Faculty Bibliography

BACKGROUND: Metformin toxicity, a challenging clinical entity, is associated with a mortality of 30%. The role of extracorporeal treatments such as hemodialysis is poorly defined at present. Here, the Extracorporeal Treatments In Poisoning workgroup, comprising international experts representing diverse professions, presents its systematic review and clinical recommendations for extracorporeal treatment in metformin poisoning. METHODS: A systematic literature search was performed, data extracted, findings summarized, and structured voting statements developed. A two-round modified Delphi method was used to achieve consensus on voting statements and RAND/UCLA Appropriateness Method to quantify disagreement. Anonymized votes and opinions were compiled and discussed. A second vote determined the final recommendations. RESULTS: One hundred seventy-five articles were identified, including 63 deaths: one observational study, 160 case reports or series, 11 studies of descriptive cohorts, and three pharmacokinetic studies in end-stage renal disease, yielding a very low quality of evidence for all recommendations. The workgroup concluded that metformin is moderately dialyzable (level of evidence C) and made the following recommendations: extracorporeal treatment is recommended in severe metformin poisoning (1D). Indications for extracorporeal treatment include lactate concentration greater than 20 mmol/L (1D), pH less than or equal to 7.0 (1D), shock (1D), failure of standard supportive measures (1D), and decreased level of consciousness (2D). Extracorporeal treatment should be continued until the lactate concentration is less than 3 mmol/L (1D) and pH greater than 7.35 (1D), at which time close monitoring is warranted to determine the need for additional courses of extracorporeal treatment. Intermittent hemodialysis is preferred initially (1D), but continuous renal replacement therapies may be considered if hemodialysis is unavailable (2D). Repeat extracorporeal treatment sessions may use hemodialysis (1D) or continuous renal replacement therapy (1D). CONCLUSION: Metformin poisoning with lactic acidosis appears to be amenable to extracorporeal treatments. Despite clinical evidence comprised mostly of case reports and suboptimal toxicokinetic data, the workgroup recommended extracorporeal removal in the case of severe metformin poisoning.

OBJECTIVES: We sought to evaluate the impact of New York City's (NYC's) 2004 carbon monoxide (CO) alarm legislation on CO incident detection and poisoning rates. METHODS: We compared CO poisoning deaths, hospitalizations, exposures reported to Poison Control, and fire department investigations, before and after the law for 2000 to 2010. Use of CO alarms was assessed in the 2009 NYC Community Health Survey. RESULTS: Investigations that found indoor CO levels greater than 9 parts per million increased nearly 7-fold after the law (P < .001). There were nonsignificant decreases in unintentional, nonfire-related CO poisoning hospitalization rates (P = .114) and death rates (P = .216). After we controlled for ambient temperature, the law's effect on hospitalizations remained nonsignificantly protective (incidence rate ratio = 0.747; 95% confidence interval = 0.520, 1.074). By 2009, 83% of NYC residents reported having CO alarms; only 54% also recently tested or replaced their batteries. CONCLUSIONS: Mandating CO alarms significantly increased the detection of potentially hazardous CO levels in NYC homes. Small numbers and detection bias might have limited the discovery of significant decreases in poisoning outcomes. Investigation of individual poisoning circumstances since the law might elucidate remaining gaps in awareness and proper use of CO alarms. (Am J Public Health. Published online ahead of print June 11, 2015: e1-e7. doi:10.2105/AJPH.2015.302577).

Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.

Although the putative pharmacological targets of synthetic cannabinoids (SCBs) abused in "K2" and "Spice" are similar to Delta(9) -tetrahydrocannabinol (Delta(9) -THC), it remains unclear why SCB toxicity is similar yet different from marijuana. There are obvious potency and efficacy differences, but also important metabolic differences that help explain the unique adverse reactions associated with SCBs. This brief review discusses the limited research on the metabolism of the SCB JWH-018 and contrasts that with the metabolism of Delta(9) -THC.