Non-invasive optical neuromonitoring of the temperature-dependence of cerebral oxygen metabolism during deep hypothermic cardiopulmonary bypass in neonatal swine

Abstract

Management of deep hypothermic (DH) cardiopulmonary bypass (CPB), a critical neuroprotective strategy, currently relies on non-invasive temperature to guide cerebral metabolic suppression during complex cardiac surgery in neonates. Considerable inter-subject variability in temperature response and residual metabolism may contribute to the persisting risk for postoperative neurological injury. To characterize and mitigate this variability, we assess the sufficiency of conventional nasopharyngeal temperature (NPT) guidance, and in the process, validate combined non-invasive frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) for direct measurement of cerebral metabolic rate of oxygen ( CMRO2). During CPB, n = 8 neonatal swine underwent cooling from normothermia to 18℃, sustained DH perfusion for 40 min, and then rewarming to simulate cardiac surgery. Continuous non-invasive and invasive measurements of intracranial temperature (ICT) and CMRO2 were acquired. Significant hysteresis ( p < 0.001) between cooling and rewarming periods in the NPT versus ICT and NPT versus CMRO2 relationships were found. Resolution of this hysteresis in the ICT versus CMRO2 relationship identified a crucial insufficiency of conventional NPT guidance. Non-invasive CMRO2 temperature coefficients with respect to NPT ( Q10 = 2.0) and ICT ( Q10 = 2.5) are consistent with previous reports and provide further validation of FD-DOS/DCS CMRO2 monitoring during DH CPB to optimize management.

Epinephrine’s effects on cerebrovascular and systemic hemodynamics during cardiopulmonary resuscitation

“…Moreover, FD-NIRS has been clinically validated against gold standard measurements of tissue oxygen saturation and provide absolute values [61,62]. Meanwhile, although DCS is a relatively new measurement modality for CBF, it has been rigorously validated against numerous clinical gold standard measures of CBF, including fluorescent microspheres, magnetic resonance imaging, and Xenon-enhanced computerized tomography in a variety of human and animal models [29,32]. Our noninvasive optical data are congruent with more widely accepted, clinically used (albeit in contexts outside of CPR) invasive measurements of CBF (laser Doppler) and cerebral tissue oxygenation (PbtO 2 ).…”

“…DCS measurement of BFI has been shown to correlate with absolute CBF in children [ 30 , 31 ]. In this animal model, we have previously demonstrated significant correlation of relative BFI with invasive laser Doppler measures of relative CBF during asphyxia and CPR [ 32 ]. Importantly, over the last decade, DCS has been increasingly used to quantify pathologic alterations in CBF in pediatric populations at high risk for neurological injury [ 29 , 33 – 36 ].…”

“…DCS calculation of BFI and relative CBF were derived from the average intensity autocorrelation function acquired over an integration time of 500 ms from a source-detector separation of 2.5 cm. The details of the DCS hardware and acquisition system have been previously detailed [32]. Importantly, the FD-DOS measurement of optical absorption and scattering properties, acquired immediately prior to each DCS frame, were used to derive BFI [41].…”

Portable Near-Infrared Technologies and Devices for Noninvasive Assessment of Tissue Hemodynamics

“…In addition to the instrumentation improvements as mentioned above, the majority of studies using the integrated system focused on the physiological or clinical applications. For the physiological studies, a variety of experimental manipulation were designed to challenge the target tissues, such as the hypercapnia to rat brain [20], cortex activation to human brain [43], plantar flexion or handgrip exercise to human skeletal muscles [58, 66], posture change to human brain [53, 56, 65], and the hypothermic to swine brain [68].…”

Part II. Comparison of Neurodevelopmental Outcomes Between Normothermic and Hypothermic Pediatric Cardiopulmonary Bypass

“…Substantial improvements in peri-operative management have led to survival rates increasing dramatically over the past few decades, especially in pediatric patients (2). Now, the focus has shifted to improving neurodevelopmental outcomes of children with congenital heart defects (CHD) which require surgical treatment (3–6). Some have termed this “Congenital Brain Disease,” finding that as children with CHD progress to school-age, they are at a higher risk of long-term neurological findings–including motor, speech and language delays, and deficits in executive functioning (3).…”