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Introduction: Opioid use disorder (OUD) is a major public health crisis worldwide. Patients with OUD inevitably experience withdrawal symptoms when they attempt to taper down on their current opioid use, abstain completely from opioids, or attempt to transition to certain medications for opioid use disorder. Acute opioid withdrawal can be debilitating and include a range of symptoms such as anxiety, pain, insomnia, and gastrointestinal symptoms. Whereas acute opioid withdrawal only lasts for 1-2 weeks, protracted withdrawal symptoms can persist for months after the cessation of opioids. Insufficient management of opioid withdrawal often leads to devastating results including treatment failure, relapse, and overdose. Thus, there is a critical need for cost-effective, nonopioid medications, with minimal side effects to help in the medical management of opioid withdrawal syndrome. We discuss the potential consideration of cannabidiol (CBD), a nonintoxicating component of the cannabis plant, as an adjunctive treatment in managing the opioid withdrawal syndrome. Materials and Methods: A review of the literature was performed using keywords related to CBD and opioid withdrawal syndrome in PubMed and Google Scholar. A total of 144 abstracts were identified, and 41 articles were selected where CBD had been evaluated in clinical studies relevant to opioid withdrawal. Results: CBD has been reported to have several therapeutic properties including anxiolytic, antidepressant, anti-inflammatory, anti-emetic, analgesic, as well as reduction of cue-induced craving for opioids, all of which are highly relevant to opioid withdrawal syndrome. In addition, CBD has been shown in several clinical trials to be a well-tolerated with no significant adverse effects, even when co-administered with a potent opioid agonist. Conclusions: Growing evidence suggests that CBD could potentially be added to the standard opioid detoxification regimen to mitigate acute or protracted opioid withdrawal-related symptoms. However, most existing findings are either based on preclinical studies and/or small clinical trials. Well-designed, prospective, randomized-controlled studies evaluating the effect of CBD on managing opioid withdrawal symptoms are warranted.

Background: Numerous worldwide clinical trials have proven the indisputably negative influence of morphine on the pharmacokinetics and pharmacodynamics of P2Y 12 receptor inhibitors in patients presenting with acute coronary syndromes. The aim of this trial was to evaluate whether oral co-administration of an anti-opioid agent, naloxone, can be considered a successful approach to overcome ‘the morphine effect’. Methods: Consecutive unstable angina patients receiving ticagrelor and morphine with or without orally administered naloxone underwent assessment of platelet reactivity using Multiplate analyzer as well as evaluation of the pharmacokinetic profile of ticagrelor and its active metabolite, AR-C124910XX, at nine pre-defined time points within the first 6 hours following oral intake of the ticagrelor loading dose. Results: The trial shows no significant differences regarding the pharmacokinetics of ticagrelor between both study arms throughout the study period. AR-C124910XX plasma concentration was significantly higher 120 min after the ticagrelor loading dose administration (p = 0.0417). However, the evaluation of pharmacodynamics did not show any statistically significant differences between the study arms. Conclusions: To conclude, this trial shows that naloxone co-administration in ticagrelor-treated acute coronary syndrome patients on concomitant treatment with morphine shows no definite superiority in terms of ticagrelor pharmacokinetic and pharmacodynamic profile.

Harm reduction is an approach to reduce the risk of harms to an individual using substances without requiring abstinence. This review discusses substance-specific interventions for opioids, alcohol, and stimulants that can minimize harms for individuals who use these substances. Topics discussed include overdose prevention, infection prevention, and low-barrier substance use disorder treatment.

This comprehensive review on opioids summarizes the scope of the current opioid epidemic, the diagnosis and treatment of opioid use disorder, and the medical and psychiatric complications of opioid use.

Opioid use disorder (OUD) is a significant health problem, and understanding mechanisms of various aspects of OUD including drug use and withdrawal is important. Preclinical models provide an ideal opportunity to evaluate mechanisms underlying opioid withdrawal. Current models are limited by their reliance upon forced opioid administration, focus on the acute (and not protracted) syndrome, and exclusion of females. In this study, male and female rats self-administered heroin (maintenance dose of 12.5 μg/kg/infusion) and opioid withdrawal after abrupt discontinuation was measured. In Phase 1, acute withdrawal symptoms were rated in male and female rats at 0, 16, 48, and 72 hr after the last self-administration session. Total somatic signs increased until 48 hr (predominantly in females), and heroin intake positively correlated with total somatic signs at the 48 and 72 hr timepoints. Measures of hyperactivity and anxiety-like behavior increased by 16 and 48 hr, respectively. In Phase 2, symptoms were assessed at baseline, acute, and protracted (168 and 312 hr after self-administration) timepoints in a subset of male and female rats from Phase 1. The total number of somatic signs did not differ across timepoints, though females displayed significantly higher body temperature at all timepoints compared with males, indicating sex-specific protracted withdrawal symptomatology. These data provide a thorough characterization of rodent opioid withdrawal symptomatology after self-administration and abrupt discontinuation that serve as a foundation for future studies designed to mimic the human experience, and demonstrate the importance of characterizing acute and protracted withdrawal with sex-specificity in preclinical models of opioid self-administration. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Background Optimal treatment of buprenorphine precipitated opioid withdrawal (BPOW) is unclear. Full agonist treatment of BPOW is limited by buprenorphine's high-affinity blockade at mu-opioid receptors (μORs). Buprenorphine's partial agonism (low intrinsic efficacy) at μORs can limit the effectiveness of even massive doses once BPOW has begun. Adjunct medications, such as clonidine, are rarely effective in severe BPOW. Ketamine is an N-methyl-D-aspartate receptor antagonist with a potentially ideal pharmacologic profile for treatment of BPOW. Ketamine reduces opioid withdrawal symptoms independently of direct μOR binding, synergistically potentiates the effectiveness of buprenorphine μOR signaling, reverses (resensitizes) fentanyl induced μOR receptor desensitization, and inhibits descending pathways of hyperalgesia and central sensitization. Ketamine's rapid antidepressant effects potentially address depressive symptoms and subjective distress that often accompanies BPOW. Ketamine is inexpensive, safe, and available in emergency departments. To date, neither ketamine as treatment for BPOW nor to support uncomplicated buprenorphine induction has been described. Case description We report a case of an illicit fentanyl-using OUD patient who experienced severe BPOW during an outpatient low-dose cross taper buprenorphine induction (ie, "microdose"). The BPOW was successfully treated in the emergency department with a combination of ketamine (0.6 mg/kg intravenous over 1 hour) combined with high-dose buprenorphine (16 mg sublingual single dose); 3 days later he was administered a month-long dose of extended-release subcutaneous buprenorphine which was repeated monthly (300 mg). At 90 days the patient remained in treatment and reported continuous abstinence from fentanyl use. Conclusions This single case observation raises important questions about the potential therapeutic role of ketamine as a treatment for BPOW. BPOW is an important clinical problem for which there is currently only limited guidance and no universally accepted approach. Prospective study comparing the effectiveness of differing pharmacologic approaches to treat BPOW is urgently needed.

In the current opioid crisis, multimodal analgesic protocols should be considered to reduce or eliminate narcotic usage in the postoperative period. We assess the impact of bupivacaine liposome used along with a standard analgesia protocol following robotic inguinal hernia repair. A retrospective review of a prospectively maintained data including robotic inguinal hernia repairs (IHR) by two surgeons in the United States was performed. Within a multimodal analgesic protocol, local anesthetic was administered intraoperatively. One group received a mix of bupivacaine and bupivacaine liposome (BL), and one received standard bupivacaine (SB). Recovery room and home opiate doses were recorded. Primary outcomes included length of stay (LOS) and postoperative medication requirements. Statistical analysis was performed using Chi-square or Fisher's exact test and Mann-Whitney U test as appropriate. 122 robotic IHRs were included; 55 received BL and 67 received SB. Hospital LOS (hours) was reduced in the BL group (2.8 ± 1.1 vs 3.5 ± 1.2; p = 0.0003). There was no significant difference in recovery room parenteral MME requirements between the groups; however, BL group had less oral MME requirements (5.0 ± 6.5 MME vs. 8.1 ± 6.9 MME, p = 0.02). The BL group had a higher rate of zero opiate doses at home (44% vs 5%, p = 0.0005). Of those that did require opiates at home, there was a significant reduction in number of narcotic pills used by the BL compared to the SB group (median 1 vs 5, respectively; p

Background Bladder cancer disproportionally affects the communities. While it is the ninth most common cancer in the world, in some parts of Iran including Kerman province it is the most common cancer among men. This study aimed to determine potential risk factors of bladder cancer in Kerman province, Iran. Methods During February to July 2020, in this matched hospital-based case-control study, 100 patients with bladder cancer and 200 healthy individuals (matched in age and sex) were recruited. Socio-demographics status, occupational exposures, common diet, history of drug use and family history of cancer, were collected using a structured questionnaire. Bivariable and multivariable logistic regression were applied and crude and adjusted odds ratios (AOR) along with their 95% confidence intervals (95%CI) were calculated. Data were analyzed using Stata version 14 software. Results Opium consumption, cigarette smoking and low level of income were associated with increased chance of bladder cancer. Compared to never use, use of opium up to 18000 Gram -year was associated with increased chance of bladder cancer (AOR: 6; 95% CI =2.3, 15.5). The chance was higher among those who used opium more than 18,000 Gram - year (AOR: 11.3; 95% CI =2.3, 15.5). In comparison with never smokers, the chance of bladder cancer increased among those who smoked up to 20 pack-year cigarette) (AOR: 3.4; 95%CI= 1.3, 8.9) and those who smoke ≥ 20 pack-year (AOR: 15.8; 95% CI= 5.9, 42.4). Conclusions The observed strong dose-response association between opium consumption, cigarette smoking and bladder cancer highlights the need for extension of harm reduction programs especially in regions with high burden of disease.

The authors conducted a scoping review to survey the evidence landscape for studies that assessed outcomes of treating patients with opioid use disorder with methadone in office-based settings.Ovid MEDLINE and the Cochrane Database of Systematic Reviews were searched, and reference lists were reviewed to identify additional studies. Studies were eligible if they focused on methadone treatment in office-based settings conducted in the United States or other highly developed countries and reported outcomes (e.g., retention in care). Randomized trials and controlled observational studies were prioritized; uncontrolled and descriptive studies were included when stronger evidence was unavailable. One investigator abstracted key information, and a second verified data. A scoping review approach broadly surveyed the evidence, and therefore study quality was not rated formally.Eighteen studies of patients treated with office-based methadone were identified, including six trials, eight observational studies, and four additional articles discussing use of pharmacies to dispense methadone. Studies on office-based methadone treatment, including primary care-based dispensing, were limited but consistently found that stable methadone patients valued office-based care and remained in care with low rates of drug use; outcomes were similar compared with stable patients in regular care. Office-based methadone treatment was associated with higher treatment satisfaction and quality of life. Limitations included underpowered comparisons and small samples.Limited research suggests that office-based methadone treatment and pharmacy dispensing could enhance access to methadone treatment for patients with opioid use disorder without adversely affecting patient outcomes and, potentially, inform modifications to federal regulations. Research should assess the feasibility of office-based care for less stable patients.

Methadone (MTD) is a synthetic analgesic drug used for treating opioid dependence and effectively used clinically for patients with severe pain. The abuse of MTD may lead to poisoning, disorder in the central nervous system and even death. The regular monitoring of MTD in biological matrices including serum, plasma and urine samples is an effective way to control abuse of MTD. In this manner, the selection of analytical monitoring of MTD in biological matrices is of paramount importance. This study was conducted to review high-performance liquid chromatography (HPLC) techniques carried out on MTD and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in the biological samples during 2015-June 2021.

Substance abuse is one of the major behavioral problems in today's human society. One of the medical uses of drugs is to relieve the pain and suffering of patients. Today, due to the widespread use of narcotics and psychotropic drugs in the control and treatment of the disease and also its use among medical students, the present study aimed to determine the attitude and practice of medical students towards the use of narcotics and psychotropic drugs. The present study was a cross-sectional analytical study that was performed on 102 medical interns of Guilan University of Medical Sciences who were selected by available methods. To collect information, a researcher-made questionnaire was used which has three sections including a checklist of demographic information, attitude assessment questionnaire of medical students and performance assessment questionnaire. The mean age of the interns was 23.8±0.21 years. In the analysis of the results, it was found that there is a significant relationship between marital status and residence status with performance score. Based on the results of the present study, the level of students' knowledge about narcotics and psychotropic drugs among them is not at the desired level. Therefore, due to the lack of knowledge of medical students about the dangerous side effects of these drugs, education on the nature, symptoms, and side effects of psychotropic substances is recommended.

Opioid therapy has been the mainstay therapy of post-operative pain management in thoracic surgery patients. With the high incidence of chronic pain in thoracic surgery patients and adverse effects of opioids, we examined the safety and efficacy of cryoneurolysis as an adjunct for narcotic-free pain management in robotic-assisted thoracoscopic lobectomies. Ten consecutive patients undergoing robotic-assisted (DaVinci) pulmonary resection and cryoneurolysis were compared to ten patients managed without intraoperative cryoneurolysis. All patients received multimodal pain regimen including paravertebral blocks as per our institutional enhanced recovery pathway. Patients with chronic pain and chronic opioid use were excluded. We compared inpatient and outpatient opioid consumption measured in morphine equivalents (mme), incidence of opioid-free outpatient recovery, and adverse events. The two groups did not differ significantly in terms of baseline demographics. Both inpatient (88.13 vs 26.92 mme) and outpatient (118.5 vs 34.5 mme) use of narcotics were significantly lower in the cryoneurolysis group (p

The important role of mitochondria in maintaining normal brain cell function has been demonstrated in several neurodegenerative diseases where mitochondrial dysfunction is a prominent feature. Accumulating evidence indicates that opioids may induce neuronal cell death and inhibit neurogenesis, two factors that are dependent on normal mitochondrial function. The aim of the present study was to examine the effects of morphine, methadone, and fentanyl on MitoTracker-stained mitochondria. Cells from the neuroblastoma/glioma hybrid cell-line NG108-15 were seeded on 96-well cell culture plates and treated with MitoTracker for 30 min prior to opioid treatment. Morphine, methadone, and fentanyl were added at various concentrations and images of mitochondria were acquired every 30 min for four hours using a high-content imaging device. The parameters total mitochondrial area, mitochondrial network, as well as the number and mean area of mitochondrial objects were analyzed using automated image analysis. Methadone and fentanyl, but not morphine, decreased the mitochondrial network, the number of mitochondrial objects, and increased the mean area of mitochondrial objects. Both methadone and fentanyl altered mitochondrial morphology with no effects seen from morphine treatment. These data suggest that methadone and fentanyl impact mitochondrial morphology negatively, which may be associated with neuronal cell death.

Intercostal nerve cryoablation (INCA) coupled with surgical stabilization of rib fractures (SSRF) has been shown to reduce post-operative pain scores but at what monetary cost. We hypothesize that in-hospital outcomes improve with the addition of INCA to SSRF and potential increased hospital charges are justified by patient benefits.Multi-institutional, retrospective review of patients undergoing SSRF with and without INCA over an 8-year period. Institutions involved were Level II or higher trauma centers. Basic demographics were obtained. Patients were included if SSRF was performed during the index hospitalization. Primary outcomes included total hospital length of stay (HLOS) and HLOS after SSRF, total hospital charges (HC), HC the day of surgery and HC after surgery. Secondary outcome included total narcotic consumption in morphine milliequivalents (MME) after SSRF. Mann-Whitney U test was used for analysis. Statistical significance p 0.05.136 patients analyzed; 92 underwent SSRF only and 44 underwent SSRF with INCA. Demographics were similar between groups. Number of ribs stabilized was comparable; 4.78 ± 1.64 SSRF only and 4.73 ± 1.66 SSRF with INCA (p = 0.463). Median ISS [16 (IQR 11.5-16) SSRF only and 14 (IQR 9-18.75) SSRF with INCA (p = 0.463)] was not statistically different. The INCA group showed a decrease in the median total HLOS, 9 versus 10 days (U = 1517.5, p = 0.026) and HLOS after SSRF, 4 versus 6 days (U = 1217.5, p 0.001). HC the day of surgery were higher for the INCA group, $93,932 versus $71,143 (U = 1106, p 0.001). However, total HC were similar between groups and total HC after SSRF was significantly less for the INCA group, $10,556 versus $20,269 (U = 1327, p = 0.001). Total median narcotic use after SSRF was significantly less for the INCA group, 88.6 vs 113.7 MME (U = 1544.5, p = 0.026).SSRF with INCA is safe and does not increase overall HC with the added benefit of decreased HLOS post-operatively and decreased narcotic consumption.

Background Sub-chronic exposure to morphine can increase the potency of propofol but decrease the potency of ketamine by unknown mechanisms. The present study was designed to investigate the effects of sub-chronic exposure to morphine on the expression of neurotransmitter receptor subunits, which might contribute to the potency changes of ketamine and propofol in vivo. Methods Sub-chronic exposure to morphine was established by administering subcutaneous injections of morphine for 5 consecutive days. The median effective dose (ED50) of ketamine and/or propofol was measured on day 1, day 3, day 7 and day 15, after the last morphine dosage. Mice in the sham group received an equal volume of normal saline. The expressions of N-methyl D-aspartate (NMDA) receptor and γ-aminobutyric acid A (GABAA) receptor subunits in the forebrain were measured. Knockdown or overexpression of a subunit was used to determine the causality between the change in anesthetic potency and the expression of an identified receptor subunit. Results After sub-chronic exposure of mice to morphine, the expression of NMDA receptor 1 (NR1) was most elevated in the forebrain on day 1 (P Conclusions Sub-chronic exposure to morphine can differentially modulate the expressions of NR1 and GABAARβ3 in mice, which may contribute to the changes in ED50 of ketamine and propofol in vivo.

Background As the obesity epidemic worsens, anesthesiologists should expect to see more obese patients presenting for surgical procedures. Opioids cause respiratory depression, which has caused complications in patients with obstructive sleep apnea. Opioids can also cause nausea, prolonging the time that patients spend in the postanesthesia care unit. Ketamine is a potential analgesic alternative that may have advantages to narcotics in the bariatric population. Objectives To determine whether an intraoperative ketamine infusion would reduce postoperative narcotic use in patients during the first 48 hours after laparoscopic gastric bypass. Setting Major academic medical center. Methods There were 54 participating patients. The intervention group (n = 27) was randomized to receive 100 μg of fentanyl with anesthesia induction, then a 20-mg bolus of ketamine, followed by a 5 μg/kg/min intraoperative ketamine infusion starting after anesthesia induction and ending after wound closure commenced. The control group (narcotic only, n = 27) also received 100 μg of fentanyl at anesthesia induction and intraoperative boluses of fentanyl at the discretion of the anesthesia team, with .3 mg of hydromorphone administered approximately 45 minutes before the completion of surgery. Results At 24 hours, the mean morphine-equivalent units (MEUs) were 12.7 (standard deviation [SD], 9.9; 95% confidence interval [CI], 8.8–16.6) for the ketamine group (n = 28) and 16.5 (SD, 9.8; 95% CI, 12.6–20.4) for the control group (n = 28). At 48 hours, the MEUs were 16.7 (SD, 12.0; 95% CI, 11.9–21.4) for the ketamine group and 22.7 (SD, 14.9; 95% CI, 16.8–28.6) for the control group. Cumulative MEUs for 24 hours (P = .039) and 48 hours (P = .058) postoperatively were lower in the ketamine group compared with the narcotic-only (control) group, although the difference at 48 hours did not reach statistical significance. Compared with the narcotic-only group, the ketamine group used 26% fewer MEUs after 24 hours and 31% fewer MEUs after 48 hours. This difference can mostly be attributed to group differences during the first 6 hours after surgery. Conclusions Ketamine successfully reduced the amount of opioids required to control bariatric patients’ pain at 24 hours postoperatively, but not over the 48-hour postoperative period.

Introduction The optimal dosing of post-operative total knee arthroplasty (TKA) narcotics is unclear. We report on the average narcotic usage in a group of patients treated with an identical multimodal pain protocol following TKA. Materials and methods 49 patients undergoing TKA participated in the survey. Patients with pre-op narcotic use, recent prior total joint arthroplasty or study refusal were excluded. All patients received a spinal anesthetic. No pre-surgery narcotics were given. All received an identical local infiltrative anesthetic combination along with a multimodal pain protocol. Patients were placed into an identical rapid rehab program. Narcotic usage during hospitalization was recorded in morphine equivalent doses (MED). Patients were given a journal to record their daily narcotic utilization. Results Pre-operative pain scores of the excluded groups had slightly higher but clinically insignificant differences compared to the study group. In the hospital, POD1 study group daily MED averaged 28 (range 0–110). POD2 had an average of 33.6 and POD 3 daily usages averaged 28.6 (range 0–100). By the end of week two, the average daily use was 19.2 and 24% patients were off all narcotics. By the end of week four, the average daily usage was 7.5 and 63% of patients were off all narcotics. By 8 weeks, there were no patients still taking narcotics. KSS averaged 76.9 (range 51–97) at the 6 week visit, and 94.2 at the 3-month visit (range 72–100). Summary This study documents the average needs of an average TKA patient treated with modern pain protocols. The majority of these patients were off narcotics by week four.

The co-association of benzodiazepines and opioids is associated with an increased risk of overdose, death, and poorer psychosocial prognosis. The aim of this study is to characterize the prevalence, pattern of use, and primary clinical outcomes in benzodiazepines users in a public opioid maintenance treatment unit.We conducted a cross-sectional study involving 236 patients treated with opioid substitutes (methadone and buprenorphine). We conducted a descriptive, bivariable, and multivariable analysis to determine clinical differences between benzodiazepines users and non-users.The prevalence of consumption of benzodiazepines was 25.4% (60). The benzodiazepines were obtained with a medical prescription (49.8%) or on the black market (42.6%). The most prescribed benzodiazepine was diazepam (29.1%), and the main reasons were to relieve insomnia (27.7%) or anxiety (26.9%) and to enhance the psychoactive effects of other drugs (19.7%). Regarding the clinical outcomes, we highlight: a very high prevalence of hepatitis C (51.7%); severe ongoing consumption of psychoactive drugs (73.7%); and a high rate of depression and anxiety (60%), significantly higher in the benzodiazepines-user group. In the multivariable analysis of benzodiazepine use, we found alcohol consumption (OR 0.482; IC 95% 0.247, 0.238) had a negative association and having hepatitis C (OR 2.544, IC 95% 1.273, 5.084) or anxiety symptoms (OR 5.591; IC 95% 2.345, 13.326) had positive associations.Our results suggest the BZD users had a complex drug addiction problem and underline the importance of adequately addressing BZD use, contemplating psychological and psychiatric approach in this particular population.Past or current use of benzodiazepines is associated with poor clinical and psychiatric outcomes. A multidisciplinary approach with a focus on infectious diseases and mental health is critical in order to enhance the treatment effectiveness and overall prognosis.Introdução: A co-associação entre benzodiazepinas e opióides associa-se a risco aumentado de overdose, morte e pior prognóstico psicossocial. Pretendemos determinar a prevalência, o padrão de consumo e as principais co-morbilidades do uso de benzodiazepinas, em utentes sob tratamento de manutenção opióide. Material e Métodos: Conduzimos um estudo transversal, envolvendo 236 doentes tratados com substitutos opióides (metadona e buprenorfina). Realizou-se uma análise descritiva, bivariável e multivariável das características clínicas entre os usuários de benzodiazepinas e os não-usuários de benzodiazepinas. Resultados: A prevalência do uso de benzodiazepinas foi de 25,4% (60). A obtenção de benzodiazepinas foi através de prescrição médica (49,8%) ou mercado negro (42,6%). A substância mais prescrita foi o diazepam (29,1%), e as principais razões para a toma foi insónia (27,7%), ansiedade (26,9%), e para potenciar os efeitos psicoativos de outras drogas (19,7%). No que respeita aos resultados clínicos sublinhamos: prevalência elevada de hepatite C (51,7%); elevado consumo continuado de substâncias psicoativas (73,7%); elevada taxa de depressão e ansiedade (60%), significativamente mais elevada nos utilizadores de benzodiazepinas. Na análise multivariável para o uso de benzodiazepinas, verificámos que o consumo de álcool (OR 0,482; IC 95% 0,247, 0,238) tem associação negativa; a hepatite C (OR 2,544; IC 95% 1,273, 5,084) e a ansiedade (OR 5,591; IC 95% 2,345, 13,326) tiveram associações positivas. Discussão: Os resultados obtidos sugerem que os utilizadores de BZD têm um problema complexo de dependência de drogas e sublinham a importância de abordar adequadamente o uso de BZD, contemplando uma abordagem psicológica e psiquiátrica nesta população em particular. Conclusão: O uso de benzodiazepinas, no passado ou atualmente, associa-se a piores indicadores físicos e psiquiátricos. A abordagem multidisciplinar com foco nas doenças infeciosas e na saúde mental é uma necessidade crítica para a efetividade do tratamento e prognóstico global.

BackgroundGuidelines advise for more than 20 years to use occlusive plastic wraps for temperature management during delivery room care but data on efficacy of different types of wrap are still scarce.MethodsA random sample of seven different types of plastic wrap was tested using prewarmed aluminium blocks.ResultsThe most effective wrap increased the time to cool by 2°C by one-third for the core and by 100% for the surface whereas the least effective wrap led to even faster heat loss compared with no wrap at all. The least effective wrap concerning all capacities tested was made from polyurethane that contains potentially toxic and narcotic monomers. Heat and water retention did not correlate to wrap thickness.DiscussionLarge differences in heat and water retention capacity warrant a careful choice of the type of wrap as some might be counterproductive. Wraps containing polyurethane should not be used.

Early life stress (ELS) disrupts brain development and subsequently affects physical and psychological health. ELS has been associated with an increased risk of relapse and inadequate treatment response in addicted patients. The current study was designed to find the effect of ELS on the rewarding effect of morphine and cannabinoid and their interaction. Pregnant female Wistar rats were used in this study. On postnatal day 2 (PND2), pups were separated from their mothers for 3 hr daily. This procedure was repeated every day at the same time until PND 14. The control group was kept in the standard nesting way with their mothers. The adult male offspring of maternal separated (MS) and standard nested (SN) rats were used. Using conditioned place preference task (CPP), the rewarding effect of morphine (0.75, 1.25, 2.5, and 5 mg/kg) was evaluated in both MS and SN groups. Besides, the rewarding effect of cannabinoids was investigated using the administration of CB1 receptor agonist (ACPA, 0.25, 0.5, 1 µg/rat) and inverse agonist (AM-251, 30, 60, and 90 ng/rat) in the nucleus accumbens (NAc). To evaluate the interaction between NAc cannabinoidergic system and morphine, the noneffective dose of ACPA and AM-251 were administered with a noneffective dose of morphine (0.75 mg/kg) on both MS and SN animals. Obtained results indicated that MS groups had a leftward shift in the rewarding effect of morphine and conditioned with low doses of morphine. However, they had a rightward shift in the rewarding effect of cannabinoids. In addition, coadministration of noneffective doses of morphine and ACPA potentiate conditioning in both MS and SN groups. Previous evidence shows that ELS induced changes in the brain, especially in the reward circuits. Here, we demonstrated that MS animals are more sensitive to the rewarding effect of morphine compared with SN animals. In addition, ELS disrupts the cannabinoid system and affect the rewarding effect of cannabinoids.

Chronic intrauterine exposure to psychoactive drugs often results in neonatal opioid withdrawal syndrome (NOWS). When nonpharmacologic measures are insufficient in controlling NOWS, morphine, methadone, and buprenorphine are first-line medications commonly used to treat infants with NOWS because of in utero exposure to opioids. Research suggests that buprenorphine may be the leading drug therapy used to treat NOWS when compared with morphine and methadone. Currently, there are no consensus or standardized treatment guidelines for medications prescribed for NOWS. Opioids used to treat NOWS exhibit large interpatient variability in pharmacokinetics (PK) and pharmacodynamic (PD) response in neonates. Organ systems undergo rapid maturation after birth that may alter drug disposition and exposure for any given dose during development. Data regarding the PK and PD of opioids in neonates are sparse. Pharmacometric methods such as physiologically based pharmacokinetic and population pharmacokinetic modeling can be used to explore factors predictive of some of the variability associated with the PK/PD of opioids in newborns. This review discusses the utility of pharmacometric techniques for enhancing precision dosing in infants requiring opioid treatment for NOWS. Applying these approaches may contribute to optimizing the outcome by reducing cumulative drug exposure, mitigating adverse drug effects, and reducing the burden of NOWS in neonates.

Background Currently, there are no national guidelines for antenatal drug testing. At Colchester Hospital, we use a strategy of screen-only using point-of-care testing to detect illicit drug use in pregnancy. To determine the suitability of this approach, we have compared the results of urine analysis by point-of-care testing with another NHS specialist clinical toxicology service that uses confirmation mass spectrometry. Methods A total of 482 anonymized random urine specimens from antenatal clinics were tested for six drug classes: amphetamine, benzodiazepines, buprenorphine, cocaine, methadone and opiates using the Alere™ Drug Screen Urine Test Cup. The manufacturer’s claims for positive cut-off and result stability were verified using spiked blank urine. Confirmatory testing was performed using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) for detection of 26 individual drugs. Results Of 473 urine samples with adequate volume for point-of-care screening, 4.4% tested positive: 19 opiate and 2 cocaine. Concordance between point-of-care screening and UPLC-MS/MS confirmation was 97.9% for all drugs and 78.9% for opiates. Using spiked urine, only positive results for opiates were stable when read up to the manufacturer’s recommended time of 60 min. Conclusions The key advantages of using point-of-care devices to detect drug use in pregnancy are that is convenient and cheap. However, the clinical utility of point-of-care testing is limited by its poor sensitivity. Best practice is to confirm results using a more specific and sensitive method. As a result of this study, we are now reviewing our own procedures to consider introducing routine confirmation by mass spectrometry.

Purpose Tumour growth and the formation of metastases are essential elements in the progression of cancer. The centre of treatment is the surgical resection of primary solid tumours. But even if the tumour can be removed without microscopic residual cells, local recurrences and distant metastases occur and determine the patient’s fate. During the operation, tumour cells are shed from the primary tumour and released into the circulation. These circulating tumour cells might play an important role in the formation of new tumour sites. Therefore, a functional innate and adaptive immune system is essential, especially in this perioperative period. Anaesthesia influences consciousness and pain perception and interacts directly with the immune system and tumour cells. Methods Review of the current literature concerning intra- and postoperative anaesthetic decisions and tumour progression. Results There are beneficial aspects for patient survival associated with total intravenous anaesthesia, the use of regional anaesthetics and the avoidance of allogeneic red blood cell transfusions. Alternatives such as irradiated intraoperative blood salvage and preoperative iron supplementation may be advantageous in cases where transfusions are limited or not wanted. The immunosuppressive properties of opioids are theoretical, but strong evidence to avoid them does not exist. The application of nonsteroidal anti-inflammatory drugs and postoperative nausea and vomiting prophylaxis do not impair the patient’s survival and may even have a positive effect on tumour regression. Conclusion Anaesthesia does play an important part in the perioperative period in order to improve the cancer-related outcome. Further research is necessary to make more concrete recommendations.

Opioid use disorder affects over 2 million Americans with an increasing number of deaths due to overdose from the synthetic opioid fentanyl and its analogs. The Food and Drug Administration–approved opioid receptor antagonist naloxone (e.g., Narcan) is used currently to treat overdose; however, a short duration of action limits its clinical utility. Methocinnamox (MCAM) is a long-lasting opioid receptor antagonist that may reverse and prevent the ventilatory-depressant effects of fentanyl. This study compared the ability of naloxone (0.0001–10 mg/kg) and MCAM (0.0001–10 mg/kg) to reverse and prevent ventilatory depression by fentanyl and compared the duration of action of MCAM intravenously and subcutaneously in two procedures: ventilation and warm-water tail withdrawal. In male Sprague-Dawley rats (N = 8), fentanyl (0.0032–0.178 mg/kg, i.v.) decreased minute volume in a dose- and time-dependent manner with a dose of 0.178 mg/kg decreasing V(E) to less than 40% of control. MCAM and naloxone reversed the ventilatory-depressant effects of 0.178 mg/kg fentanyl in a dose-related manner. The day after antagonist administration, MCAM but not naloxone attenuated the ventilatory-depressant effects of fentanyl. The duration of action of MCAM lasted up to 3 days and at least 2 weeks after intravenous and subcutaneous administration, respectively. MCAM attenuated the antinociceptive effects of fentanyl, with antagonism lasting up to 5 days and more than 2 weeks after intravenous and subcutaneous administration, respectively. Reversal and prolonged antagonism by MCAM might provide an effective treatment option for the opioid crisis, particularly toxicity from fentanyl and related highly potent analogs. SIGNIFICANCE STATEMENT: This study demonstrates that like naloxone, methocinnamox (MCAM) reverses the ventilatory-depressant effects of fentanyl in a time- and dose-related manner. However, unlike naloxone, the duration of action of MCAM was greater than 2 weeks when administered subcutaneously and up to 5 days when administered intravenously. These data suggest that MCAM might be particularly useful for rescuing individuals from opioid overdose, including fentanyl overdose, as well as protecting against the reemergence of ventilatory depression (renarconization).

This article examines injectable Opioid Agonist Treatment (iOAT), in which patients suffering from long-term, treatment refractory opioid use disorder (OUD) are prescribed injectable diacetylmorphine, the active ingredient of heroin. While iOAT is part of the continuum of care for OUD in some European countries and in some parts of Canada, it is not an available treatment in the United States. We suggest that one reason for this situation is the belief that a genuine treatment for substance use disorder cannot prescribe the same substance as that used. We examine possible rationales for this belief by considering four combinations of views on the constitutive causal basis of substance use disorders and the definition of effective treatment. We show that all but one combination counts iOAT as a genuine treatment and that there are good reasons to reject the one that does not. Specifically, we claim that medical interventions, such as iOAT, that significantly reduce the severity of a disorder deserve to be categorized as effective treatments and regarded as such in practice.

Background: Investigations into neurochemical mechanisms of opioid addiction are difficult due to the complexity of behavior and multiplicity of involved neurotransmitter and hormonal systems. The aim of this study was to examine the benefits of structured analysis of these mechanisms using the framework of the neurochemical model Functional Ensemble of Temperament (FET) and the example of maternal behavior under the condition of opium consumption in pregnancy. The FET differentiates between (a) endurance, (b) speed of integration, and (c) emotionality aspects of behavior suggesting that these systems are differentially regulated by (a) serotonin-neuropeptides-brain-derived neurotrophic factor (BDNF), (b) dopamine-GABA, and (c) opioid receptor systems, correspondingly. The FET also suggests that mu-opioid receptors (MORs) binding the endorphines (including opium’s ingredient morphine) have a stronger association with regulation endurance, whereas delta-OR have a stronger association with integration of behavior and kappa-OR – with the perceptual mobilization seen in anxiety. To test the predictions of this model, we compared the impact of massive MOR dysregulation on 3 behavioral aspects of behavior and on serotonin, BDNF, and corticosterone levels. Methods: The study used 24 female white Wistar rats which were randomly divided into (1) control group: pregnant rats without any intervention; (2) opium-exposed group: animals that were exposed to opium during pregnancy and after the delivery until the end of the study. At the end of the study, the levels of BDNF, serotonin (5-HT) in the hippocampus of the mother’s brain, and serum corticosterone, as well as 12 aspects of the maternal behavior were evaluated. The differences between control and experimental groups were assessed using the t test for independent samples. Results: The BDNF and serotonin concentrations in the hippocampus of the mother rats which were exposed to opium were lower than in the control group; the mean corticosterone in exposed mothers was higher than in the control group. Behaviorally, opium-consuming mothers showed lower endurance in 4 distinct behavioral categories (nesting, feeding, grooming, and retrieval) than the mothers in the control group. Ease of integration of behavior was affected to a lesser degree, showing a significant effect only in 1 out of 5 applied measures. Self-grooming, seen as an emotionality-related aspect of behavior, was not affected. Conclusion: Opium exposure during pregnancy in our experiment primarily reduced the endurance of rat’s maternal behavior, but the speed of integration of behavioral acts was less affected. This negative impact of opium on endurance was associated with a decrease of BDNF and serotonin levels in the hippocampus and an increase in corticosterone level in opium-consuming mothers. There is no effect of opium exposure on self-grooming behavior. This pattern supports the FET hypothesis about the role of 5-HT and BDNF in endurance, differential regulation of endurance, integrative and emotionality aspects of behavior, and differential association of the MOR system with endurance aspects, in comparison with kappa- and delta opioid receptors.

Background Extended length of stay (LOS) after surgery is costly to the health care system and can be distressing to the patient and family. Previous studies have shown conflicting data on factors associated with increased LOS and are limited by using multiple different surgeries. Our study seeks to analyze factors that are associated with extended LOS. Objective The objective of this study was to analyze data from 2 Food and Drug Administration trials of one-level cervical surgery to identify risk factors that are associated with extended LOS in the hospital. Methods Extended LOS was defined to be >1 day. Patients with LOS ≤1 day were compared with those with LOS >1 day. Data from the BRYAN and Prestige ST Trial (n = 1004) were analyzed. Subjects with LOS ≤1 day were compared with those with LOS >1 day. Variables analyzed for their effect on LOS included demographic characteristics, patient-reported outcome measures, preoperative medical conditions, preoperative neurologic status, and intraoperative factors. Results A total of 912 patients (90.84%) had an LOS ≤1 day and 92 patients (9.16%) had an extended LOS >1 day. Weak narcotic medication use (P = 0.021; odds ratio [OR], 1.72), Nurick gait (P = 0.019; OR, 1.796), and operative time (P Conclusions Nurick gait, operative time, and history of weak narcotic use are associated with extended hospital stay. These data may be useful in preoperatively counseling patients, developing quality metrics for hospitals, and helping create financial models for cost/diagnosis-related group reimbursement for single-level anterior cervical surgery.

Objective:To evaluate rates of presentation, neuroimaging, therapies, and serious neurologic disorders (SNDs) among children and young adults presenting to the emergency department with headache.Methods:We performed a cross-sectional study of a nationally representative sample survey of visits to US emergency departments between 2002 and 2017. We identified encounters of patients ≤25 years old with chief complaint of headache. We report the rates of presentation, imaging, and treatments and report proportions having concomitant diagnoses of serious neurologic disorders.Results:Among encounters ≤25 years, 2.0% had a chief complaint of headache, with no change in the yearly rates of encounters ( P = .98). Overall, 20.8% had a head computed tomography (CT), with a reduction in performance between 2007 and 2016 ( P < .01). One-quarter (25.2%, 95% confidence interval [CI] 22.2%-28.3%) were given narcotics and 2.5% (95% CI 1.7%-3.2%) had serious neurologic disorders.Conclusion:Overall, 2.0% of emergency department encounters among patients ≤25 years were for headache, with low rates of serious neurologic disorders. CT use appeared to be declining.

Objective: To track the trends and patterns of psychoactive substance abuse among medical students. Study Design: Cross-sectional questionnaire based study. Place and Duration of Study: Medical Colleges and Universities of Lahore, from Aug to Sep 2019. Methodology: Total 200 medical students from Medical Colleges and Universities were included. The data wereanalyzed and computed using SPSS-21. Frequencies and percentages related to all the factors were computed. Results: Among study participants, 96 (48%) of males and 104 (52%) of females with 154 (77%) of these students belong to 21-25 years of age group. The observed prevalence of substance abuse among students was 42 (21%). Joy seeking and a friend’s offer was the initiation of psychoactive substance use among these students. Tobacco was the most highly consumed substance among students, followed by marijuana. Besides, the results also revealed that students also consumed cocaine and methamphetamine. Among 21% abusers, 4 (9%) and 5 (11%) of the students experienced side effects and withdrawal symptoms respectively. Conclusion: The increasing consumption of tobacco and indulgence in psychoactive drugs are concerning issues because of uncontrolled consumption can cause serious brain damage. Academic burden and stress are the mediators of drug abuse among students. Therefore, stress management training and workshops should be conducted in institutes.

Multimodal, narcotic-sparing analgesic strategies are an important part of enhanced recovery after surgery protocols. Within such protocols, regional anesthetics have proven to be superior to narcotics.This study aimed to evaluate the impact of the transversus abdominis plane block within an enhanced recovery after surgery protocol on length of stay.A retrospective analysis of patients who underwent colorectal surgery in 2015 to 2016 was completed. The primary end points for this analysis were total length of stay and total narcotics consumed during hospitalization. Length of stay and total narcotic use were compared for patients who received a transversus abdominis plane block versus those that did not.The data were obtained from the data warehouse of a university teaching hospital.This study took place at a university teaching hospital.The patients were 18 years or older.The primary outcomes measured were length of stay and the total narcotics used.A total of 347 patients underwent colorectal procedures under the enhanced recovery protocol. Among these, 186 (54%) received a transversus abdominis plane block. Overall, the mean length of stay was 5.8 days (SD ±5.6), and median length of stay was 4 days. These values compare to a mean length of stay of 9.6 days and median length of stay of 7 days before implementing the enhanced recovery protocol. Patients who received a transversus abdominis plane block had a mean length of stay of 5.1 days compared to 6.6 days for those who did not receive one (p0.01). Patients who received a transversus abdominis plane block consumed 736.5 morphine milligram equivalents of opioids compared to 1150.3 morphine milligram equivalents of opioid consumed by those without a transversus abdominis plane block (p0.05), a 36% decrease in opioid use. When comparing patients who had a mean length of stay of 4 days with those whose length of stay was4 days, there was an 80% decrease in opioid use. The readmission rate was 7.8%.The lack of randomization of patients was a limitation of this study.The use of transversus abdominis plane block in the setting of a well-structured enhanced recovery protocol was associated with a statistically significant decrease in length of stay by 1.5 days and a 36% decrease in narcotic use. See Video Abstract at http://links.lww.com/DCR/B432.ANTECEDENTES:La estrategia analgésica multimodal que consume poco medicamento de tipo narcótico es parte importante en los protocolos de recuperación mejorada postoperatoria. Dentro de dichos protocolos, los anestésicos regionales han demostrado ser superiores a la administración de medicamentos narcóticos.OBJETIVO:Estudiar el impacto del bloqueo del plano muscular de los transversos del abdomen sobre la duración de la estadía dentro de un protocolo de recuperación mejorada postoperatoria.DISEÑO:Se realizó un análisis retrospectivo de los pacientes que se sometieron a cirugía colorrectal entre 2015-2016. Los criterios principales de valoración en el presente análisis fueron la duración total de la estadía y el total de medicamentos narcóticos consumidos durante la hospitalización. Se comparó la duración de la estadía y el uso total de narcóticos en los pacientes que recibieron un bloqueo anestésico del plano muscular de los transversos del abdomen con los que no lo recibieron.FUENTE DE DATOS:Banco de datos de un hospital universitario docente.AMBIENTE:Hospital Universitario Docente.PACIENTES:Adultos desde los 18 años o mayores.PRINCIPALES MEDIDAS DE RESULTADO:Duración de la estadía, cantidad total de medicamentos narcóticos administrados.RESULTADOS:Un total de 347 pacientes se sometieron a procedimientos colorrectales bajo el protocolo ERAS. Entre ellos, 186 (54%) recibieron un bloqueo del plano muscular de los transversos del abdomen. En la globalidad, la duración media de la estadía fué de 5,8 días (DE ± 5,6) y la duración media de la estadía fué de 4 días. Estos resultados fueron comparados con la estadía media de 9,6 días y una estadía media de 7 días antes de implementar el protocolo ERAS. Los pacientes que recibieron un bloqueo del plano muscular de los transversos del abdomen tuvieron una estadía media de 5,1 días en comparación con los 6,6 días de los que no recibieron el mencionado bloqueo (p0,01). Los pacientes que recibieron el bloqueo del plano muscular consumieron 736,5 miligramos de morfina o su equivalente en opioides, comparados con los 1150,3 de aquellos sin bloqueo del plano muscular (p0,05) lo que significó una disminución del 36% en la administración de opioides. Al comparar los pacientes que tuvieron una estadía media de 4 días con aquellos cuya estadía fue mayor a 4 días, se evidenció una disminución en el 80% de la administración de opioides. La tasa de reingreso fue del 7,8%.LIMITACIONES:Estudio sin sin aleatorización de pacientes.CONCLUSIÓN:El bloqueo anestésico del plano muscular de los transversos del abdomen dentro un contexto protocolar tipo ERAS o de recuperación mejorada bien estructurada, se asoció con la disminución estadísticamente significativa de la duración de la estadía en 1,5 días y una disminución del 36% en la administración de medicamentos narcóticos. Consulte Video Resumen en http://links.lww.com/DCR/B432.

INTRODUCTION No accepted standard exists regarding the number of opioids to prescribe after many surgical procedures, and previous literature has indicated that the number of opioids prescribed influences the total number of pills consumed. The goal of this study was to investigate whether prescribing less opioids after hip arthroscopy results in less total postoperative utilization without compromising analgesia and identify risk factors for increased use. METHODS This study randomized 111 patients to receive either 30 or 60 tablets of hydrocodone/acetaminophen 10 to 325 mg after hip arthroscopy. Demographic information, pain instruments, and scores including International Hip Outcome Tool (iHOT-12) were collected preoperatively. Postoperatively, patients were contacted over the course of 3 weeks to determine their Numeric Pain Rating Scale scores, total number of tablets taken/leftover, and the last day that they required narcotic pain medications, which were calculated and compared for each group. Preoperative variables that increased the risk of higher narcotic pain medication requirements were assessed. RESULTS Patients in the 60-tablet group had significantly more tablets leftover than the 30-tablet group (49.5 versus 22.0, P < 0.001) and had no significant difference in Numeric Pain Rating Scale scores at 24 hours, 48 hours, or final follow-up. The 30- and 60-tablet groups demonstrated no significant difference in average tablets consumed (9.2 and 10.5, P = 0.60), respectively. Risk factors for increased postoperative opioid use included preoperative opioid use (B = 12.62, 95% confidence interval [CI], 6.28-18.96, P < 0.001) or muscle relaxant use (B = 22.45, 95% CI, 7.59-37.31, P < 0.0036) within 1 year preoperatively. Preoperative iHOT-12 scoring also significantly predicted postoperative opioid consumption in this cohort (B = -0.25, 95% CI, -0.45 to -0.036, P < 0.022). CONCLUSION The number of leftover tablets after hip arthroscopy can be significantly reduced by prescribing 30 tablets compared with 60 tablets without affecting postoperative pain control. Total tablets prescribed in this cohort did not affect total opioid utilization. Preoperative factors including opioid or muscle relaxant use and iHOT-12 scores can be used to predict postoperative opioid requirements.

In forensic contexts of advanced decomposition, when conventional matrices are no longer available for toxicological analyses, finding alternative matrices is necessary. The skeleton, which is fundamental for anthropologists and geneticists, could be useful also for toxicological purposes. The present study aims to examine what kind of information toxicological analysis performed on bones (the cranium and the ribs) in different states of preservation could provide to the forensic practitioner. Thirty cadavers with known pharmacological history, subjected to forensic autopsy at the Institute of Legal Medicine of Milan, were selected. Rib and cranium samples were collected from each body and separated into two parts in order to create two different states of preservation: One was cleaned from soft tissues and analyzed as a well-preserved bone sample; the other was submitted to a long maceration process, simulating complete skeletonization. All specimens were then processed with accelerated solvent extraction and the eluates analyzed using Q-Exactive™ Orbitrap™ Mass Spectrometer. The analysis of blood and skeletal matrices showed positive results for the tested substances in 63% of cases, mainly benzodiazepines, antidepressants, and drug abuse. Significant Pearson correlations were observed between non-macerated vs. macerated bone samples: r = 0.79 for rib samples, r = 0.61 for cranium samples, and r = 0.69 for all bone samples. As a consequence, the positive results confirm the potential of the bone tissue as an alternative matrix in forensic toxicology, even in cases of extremely decomposed bodies. This study also highlighted important elements for reconstructing the biological profile in cases of forensic anthropological concern.

Background: Orthopaedic surgeons must consider their postoperative pain management strategies to minimize harm from prescription opioid use. Patients often reference their pain threshold to predict how they will tolerate surgical pain and the need for postoperative analgesia, but the direct relationship between these factors has not yet been studied. The purpose of this study was to determine the relationship between patients’ self-reported pain tolerance and prescription opioid usage after foot and ankle surgery. Methods: This is a retrospective follow-up of a prospective cohort study of adult patients who underwent outpatient foot and ankle surgeries. Patient and procedural demographics, opioid pills dispensed, and opioid pills consumed by the first postoperative visit were obtained. Patients were contacted at a mean of 13.1 ± 4.0 months postoperatively and asked to respond to the qualitative statement “Pain doesn’t bother me as much as it does most people.” Patients were also asked their quantitative pain threshold (0-100), with 0 being “very pain intolerant” and 100 being a “very high pain tolerance,” as well other questions regarding past surgical and narcotic consumption history. Results: Of the 700 survey respondents, the average age was 50.9 years and 34.7% were male. Bivariate analysis determined that predictors of lower postoperative opioid consumption included higher quantitative ( P = .047) and qualitative ( P = .005) pain tolerance scores. Multivariate analysis for the entire cohort demonstrated that higher qualitative pain threshold was associated with lower postoperative opioid consumption ( P = .005) but this did not meet statistical significance as an independent predictor of the top quartile of pill consumers. Conclusion: Assessment of both qualitative and quantitative score of patients’ pain threshold prior to surgery may assist the surgeon in tailoring postoperative pain control. Additionally, asking this question can create an opportunity for educating patients regarding responsible utilization of narcotic medication. Levels of Evidence: Level III

Background Opioids have long been used as an effective form of analgesia for pain in the postoperative setting; however, their addictive potential and associated complications have become a detriment. There has been an increasing movement to decrease opioid prescribing. Objective The aim of this study was to look at common bariatric surgery procedures at a single institution and compare opioid usage before and after the implementation of a multimodal pain regimen. Setting Community program, hospital-employed, and private practice, United States. Methods Six hundred twelve laparoscopic gastric bypass and laparoscopic sleeve gastrectomy patients were included in this single-institution retrospective cohort study. Data were obtained from chart review. Comparison was made between patients from 2016 and patients from a 3-month period in 2017 when the new pain management protocol had been instituted. Results The postoperative opioid usage of 516 patients from 2016 was compared with that of 96 patients from a 3-month period in 2017 after initiating the new pain management protocol. The mean intravenous hydromorphone usage of the control group, 16.0 ± 14.6 morphine milligram equivalent (or 4.0 mg ± .2), over the postoperative inpatient stay decreased to 7.3 ± 6.7 morphine milligram equivalent (or 1.8 mg ± .2) in the study group. This represents a 55% decrease. The study group did show less 30-day postoperative complications compared with the control, 1.04% and 2.13%, respectively, although this was not statistically significant. Conclusion A multimodal pain regimen is an effective way to cut opioid usage with no statistical difference in overall 30-day complications.

Cytochrome P450 2D (CYP2D) mediates the activation and inactivation of several classes of psychoactive drugs, including opioids, which can alter drug response. Tramadol is a synthetic opioid with analgesic activity of its own as well as being metabolically activated by CYP2D to O-desmethyltramadol (ODMST) an opioid receptor agonist. We investigated the impact of brain CYP2D metabolism on central tramadol and ODSMT levels, and resulting analgesic response after oral tramadol administration in rats. CYP2D inhibitors propranolol and propafenone were administered intracerebroventricularly prior to oral tramadol administration and analgesia was measured by tail-flick latency. Drug levels of tramadol and its metabolites, ODSMT and N-desmethyltramadol, were assessed in plasma and in brain by microdialysis using LC-ESI-MS/MS. Inhibiting brain CYP2D with propafenone pretreatment increased analgesia after oral tramadol administration (ANOVA p = 0.02), resulting in a 1.5-fold increase in area under the analgesia-time curve (AUC0-60, p < 0.01). This effect was associated with changes in the brain levels of tramadol and its metabolites consistent with brain CYP2D inhibition. In conclusion, under oral tramadol dosing pretreatment with a central administration of the CYP2D inhibitor propafenone increased analgesia (without altering plasma drug or metabolite levels), indicating that tramadol itself (and activity of CYP2D within the brain) contributed to analgesia.

Anecdotal evidence suggests that patients with isolated traumatic facial fractures have high narcotic usage, yet there is a lack of literature delineating this relationship. This study aimed to characterize total amount and factors predictive of narcotic usage following isolated traumatic facial fracture. Study participants (n = 35) were predominantly male (91.4%), mean age 40.5, Caucasian (34.3%), suffered some form of assault (62.9%), and remained hospitalized for an average of 3.0 days. Average morphine milligram equivalent (MME) use in the inpatient setting was 967.6 for operative (n = 30) and 37.5 for nonoperative (n = 5) patients. Average total narcotic use across inpatient and outpatient settings was 1256.6 MME for operative and 105 MME for nonoperative patients. Operative intervention predicted a significant difference in total inpatient narcotic usage (P = 0.009). For patients who underwent surgical intervention, significant variations in narcotic usage were found based on mechanism of injury (24-hour postoperative, P = 0.030), but not injury severity or number of procedures. Specifically, individuals suffering highly traumatic fractures (eg, gunshot wound) demonstrated increased total postoperative narcotic usage of 1194.1 MME (P = 0.004). Interestingly, non-narcotic analgesic use including acetaminophen and lidocaine-epinephrine resulted in significantly lower narcotic usage in the postoperative setting. These findings suggest a role for narcotic-reducing enhanced recovery after surgery protocols in the setting of isolated facial trauma.

Background Liposomal bupivacaine (LB) theoretically is longer-acting compared with conventional bupivacaine. The purpose of this study was to compare conventional bupivacaine combined with dexamethasone (control group), LB combined with conventional bupivacaine (LB group), and LB combined with dexamethasone and conventional bupivacaine (LBD group) in a perineural interscalene nerve block during ambulatory arthroscopic rotator cuff repair to determine if LB decreased postoperative narcotic consumption and pain. The effect of supplemental dexamethasone on prolonging the analgesic effect of LB was also assessed. Methods This was a prospective, double-blinded, randomized controlled trial of 76 consecutive patients who underwent outpatient arthroscopic rotator cuff repair. Patients were randomized into the 3 interscalene-block treatment groups: control group (n = 26), LB group (n = 24), and LBD group (n = 26). Outcome measures included pain measured with a visual analog scale (VAS; 0 to 10) and narcotic consumption measured in oral morphine milligram equivalents (MME). Both were measured daily on postoperative day 0 through postoperative day 4. Results Generalized estimating equation modeling revealed that narcotic consumption across all time points (postoperative days 0 to 4) was significantly lower in the LB group compared with the control group (mean difference, -8.5 MME; 95% confidence interval, -15.4 to -1.6; p = 0.015). Narcotic consumption was significantly higher in the control group on postoperative days 2 and 3 compared with the LB group (p = 0.004 and p = 0.02, respectively) and the LBD group (p = 0.01 and p = 0.003, respectively). There was no difference in narcotic consumption between the LBD and LB groups on any postoperative day. VAS pain scores in all groups were similar across all postoperative days. Conclusions Among patients undergoing outpatient arthroscopic rotator cuff repair, the addition of LB to conventional bupivacaine in interscalene nerve blocks appeared to be effective in controlling postoperative pain. Because LB with and without dexamethasone decreased postoperative narcotic use, LB should be considered for use in preoperative interscalene nerve blocks to reduce the reliance on narcotics for pain management. Level of evidence Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Background Approximately 56% of patients diagnosed with carpal tunnel syndrome present with bilateral symptoms; however, few studies have investigated bilateral simultaneous endoscopic carpal tunnel release (ECTR) and postoperative effect on return to activity. The purpose of this study was to evaluate the length of recovery in patients who received bilateral simultaneous ECTR, including pain medication requirements, return to activities of daily living, return to work, and return to recreational activities. Methods A retrospective analysis was performed on patients who underwent bilateral ECTR by a single hand fellowship–trained surgeon from 2013 to 2019. Demographic, operative, and clinical outcomes were collected via chart review and a telephone interview. Student t tests and χ2 tests were conducted for analysis. Results Eighty patients were included in the study; 40 were successfully contacted for telephone interview follow-up. Patients reported an average of 2 days of use of postoperative narcotic pain medication and an average of 5, 7, and 19 days of return to activities of daily living, work, and recreational activities, respectively. Female patients reported more days of narcotic pain medications (1 day vs 3 days, P = .0483) and an average of longer return to work than men (9 days vs 5 days, P = .0477). Manual laborers reported longer return to work (9 days vs 5 days, P = .0500). Older patients (aged >65 years) reported longer return to recreational activities (39 days vs 11 days, P = .0189). Conclusions Simultaneous bilateral ECTR is a successful procedure with shorter recovery times than reported previously. Female patients, manual laborers, and older patients experience a longer recovery and should be counseled appropriately.

Background Buprenorphine treatment is not equally effective in all patients with opioid use disorder (OUD). Two retrospective studies showed that, among African Americans (AAs), rs678849, a polymorphism in the delta-opioid receptor gene, moderated the therapeutic effect of sublingual buprenorphine. Methods We examined rs678849 as a moderator of the response to an extended-release subcutaneous buprenorphine formulation (BUP-XR) in a 24-week OUD treatment study of 127 AAs and 327 European Americans (EAs). Participants were randomly assigned to receive: (1) BUP-XR as 2 monthly injections of 300 mg followed by either 300 mg monthly or 100 mg monthly for 4 months, or (2) monthly volume-matched placebo injections. Generalized estimating equations logistic regression analyses tested, per population group, the main and interaction effects of treatment (BUP-XR vs placebo) and genotype group (rs678849*CC vs CT/TT) on weekly urine drug screens (UDS). Results Among AAs, the placebo group had higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.67, 95% CI = 0.36, 2.98), but no genotype by treatment effect (P = .80). Among EAs, the placebo group also showed higher rates of opioid-positive UDS than the BUP-XR group (log odds ratio = 1.97, 95% CI = 1.14, 2.79) but a significant genotype by treatment interaction (χ 2(1) = 4.33, P = .04). Conclusion We found a moderating effect of rs678849 on the response to buprenorphine treatment of OUD in EAs, but not AAs. These findings require replication in well-powered, prospective studies of both AA and EA OUD patients treated with BUP-XR and stratified on rs678849 genotype.

Total knee arthroplasty (TKA) is associated with increased risk of prolonged narcotic requirement compared to total hip arthroplasty (THA). This study aims to compare acute postoperative narcotic consumption between the 2 procedures and quantify amount of narcotics used by opioid prescribed.From October 2017 to August 2019, patients were surveyed at 4-week follow-up to determine amount and duration of opioids used and whether they continued to require narcotics. Among 1332 patients who self-identified as opioid naïve, 670 underwent THA and 662 underwent TKA. Descriptive analysis was performed based on data type.The total morphine equivalent dose (MED) used in the postoperative period was lower in THA than in TKA (143 ± 160 vs 259 ± 250 MED, P.001). The duration of use was shorter, total amount of pills consumed was lower, and refill rates were less in THA compared to TKA regardless of which opioid was prescribed. A smaller proportion of patients required narcotics at 4-week follow-up in THA compared to TKA. A postoperative prescription of 45 pills of any one type of narcotic was sufficient for nearly 90% of THA patients, and 60 pills of any one type of narcotic was appropriate for over 75% of TKA patients.THA is associated with less total narcotic consumption, shorter duration of use, less refills, and lower likelihood of requiring narcotics at 4-week follow-up. Percentiles of total narcotics consumed are provided to promote judicious postoperative prescribing patterns, and one could consider further reducing narcotics when utilizing our protocol, particularly for THA patients.This is a level III retrospective cohort study reviewing narcotic use in over 900 consecutive opioid-naïve patients undergoing total hip and knee arthroplasty.

Aim of the study In this study, we investigated the effect of long-term administration of orexin receptor 1 (OXR1) antagonist on naloxone-precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine-dependent rats. Materials and methods Wistar rats received subcutaneous (s.c.) injections of morphine (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) at an interval of 24 h for 7 days. In chronic groups, the OXR1 antagonist, SB-334867 (20 mg/kg, i.p.), or its vehicle, was injected repetitively from postnatal day 1 (PND1)-PND23 and then for the following seven days before each morphine injection. Meanwhile, in acute groups, SB-334867, or its vehicle, was administered before each morphine injection. In groups of rats that were designated for withdrawal experiments, naloxone (2.5 mg/kg, i.p.) was administered after the last injection of morphine. In the formalin-induced pain, the effect of OXR1 inhibition on the antinociceptive effects of morphine was measured by injecting formalin after the final morphine injection. Results Animals that received long-term SB-334867 administration before morphine injection demonstrated a significant reduction in chewing, defecation, diarrhea, grooming, teeth chattering, wet-dog shake, and writhing. Inhibiting OXR1 for a long time increased formalin-induced nociceptive behaviors in interphase and phase II of the formalin-induced pain. Conclusions Our results indicated that the inhibition of OXR1 significantly reduces the development of morphine dependence and behavioral signs elicited by the administration of naloxone in morphine-dependent rats. Furthermore, the prolonged blockade of OXR1 might be involved in formalin-induced nociceptive behaviors.

BACKGROUND AND OBJECTIVES Opioid-related overdose deaths in North America have increased drastically, partially due to the increased prevalence of illicitly manufactured fentanyl. The current study sought to assess the prevalence and intentionality of fentanyl use among individuals with opioid use disorder (OUD). METHODS For this secondary analysis (study 1) we screened a total of 1118 urine samples from 316 participants with OUD from 2016 to 2019. Fentanyl knowledge and intentionality of use were assessed in a separate OUD sample (study 2; N = 33). RESULTS In study 1, 34.6% of all urine samples tested positive for fentanyl. Overall, 149 (47.2%) participants provided more than or equal to one urine sample that tested fentanyl-positive, and 93 (29.4%) provided more than or equal to two fentanyl-positive samples. The number of fentanyl-positive samples, relative to the number of samples tested each year, increased by 330% from year 1 to 3. Study 2 found all participants had pre-existing knowledge that drugs may be adulterated with fentanyl, yet 67% were surprised by their own fentanyl-positive test result. DISCUSSION AND CONCLUSIONS Like previous studies, our data indicate the high prevalence of fentanyl exposure and low perception of fentanyl-related risk among individuals with OUD, respectively, suggesting that opioid overdose harm reduction efforts may need to focus more on drug users' understanding of risks related to fentanyl use and adulteration of drugs. SCIENTIFIC SIGNIFICANCE The current studies provide longitudinal data on fentanyl exposure prevalence and risk perception that is uniquely granular by assessing OUD treatment status, and by identifying potential associations between fentanyl exposure with the presence of other drug use and nonfatal overdose. (Am J Addict 2021;30:65-71).

Total knee arthroplasty (TKA) is associated with increased risk of prolonged narcotic requirement compared to unicompartmental knee arthroplasty (UKA). The purpose of the current study is to compare acute postoperative narcotic consumption between the 2 procedures and quantify narcotic consumption.From October 2017 to August 2019 patients were surveyed for four weeks to determine the amount and duration of opioids consumed and requirement for continued narcotics. Among 976 opioid naïve patients, 314 (32%) underwent UKA and 662 (68%) underwent TKA. Patients were analyzed according to specific narcotic prescribed. Total morphine equivalent dose (MED), number of pills, duration, refill percentage, and usage percentage for 4 weeks were calculated for each procedure.MED used in the postoperative period was lower in patients undergoing UKA than TKA (200 ± 195 vs 259 ± 250 MED, P = .002). Total number of pills consumed and duration of use was less in UKA compared to TKA regardless of which opioid was prescribed. A smaller proportion of patients required narcotics for 4 weeks after UKA (32% vs 43%, P.001), and fewer UKA patients required narcotic refills (14% vs 27%, P.001). Sixty pills of any 1 type of narcotic was sufficient for 90% of UKA patients and over 75% of TKA patients.UKA is associated with less narcotic consumption, shorter duration of use, less refills, and lower likelihood of narcotic requirement for 4 weeks. We report narcotic consumption patterns for both procedures to aid surgeons in judicious postoperative prescribing.This is a level III retrospective cohort study reviewing narcotic use in over 900 consecutive opioid naïve patients undergoing UKA or TKA.

Background Shivering is a common complication of neuraxial anaesthesia. We compared the efficacy of tramadol, clonidine and pregabalin in preventing post-spinal anaes-thesia shivering in hysteroscopic procedures. Methods A prospective, randomized, triple-blind, controlled clinical trial involving 120 ASA I-II women, aged 18-60 years. The patients were randomly allocated to receive either oral clonidine 0.2 mg (group C), tramadol 100 mg (group T), pregabalin 150 mg (group P) or placebo (group O) 90 minutes before spinal anaesthesia. The body tempe-rature was monitored at the forehead and tympanic membrane. The primary outcome was the occurrence of perioperative shivering. The secondary outcomes were the side effects and meperidine requirements to treat shivering. Results All groups had comparable demographic data. Group C showed the lowest incidence, severity and number of intraoperative and postoperative shivering attacks. The time to the first shivering attack was significantly longer in group C than the other groups and in group T than groups P and O. The severity of shivering attacks was comparable among groups C, T and P while being significantly lower than group O. Meperidine requirements were significantly lower in group C. Groups C, T and P had a significantly higher sedation score than group O. The incidences of dizziness, nausea and vomiting were highest in group T. Conclusions Tramadol, pregabalin and clonidine seem to be effective oral premedications to reduce the incidence, frequency and severity of post-spinal shivering but clonidine proved to be more effective and tolerable.

Aims To identify methadone-related deaths and determine the prevalence among youth and young adults in Sweden 2006-15. Design, setting and participants National retrospective registry study comparing data from all forensic autopsy examinations and toxicology cases involving methadone during 2006-15 in individuals aged 15-29 years with police records, previous pharmaceutical prescriptions and health-care episodes. Measurements Multinomial logistic regression. To assess the factors contributing to the deaths, we compared individuals with and without previous substance use treatment and opioid use-related diagnoses with regard to previous opioid agonist treatment (OAT), psychiatric care and previous pain medication. To assess the circumstances of deaths, we analyzed the presence of other drugs and other factors at time of death. Findings We identified 269 methadone-related deaths, and the rate increased during the study period. Seventy-two (27%) cases had not previously received substance use treatment, 112 (42%) had received treatment but had no opioid use-related diagnosis and 85 (32%) had received treatment and had an opioid use-related diagnosis. In total, only 10 individuals had been prescribed methadone during the year before death. Prescriptions of benzodiazepines (60%), antidepressants (62%) and opioids for pain (22%) the year before death were common. Most deaths occurred during sleep with a time lag from ingestion of methadone. Conclusion Prescription opioid- and methadone-related deaths increased in the group aged 15-29 years in Sweden between 2006 and 2015. Exposure to non-prescribed methadone and prescribed benzodiazepines, antidepressants and opioids for pain appears to be common in drug-related deaths in youth and young adults in Sweden.

Background The opioid epidemic has created a national healthcare crisis, and little is known about the accuracy of self-reported narcotic usage in arthroplasty. The purpose of this study is to evaluate the accuracy of self-reported opioid usage in patients undergoing outpatient arthroplasty. Methods A retrospective review was conducted on all primary unilateral arthroplasty procedures performed in 2018 at a free-standing ambulatory surgery center, yielding a cohort of 959 arthroplasties. Patient’s prescription records were queried in the Ohio Automated Rx Reporting System for 3 months before surgery and minimum 9 months after surgery. These data were cross-referenced against the patient-reported preoperative use of narcotics. Three groups were evaluated: (G1) no preoperative narcotics, (G2) accurately self-reported on narcotics, and (G3) on narcotics but did not disclose. Results One hundred fourteen patients (12%) were on preoperative opioids based on the Ohio Automated Rx Reporting System query, with only 35 of these patients (31%) self-reporting. G2 had significantly lower postoperative knee range of motion, Knee Society Pain score, Knee Society Clinical score, Knee Society Functional score, Harris Hip Score, and University of California Los Angeles activity scores than G1. Overnight stays occurred in 1.2% of patients in G1, 3% of patients in G2 (P = .5), and 6.3% of patient in G3 (P = .002). All aspects of postoperative narcotic use were significantly higher in G2 and G3 compared to G1. The relative risk for narcotic refill after 90 days in G2 was 4.6 (95% confidence interval 3.7-5.8, P Conclusion The majority of patients on preoperative narcotics did not disclose their use. Patients on narcotics preoperatively had significantly greater postoperative narcotic use including refills, total morphine milliequivalent, and risk of being on narcotics 90 days after surgery.

Background: There is a scarcity of studies investigating narcotic use after revision total knee arthroplasty (TKA). We compared immediate postsurgical narcotic consumption after revision TKA and primary TKA. Methods: A single-institution database was used to identify patients who underwent revision TKA or primary TKA between 2016 and 2019. Morphine milligram equivalents (MMEs) were calculated to discern narcotic usage, and pain visual analog score was also used. Results: A total of 7342 cases were identified: 88.65% primary TKA and 11.35% revision TKA. Opioid consumption for the first 24 hours postoperatively was significantly higher for the revision TKA group (133.1 MMEs vs 56.14 MMEs, P < .0001), as well as for the 24- to 48-hour time period. The visual analog pain scores were also higher for the revision TKA group. Conclusion: The revision TKA group had a higher opioid requirement, most significant during the first 24 hours postoperatively, and expressed more pain in the acute postoperative period.

Opiate intoxication has been associated with life-threatening effects of sympathetic suppression and respiratory depression, but current literature is limited in describing its neurotoxic effects on the central nervous system. Here, we present the case of an otherwise high-functioning adolescent male who was found unresponsive after ingestion of approximately 3–4 fake oxycodone 10–325 mg pills laced with fentanyl. Magnetic resonance imaging showed evidence of diffuse T2 hyperintensities in the corpus callosum and bilateral frontal, parietal, and cerebellum indicative of diffuse white matter injury. In addition, there were distinct areas of restricted diffusion in the bilateral basal ganglia concerning for oxidative stress-mediated neuronal loss. His neurological exam improved with supportive treatment over the course of his hospitalization. Although limited literature has shown leukoencephalopathy to be associated with opioid overdose, we present a case of additional involvement of subcortical gray matter.