Drug Overdose and Poisoning

KEY POINTS

1 With little intervention, the outcome for most victims of poisoning is excellent. Supportive care, with particular attention to maintaining an airway, oxygenation, and perfusion, is the mainstay of treatment. Becoming prematurely fixated on the details of specific antidotal therapy can lead to disastrous consequences if basic support of oxygenation and perfusion are ignored.

2 Adults suffering from overdoses rarely give a complete and accurate description of the quantity or type of medications ingested. In most adult cases, multiple substances are involved.

3 A tentative diagnosis in most overdose and poisoning cases can be made by physical examination and simple laboratory tests (electrolyte profile, creatinine, serum osmolarity, urinalysis, etc.).

4 Basic treatment principles include limiting the amount of toxin absorbed, enhancing elimination of absorbed toxin, and preventing conversion of nontoxic compounds to toxic metabolites.

5 Drugs or poisons for which specific antidotes or therapies exist (especially acetaminophen, salicylates, methanol, ethylene glycol, and digitalis) should be aggressively sought (including specific quantitative levels) and treated after initial stabilization.

Overdoses and poisonings account for approximately 15% of all intensive care unit (ICU) admissions, but most overdose patients do well and require only a brief stay. Despite myriad potential toxins, just a few account for more than 90% of all overdoses, with acetaminophen now being the single most common problem. Overall, most poisonings are oral ingestions; in adults, usually deliberate and involve multiple compounds; in children, usually accidental intake of a single agent. Most poisonings occur in otherwise healthy young patients, which partially explains the low hospital mortality (approx. 1%). (Most fatalities occur from arrhythmia, seizure, or hypoventilation-induced anoxic brain damage before patients reach the hospital or shortly after arrival.)

▪ DIAGNOSIS

Clinical History

The clinical history is often erroneous. Many patients overstate the quantity of ingested drug; others have taken a medication they conceal and the reported time of ingestion is often inaccurate. Suicidal patients may attempt to hide the type of poisons or drugs, and patients taking illicit drugs often lack accurate knowledge of what they took or fail to provide information, fearing prosecution. Occasionally, patients are victimized by surreptitious administration of a sedative, or hypnotic, agent of which they have no knowledge. In such cases, sexual assault is often the motive. Because patients may switch the contents of labeled bottles and accidental overdose may result from pharmacy dispensing errors, it is always wise to examine the contents of prescription bottles to ensure they match the label. It is important to seek the following information: (a) type of drug or toxin including ingestion of a sustained release form; (b) chronicity of use; (c) quantity consumed; (d) time elapsed since ingestion; (e) initial symptoms, including a history of vomiting or diarrhea; and (f) underlying diseases or other drugs taken.

Physical Examination

The physical examination is extremely valuable because it may allow rapid classification of patients into classic “toxic syndromes,” which can help in toxin identification and guide initial therapy. The cardinal manifestations of these syndromes and their common causes are illustrated in Table 33-1.

TABLE 33-1 MAJOR TOXIC SYNDROMES

SIGNS AND SYMPTOMS	ANTICHOLINERGIC	SYMPATHOMIMETIC	NARCOTIC/SEDATIVE	CHOLINERGIC	SEROTONIN
Mental status	Delirium	Delirium/hallucinations	Coma/lethargy	Confusion	Delirium
Skin	Dry/flushed	Sweating	Normal	Sweating	Flushed/sweating
Temperature	Elevated	Elevated	Reduced/normal	Normal	Elevated
Pulse	Rapid	Rapid	Slow	Normal/slow	Rapid
Respiration	Normal	Rapid	Slow/shallow	Bronchorrhea/wheezing	Normal/rapid
Blood pressure	Normal/elevated	Elevated	Normal/reduced	Normal or low	Normal
Eyes	Mydriasis	Mydriasis	Miosis	Miosis/lacrimation	Mydriasis
GI tract function	Decreased	Increased	Decreased	Diarrhea/vomiting	Diarrhea/nausea
Other	Seizures Myoclonus Urine retention	Seizures	Hyporeflexia	Muscle weakness Salivation Urinary incontinence	Trismus Tremor Myoclonus
Causes	Atropine Antihistamines Benztropine Baclofen Phenothiazines Propantheline Scopolamine Tricyclic antidepressants	Amphetamines Cocaine Ecstasy (MDMA) Ephedrine Caffeine Phenylephrine Phencyclidine Phenylpropanolamine Pseudoephedrine Theophylline	Opioids Ethanol Barbiturates Benzodiazepines Anticonvulsants Antipsychotics Gamma hydroxybutyrate Tramadol 1,4-Butanediol	Organophosphates Carbamates Physostigmine Pilocarpine Nerve agents, sarin	Fluoxetine Paroxetine Sertraline Trazodone Clomipramine Meperidine Addition of MAO inhibitor, e.g., linezolid

The first steps in treating a patient with poisoning are to assess the vital signs and ensure an adequate airway, oxygenation, and perfusion. The airway of the overdosed patient may be obstructed, particularly if narcotics, sedatives, or caustic agents have been ingested. Intubation and artificial ventilation are required when there is airway obstruction or the central drive to breathe is depressed. Because respiratory drive may be unstable, and vomiting is common, noninvasive ventilation is usually a poor choice for support of the overdosed patient. As a general rule, a patient sedate enough to allow unresisted endotracheal intubation almost certainly requires the airway protection and ventilatory support the procedure provides. When it takes several people to restrain a combative patient, the need for intubation should be reconsidered unless sedation is required for diagnostic evaluation (e.g., head computed tomographic [CT] scan, lumbar puncture) or for protection of the patient or staff.

Hypoventilation is a clue to narcotic, sedative, tramadol, carisoprodol, clonidine, or gamma hydroxybutyrate (GHB) overdose. Recently an industrial solvent, 1,4-butanediol, also known as GBL or GHV, with clinical effects similar to GHB has grown in popularity as a cheap recreational drug. Hyperventilation due to central nervous system (CNS) stimulation should suggest salicylate, theophylline, amphetamine, phencyclidine (PCP), or cocaine toxicity. Hyperventilation can also result from toxin-induced metabolic acidosis as seen with metformin, methanol, ethylene glycol, or propofol or from tissue hypoxia caused by cyanide or carbon monoxide (see Chapter 40). Any compound that causes methemoglobenemia, such as dapsone, amide topical anesthetics, and sulfa compounds, can also lead to hyperventilation.

Blood pressure and perfusion should be assessed and corrected rapidly if inadequate. Anticholinergic, cyclic antidepressant, or sympathomimetic
(e.g., cocaine, amphetamine) poisoning should be suspected in patients with marked tachycardia. Sinus bradycardia or conduction system block may result from overdoses of digitalis, clonidine, β-blockers, calcium channel blockers, or other cholinergic drugs.

Although hypertension is nonspecific, marked hypertension should suggest amphetamine, cocaine, thyroid hormone, methylene dioxymethamphetamine (MDMA, ecstasy), and catecholamine toxicities. Temperature may provide a valuable etiologic clue as well. Hyperthermia suggests anticholinergic, MDMA, amphetamine, or cyclic antidepressant poisoning or may be indicative of alcohol withdrawal, whereas hypothermia frequently accompanies alcohol or sedative-hypnotic overdose. (Hypothermia can be seen in any overdose that leads to prolonged environmental exposure to cool temperatures.)

Once the airway, breathing, and circulation are ensured, patients should be administered thiamine to avert the possibility of Wernicke’s encephalopathy, and a bedside glucose measurement should be obtained. Diagnosis of hypoglycemia is important because it mimics many common drug intoxications, is easily corrected, and is devastating if overlooked. The narcotic antagonist, naloxone, is frequently given; however, its use can create as many problems as it solves. For the narcotic-intoxicated patient, naloxone produces rapid return of consciousness but often precipitates vomiting (often with aspiration) and results in a combative, disoriented patient. Furthermore, the duration of action of naloxone is shorter than that of almost all narcotics, so it is common for patients to relapse into unconsciousness. Essentially all the same liabilities exist for the benzodiazepine antagonist, flumazenil.

It is important not to overlook concurrent trauma or other serious medical illness. For example, nearly one half of all head-injured motor vehicle crash victims also are intoxicated with alcohol or other substances. When trauma cannot be excluded in patients with altered mental status, it often is prudent to perform a CT or magnetic resonance image (MRI) scan of the head and neck and evaluate the cervical spine for injury while the evaluation and therapy of the overdose is ongoing. Similarly, drug or alcohol ingestion does not preclude a coexisting life-threatening medical illness such as meningitis or hypoglycemia.

The head should be examined closely for clues to other causes of coma (e.g., head trauma, subarachnoid hemorrhage) and to provide data relevant to overdose. For example, inspection of the mouth may reveal unswallowed tablets or evidence of caustic injury. Breath odor may suggest a particular toxin (Table 33-2). For instance, ketones give a sweet odor, whereas cyanide presents an almond scent. The characteristic smell of hydrocarbons is distinguished easily, as is the “garlic” odor of organophosphate ingestion. Narcotics, barbiturates, organophosphates, and phenothiazines commonly produce miosis, whereas drugs with anticholinergic properties (e.g., amphetamines, antihistamines, ecstasy, cocaine, and cyclic antidepressants) cause mydriasis. Nystagmus is often seen with ethanol, carbamazepine, PCP, or phenytoin ingestion. (Lithium, volatile solvents, and primidone also cause nystagmus.) Pupils that appear fixed and dilated can result from profound sedative overdose but are characteristic of glutethimide or mushroom poisoning. Pupils that are dilated but reactive suggest anticholinergic or sympathomimetic poisoning. Because even the slightest reaction has positive prognostic implications, the pupillary response should be tested using a bright light in a darkened room.

TABLE 33-2 CHARACTERISTIC BREATH ODORS OF VICTIMS OF POISONING

ODOR	POISON
Sweet/fruity	Ketones/alcohols
Almond	Cyanide
“Gasoline”	Hydrocarbons
Garlic	Organophosphates/arsenic
Wintergreen	Methyl salicylate
Pear	Chloral hydrate

Laboratory Testing

The electrocardiogram (ECG) can provide valuable clues in drug overdose. Ectopy is common in sympathomimetic and tricyclic poisoning. Highgrade atrioventricular (AV) block may be due to digoxin, β-blockers, calcium channel blockers, cyanide, phenytoin, or cholinergic substances. A wide QRS complex or prolonged QT interval suggests quinidine, procainamide, or cyclic antidepressant overdose.

Arterial blood gases are helpful to assess acidbase status and gas exchange and suggest salicylate
intoxication if they reveal a mixed respiratory alkalosis and metabolic acidosis. Metabolic acidosis with compensatory hyperventilation is common with cyanide or carbon monoxide exposure (see also Chapter 40) and with the propofol infusion syndrome (PRIS).

In addition to arterial blood gas determinations, measurement of hemoglobin saturation and oxygen content by co-oximetry may be helpful. Both methemoglobin and carboxyhemoglobin lead to a disparity between the measured oxygen content or measured hemoglobin saturation and that predicted from the arterial oxygen tension (PaO₂). Carboxyhemoglobin is elevated by carbon monoxide poisoning, and a number of drugs including dapsone, benzocaine, and sulfonamides can oxidize hemoglobin to methemoglobin. Profound methemoglobinemia should be suspected in patients with dyspnea seemingly without or with little lung disease and may be recognized at the bedside by the chocolate brown color it imparts to blood.

It is essential to calculate the anion and osmolar gaps. The numerical difference between the serum sodium and the sum of the chloride and bicarbonate is called the anion gap, and it normally ranges from 3 to 12 mEq/L. Six relatively common poisonings elevate the anion gap: (a) salicylates, (b) methanol, (c) ethanol, (d) ethylene glycol, (e) cyanide, and (f) carbon monoxide. Caution is advised, however, because hypoalbuminemia can reduce the anion gap obscuring an important clue to overdose. (For each reduction in albumin concentration of 1 gm/L, the anion gap declines by an average of 2.5 mEq/L.)

The osmolar gap is the difference between the calculated osmolality (1.86 [Na] + BUN/2.8 + glucose/18 + ethanol/4.6) and the osmolarity measured by a freezing point depression assay. When an osmolar gap greater than 10 mOsm exists, ethanol, ethylene glycol, isopropanol, and methanol become the most likely offenders; however, any unmeasured osmotic substance (e.g., glycerol, mannitol, sorbitol, radiocontrast agents, acetone, glycine) can widen the osmolar gap. The less commonly used method of vapor pressure osmometry does not detect methanol. Ketosis suggests ethanol, paraldehyde, or diabetes as potential culprits, although in many cases, simply not eating (starvation ketosis) is the explanation for mild ketosis. If ketones are present without systemic acidosis, isopropyl alcohol is the probable etiology.

Hypocalcemia is produced by the ingestion of ethylene glycol, oxalate, fluoride compounds, and certain rare metal ingestions: manganese, phosphorus, and barium. On rare occasions, chest or abdominal radiographs may help identify radiopaque tablets of iron, phenothiazines, tricyclic agents, or chloral hydrate. When these drugs are involved, the abdominal radiograph may help to ensure that the gut has been emptied after emesis or gastric lavage.

Use of the Drug Screen

Most qualitative drug screens assay urine or blood using thin-layer chromatography. Because there is no “standard” for which substances are included in a drug screen, it is important to know which compounds are assayed in each hospital. Urine and gastric juice are the most reliable samples for toxin assay because many drugs rapidly cleared from the serum may be detected as unabsorbed drug or excreted metabolites. Unfortunately, the drug screen has limited usefulness because significant delays often occur before the results are available, many toxins are not identified on the screen, and the results seldom change empirical therapy. Many common drugs (e.g., aspirin, acetaminophen, ethanol, methanol, ethylene glycol, GHB) are omitted from “routine” screens, and tests for each must be
requested specifically. If a particular toxin is suspected, specific assay techniques may provide more rapid and quantitative results. A negative screen alone does not exclude overdose because of problems with sensitivity and timing of the test in relation to ingestion. In other cases, the screen does not detect the offending agent (e.g., fentanyl). In some screening assays, commonly used drugs may be reported as the presence of a suspected toxin because of cross reactivity (Table 33-3). Whenever there is doubt regarding drug screen results, clinical judgment should prevail. Specific therapy is available for certain toxins for which quantitative levels should be obtained to guide management (Table 33-4).

TABLE 33-3 MEDICATIONS RESULTING IN FALSE-POSITIVE TOXICOLOGY SCREEN RESULTS

FALSE POSITIVE	CAUSE
Amphetamines	Ranitidine Chlorpromazine Bupropion Selegiline
Barbiturates	Ibuprofen Naproxen
Benzodiazepines	Oxaprozin
Cannabinoids	Pantoprazole Ibuprofen Naproxen
Opiates	Ofloxacin Levofloxacin Rifampin
Phencyclidine	Dextromethorphan Mesoridazine Venlafaxine
Cyclic antidepressants	Cyclobenzaprine

TABLE 33-4 COMPOUNDS FOR WHICH QUANTITATIVE ASSAY IS HELPFUL

Acetaminophen	Digitalis
Ethanol	Methanol
Theophylline	Salicylates
Ethylene glycol	Carbon monoxide
Iron	Lithium
Phenobarbital	Methemoglobin

▪ TREATMENT OF DRUG OVERDOSE

Physiologic support is key to all overdose management. Three basic precepts help minimize the toxic effects of drug ingestion: (a) prevent additional toxin absorption, (b) enhance drug excretion, and (c) prevent formation of toxic metabolites. Depending on the drug ingested, appropriate therapy also may include antidote administration or toxin removal.

Prevention of Toxin Absorption

After initial stabilization, the next step in the treatment of poisoning is to stop absorption. For cutaneously absorbed toxins (e.g., organophosphates, nerve agents), removing contaminated clothing and washing the skin is particularly important. Contaminated clothing needs to be placed in sealed bags and safely disposed of to avoid secondary exposure and incapacitation of health care workers. Such precautions are particularly important if dealing with potent nerve toxic agents that will be used in terrorist attacks.

For ingested toxins, induction of emesis is rarely, if ever, indicated. Long delays between ingestion and hospital presentation limit emesis effectiveness, and for patients with altered mental status or suppressed gag reflex, vomiting is dangerous. Emesis is not appropriate in ingestion of corrosive chemicals or petroleum distillates.

Although controversial, gastric lavage can be effective if undertaken within 1 to 2 h of a potentially lethal ingestion. Forgo lavage if a nontoxic substance has been ingested or if it is unlikely that a toxic quantity of the material remains in the stomach because of prior vomiting or because long periods have elapsed since ingestion. Some experts advocate lavage as long as 12 h after ingestion of substances that delay gastric emptying (e.g., opiates, tricyclic antidepressants), are corrosive (e.g., hydrocarbons), or form concretions (e.g., salicylates, meprobamate). Because lavage risks gastric perforation, aspiration, and airway compromise, it must be performed carefully and only when benefits are judged to exceed risks. For patients with altered consciousness, the airway should be protected with a cuffed endotracheal tube before attempting lavage. The procedure should be done in the left lateral decubitus position using a large orogastric tube. (Smaller tubes fail to adequately remove pill fragments.) Vomitus or aspirated gastric contents can be sent for toxicologic analysis.

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