Recovery or Death (Stage V)
On average, death occurs 18 days after the onset of symptoms. Patients cared for in intensive
care units have survived from 25 days to months with respiratory support. Death in these
patients is often from myocarditis with arrhythmia or congestive heart failure.
Diagnosis: Nuchal biopsy and saliva—viral antigen and viral RNA can be detected by
DFA test and reverse transcription polymerase chain reaction (RT-PCR), respectively (121).
Differential diagnosis: Other causes of viral encephalitis, tetanus (when opisthotonos is
present), acute inflammatory polyneuropathy, transverse myelitis, and poliomyelitis. When
there is a prolonged incubation period, clinical disease may suggest progressive multifocal
leukoencephalopathy. Spongiform changes in the brain may resemble prion disease.
Treatmentin an intensive care unit should be considered if (i) the patient received rabies
vaccine before the onset of symptoms, (ii) the patient presents at a very early stage of disease
(i.e., paresthesias), (iii) the patient is generally in good health, (iv) the acceptance of the high
probability of death or significant neurologic deficits, and (v) availability of adequate
resources. Some authors disagree about limiting therapy to cases strictly in the earliest stages
(122).
All patients should receive rabies vaccine (human diploid vaccine) and rabies immune
globulin (RIG).All individuals potentially exposed to the virus (including caregivers) should receive
both the vaccine and RIG as soon as possible. There is no time limit after exposure that the vaccine and
RIG cannot be given! Pregnancy is not a contraindication.Contacts should be traced to at least one
week prior to the onset of neurologic symtpoms in order to provide them with prophylaxis.
Postexposure prophylaxis: People previously vaccinated against rabies within two years
and who have evidence of immunity: 1.0 mL intramuscularly (IM) on days 0 and 3; no human RIG.
People not previously vaccinated against rabies 1.0 mL IM (deltoid in adults, anterior lateral
thigh in children) on days 0, 3, 7, 14, and 28, plus human RIG (20 IU/kg) within seven days of
first vaccine dose. In the absence of documented immunity, the full schedule of postexposure
prophylaxis is indicated.
A patient survived rabies without vaccine or RIG after treatment with antiviral agents
and induced coma (ketamine, midazolam, ribavirin, and amatadine—the Milwaukee Protocol).
She was discharged alert, but with choreoathetosis, dysarthria, and unsteady gait (123).
Ketamine-induced coma and ribavirn therapy has failed in other patients (121,124).
Ketamine was administered to one rabies survivor. In the mouse model, ketamine
showed no benefit. Minocycline has been suggested as therapy. But, in the mouse model,
minocycline appeared to aggravate the disease (125).
A rabies survivor was found to have deficiencies of tetrahydrobiopterin (BH4) and
related neurotransmitters. Based upon this finding, investigators monitored flow velocities,
and resistive and pulsatility indices of the middle cerebral arteries by transcranial Doppler.
Patients with vasoconstriction were treated with nitroprusside, BH4, BH4 and L-arginine (126).
CONCLUSION
Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the
beginning.
—Sir Winston Churchill,Speech in November 1942The intensivist participates in all disaster planning and is thoroughly familiar with
hospital protocols. What is simultaneously considered after the initial recognition that the
patient may be a victim of bioterrorism includes the most likely diagnosis and differential
diagnosis, the broadest emergent treatment, identification and prophylaxis of contacts where
indicated, and isolation and safety precautions. Other scenarios include: (i) the patient being
infected with two or more agents, especially with differing incubation periods; (ii) additional
victims presenting similarly but infected with a different pathogen or pathogens as a result of a
second simultaneous attack; (iii) a second attack at a later time with the same or different
agents; and (iv) genetically altered agents that renders them more resistant to treatment and/or
more difficult to identify. An even more sinister possibility is that the hospital (building,
buildings, or campus) becomes one of the primary or secondary targets.
Bioterrorism Infections in Critical Care 481