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A Brief Review of Opioid Intoxication By: Kaveh Alavi Psychiatrist, Mental Health Research Center Opioid intoxication: Medical symptoms • CNS and respiratory depression, including coma and respiratory failure: Reduced RR Respiratory rhythm irregularities Decreased sensitivity of the CO2 chemoreceptors • Noncardiogenic pulmonary edema • Hypothermia • Miosis (typically, tolerance to miosis is not developed, but miosis may not present in meperidine or lomotil overdose or in severe hypoxia) • Bradycardia • Hypotension • Decreased GI tract motility Opioid intoxication: Psychiatric symptoms • DSM-IV Criteria • Recent use of an opioid. • Clinically significant maladaptive behavioral or psychological changes (e.g., initial euphoria followed by apathy, dysphoria, psychomotor agitation or retardation, impaired judgment, or impaired social or occupational functioning) that developed during, or shortly after, opioid use. • Pupillary constriction (or pupillary dilation due to anoxia from severe overdose) and one (or more) of the following signs, developing during, or shortly after, opioid use: drowsiness or coma slurred speech impairment in attention or memory • The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder. Opioid intoxication: Symptomatology • Symptoms occur within minutes of an IV dose or within 20-30 minutes of oral ingestion. • Respiratory depressant effects are longer-lived than analgesic effects. • If happened, death is typically due to respiratory failure. • ICD-10 define “severe opioid intoxication” as a syndrome including respiratory depression (& hypoxia), hypotension and hypothermia. • DSM-IV includes a specifier as “with perceptual disturbances”. Opioid intoxication: Lab tests • Routine lab tests • HIV, HBV & HCV work-up (if needle sharing) • Urine and serum toxicology Consider mixed drug overdose. For qualitative analysis; quantitative analysis is poorly correlate with clinical conditions, because of interpersonal variability and tolerance in addicted individuals. • Baseline ABG Opioid intoxication: Treatment • Overdose with an opioid agonist can produce respiratory depression and is therefore a medical emergency. The first task is to ensure an adequate airway. Tracheopharyngeal secretions should be aspirated. An airway may be inserted. The patient should be ventilated mechanically until an opioid antagonist can be administered. Effort to ensure adequate respiratory function are paramount. Opioid intoxication: Treatment • Nancardiogenic pulmonary edema: • Oxygen • Positive pressure ventilation if required • Naloxone administration • Seizures: • IV diazepam or phenytoin • Cardiac arrhythmias • GI decontamination: • Syrup of ipecac (in alert patients) • Intubation and gastric lavage (in lethargic or comatose patients) • Activated charcoal (if bowel sounds are present) • Diuretics, dialysis and hemoperfusion are not indicated, because of large volume of distributions and reversibility with naloxone. Opioid intoxication: Treatment with opioid antagonists Naloxone • Rapid response (1-2 min): respiratory functions and mydriasis • Short half-live (60-90 min) • precipitated withdrawal (short lasting): Patient may become agitated. • Initial dose: 0.8 mg/70kg Nalmefene • Rapid response (a few minutes): respiratory functions and mydriasis • Long half-live (10 hr) • precipitated withdrawal (long lasting) • Initial dose: 0.5-1.0 mg Opioid intoxication: Treatment with naloxone • IV Naloxone • May be used SQ, IM, SL or by intratracheal tube if venous access cannot be established. • No contraindication • Rapidly restore CNS and cardiopulmonary functions (onset of action: 1-2 min) • Duration of effect: 60-90 min • T1/2 for IV or intratracheal use: 1 hr • Recommended dose to diagnose or reverse the effect of opioids: • Adults: 0.8-2.0 mg q5-10 min • Children: 0.03-0.1 mg/kg • For long-acting agents: IV infusion of naloxone 2 mg naloxone in 500 ml normal saline, 100-200 ml/hr (and titrating up, if necessary) • Prophylactic naloxone for 12-48 hr Opioid intoxication: Treatment with naloxone • Partial response: mixed overdose, hypoglycemia, head trauma, Wernicke’s encephalopathy, hypoxia or post-hypoxic encephalopathy. • In the past it was thought that if no response was observed after administering naloxone (~10 mg) or nalmefene, then CNS depression was probably not solely due to opioids. • However, buprenorphine overdose is difficult to reverse with opioid antagonists, and higher doses of naloxone may be required, although the risk of clinically significant respiratory depression from buprenorphine is uncommon given its partial µ agonism. Pentazocine overdose • Clinical picture of pentazocine intoxication is different from typical opioids, because pentazocine activates sigma opioid receptors and causes dysphoria, delusions and hallucinations. • In addition, pentazocine intoxication is associated with hypertension, tachycardia, flushing, chills, and diaphoresis. Propoxyphene overdose • In addition to usual symptoms, propoxyphene intoxication may result in seizures and cardiac arrhythmias. • Consider concomitant alcohol intoxication. Lomotil overdose • Diphenoxylate & Atropine • Lomotil intoxication is different, specially in children. • Clinical picture is biphasic: First phase is a result of anticholinergic effects of atropine: hyperpyrexia, flushing, hallucinations, lethargy, urinary retention and tachycardia. Second phase (after ~3 hr) is characteristic findings of narcotic intoxication.