Pain-related hospitalization and emergency room visit following initial analgesic prescription after outpatient surgery.

PURPOSE: Our study examined the association between outpatient postsurgical analgesic prescription and risk of insufficiently managed pain characterized by pain-associated hospital admission and emergency room (ER) visit. METHODS: Eligible individuals were children 1-17 years of age who filled an incident analgesic following an outpatient surgery during 2013-2018. Pain-associated hospital admission or ER visit were measured within 30 days following the outpatient surgical procedure. A hierarchical multivariable logistic regression model with patients nested under prescribers was fitted to test the association between incident analgesic prescription and risk of having pain-associated hospital admission or ER visit. RESULTS: Of 14 277 children meeting the inclusion criteria, 6224 (43.6%) received an incident opioid and 8053 (56.4%) received an incident non-opioid analgesic prescription respectively. There were a total of 523 (3.7%) children undergoing surgical procedures that had pain-related hospital admissions or ER visits with 5.1% initiated on non-opioid analgesics and 1.8% on opioid analgesics. The multilevel model indicated that initial opioid analgesic recipients were 32% less likely of having a pain-associated hospital admission or ER visit [aOR: 0.68 (95% CI: 0.3-0.8)]. CONCLUSION: Majority of postsurgical patients do not require additional pain management strategies. In the 3.7% of patients requiring additional pain management strategies, those initiated on non-opioid analgesics are more likely to have a pain-associated hospital admission or ER visit compared with their opioid recipient counterparts.

Ketamine for Pain in Sickle Cell Disease Reduces Opioid Usage.

CONTEXT: Pain attributable to sickle cell disease (SCD) is often unpredictable, recurrent, and requires complex treatments. Subanesthetic ketamine infusion has been studied in other diseases and disorders, but there is still limited data on its efficacy in pain management for SCD. OBJECTIVES: The primary objective is to determine if subanesthetic ketamine infusion reduces pain scores and opioid requirements in hospitalized pediatric patients with SCD. RESULTS: Forty-six admissions among 22 patients between February 2018 and December 2019 were analyzed. We observed decrease in pain scores within 24 hours of ketamine initiation in 34 of 46 admissions (mean pain score per patient before ketamine initiation: 2.2-9.7, mean pain score per patient after ketamine initiation: 0-9.7; P < .05). We observed a decrease in pain scores in the remaining 12 admissions after greater than 24 hours of ketamine initiation. Opioid usage declined after ketamine infusion, with a difference of means in oral morphine equivalents before and after ketamine of 122.8 mg/day. The side effects observed with ketamine infusion included hallucinations in 11 (23.9%) admissions. Only four (8.7%) admissions required cessation of the infusion due to side effects. The readmission rate at two weeks and four weeks after first ketamine infusion was the same (12.5%) at both time points. For all patients in the cohort, the introduction of ketamine into pain regimens did not reduce the number of admissions in the year following ketamine initiation relative to the year prior. CONCLUSION: In pediatric patients with SCD, subanesthetic ketamine was safe as a continuous infusion and effectively reduced both pain scores and opioid requirements.

Trends in Repeat Opioid Analgesic Prescription Utilization for Acute Pain in Children: 2013-2018.

OBJECTIVE: Our study examined the change in repeat opioid analgesic prescription trends in children and adolescents experiencing acute pain between 2013 and 2018. METHODS: Eligible individuals were children and adolescents between 1 and 17 years of age enrolled in a Medicaid Managed Care plan and filled an incident opioid analgesic prescription from 2013 to 2018. A repeat opioid prescription was defined as receiving a subsequent opioid prescription within 30 days from the end of the incident opioid prescription. A generalized linear regression analysis was conducted to examine changes in repeat opioid analgesic dispensing over time at quarterly intervals from January 1, 2013, to December 31, 2018. RESULTS: The cohort comprised 17,086 children and adolescents receiving an incident opioid analgesic. Of these, 1780 (10.4%) filled a repeat opioid analgesic prescription. There was a significant decline in the repeat opioid analgesic trend from 11.5% in Q1 2013 to 9.6% in Q4 2018. Stratified analyses by age, sex, and race and ethnicity in a sub-cohort of patients undergoing surgical procedures showed that a significant decline in repeat opioid utilization over time has been observed in all racial/ethnic groups stratified by age and sex, with the most significant decline found in non-Hispanic White children and Hispanic adolescents. At the end of the 6-year follow-up, the racial and ethnic variations in repeat opioid utilization associated with surgical procedures had significantly reduced in children yet persisted among adolescents. CONCLUSIONS: Approximately 10% of incident pediatric opioid analgesic recipients received a repeat opioid prescription. There has been a moderate but steady decline (∼7% per quarter) in repeat opioid analgesic utilization between 2013 and 2018.

Association Between Initial Opioid Prescription Duration and 30-Day Risk of Receiving Repeat Opioid Among Children.

OBJECTIVE: Our study evaluated the association between initial opioid prescription duration and receipt of a repeat opioid prescription in children. METHODS: Eligible individuals were children between 1 and 17 years of age who enrolled in a Medicaid Managed Care plan and filled an incident opioid prescription during 2013 to 2018. An incident prescription was defined as receipt of an opioid analgesic without a prior use for 12 months. A repeat opioid prescription was defined as receipt of a subsequent opioid prescription within 30 days since the end of incident opioid prescription. A hierarchical multivariable logistic regression model was fitted to test the association between incident opioid prescription duration and the likelihood of receiving a repeat prescription. RESULTS: The cohort consisted of 17,086 children receiving an incident opioid prescription in which 6272 (36.7%) received 1 to 3 days' supply, 8442 (49.4%) received 4 to 7 days' supply, 1434 (8.4%) received 8 to 10 days' supply, and 938 (5.5%) received >10 days' supply. Of these incident opioid recipients, 1780 (10.4%) filled a repeat opioid prescription. The multilevel model results indicated that, children receiving 4 to 7 days' supply (adjusted odds ratio [aOR]: 0.98 {0.9-1.1}), 8 to 10 days' supply (aOR: 1.03 [0.8-1.3]), and >10 days' supply (aOR: 0.85 [0.7-1.1]) had comparable likelihoods of receiving a repeat prescription as those receiving 1 to 3 days' supply. DISCUSSION: Nearly 10% of children who filled an opioid prescription for acute pain received a repeat prescription. Initial prescription duration was not associated with the risk of receiving a repeat prescription.

Intranasal Fentanyl Use in Neonates.

Background: The recent addition of intranasal medication options for procedural sedation and analgesia has decreased the need for additional painful procedures such as intravenous lines for medication administration. Intranasal fentanyl (INF) has been used in the prehospital setting, as well as in the emergency department for several years, and is increasingly utilized in other locations such as the neonatal intensive care unit (NICU). A paucity of data exists in these smallest children, so we sought to explore trends in INF use in our NICU. Objective: The objective of the study was to describe INF use in the NICU from December 2014 to December 2017. Design/Methods: A retrospective cohort study was conducted of patients receiving INF in the NICU of a large free-standing quaternary inner-city children's hospital from December 2014 to 2017. Demographic data were abstracted from the medical record including gestational age on administration, post-menstrual age, day of life on administration, sex, medication initial and total dose, reported indication, and documented adverse events. This study was approved by our local institutional review board. Results: A total of 54 patients received a total of 67 INF administrations: 32 women (59%), median day of life on administration = 57.1 (interquartile range [IQR] = 33.7-110.4), median weeks gestation = 26.0 (IQR = 24.1-36.1), post-menstrual age = 38.1 weeks (IQR = 33.1-45.4). Initial doses of medications were 1.49 µg/kg/dose INF (range = 0.5-2 µg/kg). Conclusions: Intranasal adjuncts are increasingly used in the NICU. Starting dose of INF is 1.5 µg/kg/dose, and typically, one dose is given.

Effect of Exogenous Antithrombin Administration on Anti-Xa Levels in Infants Treated With Enoxaparin.

OBJECTIVES: Determine the effect of exogenous antithrombin III administration on low molecular weight heparin anti-Xa levels in the context of enoxaparin dosing in infants. METHODS: A retrospective chart review of infants receiving concomitant antithrombin III and enoxaparin. The primary objective of this study was to determine the median change in anti-Xa level with antithrombin III supplementation. Secondary objectives were to analyze the median change in antithrombin III levels after administration of exogenous antithrombin III, the dosing of antithrombin III, and the dose of enoxaparin throughout therapy. For a safety analysis, any bleeding events were recorded. RESULTS: The study included 17 patients who received a total of 33 doses of antithrombin III. The median change in anti-Xa levels in infants receiving exogenous antithrombin III was 0.2 units/mL (p < 0.001). The median dose of antithrombin III was 50 units/kg and was administered when patients were receiving a median enoxaparin dose of 1.71 mg/kg. The median increase in antithrombin III levels was 16.5% (p < 0.001). CONCLUSIONS: These results demonstrated that administration of exogenous antithrombin III to infants who were being treated with enoxaparin results in a significant increase in anti-Xa levels. At this time, there is insufficient evidence to recommend routine administration of antithrombin III to infants on enoxaparin. However, antithrombin III supplementation could be considered a potential option for patients who are unable to adequately achieve therapeutic anti-Xa levels with enoxaparin alone.

Pharmaceutical considerations with conjoined twins.

Sharing of the vascular system in conjoined twins creates pharmaceutical dilemmas that require individualization of protocols. One of the major goals for the medical team is to determine how medications should be administered, dosed, and monitored in each set of conjoined twins. In order to achieve these goals, the team must determine the extent of shared circulation, volume of distribution, effectiveness of enteral absorption, renal clearance, and develop processes to ensure medication safety. In this article, we discuss unique challenges in medication practices in conjoined twins and present general principles that can be applied to determine optimal pharmaceutical strategies.

Phenobarbital population pharmacokinetics across the pediatric age spectrum.

OBJECTIVE: Phenobarbital is frequently used in pediatric patients for treatment and prophylaxis of seizures. Pharmacokinetic data for this patient population is lacking and would assist in dosing decisions. METHODS: A retrospective population pharmacokinetic analysis was designed for all pediatric patients <19 years of age initiated on phenobarbital at our institution from January 2011 to June 2017. Patients were included if they were initiated on intravenous or enteral phenobarbital for treatment or prophylaxis of seizures and had a serum phenobarbital concentration monitored while an inpatient. Data collection included the following: age, weight, height, gestational age, core body temperature, serum creatinine, blood urea nitrogen, aspartase aminotransferase, alanine aminotransferase, urine output over the prior 12 hours, phenobarbital doses and serum concentrations, and potential drug-drug interactions. Descriptive statistical methods were used to summarize the data. Pharmacokinetic analysis was performed with NONMEM and simulation was performed for doses of 10, 20, 30, and 40 mg kg-1  dose-1 , iv, followed by enteral doses of 3, 4, 5, and 6 mg kg-1  d-1 . RESULTS: A total of 355 patients (50.3% male, median gestational age 39 weeks (interquartile range [IQR] 35, 40), median age 0.28 years (IQR 0.06, 0.82). Median phenobarbital dose was enteral = 2.6 (IQR 1.9, 3.9) mg kg-1  dose-1 ; intravenous = 2.6 (IQR 2.2, 4.9) mg kg-1  dose-1 ) and mean serum concentration was 41.1 ± 23.9 mg/L at median 6.5 (IQR 2.9, 11.1) hours after a dose. A one-compartment proportional error model best fit the data where clearance and volume of distribution were allometrically scaled using fat-free mass. Significant covariates included serum creatinine, postmenstrual age, and drug-drug interactions on clearance, and age in years on volume of distribution. SIGNIFICANCE: Phenobarbital dosing of 30 mg kg-1  dose-1 ,iv, followed by 4 mg kg-1  d-1 had the highest probability of attaining a therapeutic concentration at 7 days. Postmenstrual age and drug-drug interactions should be incorporated into dosing decisions.

Evaluation of the Effects of Extracorporeal Membrane Oxygenation on Antiepileptic Drug Serum Concentrations in Pediatric Patients.

OBJECTIVES: Patients supported on extracorporeal membrane oxygenation (ECMO) have an increased incidence of seizures. Phenobarbital (PB) and fosphenytoin (fos-PHT) are common antiepileptic drugs (AEDs) used to manage seizures in the pediatric population; however, it is unknown what effect ECMO has on the serum concentrations of AEDs. The purpose of this study is to evaluate the effect of ECMO on AED serum concentrations. METHODS: A retrospective, matched-cohort study was performed in patients younger than 18 years who received ECMO and were treated with intravenous (IV) PB or fos-PHT at Texas Children's Hospital between 2004 and 2014. Patients receiving IV AED therapy and ECMO were matched, based on age, sex, and weight, with patients receiving IV AED therapy without ECMO. The 24-hour cumulative AED dose, serum concentrations, number of doses per serum concentration drawn ratio, volume of distribution, therapeutic serum concentrations, and time to therapeutic serum concentration were compared between both groups. The fos-PHT and PB groups were analyzed in all patients and in neonates only. RESULTS: Fourteen patients met inclusion criteria. The fos-PHT neonatal (20.1 vs 11.3 mg/kg/day, p = 0.044), PB composite (33.9 vs 21.6 mg/kg/day, p = 0.012), and PB neonatal (40.3 vs 20 mg/kg/day, p = 0.04) had larger 24-hour cumulative doses compared with non-ECMO patients. Lower serum concentrations were observed in the PB composite ECMO group (19.1 vs 35.4 mg/L, p < 0.001) and the PB neonatal ECMO group (20.5 vs 27.8 mg/L, p = 0.01) compared with non-ECMO patients. CONCLUSION: Pediatric patients receiving PB on ECMO and neonatal patients receiving fos-PHT on ECMO required larger doses, and in pediatric patients achieved lower serum concentrations, suggesting the necessity for alternative dosing strategies in these populations.

Evaluating the safety of intermittent intravenous sildenafil in infants with pulmonary hypertension.

OBJECTIVE: To compare the occurrence of hypotension following administration of intermittent intravenous (IV) and enteral sildenafil for treatment of pulmonary hypertension (PH) in infants. We hypothesized there may be more adverse effects associated with intermittent IV sildenafil compared with enteral sildenafil. METHODS: This was a retrospective matched-cohort study conducted in a tertiary care children's hospital. Patients were included if they were less than 1 year of age and received intermittent sildenafil for PH. Exclusion criteria consisted of concurrent extracorporeal membrane oxygenation during the initiation of sildenafil, the utilization of sildenafil as a one-time dose, continuation of home-dosing regimen, or inclusion in the other cohort. A total of 40 patients were matched 1:1 based on postmenstrual age and primary diagnosis. RESULTS: There was no statistically significant difference in the primary outcome, as 30% (6/20) of patients receiving IV sildenafil required a hypotension intervention compared with 10% (2/20) in the enteral cohort (P = 0.24). The majority of interventions occurred within 24 hr of the initiation of sildenafil with 4/6 patients (67%) in the IV group and 2/2 patients (100%) in the enteral group, respectively. Baseline mean arterial pressure was significantly lower in the IV patients that required an intervention compared with those that did not (44 ± 6.3 vs. 65 ± 13.4 mmHg, P = 0.0024). CONCLUSIONS: There were no statistically significant differences in safety outcomes between intermittent IV and enteral sildenafil in infants with PH. Hemodynamic parameters should be monitored closely upon sildenafil initiation. Limitations include the retrospective nature and small sample size. Pediatr Pulmonol. 2017;52:232-237. © 2016 Wiley Periodicals, Inc.

Micronutrient requirements of high-risk infants.

Micronutrient requirements are well-established for healthy full-term infants. However, few such recommendations exist for high-risk infants, including full-term infants with a variety of medical disorders or very preterm infants. Key micronutrients considered in this review are calcium, phosphorus, magnesium, iron, and zinc. The ongoing unresolved shortages, especially of intravenous forms of these minerals, remain a major problem. Considered are some aspects of how the nutrient shortages may be managed, recognizing the complexity and changing nature of the supply.