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.

Transitional care: a multidisciplinary case management-based unit.

A major challenge confronting health professionals today is the provision of safe, effective, and quality care for patients with the available reimbursement funds. Multidisciplinary case management meets this challenge by providing planned, coordinated care based on patient needs. Children dependent on technology are logical choices for case management since they often experience prolonged hospitalization and require intervention from numerous specialists. To meet this need, LeBonheur Children's Medical Center in Memphis, Tennessee opened the Transitional Care Unit (TCU), which provides the family with a conducive environment for developmental, social, and educational interaction. A retrospective chart review on 10 patients was conducted to assess the efficiency of the unit. Findings demonstrated a decrease in daily costs and hospital stay. A TCU uses scarce hospital resources while efficiently saving health care funds for the individual patient.

Moebius syndrome and central respiratory dysfunction.

Two infants, 18 months and 4 months of age, who were born with bilateral VI and VII nerve palsy (Moebius syndrome) experienced central respiratory failure requiring persistent ventilation. The computed tomography scan showed small brainstem tegmental calcifications. These findings suggest intrauterine brainstem necrosis including the respiratory center and poor prognosis for independent respiration.

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. DESIGN: Prospective, open-label study. SETTING: A university-affiliated children's hospital. PATIENTS: Ten hemodynamically stable infants (age 2 wks-10 mo) in intensive care receiving dobutamine (5) or dopamine (5). Three patients received both agents and were studied at independent times. INTERVENTIONS: Dobutamine and dopamine were administered using the Flo-Gard VP pump that delivers an intentional alteration of flow continuity (rate pulse). Heart rate and mean arterial pressure (MAP) were recorded every second. Analysis was based on the measurements obtained from the first 5 minutes on the study pump and the 2 minutes before and after the rate pulse. MEASUREMENTS AND MAIN RESULTS: Although hemodynamic changes in pre- and post-rate pulses were statistically significant (p < 0.05) in some individuals, only one infant had a greater that 10% change in MAP 2 minutes after the rate pulse. Alterations in hemodynamics were not consistent among or within patients. CONCLUSION: In infants requiring dobutamine or dopamine, no clinically significant pharmacodynamic effects were associated with alteration in continuity of drug delivery caused by the single positive rate pulse. Therefore, we conclude there is no contraindication to the use of this infusion pump in hemodynamically stable infants receiving these drugs.

Frequency and outcome of infectious disease admissions to a pediatric intensive care unit.

This prospective clinical study was designed to assess patients with primary infectious disease (ID) necessitating admission to a pediatric intensive care unit (PICU), to identify morbidity and mortality risk factors, and to better define this subpopulation of critically ill children and compare them with patients who had a noninfectious disease (NID). All patients (N = 1,151) admitted to a multidisciplinary, university-affiliated, 20-bed PICU from January through December 1988 were studied. The patients were classified as having either ID or NID as the primary indication for PICU admission. Other variables assessed included age, sex, requirement for mechanical ventilatory support, and severity of illness at admission as determined by Pediatric Risk of Mortality (PRISM) score. Of the 1,151 patients admitted, 187 (16%) had ID. Patients with ID had significantly higher PRISM scores than NID patients, but mortality rates were not significantly different between the NID group (9%) and the ID group (11%). The ID and NID groups showed no significant difference with regard to sex, number of days in the ICU, or number of days of mechanical ventilatory support. Patients with ID were significantly younger than those without. Although the highest mortality overall was in neonates, there was no difference in mortality rate for this age group between ID and NID. Fifty-five (30%) of the 187 ID patients had a diagnosis of sepsis syndrome on admission, and had significantly higher PRISM scores and mortality than patients with other ID. We concluded that patients admitted to our PICU with a diagnosis of infectious disease were significantly younger and had higher severity of illness scores than patients admitted with a diagnosis of noninfectious disease. The most frequent cause of death in both groups was multisystem organ failure. Patients with sepsis syndrome showed showed no significant difference in overall mortality, but their PRISM scores and mortality rate were significantly greater than those of the other ID patients.

Reversal of dopamine-refractory septic shock by diethyldithiocarbamate, an inhibitor of endothelium-derived relaxing factor.

Septic shock occurs when endotoxin and other bacterial substances induce the release of host products that act in concert to alter the circulation. Recently, investigators have speculated that endothelium-derived relaxing factor (EDRF), a potent endotoxin-inducible vasodilator, plays an important role in the pathogenesis of septic shock. Diethyldithiocarbamate (DTC), a copper chelator lacking intrinsic vasoactivity, inactivates EDRF. Intravenous DTC was compared with placebo and dopamine in 12 matched sets of 3 rabbits with induced Escherichia coli sepsis. Median levels of bacteremia and endotoxemia were similar in the 3 treatment groups. DTC-treated animals had higher mean arterial pressure and lower heart rates and blood lactate concentrations than either placebo- or dopamine-treated animals (P = .013, P < .001, and P = .001, respectively). These effects were independent of plasma catecholamine concentrations. DTC can reverse septic shock that is refractory to conventional therapy, and these results suggest that EDRF is an important mediator of septic shock.

Dexamethasone in the prevention of postextubation stridor in children.

To assess whether there is any advantage in the use of corticosteroid to prevent postextubation stridor in children, we conducted a prospective, randomized, double-blind trial of dexamethasone versus saline solution. The patients were evaluated and then randomly selected to receive either dexamethasone or saline solution according to a stratification based on risk factors for postextubation stridor: age, duration of intubation, upper airway trauma, circulatory compromise, and tracheitis. Dexamethasone, 0.5 mg/kg, was given every 6 hours for a total of six doses beginning 6 to 12 hours before and continuing after endotracheal extubation in a pediatric intensive care setting. There was no statistical difference in incidence of postextubation stridor in the two groups; 23 of 77 children in the placebo group and 16 of 76 in the dexamethasone group had stridor requiring therapy (p = 0.21). We conclude that the routine use of corticosteroids for the prevention of postextubation stridor during uncomplicated pediatric intensive care airway management is unwarranted.

Plasmapheresis for Guillain-Barré syndrome.

Guillain-Barré syndrome is the most common cause of paralytic illness in children. An 8-month-old infant presented with severe Guillain-Barré syndrome associated with parainfluenza 3 infection, was treated with plasmapheresis, and had complete recovery. Plasmapheresis can be technically difficult to perform in small children and infants, but should be considered. Controlled trials should be performed to determine the indications for plasmapheresis in children with Guillain-Barré syndrome.