Neonatal encephalopathy therapy optimization for better neuroprotection with inhalation of CO(2): the HENRIC feasibility and safety trial

BACKGROUND: There is an association between hypocapnia and adverse neurodevelopmental outcome in infants with neonatal encephalopathy (NE). Our aim was to test the safety and feasibility of 5% CO(2) and 95% air inhalation to correct hypocapnia in mechanically ventilated infants with NE undergoing therapeutic hypothermia. METHODS: Ten infants were assigned to this open-label, single-center trial. The gas mixture of 5% CO(2) and 95% air was administered through patient circuits if the temperature-corrected PCO(2) ≤40 mm Hg. The CO(2) inhalation was continued for 12 h or was stopped earlier if the base deficit (BD) level decreased <5 mmol/L. Follow-up was performed using Bayley Scales of Infant Development II. RESULTS: The patients spent a median 95.1% (range 44.6–98.5%) of time in the desired PCO(2) range (40–60 mm Hg) during the inhalation. All PCO(2) values were >40 mm Hg, the lower value of the target range. Regression modeling revealed that BD and lactate had a tendency to decrease during the intervention (by 0.61 and 0.55 mmol/L/h, respectively), whereas pH remained stable. The rate of moderate disabilities and normal outcome was 50%. CONCLUSIONS: Our results suggest that inhaled 5% CO(2) administration is a feasible and safe intervention for correcting hypocapnia.