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The two most common pediatric surgeries in the United States, tympanostomy tube insertion and tonsillectomy, are both performed by otolaryngologists. For this reason, a contemporary understanding of pediatric perioperative pain control is critical for otolaryngologists. The majority of these procedures are performed on an outpatient basis, with selected patients requiring one night of monitored observation after tonsillectomy. Anticipated postoperative pain and perioperative risks differ greatly between these two procedures, and the challenges of pain management usually take place after discharge. A variety of pharmacologic and nonpharmacologic strategies for perioperative pain management in children have been studied, with the goal of improving postoperative patient comfort while minimizing the likelihood of dangerous side effects. Commonly used medications include acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), and opioids. This chapter discusses current issues and recommendations with the use of these analgesic classes and presents nonpharmacologic adjuncts for perioperative pain control in children. Although we focus on care after adenotonsillectomy or tympanostomy tube placement, the strategies discussed in this chapter can be adapted to other procedures in children, acknowledging that pharyngeal surgery usually causes significant pain with the need for aggressive management strategies. ,
Pain control in pediatric patients requires several special considerations. Unlike adult patients undergoing otolaryngologic procedures, young children are not usually able to perform their own pain assessments, communicate pain severity, or administer their own pain medications. Instead, it falls upon parents or caregivers to both assess the child's pain level and administer appropriate types and dosages of analgesics. These caregivers must be educated to recognize the signs and symptoms of uncontrolled pain as well as early signs of overmedication to avoid potentially serious consequences from improper analgesic dosing.
The most obvious difference between pediatric and adult pain management is patient size. Given the variation in size and weight among children of all ages, ideal weight-based dosing is critical to achieving therapeutic effects. The smaller the patient, the narrower the margin of error to achieve levels within the therapeutic window. For example, a study of posttonsillectomy pain control in the United Kingdom, where over-the-counter acetaminophen and ibuprofen are dosed by age rather than weight, found that implementation of standardized weight-based dosing significantly improved the readmission rate for pain control without impacting postoperative hemorrhage rate.
Many opioid medications are dependent upon the cytochrome P450 2D6 (CYP2D6) pathway for breakdown into their active metabolites ( Table 5.1 ). Well-described variation in CYP2D6 activity exists, leading to four phenotypes of poor metabolizers, intermediate metabolizers, extensive metabolizers (considered “normal”), and ultrarapid metabolizers. Whereas ultrarapid metabolism and higher serum concentrations of an active metabolite may not exceed the wider therapeutic window in adults, this phenotype has been associated with respiratory depression and even death in young children after surgery.
Opioid | Enzymes of metabolism | Metabolites | FDA warnings |
---|---|---|---|
Codeine | CYP 2D6; CYP 3A4; UGT 2B7 | Morphine (active); norcodine; codeine-6-glucuronide (active) | Box warning against use in posttonsillectomy pain; contraindicated for treatment of pain or cough in age <12; warning against use in age 12–18 with obesity, OSA, or severe lung disease |
Tramadol | CYP 2D6; CYP 3A4 | O-desmethyl-tramadol (active) | Contraindicated for treatment of pain in age <12; Contraindicated for posttonsillectomy pain in age <18 |
Morphine | UGT 2B7 | Morphine-6-glucuronide (active); morphine-3-glucuronide | |
Hydromorphone | UGT 1A3; UGT 2B7 | Hydromorphine-6-glucuronide (active); hydromorphine-3-glucuronide | |
Oxycodone | CYP 3A4; CYP 2D6 | Noroxycodone (active); oxymorphone (active) | |
Hydrocodone | CYP 2D6; CYP 3A4 | Hydromorphone (active); norhydrocodone (active) |
Given the role of caregivers in managing postoperative pediatric pain in the outpatient setting, education of these caregivers before discharge, and perhaps at the time of presurgical counseling, is essential. Parents can be taught to use behavioral pain scales to assess pain levels at routine intervals. Studies demonstrate that although caregivers are able to recognize pain in children, they often underdose analgesics. , Pain management education starts preoperatively and should be incorporated into the discussion of risks and benefits of surgery. Perioperative staff, such as preoperative and postanesthesia care unit (PACU) nurses, play a central role in parental education and should reinforce analgesic dosing recommendations, teach parents the signs of pain, and detail the side effects of the prescribed medications. A standardized program including teaching in the PACU with an educational booklet, use of a timer to adhere to the analgesic regimen, instructions on how to accurately measure doses, use of a pain management diary, and reinforcement/coaching through telephone calls can be effective for parental education. An educational booklet or video has been shown to increase parental knowledge about managing their children's pain. ,
Caregiver education is particularly critical when opioids are prescribed. Evidence suggests that parents may not understand the risk of oversedation in children with obstructive sleep apnea syndrome (OSAS), and half of the parents in one study would give an opioid medication when their child exhibited signs of oversedation, demonstrating the need for improved education to recognize and manage signs of opioid toxicity. Implementation of provider education to use nonopioid analgesics first in conjunction with a guideline reducing the number of oxycodone doses prescribed after tonsillectomy resulted in both decreased opioid prescription quantity and higher odds of good pain control. Otolaryngologists should also recognize that cultural factors such as ethnicity may affect how caregivers assess and treat pain. Such education should balance our efforts to improve pain control after uncomfortable procedures like tonsillectomy with the imperative to avoid adverse drug reactions.
Myringotomy with insertion of tympanostomy tubes is the most commonly performed pediatric surgical procedure in the United States. Pain following tympanostomy tube placement is neither severe nor long lasting. Given the short duration and limited nature of the procedure, inhalational anesthetics are typically used and intravenous (IV) access is often not required. However, inhalational anesthetics are associated with higher rates of emergence delirium, which typically lasts 5–15 min. While this is usually limited in time and severity, it may result in injury to self or others. The mechanism of emergence delirium is not clear; however, pain, anxiety, and anesthetic choice are all thought to contribute.
Studies have evaluated varying approaches to preoperative, intraoperative, and postoperative analgesia for tympanostomy tube placement, both with regards to pain control and reduction of emergence delirium. No obvious benefit has been observed with one analgesic regimen compared to another, and most patients are managed postoperatively with acetaminophen and/or ibuprofen as needed. Prescription pain medications are typically not required. A randomized controlled trial (RCT) found no benefit in postoperative pain control when children were premedicated with acetaminophen and ibuprofen before tympanostomy tube placement. A large retrospective study found superior analgesia when a combination of intramuscular fentanyl and ketorolac were administered. However, another retrospective study found that choice of intraoperative analgesic among fentanyl, ketorolac, or a combination had no impact on postoperative pain control or time to discharge. Intraoperative acupuncture has been shown to reduce postoperative pain and agitation following tympanostomy tube insertion; however, this has not been widely adopted or studied.
Emergence delirium was reduced with the administration of a single IV dose of propofol and ketorolac at the conclusion of sevoflurane anesthetic for tympanostomy tube placement in a prospective observational study. However, most children undergoing tympanostomy tube placement do not require IV access and such intervention may be neither practical nor time- and cost-effective. Although dexmedetomidine is used both in the management and prevention of pediatric emergence delirium, a retrospective study of intranasal dexmedetomidine before tympanostomy tube placement found no reduction in emergence delirium scores or duration of PACU stay with its use.
After myringotomy with insertion of tympanostomy tubes, tonsillectomy is the second most common pediatric surgical procedure performed in the United States. Tonsillectomy and adenotonsillectomy, like other pharyngeal procedures, are associated with severe pain that is often poorly controlled. Pain after tonsillectomy has a stereotypic course with worsening later in the first postoperative week. Pain after tonsillectomy appears to be more severe and long lasting than after orchiopexy or inguinal hernia repair in children. In general, adenoidectomy alone causes significantly less pain than tonsillectomy, and our discussion in this chapter, like the bulk of the research, is focused on tonsillectomy or adenotonsillectomy.
Poorly controlled oropharyngeal pain is the primary cause of morbidity after tonsillectomy in children, and this may lead to a reduction in oral intake with subsequent dehydration or weight loss. Studies have found that dehydration, hemorrhage, and throat pain are the three most common reasons for unplanned posttonsillectomy emergency room (ER) presentations. , Additional reasons for presentation included nausea and vomiting, respiratory issues, and fever. , Poor pain control and choice of analgesic regimen are likely involved with each of these potential complications.
OSAS represents the most common indication for tonsillectomy (or adenotonsillectomy) in children. Patients with sleep apnea have a unique sensitivity to opioids with regard to respiratory depression, and this is further complicated by impaired upper airway function from postoperative swelling as well as the effects of general anesthesia. Administration of opioids, given their dose-dependent risk of sedation and respiratory depression, is particularly fraught in this high-risk population. Although tonsillectomy usually improves and often cures OSAS in children, the improvement is not immediate, and in fact sleep-related airway obstruction may worsen transiently in the immediate postoperative period.
This risk of respiratory depression with opioid use in “typical” OSAS patients after tonsillectomy is further compounded by the known variation in the rate of metabolism of certain opioid preparations. Several commonly used opioids, including codeine, are metabolized by the CYP2D6 pathway into active morphine metabolites ( Table 5.1 ). Ultrarapid metabolizer phenotypes with duplication of the CYP2D6 allele can cause rapid accumulation of active metabolites to supratherapeutic levels, leading to accelerated sedation and respiratory depression even with standard opioid dosing.
Although respiratory depression is the most severe risk associated with opioid use in children, other side effects may make opioids intolerable for some. Gastrointestinal side effects such as nausea, vomiting, or constipation can compound pain-related difficulties with reduced oral intake and worsen dehydration. Additional bothersome adverse effects include lightheadedness/dizziness, dry mouth, itching, and rash.
Prescription opioids also have the potential for misuse and abuse in adolescents, who are thought to be even more susceptible than adults due to the sensitivity of reward centers in the adolescent brain. , An analysis of a large commercial claims database found that 4.8% of opioid-naïve patients aged 13–21 continued to refill opioid prescriptions 90–180 days after tonsillectomy. Although older children and adolescents may be less vulnerable to respiratory depression, habit formation and potential for opioid misuse is an important consideration in this age group. Opioid prescriptions, even for children, should be accompanied by education regarding appropriate secure storage, cessation of medication when pain abates, and methods for disposal of unused medication.
Historically, codeine, usually combined with acetaminophen, was the most commonly prescribed medication used for the management of posttonsillectomy pain. However, in 2009, a report of the codeine-related posttonsillectomy death of a 2-year-old with obstructive sleep apnea (OSA) who had a duplication of the CYP2D6 allele raised awareness of the risk of codeine administration in patients with this ultrarapid metabolizer phenotype. In 2013, after a review of similar cases, the FDA issued a new box warning (its strongest warning) against the use of codeine for posttonsillectomy pain management in children. In 2017, the FDA expanded this advisory to a contraindication against the use of codeine for the treatment of pain or cough in children under 12, and a warning against its use in adolescents age 12–18 with obesity, OSA, or severe lung disease. A review of the FDA Adverse Event Reporting System (FAERS) from 1969 to 2015 identified 24 codeine-related deaths in children under 18, 21 of which occurred in children under the age of 12. Many of these patients were ultrarapid or extensive metabolizers, leading to supratherapeutic morphine levels that can be especially dangerous in the posttonsillectomy OSAS population. Unfortunately, preprocedural screening for CYP2D6 polymorphisms would be impractical and has not been shown to correlate with clinical phenotype.
On the other end of the spectrum, the subset of patients belonging to the “poor metabolizer” phenotype is unable to metabolize codeine to its active metabolite and therefore derive minimal analgesia from its administration. RCTs have found no difference in pain control with acetaminophen with codeine compared to either acetaminophen or ibuprofen alone in children after tonsillectomy. Codeine use was associated with increased nausea and decreased tolerance of a normal diet in these studies. , All of these data taken together indicate that the risks of codeine far outweigh the benefits in children, and codeine administration has decreased substantially in recent years. However, despite the strongest FDA warnings, 1 in 20 children who underwent a tonsillectomy in 2015 still received a prescription for codeine.
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