CJEM Articles: toxicology
Displaying 1-5 of 5 results
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September
2010
12
5
Brian E. Grunau, Jeffrey R. Brubacher, Matthew O. Wiens
Objective: The use of dantrolene in the treatment of hyperpyrexia related to MDMA (3,4-methylenedioxymethamphetamine) is controversial, with little data available to guide clinical decision-making. Although the treatment is recommended by several poison control centres, published data are primarily in the form of case reports and animal and in vitro experiments. We conducted a systematic review to investigate the published evidence regarding the safety and benefits of dantrolene for MDMA-related hyperpyrexia in humans.
Data sources: A systematic search of Embase and MEDLINE was conducted from the earliest possible date to November 2008.
Study selection: All human trials and case reports of MDMA related hyperpyrexia were considered.
Data extraction: Data were abstracted systematically and characteristics including use of dantrolene, adverse reactions attributed to dantrolene, peak temperature, complications from MDMA-related hyperpyrexia and survival were recorded.
Data synthesis: Our search yielded 668 articles of which 53, reporting 71 cases of MDMA-induced hyperpyrexia, met our inclusion criteria. No clinical trials, randomized controlled trials, observational studies or meta-analyses were identified. Dantrolene was used in 26 cases. Patient characteristics were similar in the dantrolene and no dantrolene groups. The proportion of survivors was higher in the dantrolene group (21/26) than in the no dantrolene group (25/45). This difference was especially pronounced in those with extreme (≥ 42°C) and severe (≥ 40°C) fever, with a survival rate of 8 of 13 and 10 of 10, respectively, in the dantrolene group compared with 0 of 4 and 15 of 27 in the no dantrolene group. There were no reports of adverse events attributable to dantrolene with the exception of a possible association with an episode of transient hypoglycemia.
Conclusion: Our systematic review suggests that dantrolene is safe for patients with MDMA-related hyperpyrexia. Dantrolene may also be associated with improved survival and reduced complications, especially in patients with extreme (≥ 42°C) or severe (≥ 40°C) hyperpyrexia, although this conclusion must be interpreted with caution given the risk of reporting or publication bias.
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September
2010
12
5
Brian E. Grunau, Marc Greidanus, Matthew O. Wiens
MDMA (3,4-methylenedioxymethamphetamine), popularly known as “Ecstasy,” was first introduced and patented by Merck & Co., Inc., in 1914 as an appetite suppressant. Currently, its primary role is as an illegal stimulant used to produce a euphoric effect during parties. This case report describes a 31-year-old man who, after taking 3 tablets of Ecstasy, presented to an emergency department with a decreased level of consciousness and became progressively hyperthermic and rigid. During the course of his acute illness, his temperature reached 42.2°C rectally. He was given mechanical ventilation. He was aggressively cooled and dantrolene was initiated. Soon after the administration of dantrolene his temperature decreased and his rigidity began to resolve. The only complication was rhabdomyolysis with a creatine kinase level increasing to over 150 µkat/L. This did not progress to acute renal failure. The patient made a full recovery and was discharged to psychiatry for assessment.
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November
2006
8
6
Debra A. Kent, Jeffrey R. Brubacher, Katherine J. Lepik, Matthew O. Wiens, Peter J. Zed, Riyad B. Abu-Laban, Roy A. Purssell, Sean K. Gorman
Background: Inadequate hospital stocking and the unavailability of essential antidotes is a worldwide problem with potentially disastrous repercussions for poisoned patients. Research indicates minimal progress has been made in the resolution of this issue in both urban and rural hospitals. In response to this issue the British Columbia Drug and Poison Information Centre developed provincial antidote stocking guidelines in 2003. We sought to determine the compliance with antidote stocking in BC hospitals and any factors associated with inadequate supply.
Methods: A 2-part survey, consisting of hospital demographics and antidote stocking information, was distributed in 2005 to all acute care hospital pharmacy directors in BC. The 32 antidotes examined (21 deemed essential) and the definitions of adequacy were based on the 2003 BC guidelines. Availability was reported as number of antidotes stocked per hospital and proportion of hospitals stocking each antidote. For secondary purposes, we assessed factors potentially associated with inadequate stocking.
Results: Surveys were completed for all 79 (100%) hospitals. A mean of 15.6 ± 4.9 antidotes were adequately stocked per hospital. Over 90% of hospitals had adequate stocks of N-acetylcysteine, activated charcoal, naloxone, calcium salts, flumazenil and vitamin K; 71%-90% had adequate dextrose 50% in water (D50W), ethyl alcohol or fomepizole, polyethylene glycol electrolyte solution, protamine sulfate, and cyanide antidotes; 51%-70% had adequate folic acid, glucagon, methylene blue, atropine, pralidoxime, leucovorin, pyridoxine, and deferoxamine; and <50% had adequate isoproterenol and digoxin immune Fab. Only 7 (8.9%) hospitals sufficiently stocked all 21 essential antidotes. Factors predicting poor stocking included small hospital size (p < 0.0001), isolation (p = 0.01) and rural location (p < 0.0001).
Conclusion: Although antidote stocking has improved since the implementation of the 2003 guidelines, essential antidotes are absent in many BC hospitals. Future research should focus on determining the reasons for this situation and the effects of corrective interventions.
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January
2003
5
1
Gillian A. Willis, Jeffrey Brubacher, Peter J. Zed, Roy A. Purssell, Sean K. Gorman
Introduction: Previous studies have demonstrated that antidotes are insufficiently stocked in Canadian and US health care facilities. The purpose of this study was to determine the adequacy of antidote stocking in British Columbia hospitals based on the current guidelines.
Methods: A written survey was mailed to hospital pharmacy directors at all 93 acute care facilities in BC. Availability of 14 essential antidotes was classified as sufficient or insufficient based on the current guidelines. Facilities were stratified into small (<50 beds), medium (50-250 beds) or large (>250 beds); teaching or non-teaching; trauma or non-trauma, urban or rural, and isolated or non-isolated.
Results: Complete responses were received from 75 (81%) of 93 hospitals. No hospital had adequate stock of all 14 antidotes. Overall, the average number (± standard deviation) of antidotes adequately stocked was 4.2 ± 2.9 per hospital. Urban hospitals had adequate stocks of 6.5 ± 2.6 antidotes while rural centres had adequate stocks of 2.6 ± 1.8 (p < 0.001). Corresponding figures were 9.0 ± 1.8 for teaching hospitals vs. 3.7 ± 2.4 for non-teaching hospitals (p < 0.001), 8.9 ± 2.0 for trauma centres vs. 3.8 ± 2.5 non-trauma centres (p < 0.001), and 2.5 ± 2.1 for isolated hospitals vs. 4.6 ± 2.9 for non-isolated hospitals (p = 0.018). Small, medium, and large hospitals adequately stocked 2.3 ± 1.7, 5.7 ± 2.2, and 7.7 ± 3.0 antidotes, respectively (p < 0.001). The 4 antidotes most adequately stocked were sodium bicarbonate (77%), N-acetylcysteine (64%), ethanol (49%) and naloxone (47%). Digoxin immune Fab fragments, glucagon, pyridoxine and rattlesnake antivenin were poorly stocked with sufficient supplies of 5%, 7%, 7% and 13%, respectively.
Conclusion: BC hospitals do not have adequate antidote stocks. Provincial stocking guidelines and coordination of antidote purchasing and stocking are necessary to correct these deficiencies.
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January
2002
4
1
Jeffrey Brubacher, William R. Henderson
Poisoning is an uncommon but potentially fatal outcome of toxic alcohol ingestion. The toxic alcohols methanol, ethylene glycol and isopropyl alcohol are commonly found in household and commercial products. Because the toxic effects are caused by the metabolites of methanol and ethylene glycol rather than the agents themselves, there is often a substantial delay between ingestion and onset of clinical toxicity. Anion and osmolar gaps are often used for the diagnosis and exclusion of these sometimes subtle overdoses. The pitfalls of using these tests to rule out alcohol ingestion are reviewed. Ethanol infusion is the traditional therapy for such overdoses. In addition to the pathophysiology and clinical findings in poisoning, recent evidence for the use of fomepizole and adjuvant therapies is reviewed.
