A Study Of Safety And Protective Effect Of Systemic Hypothermia On Neonatal Hypoxia-Ischemia Encephalopathy

Perinatal hypoxia-ischemia encephalopathy (HIE) remains a major contributor to acute mortality and permanent neurological disability in infants. The mechanisms of brain injury are complicated and not completely understood. No drug therapy has been proven to be effective so far. Hypothermia has been reported to be the most promising neuroprotective strategy in various brain injury models as well as in adult stroke. However, the long-term outcome and safety of whole-body hypothermia on neonatal HIE is not clear. The purpose of this study was to investigate the short and long term neuroprotective effects and safety of systemic hypothermia on neonatal HIE.Subjective and MethodsFourty-nine asphyxiated newborn infants fulfilled the following criteria from Aug. 2002 to Mar. 2005 were enrolled this study in our NICU: (1)Gestation age >37 week's, body weight >2.5kg. (2)with one of the following items: (1)Apgar score <4 at 1min, or <7 at 5min; (2) Assisted respiration >3min due to respiratory distress; (3) pH≤7.1 of cord or arterial blood in 60min after birth; (4)Clinical manifestation of encephalopathy during the first 6h of life; (3)Severe congenital abnormities, hemorrhage and infections were excluded. The infants were randomized to either systemic hypothermia group (HG) (n=24) or normothermia group (NG) (n=25). The infants in hypothermia group were got parental consent and maintained rectal temperature 33.0-34.0℃ for 72h by coolingPerinatal hypoxia-ischemia encephalopathy (HIE) remains a major contributor to acute mortality and permanent neurological disability in infants. The mechanisms of brain injury are complicated and not completely understood. No drug therapy has been proven to be effective so far. Hypothermia has been reported to be the most promising neuroprotective strategy in various brain injury models as well as in adult stroke. However, the long-term outcome and safety of whole-body hypothermia on neonatal HIE is not clear. The purpose of this study was to investigate the short and long term neuroprotective effects and safety of systemic hypothermia on neonatal HIE.Subjective and MethodsFourty-nine asphyxiated newborn infants fulfilled the following criteria from Aug. 2002 to Mar. 2005 were enrolled this study in our NICU: (1)Gestation age >37 week's, body weight >2.5kg. (2)with one of the following items: ①Apgar score <4 at 1min, or <7 at 5min; ② Assisted respiration >3min due to respiratory distress; ③ pH≤7.1 of cord or arterial blood in 60min after birth; ④Clinical manifestation of encephalopathy during the first 6h of life; (3)Severe congenital abnormities, hemorrhage and infections were excluded. The infants were randomized to either systemic hypothermia group (HG) (n=24) or normothermia group (NG) (n=25). The infants in hypothermia group were got parental consent and maintained rectal temperature 33.0-34.0℃ for 72h by coolingwere all happened in both groups within 72h after strating treatment. Hypocalceraia and metabolic acidosis were also easily found in both asphyxied groups: incidence of 75% hypothermia (18/24) compared with 64% normothermia(16/25). No hypothermia related electrolytes and blood gas change were observed.4) Coagulation: Both plasminogen time (PT) and thrombin time (TT) were prolonged in all infants in 72h. Platelet count was no significantly differences between hypothermia group and control group.5) Renal and liver function: All infants had acute renal and liver insufficiency because of asphyxia during treatment. Side effect of hypothermia on renal and liver function was not found.6) Skin lesion and pneumonia: One infant with skin cold injury was found in hypothermia group. Pneumonia was common in both groups and no other hypothermia related complications were observed.3. Neuroprotective effects1) Neurological signs: Significant differenece in neurological signs was not observed between both groups before treatment. But the score of neurological signs was much lower on 121k 24h> 481k 72h and 80h after treatment in HG than that of in NG2)NBNA: There was no difference of NBNA evaluation at 7d in both groups. But, the score of NBNA was much higher at 14 and 28d in hypothermia group than that of normothermia groups.3)CDCC assessment: At 3 month of age, the score of MDI and PDI was 91.8 ±8.4 > 88.6+6.9 in hypothermia group, which was higher than that of normothermia groups (MDI 82.7± 9.4> PDI 83.3 ± 8.6). Significant difference was also found at 6,12 and 18 month age.4) Prognosis: Only one death was found in hypothermia group, which is not related with HIE. There were significant fewer infants with neurological disability in hypothermia group: incidence of 0% hypothermia (0/9) compared with 41.6% normothermia(5/12).Conclusions:1) There are short and long term neuroprotective effects of systemic hypothermia on neonatal HIE.2) Systemic hypothermia is a stable, well-tolerated method for treating the term asphyxiated newborns under monitoring carefully.