Pharmacodynamics and Pharmacokinetics of Morphine After Cardiac Surgery in Children With and Without Down Syndrome.

OBJECTIVE: To compare the pharmacodynamics and pharmacokinetics of IV morphine after cardiac surgery in two groups of children-those with and without Down syndrome. DESIGN: Prospective, single-center observational trial. SETTING: PICU in a university-affiliated pediatric teaching hospital. PATIENTS: Twenty-one children with Down syndrome and 17 without, 3-36 months old, scheduled for cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: A loading dose of morphine (100 µg/kg) was administered after coming off bypass; thereafter, morphine infusion was commenced at 40 µg/kg/hr. During intensive care, nurses regularly assessed pain and discomfort with validated observational instruments (COMFORT-Behavior scale and Numeric Rating Scale-for pain). These scores guided analgesic and sedative treatment. Plasma samples were obtained for pharmacokinetic analysis. MEASUREMENTS AND MAIN RESULTS: Median COMFORT-Behavior and Numeric Rating Scale scores were not statistically significantly different between the two groups. The median morphine infusion rate during the first 24 hours after surgery was 31.3 µg/kg/hr (interquartile range, 23.4-36.4) in the Down syndrome group versus 31.7 µg/kg/hr (interquartile range, 25.1-36.1) in the control group (p = 1.00). Population pharmacokinetic analysis revealed no statistically significant differences in any of the pharmacokinetic variables of morphine between the children with and without Down syndrome. CONCLUSIONS: This prospective trial showed that there are no differences in pharmacokinetics or pharmacodynamics between children with and without Down syndrome if pain and distress management is titrated to effect based on outcomes of validated assessment instruments. We have no evidence to adjust morphine dosing after cardiac surgery in children with Down syndrome.

A prospective crossover comparison of neurally adjusted ventilatory assist and pressure-support ventilation in a pediatric and neonatal intensive care unit population.

OBJECTIVE: To compare neurally adjusted ventilatory assist ventilation with pressure-support ventilation. DESIGN: Prospective, crossover comparison study. SETTING: Tertiary care pediatric and neonatal intensive care unit. PATIENTS: Sixteen ventilated infants and children: mean age = 9.7 months (range = 2 days-4 yrs) and mean weight = 6.2 kg (range = 2.4-13.7kg). INTERVENTIONS: A modified nasogastric tube was inserted and correct positioning was confirmed. Patients were ventilated in pressure-support mode with a pneumatic trigger for a 30-min period and then in neurally adjusted ventilatory assist mode for up to 4 hrs. MEASUREMENTS AND MAIN RESULTS: Data collected for comparison included activating trigger (neural vs. pneumatic), peak and mean airway pressures, expired minute and tidal volumes, heart rate, respiratory rate, pulse oximetry, end-tidal CO2 and arterial blood gases. Synchrony was improved in neurally adjusted ventilatory assist mode with 65% (+/-21%) of breaths triggered neurally vs. 35% pneumatically (p < .001) and 85% (+/-8%) of breaths cycled-off neurally vs. 15% pneumatically (p = .0001). The peak airway pressure in neurally adjusted ventilatory assist mode was significantly lower than in pressure-support mode with a 28% decrease in pressure after 30 mins (p = .003) and 32% decrease after 3 hrs (p < .001). Mean airway pressure was reduced by 11% at 30 mins (p = .13) and 9% at 3 hrs (p = .31) in neurally adjusted ventilatory assist mode although this did not reach statistical significance. Patient hemodynamics and gas exchange remained stable for the study period. No adverse patient events or device effects were noted. CONCLUSIONS: In a neonatal and pediatric intensive care unit population, ventilation in neurally adjusted ventilatory assist mode was associated with improved patient-ventilator synchrony and lower peak airway pressure when compared with pressure-support ventilation with a pneumatic trigger. Ventilating patients in this new mode seem to be safe and well tolerated.

Health-related quality of life after prolonged pediatric intensive care unit stay.

OBJECTIVE: To investigate the long-term health-related quality of life (HRQOL) outcomes for patients requiring at least 28 days of pediatric intensive care. DESIGN: Retrospective cohort and prospective follow-up study. SETTING: A 21-bed pediatric intensive care unit (PICU) in a university-affiliated, tertiary referral pediatric hospital. PATIENTS: One hundred ninety-three patients who spent 28 days or longer in the PICU between January 1, 1997 and December 31, 2004. INTERVENTIONS: Quality of life was measured using the Pediatric Quality of Life Inventory (Peds QL 4.0) parent-proxy version at 2 to 10 yrs after discharge. The PedsQL 4.0 is a modular measure of HRQOL, which is reliable in children aged 2 to 18 yrs. It generates a total score and physical, emotional, social, school, and psychosocial subscores. MEASUREMENTS AND MAIN RESULTS: Of the 193 patients, 41 died during their PICU admission and 27 died between PICU discharge and follow-up. Quality of life questionnaires were posted to parents of 108 of the 125 survivors and 70 were returned completed. Forty children (57.1%) had scores indicating a normal quality of life, whereas 30 (42.9%) had scores indicating impaired HRQOL. Of these, 14 (20%) had scores indicating poor quality of life with ongoing disabling health problems requiring hospitalization or the equivalent. CONCLUSIONS: Our results indicate that, while long PICU stay is associated with significant mortality, the long-term HRQOL is normal for the majority of surviving children.