0
Critical Care Reviews |

Adult Toxicology in Critical Care*: Part I: General Approach to the Intoxicated Patient FREE TO VIEW

Babak Mokhlesi, MD; Jerrold B. Leiken, MD; Patrick Murray, MD; Thomas C. Corbridge, MD, FCCP
Author and Funding Information

*From the Division of Pulmonary and Critical Care Medicine (Dr. Mokhlesi), Cook County Hospital/Rush Medical College, Chicago; Evanston Northwestern Healthcare-OMEGA (Dr. Leiken), Chicago; Section of Nephrology (Dr. Murray), University of Chicago, Chicago; and Medical Intensive Care Unit (Dr. Corbridge), Northwestern University Medical School, Chicago, IL.

Correspondence to: Babak Mokhlesi, MD, Division of Pulmonary and Critical Care Medicine, Cook County Hospital/Rush Medical College, 1900 West Polk St, Chicago, IL 60612; e-mail: Babak_Mokhlesi@rush.edu



Chest. 2003;123(2):577-592. doi:10.1378/chest.123.2.577
Text Size: A A A
Published online

Intensivists are confronted with poisoned patients on a routine basis, with clinical scenarios ranging from known drug overdose or toxic exposure, illicit drug use, suicide attempt, or accidental exposure. In addition, drug toxicity can also manifest in hospitalized patients from inappropriate dosing and drug interactions. In this review article, we describe the epidemiology of poisoning in the United States, review physical examination findings and laboratory data that may aid the intensivist in recognizing a toxidrome (symptom complex of specific poisoning) or specific poisoning, and describe a rational and systematic approach to the poisoned patient. It is important to recognize that there is a paucity of evidence-based information on the management of poisoned patient. However, the most current recommendations by the American Academy of Clinical Toxicology and European Association of Poisons Centers and Clinical Toxicologists will be reviewed. Specific poisonings will be reviewed in the second section of these review articles.

Figures in this Article

A high index of suspicion for intoxication is warranted in the practice of critical care medicine. The protean manifestations of intoxication challenge even the most astute clinicians, particularly when patients present with altered mental status or when there is no history of intoxication. Recognition of a specific toxic syndrome (or toxidrome) helps (Table 1,1A ), but symptoms are often nonspecific (as in early acetaminophen poisoning) or masked by other conditions (eg, myocardial ischemia in the setting of carbon monoxide poisoning).

In the first of this two-part series, we will review the epidemiology of poisonings, both intentional and unintentional, provide an approach to the diagnosis of the poisoned patient, and discuss strategies for general supportive care. In part II, we will review the assessment and management of specific intoxications.

Since 1983, the American Association of Poison Control Centers has compiled data from the Toxic Exposure Surveillance System. In their 2000 annual report, 63 poison centers reported a total of 2,168,248 human toxic exposure cases. Adults accounted for approximately one third of exposures. Most exposures were unintentional (71% of cases) and involved a single toxic substance (92%). Fewer than 5% of cases involved an adverse reaction to a medication or food. Oral ingestion was the commonest route of exposure (Fig 1 ). Most exposures occurred at the patient’s own residence, and most patients (75%) were managed on-site with assistance from a poison information center and did not require an emergency department visit. Only 3% of patients required critical care.

The categories of substances/toxins with the largest number of deaths were analgesics, antidepressants, sedative/hypnotics/antipsychotics, stimulants, “street” drugs, cardiovascular drugs, and alcohols (Table 2 ). Of all deaths, 920 fatalities, a 5% increase compared to 1999, 88% occurred in 20- to 99-year-old individuals. The mortality rate was higher in intentional rather than unintentional exposures (79% vs 10.5%, respectively).1

History and Physical Examination

Table 3 includes clinical features mandating consideration of toxic ingestion. Although the history is important, it may be unreliable or incomplete.2Consider that family members, friends, and pharmacists may have additional information. In the absence of a classic presentation or toxidrome, separating patients with suspected poisoning into broad categories based on vital signs, ocular findings, mental status, and muscle tone can help determine drug or toxin class.3

Vital Signs

Anticholinergic and sympathomimetic substances increase heart rate, BP, and temperature. In contrast, organophosphates, opiates, barbiturates, β-blockers, benzodiazepines, alcohol, and clonidine cause hypothermia, bradycardia, and respiratory depression. Table 4 lists various toxins altering temperature. Drugs/toxins causing tachycardia or bradycardia are listed in Table 5 .

Ocular Findings

Anticholinergics and sympathomimetics cause mydriasis. In contrast to anticholingeric overdose, the pupils remain somewhat light responsive in cocaine intoxication. Table 6 lists drugs that affect pupil size. Horizontal nystagmus is common in alcohol intoxication. Other drugs causing nystagmus are lithium, carbamazepine, solvents, meprobamate, quinine, and primidone. Phencyclidine and phenytoin cause horizontal, vertical, and rotary nystagmus.

Mental Status, Behavior, and Muscle Tone

It is important to determine whether the patient is comatose, stuporous, lethargic, delirious, confused, or alert (Table 7). Some toxins cause seizures (Table 8); others alter muscle tone (Table 9).

Laboratory Evaluation

Three gaps are important in toxicology: the anion gap, osmolal gap, and oxygen saturation gap. Toxicology screening confirms (or not) toxin exposure but rarely alters management (see below).

Anion Gap

The normal range of anion gap may vary from 3 to 12 mEq/L in some laboratories.4An increase in anion gap (> 20 mEq/L) suggests lactic acidemia, uremia, ketoacidemia, or selected intoxications (Tables 10,11) . A normal anion gap does not preclude intoxication because most toxins do not elevate the anion gap or there may be a coexisting condition that lowers the gap (Table 10). Common among these conditions is hypoalbuminemia: for every 1 g/L decrease in the plasma albumin, the anion gap falls by 2.5 mEq/L.5 Intensivists should pay special attention to this correction factor to avoid missing a clinically significant anion gap. Also, in methanol or polyethylene glycol poisoning, concurrent ethanol use delays the development of an elevated anion gap metabolic acidosis. In this case, an elevated osmolal gap may be the only early clue to the diagnosis.6

Osmolal Gap

Low-molecular-weight drugs and toxins increase the discrepancy between measured and calculated plasma osmolality (Table 12 ). Normal plasma osmolality is 285 to 295 mOsm. The calculated value is determined as follows:

in which Na+ (in millimoles per liter) is multiplied by nearly two to account for accompanying anions (chloride and bicarbonate), and measured BUN, glucose, and ethanol are converted from milligrams per deciliter to mmol/L by the appropriate denominator.

The osmolal gap must be interpreted with caution. Measurement of osmolality by vapor pressure osmometry does not detect volatile alcohols such as ethanol and methanol; however, it does detect ethylene glycol. Freezing point depression osmometry, the most frequently used method, measures all of these solutes.78 Therefore, it is important for clinicians to know the method used by their institution to avoid missing methanol poisoning. By using the standard formula, the normal osmolal gap may range from − 9 mOsm to + 5 mOsm; 10 mOsm is considered the upper limit of normal.9However, an osmolal gap of 10 mOsm in a patient who started at − 9 mOsm may be significantly elevated.1012

Oxygen Saturation Gap

An oxygen saturation gap is present when there is more than a 5% difference between the saturation calculated from an arterial blood gas and the saturation measured by co-oximetry. Co-oximetry determines oxygen saturation by detecting the absorption of four different wavelengths, enabling it to directly measure levels of four types of hemoglobin species: oxyhemoglobin, reduced hemoglobin, carboxyhemoglobin, and methemoglobin. However, arterial blood gas analysis calculates oxygen saturation from the measured oxygen tension using an assumed standard oxygen-hemoglobin dissociation curve. Toxins that are associated with an elevated oxygen saturation gap include carbon monoxide, methemoglobinemia, cyanide, and hydrogen sulfide (sulfhemoglobin is not routinely measured by co-oximetry). Pulse oximetry estimates oxygen saturation by emitting a red light (wavelength of 660 nm) absorbed mainly by reduced hemoglobin and a near-infrared light (wavelength of 940 nm) absorbed by oxyhemoglobin.13Methemoglobin absorbs almost equally at both these wavelengths. At high methemoglobin levels (35%), the oxygen saturation by pulse oximetry tends to regress toward 85% and plateaus at that level despite further increments in methemoglobin levels. Thus, if the actual oxygen saturation by co-oximetry is > 85%, the pulse oximetry would be underestimating it; if it is < 85% by co-oximetry, it would be overestimating oxygen saturation.14Therefore, pulse oximetry may become unreliable in the setting of methemoglobinemia registering falsely high in patients with severe methemoglobinemia and falsely low with mild methemoglobinemia. Since many laboratories do not routinely use co-oximetry, a more commonly seen gap may be the disparity between measured oxygen saturation by blood gas and that measured by pulse oximetry.15Oxygen saturation measured by pulse oximetry may be falsely elevated in methemoglobinemia and should be utilized with caution in determining the oxygen saturation gap.1617 Carbon monoxide has a wavelength absorption coefficient similar to that of oxyhemoglobin; therefore, it is registered as oxyhemoglobin by pulse oximetry leading to overestimation of oxygen saturation when compared to co-oximetry. An abnormally high venous oxygen content (arteriolization of venous blood) is characteristic of cyanide and hydrogen sulfide poisoning.

Toxicology Screening

In spite of providing direct evidence of intoxication, screening tests alter management in < 5% of cases.1819 Toxicology screening can identify a specific toxin for which an antidote is available and in some instances quantify a toxin allowing for titrated therapy.

Most institutions offer urine testing for six or seven of the most commonly abused drugs (Table 13 ). Results are generally available in 30 min. More comprehensive urine screening (usually performed off-site) may take up to 2 to 3 h. Testing of blood or gastric contents is rarely indicated.20 However, blood quantification of certain toxins is useful, particularly in cases of alcohol (ethanol and nonethanol), acetaminophen, salicylate, phenobarbital, theophylline, digoxin, iron, and lithium intoxication. A strong argument can be made for checking acetaminophen levels in all cases of suspected intoxication given the subtle manifestations of early acetaminophen poisoning and importance of targeted therapy.

Poison Control Center Consultation

Regional poison control center consultation is highly recommended in cases of suspected poisoning and to help guide management in confirmed cases.21 These centers provide 24-h emergency and up-to-date technical information. They are staffed by nurses, pharmacists, pharmacologists, and physicians trained and certified in toxicology. The national toll-free number for poison control centers is 800-222-1222.

Airway, Breathing, Circulation

Supportive measures including the “ABCs” (airway, breathing, circulation) are often required before confirmation of intoxication. With cervical spine precautions in place (unless trauma has been excluded), airway patency must be ensured in all cases. Endotracheal intubation is not always necessary when cough and gag reflexes are present and there is adequate spontaneous ventilation, but when there is concern regarding airway protection and clinical deterioration it is better to secure the airway. Intubation is indicated in acute respiratory failure (Table 14 for causes of hypoxemia in intoxicated patients). Other specific indications include the need for high levels of supplemental oxygen in carbon monoxide poisoning and the need to protect the airway for gastric emptying. Endotracheal intubation decreases (but does not eliminate) the risk of aspiration (which is approximately 11% in the comatose patient with drug overdose).2224

Depending on the intoxication, patients may present with hypotension or hypertension, bradyarrhythmias or tachyarrhythmias. The pathogenesis of hypotension varies and may include hypovolemia, myocardial depression, cardiac arrhythmias, and systemic vasodilation. Treatment should be individualized, but an initial strategy of rapid IV normal saline solution infusion is indicated in most instances. Vasopressors may be required for refractory hypotension. The vasopressor of choice depends on the type of intoxication (see below). Hypertension occurs in the setting of sympathomimetic drugs, anticholinergics, ergot derivatives, phenylpropanolamine overdose, and withdrawal from nicotine, alcohol, and sedatives. Treatment of the hypertension depends on its chronicity and severity and the inciting agent (see below). Hypertension-induced (reflex) bradycardia generally should not be treated.

Coma Cocktail

Immediately after establishing IV access, a “cocktail” of thiamine, dextrose, and naloxone should be administered to patients with depressed mental status. This cocktail can be both therapeutic and diagnostic.25 Thiamine (100 mg by vein) is administered to treat and/or avoid Wernicke-Korsakoff syndrome in comatose patients. This strategy is not well supported by the literature, and few patients regain consciousness following thiamine infusion. Still, routine use of thiamine is safe, inexpensive, and prevents the possibility of delayed deterioration secondary to nutritional deficiency.25Thiamine is particularly important in the nutritionally deplete alcoholic. There is no evidence that dextrose should be withheld until thiamine is administered.26 Comatose patients should receive dextrose, 50 g IV. A normal value by blood dipstick does not necessarily exclude low serum glucose. A high value on dipstick testing should lead to rapid confirmation by blood draw, thus avoiding unnecessary dextrose (although administration of dextrose to hyperglycemic patients is unlikely to cause harm).25 Naloxone rapidly reverses coma, respiratory depression, and hypotension induced by opioids. An initial dose of 0.2 to 0.4 mg is administered IV (or endotracheally). If there is no response after 2 to 3 min, an additional 1 to 2 mg can be administered and repeated up to 10 mg as required. Using a higher dose up front may precipitate large cardiovascular changes in opioid dependent patients. Several opioids such as meperidine, propoxyphene, diphenoxylate, methadone, and pentazocine require large doses of naloxone,27but lack of response to 10 mg of naloxone generally excludes opioid toxicity. Opioid antagonism with naloxone lasts 1 to 4 h requiring repeat doses or continuous infusion in significant intoxication.28Acute pulmonary edema,2930 opioid withdrawal,31and seizures32 have been reported with naloxone administration.

Flumazenil should be considered in cases were benzodiazepine overdose is suspected or reversal of therapeutic conscious sedation is desired.25,33Case reports have cautioned clinicians of the risk of precipitating seizures with flumazenil when there is a suspicion of benzodiazepine plus cyclic antidepressant overdose.3435 Nonetheless, data suggest that flumazenil is safe as part of the coma cocktail even with coma induced by the combination of benzodiazepines and cyclic antidepressants.36 In a large prospective trial of unconscious patients suspected of benzodiazepine overdose, Weinbroum et al36randomized patients to receive either placebo or flumazenil in addition to usual care. Seventy-one percent of the patients had concomitant cyclic antidepressant ingestion. These investigators did not observe any significant side effects with flumazenil, even in patients with coma caused by a mixed overdose of benzodiazepine and cyclic antidepressants. We typically administer an initial 0.2 mg of IV flumazenil over 30 s followed by another 0.3-mg dose if necessary. Doses beyond 3 mg generally do not provide additional benefit. Repeat sedation may occur in the setting of high-dose or long-term use of benzodiazepines. Although flumazenil is successful in improving the Glasgow coma scale score, it does not appear to alter cost or major diagnostic/therapeutic interventions in patients presenting with decreased level of consciousness due to an intentional unknown drug overdose.37Therefore, the cost-effectiveness of routine use of flumazenil as part of the coma cocktail remains controversial,38 except in cases of acute benzodiazepine overdose.36

The route of entry for toxic substances can be dermal, ocular, GI, inhalational, or parenteral (Fig 1). Skin decontamination requires removal of the toxin with nonabrasive soap and water. Contaminated clothing may serve as a reservoir for continued exposure and must be removed with caution and placed in plastic bags or other containers that are impervious to the toxin. This will limit exposure to medical personnel and patient. Ocular decontamination may require prolonged periods of irrigation with normal saline solution using a Morgan lens (MorTan; Missoula, MT). Inhalational exposure presents a greater challenge since the toxin cannot be accessed and removed. Inhalational lung injury is beyond the scope of this review. The majority of toxin exposures and poisonings managed by intensivists occur through the GI tract. There are four methods of GI decontamination including three mechanical approaches (emesis, gastric emptying or gastric lavage [GL], and whole-bowel irrigation) and the use of activated charcoal combined with a cathartic.

Emesis

Ipecac-induced emesis should be considered only in fully alert patients, and is virtually never indicated after hospital admission. Ipecac is generally less traumatic than GL, and is therefore the preferred method of gastric emptying in pediatric patients. Ipecac may be helpful at home if administered immediately after ingestion. In the best of circumstances, a 30 to 40% removal rate can be achieved within 1 h after ingestion.39Because of questionable efficacy hours after ingestion, in-hospital use is decreasing.4041 Contraindications to its use include poisoning with corrosives, petroleum products, or antiemetics. The potential for aspiration precludes its use in situations where there is a high risk of seizures (ingestion of a rapidly acting convulsant such as strychnine) or altered consciousness.42The usual dose of ipecac syrup in adults is 30 mL followed by 16 oz of water. This dose usually induces vomiting within 20 to 30 min. The dose can be repeated once after 30 min if vomiting does not occur. There is little evidence that ipecac prevents drug absorption or systemic toxicity,43 and there are no convincing data that it significantly alters the clinical outcome of patients who are awake and alert on presentation to the emergency department. Ipecac is rarely used (approximately 1% of all overdoses reported to the poison centers),1 and its use may soon be confined to the medical history books.

Gastric Emptying

GL through a 28F to 40F Ewald tube is similarly aimed at physically removing a toxin. Prior to inserting the Ewald tube, the mouth should be inspected for foreign material and equipment should be ready for suctioning. Large gastric tubes (37F to 40F) are less likely to enter the trachea than smaller nasogastric tubes, and are necessary to facilitate removal of gastric debris. After insertion, proper position needs to be confirmed by aspirating acidic stomach contents and auscultating the left upper abdominal quadrant during insufflation of air. Experienced personnel should perform GL in a facility where resources are available to manage complications. Nonintubated patients must be alert (and be expected to remain alert) and have adequate pharyngeal and laryngeal protective reflexes. In semicomatose patients, GL should be performed only after a cuffed endotracheal tube has been inserted. Intubation for the sole purpose of gastric emptying is reasonable only if there is a high likelihood that a highly lethal agent remains in the stomach.

GL is performed by instilling 200-mL aliquots of warmed tap water until there is clearing of aspirated fluid. Stomach contents should be retained for analysis. Tap water may avoid unnecessary salt loading compared to normal saline solution. Neither irrigant has been shown to significantly alter blood cell or electrolyte concentrations.44 After clearing, the Ewald tube may be replaced by a nasogastric tube for subsequent intermittent suctioning and/or administration of activated charcoal.

GL has been advocated in the initial management of many orally ingested agents. The risks associated with this procedure include aspiration, arrhythmias, and stomach perforation.45Because of these risks, GL should not be performed in patients who have ingested a nontoxic substance, a nontoxic amount of a toxic substance, or when the toxin is no longer expected to be present in the stomach. Examples include patients who have vomited extensively prior to hospital admission, patients who present several hours after ingesting an agent that does not decrease gut motility, and patients who have received agents that are readily absorbed from the GI tract. Although GL has been common in the management of patients with toxic ingestion, its use remains controversial.46In obtunded patients, GL results in a more satisfactory clinical outcome only if performed within 1 h47or 2 h of ingestion.48 Kulig et al47 compared the utility of GL plus activated charcoal in 72 obtunded patients with 44 obtunded patients who received only activated charcoal by nasogastric tube and supportive care. They reported an improved clinical course if lavage was performed within 1 h of ingestion. In contrast, Pond et al49performed a prospective, randomized, controlled trial of 347 obtunded patients receiving GL plus activated charcoal or activated charcoal alone. There was no significant difference in outcome even when patients presented within 60 min of ingestion. Because of limited data, the American Academy of Clinical Toxicology does not recommend routine use of GL in the management of poisoning unless a patient has ingested a potentially life-threatening amount of a poison and the procedure can be undertaken within 60 min of ingestion.50Although controversial, some experts suggest that the time limit may be extended to 12 h in cases of poisoning with agents that delay gastric emptying such as tricyclic antidepressants, opioids, or salicylates. In addition, gastric emptying may be beneficial if the ingested drug is not adsorbed by activated charcoal (eg, ferrous sulfate, lithium). In cases of ingestion of a caustic liquid such as kerosene or its derivatives, GL should be avoided because of the risk of aspiration-induced lung injury. Clinical studies evaluating the efficacy of GL are limited by small study size, heterogeneity of toxins studied, and different methodologies. There is also a concern that GL may propel material into the duodenum increasing the chance of drug absorption.51

Activated Charcoal

Charcoal is a by-product of the combustion of various organic compounds such as wood, coconut parts, bone, sucrose, rice, and starch. Its adsorptive capacity is increased or activated by removing materials previously adsorbed by a process that involves steam heating and chemical treatment, thereby increasing the surface area available for adsorption to between 1,000 m2/g and 3,000 m2/g. This results in a powerful, inert, nontoxic, and nonspecific adsorbent that irreversibly binds intraluminal drugs and interferes with their absorption. It is particularly effective in binding high-molecular-weight compounds. Activated charcoal decreases serum drug levels in some cases by creating a favorable diffusion gradient between blood and gut, referred to as GI dialysis (see below).52 The efficacy of activated charcoal has lead to a resurgence of its use over the past few years.

Charcoal can be administered after both GL or ipecac-induced emesis, but it is usually administered as the sole GI decontaminating agent. Airway protection is imperative in stuporous, comatose, or convulsing patients. Prior gastric stapling is an additional risk factor for emesis and aspiration with single or repeated doses.53Charcoal aspiration has been associated with pneumonia54(including fungal pneumonia55), bronchiolitis obliterans,56ARDS,57and death.58

Despite the mentioned complications, activated charcoal is generally effective and well tolerated. Complications are infrequent. The ideal dose should give a charcoal-to-drug ratio of 10:1. However, since the quantity of poison ingested is usually unknown to the clinician, the dose is based on actual patient weight (1 g/kg). It is commonly co-administered with a cathartic (see below) to facilitate evacuation of the toxic substance and avoid constipation. Commonly used agents include magnesium sulfate, magnesium citrate, or sorbitol. Mixing the solution with juice may increase acceptance of this black and gritty adsorbent in children and adults. Single-dose activated charcoal is effective against most toxins and drugs. Table 15 lists selected toxins for which charcoal is not particularly effective. Based on volunteer studies, the effectiveness of activated charcoal decreases with time; the greatest benefit is within 1 h of ingestion.59

Catharsis

The use of cathartics with activated charcoal may reduce the transit time of drugs and toxins in the GI tract and decrease the constipating effects of charcoal. Sorbitol is the cathartic of choice. It is generally administered only with the first dose of activated charcoal. The usual dosage is 1 to 2 mL/kg of a 70% solution of sorbitol titrated to several loose stools over the first day of treatment (total dose, 1 g/kg). Magnesium-based cathartics (2 to 3 mL/kg po of a 10% solution of magnesium sulfate) may lead to magnesium accumulation in the setting of renal failure, and sodium-based products carry the risk of exacerbating hypertension or congestive heart failure. Oil-based cathartics, if aspirated, may produce lipoid pneumonia.

Cathartics have never been shown to decrease morbidity and mortality or to decrease hospital stay.60In a cross-over study, Keller et al61demonstrated that activated charcoal with sorbitol led to a 28% decrease in the absorption of salicylates when compared to activated charcoal alone. However, McNamara and colleagues62were unable to demonstrate enhanced efficacy of activated charcoal with sorbitol catharsis in a simulated acetaminophen overdose. Based on available data, the routine use of a cathartic in combination with activated charcoal is not endorsed by the American Academy of Clinical Toxicology and the European Association of Poisons Centers and Clinical Toxicologists. If a cathartic is administered, it should be limited to a single dose in order to minimize adverse effects.63

Whole-Bowel Irrigation

Whole-bowel irrigation with a polyethylene glycol, electrolyte solution (Colyte; Schwarz Pharma; Milwaukee, WI) or potassium chloride (Golytely; Braintree Laboratories; Braintree, MA), 1 to 2 L/h, in adults is used to push tablets or packages through the GI track. The optimal regimen in regards to volume infused per hour, duration of use, and dosage of activated charcoal prior to whole-bowel irrigation has not been well established.46 It may take 3 to 5 h for complete bowel irrigation to clear the rectal effluent. These isotonic solutions are not absorbed and do not cause major electrolyte shift or imbalance.64The technique is time consuming and requires a cooperative patient. Most studies supporting this approach are limited to case reports, and there are no established indications for its use. However, whole-bowel irrigation may have a role in intoxications where activated charcoal is not effective, such as ingestion of iron and sustained-release tablets, lithium, or in cases of “body packing” with packages of illicit drugs.65 Contraindications to whole-bowel irrigation include ileus, GI hemorrhage, and bowel perforation.

Forced Diuresis and Urinary pH Manipulation

Routine use of volume-loading to promote diuresis has not been well studied or supported in the literature and cannot be recommended. Its goal is to augment elimination of renally excreted toxins through inhibition of tubular reabsorption. Thus, in order to be effective, the toxin needs to undergo extensive tubular reabsorption that can be inhibited by forced diuresis. However, forced diuresis has the potential to cause electrolyte imbalance, pulmonary edema, and raised intracranial pressure.66The technique consists of achieving a urine flow rate from 3 to 6 mL/kg/h with a combination of isotonic fluids and/or diuretics.67 When tubular reabsorption of a toxin is pH sensitive, then increased urine flow does not significantly increase urinary drug elimination when added to alkaline or acid diuresis.

Manipulation of urinary pH can be used therapeutically to enhance elimination of some intoxicants (Table 16 ). The limits of urinary pH are 4.5 to 7.5 under conditions of enhanced acidification and alkalinization. Thus, elimination of very strong (negative logarithm of the acid ionization equilibrium constant [pKa] < 3) or very weak (pKa > 8) acids is unaltered by urinary pH manipulation. Other acidic or basic drugs do not undergo renal tubular absorption, irrespective of urinary pH, since they are polar in their nonionized form.

Urinary alkalinization (pH > 7) is most often used to eliminate salicylates and phenobarbital. It can be achieved by administration of IV sodium bicarbonate (1 to 2 mEq/kg every 3 to 4 h); this may be administered as two 50-mL ampules of 8.4% sodium bicarbonate (each containing 50 mEq of NaHCO3) per liter of 5% dextrose in water infused at 250 mL/h. Complications of this therapy include alkalemia (particularly in the presence of concurrent respiratory alkalosis), volume overload, hypernatremia, and hypokalemia. It is particularly important to avoid hypokalemia, which prevents excretion of alkaline urine by promoting distal tubular potassium reabsorption in exchange for hydrogen ion. Accordingly, bicarbonate administration in the presence of significant hypokalemia will not alkalinize the urine, yet will increase the risk of alkalemia. Since urinary alkalinization therapy can cause hypokalemia (due to alkalemia-induced intracellular potassium shift and increased urinary potassium loss with alkaline diuresis), addition of potassium chloride to the bicarbonate infusion is commonly required. Acetazolamide should not be used to alkalinize urine. Resultant metabolic acidosis can increase toxicity of certain poisonings (particularly in the case of salicylate poisoning).68

Urinary acidification (pH < 5.5) increases renal clearance of some nonpolar weak bases with pKa values between 6 and 12. Arginine or lysine hydrochloride or ammonium chloride have been used for urinary acidification. However, due to the potential of urinary acidification to exacerbate myoglobinuric renal tubular injury, this therapy is virtually never used. Also, systemic acidosis must be avoided in order to avoid potential additive effects with toxin-induced metabolic or respiratory acidosis.68

Multiple-Dose Activated Charcoal

Multiple-dose activated charcoal can be an effective way to enhance the elimination of toxins that have been absorbed.69 The mechanism by which this modality accomplishes enhancement of elimination is either by interrupting the enterohepatic/enterogastric circulation of drugs or through the binding of any drug that diffuses from the circulation into the gut lumen (called GI dialysis). However, it has limited application because the toxin must have a low volume of distribution, low protein binding, prolonged elimination half-life, and low pKa, which maximizes transport across mucosal membranes into the GI tract.,67 Although optimal dosage and frequency of administration following the initial dose of activated charcoal is not well established, most experts recommend a dose not < 12.5 g/h.70After the initial dose of 1 g/kg, activated charcoal may be administered at 0.5 g/kg every 2 to 4 h for at least three doses. Cathartics are generally not administered to avoid hypernatremia, hypokalemia, and hypermagnesemia. Multiple dosing should be used with caution in patients with decreased bowel sounds, abdominal distension, and persistent emesis. Unless a patient has an intact or protected airway, the administration of multidose charcoal is contraindicated. In a review of all the relevant scientific literature, the American Academy of Clinical Toxicologists reported that although multidose charcoal enhances drug elimination significantly, it has not yet been evaluated in a controlled trial of poisoned patients with the objective of demonstrating a reduction in morbidity and mortality.71Table 17 provides a list of drugs and toxins where there may be a role for multiple dosing of activated charcoal.67 However, based on experimental and clinical studies, it should be considered only in patients with a life-threatening ingestion of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.71

In situations where previously mentioned supportive measures fail to improve a patient’s condition, extracorporeal removal of toxins can be lifesaving.7273 Although clear proof that extracorporeal toxin removal favorably alters the course of any intoxication is generally lacking,74 it should be considered when the intoxication is projected to undergo delayed or insufficient clearance because of other organ dysfunction, the intoxicating agent produces toxic metabolites, or delayed toxicity is characteristic of the intoxication. In addition to physicochemical properties of the intoxicant, serum toxin levels or certain clinical features may mandate extracorporeal removal techniques. Three methods for extracorporeal removal of toxins are generally available: (1) dialysis (usually hemodialysis rather than peritoneal dialysis), (2) hemoperfusion; and (3) hemofiltration. Plasmapheresis and exchange transfusion are rarely used and will not be further discussed in this review. A complete list of drugs and toxins that may be removed by different extracorporeal removal techniques is beyond the scope of this review.6768

Hemodialysis

Hemodialysis is the primary extracorporeal method to remove toxins or drugs. Toxins for which hemodialysis may be useful should have a low molecular weight (< 500 d), be water soluble, have low protein binding (< 70 to 80%), and have a small volume of distribution (< 1 L/kg). It can especially be effective in correcting concomitant electrolyte abnormality and metabolic acidosis. Toxins in which hemodialysis may be required in an early stage of intoxication include methanol, ethylene glycol, boric acid, salicylates, and lithium. Hemodialysis can also be used for heavy metal chelation in patients with renal failure.

Hemoperfusion

Hemoperfusion is defined as direct contact of blood with an adsorbent system.75 Charcoal hemoperfusion involves pumping blood through a charcoal canister. Unlike hemodialysis, drug clearance is not limited by low water solubility, high molecular weight, or increased protein binding, but on the ability of the adsorbent to bind to the drug/toxin. However, the toxin needs to be present in the central compartment for hemoperfusion to be effective. Hemoperfusion is essentially the parenteral analog of oral activated charcoal. Complications of hemoperfusion include the following: (1) cartridge saturation; (2) thrombocytopenia that commonly occurs due to platelet adsorption, inducing up to 30% decrement in platelet count; (3) hypoglycemia and hypocalcemia; (4) access complications; (5) hypothermia, since hemoperfusion pumps do not warm blood as hemodialysis does; and (6) charcoal embolization (prevented by a filter in the line returning effluent blood to the patient).

Most drugs are extractable by hemoperfusion, which is particularly suitable for extracorporeal removal of toxins that are of high molecular weight, highly protein bound, or lipid soluble. It has been effectively used to enhance elimination of theophylline, phenobarbital, phenytoin, carbamazepine, paraquat, and glutethimide. Drugs poorly extracted by hemoperfusion include the following: heavy metals (lithium, bromide), some alcohols (ethanol, methanol), carbon monoxide, and some illicit drugs (cocaine, phencyclidine, and others). Efficacy of intoxicant removal is diminished for substances with a large volume of distribution that are highly lipid soluble and/or extensively tissue bound. These intoxicants may be more effectively removed by hemofiltration.

Hemofiltration

Hemofiltration achieves drug and toxin removal by convection. It transports solutes through a highly porous membrane that is permeable to substances with weights of up to 6,000 d, including virtually all drugs. In some cases, hemofiltration membranes are permeable to substances weighing up to 20,000 d.7677 Although the application of this technique has not been vigorously studied in poisoned patients, there are increasing numbers of case reports of extracorporeal intoxicant removal by either the continuous arteriovenous or venovenous hemofiltration methods.7880 Hemofiltration is potentially useful for removal of substances with a large volume of distribution, slow intercompartmental transfer, or extensive tissue binding. Specific highly porous hemofiltration cartridges are also particularly useful for removal of large-molecular-weight solutes or complexes, such as combined digoxin-Fab fragment complexes, or desferoxamine complexes with iron or with aluminum.

An antidote is a substance that increases the mean lethal dose of a toxin, or that can favorably affect the toxic effects of a poison. Some are toxic themselves and therefore should be used only when indicated. Table 18 lists antidotes for specific drugs/poisons. These will be discussed further next month in part II of this article.

In the current health-care climate, the practice of routinely admitting the poisoned patient to the ICU is being questioned. Brett et al81identified eight clinical risk factors that can predict ICU interventions: (1) Paco2 > 45 mm Hg, (2) need for endotracheal intubation, (3) toxin-induced seizures, (4) cardiac arrhythmias, (5) QRS duration ≥ 0.12 s, (6) systolic BP < 80 mm Hg, (7) second- or third-degree atrioventricular block, and (8) unresponsiveness to verbal stimuli. In this retrospective study, if a poisoned patient did not exhibit any of the eight characteristics, no ICU interventions (intubation, vasopressors or antiarrhythmics, and dialysis or hemoperfusion) were required. Other indications for ICU admission include a Glasgow coma scale score < 12,82 need for emergency dialysis or hemoperfusion, progressive metabolic acidosis, and a cyclic antidepressant or phenothiazine overdose with signs of anticholinergic cardiac toxicity.8384 Severe hyperkalemia, wide alterations in body temperature, and need for continuous infusion of naloxone are also reasons to admit a patient to an ICU. In addition, staffing issues such as the availability of a “sitter” in cases of attempted suicide may impact patient disposition. Table 19 provides a list of criteria for ICU admission.,67

Abbreviations: GL = gastric lavage; pKa = negative logarithm of the acid ionization equilibrium constant

Table Graphic Jump Location
Table 1. Common Toxidromes
Table Graphic Jump Location
Table 1A. Continued
Figure Jump LinkFigure 1. Route of exposure for human poisoning. Data from the 2000 Toxic Exposure Surveillance System of the American Association of Poison Control Centers.1Grahic Jump Location
Table Graphic Jump Location
Table 2. Most Lethal Human Toxin Exposures Reported to Poison Control Centers in 2000*
* 

Data obtained from cases reported by 63 poison control centers during 2000. Not all poisonings and intoxications are reported to poison control centers.1

 

No. of deaths are based on an unlimited number of substances coded per exposure.

Table Graphic Jump Location
Table 3. Clinical Features Mandating Consideration of Toxic Ingestion*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 4. Drugs Affecting Temperature
Table Graphic Jump Location
Table 5. Selected Drugs/Toxins Causing Tachycardia and Bradycardia*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 6. Selected Drugs Affecting Pupil Size*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 7. Selected Drugs Altering Mental Status
Table Graphic Jump Location
Table 8. Common Drugs and Toxins Causing Generalized Seizures*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 9. Selected Drugs Affecting Muscle Tone*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 10. Common Causes of Abnormal Anion Gap
* 

See Table 11.

Table Graphic Jump Location
Table 11. Selected Drugs Associated With an Elevated Anion Gap Metabolic Acidosis
Table Graphic Jump Location
Table 12. Drugs/Toxins Associated With an Elevated Osmolal Gap*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 13. Drugs Commonly Included in Urine Substances-of-Abuse Screens (Available in 30 min)*
* 

Immunoassay technique; modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 14. Selected Causes of Hypoxemia in Drug Overdose and Toxic Ingestion*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 15. Toxins and Drugs Not Adsorbed by Activated Charcoal
Table Graphic Jump Location
Table 16. Toxins Eliminated by Urinary Alkalinization
Table Graphic Jump Location
Table 17. Toxins and Drugs Eliminated by Multiple Dosing of Activated Charcoal*
* 

? Represents equivocal data.

Table Graphic Jump Location
Table 18. Antidotes*
* 

EDTA = ethylenediamine tetra-acetic acid.

Table Graphic Jump Location
Table 19. Criteria for Admission of the Poisoned Patient to the ICU*
* 

ECMO = extracorporeal membrane oxygenation.

Litovitz, TL, Klein-Schwartz, W, White, S, et al (2001) 2000 annual report of the American Association of Poison Control Centers toxic exposure surveillance system.Am J Emerg Med19,337-395. [PubMed] [CrossRef]
 
Wright, N An assessment of the unreliability of the history given by self-poisoned patients.Clin Toxicol1980;16,381-384. [PubMed]
 
Olson, KR, Pentel, PR, Kelley, MT Physical assessment and differential diagnosis of the poisoned patient.Med Toxicol1987;2,52-81. [PubMed]
 
Winter, SD, Pearson, R, Gabow, PA, et al The fall of the serum anion gap.Arch Intern Med1990;150,311-313. [PubMed]
 
Gabow, PA Disorders associated with an altered anion gap.Kidney Int1985;27,472-483. [PubMed]
 
Ammar, KA, Heckerling, PS Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: importance of the osmolal gap.Am J Kidney Dis1996;27,130-133. [PubMed]
 
Walker, JA, Schwartzbard, A, Krauss, EA, et al The missing gap: a pitfall in the diagnosis of alcohol intoxication by osmometry.Arch Intern Med1986;146,1843-1844. [PubMed]
 
Sweeney, TE, Beuchat, CA Limitations of methods of osmometry: measuring the osmolality of biological fluids.Am J Physiol1993;264,R469-R480. [PubMed]
 
Glasser, L, Sternglanz, PD, Combie, J, et al Serum osmolality and its applicability to drug overdose.Am J Clin Pathol1973;60,695-699. [PubMed]
 
Glaser, DS Utility of the serum osmolal gap in the diagnosis of methanol or ethylene glycol ingestion.Ann Emerg Med1996;27,343-346. [PubMed]
 
Trummel, J, Ford, M, Autin, P Ingestion of an unknown alcohol.Ann Emerg Med1996;27,368-374. [PubMed]
 
Hoffman, RS, Smilkstein, MJ, Howland, MA, et al Osmolal gaps revisited: normal values and limitations.J Toxicol Clin Toxicol1993;31,81-93. [PubMed]
 
Tremper, KK, Barker, SJ Pulse oximetry.Anesthesiology1989;70,98-108. [PubMed]
 
Barker, SJ, Tremper, KK, Hyatt, J Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry.Anesthesiology1989;70,112-117. [PubMed]
 
LeGrand, TS, Peters, JI Pulse oximetry: advantages and pitfalls.J Crit Illn1999;20,195-206
 
Hampson, NB Pulse oximetry in severe carbon monoxide poisoning.Chest1998;114,1036-1041. [PubMed]
 
Bozeman, WP, Myers, RA, Barish, RA Confirmation of the pulse oximetry gap in carbon monoxide poisoning.Ann Emerg Med1997;30,608-611. [PubMed]
 
Brett, AS Implications of discordance between clinical impression and toxicology analysis in drug overdose.Arch Intern Med1988;148,437-441. [PubMed]
 
Kellerman, AL, Fihn, SD, LoGerfo, JP, et al Impact of drug screening in suspected overdose.Ann Emerg Med1987;16,1209-1216
 
Mahoney, JD, Gross, PL, Stern, TA, et al Quantitative serum toxic screening in the management of suspected drug overdose.Am J Emerg Med1990;8,16-22. [PubMed]
 
Wigder, WN, Erickson, T, Morse, T, et al Emergency department poison advice telephone calls.Ann Emerg Med1995;25,349-352. [PubMed]
 
Marik, PE Aspiration pneumonitis and aspiration pneumonia.N Engl J Med2001;344,665-671. [PubMed]
 
Roy, TM, Ossorio, MA, Cipolla, LM, et al Pulmonary complications after tricyclic antidepressant overdose.Chest1989;96,852-856. [PubMed]
 
Aldrich, T, Morrsion, J, Cesario, T Aspiration after overdosage of sedative or hypnotic drugs.South Med J1980;73,456-458. [PubMed]
 
Hoffman, RS, Goldfrank, LR The poisoned patient with altered consciousness: controversies in the use of a “coma cocktail.”JAMA1995;274,562-569. [PubMed]
 
Reuler, JB, Girard, DE, Cooney, TG Wernicke’s encephalopathy.N Engl J Med1985;312,1035-1039. [PubMed]
 
Goldfrank, LR The several uses of naloxone.Emerg Med1984;16,110-116
 
Goldfrank, LR, Weisman, RS, Errick, JK, et al A dosing nomogram for continuous infusion intravenous naloxone.Ann Emerg Med1986;15,566-570. [PubMed]
 
Ward, CF Pulmonary edema and naloxone [letter]. J Clin Anesth. 1996;;8 ,.:690. [PubMed]
 
Schwartz, JA, Koenigsberg, MD Naloxone-induced pulmonary edema.Ann Emerg Med1987;16,1294-1296. [PubMed]
 
Chiang, WK, Goldfrank, LR Substance withdrawal.Emerg Med Clin North Am1990;8,616-632
 
Mariani, PJ Seizure associated with low-dose naloxone.Am J Emerg Med1989;7,127-129. [PubMed]
 
Doyon, S, Roberts, JR Reappraisal of the coma cocktail: dextrose, flumazenil, naloxone, and thiamine.Emerg Med Clin North Am1994;12,301-316. [PubMed]
 
Longmire, AW, Seger, DL Topics in clinical pharmacology: flumazenil, a benzodiazepine antagonist.Am J Med Sci1993;306,49-52. [PubMed]
 
Mordel, A, Winkler, E, Almog, S, et al Seizures after flumazenil administration in a case of combined benzodiazepine and tricyclic antidepressant overdose.Crit Care Med1992;20,1733-1734. [PubMed]
 
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 Med1996;24,199-206. [PubMed]
 
Barnett, R, Grace, M, Boothe, P, et al Flumazenil in drug overdose: randomized, placebo-controlled study to assess cost effectiveness.Crit Care Med1999;27,78-81. [PubMed]
 
Paloucek, F Antidotal flumazenil use: the protamine of the 90s.Crit Care Med1999;27,10-11. [PubMed]
 
Bond, GR, Requa, RK, Krenzelok, EP, et al Influence of time until emesis on the efficacy of decontamination using acetaminophen as a marker in a pediatric population.Ann Emerg Med1993;22,1403-1407. [PubMed]
 
Merigan, KS, Woodard, M, Hedges, JR, et al Prospective evaluation of gastric emptying in the self-poisoned patient.Am J Emerg Med1990;8,479-483. [PubMed]
 
Krenzelok, EP, McGuigan, M, Lheur, P Position statement: ipecac syrup. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,699-709. [PubMed]
 
Shannon, M Ingestion of toxic substances by children.N Engl J Med2000;342,186-191. [PubMed]
 
Vale, JA, Meredith, TJ, Proudfoot, AT Syrup of ipecacuanha: is it really useful?BMJ1986;293,1321-1322. [PubMed]
 
Rudolph, JP Automated gastric lavage and a comparison of 0.9% normal saline solution and tap water irrigant.Ann Emerg Med1985;14,1156-1159. [PubMed]
 
Thompson, AM, Robins, JB, Prescott, LF, et al Changes in cardiorespiratory function during gastric lavage for drug overdose.Hum Toxicol1987;6,215-218. [PubMed]
 
Zimmerman, JL Management issues in toxicology.Semin Respir Crit Care Med2001;22,23-28. [PubMed]
 
Kulig, K, Bar-Or, D, Cantrill, SV, et al Management of acutely poisoned patients without gastric emptying.Ann Emerg Med1985;14,562-567. [PubMed]
 
Comstock, EG, Faulkner, TP, Boisaubin, EV, et al Studies on the efficacy of gastric lavage as practiced in a large metropolitan hospital.Clin Toxicol1981;18,581-597. [PubMed]
 
Pond, SM, Lewis-Driver, DJ, Williams, GM, et al Gastric emptying in acute overdose: a prospective randomised controlled trial.Med J Aust1995;163,345-349. [PubMed]
 
Vale, JA Position statement: gastric lavage. American Academy of Clinical Toxicology, European Association of Poison Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,711-719. [PubMed]
 
Saetta, JP, March, S, Gaunt, ME, et al Gastric emptying procedures in the self-poisoned patient: are we forcing gastric content beyond the pylorus?J R Soc Med1991;84,274-276. [PubMed]
 
Levy, G Gastrointestinal clearance of drugs with activated charcoal.N Engl J Med1982;307,676-678. [PubMed]
 
Varga, DW, Roy, TM, Ossorio, MA Gastric stapling: a significant risk factor in the treatment of tricyclic antidepressant overdose.J Ky Med Assoc1989;87,501-503. [PubMed]
 
Givens, T, Holloway, M, Wason, S Pulmonary aspiration of activated charcoal: a complication of its misuse in overdose management.Pediatr Emerg Care1992;8,137-140. [PubMed]
 
George, DL, McLeod, R, Weinstein, RA Contaminated commercial charcoal as a source of fungi in the respiratory tract.Infect Control Hosp Epidemiol1991;12,732-734. [PubMed]
 
Elliott, CG, Colby, TV, Kelly, TM Charcoal lung: bronchiolitis obliterans after aspiration of activated charcoal.Chest1989;96,672-674. [PubMed]
 
Harris, CR, Filandrinos, D Accidental administration of activated charcoal into the lung: aspiration by proxy.Ann Emerg Med1993;22,1470-1473. [PubMed]
 
Menzies, DG, Busuttil, A, Prescott, LF Fatal pulmonary aspiration of oral activated charcoal.BMJ1988;297,459-460. [PubMed]
 
Chyka, PA, Seger, D Position statement: single-dose activated charcoal. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,721-741. [PubMed]
 
Krenzelok, EP, Keller, R, Stewart, RD Gastrointestinal transit times of cathartics combined with charcoal.Ann Emerg Med1985;14,1152-1155. [PubMed]
 
Keller, RE, Schwab, RA, Krenzelok, EP Contribution of sorbitol combined with activated charcoal in prevention of salicylate absorption.Ann Emerg Med1990;19,654-656. [PubMed]
 
McNamara, RM, Aaron, CK, Gembroys, M, et al Sorbitol catharsis does not enhance efficacy of charcoal in a simulated acetaminophen overdose.Ann Emerg Med1988;17,243-246. [PubMed]
 
Barceloux, D, McGuigan, M, Hartigan-Go, K Position statement: cathartics. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,743-752. [PubMed]
 
Davis, GR, Santa Ana, CA, Morawski, SG, et al Development of a lavage solution associated with minimal water and electrolyte absorption or secretion.Gastroenterology1980;78,991-995. [PubMed]
 
Tenenbein, M Position statement: whole bowel irrigation. American Academy of Clinical Toxicology, European Association of Poison Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,753-762. [PubMed]
 
Pond, SM Principles of techniques applied to enhance elimination of toxic compounds. Goldfrank, LR eds.Goldfrank’s toxicologic emergencies1998,53-62 Appelton and Lange. Stamford, CT:
 
Krenzelok, EP, Leikin, JB Approach to a poisoned patient.Dis Mon1996;42,513-608
 
Corbridge, TC, Murray, P Toxicology in adults. Hall, J Schmidt, GS Wood, LDH eds.Principles of critical care1998,1473-1525 McGraw Hill. New York, NY:
 
Bradberry, SM, Vale, JA Mutiple-dose activated charcoal: a review of relevant clinical studies.J Toxicol Clin Toxicol1995;33,407-416. [PubMed]
 
Ilkhanipour, K, Yealy, DM, Krenzelok, EP The comparative efficacy of various multiple-dose activated charcoal regimens.Am J Emerg Med1992;10,298-300. [PubMed]
 
Vale, JA, Krenzelok, EP, Barceloux, GD, et al Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1999;37,731-751. [PubMed]
 
Cutler, RE, Forland, SC, St. John Hammond, PG, et al Extracorporeal removal of drugs and poisons by hemodialysis and hemoperfusion.Ann Rev Pharmacol Toxicol1987;27,169-191
 
Pond, SM Extracorporeal techniques in the treatment of poisoned patients.Med J Aust1991;154,617-622. [PubMed]
 
Garella, S Extracorporeal techniques in the treatment of exogenous intoxications.Kidney Int1988;33,735-754. [PubMed]
 
Rommes, JH Haemoperfusion, indications and side-effects.Arch Toxicol1992;15,S40-S49
 
Golper, TA, Wedel, SK, Kaplan, AA, et al Drug removal by continuous arteriovenous hemofiltration: theory and clinical observations.Int J Artif Organs1985;8,307-312. [PubMed]
 
Golper, TA Drug removal during continuous renal replacement therapies.Dial Transpl1993;22,185-212
 
Bellomo, R, Kearly, Y, Parkin, G, et al Treatment of life-threatening lithium toxicity with continuous arterio-venous hemodiafiltration.Crit Care Med1991;19,836-837. [PubMed]
 
Leblanc, M, Raymond, M, Bonnardeaux, A, et al Lithium poisoning treated by high-performance continuous arteriovenous and venovenous hemodiafiltration.Am J Kidney Dis1996;27,365-372. [PubMed]
 
Menghini, VV, Albright, RC Treatment of lithium intoxication with continuous venovenous hemodiafiltration. Am J Kidney Dis. 2000;;3 ,.:E21
 
Brett, AS, Rothschild, N, Gray, R, et al Predicting the clinical course in intentional drug overdose: implications for the use of the intensive care unit.Arch Intern Med1987;147,133-137. [PubMed]
 
Hamad, AE, Al-Ghadban, A, Carvounis, CP, et al Predicting the need for medical intensive care monitoring in drug-overdosed patients.J Intensive Care Med2000;15,321-328
 
Kulling, P, Persson, H The role of the intensive care unit in the management of the poisoned patient.Med Toxicol1986;1,375-386. [PubMed]
 
Callaham, M Admission criteria for tricyclic antidepressant ingestion.West J Med1982;137,425-429. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Route of exposure for human poisoning. Data from the 2000 Toxic Exposure Surveillance System of the American Association of Poison Control Centers.1Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Common Toxidromes
Table Graphic Jump Location
Table 1A. Continued
Table Graphic Jump Location
Table 2. Most Lethal Human Toxin Exposures Reported to Poison Control Centers in 2000*
* 

Data obtained from cases reported by 63 poison control centers during 2000. Not all poisonings and intoxications are reported to poison control centers.1

 

No. of deaths are based on an unlimited number of substances coded per exposure.

Table Graphic Jump Location
Table 3. Clinical Features Mandating Consideration of Toxic Ingestion*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 4. Drugs Affecting Temperature
Table Graphic Jump Location
Table 5. Selected Drugs/Toxins Causing Tachycardia and Bradycardia*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 6. Selected Drugs Affecting Pupil Size*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 7. Selected Drugs Altering Mental Status
Table Graphic Jump Location
Table 8. Common Drugs and Toxins Causing Generalized Seizures*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 9. Selected Drugs Affecting Muscle Tone*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 10. Common Causes of Abnormal Anion Gap
* 

See Table 11.

Table Graphic Jump Location
Table 11. Selected Drugs Associated With an Elevated Anion Gap Metabolic Acidosis
Table Graphic Jump Location
Table 12. Drugs/Toxins Associated With an Elevated Osmolal Gap*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 13. Drugs Commonly Included in Urine Substances-of-Abuse Screens (Available in 30 min)*
* 

Immunoassay technique; modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 14. Selected Causes of Hypoxemia in Drug Overdose and Toxic Ingestion*
* 

Modified with permission from Corbridge and Murray.68

Table Graphic Jump Location
Table 15. Toxins and Drugs Not Adsorbed by Activated Charcoal
Table Graphic Jump Location
Table 16. Toxins Eliminated by Urinary Alkalinization
Table Graphic Jump Location
Table 17. Toxins and Drugs Eliminated by Multiple Dosing of Activated Charcoal*
* 

? Represents equivocal data.

Table Graphic Jump Location
Table 18. Antidotes*
* 

EDTA = ethylenediamine tetra-acetic acid.

Table Graphic Jump Location
Table 19. Criteria for Admission of the Poisoned Patient to the ICU*
* 

ECMO = extracorporeal membrane oxygenation.

References

Litovitz, TL, Klein-Schwartz, W, White, S, et al (2001) 2000 annual report of the American Association of Poison Control Centers toxic exposure surveillance system.Am J Emerg Med19,337-395. [PubMed] [CrossRef]
 
Wright, N An assessment of the unreliability of the history given by self-poisoned patients.Clin Toxicol1980;16,381-384. [PubMed]
 
Olson, KR, Pentel, PR, Kelley, MT Physical assessment and differential diagnosis of the poisoned patient.Med Toxicol1987;2,52-81. [PubMed]
 
Winter, SD, Pearson, R, Gabow, PA, et al The fall of the serum anion gap.Arch Intern Med1990;150,311-313. [PubMed]
 
Gabow, PA Disorders associated with an altered anion gap.Kidney Int1985;27,472-483. [PubMed]
 
Ammar, KA, Heckerling, PS Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: importance of the osmolal gap.Am J Kidney Dis1996;27,130-133. [PubMed]
 
Walker, JA, Schwartzbard, A, Krauss, EA, et al The missing gap: a pitfall in the diagnosis of alcohol intoxication by osmometry.Arch Intern Med1986;146,1843-1844. [PubMed]
 
Sweeney, TE, Beuchat, CA Limitations of methods of osmometry: measuring the osmolality of biological fluids.Am J Physiol1993;264,R469-R480. [PubMed]
 
Glasser, L, Sternglanz, PD, Combie, J, et al Serum osmolality and its applicability to drug overdose.Am J Clin Pathol1973;60,695-699. [PubMed]
 
Glaser, DS Utility of the serum osmolal gap in the diagnosis of methanol or ethylene glycol ingestion.Ann Emerg Med1996;27,343-346. [PubMed]
 
Trummel, J, Ford, M, Autin, P Ingestion of an unknown alcohol.Ann Emerg Med1996;27,368-374. [PubMed]
 
Hoffman, RS, Smilkstein, MJ, Howland, MA, et al Osmolal gaps revisited: normal values and limitations.J Toxicol Clin Toxicol1993;31,81-93. [PubMed]
 
Tremper, KK, Barker, SJ Pulse oximetry.Anesthesiology1989;70,98-108. [PubMed]
 
Barker, SJ, Tremper, KK, Hyatt, J Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry.Anesthesiology1989;70,112-117. [PubMed]
 
LeGrand, TS, Peters, JI Pulse oximetry: advantages and pitfalls.J Crit Illn1999;20,195-206
 
Hampson, NB Pulse oximetry in severe carbon monoxide poisoning.Chest1998;114,1036-1041. [PubMed]
 
Bozeman, WP, Myers, RA, Barish, RA Confirmation of the pulse oximetry gap in carbon monoxide poisoning.Ann Emerg Med1997;30,608-611. [PubMed]
 
Brett, AS Implications of discordance between clinical impression and toxicology analysis in drug overdose.Arch Intern Med1988;148,437-441. [PubMed]
 
Kellerman, AL, Fihn, SD, LoGerfo, JP, et al Impact of drug screening in suspected overdose.Ann Emerg Med1987;16,1209-1216
 
Mahoney, JD, Gross, PL, Stern, TA, et al Quantitative serum toxic screening in the management of suspected drug overdose.Am J Emerg Med1990;8,16-22. [PubMed]
 
Wigder, WN, Erickson, T, Morse, T, et al Emergency department poison advice telephone calls.Ann Emerg Med1995;25,349-352. [PubMed]
 
Marik, PE Aspiration pneumonitis and aspiration pneumonia.N Engl J Med2001;344,665-671. [PubMed]
 
Roy, TM, Ossorio, MA, Cipolla, LM, et al Pulmonary complications after tricyclic antidepressant overdose.Chest1989;96,852-856. [PubMed]
 
Aldrich, T, Morrsion, J, Cesario, T Aspiration after overdosage of sedative or hypnotic drugs.South Med J1980;73,456-458. [PubMed]
 
Hoffman, RS, Goldfrank, LR The poisoned patient with altered consciousness: controversies in the use of a “coma cocktail.”JAMA1995;274,562-569. [PubMed]
 
Reuler, JB, Girard, DE, Cooney, TG Wernicke’s encephalopathy.N Engl J Med1985;312,1035-1039. [PubMed]
 
Goldfrank, LR The several uses of naloxone.Emerg Med1984;16,110-116
 
Goldfrank, LR, Weisman, RS, Errick, JK, et al A dosing nomogram for continuous infusion intravenous naloxone.Ann Emerg Med1986;15,566-570. [PubMed]
 
Ward, CF Pulmonary edema and naloxone [letter]. J Clin Anesth. 1996;;8 ,.:690. [PubMed]
 
Schwartz, JA, Koenigsberg, MD Naloxone-induced pulmonary edema.Ann Emerg Med1987;16,1294-1296. [PubMed]
 
Chiang, WK, Goldfrank, LR Substance withdrawal.Emerg Med Clin North Am1990;8,616-632
 
Mariani, PJ Seizure associated with low-dose naloxone.Am J Emerg Med1989;7,127-129. [PubMed]
 
Doyon, S, Roberts, JR Reappraisal of the coma cocktail: dextrose, flumazenil, naloxone, and thiamine.Emerg Med Clin North Am1994;12,301-316. [PubMed]
 
Longmire, AW, Seger, DL Topics in clinical pharmacology: flumazenil, a benzodiazepine antagonist.Am J Med Sci1993;306,49-52. [PubMed]
 
Mordel, A, Winkler, E, Almog, S, et al Seizures after flumazenil administration in a case of combined benzodiazepine and tricyclic antidepressant overdose.Crit Care Med1992;20,1733-1734. [PubMed]
 
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 Med1996;24,199-206. [PubMed]
 
Barnett, R, Grace, M, Boothe, P, et al Flumazenil in drug overdose: randomized, placebo-controlled study to assess cost effectiveness.Crit Care Med1999;27,78-81. [PubMed]
 
Paloucek, F Antidotal flumazenil use: the protamine of the 90s.Crit Care Med1999;27,10-11. [PubMed]
 
Bond, GR, Requa, RK, Krenzelok, EP, et al Influence of time until emesis on the efficacy of decontamination using acetaminophen as a marker in a pediatric population.Ann Emerg Med1993;22,1403-1407. [PubMed]
 
Merigan, KS, Woodard, M, Hedges, JR, et al Prospective evaluation of gastric emptying in the self-poisoned patient.Am J Emerg Med1990;8,479-483. [PubMed]
 
Krenzelok, EP, McGuigan, M, Lheur, P Position statement: ipecac syrup. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,699-709. [PubMed]
 
Shannon, M Ingestion of toxic substances by children.N Engl J Med2000;342,186-191. [PubMed]
 
Vale, JA, Meredith, TJ, Proudfoot, AT Syrup of ipecacuanha: is it really useful?BMJ1986;293,1321-1322. [PubMed]
 
Rudolph, JP Automated gastric lavage and a comparison of 0.9% normal saline solution and tap water irrigant.Ann Emerg Med1985;14,1156-1159. [PubMed]
 
Thompson, AM, Robins, JB, Prescott, LF, et al Changes in cardiorespiratory function during gastric lavage for drug overdose.Hum Toxicol1987;6,215-218. [PubMed]
 
Zimmerman, JL Management issues in toxicology.Semin Respir Crit Care Med2001;22,23-28. [PubMed]
 
Kulig, K, Bar-Or, D, Cantrill, SV, et al Management of acutely poisoned patients without gastric emptying.Ann Emerg Med1985;14,562-567. [PubMed]
 
Comstock, EG, Faulkner, TP, Boisaubin, EV, et al Studies on the efficacy of gastric lavage as practiced in a large metropolitan hospital.Clin Toxicol1981;18,581-597. [PubMed]
 
Pond, SM, Lewis-Driver, DJ, Williams, GM, et al Gastric emptying in acute overdose: a prospective randomised controlled trial.Med J Aust1995;163,345-349. [PubMed]
 
Vale, JA Position statement: gastric lavage. American Academy of Clinical Toxicology, European Association of Poison Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,711-719. [PubMed]
 
Saetta, JP, March, S, Gaunt, ME, et al Gastric emptying procedures in the self-poisoned patient: are we forcing gastric content beyond the pylorus?J R Soc Med1991;84,274-276. [PubMed]
 
Levy, G Gastrointestinal clearance of drugs with activated charcoal.N Engl J Med1982;307,676-678. [PubMed]
 
Varga, DW, Roy, TM, Ossorio, MA Gastric stapling: a significant risk factor in the treatment of tricyclic antidepressant overdose.J Ky Med Assoc1989;87,501-503. [PubMed]
 
Givens, T, Holloway, M, Wason, S Pulmonary aspiration of activated charcoal: a complication of its misuse in overdose management.Pediatr Emerg Care1992;8,137-140. [PubMed]
 
George, DL, McLeod, R, Weinstein, RA Contaminated commercial charcoal as a source of fungi in the respiratory tract.Infect Control Hosp Epidemiol1991;12,732-734. [PubMed]
 
Elliott, CG, Colby, TV, Kelly, TM Charcoal lung: bronchiolitis obliterans after aspiration of activated charcoal.Chest1989;96,672-674. [PubMed]
 
Harris, CR, Filandrinos, D Accidental administration of activated charcoal into the lung: aspiration by proxy.Ann Emerg Med1993;22,1470-1473. [PubMed]
 
Menzies, DG, Busuttil, A, Prescott, LF Fatal pulmonary aspiration of oral activated charcoal.BMJ1988;297,459-460. [PubMed]
 
Chyka, PA, Seger, D Position statement: single-dose activated charcoal. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,721-741. [PubMed]
 
Krenzelok, EP, Keller, R, Stewart, RD Gastrointestinal transit times of cathartics combined with charcoal.Ann Emerg Med1985;14,1152-1155. [PubMed]
 
Keller, RE, Schwab, RA, Krenzelok, EP Contribution of sorbitol combined with activated charcoal in prevention of salicylate absorption.Ann Emerg Med1990;19,654-656. [PubMed]
 
McNamara, RM, Aaron, CK, Gembroys, M, et al Sorbitol catharsis does not enhance efficacy of charcoal in a simulated acetaminophen overdose.Ann Emerg Med1988;17,243-246. [PubMed]
 
Barceloux, D, McGuigan, M, Hartigan-Go, K Position statement: cathartics. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,743-752. [PubMed]
 
Davis, GR, Santa Ana, CA, Morawski, SG, et al Development of a lavage solution associated with minimal water and electrolyte absorption or secretion.Gastroenterology1980;78,991-995. [PubMed]
 
Tenenbein, M Position statement: whole bowel irrigation. American Academy of Clinical Toxicology, European Association of Poison Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1997;35,753-762. [PubMed]
 
Pond, SM Principles of techniques applied to enhance elimination of toxic compounds. Goldfrank, LR eds.Goldfrank’s toxicologic emergencies1998,53-62 Appelton and Lange. Stamford, CT:
 
Krenzelok, EP, Leikin, JB Approach to a poisoned patient.Dis Mon1996;42,513-608
 
Corbridge, TC, Murray, P Toxicology in adults. Hall, J Schmidt, GS Wood, LDH eds.Principles of critical care1998,1473-1525 McGraw Hill. New York, NY:
 
Bradberry, SM, Vale, JA Mutiple-dose activated charcoal: a review of relevant clinical studies.J Toxicol Clin Toxicol1995;33,407-416. [PubMed]
 
Ilkhanipour, K, Yealy, DM, Krenzelok, EP The comparative efficacy of various multiple-dose activated charcoal regimens.Am J Emerg Med1992;10,298-300. [PubMed]
 
Vale, JA, Krenzelok, EP, Barceloux, GD, et al Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists.J Toxicol Clin Toxicol1999;37,731-751. [PubMed]
 
Cutler, RE, Forland, SC, St. John Hammond, PG, et al Extracorporeal removal of drugs and poisons by hemodialysis and hemoperfusion.Ann Rev Pharmacol Toxicol1987;27,169-191
 
Pond, SM Extracorporeal techniques in the treatment of poisoned patients.Med J Aust1991;154,617-622. [PubMed]
 
Garella, S Extracorporeal techniques in the treatment of exogenous intoxications.Kidney Int1988;33,735-754. [PubMed]
 
Rommes, JH Haemoperfusion, indications and side-effects.Arch Toxicol1992;15,S40-S49
 
Golper, TA, Wedel, SK, Kaplan, AA, et al Drug removal by continuous arteriovenous hemofiltration: theory and clinical observations.Int J Artif Organs1985;8,307-312. [PubMed]
 
Golper, TA Drug removal during continuous renal replacement therapies.Dial Transpl1993;22,185-212
 
Bellomo, R, Kearly, Y, Parkin, G, et al Treatment of life-threatening lithium toxicity with continuous arterio-venous hemodiafiltration.Crit Care Med1991;19,836-837. [PubMed]
 
Leblanc, M, Raymond, M, Bonnardeaux, A, et al Lithium poisoning treated by high-performance continuous arteriovenous and venovenous hemodiafiltration.Am J Kidney Dis1996;27,365-372. [PubMed]
 
Menghini, VV, Albright, RC Treatment of lithium intoxication with continuous venovenous hemodiafiltration. Am J Kidney Dis. 2000;;3 ,.:E21
 
Brett, AS, Rothschild, N, Gray, R, et al Predicting the clinical course in intentional drug overdose: implications for the use of the intensive care unit.Arch Intern Med1987;147,133-137. [PubMed]
 
Hamad, AE, Al-Ghadban, A, Carvounis, CP, et al Predicting the need for medical intensive care monitoring in drug-overdosed patients.J Intensive Care Med2000;15,321-328
 
Kulling, P, Persson, H The role of the intensive care unit in the management of the poisoned patient.Med Toxicol1986;1,375-386. [PubMed]
 
Callaham, M Admission criteria for tricyclic antidepressant ingestion.West J Med1982;137,425-429. [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
Adult Toxicology in Critical Care*: Part II: Specific Poisonings
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543