For the many children who undergo tonsillectomies each year, management of post-operative pain remains a challenge. Among the obstacles is finding the best post-operative medical strategy to control pain with minimal side effects, as well as working with parents and other caregivers to ensure that children receive adequate pain medications. Adequate pain control is critical to ensure that children remain hydrated and resume regular eating as soon as possible after surgery.
“Tonsillectomy is an operation that is uncomfortable and affects children profoundly for a few days after surgery,” said David E. Tunkel, MD, director of pediatric otolaryngology at Johns Hopkins Children’s Center in Baltimore, Md. “The problem is that there is no perfect analgesic strategy.” The other problem, he said, is that parents and caregivers often don’t administer adequate doses of pain medication after surgery due to concerns about giving these medications to children.
This concern is not without warrant. An increasing number of reports of fatalities associated with codeine, one of the most time-honored drugs used to treat post-operative pain in children following
tonsillectomy, is prompting clinicians to rethink the medical strategy to control pain in this setting.
Although many otolaryngologists and other physicians have already changed their practice to omit the use of codeine and other narcotics, their use remains widespread in the post-operative pain management of children, according to Anna Messner, MD, professor and vice chair in the department of pediatric otolaryngology-head and neck surgery at Lucile Packard Children’s Hospital, Stanford University Medical Center, Stanford, Calif. “Codeine has been used for a long time, so it is hard to change established practice,” she said.
Time for a Change?
For many years, acetaminophen combined with codeine has been used to treat post-operative pain in children undergoing tonsillectomy or other otolaryngologic procedures. For many children, this is a safe and effective treatment.
The safety of codeine use in some children has been questioned over the past few years, however, with an increasing number of case reports describing children who have died after receiving codeine for post-operative pain, particularly after tonsillectomy (Pain Med. 2012;13(7):982-983). The latest report, published in 2012, documented the cases of three children who died after receiving standard treatment with codeine-acetaminophen after tonsillectomy between 2010 and 2011 (Pediatrics. 2012;129(5):e1343-1347).
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).
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.
According to Charles Monroe Myer III, MD, professor of otolaryngology-head and neck surgery at Cincinnati Children’s Hospital Medical Center, the only way to ensure the safe use of codeine and other opioids in children is to identify those who are rapid metabolizers. Although genetic testing that can identify patients with CYP2D6 is available, it is currently too expensive—approximately $400—to be used widely or as a screening tool.
To find a cheaper and more accessible way of identifying patients, Dr. Sadhasviam and colleagues are currently studying the risk factors for opioid-related complications in children who are fast metabolizers to identify problems prior to surgery or before administering post-operative pain medication.
Dr. Myer emphasized that finding an easier and cheaper way to identify children at risk of opioid-related complications would also help identify the subgroup of children who are slow metabolizers of codeine and other opioids and who therefore do not receive adequate pain relief when treated with these drugs.
Along with ultra-metabolizers of CYP2D6, children in whom opioids should be used with care or not at all are those undergoing tonsillectomy for sleep apnea. Dr. Sadhasivam emphasized the need for extreme care in using opioids in these children, who are at increased risk of respiratory depression.
Changing Practice: Alternatives to Narcotics
“Most people feel that narcotics will give better pain relief than a non-narcotic,” said Dr. Myer, “so the assumption is that acetaminophen with codeine must be better pain management than acetaminophen alone.” Evidence does not bear this out, he said.
A randomized study published in 2002 that evaluated the efficacy of acetaminophen alone or with codeine in children after tonsillectomy found no difference in the level of pain control between the two treatments (Laryngoscope. 2000;110(11):1824-1827). In addition, the study found that children treated with acetaminophen alone consumed a significantly higher percentage of a normal diet during the first six days after surgery.
Dr. Messner, the senior author of the study, said that she and her colleagues have not used codeine for a long time because of these results. “At our institution, we don’t give narcotics to kids younger than age 7,” she said, adding that they do consider hydrocodone with acetaminophen for older children who have a T&A for the diagnosis of sleep apnea.
In place of codeine, she and her colleagues routinely use acetaminophen alone, administering 15 mg per kilogram per dose every four hours. Alternately, patients also may switch between acetaminophen and ibuprofen every three hours. She emphasized that this is not an evidence-based approach to treatment, but is one with which they have had good results.
Dr. Myer and his colleagues at Cincinnati Children’s Hospital have had good results with around-the-clock dosing with acetaminophen and ibuprofen and once-a-day dexamethasone for three post-operative days, and currently follow a protocol for post-operative pain management that incorporates this strategy (see “Protocol for Post-Tonsillectomy Pain Control,” p. 28)
Along with recommending ibuprofen at 10 mg per kilogram per dose for a maximum of two doses every 24 hours starting on day two, Dr. Sadhasivam said that the surgical staff he works with also are comfortable administering ibuprofen on the first day after surgery without significant concern of increased bleeding. They often do this because of the increased pain on post-operative day one. “Most physicians do not think that acetaminophen and ibuprofen will work well enough for pain management and [think] they have to give a stronger opioid to treat post-operative pain,” he said. “But if you give these non-opioid medications around the clock, they help reduce pain significantly, and you can avoid the risk of opioids by avoiding or reducing the opioid use.”
Since implementing this protocol more than a year ago, he and his staff have seen a reduction in pain, as evidenced by the fewer calls regarding pain concerns. In addition, they have not had any patient return to the emergency room due to increased pain or significant bleeding caused by ibuprofen or dexamethasone.
The use of ibuprofen in place of codeine is increasing. Concerns over an increased risk of bleeding after surgery have not been supported by evidence, which consistently shows no increased bleeding risk (Cochrane Database Syst Rev. 2005;(2):CD003591). Based on this evidence, the 2011 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Clinical Practice Guideline on Tonsillectomy in Children states that ibuprofen can be used safely for pain control after surgery (Otolaryngol Head Neck Surg. 2011;144(1S):S1-S30).
Further support from AAO-HNS on the use of ibuprofen, as well as caution regarding the use of narcotics, can be found on the AAO-HNS website in a Q&A with Dr. Messner and Dr. Tunkel (available at entnet.org).
Need to Adequately Manage Post-Operative Pain
Along with choosing the most effective and safe analgesic to manage post-operative pain, clinicians must also educate parents and caregivers on the importance of administering adequate pain medication. “We need to educate parents that it is okay to give children safe pain medication,” said Dr. Tunkel, who is also chair of the AAO-HNS Pediatric Otolaryngology Committee.
The importance of including parents in the successful management of pain is highlighted in the AAO-HNS guidelines, in which a number of recommendations are provided to caregivers on helping to manage pain in their children (see “Parent Education: Post-Tonsillectomy Pain Management Guidelines for Caregivers,” p. 26).
Dr. Tunkel emphasized that parents often do not provide adequate pain medication to their children despite rating their children’s pain as very high, furthering the need for clear communication from otolaryngologists and other physicians regarding the importance of compliance with the prescribed pain medications.
The Bottom Line
Adequate pain control in children after tonsillectomy is critical to ensure proper hydration and a return to normal eating after surgery. The once well-established use of acetaminophen and codeine has come under scrutiny following an increasing number of codeine-related fatalities in young children undergoing tonsillectomy. Until a good way to screen children who are at risk of opioid-related complications is available, many physicians recommend against the use of narcotics in young children—particularly those undergoing tonsillectomy for sleep apnea.
Alternative strategies using around-the-clock dosing of acetaminophen and ibuprofen have shown good results without the risks of opioids or increased bleeding risk with ibuprofen. Although this approach to pain management is not yet an established evidence-based strategy, it has received endorsement by the AAO-HNS as a viable option. Along with choosing the safest and most effective pain analgesic, compliance with safe pain medications is also critical, and parents must be educated on the importance of adequate pain control for their children.