Page 1751 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

1220 PART 11: Special Problems in Critical Care

by the mnemonic SLUDGE (salivation, lacrimation, urination, diarrhea, repeated once. A continuous infusion is then administered at a rate of
gastrointestinal cramps, and emesis). Blurred vision, miosis, bradycar- 200 to 500 mg/h, titrated to achieve the desired effect. Continuous infu-
dia, and wheezing are also muscarinic effects. Nicotinic effects are less sion of pralidoxime may be necessary for over 24 hours, depending on
sustained and characterized by fasciculations, muscle weakness (that can the half-life and lipid solubility of the poison, after which the dose may
progress to paralysis), hypertension, and tachycardia. Organophosphates be gradually reduced and stopped while the patient is observed for signs
penetrate the blood-brain barrier to cause anxiety, confusion, psychosis, of recurrent muscle weakness.
seizures, and ataxia.
The two principal cholinesterases are RBC cholinesterase (also called ■ SALICYLATES
acetylcholinesterase or AChE), which is present in red blood cells and Acetylsalicylic acid or aspirin is converted rapidly to salicylic acid, its
nerve endings, and pseudocholinesterase (PChE), which is found pri- active moiety. Salicylic acid is readily absorbed from the stomach and
marily in liver and serum. Carbamates and organophosphates inhibit small bowel. At therapeutic doses, it is metabolized by the liver and
both. Clinical toxicity is due primarily to inhibition of AChE, but PChE eliminated in 2 to 3 hours. Chronic ingestion can increase the half-life
is more readily quantified. Levels may not correlate with the severity of to more than 20 hours. Overdose can be accidental or deliberate, acute
346
poisoning. A falsely low PChE may be seen in liver disease, anemia, or chronic. A number of over-the-counter combination formulations
341
and malnutrition, and as a normal genetic variant (familial succinyl- and herbal remedies contain salicylates. The use of alternate analgesics,
choline sensitivity). Normal levels of enzyme activity do not exclude child-resistant containers, and package-size restrictions has decreased
poisoning because of wide variations in normal levels. In the absence the incidence of poisoning. 347,348
of a baseline levels, serial measurements may confirm the diagnosis. 342 Therapeutic serum levels of salicylates are 10 to 30 mg/dL. Clinical
During initial patient stabilization, attention should be paid to the features of intoxication occur in most individuals with serum levels above
respiratory status. Bronchoconstriction, excess secretions, muscle weak- 40 to 50 mg/dL; in chronic intoxication, severe poisoning occurs at lower
ness, and an altered mental status all increase the risk of respiratory serum levels (particularly in elderly patients). In toxic amounts, salicylates
failure requiring. In agricultural exposures, it is important to remove all are metabolic poisons that affect a number of organ systems by uncou-
contaminated clothing and cleanse hair and skin thoroughly to decrease pling oxidative phosphorylation and interfering with the Krebs cycle. 349
skin absorption. Health care workers must protect themselves from Minor intoxication causes tinnitus, vertigo, nausea, vomiting, and
accidental exposure by wearing appropriate gloves and gowns. Activated diarrhea. More significant ingestions cause acid-base disturbances.
charcoal and gastric lavage may be useful if done immediately after Respiratory alkalosis is caused by direct central ventilatory stimula-
ingestion, but the airway must be protected. tion. Organic acids (including lactate and ketoacids) accumulate with
Symptomatic patients should receive atropine immediately. Treatment uncoupling of oxidative phosphorylation to cause an elevated anion
should not await results of AChE or PChE levels. Atropine competitively gap metabolic acidosis. Salicylic acid itself contributes minimally to the
blocks acetylcholine at muscarinic receptors but has no effect on nicotinic measured anion gap (only 3 mEq/L with a 50 mg/dL level). Adults com-
receptors. Atropine crosses the blood-brain barrier and can cause CNS monly present with respiratory alkalosis or combined metabolic acidosis
toxicity that is difficult to distinguish from organophosphate toxicity. and respiratory alkalosis. Children may develop pure metabolic aci-
350
In this situation, glycopyrrolate (which does not penetrate the CNS) is dosis. Severe poisoning also causes noncardiogenic pulmonary edema,
a reasonable alternative to atropine. In addition, regimens including mental status changes, seizures, coma, gastrointestinal bleeding, liver
343
combinations of atropine and glycopyrrolate have been proposed that failure, renal failure, and death. Systemic symptoms generally begin
351
would allow for less atropine. One study suggests decreased mortality with within 4 to 8 hours after ingestion, although reports exist of delayed
this combination when compared with a historical control of atropine presentations up to 35 hours (in enteric-coated aspirin). 352
alone patients. The dose of atropine required to achieve atropinization Thisted and colleagues reported clinical findings of 177 consecutive
344
(characterized by clear pulmonary examination and heart rate >80 beats admissions to an ICU with acute salicylate poisoning. Neurologic
353
per minute) varies depending on the severity of poisoning. Doses of abnormalities occurred in 61% of cases, acid-base disturbances in 50%,
340
up to 40 mg/d may be required. If atropinization occurs after 1 to 2 mg of pulmonary complications in 47%, coagulation disorders in 38%, fever in
atropine, the diagnosis of acetylcholinesterase inhibitor poisoning should 20%, and hypotension in 14%. In a separate 2-year review of salicylate
be questioned. The initial dose of atropine is 2 mg IV. This dose should deaths in Ontario, 31.4% of patients were dead on arrival. ICU mor-
354
be doubled every 3 to 5 minutes until atropinization has been achieved. tality has been reported to be 15% when diagnosis is delayed, compared
Continuous atropine infusion can then be started at 10% to 20% of the to approximately 5% in cases recognized early. The clinical features of
355
loading dose required to achieve atropinization hourly while closely moni- salicylate intoxication are reviewed in Tables 124-26 and 124-27.
toring for atropine toxicity (delirium and hyperthermia). 340
Pralidoxime (2-PAM) reverses nicotinic and muscarinic effects of
organophosphate poisoning by reactivating AChE and protecting the
enzyme from further inhibition. In carbamate poisoning, pralidoxime TABLE 124-26 Clinical Findings in 177 Patients Admitted to an ICU With Acute
may not be needed because of the more rapid resolution of symptoms Salicylate Poisoning
and reversible nature of enzyme inhibition. It has historically been sug- Clinical Signs Percent
gested that pralidoxime may enhance carbaryl (or Sevin, a carbamate
insecticide) toxicity, although current recommendations recognize the Neurologic abnormalities (depressed consciousness) 61
345
difficulty oftentimes present in distinguishing carbamate and OP toxic- Acid-base disturbances 50
ity and therefore recommend oxime therapy in addition to atropine as Pulmonary complications 43
needed. To be effective, pralidoxime should be given within the first
334
6 hours of poisoning (although treatment in the first 24-48 hours may Coagulation disorders 38
still be effective), prior to irreversible phosphorylation of cholinesterase Hyperpyrexia 20
(a process referred to as “aging”). After this critical period, restoration Circulatory disorders (hypotension) 14
of normal cholinesterase function requires regeneration of the enzyme,
a process that may take weeks to complete. Antimuscarinic effects allow Electrocardiographic abnormalities (Wide QRS, first- and second-degree 10
for atropinization more quickly, and with lower doses of atropine. The atrioventricular block, ventricular arrhythmias)
initial dose of pralidoxime is 1 to 2 g IV given over approximately 10 to Renal abnormalities (oliguria) 7
20 minutes. Clinical response should be evident within 30 minutes. If Data from Thisted B, Krantz T, Stroom J, et al. Acute salicylate self-poisoning in 177 consecutive patients
there is no improvement in fasciculations or weakness, the dose may be treated in ICU. Acta Anaesthesiol Scand. May 1987;31(4):312-316.

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