The Efficacy of Antivenin Latrodectus (Black Widow) Equine Immune F(ab')2 Versus Placebo in the Treatment of Latrodectism: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.

STUDY OBJECTIVE: The antivenom currently available for treatment of systemic black widow envenomation (latrodectism) is composed of equine whole immunoglobin. Although considered effective, it has been associated with anaphylaxis and 2 reported fatalities. We test the efficacy and safety of new equine antivenom composed of purified F(ab')2 antibody fragments. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at 16 sites across the United States. Subjects aged 10 years or older with moderate to severe pain because of black widow spider envenomation received F(ab')2 antivenom or placebo. The primary outcome measure was treatment failure, which was defined as failure to achieve and maintain clinically significant reduction in pain for 48 hours posttreatment. Secondary measures of pain intensity differences and summed pain intensity difference were computed. Adverse events were recorded. RESULTS: Sixty patients were treated (29 antivenom and 31 placebo). The mean age was 39 years and 68% were male. There were 15 treatment failures in the antivenom group and 24 in the placebo group (P=.019). Differences in pain intensity difference between groups were lower at each postbaseline point, and the mean summed pain intensity difference was greater for the antivenom group (difference 2,133; 95% confidence interval 177 to 4,090). No deaths or serious drug-related adverse events were detected. CONCLUSION: The F(ab')2 antivenom met the predefined primary outcome of reduced treatment failures. Secondary outcomes of pain intensity difference and summed pain intensity difference also supported efficacy. The rate of symptom improvement in the placebo group was higher than expected, which may be related to enrollment criteria or placebo effect.

A review of methylene blue treatment for cardiovascular collapse.

BACKGROUND: Historically, methylene blue (MB) has been used for multiple purposes, including as an antidote for toxin-induced and hereditary methemoglobinemia, ifosfamide-induced encephalopathy, and ackee fruit and cyanide poisoning; as an aniline dye derivative, antimalarial agent, and antidepressant. DISCUSSION: Most recently, the use of MB has been advocated as a potential adjunct in the treatment of shock states. Our article reviews the role of MB in septic shock, anaphylactic shock, and toxin-induced shock. MB is proposed to increase blood pressure in these shock states by interfering with guanylate cyclase activity, and preventing cyclic guanosine monophosphate production and vasodilatation. SUMMARY: MB may be an adjunct in the treatment of septic shock, anaphylactic shock, and toxin-induced shock.

A retrospective review of whole bowel irrigation in pediatric patients.

BACKGROUND: Traditionally whole bowel irrigation (WBI) has been advocated for ingestions involving substances not bound with activated charcoal as well as extended release and enteric coated medications. Other than isolated case reports, little exists in the literature regarding the use of WBI in poisoned pediatric patients. The purpose of this study is to better understand the use of WBI in pediatric patients. METHOD: A retrospective chart review of California Poison Control System electronic database for human poisoning cases between the years 2000 and 2010 was performed. RESULTS: A total of 176 cases were identified. The most common age of poisoned patients that received WBI was 2 years. There were more pediatric patients who received WBI between 2000 and 2005 then between 2006 and 2010. The top three substances in which WBI was used were calcium channel blockers, iron, and antidepressants. There were 72 cases involving sustained release and delayed release substances. The top five sustained release/delayed release substances were nifedipine, bupropion, verapamil, diltiazem, and felodipine. Adverse drug reactions were noted in 17 patients, vomiting in 16 patients and abdominal pain in one patient. In 36 cases, abdominal radiographs were performed. Sixteen were positive, and in four cases, repeat abdominal radiographs demonstrated a decrease in opacities. Twelve patients had documented pills in their effluent. CONCLUSION: Transient adverse drug reactions, vomiting and abdominal pain, were associated with WBI. Polyethylene glycol plus electrolyte lavage solution (PEG-ELS) was more frequently administered through the nasogastric tube. Patients who underwent WBI through nasogastric tube received higher doses of PEG-ELS.

Multiple centrally acting antidotes protect against severe organophosphate toxicity.

BACKGROUND: Accumulation of acetylcholine in the central nervous system is believed to account for the rapid lethality of organophosphate pesticides and chemical nerve agents. Diazepam is known to supplement atropine therapy, but its specific mechanism of action is uncertain. OBJECTIVES: To test four centrally acting agents for early antidotal efficacy in severe dichlorvos poisoning in the murine model. METHODS: The up-and-down method was used to dose four candidate antidotes: diazepam, xylazine, morphine, and ketamine. Antidotes were administered subcutaneously to unsedated adult Sprague-Dawley rats who were pretreated with 3 mg/kg intraperitoneal glycopyrrolate. All animals received 20 mg/kg of dichlorvos subcutaneously 5 minutes later. A blinded observer adjudicated the outcomes of 10-minute mortality and survival time. RESULTS: All animals pretreated with either no antidote (8/8 deaths) or glycopyrrolate alone (8/8) died within 10 minutes of dichlorvos injection. Pretreatment with diazepam (3/9 deaths), or xylazine (3/9), decreased lethality substantially (Fisher p = 0.007; median effective doses, 0.12 mg/kg and 3.0 mg/kg, respectively). Intermediate doses of morphine (3.1 to 5.5 mg/kg) resulted in survival, but higher doses did not, presumably because of excessive respiratory depression (7/11 deaths; p = 0.09). Ketamine (7/8 deaths) was ineffective as an antidote. Survival times also were prolonged in the diazepam and xylazine groups (log-rank p < 0.001) and, to a lesser degree, the morphine group (p = 0.07). CONCLUSIONS: Doses of diazepam, xylazine, and morphine below those used for deep sedation protect against severe dichlorvos poisoning, implying that several distinct central mechanisms are each sufficient to avert lethality. These findings suggest new possibilities for prophylaxis or therapy.