OBJECTIVE: We aimed to evaluate the effect of therapeutic hypothermia (TH) on brain MRI findings, neurological outcome, and mortality in patients with perinatal hypoxic ischemic encephalopathy (HIE) and compare between two modalities of TH: whole body cooling (WBC) and selective head cooling (SHC).
PATIENTS AND METHODS: Sixty-two inborn babies with HIE admitted to the NICU of a Kuwaiti teaching hospital between 2006 and 2013 were retrospectively reviewed. Patients were divided into two groups: group 1 (2006–2008, n = 30) never received hypothermia, and group 2 (2009–2013, n = 32) treated with hypothermia. Group 2 patients were chronologically divided into two subgroups: 2a, the SHC, (2009–2010, n = 15) and 2b, the WBC, (2011–2013, n = 17). Brain MRI taken 7–10 days after birth, neurological status and mortality at time of hospital discharge were evaluated.
RESULTS: Patients who received TH showed significantly fewer MRI hypoxic changes (P = 0.04) and had better neurological outcome. Their need for anticonvulsants diminished (P = 0.04). However, their need for inotropes and duration of mechanical ventilation were increased (P = 0.001 & 0.02 respectively). No significant difference in mortality was found between the two groups (P = 0.6). In regression analysis, only MRI hypoxic changes predicted the occurrence of neurological abnormalities (P = 0.001). No difference in brain MRI findings, neurological outcome and mortality was observed between subgroups 2a and 2b (P > 0.05).
CONCLUSION: TH improved the neurological outcome of HIE patients but had no effect on mortality. There was no difference between the two modalities of TH on patients’ outcome.
EdwardsAD, BrocklehurstP, GunnAJ, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: Synthesis and meta-analysis of trial data. BMJ2010;340:c363.
5.
HigginsRD, RajuT, EdwardsAD, et al
. Hypothermia and other treatment options for neonatal encephalopathy. An executive summary of the Eunice Kennedy Shriver NICHD workshop. J Pediatr2011;159(5):851–858.e1.
6.
MerrillL
. Therapeutic hypothermia to treat hypoxic ischemic encephalopathy in newborns: Implications for nurses. Nurs Women Health2012;16(2):126–34.
7.
GluckmanPD, WyattJS, AzzopardiD, et al
. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: Multicentre randomised trial. Lancet 3659460;663–70.
8.
AzzopardiDV, StrohmB, EdwardsAD, et al
. Moderate hypothermia to treat perinatal asphyxial encephalopathy. New Engl J Med2009;361(14):1349–58.
9.
AkcaO
. Complications of hypothermia. In: MayerSA SD(ed). Therapeutic hypothermia. New York, Marcel Dekker, 2005, pp 179–210.
10.
FilippiL, CatarziS, PadriniL, FioriniP, la MarcaG, GuerriniR, DonzelliGP
. Strategies for reducing the incidence of skin complications in newborns treated with whole-body hypothermia. J Mat fetal Neonat Med2012;25(10):2115–21.
11.
GeurtsM, MacleodMR, KollmarR, KremerPH, van der WorpHB
. Therapeutic hypothermia and the risk of infection: A systematic review and meta-analysis. Crit Care Med2014;42(2):231–42.
12.
ShankaranS, BarnesPD, HintzSR, et al
. Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal EdF2012;97(6):398–404.
13.
ShankaranS, LaptookAR, EhrenkranzRA, et al
. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. New Engl J Med2005;353(15):1574–84.
14.
SarnatHB, SarnatMS
. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol1976;33(10):696–705.
15.
Al-AlfyA, CarrollJE, DevarajanLV, MoussaMA
. Term infant asphyxia in Kuwait. Ann Trop Paediatr1990;10(4):355–61.
16.
AiredeAI
. Birth asphyxia and hypoxic-ischaemic encephalopathy: Incidence and severity. Ann Trop Pediatr1991;11(4):331–5.
17.
RobertsonNJ, NakakeetoM, HagmannC, et al
. Therapeutic hypothermia for birth asphyxia in low-resource settings: A pilot randomised controlled trial. Lancet2008;372(9641):801–3.
18.
ItooBA, Al-HawsawiZM, KhanAH
. Hypoxic ischemic encephalopathy. Incidence and risk factors in North Western Saudi Arabia. Saudi Med J2003;24(2):147–53.
19.
JohnstonMV, HagbergH
. Sex and the pathogenesis of cerebral palsy. Dev Med Child Neurol2007;49(1):74–78.
20.
QureshiAM, ur RehmanA, SiddiqiTS
. Hypoxic ischemic encephalopathy in neonates. J Ayub Med Coll Abbottabad2010;22(4):190–3.
21.
SarkarS, DonnSM, BapurajJR, BhagatI, BarksJD
. Distribution and severity of hypoxic-ischaemic lesions on brain MRI following therapeutic cooling: Selective head versus whole body cooling. Arch Dis Child Fetal Neonatal Ed2012;97(5):F335–9.
MosalliR
. Whole body cooling for infants with hypoxic-ischemic encephalopathy. J Clin Neonatol2012;1(2):101–6.
24.
BattinMR, ThoresenM, RobinsonE, PolinRA, EdwardsAD, GunnAJ
. Does head cooling with mild systemic hypothermia affect requirement for blood pressure support?. Pediatrics (2009;123(3):1031–6.
25.
PoldermanKH, HeroldI
. Therapeutic hypothermia and controlled normothermia in the intensive care unit: Practical considerations, side effects, and cooling methods. Crit Care Med2009;37(3):1101–20.
26.
AdelsonPD, RaghebJ, KanevP, et al
. Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children. Neurosurgery2005;56(4):740–53.
27.
GlassHC, GliddenD, JeremyRJ, BarkovichAJ, FerrieroDM, MillerSP
. Clinical neonatal seizures are independently associated with outcome in infants at risk for hypoxic-ischemic brain injury. J Pediatr2009;155(3):318–23.
28.
InderTE, HuntRW, MorleyCJ, et al
. Randomized trial of systemic hypothermia selectively protects the cortex on MRI in term hypoxic-ischemic encephalopathy. J Pediatr2004;145(6):835–7.
29.
RutherfordMA, AzzopardiD, WhitelawA, CowanF, RenowdenS, EdwardsAD, ThoresenM
. Mild hypothermia and the distribution of cerebral lesions in neonates with hypoxic-ischemic encephalopathy. Pediatrics2005;116(4):1001–6.
30.
RutherfordM, RamenghiLA, EdwardsAD, et al
. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: A nested substudy of a randomised controlled trial. Lancet Neurol2010;9(1):39–45.
31.
LowE, BoylanGB, MathiesonSR, MurrayDM, KorotchikovaI, StevensonNJ, LivingstoneV, RennieJM
. Cooling and seizure burden in term neonates: An observational study. Arch Dis Child Fetal Neonatal EdF2012;97(4):267–72.
32.
CheongJL, ColemanL, HuntRW, et al
. Prognostic utility of magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: Substudy of a randomized trial. Arch Pediatr Adolesc Med2012;166(7):634–40.
33.
NewellRCR, EllsburyD, UrsprungR, SmithPB, CottonCM, SpitzerAR
. Emerging use of therapeutic hypothermia for hypoxic ischemic encephalopathy. EJ Neonatol Res2013;3(2):38–46.
34.
TaginMA, WoolcottCG, VincerMJ, WhyteRK, StinsonDA
. Hypothermia for neonatal hypoxic ischemic encephalopathy: An updated systematic review and meta-analysis. Arch Pediatr Adolesc Med2012;166(6):558–66.
