Risks and benefits of oral modified-release compared with oral immediate-release opioid use after surgery: a systematic review and meta-analysis.

Prescription of modified-release opioids for acute postoperative pain is widespread despite evidence to show their use may be associated with an increased risk of adverse effects. This systematic review and meta-analysis aimed to examine the available evidence on the safety and efficacy of modified-release, compared with immediate-release, oral opioids for postoperative pain in adults. We searched five electronic databases from 1 January 2003 to 1 January 2023. Published randomised clinical trials and observational studies on adults who underwent surgery which compared those who received oral modified-release opioids postoperatively with those receiving oral immediate-release opioids were included. Two reviewers independently extracted data on the primary outcomes of safety (incidence of adverse events) and efficacy (pain intensity, analgesic and opioid use, and physical function) and secondary outcomes (length of hospital stay, hospital readmission, psychological function, costs, and quality of life) up to 12 months postoperatively. Of the eight articles included, five were randomised clinical trials and three were observational studies. The overall quality of evidence was low. Modified-release opioid use was associated with a higher incidence of adverse events (n = 645, odds ratio (95%CI) 2.76 (1.52-5.04)) and worse pain (n = 550, standardised mean difference (95%CI) 0.2 (0.04-0.37)) compared with immediate-release opioid use following surgery. Our narrative synthesis concluded that modified-release opioids showed no superiority over immediate-release opioids for analgesic consumption, length of hospital stay, hospital readmissions or physical function after surgery. One study showed that modified-release opioid use is associated with higher rates of persistent postoperative opioid use compared with immediate-release opioid use. None of the included studies reported on psychological function, costs or quality of life.

Predictors of persistent postoperative opioid use following colectomy: a population-based cohort study from England.

This retrospective cohort study on adults undergoing colectomy from 2010 to 2019 used linked primary (Clinical Practice Research Datalink), and secondary (Hospital Episode Statistics) care data to determine the prevalence of persistent postoperative opioid use following colectomy, stratified by pre-admission opioid exposure, and identify associated predictors. Based on pre-admission opioid exposure, patients were categorised as opioid-naïve, currently exposed (opioid prescription 0-6 months before admission) and previously exposed (opioid prescription within 7-12 months before admission). Persistent postoperative opioid use was defined as requiring an opioid prescription within 90 days of discharge, along with one or more opioid prescriptions 91-180 days after hospital discharge. Multivariable logistic regression analyses were conducted to obtain odds ratios for predictors of persistent postoperative opioid use. Among the 93,262 patients, 15,081 (16.2%) were issued at least one opioid prescription within 90 days of discharge. Of these, 6791 (45.0%) were opioid-naïve, 7528 (49.9%) were currently exposed and 762 (5.0%) were previously exposed. From the whole cohort, 7540 (8.1%) developed persistent postoperative opioid use. Patients with pre-operative opioid exposure had the highest persistent use: 5317 (40.4%) from the currently exposed group; 305 (9.8%) from the previously exposed group; and 1918 (2.5%) from the opioid-naïve group. The odds of developing persistent opioid use were higher among individuals who used long-acting opioid formulations in the 180 days before colectomy than those who used short-acting formulations (odds ratio 3.41 (95%CI 3.07-3.77)). Predictors of persistent opioid use included: previous opioid exposure; high deprivation index; multiple comorbidities; use of long-acting opioids; white race; and open surgery. Minimally invasive surgical approaches were associated with lower odds of persistent opioid use and may represent a modifiable risk factor.

Opioid prescription at postoperative discharge: a retrospective observational cohort study.

Opioid misuse is now considered a major public health epidemic in North America, with substantial social and financial consequences. As well as socio-economic and commercial drivers, modifiable risk-factors that have resulted in this crisis have been identified. The purpose of this study was to identify whether, within England, modifiable drivers for persistent postoperative opioid use were present. This was a retrospective cohort study of practice at 14 National Health Service hospitals across England. Data were collected retrospectively and validated for adult patients undergoing elective intermediate and major or complex major general surgical procedures between 1 and 31 March 2019. Of the 509 patients enrolled from 14 centres, 499 were included in the data analysis. In total, 31.5% (157/499) patients were in the intermediate surgery cohort and 68.5% (342/499) were in the major or complex major surgery cohort, with 21.0% (33/157) and 21.6% (74/342) discharged with opioid medicines to be taken at regular intervals, respectively. There were similar median oral morphine equivalent doses prescribed at discharge. Of patients prescribed regular opioid medicines, 76.6% (82/107) had a specified duration at discharge. However, 72.9% (78/107) had no written deprescribing advice on discharge. Similarly, of patients prescribed 'when required' opioids, 59.6% (93/156) had a specified duration of their prescription and 33.3% (52/156) were given written deprescribing advice. This study has identified a pattern of poor prescribing practices, a lack of guidance and formal training at individual institutions and highlights opportunities for improvement in opioid-prescribing practices within England.

An international multidisciplinary consensus statement on the prevention of opioid-related harm in adult surgical patients.

This international multidisciplinary consensus statement was developed to provide balanced guidance on the safe peri-operative use of opioids in adults. An international panel of healthcare professionals evaluated the literature relating to postoperative opioid-related harm, including persistent postoperative opioid use; opioid-induced ventilatory impairment; non-medical opioid use; opioid diversion and dependence; and driving under the influence of prescription opioids. Recommended strategies to reduce harm include pre-operative assessment of the risk of persistent postoperative opioid use; use of an assessment of patient function rather than unidimensional pain scores alone to guide adequacy of analgesia; avoidance of long-acting (modified-release and transdermal patches) opioid formulations and combination analgesics; limiting the number of tablets prescribed at discharge; providing deprescribing advice; avoidance of automatic prescription refills; safe disposal of unused medicines; reducing the risk of opioid diversion; and better education of healthcare professionals, patients and carers. This consensus statement provides a framework for better prescribing practices that could help reduce the risk of postoperative opioid-related harm in adults.

Changes in trends and pattern of strong opioid prescribing in primary care.

BACKGROUND: This study evaluated the prescribing trends of four commonly prescribed strong opioids in primary care and explored utilization in non-cancer and cancer users. METHODS: This cross-sectional study was conducted from 2000 to 2010 using the UK Clinical Practice Research Datalink. Prescriptions of buprenorphine, fentanyl, morphine and oxycodone issued to adult patients were included in this study. Opioid prescriptions issued after patients had cancer medical codes were defined as cancer-related use; otherwise, they were considered non-cancer use. Annual number of prescriptions and patients, defined daily dose (DDD/1000 inhabitants/day) and oral morphine equivalent (OMEQ) dose were measured in repeat cross-sectional estimates. RESULTS: In total, there were 2,672,022 prescriptions (87.8% for non-cancer) of strong opioids for 178,692 users (59.9% female, 83.9% non-cancer, mean age 67.1 ± 17.0 years) during the study period. The mean annual (DDD/1000 inhabitants/day) was higher in the non-cancer group than in the cancer group for all four opioids; morphine (0.73 ± 0.28 vs. 0.12 ± 0.04), fentanyl (0.46 ± 0.29 vs. 0.06 ± 0.24), oxycodone (0.24 ± 0.19 vs. 0.038 ± 0.028) and buprenorphine (0.23 ± 0.15 vs. 0.008 ± 0.006). The highest proportion of patients were prescribed low opioid doses (OMEQ ≤ 50 mg/day) in both non-cancer (50.3%) and cancer (39.9%) groups, followed by the dose ranks of 51-100 mg/day (26.2% vs. 28.7%), 101-200 mg/day (15.1% vs. 19.2%) and >200 mg/day (8.25% vs. 12.1%). CONCLUSIONS: There has been a huge increase in strong opioid prescribing in the United Kingdom, with the majority of prescriptions for non-cancer pain. Morphine was the most frequently prescribed, but the utilization of oxycodone, buprenorphine and fentanyl increased markedly over time.