Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Late hemotoxicity following North American rattlesnake envenomation treated with crotalidae immune F(ab')2 (equine) antivenom and crotalidae immune polyvalent Fab (ovine) antivenom reported to the North American Snakebite Sub-registry.

INTRODUCTION: Late hemotoxicity is common following rattlesnake envenomation treated with crotalidae immune polyvalent Fab (ovine) (FabAV). Initial clinical trials showed crotalidae immune F(ab')2 (equine) (Fab2AV) to be superior to FabAV in preventing late hemotoxicity, but this effect has not been demonstrated in broader populations. This study investigated late hemotoxicity in patients receiving Fab2AV or FabAV after rattlesnake envenomation. METHODS: This is a retrospective analysis of prospectively collected data from patients with snakebite reported to the ToxIC North American Snakebite Registry (NASBR) between January 1, 2019, and December 31, 2020. Inclusion criteria were rattlesnake envenomation and administration of antivenom. Patients were excluded if they received more than one type of antivenom. The primary outcome was occurrence of late hemotoxicity (platelets ≤120 k/mm3 or fibrinogen ≤170 mg/dL) in patients receiving Fab2AV and FabAV. Data collected included demographics, envenomation characteristics, laboratory values, and treatment administered. Statistics including t-test and Fisher's exact test were used. RESULTS: A total of 201 rattlesnake envenomated patients receiving antivenom were reported to the NASBR in the study period; 144 were included. 49 received Fab2AV alone, 45 received FabAV alone and 50 received both antivenoms. Baseline patient and envenomation characteristics were similar between the groups. Late hemotoxicity occurred in 2/49 patients in the Fab2AV group (4% (95% CI 0.7-12.6)) and in 19/45 patients in the FabAV group (42% (95% CI 28.4-59.0); absolute risk reduction 39.1% (95% CI 21.2-46.2) (p = 0.001). On follow up, 0 patients (0%) receiving Fab2AV were retreated with antivenom; 4 patients (9%) receiving FabAV were retreated (p = 0.049). CONCLUSIONS: In the North American Snakebite Registry, late hemotoxicity was less common in rattlesnake envenomated patients treated with Fab2AV compared to FabAV.