Variability in opioid conversion calculators in critically ill children transitioned from fentanyl to hydromorphone.

PURPOSE: Opioid conversion calculators (OCCs) are used to convert between opioids. The purpose of this study was to describe the variability in OCC results in critically ill children transitioned from fentanyl to hydromorphone infusions. METHODS: This was a descriptive, retrospective study. Seventeen OCCs were identified and grouped into 6 groups (groups 1-6) based on the equianalgesic conversions. The OCCs were used to calculate the hydromorphone rate in critically ill children (<18 years) converted from fentanyl to hydromorphone. Information from a previous study on children stabilized on hydromorphone (defined as the first 24-hour period with no change in the hydromorphone rates, <3 hydromorphone boluses administered, and 80% of State Behavior Scale scores between 0 and -1) were utilized. The primary objective was to compare the median hydromorphone rates calculated using the 17 OCCs. The secondary objective was to compare the percent variability of the OCC-calculated hydromorphone rates to the stabilization rate. RESULTS: Seventeen OCCs were applied to data on 28 children with a median age and hydromorphone rate of 2.4 years and 0.08 mg/kg/h, respectively. The median hydromorphone rate calculated using the 17 OCCs ranged from 0.06 to 0.12 mg/kg/h. Group 3 and group 6 OCCs resulted in a calculated hydromorphone rate that was higher than the stabilization rate in 96% and 75% of patients, respectively. Use of group 4 and group 5 OCCs resulted in a calculated hydromorphone rate that was lower than the stabilization rate in 64% and 75% of patients, respectively. CONCLUSION: Given the considerable variability of OCCs, caution should be used when applying OCCs to critically ill children.

Delirium Assessment Treatment Strategies in Critically Ill Pediatric Patients: A Pediatric Pharmacy Association Practice-Based Research Network Survey Study.

OBJECTIVES: The purpose of this study was to describe overall screening, prevention, and treatments for pediatric delirium at various neonatal intensive care units (NICUs), cardiac intensive care units (CICUs), and pediatric intensive care units (PICUs) from the Pediatric Pharmacy Association (PPA) membership. The primary objective was to identify the number of respondents that had a defined delirium-based protocol. The secondary objectives included identification of delirium assessment tools used, first- and second-line delirium treatment options, and monitoring practices for antipsychotics for delirium management. METHODS: A cross-sectional questionnaire was distributed to PPA members from February 8, 2022, to March, 25, 2022. Comparisons between the NICUs, PICUs, and CICUs were conducted by using chi-square tests, with a priori p value of <0.05. RESULTS: The questionnaire was completed by 84 respondents at 62 institutions; respondents practiced in the PICU or mixed PICU (n = 48; 57.1%), CICU (n = 13; 15.5%), and NICU (n = 23; 27.4%). Sixty-one respondents (72.6%) noted their units routinely screen for delirium, and there was a significant difference between the respondents of different units that use a delirium scoring tool (p < 0.01). Only 33 respondents (39.3%) had a defined delirium protocol, and there was no difference between units (p = 0.31). The most common agents used for delirium treatment were quetiapine and risperidone. There was variability in the monitoring used between respondents, but the majority (n = 74; 88%) monitor electrocardiograms to assess the corrected QT interval, but practice variability existed. CONCLUSIONS: Most respondents did not have a defined delirium protocol. Variations were noted in the treatment options and monitoring for critically ill pediatric patients with delirium.

Effect of Phytonadione on Correction of Coagulopathy in Pediatric Patients With Septic Shock.

OBJECTIVES: The purpose of this study was to evaluate phytonadione in children with septic shock with disseminated intravascular coagulopathy (DIC). The primary objective was to identify the number of patients with an international normalized ratio (INR), defined as ≤1.2, following phytonadione. Secondary objectives were to compare patients who achieved a normalized INR versus those with INR >1.2 and to determine factors associated with a normalized INR. METHODS: A retrospective study of children <18 years of age receiving phytonadione from October 1, 2013, to August 31, 2020, with a diagnosis of septic shock, were included. Data collection included demographics, phytonadione regimen, INR values, Pediatric Index of Mortality 2 (PIM2) and Pediatric Risk of Mortality III (PRISM III) scores, fresh frozen plasma (FFP) and cryoprecipitate use. A logistic regression model and generalized linear model were used to explore factors associated with a normalized INR and evaluate phytonadione dosing. RESULTS: Data for initial phytonadione course for 156 patients were evaluated. Sixty-six (42.3%) patients had a normalized INR. Most patients (n = 145; 92.9%) received ≤3 phytonadione doses, with the largest reduction in INR occurring after the second dose. In the logistic regression model, baseline INR, FFP, cryoprecipitate, vasopressors, PIM2, PRISM III, or cumulative phytonadione dose were not associated with achieving a normalized INR. CONCLUSIONS: Less than half of patients achieved a normalized INR. The median cumulative dose of phytonadione and receipt of FFP or cryoprecipitate was not associated with an increased odds of a normalized INR. Future studies are needed to further explore phytonadione use in children with sepsis-induced coagulopathy.

Melatonin Use in Infants Admitted to Intensive Care Units.

OBJECTIVES: Sleep deprivation is a risk factor for delirium development, which is a frequent complication of intensive care unit admission. Melatonin has been used for both delirium prevention and treatment. Melatonin safety, efficacy, and dosing information in neonates and infants is lacking. The purpose of this study was to describe melatonin use in infants regarding indication, dosing, efficacy, and safety. METHODS: This descriptive, retrospective study included infants <12 months of age admitted to an intensive care unit receiving melatonin. Data collection included demographics, melatonin regimen, sedative and analgesic agents, antipsychotics, and delirium-causing medications. The primary objective was to identify the melatonin indication and median dose. The secondary objectives included change in delirium, pain, and sedation scores; change in dosing of analgesic and sedative agents; and adverse event identification. Wilcoxon signed rank tests and linear mixed models were employed with significance defined at p < 0.05. RESULTS: Fifty-five patients were included, with a median age of 5.5 months (IQR, 3.9-8.2). Most (n = 29; 52.7%) received melatonin for sleep promotion. The median body weight-based dose was 0.31 mg/kg/dose (IQR, 0.20-0.45). There was a statistical reduction in cumulative morphine equivalent dosing 72 hours after melatonin administration versus before, 17.1 versus 21.4 mg/kg (p = 0.049). No adverse events were noted. CONCLUSIONS: Most patients (n = 29; 52.7%) received melatonin for sleep promotion at a median dose was 0.31 mg/kg/dose. Initiation of melatonin was associated with a reduction of opioid exposure; however, there was no reduction in pain/sedation scores.

Comparison of dosing strategies in obese patients prescribed intravenous acyclovir and evaluation of rate of acute kidney injury.

INTRODUCTION: There is limited guidance on the most appropriate dosing strategy for intravenous (IV) acyclovir in obese patients. The manufacturer's labelling suggests using ideal body weight (IBW); however, previous pharmacokinetic studies of obese patients have shown more rapid systemic clearance and lower area under the curve and peak concentrations compared with patients with a body mass index (BMI) < 30 kg/m2. Although pharmacokinetic data suggest that plasma concentrations of acyclovir are best predicted when using adjusted body weight (AdjBW) doses, there is concern about higher rates of acute kidney injury (AKI). METHODS: This was a retrospective cohort review of adult patients with a BMI ≥ 30 kg/m2 prescribed IV acyclovir ≥ 48 hours between 1 January 2014 and 31 August 2021 at a 511-bed academic medical centre. The primary objective was to compare AdjBW with IBW dosing in obese patients who had been prescribed IV acyclovir and to determine whether AdjBW dosing results in higher rates of AKI. RESULTS: Ninety-four patients were included: 61 were in the IBW cohort and 33 were in the AdjBW cohort. The median BMI [IQR] for all patients was 34.7 kg/m2 [31.8-40.6]. Patients in the AdjBW cohort received a significantly higher median acyclovir dose of 800 mg/dose [IQR 700-850] compared with 600 mg/dose [IQR 500-700] for the IBW cohort (P ≤ 0.0001). No patients dosed using AdjBW developed AKI compared with eight (13.1%) in the IBW group. CONCLUSION: In this study, 8.5% of all obese patients receiving acyclovir developed AKI. Further studies are needed to confirm dosing recommendations.

Sculpting a teaching and learning curriculum to better meet the career needs of postgraduate year 1 and 2 pharmacy residents.

PURPOSE: To describe implementation of the University of Oklahoma College of Pharmacy (OUCOP) teaching and learning curriculum (TLC) for postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) residents, including the required components, evaluation structure, residency graduate outcomes and perceptions captured by a survey following program completion, generalizability to other institutions, and opportunities for future directions. SUMMARY: As part of their residency training, pharmacy residents are required to develop and refine teaching, precepting, and presentation skills. To meet the required and elective competency areas, goals, and objectives on teaching, precepting, and presentation skills, many American Society of Health-System Pharmacists-accredited residency programs have utilized TLC programs. OUCOP offers 2 distinct TLC programs for PGY1 and PGY2 residents, respectively. CONCLUSION: The OUCOP TLC program provided residents with opportunities for development of teaching and presentation skills in a variety of settings. The majority of residency graduates currently practice as a clinical specialist, and the majority lecture, precept, and deliver continuing education presentations. Graduates felt that the mentorship and diversity of teaching activities were the most beneficial qualities of the program. In addition, the majority noted that mentorship in lecture preparation was helpful in creating presentations after graduation. On the basis of the feedback from the survey, several changes have been made to better prepare residents for their postgraduate careers. TLC programs should conduct ongoing assessments to continue to foster the development of precepting and teaching skills for residents' future careers.

Characterization of early versus late opioid iatrogenic withdrawal syndrome in critically ill children transitioning from fentanyl -infusions to methadone.

OBJECTIVE: Methadone is used to prevent opioid iatrogenic withdrawal syndrome (IWS) in children, but the optimal dose and overlap time with an opioid infusion have not been elucidated. The purpose was to compare clinical manifestations among patients who developed opioid IWS within 24 hours (early) versus ≥24 hours (late) of fentanyl discontinuation when enteral methadone was initiated. DESIGN: A retrospective, descriptive study. SETTING: Pediatric and cardiovascular intensive care units at a tertiary care health system. PARTICIPANTS: Sixty-seven children received fentanyl infusions for ≥3 days and initiated on methadone prior to fentanyl discontinuation. MAIN OUTCOME MEASURES: The primary objective was to compare clinical characteristics between those with early versus late opioid IWS. Opioid IWS was defined as a Withdrawal Assessment Tool-1 score ≥3 within 5 days of fentanyl discontinuation. Secondary objectives included a comparison of time to IWS, clinical characteristics, and risk factors among patients with and without IWS. RESULTS: Fifty children (74.6 percent) developed opioid IWS within a median time of 3.5 hours. No differences were noted for those with and without IWS. Thirty-seven patients (74.0 percent) with IWS developed early IWS. A higher percentage of males in the late versus early group developed IWS, 100 percent versus 51.4 percent, p = 0.002. The median overlap time with methadone and fentanyl was shorter in the early versus late IWS group without reaching statistical significance, 27.5 versus 64.0 hours, p = 0.127. CONCLUSIONS: The majority developed opioid IWS, with most developing early IWS, despite methadone initiation. Future studies should evaluate the optimal methadone dosing and overlap time to prevent opioid IWS.

Impact of a Pharmacist-Managed Outpatient Parenteral Antimicrobial Therapy (OPAT) Service on Cost Savings and Clinical Outcomes at an Academic Medical Center.

Background: Outpatient antimicrobial therapy (OPAT) is managed by a variety of teams, but primarily through an infectious disease clinic. At our medical center, OPAT monitoring is performed telephonically by pharmacists through a collaborative practice agreement under the supervision of an infectious disease physician. The effect of telephonic monitoring of OPAT by pharmacists on patient outcomes is unknown. Methods: This retrospective cohort study was conducted between July 2017 and July 2018 at a 350-bed academic medical center and included adult patients discharged home on IV antibiotics or oral linezolid. The experimental group comprised patients discharged with a consultation for the OPAT management program, whereas the control group comprised patients discharged home without a consultation. The primary outcome was 30-day readmission. Results: In total, 399 patients were included: 243 patients in the OPAT management program group and 156 patients in the control group. The 30-day readmission rates were similar in each cohort (20% vs 19%; P = .8193); however, the 30-day readmission rates were lower in the OPAT management program for patients discharged on vancomycin (19.4% vs 39.1%; P = .004). Conclusions: We did not find a difference in 30-day readmissions between patients receiving pharmacy-driven OPAT management services and those who did not. Patients receiving vancomycin via OPAT had lower 30-day readmissions when included in the pharmacist-driven OPAT management program. Institutions with limited resources may consider reserving OPAT management services for patients receiving antimicrobials that require pharmacokinetic dosing and/or close monitoring.

Impact of Transitioning a Senior Seminar Capstone Course to an Intensive Hybrid Course.

Objective. To compare outcomes (grades, resources, and perceptions) from a weekly in-person seminar capstone course (pre-revision group) to an intensive hybrid course design that included a two-day, in-person conference (10- and 25-minute student presentations) and asynchronous seminar skills sessions (post-revision group).Methods. Students' scores on seminar presentation rubrics were compared before and after the course revision. Between the groups, we compared resources, such as number of faculty and hours of involvement, and student time away from advanced pharmacy practice experiences (APPEs). We also assessed student and faculty satisfaction and perception. Comparisons between groups were made using statistical tests, and descriptive statistics were used to summarize student performance and survey responses.Results. The study included 370 students, 205 in the pre-revision group and 165 in the post-revision group. No significant difference was found in mean overall scores for the 25-minute presentation between groups; however, the post-revision group had significantly lower subscores for objectives and slides and significantly higher subscores for critical analysis. The survey was completed by 82% of faculty and 43% of students from the class of 2018. Most students (80%) found all of the asynchronous sessions helpful, and 70.6% preferred the intensive hybrid course format. Compared to the weekly format, all faculty reported student presentations were similar or better in quality and workload was similar or decreased with the intensive hybrid format.Conclusion. Changing the senior seminar capstone course to an intensive hybrid design reduced faculty workload and decreased student time away from APPEs while maintaining similar presentation grades and quality.

Vasopressin-Induced Hyponatremia in Infants Following Cardiovascular Surgery.

BACKGROUND: Vasopressin is increasingly used in infants following cardiac surgery. Hyponatremia is a noted adverse event, but incidence and risk factors remain undefined. OBJECTIVE: The primary objective was to identify the incidence of vasopressin-induced hyponatremia. Secondary objectives included comparing baseline and change in serum sodium concentrations between infants receiving vasopressin with and without hyponatremia, and comparing vasopressin dose, duration, and clinical characteristics in those with and without hyponatremia. METHODS: This Institutional Review Board-approved, retrospective case-control study included infants <6 months following cardiac surgery receiving vasopressin for ≥6 hours at a tertiary care, academic hospital. Patients who developed hyponatremia, cases, were matched to controls in a 1:2 fashion. Demographics and clinical characteristics were collected. Descriptive and inferential statistics were employed. A conditional logistic regression was used to assess odds of hyponatremia. RESULTS: Of the included 142 infants, 20 (14.1%) developed hyponatremia and were matched with 40 controls. There was significant difference in median nadir between controls and cases, 142.0 versus 128.5 mEq/L (<0.001). A significantly higher number of cases received corticosteroids, loop diuretics, and chlorothiazide versus controls. The regression analysis demonstrated that each additional hour of vasopressin increased the odds of developing hyponatremia by 5% (adjusted odds ratio 1.05 [confidence interval 1-1.1]). CONCLUSIONS AND RELEVANCE: Vasopressin-induced hyponatremia incidence was <15%. Vasopressin duration was independently associated with hyponatremia development.

Efficacy and Safety of Prolonged Magnesium Sulfate Infusions in Children With Refractory Status Asthmaticus.

Objectives: There is a paucity of data on the use of intravenous magnesium sulfate infusion in children with refractory status asthmaticus. The purpose of this study was to evaluate the efficacy and safety of prolonged magnesium sulfate infusion as an advanced therapy. Methods: This is a single center retrospective study of children admitted to our pediatric intensive care unit (PICU) with status asthmaticus requiring continuous albuterol. Treatment group included patients receiving magnesium for ≥4 h and control group included those on other therapies only. Patients were matched 1:4 based on age, sex, obesity, pediatric index of mortality III and pediatric risk of mortality III scores. Primary outcomes included PICU length of stay (LOS) and mechanical ventilation (MV) requirement. Secondary outcomes included mortality, extracorporeal membrane oxygenation (ECMO) requirement, analyses of factors associated with PICU LOS and MV requirement and safety of magnesium infusion. Logistic and linear regressions were employed to determine factors associated with MV requirement and PICU LOS, respectively. Results: Treatment and control groups included 27 and 108 patients, respectively. Median initial infusion rate was 15 mg/kg/hour, with median duration of 28 h. There was no difference in the MV requirement between the treatment and control groups [7 (25.9%) vs. 20 patients (18.5%), p = 0.39]. Median PICU LOS and ECMO use were significantly higher in treatment vs. control group [(3.63 vs. 1.09 days, p < 0.01) and (11.1 vs. 0%, p < 0.01), respectively]. No mortality difference was noted. On regression analysis, patients receiving ketamine and higher prednisone equivalent dosing had higher odds of MV requirement [OR 19.29 (95% CI 5.40-68.88), p < 0.01 and 1.099 (95% CI 1.03-1.17), p < 0.01, respectively]. Each mg/kg increase in prednisone equivalent dosing corresponded to an increase in PICU LOS by 0.13 days (95% CI 0.096-0.160, p < 0.01). Magnesium infusions were not associated with lower MV requirement or lower PICU LOS after controlling for covariates. Fourteen (51.9%) patients in the treatment group had an adverse event, hypotension being the most common. Conclusion: Magnesium sulfate infusions were not associated with MV requirement, PICU LOS or mortality.

Evaluation of Ceftazidime Use in the Neonatal Intensive Care Unit and Association With Cephalosporin-Resistant Gram-Negative Bacteria.

BACKGROUND: Cefotaxime shortage in 2015 led to increased ceftazidime use in the neonatal intensive care unit (NICU). OBJECTIVE: The purpose was to explore whether ceftazidime increases risk for development of resistant gram-negative organisms. METHODS: Retrospective evaluation of NICU patients with cultures positive for Escherichia coli, Pseudomonas aeruginosa, Klebsiella species, or Stenotrophomonas maltophilia between January1, 2015 and August 31, 2020. Isolates were excluded if obtained from same patient and source within 90 days or if patient ≤7 days of life or admitted from a referring hospital. Data collection included demographics and clinical parameters, and culture/susceptibility data. The primary objective was comparison of pathogens and clinical parameters in those with and without third-generation cephalosporin resistance. The secondary objectives included a comparison between those with and without ceftazidime exposure and identification of factors associated with resistance. Comparisons were made using χ2, Fisher exact tests, or Wilcoxon tests. A logistic regression was used to identify risk factors for resistance. RESULTS: Overall, 349 isolates, representing 215 patients, were included. The most common source was endotracheal (n = 192, 55.0%) and pathogens were E coli (31.8%) and P aeruginosa (29.2%). Overall, 12.3% (n = 43) were resistant and these were obtained after longer parenteral nutrition (PN), central line access, and antibiotic days versus susceptible isolates. Higher resistance was noted after ceftazidime exposure versus no exposure, 19.1% versus 6.6%. Each day of ceftazidime was associated with 13% greater odds of P aeruginosa resistance (adjusted odds ratio: 1.13 [95% confidence interval: 1.03-1.23]). CONCLUSION AND RELEVANCE: Ceftazidime duration was associated with increased risk for P aeruginosa resistance. Additional studies are needed to confirm these findings.

Incidence of Cytomegalovirus DNAemia in Pediatric Post-Renal Transplant Patients Receiving Weight-Based vs Body Surface Area-Based Valganciclovir Chemoprophylaxis.

OBJECTIVE: To determine the incidence of cytomegalovirus (CMV) DNAemia and disease, identify potential risk factors, and assess the safety and efficacy of weight-based valganciclovir dosing in pediatric post-renal transplant patients. METHODS: This single-center, retrospective study included patients ≤21 years who received a kidney transplant between January 1, 2011, and November 1, 2019, with 3 to 24 months of follow-up data. Demographics and clinical characteristics were collected to assess for potential risk factors. Descriptive statistics and logistic regressions were used to determine rates of CMV DNAemia considering clinical characteristics and chemoprophylaxis. RESULTS: Fifty-seven patients were included. The incidence of CMV DNAemia was 43.9%. Cytomegalovirus seropositive status was associated with increased risk of CMV DNAemia. Patients receiving valganciclovir for <150 days had 8.33 (95% CI, 1.68-41.29) greater odds of developing CMV DNAemia than patients receiving valganciclovir for 180 ± 30 days, p = 0.01. The median time to detectable CMV PCR after transplant was 140 days (range, 12-511 days). Cytomegalovirus DNAemia was not statistically different between those receiving weight-based vs FDA-approved valganciclovir dosing; however, patients receiving the FDA-approved dosing were more likely to develop neutropenia. Among the intermediate-risk group, the adjusted relative risk of CMV DNAemia was 0.62 (95% CI, 0.36-1.09) for those not receiving chemoprophylaxis compared with those who did. CONCLUSIONS: Risk of CMV DNAemia is higher among patients receiving valganciclovir for <150 days. Further exploration of weight-based valganciclovir dosing for CMV chemoprophylaxis in high- and intermediate-risk post-renal transplant patients is needed to minimize adverse drug effects while maintaining efficacy.

Frequency and Severity of Chlorothiazide-Induced Hyponatremia in the Neonatal Intensive Care Unit.

OBJECTIVE: Although thiazide diuretics are commonly used in the neonatal intensive care unit (NICU), the risk of thiazide-induced hyponatremia in infants has not been well documented. The primary objective of this study was to determine the frequency and severity of hyponatremia in neonates and infants receiving enteral chlorothiazide. Secondary objectives included identifying: (1) percent change in serum sodium from before chlorothiazide initiation to nadir, (2) time to reach nadir serum sodium concentration, and (3) percentage of patients on chlorothiazide receiving sodium supplementation. STUDY DESIGN: This was a retrospective cohort study of NICU patients admitted between July 1, 2014, and July 31, 2019, who received ≥1 dose of enteral chlorothiazide. Mild, moderate, and severe hyponatremia were defined as serum sodium of 130 to 134 mEq/L, 120 to 129 mEq/L, and less than 120 mEq/L, respectively. Data including serum electrolytes, chlorothiazide dosing, and sodium supplementation were collected for the first 2 weeks of therapy. Descriptive and inferential statistics were performed in SAS software, Version 9.4. RESULTS: One hundred and seven patients, receiving 127 chlorothiazide courses, were included. The median gestational age at birth and postmenstrual age at initiation were 26.0 and 35.9 weeks, respectively. The overall frequency of hyponatremia was 35.4% (45/127 courses). Mild, moderate, and severe hyponatremia were reported in 27 (21.3%), 16 (12.6%), and 2 (1.6%) courses. The median percent decrease in serum sodium from baseline to nadir was 2.9%, and the median time to nadir sodium was 5 days. Enteral sodium supplements were administered in 52 (40.9%) courses. Sixteen courses (12.6%) were discontinued within the first 14 days of therapy due to hyponatremia. CONCLUSION: Hyponatremia occurred in over 35% of courses of enteral chlorothiazide in neonates and infants. Given the high frequency of hyponatremia, serum sodium should be monitored closely in infants receiving chlorothiazide. Providers should consider early initiation of sodium supplements if warranted. KEY POINTS: · One-third of infants on chlorothiazide develop hyponatremia.. · Nadir serum sodium typically occurs within 5 days.. · Monitor sodium closely after chlorothiazide initiation..

Exploring Residency Program Directors, Preceptors, and Residents' Intentions to Participate in Multicenter Pediatric Pharmacy Resident Research Projects.

OBJECTIVE: The purpose was to explore preceptors, residency program directors (RPDs), and residents' beliefs and intentions in participating in multicenter pediatric resident research projects (PRRPs). METHODS: This exploratory qualitative study used the theory of planned behavior to explore beliefs, attitudes, and intentions toward participation in a multicenter PRRP. Two focus groups were formed: RPDs/preceptors and pharmacy residents. The primary objective was to identify attitudes/salient beliefs, subjective norms, and perceived behavioral controls regarding participation in multicenter PRRPs. The secondary objectives included identifying potential barriers and mitigation strategies for multicenter PRRPs. Descriptive statistics and a thematic analysis were performed. RESULTS: The 2 focus groups included 24 participants: RPDs/preceptors (n = 16) and pharmacy residents (n = 8). The RPD/preceptor group had a mean of 7.4 ± 5.4 years of research experience; all residents had prior research experience as students. Participants shared and contrasted their salient beliefs, subjective norms, and perceived behavioral control beliefs about logistical challenges, networking, mentoring, sample size, collaboration, workload, shared responsibilities for data collection and the institutional review board application, and resources associated with participation in multicenter PRRPs. Other items that participants felt were important were discussion of authorship order and dedicated research time for residents. CONCLUSIONS: Participants provided favorable comments toward multicenter PRRPs but acknowledged some barriers. The resident, preceptor, and RPD intention to participate in multi-center PRRPs is very likely if they perceive this as an opportunity for increased networking and mentorship, increased likelihood of publication, enhanced research skill experience, and shared resources and responsibilities.

A Pilot Evaluation of the Possible Association of Metronidazole With Neurodevelopmental Outcomes in Premature Neonates.

OBJECTIVE: Metronidazole is recommended as a first-line treatment of necrotizing enterocolitis (NEC) in neonates. Metronidazole-associated neurotoxicity has been reported, but long-term neurodevelopmental effects in neonates have not been explored. The primary objective was to evaluate the relationship of cumulative metronidazole dose with each Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) composite score in neonates with NEC. Secondary objectives included comparison of seizure rates, mean Bayley-III scores, and neurodevelopmental impairment defined as 2 of 3 Bayley-III composite scores ≤ 79 or 1 score ≤ 70 between the metronidazole exposed and non-exposed groups. METHODS: This multisite, retrospective cohort study compared infants with a birth weight < 1500 grams between January 1, 2011, and December 31, 2016, who developed stage 2 or greater NEC or spontaneous intestinal perforation and were followed up at a developmental clinic visit at approximately 1 year of age. Patients were excluded if admitted >72 hours of life, had congenital neurodevelopmental anomalies, hypoxic ischemic encephalopathy, grade III or IV intraventricular hemorrhage, or seizures prior to treatment of NEC. Included patients were stratified into 2 groups based on metronidazole exposure versus no metronidazole. Data were assessed using descriptive and inferential statistical techniques, using SAS 9.4. RESULTS: Forty-one patients were included. Seven patients received metronidazole and 34 patients were in the non-metronidazole group. The only statistical difference noted between groups was for gestational age, with the non-exposed group being more premature. There was no statistical difference in Bayley-III scores, seizure rates, or neurodevelopmental impairment between groups. CONCLUSION: No differences in neurodevelopmental outcomes were found between those with and without metronidazole exposure. Further studies are needed to validate our results.

Comparison of Amikacin Pharmacokinetics in Neonates With and Without Congenital Heart Disease.

OBJECTIVES: The primary objective was to compare the volume of distribution (Vd), clearance (CL), elimination rate (Ke), and half-life (t½) of amikacin in neonates with cyanotic defects, acyanotic defects, and controls, adjusted for gestational and postnatal age. Secondary objectives were to compare the incidence of acute kidney injury (AKI) between controls and the congenital heart disease (CHD) group and to identify potential risk factors. METHODS: This retrospective cohort study included neonates receiving amikacin from January 1, 2013 to August 31, 2016. Patients were excluded if concentrations were not appropriately obtained or if AKI or renal anomalies were identified prior to amikacin initiation. Congenital heart disease was classified as acyanotic or cyanotic. Patients with CHD were matched 1:1 with non-CHD controls according to postmenstrual age. Bivariate analyses were performed using Wilcoxon-Mann-Whitney test, Pearson χ2 tests, or Fisher exact as appropriate with a p value <0.05. Regression analyses included logistic and analysis of covariance. RESULTS: Fifty-four patients with CHD were matched with 54 controls. Median (IQR) postnatal age (days) at amikacin initiation significantly differed between CHD and controls, 3.0 (1.0-16.0) versus 1.0 (1.0-3.0), p = 0.016. After adjusting for gestational and postnatal age, there was no difference in the mean (95% CI) Vd (L/kg) and CL (L/kg/hr) between CHD and controls, 0.47 (0.44-0.50) versus 0.46 (0.43-0.49), p = 0.548 and 0.05 (0.05-0.05) versus 0.05 (0.05-0.05), p = 0.481, respectively. There was no difference in Ke or t½ between groups. There was no difference in AKI between the CHD and controls, 18.5% versus 9.3%, p = 0.16. CONCLUSIONS: Clinicians should consider using standard amikacin dosing for neonates with CHD and monitor renal function, since they may have greater AKI risk factors.

Conversion From Continuous Infusion Fentanyl to Continuous Infusion Hydromorphone in the Pediatric Intensive Care Unit.

BACKGROUND: Opioid rotations from fentanyl to hydromorphone may reduce opioid/sedative exposure in critically ill children. OBJECTIVE: The primary objective was to determine the conversion percentage from fentanyl to hydromorphone infusions using equianalgesic conversions (0.1 mg fentanyl = 1.5 mg hydromorphone). Secondary objectives included identification of the median time and hydromorphone rate at stabilization (defined as the first 24-hour period no hydromorphone rates changed, 80% of State Behavioral Scale [SBS] scores between 0 and -1, and <3 hydromorphone boluses administered). Additional outcomes included a comparison of opioid/sedative requirements on the day of conversion versus the three 24-hour periods prior to conversion. METHODS: This retrospective study included children <18 years old converted from fentanyl to hydromorphone infusions over 6.3 years. Linear mixed models were used to determine if the mean cumulative opioid/sedative dosing differed from the day of conversion versus three 24-hour periods prior to conversion. RESULTS: A total of 36 children were converted to hydromorphone. The median conversion percentage of hydromorphone was 86% of their fentanyl dose (interquartile range [IQR] = 67-100). The median hydromorphone rate at stabilization was 0.08 mg/kg/h (IQR = 0.05-0.1). Eight (22%) were stabilized on their initial hydromorphone rate; 8 (22%) never achieved stabilization. Patients had a significant decrease in opioid dosing on the day of conversion versus the 24-hour period prior to conversion but no changes in sedative dosing following conversion. CONCLUSION AND RELEVANCE: A median 14% fentanyl dose reduction was noted when transitioning to hydromorphone. Further exploration is needed to determine if opioid rotations with hydromorphone can reduce opioid/sedative exposure.