Milwaukee Protocol for Rabies
Direct Answer
The Milwaukee Protocol should no longer be used for treating clinical rabies, as it has been definitively shown to be ineffective with at least 64 documented failures and no reproducible evidence of efficacy. 1, 2
What the Milwaukee Protocol Was
The Milwaukee Protocol was an experimental treatment approach developed after a single patient survived rabies in Milwaukee in 2004. The protocol included:
- Therapeutic (induced) coma to reduce brain metabolic demands 2
- Ketamine administration 3, 2
- Ribavirin as an antiviral agent 3, 2
- Amantadine as an antiviral 3, 2
- Intensive supportive care 4, 2
The protocol details changed over time as it was modified and promoted for two decades following the initial survivor 2.
Why It Failed
Over the last two decades, no subsequent detailed reports have documented evidence of efficacy, with at least 64 cases resulting in failure of the protocol. 2
- Ribavirin and interferon-α have proved to be disappointing agents for rabies therapy 3
- There is insufficient evidence to support the continued use of ketamine or amantadine for rabies treatment 3
- Rabies remains virtually always fatal after clinical disease develops, with only approximately 33 well-documented survivors worldwide (defined as survival at six months after onset), many with serious neurological sequelae 1, 2
Current Recommendations
The focus must remain on prevention through post-exposure prophylaxis, which is nearly 100% effective when administered properly before clinical symptoms develop. 4
Standard Post-Exposure Prophylaxis (Not Milwaukee Protocol)
For previously unvaccinated individuals exposed to rabies:
- Immediate wound cleansing with soap and water for 15 minutes, followed by povidone-iodine solution if available 5, 6
- Human Rabies Immunoglobulin (HRIG) at 20 IU/kg body weight, infiltrated around and into all wounds, with remainder given intramuscularly at a site distant from vaccine 5, 6
- 4-dose vaccine schedule (HDCV or PCECV) administered intramuscularly on days 0,3,7, and 14 7, 5
- For immunocompromised patients, a 5-dose schedule on days 0,3,7,14, and 28 is required 7, 5
Once Clinical Rabies Develops
Critical care supportive measures remain the only available approach, though outcomes are almost universally fatal. 2 The time has come to abandon the failed Milwaukee protocol and consider new approaches based on current knowledge of rabies pathogenesis 2.
Key Clinical Pitfall
Do not confuse the Milwaukee Protocol (a failed treatment for clinical rabies) with post-exposure prophylaxis (highly effective prevention before symptoms develop). The Milwaukee Protocol has been aggressively promoted despite lack of efficacy, leading to confusion about rabies management 2. Post-exposure prophylaxis must be initiated immediately after any potential rabies exposure, as it is nearly 100% effective when given before clinical symptoms appear 4.