Modern lethality rate of suspected cyclopeptide mushroom poisoning in the US: The power of supportive care!

Objective: This study was designed to estimate the mortality of suspected cyclopeptide‐containing mushroom ingestions reported to the National Poison Data System. Background: Although silibinin reportedly improves survival in suspected cyclopeptide‐containing (hepatotoxic) mushrooms, the untreated mortality rate often cited as greater than 20% is based on decades old data. An ongoing open‐label trial of silibinin seeks US Food and Drug Administration approval. Our recent analysis of data from a single poison control center (PCC) suggested a lower mortality rate of 8.3% following suspected cyclopeptide‐mushroom ingestion. This new study was designed to validate our PCC's findings in the National Poison Data System (NPDS) by increasing the sample size, and accounting for geographical and local practice variations. Methods: A 10‐year (1/1/2008‐12/31/2018) retrospective review of suspected cyclopeptide‐containing mushroom ingestions reported to NPDS used the same inclusion/exclusion criteria as an ongoing silibinin trial (NCT00915681): Age >2; history of eating foraged mushrooms; gastrointestinal symptoms (cramping abdominal pain, nausea, vomiting, and/or watery diarrhea) within 48 hours of mushroom ingestion; and aminotransferases (AST or ALT) above the upper limit of normal value for the lab reference range within 48 hours after mushroom ingestion. We systematically followed up on all cases that met inclusion criteria with their respective PCC to confirm, eligibility, diagnosis, treatment, and mortality or transplant outcomes. De‐identified data were gathered by survey using a standardized abstraction tool. Results: 8,953 mushroom exposures were reported to NPDS, of which 296 were retained based on study inclusion criteria. The survey response rate was 57% (27/47 PCCs), as was the case response rate (168/296). Based on survey responses, 33 cases were subsequently excluded, largely because of the absence of confirmed foraging, or a non‐mushroom diagnosis, leaving 135 included cases. The geographic distribution was: Northeast, 34%; Southeast, 15%; West coast, 31%; Midwest, 16%; South Central, 4%. The overall mortality rate was 9% (12/135). Mortality in silibinin/silymarin‐treated vs untreated cases was 10% (4/39), vs 8% (8/96), respectively. Mycologist identification occurred in 17.8% of cases (24/135), of which 70.8% (17/24) were cyclopeptide‐containing mushrooms. Among identified cases, the mortality rate was; 13% (1/8) vs 11% (1/9), in silibinin/silymarin‐treated vs untreated cases, respectively. Conclusion: In this retrospective review of NPDS data, the mortality rate was 8% in patients with presumed cyclopeptide‐mushroom poisoning who met enrollment criteria for the ongoing silibinin trial but did not receive silibinin. This modern fatality rate is much lower than the greater than 20% previously reported and likely represents improved supportive care. Using the same criteria for cyclopeptide‐mushroom poisoning, a well‐designed randomized controlled trial would require more than 300 patients to find a statistically significant 50% reduction (from 8% to 4%) in mortality with an alpha of 0.05 and beta of 0.2. As the current open‐label trial plans to enroll 50 patients, it is likely underpowered to demonstrate evidence of silibinin's efficacy.