A. Introduction. Drug overdose is common in medical practice and, if not managed expediently and appropriately, can be lethal. More than 2,100,000 poisonings were estimated to have occurred in the United States in 2015, accounting for more than 1200 deaths, and poisoning has recently surpassed motor vehicle collisions as the leading cause of injury-related death. Analgesics (acetaminophen and aspirin), antidepressants, sedatives, antipsychotics, stimulants (including many street drugs), opioids, and cardiovascular medications are the most commonly fatal.
B. General Approach to the Overdose Patient
a. ABCs. Initial attention should focus on airway, breathing, and circulatory system management. Intravenous access, supplemental oxygen, and cardiac monitoring are often required. Serial monitoring of vital signs and respiratory and mental status allows one to follow the progress of intoxication.
b. Patient history. The patient history is of critical importance and should be obtained from the patient, friends, caregivers, and paramedics. Pill counts and attention to empty bottles found at the site are useful.
c. Physical examination. Areas of focus include the patient’s vital signs with pulse oximetry, mental status, pupillary size and responsiveness, skin moisture, and bowel sounds. Table 93.1 summarizes physical examination findings for four of the major types of overdoses.
Table 93.1 Clinical Manifestations of Common Overdoses
* In patients with clinical manifestations of an anticholinergic syndrome, tricyclic overdose should be considered.
BP = blood pressure; HR = heart rate; RR = respiratory rate.
i. Electrocardiography. An electrocardiogram (EKG) is indicated for almost all patients with ingestion to rule out any potential cardiac effects of ingested drugs or other unreported coingestions. Particularly notable are dysrhythmias and widening of the QRS.
ii. A chest radiograph, complete blood count (CBC), serum electrolytes, liver panel, blood glucose, and renal panel can be useful for evaluating possible concomitant disease or toxicologic effects.
iii. Drug levels and toxicologic screens. Drug-specific urine and serum analysis are useful in the management of ingestion patients. Typically, urine toxicology will screen for drugs of abuse, but a positive screen can remain positive for days. Thus, these tests provide no quantitative information regarding timing of exposure and should not be relied on to explain an acute change in mental status. Most commonly, serum ethanol, acetaminophen, and salicylate levels are requested when an unknown ingestion has occurred, but a more extensive serum analysis can be performed if clinically indicated.
e. Gut decontamination
i. Activated charcoal (50 g by mouth or nasogastric tube) is the preferred agent for limiting absorption of acute ingestions. Activated charcoal works best when given within 1 hour of ingestion. It should never be given to a patient who cannot protect his or her airway unless that patient is intubated because aspiration of charcoal can have dire pulmonary consequences. Some toxins (e.g., theophylline, carbamazepine, phenobarbital) may require multiple intermittent doses of activated charcoal. Sorbitol has previously been used as a cathartic, but its efficacy is questionable, and it should be withheld in most cases.
ii. Gastric lavage has no clear evidence supporting a clinical benefit and is associated with risks including aspiration and esophageal injury. It should therefore only be considered within 1 hour of a massive or life-threatening ingestion. If lavage is performed, activated charcoal should be given immediately afterward.
iii. Emetics (e.g., syrup of ipecac) are of no benefit compared with activated charcoal alone and are best avoided.
iv. Whole-bowel irrigation with polyethylene glycol (2 L/hr until stools run clear) may be indicated for some ingestions such as iron, lithium, or sustained-release preparations.
f. Antidotes. The first goal in clinical toxicology is to treat the patient symptomatically, providing respiratory and cardiovascular support as needed. There are occasions, however, when an antidote may be both indicated and available (e.g., N-acetylcysteine [NAC] in the setting of acetaminophen overdose, glucagon for β-blocker overdose, or digoxin Fab [Digibind] for digoxin overdose).
The Poison Control Network can be reached by calling 1-800-222-1222. They can assist with diagnosis and management of the poisoned patient.
C. Specific Toxic Syndromes (“Toxidromes”)
a. Opioid receptor agonists include morphine and related narcotics such as heroin and oxycodone. Acute toxicity can result from both iatrogenic overdose in the hospitalized patient and accidental overdose in the intravenous drug user. Since 2000, use and abuse of opiates has been steadily increasing, leading to a marked increase in the number and profile of deaths due to narcotics.
i. Clinical manifestations of opioid overdose. Patients are typically lethargic with constricted pupils. There may be needle marks or other paraphernalia suggesting intravenous drug use. A memory aid for the opioid toxidrome may be derived from the street term for heroin, “DOPE.”
MNEMONIC: Clinical Manifestations of Opioid Agonist Overdose (“DOPE”)
Decreased respiratory drive
1. Respiratory depression is the major clinical concern and may lead to hypoventilation, hypoxemia, and death. In the setting of persistent hypoxemia, consider noncardiogenic pulmonary edema, which can result directly from opiate use, or indirectly from naloxone (Narcan) administration. Seizures may occur with some opioid compounds, including meperidine.
2. Hypotension may occur with opioid overdose.
3. Treatment. The establishment of a patent airway and adequate ventilation are critical first steps. The opioid antagonist naloxone (0.2–2 mg IV repeated every 2–3 minutes if no response, up to a total dose of 10–20 mg; lasts 20–60 minutes) may produce dramatic reversal of some of the acute symptoms of opioid overdose, including respiratory depression. However, the effects of the opioid often outlast the effects of naloxone, warranting frequent monitoring and either repeat doses, or continuous IV infusion of naloxone in some patients.
4. Withdrawal can occur when patients are admitted to the hospital and no longer have access to opiates. Patients will typically be agitated, tachycardic, hypertensive, and diaphoretic. As opposed to alcohol withdrawal, opiate withdrawal is not fatal by itself. It can be treated with opioid adjuncts (methadone) or supportive medications such as clonidine and benzodiazepines.
b. Stimulants include cocaine and amphetamines (e.g., “speed,” “meth”).
i. Clinical manifestations of stimulant overdose. The clinical syndrome results primarily from stimulation of adrenergic receptors, leading to tachypnea, tachycardia, vasoconstriction, and psychostimulation, including hyperactivity.
ii. Major concerns include tachycardia, hypertension, and vasospasm of the coronary arteries. The last may lead to myocardial infarction, even with otherwise normal coronary arteries.
iii. Treatment in the acute setting is primarily supportive.
1. Benzodiazepines reduce agitation and often effectively treat hypertension and tachycardia. Persistent hypertension may be treated with a peripheral vasodilator such as nitroprusside.
2. Chest pain should be treated as any acute coronary syndrome with aspirin, nitrates, and oxygen. Benzodiazepine use should be liberal. β-blockers should be avoided in patients with cocaine toxicity because they may generate unopposed α-adrenergic effects and worsen hypertension.
c. Cholinergic agonists. Organophosphate and carbamate insecticides inhibit acetylcholinesterase and are a common cause of a pure cholinergic syndrome. They may be ingested, inhaled, or absorbed through the skin. The resulting toxidrome therefore primarily occurs in farm workers or those exposed to these agents as a course of their occupation. The chemical warfare agents Sarin and VX work through the same mechanism.
i. Clinical manifestations of cholinergic agonist toxicity typically begin within 1–2 hours. Sustained stimulation of acetylcholine (ACh) receptors causes muscarinic effects (nausea, vomiting, urinary incontinence, diarrhea, sweating, bradycardia), nicotinic effects (tremor, respiratory muscle paralysis), and central nervous system (CNS) effects (agitation to seizure or coma). Many of the important features can be remembered using the mnemonic “SLUDGE.”
MNEMONIC: Clinical Manifestations of Cholinergic Agonist Toxicity (“SLUDGE”)
ii. Major concerns include respiratory muscle paralysis with subsequent hypoxemia, bronchospasm, seizures, and hypotension secondary to dehydration.
1. Supportive measures. Contaminated clothing should be removed and the patient washed thoroughly with soapy water. Respiration and blood pressure should be maintained. Intubation may be indicated. Benzodiazepines should be administered for seizures.
2. Atropine, repeated frequently, is administered to block the action of ACh at the receptor until oral secretions are controlled.
3. Pralidoxime (2-PAM) is the specific antidote to organophosphates, reversing effects at all receptors. Ideally, it is given within 24–36 hours of exposure.
d. Anticholinergic agents antagonize the activity of ACh at muscarinic and CNS receptors. Many common drugs, including atropine, antihistamines, phenothiazines, antipsychotics, and tricyclic antidepressants, can produce anticholinergic effects. Exposure to deadly nightshade (Atropa belladonna) or jimsonweed may also cause toxicity.
i. Clinical manifestations of cholinergic antagonist toxicity include the following:
1. Restlessness, irritability, and delusions (“mad as a hatter”)
2. Dilation of cutaneous blood vessels (“red as a beet”)
3. Decreased apocrine and salivary gland secretion, most easily checked at the axilla (“dry as a bone”)
4. Mydriasis and cycloplegia (“blind as a bat”)
5. Tachycardia (“fast as a rabbit”)
6. Decreased gastrointestinal motility with decreased bowel sounds (“slow as a mule”)
7. Increased bladder sphincter tone (“tight as a drum”)
1. Supportive treatment. Respiratory and circulatory support may be necessary. Cardiac monitoring for evaluation of arrhythmias may be necessary. Benzodiazepines can be used for agitation.
2. Decontamination with activated charcoal may be indicated, especially if given early. Hemodialysis and hemoperfusion are not effective.
3. Physostigmine may be used in the setting of pure anticholinergic toxicity, but it carries the risks for cardiac arrhythmias and seizures and therefore should only be used for severe toxicity.
e. Acetaminophen is the most commonly reported drug overdose.
i. Clinical manifestations of acetaminophen toxicity can be divided into four stages.
1. In the first 24 hours, patients may be symptom-free or have mild nausea and malaise.
3. Fulminant hepatic failure with coagulopathy and encephalopathy occurs by days 3–4.
4. Recovery (if the patient survives) takes place over the ensuing week.
ii. Treatment is based on acetaminophen serum levels drawn 4 hours post-ingestion.
1. NAC works by replenishing glutathione, an essential component in the metabolism of acetaminophen. It is best given early but has beneficial effects out to 24 hours from ingestion, and possibly longer.
When given within 8 hours of acetaminophen ingestion, NAC will almost always prevent serious hepatic injury.
2. Supportive care includes monitoring for coagulopathy, renal failure, and hepatic encephalopathy, any of which may indicate a need for liver transplantation.
3. Activated charcoal should be given for decontamination if the patient is awake and compliant.
f. Salicylate is most commonly found in aspirin but is also contained in many topical preparations.
i. Clinical manifestations are numerous and commonly include:
1. Respiratory alkalosis, which occurs secondary to direct stimulation of the respiratory centers of the brain.
2. Anion gap metabolic acidosis, which can lead to a compensatory respiratory alkalosis
3. Tinnitus, which may occur either with acute or chronic ingestions
4. Arrhythmias, pulmonary edema, coma, seizures, and acute renal failure
ii. Treatment must be instituted early for maximal benefit.
1. Sodium bicarbonate increases elimination of salicylate in the urine and should be titrated to maintain a urine pH of 7.5–8.
2. Dialysis is effective when levels are greater than 100 mg/dL in acute ingestions, or with severe acidosis or toxic effects.
g. Tricyclic antidepressants (TCAs)
i. Clinical manifestations. TCA overdose may produce any of three syndromes. Symptoms often begin within 30 minutes of ingestion.
1. Anticholinergic effects include dry skin, dilated pupils, urinary retention, tachycardia, and myoclonic jerking.
2. Cardiovascular effects result from both TCA blockade of the myocardial fast sodium channel (similar to a type Ia antiarrhythmic) and blockade of α1-adrenergic receptors. Effects include decreased myocardial contractility, bradycardia, and hypotension.
3. Seizures may result in rhabdomyolysis, brain damage, and death.
ii. Approach to the patient. Rapid diagnosis is imperative and is made on the basis of patient history, physical examination findings, and EKG findings (e.g., QRS prolongation >100 msec, elevated R wave in avR, rightward shift of the terminal 40 msec of the QRS complex).
1. Supportive measures include supporting respiration and circulation as needed.
3. Seizures should be treated with benzodiazepines.
4. Cardiac effects as demonstrated by hypotension or QRS prolongation may be reversed through sodium bicarbonate infusion with a goal serum pH of 7.45–7.55, with hopes of stabilizing the myocardium to improve contractility and prevent arrhythmia.
h. Phenothiazines include both antipsychotics (clozapine, haloperidol) and antiemetics (prochlorperazine, promethazine).
i. Clinical manifestations of phenothiazine overdose. Like TCAs, phenothiazines have multiple pharmacologic effects and produce a similar clinical syndrome.
1. At low doses, anticholinergic effects may predominate, including dry mouth, tachycardia, and urinary retention.
2. Cardiac effects may include QRS or QT interval prolongation.
3. Extrapyramidal dystonic effects from dopamine receptor antagonism include torticollis, jaw muscle spasm, and oculogyric crisis. Akathisia is an uncomfortable condition of motor restlessness.
4. Neuroleptic malignant syndrome (NMS) is an idiosyncratic and occasionally fatal reaction comprising lead-pipe rigidity, altered mental status, and autonomic instability and including high fever, diaphoresis, and tachycardia.
1. Supportive care includes respiratory and cardiovascular support as well as cooling of fever.
2. Decontamination with multiple doses of activated charcoal may be beneficial.
3. Diphenhydramine can be used to treat dystonic reactions and akathisia.
4. Benzodiazepines can be used to treat seizures and musculoskeletal rigidity.
5. Dantrolene, a skeletal muscle relaxant, and bromocriptine can be used in the management of NMS.
Suggested Further Readings
Altyar A, Kordi L, Skrepnek G. Clinical and economic characteristics of emergency department visits due to acetaminophen toxicity in the USA. BMJ Open 2015;5.Find this resource:
Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med 2010;152:85–92.Find this resource:
Erickson TB, Thompson TM, Lu JJ. The approach to the patient with an unknown overdose. Emerg Med Clin North Am 2007;25:249–81.Find this resource:
Frank RG, Pollack HA. Addressing the fentanyl threat to public health. N Engl J Med 2017;376:605–7.Find this resource:
Volkow ND, Collins FS. The role of science in addressing the opioid crisis. N Engl J Med 2017;377:391–4.Find this resource: