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

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/mm(3), 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.

Delayed cardiogenic shock and acute lung injury after aneurysmal subarachnoid hemorrhage.

Both cardiac and lung injury after aneurysmal subarachnoid hemorrhage has been attributed to an adrenergic surge. Cardiogenic shock is very uncommon. We describe a 55-yr-old woman with a delayed cardiogenic shock emerging within hours after aneurysmal rupture. Cardiac damage was documented by increased serum troponin T, CPK-mb fraction, and severe wall motion abnormality, which included an akinetic apex on echocardiography (ejection fraction of 33%). Her coronary angiogram was normal. Decreased cardiac index, increased systemic and pulmonary vascular resistance indices, and persistent oxygen desaturation despite improving ventricular contractility documented both cardiac and pulmonary injury. After treatment with dobutamine and milrinone all manifestations resolved.

Iodine toxicity treated with hemodialysis and continuous venovenous hemodiafiltration.

Continuous mediastinal irrigation with povidone-iodine is used commonly for treating severe postoperative mediastinitis. However, concurrent iodine toxicity has been reported, particularly in patients with renal dysfunction (likely because absorbed iodine is renally excreted). The authors were consulted on a 45-year-old patient with mediastinitis who had renal and hepatic dysfunction while being treated with mediastinal irrigation of povidone-iodine. The povidone-iodine irrigation was discontinued because he had toxic plasma iodine levels. Despite this, his condition worsened, and the iodine levels remained elevated. Thus, hemodialysis (HD) was initiated using high-flux membranes followed by continuous venovenous hemodiafiltration (CVVHDF; 2 L/h of hemofiltration and 2 L/h of HD). Plasma and effluent iodine levels were measured repeatedly to determine iodine clearance by these 2 modalities (HD, 120 mL/min; CVVHDF, 37 mL and 44 mL/min on days 1 and 2, respectively). Hepatic and renal functions improved with decreasing plasma iodine levels. Based on this experience and after reviewing the literature the authors conclude that: (1) iodine irrigation can increase blood iodine levels significantly, especially in the setting of renal failure, and lead to increased morbidity and mortality; (2) plasma iodine levels should be monitored in patients with renal insufficiency; and (3) HD and CVVHDF are effective at clearing iodine. The authors suggest that patients that are at high risk or already developing signs of iodine toxicity should have the iodine irrigation discontinued and may benefit from renal replacement therapy (RRT). Alternatively, concomitant RRT during iodine irrigation may be attempted to maintain the systemic iodine levels at nontoxic levels.