Opioids have long held a prominent role in the management of perioperative pain in adults and children. Published reports concerning the appropriate, and inappropriate, use of these medications in pediatric patients have appeared in various publications over the last 50 years. For this document, the Society for Pediatric Anesthesia appointed a taskforce to evaluate the available literature and formulate recommendations with respect to the most salient aspects of perioperative opioid administration in children. The recommendations are graded based on the strength of the available evidence, with consensus of the experts applied for those issues where evidence is not available. The goal of the recommendations was to address the most important issues concerning opioid administration to children after surgery, including appropriate assessment of pain, monitoring of patients on opioid therapy, opioid dosing considerations, side effects of opioid treatment, strategies for opioid delivery, and assessment of analgesic efficacy. Regular updates are planned with a re‐release of guidelines every 2 years. It is part of our core mission to provide high quality and ethical care to pediatric patients in the perioperative time frame.The Society for Pediatric Anesthesia (SPA) initiated and supported the formulation of these recommendations with the intent of providing guidance for pediatric anesthesiologists that is (where possible) evidence‐based or a synthesis of expert opinion where evidence is lacking. The authors did not attempt to make this manuscript all encompassing, but rather were interested in addressing the issues that were felt to be in need of clarification at this time. This document should not be interpreted as an endorsement of the primacy of opioids in the management of perioperative pain. Rather, this project begins with the admonition that clinicians should use all methods possible to minimize the use of opioids, including the administration of adjunctive systemic medications, regional anesthesia, and alternative medicine techniques.2This document addresses topics related to the use of opioid medications including methods of administration, assessment of pain, optimization of therapy, and monitoring of pediatric patients on opioid therapy. This discussion will largely be limited to pharmaceuticals available in North America; however, the principles of care apply broadly to any medications in the opioid class. The “perioperative time frame” refers to administration of opioids as part of the anesthetic for an operation and the recovery period. The length of time will be different based on variations in the surgeries involved and multiple patient factors including age and pain sensitization. For the purposes of this paper, the recovery time frame will be defined as the period for which most surgical patients would be expected to require opiates for each specific procedure. For major surgeries, this would include time as an inpatient with emphasis on parenteral administration of opioids during that time period. We will also address the brief time pediatric postoperative patients receive oral opioids at home. We will address the treatment of chronic pain patients that come for surgery but not the use of opioids for, or the treatment of, chronic pain that might develop after surgery.3These recommendations are intended to address questions related to the use of opioid medications for children undergoing surgery or painful procedures. This document is not comprehensive in nature. We have chosen to highlight the areas of appropriate opioid delivery methods, monitoring, and pain assessment since these aspects have high variability between care delivery systems and bear most directly on the safe use of these agents. Issues involving children with chronic pain and pain sensitization as well as previous opioid therapy are also addressed since these patients are often the most difficult to manage in the perioperative time frame.4These recommendations are intended to enable maximum patient benefit from opioid medications in order to provide potent analgesia and best outcomes for children after surgery.5The SPA board approved the appointment of nine primary authors to review the published evidence and make recommendations on issues related to the safe use of opioids in children. Those appointed come from a diverse array of institutions and sub‐specialty backgrounds including pain medicine, clinical pharmacology, clinical trials, addiction medicine, general operating room anesthesia, and perioperative nursing. We also engaged four senior anesthesiologists with extensive histories of contribution to the specialty of pediatric anesthesiology, pain management, and opioid investigation.6perioperative time frame and specifically on the process of opioid delivery and monitoring of patients treated with opioids. The panel also agreed the document should attempt to target those issues most pressing for health care providers who manage pediatric patients in the perioperative time frame. Selected topics were to include age‐related effects of opioids; patient‐controlled analgesia (PCA); postoperative outpatient opioid administration; monitoring of patients on opioids; pain assessment and opioid efficacy; opioid side effects and treatment; perioperative management of patients on chronic opioids; and management of patients with opioid addiction. Several sections that were initially written for this manuscript were eliminated due to editorial considerations of overlapping content with other published reports.The expert panel was convened and met in person twice prior to beginning the process of formulating these recommendations. The members agreed that this manuscript should focus on the The members of the taskforce searched academic databases for relevant articles on opioid administration in children associated with surgical pain relief including effectiveness, techniques for delivery, monitoring, and side effects. A list of the databases searched and the search terms used is presented in Table Level A: Based on prospective, randomized trials, or pharmacokinetic and pharmacodynamic trials that meet the highest standards for investigation and reporting.Level B: Based on prospective, observational data or appropriately conducted retrospective analysis with consideration of appropriate confounders and compensation for the influence of these factors.Level C: Based on case reports, case series, or consensus involving experts who presented a well‐defined process for formulating conclusions.The strength of evidence available for specific recommendations was based on a three‐tiered classification system that we patterned after evidence‐based practice guidelines from the American Society or AnesthesiologistsFor each recommendation, we have taken the level at which the preponderance of evidence was derived and clearly designated it as such. A list of the recommendations and strength of evidence is provided in Table 7What is the evidence for changes in opioid pharmacokinetics and pharmacodynamics with age?How should opioid dosing be adjusted with age?Specifically, what is the effect of age on the issue of opioid induced respiratory depression?To be discussed in this section:Recommendations for dosing opioids in children are cited in a number of publications.7.1Morphine is a commonly employed agent for pain control in newborns, infants, and children. There is consistent evidence that the greatest variation in pharmacokinetic parameters occurs in neonates and very young infants. Neonates have a larger volume of distribution and decreased protein binding which results in a greater free fraction of the opioid. Glomerular filtration rate (GFR) and hepatic enzyme development are relatively immature in neonates (0‐28 days of life) resulting in a decreased clearance of morphine at approximately one‐fifth to less than one‐tenth of that in older children and adults.Recommendation: A validated, age‐adjusted morphine dosing regimen should be used for all pediatric patients but particularly for neonates where the dose and dosing interval will need to be altered significantly.Strength of evidence: A.7.2There is considerably less evidence concerning pharmacokinetics and pharmacodynamics of opioids other than morphine. Data on fentanyl, sufentanil, and alfentanil indicate each of these drugs undergo much more rapid clearance in infants and older children relative to neonates.The pharmacokinetics of methadone has been studied in adolescents undergoing major spinal surgery and appears to be similar to that in adults including an elimination half‐life of 44.4 hours.Recommendation: Dosage of most synthetic opioids should be decreased in neonates during the first 2‐4 weeks of life . For remifentanil, the effective half‐life in neonates is similar to that of older children and adults, and thus requires no adjustment. Methadone pharmacodynamics effects are prolonged compared to morphine and the pharmacokinetic profile appears to be consistent across pediatric age ranges.Strength of evidence: B.7.32 correlated with increasing plasma fentanyl concentrations, but did not differ between groups of infants vs children (1‐5 years of age) vs adults.Evidence concerning the respiratory depressant effects of opioids in children vs adults is sparse. In one study, Lynn et al evaluated the respiratory depressant effects in 30 newborns‐toddlers receiving morphine infusions after cardiac surgery. No age‐related differences in respiratory effects were observed at similar morphine concentrations.Recommendation: Term infants (older than 3 months of age) are not at increased risk of respiratory depression due to opioids when compared to older children and adults at the same blood concentration of opioid. The dose of opioids (dose/kg) should be similar to older infants and children after 6 months of age . When beginning opioid dosing in infants younger than 3 months of age, the patient should be in a highly monitored environment .Strength of evidence: B.8How does PCA opioid delivery compare to other modes of opioid delivery?What is the best opioid to use for PCA therapy?What is the evidence surrounding the use of NCA or parent‐controlled analgesia?What kinds of adjunctive medications should be added to PCA opioid therapy?Issues to be discussed in this section:8.1Patient‐controlled analgesia delivery of opioids has become the standard for analgesia after major surgery in children. This section will compare this delivery method vs other opioid delivery modalities. There are many adult studies comparing PCA to intramuscular (IM) opioids. One meta‐analysis examined 15 randomized controlled trials including 787 adult patients found PCA provided greater patient satisfaction and improved pain relief, as reported by visual analog scale (VAS) scores, and no difference in side effects.Recommendation: The use of PCA opioid delivery is preferable to IM opioid delivery for perioperative pain control. IM administration of opioids is not recommended as a primary pain control modality.Strength of Evidence: B.8.2There were no randomized controlled studies identified that compared PCA with intermittent opioid administration in the pediatric population. A number of cohort studies supported the use of PCA as efficacious and with acceptable rates of adverse events in a variety of postoperative settings  and with a variety of opioid choices .Recommendation: PCA opioid delivery is safe, efficacious, and correlated with higher patient satisfaction when compared to intermittent intravenous opioid analgesia.Strength of evidence: B (largely based on adult data).8.3The evidence is sparse and inconclusive concerning the choice of opioid for PCA in children. One randomized controlled trial of morphine vs meperidine in 50 orthopedic patients 8‐16 years old showed no difference in side effects, but lower numerical rating scale pain scores in patients receiving morphine.Recommendation: There is insufficient and conflicting evidence to recommend the use of a specific opioid over another for PCA postoperative pain control. Due to the risk of accumulation of toxic metabolites (normeperidine) that may cause seizures, meperidine is not recommended by our expert panel.Note: Meperidine use for postoperative shivering is not addressed in this recommendation.Strength of evidence: B.8.4Randomized controlled trials that have compared continuous opioid infusion with PCA to PCA alone have suggested that the addition of continuous infusion may have many possible effects on the overall impact of PCA therapy. Comparative studies of 6‐12 year olds postappendectomyIn terms of the risk of adding continuous infusion to PCA, a meta‐analysis of randomized controlled trials (including both adult and pediatric patients) indicated that pediatric patients have an overall lower risk of serious adverse events associated with a continuous infusion combined with PCA when compared to the adult population.Recommendation: There is conflicting and insufficient evidence to indicate a difference in overall analgesia, sleep patterns, or adverse events with the addition of continuous opioid infusion to PCA in children. Use of a basal infusion should be individualized based on consideration of the clinical situation, pain severity, and risk factors.Strength of Evidence: B.8.5Many pediatric patients are either developmentally or physically unable to activate their PCA pump and require assistance from a caregiver. When control of the bolus dose delivery is turned over to a caregiver, the technique is referred to as PCA by proxy (PCA‐P) or NCA. One retrospective study of 302 children managed with NCA vs intermittent IV dosing documented similar numbers of adverse events in both cohorts. This study was confounded by the fact that the NCA cohort tended to be younger and had more medical co‐morbidities.parent‐controlled analgesia has been associated with acceptable safety and effective postoperative analgesia delivery for children who are unable to use PCA themselves.The use of authorized Recommendation: There is evidence that NCA and parent‐controlled analgesia is associated with safety and efficacy outcomes that are similar to that of standard PCA therapy. These methods must be applied in an institutionally sanctioned program with appropriate training and monitoring.Strength of evidence: B.8.68.6.1There is supportive evidence for the opioid sparing effect of ketorolac when added to PCA analgesia. A randomized controlled study of 68 children comparing ketorolac to placebo every 6 hours found better pain control and a 42% reduction in morphine administered by PCA after PACU discharge.Recommendation: The use of ketorolac should be strongly considered as an adjunct to PCA for pediatric perioperative pain control. Most evidence available for nonsterioidal anti‐inflammatory drug (NSAID) effect on PCA dosing involves ketorolac, however there is good reason to assume another NSAID would have a similar PCA dose sparing effect.Strength of evidence: A.8.6.2There is supportive evidence for an opioid sparing effect when acetaminophen is added to PCA therapy in pediatric patients. A study of 80 children after appendectomy showed a significant morphine sparing effect with diclofenac, but a nonsignificant effect (17% less) with oral acetaminophen.There is evidence that acetaminophen is less effective for neonates than older children, particularly for procedural pain.Recommendation: The use of acetaminophen should be considered as an adjunct to PCA for pediatric perioperative pain control.Strength of evidence: A.9What is the role of educational resources?What is the evidence for the choice of specific opioid therapy, dosing strategies for outpatient opioids, use of combined opioid and benzodiazepine therapy, or the prescribing practices for opioid medications for outpatients?Topics in this section:9.1There is evidence that pain is poorly managed at home after surgery in children.http://mychildisinpain.org.uk, combine excellent graphics with informative text and video presentations to provide up to date information on how parents should approach pain management and include specific information on medication issues.Educational materials can take many forms. In adult patients the use of an informational brochure has been shown to significantly improve the percentage of patients who disposed of unused opioid pain medications after surgery.Recommendation: Educational resources must be provided to inform parents of the appropriate indications for pain medications and strategies for the safe use of opioids, nonopioids and other measures to manage their child's postoperative pain. Parents should receive both verbal and written detailed discharge instructions regarding home pain management with instructions regarding safe storage and disposal of leftover medications.Strength of evidence: C.9.2There is a paucity of pediatric literature upon which to formulate evidence‐based recommendations for opioid dosing after surgery and discharge home. One exception is the strong evidence against the use of codeine, particularly in children undergoing tonsillectomy and for other surgeries.Similarly, tramadol is a prodrug metabolized by enzyme complexes CYP3A4 and predominantly 2D6. Like codeine, there can be ultra‐rapid metabolizers for CYP2D6 leading to apnea. It also carries a risk of seizures.Recommendation: Codeine should be avoided in children and nursing mothers as a postoperative analgesic. This is particularly true if they have symptoms of obstructive sleep apnea or sleep disordered breathing.Strength of evidence: A.Recommendation: There is evidence to advise against the use of tramadol for specific populations of pediatric patients, particularly young patients (under 12) and those with OSA.Strength of evidence: B.9.3There are only two randomized prospective studies evaluating the appropriate dosing of opioids in postoperative pediatric patients. In one study, Sutters et al compared “around the clock” (ATC) dosing to an “as needed” administration (PRN) strategy. In this case, children who received ATC acetaminophen with hydrocodone were compared to those who received the same medications “as needed” for complaints of pain.Recommendation: There is insufficient evidence to recommend PRN vs scheduled dosing strategies for opioids after surgery in children. Expert consensus is to use a PRN strategy until further evidence is available.Strength of evidence: C.9.4A recent FDA review determined that the use of opioid medications in combination with benzodiazepines in adults has increased, and that this practice has resulted in serious side effects.Recommendation: Opioid pain medications should not be prescribed with benzodiazepines except in children for whom there is a specific indication and alternative treatment options are inadequate. Doses should be limited to the lowest effective level and parents should be warned about the potential for excessive sedation and respiratory depression.Strength of evidence: C.9.5Several federal agencies and physician organizations  have weighed in on the over prescription of opioids for postoperative patients. These organizations highlight the growing incidence of opioid overdose in pediatric patients, particularly teenagers. The most common source of prescription opioids is drug supplies from leftover prescriptions  where opioid prescriptions were overly generous in order to avoid any possible requirement for refilling prescriptions. Recent studies have found children are prescribed amounts of opioids that significantly exceed the total administered at home. Parents rarely received instructions regarding safe disposal of leftover opioids.Recommendation: Opioid prescriptions should be limited to that required for the expected period of severe pain after surgery . Patients should be educated concerning the appropriate storage and disposal of opioids.Strength of evidence: B.10What are the strategies for providing analgesia for patients with chronic pain?How do we approach analgesia for patients with central sensitization?Many pediatric patients present for surgery with a history of chronic pain, be it pain related to “central sensitization”,Topics in this section:It is critical to differentiate certain terms associated with chronic opioid use. Physical dependence describes the alterations in physiologic response that result from opioid binding and receptor‐mediated activity. In this subgroup, sudden discontinuation of opioids leads to opioid withdrawal or abstinence syndrome. Opioid tolerance refers to the pharmacologic adaptation that occurs after chronic exposure to opioids where there is a shift in the dose‐response curve and patients require increasing amounts of drug to maintain the same pharmacologic effects. Finally, drug addiction refers to a complex phenomenon where the use of a drug becomes the central point of focus for the user's life  even in the face of obvious physical or psychological harm. Patients who exhibit addiction are usually physically dependent on an opioid. Dependence and addiction may exist in conjunction with each other or as independent entities and must be identified and appreciated in order to appropriately (and safely) treat pain in this challenging population.10.1Recommendations for pediatric patients presenting for surgery who are on opioids for chronic pain syndromes are entirely extrapolated from the adult literature. There is a single observational study showing that pediatric patients previously placed on opioid infusions in an intensive care unit do not have increased perioperative opioid requirements if they have previously been successfully weaned off the opioids.In the adult literature, recommendations for perioperative management of patients with chronic pain using opioids are based on case reports, common sense, or consensus rather than randomized studies. Although not scientifically tested, these recommendations have been advocated in the setting of receptor down‐regulation and appreciation of the physiological and psychological changes that accompany chronic pain and opioid treatment. In all cases, perioperative care is advised to begin with preoperative administration and continuation of the daily maintenance (or baseline) opioid dose.While these recommendations will not review adjunctive pain medication use in detail, it is important to note that multiple studies in children support adjunctive therapies such as nonopioid pain relievers , and/or regional anesthesia techniques to improve pain control for chronic pain patients undergoing surgery.Recommendation: For pediatric patients with chronic pain who are maintained on opioids, continue established preoperative dosing during the perioperative period as a baseline. Acute postsurgical analgesia should be provided over and above the baseline opioids. Use of nonopioid analgesia is encouraged including regional analgesia techniques, alpha‐2 agonists, ketamine, acetaminophen, nonsteroidal anti‐inflammatory drugs, and neuropathic pain medications such as gabapentinoids or antidepressants.Strength of evidence: C.Recommendation: If the patient with chronic pain on chronic opioid therapy undergoes a procedure that is intended to remove the source of the patient's pain, they should be monitored for over sedation and should be discharged home with a defined opioid weaning plan. Opioid weaning in this case should be managed by a physician with special training or expertise in pain medicine. Limited supplies of opioids should be prescribed and refilled at frequent intervals that include face‐to‐face follow up visits.Strength of evidence: C (based on extrapolation of adult data and expert consensus).Recommendation: If a patient with chronic pain on opioid therapy undergoes surgery and the patient's underlying pain source was independent of the surgery, the patient's baseline pain should continue to be managed by the physician who had been doing so preoperatively. Opioid analgesics for the perioperative pain, if needed, should be prescribed in limited quantities consistent with the degree of physiologic trespass.Strength of evidence: C (based on extrapolation of adult data and expert consensus).10.2Perioperative pain management for pediatric patients with central sensitization is largely based on consensus. In the pediatric population the cohort is largely made up of patients with fibromyalgia, former premature newborns with extensive procedure history from the intensive care nursery, those with cancer, and those with an extensive surgical history. These patients are characterized by increased sensitivity to painful or nonpainful stimuli. There is evidence in adults with fibromyalgia that they are at risk for increased acute and chronic postoperative pain.Recommendation: For pain management of patients with central sensitization—strategies should be similar to those for pediatric pain patients on chronic opioids . Opioids should be prescribed as needed. These patients benefit from the involvement of a pain physician for the purposes of assuring appropriate use and discontinuation of medications in a reasonable time frame.Strength of evidence: C.11How should we assess pain intensity?Is there evidence for pain behavior observation, assessing the response to treatment, postoperative recovery and function?Pediatric anesthesiologists are routinely asked to assist in perioperative pain management, and there is wide agreement that appropriate assessment of pain is necessary in order to better guide care during the perioperative and postoperative period.Topics covered in this section:Recommendation: Regular pain assessments should be part of the perioperative care/treatment of pediatric patients who are receiving opioid medications. These assessments should be made using validated measures. The pain assessment should consider the unique circumstances of the child's psychological state and the extent of surgery.Strength of evidence: B.11.1Observational studies demonstrate children greater than 4 years of age can reliably use self‐report instruments to describe and score pain intensity. However, children less than 8 years of age have exhibited difficulty distinguishing between sensory pain ,Systematic reviews and consensus panels have identified several self‐report measures that are considered well established in measuring pain intensity during procedures, after surgery, and for use in clinical analgesic trials.Several observational studies have reported average self‐reported numeric or faces pain intensity scores children associate with perceptions of pain severity and their need for analgesia .Recommendation: Pain intensity scores can be used to assess a child's perceived degree of discomfort. However, decisions to administer analgesics should take into consideration patient functional behaviors, situational factors such as pain source, self‐reported pain scores, parental observation, and other potential sources of distress, rather than arbitrarily selected pain score cutoffs.Strength of evidence: B.11.2Behavior and posture‐related scales 2, Increased Vital Signs, Expression, Sleepless [CRIES])Combined behavioral/physiologic parameter scales .Recommendation: Changes in pain scores should be used in conjunction with other verbal/behavioral measures as indicators of pain relief and analgesic response (eg side effects) when making analgesic decisions.Strength of evidence: B.11.4Although an acute pain insult can induce changes in physiologic vital sign parameters such as heart rate and blood pressure, observational data have shown that these changes are nonspecific and poor sensitivity pain indicators.Recommendation: Physiologic parameters should be used to assess the child's nociceptive response when it is not possible to assess pain with self‐report of behavioral measures . It is recommended that other potential sources of physiologic distress  be considered and/or ruled out when making treatment decisions.Strength of evidence: B.11.5Consensus opinion supports assessment of the child's physical functioning when assessing recovery from pain and surgery, yet there is insufficient evidence regarding valid or reliable measures to assess children's physical function related to acute postoperative pain.Recommendation: A child's functional recovery should be assessed to inform treatment plans.Strength of evidence: C.11.6Observational studies have demonstrated children as young as 4 years can reliably identify a pain location (ie body map) that is consistent with clinical findings.Recommendation: Assessing pain location is recommended to differentiate incisional pain from other potential sources of postoperative pain. The nature of pain should be assessed to assist in the differentiation of pain type.Strength of evidence: B.12How should we utilize physiologic assessment of pain?Is there a strategy for monitoring sedation from opioids?What is the role of the institution in monitoring practice?Because of variability in both efficacy and adverse effects of opioid analgesics among pediatric patients in the immediate postoperative time period monitoring (through technology and human observation) should include vital signs and level of sedation to assess adverse effects of opioids. The ASA, the Anesthesia Patient Safety Foundation (APSF), the Joint Commission, Centers for Medicare and Medicaid Services (CMS), and the American Pain Society (APS) have promulgated practice guidelines incorporating the recommendations for monitoring discussed below.Topics covered in this section:12.1There are no prospective randomized trials investigating the minimum monitoring requirements concerning pediatric patients on PCA opioid infusions. Additionally, there are no clinical trials correlating levels of monitoring with significant adverse outcomes. In spite of this, a national survey of members of SPA, representing 252 institutions in the United States, showed 90% of pediatric anesthesiologists monitored patients on PCA with continuous pulse oximetry.2 monitors have been evaluated in pediatric populations,Transcutaneous PaCONew technologies, such as respiratory volume monitoring,Neonates (because of immaturity of respiratory control mechanisms as well as drug metabolism and clearance)Patients with cerebral palsy Patients with neuromuscular diseases Patients with cognitive impairment Patients with sleep disordered breathing and obstructive sleep apnea patients Patients receiving poly‐pharmacy (co‐administration of benzodiazepines and/or sedatives)Patients who have had an increase in PRN bolus dose or PCA dose of opioid, or addition of basal infusion rate to PCAOpioid naïve patients (particularly on the first postoperative night)Patients on supplemental oxygen (which impairs the sensitivity and response time of pulse oximetry as a monitor for apnea/hypopnea)Patients receiving neuraxial opioids.Although there are no studies to specifically differentiate the monitoring requirements for populations that are logically at increased risk for opioid associated respiratory depression, additional vigilance is recommended in such patients. These populations include:Meta‐analysis of adult studies has shown the risk of respiratory depression to be similar between "as needed" bolus administration of opioid and PCA bolus administration.Recommendation: Physiologic monitoring of children receiving initial intravenous opioid treatment should include pulse oximetry for the first 24 hours unless the patient is awake and actively being observed. Continuous monitoring of respiratory rate and electrocardiogram should be considered in pediatric patients who are on oxygen, or who have risk factors for respiratory depression. Physiological monitoring may be suspended when the patient is alert, awake, and/or ambulating.Strength of evidence: C.Recommendation: Although not specifically addressed in the literature, the expert panel recommends frequent assessment of the quality, as well as the rate of respirations, should be performed by direct observation and recorded in the medical record. Increased frequency and intensity of these observations is recommended for children in high‐risk groups in addition to standard electronic monitoring.Strength of evidence: C.12.2Of all the populations outlined above, the most commonly encountered and well studied is the growing cohort of pediatric patients with sleep apnea. Brown et alObesity is strongly associated with obstructive sleep apnea. Sleep apnea is also more common in certain pediatric populations including African Americans, Hispanic Americans, premature babies, toddlers who attend daycare, and children of lower socioeconomic status.Some adverse respiratory events may be traced to inaccurate dosing due to obesity. Specifically opiate dosing based on total body weight can result in dangerous respiratory depression.Recommendation: Patients with obstructive sleep apnea, obesity (>95 percentile BMI), and recurrent nighttime oxygen desaturations are at higher risk for opioid induced respiratory depression. Opioid dosing should be based on ideal or lean body weight and the dose of opioid should be reduced by 50% to 67% for OSA patients. Additionally, extended respiratory monitoring is required when opioids are being administered to this population in the perioperative period.Strength of evidence: B.12.3Excessive sedation has been found to predict/precede opioid‐related respiratory depression and was observed prior to opioid‐related death/neurological injury in a majority of children.Recommendation: Patients receiving opioid analgesia perioperatively should have regular assessment of their level of sedation using a validated sedation score that evaluates level of alertness or mentation, rather than utilizing a procedural sedation scale. This rating should be part of the medical record along with measures of pain and physiological status.Strength of Evidence: C.12.4Surveillance for opioid‐related adverse events has been recommended including regular review of rapid response team and/or code team calls and the need for naloxone administration. Publications of institutional review procedures of this nature provide information regarding risk for adverse events in both adults and children.Recommendation: Review of code team calls or emergency response calls and delivery of emergent naloxone doses should be part of institutional efforts to critically evaluate and reduce preventable opioid‐related adverse events.Strength of evidence: B.13Prevalence and management of pruritis, emesis, and ileus.Topics covered in this section:13.1Opioid‐induced pruritus is a common problem, with reported incidences between 2% and 10% for intravenous morphine.Naloxone has a mixed track record in pediatric perioperative care. West et al found no effect on itch in a randomized controlled pediatric trial of naloxone/morphine admixture in PCA.Recommendation: Naloxone infusion is helpful in treating and possibly preventing opioid‐induced pruritus.Strength of evidence: A.Recommendation: Expert consensus supports the use of nalbuphine although there is conflicting evidence concerning its effectiveness at this time.Strength of evidence: C.13.2There are many studies of perioperative nausea and vomiting in children, but few evaluating the effect of opioid on the incidence of perioperative nausea and vomiting. Most of these have been studies in surgical populations with a high incidence of nausea and vomiting such as tonsillectomy and adenoidectomy or strabismus surgery. Perioperative opioids are known to increase postoperative nausea and vomiting when compared to nonsteroidal anti‐inflammatory drugs.Similarly in some instances the same studies as mentioned for investigation of pruritus, the use of low‐dose continuous naloxone infusion has been studied for the prevention of nausea and vomiting. A randomized controlled trial of pediatric patients using postoperative PCA found less nausea with 0.25 mcg/kg/h naloxone infusion when compared to placebo. A dose finding study involving 59 pediatric patients found that infusion rates greater than or equal to 1 mcg/kg/h led to significantly less nausea than lower infusion rates.Recommendation: Opioid use should be minimized where possible to decrease the incidence of nausea and vomiting (see section on Impact of Adjunctive Medications on Opioid Dosing and Side Effects for specific medication recommendations).Strength of evidence: A.Recommendation: Naloxone infusion should be considered for intravenous opioid therapy for the prevention or treatment of nausea and vomiting.Strength of evidence: A.Recommendation: It is reasonable to consider common anti‐emetic medications for the treatment or prevention of nausea and vomiting while on intravenous opioid therapy. Preference should be for nonsedating medications.Strength of evidence: A.13.3A common complication of opioids in both the acute and chronic care setting is slowing of bowel motility and specifically constipation or ileus. In the acute care setting, this can result in significant morbidity and delayed discharge. Postoperative opioid‐related decreased bowel motility or ileus is well documented in the adult populationRecommendation: Postoperative opioid‐induced ileus may be improved with methylnaltrexone in infants and children.Strength of evidence: B.14http://www.pedsanesthesia.org) as well as peer reviewed publication.The role of opioids in the treatment of pediatric perioperative pain is evolving, and professional as well as public concern about their appropriate application is currently at a high point. In spite of these concerns, opioids remain a part of the perioperative pain treatment armamentarium. These recommendations have been formulated as a guide to reinforce current concepts of safe and appropriate use of these potent medications. We do not present them as a comprehensive guide for all patient encounters, but rather as a specific set of recommendations for practice involving specific situations where opioids are employed. To the greatest extent possible we have utilized published evidence to formulate these recommendations however it is clear that many of these recommendations lack sufficient evidence to make firm, evidence‐based conclusions. We hope that researchers involved in pediatric pain management will utilize some of the discussions and conclusions as a guide for future clinical trials and outcome analysis. The taskforce involved in these recommendations will update them every 2 years and disseminate the updated recommendations through the SPA Website (Joseph P. Cravero is a Section Editor at Pediatric Anesthesia; Lynne Maxwell is an Associate Editor at Pediatric Anesthesia; Terri Voepel‐Lewis is an Associate Editor at Pediatric Anesthesia.No IRB approval was required or obtained.


The longevity for people with intellectual disability (ID) has significantly increased in developed countries during the past decades. Consequently, the incidence of cancer is expected to increase in this group. The aim of the present study was to investigate the prescription of pain medication in older cancer patients with intellectual disability (ID) compared to older patients in the general population, surviving or living with a cancer diagnosis.n = 7936). For comparisons, we used a referent cohort, one-to-one matched with the general population by year of birth and sex . People with at least one diagnosis of cancer during 2002–2012 were identified using the Swedish National Patient Register, resulting in 555 cancer patients with ID and 877 cancer patients from the general population. These two cohorts of cancer patients were compared with respect to prescription of pain medication for the period 2006–2012. Outcome data were aggregated so that each patient was categorized as either having or not having at least one prescription of each investigated drug group during the study period, and relative risks (RRs) for prescription were estimated for prescription in the ID cohort vs the gPop cohort.This Swedish national registry-based study, included people with ID aged 55 years or older in 2012, and alive at the end of that year  and weak opioids (RR 0.63). They were, however, more likely to be prescribed paracetamol (RR 1.16), antidepressants (RR 2.09), anxiolytics (RR 2.84), and “other hypnotics, sedatives, and neuroleptics” (RR 1.39). No statistically significant differences between the two cohorts were found for strong opioids, antiepileptics, tricyclic antidepressants, or hypnotics and sedatives.In the studied cohort of older people surviving or living with cancer, prescriptions for pain-treatment was less common in patients with ID compared to the general population. These results may suggest that pain is not sufficiently treated among cancer patients with ID, a situation that most likely would compromise the quality of life in this group. Pain is a common symptom in cancer and thus a major problem. About one-third of cancer patients have pain at the time of diagnosis and two-thirds in the advanced stage of their disease , 2. In aSymptom assessment and the intensity of pain is preferably self-reported, measured using numerical rating scales . Self-reThe longevity for people with intellectual disability (ID) has significantly increased in developed countries due to better living conditions and medical advances . ConsequThe aim of the present study was to investigate the prescription of pain medication in older cancer patients with ID compared to older patients in the general population, surviving or living with a cancer diagnosis.This was a register-based study, using Swedish national registers both to identify the study cohorts and to collect data on cancer diagnoses and drug prescriptions.Swedish national registers used in the current studyThe LSS register [register  covers sNational Patient Register [National data on inpatient and outpatient specialist healthcare visits are collected in the Register . One priSwedish Prescribed Drug Register (PDR), which was established in July 2005. Prescribed drugs are registered coded according to the Anatomic Therapeutic Chemical (ATC) classification system at the time of dispensation.All dispensed prescribed medication in Sweden, corresponding to 84% of all drugs sold,  is recorThe Swedish National Board of Health and Welfare is the register holder for these three registers.Swedish Population Register contains data on all persons living in Sweden and includes data as name, age, gender, current residential address, and place of birth. Statistics Sweden is the responsible authority for this register, which is an extract of the census kept at the national tax offices.The n = 7936). Statistics Sweden provided us with a cohort of people from the general population (gPop cohort), one-to-one matched by sex and year of birth.Through the LSS register, we identified all people with at least one registered measure of service and support during 2012, aged at least 55 years and alive at the end of that year. These comprised the ID cohort (We used data from the NPR for the period 2002–2012 to identify cancer diagnoses (ICD-10 diagnoses C00-C97) during this time-period for these two cohorts. At least one diagnosis of cancer was found for 555 (7%) people in the ID cohort and 877 (11%) people in the gPop cohort .COX inhibitors (i.e. NSAIDs) excluding COX2 inhibitors and glucosamine, paracetamols, strong opioids, weak opioids, antiepileptics used for treatment of pain, and tricyclic antidepressants used for treatment of pain  during this time. In addition, as some of the pharmaceuticals investigated have other main indicators for prescription, we identified those with at least one diagnosis of epilepsy (G40 and G41 in ICD-10) or depression (F32 and F33).Analyses of dichotomous outcomes (e.g. having at least one prescription) were performed using generalized linear models (GLM), estimating relative risks (RRs) with 95% confidence intervals (CIs). Analyses were adjusted for diagnosis of pain, and for epilepsy and depression, when appropriate (e.g. diagnosis of epilepsy was adjusted for when investigating prescription of antiepileptic).p-value below 0.05 was considered statistically significant.All analyses were performed using IBM SPSS Statistics version 25.0 , Armonk, NY, USA). Analyses were only performed if the two groups to be compared comprised at least five observations. A two-sided Cancer patients with ID were almost three times more likely than those in the gPop cohort to have at least one prescription of anxiolytics and more than twice as likely to have a prescription of antidepressants Table . The latOlder cancer patients with ID were less likely to receive prescriptions for pain medications compared with their age-peers in the general population. This is in concordance with previous studies where we have reported that in general , 32 as wFurthermore, in our study, cancer patients in the ID cohort were more likely to be prescribed anxiolytics and antidepressants than those in the gPop cohort. Some of these medications are being prescribed for challenging behaviour either due to undiagnosed mental illness or poorly recognized pain , 38. PreSymptom-assessment is hampered in patients with ID due to communication difficulties. Low-level reports of pain are perhaps due to communication challenges rather than absence of pain and the misconception that people with ID are insensitive to pain or considered to have a higher pain threshold . InterprIn the present study, we used the NPR to identify cancers in both the ID and the gPop cohort. This register contains all diagnoses made in inpatient and outpatient specialist care in Sweden. As cancer diagnoses are rarely made in primary care only, we are likely to have identified all cases in the two cohorts. Even if the timeframe was restricted (2002–2012), the material consisted of a large cohort of 7936 older people with ID, whereof 555 with a cancer diagnosis.Unfortunately, as both the diagnostic data and the data on drug prescription are limited to a defined time period, we are not able to determine the date of the first diagnosis or the first prescription. Therefore, it would be interesting in future research to study the prescriptions before diagnosis and how prescriptions change over the course of cancer.The included ID cohort having received services and support for people with ID i.e. we considered as a proxy of ID and/or ASD. As the LSS register does not include any information on any diagnoses, this approach may have caused us to include people with ASD but without ID in the ID cohort. It has been approximated that during the period 2004–2010, the group of people with ASD receiving LSS support was about half the size of the group of people with ID receiving the same support . HoweverAnother weakness with this data source may be that people without LSS support, i.e. those with milder ID or with informal caregivers (e.g. parents or other relatives) only, are not included. However, several facts speak against such a selection. First, all people in the ID cohort were born before the LSS act was passed in 1993. While the LSS act states that people themselves have to apply for support, prior to 1993 people with ID diagnoses were more or less automatically registered for service and support. Having been so, they would continue to receive support even after the introduction of the LSS act. Second, the Swedish welfare system is constructed so that help is provided by the society rather than informal caregivers. Thus, it is unlikely that a person with ID would not have any type of service and support by the municipality. Thirdly, considering the age group studied, the number of people with parents alive and sufficiently healthy to take care of an adult child with ID, without any help from the municipality, is suspected to be small.Since the study-cohorts consist of people that have survived or are living with their cancer, thus excluding cancer diagnosis with a more dismal prognosis, the distribution of cancer diagnoses might be distorted and the true need for pain medication in patients with cancer and ID is most likely not reflected in our results. However, as the same is true for the gPop cohort (i.e. this too is a cohort of survivors), the cohort comparisons should not have been affected by the exclusion of more severe diagnoses.The Swedish PDR comprises data on all prescribed drugs dispensed at all pharmacies in Sweden. However, this register does not contain information about over-the-counter-drugs or drugs provided to patients in inpatient care. Among the drugs reported in the present study, only paracetamol can be purchased without a prescription, and the interference of over-the-counter purchases should, therefore, be minor.In the studied cohort of older people surviving or living with cancer, prescriptions for pain-treatment were less common in patients with ID compared to the general population. These results may suggest that pain is not sufficiently treated among cancer patients with ID, a situation that most likely would compromise the quality of life in this group. It is important to be sure pain is fully managed for people at all stages, and that behaviour which may be caused by pain, is recognized as pain and treated appropriately. There is a need for further investigations on how pain is assessed and treated in people with ID.


Posterior spinal fusion for adolescent idiopathic scoliosis is one of the most invasive surgical procedures performed in children and adolescents. Because of the extensive surgical incision and massive tissue trauma, posterior spinal fusion causes severe postoperative pain. Intravenous patient-controlled analgesia with opioids has been the mainstay of postoperative pain management in these patients. However, the use of systemic opioids is sometimes limited by opioid-related side effects, resulting in poor analgesia. To improve pain management while reducing opioid consumption and opioid-related complications, concurrent use of analgesics and analgesic modalities with different mechanisms of action seems to be rational. The efficacy of intrathecal opioids and nonsteroidal anti-inflammatory drugs as components of multimodal analgesia in scoliosis surgery has been well established. However, there is either controversy or insufficient evidence regarding the use of other analgesic methods, such as continuous ketamine infusion, perioperative oral gabapentin, acetaminophen, continuous wound infiltration of local anesthetics, a single dose of systemic dexamethasone, and lidocaine infusion in this patient population. Moreover, appropriate combinations of analgesics have not been established. The aim of this literature review is to provide detailed information of each analgesic technique so that clinicians can make appropriate choices regarding pain management in patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion. Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine defined as a lateral curvature of the spine in the coronal plane of more than 10° with no known cause and a predilection for adolescent girls . PosteriWe searched the PubMed, Web of Science, and Cochrane Library to identify articles on postoperative analgesia in patients undergoing correction surgery for AIS using the keywords “scoliosis,” “analgesia,” “postoperative,” and “children.” One hundred and sixty-two potentially eligible records were retrieved. Articles were selected based on their relevance to the topic and limited to humans and publication in the English language up to November 2017. Case reports, case series, systematic reviews, meta-analyses, and scientific abstracts were excluded. Given that our focus was on postoperative pain management in patients undergoing PSF for AIS, articles that did not include PSF were excluded. After excluding 126 studies , 31 studies were included in the review. Additional references were identified from reference lists in the publications yielded by our initial search. This article was not intended to be a systematic review, so we did not apply the strict methodology recommended by PRISMA [PCA allows patients to self-administer analgesics, mainly opioids, intermittently as needed. IV PCA has been used as the “gold standard” treatment in adults with moderate to severe pain. There is also evidence showing that PCA is safe and effective in children . MorphinIn summary, IV PCA with morphine is the best established and most widely used analgesia technique for scoliosis correction surgery. However, considering the high incidence of minor complications, such as postoperative nausea and vomiting (PONV) and pruritus, other techniques should be considered for the combination with IV PCA to minimize the use of morphine.n = 413) and IV PCA (n = 200), the averages of all pain scores and scores at 2, 4, 6, 8, 12, 24, 36, and 48 h were significantly better in the epidural analgesia group. However, the need for temporary cessation and permanent discontinuation of pain management was greater in the epidural analgesia group than in the IV PCA group  [n = 30, 7.3%), neurologic changes , and oversedation . The neurologic changes were mild asymmetric differences in the sensation of light touch on the lower extremities that resolved after temporary cessation of the epidural infusion. The most common reasons for permanent discontinuation of epidural analgesia were uncontrollable pain  and neurologic changes . There were no permanent neurologic injuries. In a small randomized controlled trial that compared epidural analgesia (n = 19) and IV PCA (n = 19), seven patients (37%) in the epidural analgesia group experienced poor analgesia and required a change to IV PCA within 24 h, although the average and lowest pain scores on postoperative days 2 and 3 were significantly lower in the epidural group [n = 3), insufficient analgesia (n = 3), and displacement of the epidural catheter (n = 2). The epidural catheter was removed on postoperative day 2 in one patient because of the development of a leak at the skin level. There was a further patient in whom a leak into the spinal space was suspected because of prolonged muscle weakness. It is likely that the efficacy and safety of epidural analgesia depend on the experience of health care providers. The frequency of the most common minor complications, such as PONV (in up to 85.7% of cases) and pruritus (in up to 42.9%), also varies depending on the report. Some studies have shown that epidural analgesia has a lower incidence of these adverse effects than IV PCA, while others have found no difference between the two techniques. There are some epidural analgesia-specific complications. In a randomized controlled study, 4 of 15 patients showed motor blockade of more than one  after receiving an initial bolus of epidural ropivacaine [Epidural analgesia is also widely used as an adjunct to IV PCA for postoperative analgesia in patients undergoing PSF for scoliosis , 40–43. ctively) . The mos PCA n = 0, the avivacaine . No epidIn summary, epidural analgesia is effective as a postoperative analgesia strategy and may provide better analgesia than IV PCA in patients undergoing PSF for AIS. However, it should be used with caution because there might be some drawbacks, such as the problem of inadequate assessment of motor function and the need to retain the urinary catheter.Intrathecal administration of opioids is another analgesic strategy –51. In mIn summary, ITO is effective for the reduction of opioid consumption and pain intensity in the early postoperative period after scoliosis correction surgery. Further, ITO is associated with less intraoperative blood loss. However, a higher ITO dose (morphine ≥ 20 μg/kg) should be avoided in view of the potential risk of respiratory depression.N-methyl-d-aspartate receptor and has an analgesic effect at subanesthetic doses. Recent meta-analyses have shown that supplemental perioperative ketamine decreases the intensity of postoperative pain and cumulative morphine consumption without increasing adverse events in patients undergoing various types of surgery [n = 16) or the same volume of saline (n = 18) [n = 29) had morphine consumption and sedation and pain scores that were similar to those in a saline-treated group (n = 21) for 96 h postoperatively [n = 17) decreased the cumulative morphine consumption by 20% when compared with a control group (n = 19) at 24 and 48 h after surgery. In that study, pain scores, sedation scale scores, and the incidence of PONV did not differ between the two groups, but antiemetic consumption was lower in the ketamine group [Ketamine is an anesthetic agent that works by binding to the  surgery , 53. The surgery . However(n = 18) . Intraopratively . One ranratively . In contne group . KetaminIn summary, there are insufficient data to support the routine use of ketamine as an adjuvant to postoperative analgesia in patients undergoing PSF for AIS. Further research is needed to determine the optimal timing, dose, and mode of the administration of ketamine when used for postoperative analgesia in these patients.n = 18) did not reduce postoperative cumulative morphine consumption or pain intensity in the 72 h following surgery when compared with placebo (n = 17) [n = 29) reduced the total morphine consumption in the recovery room and on postoperative days 1 and 2 by 30, 16, and 23%, respectively, in comparison with placebo (n = 30) [Gabapentin and pregabalin were originally developed as anticonvulsants and have been used widely to treat chronic neuropathic pain. Recent meta-analyses show that these agents are useful as adjuvant analgesia for reducing postoperative pain, including after spine surgery –57. Howe(n = 17) . In cont(n = 30) .Table 5RIn summary, gabapentin may have the potential to reduce pain after PSF in patients with AIS, but the optimal dosage and duration of administration are unclear. Furthermore, there is no strong evidence of the effectiveness of gabapentin as an analgesic adjuvant in this patient population, so further research is needed to confirm its efficacy.Addition of scheduled acetaminophen and/or nonsteroidal anti-inflammatory drugs (NSAIDs) to opioid-based analgesia improves analgesia and reduces opioid requirements, so preemptive use of these agents in adults is included in the recommendations of several guidelines , 34. TheIn summary, acetaminophen and NSAIDs should be added as analgesic adjuvants unless contraindicated. High-dose ketorolac should be avoided because it may interfere with bone healing.n = 129) and did not (n = 115) receive CWI, significantly fewer patients receiving CWI of bupivacaine 0.5%  required a continuous basal infusion of morphine (32.6% vs 85.2%), resulting in an overall reduction of opioid use on postoperative day 1 (18.9 mg vs 26.4 mg) [n = 62) or did not (n = 25) receive CWI, CWI of bupivacaine 0.25% (4 ml/h for 100 h subcutaneously) decreased the opioid consumption by 38% within 24 h after scoliosis correction surgery [Continuous wound infiltration (CWI), whereby local anesthetics are administered continuously by an elastomeric pump via a catheter inserted at the surgical wound site, is being used increasingly as part of multimodal analgesia. In a recent meta-analysis comparing the analgesic effect of CWI with that of epidural analgesia in patients undergoing abdominal surgery, postoperative pain scores were similar between the two groups, and the incidence of urinary retention was significantly lower in the CWI group . There a26.4 mg) . In that surgery . There w surgery .Table 7RIn summary, CWI seems to be a useful analgesic adjuvant in patients undergoing PSF for AIS. The currently available data are only from retrospective trials, so further prospective studies are needed to evaluate the safety and efficacy of CWI in this patient population.Diazepam is often used to prevent and treat muscle spasm after surgery for scoliosis. In general, diazepam is administered at a dose of 0.05–0.1 mg/kg every 6–12 h orally or IV as needed , 29, 32.Apart from the analgesics mentioned above, there are some agents that may improve analgesia, but they have not been studied in patients undergoing corrective surgery for AIS.The efficacy of glucocorticoids for reducing pain and inflammation after surgery has been explored. A meta-analysis that included 5796 surgical patients demonstrated that a single IV dose of dexamethasone (1.25–20 mg) was associated with reductions in postoperative pain scores, opioid consumption, need for rescue analgesia, and length of stay in the post-anesthesia care unit, as well as a prolonged time to the first analgesic dose in comparison with the control group, without increasing the risks of infection or delayed wound healing . AlthougIV lidocaine infusion has been shown to have analgesic and anti-inflammatory properties. A meta-analysis that included 2802 surgical patients showed that an IV infusion of lidocaine started at the time of surgery reduced the pain immediately after surgery (for up to 4 h) and until 24 h in patients undergoing laparoscopic or open abdominal surgery without increasing the risk of lidocaine-associated adverse effects, including death, arrhythmias, other cardiac conduction disorders, or signs of lidocaine toxicity . MoreoveAs mentioned earlier, the high incidence of opioid-related adverse effects, particularly PONV and pruritus, is problematic in the management of postoperative pain in patients undergoing PSF for AIS. There are several measures that can minimize these complications. Prophylactic administration of antiemetics is the mainstay for the prevention of PONV. For patients at high risk for PONV, several antiemetics with different mechanisms of action may be needed, given that none of these agents alone has adequate prophylactic potency . DexametPatients undergoing PSF often develop persistent postoperative pain (PPP) in addition to acute pain in the immediate postoperative period. A retrospective survey reported that 55 (52%) of 105 patients had ongoing pain at the time of discharge from hospital . In a reIn summary, a potent analgesic technique such as IV PCA or epidural anesthesia is needed for pain management after PSF for AIS. Given the complex causes of pain and the high incidence of opioid-related complications, a multimodal approach to improve analgesia and reduce opioid consumption is essential. The efficacy of intrathecal opioids and NSAIDs as components of multimodal analgesia in PSF is well established. However, there is not enough evidence for the use of other analgesics or analgesic modalities in this patient population. PPP is also problematic in this patient population. Although several preventive strategies have been proposed, no promising results have been obtained. Further studies are needed to establish the safety and efficacy of these techniques and to identify the optimal multimodal regimen.


Our previous randomized controlled trial (RCT) of children with obstructive sleep apnea (OSA) showed no significant differences between adenotonsillectomy (ATE) and adenotonsillomy (ATE) in improving nocturnal respiration and symptoms after one year. This is the continuous report with the evaluation of postoperative morbidity concerning bleeding and pain.n = 40) or ATT (n = 39). From one to ten days postoperatively, parents filled in a logbook with six pain-related outcomes . Peri- and postoperative bleeding were also registered.A double-blinded RCT including 79 children, aged 2–6 years, with moderate to severe OSA, randomized to either ATE , and first day the caregiver estimated pain VAS ≤ 5 . Two (5%) cases of postoperative bleeding occurred in the ATE group, one of which needed a return to theatre. No case of postoperative bleeding was seen in the ATT group.63 patients (80%) returned the logbook. There were significant differences between groups in only two of the six pain-related outcomes in favor of the ATT group; first day when the children graded themselves as pain free  and registered at ClinicalTrials.gov . Tonsil surgery remains one of the most commonly performed surgical procedures in children with more than half a million tonsillectomies performed annually in the US, and in Sweden where this study took place, more than 9000 pediatric tonsil operations were performed in 2013 , and sinThe present study is a continuous report for the same study population as in a recently published study where polysomnographic outcomes one year after adenotonsillectomy (ATE) versus adenotonsillotomy (ATT) were evaluated .The objective of this prospective, randomized double-blinded study was to evaluate and compare secondary outcomes such as postoperative morbidity concerning pain and bleeding after ATE and ATT in a pediatric population.z score > 1.67) and with no co-morbidities. Study participants were randomly assigned to one of two intervention groups; adenotonsillectomy (ATE) or adenotonsillotomy (ATT). The trial was originally designed to evaluate the primary outcome polysomnographic Apnea–Hypopnea Index and this has recently been presented , tonsil hypertrophy 3–4 according to Brodsky [resented . In the Randomization took place in the operating room (OR), where the surgeon opened a sealed envelope, randomly assigning study patients to one of the two intervention groups (ATE or ATT). 90 sealed envelopes were made before the study started, 45 for ATE and 45 for ATT, giving a 1:1 allocation ratio. No one but the surgeon and the staff in the OR knew which surgical method was performed. The surgeon did not meet the patients or parents after the operation, they were discharged by another doctor the day after surgery. Thus patients and care providers were double-blinded for intervention method, as was the researchers when analyzing the data.ATT was performed with coblation® (cold ablation) technique, with partial intracapsular removal of tonsil tissue until remaining tonsils reached the plane between the anterior and posterior tonsillar pillars, whereas in the ATE-group tonsils were bluntly extracapsulary dissected with cold steel technique. In both groups, adenoidectomy with cold steel (ring knife) was performed in the same session. Perioperative hemostasis was obtained with compression, bipolar diathermia or with the coblation device. Perioperative blood loss was documented by the surgeon in the OR (operation room).At discharge the day after surgery, caregivers were given a schedule for analgesics: for children < 17 kg ibuprofen 20–35 mg/kg/day, for children ≥ 17 kg diclofenak 2–3 mg/kg/day, and for all children paracetamol 80–100 mg/kg/day on day 1–3 after surgery and 65–75 mg/kg/day from day 4 and onward. Total treatment time was recommended to be as long as the child had signs of pain. No restrictions for food intake were given.Pain, analgesics given and food intake were registered in a logbook for each day, altogether ten days after surgery. The children’s pain was assessed three times daily from both children and caregivers. The children used the Faces Pain Scale-Revised (FPS-R), a standardized 6-faces Likert-type self-report pain scale scored 0–10 Fig. , validatThe groups were compared regarding six pain-related outcomes: (1) first day when the child estimated pain free (FPS-R 0); (2) first day when the caregiver estimated the child to be pain free (VAS 1); (3) first day when the child estimated pain FPS-R < 6; (4) first day when the caregiver estimated the child’s pain as VAS ≤ 5; (5) first day with no analgesic use; and (6) first day with normal diet  and normal type of food texture).Further, we evaluated two bleeding variables: (1) perioperative blood loss; (2) cases of postoperative bleeding.The outcomes 1–6, were determined using Kaplan–Meier analysis, with time-to-event, where event were defined as “free from pain”(child’s + caregiver’s report), “reduced pain”(child’s + caregiver’s report), “no analgesics needed” or “normal diet”. Log-Rank tests were used for comparison between groups.Perioperative blood loss in milliliter was analyzed by t-test for independent samples.The difference in cases of postoperative bleeding was analyzed using Fisher’s exact test.Data were analyzed with IBM SPSS Statistics 20.Seventy-nine patients (53 boys and 26 girls) were included and underwent surgical intervention, 40 in the ATE group and 39 in the ATT group, baseline characteristics were comparable for the two groups and are presented in Table For the pain-related outcomes Table , 63 patip < 0.001  55.1 ± 33.9 ml vs 28.6 ± 15.6 ml in the ATT group, p = 0.021(Log Rank Test), and also the first day the caregiver estimated the child´s pain reduced to VAS ≤ 5: 1 (0–4.5) after ATE and 0 (0–1) after ATT, p = 0.007 (Log Rank Test). For the other pain-related outcomes no significant differences between the groups were shown. Kaplan–Meier curves and p values from Log Rank Tests for pain outcomes are presented in Fig. Two of the six pain-related outcomes showed significant differences between surgical technique (ATE compared to ATT); the first day when the children graded themselves as pain free (FPS-R 0), which occurred at day median (interquartile range) 8 (5–10) in the ATE-group and day 5 3–8) in the ATT group, –8 in thep = 0.494), Table Postoperative bleeding occurred in two cases (5%) in the ATE group, one within 24 h after surgery needed repeated surgery, whereas the other was readmitted for 24 h observation 7 days after surgery, but needed no surgical intervention. In the ATT group, there was no case of postoperative hemorrhage. The difference between groups was not significant  8 (5–10) after ATE and day 5 (3–8) after ATT, and the first day caregiver reported reduction of the child’s pain to VAS ≤ 5 was day median (IQR) 1(1–4.5) for ATE and day 0 (1–2) for ATT. Other pain-related variables showed no significant differences between the groups in this small sample.Comparable results with our study were found in a review by Walton et al. , evaluatMoreover, Lister et al. performed a randomized blinded study in which the tonsil on one side was removed with electrosurgical TE, and the other side with microdebrider TT in the same individual, with significantly less pain on the TT side until postoperative day 10 . A propoThe surgical depth of TT tends to vary in previous studies, TTs were often performed all the way to the tonsillar capsule, which is deeper than in our study where TTs were less invasive, stopping at the level of the anterior and posterior pillars. Possibly, the depth of TT could be another factor correlating to the level of postoperative pain. Also, the technique for TT and TE varies in previous studies, making direct comparisons to our results difficult. For example, a randomized study compared cold technique TT  with cold steel TE in a pediatric population, showing less postoperative analgesic use in the TT group, but no differences in pain scoring .Our results demonstrate smaller group differences in pain-related outcomes than some previous non-blinded randomized studies , 21. ThiAnother possible explanation of the smaller group differences is that all the TEs in our study were performed with cold steel technique. A large Swedish study of > 18,000 children 1–18 years undergoing TE, reported less postoperative pain if TE was performed with cold technique than with hot technique . The stuA significant difference in perioperative blood loss was seen, with higher values in the ATE group, but this can be considered of little clinical relevance since the bleeding volumes were relatively small in both groups; 55.1 ± 33.9 ml for TE and 28.6 ± 15.6 ml for TT.Two cases (5%) of postoperative hemorrhage occurred in the ATE group, one (2.5%) primary (within 24 h) with a return to theatre and one secondary (7 days after surgery). No case of postoperative bleeding was reported in the ATT group.In comparison, another recent study compared TT and TE in children with OSA reported a postoperative bleeding frequency of 0.2% after TT and 2.9% after TE, of which 1.6% needed a return to theatre .Moreover, the aforementioned Swedish study by Elinder et al. of TE in > 18,000 children, reported a primary bleeding frequency of 2.0% for children undergoing tonsillectomy on OSA indication, with increased risk at older ages .The present study showed no significant difference between the groups regarding postoperative bleeding, which may be due to the small sample size.The primary strength of the present study is the randomized, double-blinded design, minimizing the risk of selection bias as well as interpreter- and expectation bias. Moreover, the young age of the children in the study, 2–6 years, is another strength since these are the age groups where tonsil surgery incidence peaks and, therefore, of high clinical interest. Only a few previous studies have included children as young as 2 years.However, the young age of the included children is also a weakness of the study, as there is no validated tool for assessing pain in children younger than four years, which was the case for 65% of the study population. We used the FPS-R, validated for children 4 years and older , and thiAnother weakness is that TT can be performed with several techniques and this study analyzed only a conservative ATT performed with coblation and, therefore, the generalizability can be limited. We chose coblation since it is the most common method for TT in Sweden . FurtherThe results from this RCT are in line with previous comparative studies between ATT and ATE. Children operated with ATT had significantly less postoperative pain in one-third of the outcomes, and less bleeding than ATE. However, as the differences in morbitiy between the surgical methods were minor the clinical significance is uncertain.


PONV occurred more frequently in the N group than in the C group (p < 0.05). Neither individual nor all risk factors were associated with PONV occurrence (p > 0.10). In conclusion, nefopam alone did not show a definite decrease in postoperative pain. It instead increased PONV regardless of risk factors.Arthroscopic rotator cuff repair causes acute postoperative hyperalgesia. Multimodal analgesia is preferable to opioid-based intravenous patient-controlled analgesia (IV-PCA) due to postoperative nausea and vomiting (PONV). We evaluated the effect of nefopam as a postoperative non-opioid analgesic after shoulder surgeries. A total of 180 adult patients were enrolled for arthroscopic rotator cuff repair. They were randomly assigned to nefopam (N) or control (C) groups and each group was reclassified according to the interscalene block (B) into NB, CB and NX, CX. Nefopam was applied at a constant dose intravenously during recovery. Pain scores were measured with a Visual Analogue Scale (VAS) before (T0), immediately after (T1), 30 min (T2) and 12 h (T3), 24 h (T4) and 48 h (T5) after surgery. There was no significant difference in demographic data. The overall VAS scores did not differ with regard to nefopam use, except for the NB group at T4 in intention to treat (ITT) analysis ( In general, even though postoperative pain after arthroscopic rotator cuff repair is less than that experienced in other types of orthopedic surgery ), pain control is required. Severe pain typically develops on the first postoperative day  and is oInterscalene block (ISB) definitely decreases postoperative pain. It is being more frequently used as a first-choice analgesic but it cannot be applied after all operations. Consequently, multimodal analgesic methods, such as oral agents or intravenous (IV) analgesics, are used instead . In this® 30 mg, Acupan inj. 20 mg, Pharmbio Korea Co., Ltd. Seoul., Korea) is one of them. Its mechanism has not yet been described in detail. However, nefopam affects postoperative pain not by acting on direct opioid receptors but by affecting triple neurotransmitter uptake inhibitors, such as norepinephrine, serotonin and the dopamine receptor [Nefopam hydrochloride  in arthroscopic shoulder surgery.We conducted a randomized controlled trial of patients with a rotator cuff tear that was less than 2 cm. These patients had visited Seoul St. Mary’s hospital. Ethical approval for this study  was provided by the Ethical Committee IRB (Institute Research Board) and participants provided informed consent before being part of this study.Patients with American Society of Anesthesiologists physical status (ASA-PS) I–II were enrolled in this study if they were scheduled for elective arthroscopic rotator cuff repair due to medium (1–3 cm) tear. The exclusion criteria included an age under 20 or over 70 years of age, severe renal or hepatic insufficiency, severe cardiac disease, seizures, epilepsy, taking monoamine oxidase inhibitors, glaucoma, cerebrovascular disease, allergies or hypersensitivity to nefopam. Patients who could not understand the visual analog scale (VAS) were also excluded. The enrolled patients were assigned into two groups according to a computer-generated randomized table of numbers. First, the groups were divided into those that were administered nefopam (N) and those who were not administered nefopam (C) before each group was divided into ISB (B) and not (X), respectively. That is, patients were divided into four groups, which included the following sub-division categories: only nefopam (NX), nefopam with ISB (NB), without nefopam and ISB (CX) and ISB without nefopam (CB). This random allocation process was conducted by two medical staffs who were not involved in the study outcome evaluations. They generated the random allocation sequence and were involved directly in drug preparation and ISB. In accordance with the orthopedic surgical method at our hospital, the operation was performed in two operating rooms. Furthermore, the orthopedic surgeon and medical staff members who assessed outcomes were blinded after being assigned to each group. Only the patients knew whether to use nefopam and ISB after being allocated according to the RCT  table.The severity of pain was assessed using a VAS from 0 (no pain) to 10 . Significant analgesic efficacy was defined as VAS being reduced by 2-fold or 30% compared with the VAS immediately before the assessment ,13,14. AThe primary outcomes were pain severity at T2 in the X subgroups (NX and CX) and at T4 in the B subgroups (NB and CB). The secondary outcomes were pain severity at the remaining time points , the number of rescue drugs administered and the relationship between PONV events and nefopam. The risk factors for PONV  were assessed using the Apfel score  and the p-value < 0.05 was considered to be statistically significant and statistical analyses were conducted using SAS Version 9.4 .To assess the extent of the pain reduction due to nefopam in shoulder surgery, 75 patients were recruited in each group to provide a study that had a power of 80% and an effect size of 0.5 according to our previous pilot study. Data are presented as means ± standard deviations, medians and interquartile range or numbers, including percentages based on each variables’ characteristics. Wilcoxon rank-sum test was performed for continuous variables and Chi-square test or Fischer’s exact test was performed for categorical variables. The relationship between nefopam and baseline risk factors was analyzed by logistic regression. A A total of 180 patients were enrolled without exclusion. After allocation, three in the NB group (assigned to ISB) were excluded due to them missing a nefopam infusion after surgery. During the follow-up period, six in the C group (three in CB and three in CX) did not have their VAS checked and one in the NB group dropped out due to them needing an additional IV-PCA. Finally, among the remaining 170 patients, 84 in the C group and 86 in the group N were analyzed. A CONSORT  diagram explaining the flow of participants is shown in p > 0.05). There were no differences in ASA-PS classification, age, sex, height, or weight between the groups . The opep > 0.1) (The median VAS score was 3 or less in both the N and C subgroups regardless of ISB. There were no significant differences in the VAS score between the N and C groups regardless of ISB (p > 0.1) . The maxp > 0.1) . There was no significant difference in VAS between the groups according to sex .p = 0.058). However, this p-value nearly reached statistical significance. In the per-protocol (PP) analysis, the p-values were also found to be significant (p = 0.037) (p = 0.03)  . In othe = 0.03) . After a = 0.03) .p = 0.187)  .p = 0.023, There was no relation between the occurrence of PONV and the presence of individual and all PONV risk factors . Receivip = 0.058), although the Per Protocol (PP) analysis did indicate significant differences (p = 0.037) between N and C groups. This result was significant at the 1% level but not the 5% level. Based on this analysis, we recommend that further studies should focus on the early postoperative analgesic effect of nefopam. Similar to previous studies [p = 0.03), suggesting a continuous analgesic effect of nefopam postoperatively  (There were no significant differences between the N and C groups in the use of postoperative rescue drugs (= 0.187) . The timThe following factors may have affected our study. First, this study examined pain from arthroscopic shoulder surgery and did not include patients with severe pain who underwent more major orthopedic interventions, such as spinal surgery or total hip or knee replacement, which are associated with VAS scores greater than 7. Among the patients who received ISB, the VAS score remained below 4 during the entire postoperative period. Even among patients not receiving nerve block, the VAS score had an average that was less than 7. In addition, 24 h after surgery, the VAS score was less than 4 regardless of the use of a nerve block. Second, although arthroscopic shoulder surgery causes the worst pain within 24 h after surgery, the restriction of motion due to the shoulder immobilizer, an aspect of postoperative management, results in less pain than usual and the pain continues intermittently with a similar pain severity for a long time. Thus, we cannot clearly ascertain the analgesic effect of nefopam in contrast to other orthopedic surgeries . More dep = 0.023)  . We can In this study, there were no acute postoperative analgesic or anti-hyperalgesic effects  when nefThere were some limitations of our study. First, there are limitations on the dose and usage of nefopam. In previous studies, nefopam was applied as a preoperative, intraoperative and postoperative continuous infusion through IV-PCA. In other words, using only the nefopam without opioids means that we are unable to prove the definite effect as an alternative or find a maximizing effect only through continuous administration. Since all patients were only given a limited dose for a short period of time, administering this low dose in the short term prevented us from demonstrating typical results. Further studies of the opioid-equivalent analgesic dosage and injection method will be needed. Second, in our orthopedics departments, rescue drugs are injected at regular time intervals whenever patients complain postoperative pain. Therefore, this does means that the patient’s pain status and evaluation are not directly measured by our rescue drug protocol. Therefore, PRNs and rescue drugs must be taken into account when considering objective indicators in future analysis.Arthroscopic rotator cuff repair produces pain that is less severe than other open orthopedic surgeries but is accompanied by early, intense and long-lasting postoperative pain. Despite the non-opioid, centrally acting analgesic action of nefopam, there are currently no definitive answers regarding its anti-hyperalgesic and analgesic effects when applied as a single agent preemptively and immediately after surgery in a certain dose. This result might be expected to be influenced by the dose and application method of nefopam. To confirm the efficacy of nefopam, the studies in the near future should analyze various timely appropriate methods of administering nefopam as a single agent (not a combination) rather than the continuous intraoperative and postoperative infusion approach of previous studies.This study was approved by Institutional review board (IRB) (Registration number: KC15OISI0446) and Clinical Research information service (CRIS) (Registration number: KCT00023254).