Friday, February 19, 2010

Factors Behind Rx-Opioid Overdose Deaths Examined

Increasing incidences of fatal overdoses associated with prescribed opioid analgesics have raised concerns among government agencies, healthcare providers, and the public. A recent report from Lynn Webster, MD, and colleagues reveals some interesting factors that may influence accidental overdose deaths.

U.S. government data indicate that unintentional opioid-analgesic-related deaths increased by 214% from 2001 to 2005, reaching about 8,500 fatalities nationwide [NDIC 2009]. Yet, relatively little is known to help predict such tragic events and, thereby, possibly prevent them. At the recent AAPM (American Academy of Pain Medicine) annual meeting, Webster — of Lifetree Clinical Research and Pain Clinic, Salt Lake City, UT — and coauthors presented a case series report on 20 unintentional opioid-analgesic overdose fatalities [Webster et al. 2010]. Data had been gathered during a 3-year period from medical records included in legal actions surrounding the deaths. Here is a summary of findings:
  • All decedents had been taking at least 60 mg/day of morphine-equivalent opioids for at least 1 year.

  • The primary opioids involved in the deaths were methadone (50%, n=10) and hydrocodone (20%, n=4).

  • Most deaths (65%, n=13) occurred within 1 week of a change in opioid dose and 3 of those occurred within the first day.

  • A majority of deaths (55%, n=11) were discovered in the morning and, overall, 60% (n=12) of decedents were found in bed.

  • Three quarters of decedents fell into the 14-35 and 46-59 age brackets, males outnumbered females by a 3 to 2 ratio. Four of the decedents were obese (BMI>30).

  • In three-quarters of cases (n=15) physician prescribing error was judged to be the cause of death. The remaining 5 cases were associated with either patient noncompliance, excessive medication consumption, a defective medication patch, illicit substance use, or benzodiazepine/sedative overdose.
COMMENTARY: Obviously, this is a small and select case series, and Webster et al. caution that their findings cannot be generalized to all opioid overdose fatalities. Still, data of this sort are vital for understanding causes of such deaths and similar data gathering and reporting should be standard practice during postmortem investigations. Unfortunately, information available today from coroner or medical examiner reports or other sources is generally too meager and unreliable for meaningful analyses.

Webster and colleagues emphasize that their findings typify trends in methadone-related overdoses, which represents half of the fatalities in their sample cases and a third of all opioid-related deaths nationwide. Furthermore, in their report, physician error was deemed a major contributing factor in most fatalities but we are not informed if methadone prescribing was particularly problematic or any other details of the alleged errors. It would be instructive to know specifics; for example, having received therapy for a year or more, all patients in the cases were to a degree opioid-tolerant, so errors may have occurred due to miscalculating doses for opioid increases or rotation to a different opioid, the introduction of an interacting medication, a change in patient physical condition, or other factors. The brief conference report is uninformative in this regard.

The large proportion of decedents found in bed in the morning may suggest a relationship between sleep and overdose, according Webster and his coauthors. In some cases, however, body mass index might have played a role, since obesity carries risks of respiratory depression even in the absence of sleep apnea syndrome. Generally, the need for family or other caretakers to more closely monitor patients during sleep after starting opioid therapy or following any change in dose or medication is not as prominently stressed in the literature as it should be. And, it may take a week or longer before harmful opioid effects are fully realized, causing overdose.

In sum, this report by Webster and his team raises some very interesting and important possibilities for consideration. If many more cases of this sort could be accumulated, with more details, it might lead to a substantial database of potentially life-saving information for analysis.

> NDIC (U.S. National Drug Intelligence Center). National Prescription Drug Threat Assessment 2009. 2009(Apr). Document ID: 2009-L0487-001 [
available here].
> Webster LR, Dove B, Murphy A. Select Medical-Legal Reviews of Unintentional Overdose Deaths. Presented at: 2010 AAPM Annual Meeting; February 3-6, 2010; San Antonio, TX [
poster available here].