Cost-Effectiveness and Guidelines for Opioid Substitution Treatment

There was evidence indicating that in the treatment of opioid use disorder, injectable hydromorphone, or injectable methadone provided more benefit at less cost compared with injectable diacetylmorphine over a 6-month time horizon. Evidence suggests that in the treatment of opioid use disorder, both injectable hydromorphone and injectable diacetylmorphine are likely to provide more benefit at less cost than methadone maintenance treatment. Treatment with injectable hydromorphone was more cost-effective than injectable diacetylmorphine in opioid use disorder patients who do not respond to or relapse from drug treatments. The evidence is limited because observed data were collected during a short-term follow-up, and long-term cost-effectiveness outcomes were based on extrapolations beyond data from the actual studies. One guideline provided a weak recommendation, supported by low-quality evidence, for using slow-release oral morphine in older adults with adequate renal function in whom buprenorphine and methadone maintenance have been ineffective to treat opioid use disorder or could not be tolerated. Another guideline recommends using injectable hydromorphone or injectable diacetylmorphine for individuals with severe opioid use disorders who relapsed previous treatments failed. No relevant cost-effectiveness evidence or guidelines with recommendations regarding the use of oral hydromorphone, fentanyl patches, or fentanyl buccal tablets for opioid use disorder treatment were identified; therefore, no summary can be provided.

Opioid use in Older Orthopedic Rehabilitation Inpatients: A Retrospective Study

Background: While there is much evidence about pain management for orthopedic patients in the immediate perioperative setting, little is known about how opioids are used during inpatient rehabilitation in the days and weeks that follow, particularly in older adults. A safe upper limit of 50 oral morphine equivalents (OME) is frequently cited in guidelines. This study’s objective is to characterize the use of opioids in an older adult population undergoing orthopedic rehabilitation. Methods: This is a retrospective observational study of adults aged ≥50 years old admitted for orthopedic rehabilitation between November 2019 and June 2021 at an academic rehabilitation hospital in Toronto, Canada. Acute care admissions preceding rehabilitation were for either a surgical or non-surgical orthopedic indication. Participants were divided into opioid-naïve individuals who received opioids, opioid-naïve individuals who did not receive opioids, and pre-existing chronic users of opioids. Demographic, clinical, and medication administration data were collected through the electronic health record and manual chart review. Average daily opioid dose for the first seven days of each stay was characterized using OME. Linear regression was used to assess for variables independently associated with opioid dose. Results: A total of 643 patients undergoing orthopedic rehabilitation were included: 125 (19.4%) involved chronic opioid users, 416 (64.7%) were opioid-naïve patients who received opioids, and 102 (15.9%) were opioid-naïve patients who did not receive opioids, with median age respectively of 72, 79, and 83. Median daily OME over the first week for chronic users was 30.3 and for opioid-naïve users was 6.9. Opioid dose was significantly positively associated with reported pain as defined by day 3 pain score and knee replacement; it was inversely associated with admission for a non-surgical indication and age. Conclusions: Opioids are frequently but heterogeneously used in older adults undergoing orthopedic rehabilitation. Median OME use in this cohort of older adults was substantially lower than the 50 OME threshold suggested in guidelines. Dedicated guidance for opioid use is warranted for this unique patient population.

Oral morphine versus transmucosal diamorphine for breakthrough pain in children: methods and outcomes: UK (DIPPER study) consensus

ObjectivesNo randomised controlled trials have been conducted for breakthrough pain in paediatric palliative care and there are currently no standardised outcome measures. The DIPPER study aims to establish the feasibility of conducting a prospective randomised controlled trial comparing oral and transmucosal administration of opioids for breakthrough pain. The aim of the current study was to achieve consensus on design aspects for a small-scale prospective study to inform a future randomised controlled trial of oral morphine, the current first-line treatment, versus transmucosal diamorphine.MethodsThe nominal group technique was used to achieve consensus on best practice for mode of administration, dose regimen and a range of suitable pain intensity outcome measures for transmucosal diamorphine in children and young people with breakthrough pain. An expert panel of ten clinicians in paediatric palliative care and three parent representatives participated. Consensus was achieved when agreement was reached and no further comments from participants were forthcoming.ResultsThe panel favoured the buccal route of administration, with dosing according to the recommendations in the Association for Paediatric Palliative Medicine formulary (fifth Edition, 2020). The verbal Numerical Rating Scale was selected to measure pain in children 8 years old and older, the Faces Pain Scale-Revised for children between 4 and 8 years old, and Face, Legs, Activity, Cry and Consolability (FLACC)/FLACC-Revised as the observational tools.ConclusionsThe nominal group technique allowed consensus to be reached for a small-scale, prospective, cohort study and provided information to inform the design of a randomised controlled trial.

Impact of intraoperative methadone use on postoperative opioid requirements after cardiac surgery

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Inadequate pain control after cardiac surgery increases postoperative morbidity. Increasing evidence suggests that perioperative intravenous (IV) methadone results in improved analgesia. This study evaluated the effect of intraoperative IV methadone on postoperative opioid requirements and surgical recovery. Methods A retrospective review of patients undergoing coronary artery bypass graft (CABG), valvular surgery or both between April 2017 and August 2018 was conducted. Patients were separated into a usual care cohort of those who received short-acting opioids (ie, IV fentanyl, hydromorphone, or morphine) alone or a methadone cohort of those who received IV methadone plus short-acting opioids. Opioid requirements were assessed within the first 24 hours of surgery (postoperative day [POD] 0) and 25 to 48 hours after surgery (POD 1) as oral morphine milligram equivalents (MME). Postoperative pain scores, adjunctive analgesia, time to extubation, use of noninvasive respiratory support (continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]), and intensive care unit (ICU) and hospital length of stay (LOS) were also evaluated. Results A total of 117 patients were evaluated (methadone cohort, n = 52; usual care cohort, n = 65). Median cumulative intraoperative opioid consumption was less in the methadone cohort (150 MME vs 314.1 MME; P < 0.0001). The methadone cohort required 44% fewer MME than the usual care cohort on POD 0 (median MME, 15.8 vs 36; P = 0.025), with low and not significantly different opioid use in both cohorts on POD 1 (15.5 MME vs 7.5 MME; P = 0.47). Weight-based methadone dosing ranged from 0.1 to 0.4 mg/kg (mean, 0.22 mg/kg). There were no significant differences in pain scores, time to extubation, use of CPAP or BiPAP, or ICU and hospital LOS. Conclusion Intraoperative IV methadone in cardiac surgery patients was safe and significantly reduced intraoperative and postoperative opioid requirements on POD 0.

Persistent Opioid Use After Cardiac Implantable Electronic Device Procedures

Background: Prescription opioids are a major contributor to the ongoing epidemic of persistent opioid use (POU). The incidence of POU among opioid-naïve patients after cardiac implantable electronic device (CIED) procedures is unknown. Methods: This retrospective cohort study used data from a national administrative claims database from 2004 to 2018 of patients undergoing CIED procedures. Adult patients were included if they were opioid-naïve during the 180-day period before the procedure and did not undergo another procedure with anesthesia in the next 180 days. POU was defined by filling an additional opioid prescription >30 days after the CIED procedure. Results: Of the 143 400 patients who met the inclusion criteria, 15 316 (11%) filled an opioid prescription within 14 days of surgery. Among these patients, POU occurred in 1901 (12.4%) patients 30 to 180 days after surgery. The likelihood of developing POU was increased for patients who had a history of drug abuse (odds ratio, 1.52; P =0.005), preoperative muscle relaxant (odds ratio, 1.52; P <0.001) or benzodiazepine (odds ratio, 1.23; P =0.001) use, or opioid use in the previous 5 years (OR, 1.76; P <0.0001). POU did not differ after subcutaneous implantable cardioverter defibrillator or other CIED procedures (11.1 versus 12.4%; P =0.5). In a sensitivity analysis excluding high-risk patients who were discharged to a facility or who had a history of drug abuse or previous opioid, benzodiazepine, or muscle relaxant use, 8.9% of the remaining cohort had POU. Patients prescribed >135 mg of oral morphine equivalents had a significantly increased risk of POU. Conclusions: POU is common after CIED procedures, and 12% of patients continued to use opioids >30 days after surgery. Higher initially prescribed oral morphine equivalent doses were associated with developing POU.

Auricular field nerve stimulation using the NSS-2 BRIDGE® device as an alternative to opioids following kidney donor surgery

Objectives The purpose of this study was to investigate the role that the NSS-2 BRIDGE® device, an auricular field nerve stimulator, may play in reducing opioid requirement and pain in kidney donor surgery. It was not a randomized study. Electrophysiologic studies have demonstrated that the stimulation of the cranial nerves produced by the NSS-2 BRIDGE® device modulates the ascending/descending spinal pain pathways, especially at the level of the limbic system. Methods The design compared the effects of the NSS-2 BRIDGE® device (NSS 2-BRIDGE® device group; n=10) to a control group (n=10). In both groups, the surgery was performed using the same standard enhanced recovery after surgery protocol based on the use of a multimodal analgesic approach. For the active treatment group, the NSS-2 BRIDGE® device was placed in the post anesthesia care unit. The primary endpoint was opioid requirement (oral morphine equivalent, OME in mg) at 24 h post-surgery. Secondary endpoints included pain (0–10), at 24 and 48 h, time to discharge from the recovery room, incidence of post-operative nausea and vomiting at 24 h, time to oral intake, time to ambulation, and time to discharge from the hospital. Data was analyzed using unpaired t-test and presented as mean ± standard deviation. Results Compared to control, the use of the NSS-2 BRIDGE® was associated with a 75.4% reduction in OME (33.6 vs. 8.3 mg; p=0.03) and 41.5% reduction in pain (5 vs. 3.28; p=0.06) at 24 h and a 73.3% difference in pain at 48 h (1.6 ± 1.6 vs. 6.0 ± 2.8; p=0.0004). There was no difference in non-opioid analgesics administration between groups. Conclusions The tolerability of NSS-2 BRIDGE® device was reported by most to be excellent. This study suggests that the NSS-2 BRIDGE® device may represent a complementary approach for controlling postoperative opioid consumption and pain in patients undergoing kidney donation.

Efficacy of Ultrasound-Guided Serratus Anterior Plane Block for Postoperative Analgesia in Patients Undergoing Breast Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Objective. Serratus anterior plane block (SAPB) provides effective thoracic analgesia. This systematic review and meta-analysis was conducted to assess the safety and efficacy of SAPB for postoperative analgesia after breast surgery. Methods. A systematic literature search was performed using Embase, PubMed, Web of Science, and the Cochrane Library for eligible randomised controlled trials. The primary outcomes involved the administration of intraoperative and postoperative opioids. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence for making recommendations. Results. Overall, 13 studies comprising 826 patients met the inclusion criteria (412 in the SAPB group and 414 in the control group). Patients treated with SAPB exhibited a significantly lower postoperative opioid consumption (mean difference, −38.51 mg of oral morphine equivalent; 95% confidence interval (CI), −60.97 to −16.05; P < 0.01 ; I2 = 100%), whereas no difference was observed in the intraoperative opioid consumption (mean difference, −9.85 mg of oral morphine equivalent; 95% CI, −19.52 to −0.18; P = 0.05 ; I2 = 94%). In addition, SAPB significantly decreased the occurrence of postoperative nausea and vomiting (risk ratio, 0.32; 95% CI, 0.19–0.55; P < 0.05 ;I2 = 38%) and reduced pain scores during the postoperative period (1 h: standardised mean difference (SMD), −1.23; 95% CI, −2.00 to −0.45; I2 = 92%; 2 h: SMD, −0.71; 95% CI, −1.00 to −0.41; I2 = 48%; 4 h: SMD, −1.52; 95% CI, −2.77 to −0.27; I2 = 95%; 6 h: SMD, −0.80; 95% CI, −1.51 to −0.08; I2 = 81%; 8 h: SMD, −1.12; 95% CI, −1.98 to −0.27; I2 = 92%; 12 h: SMD, −0.78; 95% CI, −1.21 to −0.35; I2 = 83%; and 24 h: SMD, −0.71; 95% CI, −1.20 to −0.23; I2 = 87%; P < 0.05 for all). Conclusion. SAPB was safe and effective after breast surgery to relieve postsurgical pain. However, additional well-developed trials are required to validate these findings.

Impact of Legislation on Opioid Prescribing following Hysterectomy and Hysteroscopy in Arizona and Florida

<b><i>Objectives:</i></b> This study aimed to determine the oral morphine equivalents (OMEs) prescribed and refill rates following hysterectomy and hysteroscopy in the setting of opioid prescribing practice changes in 2 states. <b><i>Design:</i></b> This is a retrospective cohort analysis consisting of 2,916 patients undergoing hysterectomy or hysteroscopy between July 2016 and September 2019 at 2 affiliated academic hospitals in states that underwent legislative changes in opioid prescribing in 2018. <b><i>Methods:</i></b> Participants were identified using the Current Procedural Terminology procedure codes in Arizona and Florida. Hysterectomy was chosen as the most invasive gynecologic procedure, while hysteroscopy was chosen as the least invasive. Medical records were abstracted to find opioid prescriptions from 90 days before surgery to 30 days after discharge. Patients with opioid use between 90 and 7 days before surgery were excluded. Prescriptions were converted to OMEs and were calculated per quarter year. Statistical analysis included Wilcoxon rank sum <i>t</i> tests for OMEs and χ² <i>t</i> tests for refill rates. Interrupted time-series analysis was used to determine significant change in OMEs before and after legislative change. Statistical analysis was performed using SAS version 9.4 (SAS Institute, Cary, NC, USA). <b><i>Results:</i></b> In Arizona, 1,067 hysterectomies were performed; 459 (43%) vaginal, 561 (52.6%) laparoscopic/robotic, and 47 (4.4%) abdominal. There were 530 hysteroscopies. Overall median OMEs decreased from 225 prior to July 2018 to 75 after July 2018 (<i>p</i> &#x3c; 0.0001). The opioid refill rate remained unchanged at 7.4% (<i>p</i> = 0.966). In Florida, there were 769 hysterectomies; 241 (31.3%) vaginal, 476 (61.9%) laparoscopic/robotic, and 52 (6.8%) abdominal. There were 549 hysteroscopies. Overall median OMEs decreased from 150 prior to July 2018 to 0 after July 2018 (<i>p</i> &#x3c; 0.0001). The opioid refill rate was similar (7.8% before July 2018 and 7.3% after July 2018; <i>p</i> = 0.739). <b><i>Limitations:</i></b> Limitations include involvement of a single hospital institution with a total of 10 fellowship-trained surgeons and biases inherent to retrospective study design. <b><i>Conclusions:</i></b> Legislative and provider-led changes coincided with decreases in opioid prescribing after 2018 in both states without increasing rates of refills and showed actual data reflected in the medical record. Gynecologists must actively participate in safe prescribing practices to decrease opioid dependence and misuse.

Palliative care and euthanasia: A Nepalese scenario

Palliative care, namely the relief of pain, is a priority for cases of incurable diseases in Nepal. However, since oral morphine is not available, pain control is often inadequate. Euthanasia is not permissible by law but could be a better solution in some cases and should be made understandable to patients and physicians as in developed countries. Should euthanasia be legal? If cheap and effective palliative care were easily accessible, most terminally ill Nepalese would avoid pressure to practise euthanasia because it is a cheaper option.

Persistent Postoperative Opioid Prescription Fulfillment and Peripheral Nerve Blocks for Ambulatory Shoulder Surgery: A Retrospective Cohort Study

Background There is need to identify perioperative interventions that decrease chronic opioid use. The authors hypothesized that receipt of a peripheral nerve block would be associated with a lower incidence of persistent postoperative opioid prescription fulfillment. Methods This was a retrospective population-based cohort study examining ambulatory shoulder surgery patients in Ontario, Canada. The main outcome measure was persistent postoperative opioid prescription fulfillment. In opioid-naive patients (no opioid prescription fulfillment in 90 days preoperatively), this was present if an individual fulfilled an opioid prescription of at least a 60-day supply during postoperative days 90 to 365. In opioid-exposed (less than 60 mg oral morphine equivalent dose per day within 90 days preoperatively) or opioid-tolerant (60 mg oral morphine equivalent dose per day or above within 90 days preoperatively) patients, this was classified as present if an individual experienced any increase in opioid prescription fulfillment from postoperative day 90 to 365 relative to their baseline use before surgery. The authors’ exposure was the receipt of a peripheral nerve block. Results The authors identified 48,523 people who underwent elective shoulder surgery from July 1, 2012, to December 31, 2017, at one of 118 Ontario hospitals. There were 8,229 (17%) patients who had persistent postoperative opioid prescription fulfillment. Of those who received a peripheral nerve block, 5,008 (16%) went on to persistent postoperative opioid prescription fulfillment compared to 3,221 (18%) patients who did not (adjusted odds ratio, 0.90; 95% CI, 0.83 to 0.97; P = 0.007). This statistically significant observation was not reproduced in a coarsened exact matching sensitivity analysis (adjusted odds ratio, 0.85; 95% CI, 0.71 to 1.02; P = 0.087) or several other subgroup and sensitivity analyses. Conclusions This retrospective analysis found no association between receipt of a peripheral nerve block and a lower incidence of persistent postoperative opioid prescription fulfillment in ambulatory shoulder surgery patients. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New