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Context: To describe the role of opioid antagonist induction in reducing stress response and withdrawal symptoms., Objective: Complexity of naltrexone induction is limiting broader applicability of opioid antagonist-assisted abstinence. The aim of this clinical trial was to assess the stress response to 2 low-dose naltrexone induction protocols under minimal oral sedation., Design: Double-blind randomized controlled trial., Setting: Open setting in-patient unit., Participants: Adults with opioid use disorder, and at least a year-long history of opioid use., Intervention Protocol: Patients received either a single 12.5 mg naltrexone oral dose (SI group) or escalating dosage regimen starting from 50 μg up to a cumulative dose of 12.5 mg (ED group)., Main Outcome Measure: Differences in cortisol and adrenocorticotropic hormone (ACTH) concentrations 1 hour after the start of naltrexone induction., Results: In all, 124 patients were enrolled and 68 remained in the trial at the point of randomization-33 in SI and 35 in ED group. Eight patients were excluded from final analysis. Plasma cortisol and ACTH concentrations were significantly higher in SI group; mean difference between groups 313 nmol/L (95% confidence interval [CI] 182-444, P < 0.001) and 36.9 pg/mL (95% CI 12.3-61.4, P = 0.004), respectively., Secondary Outcomes: SI patients experienced significant increases in plasma cortisol and ACTH concentrations, and withdrawal scores. In ED group these measures remained at or below baseline throughout the 24-hour period from start of naltrexone induction., Conclusions: Contrary to a single 12.5-mg dose, the escalating naltrexone dosing regimen produced no significant increase in stress response and withdrawal scores during antagonist induction.

Objectives: Opioid antagonist induction under general anesthesia or heavy sedation has been criticized due to its associated morbidity and mortality. Information on the potential causes of these complications is limited. We aimed to compare electrolyte concentration changes during rapid opioid antagonist induction under general anesthesia and conscious sedation, and to find out whether these changes are associated with cardiovascular complications., Methods: We used a pooled database analysis of 2 prospective randomized controlled clinical trials carried out in Lithuania between 2002 and 2014. Opioid-dependent patients underwent opioid antagonist induction under general anesthesia (n = 50) or conscious sedation (n = 68). Electrolyte levels were measured before the procedure, 3 hours after antagonist induction, and 3 hours after the end of the procedure., Results: General anesthesia was associated with initial hyperkalemia, which was followed by rapid reduction in potassium concentration (P < 0.01). Plasma potassium increase was noted in 92% of cases, and in 24%, these levels increased above 6.0 mmol/L, with a highest value of 6.7 mmol/L. Potassium concentration changes in the conscious sedation group were not statistically significant. There were no differences in sodium, calcium, chloride, and magnesium concentrations in both groups., Conclusions: Plasma potassium concentration changes in the general anesthesia group were significant, whereas conscious sedation had no effect on electrolyte levels. Our data support the recommendation of the American Society of Addiction Medicine and other professional societies that opioid antagonist induction under general anesthesia must not be offered.

Objective: N-methyl-D-aspartate antagonists were shown to be effective in suppressing the symptoms of opiate withdrawal. Intravenous anesthetic, ketamine, is the most potent N-methyl-D-aspartate antagonist available in clinical practice. The present study was designed to evaluate the effects of subanesthetic ketamine infusion, as little human data are available on ketamine in precipitated opiate withdrawal., Materials and Methods: A total of 58 opiate-dependent patients were enrolled in a randomized, placebo-controlled, double-blind study. Patients underwent rapid opiate antagonist induction under general anesthesia. Prior to opiate antagonist induction patients were given either placebo (normal saline) or subanesthetic ketamine infusion of 0.5 mg/kg/h. Further evaluations were divided into three phases: anesthetic, early postanesthetic (48 hours), and remote at 4 months after procedure. Cardiovascular, respiratory, renal, and gastrointestinal responses to opiate antagonist induction were monitored during anesthesia phase. Changes in plasma cortisol concentrations were measured as stress-response markers. Evaluations during early postanesthetic phase were based on Subjective and Objective Opiate Withdrawal Scales. Remote effects were assessed according to questionnaire based on Addiction Severity Index., Results: Altogether, 50 patients were included in the final analysis. Ketamine group presented better control of withdrawal symptoms, which lasted beyond ketamine infusion itself. Significant differences between Ketamine and Control groups were noted in anesthetic and early postanesthetic phases. There were no differences in effects on outcome after 4 months., Conclusion: In this study, subanesthetic ketamine infusion was an effective adjuvant in the correction of acute precipitated opiate withdrawal although it had no long-term effects on treatment of opiate dependence.

Objective: To evaluate safety and effectiveness of opiate antagonist detoxification under general anesthesia according to available prospective and retrospective data., Methods: We analyzed all detoxification cases that were performed in Vilnius University Emergency Hospital in the period of 2002-2005. Data of 65 patients from prospective, randomized, double-blind, placebo-controlled study and 21 retrospective cases were included in the study., Results: Full opiate receptor blockade was achieved in 85 cases (98.84%). No complications related to detoxification procedure or general anesthesia were recorded. Differences in procedure protocols and possible implications for clinical practice are discussed., Conclusions: The protocol of the prospective study may be recommended as a safe and effective detoxification method.