Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability

Abstract

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO₂) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate-pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO₂ relative to baseline at CPB initiation; following correction, CMRO₂ did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO₂ decreased with CPB time; these temporal trends persisted for 0-8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8-24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB.

Keywords: cardiopulmonary bypass; cerebral hemodynamics; diffuse optics; hemoconcentration; mild hypothermia.

Figure 1

Protocol Timeline. Continuous diffuse optical neuromonitoring was performed concurrently with episodic cerebral microdialysis sampling (MD, green circles) and arterial blood gas sampling (BG, red circles) before/during/after cardiopulmonary bypass (CPB). Optical statistical analysis was performed using three linear mixed-effects models looking at three distinct periods: mild hypothermic CPB, hyper-acute survival, and acute survival. The intercepts from these models show the initial changes from baseline (i.e., acute effects) for each period; the slopes indicate trends during each period.

Figure 2

Impact of Hematocrit Correction on Blood Flow and Oxygen Metabolism During Mild Hypothermic Cardiopulmonary Bypass (MH-CPB). Linear mixed-effects regression analyses of percent changes from baseline in (a) hematocrit (Hct), (b) arterial oxygen content (CaO₂), (c) cerebral blood flow (CBF), and (d) cerebral metabolic rate of oxygen (CMRO₂) during the 140 min of MH-CPB. The linear fit (solid lines) and 95% CI (shaded regions) across the 27 swine are shown in all plots. In panel (c), CBF was derived in two ways: (1) from DCS measurements assuming constant Hct (blue line), and (2) from DCS measurements, blood gas Hct measurements, and FD-DOS scattering measurements using Equation 8 (red line). In panel (d), CMRO₂ was derived from Equation (3) using (1) the “constant Hct” CBF measurements (blue line), and (2) the “Hct corrected” CBF measurements (red line).