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

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; I(2): 0%; p<0.002), pulmonary disease (OIRD vs control: 17.8% vs 10.3%; OR: 2.2; 95% CI: 1.3 to 3.6; I(2): 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; I(2): 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; I(2): 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.