Pediatric Transport-Specific Illness Severity Scores Predict Clinical Deterioration of Transported Patients.

OBJECTIVE: The Transport Risk Assessment in Pediatrics (TRAP) and Transport Pediatric Early Warning Scores (T-PEWS) are transport-specific pediatric illness severity scores that are adjunct assessment tools for determining disposition of transported patients. We hypothesized that these scores would predict the risk of clinical deterioration in transported patients admitted to general pediatric wards. METHODS: Activation of a rapid response team (RRT) in the first 24 hours of admission was used as a marker of deterioration. All pediatric transports between March 2017 and February 2020 admitted via critical care transport were included. Transports to the emergency department (ED) were excluded. This retrospective chart review evaluated TRAP and T-PEWS scores at 3 points: (1) arrival of transport team at referring hospital, (2) admission to the children's hospital, and (3) RRT activation, if occurring within 24 hours of admission. RESULTS: There were 1137 team transports during this period. Three hundred ninety-nine patients transported to the ED were excluded, leaving 738 included patients; 405 (55%) admitted to the general wards and 333 (45%) admitted to the pediatric intensive care unit. Twenty-five patients admitted to the wards (6%) had an RRT activation within 24 hours of admission. Statistical analysis used 2-sample t tests. There was a statistically significant difference in scores for ward admissions between those who had RRT activation and those who did not. CONCLUSIONS: Both TRAP and T-PEWS can be used to predict the risk of clinical deterioration in transported patients admitted to general wards. These scores may assist in assessing which patients admitted to the wards need closer observation.

Assessment of midazolam pharmacokinetics in the treatment of status epilepticus.

OBJECTIVES: Refractory status epilepticus (RSE) is often treated with midazolam boluses and continuous infusions, but there is considerable variability in dosing and efficacy. We aimed to evaluate the performance of a clinical midazolam dose escalation pathway for the treatment of pediatric RSE that was designed based on a novel midazolam pharmacokinetic model. DESIGN: Prospective pharmacokinetic study of midazolam bolus and escalation of continuous midazolam infusion. SETTING: Pediatric Intensive Care Unit in quaternary-care academic hospital. SUBJECTS: Children between two months to seventeen years of age who received clinically-indicated midazolam infusion for treatment of RSE. INTERVENTION: Blood sampled at regular intervals during treatment. Main study outcome measure was the accuracy of a pharmacokinetic model to predict serum midazolam concentrations. MEASUREMENTS AND MAIN RESULTS: We analysed data from six subjects. Three subjects had serum midazolam concentrations close to those predicted by our initial model (accuracy 88.9-170.2 %) which incorporates body weight, hepatic function, and renal function. For the other three subjects, all of whom were receiving pre-existing chronic benzodiazepine therapy prior to the RSE episode, the model grossly overestimated serum concentrations (predictive error 420.3-722.5 %). Once the model was corrected for the impact of pre-existing chronic benzodiazepine use on clearance, predicted concentrations more closely reflected those measured in subjects. CONCLUSION: We evaluated a clinical midazolam RSE treatment pathway but discovered that the model on which the pathway was based was not accurate for all patients. We therefore developed a novel pharmacokinetic midazolam model in children with RSE treated with continuous midazolam infusion. This model incorporates body weight, hepatic and renal function, and importantly, a correction factor for pre-existing chronic benzodiazepine use. Once validated, this model may guide dosing and drive the development of more effective treatment pathways for continuous midazolam in RSE.

Vecuronium- and Esmolol-Induced Pseudohypernatremia Due to Drug Interference With Ion-Selective Electrodes.

OBJECTIVES: We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry analyzer as part of the basic metabolic panel (Vitros 5600; Ortho Clinical Diagnostics, Raritan, NJ), but not by blood gas analyzers (RAPIDLab 1265; Siemens, Tarrytown, NY). Both instruments use direct ion-selective electrode technology, albeit with different sodium ionophores (basic metabolic panel: methyl monensin, blood gas: glass). We questioned if the basic metabolic panel hypernatremia represents artefactual pseudohypernatremia. DESIGN: We added vecuronium bromide or esmolol hydrochloric acid to pooled plasma samples and compared sodium values measured by both methodologies. We queried sodium results from the electronic medical records of patients admitted at Children's Hospital of Philadelphia from 2016 to 2018 and received vecuronium and/or esmolol infusion treatment during their admissions. SETTING: PICU of a quaternary, free-standing children's hospital. PATIENTS: Children admitted to the hospital who received vecuronium and/or esmolol infusion. MEASUREMENTS AND MAIN RESULTS: Sodium was measured in pooled plasma samples by basic metabolic panel and blood gas methodologies after adding vecuronium bromide or esmolol hydrochloric acid, leading to a dose-response increase in basic metabolic panel sodium measurements. A repeated measures regression analysis of our electronic medical records showed that the vecuronium dose predicted the Δ sodium (basic metabolic panel-blood gas) sodium within 12 hours of the vecuronium administration (p < 0.0018). Esmolol showed a similar trend (p = 0.13). This occurred primarily in central line samples with continuous vecuronium or esmolol infusions. CONCLUSIONS: Vecuronium and esmolol can falsely elevate direct ion-selective electrode sodium measurements on Vitros chemistry analyzers. Unexpectedly high sodium measurements in patients receiving vecuronium and/or esmolol infusions should be further investigated with an alternate sample type (i.e., peripheral blood) or measurement methodology (i.e., blood gas) to guide treatment decisions.

Safety of intravenous lacosamide in critically ill children.

PURPOSE: Acute seizures are common in critically ill children. These patients would benefit from intravenous anti-seizure medications with few adverse effects. We reviewed the usage and effects of intravenous lacosamide in critically ill children with seizures or status epilepticus. METHODS: This retrospective series included consecutive patients who received at least one dose of intravenous lacosamide from April 2011 to February 2016 in the pediatric intensive care unit of a quaternary care children's hospital, including patients with new lacosamide initiation and continuation of outpatient oral lacosamide. Dosing and prescribing practices were reviewed. Adverse effects were defined by predefined criteria, and most were evaluated during the full admission. RESULTS: We identified 51 intensive care unit admissions (47 unique patients) with intravenous lacosamide administration. Lacosamide was utilized as a third or fourth-line anti-seizure medication for acute seizures or status epilepticus in the lacosamide-naïve cohort. One patient experienced bradycardia and one patient experienced a rash that were considered potentially related to lacosamide. No other adverse effects were identified, including no evidence of PR interval prolongation. CONCLUSIONS: Lacosamide was well tolerated in critically ill children. Further study is warranted to evaluate the effectiveness of earlier lacosamide use for pediatric status epilepticus and acute seizures.