Post-surgery codeine still killing children, new study says

Years after Canadian researchers sounded the alarm about the dangers of prescribing codeine-based painkillers after surgery, children are still dying because of the practice.

A new study, published in Monday's edition of the journal Pediatrics, details the deaths and near-death of three youngsters shortly after ear, neck and throat surgery – and there are "many more cases, no question," the lead researcher said.

"No one should accept that a child dies after being prescribed codeine," Gideon Koren, director of the Motherisk program at the Hospital for Sick Children in Toronto, said in an interview. "This is a totally unsafe practice."

The three children in the study – two Canadians and one American – all overdosed on morphine. There is a common genetic trait that leads some people to metabolize codeine ultra-rapidly. What that means, practically, is the body converts codeine to morphine so fast that it accumulates to toxic levels.

The children are not identified by name, but their treatment is outlined in detail in the article. The incidents occurred in 2010 and 2011, and were investigated by coroners:

A four-year-old first nations boy had his tonsils and adenoids removed at a regional hospital in Northern Ontario. Upon discharge, he received an “age-appropriate dose” of a liquid codeine-based painkiller. After four doses, he died of morphine overdose;
A three-year-old girl had her tonsils removed at a children’s hospital in southwestern Ontario and was given a prescription for a combination codeine-acetaminophen painkiller. Six hours after discharge, she was found in her bed with no vital signs. The girl survived only because she received emergency treatment for the overdose promptly;
A five-year-old boy had myringotomy tubes (to reduce pressure in the ears) reinstalled at a children’s hospital in the U.S. South. After surgery, he was prescribed acetaminophen and codeine to be taken every four hours. The boy was found dead 24 hours after discharge.

All three children had multiple copies of a gene variant known as allele CYP2D6, but Dr. Koren said that "children without this genetic trait are also at risk. Codeine makes you breathe more shallowly and that's a danger if you have apnea, asthma or other conditions too."

Tonsils and adenoids are most commonly removed to treat apnea, a disorder characterized by a reduction or pause in breathing during sleep. But in about 20 per cent of cases, the condition does not improve with the operation.

In 2009, the research team reported on the case of a two-year-old Ontario boy who died of morphine overdose after having his tonsils removed.

The much-publicized case was expected to fundamentally alter prescribing practices, but "changing the habits of doctors is very difficult," Dr. Koren said.

It is recommended that children be treated for pain with ibuprofen (Advil, Motrin and other brands) or acetaminophen (Tylenol) rather than a combination of acetaminophen and codeine (Tylenol 3). Children should not be treated with acetylsalicylic acid (known by the brand name Aspirin) because it can trigger a rare but fatal condition called Reye's syndrome.

The reason that some physicians continue to prescribe codeine-based drugs is because they are more powerful painkillers and because ibuprofen increases the risk of bleeding, a concern after surgery.

"I understand the worries about bleeding. This is an issue," Dr. Koren said.

Aside from a total ban on codeine-based medicine, he said there are other potential solutions to this problem. Children could be tested for multiple copies of the allele CYP2D6 or, if children are prescribed codeine, they could be kept overnight in hospital for observation. (Routine procedures like tonsillectomy, adenotonsillectomy and myringotomy are now usually performed as day surgery.) "Some will say these are costly solutions. But children are dying with our current approach," Dr. Koren said.

Earlier research showed that it is also dangerous for breastfeeding mothers to take codeine-based medications. In 2005, Tariq Jamieson of Toronto died at 12 days old of a morphine overdose after ingesting the drug through his mother's breast milk. Tariq's mother had the genetic trait that made her metabolize codeine quickly, the tragic result of which was the poisoning of her son.

A subsequent study found that one-quarter of babies whose mothers took codeine while breastfeeding suffered serious breathing problems.

Today, it is virtually unheard of for women to take codeine-based painkillers for more than two to three days after giving birth (at which time their milk comes in).

"The change of practice happened with breastfeeding mothers. Now it needs to happen with children," Dr. Koren said.