Selective cerebral hypothermia for post-hypoxic neuroprotection in neonates using a solid ice cap.

摘要

OBJECTIVE: The main objective of this study was to study the safety and efficacy of a simple, cost-effective method of selective head cooling with mild systemic hypothermia in newborn infants with hypoxic ischaemic encephalopathy. DESIGN: Ethical approval was obtained for a randomized controlled study in which 20 asphyxiated neonates with clinical signs of hypoxic ischaemic encephalopathy would be randomised into cooled and non-cooled groups. However, after cooling the first 4 babies, it was clear that repeated revisions to the cooling technique had to be made which was inappropriate in the context of a randomised controlled trial. The study was therefore stopped and the data for the 4 cooled infants are presented here in the form of a technical report. Hypothermia was achieved by applying an insulated ice cap to the heads of the infants and replacing it at 2-3-hourly intervals, aiming to achieve a target rectal temperature of 35-35.5 degrees C and a target scalp temperature of 10-28 degrees C. SETTING: This study was carried out between July 2000 and September 2001 in the neonatal units of Groote Schuur Hospital and Mowbray Maternity Hospital, Cape Town. SUBJECTS: Term infants with signs of encephalopathy were recruited within the first 8 hours of life if they had required resuscitation at birth and had significant acidosis within the first hour of life. RESULTS: Target rectal temperature was achieved in all infants, but large variations in incubator and scalp temperatures occurred in 3 of the 4 infants. Reducing the target core temperature in a stepwise manner did not prevent excessive temperature variation and resulted in a longer time to reach target temperature. There was least variation in scalp temperature when the ice pack was covered in two layers of mutton cloth before application, but the resulting scalp temperatures were above the target temperature. The maximum scalp temperature variation was reduced from 22 degrees C to 12 degrees C using this method. Nasopharyngeal temperatures variedexcessively within less than a minute, suggesting that air cooling via mouth breathing was occurring. The surface site that correlated best with deep rectal temperature was the back, with the infant supine. During cooling, the respiratory rate and heart rate dropped while the mean arterial blood pressure was elevated. There were no irreversible adverse events due to cooling, but infants did become agitated and exhibited shivering which required sedation and analgesia. CONCLUSIONS: Nasopharyngeal temperature monitoring was not reliable as an acute clinical indicator of brain temperature in these spontaneously breathing infants, and the back temperature in supine infants correlated better with deep rectal temperature than did exposed skin temperature. This method of cooling achieved systemic cooling but there were large variations in regional temperatures in 3 of the 4 infants. The variations in temperature were probably due to the excessive cooling effect of the ice cap, coupled with the use of external heating to maintain systemic temperature at 35-35.5 degrees C. Variation in temperature was reduced when additional insulation was provided. However, the additional insulation resulted in the loss of the selective cerebral cooling effect. This cooling technique was therefore not an appropriate method of selective head cooling, but did successfully induce systemic hypothermia. This method of insulating an ice cap could therefore be used to induce whole-body cooling but the use of lower core temperatures of 33-34 degrees C is recommended as this will probably result in fewer regional temperature fluctuations. Ideally a more uniform method of cooling should be used.