Anesthetics, widely used in magnetic resonance imaging (MRI) studies to avoid movement artifacts, could have profound effects on cerebral blood flow (CBF) and cerebrovascular coupling relative to the awake condition. Quantitative CBF and tissue oxygenation (blood oxygen level-dependent [BOLD]) were measured, using the continuous arterial-spin-labeling technique with echo-planar-imaging acquisition, in awake and anesthetized (2% isoflurane) rats under basal and hypercapnic conditions. All basal blood gases were within physiologic ranges. Blood pressure, respiration, and heart rates were within physiologic ranges in the awake condition but were depressed under anesthesia (P < 0.05). Regional CBF was heterogeneous with whole-brain CBF values of 0.86 +/- 0.25 and 1.27 +/- 0.29 mL. g-1. min-1 under awake and anesthetized conditions, respectively. Surprisingly, CBF was markedly higher (20% to 70% across different brain conditions) under isoflurane-anesthetized condition compared with the awake state (P < 0.01). Hypercapnia decreased pH, and increased Pco(2) and Po(2). During 5% CO(2) challenge, under awake and anesthetized conditions, respectively, CBF increased 51 +/- 11% and 25 +/- 4%, and BOLD increased 7.3 +/- 0.7% and 5.4 +/- 0.4%. During 10% CO(2) challenge, CBF increased 158 +/- 28% and 47 +/- 11%, and BOLD increased 12.5 +/- 0.9% and 7.2 +/- 0.5%. Since CBF and BOLD responses were substantially higher under awake condition whereas blood gases were not statistically different, it was concluded that cerebrovascular reactivity was suppressed by anesthetics. This study also shows that perfusion and perfusion-based functional MRI can be performed in awake animals.

This case series describes several patients with cardiac conduction abnormalities and life-threatening ventricular arrhythmias temporally related to loperamide abuse. With the recent efforts to restrict the diversion of prescription opioids, increasing abuse of loperamide as an opioid substitute may be seen. Toxicologists should be aware of these risks and we urge all clinicians to report such cases to FDA Medwatch(®).

Our two cases suggest that baclofen intoxication may result in very prolonged and profound coma and may, in fact, mimic brain death. Conclusion. The determination of brain death in the comatose overdose patient must proceed with caution. An adequate period of time to allow drug clearance must be allowed.

The acute withdrawal syndrome appears to be characterized mainly by anxiety and tachycardia in the absence of any neurological findings or electrolyte disturbances. We describe two patients with symptoms consistent with withdrawal presumably due to synthetic cannabinoid use. The most appropriate treatment for such patients remains unknown, however benzodiazepines are a reasonable first line approach and quetiapine may have some efficacy.

The American College of Medical Toxicology established the Toxicology Investigators Consortium (ToxIC) Case Registry in 2010. The Registry contains all medical toxicology consultations performed at participating sites. The Registry has continued to grow since its inception, and as of December 31, 2015, contains 43,099 cases. This is the sixth annual report of the ToxIC Registry, summarizing the additional 8115 cases entered in 2015. Cases were identified by a query of the Registry for all cases entered between January 1 and December 31, 2015. Specific data reviewed for analysis included demographics (age, race, gender), source of consultation, reason for consultation, agents and agent classes involved in exposures, signs, symptoms, clinical findings, fatalities, and treatment. By the end of 2015, there were 50 active sites, consisting of 101 separate health-care facilities; 51.2 % of cases involved females. Adults between the ages of 19 and 65 made up the majority (64.2 %) of Registry cases. Caucasian race was the most commonly reported (55.6 %); 9.6 % of cases were identified as Hispanic ethnicity. Inpatient and emergency department referrals were by far the most common referral sources (92.9 %). Intentional pharmaceutical exposures remained the most frequent reason for consultation, making up 52.3 % of cases. Of these intentional pharmaceutical exposures, 69 % represented an attempt at self-harm, and 85.6 % of these were a suicide attempt. Nonopioid analgesics, sedative-hypnotics, and antidepressant agents were the most commonly reported agent classes in 2015. Almost one-third of Registry cases involved a diagnosed toxidrome (32.8 %), with a sedative-hypnotic toxidrome being the most frequently described. Significant vital sign abnormalities were recorded in 25.3 % of cases. There were 98 fatalities reported in the Registry (1.2 %). Adverse drug reactions were reported in 4.3 % of cases. Toxicological treatment was given in 65.3 % of cases, with 33.0 % receiving specific antidotal therapy. Exposure characteristics and trends overall were similar to prior years. While treatment interventions were required in the majority of cases, fatalities were rare.

Summary:Anesthetics, widely used in magnetic resonance imaging (MRI) studies to avoid movement artifacts, could have profound effects on cerebral blood flow (CBF) and cerebrovascular coupling relative to the awake condition. Quantitative CBF and tissue oxygenation (blood oxygen level-dependent [BOLD]) were measured, using the continuous arterial-spinlabeling technique with echo-planar-imaging acquisition, in awake and anesthetized (2% isoflurane) rats under basal and hypercapnic conditions. All basal blood gases were within physiologic ranges. Blood pressure, respiration, and heart rates were within physiologic ranges in the awake condition but were depressed under anesthesia (P < 0.05). Regional CBF was heterogeneous with whole-brain CBF values of 0.86 ± 0.25 and 1.27 ± 0.29 mL · g −1 · min −1 under awake and anesthetized conditions, respectively. Surprisingly, CBF was markedly higher (20% to 70% across different brain conditions) under isoflurane-anesthetized condition compared with the awake state (P < 0.01). Hypercapnia decreased pH, and increased PCO 2 and PO 2 . During 5% CO 2 challenge, under awake and anesthetized conditions, respectively, CBF increased 51 ± 11% and 25 ± 4%, and BOLD increased 7.3 ± 0.7% and 5.4 ± 0.4%. During 10% CO 2 challenge, CBF increased 158 ± 28% and 47 ± 11%, and BOLD increased 12.5 ± 0.9% and 7.2 ± 0.5%. Since CBF and BOLD responses were substantially higher under awake condition whereas blood gases were not statistically different, it was concluded that cerebrovascular reactivity was suppressed by anesthetics. This study also shows that perfusion and perfusion-based functional MRI can be performed in awake animals.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Background: Treatment progress is routinely monitored by urine testing in patients with opioid use disorder (OUD) undergoing buprenorphine medication-assisted treatment (MAT). However, interpretation of urine test results could be challenging. This retrospective study aims to examine the results of quantitative buprenorphine, norbuprenorphine, and creatinine levels in urine testing in relation to sublingual buprenorphine dosage to facilitate an accurate interpretation of urine testing results. Methods: We reviewed the medical charts of 41 consecutive patients, who were residing in halfway houses where their medication intake was closely monitored and who had enrolled in an office-based MAT program at an urban clinic between July 2018 and June 2019. The patients’ urine testing results were reviewed, and demographic variables were recorded. We focused on the patients treated with 8-, 12-, or 16-mg/day of buprenorphine, examining their urine buprenorphine, norbuprenorphine, and creatinine levels. Analysis of variance tested the statistical association between the dosage and urine testing results on the norbuprenorphine-to-creatinine ratio. Results: A total of 240 urine samples from 41 patients were included for this study. The 41 patients received a mean buprenorphine dose of 10.5 ± 3.7 mg/day (range, 4-20 mg/day). Then, this study examined the distribution of the 240 urine samples and then focused on 184 urine samples that came from the 33 patients who were treated with 8-, 12-, and 16-mg/day of buprenorphine, the 3 most common dosages. All of the 184 urine samples had a creatinine level of >20 mg/dL and buprenorphine-to-norbuprenorphine ratio <50:1. The average norbuprenorphine-to-creatinine ratio in the 8 mg/day dosage group was 3.85 ± 2.24 × 10−4 (n = 66; range, 0.44-11.12). The respective ratios in the 12- and 16-mg dosage groups were 5.64 ± 3.40 × 10−4 (n = 83; range, 1.55-22.72) and 6.23 ± 4.92 × 10−4 (n = 35; range, 1.37-27.12). The 3 dosage groups differed significantly in the mean ratios ( P < .01), except when the 12- and 16-mg dosage groups were compared ( P = .58). The results of this study thus suggest that prescribers should pay attention to the following features: (1) unexpected substance(s) in urine testing, (2) creatinine level under 20 mg/dL, (3) buprenorphine-to-creatinine ratio over 50:1, (4) buprenorphine dosage over 24 mg/day, and (5) norbuprenorphine-to-creatinine ratio consistently under 0.5 × 10−4 in patients treated with 8 mg/day or 1.5 × 10−4 in patients treated with 12 mg/day or more. Conclusion: This study suggested parameters for interpreting quantitative urine test results in relation to buprenorphine intake dose in office-based opioid treatment programs.