Stephanie A. Storgion

Prevalence of adverse events in pediatric intensive care units in the United States.

Objectives: Selection of relevant patient safety interventions for the pediatric intensive care (PICU) requires identification of the types and severity of adverse events (AEs) and adverse drug events (ADEs) that occur in this setting. The studys objectives were to: 1) determine the rates of AEs/ADEs, including types, severity, and preventability, in PICU patients; 2) identify population characteristics associated with increased risk of AEs/ADEs; 3) develop and test a PICU specific trigger tool to facilitate identification of AEs/ADEs. Design, Setting, Patients: Retrospective, cross-sectional, randomized review of 734 patient records who were discharged from 15 U.S. PICUs between September and December 2005. Intervention: A novel PICU-focused trigger tool for AE/ADE detection. Measurements and Results: Sixty-two percent of PICU patients had at least one AE. A total of 1488 AEs, including 256 ADEs, were identified. This translates to a rate of 28.6 AEs and 4.9 ADEs per 100 patient-days. The most common types of AEs were catheter complications, uncontrolled pain, and endotracheal tube malposition. Ten percent of AEs were classified as life-threatening or permanent; 45% were deemed preventable. Higher adjusted rates of AEs were found in surgical patients (p = .02), patients intubated at some point during their PICU stay (p = .002), and patients who died (p < .001). Surgical patients had higher preventable adjusted AE (p = .01) and ADE rates (p = .02). The adjusted cumulative risk of an AE per PICU day was 5.3% and 1.6% for an ADE alone. There was a 4% increase in adjusted ADEs rates for every year increase in age. Conclusions: AEs and ADEs occur frequently in the PICU setting. These data provide areas of focus for evidence-based prevention strategies to decrease the substantial risk to this vulnerable pediatric population.

Altered Phenytoin Pharmacokinetics in Children with Severe, Acute Traumatic Brain Injury

The purpose of this study was to determine if phenytoin protein binding and metabolism were altered in prepubescent pediatric patients within the first 10 days following severe, acute traumatic brain injury. Patients (n = 10) received phenytoin loading doses (15–20 mg/kg) followed by a maintenance regimen (7 mg/kg/day) initiated within 12 hours of the loading dose. Phenytoin serum concentrations were measured serially on days 1, 2, 3, 5, 7, 9, and 10 at 1, 6, and 12 hours. Time‐invariant and time‐variant Michaelis‐Menten pharmacokinetic models were fit to the unbound phenytoin concentration‐time data (ADAPT II™). Albumin concentrations significantly decreased over time (p < 0.001) and were predictive of the phenytoin binding ratio (r2 = 0.373, p < 0.0001). The time‐variant model provided a superior fit of the data in 7 patients with no difference between models in 3 patients. Rapid inhibition of metabolism (Vmaxbaseline = 2.82 ± 2.35 mg/kg/day) was observed initially following injury. This was followed by induction of metabolism as reflected by a Vmaxinduced of 20.79 ± 13.71 mg/kg/day, which was approximately twofold higher than reported values for nonstressed children. Children with severe, acute neurotrauma were found to have markedly altered protein binding and phenytoin metabolism.

Are pediatric critical care medicine fellowships teaching and evaluating communication and professionalism

Objectives: To describe the teaching and evaluation modalities used by pediatric critical care medicine training programs in the areas of professionalism and communication. Design: Cross-sectional national survey. Setting: Pediatric critical care medicine fellowship programs. Subjects: Pediatric critical care medicine program directors. Interventions: None. Measurements and Main Results: Survey response rate was 67% of program directors in the United States, representing educators for 73% of current pediatric critical care medicine fellows. Respondents had a median of 4 years experience, with a median of seven fellows and 12 teaching faculty in their program. Faculty role modeling or direct observation with feedback were the most common modalities used to teach communication. However, six of the eight (75%) required elements of communication evaluated were not specifically taught by all programs. Faculty role modeling was the most commonly used technique to teach professionalism in 44% of the content areas evaluated, and didactics was the technique used in 44% of other professionalism content areas. Thirteen of the 16 required elements of professionalism (81%) were not taught by all programs. Evaluations by members of the healthcare team were used for assessment for both competencies. The use of a specific teaching technique was not related to program size, program director experience, or training in medical education. Conclusions: A wide range of techniques are currently used within pediatric critical care medicine to teach communication and professionalism, but there are a number of required elements that are not specifically taught by fellowship programs. These areas of deficiency represent opportunities for future investigation and improved education in the important competencies of communication and professionalism.

Hemodynamic response to intentionally altered flow continuity of dobutamine and dopamine by an infusion pump in infants.

Study Objective. To evaluate the effect of an intentional alteration in infusion pump flow continuity on the hemodynamic stability of infants receiving either dobutamine or dopamine.

Enteral Topiramate in a Pediatric Patient with Refractory Status Epilepticus: A Case Report and Review of the Literature

We describe the use of topiramate in a healthy 12-year-old (88-kg) male who developed refractory generalized convulsive status epilepticus. Seizures persisted despite aggressive use of benzodiazepines (intravenous lorazepam; oral clorazepate), barbiturates (i.e., phenobarbital, pentobarbital), and hydantoins. The childs seizures were controlled with nasogastrically administered topiramate in doses up to 500 mg twice daily (11.4 mg/kg/day). The patient did not display any clinical or laboratory signs of metabolic acidosis while receiving topiramate. Topiramate should be considered as a treatment option in refractory status epilepticus.

SEVERE, ACUTE NEUROTRAUMA ALTERS PHENYTOIN (DPH) PHARMACOKINETICS (PK) IN CHILDREN. |[dagger]| 463

In adults following acute, severe neurotrauma the metabolism of DPH is increased and albumin concentrations decrease. We evaluated 10 prepubescent children (3-11 yrs) who had severe, acute closed head injury (GCS 3-6) to determine the PK of IV DPH. Patients received a loading dose (17.7 ± 3.3 mg/kg) followed by a maintenance dose of 6.8 ± 1.6 mg/kg/day. DPH serum concentration-time data were collected up to 10 days following injury. DPH and albumin concentrations were determined by FPIA and RID, respectively. The Michaelis-Menten (MM) PK model and a time-variant MM model were fit to the total and unbound DPH concentration-time data (ADAPT II™). Unbound concentration-time data were the most reliable since albumin decreased over time (p<0.001). Also, the unbound fraction of DPH was inversely correlated with albumin concentration (r=0.578, p<0.001). The DPH PK parameters (mean ± sd) are summarized as follows:Table V, volume; Km, MM constant; Kind, rate constant of induction; Vmax, maximal velocity †Time variant MM model[Vmax=Vmaxinitial + Vmaxinduced (l-e-kind•T) for time-variant MM model] The time-variant MM model provided a superior fit of the data in 8 patients with no difference between models in 2 patients. In view of the Vmax for DPH reported for normal, non-stressed children (ie. 9.5-11 mg/kg/day), our PK data demonstrate that severe, acute neurotrauma markedly alters the metabolism of this drug. Specifically, a previously unrecognized rapid inhibition of metabolism (ie. mean Vmax = 0.11 mg/kg/day) occurs during the first hours post injury. This is followed by an induction of clearance as reflected by a Vmax (20.8 mg/kg/day) which is approximately 2 fold higher than “normal” values by 10 days post injury. These changes in DPH metabolism are associated with neurotrauma, and explain to a great degree, the variable dose requirements for DPH in these patients.

Extracorporeal Membrane Oxygenation (ECMO) Risk Stratification in Newborns with Congenital Diaphragmatic Hernia (CDH)

BACKGROUND A means for early postnatal stratification of ECMO risk in CDH newborns could be used to comparatively assess the utilization and outcomes of ECMO use between centers. While multiple CDH mortality risk calculators are available, no validated tool exists specifically for prediction of ECMO use. The purpose of this study was to derive and validate an ECMO risk stratification model. METHODS The study population was obtained from CDH Study Group registry for the period between 2007 and 2016. Only centers offering ECMO were included. The cohort was restricted to ECMO candidates and then divided into derivation and validation sets. Using all relevant perinatal predictors in the registry, univariate analysis was performed for the composite outcome of ECMO use or death without ECMO use. The model was derived using the derivation cohort with multivariable logistic regression and automatic stepwise forward selection (P < 0.05 for qualifying variables), and a c-statistic was obtained. The model was then tested on the validation cohort. Sample reuse validation and bootstrap validation were performed. The validated model was then tested for accuracy on CDH subgroups. RESULTS There were 1992 patients in the derivation cohort. Four significant variables were identified in the final ECMO risk model: 1-min and 5-min Apgar scores and highest and lowest post-ductal partial pressure of CO2 during the first 24 h of life. The model c-statistic was 0.824 which was confirmed with cross-validation and bootstrap optimism correction. The validation cohort c-statistic was 0.823 (N = 993). The model had good discrimination for left and right CDH, inborn and outborn patients, patients born before and after 2011, and high and low volume centers. The model performed significantly better for postnatally diagnosed patients. CONCLUSIONS This study represents proof-of-concept that a risk model can accurately estimate the probability of ECMO use in CDH newborns. This stratification could assist centers as a metric for assessment of ECMO usage and outcomes. Refinement and prospective validation of this model should be carried out prior to clinical application. LEVEL OF EVIDENCE 3.

Argatroban in Post-Cardiovascular Surgery Patient with Heparin-Induced Thrombocytopenia Requiring Hemodialysis and Continuous Hemofiltration

Objective: To describe the use of argatroban in a postoperative cardiovascular surgery patient with heparin-induced thrombocytopenia (HIT) requiring hemodialysis and continuous veno-veno hemofiltration (CVVH). Case Summary: A 23-year-old white woman with HIT developed acute renal failure after cardiovascular surgery. Argatroban was used as a substitute for heparin during hemodialysis and CVVH. Both activated partial thromboplastin time (aPTT) and activated clotting time (ACT) were used to guide the dosage of argatroban. The patient was successfully dialyzed without clotting of the circuit. The dosage required in our patient was much lower than the manufacturers recommendation. Discussion: Argatroban is a selective thrombin inhibitor that does not cross-react with heparin-induced antibodies. It is metabolized by the liver, and dosage adjustment is recommended in patients with severe hepatic impairment. The correct dosage for patients with unstable hemodynamics is not known. Our patient had apparently normal hepatic function at the initiation of therapy, but the dosage of argatroban recommended by the manufacturer resulted in prolonged elevation of the aPTT and ACT with associated gastrointestinal bleeding. This may be due to hepatic congestion secondary to poor cardiac function and/or severe generalized edema. Conclusions: When argatroban is considered for therapy in place of heparin for CVVH, it needs to be used with extreme caution since the correct initial dosage in patients with mild hepatic impairment and unstable hemodynamics is unclear.