Does hypothermia impair cerebrovascular autoregulation in neonates during cardiopulmonary bypass?

BACKGROUND: Autoregulation monitoring has been proposed as a means to identify optimal arterial blood pressure goals during cardiopulmonary bypass, but it has been observed that cerebral blood flow is pressure passive during hypothermic bypass. When neonates cooled during cardiopulmonary bypass are managed with vasodilators and controlled hypotension, it is not clear whether hypothermia or hypotension were the cause of impaired autoregulation. AIM: We sought to measure the effect of both arterial blood pressure and hypothermia on autoregulation in a cohort of infants cooled for bypass, hypothesizing a collinear relationship between hypothermia, hypotension, and dysautoregulation. METHODS: Cardiopulmonary bypass was performed on 72 infants at Texas Children's Hospital during 2015 and 2016 with automated physiologic data capture, including arterial blood pressure, nasopharyngeal temperature, cerebral oximetry, and a cerebral blood volume index derived from near infrared spectroscopy. Cooling to 18°C, 24°C, and 30°C was performed on 33, 12, and 22 subjects, respectively. The hemoglobin volume index was calculated as a moving correlation coefficient between mean arterial blood pressure and the cerebral blood volume index. Positive values of the hemoglobin volume index indicate impaired autoregulation. Relationships between variables were assessed utilizing a generalized estimating equation approach. RESULTS: Hypothermia was associated with hypotension, dysautoregulation, and increased cerebral oximetry. Comparing the baseline temperature of 36°C with 18°C, arterial blood pressure was 44 mm Hg (39-52) vs 25 mm Hg (21-31); the hemoglobin volume index was 0.0 (-0.02 to 0.004) vs 0.5 (0.4-0.7) and cerebral oximetry was 59% (57-61) vs 88% (80-92) (Median, 95% CI of median; P<.0001 for all three associations by linear regression with generalized estimation of equations with data from all temperatures measured). CONCLUSIONS: Arterial blood pressure, temperature, and cerebral autoregulation were collinear in this cohort. The conclusion that hypothermia causes impaired autoregulation is thus confounded. The effect of temperature on autoregulation should be delineated before clinical deployment of autoregulation monitors to prevent erroneous determination of optimal arterial blood pressure. Showing the effect of temperature on autoregulation will require a normotensive hypothermic model

Elevated Diastolic Closing Margin Is Associated with Intraventricular Hemorrhage in Premature Infants.

OBJECTIVE: To determine whether the diastolic closing margin (DCM), defined as diastolic blood pressure minus critical closing pressure, is associated with the development of early severe intraventricular hemorrhage (IVH). STUDY DESIGN: A reanalysis of prospectively collected data was conducted. Premature infants (gestational age 23-31 weeks) receiving mechanical ventilation (n = 185) had ∼1-hour continuous recordings of umbilical arterial blood pressure, middle cerebral artery cerebral blood flow velocity, and PaCO2 during the first week of life. Models using multivariate generalized linear regression and purposeful selection were used to determine associations with severe IVH. RESULTS: Severe IVH (grades 3-4) was observed in 14.6% of the infants. Irrespective of the model used, Apgar score at 5 minutes and DCM were significantly associated with severe IVH. A clinically relevant 5-mm Hg increase in DCM was associated with a 1.83- to 1.89-fold increased odds of developing severe IVH. CONCLUSION: Elevated DCM was associated with severe IVH, consistent with previous animal data showing that IVH is associated with hyperperfusion. Measurement of DCM may be more useful than blood pressure in defining cerebral perfusion in premature infants.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Oxford University Press

Limiting Circulatory Arrest Using Regional Low Flow Perfusion

Deep hypothermic circulatory arrest (DHCA) is commonly used for neonatal cardiac surgery. However, prolonged exposure to DHCA is associated with neurologic morbidity. The Norwood operation and aortic arch advancement are procedures that typically require DHCA during surgical correction. Regional low flow perfusion (RLFP) can be used to limit or exclude the use of circulatory arrest. This technique involves cannulation of the innominate or subclavian artery using a Gore-Tex graft, allowing isolated cerebral perfusion. Data was collected in 34 patients undergoing either neonatal aortic arch reconstruction or the Norwood procedure using RLFP. All patients had two arterial pressure monitors using either the umbilical or femoral artery catheters and radial or brachial catheters. Adequacy of perfusion was determined using cerebral saturation, blood flow velocity, mean arterial pressures, and arterial blood gas results. Cerebral saturation and blood flow velocity were monitored using the near-infrared spectroscopy (NIRS) (INVOS 5100, Somanetics Corp, Troy, MI) and a transcranial Doppler pulse-wave ultrasound (TCD) (EME Companion, Nicolet Biomedical, Madison, WI), respectively throughout the entire bypass period. Blood gases were monitored using a point of care blood gas analyzer (Gem Premier, Mallinckrodt Sensor System, Inc., Ann Arbor, MI). Data collected revealed total bypass times for repair between 69–348 min, with a mean of 180 min. Regional low flow perfusion times lasted between 6–158 min, with an average of 50 min., and DHCA times ranged from 0–66 min, with a mean of 19 min. The perfusion techniques used allowed patient clinical data to remain consistent throughout the cardiopulmonary bypass period, regardless of lower flows (Figure 1) The 30-day postoperative mortality rate was 2.9 %, with no evidence of neurologic injury during follow up. In conclusion, regional low flow cerebral perfusion might benefit patients by limiting the use of circulatory arrest during cardiac surgery. Further study is necessary to evaluate patient outcomes, comparing regional cerebral perfusion and circulatory arrest techniques