Background: AMP mortality remains extremely high in developing countries like India even after mild to moderate ingestions as access to care is problematic, presentation is often late, the diagnosis is easily missed, hospital resources are scarce, and liver transplant is unavailable. Cohorts of AMP in northeast Assam have been reported since 1951 with a substantial annual death toll (67 in 2008) and hospital mortality rates exceeding 50%. Mortality in developed countries after large ingestions also remains high. Intravenous silibinin, an approved antidote across Europe and currently under Open IND clinical trial evaluation in the USA, is unavailable in India.
Rationale: Aggressive intravenous hydration (Vesconi,et al,1985) reverses prerenal azotemia, facilitates amatoxin clearance, and prevents the development of early ATN/ARF which invariably leads to poor outcomes. Dogs who underwent pre-placement of a surgical biliary fistula (Fauser and Faulstich,1973) developed less hepatotoxicity and survived known fatal doses of amatoxin. Nasobiliary drainage by ERCP (Madhok,et al,2006) removes sequestered amatoxin, eliminates enterohepatic circulation and may improve outcomes but is not widely available, particularly in developing countries. Percutaneous cholecystostomy (PC) and surgical open cholecystostomy (SOC) are biliary drainage alternatives that are relatively safe, easily performed (20 minutes), and readily available, even in remote locations.
Results: In April, 2011 a cohort of 14 AMP patients presented to North Lakhimpur Civil Hospital in northeastern Assam, India. All developed coagulopathy and evidence of fulminant hepatic failure. PC was considered but the necessary equipment was unavailable. After 8 deaths (many associated with early renal failure later attributed to timid intravenous hydration), informed consent was obtained for SOC which was performed on the remaining 6 patients. 3 died shortly thereafter secondary to multi-system failure. The remaining 3 patients peaked (4.2-5.2) INRs 24 hours later before going on to survive with rapid recoveries. Biliary drains were removed 8 days post-op in order to minimize the risk of bile peritonitis.
Conclusions: AMP patients require sustained aggressive intravenous hydration in order to avoid early renal failure. Early biliary drainage by ultrasound guided PC or SOC should be considered for all patients with confirmed AMP in developing countries when intravenous silibinin is unavailable. Biliary drainage is usually unnecessary in mild to moderate poisonings when intravenous silibinin is administered, but may improve outcomes after large ingestions.