Drug Overdoses: Current Trends

Drug overdose remains a significant concern worldwide, with nearly half a million deaths annually. In the United States, drug overdoses are the leading cause of death for adults younger than 55 years. Drug-related deaths now outnumber those attributed to motor vehicle accidents and homicides. According to information from the Centers for Disease Control and Prevention (CDC), the drugs most commonly involved in overdose deaths include opioids (eg, fentanyl, heroin, oxycodone), cocaine, methamphetamines, and benzodiazepines. There are other drugs that can cause death including MDMA and various synthetic drugs.

Naloxone has been lifesaving in many scenarios, so the CDC recently issued recommendations regarding its use in patients taking opioids. The CDC recommends that clinicians strongly consider prescribing or coprescribing naloxone and providing education about its use in these types of patients taking opioids:

  • Those who are receiving opioids at a dosage of 50 morphine milligram equivalents per day or greater
  • Those who have respiratory conditions such as chronic obstructive pulmonary disease or obstructive sleep apnea (regardless of opioid dose)
  • Those who have been prescribed benzodiazepines (regardless of opioid dose)
  • Those who have a nonopioid substance use disorder, report excessive alcohol use, or have a mental health disorder (regardless of opioid dose)

The CDC also recommends naloxone in patients who are at high risk for experiencing or responding to an opioid overdose, including the following:

  • Those known to use heroin or illicit synthetic opioids or misuse prescription opioids
  • Those using other illicit drugs such as stimulants, including methamphetamine and cocaine
  • Those receiving treatment for opioid use disorder, including medication-assisted treatment with methadone, buprenorphine, or naltrexone
  • Those with a history of opioid misuse who were recently released from incarceration or other controlled settings where tolerance to opioids has been lost

Most of the deaths from synthetic opioids are from fentanyl. Most of the increases in fentanyl deaths in recent years do not involve prescription fentanyl but are related to illicitly made fentanyl mixed with or sold as heroin—with or without the users' knowledge—and increasingly sold as counterfeit pills.

In the event of an overdose, pertinent history may be obtained from bystanders, family, friends, or emergency medical services (EMS) providers. Pill bottles, drug paraphernalia, or eyewitness accounts may assist in the diagnosis of opioid toxicity. Occasionally, a trial of naloxone administered by an EMS provider is helpful to establish the diagnosis in the prehospital setting.

Patients with opioid toxicity characteristically have a depressed level of consciousness. Opioid toxicity should be suspected when the clinical triad of central nervous system (CNS) depression, respiratory depression, and pupillary miosis are present. Clinicians must be aware that opioid exposure does not always result in miosis (pupillary constriction), and that respiratory depression is the most specific sign. Drowsiness, conjunctival injection, and euphoria are frequently seen.

Drug screens are widely available but rarely alter clinical management in patients with uncomplicated overdoses. Drug screens are most sensitive when performed on urine. Positive results are observed up to 36-48 hours postexposure, but wide variations are possible depending on test sensitivity, dose, route of opioid administration, and the patient's metabolism. In patients with moderate to severe toxicity, performing these baseline studies is appropriate:

  • Complete blood cell (CBC) count
  • Comprehensive metabolic panel
  • Creatine kinase (CK) level
  • Arterial blood gas (ABG) determinations

According to American Heart Association guidelines, clear evidence suggests that cocaine can precipitate acute coronary syndrome, and that trying agents that show efficacy in the management of acute coronary syndrome may be reasonable in patients with severe cardiovascular toxicity. Agents that may be used as needed to control hypertension, tachycardia, and agitation include:

  • Alpha-blockers (eg, phentolamine)
  • Benzodiazepines (eg, lorazepam, diazepam)
  • Calcium channel blockers (verapamil)
  • Morphine
  • Sublingual nitroglycerin

The American Heart Association does not recommend any one of these agents over another in the treatment of cardiovascular toxicity due to cocaine; however, benzodiazepines are often used as first-line treatment.

Cardiopulmonary complaints are the most common presenting manifestations of cocaine abuse and include chest pain (frequently observed in long-term use or overdose), MI, arrhythmia, and cardiomyopathy. In individuals with cocaine-associated MI, median times to the onset of chest pain vary with the route or form of cocaine use: 30 minutes for intravenous use, 90 minutes for crack, and 135 minutes for intranasal use.

Temperature dysregulation is also a problem with cocaine intoxication. Hyperthermia is a marker for severe toxicity, and it is associated with numerous complications, including renal failure, disseminated intravascular coagulation, acidosis, hepatic injury, and rhabdomyolysis. Dopamine plays a role in the regulation of core body temperature, so increased dopaminergic neurotransmission may contribute to psychostimulant-induced hyperthermia in cocaine users, including those with excited delirium.

No laboratory studies are indicated if the patient has a clear history of cocaine use and mild symptoms.

If a history of cocaine use is absent or if the patient has moderate to severe toxicity, appropriate laboratory tests may include:

  • CBC count
  • Electrolytes, blood urea nitrogen, creatinine, and glucose levels (basic metabolic panel)
  • Glucose level
  • Pregnancy test
  • Calcium level
  • ABG analysis
  • CK level
  • Troponin level (cocaine use does not affect the specificity of troponin assays)
  • Urinalysis
  • Toxicology screens

Acute and long-term methamphetamine use may lead to abnormal findings on examination of the following organ systems:

  • Cardiovascular
  • CNS
  • Gastrointestinal
  • Renal
  • Skin
  • Dental

There are specific cardiovascular findings associated with acute and long-term methamphetamine use:

  • Tachycardia and hypertension is frequently observed
  • Atrial and ventricular arrhythmias may occur
  • Chest pain from cardiac ischemia and infarction following methamphetamine use has been reported, and patients are at risk because of accelerated atherosclerosis from chronic use; acute aortic dissection or aneurysm has been associated with methamphetamine abuse
  • Hypotension may be observed with methamphetamine overdose with profound depletion of catecholamines
  • Acute and chronic cardiomyopathy results directly from methamphetamine cardiac toxicity and indirectly from chronic hypertension and ischemia; intravenous use may result in endocarditis; patients may have dyspnea, edema, and other signs of acute congestive heart failure exacerbation

The euphoric effects produced by methamphetamine, cocaine, and various designer amphetamines are similar and may be difficult to clinically differentiate. A distinguishing clinical feature is the longer pharmacokinetic and pharmacodynamic half-life of methamphetamine, which may be as much as 10 times longer than that of cocaine.

Methamphetamine can cause significant CNS and psychiatric activation, so patients who present to emergency departments for acute intoxication often require physical restraint and pharmacologic intervention. Hyperactive or agitated patients can be treated with droperidol or haloperidol, which are butyrophenones that antagonize CNS dopamine receptors and mitigate the excess dopamine produced from methamphetamine toxicity. These medications should be administered intravenously, with doses adjusted based on the symptoms. Droperidol has been subject to a black box warning by the US Food and Drug Administration based on concerns of QT prolongation and the potential for torsades de pointes. As a result, some institutions restrict its use. However, it is important to note that the black box warning specifies dementia-related psychosis and is not supported by the literature for doses below 2.5 mg.

If sedation fails to reduce blood pressure, antihypertensive agents such as beta-blockers and vasodilators are effective in reversing methamphetamine-induced hypertension and tachycardia. With regard to choice of beta-blockers, labetalol is preferred because of its combined anti–alpha-adrenergic and anti–beta-adrenergic effects. Labetalol has been shown to safely lower mean arterial pressure in patients with positive cocaine test results. Carvedilol, like labetalol, is a nonselective beta-blocker with alpha-blocking activity and may also be effective for this indication. Esmolol is advantageous because of its short half-life but must be administered via intravenous drip. Metoprolol has excellent CNS penetration characteristics and may also ameliorate agitation.

Oral benzodiazepine overdoses, without co-ingestion of another drug, rarely result in significant morbidity (eg, aspiration pneumonia, rhabdomyolysis) or mortality; however, in mixed-drug overdoses, they can potentiate the effect of alcohol or other sedative-hypnotic agents. Overdose of ultrashort-acting benzodiazepines (eg, triazolam) is also more likely to result in apnea and death than overdose with longer-acting benzodiazepines. Of the individual benzodiazepines, alprazolam is relatively more toxic than others in overdose.

Immunoassay screening techniques are most commonly performed when benzodiazepine overdose is suspected. These tests typically detect benzodiazepines that are metabolized to desmethyldiazepam or oxazepam; thus, a negative screening result does not rule out the presence of a benzodiazepine.

As with any overdose, the first step is an assessment of the patient's airway, breathing, and circulation, and any issues should be addressed rapidly. In any patient with an altered mental status, blood glucose level should be checked immediately. The cornerstone of treatment in benzodiazepine overdoses is good supportive care and monitoring. Single-dose activated charcoal is not routinely recommended because the risks far outweigh the benefit. Altered mental status greatly increases the risk of aspiration following an oral activated charcoal dose.

Flumazenil is a competitive benzodiazepine receptor antagonist and the only available specific antidote for benzodiazepines. Its use in acute benzodiazepine overdose is controversial, however, and its risks usually outweigh any benefit. In long-term benzodiazepine users, flumazenil may precipitate withdrawal and seizures; in patients taking benzodiazepines for a medical condition, flumenazil may result in exacerbation of the condition. Flumazenil should not be used in patients with long-term benzodiazepine use or in any patient at an increased risk of having a seizure, including those with a seizure history, head injury, co-ingestion of a benzodiazepine and tricyclic antidepressant or other proconvulsant, or even a possible ingestion of a proconvulsant.

In general, when it is the sole agent used, the clinical presentation of heroin poisoning and its diagnosis hold little challenge for experienced healthcare practitioners. The diagnosis of heroin poisoning should be suspected in all comatose patients, especially in the presence of respiratory depression and miosis.

Respiratory depression, due to heroin's effect on the brain's respiratory centers, is a hallmark sign of overdose. However, the presence of tachypnea should prompt the search for complications of heroin use, such as pneumonia, acute lung injury, and pneumothorax, or an alternative diagnosis, such as shock, acidosis, or CNS injury. Tachypnea may also be seen in overdoses of pentazocine or meperidine.

Symptoms generally develop within 10 minutes of intravenous heroin injection. Patients who survive heroin poisoning commonly admit to using more than their usual dose, using heroin again after a prolonged period of abstinence, or using a more concentrated street sample. Coma, respiratory depression, and miosis are the hallmarks of opioid overdose.

Mild hypotension and mild bradycardia are commonly observed with heroin use. These are attributable to peripheral vasodilation, reduced peripheral resistance and histamine release, and inhibition of baroreceptor reflexes. In the setting of heroin overdose, hypotension remains mild. The presence of severe hypotension should prompt a search for other causes of hypotension, such as hemorrhage, hypovolemia, sepsis, pulmonary emboli, and other causes of shock.

Gastric lavage in the setting of oral heroin overdose is generally not recommended because it has no documented value. Furthermore, gastric lavage is contraindicated in "body packers" and "body stuffers," who have ingested packages of drugs, because the procedure may rupture a package. Activated charcoal is becoming increasingly controversial because of the risk of aspiration and charcoal pneumonitis. It may be indicated for orally ingested narcotics with large enterohepatic circulation (eg, propoxyphene, diphenoxylate) but is of no value in pure heroin overdose.

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