Opiate Intoxication Although mild opiate intoxication can be stimulating, severe

Opiate Intoxication Although mild opiate intoxication can be stimulating, severe

intoxication causes a maladaptive mental state with symptoms such as apathy; this is associated with pupillary constriction (characteristically midpoint with meperidine) or dilation if the patient has anoxia from severe overdose, central nervous system depression, and respiratory depression. Meperidine, propoxyphene, or pentazocine have active metabolites that may cause seizures.

Severe opiate intoxication is a life-threatening condition because of the high likelihood of respiratory depression or arrest. Opiate overdose is a common cause of death, especially among teenagers and young adults, and is particularly likely among individuals with low levels of tolerance, including inex- perienced users, or patients who have recently detoxified or been abstinent for a period of time. Death from opiate over- dose is an underappreciated risk, and, just as one would assess risk of suicide in depressed patients, clinicians evaluating a patient presenting with opiate intoxication should evaluate the risk of overdose, including level of tolerance and past history of overdose episodes.

The presence of miosis and respiratory depression at presentation is an indication for immediate treatment. An intravenous dose of the pure opiate antagonist naloxone HCl 0.4–0.8 mg usually reverses opiate-induced respiratory and CNS depression in two minutes. The dose may be repeated every 2–3 min if previous dose was not effective. Response occurs in the majority of patients after up to four doses but larger doses may be needed in cases of intoxication by highly potent opiates such as fentanyl or long-acting agents such as methadone. Naloxone has a duration of action of 1–2 h, which is shorter than that of opiates. When a response has been achieved, a naloxine infusion should therefore be initiated (initial dose 0.4 mg/h) and maintained for a minimum of 12 h.

219 When using naloxone it is important to note that:

DRUGS FOR TREATING SUBSTANCE ABUSE DISORDERS

1. CNS depression in patients with opiate overdose may be due to other causes, particularly if standard doses of naloxone are not effective.

2. Naloxone may suddenly precipitate an opiate withdrawal syndrome and should therefore be administered cautiously. Patients with precipitated withdrawal may become suddenly anxious, irritable, or combative, and try to leave the emer- gency ward against advice; such patients should be treated supportively, and naloxone discontinued temporarily until symptoms clear, after which naloxone may need to be resumed in response to resumed intoxication and respira- tory depression, especially in the presence of longer-acting agonists. Such patients should be prevented, if at all possible, from leaving the emergency ward or clinic, since respira- tory depression may return quickly once the naloxone wears off, or the patients may seek out and take more opiates. If opiate withdrawal persists, treatment should be initiated (see below).

3. Naloxone may not reverse the effects of buprenorphine. This partial opiate agonist, long available in parenteral form for analgesia, is now marketed in sublingual form [brand names Suboxone (buprenorphine-naloxone) and Subutex (buprenorphine)] as an alternative to methadone for agonist maintenance treatment of opioid dependence. Buprenor- phine by itself produces less respiratory depression than other full opiate agonists, even at high doses, but death from overdose has been associated with combinations of buprenorphine and benzodiazepines.