Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage
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Purpose
Annually, almost 5,000 extremely low birth weight (9 ounces to about 2 lbs) infants born in the US survive with severe bleeding in the brain (intraventricular hemorrhage); this devastating complication of prematurity is associated with many problems, including mental retardation, cerebral palsy, and learning disabilities, that result in profound individual and familial consequences. In addition, lifetime care costs for these severely affected infants born in a single year exceed $3 billion. The huge individual and societal costs underscore the need for developing care strategies that may limit severe bleeding in the brain of these tiny infants. The overall goal of our research is to evaluate disturbances of brain blood flow in these tiny infants in order to predict which of them are at highest risk and to develop better intensive care techniques that will limit severe brain injury.
- Since most of these infants require ventilators (respirators) to survive, we will investigate how 2 different methods of ventilation affect brain injury. We believe that a new method of ventilation, allowing normal carbon dioxide levels, will normalize brain blood flow and lead to less bleeding in the brain.
- We will also examine how treatment for low blood pressure in these infants may be associated with brain injury. We believe that most very premature infants with low blood pressure actually do worse if they are treated. We think that by allowing the infants to normalize blood pressure on their own will allow them to stabilize blood flow to the brain leading to less intraventricular hemorrhage.
- In 10 premature infants with severe brain bleeding, we have developed a simple technique to identify intraventricular hemorrhage before it happens. Apparently, the heart rate of infants who eventually develop severe intraventricular hemorrhage is less variable than infants who do not develop this. We plan to test this method in a large group of infants, to be able to predict which infants are at highest risk of developing intraventricular hemorrhage and who could most benefit from interventions that would reduce disturbances of brain blood flow.
| Condition | Intervention |
|---|---|
|
Intraventricular Hemorrhage Autoregulation |
Device: Hypercapnia Other: Normocapnia |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage |
- The effect of hypercapnia vs. normocapnia on the development of intraventricular hemorrhage during the first week of life [ Time Frame: During first week of life ] [ Designated as safety issue: Yes ]
- The effect of hypercapnia and hypotension on the capacity for cerebral autoregulation [ Time Frame: First week of life ] [ Designated as safety issue: No ]
- The development of intraventricular hemorrhage based upon abnormal heart rate variability [ Time Frame: first week of life ] [ Designated as safety issue: No ]
- The effect of hypercapnia vs. normocapnia on the development of chronic lung disease during premature infants' initial hospitalization [ Time Frame: By 36 weeks corrected gestational age. ] [ Designated as safety issue: Yes ]
- The effect of hypercapnia vs. normocapnia on the development of respiratory complications (number of days on mechanical ventilation, air leaks, number of reintubations) [ Time Frame: During the initial newborn hospitalization ] [ Designated as safety issue: Yes ]
- The effect of hypercapnia vs. normocapnia survival and length of hospital stay. [ Time Frame: During the initial newborn hospitalization ] [ Designated as safety issue: Yes ]
- The effect of hypercapnia vs. normocapnia on the development of periventricular leukomalacia [ Time Frame: During the initial hospitalizaiton ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 160 |
| Study Start Date: | June 2008 |
| Estimated Study Completion Date: | May 2013 |
| Estimated Primary Completion Date: | May 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: A
Hypercapnic ventilation. The goal will be to maintain tcPCO2 55 mm Hg (50-60 mm Hg) and pH ≥7.20 (based on intermittent arterial blood gas determinations) during the first week of life, or until extubation. A written, laminated hypercapnic ventilator algorithm will be placed at the bedside.
|
Device: Hypercapnia
tcPCO2 50-60 mm Hg
Other Names:
|
|
Placebo Comparator: B
Normocapnic ventilation. The goal will be to maintain tcPCO2 40 mm Hg (35-45 mm Hg) and pH ≥7.25 (based on intermittent arterial blood gas determinations) during the first week of life, or until extubation. A written, laminated normocapnic ventilator algorithm will be placed at the bedside.
|
Other: Normocapnia
tcPCO2 35-45 mm Hg
Other Name: Normocarbia
|
Eligibility| Ages Eligible for Study: | up to 7 Days |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- ventilated ELBW (401-1000 grams) infants
- 23 to 30 weeks' gestation
- umbilical arterial catheter placed during newborn resuscitation
Exclusion Criteria:
- presence of complex congenital anomalies or chromosomal abnormality
- presence of central nervous system malformation
- infants with hydrops fetalis
- infants in extremis
- infants with early (<3 hour of age) intraventricular hemorrhage
Contacts and Locations| Contact: Jeffrey R. Kaiser, MD, MA | 501-364-1056 | kaiserjeffreyr@uams.edu |
| Contact: Natalie C. Sikes, RN | 501-686-7580 | sikesnataliec@uams.edu |
| United States, Arkansas | |
| University of Arkansas for Medical Sciences | Recruiting |
| Little Rock, Arkansas, United States, 72205 | |
| Contact: Jeffrey R. Kaiser, MD, MA 501-364-1056 kaiserjeffreyr@uams.edu | |
| Contact: Natalie C. Sikes, RN 501-686-7580 sikesnataliec@uams.edu | |
| Principal Investigator: Jeffrey R. Kaiser, MD, MA | |
| Principal Investigator: | Jeffrey R. Kaiser, MD, MA | University of Arkansas |
More Information
Publications:
| Responsible Party: | University of Arkansas |
| ClinicalTrials.gov Identifier: | NCT00665769 History of Changes |
| Other Study ID Numbers: | 102864, 1RO1NS60674-01A1 |
| Study First Received: | April 22, 2008 |
| Last Updated: | January 18, 2012 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Keywords provided by University of Arkansas:
|
hypercapnia normocapnia chronic lung disease periventricular leukomalacia intraventricular hemorrhage |
hypotension cerebral autoregulation heart rate variability autonomic nervous system detrended fluctuation analysis |
Additional relevant MeSH terms:
|
Infant, Newborn, Diseases Hemorrhage Cerebral Hemorrhage Fetal Diseases Pathologic Processes Intracranial Hemorrhages Cerebrovascular Disorders |
Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Pregnancy Complications |
ClinicalTrials.gov processed this record on May 16, 2013