ETCare: a randomized, controlled, masked trial comparing two solutions for upper airway care in the NICU.

BACKGROUND: Small quantities of normal saline are sometimes instilled into the endotracheal tube of intubated neonates, to assist with the removal of thick secretions and maintain patency of the endotracheal tube. However, saline is detrimental to the innate immune system of the upper airway mucosa, rapidly unfolding and inactivating antimicrobial peptides such as LL-37. We previously reported the preparation and feasibility testing of 'ETCare', a low-sodium, physiologically based solution for airway care, and we now report results of a randomized, masked, controlled, two-centered study testing ETCare vs sterile saline among 60 intubated NICU patients. STUDY DESIGN: Sixty intubated NICU patients were randomized to having their airway care with ETCare vs saline. Three hypotheses were tested: (1) tolerance - patients will tolerate ETCare for airway care as well as they tolerate saline, (2) nosocomial infections - ETCare will result in fewer tracheal aspirates where organisms grow and fewer cases of nosocomial sepsis, and (3) chronic lung disuse - ETCare will result in fewer patients discharged home on supplemental O2. RESULTS: Thirty NICU patients with an endotracheal tube in place were randomized to receive their airway care with ETCare, and 30 to receive their care with saline. Only the pharmacist was aware of the randomization; the two solutions were visually indistinguishable and were dispensed in identical syringes. Tolerance of the solutions was similar. The ETCare recipients had trends toward fewer positive blood cultures (odds ratios (OR), 0.48; 95% confidence interval (CI), 0.13 to 1.68), and fewer discharges home on supplemental O2 (OR, 0.43; 95% CI, 0.14 to 1.32; P=0.075). CONCLUSIONS: On the basis of this study and our previous 10-patient feasibility trial, we maintain that, for airway care, intubated NICU patients tolerate ETCare as well as saline. Data from this study can be used in estimating the sample sizes needed for a phase III trial. We speculate that such a trial will demonstrate that, compared with saline, ETCare will result in fewer nosocomial infections and less chronic lung disease.

Treating feeding intolerance with an enteral solution patterned after human amniotic fluid: a randomized, controlled, masked trial.

OBJECTIVE: Feeding intolerance is a common problem in the neonatal intensive care unit (NICU) and some cases might be causally related to atrophic changes in the small bowel mucosa. We speculated that for such patients, feeding tolerance might improve after oral administration of enterocyte growth factors in a sterile, isotonic solution patterned after amniotic fluid. STUDY DESIGN: Twenty neonates meeting criteria for feeding intolerance were eligible for this trial. They were randomized to either Group 1 (test solution) or Group 2 (control). Group 1 received 2.5 ml of test solution/kg every 3 h by oral-gastric or nasal-gastric (OG/NG) tube. This was begun when the patient was NPO because of feeding intolerance and continued until 80 ml/k/day of milk feedings were tolerated, or for a maximum of 7 days. Group 2 received a sham OG/NG administration every 3 h, until 80 ml/k/day of milk feedings were tolerated, or for a maximum of 7 days. Only the bedside nurse and the NICU pharmacist were aware which patients received the test solution and which received the sham administrations. The volumes of milk feedings were increased by order of the attending neonatologist and nurse practitioner. The study outcome was enteral calories/kg/day during and for 7 days after the cessation of the treatments. RESULTS: Eleven patients were randomized to receive the test solution and nine to receive sham administrations. At study entry, the two groups were not different in gestational age, postnatal age, signs of feeding intolerance or cal/k/day taken enterally during the previous 3 days. The study doses were given for an average of just under 6 days (range, 2 to 7 days). During the week following the administrations, the test solution recipients trended toward more enteral calories. Specifically, they had an increase averaging 78+/-20.8 cal/k/day more than before the study, whereas the sham recipients had an increase averaging 55.9+/-33 cal/k/day more than before the study (P=0.05 for a one-sided test and P=0.10 for a two-sided test). The test solution recipients also had a trend toward fewer formula changes than did the sham recipients (P=0.10). In this small, randomized, controlled, masked trial, the administration of a sterile, non-caloric, growth factor containing solution patterned after human amniotic fluid was associated with trends that we interpret as reflecting better tolerance of milk feedings. On this basis, we suggest that a phase III efficacy trial should be accomplished, using the present data for sample size calculations.

Intravenous administration of darbepoetin to NICU patients.

OBJECTIVE: Darbepoetin can be administered either intravenously (i.v.) or subcutaneously (s.c.). However, no information is available regarding pharmacokinetics and pharmacodynamics following its i.v. administration to neonates. STUDY DESIGN: We administered a single i.v. dose (4 microg/kg) of darbepoetin to 10 neonates who had a hemoglobin < or =10.5 g/dl. Blood was obtained for immature reticulocyte fraction (IRF) and absolute reticulocyte count (ARC), before and 48 h following the dose. Blood was also drawn for pharmacokinetic analysis once before and at four pre-set intervals after dosing. RESULTS: The study subjects ranged from 704 to 3025 g (median, 1128 g) birth weight, and were 26.0-40.0 weeks (median, 29.2 weeks) gestation at delivery. When the darbepoetin dose was given, ages ranged from 3 to 28 days (median, 8.5 days) with a hemoglobin of 9.8 +/- 0.7 g/dl (mean +/- s.d.). Doses were administered by i.v. infusion over 4 h. No adverse effects of the infusions were detected. The half-life of darbepoetin (t (1/2)) was 10.1 h (range 9.0-22.7 h), the volume of distribution was 0.77 l/kg (range 0.18-3.05 l/kg) and the clearance was 52.8 ml/h/kg (range 22.4-158.0 ml/h/kg). In the preterm neonates, there was no significant correlation between gestational age, or age at darbepoetin administration, and pharmacokinetic parameters. However, in the term and near-term neonates, volume of distribution correlated significantly with both gestational and age at darbepoetin administration (P < 0.05). Forty-eight hours after dosing, the IRFs and ARCs were elevated in six subjects and not in four. Those with predosing reticulocyte counts >200,000/microl did not have an increase in reticulocytes by 48 h (P < 0.05). CONCLUSIONS: Darbepoetin administered i.v. to neonates had a shorter t (1/2), a larger volume of distribution and more rapid clearance than reported in children. We observed a significantly shorter t (1/2) and a less consistent rise in IRF and ARC after i.v. dosing than we previously reported following 4 microg/kg administered SC.