Perioperative Naltrexone Management: A Scoping Review by the Perioperative Pain and Addiction Interdisciplinary Network.

Substance use disorders, including alcohol use disorder, are a public health concern that affect more than 150 million people globally. The opioid antagonist naltrexone is being increasingly prescribed to treat opioid use disorder, alcohol use disorder, and chronic pain. Perioperative management of patients on naltrexone is inconsistent and remains a controversial topic, with mismanagement posing a significant risk to the long-term health of these patients. This scoping review was conducted to identify human studies in which the perioperative management of naltrexone was described. This review includes a systematic literature search involving Medline, Medline In-Process, Embase, PsycINFO, and Web of Science. Seventeen articles that describe perioperative naltrexone management strategies were included, including thirteen guidelines, one case report, and three randomized trials. Despite its use in patients with alcohol use disorder and chronic pain, no clinical studies, case reports, or guidelines addressed naltrexone use in these clinical populations. All of the guideline documents recommended the preoperative cessation of naltrexone, irrespective of dose, indication, or route of administration. None of these guideline documents were designed on the basis of a systematic literature search or a Delphi protocol. As described by the primary studies, perioperative pain relief varied depending on naltrexone dose and route of administration, time since last naltrexone administration, and underlying substance use disorder. None of the studies commented on the maintenance of recovery for the patient's substance use disorder in the context of perioperative naltrexone management. The current understanding of the risks and benefits of continuing or stopping naltrexone perioperatively is limited by a lack of high-quality evidence. In patients with risk factors for return to use of opioids or alcohol, the discontinuation of naltrexone should have a strong rationale. Future studies and guidelines should seek to address both acute pain management and maintaining recovery when discussing perioperative naltrexone management strategies.

Psychotherapy for Ketamine's Enhanced Durability in Chronic Neuropathic Pain: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Chronic pain affects approximately 8 million Canadians (~20%), impacting their physical and mental health while burdening the health care system with costs of upwards of US $60 billion a year. Indeed, patients are often trialed on numerous medications over several years without reductions to their symptoms. Therefore, there is an urgent need to identify new therapies for chronic pain to improve patients' quality of life, increase the availability of treatment options, and reduce the burden on the health care system. OBJECTIVE: The primary objective of this study is to examine the feasibility of a parallel 3-arm pilot randomized controlled trial whereby patients are randomized to either intravenous ketamine alone, cognitive behavioral therapy (CBT) and mindfulness meditation (MM) training (CBT/MM), or the combination of intravenous ketamine and CBT/MM. The secondary outcome is to assess the durability and efficacy of combination intravenous ketamine and CBT/MM for treatment of chronic pain as compared to CBT/MM or intravenous ketamine alone (assessed at week 20 of the study). METHODS: This is a single-center, 16-week, 3-arm pilot study that will take place at the Chronic Pain Clinic at St. Michael's Hospital, Toronto, Ontario, which receives 1000 referrals per year. Patients will be enrolled in the study for a total of 20 weeks. Participants who are allocated CBT/MM therapy will receive remote weekly psychotherapy from week 1 to week 16, inclusive of health coaching administered through the NexJ Health Inc (NexJ Health) platform. Patients who are allocated ketamine-infusion therapy will receive monthly ketamine infusion treatments on weeks 2, 7, and 12. Patients who are allocated ketamine+CBT/MM will receive weekly psychotherapy from weeks 1 to 16, inclusive, as well as ketamine infusion treatments on weeks 2, 7, and 12. We will be assessing recruitment rates, consent rates, withdrawal rates, adherence, missing data, and adverse events as pilot outcome measures. Secondary clinical outcomes include changes relative to baseline in pain intensity and pain interference. RESULTS: As of November 1, 2023, the recruitment process has not been initiated. Given the recruitment, consent, and intervention target of 30 participants for this feasibility study, with each patient undergoing monitoring and treatments for a course of 20 weeks, we expect to complete the study by December 2025. CONCLUSIONS: This study assesses the feasibility of conducting a 3-arm randomized controlled trial to examine the effects of ketamine administration with the concurrent use of CBT/MM in a population with chronic neuropathic pain. The results of this pilot randomized controlled trial will inform the development of a larger-scale randomized controlled trial. Future studies will be aimed at including a sufficiently powered sample that will inform decisions about optimal treatment calibration and treatment effect duration. TRIAL REGISTRATION: ClinicalTrials.gov NCT05639322; https://classic.clinicaltrials.gov/ct2/show/NCT05639322. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/54406.

Subcortical brain volumes in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Despite treatment with therapeutic hypothermia, hypoxic-ischemic encephalopathy (HIE) is associated with adverse developmental outcomes, suggesting the involvement of subcortical structures including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period. The aims were: (1) to examine subcortical macrostructure in neonates with HIE compared to age- and sex-matched healthy neonates within the first week of life; (2) to determine whether subcortical brain volumes are associated with HIE severity. METHODS: Neonates (n = 56; HIE: n = 28; Healthy newborns from the Developing Human Connectome Project: n = 28) were scanned with MRI within the first week of life. Subcortical volumes were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, gestational age, postmenstrual age, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity. RESULTS: Neonates with HIE had smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to controls (all, p < 0.02). Within the HIE group, mild HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p < 0.007) and the left hippocampus and thalamus (both, p < 0.04). CONCLUSIONS: Findings suggest that, despite advances in neonatal care, HIE is associated with significant alterations in subcortical brain macrostructure. IMPACT: Compared to their healthy counterparts, infants with HIE demonstrate significant alterations in subcortical brain macrostructure on MRI acquired as early as 4 days after birth. Smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia, and cerebellum, were seen in infants with HIE. Mild and moderate HIE were associated with smaller subcortical volumes.