Reducing Mortality During Spinal Infusion Of Opioids

After evaluating a cluster of deaths most likely related to intrathecal (spinal) opioid infusions in non-cancer pain patients, a group of researchers is confident that such future complications are preventable.

In 2006, Medtronic, Inc. and a team of noted experts investigated what might have caused the deaths of three patients early on in their treatment of pain using intrathecal infusion pumps containing opioids. They augmented their own findings with related data from other large databases.

Robert J. Coffey, MD, and his co-authors write in the October issue of the journal Anesthesiology that, "Patients with non-cancer pain treated with intrathecal opioid therapy experience increased mortality compared to similar patients treated using other therapies." They further note that "Our analyses suggest that a number of clinical factors likely caused or contributed to patient mortality, and despite limitations in the data, communication of these findings to physicians may help to reduce patient mortality."

In a companion editorial to the study, James P. Rathmell, M.D., from the Department of Anesthesia at Harvard Medical School, said that intrathecal drug delivery has earned a place in the armamentarium of pain practitioners, especially for chronic non-cancer pain, and its use has grown dramatically.

"The evidence to support efficacy in this realm is growing, but efficacy and long-term safety has yet to be established," he said. "Dr. Coffey's study concludes that patients with non-cancer pain treated with intrathecal opioid therapy experienced increased mortality compared to similar patients treated using other therapies. This is a striking conclusion, and many questions arise."

One such question is: What can we learn from this analysis to improve the safety of intrathecal drug therapy?

Dr. Coffey and the co-authors believe that "Physicians and industry may be able to reduce the mortality risks described in this article by conducting further investigations and educational efforts and, ultimately, by making changes in medical practices."

According to the researchers, "Even a cautious interpretation of these results raises the question of what physicians and industry can do now, albeit with incomplete and imperfect information, to reduce the preventable proportion of mortality associated with this therapy."

Physicians are urged to critically examine prescribing information, precautions (including special populations) and warnings contained in drug labels. Particularly, physicians need to be on guard against rare but potentially fatal respiratory problems that can occur with the use of intrathecal morphine.

"Improvements in physician education and knowledge of drug delivery devices including greater simplicity, and improved device-generated alerts also are important changes to enhance patient safety," the study authors said.

Dr. Rathmell echoed the sentiments of Dr. Coffey and his research group. "Every practitioner using intrathecal therapy must understand that there is a risk of fatality, particularly after implantation. In the absence of data to guide practice, we must adopt a common sense approach," he said.

Dr. Rathmell suggested the following ways in which physicians may be able to minimize their contributions to the risks of intrathecal opioid delivery:

• Initiating intrathecal therapy with the lowest dose that can be reasonably predicted to provide effectiveness
• Avoiding use of accompanying central nervous system depressants in the immediate post-implantation period
• Gaining an expert understanding of the intrathecal drug pump, its construction and proper programming
• Personally overseeing all aspects of the initial programming
• Avoiding use of excessively concentrated solutions during initiation of therapy to minimize the delay in onset of drug effects associated with slow infusion rates
• Routinely calculating when the new drug will first enter the intrathecal space and warning patients and their caregivers to be most vigilant during this time