Incidence of immediate hypersensitivity reaction and serum sickness following administration of Crotalidae polyvalent immune Fab antivenom: a meta-analysis.

OBJECTIVES: Crotalidae polyvalent immune Fab (ovine) (FabAV) is commonly used in the treatment of symptomatic North American crotaline snake envenomation. When approved by the U.S. Food and Drug Administration in 2000, the incidences of immediate hypersensitivity reactions and serum sickness were reported as 0.14 and 0.18, respectively. The objective of this meta-analysis was to evaluate the incidence of immediate hypersensitivity reactions and serum sickness reported in studies of patients treated with FabAV therapy after North American crotaline envenomation. METHODS: The authors searched PubMed, Ovid MEDLINE, and EMBASE from January 1, 1997, to September 20, 2010, for English-language medical literature and cross-referenced bibliographies of reviewed articles. The published abstracts of the major toxicology conferences were also searched. All prospective and retrospective cohort studies with patients receiving FabAV therapy for North American crotaline envenomations were eligible for data abstraction. Two content experts reviewed full-text articles and extracted relevant study design and outcome data. Proportions of immediate hypersensitivity and serum sickness for each study were analyzed in a random-effects model to produce an overall estimate of immediate hypersensitivity and serum sickness incidence associated with FabAV administration. RESULTS: The literature search revealed 11 unique studies of patients who received FabAV that contained information on immediate hypersensitivity reactions and serum sickness. The meta-analysis produced a combined estimate of the incidence of immediate hypersensitivity of 0.08 (95% confidence interval [CI] = 0.05 to 0.11) and a combined estimate of the incidence of serum sickness of 0.13 (95% CI = 0.07 to 0.21). CONCLUSIONS: In this systematic literature review and meta-analysis, the combined estimates of the incidence of immediate hypersensitivity reactions and serum sickness from FabAV in the treatment of symptomatic North American crotaline envenomations appear to be lower than previously reported, at 0.08 and 0.13, respectively.

Systematic review of parkinsonian syndromes in short- and long-term survivors of paraquat poisoning.

OBJECTIVE: The objective of this study was to assess whether high-dose paraquat exposure was associated with the development of parkinsonism. METHODS: We carried out a systematic review of all published cases of paraquat toxicity meeting a case-definition of paraquat poisoning and who either recovered or lived for at least 30 days (primary analysis) or lived for 15 to 30 days (secondary analysis). Cases were included if they contained sufficient information to determine whether they had signs of parkinsonism. RESULTS: Our search yielded 818 publications containing 83 cases. The primary analysis yielded 70 cases. None manifested signs of parkinsonism. An additional 13 were in the secondary analysis and none exhibited signs of parkinsonism. CONCLUSION: An analysis the world's entire published experience found no connection between high-dose paraquat exposure in humans and the development of parkinsonism.

Massive acetylcysteine overdose associated with cerebral edema and seizures.

CONTEXT: Acetylcysteine is a safe and effective treatment for the prevention of hepatic injury due to acetaminophen poisoning. While dosing errors are common, in most cases, overdoses produce minimal clinical effects. CASE REPORT: We describe a patient who received 150 g of IV acetylcysteine over 32 h when the clinician ordered the infusion doses be administered as an hourly dose (100 mg/kg/h) rather than administered over the infusion duration (100 mg/kg over 16 h). After approximately 28 h of receiving 100 mg/kg/h, the patient developed delirium, and seizures that progressed to cerebral edema, uncal herniation, and ultimately severe brain injury. No other cause for her symptoms was identified during an extensive workup. DISCUSSION: This case suggests that massive IV acetylcysteine overdose can cause cerebral dysfunction and life-threatening effects.

Short-term outcomes after Fab antivenom therapy for severe crotaline snakebite.

STUDY OBJECTIVES: We seek to determine the short-term outcomes associated with the use of Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) therapy for severe crotaline snake envenomation and to better define the incidence of hypersensitivity reactions associated with FabAV use. METHODS: We conducted a multicenter observational case series study of patients who received FabAV at 17 US hospitals in 2002 to 2004. A 7-point score incorporating local, systemic, and hematologic venom effects was used to grade envenomation severity before and after FabAV therapy. The primary outcome for response to therapy was the change in overall envenomation severity after FabAV administration. The primary safety outcomes were the rates of immediate hypersensitivity reactions and serum sickness. RESULTS: The outcome-evaluable population included 209 patients, of whom 28 had severe envenomation. All severely envenomated patients improved after receiving FabAV. The median severity scores of severely envenomated patients were 5 (interquartile range [IQR] 5 to 5) before FabAV, 1 (IQR 1 to 2) at the last FabAV loading dose, and 1 (IQR 0 to 1) at the last clinical observation. The proportion of patients with progressive pain, progressive swelling, cardiovascular effects, respiratory effects, neurologic effects, gastrointestinal effects, coagulopathy, and thrombocytopenia all improved after FabAV therapy. The safety population included 247 patients. Immediate hypersensitivity reactions were reported in 6.1% (95% confidence interval 3.4% to 9.8%) of patients. Serum sickness was reported in 5% (95% confidence interval 0.6% to 17%) of patients with a minimum of 6 days of follow-up after the last dose of FabAV. CONCLUSION: FabAV therapy is associated with clinical improvement in severe crotaline snake envenomation. Immediate hypersensitivity and serum sickness rates may be less than described in the FabAV prescribing information.

Treatment of chronically digoxin-poisoned patients with a newer digoxin immune fab--a retrospective study.

CONTEXT: Digoxin is used in the treatment of patients with cardiac dysfunction, though toxicity sometimes results from the use of this medication. In 1986, the US Food and Drug Administration (FDA) approved a digoxin immune Fab for the treatment of such patients. In 2001, the FDA approved a newer digoxin immune Fab, a digoxin-specific antibody (DSAb) known as DigiFab (Protherics Inc, Brentwood, Tennessee), though minimal literature exists on the clinical effects of this DSAb. OBJECTIVES: To characterize a cohort of patients presenting with chronic digoxin toxicity and to describe the clinical course of these patients with the use of DSAb. METHODS: A retrospective study included patients with life-threatening cardiotoxicity and serum digoxin level greater than 2 ng/mL who were treated at two US hospitals from 2003 to 2006. Trained investigators abstracted data from patients' medical records and assessed changes in clinical and laboratory parameters at regular intervals (0-4, >4-12, >12-24, and >24-72 hours) after treatment with DSAb. An expert panel reviewed electrocardiogram results to identify life-threatening manifestations of digoxin toxicity before and after DSAb treatment. Efficacy of treatment was assessed as rates of improvement in clinical parameters and cardiotoxic effects. Rates of adverse drug reactions were used to characterize safety. All data were analyzed with descriptive statistics. RESULTS: Fourteen patients (mean [SD] age, 71.3 [10.4] years) were treated for chronic digoxin toxicity. At presentation, 12 patients had a heart rate of less than 45 beats per minute, 1 had third-degree heart block, and 1 had asystole. Mean serum digoxin level was 3.6 ng/mL. Eleven patients had abnormal renal function. After administration of DSAb, clinical parameters improved in all patients. Within 24 hours, cardiotoxicity resolved in 7 of 9 evaluable patients. Two adverse drug reactions possibly related to DigiFab occurred, both of which resolved with conventional measures. Two patients died from conditions unrelated to treatment. CONCLUSION: The newer DSAb appears to be a safe and effective treatment for resolving digoxin toxicity in adults, as indicated by electrocardiogram and clinical assessments. Because patients with multiple comorbidities may be at greater risk for digoxin toxicity, they should be closely monitored during treatment with digoxin.

Low-molecular-weight heparin overdose: management by observation.

OBJECTIVE: To describe 3 episodes of low-molecular-weight heparin (LMWH) overdose in 2 patients and discuss the clinical presentations, outcomes, and therapeutic options. CASE SUMMARIES: The first patient, a 35-year-old female, presented after an intentional overdose of 72,000 units of dalteparin. The peak measured anti-Xa activity was 6.2 U/mL at 7.5 hours postinjection. No interventions were performed and there were no bleeding complications. The patient presented 20 days later following another overdose of 72,000 units. Anti-Xa activity was 4.5 U/mL 2 hours postinjection. No treatment was given and the patient was discharged with plans for follow-up the next day. There was no evidence of bleeding complications on follow-up. The second patient, a 29-year-old male, presented after an intentional overdose of 480 mg of enoxaparin. The anti-Xa activity was 1.9 U/mL measured 2 hours postinjection. The patient was observed without intervention. There were no bleeding complications. DISCUSSION: To our knowledge, there is only one previous report of an LMWH overdose in the literature, an iatrogenic overdose in an infant treated with protamine. In our 3 presented episodes of LMWH overdose, no therapeutic interventions were performed and there were no bleeding complications. Review of the literature regarding the efficacy of protamine and recombinant factor VIIa for reversal of LMWH coagulopathy revealed that protamine is only partially effective and recombinant factor VIIa is effective in in vitro studies and case reports. CONCLUSIONS: In cases of LMWH overdose, observation seems to be appropriate in the absence of clinically significant bleeding. Prolonged monitoring may be necessary for patients with renal failure. Use of protamine or recombinant factor VIIa is not supported by this case series in patients without significant bleeding. There is a lack of data regarding how to treat patients with significant bleeding.

Massive ethylene glycol ingestion treated with fomepizole alone-a viable therapeutic option.

Fomepizole is used to treat and prevent toxicity from ethylene glycol poisoning. Treatment with fomepizole without hemodialysis in massive ethylene glycol ingestion has been rarely reported in the literature; however, published literature and practice guidelines recommend considering dialysis for ethylene glycol levels >50 mg/dL. We report a case of massive ethylene glycol ingestion resulting in the highest serum ethylene glycol concentration in a patient without ethanol co-ingestion who was treated with fomepizole and was not hemodialyzed. A 48-year-old male presented to the emergency department after reportedly ingesting >1 liter of antifreeze in an attempt at self-harm. He denied concomitant ethanol consumption. His initial presenting serum ethylene glycol level was 700 mg/dL, with normal renal function, and a metabolic acidosis with a high anion gap. One hour after presentation, he was started on intravenous fomepizole. Treatment with fomepizole continued until the patient's plasma ethylene glycol concentration was 16 mg/dL. His metabolic acidosis quickly resolved, he had no adverse reactions to the treatment, and his renal function remained normal. Ultimately, he was discharged to a psychiatric unit without sequelae. Published literature and practice guidelines suggests considering hemodialysis initiation in patients with an ethylene glycol level > 50 mg/dL. This recommendation is anecdotally, rather than evidence, based. With the potential risks inherent in hemodialysis, our case provides evidence that treatment with fomepizole without hemodialysis appears to be a viable alternative option in patients with even extremely high plasma ethylene glycol concentrations as long as their renal function is intact.

Crotaline Fab antivenom appears to be effective in cases of severe North American pit viper envenomation: an integrative review.

BACKGROUND: In 2000, the United States Food and Drug Administration approved Crotalidae Polyvalent Immune Fab (Ovine) (hereafter, FabAV), "for the management of patients with minimal to moderate North American Crotalid envenomation." Because whole-IgG pit viper antivenom is no longer available in the United States, FabAV is currently the only specific treatment option available to United States clinicians treating snakebite victims of any severity. No clinical trial data are available concerning the effectiveness of FabAV for treatment of severe snakebite, but several published articles describe its use in this setting. METHODS: We performed a comprehensive review of the English-language medical literature to identify all publications (1996 to July, 2008) containing data about the administration of FabAV. Two trained reviewers separately extracted case-level data concerning the administration of FabAV to patients with severe envenomation by North American crotaline snakes to a standardized form. Descriptive statistics were used. In addition, we hand-searched the US National Poison Data System reports for the years 2000-2006 to identify and describe any reports of death that occurred after FabAV administration. RESULTS: The literature review found 147 unique publications regarding FabAV. Twenty-four evaluable cases of severe human envenomation treated with FabAV were identified in 19 publications. Seven cases were described in five cohort studies, and 17 cases were described in 14 single patient case reports or non-cohort case series. Sixty-five specific severe venom effects were reported in these 24 patients, of which 50 effects (77%) improved or resolved after FabAV therapy. Initial control of all severe venom effects was achieved in 12 patients (50%). The rate at which initial control was achieved was significantly higher among patients reported in the cohort series than in the case series and non-cohort reports (100% vs. 29%, P = 0.005). The median dose of FabAV used to obtain initial control was 6 vials (range: 4 - 18 vials). Nine patients had severe venom effects that persisted despite FabAV therapy. Recurrent and/or delayed-onset severe defibrination syndrome occurred in 12 patients, most of whom did not receive recommended maintenance FabAV dosing. No patient developed systemic bleeding. CONCLUSION: In this structured literature review, FabAV appears to be effective in the management of severe crotaline snake envenomation. Incomplete response to therapy, recurrence of venom effects, and delayed-onset venom effects were reported in case reports, but not reported in cohort studies.