General Toxicology and Toxidromes

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Chapter 78 General Toxicology and Toxidromes

Aaron B. Skolnik, MD , Susan R. Wilcox, MD

2 What are the common toxidromes?

Toxidromes are syndromes associated with particular classes of toxins. They may be useful in making the diagnosis of poisoning and initiating treatment as patients are often too ill to wait for the results of laboratory or other testing (Table 78-1).

^{Table 78-1} Toxidromes

Toxidrome	Clinical findings	Example agents
Cholinergic	Diarrhea, fecal incontinence, enuresis, miosis, tachycardia followed by bradycardia, lacrimation, sialorrhea, sweating, muscle fasciculations followed by weakness and/or paralysis, altered mental status	Organophosphate and carbamate insecticides Amanita muscaria Nicotine
Anticholinergic	Agitated delirium, flushing, decreased sweating, tachycardia, mydriasis, urinary retention, decreased peristalsis, hyperthermia	Atropine Benztropine Scopolamine Diphenhydramine
Sympathomimetic	Mydriasis, hyperthermia, seizures, hyperactivity, hypertension, tachycardia, diaphoresis, delusions, piloerection	Cocaine Methamphetamine MDMA
Sympatholytic	Miosis, hypotension, bradycardia or reflex tachycardia, CNS depression	Clonidine Methyldopa Oxymetazoline
Opioid	Miosis, CNS depression, respiratory depression or apnea, may have hypotension	Heroin Morphine Fentanyl Oxycodone
Serotonin syndrome	Mental status changes, autonomic hyperactivity, neuromuscular abnormalities, akathisia, tremor, clonus, muscle hypertonicity, hyperthermia	Sertraline Fluoxetine Citalopram Linezolid Trazodone Meperidine Tramadol
Neuroleptic malignant syndrome	Fever, “lead pipe” muscular rigidity, altered mental status, autonomic dysfunction (in setting of recent treatment with neuroleptics)	Haloperidol Chlorpromazine Promethazine Prochlorperazine Ziprasidone Quetiapine

CNS, Central nervous system; MDMA, methylenedioxymethamphetamine.

3 What laboratory testing is indicated in the poisoned patient?

Laboratory testing in critically ill poisoned patients should be dictated by the suspected toxin(s) and the findings of the history and physical examination. Laboratory testing should include serum electrolytes and calculation of the anion gap. If the anion gap is elevated, serum osmolarity and calculation of the osmolar gap are often useful. Further laboratory testing might include transaminase and prothrombin time (PT) for a patient who has ingested acetaminophen. Arterial blood gas testing is useful in a critically ill patient poisoned by salicylates as is a carboxyhemoglobin level in a patient with carbon monoxide exposure. Urinalysis may show oxalate crystals suggesting ethylene glycol poisoning or may even fluoresce under a Wood lamp if a patient has ingested a commercial antifreeze preparation.

4 What is the value of serum and urine toxicology screens in the poisoned patient?

In many hospitals, a basic serum toxicology screen includes levels of acetaminophen, salicylate, and volatile alcohols. This is a good starting point when ingestants are unknown as it includes treatable toxins for which serum levels guide therapy. Quantitative levels of tricyclic antidepressants are of no value in determining treatment, and many hospitals use a qualitative screen. Urine drug screens are often used to test for metabolites of drugs of abuse and are often not valuable in making a toxicologic diagnosis. Some hospitals have comprehensive blood or urine toxicology testing that can isolate many obscure compounds. However, the results of these tests often become available long after the window for appropriate treatment has closed for patients. It is important to know the availability of toxicologic testing at your hospital and to be aware of the limitations of testing. Cross-reactivity with particular assays may also lead to false positives. Treating patients on the basis of their clinical status rather than their test results is often the safest plan.

5 What other diagnostic testing is useful in the poisoned patient?

Electrocardiography is a noninvasive test that rapidly supplies a great deal of information about a number of potential toxins and has prognostic value in cyclic antidepressant and sodium channel blocker poisoning. It is sound practice to obtain at least one electrocardiogram in all poisoned patients. Chest radiography should be obtained if a patient has significant pulmonary symptoms or findings or requires airway management.

6 What is the role of gastric lavage in the management of the poisoned ICU patient?

Usually, there is no role for gastric lavage (stomach pumping) in the critically poisoned patient. Gastric lavage involves the passage of a large-bore orogastric tube and the repeated instillation and aspiration of fluid to remove potentially toxic stomach contents. In animal and volunteer studies, the recovery of drugs is highly variable and declines quickly as the time from ingestion increases. Clinical studies have not confirmed a benefit of gastric lavage alone even when performed rapidly (<60 minutes) after ingestion. Given that significant time typically elapses before arrival of a poisoned patient in the intensive care unit (ICU), gastric lavage in the ICU is likely to be of no benefit. In addition, orogastric lavage has been associated with complications including aspiration, hypoxia, hypercapnia, electrolyte disturbances, and mechanical injuries to the pharynx, esophagus, and stomach.

7 What is the role of activated charcoal in the treatment of poisoned patients?

A single dose of activated charcoal may be useful in the management of some patients. Activated charcoal reduces the bioavailability of some substances, with the magnitude of reduction declining with increasing time from the ingestion. Evidence is insufficient from clinical studies that single-dose activated charcoal improves outcomes in poisoned patients. Most of the time, the decision to give activated charcoal is made in the emergency department because of the proximity to the time of ingestion. Consider ICU administration of activated charcoal on a case-by-case basis if the risk of the ingested poison outweighs the aspiration risk of charcoal administration, if the patient has a patent or protected airway, and if the ingested toxin is well adsorbed to activated charcoal (Box 78-1).

8 Does multiple-dose activated charcoal (MDAC) reduce the absorption of poisons from the gastrointestinal tract?

MDAC is repeated administration of enteral activated charcoal in an effort to increase drug elimination via diffusion along concentration gradients into the gut and preventing the reabsorption of drugs with significant enterohepatic circulation. The process has been referred to as “gastrointestinal dialysis,” and drugs amenable to MDAC share some characteristics with dialyzable drugs, including a low (< 1 L/kg) volume of distribution and low protein binding. MDAC has demonstrated enhanced elimination of carbamazepine, dapsone, theophylline, quinine, and phenobarbital. It has been proposed as treatment for a number of other agents, including salicylate and digoxin, and may also be considered for poisoning by sustained-release preparations of drugs.

9 Is there a role for syrup of ipecac in treating poisoning?

Syrup of ipecac no longer has a role in acute poisoning treatment. Ipecac syrup induces vomiting, but its recovery of drugs in experimental models is erratic and unreliable. In the pediatric population, administration of ipecac in the home did not improve outcomes or reduce emergency department utilization. In addition, the induction of persistent vomiting poses a risk for aspiration and inability to cooperate with further therapies. The American Academy of Clinical Toxicology and the American Academy of Pediatrics recommend against the routine administration of ipecac to poisoned patients in the emergency department and in the home.

10 What is whole-bowel irrigation (WBI), and does its use benefit poisoned patients?

WBI is the administration of large volumes of polyethylene glycol solution, with the intent of flushing drugs or toxins out of the gastrointestinal tract via liquid stools. Data on the efficacy of WBI for removing drugs from the body are mixed, and clinical evidence is insufficient to recommend its routine use. In addition, the administration of WBI is likely to cause significant discomfort to patients. WBI is an option for possibly expediting the gastrointestinal luminal clearance of sustained-release preparations, toxic heavy metals, or packets of illicit drugs smuggled within the body (“body packers”).

11 What is the role of dialysis in the care of the poisoned patient?

Drugs amenable to removal via hemodialysis share a number of important characteristics. They must:

Be small enough and lack charge such that they will cross a dialysis membrane

Be highly water soluble and have a small volume of distribution (<1 L/kg is a good rule of thumb) so that they are concentrated in the blood (rather than the tissues) in sufficient quantity for removal

Have low protein binding in general, although dialysis can occasionally be used to remove free drug when protein binding is fully saturated in a massive overdose

12 Which drugs can be removed from the body via hemodialysis?

Lithium and salicylate are two drugs commonly removed via hemodialysis in overdose. When considering hemodialysis in a poisoned patient, the risks of the procedure including venous and/or arterial access, discomfort, transient anticoagulation, and hemodynamic shifts must be weighed carefully against the severity of the poisoning. Acetaminophen can easily be removed by hemodialysis, but this is rarely done, because antidotal treatment with N-acetylcysteine usually works well, is noninvasive, and carries less risk to the patient.

13 What antidotes are commonly useful in the ICU?

See Table 78-2.

^{Table 78-2} Antidotes Commonly Used in the Intensive Care Unit

Antidote	Pharmacologic effects	Typical uses
Benzodiazepines	Potentiator of GABA inhibitory neurotransmission in the CNS	Alcohol or sedative/hypnotic withdrawal Antiepileptic Anxiolysis, sedation Relaxation of muscle rigidity Treatment of agitation associated with sympathomimetic or anticholinergic syndromes

Sodium bicarbonate Can produce alkalemia in the serum and in urine, provides sodium ion load Treatment of sodium channel blockade due to:

Tricyclic antidepressants

Class Ia and Ic antiarrhythmics

Cocaine, diphenhydramine

Serum and urinary alkalinization to prevent tissue distribution and improve renal clearance of:

Flumazenil CNS benzodiazepine receptor antagonist

Reversal of CNS and respiratory depression due to benzodiazepines (in patients without history of long-term benzodiazepine use)

Glucose Cellular energy source

Empiric treatment for altered mental status or seizure without clear cause

With high-dose insulin infusion for calcium channel blocker poisoning

Naloxone Opioid mu, kappa, and delta receptor antagonist

Reversal of respiratory and/or CNS depression suspected to be caused by opiates, opioids

Octreotide Long-acting somatostatin analog, inhibits pancreatic insulin release Suppression of drug-induced insulin secretion caused by:

Sulfonylureas, quinine

Hydroxocobalamin Binds cyanide ions to form cyanocobalamin, which is excreted in the urine

Treatment of cyanide toxicity

Physostigmine CNS and peripheral acetylcholinesterase inhibitor, increasing stimulation of nicotinic and muscarinic ACh receptors

Transient reversal of severe antimuscarinic syndromes not caused by cyclic antidepressants

Deferoxamine Binds free iron in the blood, enhances urinary elimination

Treatment of iron toxicity

ACh, Acetylcholine; CNS, central nervous system; GABA, γ-aminobutyric acid.

Key Points Toxicology

1. The diagnostic evaluation for the poisoned critically ill patient should be determined by the history and physical examination.

2. Urine and serum toxicology screens vary among hospitals and may not be of significant clinical utility.

3. Gastric lavage no longer has a role in the management of the poisoned patient.

4. Hemodialysis is beneficial in the management of several common poisonings.

5. Poisonings with antidotes must be recognized and treatment initiated promptly.

1 Alapat P.M., Zimmerman J.L. Toxicology in the critical care unit. Chest. 2008;133:1006–1013.

2 Anonymous: Position paper: ipecac syrup. J Toxicol Clin Toxicol. 2004;42:133–143.

3 Boyle J.S., Bechtel L.K., Holstege C.P. Management of the critically poisoned patient. Scand J Trauma Resusc Emerg Med. 2009;17:29.

4 Chyka P.A., Seger D., Krenzelok E.P., et al. Position paper: single-dose activated charcoal. Clin Toxicol. 2005;43:61–87.

5 Erickson T.B., Thompson T.M., Lu J.J. The approach to the patient with an unknown overdose. Emerg Med Clin North Am. 2007;25:249–281.

6 Higgins R.M., Connolly J.O., Hendry B.M. Alkalinization and hemodialysis in severe salicylate poisoning: comparison of elimination techniques in the same patient. Clin Nephrol. 1998;50:178–183.

7 Holstege C.P., Dobmeier S.G., Bechtel L.K. Critical care toxicology. Emerg Med Clin North Am. 2008;26:715–739. viii-ix

8 Kolecki P.F., Curry S.C. Poisoning by sodium channel blocking agents. Crit Care Clin. 1997;13:829–848.

9 Mokhlesi B., Leiken J.B., Murray P., et al. Adult toxicology in critical care: part I: general approach to the intoxicated patient. Chest. 2003;123:577–592.

10 O’Malley G.F. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am. 2007;25:333–346.

11 Vale J.A., Kulig K. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists: Position paper: gastric lavage. J Toxicol Clin Toxicol. 2004;42:933–943.

12 Wells K., Williamson M., Holstege C.P., et al. The association of cardiovascular toxins and electrocardiographic abnormality in poisoned patients. Am J Emerg Med. 2008;26:957–959.

13 Wu A.H., McKay C., Broussard L.A. National Academy of Clinical Biochemistry laboratory medicine practice guidelines: recommendations for the use of laboratory tests to support poisoned patients who present to the emergency department. Clin Chem. 2003;49:357–379.

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