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Meta-Analysis
. 2018 Dec 14;8(12):e024086.
doi: 10.1136/bmjopen-2018-024086.

Risk factors for opioid-induced respiratory depression in surgical patients: a systematic review and meta-analyses

Kapil Gupta  1 , Mahesh Nagappa  2 , Arun Prasad  3 , Lusine Abrahamyan  4 , Jean Wong  3 , Toby N Weingarten  5 , Frances Chung  3
Affiliations
Meta-Analysis

Risk factors for opioid-induced respiratory depression in surgical patients: a systematic review and meta-analyses

Kapil Gupta et al. BMJ Open. .

Abstract

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 Clinicaltrials.gov (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.

Keywords: anaesthesia; opioids; postoperative complications; respiratory depression; risk factors; surgery.

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Conflict of interest statement

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).

Figures

Figure 1
Figure 1
Flow diagram of search strategy used for systematic review and meta-analysis.
Figure 2
Figure 2
Meta-analysis evaluating the risk factors for respiratory events between OIRD and control groups in patients undergoing surgery. The pooled OR for each risk factor is plotted along with the 95% CI summarises the effect size using the inverse variance random effects model. Age and BMI represented as mean±SD. ASA, American Society of Anesthesiologists; BMI, body mass index; I2, heterogeneity; OIRD, opioid-induced respiratory depression; OSA, obstructive sleep apnoea.
Figure 3
Figure 3
Meta-analysis evaluating the risk factors for respiratory events between OIRD and control groups in patients undergoing surgery. The pooled OR for each risk factor is plotted along with the 95% CI summarises the effect size using the inverse variance random effects model. I2, heterogeneity; LOS, length of hospital stay represented as mean±SD; MEDD, morphine equivalent daily dose; OIRD, opioid-induced respiratory depression; PCA, patient-controlled analgesia.
See this image and copyright information in PMC

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