Therapeutic hypothermia (TH) has become the standard of care treatment to improve morbidity and mortality in infants with hypoxic-ischemic encephalopathy (HIE). Although TH has clearly proven to be beneficial, recent studies suggest optimization of respiratory management as an approach to prevent further damage and improve neurodevelopmental outcome. The ventilatory management of asphyxiated neonates presents a challenge because both the hypoxic insult and TH have an impact on respiratory functions. Although the danger of recurrence of hypocapnia is well recognized, a brief period of severe hyperoxia also can be detrimental to the previously compromised brain and have been shown to increase the risk of adverse neurodevelopmental outcomes. Therefore, judicious ventilatory management with rigorous monitoring is of particular importance in patients with HIE. In the present review, we provide an overview of the currently available evidence on pulmonary function, respiratory morbidities, and ventilation strategies in HIE and we highlight possible future research directions.

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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.

During volume guarantee ventilation with a Dräger VN500 ventilator, without leak compensation the expired tidal volume declined after 50% leak. With leak compensation, the tidal volume was maintained even with a large leak. With leak compensation, there was a more stable peak inflating pressure, although the PCO2 was slightly higher.

Hypothermia increased the risk of hypocapnia in neonates with HIE during transport.

Therapeutic hypothermia during transport is feasible and safe, allowing for significantly earlier initiation and achievement of target temperature, possibly providing further benefit for neonates with hypoxic-ischemic encephalopathy.