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    Monday, June 13, 2005

    Rabies Cocktail: The doctors who successfully treated the only known (unimmunized) rabies survivor are publishing their recipe this week:

    The strategy consisted of a multi-drug cocktail. Ketamine and amantadine, members of one class of drug that protects brains against damage, with additional specific activity against rabies in animal models, were used. A second class of brain protectors, benzodiazepines with supplemental barbiturates, were also used at levels that suppress brain activity and metabolism and induce a coma-like sedation. Her brain activity was monitored with the help of an electroencephalogram or EEG.

    Even though recent literature had confirmed the futility of antiviral therapy, it was thought, in consultation with the U.S. Centers for Disease Control and Prevention, that ribavirin could prove beneficial. Ribavirin was administered in the hope that it could protect the heart from the virus.

    Although Giese survived and continues to improve five months since her hospitalization, Dr. Willoughby cautions against over-interpreting survival from rabies by a single individual. Jeanna is young, athletic, with a clinical syndrome more consistent with the milder paralytic form than "furious" rabies. "Since the bat was not recovered to isolate and detect rabies virus, we cannot rule out an unusual, more temperate or mutated rabies virus and not the classical variety," he said.

    The paper isn't available on the New England Journal of Medicine's website yet, but I've got the dead tree version right here on my lap. First, they put her in a coma using a continuous intravenous infusion of ketamine and midazolam. They gave her transfusions if necessary to keep her hemoglobin above 10, and they adjusted her ventilator to keep her oxygen level in the normal range and her carbon dioxide level a little on the high side. They kept her brain activity, as monitored by the EEG, as quiet as possible with extra doses of sedatives if needed.

    Then, they added the antivirals. First was ribavirin, a drug used for respiratory syncitial virus and hepatitis C, administered every six hours. Next, they added amantadine, a drug used for Parkinson's and influenza, administered once a day. They chose this because it has shown some effect against rabies virus in the lab, and because it has the added benefit of putting neurons to sleep in areas that ketamine doesn't.

    They began weaning her off her sedatives after about a week. After 27 days, she was taken off the ventilator. After 76 days, she was discharged to home. The authors say that when they saw her four and a half* months after her initial presentation, she was functioning independently although she did have some fine motor coordination problems, such as difficulty with typing and writing, and a lurching gait. Although not completely returned to normal, it's certainly better than the alternative, which was certain death.

    *corrected from the original post when I realized my math error.

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