The Impact of Genetic Variation on Sensitivity
to Opioid Analgesics in Patients with
Postoperative Pain: A Systematic Review and
Meta-Analysis

Background: Individual response to opioid analgesics varies among patients. Objective: This study sought to clarify the impact of distinct genetic variations on pain, opioid consumption, and opioid side effects in patients with postoperative pain. Study Design: A systematic review and meta-analysis of associations between genetic singlenucleotide polymorphisms (SNPs) and opioids used for acute postoperative pain. Setting: This meta-analysis examined all studies involving an association between genetic polymorphisms and the analgesic efficacy or clinical outcome of opioid analgesics for postoperative pain. Methods: A literature search was performed up to January 31, 2014, using the PubMed, EMBase, ISI Web of Science, and Cochrane Library databases. Results: Fifty-nine studies were included in this systematic review, and 23 studies (a total of 5,902 patients) were included in the final meta-analysis. The results showed that human μ-opioid receptor gene (OPRM1) 118G allele variant carriers consumed more opioids for analgesia (SMD = -0.17, 95% CI = [-0.25, -0.10], P < 0.00001), but reported higher pain scores (MD = -0.11, 95% CI = [-0.17, -0.04], P = 0.002) and less nausea and vomiting (odds ratio = 1.30, 95% CI = [1.08, 1.55], P = 0.005) than the homozygous 118AA patients during the first 24 hour but not the 48 hour postoperative period. Moreover, CYP3A4*1G carriers consumed less opioids than homozygous CYP3A4*1/*1 patients during the first 24 hours postoperative period (MD = 45.12, 95% CI = [36.17, 54.06], P < 0.00001). No significant differences were found in CYP3A5*3, ABCB1 C3435T, and G2477T/A genetic polymorphisms. Limitations: Some potential non-genetic factors can modify the effects of gene SNP on pain and opioid consumption during the postoperative period, such as age, gender, mood, anxiety, and drug-drug interactions. But further analyses could not be performed in the present meta-analysis due to limited information. Conclusion: The results indicate that among the genetic SNPs we studied which include those affecting analgesic drug metabolism, transport of analgesic agents across the blood-brain barrier, and their activity at target receptors and ion channels and in the modulation of neurotransmitter pathways, the A118G allele variant of OPRM1 has the most potent influence on pain management of postoperative patients. Opioid receptor gene information may provide valuable information for clinicians to properly manage the analgesic use of opioids individually for better pain management. Key words: Postoperative pain, meta-analysis, single-nucleotide polymorphism, opioid

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Misuse of medication in adult substance misuse services: a systematic review protocol

BMJ Open ◽

10.1136/bmjopen-2020-047283 ◽

2021 ◽

Vol 11 (6) ◽

pp. e047283

Author(s):

Rosalind Gittins ◽

Louise Missen ◽

Ian Maidment

Keyword(s):

Systematic Review ◽

Substance Misuse ◽

Data Extraction ◽

Meta Analysis ◽

Grey Literature ◽

Opioid Analgesics ◽

Physical And Mental Health ◽

Qualitative Synthesis ◽

Treatment Services ◽

The Impact

IntroductionThere is a growing concern about the misuse of over the counter (OTC) and prescription only medication (POM) because of the impact on physical and mental health, drug interactions, overdoses and drug-related deaths. These medicines include opioid analgesics, anxiolytics such as pregabalin and diazepam and antidepressants. This protocol outlines how a systematic review will be undertaken (during June 2021), which aims to examine the literature on the pattern of OTC and POM misuse among adults who are accessing substance misuse treatment services. It will include the types of medication being taken, prevalence and demographic characteristics of people who access treatment services.Methods and analysisAn electronic search will be conducted on the Cochrane, OVID Medline, Pubmed, Scopus and Web of Science databases as well as grey literature. Two independent reviewers will conduct the initial title and abstract screenings, using predetermined criteria for inclusion and exclusion. If selected for inclusion, full-text data extraction will be conducted using a pilot-tested data extraction form. A third reviewer will resolve disagreements if consensus cannot be reached. Quality and risk of bias assessment will be conducted for all included studies. A qualitative synthesis and summary of the data will be provided. If possible, a meta-analysis with heterogeneity calculation will be conducted; otherwise, Synthesis Without Meta-analysis will be undertaken for quantitative data. The reporting of this protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Ethics and disseminationEthical approval is not required. Findings will be peer reviewed, published and shared verbally, electronically and in print, with interested clinicians and policymakers.PROSPERO registration numberCRD42020135216.

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Efficacy of tramadol for postoperative pain management in dogs: systematic review and meta-analysis

Veterinary Anaesthesia and Analgesia ◽

10.1016/j.vaa.2021.01.003 ◽

2021 ◽

Author(s):

Pablo A. Donati ◽

Lisa Tarragona ◽

Juan V.A. Franco ◽

Veronica Kreil ◽

Rodrigo Fravega ◽

...

Keyword(s):

Systematic Review ◽

Pain Management ◽

Postoperative Pain ◽

Meta Analysis ◽

Postoperative Pain Management

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Postoperative pain management after esophagectomy: a systematic review and meta-analysis

Diseases of the Esophagus ◽

10.1093/dote/dox052 ◽

2017 ◽

Vol 30 (10) ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

E. Visser ◽

M. Marsman ◽

P. S. N. van Rossum ◽

E. Cheong ◽

K. Al-Naimi ◽

...

Keyword(s):

Systematic Review ◽

Pain Management ◽

Postoperative Pain ◽

Meta Analysis ◽

Postoperative Pain Management

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State-level and system-level opioid prescribing policies: The impact on provider practices and overdose deaths, a systematic review

Journal of Opioid Management ◽

10.5055/jom.2016.0322 ◽

2016 ◽

Vol 12 (2) ◽

pp. 109 ◽

Cited By ~ 20

Author(s):

Francesca L. Beaudoin, MD, MS ◽

Geetanjoli N. Banerjee, MPH ◽

Michael J. Mello, MD, MPH

Keyword(s):

Systematic Review ◽

Systematic Reviews ◽

Meta Analysis ◽

State Level ◽

Opioid Analgesics ◽

System Level ◽

Prescribing Practices ◽

Opioid Prescribing ◽

Patient Level ◽

The Impact

Objective: In response to persistent public health concerns regarding prescription opioids, many states and healthcare systems have implemented legislation and policies intended to regulate or guide opioid prescribing. The overall impact of these policies is still uncertain. The aim of this systematic review was to examine the existing evidence of provider-level and patient-level outcomes preimplementation and postimplementation of policies and legislation constructed to impact provider prescribing practices around opioid analgesics. Design: A systematic search of MEDLINE, EMBASE, the Web of Science, and the Cochrane Database of Systematic Reviews was conducted to identify studies evaluating the impact of opioid prescribing policies on provider-level and patient-level outcomes. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Results: Eleven studies were included in the review. A meta-analysis was not possible due to between-study heterogeneity. Six of the studies assessed state-level policies, and five were at the level of the healthcare system or hospital. Studies showed temporal associations between policy implementation and reductions in opioid prescribing, as well as opioid-related overdoses. Results were mixed regarding the impact of policies on misuse. The majority of the studies were judged to be of low quality based on the GRADE criteria.Conclusions: There is low to moderate quality evidence suggesting that the presence of opioid prescribing policy will reduce the amount and strength of opioid prescribed. The presence of these policies may impact the number of overdoses, but there is no clear evidence to suggest that it reduces opioid misuse.

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