Although the number of documented cases of codeine-related deaths remains small, a recently published study that looked at the complications and legal outcomes of tonsillectomy malpractice claims found that the incidence of codeine-related deaths was much higher than the researchers expected (Laryngoscope. 2012;122(1):71-74).
Explore This IssueSeptember 2012
Using data from the LexisNexis Mega Jury Verdicts and Settlements database from 1984 through 2010 for complications resulting from tonsillectomy, the researchers found that 18 percent of death claims and 5 percent of injury claims resulted from the use of opioids, largely codeine. “This database showed that opioids are the second most common cause of death in patients who undergo tonsillectomy after post-tonsillectomy bleeding,” said Senthilkumar Sadhasivam, MD, MPH, assistant professor of clinical anesthesia and pediatrics and director of peri-
operative pain service in the division of pediatrics at Cincinnati Children’s Hospital Medical Center in Ohio, who was involved with the study.
Along with continuing to raise the incidence of death claims over the 16 years of the study’s current analysis, opioids have also contributed to high monetary awards due to the severity of the complications in terms of deaths and anoxic injuries, he said.
The study found that death and anoxic brain injury claims were associated with the greatest indemnity, with a median payment of more than $900,000 per case. Codeine ultra-rapid metabolizer status, relative overdosing of opioids, inadequate monitoring/premature discharge of the patient and pharmacy errors are commonly reported reasons for opioid-related death and hypoxic injury claims.
Identifying Children at Risk
What these case studies reveal is that all of the children who died following codeine administration had extra copies of the liver enzyme CYP2D6, which metabolizes codeine to its more potent form of morphine. Referred to as ultra-rapid metabolizers, these children metabolize codeine so rapidly to morphine that it leads to respiratory depression or arrest. Even extensive metabolizers are at higher risk of having fatal respiratory depression with codeine (Pediatrics. 2012;129(5):e1343-e1347).
Although some suggest substituting hydrocodone or other opioids for codeine, Dr. Sadhasivam emphasized that hydrocodone, tramadol and oxycodone are all metabolized by CYP2D6 and can therefore cause even more problems, because the CYP2D6 metabolites of hydrocodone and oxycodone are more potent than morphine. “Unfortunately, there are no safe opioid alternatives to codeine for young children with sleep apnea or other respiratory or airway disease,” he said. There are other genetic varitions aside from CYP2D6 that also unpredictably increase respiratory depression with most commonly used opioids, he added.