Opioid Coprescription Through Risk Mitigation Guidance and Opioid Agonist Treatment Receipt.

Importance: At the onset of the COVID-19 pandemic, the government of British Columbia, Canada, released clinical guidance to support physicians and nurse practitioners in prescribing pharmaceutical alternatives to the toxic drug supply. These alternatives included opioids and other medications under the risk mitigation guidance (RMG), a limited form of prescribed safer supply, designed to reduce the risk of SARS-CoV-2 infection and harms associated with illicit drug use. Many clinicians chose to coprescribe opioid medications under RMG alongside opioid agonist treatment (OAT). Objective: To examine whether prescription of hydromorphone tablets or sustained-release oral morphine (opioid RMG) and OAT coprescription compared with OAT alone is associated with subsequent OAT receipt. Design, Setting, and Participants: This population-based, retrospective cohort study was conducted from March 27, 2020, to August 31, 2021, included individuals from 10 linked health administrative databases from British Columbia, Canada. Individuals who were receiving OAT at opioid RMG initiation and individuals who were receiving OAT and eligible but unexposed to opioid RMG were propensity score matched at opioid RMG initiation on sociodemographic and clinical variables. Data were analyzed between January 2023 and February 2024. Exposure: Opioid RMG receipt (≥4 days, 1-3 days, or 0 days of opioid RMG dispensed) in a given week. Main Outcome and Measures: The main outcome was OAT receipt, defined as at least 1 dispensed dose of OAT in the subsequent week. A marginal structural modeling approach was used to control for potential time-varying confounding. Results: A total of 4636 individuals (2955 [64%] male; median age, 38 [31-47] years after matching) were receiving OAT at the time of first opioid RMG dispensation (2281 receiving ongoing OAT and 2352 initiating RMG and OAT concurrently). Opioid RMG receipt of 1 to 3 days in a given week increased the probability of OAT receipt by 27% in the subsequent week (adjusted risk ratio, 1.27; 95% CI, 1.25-1.30), whereas receipt of opioid RMG for 4 days or more resulted in a 46% increase in the probability of OAT receipt in the subsequent week (adjusted risk ratio, 1.46; 95% CI, 1.43-1.49) compared with those not receiving opioid RMG. The biological gradient was robust to different exposure classifications, and the association was stronger among those initiating opioid RMG and OAT concurrently. Conclusions and Relevance: This cohort study, which acknowledged the intermittent use of both medications, demonstrated that individuals who were coprescribed opioid RMG had higher adjusted probability of continued OAT receipt or reengagement compared with those not receiving opioid RMG.

Erector spinae plane block did not improve postoperative pain-related outcomes and recovery after video-assisted thoracoscopic surgery : a randomised controlled double-blinded multi-center trial.

INTRODUCTION: There is a sizable niche for a minimally invasive analgesic technique that could facilitate ambulatory video-assisted thoracoscopic surgery (VATS). Our study aimed to determine the analgesic potential of a single-shot erector spinae plane (ESP) block for VATS. The primary objective was the total hydromorphone consumption with patient-controlled analgesia (PCA) 24 h after surgery. METHODS: We conducted a randomized, controlled, double-blind study with patients scheduled for VATS in two major university-affiliated hospital centres. We randomized 52 patients into two groups: a single-shot ESP block using bupivacaine or an ESP block with normal saline (control). We administered a preoperative and postoperative (24 h) quality of recovery (QoR-15) questionnaire and assessed postoperative pain using a verbal numerical rating scale (VNRS) score. We evaluated the total standardized intraoperative fentanyl administration, total postoperative hydromorphone consumption (PCA; primary endpoint), and the incidence of adverse effects. RESULTS: There was no difference in the primary objective, hydromorphone consumption at 24 h (7.6 (4.4) mg for the Bupivacaine group versus 8.1 (4.2) mg for the Control group). Secondary objectives and incidence of adverse events were not different between the two groups at any time during the first 24 h following surgery. CONCLUSION: Our multi-centre randomized, controlled, double-blinded study found no advantage of an ESP block over placebo for VATS for opioid consumption, pain, or QoR-15 scores. Further studies are ongoing to establish the benefits of using a denser block (single-shot paravertebral with a continuous ESP block), which may provide a better quality of analgesia.

Efficacy of bilateral catheter superficial parasternal intercostal plane blocks using programmed intermittent bolus for opioid-sparing postoperative analgesia in cardiac surgery with sternotomy: A randomized, double-blind, placebo-controlled trial.

STUDY OBJECTIVE: This study investigated whether catheter superficial parasternal intercostal plane (SPIP) blocks, using a programmed intermittent bolus (PIB) with ropivacaine, could reduce opioid consumption while delivering enhanced analgesia for a period exceeding 48 h following cardiac surgery involving sternotomy. DESIGN: A double-blind, prospective, randomized, placebo-controlled trial. SETTING: University-affiliated tertiary care hospital. PATIENTS: 60 patients aged 18 or older, scheduled for cardiac surgery via sternotomy. INTERVENTIONS: The patients were randomly assigned in a 1:1 ratio to either the ropivacaine or saline group. After surgery, patients received bilateral SPIP blocks for 48 h with 0.4% ropivacaine (20 mL per side) for induction, followed by bilateral SPIP catheters using PIB with 0.2% ropivacaine (8 mL/side, interspersed with a 2-h interval) or 0.9% normal saline following the same administration schedule. All patients were administered patient-controlled analgesia with hydromorphone. MEASUREMENTS: The primary outcome was the cumulative morphine equivalent consumption during the initial 48 h after the surgery. Secondary outcomes included postoperative pain assessment using the Numeric Rating Scale (NRS) at rest and during coughing at designated intervals for three days post-extubation. Furthermore, recovery indicators and ropivacaine plasma levels were diligently documented. MAIN RESULTS: Cumulative morphine consumption within 48 h in ropivacaine group decreased significantly compared to saline group (25.34 ± 31.1 mg vs 76.28 ± 77.2 mg, respectively; 95% CI, -81.9 to -20.0, P = 0.002). The ropivacaine group also reported lower NRS scores at all recorded time points (P < 0.05) and a lower incidence of nausea and vomiting than the saline group (3/29 vs 12/29, respectively; P = 0.007). Additionally, the ropivacaine group showed significant improvements in ambulation (P = 0.018), respiratory exercises (P = 0.006), and self-reported analgesia satisfaction compared to the saline group (P = 0.016). CONCLUSIONS: Bilateral catheter SPIP blocks using PIB with ropivacaine reduced opioid consumption over 48 h, concurrently delivering superior postoperative analgesia in adult cardiac surgery with sternotomy.

Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.

Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.

Pharmacokinetic-pharmacodynamic analysis of drug liking blockade by buprenorphine subcutaneous depot (CAM2038) in participants with opioid use disorder.

Buprenorphine is used to treat opioid use disorder (OUD). Weekly and monthly subcutaneous long-acting buprenorphine injections (CAM2038) provide more stable buprenorphine plasma levels and reduce the treatment burden, misuse, and diversion associated with sublingual transmucosal buprenorphine formulations. To characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship, a maximum inhibition (Imax) model was developed relating CAM2038 buprenorphine plasma concentration to drug liking maximum effect (Emax) visual analog scale (VAS; bipolar) score after intramuscular hydromorphone administration. Data included time-matched observations of buprenorphine plasma concentration and drug liking Emax VAS score after hydromorphone 18 mg administration in 47 non-treatment-seeking adults with moderate to severe OUD in a phase 2 study. Analysis used non-|linear mixed-effects modeling (NONMEM®). The final Imax model adequately described the PK/PD relationship between buprenorphine plasma concentration and drug liking Emax VAS score. Simulations showed drug liking was effectively blocked at low buprenorphine plasma concentrations (0.4 ng/mL) where the upper 95% confidence interval of the drug liking Emax VAS score was below the pre-defined 11-point complete blockade threshold. The buprenorphine plasma concentration required to achieve 90% of the maximal effect (IC90) of drug liking was 0.675 ng/mL. Interindividual variability in responses to buprenorphine was observed; some participants experienced fluctuating responses, and a few did not achieve drug liking blockade even with higher buprenorphine plasma concentrations. This affirms the need to individualize treatment and titrate doses for optimal treatment outcomes. PK/PD models were also developed for desire to use VAS and Clinical Opiate Withdrawal Scale (COWS) scores, with results aligned to those for drug liking.

Put It in the Air? Nebulized Opioids in the Emergency Department.

The emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last several years, investigations into the use of medications via the nebulization route have greatly increased, with varying degrees of efficacy identified. This route has multiple theoretical advantages. Medications affecting bronchopulmonary function or secretions can be administered directly to the site of action, possibly utilizing a lower dose and hence minimizing side effects. It is also possible to have a faster onset of action compared with other routes, given the enhanced surface area for absorption. One group of medications that has been explored via this route of administration, and is frequently administered in EDs across the nation, is opioids, most notably fentanyl, hydromorphone, and morphine. However multiple questions exist regarding the implementation of these therapies via this route, including efficacy, dosing, and the functional aspects of medication administration that are more complex than that of more traditional routes. The intent of this review is to explore the supporting literature behind the use of nebulized opioids, most specifically fentanyl, hydromorphone, and morphine, in the ED for the treatment of acute pain presentations and provide the most up-to-date guidance for practitioners.

Hydromorphone vs sufentanil in patient-controlled analgesia for postoperative pain management: A meta-analysis.

BACKGROUND: Patient-controlled analgesia (PCA) is an effective method of postoperative pain, there have been many studies performed that have compared the efficacy of hydromorphone with continuous sufentanil. The purpose of this systematic review is to compare the efficacy and safety of hydromorphone and sufentanil. METHODS: Seven databases were searched for controlled trials to compare the efficacy and safety of hydromorphone and sufentanil. After selecting the studies, extracting the data, and assessing study quality, the meta-analysis was performed on several of the studies with RevMan 5.3. RESULTS: Thirteen studies comprised of 812 patients were found. The pain intensity of the hydromorphone group was significantly lower than that of the sufentanil group at 12 hours. With no statistical difference at 24 to 48 hours (MD12 = -1.52, 95% CI [-2.13, -1.97], P <.05). The sedation intensity of the hydromorphone group at 12, 24, and 48 hours were lower than those of the sufentanil group, with no statistical difference (MD12 = -0.03, 95% CI [-0.18, 0.12], P > .05; MD24 = -0.20, 95% CI [-0.42, 0.03], P > .05; MD48 = -0.03, 95% CI [-0.18, 0.11)], P > .05). The PCA requests in the hydromorphone group were less than that in the sufentanil group, and there was no significant difference (RR = -0.20, 95% CI [-1.93,1.53], P > .05). The incidence of adverse events in the hydromorphone group was less than that in the sufentanil group, and there was a statistical difference: (RR = 0.61, 95% CI [0.47,0.79], P < .05). CONCLUSION: Compared with sufentanil, PCA with hydromorphone was more effective in relieving pain and PCA requests 12, 24, and 48 hours after operation, and significantly reduced the incidence of adverse events, but it did not have an advantage in sedation intensity.

Tapentadol in Cancer Patients with Neuropathic Pain: A Comparison of Methadone, Oxycodone, Fentanyl, and Hydromorphone.

Tapentadol has µ-opioid receptor stimulating and noradrenaline reuptake inhibiting properties, and should be effective for neuropathic pain (NP). However, the efficacy of tapentadol for NP in cancer patients is unclear. Ashiya Municipal Hospital (Hyogo, Japan) enrolled five groups of Japanese cancer patients between January 1, 2013, and December 31, 2019. Patients with NP were administered tapentadol (n = 29), methadone (n = 32), oxycodone (n = 20), fentanyl (n = 26), or hydromorphone (n = 20). The primary endpoint was the difference in the verbal rating scale (VRS) scores between days 0 and 7. The secondary endpoint was the tolerability of each opioid. Before administering opioids among the five groups, there was no significant difference in the VRS score (p = 0.99). The mean reduction in the VRS score on day 7 was significantly greater in the tapentadol group than in the oxycodone group (p = 0.0024) and was larger than that of the methadone, fentanyl, and hydromorphone groups. Regarding safety, the discontinuation rate in the tapentadol group was the lowest of all groups (tapentadol vs. methadone vs. oxycodone vs. fentanyl vs. hydromorphone, 0.0% vs. 6.3% vs. 5.0% vs. 3.8% vs. 10.0%, respectively). This study suggests that tapentadol could be efficacious for cancer patients with NP, and a preferred option in cases that require immediate dose adjustment or for those at high risk for adverse effects. However, the pain intensity was evaluated without pain assessment scales specific to NP. Thus, we think that it is desirable to validate our findings using assessment scales, such as the painDETECT questionnaire in future.

A randomized study of IV prochlorperazine plus diphenhydramine versus IV hydromorphone for migraine-associated symptoms: A post hoc analysis.

OBJECTIVE: We conducted a randomized trial among emergency department patients with migraine to determine the relative impact on migraine-associated symptoms of hydromorphone, an opioid, versus prochlorperazine, an antidopaminergic antiemetic. METHODS: This was a post hoc analysis of data from a double-blind study registered at http://clinicaltrials.gov (NCT02389829). Patients who met International Classification of Headache Disorders, 3rd edition criteria for migraine without aura or for probable migraine without aura were eligible for participation. Participants received either hydromorphone 1 mg IV or prochlorperazine 10 mg IV plus diphenhydramine 25 mg IV and could receive a second dose of the same medication 1 h later if needed. The outcomes were sustained relief of nausea, photophobia, and phonophobia. RESULTS: A total of 127 patients were enrolled, of whom 63 received prochlorperazine and 64 received hydromorphone. Of 49 patients in the prochlorperazine arm who reported nausea at baseline, 34 (69.4%) reported complete resolution without relapse versus 15/49 (30.6%) in the hydromorphone arm (absolute risk reduction [ARR] = 38.8%, 95% CI: 20.5%-57.0%, p < 0.001). Of 55 patients in the prochlorperazine arm who reported photophobia at baseline, 23 (41.8%) reported complete resolution without relapse versus 13/62 (20.9%) patients treated with hydromorphone (ARR = 20.8%, 95% CI: 4.3%-37.3%, p = 0.014). Of 56 patients in the prochlorperazine arm who reported phonophobia at baseline, 25 (44.6%) reported complete resolution without relapse versus 16/59 (27.1%) in the hydromorphone arm (ARR = 17.5%, 95% CI: 0.3%-34.8%, p = 0.049). For adverse events, three patients in the prochlorperazine arm reported anxiety or restlessness, and nine patients in the hydromorphone arm reported dizziness or weakness. CONCLUSIONS: Prochlorperazine plus diphenhydramine is more efficacious than hydromorphone for the treatment of migraine-associated symptoms.

Hyperbaric oxygen therapy and fluorescence angiography in arterial insufficiency secondary to injection of crushed hydromorphone.

INTRODUCTION: Foreign body emboli can lead to acute arterial insufficiency. We present a case report of upper extremity arterial insufficiency in an intravenous (IV) drug user secondary to intra-arterial injection of crushed tablet particles successfully treated with hyperbaric oxygen (HBO2) therapy. CASE: A 37-year-old right-hand-dominant male developed pain and swelling of the left hand after attempting to inject crushed hydromorphone tablets into his venous circulation. Angiography revealed incomplete distal filling of the proper digital arteries, princeps pollicis, and radialis indicis branches of the left hand. The patient was treated with HBO2 for acute arterial insufficiency, secondary to these findings. Fluorescence angiography was performed prior to, during and after completion of HBO2, which showed improved perfusion of the hand upon completion of serial imaging. The patient underwent subsequent partial amputation of the left second digit and removal of the thenar and third finger pads. DISCUSSION: Much of the literature on treatment of arterial insufficiency with HBO2 are in relation to chronic problem wounds. However, there is limited data on adjunctive treatment with HBO2 for foreign body embolism. Fluorescence angiography and clinical exam were used to track tissue perfusion and progression throughout course of therapy with HBO2. CONCLUSION: Acute arterial insufficiency induced by foreign body embolism was successfully treated with HBO2 and provided increased tissue salvage of the patient's hand. The use of fluorescence angiography as a secondary measure of perfusion can provide additional insight regarding qualitative tissue oxygenation and may be a viable tool to track patient progress during HBO2 treatment.

Effectiveness of analgesia with hydromorphone hydrochloride for postoperative pain following surgical repair of structural congenital malformations in children: a randomized controlled trial.

BACKGROUND: Effective postoperative analgesia is needed to prevent the negative effects of postoperative pain on patient outcomes. To compare the effectiveness of hydromorphone hydrochloride and sufentanil, combined with flurbiprofen axetil, for postoperative analgesia in pediatric patients. METHODS: This prospective randomized controlled trial included 222 pediatric patients scheduled for repair of a structural congenital malformation under general anesthesia. Patients were randomized into 3 groups: hydromorphone hydrochloride 0.1 mg/kg (H1), hydromorphone hydrochloride 0.2 mg/kg; (H2) or sufentanil 1.5 µg/kg (S). Analgesics were diluted in 0.9% saline to 100 ml and infused continuously at a basic flow rate of 2 mL per h. The primary outcome measure was the Face, Legs, Activity, Cry, and Consolability (FLACC) pain score. Secondary outcomes included heart rate (HR), respiration rate (RR), SpO2, Ramsay sedation scores, scores on the Paediatric Anaesthesia Emergence Delirium (PAED) scale, adverse reactions, parent satisfaction with analgesia. RESULTS: The FLACC score was significantly lower in H1 and H2 groups compared to S. The Ramsay sedation score was significantly higher in H1 and H2 groups compared to S. Recovery time was shorter in H1 group compared to patients H2 group or S group. There were no significant differences in the PAED scale, HR, RR, SpO2, adverse reactions, satisfaction of parents with analgesia, or length and cost of hospital stay. CONCLUSIONS: Hydromorphone hydrochloride is a more effective analgesic than sufentanil for postoperative pain in pediatric patients following surgical repair of a structural congenital malformation, however, hydromorphone hydrochloride and sufentanil had similar safety profiles in this patient population. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-INR-17013935). Clinical trial registry URL: Date of registration: December 14, 2017.

Pattern of hydromorphone use in King Abdulaziz Medical City-Central Region (KAMC-CR).

Hydromorphone is a semi-synthetic opioid that acts mainly on the µ-opioid receptor. Hydromorphone has a fast onset of action, usually within 5 min, and its effectiveness peaks at approximately 20 min, which makes it favourable in the postoperative setting. It plays a role in the management of moderate to severe chronic pain. The most common adverse effects of hydromorphone are hypotension, bradycardia, and respiratory distress. The aim of this study was to determine the trend in the use of hydromorphone analgesics and to evaluate hydromorphone-related toxicity in King Abdulaziz Medical City-Central Region (KAMC-CR). A retrospective, cross-sectional study was carried out in KAMC-CR, and medical and pharmacological data were retrieved from electronic health records for adult patients who used hydromorphone between December 2014 and December 2015. The characteristics of the enrolled patients, including measured blood pressure, heart rate, respiration rate, oxygen saturation, and pain severity score, were collected. Moreover, we identified patients who received naloxone as a hydromorphone antidote. A total of 153 patients were included; 64.1% were male and 35.8% were female. The mean age of the included patients was 55.5 years old (+/- 18.6). Although the majority of patients reported an improvement in pain severity, 75 patients (49%) needed naloxone to overcome adverse effects of hydromorphone. The mean age of patients who received naloxone was 56.2 years old (+/- 20.5), their mean weight was 75.9 kg (+/- 17.2), and 61.3% of them were male (n = 46). Among those who received naloxone, 84% patients (n = 63) had received hydromorphone intravenously. The risk of respiratory depression was significantly higher in patients who received hydromorphone intravenously (IV) than in those who received it orally (p = 0.02). Hydromorphone can have adverse effect. Thus, we recommend evaluating cardiac parameters, oxygen saturation, respiration rate, and pain severity before administering hydromorphone, particularly in patients who have a high risk of cardiorespiratory adverse events, such as patients with cardiac disease, asthma, or chronic obstructive pulmonary disease. Additionally, we recommend the use of appropriate hydromorphone doses in cases of conversion from other opioid therapy or changes between oral and IV routes of the administration of hydromorphone. Moreover, we recommend establishing a policy to restrict the prescription of hydromorphone to avoid the overuse of hydromorphone and minimize the risk of adverse effects and medication errors.

Pre-warming following premedication limits hypothermia before and during anesthesia in Sprague-Dawley rats (Rattus norvegicus).

In humans and other mammals, general anesthesia impairs thermoregulation, leading to warm core blood redistributing to the periphery. This redistribution is an important contributor to hypothermia that can be reduced with pre-warming before anesthesia. Additionally, sedation following premedication has been associated with hypothermia in dogs. In a prospective, randomized, cross-over study, 8 adult male and female rats (weighing 388 to 755 g) were sedated with intramuscular ketamine-midazolam-hydromorphone, then placed in an unwarmed cage or warmed box for 14 minutes, followed by 30 minutes of isoflurane anesthesia with active warming. Core body temperature was monitored throughout. After sedation, warmed rats gained 0.28°C ± 0.13°C and unwarmed rats lost 0.19°C ± 0.43°C, a significant difference between groups (P = 0.004). After anesthesia, warmed rats maintained higher core temperatures (P < 0.0001) with 2/8 and 6/8 of warmed and unwarmed rats becoming hypothermic, respectively. Pre-warming during sedation and active warming during general anesthesia is effective in minimizing hypothermia.

Chez l'humain et les autres mammifères, l'anesthésie générale perturbe la thermorégulation, menant au sang chaud interne se redistribuant vers la périphérie. Cette redistribution est une composante majeure de l'hypothermie et peut être réduite par le réchauffement préemptif. De plus, la sédation suivant la prémédication a été associé à l'hypothermie chez les chiens. Dans cette étude prospective, randomisée et croisée, 8 rats adultes mâles et femelles (388 à 755 g) ont été sédationnés avec ketamine-midazolam-hydromorphone au niveau intramusculaire puis placés dans une cage non-chauffée ou une boîte réchauffée durant 14 minutes, suivi d'une période d'anesthésie générale de 30 minutes sur tapis chauffant. La température interne a été suivi tout au long de l'expérimentation. Après la sédation, les rats réchauffés ont gagné 0,28 °C ± 0,13 °C alors que les rats non-réchauffés ont perdu 0,19 °C ± 0,43 °C, une différence significative entre les groupes (P = 0,004). Après l'anesthésie, les rats réchauffés ont maintenu une température interne supérieure (P < 0,0001) avec 2/8 et 6/8 des rats réchauffés et non-réchauffés hypothermes, respectivement. Le réchauffement préemptif durant la sédation suivi de réchauffement actif durant l'anesthésie générale est efficace pour minimiser l'hypothermie.(Traduit par les auteurs).

Service delivery models for injectable opioid agonist treatment in Canada: 2 sequential environmental scans.

BACKGROUND: Injectable opioid agonist treatment (iOAT) is an emerging evidence-based option in the continuum of care for opioid use disorder in parts of Canada. Our study objective was to identify and describe iOAT programs operating during the ongoing opioid overdose crisis. METHODS: We conducted 2 sequential environmental scans. Programs were eligible to participate if they were in operation as of Sept. 1, 2018, and Mar. 1, 2019. Information was collected over 2-3 months for each scan (September-October 2018, March-May 2019). Programs that participated in the first scan and newly established programs were invited to participate in the second scan. The scans included questions about location, service delivery model, clinical and operational characteristics, numbers and demographic characteristics of clients, and program barriers and facilitators. Descriptive analysis was performed. RESULTS: We identified 14 unique programs across the 2 scans. Eleven programs located in urban centres in British Columbia and Ontario participated in the first scan. At the time of the second scan, 2 of these programs were on hold and 2 of 3 newly established programs were in Alberta. The total capacity of all participating programs was 420 clients at most. Four service delivery models were identified; iOAT was most commonly integrated within existing health and social services. All programs offered hydromorphone, and 1 program also offered diacetylmorphine. In the first scan, 73% of clients (133/183) were male; the mean age of clients was 47 years. Limited capacity, pharmacy operations and lack of diacetylmorphine access were among the most frequently reported barriers. The most commonly reported facilitators included client-centred care, client relationships and access to other health and social support. INTERPRETATION: Evidence indicates that iOAT can be successfully implemented using diverse service delivery models. Future work should facilitate scale-up of this evidence-based treatment where gaps persist in high-risk communities.

Comparing rapid micro-induction and standard induction of buprenorphine/naloxone for treatment of opioid use disorder: protocol for an open-label, parallel-group, superiority, randomized controlled trial.

BACKGROUND: Buprenorphine/naloxone (Suboxone) is a current first-line treatment for opioid use disorder (OUD). The standard induction method of buprenorphine/naloxone requires patients to be abstinent from opioids and therefore experience withdrawal symptoms prior to induction, which can be a barrier in starting treatment. Rapid micro-induction (micro-dosing) involves the administration of small, frequent does of buprenorphine/naloxone and removes the need for a period of withdrawal prior to the start of treatment. This study aims to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone in patients with OUD. METHODS: This is a randomized, open-label, two-arm, superiority, controlled trial comparing the safety and effectiveness of rapid micro-induction versus standard induction of buprenorphine/naloxone for the treatment of OUD. A total of 50 participants with OUD will be randomized at one Canadian hospital. The primary outcome is the completion of buprenorphine/naloxone induction with low levels of withdrawal. Secondary outcomes are treatment retention, illicit drug use, self-reported drug use behaviour, craving, pain, physical health, safety, and client satisfaction. DISCUSSION: This is the first randomized controlled trial to compare the effectiveness and safety of rapid micro-induction versus standard induction of buprenorphine/naloxone. This study will thereby generate evidence for a novel induction method which eliminates substantial barriers to the use of buprenorphine/naloxone in the midst of the ongoing opioid crisis. Trial registration ClinicalTrials.gov, NCT04234191; date of registration: January 21, 2020; https://clinicaltrials.gov/ct2/show/NCT04234191.

Opioid rotation from transdermal fentanyl to continuous subcutaneous hydromorphone in a cachectic patient: A case report and review of the literature.

Opioid rotation from transdermal fentanyl to an alternate opioid is often necessitated in advanced disease, but is fraught with uncertainty due to variable absorption from the patch in end-stage illness and the lack of a clearly established opioid rotation ratio. The manufacturer of transdermal fentanyl provides opioid rotation recommendations only for rotation from the oral morphine equivalent daily dose (MEDD) of opioid to the patch, not in the opposite direction. This is a case report of a single patient with cancer and cachexia admitted to the palliative care unit of a large academic medical centre in Canada. The patient is a 50-year-old female with widely metastatic breast cancer who developed opioid toxicity when maintenance transdermal fentanyl patch therapy (100 µg patch applied every 72 h) was rotated to subcutaneous hydromorphone infusion to improve pain control. Hydromorphone was initiated at a rate of 1 mg/h by continuous infusion based on an opioid rotation ratio for transdermal fentanyl (µg/h):MEDD (mg/day) of 1:2.4. Opioid toxicity eventually resolved with downward titration of hydromorphone to only 30% of the initially estimated equianalgesic dose. This case highlights the need for close follow-up of all patients undergoing opioid rotation from transdermal fentanyl and reinforces the need to reduce the initial dose of the new opioid by 30%-50% of the calculated MEDD, especially when rotating from a high dose of transdermal fentanyl, or if there are factors potentially impairing absorption from the patch such as age, cachexia and weight loss, or if rotation is performed for reasons other than uncontrolled pain.

Longitudinal patterns of cocaine use among patients receiving injectable hydromorphone or diacetylmorphine for the treatment of opioid use disorder: A growth curve modeling approach.

BACKGROUND AND AIMS: Cocaine use is prevalent among people receiving injectable opioid agonist treatment. Investigations of cocaine use in this population have been descriptive and the potential heterogeneity existing in patterns of use have not been characterized. As such, among patients receiving injectable opioid agonist treatment, this study aimed to: 1) quantify intra- and inter-individual variation in cocaine use over 24-months and; 2) determine how predictors of interest explained this variation. METHODS: Participants were patients receiving injectable opioid agonist treatment for opioid use disorder. Study visits were completed at baseline prior to receiving treatment, and 3,6,9,12,18, and 24 months after baseline. A multi-level regression approach to growth curve modeling was employed to estimate and explain intra- (within-person) and inter-individual (between-person) variation in cocaine use. RESULTS: Significant intra and inter-individual variation in cocaine use was identified over 24-months. Treatment engagement was on average associated with reductions in the prior month number of days of cocaine use (range: 0-30)(Estimate (standard error): -0.05(0.02), p = 0.003). On average, men reported less cocaine use compared to women (Estimate (standard error): -5.91(1.57), p=<0.001), and participants reporting ever regularly using cocaine at baseline reported more cocaine use over 24-months compared to participants reporting never regularly using cocaine (Estimate (standard error): 4.72 (1.91), p = 0.013). CONCLUSIONS: Significant reductions in cocaine use were observed and significant heterogeneity in patterns of cocaine use was identified. These heterogeneous cocaine use profiles suggest that an individualized approach to care will be critical in responding to patients' cocaine use in injectable opioid agonist treatment.

Rifampin Reduces the Plasma Concentrations of Oral and Intravenous Hydromorphone in Healthy Volunteers.

BACKGROUND: Several opioids are metabolized by the inducible cytochrome P450 (CYP) 3A isozymes. Coadministration with strong inducers of drug metabolism, such as rifampin, can dramatically reduce systemic exposure to these opioids. As the CYP metabolism of hydromorphone is of minor importance, we studied in healthy volunteers whether hydromorphone would be an effective analgesic for patients who concomitantly receive the prototypical enzyme inducer rifampin. METHODS: In this paired, randomized, crossover study, 12 participants received oral placebo or rifampin for 8 days. Oral hydromorphone (2.6 mg) was administered on day 6 followed by intravenous hydromorphone (0.02 mg/kg) on day 8. Hydromorphone and hydromorphone-3-glucuronide (HM3G) plasma concentrations were measured for 24 hours and psychomotor responses, including perceived drug effect, change in pupil diameter, and cold pressor threshold were evaluated for 6 hours. Our primary outcome was the change in the area under the concentration-time curve (AUC0-last) of oral and intravenous hydromorphone after pretreatment with rifampin or placebo. Pharmacodynamic parameters and other pharmacokinetic parameters were analyzed as secondary outcomes. RESULTS: Rifampin reduced the AUC0-last of oral and intravenous hydromorphone by 43% (ratio to control: 0.57, 90% confidence interval [CI], 0.50-0.65) and 26% (ratio to control: 0.74, 90% CI, 0.69-0.79), respectively. The maximum concentration of oral hydromorphone was reduced by 37% (ratio to control: 0.63, 90% CI, 0.55-0.72), and oral bioavailability decreased from 33% to 26% (ratio to control: 0.78, 90% CI, 0.67-0.91) in the rifampin phase compared with placebo. The HM3G-to-hydromorphone ratio increased by 50% (90% CI, 25-79) and 42% (90% CI, 29-55) after oral and intravenous hydromorphone, respectively. Rifampin did not significantly affect the pharmacodynamic parameters. CONCLUSIONS: Rifampin significantly reduces the concentrations of oral and intravenous hydromorphone. This interaction is due to an increase in the first-pass and systemic metabolism of hydromorphone, likely involving induction of uridine 5'-diphospho- glucuronosyltransferase enzymes by rifampin. The enhancement of hydromorphone elimination should be considered when managing pain of patients who are treated with strong enzyme inducers.