William Kerns

Insulin-glucose as adjunctive therapy for severe calcium channel antagonist poisoning.

CASE REPORT This case series documents the clinical courses of 4 patients after verapamil overdose and 1 patient after amlodipine-atenolol overdose. All subjects had hypodynamic circulatory shock (hypotension, bradycardia, and acidosis) that was not adequately responsive to conventional treatment. After initiation of insulin-dextrose infusion, the hemodynamic status of all 5 patients stabilized and all patients survived. Plasma drug concentrations are reported for all cases and verapamil levels were extremely high in 2 patients (3710 ng/mL and 3980 ng/mL). However, because patients were not treated according to a standard protocol, each patient received variable other supportive measures and inotropic agents, and the infusion rates of insulin were variable among patients. This report provides preliminary evidence toward a larger trial of insulin-dextrose to treat hypodynamic shock from calcium channel blocker overdose.

Gamma Hydroxybutyric Acid (GHB) Intoxication

Gamma hydroxybutyric acid (GHB) is a naturally occurring analog of gamma-aminobutyric acid (GABA) that has been used in research and clinical medicine for many years. In the past decade it has become very popular as a dietary supplement and recreational drug. Acute overdose leads to profound alteration of mental status and variable amounts of respiratory depression. With proper management, most patients recover fully within six hours. However, respiratory arrest and death have been reported in severe GHB intoxication. In addition to acute overdose, there is a GHB withdrawal syndrome that is similar to sedative/hypnotic and ethanol withdrawal. Recently several congeners of GHB, gamma butyrolactone and 1,4-butanediol, have emerged as drugs of abuse and show toxidromes similar to GHB. Emergency physicians should be familiar with the presentation and management of GHB-related emergencies.

Insulin Improves Survival in a Canine Model of Acute β-Blocker Toxicity

STUDY OBJECTIVE To compare the efficacy of a novel antidote, insulin, with standard treatments, glucagon and epinephrine, in a canine model of acute beta-blocker toxicity. METHODS Anesthetized dogs were fitted with instruments by means of thoracotomy and vascular cutdown for multiple cardiodynamic, hemodynamic, metabolic, and electrical measures. After basal measurements were taken, animals received intravenous propranolol (.25 mg/kg/minute) continuously for the remainder of the experiment. Toxicity was defined as a 25% decrease in the product of heart rate times mean blood pressure. Thirty minutes after the development of toxicity, toxic measures were taken (treatment 0 minutes), and then the animals (n = 6 each group) received either sham (saline solution), insulin (4 IU/minute with glucose clamped), glucagon (50 micrograms/kg bolus, then 150 micrograms/kg/hour infusion), or epinephrine (1 microgram/kg/minute). Animals were monitored until death or for 240 minutes. RESULTS Propranolol decreased contractility, left ventricular pressure, and systemic blood pressure, and resulted in death of all sham-treated animals by 150 minutes. Six of six insulin-treated, four of six glucagon-treated, and one of six epinephrine-treated animals survived. Survival was greater for insulin-treated animals, compared with either glucagon-treated (P < .05) or epinephrine-treated animals (P < .02) by the log-rank test. Insulin-treated animals were characterized by improved cardiodynamics and hemodynamics, increased myocardial glucose uptake, and decreased serum potassium. CONCLUSION Insulin is a superior antidote compared with glucagon or epinephrine in an anesthetized canine model of acute beta-blocker toxicity.

Cocaine-induced wide complex dysrhythmia.

Cocaine is a local anesthetic with the potential to induce dysrhythmia due to direct myocardial sodium channel antagonism similar to class I antidysrhythmic drugs. The hallmark of myocardial sodium channel poisoning is wide complex dysrhythmia, and the current accepted treatment is intravenous bicarbonate. Wide complex dysrhythmio due to cocaine in the absence of myocardial infarction is rare, and optimum management is undefined. We report three cases of acute cocaine intoxicating during which patients developed wide complex dysrhythmia consistent with sodium channel poisoning. In one case, wide complex tachycardia resolved without direct treatment. In the other cases, wide complex dysrhythmia resolved following intravenous bicarbonate therapy directed at reversing sodium channel blockade.

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.

Intravenous fat emulsion: a potential novel antidote.

Intravenous fat emulsions (IFE) are traditionally used as a component of parenteral nutrition therapy. Recently, IFE was used to resuscitate severe local anesthetic drug toxicity. This review focuses on the potential role of IFE in treatment of toxicity due to local anesthetics and other lipid-soluble drugs. The general properties of IFE, metabolic fate, and associated adverse events are described. Cases of local anesthetic toxicity treated with IFE are presented along with a discussion of the possible antidotal mechanisms. Initial investigations into the antidotal use of IFE for lipophilic central nervous and cardiovascular drug toxicity are also reviewed.

Glycolate Kinetics and Hemodialysis Clearance in Ethylene Glycol Poisoning

OBJECTIVE Toxic manifestations following ethylene glycol exposure are due to accumulation of metabolites, particularly glycolate. We characterized glycolate elimination kinetics and dialysis properties in a series of ethylene glycol poisonings. METHODS Patients who ingested ethylene glycol and received fomepizole (4-methylpyrazole; 4-MP) +/- hemodialysis were prospectively evaluated. Serial blood samples for ethylene glycol, glycolate, pH, and bicarbonate were drawn to determine glycolate elimination rate, t1/2, and correlations between initial glycolate and initial markers of acidosis. Dialyzer inlet and outlet samples were obtained to measure hemodialysis glycolate clearance. Plasma ethylene glycol and glycolate were determined by gas chromatography. RESULTS Ten patients, mean age 49 years (range 28-73 years), presented a mean of 10.5 hours (range 3.5-21.5 hours) after ethylene glycol ingestion. Mean initial ethylene glycol was 18.5 mmol/L (range 0.8-62.2 mmol/L) (115 mg/dL; range 5-386 mg/dL) and glycolate was 17.0 mmol/L (range 10.0-23.7 mmol/L). Nine of 10 underwent hemodialysis. Nonhemodialysis (n = 4) elimination rate was 1.08 +/- 0.67 mmol/L/h (mean +/- SD) and t1/2 was 626 +/- 474 minutes. Elimination t1/2 during hemodialysis (n = 8) was 155 +/- 42 minutes. Hemodialysis clearance (n = 5) was 170 +/- 23 mL/min with flow rates 250-400 mL/min. Pearson correlation coefficients were: anion gap vs glycolate r2 = 0.65 (p = 0.005), bicarbonate vs glycolate r2 = 0.10 (NS) and pH vs glycolate r2 = 0.06 (NS). CONCLUSION Glycolate has a slow elimination rate and long half-life. Hemodialysis effectively clears glycolate. An increased anion gap correlates with the presence of glycolate. Hemodialysis is projected as useful for ethylene glycol-poisoned patients with anion gap acidosis and low ethylene glycol blood levels.

Formate Kinetics in Methanol Poisoning

Objective: We sought to describe the kinetics, dialysis clearance, and laboratory markers of formate (FA), the toxic metabolite of methanol (meOH). Methods: Data were obtained from a prospective, multicenter study of fomepizole±dialysis for methanol poisoning. Inclusion criteria confirmed methanol exposure or suspicion of exposure plus either acidemia or abnormal osmolar gap. Dialysis indications were [meOH]>50 mg/dL, pH<7.1, refractory acidosis, or visual toxicity. Serial plasma formate, methanol, pH, and electrolyte measurements were made. Formate was determined by gas chromatography. Endogenous and dialysis elimination half-lives were calculated as t1/2=0.693/Ke, with Ke (elimination constant) derived from the slope of log (FA) vs. time. Half-lives were compared with an unpaired Students t-test. Dialysis clearance was calculated using the Fick Principle. Pearson correlation analysis compared initial formate with initial pH, serum bicarbonate, and anion gap. Results: Eleven patients were treated in the study. Eight had detectable formate with mean [FA] of 15.1 mmol/L (range 0.5–34.8). Endogenous elimination half-life was 205±90 minutes. Elimination half-life during dialysis (n=5) was 150±37 minutes, which was not different (t=0.22; NS). The overall dialysis formate clearance rate was 223±25 mL/min. Correlation coefficients were: pH vs. formate r2=0.93; bicarbonate vs. formate r2=0.81; and anion gap vs. formate r2=0.76 (all p<0.05). Conclusions: Although dialysis clears formate, it did not significantly enhance endogenous elimination in our series of patients. Low pH, low bicarbonate, and elevated anion gap correlate independently with formate presence.

INCIDENCE OF ASPIRATION PNEUMONIA IN INTUBATED PATIENTS RECEIVING ACTIVATED CHARCOAL

Several case reports and animal studies raise concerns over the risk of aspiration pneumonia when administering activated charcoal (AC) to intubated patients. Therefore, we sought to determine the incidence of aspiration pneumonia in intubated overdose patients who then received AC. We conducted a retrospective review from January 1994 to April 1997 of intubated patients who then received AC. Patients were transferred to, or primarily treated at, an 843-bed tertiary medical center with an annual emergency department volume of 100,000 patients. Objective evidence of infiltrate on chest radiograph during initial 48 h of hospitalization was used to determine the incidence of aspiration pneumonia. Patients with known preexisting pneumonia or with administration of AC before intubation were excluded. There were 64 patients identified. Fourteen were excluded for clinical aspiration before intubation, receiving activated charcoal before intubation, or abnormal immediate post-intubation chest radiographs. The remaining 50 patients, ages 1-64 years, 33% male, overdosing on a large variety of substances, required acute intubation and then received AC. Only two patients of these 50 (4%) with initial negative radiographs developed a new infiltrate after intubation and AC. Administration of AC to intubated overdose patients is associated with a low incidence of aspiration pneumonia.

Copperhead Envenomations In The Carolinas

Introduction: Although the copperhead (Akistrodon contortrix) is responsible for most Crotaline envenomations in the Carolinas, manifestations and treatment are poorly characterized. Objective: We sought to describe the clinical course after copperhead bites. Method: Structured review of copperhead exposures reported to a regional poison center from 1997–2000. Hospital records were reviewed when available. Phone followup was attempted. Results: A total of 178 cases were identified. Of these 75% were males. The median age was 31 yr (range 2–93). The bite site included hand (52%), foot (36%), leg (7%), and arm (5%). Classification included dry (7%), mild (48%), moderate (39%), and severe (6%). The most common symptom was pain (93%). Local findings included swelling (94%), fang marks (93%), ecchymosis (53%), erythema (37%), bullae (13%), and tissue necrosis (8%). Eleven of 37 patients developed abnormal PT and/or PTT. Two patients bled. Patients were treated at a healthcare facility in 160 cases, with 79 patients admitted. Opioid analgesics were the most common therapy (81%). Equine-derived antivenin was given in 14 cases (range 2–30 vials). Antivenin reactions developed in three. Two patients received blood products. Surgical treatment included debridement (6), grafting (2), digit amputation (1), digit dermotomy (1), and fasciotomy (1). No patients died. In followup, 18 patients reported limb dysfunction ranging from 5–365 days. Conclusion: Copperhead bites typically result in mild to moderate envenomation due to local tissue effects. Significant systemic manifestations are rare. Limb dysfunction can be prolonged.