Reno-protective Effect of Brain Cooling in Newborn With Hypoxia
Condition: Hypoxic Ischemic Encephalopathy
MeSH terms: Brain Diseases; Brain Ischemia; Hypoxia-Ischemia, Brain
Study type: Observational

Summary: 
      This study aims to determine the effect of therapeutic hypothermia on reducing AKI in term
      and late-preterm infants with hypoxic ischemic encephalopathy as estimated by measurment of
      serum(s) neutrophil gelatinase-associated lipocalin(NGAL) and serum (s) cystatin-C.
    

Detailed description: 
      The study will be conducted at the NICU of Mansoura University children's Hospital and
      regional General Hospital where brain cooling is not available.

      Infants will be identified in the delivery room or the NICU based on a per-specified
      inclusion and exclusion criteria. The admitting physician will inform the study team upon
      admitting the infants to prepare for obtaining consent form.

      When a patient is admitted and satisfies the inclusion criteria, one of the investigators or
      delegate will approach the parent(s). Patient identification will be done by admitting
      residents or the nurse practitioners. Parents will be approached by the residents or the
      nurse practitioners while the signature of the consent form in case of agreement will be
      obtained by one of the investigators who are not responsible about the care of the infant.
      Using language understandable to the parent(s), the study protocol will be described in
      detail outlining the procedure and describing any potential risks. All parents will be
      specifically informed that a decision not to participate in the research study will in no way
      compromise their child's care. If the parent(s) agree that their child participate in the
      study, written informed consent will be obtained. A copy of the consent form will be kept
      with the investigators.

      Infants will be classified into two groups, either group 1 (Cooled group) or group 2
      (Non-cooled group) who missed opportunity to be identified within proper time.Categorization
      will be center-based according to the feasibility of cooling devices at proper time (the
      first 12 hours of the baby's life).

      Group 1 (Cooled group) Cooling procedure We will fit a cooling cap (Olympic Medical Cool Care
      System, Olympic Medical) around the head for 72 h. The system consists of a small
      thermostatically controlled cooling unit with a pump that circulated water through the cap.
      The initial water temperature is set between 8°C and 12°C. All infants will be nursed under a
      radiant overhead heater, which is servo-controlled to the infant's abdominal skin temperature
      and adjusted to maintain the rectal temperature at 33.5-34.5ºC. Adjustments will be made to
      the cooling cap water temperature to stay within these limits. At the start of hypothermia,
      the overhead heater will be turned off for 20-30 min to accelerate cooling, and then turned
      back on once the rectal temperature had fallen to 35.5ºC.

      Rewarming procedure At the end of the 72 h cooling period, the infants will slowly rewarmed
      at no more than 0.5ºC /h until their temperature was within normal temperature range
      (36.5-37.5ºC). The overhead heater can be adjusted as needed, to rewarm the infant. The
      infant's temperature will be be carefully monitored for at least 4 hours to prevent rebound
      hyperthermia, as this might be detrimental.

      Group 2 (Non-cooled group):

      Infants in the non-cooled group received the standard of care and will placed under radiant
      heaters or in incubators, which will be servo-controlled according to the abdominal skin
      temperature to maintain the rectal temperature at 37.0± 0.2°C.

      Laboratory test results Serum creatinine, electrolyte levels, and liver function tests will
      be assessed before the start of cooling (baseline); at 72 during cooling; and then on days
      and 10 of life as clinically indicated. Blood sample for sNGAL and cystatine C will be
      obtained at Day 1, 4 and 10 of life.

      Statistical Analysis Statistical analysis will be performed using SPSS statistical software
      (version 16; SPSS, Chicago, Illinois). Student-t test or Mann-Whitney test will be used to
      compare continuous variables and Chi-square test or Fisher's exact test will be used for
      categorical variables. The diagnostic accuracy of the sNGAL and cystatine C tested in this
      study for identifying AKI will be evaluated by constructing receiver operating
      characteristics (ROC) curves. A p-value of <0.05 is considered to be statistically
      significant. All data will be expressed as mean ± standard deviation unless otherwise stated.
    

Intervention name(s): Therapeutic hypothermia
Intervention type(s): Procedure
Intervention description(s): Infants in cooled group will be fitted a cooling cap (Olympic Medical Cool Care System, Olympic Medical) around the head for 72 h. infants will be nursed under a radiant overhead heater, which is servo-controlled to the infant's abdominal skin temperature and adjusted to maintain the rectal temperature at 33.5-34.5ºC. At the end of the 72 h cooling period, the infants will be slowly rewarmed at no more than 0•5ºC /h until their temperature become within normal temperature range (36.5-37.5ºC).
Other intervention name(s): Cooling
Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Infants will be enrolled into two groups either group 1(cooled group) if identified within
        12 hours of age and admitted at hospital with a validated cooling facility or group 2(non
        cooled group) if identified older than 12 hours of age or admitted at hospital out of reach
        of a validated cooling facility (cooling still not governmentally submitted in Egypt at
        wide scale).
      
Keywords: Acute kidney injury; Perinatal asphyxia; Therapeutic hypothermia; Serum NGAL; Serum cystatin-C