Updates From the Other Side of the Drape: Recent Advances in Multimodal Pain Management and Opioid Reduction Among Pediatric Surgical Patients.

As the management of acute pain for children undergoing surgical procedures as well as recognition of the short and long term risks of exposure to opioids has evolved, multimodal and multidisciplinary approaches using organized pathways has resulted in improved perioperative outcomes and patient satisfaction. In this 2023 symposium held at the American Academy of Pediatrics on Surgery meeting, a multidisciplinary discussion on current enhanced recovery after surgery pathways, alternate methods of effective pain control and education and advocacy efforts for opioid reduction were discussed, and highlights are included in this article.

Molecular detection of bacteria, placental inflammation, and neonatal sepsis risk.

OBJECTIVE: To identify bacteria in umbilical cord tissue and investigate the association with placental inflammation and neonatal sepsis risk score. STUDY DESIGN: Retrospective cohort study from 2017-2019. RNA was extracted from umbilical cord tissue and NanoString nCounter used to identify seven bacteria genera. Sepsis risk score was calculated using the Kaiser sepsis calculator. Placental histopathology was abstracted from medical records. RESULTS: Detection of bacterial RNA in the umbilical cord (n = 96/287) was associated with high-stage maternal and fetal acute placental inflammation (maternal 35.4% vs 22.5%, p = 0.03 and fetal 34.4% vs 19.4%, p < 0.01) and maternal vascular malperfusion (36.5% vs 23.0%, p = 0.02). Detection of Ureaplasma spp. was also associated with increased sepsis risk score (1.5/1000 [0.6, 8.6] vs 0.9/1000 [0.2, 2.9], p = 0.04). CONCLUSION: Umbilical cord bacterial pathogens are linked to fetal and maternal placental inflammation and maternal vascular malperfusion during gestation and associated with increased sepsis risk score in the neonate.

Association of placental histology and neonatal hematologic outcomes.

OBJECTIVE: The objective of the paper was to investigate how neonatal hematologic outcomes vary by major placental histopathology categories. STUDY DESIGN: Placental pathology reports from 5263 subjects were coded into individual placental lesions. Infant hematologic data (complete blood count parameters (n = 1945), transfusions, and phototherapy) were compared by placental pathologic phenotype. RESULTS: Red blood cell transfusions were more likely with maternal vascular malperfusion (MVM; OR 9.4 [2.2, 40.8]) and chronic inflammation (1.7 [1.04, 2.7]). White blood cells were decreased with MVM (10.6 103/µL vs 16.4) and elevated with acute inflammation (AI; 18.6 vs 11.9). Thrombocytopenia was associated with MVM (OR 3.7 [2.2, 5.1]) and fetal vascular malperfusion (FVM; OR 2.6 [1.5, 4.6]). Platelet transfusions were more likely with MVM (OR 8.3 [4.6, 15.0]) and FVM (OR 2.9 [1.4, 6.1]). Phototherapy was associated with MVM (OR 3.3 [2.7, 4.0]) and AI (OR 0.8 [0.6, 0.9]). CONCLUSIONS: Neonatal hematologic outcomes are associated with the in utero environment described by placental pathology.

Leftover Opioid Analgesics and Disposal Following Ambulatory Pediatric Surgeries in the Context of a Restrictive Opioid-Prescribing Policy.

BACKGROUND: Opioid analgesics are commonly prescribed for postoperative analgesia following pediatric surgery and often result in leftover opioid analgesics in the home. To reduce the volume of leftover opioids and overall community opioid burden, the State of Tennessee enacted a policy to reduce initial opioid prescribing to a 3-day supply for most acute pain incidents. We aimed to evaluate the extent of leftover opioid analgesics following pediatric ambulatory surgeries in the context of a state-mandated restrictive opioid-prescribing policy. We also aimed to evaluate opioid disposal rates, methods of disposal, and reasons for nondisposal. METHODS: Study personnel contacted the parents of 300 pediatric patients discharged with an opioid prescription following pediatric ambulatory surgery. Parents completed a retrospective telephone survey regarding opioid use and disposal. Data from the survey were combined with data from the medical record to evaluate proportion of opioid doses prescribed that were left over. RESULTS: The final analyzable sample of 185 patients (62% response rate) were prescribed a median of 12 opioid doses (interquartile range [IQR], 12-18), consumed 2 opioid doses (IQR, 0-4), and had 10 opioid doses left over (IQR, 7-13). Over 90% (n = 170 of 185) of parents reported they had leftover opioid analgesics, with 83% of prescribed doses left over. A significant proportion (29%, n = 54 of 185) of parents administered no prescribed opioids after surgery. Less than half (42%, n = 71 of 170) of parents disposed of the leftover opioid medication, most commonly by flushing down the toilet, pouring down the sink, or throwing in the garbage. Parents retaining leftover opioids (53%, n = 90 of 170) were most likely to keep them in an unlocked location (68%, n = 61 of 90). Parents described forgetfulness and worry that their child will experience pain in the future as primary reasons for not disposing of the leftover opioid medication. CONCLUSIONS: Despite Tennessee's policy aimed at reducing leftover opioids, a significant proportion of prescribed opioids were left over following pediatric ambulatory surgeries. A majority of parents did not engage in safe opioid disposal practices. Given the safety risks related to leftover opioids in the home, further interventions to improve disposal rates and tailor opioid prescribing are warranted after pediatric surgery.

Polymerase Gamma Mitochondrial DNA Depletion Syndrome Initially Presenting as Disproportionate Respiratory Distress in a Moderately Premature Neonate: A Case Report.

A 32-week premature infant presented with respiratory failure, later progressing to pulmonary hypertension (PH), liver failure, lactic acidosis, and encephalopathy. Using exome sequencing, this patient was diagnosed with a rare Polymerase Gamma (POLG)-related mitochondrial DNA (mtDNA) depletion syndrome. This case demonstrates that expanding the differential to uncommon diagnoses is important for complex infants, even in premature neonates whose condition may be explained partially by their gestational age (GA). It also shows that patients with complex neonatal diseases with significant family history may benefit from exome sequencing for diagnosis.

Financial and Clinical Ramifications of Introducing a Novel Pediatric Enhanced Recovery After Surgery Pathway for Pediatric Complex Hip Reconstructive Surgery.

BACKGROUND: Enhanced recovery after surgery pathways confer significant perioperative benefits to patients and are currently well described for adult patients undergoing a variety of surgical procedures. Robust data to support enhanced recovery pathway use in children are relatively lacking in the medical literature, though clinical benefits are reported in targeted pediatric surgical populations. Surgery for complex hip pathology in the adolescent patient is painful, often requiring prolonged courses of opioid analgesia. Postoperative opioid-related side effects may lead to prolonged recovery periods and suboptimal postoperative physical function. Excessive opioid use in the perioperative period is also a major risk factor for the development of opioid misuse in adolescents. Perioperative opioid reduction strategies in this vulnerable population will help to mitigate this risk. METHODS: A total of 85 adolescents undergoing complex hip reconstructive surgery were enrolled into an enhanced recovery after surgery pathway (October 2015 to December 2018) and were compared with 110 patients undergoing similar procedures in previous years (March 2010 to September 2015). The primary outcome was total perioperative opioid consumption. Secondary outcomes included hospital length of stay, postoperative nausea, intraoperative blood loss, and other perioperative outcomes. Total cost of care and specific charge sectors were also assessed. Segmented regression was used to assess the effects of pathway implementation on outcomes, adjusting for potential confounders, including the preimplementation trend over time. RESULTS: Before pathway implementation, there was a significant downward trend over time in average perioperative opioid consumption (-0.10 mg total morphine equivalents/90 days; 95% confidence interval [CI], -0.20 to 0.00) and several secondary perioperative outcomes. However, there was no evidence that pathway implementation by itself significantly altered the prepathway trend in perioperative opioid consumption (ie, the preceding trend continued). For postanesthesia care unit time, the downward trend leveled off significantly (pre: -5.25 min/90 d; 95% CI, -6.13 to -4.36; post: 1.04 min/90 d; 95% CI, -0.47 to 2.56; Change: 6.29; 95% CI, 4.53-8.06). Clinical, laboratory, pharmacy, operating room, and total charges were significantly associated with pathway implementation. There was no evidence that pathway implementation significantly altered the prepathway trend in other secondary outcomes. CONCLUSIONS: The impacts of our pediatric enhanced recovery pathway for adolescents undergoing complex hip reconstruction are consistent with the ongoing improvement in perioperative metrics at our institution but are difficult to distinguish from the impacts of other initiatives and evolving practice patterns in a pragmatic setting. The ERAS pathway helped codify and organize this new pattern of care, promoting multidisciplinary evidence-based care patterns and sustaining positive preexisting trends in financial and clinical metrics.

Child Pain Intensity and Parental Attitudes toward Complementary and Alternative Medicine Predict Post-Tonsillectomy Analgesic Use.

Parental attitudes regarding pain interventions and perceptions of their child's pain intensity likely influence the decision to administer postoperative analgesics. Our study examined the impact of daily fluctuations in child pain intensity and parental attitudes regarding complementary and alternative medicine (CAM) on analgesic administration following pediatric tonsillectomy. Parents of children undergoing tonsillectomy (n = 33) completed a survey assessing CAM attitudes and a 7-day postoperative electronic daily diary to record their child's daily pain intensity and analgesic medications (acetaminophen, ibuprofen, or oxycodone). Generalized linear mixed models with Poisson distributions evaluated the effects of within-person (child's daily pain intensity) and between-person (average postoperative pain, parental CAM attitudes) components on the number of medication doses administered. Higher daily pain intensity was associated with more oxycodone doses administered on a given day, but not acetaminophen or ibuprofen. Positive parental CAM attitudes were associated with less oxycodone use, beyond the variations accounted for by the child's daily pain intensity and average postoperative pain. Both parental CAM attitudes and their child's daily pain intensity were independently associated with parental decisions to administer opioids following tonsillectomy. Understanding factors influencing individual variability in analgesic use could help optimize children's postoperative pain management.

Variation Between and Within Hospitals in Single Injection Caudal Local Anesthetic Dose: A Report From the Pediatric Regional Anesthesia Network.

BACKGROUND: Given that variation exists in health care utilization, expenditure, and medical practice, there is a paucity of data on variation within the practice of anesthesia. The Pediatric Regional Anesthesia Network (PRAN) data lend itself to explore whether different medical practice patterns exist and if there are nerve blocks with more local anesthetic dosing variation than others. The primary aim of this study was to quantify variation in single injection caudal block dosing, and the secondary aim was to explore possible causes for variation (eg, number of blocks performed versus geographic location). METHODS: We queried the PRAN database for single injection caudal blocks in children <1 year of age. Data were analyzed for local anesthetic dose, variation within and across institutions, and possible causes. RESULTS: Mean dose of bupivacaine equivalents per kilogram (BE·kg) among sites ranged from 1.39 to 2.22 with an interdecile range (IDR) containing the mid 80% of all doses ranging from 0.21 to 1.48. Mean dose (BE·kg) was associated with site, age, weight, and local anesthetic used (all P < .0001). Cohen's F effect size estimate was 10 times higher for site (0.65) than for age (0.05) or weight (0.02). Variation (IDR) was not related to number of blocks done at each site (P = .23). Mean volume per kilogram was 0.9± ± 0.2 (mean ± ±standard deviation) and was more strongly associated with site (Cohen's F 0.3) than age (0.04) or weight (0.07). CONCLUSIONS: Wide variation in caudal local anesthetic dosing and administered volume exists. This variation is independent of the number of cases performed at each center but rather is determined by study site (ie, variation between centers) with considerable additional variation within study centers, suggesting additional variability dependent on individual practitioners. While there are legitimate reasons to vary dosing, the current approach is inconsistent and not supported by strong evidence over giving a standardized dose.

Cord blood alpha klotho is decreased in small for gestational age preterm infants with placental lesions of accelerated aging.

BACKGROUND: Intrauterine growth restriction is often accompanied by placental vascular disease, of which histologic maternal vascular malperfusion is prominent. Maternal vascular malperfusion is characterized by accelerated villous maturation consistent with placental aging. Alpha klotho is an anti-aging protein produced by the placenta. We hypothesize that cord blood alpha klotho varies with maternal vascular malperfusion and small for gestational age infants through dysregulated angiogenesis. METHODS: Nested case-control study of 54 preterm infants (N = 22 small for gestational age infants, 32 appropriate for gestational age infants, mean gestational age = 33.7 ±â€¯2.7 weeks) and validation sample (N = 39) from a longitudinal birth cohort at Prentice Women's Hospital, Chicago, IL. Cord blood alpha klotho was measured via enzyme-linked immunoassay; concentrations were linked to multiplex data of cord blood angiogenic growth factors. RESULTS: Median cord blood alpha klotho was decreased in small for gestational age infants (1200 [859, 2083] pg/mL) versus controls (3193 [1703, 3963] pg/mL; p < 0.01) and with severe maternal vascular malperfusion (1170 [760, 2645] pg/mL; P < 0.01), consistent with validation sample. Alpha klotho was decreased with maternal vascular malperfusion sublesions signifying accelerated villous maturation, including increased syncytial knots (1230 [805, 3606] pg/mL; p < 0.05) and distal villous hypoplasia (1170 [770, 3390] pg/mL; p < 0.05). Among 15 angiogenic markers, alpha klotho correlated directly with angiopoietin-2 (beta-coefficient = 2.6, p = 0.01). CONCLUSIONS: Cord blood alpha klotho is decreased with small for gestational infants and maternal vascular malperfusion sublesions of accelerated placental villous maturation, and correlated with angiopoietin-2. Alpha klotho may play a role in vascular-mediated accelerated placental aging leading to intrauterine growth restriction.

Individual short-acting opioids and the risk of opioid-related adverse events in adolescents.

PURPOSE: Hydrocodone, codeine, oxycodone, and tramadol are frequently prescribed to adolescents for moderate pain related to minor trauma or dental, surgical, or medical procedures. Pharmacokinetic and pharmacodynamic differences between these opioids could affect their relative safety. We aimed to compare occurrence of opioid-related adverse events in adolescents without cancer or other severe conditions taking hydrocodone, codeine, oxycodone, and tramadol. METHODS: Retrospective cohort study of 201 940 Tennessee Medicaid enrollees 12 to 17 years of age without cancer, other severe conditions, or evidence of substance abuse with 529 731 filled prescriptions for study opioids. Adverse events were defined as an emergency department visit, hospital admission, or death related to opioid use, confirmed by medical record review. Serious events had opioid-related escalation of care, hospitalization, or death. Propensity-score adjusted hazard ratios (HRs) were calculated with hydrocodone as the reference category. RESULTS: The incidence of opioid-related adverse events per 10 000 person-years of opioid exposure was 97.5 for hydrocodone (127 events/13 026 person-years), 91.2 for codeine (58/6,359), 229.7 for oxycodone (43/1,872), and 317.7 for tramadol (47/1479). The HRs for tramadol in comparison with hydrocodone for all and serious events were 2.98 (2.03-4.39) and 2.94 (1.81-4.75), respectively. Increased risk for tramadol was consistently present when the adverse events were restricted to those with neurologic-respiratory depression/other symptoms of possible overdose. CONCLUSION: In adolescents without cancer or other severe conditions prescribed short-acting opioids, the incidence of both all opioid-related adverse events and more serious events with opioid-related escalation of care, hospitalization, or death was consistently greater for tramadol than for hydrocodone.

Stellate Ganglion Catheter Effective for Treatment of Ventricular Tachycardia Storm in a Pediatric Patient on Extracorporeal Membrane Oxygenation: A Case Report.

Ventricular tachycardia (VT) storm, defined as recurrent VT requiring electrical cardioversion ≥3 times within 24 hours, is a rare presentation of long-QT syndrome. Pharmacologic autonomic modulation and/or left cardiac sympathetic denervation are established therapies in long-QT syndrome in adults but may not be effective or practical in the emergent treatment of VT storm. We present a novel case of a child with drug-refractory VT storm and prolonged QT requiring extracorporeal membrane oxygenation (ECMO) support. Continuous stellate ganglion blockade was remarkably effective in stabilizing his rhythm and should be considered in similar pediatric cases.

Pediatric Electroconvulsive Therapy: An Anesthesiologist's Perspective.

Proper planning and communication between psychiatry and anesthesiology teams is vital to conferring the greatest therapeutic benefit to children presenting for electroconvulsive therapy while minimizing risk. Anesthesia for the child undergoing electroconvulsive therapy should ideally provide deep hypnosis, ensure muscle relaxation to reduce injury, have minimal effect on seizure dynamics, and allow for rapid recovery to baseline neurologic and cardiopulmonary status. Unique factors for pediatric electroconvulsive therapy include the potential need for preoperative anxiolytic and inhalational induction of anesthesia, which must be weighed against the detrimental effects of anesthetic agents on the evoked seizure quality required for a successful treatment.

Outpatient Opioid Prescriptions for Children and Opioid-Related Adverse Events.

BACKGROUND AND OBJECTIVES: Little is known about opioid prescribing for children without severe conditions. We studied the prevalence of and indications for outpatient opioid prescriptions and the incidence of opioid-related adverse events in this population. METHODS: This retrospective cohort study between 1999 and 2014 included Tennessee Medicaid children and adolescents aged 2 to 17 without major chronic diseases, prolonged hospitalization, institutional residence, or evidence of a substance use disorder. We estimated the annual prevalence of outpatient opioid prescriptions and incidence of opioid-related adverse events, defined as an emergency department visit, hospitalization, or death related to an opioid adverse effect. RESULTS: There were 1 362 503 outpatient opioid prescriptions; the annual mean prevalence of opioid prescriptions was 15.0%. The most common opioid indications were dental procedures (31.1% prescriptions), outpatient procedure and/or surgery (25.1%), trauma (18.1%), and infections (16.5%). There were 437 cases of opioid-related adverse events confirmed by medical record review; 88.6% were related to the child's prescription and 71.2% had no recorded evidence of deviation from the prescribed regimen. The cumulative incidence of opioid-related adverse events was 38.3 of 100 000 prescriptions. Adverse events increased with age (incidence rate ratio = 2.22; 95% confidence interval, 1.67-2.96; 12-17 vs 2-5 years of age) and higher opioid doses (incidence rate ratio = 1.86 [1.45-2.39]; upper versus lower dose tertiles). CONCLUSIONS: Children without severe conditions enrolled in Tennessee Medicaid frequently filled outpatient opioid prescriptions for acute, self-limited conditions. One of every 2611 study opioid prescriptions was followed by an opioid-related adverse event (71.2% of which were related to therapeutic use of the prescribed opioid).

Anesthetic considerations for pediatric electroconvulsive therapy.

Electroconvulsive therapy is being used more frequently in the treatment of many chronic and acute psychiatric illnesses in children. The most common psychiatric indications for pediatric electroconvulsive therapy are refractory depression, bipolar disorder, schizophrenia, catatonia, and autism. In addition, a relatively new indication is the treatment of pediatric refractory status epilepticus. The anesthesiologist may be called upon to assist in the care of this challenging and vulnerable patient population. Unique factors for pediatric electroconvulsive therapy include the potential need for preoperative anxiolytic and inhalational induction of anesthesia, which must be weighed against the detrimental effects of anesthetic agents on the evoked seizure quality required for a successful treatment. Dexmedetomidine is likely the most appropriate preoperative anxiolytic as oral benzodiazepines are relatively contraindicated. Methohexital, though becoming less available at many institutions, remains the gold standard for induction of anesthesia for pediatric electroconvulsive therapy though ketamine, propofol, and sevoflurane are becoming increasingly viable options. Proper planning and communication between the multidisciplinary teams involved in the care of children presenting for electroconvulsive therapy treatments is vital to mitigating risks and achieving the greatest therapeutic benefit.