Characteristics of drug-related deaths where individuals are found submerged in a bath or hot tub in the United Kingdom, 1997-2023.

INTRODUCTION: Recent media reports highlight that drug-related fatalities can occur while individuals are immersed in water in domestic settings. We aimed to determine the case characteristics, circumstances of death and type of implicated drugs among individuals dying due to unintentional drug-related causes found immersed in a bath or hot tub. METHODS: Retrospective cohort study in the United Kingdom using coronial records from the National Programme on Substance Abuse Deaths, 1997-2023. Information was available on decedent socio-demographics, characteristics of death and drugs implicated in death. RESULTS: One hundred fifty-six decedents were found immersed in the bath and six in a hot tub, a mean of 6.4 deaths per year (SD 3.7; range 1-13). Overall decedents were predominantly male (n = 94, 58.0%), of White ethnicity (n = 98, 60.5%) with a mean age of 40 years (SD 13; range 19-74). Only 12 decedents had any physical contributory factor to death other than poisoning or drowning. The median number of drugs detected at post-mortem was 3 (interquartile range 2, 5) with multiple drug toxicity implicated in the majority of cases (n = 90, 55.6%). The most common implicated drugs were heroin (n = 53, 32.7%), alcohol (n = 46, 28.4%) and cocaine (n = 33, 20.4%). DISCUSSION AND CONCLUSIONS: Over the last two decades in the United Kingdom there have been consistent numbers of unintentional drug-related deaths each year where individuals were found in a bath or hot tub. Polysubstance, opioid and alcohol use are overrepresented. Targeted advice to avoid bathing while intoxicated would appear to be an appropriate harm reduction message.

Wastewater-based evaluation of the efficacy of oxycodone regulations in Australia.

BACKGROUND AND AIMS: Between 2018 and 2020, Australia implemented major policy changes to improve the quality and safety of opioid prescribing, with a specific focus on oxycodone. This study used wastewater-based epidemiology to assess the efficacy of Australia's regulatory reforms by measuring change in consumption of oxycodone via exploratory analysis. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: Wastewater analysis data on oxycodone consumption was from the National Wastewater Drug Monitoring Program. The program captures data from more than 50 wastewater treatment plant catchments across Australia, equivalent to more than 50% of the national population. Geographic trend analyses were conducted for both major cities and regional areas within all states and territories of Australia over a 6-year period between 2017 and 2023. FINDINGS: Oxycodone consumption showed a statistically significant increase nationally from 78 mg/day/1000 people (95% confidence interval [CI] = 71, 84) in 2017 to 120 mg/day/1000 people in August 2019 (95% CI = 110, 120), an increase of 52% (95% CI = 42, 62, P < 0.0001). From August 2019 to December 2020, there was a statistically significant decrease from 120 to 65 mg/day/1000 people (95% CI = 60, 71), a decrease of 45% (95% CI = 40, 51), followed by a modest 2.4% increase to the end of the study period in April 2023 (95% CI [2.0,2.7]). CONCLUSIONS: A 45% reduction in oxycodone consumption in Australia from 2019 to 2020 coincided with national policy changes that aimed to reduce consumption of prescription opioids. The overall declining trend in consumption was suggestive of the effectiveness of national interventions in reducing pharmaceutical opioid use. Wastewater-based epidemiology provides an effective approach for assessing the effectiveness of controlled substances policy changes.

Posterior quadratus lumborum block versus intrathecal morphine analgesia after scheduled cesarean section: a prospective, randomized, controlled study.

BACKGROUND: During the postoperative period of elective cesarean section, intrathecal morphine is effective in the multimodal analgesic regimen, but can cause significant adverse effects. Bilateral posterior quadratus lumborum block could be alternatively used. The aim of this study was to compare efficacy and safety of both strategies as part of a multimodal analgesic regimen. METHODS: This was a prospective, randomized, blinded, controlled study. 104 parturients were randomly selected to receive intrathecal morphine or posterior quadratus lumborum block during cesarean section under spinal anesthesia. The primary endpoint was patient-controlled 24-hour cumulative intravenous morphine use. Secondary endpoints were 48-hour cumulative morphine use, static/dynamic pain scores, functional recovery (ObsQoR-11 questionnaire) and adverse effects. RESULTS: There was no statistical difference in the mean cumulative morphine dose at 24-hour between groups (posterior quadratus lumborum block group, 13.7 (97.5% CI 10.4 to 16.9) mg; intrathecal morphine group, 11.1 (97.5% CI 8.4 to 13.8) mg, p=0.111). Pain scores did not show any difference between groups, excepted at 6 hours for the pain at cough/movement in favor of the posterior quadratus lumborum block group (p=0.013). A better recovery quality was observed at 24 hours in the posterior quadratus lumborum block group (p=0.009). Pruritus was more frequent in intrathecal morphine group parturients (35% vs 2%) CONCLUSIONS: No difference in cumulative morphine dose at 24 hours was observed in posterior quadratus lumborum block group compared with intrathecal morphine group. Posterior quadratus lumborum block can be considered an alternative to intrathecal morphine in cesarean postoperative analgesia, especially in cases of intolerance to morphine. TRIAL REGISTRATION NUMBER: NCT04755712.

Persistent pain after total temporomandibular joint replacement surgery: clinical characteristics, comorbidities, and risk factors.

Chronic post-surgical pain (CPSP) after temporomandibular joint (TMJ) surgery is an under-recognized problem. The aim of this study was to document the characteristics of CPSP and identify patient risk factors and comorbidities associated with the development of CPSP after total TMJ replacement (TJR). This was a retrospective cohort study of patients who underwent TJR between 2000 and 2018 at Massachusetts General Hospital, Boston, USA. The primary outcome was the presence of CPSP and use of pain medications after TJR. The secondary outcome was the risk factors associated with the development of CPSP. A total 88 patients were included (79 females, 9 males). The mean follow-up was 4.2 years. Overall, 68 (77.3%) had CPSP and 20 (22.7%) had no CPSP. Of those with CPSP, 32.4% had severe pain and 45.6% continued to take pain medications. Of the 27 patients with data available on the characteristics of the pain, the majority had myofascial pain, while some developed neuropathic pain. A significant difference was noted between the CPSP and non-CPSP groups in terms of preoperative pain, smoking behavior, and use of opioids, non-steroidal anti-inflammatory drugs, muscle relaxants, and neuropathic pain medications.

Examining the effect of prescription drug monitoring program integration and mandatory use policies on the distribution of methadone and buprenorphine for opioid use disorder, United States, 2009-2021.

BACKGROUND: Prescription drug monitoring programs (PDMPs) have been shown to reduce opioid prescribing for pain, but it is not well understood whether PDMPs influence utilization of medications for opioid use disorder. PDMP integration and mandatory use policies are two approaches implemented by states to increase use of PDMPs by prescribers. This study examined the effect of these approaches on distribution of methadone and buprenorphine from 2009 to 2021 for 50 states and DC. METHODS: The effect of PDMP integration and mandatory use policies on four outcomes (distribution of buprenorphine to opioid treatment programs, distribution of buprenorphine to pharmacies, distribution of methadone to opioid treatment programs, and the total combined distribution of methadone and buprenorphine) was estimated using a Callaway and Sant'Anna difference-in-differences model, controlling for co-occurring opioid-related state policies. RESULTS: Distribution of buprenorphine to pharmacies decreased 8 % (95 % CI -14 %, -1 %) following implementation of mandatory use policies. Distribution of methadone to opioid treatment programs increased 17 % (95 % CI 4 %, 34 %) and the total combined distribution of methadone and buprenorphine increased 6 % (95 % CI -0 %, 14 %) following the joint implementation of both approaches. CONCLUSION: Distribution of methadone and buprenorphine has increased since 2009, but less than a quarter of people with opioid use disorder currently receive these medications. We observed a small net benefit of PDMP integration and mandatory use policies on distribution of methadone and buprenorphine. Policymakers should continue to assess the impact of PDMPs on access to medications for opioid use disorder and consider additional approaches to increase access to treatment.

Elucidating the molecular symphony: unweaving the transcriptional & epigenetic pathways underlying neuroplasticity in opioid dependence and withdrawal.

The persistent use of opioids leads to profound changes in neuroplasticity of the brain, contributing to the emergence and persistence of addiction. However, chronic opioid use disrupts the delicate balance of the reward system in the brain, leading to neuroadaptations that underlie addiction. Chronic cocaine usage leads to synchronized alterations in gene expression, causing modifications in the Nucleus Accumbens (NAc), a vital part of the reward system of the brain. These modifications assist in the development of maladaptive behaviors that resemble addiction. Neuroplasticity in the context of addiction involves changes in synaptic connectivity, neuronal morphology, and molecular signaling pathways. Drug-evoked neuroplasticity in opioid addiction and withdrawal represents a complicated interaction between environmental, genetic, and epigenetic factors. Identifying specific transcriptional and epigenetic targets that can be modulated to restore normal neuroplasticity without disrupting essential physiological processes is a critical consideration. The discussion in this article focuses on the transcriptional aspects of drug-evoked neuroplasticity, emphasizing the role of key transcription factors, including cAMP response element-binding protein (CREB), ΔFosB, NF-kB, Myocyte-enhancing factor 2 (MEF2), Methyl-CpG binding protein 2 (MeCP2), E2F3a, and FOXO3a. These factors regulate gene expression and lead to the neuroadaptive changes observed in addiction and withdrawal. Epigenetic regulation, which involves modifying gene accessibility by controlling these structures, has been identified as a critical component of addiction development. By unraveling these complex molecular processes, this study provides valuable insights that may pave the way for future therapeutic interventions targeting the mechanisms underlying addiction and withdrawal.

Perioperative pain management interventions in opioid user patients: an overview of reviews.

BACKGROUND: Every year, many opioid users undergo surgery, experiencing increased postoperative complications, inadequate pain control, and opioid-related adverse effects. This overview aims to summarise and critically assess the systematic reviews about perioperative pain management interventions, identify the knowledge gaps, and potentially provide high-quality recommendations to improve postoperative analgesia and surgical outcomes. METHODS: A systematic search was conducted from the following databases, PubMed, Cochrane Database of Systematic Reviews, Embase, APA PsycINFO, CINAHL, AMED, Scopus, PROSPERO, ProQuest, and Epistemonikos, in June 2023. Additionally, reference lists were reviewed. The identified studies were assessed based on eligibility criteria and data extracted by a self-designed form and two independent reviewers. Qualitative data were synthesised, and all included studies were assessed by The Assessment of Multiple Systematic Reviews 2 (AMSTAR 2) checklist. RESULTS: Nine studies were included. The methodological quality of the studies was mostly critically low. Various interventions were identified, including perioperative management of buprenorphine, ketamine administration, multimodal analgesia, higher doses of medications, patient education, and interprofessional collaboration. The level of certainty of the evidence ranged from very low to high. One high-quality study showed that ketamine administration may improve perioperative analgesia supported with moderate to very low-quality evidence, and low and critically low studies indicated the efficacy of perioperative continuation of buprenorphine with low to very low-quality evidence. CONCLUSION: Perioperative continuation of buprenorphine and ketamine administration as a multimodal analgesia approach, with moderate to very low-quality evidence, improves pain management in opioid users and decreases opioid-related adverse effects. However, high-quality systematic reviews are required to fill the identified gaps in knowledge.

The cell-permeant antioxidant D-thiol ester D-cysteine ethyl ester overcomes physical dependence to morphine in male Sprague Dawley rats.

The ability of morphine to decrease cysteine transport into neurons by inhibition of excitatory amino acid transporter 3 (EAA3) may be a key molecular mechanism underlying the acquisition of physical and psychological dependence to morphine. This study examined whether co-administration of the cell-penetrant antioxidant D-thiol ester, D-cysteine ethyl ester (D-CYSee), with morphine, would diminish the development of physical dependence to morphine in male Sprague Dawley rats. Systemic administration of the opioid receptor antagonist, naloxone (NLX), elicited pronounced withdrawal signs (e.g., wet-dog shakes, jumps, rears, circling) in rats that received a subcutaneous depot of morphine (150 mg/kg, SC) for 36 h and continuous intravenous infusion of vehicle (20 µL/h, IV). The NLX-precipitated withdrawal signs were reduced in rats that received an infusion of D-CYSee, but not D-cysteine, (both at 20.8 µmol/kg/h, IV) for the full 36 h. NLX elicited pronounced withdrawal signs in rats treated for 48 h with morphine (150 mg/kg, SC), plus continuous infusion of vehicle (20 µL/h, IV) that began at the 36 h timepoint of morphine treatment. The NLX-precipitated withdrawal signs were reduced in rats that received a 12 h infusion of D-CYSee, but not D-cysteine, (both at 20.8 µmol/kg/h, IV) that began at the 36 h timepoint of morphine treatment. These findings suggest that D-CYSee may attenuate the development of physical dependence to morphine and reverse established dependence to the opioid in male Sprague Dawley rats. Alternatively, D-CYSee may simply suppress the processes responsible for NLX-precipitated withdrawal. Nonetheless, D-CYSee and analogues may be novel therapeutics for the treatment of opioid use disorders.

Predictors of Postoperative Morphine Milligram Equivalents in Cardiac Surgery.

OBJECTIVES: Given both the short- and long-term deleterious effects of opioids, there has been an increased focused on reducing the use of postoperative opioid analgesia. As patients undergoing cardiac surgery often require high levels opioids postoperatively, understanding risk factors for increased postoperative opioid use may be helpful for the development of patient-specific opioid-sparing pain regimens for this patient population. DESIGN: A retrospective analysis of data from our electronic medical records and the Society of Thoracic Surgeon's database. SETTING: A single-institution study at an academic medical center. PARTICIPANTS: All patients undergoing open adult cardiac surgery were included. Exclusion criteria were patients with continuous intravenous narcotic drips and operative mortality. INTERVENTIONS: As this was a retrospective study, no interventions were conducted on the participants. MEASUREMENTS AND MAIN RESULTS: Data for patient postoperative opioid requirements were extracted from the electronic medical record. Total opioid use on postoperative days 0 to 3 was converted to morphine milligram equivalent (MME) via standard conversion factors. The study cohort comprised 1604 patients, including 456 females and 1066 coronary artery bypass grafting (CABG) recipients. MME was 31.0% greater in patients undergoing CABG (p < 0.001), 76.3% greater in patients with liver disease (p = 0.005), and 48.8% greater in patients with patient-controlled analgesia (p <0.001) during postoperative days 0 to 3. Younger age (p < 0.001) and higher body mass index (BMI) (p < 0.001) also were associated with increased MME prescription. CONCLUSIONS: CABG, liver disease, patient-controlled analgesia, younger age, and higher BMI are associated with increased narcotic use after cardiac surgery. Implementation of more aggressive perioperative multimodal opioid-sparing regimens should be considered for these patient groups.

Practice review: Pharmacological management of severe chronic breathlessness in adults with advanced life-limiting diseases.

BACKGROUND: Severe and refractory chronic breathlessness is a common and burdensome symptom in patients with advanced life-limiting disease. Its clinical management is challenging because of the lack of effective interventions. AIM: To provide practice recommendations on the safe use of pharmacological therapies for severe chronic breathlessness. DESIGN: Scoping review of (inter)national guidelines and systematic reviews. We additionally searched for primary studies where no systematic review could be identified. Consensus on the recommendations was reached by 75% approval within an international expert panel. DATA SOURCES: Searches in MEDLINE, Cochrane Library and Guideline International Network until March 2023. Inclusion of publications on the use of antidepressants, benzodiazepines, opioids or corticosteroids for chronic breathlessness in adults with cancer, chronic obstructive pulmonary disease, interstitial lung disease or chronic heart failure. RESULTS: Overall, the evidence from eight guidelines, 14 systematic reviews and 3 randomised controlled trials (RCTs) on antidepressants is limited. There is low quality evidence favouring opioids in patients with chronic obstructive pulmonary disease, cancer and interstitial lung disease. For chronic heart failure, evidence is inconclusive. Benzodiazepines should only be considered for anxiety associated with severe breathlessness. Antidepressants and corticosteroids should not be used. CONCLUSION: Management of breathlessness remains challenging with only few pharmacological options with limited and partially conflicting evidence. Therefore, pharmacological treatment should be reserved for patients with advanced disease under monitoring of side effects, after optimisation of the underlying condition and use of evidence-based non-pharmacological interventions as first-line treatment.

Risk factors for persistent postoperative opioid use: an entity distinct from chronic postsurgical pain.

Despite a decline in opioid prescriptions over the past decade, patients commonly receive opioid analgesics as a treatment for postoperative pain in the USA. One complication that patients may experience after surgery is persistent postoperative opioid use (PPOU), or opioid use beyond the typical recovery period. Often defined as beyond 3 months postsurgery, PPOU is frequently conflated with chronic postsurgical pain (CPSP), where pain persists well after the expected healing time following surgery. This narrative review explores the distinct risk factors for each condition, their interrelation, and potential future research directions.For PPOU, major risk factors include the risky use of substances including misuse and use disorders; depression and other mental health disorders; a history of chronic pain before surgery including back pain; and certain surgical types (ie, total knee arthropathy, open cholecystectomy, total hip arthropathy). Conversely, CPSP risk factors include the type of surgery (ie, thoracic and breast surgeries), mental health conditions (particularly catastrophizing), and pain in both the preoperative and postoperative phases. Despite the overlap of some factors, studies typically employ different frameworks when examining PPOU and CPSP, with a biopsychosocial model applied for CPSP and little emphasis on an individual's social environment employed for PPOU. Additionally, existing studies predominantly rely on retrospective insurance claims data, which may not capture the full scope of risk factors.To fill gaps in understanding, investigations may prospectively assess and analyze patient-reported outcomes, implement similar frameworks, and concurrently measure both conditions to advance the scientific understanding of PPOU and CPSP.

Postoperative Pain and Perioperative Antibiotic Management in Functional Rhinoplasty.

Post-rhinoplasty pain control should use a multimodal regimen. Evidence suggests decreasing routine prescriptions of narcotics is reasonable for most individuals, and acetaminophen and nonsteroidal antiinflammatory drug combinations may be equivalent to as-needed opioids for postsurgical pain management. Preoperative pain counseling is important to set post-rhinoplasty pain expectations and reduce opioid use. A single intravenous dose of prophylactic antibiotics before incision is sufficient for most cases of functional rhinoplasty. Additional considerations are given to complex revision cases, use of allogenic grafts or implants, external osteotomies, or patients with immunosuppression or at risk of endocarditis.

Patient and navigator experiences with the opioid use disorder treatment system in Philadelphia, PA.

BACKGROUND: In 2022, 1413 people in Philadelphia died of an unintentional drug overdose. Addressing the complex challenges within the opioid use disorder (OUD) treatment system requires a comprehensive grasp of multiple system-level siloes from the perspective of patients who are accessing services and certified recovery specialists. Identifying facilitators and barriers to treatment entry and retention are critical. METHODS: We conducted 13 focus groups with 70 people with a history of opioid use in Philadelphia, Pennsylvania. The study recruited participants from non-profit organizations, OUD treatment programs, and street intercept. Certified Recovery Specialists (CRS), people with experience in residential, outpatient, methadone, and buprenorphine programs in Philadelphia, identity-specific groups with Black women, Black men, and Latino men, pregnant and parenting people, and people accessing harm reduction services participated in focus groups. Focus group guides varied by group, but the overarching focus remained on understanding participants' experiences in navigating the OUD treatment system. The research team summarized and edited CRS focus groups and coded all other focus groups for thematic analysis. RESULTS: Most focus group participants (mean age = 45.1 years; 52.9 % men, 40 % Black) had a history with multiple treatment types and reported experiences with different modalities. Salient themes that emerged from analysis included frustrations with the assessment process; reflections on facilitators and barriers by treatment type (residential, methadone, and buprenorphine); and recommendations across treatment modalities. Assessment centers, rather than being easy points of treatment entry, were identified as a major barrier to OUD treatment initiation; issues discussed included length of assessment, limited operating hours, and inadequate withdrawal management. DISCUSSION: The data from the present study were used to develop recommendations for policymakers and other stakeholders of OUD treatment programs to improve care across the spectrum of services. Expansion of residential programs that can support patients with complex comorbid conditions and wounds is needed to prevent delays for patients deemed ineligible for lower levels of care. Housing and income were identified as significant deterrents to initiating drug treatment and greater resources are needed. Greater investment in the OUD workforce is needed, especially expanding staff with lived experience. Findings can enhance OUD treatment programs elsewhere.

Correlates of Current Methamphetamine Use and Opioid Co-Use Among Latina Women in a Low-Income Community.

Using data from Proyecto SALTO, a 15-year follow-up study of a cohort of Mexican American women in a low-income community in San Antonio, Texas, this study examines emerging patterns of current methamphetamine (MA) use, including opioid co-use, among this understudied population. A bivariate analysis compared individuals with and without current MA use and identified sociodemographic correlates and co-occurring mental health and substance use. A secondary analysis compared those with current MA use, opioid use, and concurrent MA and opioid use. Nineteen percent of the sample had current MA use. MA use was associated with having a lower income (OR = 7.04-1.93, SE = 1.59-5.46), residential instability (OR = 5.19, SE = 1.99), and suicidal ideation (OR = 2.62, SE = 0.93). Participants with MA use had more than four times the odds of using opioids than those without MA use. Women with concurrent MA and opioid use differed in sociodemographics and behavioral risks compared to those with only MA or only opioid use. These findings explore the social, mental health, and structural inequities that exacerbate risks and harms associated with high-risk substance use among marginalized Latino populations. Prevention and intervention strategies should adopt a holistic approach that considers and addresses polysubstance use, mental health, and the sociocultural contexts in which individuals live.

Anxiety and risk-taking behavior maps onto opioid and alcohol polysubstance consumption patterns in male and female mice.

Polysubstance use is prevalent in the population but remains understudied in preclinical models. Alcohol and opioid polysubstance use is associated with negative outcomes, worse treatment prognosis, and higher overdose risk; but underlying mechanisms are still being uncovered. Examining factors that motivate use of one substance over another in different contexts in preclinical models will better our understanding of polysubstance use and improve translational value. Here we assessed baseline anxiety-like and locomotive behavior and then measured voluntary consumption of multiple doses of alcohol and fentanyl in group housed male and female mice using our novel Socially Integrated Polysubstance (SIP) system. Fifty-six male (n=32) and female (n=24) adult mice were housed in groups of 4 for one week with continuous access to food, water, two doses of ethanol (5% and 10%) and two doses of fentanyl (5 ug/ml and 20 ug/ml). Our analyses revealed sex differences across multiple domains - female mice consumed more liquid in the dark cycle, had higher activity, a higher preference for both ethanol and fentanyl over water, and their fentanyl preference increased over the seven days. We then used machine-learning techniques to reveal underlying relationships between baseline behavioral phenotypes and subsequent polysubstance consumption patterns, where anxiety-and risk-taking-like behavioral phenotypes mapped onto discrete patterns of polysubstance use, preference, and escalation. By simulating more translationally relevant substance use and improving our understanding of the motivations for different patterns of consumption, this study contributes to the developing preclinical literature on polysubstance use with the goal of facilitating better treatment outcomes and novel therapeutic strategies.

Naloxone cascade of care among people who regularly inject drugs in Australia, 2020-2022.

BACKGROUND: Examining take-home naloxone (THN) uptake using a 'cascade of care' framework could help identify targets for increasing THN training and carriage among people who may witness or experience opioid overdose. We describe the THN cascade and factors associated with engagement among people who inject drugs. METHODS: People aged ≥18 years in Australia who inject drugs were interviewed from 2020 to 2022, reporting lifetime THN awareness and acquisition and past-month carriage. We examined factors associated with engagement using multivariable logistic regression. RESULTS: Of 2,149 participants (64 % men, mean age 44.5), 85 % had heard of naloxone, of whom 76 % were aware of THN programs. Of these, 72 % had ever participated in THN training/brief education, 92 % of whom had acquired THN. Of those who had ever acquired THN and reported past-month opioid use, 63 % always/often carried THN when using opioids. Past six-month opioid agonist treatment (OAT) (adjusted odds ratio [AOR] 2.55; 95 %CI 1.91-3.42) and ≥daily injecting (1.32; 1.01-1.73) were associated with awareness. OAT (1.79; 1.38-2.33), past-year opioid overdose (1.68; 1.18-2.42) and older age (1.02; 1.00-1.03) were associated with acquisition. Primarily injecting methamphetamine (versus heroin) in the past month was associated with lower awareness (0.43; 0.31-0.58) and acquisition (0.59; 0.44-0.78). Reporting no accommodation (squatting/sleeping rough) was associated with reduced odds of carriage (0.46; 0.24-0.88). CONCLUSION: Participants reported high THN awareness and acquisition, with lower carriage. Future efforts should focus on improving THN access and reducing barriers to carriage, particularly for people experiencing homelessness or who primarily inject non-opioids.

Effectiveness of intramuscular naloxone 1,600 µg in addition to titrated intravenous naloxone 100 µg for opioid poisoning: a randomised controlled trial.

INTRODUCTION: Naloxone is an effective antidote, but its short half-life means repeated doses, and infusions are often required. We investigated the effectiveness of adding intramuscular naloxone to titrated intravenous naloxone in opioid overdose in preventing recurrence of respiratory depression. METHODS: This double-blinded randomised placebo-controlled trial was conducted in patients with suspected opioid poisoning and respiratory depression (respiratory rate <10 breaths/min or oxygen saturation <93%). Patients were randomised to receive either intramuscular naloxone 1,600 µg or saline placebo. All patients received titrated intravenous naloxone 100 µg and were managed on an opioid poisoning care pathway. The primary outcome was recurrence of respiratory depression within 4 h. Secondary outcomes were the proportion receiving naloxone infusions, number of naloxone boluses administered, reversal of respiratory depression at 10 min, and precipitation of opioid withdrawal (any symptom). RESULTS: Recurrence of respiratory depression within 4 h was less common in 28/69 (41%) patients receiving intramuscular naloxone versus 48/67 (72%) patients receiving placebo (difference 31%, 95% CI: 13-46%; P < 0.001). Fewer naloxone infusions (5/69; 7% versus 25/67; 37%, difference 30%, 95% CI: 15 to 55%; P < 0.001) and fewer naloxone doses were administered (median 2, IQR: 1 to 5, versus median 5, IQR: 2 to 8; P = 0.001) in the intramuscular group. Reversal of respiratory depression at 10 min was similar between groups (51/69; 74% intramuscular naloxone versus 47/67; 70% placebo; P = 0.703). Opioid withdrawal occurred in 35/69 (51%) given intramuscular naloxone compared to 28/67 (42%) in the placebo group (difference 9%; 95% CI: -8 to 27%; P = 0.308). DISCUSSION: The favourable pharmacokinetics of intramuscular naloxone, particularly its longer duration of activity, likely explains the improved effectiveness with lower recurrence of respiratory depression. CONCLUSION: The addition of intramuscular naloxone 1,600 µg to titrated intravenous naloxone prolonged effective reversal of respiratory depression, with fewer naloxone doses and infusions given, and no significant difference in patients developing withdrawal.

Decrease of the peak heights of EEG bicoherence indicated insufficiency of analgesia during surgery under general anesthesia.

BACKGROUND: Studies show that the two peak heights of electroencephalographic bicoherence (pBIC-high, pBIC-low) decrease after incision and are restored by fentanyl administration. We investigated whether pBICs are good indicators for adequacy of analgesia during surgery. METHODS: After local ethical committee approval, we enrolled 50 patients (27-65 years, ASA-PS I or II) who were scheduled elective surgery. Besides standard anesthesia monitors, to assess pBICs, we used a BIS monitor and freeware Bispectrum Analyzer for A2000. Fentanyl 5 µg/kg was completely administered before incision, and anesthesia was maintained with sevoflurane. After skin incision, when the peak of pBIC-high or pBIC-low decreased by 10% in absolute value (named LT10-high and LT10-low groups in order) or when either peak decreased to below 20% (BL20-high and BL20-low groups), an additional 1 g/kg of fentanyl was administered to examine its effect on the peak that showed a decrease. RESULTS: The mean values and standard deviation for pBIC-high 5 min before fentanyl administration, at the time of fentanyl administration, and 5 min after fentanyl administration for LT10-high group were 39.8% (10.9%), 26.9% (10.5%), and 35.7% (12.5%). And those for pBIC-low for LT10-low group were 39.5% (6.0%), 26.8% (6.4%) and 35.0% (7.0%). Those for pBIC-high for BL20-high group were 26.3% (5.6%), 16.5% (2.6%), and 25.7% (7.0%). And those for pBIC-low for BL20-low group were 26.7% (4.8%), 17.4% (1.8%) and 26.9% (5.7%), respectively. Meanwhile, at these trigger points, hemodynamic parameters didn't show significant changes. CONCLUSION: Superior to standard anesthesia monitoring, pBICs are better indicators of analgesia during surgery. TRIAL REGISTRY: Clinical trial Number and registry URL: UMIN ID: UMIN000042843 https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno = R000048907.

Discharge Opioid Prescription and Consumption Following Surgery: The POPCORN Observational Study.

Background: Few studies have evaluated opioid consumption after various inpatient surgical procedures. Objectives: To describe opioid prescription patterns and to characterize patient-reported use of opioids after surgery. Methods: This single-centre prospective observational study was conducted between February and October 2021 at the Jewish General Hospital in Montréal, Quebec. Patients 18 years of age or older who underwent a surgical procedure, were hospitalized for 24 hours or longer after the procedure, and had an opioid prescription at the time of discharge were included. Data were collected for the quantity of opioids prescribed, as documented in hospital records, and the quantity consumed, as reported by participants. Various potential predictors of opioid consumption were explored, and data were also collected on patients' use of non-opioid coanalgesia, scores on the Numeric Rating Scale for pain, opioid renewal requests, and proper opioid disposal during the 30-day follow-up period. Results: A total of 150 participants completed the study. The median dose prescribed was 10 opioid pills (75.0 morphine milligram equivalents). By the end of the follow-up period, a median of 1 pill (7.5 morphine milligram equivalents) had been consumed from the total amount in the discharge prescription. Overall, 66 participants (44.0%) did not consume any of the opioids prescribed at discharge. Of the total number of pills prescribed, 58.2% (1193/2050) were unused, and 7.0% (5/71) of participants with unused pills disposed of them properly. Conclusions: Following discharge from hospital, postoperative patients consumed a median proportion of only 10% of prescribed opioid pills. More than half of all prescribed pills were unused. Protocols implementing specific prescribing strategies warrant further investigation to evaluate their potential impact on opioid prescription and consumption.

Contexte: Peu d'études ont évalué la consommation d'opioïdes après diverses interventions chirurgicales en milieu hospitalier. Objectifs: Décrire les schémas de prescription d'opioïdes et caractériser leur utilisation déclarée par les patients après une intervention chirurgicale. Méthodologie: Cette étude observationnelle prospective monocentrique a été menée entre février et octobre 2021 à l'Hôpital général juif de Montréal, au Québec. Les patients d'au moins 18 ans ayant subi une intervention chirurgicale, ayant été hospitalisés pendant au moins 24 heures après l'intervention et qui avaient une prescription d'opioïdes au moment de leur congé ont été inclus dans l'étude. Des données ont été recueillies sur la quantité d'opioïdes prescrite, telle que documentée dans les dossiers de l'hôpital, et sur la quantité consommée, telle que déclarée par les participants. Divers prédicteurs potentiels de la consommation d'opioïdes ont été étudiés et des données ont aussi été recueillies, sur une période de suivi de 30 jours, sur l'utilisation de coanalgésie non opioïde par les patients, leurs scores sur l'échelle d'évaluation numérique de la douleur, les demandes de renouvellement d'opioïdes et l'élimination appropriée de ces dernières. Résultats: Au total, 150 participants ont complété l'étude. La dose médiane prescrite était de 10 comprimés d'opioïdes (75,0 équivalents en milligrammes de morphine). À la fin de la période de suivi, une moyenne de 1 comprimé (7,5 équivalents en milligrammes de morphine) avait été consommée sur la quantité totale indiquée dans l'ordonnance remise au moment du congé. Dans l'ensemble, 66 participants (44,0 %) n'ont consommé aucun des opioïdes prescrits au moment du congé. Sur le nombre total de comprimés prescrits, 58,2 % (1193/2050) n'ont pas été utilisés et 7,0 % (5/71) des participants ayant des comprimés inutilisés s'en sont débarrassés correctement. Conclusions: Suite au congé de l'hôpital, les patients postopératoires ne consommaient qu'une proportion médiane de 10 % des comprimés d'opioïde prescrits. Plus de la moitié de tous les comprimés prescrits n'ont pas été utilisés. Les protocoles mettant en oeuvre des stratégies de prescription spécifiques justifient des recherches plus approfondies pour évaluer leur incidence potentielle sur la prescription et la consommation d'opioïdes.