Single-Dose Intraoperative Methadone for Pain Management in Pediatric Tonsillectomy: A Randomized Double Blind Clinical Trial.

BACKGROUND: More than 500,000 elective tonsillectomies are performed in US children annually. Pain after pediatric tonsillectomy is common, often severe, and undertreated. There is no consensus on the optimal management of perioperative tonsillectomy pain. Methadone, with an elimination half-life of 1-2 days, has a longer duration of effect than short-duration opioids such as fentanyl. The primary objective of this study was to investigate the intraoperative use of methadone for pediatric tonsillectomy. It tested the hypothesis that methadone would result in less postoperative opioid use compared with short-duration opioids in children post-tonsillectomy. METHODS: This double-bind, randomized, parallel group trial in children (3-17 years) undergoing tonsillectomy compared single-dose intravenous methadone (0.1 mg/kg then 0.15 mg/kg age-ideal body weight, in a dose escalation paradigm) versus as-needed short-duration opioid (fentanyl) controls. Opioid use, pain, and side effects were assessed in-hospital and 7 days postoperatively via electronic surveys. The primary outcome was total 7-day opioid use in oral morphine equivalents per kilogram (OME/kg). Secondary outcomes were opioid use in the Post-Anesthesia Care Unit (PACU), daily pain scores, and total number of 7-day opioid doses used. RESULTS: Data analysis included 60 children (20/group), age 5.9±3.7 years (mean±SD; median 4, range 3-17). Total 7-day opioid use (OME/kg median [interquartile range]) was 1.5 [1.2,2.1] in controls, 0.9 [0.1,1.4] after methadone 0.1 mg/kg (P=0.045), and 0.5 [0,1.4] after methadone 0.15 mg/kg (P=0.023). PACU opioid use (OME/kg) in controls was 0.15 [0.1,0.3], 0.04 [0,0.1] after methadone 0.1 mg/kg (P=0.061) and 0.0 [0,0.1] after methadone 0.15mg/kg (P=0.021). Postoperative pain scores were not different between groups. No serious opioid-related adverse events occurred. CONCLUSIONS: This small initial study in children undergoing tonsillectomy found that single-dose intraoperative methadone at 0.15 mg/kg age ideal body weight was opioid-sparing compared with intermittent fentanyl.

Evaluation of Analgesic Practice Changes Following the Nuss Procedure in Pediatric Patients.

INTRODUCTION: Pectus excavatum repair by the Nuss procedure results in severe postoperative pain. Regional blocks and intercostal nerve cryoablation (INC) have emerged as potential strategies to manage analgesia. This study compares pain-related outcomes following these perioperative interventions. METHODS: We reviewed charts of patients <18 y who underwent the Nuss procedure at Duke Children's Hospital from July 2018 to June 2022. Patients were divided into three groups by analgesic strategy: no block, regional catheters, or INC, representing the chronologic change in our practice. The primary outcome was total and daily in-hospital opioid utilization measured by oral morphine equivalents (OMEs). Secondary outcomes included average daily pain scores, length of stay, opioid refills after discharge, and complications. RESULTS: Twenty-one patients were included and analyzed: no block (n = 6), regional catheters (n = 7), and INC (n = 8). INC-treated patients required significantly lower total postoperative, in-hospital OMEs (64 ± 47 [mean ± standard deviation]) than those with no block (270 ± 217, P = 0.04) or those with regional catheters (273 ± 176, P = 0.03). INC was associated with longer average operative times (161 ± 36 min) than no block (105 ± 21 min, P = 0.005) or regional catheters (90 ± 11 min, P < 0.001). INC-treated patients had shorter hospital length of stays (median 68 h) than those with regional catheters (median 74 h, P = 0.006). CONCLUSIONS: INC was associated with longer operative times but decreased in-hospital OMEs when compared to bilateral regional block catheters and multimodal analgesia alone.

What we know and what we don't know about the perioperative use of methadone in children and adolescents.

Postoperative pain control is essential to optimizing patient outcomes, improving satisfaction, and allowing patients to resume their baseline functional activities. Methadone, a synthetic mu-opioid agonist, has multiple pharmacologic properties that may be optimal for perioperative use. Compared to other opioids, methadone has a longer duration of action, rapid onset, extended dosing intervals, high oral bioavailability, low cost, lack of active metabolites, and action on multiple receptors. The current literature examining the use of methadone in the perioperative care of children and adolescents is limited and most often reported within the context of spine or cardiothoracic surgery. Overall, these studies support the hypothesis that perioperative methadone in pediatric patients may decrease postoperative pain, opioid consumption, length-of-stay, and the incidence of some opioid-related side effects, like constipation and urinary retention. A variety of protocols for the perioperative use of methadone have been described, including a single intraoperative dose as well as multiple small doses within multimodal pain protocols. The superiority of these protocols has not been established. Like all opioids, methadone has a side effect profile which includes nausea, vomiting, reduced GI motility, sedation, and respiratory depression at high doses. There is also a concern that it can cause QTc prolongation in patients. The primary aim of this educational review is to examine the pharmacologic data, published perioperative protocols, dosing considerations, and risks and benefits associated with inclusion of methadone in analgesic regimens for surgical patients. A secondary aim is to introduce opportunities for research around the perioperative use of methadone in children and adolescents. Based on our review, we would prioritize establishing optimal procedure-specific methadone protocols, determining generalizability for use in routine pediatric surgeries, and investigating methadone safety and efficacy prospectively as the primary opioid for pain management in the postanesthesia care unit or postsurgical floors.

Analgesic Effects of a Novel Combination of Regional Anesthesia After Pediatric Cardiac Surgery: A Retrospective Cohort Study.

OBJECTIVE: The objective of this study was to determine whether the use of regional anesthesia in children undergoing congenital heart surgery was associated with differences in outcomes when compared to surgeon-delivered local anesthetic wound infiltration. DESIGN: A retrospective cohort study. SETTING: At a single pediatric tertiary care center. PARTICIPANTS: Pediatric patients who underwent primary repair of septal defects between January 1, 2018, and March 31, 2022. INTERVENTIONS: The patients were grouped by whether they received surgeon-delivered local anesthetic wound infiltration or bilateral pectointercostal fascial blocks (PIFBs) and a unilateral rectus sheath block (RSB) on the side ipsilateral to the chest tube. MEASUREMENTS AND MAIN RESULTS: Using overlap propensity score-weighted models, the authors examined postoperative opioid requirements (morphine milliequivalents per kilogram), pain scores, length of stay, and time under general anesthesia (GA). Eighty-nine patients were eligible for inclusion and underwent analysis. In the first 12 hours postoperatively, the block group used fewer morphine equivalents per kilogram versus the infiltration group, 0.27 ± 0.2 v 0.64 ± 0.42, with a weighted estimated decrease of 0.39 morphine equivalents per kilogram (95% CI -0.52 to -0.25; p < 0.001), and had lower pain scores, 3.2 v 1.6, with a weighted estimated decrease of 1.7 (95% CI -2.3 to -1.1; p < 0.001). The length of stay and time under GA also were shorter in the block group with weighted estimated decreases of 22 hours (95% CI -33 to -11; p = 0.001) and 18 minutes (95% CI -34 to -2; p = 0.03), respectively. CONCLUSIONS: Bilateral PIFBs and a unilateral RSB on the side ipsilateral to the chest tube is a novel analgesic technique for sternotomy in pediatric patients. In this retrospective study, these interventions were associated with decreases in postoperative opioid use, pain scores, and hospital length of stay without prolonging time under GA.

Percutaneous endoscopic gastrostomy vs surgical gastrostomy in infants with congenital heart disease.

BACKGROUND: Infants with congenital heart disease often require feeding tube placement to supplement oral intake. Gastrostomy tubes may be placed by either surgical or percutaneous endoscopic methods, but there is currently no data comparing outcomes of these procedures in this population. AIMS: The aim of our retrospective study was to investigate the perioperative outcomes between the 2 groups to determine if there are clinically significant differences. METHODS: We reviewed the charts of all infants with congenital heart disease at a single academic institution having isolated surgical or percutaneous endoscopic gastrostomy tube placement from January 2011 to December 2015. Anesthetic time, defined by cumulative minimum alveolar concentration hours of exposure to volatile anesthetic, was the primary outcome. Operative time, intraoperative complications, and postoperative intensive care admissions were secondary outcomes. RESULTS: One hundred and one infants with congenital heart disease were included in this study. Anesthetic exposure was shorter in the endoscopic group than the surgical group (0.20 MAC-hours vs 0.56 MAC-hours, 95% confidence interval 0.23, 0.49, P < .001). Average operative times were also shorter in the endoscopic gastrostomy vs the surgical group (8 ± 0.7 minutes vs 35 ± 1.3 minutes, 95% confidence interval 23.7, 31.0, P < .001). Adjusting for prematurity and preoperative risk category, the surgical group was associated with a 3.45 fold increase in the likelihood of a higher level of care postoperatively (95% confidence interval 1.20, 9.90, P = .02). CONCLUSION: In infants with congenital heart disease, percutaneous endoscopic gastrostomy placement is associated with reduced anesthetic exposure and fewer postoperative intensive care unit admissions compared to surgical gastrostomy.

Epidemiologic Analysis of Elective Operative Procedures in Infants Less Than 6 Months of Age in the United States.

BACKGROUND: This study uses publicly available data to analyze the total number of elective, potentially deferrable operative procedures involving infants <6 months of age in the United States. We investigated the factors associated with the performance of these procedures in this population. METHODS: The State Ambulatory Surgery Database was used to identify patients in California, North Carolina, New York, and Utah during the years of 2007-2010 who were younger than 6 months of age at the time that they underwent outpatient (ambulatory) surgery. Operations that could reasonably be postponed until 6 months of age were classified as potentially deferrable procedures. Hernia repairs were analyzed separately from other deferrable procedures. Primary outcomes included the total number of elective procedures and the number and rates of potentially deferrable procedures per state per year in this population. RESULTS: Over the study period, a total of 27,540 procedures were identified as meeting inclusion criteria; of those, 7832 (28%) were classified as potentially deferrable, 4315 of which were hernia repairs. The average rates of potentially deferrable nonhernia procedures in California, North Carolina, New York, and Utah were 8.3, 43.8, 30.0, and 11.7 per 10,000 person-years, respectively. In multivariable analysis, private insurance (odds ratio [OR] = 1.36), self-pay status (OR = 1.50), and treatment in a different state (OR = 0.48-3.16) were independent predictors of a potentially deferrable procedure being performed on an infant younger than 6 months. CONCLUSIONS: Potentially deferrable procedures are still performed in infants <6 months of age. There appears to be significant variation in timing of these procedures among states. Insurance status and geography may be independent predictors of a procedure being potentially deferrable.

The impact of body mass index on the risk of high spinal block in parturients undergoing cesarean delivery: a retrospective cohort study.

PURPOSE: To investigate the hypothesis that the risk of high spinal block is not increased in obese parturients undergoing cesarean delivery compared to non-obese parturients. METHODS: This is a retrospective study at an academic center. We searched the perioperative database for women who underwent cesarean delivery under spinal or combined spinal epidural anesthesia with hyperbaric bupivacaine ≥10.5 mg. A body mass index (BMI) ≥30 kg/m2 was defined as obese. We categorized obesity into: obesity class I (BMI = 30-34.9 kg/m2), obesity class II (BMI = 35-39.9 kg/m2), obesity class III (BMI = 40-49.9 kg/m2), and super obese (BMI ≥50 kg/m2). The primary outcome was high spinal block defined as need to convert to general anesthesia within 20 min of spinal placement as a result of altered mental status, weakness, or respiratory distress resulting from the high block, or a recorded block height ≥T1. RESULTS: The analysis included 5015 women. High spinal blocks occurred in 29 patients (0.6%). The risk of high spinal was significantly different according to BMI (p = 0.025). In a multivariate model, BMI (p = 0.008) and cesarean delivery priority (p = 0.009) were associated with high blocks. BMI ≥50 kg/m2 was associated with greater odds of high block compared to BMI <30 kg/m2 [odds ratio (95% confidence interval): 6.3 (2.2, 18.5)]. Scheduled cesarean delivery was also associated with greater odds of high block compared with unscheduled delivery. CONCLUSIONS: At standard spinal doses of hyperbaric bupivacaine used in our practice (≥10.5 mg), there were greater odds of high block in those with BMI ≥50 kg/m2.

Evaluation of failed and high blocks associated with spinal anesthesia for Cesarean delivery following inadequate labour epidural: a retrospective cohort study.

PURPOSE: The purpose of this retrospective cohort study was to investigate factors associated with failed and high spinal blocks in patients who received spinal anesthesia for Cesarean delivery following a labour epidural that was inadequate for surgical anesthesia. METHODS: We searched our perioperative database for women with a labour epidural who received spinal or combined spinal-epidural anesthesia for Cesarean delivery due to the inadequacy of the existing epidural. The primary outcome was the occurrence of failed spinal blocks, and the secondary outcome was the occurrence of high blocks following spinal administration. RESULTS: Of the 263 patients in the analysis, there were 29 (11%) failed spinals and nine (3%) high spinals. There was a significant difference between patients with failed spinals and those with successful spinals with regards to receipt of an epidural top-up dose for Cesarean delivery within 30 min of the spinal, type of neuraxial block, body mass index, age, and dose of hyperbaric bupivacaine. In a multivariable analysis, only receipt of an epidural top-up dose was associated with failure (OR, 6.0; 95% CI, 2.1 to 17.0; P < 0.001). As for the risk of a high spinal, patient characteristics and block details were not different amongst patients, except for a younger age in those with a high block. CONCLUSIONS: Administration of spinal anesthesia within 30 min of an epidural top-up dose is associated with increased risk of failure. We speculate that this may be due in part to the presence of a large volume of local anesthetic in the epidural space, which may be mistaken for cerebrospinal fluid during spinal placement.

RéSUMé: OBJECTIF: L'objectif de cette étude de cohorte rétrospective était d'explorer les facteurs associés aux blocs rachidiens inefficaces ou élevés chez les patientes ayant reçu une rachianesthésie pour une césarienne après une péridurale pour le travail qui ne convenait pas à une anesthésie chirurgicale. MéTHODE: Nous avons effectué une recherche dans notre base de données périopératoire et recueilli les données des femmes ayant reçu une péridurale pour le travail et qui ont reçu une anesthésie rachidienne ou une péridurale et rachidienne combinée pour un accouchement par césarienne en raison de l'inefficacité de la péridurale en place. Le critère d'évaluation principal était la survenue de blocs rachidiens inadéquats, et le critère secondaire était la survenue de blocs élevés suite à l'administration rachidienne. RéSULTATS: Parmi les 263 patientes analysées, on a dénombré 29 (11 %) rachianesthésies inadéquates et neuf (3 %) rachianesthésies élevées. Une différence significative a été observée à plusieurs égards entre les patientes chez lesquelles la rachianesthésie avait échoué et celles chez lesquelles elle avait réussi, soit : la réception d'une dose complémentaire de péridurale pour la césarienne dans les 30 minutes avant la rachianesthésie, le type de bloc neuraxial, l'indice de masse corporel, l'âge et la dose de bupivacaïne hyperbare. Dans une analyse multivariée, seule la réception d'une dose supplémentaire de péridurale était associée à un échec (RC, 6,0; IC 95 %, 2,1 à 17,0; P < 0,001). En ce qui touche au risque de rachianesthésie élevée, les caractéristiques des patientes et les spécificités du bloc n'ont pas joué de rôle significatif chez les patientes, hormis l'âge plus jeune des femmes chez lesquelles le bloc était élevé. CONCLUSION: L'administration d'une rachianesthésie dans les 30 minutes suivant une dose péridurale supplémentaire est associée à un risque accru d'échec du bloc. Nous pensons que cela pourrait être en partie dû à la présence d'un important volume d'anesthésique local dans l'espace péridural, lequel pourrait être interprété comme du liquide céphalorachidien pendant la mise en place de la rachianesthésie.

Chronic Postsurgical Pain in Children and Adolescents: A Call for Action.

Chronic postsurgical pain (CPSP) affects a significant proportion of children and adolescents after major surgery and is a detriment to both short- and long-term recovery outcomes. While clinical characteristics and psychosocial risk factors for developing CPSP in children and adults are well established in the literature, there has been little progress on the prevention and management of CPSP after pediatric surgery. Limited evidence to support current pharmacologic approaches suggests a fundamentally new paradigm must be considered by clinicians to both conceptualize and address this adverse complication. This narrative review provides a comprehensive evaluation of both the known and emerging mechanisms that support our current understanding of CPSP. Additionally, we discuss the importance of optimizing perioperative analgesic strategies to mitigate CPSP based on individual patient risks. We highlight the importance of postoperative pain trajectories to identify those most at risk for developing CPSP, the early referral to multi-disciplinary pain clinics for comprehensive evaluation and treatment of CPSP, and additional work needed to differentiate CPSP characteristics from other chronic pain syndromes in children. Finally, we recognize ongoing challenges associated with the universal implementation of available knowledge about pediatric CPSP into practically useful care plans for clinicians.

The Pharmacological Treatment of Neuropathic Pain in Children.

The International Association for the Study of Pain (IASP) defines neuropathic pain as pain caused by a lesion or disease of the somatosensory nervous system. It is characterized as a clinical condition in which diagnostic studies reveal an underlying cause of an abnormality in the peripheral or central nervous system. Many common causes of neuropathic pain in adults are rare in children. The purpose of this focused narrative review is, to 1) provide an overview of neuropathic pain in children, 2) highlight unique considerations related to the diagnosis and mechanisms of neuropathic pain in children, and 3) perform a comprehensive analysis of the pharmacological treatments available. We emphasize that data for routine use of pharmacological agents in children with neuropathic pain are largely inferred from adult literature with little research performed on pediatric populations, yet have clear evidence of harms to pediatric patients. Based on these findings, we propose risk mitigation strategies such as utilizing topical treatments whenever possible, assessing pain phenotyping to guide drug class choice, and considering pharmaceuticals in the broader context of the multidisciplinary treatment of pediatric pain. Furthermore, we highlight important directions for future research on pediatric neuropathic pain treatment.

Impact of state legislation and institutional protocols on opioid prescribing practices following pediatric tonsillectomy.

Objectives: Tonsillectomy is a common pediatric surgery, and pain is an important consideration in recovery. Due to the opioid epidemic, individual states, medical societies, and institutions have all taken steps to limit postoperative opioids, yet few studies have examined the effect of these interventions on pediatric otolaryngology practices. The primary aim of this study was to characterize opioid prescribing practices following North Carolina state opioid legislation and targeted institutional changes. Methods: This single center retrospective cohort study included 1552 pediatric tonsillectomy patient records from 2014 to 2021. The primary outcome was number of oxycodone doses per prescription. This outcome was assessed over three time periods: (1) Before 2018 North Carolina opioid legislation. (2) Following legislation, before institutional changes. (3) After institutional opioid-specific protocols. Results: The mean (± standard deviation) number of doses per prescription in Periods 1, 2, and 3 was: 58 ± 53, range 4-493; 28 ± 36, range 3-488; and 23 ± 17, range 1-139, respectively. In the adjusted model, Periods 2 and 3 had lower doses by -41% (95% CI -49%, -32%) and -40% (95% CI -55%, -19%) compared to Period 1. After 2018 North Carolina legislation, dosage decreased by -9% (95% CI -13%, -5%) per year. Despite interventions, ongoing variability in prescription regimens remained in all periods. Conclusion: Legislative and institution specific opioid interventions was associated with a 40% decrease in oxycodone doses per prescription following pediatric tonsillectomy. While variability in opioid practices decreased post-interventions, it was not eliminated. Level of evidence: 3.

Successful Combination of Neuraxial and Regional Anesthesia in a Child With Advanced Spinal Muscular Atrophy Type 1 Receiving Maintenance Nusinersen Therapy: A Case Report.

Spinal muscular atrophy (SMA) is an autosomal recessive condition characterized by degeneration of the anterior horn cells of the spinal cord, which causes progressive muscle atrophy and weakness. SMA type 1 is the most common type and is associated with severe disability and early mortality. Concomitant restrictive respiratory physiology often manifests with significant implications for anesthetic management. Here, we describe a successful spinal anesthetic for orthopedic surgery in an SMA type 1 patient receiving intrathecal nusinersen maintenance therapy, an antisense oligonucleotide designed to increase expression of the survival motor neuron protein, and the first US Food and Drug Administration-approved drug to treat SMA.

Children And The Opioid Epidemic: Age-Stratified Exposures And Harms.

Using North Carolina Medicaid 2016-18 claims data, we found that approximately one in ten adolescents (10.8 percent) filled at least one opioid prescription per year. Dentists, advanced practice providers, and surgeons were common prescribers of opioids to children. In addition, half of children who experienced opioid-related adverse events had filled opioid prescriptions in the prior six months.

Frequency of hypoglycemia and its significance in chronic kidney disease.

BACKGROUND AND OBJECTIVES: This study set out to determine the incidence of hypoglycemia in patients with chronic kidney disease (CKD), with and without diabetes, and the association of hypoglycemia with mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective cohort analysis of 243,222 patients who had 2,040,206 glucose measurements and were cared for at the Veterans Health Administration. CKD was defined as an estimated GFR of <60 ml/min per 1.73 m(2). Hypoglycemia was set at <70 mg/dl. Mortality was measured 1 day after glucose measurement. RESULTS: The incidence of hypoglycemia was higher in patients with CKD versus without CKD. Among patients with diabetes, the rate was 10.72 versus 5.33 per 100 patient-months and among patients without diabetes was 3.46 versus 2.23 per 100 patient-months, for CKD versus no CKD, respectively. The odds of 1-d mortality were increased at all levels of hypoglycemia but attenuated in CKD versus no CKD. Adjusted odds ratios for 1-d mortality that were associated with glucose values of <50, 50 to 59, and 60 to 69 mg/dl, respectively, versus glucose of >or=70 mg/dl were 6.09, 4.10, and 1.85 for inpatient records from patients with CKD; 9.95, 3.79, and 2.54 for inpatients records from patients without CKD; 6.84, 3.28, and 3.98 for outpatient records from patients with CKD; and 13.28, 7.36, and 4.34 for outpatient records from patients without CKD. CONCLUSIONS: CKD is a risk for hypoglycemia, with or without diabetes. The excessive mortality associated with hypoglycemia makes this complication a significant threat to patient safety in CKD.

The frequency of hyperkalemia and its significance in chronic kidney disease.

BACKGROUND: Hyperkalemia is a potential threat to patient safety in chronic kidney disease (CKD). This study determined the incidence of hyperkalemia in CKD and whether it is associated with excess mortality. METHODS: This retrospective analysis of a national cohort comprised 2 103 422 records from 245 808 veterans with at least 1 hospitalization and at least 1 inpatient or outpatient serum potassium record during the fiscal year 2005. Chronic kidney disease and treatment with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers (blockers of the renin-angiotensin-aldosterone system [RAAS]) were the key predictors of hyperkalemia. Death within 1 day of a hyperkalemic event was the principal outcome. RESULTS: Of the 66 259 hyperkalemic events (3.2% of records), more occurred as inpatient events (n = 34 937 [52.7%]) than as outpatient events (n = 31 322 [47.3%]). The adjusted rate of hyperkalemia was higher in patients with CKD than in those without CKD among individuals treated with RAAS blockers (7.67 vs 2.30 per 100 patient-months; P < .001) and those without RAAS blocker treatment (8.22 vs 1.77 per 100 patient-months; P < .001). The adjusted odds ratio (OR) of death with a moderate (potassium, >or=5.5 and <6.0 mEq/L [to convert to mmol/L, multiply by 1.0]) and severe (potassium, >or=6.0 mEq/L) hyperkalemic event was highest with no CKD (OR, 10.32 and 31.64, respectively) vs stage 3 (OR, 5.35 and 19.52, respectively), stage 4 (OR, 5.73 and 11.56, respectively), or stage 5 (OR, 2.31 and 8.02, respectively) CKD, with all P < .001 vs normokalemia and no CKD. CONCLUSIONS: The risk of hyperkalemia is increased with CKD, and its occurrence increases the odds of mortality within 1 day of the event. These findings underscore the importance of this metabolic disturbance as a threat to patient safety in CKD.