Survey of the clinical assessment and utility of near-infrared cerebral oximetry in cardiac surgery.

OBJECTIVES: Near-infrared cerebral oximetry increasingly is used for monitoring during cardiac surgery. Nonetheless, the scientific basis for incorporating this technology into clinical practice, the indications for when to do so, and standard diagnostic and treatment algorithms for defining abnormal values are yet to be rigorously defined. The authors hypothesized that there would be (1) variation in clinical use and practices for near-infrared spectroscopy (NIRS), and (2) variation in management of patients when clinicians are provided with NIRS information. In order to test this hypothesis, they sought to assess the nature and strength of response heterogeneity among anesthesiologists and cardiac perfusionists when provided with cardiac surgery patient scenarios and cerebral oximetry data. DESIGN: A prospectively collected survey. SETTING: A hospital-based, multi-institutional, multinational study. PARTICIPANTS: By e-mail, the authors surveyed the membership of the Society of Cardiovascular Anesthesiologists and the online Cardiovascular Perfusion Forum. INTERVENTIONS: This survey was focused on ascertaining what actions clinicians would take in each scenario, given case information and cerebral oximetry tracings. Questions were based on 11 patient scenarios selected to represent small, large, symmetric, or asymmetric decreases in measured regional cerebral oxygen saturation (rScO2) encountered during cardiac surgery. Information on the respondents' (n = 796; 73% anesthesiologists) clinical practice, demography, and cerebral oximetry utilization was collected. An index of dispersion was used to assess response heterogeneity overall and within demographic subgroups. MEASUREMENTS AND MAIN RESULTS: The majority of respondents indicated that cerebral oximetry monitoring was either useful or an essential monitor, especially perfusionists and clinicians who used cerebral oximetry most frequently. There were marked differences in responses between perfusionists and anesthesiologists for 4 of the 6 scenarios (p<0.005 for each of these 4 scenarios) occurring during cardiopulmonary bypass. Scenarios having greatest rScO2 reduction or asymmetry in rScO2 were associated with the highest dispersion, indicating least agreement in management. Scenarios with mild or moderate rScO2 reduction were associated with the lowest dispersion, indicating greater agreement in management. CONCLUSIONS: Although experimental data gradually are accumulating to support the role for cerebral oximetry monitoring during cardiac surgery, the results of the present survey support the view that its role remains poorly defined, and consensus for its appropriate use is lacking. Importantly, the authors observed marked variation in the use, perceived utility, and management of patients for 4 of the 6 CPB scenarios between perfusionists and anesthesiologists who share the management of CPB. These findings support the need for well-designed, adequately-powered clinical trials examining the value of this technology.

Brainstem and hypothalamic regulation of sleep pressure and rebound in newborn rats.

Sleep pressure and rebound comprise the two compensatory or "homeostatic" responses to sleep deprivation. Although sleep pressure is expressed by infant rats as early as postnatal day (P)5, sleep rebound does not appear to emerge until after P11. We reexamined the developmental expression of these sleep-regulatory processes in P2 and P8 rats by depriving them of sleep for 30 min using a cold, arousing stimulus delivered to a cold-sensitive region of the snout. This method effectively increased sleep pressure over the 30-min period (i.e., increases in the number of arousing stimuli presented over time). Moreover, sleep rebound (i.e., increased sleep during the recovery period) is demonstrated for the first time at these ages. Next, we showed that precollicular transections in P2 rats prevent sleep rebound without affecting sleep pressure, suggesting that the brainstem is sufficient to support sleep pressure, but sleep rebound depends on neural mechanisms that lie rostral to the transection. Finally, again in P2 rats, we used c-fos immunohistochemistry to examine neural activation throughout the neuraxis during sleep deprivation and recovery. Sleep deprivation and rebound were accompanied by significant increases in neural activation in both brainstem and hypothalamic nuclei, including the ventrolateral preoptic area and median preoptic nucleus. This early developmental expression of sleep pressure and rebound and the apparent involvement of brainstem and hypothalamic structures in their expression further solidify the notion that sleep-wake processes in newborns-defined at these ages without reference to state-dependent EEG activity-provide the foundation on which the more familiar processes of adults are built.

Developmental divergence of sleep-wake patterns in orexin knockout and wild-type mice.

Narcolepsy, a disorder characterized by fragmented bouts of sleep and wakefulness during the day and night as well as cataplexy, has been linked in humans and nonhuman animals to the functional integrity of the orexinergic system. Adult orexin knockout mice and dogs with a mutation of the orexin receptor exhibit symptoms that mirror those seen in narcoleptic humans. As with narcolepsy, infant sleep-wake cycles in humans and rats are highly fragmented, with consolidated bouts of sleep and wakefulness developing gradually. Based on these common features of narcoleptics and infants, we hypothesized that the development of sleep-wake fragmentation in orexin knockout mice would be expressed as a developmental divergence between knockouts and wild-types, with the knockouts lagging behind the wild-types. We tested this hypothesis by recording the sleep-wake patterns of infant orexin knockout and wild-type mice across the first three postnatal weeks. Both knockouts and wild-types exhibited age-dependent, and therefore orexin-independent, quantitative and qualitative changes in sleep-wake patterning. At 3 weeks of age, however, by which time the sleep and wake bouts of the wild-types had consolidated further, the knockouts lagged behind the wild-types and exhibited significantly more bout fragmentation. These findings suggest the possibility that the fragmentation of behavioural states that characterizes narcolepsy in adults reflects reversion back toward the more fragmented sleep-wake patterns that characterize infancy.

Endothelial vasodilator production by uterine and systemic arteries. IX. eNOS gradients in cycling and pregnant ewes.

The follicular phase (FOL) and pregnancy exhibit increases in uterine blood flow (UBF), estrogen levels, and uterine artery (UA) endothelial nitric oxide synthase (eNOS) expression. UA branching within the mesometrium increases the total vascular cross-sectional area, which reduces the vascular perfusion pressure gradient, thus locally decreasing the blood flow velocity. Shear stress (SS) activates eNOS and may be associated with UBF elevations during FOL and pregnancy. We hypothesized that regional differences in eNOS responses are observed with both decreases in vessel diameter and during the ovarian cycle and pregnancy. Endothelial isolated proteins were collected from renal (RA) and internal iliac arteries (II) as well as from primary (UA 1 degrees ), secondary (UA 2 degrees), and tertiary (UA 3 degrees) UA branches of nonpregnant luteal phase (LUT; n = 6) and FOL (n = 6) as well as midpregnant (MP; 82 +/- 1 days gestation, n = 6) and late pregnant (LP; 127 +/- 3 days gestation, n = 6) ewes (term = 145 +/- 3 days gestation) for Western blot analysis. LUT RA, II, and UA 1 degrees eNOS levels were similar. There was a 60.7 +/- 9.8% reduction in eNOS expression in UA 2 degrees and UA 3 degrees. A similar decreasing eNOS regional expression gradient was observed in LP ewes. No eNOS regional expression gradient was observed in FOL or MP ewes because eNOS increased in UA 2 degrees and UA 3 degrees. In UA 2 degrees and UA 3 degrees, MP > LP = FOL > LUT. Thus, with increasing UBF, FOL and pregnancy rises in SS may regulate eNOS protein expression in smaller diameter UAs. A decrease in LUT and LP UA 2 degrees and UA 3 degrees endothelial eNOS suggest a possible negative feedback mechanism due to downregulation of eNOS if SS is normalized.