Dextromethorphan poisoning: Management

INTRODUCTION — The management of dextromethorphan (DXM) poisoning will be reviewed here. The epidemiology, pertinent pharmacology, and clinical features of dextromethorphan poisoning are discussed separately. (See "Dextromethorphan misuse and poisoning: Clinical features and diagnosis".)

Related issues such as methylenedioxymethamphetamine (MDMA) misuse, serotonin syndrome, anticholinergic (antimuscarinic) poisoning, ketamine intoxication, phencyclidine (PCP) intoxication, ethanol intoxication, and a general approach to management of the poisoned patient are presented elsewhere. (See "MDMA (ecstasy) intoxication" and "Serotonin syndrome (serotonin toxicity)" and "Anticholinergic poisoning" and "Ketamine poisoning" and "Phencyclidine (PCP) intoxication in children and adolescents" and "Ethanol intoxication in children: Clinical features, evaluation, and management" and "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure".)

CLINICAL FEATURES AND DIAGNOSIS — The clinical features and diagnosis of dextromethorphan (DXM) poisoning are discussed separately. (See "Dextromethorphan misuse and poisoning: Clinical features and diagnosis".)

SUPPORTIVE CARE — Recommendations for care of children and adults with dextromethorphan (DXM) poisoning are derived from case series and reports and are driven by physical findings. The management of DXM poisoning is primarily supportive. (See "Dextromethorphan misuse and poisoning: Clinical features and diagnosis", section on 'Clinical features'.)

In addition, to careful assessment and support of airway, breathing, and circulation as needed, the clinician should anticipate and aggressively manage dissociative signs and symptoms (eg, psychosis, hallucinations, agitation), hyperthermia, rhabdomyolysis, and dehydration [1-4]. Specific antidotal therapy may be necessary for patients who manifest coma and respiratory depression, serotonin syndrome, or concomitant anticholinergic poisoning. (See 'Naloxone (for respiratory depression and coma)' below and 'Management of potential co-ingestants' below.)

Restraint and sedation — Early management of agitation or violent behavior is essential to prevent patient and staff injury. The emergency provider should exclude life-threatening hypoglycemia and hypoxia as contributing factors to agitation as soon as is safely possible. Verbal reassurance and placement of the patient in a calm, quiet, and subdued environment may suffice in the adolescent or adult with mild to moderate DXM intoxication.

In the markedly agitated or floridly psychotic patient, initial control often requires supine physical restraint that is rapidly followed by sedation with intravenous or intramuscular benzodiazepines (eg, lorazepam 0.1 mg/kg; maximum initial dose: 2 mg, repeat in 10 to 30 minutes as needed). Parenteral neuroleptic medication (eg, haloperidol) should be avoided in patients with DXM overdose because it may exacerbate hyperthermia or anticholinergic symptoms. (See "Assessment and emergency management of the acutely agitated or violent adult" and "Emergency department approach to acute-onset psychosis in children", section on 'Patient and staff safety'.)

Hyperthermia — Active cooling measures should be instituted promptly in patients with elevated rectal temperature and with other findings that indicate severe hyperthermia (eg, pulmonary edema, rhabdomyolysis). (See "Severe nonexertional hyperthermia (classic heat stroke) in adults", section on 'Diagnosis'.)

Augmentation of evaporative cooling is considered the treatment of choice because it is effective, noninvasive, and easily performed. The naked patient is sprayed with a mist of lukewarm water while air is circulated with large fans. Shivering may be suppressed with intravenous benzodiazepines such as diazepam (5 mg IV) or lorazepam (1 to 2 mg IV). Cold inspired oxygen, cold gastric lavage, cooling blankets, and cold intravenous fluids may be helpful adjuncts. (See "Severe nonexertional hyperthermia (classic heat stroke) in adults", section on 'Management' and "Heat stroke in children", section on 'Rapid cooling'.)

Some experts advocate that patients with marked hyperthermia (temperature >40°C) might benefit from rapid sequence intubation followed by prolonged paralysis to stop heat generation from muscle activity.

There is NO ROLE for antipyretic agents such as acetaminophen or aspirin in the management of drug-induced hyperthermia, since the underlying mechanism does not involve a change in the hypothalamic temperature set-point. Alcohol sponge baths should also be avoided because large amounts of the isopropyl alcohol may be absorbed through dilated cutaneous vessels and produce toxicity.

Rhabdomyolysis — Hyperthermia, agitation, seizures, and muscle rigidity may lead to muscle cell breakdown (rhabdomyolysis) with significant risk for renal failure. Patients with rhabdomyolysis typically present with the triad of pigmented granular casts in the urine, a red to brown color of the urine supernatant, and a marked elevation in the plasma concentration of creatine kinase (CK). Primary management goals consist of (see "Prevention and treatment of heme pigment-induced acute kidney injury (including rhabdomyolysis)"):

●Fluid repletion with normal saline infusion (20 to 40 mL/kg per hour up to 1 to 2 L per hour); the emergency provider should closely monitor urine output with the goal of maintaining a minimum urine flow of 4 mL/kg per hour; 200 mL per hour in adults. Once diuresis is established, alkalinization of the urine and mannitol diuresis is commonly employed but efficacy is uncertain.

●Evaluation for significant electrolyte abnormalities (hyperkalemia, hyperphosphatemia, and hypocalcemia); management of hyperkalemia is of particular importance. Hypocalcemia is usually transient and calcium administration should be avoided unless severe symptoms (eg, tetany) are present.

Serotonin syndrome (serotonin toxicity) — In addition to supportive care aimed at agitation and hyperthermia as described above, patients suspected of serotonin syndrome frequently require aggressive sedation with benzodiazepines (table 1). In severe cases, serotonin receptor blockade with cyproheptadine may be indicated. (See "Serotonin syndrome (serotonin toxicity)".)

Seizure — Seizures are best managed with a benzodiazepine (eg, 0.1 mg/kg lorazepam, maximum dose: 2 mg; repeat every 2 to 3 minutes up to three doses). Phenobarbital in an initial dose of 15 to 20 is preferred to phenytoin as second line treatment if seizures persist. (See "Management of convulsive status epilepticus in children" and "Convulsive status epilepticus in adults: Classification, clinical features, and diagnosis".)

GASTROINTESTINAL DECONTAMINATION — Dextromethorphan (DXM) and other components of over-the-counter (OTC) cough medications bind well to activated charcoal (AC), the primary means of decontamination in overdose.

We suggest that patients who ingest DXM-containing medicines and who present within one hour of known or suspected ingestion receive AC (1 g/kg, maximum dose 50 g) by mouth or nasogastric tube. AC should be withheld in patients who are sedated and may not be able to protect their airway, unless tracheal intubation is performed first. However, tracheal intubation should not be performed solely for the purpose of giving AC. The greatest benefit occurs if AC is given within one hour. The efficacy of AC as a function of time from ingestion is discussed in detail separately. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Evidence of efficacy and adverse effects'.)

The recommendation for AC administration following DXM overdose derives from indirect evidence of benefit in volunteers, animal studies, and evidence of benefit following ingestions of other medications. Because of adverse effects, such as vomiting and dehydration, the combination of a cathartic (eg, sorbitol) and AC should be used sparingly, if at all, and only a single dose of a cathartic should be given to any patient. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Activated charcoal' and "Gastrointestinal decontamination of the poisoned patient", section on 'Cathartics'.)

We recommend not performing gastric emptying by gastric lavage or by syrup of ipecac-induced emesis in patients who ingest DXM. This recommendation is based on randomized controlled trials showing minimal benefit and possible risk to patients who undergo gastric emptying after poisoning. (See "Gastrointestinal decontamination of the poisoned patient".)

NALOXONE (FOR RESPIRATORY DEPRESSION AND COMA) — Naloxone administration has reversed respiratory depression and coma following dextromethorphan poisoning in some patients [5-8]. Patients with deep coma and respiratory depression should receive intravenous naloxone (0.1 mg/kg, maximum initial dose: 2 mg). Some patients may require total doses of naloxone approaching 10 mg to fully reverse symptoms of respiratory depression [5]. Patients who improve after naloxone administration still warrant hospital admission and intensive monitoring for recurrence of symptoms. (See "Acute opioid intoxication in adults", section on 'Basic measures and antidotal therapy' and "Opioid intoxication in children and adolescents", section on 'Naloxone'.)

Naloxone administration should not delay the timely provision of supportive care (eg, bag-valve-mask ventilation) in patients who do not initially respond.

MANAGEMENT OF POTENTIAL CO-INGESTANTS — In addition to dextromethorphan (DXM), over-the-counter cough formulations frequently contain other pharmaceutical agents whose toxicity may complicate DXM poisoning, such as acetaminophen, chlorpheniramine or other antihistamines, or pseudoephedrine.

Acetaminophen — Patients with acetaminophen concentrations in the possible toxic range, based on the Rumack-Matthew nomogram (figure 1) should receive oral or intravenous antidote therapy with N-acetylcysteine. (See "Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and evaluation" and "Acetaminophen (paracetamol) poisoning: Management in adults and children".)

Antihistamines — DXM intoxication is frequently complicated by anticholinergic poisoning caused by coingestion of antihistamines in the cough and cold formulation. (See "Over-the-counter cough and cold preparations: Approach to pediatric poisoning", section on 'Antihistamines'.)

Both DXM and anticholinergic poisoning have similar presenting signs and symptoms that makes management decisions difficult. (See "Dextromethorphan misuse and poisoning: Clinical features and diagnosis", section on 'Differential diagnosis' and "Dextromethorphan misuse and poisoning: Clinical features and diagnosis", section on 'Clinical features'.)

Agitation and delirium caused by anticholinergic poisoning is initially treated with benzodiazepines (lorazepam 0.1 mg; maximum dose: 2 mg). Some experts recommend that patients with anticholinergic poisoning manifesting both peripheral signs (eg, flushing, dry skin, hyperthermia) and central effects (agitated delirium, seizures) receive physostigmine. However, this recommendation is controversial and consultation with a medical toxicologist or regional poison center should be obtained before physostigmine is administered. (See "Anticholinergic poisoning".)

Phenylephrine and similar decongestants — Phenylephrine and other alpha-1 adrenergic agonists can precipitate a hypertensive emergency in overdose that may require emergent administration of intravenous antihypertensive medication (eg, phentolamine 0.1 mg/kg; maximum dose: 5 mg). (See "Drugs used for the treatment of hypertensive emergencies", section on 'Phentolamine'.)

DISPOSITION — Most patients with uncomplicated dextromethorphan (DXM) poisoning have resolution of symptoms within four to six hours after ingestion [9-11]. Patients with complicated courses marked by hyperthermia, rhabdomyolysis, or serotonin syndrome warrant intensive care until symptoms resolve. (See 'Supportive care' above.)

Patients who are suicidal require psychiatric evaluation prior to discharge and should also be carefully evaluated for coingestions including the measurement of an acetaminophen concentration.

Patients who are asymptomatic for six hours after ingestion of DXM, who have nontoxic acetaminophen concentrations, and who are not suicidal, may be discharged home.

ADDITIONAL RESOURCES

Regional poison control centers — Regional poison control centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison control centers".)

Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by specific agents other than drugs of abuse".)

SUMMARY AND RECOMMENDATIONS

●Clinical features and diagnosis – The clinical features and diagnosis of dextromethorphan (DXM) poisoning are discussed separately. (See "Dextromethorphan misuse and poisoning: Clinical features and diagnosis".)

●Supportive care – Management of DXM poisoning is primarily supportive. In addition, to careful assessment and support of airway, breathing, and circulation as needed, the clinician should anticipate and aggressively manage agitation, hyperthermia, rhabdomyolysis, and/or serotonin syndrome when they occur. (See 'Supportive care' above.)

●Gastrointestinal decontamination – In a patient who ingests DXM-containing medicines and presents within one hour of known or suspected ingestion, we suggest administering activated charcoal (AC) (1 g/kg; maximum dose: 50 g) by mouth or nasogastric tube (Grade 2C). Charcoal should be withheld in patients who are sedated and may not be able to protect their airway, unless tracheal intubation is performed first. However, tracheal intubation should not be performed solely for the purpose of giving charcoal. (See 'Gastrointestinal decontamination' above.)

In a patient with a DXM ingestion, we recommend against performing gastric emptying procedures (Grade 1B).

●Naloxone – Patients with deep coma and respiratory depression should receive intravenous naloxone (0.1 mg/kg, maximum initial dose: 2 mg). Some patients may require total doses of naloxone approaching 10 mg to adequately reverse symptoms. Naloxone administration should not delay the timely provision of supportive care (eg, bag-valve-mask ventilation with 100 percent oxygen) in patients with respiratory depression. (See 'Naloxone (for respiratory depression and coma)' above.)

●Potential for co-ingestants – In addition to DXM, over-the-counter cough formulations frequently contain other pharmaceutical agents (eg, chlorpheniramine or other antihistamines, acetaminophen, pseudoephedrine) whose toxicity may complicate DXM poisoning and require specific treatment. (See 'Management of potential co-ingestants' above.)