Article Text

Download PDFPDF

Risk factors for opioid-induced respiratory depression in surgical patients: a systematic review and meta-analyses
  1. Kapil Gupta1,
  2. Mahesh Nagappa2,
  3. Arun Prasad3,
  4. Lusine Abrahamyan4,
  5. Jean Wong3,
  6. Toby N Weingarten5,
  7. Frances Chung3
  1. 1 Department of Anesthesia and Pain Management, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
  2. 2 Department of Anesthesia and Perioperative Medicine, London Health Sciences Centre and St. Joseph Health Care, Western University, London, Ontario, Canada
  3. 3 Department of Anesthesia and Pain Management, University Health Network, University of Toronto, Toronto, Ontario, Canada
  4. 4 Institute of Health Policy, Management and Evaluation, University of Toronto THETA Collaborative, Toronto General Research Institute, Toronto, Ontario, Canada
  5. 5 Department of Anesthesia and Perioperative Medicine, Mayo Clinic Rochester, Rochester, Minnesota, USA
  1. Correspondence to Dr Frances Chung; Frances.Chung{at}


Objective This systematic review and meta-analysis aim to evaluate the risk factors associated with postoperative opioid-induced respiratory depression (OIRD).

Design Systematic review and meta-analysis.

Data sources PubMed-MEDLINE, MEDLINE in-process, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed and (January 1946 to November 2017).

Eligibility criteria The inclusion criteria were: (1) adult patients 18 years or older who were administered opioids after surgery and developed postoperative OIRD (OIRD group); (2) all studies which reported both OIRD events and associated risk factors; (3) all studies with reported data for each risk factor on patients with no OIRD (control group) and (4) published articles in English language.

Data analysis We used a random effects inverse variance analysis to evaluate the existing evidence of risk factors associated with OIRD. Newcastle-Ottawa scale scoring system was used to assess quality of study.

Results Twelve observational studies were included from 8690 citations. The incidence of postoperative OIRD was 5.0 cases per 1000 anaesthetics administered (95% CI: 4.8 to 5.1; total patients: 841 424; OIRD: 4194). Eighty-five per cent of OIRD occurred within the first 24 hours postoperatively. Increased risk for OIRD was associated with pre-existing cardiac disease (OIRD vs control: 42.8% vs 29.6%; OR: 1.7; 95% CI: 1.2 to 2.5; I2: 0%; p<0.002), pulmonary disease (OIRD vs control: 17.8% vs 10.3%; OR: 2.2; 95% CI: 1.3 to 3.6; I2: 0%; p<0.001) and obstructive sleep apnoea (OIRD vs control: 17.9% vs 16.5%; OR: 1.4; 95% CI: 1.2 to 1.7; I2: 31%; p=0.0003). The morphine equivalent daily dose of the postoperative opioids was higher in the OIRD group than in the control; (24.7±14 mg vs 18.9±13.0 mg; mean difference: 2.8; 95% CI: 0.4 to 5.3; I2: 98%; p=0.02). There was no significant association between OIRD and age, gender, body mass index or American Society of Anesthesiologists physical status.

Conclusion Patients with cardiac, respiratory disease and/or obstructive sleep apnoea were at increased risk for OIRD. Patients with postoperative OIRD received higher doses of morphine equivalent daily dose.

  • opioids
  • respiratory depression
  • risk factors
  • postoperative complications
  • anaesthesia
  • surgery

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

View Full Text

Statistics from


  • KG and MN shared first authorship

  • Contributors KG, MN, FC: designed the study, conducted the study, analysed the data and wrote the manuscript. AP: helped to design the study and wrote the manuscript. LA, TNW: helped with interpretation of data and manuscript writing. JW: helped with manuscript writing.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests JW reports grants from the Ontario Ministry of Health and Long-Term Care, Anesthesia Patient Safety Foundation and Acacia Pharma outside of the submitted work. FC reports research support from the Ontario Ministry of Health and Long-Term Care, University Health Network Foundation, Acacia Pharma, Medtronic grants to institution outside of the submitted work, up-to-date royalties, STOP-Bang proprietary to University Health Network. TNW currently serves as a consultant to Medtronic in the role as chairman of the Clinical Endpoint Committee for the Prodigy Trial; has received unrestricted investigator-initiated grants from Merck (active) and Baxter (completed), and research support from Respiratory Motion (study equipment) and research support from Respiratory Motion (study equipment).

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data available.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.