Hypocapnia, Hypoxic-Ischaemic Encephalopathy, Perinatal Asphyxia
Conditions
Keywords
Hypothermia treatment, Hypocapnia, Inhaled CO2, Neuroprotection
Brief summary
This is a Phase I, open-label, single center trial to evaluate the feasibility and safety of low concentration CO2 gas mixture (5% CO2 + 95% air) inhalation in asphyxiated, cooled, mechanically ventilated newborns at risk of hypocapnia with The hypothesis is that hypocapnia, which is driven by hyperventilation in the presence of metabolic acidosis, is deleterious to the injured brain and can be safely avoided with low concentration CO2 inhalation.
Detailed description
Specific aims: 1. To test the feasibility of low concentration inhalative CO2 gas mixture (5% CO2 + 95% air) administration to achieve a desired range of pCO2 of 40-60 mmHg in asphyxiated, cooled, mechanically ventilated newborns at risk of hypocapnia with moderate to severe hypoxic-ischemic encephalopathy. 2. To test the safety of CO2 gas mixture (5% CO2 + 95% air) inhalation in asphyxiated, cooled, mechanically ventilated newborns at risk of hypocapnia with moderate to severe hypoxic-ischemic encephalopathy. Term infants (≥ 36 weeks of gestation) will have to be at risk of hypocapnia to be eligible, as defined by a temperature corrected pCO2 ≤ 40 mmHg in blood gas analysis, at any time within six hours of life. The gas mixture will be administered through patient circuits in conventional ventilators. Administered CO2 level will be closely monitored at the inhalation circuit (constant 5% = 36 mmHg). Blood gas samples will be taken hourly to ensure targeted and tolerable pCO2 levels.
Interventions
OTHER5% carbon-dioxide inhalation
5% CO2 (36 mmHg) and 95% air gas mixture inhalation, for a maximum of 12 hours or until metabolic acidosis recovery occurs as measured by BE \> -5 mmol/L in arterial blood gas samples
Sponsors
Semmelweis University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Hours
Healthy volunteers
No
Inclusion criteria
* At any time within six hours of life the temperature corrected pCO2 is less than or equal to 40 mmHg after the parameters of mechanical ventilation is set according to standard protocol (SIMV+VG 5ml/kg, fr 20/min, PEEP 5 H20cm, Ti 0,35-0,45 sec). * Moderate hypoxic- ischaemic encephalopathy, fulfilling TOBY criteria (A, B, C). * ≥ 36. gest. week * \< 6th hours of life * Hypothermia treatment * Parental consent form * Spontaneous breathing * Endotracheal intubation * AUC, VUC in place
Exclusion criteria
* Major birth defect * Meconium aspiration syndrome * Need for combined catecholamine therapy * FiO2 \> 40% * Htc \< 35% * Acid-base status: pH \< 6.8, lactate \> 15mM * Excessive bicarbonate administration during initial stabilization (\> 1mmol/kg)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation. | 3 days |
Secondary
| Measure | Time frame |
|---|---|
| Time until the end point of metabolic acidosis (BE > -5 mmol/L) | During CO2 inhalation (max. 12 hours) |
| Time until the end point of acidosis (pH > 7.25) | During therapeutic hypothermia (max. 72 hours) |
| Severe hypotension (mean arterial pressure less than 25 mmHg), despite full inotrope support and volume replacement. | During therapeutic hypothermia (max. 72 hours) |
| Number of seizures, either detected clinically or by amplitude integrated EEG monitoring | Within one week |
| Reduction in Lac/NAA ratio on magnetic resonance spectroscopy | Within seven days |
| Preserved fractional anisotropy measured on diffusion weighted MRI | Within seven days |
| Death | Within one month |
| Intracranial haemorrhage detected by MRI | Within seven days |
Countries
Hungary
Outcome results
None listed