Steven A. Seifert

Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop

BackgroundEnvenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists.MethodsA geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm.ResultsA unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy.ConclusionsClinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.

An analysis of energy-drink toxicity in the National Poison Data System

Context. Small studies have associated energy drinks—beverages that typically contain high concentrations of caffeine and other stimulants—with serious adverse health events. Objective. To assess the incidence and outcomes of toxic exposures to caffeine-containing energy drinks, including caffeinated alcoholic energy drinks, and to evaluate the effect of regulatory actions and educational initiatives on the rates of energy drink exposures. Methods. We analyzed all unique cases of energy drink exposures reported to the US National Poison Data System (NPDS) between October 1, 2010 and September 30, 2011. We analyzed only exposures to caffeine-containing energy drinks consumed as a single product ingestion and categorized them as caffeine-containing non-alcoholic, alcoholic, or “unknown” for those with unknown formulations. Non-alcoholic energy drinks were further classified as those containing caffeine from a single source and those containing multiple stimulant additives, such as guarana or yerba mate. The data were analyzed for the demographics and outcomes of exposures (unknown data were not included in the denominator for percentages). The rates of change of energy drink-related calls to poison centers were analyzed before and after major regulatory events. Results. Of 2.3 million calls to the NPDS, 4854 (0.2%) were energy drink-related. The 3192 (65.8%) cases involving energy drinks with unknown additives were excluded. Of 1480 non-alcoholic energy drink cases, 50.7% were children < 6 years old; 76.7% were unintentional; and 60.8% were males. The incidence of moderate to major adverse effects of energy drink-related toxicity was 15.2% and 39.3% for non-alcoholic and alcoholic energy drinks, respectively. Major adverse effects consisted of three cases of seizure, two of non-ventricular dysrhythmia, one ventricular dysrhythmia, and one tachypnea. Of the 182 caffeinated alcoholic energy drink cases, 68.2% were < 20 years old; 76.7% were referred to a health care facility. Educational and legislative initiatives to enhance understanding of the health consequences of energy drink consumption were significantly associated with a decreased rate of energy drink-related cases (p = 0.036). Conclusions. About half the cases of energy drink-related toxicity involved unintentional exposures by children < 6 years old. Educational campaigns and legal restrictions on the sale of energy drinks were associated with decreasing calls to poison centers for energy drink toxicity and are encouraged.

Olanzapine overdose mimicking opioid intoxication

We report significant central nervous system depression and the previously unreported phenomenon of pupillary constriction after acute overdose of olanzapine (Zyprexa) in 4 patients. Phase 2 trials describe a typically benign course in overdose, and published abstracts note a wide spectrum of clinical effects with supratherapeutic ingestion of olanzapine. Our patients demonstrated profound central nervous system depression, and 2 required advanced airway support. All 4 patients recovered with supportive care. Olanzapine should be added to opioid and alpha(2)-adrenergic agonist intoxication in the differential diagnosis of the patient with depressed mental status and miosis.

AAPCC database characterization of native U.S. venomous snake exposures, 2001–2005

Background. Differences in victim demographics, clinical effects, managements, and outcomes among native viperid (rattlesnake, copperhead, and cottonmouth) and elapid (coral snake) species have not been systematically characterized. Methods. The database of the American Association of Poison Control Centers from 2001 through 2005 was analyzed. Results. Between 2001 and 2005, there were 23,676 human exposures (average = 4,735/year) to native venomous snakes in the United States reported to U.S. poison centers in all states except Hawaii: 98% were to viperid snakes and 2% to elapids. Overall, 77% of victims were male, 70% were adults >20 years, and 12% were aged less than 10 years. Sixty-five cases involved pregnant women, with rattlesnake bites resulting in moderate or greater effects in over 70%. The overall hospital admission rate was 53%. Outcomes were generally more severe with rattlesnake and copperhead envenomations and in children <6 years of age. The fatality rate of reported cases was 0.06%. Conclusions. Native U.S. venomous snakebite results in considerable morbidity and mortality. Rattlesnake and copperhead envenomations, and those in children <6 years of age, produce the most severe outcomes, but coral snakebites result in similar hospital admission rates.

Linking pharmacology to clinical reports: cyclobenzaprine and its possible association with serotonin syndrome.

The link between cyclobenzaprine (Flexeril) administration and serotonin syndrome (SS) is subject to debate. Establishing such a connection is difficult because of the limited number of case reports available and the almost complete ignorance of its preclinical pharmacology. In this context, evidence is provided here that cyclobenzaprine blocks the serotonin and norepinephrine transporters and binds to another set of five serotonin receptors. SS should be considered when indicative signs occur in the context of cyclobenzaprine use.

Poisoning in the United States: 2012 Emergency Medicine Report of the National Poison Data System

Deaths from drug overdose have become the leading cause of injury death in the United States, where the poison center system is available to provide real-time advice and collect data about a variety of poisonings. In 2012, emergency medical providers were confronted with new poisonings, such as bath salts (substituted cathinones) and Spice (synthetic cannabinoid drugs), as well as continued trends in established poisonings such as from prescription opioids. This article addresses current trends in opioid poisonings; new substances implicated in poisoning cases, including unit-dose laundry detergents, bath salts, Spice, and energy drinks; and the role of poison centers in public health emergencies such as the Fukushima radiation incident.

Massive ibuprofen ingestion with survival.

Objective: To report a massive, 100 g ibuprofen ingestion in an adolescent, with survival. Case Report: The patient developed coma, metabolic acidosis, and mild thrombocytopenia, but improved rapidly with supportive care. Renal function remained normal and no gastrointestinal bleeding occurred. Conclusions: Massive ingestion of ibuprofen may result in a variable picture with some elements of significant toxicity, but supportive care usually results in survival without sequelae.

Comparison of F(ab')2 versus Fab antivenom for pit viper envenomation: A prospective, blinded, multicenter, randomized clinical trial

Abstract Background. Crotalidae Polyvalent Immune Fab (Ovine) has been the only antivenom commercially available in the US since 2007 for treatment of Crotalinae envenomation. Late coagulopathy can occur or recur after clearance of Fab antivenom, often after hospital discharge, lasting in some cases more than 2 weeks. There have been serious, even fatal, bleeding complications associated with recurrence phenomena. Frequent follow-up is required, and additional intervention or hospitalization is often necessary. F(ab’)2 immunoglobulin derivatives have longer plasma half life than do Fab. We hypothesized that F(ab’)2 antivenom would be superior to Fab in the prevention of late coagulopathy following treatment of patients with Crotalinae envenomation. Methods. We conducted a prospective, double-blind, randomized clinical trial, comparing late coagulopathy in snakebitten patients treated with F(ab’)2 with maintenance doses [F(ab’)2/F(ab’)2], or F(ab’)2 with placebo maintenance doses [F(ab’)2/placebo], versus Fab with maintenance doses [Fab/Fab]. The primary efficacy endpoint was coagulopathy (platelet count < 150 K/mm3, fibrinogen level < 150 mg/dL) between end of maintenance dosing and day 8. Results. 121 patients were randomized at 18 clinical sites and received at least one dose of study drug. 114 completed the study. Of these, 11/37 (29.7%) in the Fab/Fab cohort experienced late coagulopathy versus 4/39 (10.3%, p < 0.05) in the F(ab’)2/F(ab’)2 cohort and 2/38 (5.3%, p < 0.05) in the F(ab’)2/placebo cohort. The lowest heterologous protein exposure was with F(ab’)2/placebo. No serious adverse events were related to study drug. In each study arm, one patient experienced an acute serum reaction and one experienced serum sickness. Conclusions. In this study, management of coagulopathic Crotalinae envenomation with longer-half-life F(ab’)2 antivenom, with or without maintenance dosing, reduced the risk of subacute coagulopathy and bleeding following treatment of envenomation.

Black widow spider envenomation in pregnancy

Objective. Little data exist regarding the optimal treatment and outcomes of pregnancies complicated by black widow spider envenomation. Our objective is to evaluate the clinical effects, medical outcomes, and treatment differences between pregnant and nonpregnant women. Methods. This observational study is based on a review of the database maintained by the American Association of Poison Control Centers from 2003 to 2007. Results. Of the 12,640 human black widow spider envenomations reported at 61 poison centers in the United States, 3194 (25.3%) involved women of reproductive age, defined as age 15–45 years of age, with 97 (3.0% of reproductive-age women) being pregnant. Comparing pregnant and nonpregnant women, there were no significant differences in recommended or administered treatments. Pregnant women were more likely than nonpregnant women (OR: 1.84, 95% CI: 1.20–2.83) to have outcomes coded as minor, moderate, or major rather than no effect. Significantly higher percentages of pregnant patients were treated at a healthcare facility where they were either released (36.1% vs. 19.9%, p  < 0.001) or admitted (13.4% vs. 4.0%, p  < 0.001), than nonpregnant women. There were no documented pregnancy losses. Conclusions. Black widow spider envenomation is a rare occurrence in pregnant women and the short-term outcomes appear to be favorable.

Continuous IV Crotalidae Polyvalent Immune Fab (Ovine) (FabAV) for selected North American Rattlesnake bite patients

BACKGROUND In patients bitten by North American rattlesnakes and treated with Crotalidae Polyvalent Immune Fab (Ovine) (FabAV), late hematologic abnormalities-persistent, recurrent, or late, new onset of hypofibrinogenemia, prolonged PT/INR, prolonged PTT, and/or thrombocytopenia beyond 48 h post-envenomation-are common, difficult to manage, and may result in morbidity and mortality are common, difficult to manage, and may result in morbidity and mortality. The optimal management of late hematologic abnormalities, particularly the use of further treatment with antivenom, has not been well defined. The current FabAV treatment regimen is to give antivenom as a bolus dose over a one-hour period. We describe our experience using a continuous intravenous infusion of FabAV for late hematologic effects and/or associated bleeding complications in rattlesnake envenomation. METHODS This is a retrospective, observational case series of patients envenomated by North American rattlesnakes at three medical centers managed with a continuous intravenous infusion of FabAV for late hematologic abnormalities and/or associated bleeding complications. Indications, dilution and infusion protocols, and duration of therapy were individualized. RESULTS Five cases were identified between July 2010 and September 2011. All patients had profound late hematologic abnormalities and/or were associated with bleeding complications. Several patients had received repeat bolus infusions of FabAV, with or without human blood products, with either inadequate or only transient beneficial response. All patients were then managed with a continuous intravenous infusion of FabAV and all appeared to respond to the continuous intravenous infusion of FabAV, titrated to effect, with cessation of progression and, in most cases, improvement in hematologic abnormalities. Rates of infusion varied from 2 to 4 vials per 24 h (mean = 3.1 ± 0.4 vials/day). The termination of FabAV infusion was between day 6 and day 14 from the time of envenomation (mean = 10 ± 3 days), after which hematologic values were normalized or were normalizing in all patients and continued to do so. DISCUSSION The use of FabAV as a continuous intravenous infusion, particularly after the acute phase of envenomation has passed, provides a continuous source of circulating antibodies to neutralize venom components reaching circulation from tissue stores and allows natural replenishment of hematologic factors such as platelets and/or fibrinogen. This method is an efficient use of FabAV, avoiding the wasteful excess of a bolus dose, may be more effective, eliminating the potential for destruction of hematologic factors when protective antivenom levels are lost between bolus FabAV doses, and appears to be safe. Further assessments of the stability and sterility of the product during infusion are needed. The need to continue hospitalization is the major drawback, but continued observation and inpatient care may be needed for other indications (e.g. bleeding) in this subset of patients. CONCLUSIONS A continuous intravenous infusion of FabAV between 2 and 4 vials per day, titrated to effect, and continued for 6-14 days post-envenomation appeared to be associated with reversal of late hematologic effects of rattlesnake envenomation and, when combined with indicated human blood products, control of significant bleeding. Continuous intravenous infusion of FabAV may be safer, more efficacious, and more cost-effective than observation without FabAV treatment or as-needed bolus dosing in selected patients with late hematologic abnormalities.