In response to Drs DeBalli and Cook, not all nerve agent
casualties will necessarily be trauma related. Succinylcholine is
a preferred method to facilitate endotracheal intubation
because of its fast onset and short duration of action through
metabolism by pseudocholinesterase.
6,7
A patient exposed to
sarin who receives succinylcholine would have prolonged neu-
romuscular blockade, eliminating a major reason why succi-
nylcholine is preferred in rapid sequence intubation. Although
organophosphate insecticides and nerve agents both inhibit
acetylcholinesterase, the 2 classes of chemicals do not behave
exactly the same. There is no evidence for their suggestion that
the duration of paralysis in patients receiving succinylcholine
after nerve agent exposure would be less than 4 hours in most
cases. Furthermore, if an oxime is not administered soon
enough, the cholinesterase enzymes will be irreversibly inacti-
vated. The period of regeneration of cholinesterase enzymes
could last from weeks to several months.
8
This is in contrast
with a genetic variation of pseudocholinesterase, in which an
individual still retains partial ability to metabolize succinyl-
choline.
9
Sparks et al
10
found enhanced mortality from succi-
nylcholine in mice when serum pseudocholinesterase is inhib-
ited 55% to 94%.
An alternative to the use of succinylcholine is awake intu-
bation. In fact, some anesthesia providers experienced in com-
bat anesthesia avoid the use of NMB agents when faced with a
difficult airway and opt for awake intubation.
6
A second alternative, as Deballi and Cook describe, would
be to use a rapid onset nondepolarizing NMB agent such as
rocuronium. Although a higher acetylcholine concentration at
the neuromuscular junction would necessitate a higher than
normal dose, once the nerve agent effect wears off, reversal
agents such as neostigmine are available for nondepolarizing
blocking agents. Furthermore, in a mass casualty scenario,
unnecessarily tying up a large number of ventilators for pro-
longed periods would adversely impact normal health care
operations.
To add to what Drs Schier and Hoffman have correctly
pointed out, in addition to respiratory arrest, a short infusion
of pralidoxime may cause blurred vision and dizziness that
may be confused with worsening anticholinesterase poison-
ing.
11
The optimal dosing regimen is difficult to ascertain.
Much research has been based on animal studies. Interspecies
variability poses a problem. Because atropine may prolong sur-
vival and give the oxime more time to work, the oxime con-
centration needed for therapeutic effect might be lower.
12
Additionally, poisoned individuals can differ from healthy vol-
unteers with regard to hemodynamic condition and water and
electrolyte balance.
13
Medicis et al
11
found that in patients
exposed to organophosphate, the mean elimination half-life
for pralidoxime was 3.44 hours compared with 1.2 hours in
healthy patients.
Maj Ernest C. Lee, MD, MPH, USAF, MC
Occupational and Environmental Medicine
Harvard School of Public Health
Boston, Mass
Disclaimer: The views expressed in this letter are those of the author and do not
reflect the official policy or position of the US Air Force, Department of Defense,
or the US government.
1. Shih T, McDonough JH Jr, Koplovitz I. Anticonvulsants for soman-induced sei-
zure activity. J Biomed Sci. 1999;6:86-96.
2. McDonough JH, Zoeffel LD, McMonagle J, et al. Anticonvulsant treatment of
nerve agent seizures: anticholinergics versus diazepam in soman-intoxicated guinea
pigs. Epilepsy Res. 2000;38:1-14.
3. Wood SJ, Tattersall JE. An improved brain slice model of nerve agent-induced
seizure activity. J Appl Toxicol. 2001;21:S83-S86.
4. Koplovitz I, Schulz S, Shutz M, et al. Combination anticonvulsant treatment of
soman-induced seizures. J Appl Toxicol. 2001;21:S53-S55.
5. McDonough JH Jr, McMonagle J, Copeland T, et al. Comparative evaluation
of benzodiazepines for control of soman-induced seizures. Arch Toxicol. 1999;
73:473-478.
6. Pellegrini JE, Baker AB, Fontenot DJ, Cardenas AF. The effect of oral pyridostig-
mine bromide nerve agent prophylaxis on return of twitch height in persons re-
ceiving succinylcholine. Mil Med. 2000;165:252-255.
7. Baraka A, Wakid N, Mansour R, Haddad W. Effect of neostigmine and pyridostig-
mine on the plasma cholinesterase activity. Br J Anaesth. 1981;53:849-851.
8. Treatment of chemical agent casualties and conventional military chemical in-
juries: FM8-285: part 1, chemical agent casualties. Available at: http://www.vnh
.org/FM8285/Chapter/chapter2.html. Accessibility verified November 7, 2003.
9. Sdrales LM, Miller RD. Anesthesia Review: A Study Guide to Anesthesia. 5th
ed. Philadelphia, Pa: Churchill Livingstone; 2001.
10. Sparks SE, Quistad GB, Casida JE. Organophosphorus pesticide-induced bu-
tyrylcholinesterase inhibition and potentiation of succinylcholine toxicity in mice.
J Biochem Mol Toxicol. 1999;13:113-118.
11. Medicis JJ, Stork CM, Howland MA, Hoffman RS, Goldfrank LR. Pharmaco-
kinetics following a loading plus a continuous infusion of pralidoxime compared
with the traditional short infusion regimen in human volunteers. J Toxicol Clin
Toxicol. 1996;34:289-295.
12. Sundwall A. Minimum concentrations of N-methylpyridinium-2-aldoxime meth-
ane sulphonate (P2S) which reverse neuromuscular block. Biochem Pharmacol.
1961;8:413-417.
13. Willems JL, Langenberg JP, Verstraete AG, et al. Plasma concentrations of pra-
lidoxime methylsulphate in organophosphorus poisoned patients. Arch Toxicol.
1992;66:260-266.
Level of Exercise and Risk of
Cardiovascular Disease
To the Editor: Dr Mora and colleagues
1
found that both ex-
ercise capacity and heart rate recovery after exercise were re-
lated to risk of cardiovascular and all-cause mortality. They con-
cluded that their “findings support the potential use of exercise
testing as a risk-stratification tool for primary prevention in
asymptomatic women....” Although the authors controlled
for several cardiac risk factors, they did not include current level
of exercise in their analysis. It is possible that simply asking
women whether they regularly engage in strenuous exercise
or hard physical labor would also similarly identify those women
at increased risk of cardiovascular death.
Lorraine L. Tosiello, MD
Nallu Reddy, MD
Department of Internal Medicine
Overlook Hospital
Summit, NJ
1. Mora S, Redberg RF, Cui Y, et al. Ability of exercise testing to predict cardio-
vascular and all-cause death in asymptomatic women: a 20-year follow-up of the
Lipid Research Clinics Prevalence Study. JAMA. 2003;290:1600-1607.
In Reply: We agree with Drs Tosiello and Reddy about the
importance of assessing physical activity as part of a compre-
hensive approach to cardiovascular risk stratification. Previous
studies have clearly demonstrated a lower incidence of cardio-
LETTERS
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