Faculty Bibliography

Background: Synthetic cannabinoid receptor agonists (SCRAs) are heterogeneous compounds developed as probes of the endogenous cannabinoid system or potential therapeutic agents, which clandestine laboratories subsequently synthesize and market as abusable designer drugs. Objectives: We assessed clinical toxicity associated with SCRA overdose, and hypothesized associations with agitation and cardiotoxicity. Methods: This subgroup analysis of a large drug overdose cohort study involved consecutive ED patients at two large urban teaching hospitals collected between 2009-13. Clinical characteristics of patients with exposure to SCRAs (SRCA subgroup) were compared with patients who smoked regular marijuana (MJ subgroup). Data included demographics, exposure details, vital signs, mental status, and basic chemistries gathered as part of routine clinical care. Study outcomes included altered mental status (agitation, GCS), and cardiotoxicity (myocardial injury, dysrhythmia). Dysrhythmia was defined as ventricular tachycardia or fibrillation. Assuming 30% prevalence of the predictor and outcome, we calculated the need to enroll 84 patients to show 3.5-fold relative risk with 80% power and 5% alpha. Results: 89 patients reported exposure to any cannabinoid, of whom 17 reported SCRAs (17 SCRA, 72 MJ, mean age 38.7, 78% males). There were no significant differences between SRCA and MJ with respect to demographics (age, sex, race), exposure history (suicidality, misuse, intent), or vital signs. Laboratory variables associated with SCRA were lower mean bicarbonate (p<0.05) and elevated mean serum glucose (p<0.05). Mental status agitation was significantly more likely in SCRA subgroup (OR 3.3, CI 1.1-9.6). Cardiotoxicity was more pronounced in SCRA subgroup (dysrhythmia OR 9.8, CI 1.0-116). Conclusion: Clinical toxicity of SCRA overdose was much more severe than MJ, including metabolic abnormalities, neurotoxicity and cardiotoxicity. Future studies should assess optimal treatment modalities to prevent adverse clinical outcomes

STUDY OBJECTIVE: Calcium channel blocker poisonings account for a substantial number of reported deaths from cardiovascular drugs. Although supportive care is the mainstay of treatment, experimental therapies such as high-dose insulin-euglycemia and lipid emulsion have been studied in animal models and used in humans. In the most severe cases, even aggressive care is inadequate and deaths occur. In both experimental models and clinical cases of vasodilatory shock, methylene blue improves hemodynamic measures. It acts as a nitric oxide scavenger and inhibits guanylate cyclase that is responsible for the production of cyclic guanosine monophosphate (cGMP). Excessive cGMP production is associated with refractory vasodilatory shock in sepsis and anaphylaxis. The aim of this study is to determine the efficacy of methylene blue in an animal model of amlodipine-induced shock. METHODS: Sprague-Dawley rats were anesthetized, ventilated, and instrumented for continuous blood pressure and pulse rate monitoring. The dose of amlodipine that produced death within 60 minutes was 17 mg/kg per hour (LD50). Rats were divided into 2 groups: amlodipine followed by methylene blue or amlodipine followed by normal saline solution, with 15 rats in each group. Rats received methylene blue at 2 mg/kg during 5 minutes or an equivalent amount of normal saline solution in 3 intervals from the start of the protocol: minutes 5, 30, and 60. The animals were observed for a total of 2 hours after the start of the protocol. Mortality risk and survival time were analyzed with Fisher's exact test and Kaplan-Meier survival analysis with the log rank test. RESULTS: Overall, 1 of 15 rats (7%) in the saline solution-treated group survived to 120 minutes compared with 5 of 15 (33%) in the methylene blue-treated group (difference -26%; 95% confidence interval [CI] -54% to 0.3%). The median survival time for the normal saline solution group was 42 minutes (95% CI 28.1 to 55.9 minutes); for the methylene blue group, 109 minutes (95% CI 93.9 to 124.1 minutes). Pulse rate and mean arterial pressure (MAP) differences between groups were analyzed until 60 minutes. Pulse rate was significantly higher in the methylene blue-treated group beginning 25 minutes after the start of the amlodipine infusion (95% CI 30 to 113 minutes) that was analyzed until 60 minutes. MAP was significantly higher in the methylene blue-treated group starting 25 minutes after the amlodipine infusion (95% CI 2 to 30 minutes) that was analyzed until 60 minutes. CONCLUSION: Methylene blue did not result in a significant difference in mortality risk. There was an increased pulse rate, MAP, and median survival time in the methylene blue group.

Abstract Context. The optimal method of cooling hyperthermic patients is controversial. Although controlled data support ice water submersion, many authorities recommend a mist and fan technique. We report two patients with drug-induced hyperthermia, to demonstrate the rapid cooling rates of ice water submersion. Case details. Case 1. A 27-year-old man presented with a sympathomimetic toxic syndrome and a core temperature of 41.4 degrees C after ingesting 4-fluoroamphetamine. He was submerged in ice water and his core temperature fell to 38 degrees C within 18 minutes (a mean cooling rate of 0.18 degrees C/min). His vital signs stabilized, his mental status improved and he left on hospital day 2. Case 2. A 32-year-old man with a sympathomimetic toxic syndrome after cocaine use was transported in a body bag and arrived with a core temperature of 44.4 degrees C. He was intubated, sedated with IV benzodiazepines, and submerged in ice water. After 20 mins his temperature fell to 38.8 degrees C (a cooling rate of 0.28 degrees C/min). He was extubated the following day, and discharged on day 10. Discussion. In these two cases, cooling rates exceeded those reported for mist and fan technique. Since the priority in hyperthermia is rapid cooling, clinical data need to be collected to reaffirm the optimal approach.

OBJECTIVE: Methanol poisoning can induce death and disability. Treatment includes the administration of antidotes (ethanol or fomepizole and folic/folinic acid) and consideration of extracorporeal treatment for correction of acidemia and/or enhanced elimination. The Extracorporeal Treatments in Poisoning workgroup aimed to develop evidence-based consensus recommendations for extracorporeal treatment in methanol poisoning. DESIGN AND METHODS: Utilizing predetermined methods, we conducted a systematic review of the literature. Two hundred seventy-two relevant publications were identified but publication and selection biases were noted. Data on clinical outcomes and dialyzability were collated and a two-round modified Delphi process was used to reach a consensus. RESULTS: Recommended indications for extracorporeal treatment: Severe methanol poisoning including any of the following being attributed to methanol: coma, seizures, new vision deficits, metabolic acidosis with blood pH