Sex-specific associations between cerebrovascular blood pressure autoregulation and cardiopulmonary injury in neonatal encephalopathy and therapeutic hypothermia

Abstract

BackgroundCardiopulmonary injury is common in neonatal encephalopathy, but the link with cerebrovascular dysfunction is unknown. We hypothesized that cerebral autoregulation is associated with cardiopulmonary injury in neonates treated with therapeutic hypothermia (TH) for neonatal encephalopathy.MethodsThe cerebral hemoglobin volume index (HVx) from near-infrared spectroscopy was used to identify the mean arterial blood pressure (MAP) with optimal autoregulatory vasoreactivity (MAPOPT). We measured associations between MAP relative to MAPOPT and indicators of cardiopulmonary injury (duration of mechanical respiratory support and administration of inhaled nitric oxide (iNO), milrinone, or steroids).ResultsWe identified associations between cerebrovascular autoregulation and cardiopulmonary injury that were often sex-specific. Greater MAP deviation above MAPOPT was associated with shorter duration of intubation in boys but longer ventilatory support in girls. Greater MAP deviation below MAPOPT related to longer intensive care stay in boys. Milrinone was associated with greater MAP deviation below MAPOPT in girls.ConclusionMAP deviation from MAPOPT may relate to cardiopulmonary injury after neonatal encephalopathy, and sex may modulate this relationship. Whereas MAP above MAPOPT may protect the brain and lungs in boys, it may be related to cardiopulmonary injury in girls. Future studies are needed to characterize the role of sex in these associations.

Relationships between cerebral autoregulation and markers of kidney and liver injury in neonatal encephalopathy and therapeutic hypothermia

“…MAP OPT was identified in 65 (87%) neonates during hypothermia at a mean of 45±10 mmHg, in 58 (89%) during rewarming at 50±10 mmHg, and in 60 (95%) during normothermia at 50±10 mmHg. As we previously reported, 14 MAP OPT values were similar among boys and girls ( p >0.20). Blood pressure deviation from MAP OPT during hypothermia and rewarming was also similar between boys and girls ( p ≥0.15).…”

“…Blood pressures were similar between the boys and girls as previously reported. 14 We stopped HVx monitoring early during rewarming in neonates who were transferred to another unit for potential ECMO (n=5), withdrawal of care (n=3), or technical complications (n=2). HVx monitoring was stopped early in two additional neonates because NIRS (n=1) or arterial blood pressure (n=1) monitoring was discontinued after rewarming.…”

“…Neonates reported in the current study include those from our pilot studies on brain injury 4 – 6 , 9 and are the same cohort used in a separate study that identified a relationship between cerebral autoregulation and cardiopulmonary injury in NE. 14 …”

“…ICM+ software (Cambridge Enterprises, Cambridge, UK) synchronously sampled NIRS and arterial blood pressure signals to calculate HVx as previously described. 4 – 6 , 10 , 14 , 15 After we determined that neonates did not have unilateral intracranial lesions on MRI, the right and left HVx values were averaged for sorting into 5-mmHg bins of MAP. The most negative HVx identified the MAP OPT with most robust autoregulatory vasoreactivity.…”

Therapeutic hypothermia and targeted temperature management for traumatic brain injury: Experimental and clinical experience

“…The importance of gender in the effects of temperature modifications after brain injury has also been emphasized. [ 138 143 144 145 ] For example, in a model of neonatal hypoxia-ischemia, Smith et al . reported that the beneficial effect of therapeutic hypothermia differed between male and female.…”