Treating post-operative pain with morphine can cause life-threatening respiratory problems in some children who have had their tonsils and/or adenoids removed, according to a study published in the January 26, 2015, online edition of the journal Pediatrics.
The study has identified a significant risk for potentially-fatal breathing disruption when morphine is administered at home after surgery to treat pain in children who undergo tonsillectomy with or without adenoidectomy.
The study also showed ibuprofen is a safe and effective alternative.
The research builds on a 2009 study and a 2012 study — both by researchers at the Hospital for Sick Children (SickKids) and McMaster University, Toronto, Ontario — that found codeine administered for post-operative pain in the same population of children could cause respiratory problems and fatal outcomes for children who are genetically ultra-rapid metabolisers of codeine. Previously, codeine had been the standard treatment for post-operative pain in this population across North America.
As a result of the 2009 paper, both Health Canada and the US Food and Drug Administration (FDA) issued warnings about the risks associated with giving codeine to this population of children. The FDA gave paediatric codeine a Boxed Warning as well as a contraindication. While no official recommendation of a safe and effective alternative had been made in response to these warnings, many centres prescribed morphine to these children believing that the response to the drug would be more predictable.
For the current study, 91 children aged 1 to 10 years were randomised to receive post-operative painkillers at home following their outpatient tonsillectomy surgery to treat obstructive sleep apnoea. Parents were given a prescription to fill and were instructed about the use of a home pulse oximeter to measure oxygen saturation and apnoea events the night before and the night after surgery. Parents were also taught to use the Objective Pain Scale and Faces Scale to assess their children’s pain levels on post-operative days 1 and 5.
From September 2012 to January 2014, one group of children were given post-operative standard doses of oral morphine (0.2-0.5 mg/kg) and acetaminophen (10-15 mg/kg) every 4 hours to treat their pain, while the other group was prescribed standard doses of oral ibuprofen (10 mg/kg) every 6 hours and acetaminophen (10-15 mg/kg) every 4 hours.
Pain was effectively managed and comparable in both groups.
On the first post-operative night, 68% of children in the ibuprofen group showed improvement in oxygen desaturation incidents. On the same night, only 14% of children in the morphine group improved. In fact, in the short term, the condition of these children worsened, with substantially more desaturation events in the morphine group — roughly 11 to 15 events per hour. Both groups had similar minimal levels of other adverse drug reactions and bleeding.
Last year, midway through the planned study period, an interim analysis was conducted by the study’s Drug Safety Monitoring Board. In addition to the general findings, which strongly demonstrated serious respiratory risk associated with morphine, one child suffered a life-threatening adverse drug reaction including oxygen desaturation after being treated with morphine. These severe outcomes prompted the Board to halt the study period early and the research team notified both hospitals’ Research Ethics Boards.
“The evidence here clearly suggests children with obstructive sleep apnoea should not be given morphine for post-operative pain,” said Gideon Koren, MD, Motherisk Program, SickKids. “We already know that they should not get codeine either. The good news is that we now have evidence that indicates ibuprofen is safe for these kids, and is just as effective in controlling their pain, so there’s a good alternative available for clinicians to prescribe.”
“These results should prompt clinicians to re-evaluate their post-tonsillectomy pain treatment regimen,” said co-author Doron Sommer, MD, McMaster Children’s Hospital. “Due to the unpredictable respiratory side-effects of morphine, its use as a first-line treatment with current dosage ranges should be discontinued for outpatient tonsillectomy.”
At both SickKids and McMaster Children’s Hospital, the use of morphine for post-operative pain from paediatric tonsillectomy is reserved for exceptional cases where it is deemed necessary and safe with appropriate monitoring.