epinephrine.
“In an indirect comparison of dobutamine versus epinephrine, a network meta-analysis showed no clear effect on mortality (OR 1.18; 95% CI 0.47–3.97) [362].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [362]
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Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021.
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Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021
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Surviving Sepsis campaign: international guidelines for Management of Sepsis and Septic Shock 2026
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- Authors
- Belletti, A., Benedetto, U., Biondi-Zoccai, G., Leggieri, C., Silvani, P., Angelini, G. D., Zangrillo, A., & Landoni, G.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- University of Bristol (GB)
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Landoni, Giovanni
- ORCID
- Venue
- Journal of Critical Care
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 37
- Pages
- 91-98
- ISSN
- 0883-9441 (ISSN-L)
- OpenAlex
- W2518614997
- Cited by
- 88
- References
- 96
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 9 · 2023: 13 · 2022: 9 · 2021: 13 · 2020: 8 · 2019: 5 · 2018: 10 · 2017: 2 · 2016: 3
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- Journal of Critical Care (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion, cc-by-nc-nd)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion, cc-by-nc-nd)
- Funders
- British Heart Foundation
- National Institute of Health Research Bristol Cardiovascular Biomedical Research Unit
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Hemodynamic Monitoring and Therapy
- Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
- Keywords
- septic shock, severe sepsis, vasoactive drugs, inotropic agents, vasopressors, levosimendan, dobutamine, epinephrine, vasopressin, norepinephrine, dopamine, inodilators, survival, mortality
- MeSH terms
- Simendan, Arginine Vasopressin, Cardiotonic Agents, Dobutamine, Dopamine, Epinephrine, Humans, Hydrazones, Norepinephrine, Pyridazines, Shock, Septic, Vasoconstrictor Agents, Vasopressins, Odds Ratio, Randomized Controlled Trials as Topic, Treatment Outcome, 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.
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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