Presented at the Neonatal Society 2005 Summer Meeting.
Ferguson J1, Britton F2, Simmonds M1, Whitelaw A1, Thoresen M1
1 Department of Clinical Science, University of Bristol, UK
2 Department of Haematology, Southmead Hospital, Bristol, UK
Introduction: The coagulation cascade is a series of enzymatic reactions which are temperature dependent. Several decades ago, severe accidental hypothermia in infants was not uncommon and reports described pulmonary and intracranial haemorrhages (1). Hypothermia is now being evaluated as cerebral protection in infants with hypoxic-ischaemic encephalopathy and 2 studies have shown improved outcome in the cooled group at 18 months follow up. Cooling is either applied as mild total body cooling down to 33.5ºC or as total body cooling to 34.5ºC combined with selective head cooling (SHC) using a cooling cap around the head. There is a possibility that therapeutic hypothermia might increase the risk of intracranial haemorrhage in such infants, particularly if hypoxia has already deranged coagulation. In theory this risk might be further increased if selective head cooling is used as cortical temperatures of 28-29ºC have been documented experimentally (2). Standard clotting assays are performed in routine hospital laboratories at 37ºC
Aims: The object of this study was to assess the effect of temperatures likely to occur in cerebral tissue during SHC on coagulation in an experimental model of hypoxic-ischemic encephalopathy.
Methods: The study was carried out according to UK Home Office license regulations. 8 newborn pigs less than 24 hours old were anaesthetized with 0.8% halothane and were maintained at normothermia (39ºC which is normal for pigs). A median of 4 blood samples were then taken over a period of 4 – 12 hours for each pig. Each blood sample was taken into citrate, centrifuged and frozen at –80ºC until analysis. Activated Partial Thromboplastin Time (APTT) was measured on each sample, at 39ºC and 29ºC using thermostatically-controlled waterbaths.
Results: APTT was significantly longer when measured at 29ºC (mean (SD) 26.7 (10.6)) than at 39ºC . 20.8 (8.3) seconds. (p<0.01). Median difference was 5 seconds, almost 25% of normal APTT.
Conclusion: With a temperature difference of 10ºC which is the maximum one could expect between brain cortex and core temperature with selective head cooling, there was only a 25% prolongation of coagulation time.This prolongation is not expected to greatly increase the risk of intracranial bleeding.With whole body cooling, the effect would be less. We have not observed brain haemorrhages in studies using SHC for 24 hrs in piglets (3). The major risks for intracranial bleeding in the term infant remain traumatic delivery and liver damage.
References
1. Chadd MA, Gray OP. Arch Dis Child 1972; 41: 819-21.
2. Thoresen M, Simmonds M, Satas S, Tooley J, Silver I 2001. Ped Res 49:594-599
3.Tooley JR, Satas S, Porter H, Silver IA, Thoresen M 2003 Annal Neurol 53:65-72