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Respiratory Depression
Patients receiving long-term opioid therapy usually develop tolerance to the respiratory-depressant effects of these agents. Occasionally, respiratory depression occurs when pain is abruptly relieved and the sedative effects of opioids are no longer opposed by the stimulating effects of pain.196 In a symptomatic patient, physical stimulation may be enough to prevent significant hypoventilation. Opioid antagonists (e.g., naloxone) should be given cautiously to patients who are receiving opioids on a long-term basis. Because patients who have become tolerant to opioids show great sensitivity to the effects of antagonist drugs, symptomatic respiratory depression should be treated carefully using a dilute solution of naloxone (0.4 mg in 10 mL of saline), administered as 0.5 mL (0.02 mg) bonuses every minute. The dose of naloxone should be titrated to the patient's respiratory rate. A return to full alertness is often accompanied by a severe withdrawal syndrome and a return of pain. Naloxone titration, when indicated for the reversal of opioid-induced respiratory depression, should be given incrementally in doses that improve respiratory function but do not reverse analgesia. Repeated doses may be required,21; 376 or alternatively, an infusion of two ampules (total, 0.8 mg) in 250 mL of 5 percent dextrose in water may be continuously infused and titrated toward this goal.
Far more common than acute respiratory depression is subacute overdose, in which sedation gradually builds and is followed by a slowing of respiratory rate and then by ventilatory failure. The degree of sedation rather than the respiratory rate is a better indicator of impending respiratory depression 243 The risk of this complication is highest during titration of opioids with long plasma half-lives, such as methadone and levorphanol, and is best managed by withholding one or two doses and then reducing the standing dose by 25 percent of its current level until symptoms have resolved. At that time, a cautious titration can be resumed. The maintenance of 25 percent of the dose has been found to be adequate to prevent acute opioid withdrawal.21
Clinicians are often concerned that high doses of opioids used for palliation may harm or kill a patient, particularly when doses are increased to alleviate pain.79 This double effect of intended benefit and potential harm 390 is seen in the clinical situation when the intended treatment may have inextricably linked deleterious side effects. The administration of medication is always a risk-versus-benefit calculation. When the patient's death is imminent because of the progression of primary disease, an increased risk of earlier death counts little against the benefit of pain relief and painless death. The ethical duty to benefit the patient through relieving pain is by itself adequate to support increasing doses to alleviate pain, even if there might be life-shortening and expected side effects. Because many patients in the terminal phase have been receiving opioid pain medications for a significant period of time, the fear of shortening life by medication is usually unfounded. Respiratory depression is not often a significant limiting factor in pain management because, with repeated doses, tolerance develops to this effect, allowing for adequate pain treatment with escalating doses without respiratory compromise.164 The person dying from cancer should not be allowed to live out life with unrelieved pain because of fear of side effects; rather, appropriate, aggressive palliative support should be given.416; 79
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