Pharmacological agents for procedural sedation and analgesia in the emergency department and intensive care unit: a systematic review and network meta-analysis of randomised trials

Sameer Sharif; Jasmine Kang; Behnam Sadeghirad; Fayyaz Rizvi; Ben Forestell; Alisha Greer; Mark Hewitt; Shannon M Fernando; Sangeeta Mehta; Mohamed Eltorki; Reed Siemieniuk; Mark Duffett; Maala Bhatt; Lisa Burry; Jeffrey J Perry; Andrew Petrosoniak; Pratik Pandharipande; Michelle Welsford; Bram Rochwerg

doi:10.1016/j.bja.2023.11.050

Pharmacological agents for procedural sedation and analgesia in the emergency department and intensive care unit: a systematic review and network meta-analysis of randomised trials

Br J Anaesth. 2024 Mar;132(3):491-506. doi: 10.1016/j.bja.2023.11.050. Epub 2024 Jan 6.

Authors

Sameer Sharif¹, Jasmine Kang², Behnam Sadeghirad³, Fayyaz Rizvi², Ben Forestell⁴, Alisha Greer⁵, Mark Hewitt⁵, Shannon M Fernando⁶, Sangeeta Mehta⁷, Mohamed Eltorki⁸, Reed Siemieniuk⁹, Mark Duffett¹⁰, Maala Bhatt¹¹, Lisa Burry¹², Jeffrey J Perry¹³, Andrew Petrosoniak¹⁴, Pratik Pandharipande¹⁵, Michelle Welsford⁴, Bram Rochwerg¹⁶

Affiliations

¹ Department of Medicine, Division of Emergency Medicine, McMaster University, Hamilton, ON, Canada; Department of Medicine, Division of Critical Care, McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. Electronic address: sameer.sharif@medportal.ca.
² Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
³ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; Department of Anesthesia, McMaster University, Hamilton, ON, Canada.
⁴ Department of Medicine, Division of Emergency Medicine, McMaster University, Hamilton, ON, Canada.
⁵ Department of Medicine, Division of Emergency Medicine, McMaster University, Hamilton, ON, Canada; Department of Medicine, Division of Critical Care, McMaster University, Hamilton, ON, Canada.
⁶ Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada; Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
⁷ Department of Medicine, Sinai Health System; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.
⁸ Department of Pediatrics, Division of Pediatric Emergency Medicine, McMaster University, Ottawa, ON, Canada.
⁹ Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
¹⁰ Department of Pediatrics, McMaster University, Hamilton, ON, Canada.
¹¹ Department of Medicine, Sinai Health System, Interdepartmental Division of Critical Care Medicine, Toronto, ON, Canada.
¹² Department of Medicine, Sinai Health System; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Pharmacy, Sinai Health System, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
¹³ Department of Emergency Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁴ Department of Medicine, Division of Emergency Medicine, University of Toronto, Toronto, ON, Canada.
¹⁵ Department of Anesthesiology, Division of Critical Care, Vanderbilt University School of Medicine, Nashville, TN, USA.
¹⁶ Department of Medicine, Division of Critical Care, McMaster University, Hamilton, ON, Canada; Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.

PMID: 38185564
DOI: 10.1016/j.bja.2023.11.050

Abstract

Background: We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications.

Methods: We searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates.

Results: We included 82 RCTs (8105 patients, 78 conducted in the ED and four in the ICU) of which 52 studies included adults, 23 included children, and seven included both. Compared with midazolam-opioids, recovery time was shorter with propofol (mean difference 16.3 min, 95% confidence interval [CI] 8.4-24.3 fewer minutes; high certainty), and patient satisfaction was better with ketamine-propofol (mean difference 1.5 points, 95% CI 0.3-2.6 points, high certainty). Regarding AEs, compared with midazolam-opioids, respiratory AEs were less frequent with ketamine (relative risk [RR] 0.55, 95% CI 0.32-0.96; high certainty), gastrointestinal AEs were more common with ketamine-midazolam (RR 3.08, 95% CI 1.15-8.27; high certainty), and neurological AEs were more common with ketamine-propofol (RR 3.68, 95% CI 1.08-12.53; high certainty).

Conclusion: When considering procedural sedation and analgesia in the ED and ICU, compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory adverse events are less common with ketamine.

Keywords: analgesia; critical care; emergency; network meta-analysis; procedural sedation; systematic review.

Publication types

Meta-Analysis
Systematic Review
Review

MeSH terms

Analgesia* / methods
Analgesics / therapeutic use
Conscious Sedation / methods
Emergency Service, Hospital*
Humans
Hypnotics and Sedatives* / therapeutic use
Intensive Care Units*
Network Meta-Analysis*
Patient Satisfaction
Randomized Controlled Trials as Topic*

Substances

Hypnotics and Sedatives
Analgesics