Page 1017 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

748 PART 5: Infectious Disorders

Isolation of proven cases is not required since human-to-human ensues. Progression to hypercapnic and secondary hypoxic respiratory
transmission does not occur. Standard precautions should be applied to failure has been noted to occur within 24 hours in severe foodborne
care of patients with draining lesions or pneumonia. Decontamination botulism. 37-39
of soiled linen and equipment can be done with heat and standard dis- The diagnosis of botulism in the scenario of a bioterrorist attack
infectants. 34 should be made on the basis of its clinical and epidemiologic features
First-line therapy recommendations for treatment of adults in a con- mentioned above. This is because the definitive diagnosis can be delayed
tained casualty setting are streptomycin 1 g IM twice daily or gentami- for days. The differential diagnosis for isolated cases includes stroke
cin 5 mg/kg IM or IV once daily, for 10 days. Alternative therapies are syndromes, intoxication, Guillain-Barré (Miller-Fischer variant), myas-
doxycycline 100 mg IV twice daily for 14 to 21 days, chloramphenicol thenia gravis, and tick paralysis. However, for multiple cases presenting
15 mg/kg IV four times daily for 14 to 21 days, or ciprofloxacin 400 mg within a short period of time, the differential would be organophosphate
IV twice daily for 10 days. Of note, in the 1950s a fully virulent strepto- and nerve agent poisoning (Table 81-4).
mycin-resistant strain was developed that could potentially be used in Routine laboratory tests, CSF examination, and brain imaging are unre-
a bioterrorist attack. Fortunately the strain was sensitive to gentamicin. markable. Electromyography (EMG) studies show normal nerve conduc-
Since gentamicin has broader gram-negative coverage and is more read- tion velocity, normal sensory function, and decreased amplitude of action
ily available, it may be a more attractive first-line agent, especially if the potentials in affected muscle groups. An incremental increase in amplitude
diagnosis of tularemia is considered but in doubt. 34,35 after repetitive 30- to 50-Hz stimulation helps distinguish botulism from
In a mass casualty setting where hospital resources are overwhelmed, Guillain-Barré syndrome and myasthenia gravis, but not Eaton-Lambert
adults can be treated with doxycycline 100 mg orally or ciprofloxacin syndrome. The edrophonium test can be transiently positive. 39
500 mg orally, twice daily for 14 days. Recovery from the illness is usu- Ventilatory failure should be watched for by following vital capacity
ally within 5 to 7 days. Currently vaccination is only recommended for and carbon dioxide tension on arterial blood gases. Patients without gag
microbiology laboratory workers handling cultures. 34,35 reflex are at high risk for aspiration and may need endotracheal intuba-
tion. In one large series of patients, many had significant hypoxia with-
BOTULINUM out significant hypercapnia. The time to mechanical ventilation was up
to 5 days after the onset of symptoms, and was required for an average
Clostridium botulinum is a ubiquitous spore-forming anaerobic bacillus
that produces a group of seven potent neurotoxins (types A through G).
Botulism is the clinical syndrome produced by these toxins, and naturally TABLE 81-4 Differential Diagnosis of a Large Number of Afebrile People
occurs in three forms: foodborne, intestinal, and wound. Sporadic outbreaks Presenting With Paralysis
of botulism occur throughout the United States due to contamination of Nerve Agent/
food sources. No waterborne cases have ever been reported. 37 Organophosphate Toxicity Botulinum Toxin 2
All cases of botulism occur secondary to absorption of toxin from gut,
lung, or wounds into the bloodstream. Toxin is not absorbed through Mechanism of action Inhibits acetylcholinesterase Inhibits presynaptic acetylcholine
intact skin. Once absorbed it is carried to the peripheral neuromuscular Routes of acquiring neurotransmission
junctions, where it binds irreversibly. The toxin is made of two polypep- Inhalation and dermal Inhalation, ingestion, and contamina-
tide subunits (light and heavy chains). Toxin is endocytosed into the tion of wounds; not dermally active
nerve terminus by virtue of its heavy chain. Subsequently, the light chain Onset to action Minutes to hours 12 hours to several days
cleaves various components of the synaptic fusion complex, preventing
release of acetylcholine into the synaptic cleft. This causes presynaptic Central nervous Agitation, confusion, delirium, Patients remain conscious but
inhibition of neuromuscular transmission, affecting cholinergic, musca- system effects seizures, coma anxious
rinic, and nicotinic receptors. Recovery may take weeks or months and is Motor system Muscle fasciculations, pain, Bulbar palsy (dysarthria, dysphonia,
dependent on regeneration of new motor axons to reinnervate muscle. 38 ( nicotinic receptors) progressive weakness to rigid dysphagia, diplopia), progressive
Botulinum toxin is likely to be used as an aerosol agent in a bioterrorist paralysis descending flaccid muscle paralysis
attack. Aside from the general epidemiologic clues to a bioterrorist attack, Autonomic system Salivation, lacrimation, urinary Dry mouth, variable degree of
identification of toxin types C, D, F, and G should arouse suspicion, since (muscarinic receptors) incontinence, diarrhea, vomiting gastrointestinal symptoms
types A, B, and E are the most common forms found in the United States.
Botulinum toxin is the most potent toxic agent (per weight) known. Toxin Respiratory signs Variable bronchoconstriction, Comparatively slower progression
rapid progression to respira-
to respiratory failure
A given in doses of 0.09 to 0.15 μg IV or IM, 0.7 to 0.9 μg inhaled, or 70 μg
orally is enough to kill a 70-kg human. The toxin itself is colorless, odor- tory failure within minutes
less, and a relatively large protein (150,000 da). It quickly denatures under Ocular signs Progressive miosis Mydriasis, early ptosis, 4th and 6th
environmental conditions: 12 hours in air, 3 hours in sunlight, several cranial nerve palsy
minutes with heat >100°C, and 20 minutes at 0.4% mg/mL free available Cardiovascular Bradyarrythmias > tachycardia None
chlorine in water. 37-39 Electromyography Normal nerve conduction, Normal nerve conduction,
The incubation period for foodborne botulism can vary from hours decreased amplitude at low rates increased amplitude at high rates
to days, but typically is between 12 and 72 hours, similar to that of the of repetitive nerve stimulation of repetitive stimulation
inhalational form. The rapidity of the onset of symptoms varies with
the dose of the toxin, but most often is acute. Patients present initially Diagnosis Blood butyrocholinesterase Mouse neutralization bioassay,
with cranial nerve palsies and prominent bulbar signs of blurred vision, and erythrocyte-cholinesterase specific toxin typing
mydriasis, ptosis, diplopia, dysphonia, dysarthria, and dysphagia. A levels
progressive symmetric descending flaccid muscle paralysis follows, the Decontamination Only for dermal agents, char- None needed if inhalational. If
rapidity of which is also variable. It is important to note that the patient coal and absorptive resins, do ingested give activated charcoal
remains conscious throughout this time and is not febrile. Patients not wipe (blot only)
may also manifest with anticholinergic signs and postural hypoten- Therapy Atropine, pralidoxime, Trivalent or heptavalent antitoxin,
sion. Nausea and vomiting may occur as nonspecific sequelae of an anticonvulsants, antiarrhythmics, anxiolytics, ventilatory support
ileus. The upper airway may collapse due to weakness of oropharyngeal ventilator support
musculature, and handling of secretions may be problematic if the gag
reflex is absent. Later the diaphragm is involved and respiratory failure Recovery Hours to a few days Weeks to months in severe cases

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