As presented in Moore TJ (1) and discussed in Med Page Today (September 10, 2007) reports to the FDA of drug related injury, disability and death nearly tripled during the period of 1998 – 2005. Analgesics and immune system modulators accounted for the majority of adverse events. Oxycodone was suspected in 5548 of 15107 reported deaths. Michael Ashburn (our new director of pain medicine) has published three papers investigating aspects of opioid analgesia related adverse events. In 1990 he and his colleagues (2) determined the frequency of hypoxemia and apnea after sedation with midazolam and fentanyl. Using volunteers they found that midazolam alone (0.05 mg/kg) had no effect. Fentanyl alone (2 mcg/kg) produced hypoxemia (oxygen saturation less than 90%) in half the subjects but no apnea. However, the combination of midazolam and fentanyl produced hypoxemia in 11 of 12 subjects and apnea in 6 of 12 subjects. In 1994, Ashburn, Love and Pace (3) reported on respiratory related critical events associated with patient controlled analgesia. They evaluated 3785 patients who received PCA for a total of 11521 patient care days. Fourteen critical events occurred and four of these led to increased patient care requirements. More recently (2003) he and his associates (4) determined that opioid related adverse events had an incidence of 2.7% in a population of 60,722 surgical patients who received opioids and these were associated with a longer length of stay and an increased median cost of $840. The commonest adverse events were nausea and vomiting (67%) followed by rash, hives or itching (33.5%). White and Kehlet (5) caution about the reliance on opioids alone for the control of acute perioperative or for chronic pain. They cite reports of rapidly emerging opioid tolerance and hyperalgesia in cancer patients receiving oral morphine. They summarize a number of studies suggesting that since the Joint Commission standards for pain control there has been in increase in opioid-induced adverse events which include respiratory depression. The dangers of opioids are now being reflected in the FDA data which confirms the findings of earlier studies. Though opioids are important analgesics they also have significant risks. References: 1) Moore TJ: Serious adverse drug events reported to the Food and Drug Administration, 1998 – 2005. Arch Intern Med 2007;167:1752; 2) Bailey PL et al: Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. Anesthesiology 1990;73:826-30; 3) Ashburn MA et al: Respiratory-related critical incidents with intravenous patient-controlled analgesia. Clin J Pain 1994;10:52-6; 4) Oderda GM et al: Cost of opioid-related adverse drug events in surgical patients. J Pain Symptom Management 2003;25:276-83. 5) White PF, Kehlet H: Improving pain management: Are we jumping from the frying pan into the fire? Anesth Analg 2007;105:10 – 12.
David S. Smith, M.D., Ph.D.