The pharmacokinetics of isoproterenol in critically ill pediatric patients.

The pharmacokinetics of isoproterenol (ISO) in infants and children have never been reported. The authors studied ISO pharmacokinetics in two disparate groups of pediatric intensive care unit patients: postoperative cardiac patients (POC, n = 10), and reactive airway disease patients (RAD, n = 9). In all, 44 blood samples were taken at steady-state from the 19 patients, whereas from 15 patients samples were also taken just before and after discontinuation of ISO infusion. There were 12 male and 7 female patients in the study, and their ages ranged from 2 days to 14 years. The average ISO dosing rate was 0.30 micrograms/kg/minute for the whole study population, ranging from 0.01 to 5.5 micrograms/kg/minute. The POC patients received a significantly lower dosing rate than the RAD patients (0.029 +/- 0.002 vs 0.50 +/- 0.21 micrograms/kg/minute, P < .0001); the average steady-state plasma concentrations of ISO were also lower in the POC patients (1.3 +/- 0.3 versus 13.9 +/- 4.9 ng/mL, P < .0001). The steady-state plasma concentration, normalized to a dosing rate of .05 micrograms/kg/minute, was 1.9 +/- 0.3 ng/mL for all patients, and the clearance was 42.5 +/- 5.0 mg/kg/minute. Postoperative cardiac patients had a significant higher normalized steady-state plasma concentration and moderately significant lower clearance than did RAD patients (2.1 +/- 0.3 versus 1.7 +/- 0.4 ng/mL, P < .05 and 33.2 +/- 4.9 versus 48.4 +/- 7.3, P < .06, respectively). The average plasma half-life of ISO was 4.2 +/- 1.5 minutes, and the volume of distribution was 216 +/- 57 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain-death criteria currently used by pediatric intensivists.

A survey was done to identify how pediatric intensivists determine brain death in children. Forty-nine pediatric intensive-care units (PICUs) were surveyed. The questionnaire explored the following areas: 1) clinical and confirmatory studies performed, 2) types of physicians involved, and 3) reevaluation intervals. Thirty-four centers responded to the questionnaire. Sixty-nine percent were children's hospitals, and 94% were university affiliates. The mean number of PICU beds was 17, with a mean admission rate of 890 patients per year, and the mean mortality rate for these units was 6%. There was general agreement on the sufficiency of clinical examination to determine cortical and brain-stem function. All the pediatric intensivists noted that a positive apnea test, absent cephalic reflexes, fixed and dilated pupils, and no motor response to pain were reliable signs of brain death. Radionuclide cerebral-flow scan and EEG were the confirmatory tests routinely used. Most physicians (77%) felt a second clinical examination was required within 12 to 24 hours. The opinion of more than one physician, one of whom was a neurospecialist, was required in 80% of the surveyed institutions.

Estimation of arterial carbon dioxide by end-tidal and transcutaneous PCO2 measurements in ventilated children.

Simultaneous measurements of arterial, end-tidal, and transcutaneous carbon dioxide (PaCO2, PetCO2, PtcCO2, respectively) were obtained in 134 children receiving mechanical ventilation (ages, 2 days to 16 years; mean, 2.5 years). The mean +/- SD PetCO2 bias (PaCO2 - PetCO2) was 3.4 +/- 6.6 mmHg. When the PetCO2 bias was plotted against the PaO2/PAO2 ratio, a change in the scatter was obvious at about 0.3. The PetCO2 bias for patients with PaO2/PAO2 under 0.3 was 7.8 +/- 7.3 mmHg compared to 0 +/- 3.4 in patients with PaO2/PAO2 above 0.3 (P less than 0.001). PetCO2 differed significantly from PaCO2 (P less than 0.001) only for patients with PaO2/PAO2 under 0.3. The slope (PaCO2 versus PetCO2) for these patients was 1.59, while the slope for patients with PaO2/PAO2 above 0.3 coincided with the line of identity (1.00). The mean +/- SD PtcCO2 bias (PaCO2 - PtcCO2) was -1.3 +/- 7.2 mmHg. Skin perfusion was recorded at the area close to the transcutaneous CO2 monitor electrode and was defined as normal when capillary refill was below 3 seconds. The PtcCO2 bias for patients with normal skin perfusion was -0.2 +/- 5.4 mmHg (P = 0.73) compared to -4.1 +/- 9.9 for patients with decreased skin perfusion (P = 0.01). The slope of PtcCO2 against PaCO2 was closer to identity in patients with normal skin perfusion (1.17) than in patients where it was decreased (slope, 1.40). We suggest that PaCO2 estimation by both PetCO2 and PtcCO2 is sufficiently precise and reliable for clinical use in critically ill children. Certain limitations stem from the nature of the techniques.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of dopamine in infants and children.

OBJECTIVE: We studied the pharmacokinetics of dopamine in hemodynamically stable children. DESIGN: Prospective clinical trial. SETTING: Pediatric ICU. PATIENTS: Children (age 3 months to 13 yrs) recovering from cardiac surgery or shock. INTERVENTION: Plasma dopamine concentrations were measured at the steady state or at termination of infusion using high-performance liquid chromatography. RESULTS: The half-lives of distribution and elimination were 1.8 +/- 1.1 and 26 +/- 14 (SD) mins, respectively. The apparent volume of distribution was 2952 +/- 2332 mL/kg. The clearance rate was 454 +/- 900 mL/kg.min. Dopamine clearance was linearly related to dose only in patients who were also receiving dobutamine (r2 = .76, p less than .05). Hepatic and renal dysfunction did not affect the pharmacokinetics of dopamine. CONCLUSIONS: A relationship between dopamine and dobutamine that affects the disposition of these two drugs may exist. The pharmacokinetics of dopamine are variable even in hemodynamically stable children. Hepatic or renal function does not adversely affect the pharmacokinetics of dopamine.

The pharmacokinetics of dobutamine in pediatric intensive care unit patients.

Dobutamine is used for hemodynamic support in critically ill patients; however, due to the relative insensitivity of most available assays, there is little detailed information about its pharmacokinetics. We studied the pharmacokinetics of dobutamine in 27 children and infants using a high-sensitivity HPLC technique. The patients' ages ranged from 0.13 to 16.6 years; 17 received dobutamine for treatment of shock while 10 received it for treatment of post-cardiac surgery. Blood samples were collected before (N = 27) and after (N = 10, 9 time points each) the cessation of dobutamine infusion. The duration of dobutamine infusion before sampling was 1.87 +/- 0.29 days (range: 0.2-5.5; median: 1). The steady-state plasma concentration of dobutamine (infusion rate corrected to 5.0 micrograms/kg/min) was 105 +/- 19 ng/ml (range: 3.79-400; median: 76). The clearance rate was 151.1 +/- 47.5 ml/kg/min (range: 12.5-1319; median: 66). Most post-infusion time-concentration data were best fit to a biexponential function suggestive of a two-compartment model. The t1/2 alpha was 1.65 +/- 0.20 min (range: 0.64-3.01; median: 1.52) while the t1/2 beta was 25.8 +/- 11.5 min (range: 4.6-68.6; median: 16.9). Neither age, weight, sex, disease state, duration of infusion, nor blood measures of renal or hepatic dysfunction were found to be covariates of the above parameters. It was found, however, that the concomitant administration of dopamine altered dobutamine's pharmacokinetics, indicating the possible presence of a competitive component in dobutamine's disposition.

Vecuronium by continuous infusion for neuromuscular blockade in infants and children.

Vecuronium's short half-life and minimal cardiopulmonary side-effects make it a suitable drug for continuous infusion. Vecuronium is used frequently in critically ill patients to increase their total compliance and to minimize the adverse effects of mechanical ventilation. This crossover, prospective study evaluates the use of vecuronium by continuous infusion vs. hourly boluses. Patients were assigned randomly to either method; 12 h later each group was transferred to the other method. Neuromuscular blockade (NMB) was followed with the Train-of-Four method. Cardiopulmonary variables were followed hourly. The total dosage/kg body weight was calculated for each method. Six patients were started with continuous drip and the other six with hourly boluses. There were no significant differences in the cardiopulmonary variables through the two periods, although statistically there was a significant difference in the total dosage/kg body weight required for each method. The mean of total vecuronium used in the drip was 0.79 mg/kg.12 h (range 0.1 to 1.8). The mean of the hourly boluses was 1.34 mg/kg.12 h (range 1.0 to 2.55). Patients on continuous infusion required less vecuronium to maintain a similar NMB (p less than .01).