Human rabies has a very high fatality rate and there have only been about 33 well-documented survivors, defined as survival at six months after onset of clinical rabies. Many have had serious neurological sequelae. After a young patient survived rabies in Milwaukee in 2004, the approach dubbed the "Milwaukee protocol" has been aggressively promoted as an effective therapy. The protocol has included therapeutic (induced) coma, ketamine, ribavirin, and amantadine and details of the protocol have changed over time. Over the last two decades no subsequent detailed reports have documented evidence of efficacy. There have been at least 64 cases with failure of the protocol. Likely critical care, which has been used for over 50 years, is an important component of an aggressive approach. The time has now come to abandon the failed Milwaukee protocol for the therapy of rabies and consider new approaches based our current knowledge of rabies pathogenesis.
Keywords: Milwaukee protocol; amantadine; ketamine; ribavirin; therapeutic coma.
© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.