Introduction
Background
Pain is arguably the most common reason why patients seek treatment, especially in the ED. The modern physician wields many tools to relieve pain, the most potent of which are opioids. The term narcotic specifically refers to any substance that induces sleep, insensibility, or stupor, and it is used to refer to opioids or opioid derivatives. It is derived from the Greek "narke" that means "numbness or torpor." It is common that the public uses the term narcotics for any illicit psychoactive substance.
In cultivation since approximately 1500 BC, pure opium is a mixture of alkaloids extracted from the sap of unripened seedpods of Papaver somniferum (poppy). Opiates, such as heroin, codeine, or morphine, are natural derivatives of these alkaloids. The term opiate is often used (albeit slightly incorrectly) to refer to synthetic opiate derivatives, such as oxycodone, as well as true opiates.
Although opioids constitute a relatively small percentage of pure overdoses encountered in the ED, they merit particular attention because of the potential mortality/morbidity they cause when unrecognized and untreated, as well as the relative ease of reversing their effects. The notable prevalence of opioids in current prescribing patterns mandates that physicians maintain a high index of suspicion when treating the patient who is unconscious for unknown reasons.
Opioid use and abuse have been reported as increasing in frequency in the past few years, a trend that has been blamed in increasing utilization of opioids by medical personnel as well as illicit drug abuse.1 While increased availability certainly plays a role in opioid abuse, the link between legitimate use and abuse is not well proven.2,3 . The increasing abuse of opioids has received increasing attention in recent years.4,5
Pathophysiology
Activation of opioid receptors results in inhibition of synaptic neurotransmission in the central nervous system (CNS) and peripheral nervous system (PNS). Opioids bind to and enhance neurotransmission at 3 major classes of opioid receptors. It is also recognized that several poorly defined classes of opioid receptors exist with relatively minor effects. The physiological effects of opioids are mediated principally through mu and kappa receptors in the CNS and periphery. Mu receptor effects include analgesia, euphoria, respiratory depression, and miosis. Kappa receptor effects include analgesia, miosis, respiratory depression, and sedation. Two other opiate receptors that mediate the effects of certain opiates include sigma and delta sites. Sigma receptors mediate dysphoria, hallucinations, and psychosis; delta receptor agonism results in euphoria, analgesia, and seizures. The opiate antagonists (eg, naloxone, nalmefene, naltrexone) antagonize the effects at all 4 opiate receptors.
Common classifications divide the opioids into agonist, partial agonist, or agonist-antagonist agents and natural, semisynthetic, or synthetic. Opioids decrease the perception of pain, rather than eliminate or reduce the painful stimulus. Inducing slight euphoria, opioid agonists reduce the sensitivity to exogenous stimuli. The GI tract and the respiratory mucosa provide easy absorption for most opioids.
Peak effects generally are reached in 10 minutes with the intravenous route, 10-15 minutes after nasal insufflation (eg, butorphanol, heroin), 30-45 minutes with the intramuscular route, 90 minutes with the oral route, and 2-4 hours after dermal application (ie, fentanyl). Following therapeutic doses, most absorption occurs in the small intestine. Toxic doses may have delayed absorption because of delayed gastric emptying and slowed gut motility.
Most opioids are metabolized by hepatic conjugation to inactive compounds that are excreted readily in the urine. Certain opioids (eg, propoxyphene, fentanyl, buprenorphine) are more lipid soluble and can be stored in the fatty tissues of the body. All opioids have a prolonged duration of action in patients with liver disease (eg, cirrhosis) because of impaired hepatic metabolism. This may lead to drug accumulation and opioid toxicity. Opiate metabolites are excreted in the urine. Impaired renal function can lead to toxic effects from accumulated drug or active metabolites (eg, normeperidine).
Frequency
United States
Opioids are prescribed widely, often in concert with other analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs) or muscle relaxants. Given all toxicologic presentations, pure opioid ingestions are generally a small proportion of ED overdose cases. The etiology of overdoses presenting to an ED often reflects local prescribing tendencies. Polypharmacy overdoses that include opioids can be a challenge for even the most experienced clinician. Fortunately, pharmacologic reversal of the opioid component can assist in the diagnosis of these potentially complex cases.
Data from the Drug Abuse Warning Network (DAWN) from 1990-1996 indicated that the abuse of opioid analgesics (as recorded from the number of hospital ED visits) is low; compared with the abuse of other drugs, the abuse of opioid analgesics accounts for 3.8-5.1% of ED presentations.
In 1998, a total of 36,848 opiate exposures (pure and mixed preparations) were reported to US poison control centers, of which 1227 (3.3%) resulted in major toxicity and 161 (0.4%) resulted in death.
Mortality/Morbidity
The predominant cause of morbidity and mortality from pure opioid overdoses is respiratory compromise. Less commonly, acute lung injury, status epilepticus, and cardiotoxicity occur in the overdose setting. Case reports of increased incidence of mortality have been documented in patients with coexistent stenosing lesions of the upper airway.6
Clinical
History
- Pertinent history may be obtained from bystanders, family, friends, or EMS providers. Pill bottles, drug paraphernalia, or eyewitness accounts may assist in the diagnosis.
- Occasionally, a trial of naloxone administered by EMS is helpful to establish the diagnosis in the prehospital setting.
- Ingestion time, quantity, and co-ingestants are important aspects of the history and should be ascertained.
Physical
- Opioid toxicity characteristically presents with a depressed level of consciousness. Opiate toxicity should be suspected when the clinical triad of CNS depression, respiratory depression, and pupillary miosis are present. It is important for the clinician to 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 seen frequently. Needle tracks are observed occasionally, depending on the route of abuse. Street users commonly use heroin and morphine by subcutaneous ("skin popping") and intravenous ("mainlining") injection. Raw opium usually is eaten or smoked, and sometimes the powder is sniffed ("snorted"). Transdermal opioid patches, such as fentanyl, also may produce toxicity.
- Other important presenting signs are ventricular arrhythmias, acute mental status changes, and seizures. Reliance on pupillary miosis to diagnose opioid intoxication can be misleading. If sufficiently severe, hypertension and pupillary dilation may present because of CNS hypoxia. Morphine, meperidine, pentazocine, diphenoxylate/atropine (Lomotil), and propoxyphene sometimes are associated with mydriasis or midpoint pupils.
- The respiratory effort frequently is impaired opiate intoxication. Both bradypnea and hypopnea are observed. Rates as slow as 4-6 breaths per minute often are observed with moderate-to-severe intoxication. The body retains the hypoxic drive to breathe but may be overridden by the CNS sedative effects of a severe overdose.
- Mild peripheral vasodilation may occur and result in orthostatic hypotension. However, persistent or severe hypotension should raise the suspicion of co-ingestants and prompt reevaluation. Opioids prolong GI transit times, possibly causing delayed and prolonged absorption. Initial tendencies for nausea and emesis are transient. Pink frothy sputum, muscular rigidity, dyspnea, hypoxia and bronchospasm strongly suggest acute lung injury.
- Nightmares, anxiety, agitation, euphoria, dysphoria, depression, paranoia, and hallucinations are encountered infrequently, mainly with high doses. Pruritus, flushed skin, and urticaria may arise because of histamine release. Generalized seizures are infrequent; they occur most commonly in infants and children because of initial CNS excitation. In contrast, seizure activity in adults is suggestive of meperidine or propoxyphene ingestions. Hearing loss has been associated with heroin and alcohol but is generally considered recoverable.
More on Toxicity, Opioids |
 Overview: Toxicity, Opioids |
| Differential Diagnoses & Workup: Toxicity, Opioids |
| Treatment & Medication: Toxicity, Opioids |
| Follow-up: Toxicity, Opioids |
| References |
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Further Reading
Keywords
opioid toxicity, opioid poisoning, opiate addiction, opiate withdrawal, opiate intoxication, opioid analgesics, narcotic toxicity, narcotic poisoning, narcotic overdose, pain relievers, narcotic abuse, narcotic use, opioids, opioid derivatives, opiates, opium, Palaver somniferous, poppy, heroin, codeine, morphine, fentanyl, opioid ingestion, opiate exposures
