Post-Tonsillectomy Analgesia: An Old Problem Revisited
Post-Tonsillectomy Analgesia: An Old Problem Revisited David E. Tunkel, MD Director, Pediatric Otolaryngology Johns Hopkins Medical Institutions Charles M. Myer, III Professor, Department of Otolaryngology-Head and Neck Surgery University of Cincinnati Academic Health Center Tonsillectomy is undoubtedly a painful procedure, for children and perhaps for parents as well. Safe and effective analgesia is problematic. A recent FDA advisory has alerted us to concerns about a long-used regimen for post-tonsillectomy management, with reports of deaths of children after tonsillectomy, deaths attributed to abnormal metabolism of codeine1. What Do We Know About Post-tonsillectomy Pain Issues? Post-tonsillectomy pain is common and seems to worsen during the first week after surgery. Even with preoperative counseling, parents and caregivers are often surprised by this discomfort. Even when analgesics are prescribed and pain is recognized, prescribed doses are often not given by caregivers2. A well-designed study found no differences in the analgesic effects of acetaminophen and acetaminophen with codeine after tonsillectomy3. Many children cannot metabolize codeine to active metabolites, potentially causing side effects without providing effective analgesia. Genetic variations in CYP2D6 in a small but significant percentage of children (one percent to seven percent, as high as 28 percent in some ethnic groups) can lead to ultra-rapid metabolism of codeine, giving higher levels of active metabolites with potential respiratory depression4. Several recent reports have associated the ultra-rapid metabolism genotype with post-T&A deaths or severe respiratory depression in children. Additional opiate-associated adverse effects after tonsillectomy in children have likely occurred, as demonstrated by litigation for anoxic events after surgery5, 6. In fact, 18 percent of malpractice claims about tonsillectomy involved opiate toxicity, second only to postoperative bleeding. Most tonsillectomies in children are now performed for sleep-disordered breathing. Children with obstructive sleep apnea (OSAS) are more sensitive to the respiratory depressant effects of opiates7. In fact, a recent report documented postoperative hypoxia in children who received opiates at home after adenotonsillectomy 8. This hypoxia occurred both with normal and abnormal CYP2D6 genotypes. Non-steroidal anti-inflammatory agents (NSAIDs), such as ibuprofen, have been used for post-tonsillectomy analgesia, and well-designed trials have not shown any increase in post-operative hemorrhage. Ketorolac is the exception here, as increased bleeding has been seen with this drug. NSAID use was supported in the recent AAO-HNS clinical practice guideline on pediatric tonsillectomy9. Many otolaryngologists still prefer to avoid NSAIDs. With These Issues Identified, How Can We Reduce Pain in Children after Tonsillectomy? How do we avoid the low probability-high morbidity events, but still provide comfort to children after tonsillectomy? Indications for prolonged monitoring of children after tonsillectomy are well described. These indicators identify children at risk for respiratory compromise after surgery, or for incomplete cure of OSAS after surgery. They include young age, obesity, neuromotor disease, chromosomal abnormalities such as Down’s syndrome, and severe abnormalities on preoperative sleep studies. These same clinical indicators can be used as markers for judicious use (or avoidance) of opiates after tonsillectomy. The young child with OSAS has the greatest risk for an adverse event with narcotics. The reported codeine-associated mortalities occurred in children younger than six years old. Parents can make substantial measurement errors with small dose volumes. These young children may have increased opiate sensitivity because of OSAS. If a young child also has a genotype that allows rapid metabolism of codeine, the risk is even greater. While recommendations have been discussed about the youngest age for safe narcotic use, no consensus statement or evidence-based guideline yet exists. Non-opiate analgesic regimens are being instituted and evaluated, particularly for young children10. A recent report from a large children’s hospital described a “non-opiate” regimen of around the clock acetaminophen immediately after tonsillectomy, daily dexamethasone doses for three days, and rescue doses of ibuprofen starting on postoperative day two. No increases in inadequate pain control or postoperative bleeding were seen, and no serious complications were noted5. If opiates are used in a young child, parents should be counseled about correct dosing and potential adverse effects. Consider overnight monitoring for the aforementioned clinical indications, although opiate-related adverse effects have been seen in hospitalized patients. While genetic testing for CYP2D6 variations has been suggested, this is not available and may be impractical for screening children prior to tonsillectomy. Nevertheless, genotype analysis in the future may allow selection or avoidance of certain opiates, appropriate dosing, and identification of individuals at-risk for adverse effects11. While codeine was the focus in the recent FDA advisory, it is likely that other opiates that share the CYP2D6 pathway may cause the same adverse effects from ultra-rapid metabolism. We continue to search for improved tonsillectomy with less post-operative pain and reduced hemorrhage risk. The goals of post-operative analgesia should be well stated and shared by the surgical team, the nursing staff, and most importantly the family. This involves education about the risks of each analgesic regimen. We should assess technical developments in the tonsillectomy procedure that could reduce pain, but we also should be aware of any potential drawbacks of such modifications. It does not seem wise to use medications that are not approved for acute pain management in children after tonsillectomy, especially after ambulatory surgery. New opiate and non-opiate pain regimens should be evaluated systematically for efficacy and safety. The “take to the OR” message here: There is no perfect method for pain control after tonsillectomy in children, but we must recognize the low probability, but serious issue of respiratory compromise from opiates while providing analgesia to our patients. We should avoid codeine use in young children. Use acetaminophen and ibuprofen in young children and/or those with severe OSAS. Use opiates judiciously in older children with precise dosing and careful counseling, with postoperative monitoring when indicated. This discussion will obviously continue, as we go from case reports to systematic analysis of efficacy and risks of analgesic regimens. References http://www.fda.gov/Drugs/DrugSafety/ucm313631.htm. Fortier MA, Maclaren JE, Martin SR, Perret-Karimi D, Kain ZN. Pediatric pain after ambulatory surgery; where’s the medication. Pediatrics 2009; 124:e588-595. Moir MS, Bailr E, Shinnick P, Messner A. Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope 2000; 110:1824-1827. Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, ultrarapid-metabolism genotype, and postoperative death. New Engl J Med 2009; 361:827-828. Subramanyam R, Varughese A, Willging JP, Sadhasivam S. Future of pediatric tonsillectomy and perioperative outcomes. Int J Pediatr Otorhinolaryngol 2012; Nov 15. pii: S0165-5876(12)00587-3. doi:10.1016/j.ijporl.2012.10.016. [Epub ahead of print]. Stevenson AN, Myer CM, Shuler MD, Singer PS. Complications and legal outcomes of tonsillectomy malpractice claims. Laryngoscope 2012; 122:71-74. Brown KA, Laferriere A, Lakheeram I, Moss IR. Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates. Anesthesiology 2006; 105:665-669. Khetani JD, Madadi P, Sommer DD, Reddy D, Sistonen J, Ross CJ, Carleton BC, Hayden MR, Koren G. Apnea and oxygen desaturations in children treated with opioids after adenotonsillectomy for obstructive sleep apnea syndrome; a prospective pilot study. Paediatr Drugs 2012Dec 1;14(6):411-415. Baugh RF, Archer SM, Mitchell RB, Rosenfeld RM, et al. Clinical practice guideline; tonsillectomy in children. Otolaryngol Head Neck Surg. 2011; 144 (1Suppl):S1-30. Sadhasivam S, Myer CM. Preventing opioid-related deaths in children undergoing surgery. Pain Med 2012; 137:982-983. Crews KR, Gaedigk A, Dunnenberger HM, Klein TE, Shen DD, Callaghan JT, Kharasch ED, Skaar T. Clinical pharmacogenetics implementation consortium guidelines for codeine therapy in the context of the cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther 2012; 91:321-326.
Post-Tonsillectomy Analgesia: An Old Problem Revisited
David E. Tunkel, MD
Director, Pediatric Otolaryngology
Johns Hopkins Medical Institutions
Charles M. Myer, III
Professor, Department of Otolaryngology-Head and Neck Surgery
University of Cincinnati Academic Health Center
Tonsillectomy is undoubtedly a painful procedure, for children and perhaps for parents as well. Safe and effective analgesia is problematic. A recent FDA advisory has alerted us to concerns about a long-used regimen for post-tonsillectomy management, with reports of deaths of children after tonsillectomy, deaths attributed to abnormal metabolism of codeine1.
What Do We Know About Post-tonsillectomy Pain Issues?
- Post-tonsillectomy pain is common and seems to worsen during the first week after surgery. Even with preoperative counseling, parents and caregivers are often surprised by this discomfort.
- Even when analgesics are prescribed and pain is recognized, prescribed doses are often not given by caregivers2.
- A well-designed study found no differences in the analgesic effects of acetaminophen and acetaminophen with codeine after tonsillectomy3.
- Many children cannot metabolize codeine to active metabolites, potentially causing side effects without providing effective analgesia.
- Genetic variations in CYP2D6 in a small but significant percentage of children (one percent to seven percent, as high as 28 percent in some ethnic groups) can lead to ultra-rapid metabolism of codeine, giving higher levels of active metabolites with potential respiratory depression4.
- Several recent reports have associated the ultra-rapid metabolism genotype with post-T&A deaths or severe respiratory depression in children. Additional opiate-associated adverse effects after tonsillectomy in children have likely occurred, as demonstrated by litigation for anoxic events after surgery5, 6. In fact, 18 percent of malpractice claims about tonsillectomy involved opiate toxicity, second only to postoperative bleeding.
- Most tonsillectomies in children are now performed for sleep-disordered breathing. Children with obstructive sleep apnea (OSAS) are more sensitive to the respiratory depressant effects of opiates7. In fact, a recent report documented postoperative hypoxia in children who received opiates at home after adenotonsillectomy 8. This hypoxia occurred both with normal and abnormal CYP2D6 genotypes.
- Non-steroidal anti-inflammatory agents (NSAIDs), such as ibuprofen, have been used for post-tonsillectomy analgesia, and well-designed trials have not shown any increase in post-operative hemorrhage. Ketorolac is the exception here, as increased bleeding has been seen with this drug. NSAID use was supported in the recent AAO-HNS clinical practice guideline on pediatric tonsillectomy9. Many otolaryngologists still prefer to avoid NSAIDs.
With These Issues Identified, How Can We Reduce Pain in Children after Tonsillectomy?
How do we avoid the low probability-high morbidity events, but still provide comfort to children after tonsillectomy?
- Indications for prolonged monitoring of children after tonsillectomy are well described. These indicators identify children at risk for respiratory compromise after surgery, or for incomplete cure of OSAS after surgery. They include young age, obesity, neuromotor disease, chromosomal abnormalities such as Down’s syndrome, and severe abnormalities on preoperative sleep studies.
- These same clinical indicators can be used as markers for judicious use (or avoidance) of opiates after tonsillectomy.
- The young child with OSAS has the greatest risk for an adverse event with narcotics. The reported codeine-associated mortalities occurred in children younger than six years old. Parents can make substantial measurement errors with small dose volumes. These young children may have increased opiate sensitivity because of OSAS. If a young child also has a genotype that allows rapid metabolism of codeine, the risk is even greater.
- While recommendations have been discussed about the youngest age for safe narcotic use, no consensus statement or evidence-based guideline yet exists. Non-opiate analgesic regimens are being instituted and evaluated, particularly for young children10. A recent report from a large children’s hospital described a “non-opiate” regimen of around the clock acetaminophen immediately after tonsillectomy, daily dexamethasone doses for three days, and rescue doses of ibuprofen starting on postoperative day two. No increases in inadequate pain control or postoperative bleeding were seen, and no serious complications were noted5.
- If opiates are used in a young child, parents should be counseled about correct dosing and potential adverse effects. Consider overnight monitoring for the aforementioned clinical indications, although opiate-related adverse effects have been seen in hospitalized patients.
- While genetic testing for CYP2D6 variations has been suggested, this is not available and may be impractical for screening children prior to tonsillectomy. Nevertheless, genotype analysis in the future may allow selection or avoidance of certain opiates, appropriate dosing, and identification of individuals at-risk for adverse effects11.
- While codeine was the focus in the recent FDA advisory, it is likely that other opiates that share the CYP2D6 pathway may cause the same adverse effects from ultra-rapid metabolism.
- We continue to search for improved tonsillectomy with less post-operative pain and reduced hemorrhage risk. The goals of post-operative analgesia should be well stated and shared by the surgical team, the nursing staff, and most importantly the family. This involves education about the risks of each analgesic regimen.
- We should assess technical developments in the tonsillectomy procedure that could reduce pain, but we also should be aware of any potential drawbacks of such modifications.
- It does not seem wise to use medications that are not approved for acute pain management in children after tonsillectomy, especially after ambulatory surgery. New opiate and non-opiate pain regimens should be evaluated systematically for efficacy and safety.
The “take to the OR” message here: There is no perfect method for pain control after tonsillectomy in children, but we must recognize the low probability, but serious issue of respiratory compromise from opiates while providing analgesia to our patients. We should avoid codeine use in young children. Use acetaminophen and ibuprofen in young children and/or those with severe OSAS. Use opiates judiciously in older children with precise dosing and careful counseling, with postoperative monitoring when indicated. This discussion will obviously continue, as we go from case reports to systematic analysis of efficacy and risks of analgesic regimens.
References
- http://www.fda.gov/Drugs/DrugSafety/ucm313631.htm.
- Fortier MA, Maclaren JE, Martin SR, Perret-Karimi D, Kain ZN. Pediatric pain after ambulatory surgery; where’s the medication. Pediatrics 2009; 124:e588-595.
- Moir MS, Bailr E, Shinnick P, Messner A. Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope 2000; 110:1824-1827.
- Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G. Codeine, ultrarapid-metabolism genotype, and postoperative death. New Engl J Med 2009; 361:827-828.
- Subramanyam R, Varughese A, Willging JP, Sadhasivam S. Future of pediatric tonsillectomy and perioperative outcomes. Int J Pediatr Otorhinolaryngol 2012; Nov 15. pii: S0165-5876(12)00587-3. doi:10.1016/j.ijporl.2012.10.016. [Epub ahead of print].
- Stevenson AN, Myer CM, Shuler MD, Singer PS. Complications and legal outcomes of tonsillectomy malpractice claims. Laryngoscope 2012; 122:71-74.
- Brown KA, Laferriere A, Lakheeram I, Moss IR. Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates. Anesthesiology 2006; 105:665-669.
- Khetani JD, Madadi P, Sommer DD, Reddy D, Sistonen J, Ross CJ, Carleton BC, Hayden MR, Koren G. Apnea and oxygen desaturations in children treated with opioids after adenotonsillectomy for obstructive sleep apnea syndrome; a prospective pilot study. Paediatr Drugs 2012Dec 1;14(6):411-415.
- Baugh RF, Archer SM, Mitchell RB, Rosenfeld RM, et al. Clinical practice guideline; tonsillectomy in children. Otolaryngol Head Neck Surg. 2011; 144 (1Suppl):S1-30.
- Sadhasivam S, Myer CM. Preventing opioid-related deaths in children undergoing surgery. Pain Med 2012; 137:982-983.
- Crews KR, Gaedigk A, Dunnenberger HM, Klein TE, Shen DD, Callaghan JT, Kharasch ED, Skaar T. Clinical pharmacogenetics implementation consortium guidelines for codeine therapy in the context of the cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther 2012; 91:321-326.