Pamela D. Reiter

Intravenous levetiracetam in the management of acute seizures in children.

Levetiracetam may be effective in children with acute seizures or status epilepticus. We performed a retrospective chart review of children who received intravenous levetiracetam within 30 minutes of a seizure. Seventy-three patients during a 2-year study period met our inclusion criteria. The mean (+/- S.D.) age and weight of the patients were 5.59 +/- 5.6 years (range, 1 day to 17.8 years) and 23.1 +/- 21 kg (range, 1.97-97 kg), respectively. Patients received a mean (+/- S.D.) levetiracetam dose of 29.4 +/- 13.5 mg/kg. Most children (n = 49, or 67%) received additional antiepileptic drugs to abort their seizure. Overall, the mean (+/- S.D.) total (abortive plus chronic) number of concomitant antiepileptic drugs used by the population was 2.53 +/- 1.7 (1.07 +/- 0.98 as additional abortive therapy, and 1.42 +/- 1.29 as chronic therapy). Most patients received levetiracetam for serial seizures (79%), whereas 12% and 8% manifested a single seizure or status epilepticus, respectively. Clinical effectiveness at 1, 12, 24, 48, and 72 hours after the initial levetiracetam dose constituted the primary study outcome. Eighty-nine percent of patients remained seizure-free at 1 hour. This rate decreased at each evaluation time point. Most patients (71%) were placed on maintenance levetiracetam within 24 hours of their loading dose. The predictive ability of patient and drug regimen variables in outcomes was poor. Only the number of concomitant antiepileptic drugs consistently predicted outcomes. Levetiracetam was well tolerated at the doses studied, and appears most effective in single seizure events.

Effect of Short-Term Erythropoietin Therapy in Anemic Premature Infants

OBJECTIVE:To determine the effectiveness of a 10-day subcutaneous erythropoietin (rHuEpo) course of 300 units per kg per dose plus oral iron compared to oral iron alone in anemic infants during their convalescent phase of illness.STUDY DESIGN:Prospective, randomized trial performed at a 40-bed, teaching, referral, level III, neonatal intensive care unit. Infants with a gestational age at birth of less than 32 weeks, hematocrit of less than or equal to 28% with a corrected reticulocyte count of less than or equal to 5%, postconceptual age of less than 48 weeks or 5 months chronological age, and a diagnosis of anemia of prematurity were considered for inclusion. Major outcome parameters included hematocrit, corrected reticulocyte count and red cell transfusion requirements.RESULTS:A total of 60 infants were enrolled (n=30 per group). Infants randomized to rHuEpo had a significantly higher post-treatment hematocrit and corrected reticulocyte count than infants in the iron only group (p<0.001). There was a trend towards fewer red cell requirements in the rHuEpo group.CONCLUSIONS:The rHuEpo regimen studied here was associated with an acute improvement in hematocrit and corrected reticulocyte counts. This study did not demonstrate a statistically significant decrease in transfusion therapy, in part related to increased subsequent use of rHuEpo in the control group. Taken together, these data demonstrate that this regimen can effectively treat anemia in convalescent premature infants.

Comparison of 6-Hour Infusion versus Bolus Furosemide in Premature Infants

Study Objective. To compare the renal, hemodynamic, and pulmonary effects of a 6‐hour infusion of furosemide versus conventional bolus administration in premature infants.

Development of recommendations for dosing of commonly prescribed medications in critically ill obese children

PURPOSE The development and use of a decision support tool to help formulate recommendations for dosing of commonly prescribed medications in critically ill obese children are described. METHODS Medications prescribed in 2010 to critically ill infants and children (younger than 18 years) were identified from the Pediatric Health Information System. The most commonly prescribed and therapeutically monitored medications were extracted. Supportive evidence for obesity dosing was identified through a standardized computerized search involving medical subject heading terminology and age filters using PubMed and Ovid. A usefulness scoring system was developed to rate the strength and applicability of the literature to critically ill obese children. A decision supporttool was then created to aid in the formulation of a dosing weight for each medication based on the usefulness score, published pharmacokinetic properties, clinical studies available in the primary literature, and consideration of clinical consequences of underdosing or overdosing. RESULTS A total of 113 medications were evaluated, and 122 discrete citations, supporting 66 medications, were reviewed. Seventy-two percent of citations had general obesity dosing information, and 13% had pediatric-specific information. The overall mean usefulness score was 5.1±4.7 (median, 7). The decision support tool was incorporated to make final dosing weight recommendations for obese children. Ultimately, total body weight was recommended for 52 medications, adjusted weight for 43 medications, and ideal body weight for 18 medications. CONCLUSION The inadequacy of obesity dosing information for most medications commonly ordered for children admitted to a pediatric intensive care unit led to the development of a decision support tool to aid in formulating dosing recommendations.

Patterns of Off-Label Prescribing in the Pediatric Intensive Care Unit and Prioritizing Future Research

OBJECTIVES To characterize off-label prescribing among US pediatric intensive care units (PICUs), determine characteristics associated with off-label use, and identify medications in highest need for additional study. METHODS Medications prescribed for ≥1% PICU patients (age < 18 years) in 2010 were identified from 39 childrens hospitals. Use in a patient younger than the Food and Drug Administration (FDA)-approved age for any indication was considered off-label. Hierarchical multivariable modeling was used to identify characteristics associated with off-label use, accounting for center effects. Highest-impact drugs were defined by: 1) high off-label use (off-label use in at least 5% of the PICU cohort), 2) high risk medication, and 3) high priority status by the FDA or Best Pharmaceuticals for Children Act (BPCA). RESULTS A total of 66,896 patients received ≥1 medication of interest (n = 162) during their PICU stay. A median of 3 (interquartile range, 2-6) unique drugs per patient were used off-label. Those who received ≥1 drug off-label (85% of the cohort) had longer median PICU (2 days vs 1 day) and hospital (6 days vs 3 days) lengths of stay and higher mortality (3.6% vs 0.7%), p < 0.001. Factors independently associated with off-label drug use included: age 1 to 5 years, chronic conditions, acute organ failures, mechanical ventilation, arterial or venous catheters, dialysis, and blood products. Half of prescribed medications (n = 84) had been used off-label: 26 with significant off-label use, 30 high-risk medications, and 47 with high FDA/BPCA priority. The highest impact medications identified were: dexmedetomidine, dopamine, hydromorphone, ketamine, lorazepam, methadone, milrinone, and oxycodone. CONCLUSIONS Most PICU patients are exposed to off-label medication use, with uncertain evidence. Future medication research in this population should focus on medications with high impact potential.

Persistent Hiccups Associated with Epidural Ropivacaine in a Newborn

OBJECTIVE: To report a case of persistent hiccups associated with epidural ropivacaine in a newborn infant. CASE SUMMARY: A term female infant (3.05 kg) received epidural ropivacaine for pain control during and after an operative procedure to correct a tracheoesophageal fistula. Three intermittent doses of ropivacaine were administered during the operative period (total dose 2.29 mg/kg) followed by a continuous epidural (caudal) infusion (0.1% ropivacaine; initial dose 0.23 mg/kg/h plus fentanyl 0.46 μg/kg/h). The infant was extubated in the recovery area and transferred to the intensive care unit. Within hours of transfer, she developed persistent hiccups. The epidural infusion was titrated for pain control, up to 0.32 mg/kg/h (ropivacaine). The hiccup frequency increased to every 10-30 seconds, with the patient appearing hypotonic with lip trembling and intermittent tongue fasciculation. An electroencephalogram did not show any epileptiform activity or focal features consistent with seizure activity. The epidural infusion was reduced to 0.26 mg/kg/h (ropivacaine), with dramatic improvement in hiccups and tone. The infusion was discontinued and complete resolution of hiccups was observed. DISCUSSION: Ropivacaine is commonly used for infiltration anesthesia and peripheral and epidural block anesthesia. Use of the Naranjo probability scale determined that our patients hiccups were probably caused by ropivacaine. To our knowledge, this is the first report of persistent hiccups associated with epidural ropivacaine. CONCLUSIONS: Clinicians should consider the potential of neurotoxicity, manifested as persistent hiccups, when epidural ropivacaine is administered to young infants.

Comparison of 3 Body Size Descriptors in Critically Ill Obese Children and Adolescents: Implications for Medication Dosing

OBJECTIVE To compare 3 methods of weight determination for medication dose calculations in obese children and to discuss feasibility for use in routine care. METHODS This was a patient safety and quality improvement study evaluating patients (2-19 years old) admitted to the pediatric intensive care unit during a 13-month period (July 2010-July 2011). Patients identified as obese (≥95th percentile body mass index [BMI] for age), including severely obese (≥99th percentile BMI for age), were included in the weight method comparison portion of this study. Lean body mass estimations, using equations derived by the Peters and Foster methods, were compared to ideal body weight estimates by using the BMI method. Absolute differences between values generated by the 3 methods, intraclass correlation (ICC), and Bland-Altman plots were calculated. RESULTS A total of 1369 patients met initial criteria; 176 met criteria for the dosing weight comparison (age ± SD = 9.28 ± 5 years; actual weight ± SD = 55.5 ± 33.9 kg; 46% female). Sixty were severely obese and 116 were obese. Mean ICC between methods was 0.968 (95% Confidence interval (CI): 0.959, 0.975). The Peters method estimated higher weights than the Foster or BMI method. Bland-Altman plots illustrated good agreement between methods in children with weight below 50 kg, but decreased agreement above 50 kg, which was influenced by sex. CONCLUSIONS All methods demonstrated strong correlation and acceptable agreement in children below 50 kg. Systematic biases were identified in children above 50 kg where variance was higher. The BMI method was least complex to calculate and the most feasible method for daily use.

Effect of a closed drug-delivery system on the incidence of nosocomial and catheter-related bloodstream infections in infants

We conducted a prospective, cohort study at two affiliated level III neonatal intensive care units to evaluate the effect of a closed drug-delivery system on the incidence of nosocomial and catheter-related bloodstream infections (CRBSI) in infants. A total of 300 infants (n=150 at each site) were enrolled over a 4-year study period. There was no difference in the rate of CRBSI per 1000 catheter days between the two sites (16.2+/-39 vs. 8.9+/-24, P=0.054, 95% CI-14.8 to 0.13). Infants at site A (closed drug-delivery system) had a higher rate of infectious nosocomial respiratory complications per 100 hospital days than infants at site B (open delivery system) (1.1+/-2.2 vs. 0.5+/-1.5, P=0.009), however, there was no difference in the overall number of confirmed or suspected nosocomial infection events per patient between study sites. Logistic regression revealed that the number of additional peripheral catheters, gestational age and duration of parenteral nutrition all significantly contributed to the risk of developing one or more CRSBI. The closed drug-delivery system failed to reduce the incidence of CRBSI or overall rate of nosocomial infections in premature infants.

Marijuana Misadventures in Children: Exploration of a Dose-response Relationship and Summary of Clinical Effects and Outcomes

Objectives This study aimed to explore a dose-response relationship of delta-9-tetrahydrocannabinol (THC) in THC-naïve children after unintentional acute exposure and compare clinical outcomes with non-naïve children. Methods A retrospective review was performed on children aged 31 days to 20 years who presented to Childrens Hospital Colorado for care related to acute THC toxicity. The children were divided into groups based on exposure: group 1 (THC naïve) and group 2 (THC non-naïve). Results A total of 38 children (age, 3.5 [3] years) met inclusion for group 1 and an equal number of children (age, 15.1 [3.9] years) met the criteria for comparison in group 2. Eight naïve patients had documentation of estimated THC dose ingested (mean [SD], 7.13 [5.8] mg/kg; range, 2.9–19.5 mg/kg). A direct relationship between estimated oral THC dose, level of medical intervention required, and hospital disposition was observed. Lethargy/somnolence was more common in the naïve group (84% vs. 26%, P < 0.0001) whereas problems in cognition, perception, and behavior were more common in the non-naïve group (4% vs 11%, P = 0.01). The duration of clinical effect and length of hospital stay were longer in the naïve group (19.3 vs 5.0 hours, P < 0.0001) and (0.73 vs 0.19 days, P < 0.0001) respectively. Conclusions There seems to be a direct relationship between the estimated oral THC dose (mg/kg), hospital disposition, and level of medical intervention required. Symptoms and duration of effects after THC exposure varied based on the route of exposure, age of patient, and history of previous THC experience.

1151: IMPLEMENTING A VENOUS THROMBOEMBOLISM PREVENTION PROGRAM IN THE PEDIATRIC INTENSIVE CARE UNIT.

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) calculated: (1) for a 30% collection rate: (-)