Opioid analgesic use among patients with kidney disease: a systematic review.

INTRODUCTION: Opioid analgesics are often used to manage moderate to severe pain. A significant proportion of patients taking opioids have compromised kidney function. This systematic review aimed to examine the available evidence on the safety and analgesic effect of opioid use in adults with kidney disease. METHODS: We searched eight electronic databases from inception to 26th January 2023. Published original research articles in English reporting on opioid use and pharmacokinetic data among adults with reduced renal function were included. Article screening, data extraction, and quality assessment were conducted by at least two investigators independently. This review was registered prospectively on PROSPERO (ID: CRD42020159091). RESULTS: There were 32 observational studies included, 14 of which reported on morphine use, three involved fentanyl use, two involved hydromorphone use and 13 articles reported on other opioids including codeine, dihydrocodeine, and buprenorphine. CONCLUSION: There is limited and low-quality evidence to inform the safety and analgesic effect of opioid use in reduced renal function. Morphine remains the opioid for which there is the most evidence available on safety and analgesic effect in the context of renal disease. Greater caution and consideration of potential risks and benefits should be applied when using other opioids. Further high-quality studies examining clinical outcomes associated with the use of different opioids and opioid doses in renal disease are warranted.

The use of interventional procedures for cancer pain. A brief review.

CONTEXT: Pain is a common experience in people living with cancer. Concerns around opioid prescribing have seen a move toward a multi-modality management approach, which includes interventional pain procedures. PURPOSE: In this paper we discuss the interventional pain procedures used to treat cancer pain at two major tertiary centers in Australia. METHODS AND RESULTS: This expert review provides practical insights on cancer pain management from healthcare providers in different specialties. These insights can be used to guide the management of a wide range of cancer pain types. CONCLUSIONS: Furthermore, this review identifies the need for a systematic and comprehensive approach to the management of cancer pain that is broader than that of a single specialty. With recent advances in pain management procedures, an interdisciplinary approach is essential in order to provide an up to date, patient tailored approach to pain management. This review will help inform the development of a cancer pain intervention registry.

Supply of opioids and information provided to patients after surgery in an Australian hospital: A cross-sectional study.

Opioids are commonly prescribed to manage pain after surgery. However, excessive supply on discharge can increase patients' risk of persistent opioid use and contribute to the reservoir of unused opioids in the community that may be misused. This study aimed to evaluate the use of opioids in Australian surgical patients after discharge and patient satisfaction with the provision of opioid information after discharge. This prospective cohort study was conducted at a tertiary referral and teaching hospital. Surgical patients were called 7-28 days after discharge to identify their opioid use and the information that they received after discharge. In total, 66 patients responded. Most patients underwent orthopaedic surgery (45.5%; 30/66). The median days of opioids supplied on discharge was 5 (IQR 3-5). In total, 40.9% (27/66) of patients had >50% of their opioids remaining. Patients undergoing orthopaedic surgery were less likely to have >50% of their opioids remaining (P = 0.045), whilst patients undergoing urological or renal surgeries were significantly more likely (P = 0.009). Most patients recalled receiving information about their opioids (89.4%; 59/66). However, the majority (51.5%; 34/66) did not recall receiving any information about the signs of opioid toxicity and interactions between opioids and alcohol. In conclusion, around 40% of patients had more than half of their opioid supply remaining after they ceased taking their opioid. Although most patients recalled receiving information about their opioids, more than half did not recall receiving any information about the signs of opioid toxicity or interactions between opioids and alcohol.

Opioid-sparing effect of cannabinoids for analgesia: an updated systematic review and meta-analysis of preclinical and clinical studies.

Cannabinoid co-administration may enable reduced opioid doses for analgesia. This updated systematic review on the opioid-sparing effects of cannabinoids considered preclinical and clinical studies where the outcome was analgesia or opioid dose requirements. We searched Scopus, Cochrane Central Registry of Controlled Trials, Medline, and Embase (2016 onwards). Ninety-two studies met the search criteria including 15 ongoing trials. Meta-analysis of seven preclinical studies found the median effective dose (ED50) of morphine administered with delta-9-tetrahydrocannabinol was 3.5 times lower (95% CI 2.04, 6.03) than the ED50 of morphine alone. Six preclinical studies found no evidence of increased opioid abuse liability with cannabinoid administration. Of five healthy-volunteer experimental pain studies, two found increased pain, two found decreased pain and one found reduced pain bothersomeness with cannabinoid administration; three demonstrated that cannabinoid co-administration may increase opioid abuse liability. Three randomized controlled trials (RCTs) found no evidence of opioid-sparing effects of cannabinoids in acute pain. Meta-analysis of four RCTs in patients with cancer pain found no effect of cannabinoid administration on opioid dose (mean difference -3.8 mg, 95% CI -10.97, 3.37) or percentage change in pain scores (mean difference 1.84, 95% CI -2.05, 5.72); five studies found more adverse events with cannabinoids compared with placebo (risk ratio 1.13, 95% CI 1.03, 1.24). Of five controlled chronic non-cancer pain trials; one low-quality study with no control arm, and one single-dose study reported reduced pain scores with cannabinoids. Three RCTs found no treatment effect of dronabinol. Meta-analyses of observational studies found 39% reported opioid cessation (95% CI 0.15, 0.64, I2 95.5%, eight studies), and 85% reported reduction (95% CI 0.64, 0.99, I2 92.8%, seven studies). In summary, preclinical and observational studies demonstrate the potential opioid-sparing effects of cannabinoids in the context of analgesia, in contrast to higher-quality RCTs that did not provide evidence of opioid-sparing effects.

Opioid-related adverse drug events in surgical patients: risk factors and association with clinical outcomes.

BACKGROUND: Opioid analgesics are commonly used to treat acute post-operative pain. The primary objective of this study was to identify the risk factors for opioid-related adverse drug events (ORADEs) in surgical patients and the association between ORADEs and clinical outcomes. RESEARCH DESIGN AND METHODS: A retrospective cohort study was conducted using data from July 2016 to April 2020. ORADEs were defined using the International Classification of Diseases 10th Revision Australian Modification codes. Multivariate logistic regression was performed to identify ORADE risk factors. To investigate the association between ORADEs and clinical outcomes, propensity score matching was performed. RESULTS: Among 17,886 surgical patients who received opioid analgesics during hospital stay, 1,814 patients (10.2%) experienced ORADEs. Risk factors for general ORADEs included advanced age, comorbidities, concurrent use of benzodiazepines or gabapentinoids and a higher opioid daily dose. Patients who experienced ORADEs were associated with longer length of stay (Rate Ratio 3.00, 95% CI 2.97-3.04) but similar 28-day readmission rate (Odds Ratio 0.89, 95% CI 0.71-1.11). CONCLUSIONS: Risk factors for general ORADEs were advanced age, specific comorbidities, use of benzodiazepines or gabapentinoids and higher opioid dose. Routine use of opioids with gabapentinoids should be avoided and only used after careful consideration.

Postoperative use of slow-release opioids: The impact of the Australian and New Zealand College of Anaesthetists/Faculty of Pain Medicine position statement on clinical practice.

Dose titration with immediate-release opioids is currently recommended for acute pain. The Australian and New Zealand College of Anaesthetists and the Faculty of Pain Medicine released a statement in March 2018 supporting their use in the treatment of opioid-naïve patients; however, the impact of this statement on clinical practice is currently unknown. This retrospective cohort study was conducted to compare opioid prescribing patterns before and after the release of the recommendations. Data were collected on 184 patients (2017, n = 78; 2018, n = 106) admitted to the Prince of Wales Hospital in November 2017 and 2018, which consisted of demographic data, opioid prescriptions and discharge opioid information. The main outcome is the number of prescriptions of slow-release opioids in 2017 versus 2018 after the recommendations were published. Confounding factors were accounted for using logistic and multiple regression as appropriate. There was a 29% decrease in slow-release opioid prescriptions during hospitalisation (n = 31, 40% versus n = 12, 11%; P < 0.001) and 17% decrease at discharge (n = 20, 26% versus n = 9, 9%; P = 0.02) post-publication. After adjusting for confounders, the odds of slow-release opioids being prescribed postoperatively and at discharge reduced by 86% and 88%, respectively (postoperative period: odds ratio 0.14, P < 0.05; discharge: odds ratio 0.12, P < 0.05). In addition, orthopaedic patients were more likely to receive slow-release opioids, consistent with existing literature. As the use of slow-release opioids has been associated with increased harm and protracted opioid use compared to immediate-release opioids, it is hoped that wider dissemination of these recommendations and a change in prescribing practice can be a step towards overcoming the opioid crisis.

Responsible Prescribing of Opioids for Chronic Non-Cancer Pain: A Scoping Review.

Chronic non-cancer pain is common and long-term opioid therapy is frequently used in its management. While opioids can be effective, they are also associated with significant harm and misuse, and clinicians must weigh any expected benefits with potential risks when making decisions around prescribing. This review aimed to summarise controlled trials and systematic reviews that evaluate patient-related, provider-related, and system-related factors supporting responsible opioid prescribing for chronic non-cancer pain. A scoping review methodology was employed, and six databases were searched. Thirteen systematic reviews and nine controlled trials were included for analysis, and clinical guidelines were reviewed to supplement gaps in the literature. The majority of included studies evaluated provider-related factors, including prescribing behaviours and monitoring for misuse. A smaller number of studies evaluated system-level factors such as regulatory measures and models of healthcare delivery. Studies and guidelines emphasise the importance of careful patient selection for opioid therapy, development of a treatment plan, and cautious initiation and dose escalation. Lower doses are associated with reduced risk of harm and can be efficacious, particularly when used in the context of a multimodal interdisciplinary pain management program. Further research is needed around many elements of responsible prescribing, including instruments to monitor for misuse, and the role of policies and programs.

Medication Use and Pain Management in Pregnancy: A Critical Review.

BACKGROUND: Pain during pregnancy is common, and its management is complex. Certain analgesics may increase the risk for adverse fetal and pregnancy outcomes, while poorly managed pain can result in adverse maternal outcomes such as depression and hypertension. Guidelines to assist clinicians in assessing risks and benefits of exposure to analgesics for the mother and unborn infant are lacking, necessitating evidence-based recommendations for managing pain in pregnancy. METHODS: A comprehensive literature search was conducted to assess pregnancy safety data for pharmacological and nonpharmacological pain management methods. Relevant clinical trials and observational studies were identified using multiple medical databases, and included studies were evaluated for quality and possible biases. RESULTS: Paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) are appropriate for mild to moderate pain, but NSAIDs should be avoided in the third trimester due to established risks. Short courses of weaker opioids are generally safe in pregnancy, although neonatal abstinence syndrome must be monitored following third trimester exposure. Limited safety data for pregabalin and gabapentin indicate that these are unlikely to be major teratogens, and tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors have limited but overall reassuring safety data. Many of the included studies were limited by methodological issues. CONCLUSIONS: Findings from this review can guide clinicians in their decision to prescribe analgesics for pregnant women. Treatment should be tailored to the lowest therapeutic dose and shortest possible duration, and management should involve a discussion of risks and benefits and monitoring for response. Further research is required to better understand the safety profile of various analgesics in pregnancy.

The Pain Course: Exploring the Feasibility of an Internet-delivered Pain Management Program When Offered by a Tertiary Pain Management Service.

BACKGROUND: This study examined the acceptability and preliminary outcomes of an internet-delivered pain management program, the Pain Course, when offered by a specialist pain management clinic in a large public hospital. METHODS: A single-group feasibility open-trial design was used and 39 patients participated in the program, which ran for 8 weeks. Participants were supported through the program with weekly contact from a Clinical Psychologist at the clinic. RESULTS: All participants provided data at posttreatment and >90% of participants completed all 5 lessons of the course. High levels of satisfaction were observed and relatively little clinician time (M=71.99 min/participant; SD=32.82 min) was required to support patients through the program. Preliminary evidence of clinical improvements in depression symptoms (avg. improvement=38%; Cohen d=0.74), but not disability levels or anxiety symptoms, was observed in the overall sample. However, evidence of improvements was observed across all the primary outcomes among patients who had clinical levels of difficulties with disability (n=20; avg. improvement=11%; Cohen d=0.64), depression (n=17; avg. improvement=35%; Cohen d=1.24) and anxiety (n=8; avg. improvement=29%; Cohen d=0.57). CONCLUSIONS: These findings highlight the potential value of internet-delivered programs when provided by specialist pain management clinics as a part of their services and the value of larger scale studies in this area.

Opioid-Sparing Effect of Cannabinoids: A Systematic Review and Meta-Analysis.

Cannabinoids, when co-administered with opioids, may enable reduced opioid doses without loss of analgesic efficacy (ie, an opioid-sparing effect). The aim of this study was to conduct a systematic review to determine the opioid-sparing potential of cannabinoids. Eligible studies included pre-clinical and clinical studies for which the outcome was either analgesia or opioid dose requirements. Clinical studies included controlled studies and case series. We searched Scopus, Cochrane Database of Systematic Reviews, Medline, and Embase. Nineteen pre-clinical and nine clinical studies met the search criteria. Seventeen of the 19 pre-clinical studies provided evidence of synergistic effects from opioid and cannabinoid co-administration. Our meta-analysis of pre-clinical studies indicated that the median effective dose (ED50) of morphine administered in combination with delta-9-tetrahydrocannabinol (delta-9-THC) is 3.6 times lower (95% confidence interval (CI) 1.95, 6.76; n=6) than the ED50 of morphine alone. In addition, the ED50 for codeine administered in combination with delta-9-THC was 9.5 times lower (95% CI 1.6, 57.5, n=2) than the ED50 of codeine alone. One case series (n=3) provided very-low-quality evidence of a reduction in opioid requirements with cannabinoid co-administration. Larger controlled clinical studies showed some clinical benefits of cannabinoids; however, opioid dose changes were rarely reported and mixed findings were observed for analgesia. In summary, pre-clinical studies provide robust evidence of the opioid-sparing effect of cannabinoids, whereas one of the nine clinical studies identified provided very-low-quality evidence of such an effect. Prospective high-quality-controlled clinical trials are required to determine the opioid-sparing effect of cannabinoids.

Wound infusion with local anaesthesia after laparotomy: a randomized controlled trial.

BACKGROUND: The use of a continuous local anaesthesia infusion after laparotomy may reduce opioid requirements and facilitate earlier return of bowel function, independent mobilization and hospital discharge. METHODS: We performed a double-blinded, randomized controlled trial on 55 patients who underwent laparotomy. Patients were randomly allocated to receive a continuous infusion of either 0.2% ropivacaine or normal saline into their midline abdominal wound at the fascial level. The end points of the study were: total opioid requirements at 24 and 48 h; time to first flatus, bowel movement and independent ambulation; length of hospital stay; complications; and daily mean patient-reported pain scores at rest and movement. RESULTS: The two treatment groups were well controlled for factors that influence analgesia requirements, including age, weight, length of wound incision and type of operation. Patients allocated to ropivacaine infusion used, on average, 32 mg less morphine at 48 h (95% confidence interval 7, 57; P= 0.01). This was highly statistically significant after adjusting for age, gender and type of operation (P= 0.0006). Ropivacaine infusion was associated with a significantly decreased time to independent mobilization (P= 0.02), time to first flatus (P= 0.02) and reduced post-operative ileus (2/28 versus 9/27, χ(2) = 5.89, P= 0.02). There was no significant effect of ropivacaine infusion on time to first bowel movement (P= 0.94) nor length of hospital stay (P= 0.77). CONCLUSIONS: Local anaesthesia infusion at the fascial plane provides effective analgesia. This improves patient recovery through earlier return to bowel function and mobilization.