Hypoxic-Ischemic Encephalopathy Therapy Optimization in Neonates for Better Neuroprotection With Inhalative CO2
- Conditions
- Hypoxic-Ischaemic EncephalopathyPerinatal AsphyxiaHypocapnia
- Interventions
- Other: 5% carbon-dioxide inhalation
- Registration Number
- NCT02700854
- Lead Sponsor
- Semmelweis University
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 10
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 5% carbon-dioxide inhalation 5% carbon-dioxide inhalation 5% carbon-dioxide will be administered through patient circuits to asphyxiated, cooled, mechanically ventilated newborns at risk for hypocapnia
- Primary Outcome Measures
Name Time Method Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation. 3 days
- Secondary Outcome Measures
Name Time Method Time until the end point of metabolic acidosis (BE > -5 mmol/L) During CO2 inhalation (max. 12 hours) Death Within one month Severe hypotension (mean arterial pressure less than 25 mmHg), despite full inotrope support and volume replacement. During therapeutic hypothermia (max. 72 hours) Intracranial haemorrhage detected by MRI Within seven days Reduction in Lac/NAA ratio on magnetic resonance spectroscopy Within seven days Preserved fractional anisotropy measured on diffusion weighted MRI Within seven days Number of seizures, either detected clinically or by amplitude integrated EEG monitoring Within one week Time until the end point of acidosis (pH > 7.25) During therapeutic hypothermia (max. 72 hours)
Trial Locations
- Locations (1)
Semmelweis University, 1st Department of Pediatrics
🇭🇺Budapest, Hungary