Neonatal encephalopathy therapy optimization for better neuroprotection with inhalation of CO2: the HENRIC feasibility and safety trial

Abstract

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.

Carbon dioxide levels in neonates: what are safe parameters?

“…Although NE infants with cumulative pCO 2 above the 50th percentile were more likely to have seizures and needed more time to achieve spontaneous respiration, only the time to spontaneous respiration of more than 10 min had a significant association with adverse outcomes. 41 Hansen et al 39 retrospectively studied 23 neonates with moderate to severe NE treated with 72 h of hypothermia and it was found that those from the group with adverse neurodevelopmental outcomes had greater PaCO 2 variability than those from the group with favourable neurodevelopmental outcomes. The hypoxic-ischaemic encephalopathy therapy optimization in neonates for better neuroprotection with inhaled CO 2 (HENRIC) study, which involved 10 term infants, recently demonstrated that inhaled 5% CO 2 was feasible and safe for correcting hypocarbia in NE.…”

“…The hypoxic-ischaemic encephalopathy therapy optimization in neonates for better neuroprotection with inhaled CO 2 (HENRIC) study, which involved 10 term infants, recently demonstrated that inhaled 5% CO 2 was feasible and safe for correcting hypocarbia in NE. 41 …”

“…The hypoxic-ischaemic encephalopathy therapy optimization in neonates for better neuroprotection with inhaled CO 2 (HENRIC) study, which involved 10 term infants, recently demonstrated that inhaled 5% CO 2 was feasible and safe for correcting hypocarbia in NE. 41 Congenital diaphragmatic hernia. CDH is associated with pulmonary hypoplasia and respiratory distress at birth and infants with CDH frequently require mechanical ventilation following delivery.…”

Inhaled H2 or CO2 Do Not Augment the Neuroprotective Effect of Therapeutic Hypothermia in a Severe Neonatal Hypoxic-Ischemic Encephalopathy Piglet Model

“…Hypocapnia may signal impaired restoration of cellular metabolism, predicting unfavorable outcome of resuscitation efforts [54]. Furthermore, hypocapnia can be a consequence of relative hyperventilation in response to metabolic acidosis, and prevention of hypocapnia by inhalation of 5%CO 2 may enhance the efficacy of TH [55]. The question of whether increased CO 2 levels (hypercapnia) maintained while establishing normoxia after asphyxia would convey neuroprotection has been proposed by a set of rat studies employing asphyxia very similar to the one employed in piglets in the present study [19,20,54].…”

“…Alternatively, hypothermia, H 2 or graded restoration of normocapnia may target the activation of similar or even the same pro-survival mechanisms, and either one may activate these alone as efficiently as combined with each other. For instance, TH, CO 2 , and even H 2 are known to reduce neuronal excitability and metabolism, providing means for the occlusion of protective effects [55][56][57][58].…”