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Genetic risk signatures of opioid-induced respiratory depression following pediatric tonsillectomy.

ABSTRACT: Background: Respiratory depression is a clinically and economically important but preventable complication of opioids. Genetic factors can help identify patients with high risk for respiratory depression. Methods: In this prospective genotype blinded clinical study, we evaluated the effect of a panel of variants in candidate genes on opioid-related respiratory depression in 347 children following tonsillectomy. Results: Using unsupervised hierarchical clustering and a combination of candidate genotypes and clinical variables, we identified several distinct clusters of patients at high risk (36-38%) and low risk (10-17%) of respiratory depression; the relative risk of respiratory depression for high versus low risk clusters was 2.1-3.8 (p = 0.003). Conclusion: Genetic risk predictions (genetic signatures) along with clinical risk factors effectively identify children at higher and lower risks of opioid-induced respiratory depression. Genetic signatures of respiratory depression offer strategies for improved clinical decision support to guide clinicians to balance the risks of opioid adverse effects with analgesia. Original submitted 9 July 2014; Revision submitted 19 September 2014.

SUBMITTER: Biesiada J

PROVIDER: S-EPMC4287371 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Genetic risk signatures of opioid-induced respiratory depression following pediatric tonsillectomy.

Biesiada Jacek J Chidambaran Vidya V Wagner Michael M Zhang Xue X Martin Lisa J LJ Meller Jaroslaw J Sadhasivam Senthilkumar S

Pharmacogenomics 20141101 14

Background: Respiratory depression is a clinically and economically important but preventable complication of opioids. Genetic factors can help identify patients with high risk for respiratory depression. Methods: In this prospective genotype blinded clinical study, we evaluated the effect of a panel of variants in candidate genes on opioid-related respiratory depression in 347 children following tonsillectomy. Results: Using unsupervised hierarchical clustering and a combination of candidate ge ...[more]

PMID: 25493568

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Project description: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.

Dataset Information

Genetic risk signatures of opioid-induced respiratory depression following pediatric tonsillectomy.

Publications

Genetic risk signatures of opioid-induced respiratory depression following pediatric tonsillectomy.

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