Identification of Pressure Passive Cerebral Perfusion and Its Mediators after Infant Cardiac Surgery

Abstract

Cerebrovascular pressure autoregulation (CPA) regulates cerebral blood flow (CBF) in relation to changes in mean arterial blood pressure (MAP). Identification of a pressure-passive cerebral perfusion and the potentially modifiable physiologic factors underlying it has been difficult to achieve in sick infants. We previously validated the near-infrared spectroscopy-derived hemoglobin difference (HbD) signal (cerebral oxyhemoglobin Ϫ deoxyhemoglobin) as a reliable measure of changes in CBF in animal models. We now sought to determine whether continuous measurements of ⌬HbD would correlate to middle cerebral artery flow velocity (CBFV), allow identification and quantification of pressure-passive state, and help to delineate potentially modifiable factors. We enrolled 43 infants (2 d to 7 mo old) who were undergoing open cardiac surgery and cardiopulmonary bypass. At 6 and 20 h after surgery, we measured changes in HbD, CBFV (by transcranial Doppler), and MAP at different end-tidal CO 2 levels. We assigned a pressure-passive index (PPI) to each study on the basis of the relative duration of significant coherence between ⌬MAP and ⌬HbD. We found a significant relationship between ⌬HbD and ⌬CBFV at both time points. At 6 h after surgery, we showed high concordance (coherence Ͼ0.5; PPI Ն41%) between ⌬MAP and ⌬HbD, consistent with disturbed CPA in 13% of infants. End-tidal CO 2 values Ն40 mm Hg and higher MAP variability both were associated with increased odds (p Ͻ 0.001) of autoregulatory failure. This approach provides a means to identify and quantify disturbances of CPA. High Recent advances in infant cardiac surgery and critical care medicine have translated into high survival rates for infants with congenital heart disease. As mortality has decreased, the clinical focus has shifted to the prevention of perioperative neurologic injury (1). Previous studies have focused primarily on intraoperative cerebral hypoxia-ischemia as a key mechanism for neurologic dysfunction. However, recently it has become clear that multiple potential mechanisms, operating at different times, may be implicated in the pathogenesis of neurologic dysfunction after infant cardiac surgery (2). In the current research, we focused on the early postoperative period because of its high risk for hemodynamic instability and therefore potential for brain injury.

Rapid Assessment of Cerebral Autoregulation by Near-Infrared Spectroscopy and a Single Dose of Phenylephrine

“…The notion of cerebral Hb signals being surrogates of CBF has led investigators to use the associative relationship between continuously monitored cerebral Hb signals and spontaneous fluctuations in arterial blood pressure for dynamic AR determination by analysis in the frequency domain (3,23,24) or by analysis in the time domain (25)(26)(27). In addition, Brady et al (25) and Lee et al (26) verified the reliability of such AR determination by NIRS with AR determination by laser Doppler flowmetry during slow induction of hypotension in anesthetized piglets.…”

“…under inhalational anesthetics, hypercapnia, or ischemia (28). It is therefore obvious that this AR technique runs the risk to have low signal-to-noise ratios and has shown in clinical settings to require prolonged sampling times, extensive averaging, or incorporation of exclusion rules for adequate AR calculation (3,(23)(24)(25)(26)(27). In contrast to dynamic AR determinations based on spontaneous blood pressure fluctuations, the PE technique is performed faster, has a better signal-to-noise ratio, and evaluates only CBF-changes specific to systemic blood pressure changes.…”

The Ontogeny of Cerebrovascular Pressure Autoregulation in Premature Infants

“…[15][16][17][18] Pressure-passivity of the cerebral circulation has been observed in premature infants by a variety of methods, a finding inconsistently associated with outcome. [18][19][20][21][22] Thus, the clinical relevance of pressure passivity in the premature infant has mostly been implied from adult data. The mammalian cerebral vasculature develops muscularity at approximately two-thirds gestation, which corresponds to 26-27 weeks' gestation in humans, so extremely premature infants may lack the necessary arteriolar tone needed to impart pressure autoregulation.…”

Ontogeny of cerebrovascular critical closing pressure

“…The median (interquartile range) CrCP was 22 mm Hg (19)(20)(21)(22)(23)(24)(25). CrCP increased significantly with GA from 19 mm Hg (15-22 mm Hg) at 23 wk to 31 mm Hg (30,31 mm Hg) at 31 wk gestation.…”

“…The need for highquality resolution of systolic and diastolic ABP resulted in some data dropout and may have added unexpected bias. Additionally, Articles Rhee et aldespite concerns that CBFV measurements may not be reliable proxies for CBF due to possible vessel diameter changes, good correlations have been observed between relative changes of CBFV and near-infrared spectroscopy measures of cerebral hemodynamics as well as by magnetic resonance angiography (19)(20)(21)(22). Further, without using Doppler CBFV, we would not have been able to calculate the CrCP.…”