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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.
Specific aims:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5% carbon-dioxide inhalation | Experimental | 5% carbon-dioxide will be administered through patient circuits to asphyxiated, cooled, mechanically ventilated newborns at risk for hypocapnia |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5% carbon-dioxide inhalation | Other | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of time spent in the desired pCO2 range of 40-60 mmHg (temp. corrected) during CO2 inhalation. | 3 days |
| Measure | Description | Time Frame |
|---|---|---|
| Number of seizures, either detected clinically or by amplitude integrated EEG monitoring | Within one week | |
| Time until the end point of metabolic acidosis (BE > -5 mmol/L) | During CO2 inhalation (max. 12 hours) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Miklós Szabó, MD, PhD | Semmelweis University, 1st Department of Pediatrics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Semmelweis University, 1st Department of Pediatrics | Budapest | 1085 | Hungary |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12097540 | Background | Laffey JG, Kavanagh BP. Hypocapnia. N Engl J Med. 2002 Jul 4;347(1):43-53. doi: 10.1056/NEJMra012457. No abstract available. | |
| 21146184 | Background | Pappas A, Shankaran S, Laptook AR, Langer JC, Bara R, Ehrenkranz RA, Goldberg RN, Das A, Higgins RD, Tyson JE, Walsh MC; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Hypocarbia and adverse outcome in neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2011 May;158(5):752-758.e1. doi: 10.1016/j.jpeds.2010.10.019. Epub 2010 Dec 10. |
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| ID | Term |
|---|---|
| D020925 | Hypoxia-Ischemia, Brain |
| D016857 | Hypocapnia |
| ID | Term |
|---|---|
| D002545 | Brain Ischemia |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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|
| 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) |
| 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 |
| Death | Within one month |
| 15613575 | Background | Klinger G, Beyene J, Shah P, Perlman M. Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? Arch Dis Child Fetal Neonatal Ed. 2005 Jan;90(1):F49-52. doi: 10.1136/adc.2003.048785. |
| 19797281 | Background | Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009 Oct 1;361(14):1349-58. doi: 10.1056/NEJMoa0900854. |
| D009422 | Nervous System Diseases |
| D002534 | Hypoxia, Brain |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000860 | Hypoxia |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |