Published Online January 26, 2016
The Pharmacogenomics Journal

Respiratory depression is among the most serious side effects of morphine-induced anesthesia. Now, researchers have found that genetic variants in children are crucial to ensuring safer, shorter post-operative stays.

The variants are in a liver transporter gene called ABCC3. This gene facilitates hepatic morphine metabolite efflux, the mechanism that allows morphine and its active metabolite to dissipate throughout the body.

The study, published in The Pharmacogenomics Journal, involved 316 children undergoing tonsillectomy.

The team found that children with these variants and respiratory depression had postoperative stays about three times longer than children without the variants. These are the first reports to show a direct association of ABCC3 variants with opioid-related respiratory depression.

Senthilkumar Sadhasivam, MD, MPH, and Vidya Chidambaran, MD, both of the Division of Anesthesia, led the study.

“If we can routinely do ABCC3 genotyping preoperatively,” Sadhasivam says, “we can reliably identify at-risk children and tailor their pain management to minimize their postoperative risk.”

For example, a genetic screening test could help guide perioperative strategies, including the possible use of fentanyl as an alternative to morphine.

The next steps for this research have already begun. The biotech company Assurex has licensed the team’s intellectual property, including associations with ABCC3 variants.

“We are excited that this discovery would come to clinical practice sooner because of this commercialization agreement,” Sadhasivam says.

Meanwhile, the team is working to develop clinical decision algorithms based on multiple genes to improve predictive reliability.