143 General Approach to the Poisoned Patient
Key Points• The mainstay of treatment of a poisoned patient is good symptomatic and supportive care.
• Observation is one of the most critical aspects in the management of poisoned patients.
• The most common substance categories associated with fatalities are sedative-hypnotics, antipsychotics, cardiovascular medications, opioids, and acetaminophen combination products.
• All substances can be poisonous; toxicity usually depends on the dose and the duration of exposure.
• Toxidromes are symptom complexes that may provide clues to the identity of the offending agent on the basis of specific pharmacologic principles; they represent “physiologic fingerprints.”
• In general, hypotension in the setting of poisoning is best treated with direct-acting pressors.
• In patients with an unknown ingestion, activated charcoal is the most efficacious decontamination method, but its use should be limited to those who are awake and alert and/or have a protected airway (self-protected or intubated).
Epidemiology
It is believed that approximately 5.3 million poisoning exposures take place every year in the United States, but only about half are reported to poison control centers. The American Association of Poison Control Centers reported 2,479,355 cases of poisoning during 2009, with 93.8% occurring at a residence and just 1.5% at the workplace. Children younger than 3 years were involved in 46.0% of reported poisonings. About 82% of the poisonings were unintentional, and suicide attempts accounted for just 8.9% of cases.1
Presenting Signs and Symptoms
A poisoned patient may have many different clinical symptoms, including cardiac dysrhythmias, altered mental status, seizures, nausea and vomiting, and respiratory depression. In many cases the offending agent is initially unknown. Vital signs, including pulse oximetry values, are important to obtain (Table 143.1) and should be measured often in a poisoned patient. Vital signs (temperature, pulse, respirations, blood pressure, pulse oximetry) are helpful because they can provide clues to the type of poisoning. Physical findings such as pupil size, odor, seizure activity, and dermatologic changes can also provide clues to the offending agent (Tables 143.2 to 143.4). Emergency physicians (EPs) should be sure to examine for diaphoresis under the axilla, which may be the only body part that exhibits this finding. It is essential to note that patients with mixed ingestions may not have the classic initial signs and symptoms.
Table 143.1 Classic Examples of Ingested Substances Associated with Changes in Vital Signs*
| CHANGE IN VITAL SIGN | ASSOCIATED SUBSTANCES |
|---|---|
| Bradycardia |
* This is not an all-inclusive list. Victims of multiple substance exposure often do not have the classic signs and symptoms.
Table 143.2 Specific Substances Associated with Pupillary Changes*
| PUPILLARY CHANGE | ASSOCIATED SUBSTANCES |
|---|---|
| Miosis | |
| Mydriasis |
* Patients with mixed ingestions often do not have the classic pupillary changes.
Table 143.3 Specific Substances Associated with Skin Changes
| SKIN CHANGE | ASSOCIATED SUBSTANCES |
|---|---|
| Diaphoresis | |
| Red skin | |
| Blue skin | Methemoglobin-forming agents (e.g., nitrates, nitrites, aniline dyes, dapsone, phenazopyridine) |
| Blisters |
Table 143.4 Specific Substances Associated with Odors
| ODOR | ASSOCIATED SUBSTANCE |
|---|---|
| Bitter almonds | Cyanide |
| Carrots | Water hemlock |
| Fruity | Ketones (from diabetic ketoacidosis), isopropanol (metabolized to acetone) |
| Garlic | Arsenic, organophosphates |
| Gasoline | Hydrocarbons |
| Mothballs | Camphor |
| Peanuts | Certain rodenticides |
| Pears | Chloral hydrate |
| Rotten eggs | Hydrogen sulfide, sulfur dioxide |
| Wintergreen | Methyl salicylates |
The history obtained from the patient may be unreliable.2 It is crucial for emergency department (ED) personnel to also obtain additional history from family and friends. The paramedics who brought the patient can provide information about the scene where the overdose took place. What behavior did the patient have at the scene or before arrival? Were there seizures, emesis, changing vital signs? Were there any medicine bottles were found and, if so, were any pills were missing from the bottles? The patient’s primary care physician or psychiatrist may provide important information. Frequently, the patient’s pharmacy can be called to obtain lists of current medications and the last fill date. It is crucial to obtain an occupational history and to review past medical records for any poisoned patient. The initial work-up should determine whether a specific patient has been exposed to an agent for which an antidote (or other specific treatment) exists (Box 143.1).
Differential Diagnosis and Medical Decision Making
Toxidromes
Several drugs and toxins are associated with specific toxidromes (Table 143.5). Toxidromes are symptom complexes that may provide clues to the identity of the offending agent. They are based on specific pharmacologic principles and represent the “physiologic fingerprints” of the associated substances. An anticholinergic toxidrome, for example, is caused by parasympatholytic substances such as antihistamines, jimsonweed, tricyclic antidepressants (TCAs), and phenothiazines. Affected patients may exhibit hypertension, tachycardia, fever, delirium, and mydriasis. Sympathomimetic toxidromes resemble anticholinergic toxidromes except that parasympatholytic agents produce silent bowel sounds and dry skin.
| TOXIDROME | FEATURES | EXAMPLES OF CAUSES* |
|---|---|---|
| Anticholinergic: “Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter, full as a flask, tachy as a pink flamingo” |
CNS, Central nervous system; GI, gastrointestinal; LSD, lysergic acid diethylamide; MAOIs, monoamine oxidase inhibitors.
* This is by no means a comprehensive listing of causes of toxidromes.
† Killer BBBs are the true life threats of this toxidrome and indicate very severe poisoning.
‡ Meperidine dilates the pupils; propoxyphene and pentazocine may not cause miosis.
§ With transdermal patch–released medications, toxidromes may have a slower onset.
The following diagnostic studies should be performed in poisoned patients: serum acetaminophen and acetylsalicylic acid measurements, blood ethanol measurement, blood chemistry panel, electrocardiogram (ECG), pulse oximetry, and serum glucose measurement (Box 143.2). Toxicology screening may confirm exposure to a toxicant but does not usually change management (see later discussion). A blood chemistry profile can be extremely useful, especially in determining the anion gap.3,4 The anion gap is calculated by the formula (mEq/L) + Na+ − [Cl− + HCO3− ]; the normal range of anion gap varies from 3 to 12 mEq/L. An increase in the anion gap may indicate an intoxication, but EP must be aware that a normal anion gap does not rule out poisoning. Conditions such as hypoalbuminemia can alter the anion gap. Every 1-g/L decrease in plasma albumin leads in a drop in the anion gap of 2.5 mEq/L. Multiple conditions can cause metabolic acidosis with an elevated anion gap, and the mnemonic “A CAT MUD PILES” is an easy way to remember most of them (Box 143.3). It is important to note than any toxin that can cause seizures or other processes leading to lactic acidosis can also cause an anion gap. A decreased anion gap can be seen with bromide and lithium poisonings.
Box 143.2 Key Points for Ordering Diagnostic Studies in a Poisoned Patient
Treat the patient, not the laboratory results.
Order laboratory tests according to the signs and symptoms.
The test results may not correlate with the toxidromes.
Drug screens lack clinical significance in some cases.
A test may not be rapidly available; check with the laboratory about turnaround times.
It is important to know what the specific laboratory drug panel covers.
Measurement of serum osmolality may be useful for some toxin ingestions and should be ordered if toxic alcohols are suspected but results of toxic alcohol testing will be delayed (see Chapter 151).
Toxicology Screens
Toxicology screens are of variable utility. Urine screens were specifically designed for the drugs of abuse but have high false-positive and false-negative rates (Box 143.4). Qualitative findings (i.e., yes/no tests) do not provide information about the exact time of ingestion or the severity of impairment (Table 143.6). Serum is useful for determining quantitative levels of a specific drug (Box 143.5). Treatment is best based on the signs and symptoms. When in doubt, talk to your laboratory manager regarding your particular laboratory assay’s false-negative and false-positive rates, as well as which specific substances cross-react to cause a false-positive result. A comprehensive urine toxicology test, though not performed in most laboratories, can be helpful in cases in which the exact substance must be known. An example would be an intoxicated 3-year-old child whose parents deny any exposure.
Box 143.4 Drug Detection on Routine Urinary Drug Screens
Table 143.6 Detection Periods for Toxic Substances in Urine*
| SUBSTANCE | DETECTION PERIOD† |
|---|---|
| Amphetamines | 2-4 days |
| Barbiturates: | |
| Short acting (e.g., secobarbital) | 1 day |
| Long acting (e.g., phenobarbital) | 2-4 wk |
| Benzodiazepines | 3-30 days |
| Cannabis: | |
| Single use | 24-72 hr |
| Habitual use | Up to 12 wk |
| Cocaine metabolite | 2-4 days |
| Codeine, morphine | 2-5 days |
| Ethanol | 6-24 hr |
| Euphorics (e.g., methylenedioxymethamphetamine) | 1-4 days |
| Heroin | 2-4 days |
| Lysergic acid diethylamide | 1-4 days |
| Methadone | 3-4 days |
| Methaqualone | 14 days |
| Opioids | 2-4 days |
| Phencyclidine | 2-7 days for casual use, several months for heavy use |
| Phenobarbital | 10-30 days |
| Propoxyphene | 6 hr-2 days |
| Steroids (anabolic), used as performance enhancers | |
| Oral | 1 mo |
| Parenteral | 14 days |
* These represent the approximate detection period. It may vary according to preparation and chronicity of use.
† Time after ingestion during which the substance can be detected.
If a sample tests positive on initial screening, a second method should be used to confirm the initial result. Positive results from two different methods operating on different chemical principles greatly decrease the possibility that a methodologic problem or a “cross-reacting” substance could have created the positive result. A confirmation assay should usually be carried out with a method that has comparable sensitivity and higher specificity (or selectivity) than a screening assay. Examples of confirmation methods are gas chromatography, gas chromatography with mass spectrometry, and high-performance liquid chromatography (Table 143.7).
Table 143.7 False-Positive Results of Urine Drug Screening
Radiographic Evaluation
Table 143.8 summarizes the radiographic findings associated with toxic ingestions.
Table 143.8 Radiographic Findings Associated with Toxic Ingestions
| RADIOGRAPHIC FINDING | CAUSES |
|---|---|
| Concretions* |
* Should be suspected if the patient’s clinical or laboratory status waxes and wanes.
Treatment
After initial stabilization of a critically ill patient, specific antidote therapy is administered if applicable (Table 143.9), a detailed history is elicited, and a physical examination is performed. Patients who are externally contaminated with a toxicant that may injure staff must be decontaminated immediately to avoid incapacitation of health care staff and the facility. Patients should undergo skin and eye decontamination, including removal of all clothing and washing of the skin with soap and water if indicated. Care should be taken to protect health care providers from exposure.
| TOXINS | ANTIDOTES* |
|---|---|
| Acetaminophen | N-acetylcysteine, 140 mg/kg PO, then 70 mg/kg q4h for up to 17 doses, or 150-mg/kg IV over 1-hr period with 50 mg/kg over 4 hr followed by 100 mg/kg over 16 hr |
| Anticholinergics | Physostigmine, 0.5-2 mg IV in adults or 0.2 mg/kg in children over 2-min period for anticholinergic delirium, seizures, or arrhythmias |
| Arsenic, lead, or mercury |
Calcium, as 1 g calcium chloride IV in adults or 20-30 mg/kg per dose in children delivered over a few minutes with continuous monitoring
When decreased myocardial activity is noted, a 1 U/kg regular insulin bolus can be initiated. If the blood sugar is less than 400 mg/dL, 0.5 g/kg of dextrose should be given with the insulin. After the insulin bolus, an insulin infusion of 0.5-1 U/kg/hour should be started along with a continuous dextrose drip of 0.5/kg/hour. The dextrose drip is titrated to maintain blood sugars between 100 and 250 mg/dL. Cardiac function should be monitored every 15-20 minutes, and blood glucose should be monitored every 15 sec initially and then can be spread out to every 30-60 min checks as blood glucose is consistently measured in the 100-250 mg/dL range. In addition, frequently monitor potassium concentration and judiciously replete as necessary.
Hydroxocobalamin, 5-g infusion IV over 30-min period in adults, 70 mg/kg in children. Each 5 g neutralizes about 40 µmol/L of cyanide in blood
Sodium thiosulfate, 50 mL of 25% solution (12.5 g; 1 ampule) in adults or 1.65 mL/kg IV in children
Sodium nitrate, 10 mL of 3% solution (300 mg; 1 ampule) in adults or 0.33 mL/kg slowly IV in children
Fomepizole, 15 mg/kg, then 10 mg/kg q12h for 4 doses, then increase dose to 15 mg/kg q12h until serum ethylene glycol level less than 20 mg/dL; dose should be adjusted during dialysis
Ethanol: loading dose, 10 mL/kg of 10% solution; maintenance dose, 0.15 mL/kg/hr of 10% solution; rate should be doubled during dialysis
Folate or leucovorin, 50 mg IV q4h in adults
Ethanol: loading dose, 10 mL/kg of 10% solution; maintenance dose, 0.15 mL/kg/hr of 10% solution; rate should be adjusted during dialysis
Fomepizole, 15 mg/kg, then 10 mg/kg q12h for 4 doses, then increase to 15 mg/kg q12h until serum methanol level less than 20 mg/dL; dose should be adjusted during dialysis
EDTA, Ethylenediaminetetraacetic acid; IM, intramuscularly; IV, intravenously; PO, orally; SC, subcutaneously.
* These are typical doses. Dosing may vary according to the patient and clinical picture. Consult with your medical toxicologist and pharmacist when in doubt. Your local poison center may be reached at 1-800-222-1222.
† May cross-react with penicillin in allergic patients.
‡ Should not be used if the patient has signs of tricyclic antidepressant toxicity or a history of seizures.
§ Has a much longer half-life than naloxone does.
Treatment of drug-induced acute coronary syndromes is similar to that recommended for drug-induced hypertensive emergencies. Catheterization studies have shown that (1) nitroglycerin and phentolamine (an alpha-blocker) reverse cocaine-induced vasoconstriction, (2) labetalol has no significant effect, and (3) propranolol worsens it. Therefore, benzodiazepines and nitroglycerin are first-line agents, phentolamine is a second-line agent, and propranolol is contraindicated for drug-induced coronary syndromes.5,6
“Coma cocktail”
Naloxone reverses the coma and respiratory depression induced by opioids. It can also be used diagnostically. An initial dose of 0.2 to 0.4 mg is administered intravenously, and if no response is seen after 2 to 3 minutes, an additional 1 to 2 mg can be administered; doses can be repeated up to a total of 10 mg as needed. More than 10 mg may be required and may have to be given as an intravenous drip with higher grades of heroin, pentazocine, diphenoxylate, meperidine, propoxyphene, and methadone overdose.7 Naloxone has a short half-life (20 to 30 minutes), and its effect does not last as long as the effects of most opioids. Therefore, if respiratory depression develops after an initial dose of naloxone, a naloxone drip should be started and the patient admitted to the intensive care unit. The naloxone is mixed with D5W and given at a rate that delivers two thirds of the initial reversal dose per hour.8 Acute pulmonary edema, opioid withdrawal, and seizures have been reported with naloxone administration.9–11
Thiamine, 100 mg given intravenously or orally, should be reserved for alcoholic, malnourished patients. Despite traditional belief, giving thiamine to every comatose patient to prevent Wernicke-Korsakoff syndrome is not well supported by the literature. No evidence has shown that dextrose should be withheld until thiamine is administered.12
Flumazenil is a benzodiazepine reversal agent that can be used for a pure acute benzodiazepine overdose or when reversal of therapeutic conscious sedation is desired. It can potentially reverse the seizure-protecting properties of benzodiazepines in mixed drug ingestions (TCAs).13 Because flumazenil can induce acute withdrawal symptoms in long-term benzodiazepine abusers, it is contraindicated in patients with a history of long-term benzodiazepine use, seizure disorder, and concomitant TCA ingestion. Flumazenil should not be used routinely to arouse an unconscious patient with overdose because it is often unknown whether a patient is a chronic benzodiazepine user. In a large prospective trial of unconscious patients suspected of benzodiazepine overdose, investigators did not observe any significant side effects with flumazenil.14 However, serious complications of flumazenil have now been reported, including seizures, ventricular arrhythmias, and benzodiazepine withdrawal in patients who are chronic users.15 If partial reversal of benzodiazepine intoxication is necessary, the smallest possible dose of flumazenil, 0.05 to 0.1 mg, should be diluted in 10 mL of saline or D5W and given slowly intravenously, over a period of several minutes. If there is no initial response, 0.3 mg may be given. If there is still no response, 0.5 mg can be given every 30 seconds for a maximum dose of 3 mg. Goals are respiratory sufficiency and verbal responsiveness, not complete arousal.
Decontamination
Use of syrup of ipecac to induce emesis is no longer part of the treatment of any ingestion. Persistent vomiting after the use of ipecac is likely to delay the administration of activated charcoal. No evidence from clinical studies has shown that ipecac improves the outcome of poisoned patients, and its routine administration in the ED should be abandoned.16 The only useful clinical situation would be a patient with a life-threatening ingestion many hours from medical care.with no other forms of decontamination available.
Gastric lavage is a time-consuming procedure that also poses a risk for aspiration and other injury. The concept is to try to wash out the stomach contents before absorption. It may still be useful when the toxin has not yet passed the pylorus. Gastric lavage should not be used routinely for the management of poisoned patients, however. In general, there is no advantage to gastric emptying more than 60 minutes after the ingestion. Gastric lavage is performed by inserting a 36- to 40-French tube into the patient’s stomach and “washing out” the stomach with 300-mL aliquots of normal saline until clear. Unless a patient is intubated, gastric lavage is contraindicated if the airway protective reflexes are lost. It is also contraindicated if a hydrocarbon with high aspiration potential or a corrosive substance has been ingested. Gastric lavage should not be considered unless a patient has ingested a potentially life-threatening amount of a poison, no antidote exists, and the procedure can be undertaken within 60 minutes of the ingestion.17 Multiple studies have shown no advantage of gastric emptying over activated charcoal in decreasing absorption.
In a patient with an unknown ingestion, administration of activated charcoal is the most efficacious decontamination method, with very few adverse side effects. Activated charcoal is produced by heating wood pulp, washing it, and then activating it with steam or acid. It has a large surface area for direct adsorption of agents in the gastrointestinal tract. It is usually safe and inexpensive, and it adsorbs most toxins (Box 143.6). This agent should be administered at a dose of 1 to 2 g/kg in overdose patients who are awake and alert or have a protected airway.
Box 143.6 Use of Activated Charcoal for Toxic Ingestions
Charcoal does not adsorb all poisons. Infrequent complications include intestinal obstruction and aspiration pneumonitis. The effectiveness of activated charcoal has been found in volunteer studies to decrease with time; the greatest benefit occurs within 1 hour of ingestion, and single-dose activated charcoal should not be administered routinely for the management of poisoned patients. Administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to 1 hour previously; insufficient data support or exclude its use more than 1 hour after ingestion.18
Multiple-dose activated charcoal (every 4 hours) may be useful for the ingestion of some drugs with enterenteric enterohepatic circulation (see Box 143.6). Studies have shown decreases in the half-life of these drugs; however, clinical benefit of this approach has not been well established. Repetitive doses of charcoal, 0.25 to 1 g/kg, are given every 4 to 6 hours. Although many studies in animals and volunteers have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapy has not yet been shown in a controlled study to reduce morbidity and mortality. On the basis of experimental and clinical studies, therefore, administration of multiple-dose activated charcoal should be considered if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.19
Not a single study has shown any benefit from the use of cathartics in poisoned patients. Cathartics include magnesium sulfate, sorbitol, and magnesium citrate. Drugs and toxins are usually absorbed within 30 to 90 minutes, and cathartics and laxatives take hours to work. Serious fluid and electrolyte shifts can occur as a result of the use of cathartics, and a few infant deaths have been reported. Complications of cathartics include electrolyte imbalance, dehydration, and hypermagnesemia. Administration of a cathartic alone has no role in the management of a poisoned patient and is not recommended as a method of gut decontamination.20
Whole-bowel irrigation should not be used routinely in the management of a poisoned patient. Although some volunteer studies have shown substantial decreases in the bioavailability of ingested drugs with this method, no controlled clinical trials have been performed, and there is no conclusive evidence that whole-bowel irrigation improves outcome in a poisoned patient.21 Whole-bowel irrigation consists of the administration of a polyethylene glycol solution until the rectal effluent is clear. Whole-bowel irrigation should be reserved for life-threatening intoxications from sustained-release (CR, SR, LA, XL) beta-blockers, calcium channel blockers, lithium, iron, and lead. Most of the time, placement of a nasogastric tube is required for administration. Oral administration of charcoal followed by whole-bowel irrigation is the safest way to decontaminate people whose bodies have been stuffed with packets of illegal drugs. The dose is 20 mL/kg/hr, which translates to about 2 L/hr for adults and 0.5 L/hr for children. The end point is a clear rectal effluent, which usually requires 4 to 6 hours of treatment.
Enhancement of Elimination
Urine alkalinization should be considered first-line treatment in patients with moderately severe salicylate poisoning whose condition does not meet the criteria for hemodialysis. Alkalinization traps weak acids in an ionized state, thereby decreasing their reabsorption. Urine alkalinization increases ion trapping and thus urinary elimination of chlorpropamide, 2,4-dichlorophenoxyacetic acid, diflunisal, fluoride, mecoprop, methotrexate, phenobarbital, and salicylate. If the patient is acidemic, immediate correction with 1 to 2 mEq/kg of sodium bicarbonate can be performed immediately. Then a bicarbonate intravenous infusion of 100 to 150 mEq sodium dicarbonate in 1 L of D5W at 150 to 200 mg/hr. Sodium bicarbonate is administered as an intravenous drip at a rate of 0.5 to 2 mEq/kg/hr after a bolus of 1 to 2 mEq/kg. The dosage should be titrated to keep urine pH at 7.5 to 8.0. Urine pH should be tested every 30 minutes then once an hour to ensure adequate alkalinization. Check serum pH and potassium hourly. Urine alkalinization cannot be recommended as first-line treatment in cases of phenobarbital poisoning, for which multiple-dose activated charcoal is superior.22
In an unstable overdosed patient, consultation with a nephrologist for emergency hemodialysis may be indicated before the results of definitive diagnostic studies or drug level measurements are available. Toxins for which hemodialysis may be useful should have the following features: low molecular weight (<500 D), water solubility, low protein binding (<70% to 80%), and small volume of distribution (<1 L/kg). Toxins for which hemodialysis may be required include methanol, ethylene glycol, boric acid, salicylates, and lithium (Box 143.7).
Documentation
Patient Instructions
Documentation of discussion with patient or parent regarding diagnosis, warning signs, what to do, follow-up, and when to return
With pediatric accidental ingestions, documentation of poison prevention counseling
Families should be given the phone number for their poison control center to address further concerns (1-800-222-1222)
Any time there is concern about the situation surrounding the ingestion or an ingestion has occurred in an infant younger than 12 months, social services should be contacted
1 Bronstein AC, Spyker DA, Cantilena LR, Jr., et al. 2009 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 27th Annual Report. Clin Toxicol (Phila). 2010;48:979–1178.
2 Wright N. An assessment of the unreliability of the history given by self-poisoned patients. Clin Toxicol. 1980;16:381–384.
3 Winter SD, Pearson R, Gabow PA, et al. The fall of the serum anion gap. Arch Intern Med. 1990;150:311–313.
4 Gabow PA. Disorders associated with an altered anion gap. Kidney Int. 1985;27:472–483.
5 Baumann BM, Perrone J, Hornig SE, et al. Randomized, double blind, placebo-controlled trial of diazepam, nitroglycerin, or both for treatment of cocaine-associated acute coronary syndromes. Acad Emerg Med. 2000;7:878–885.
6 Honderick T. Lorazepam in the acute management of cocaine associated chest pain. Acad Emerg Med. 2000;7:515.
7 Goldfrank LR. The several uses of naloxone. Emerg Med. 1984;16:110–116.
8 Goldfrank LR, Weisman RS, Errick JK, et al. A dosing nomogram for continuous infusion intravenous naloxone. Ann Emerg Med. 1986;15:566–570.
9 Schwartz JA, Koenigsberg MD. Naloxone-induced pulmonary edema. Ann Emerg Med. 1987;16:1294–1296.
10 Goldfrank LR. Substance withdrawal. Emerg Med Clin North Am. 1990;8:616–632.
11 Mariani PJ. Seizure associated with low-dose naloxone. Am J Emerg Med. 1989;7:127–129.
12 Reuler JB, Girard DE, Cooney TG. Wernicke’s encephalopathy. N Engl J Med. 1985;312:1035–1039.
13 Mordel A, Winkler E, Almog S, et al. Seizures after flumazenil administration in a case of combined benzodiazepine and tricyclic antidepressant overdose. Crit Care Med. 1992;20:1733–1734.
14 Weinbroum A, Rudick V, Sorkine P, et al. Use of flumazenil in the treatment of drug overdose: a double-blind and open clinical study in 110 patients. Crit Care Med. 1996;24:199–206.
15 Gueye P, Hoffman J. Empiric use of flumazenil in comatose patients: limited applicability of criteria to define low risk. Ann Emerg Med. 1996;27:730–735.
16 American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position paper: ipecac syrup. J Toxicol Clin Toxicol. 2004;42:133–143.
17 American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position statement: gastric lavage. J Toxicol Clin Toxicol. 1997;35:711–719.
18 American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position statement: activated charcoal. J Toxicol Clin Toxicol. 1997;35:721–741.
19 American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol. 1999;37:731–751.
20 American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position statement: cathartics. J Toxicol Clin Toxicol. 1997;35:743–752.
21 American Academy of Clinical Toxicology, European Association of Poisons Centres, Clinical Toxicologists. Position paper: whole bowel irrigation. J Toxicol Clin Toxicol. 2004;42:843–854.
22 Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization. J Toxicol Clin Toxicol. 2004;42:1–26.
