Valerie Pollard

Validation in Volunteers of a Near-infrared Spectroscope for Monitoring Brain Oxygenation In Vivo

Cerebral oximeters based on near-infrared spectroscopy may provide a continuous, noninvasive assessment of cerebral oxygenation. We evaluated a prototype cerebral oximeter (Invos 3100; Somanetics, Troy, MI) in 22 conscious, healthy volunteers breathing hypoxic gas mixtures. Using the first 12 subjects (training group), we developed an algorithm based on the mathematic relationship that converts detected light from the field surveyed by the probe to cerebral hemoglobin oxygen saturation (CSf O2). To develop the algorithm, we correlated the oximeter result with the estimated combined brain hemoglobin oxygen saturation (CScomb O2, where CScomb O2 = Sa O2 times 0.25 + Cj O2 times 0.75 and Sj O2 = jugular venous saturation). We then validated the algorithm in the remaining 10 volunteers (validation group). A close association (r2 = 0.798-0.987 for individuals in the training group and r2 = 0.794-0.992 for individuals in the validation group) existed between CSf O2 and CScomb O2. We conclude that continuous monitoring with cerebral oximetry may accurately recognize decreasing cerebral hemoglobin oxygen saturation produced by systemic hypoxemia. (Anesth Analg 1996;82:269-77)

The influence of carbon dioxide and body position on near-infrared spectroscopic assessment of cerebral hemoglobin oxygen saturation.

Near-infrared spectroscopy may allow continuous and noninvasive monitoring of regional brain hemoglobin oxygen saturation by measuring the differential absorption of infrared light by oxyhemoglobin and deoxyhemoglobin. We have previously examined the correlation between the spectroscopic signal generated by a prototype cerebral oximeter (Invos 3100 Registered Trademark; Somanetics, Troy, MI), and global brain hemoglobin oxygen saturation calculated from arterial and jugular venous bulb oxygen saturations. Because the technology does not distinguish between arterial and venous hemoglobin saturation, changes in the proportion of cerebral arterial and venous blood volume, which may result from changes in blood flow or venous distending pressure, may confound measurements. In eight conscious volunteers breathing hypoxic oxygen mixtures, we examined the influence of supine, 20 degrees Trendeleburg, and 20 degrees reverse Trendelenburg positions on the correlation of the spectroscopic measurement of cerebral oxygen saturation in the field assessed by the probe (CSf O2) and the calculated brain hemoglobin oxygen saturation (CScomb O2), estimated as 0.25 times arterial saturation plus 0.75 times jugular venous bulb oxygen saturation. We found that changes in position did not influence the association between CSf O2 and CScomb O2 (r2 = 0.69-0.885) during hypoxic challenge. In a second set of eight volunteers, we studied the influence of hypercapnia and hypocapnia and body position on the association between CSf O2 and CScomb O2, and found that they were less well correlated (r2 = 0.366-0.976) in individual patients. Because changes in body position and PaCO2 confound the relationship between CSf O2 and CScomb O2, changes in CS (f) O2 can best be assessed if position and PaCO2 are constant. (Anesth Analg 1996;82:278-87)

Cerebral blood flow during experimental endotoxemia in volunteers

OBJECTIVE To measure cerebral blood flow, cerebral metabolic rate for oxygen, cerebral oxygen delivery, and cerebral vascular resistance during experimental endotoxemia in volunteers. DESIGN Experimental, prospective study. SETTING University general clinical research center. SUBJECTS Healthy volunteers (six male, four female, 30.1 +/- 1.9 yrs of age). INTERVENTIONS Volunteers had radial, pulmonary arterial, and jugular venous bulb catheters inserted. All volunteers received a bolus of Escherichia coli endotoxin (4 ng/kg). Cerebral blood flow was measured, using the Kety-Schmidt technique. MEASUREMENTS AND MAIN RESULTS Cerebral and systemic hemodynamics and oxygenation variables were measured at baseline and hourly for 5 hrs after endotoxin administration. A systemic hyperdynamic response characterized by an increase in body temperature (97.9 +/- 0.02, 100.2 +/- 0.02, and 99.7 +/- 0.02 degrees F [36.6 +/- 0.01, 37.9 +/- 0.1, and 37.6 +/- 0.1 degrees C] at baseline, 3, and 5 hrs, respectively), cardiac index (3.7 +/- 0.2, 6.2 +/- 0.2, and 5.7 +/- 0.2 L/min/m2 at baseline, 3, and 5 hrs), and heart rate (70 +/- 2.6, 96 +/- 2.6, and 93 +/- 2.9 beats/min at baseline, 3, and 5 hrs), and a decrease in mean arterial pressure (99.3 +/- 2.2, 84.4 +/- 2.8, and 84 +/- 3.4 mm Hg at baseline, 3, and 5 hrs) and systemic vascular resistance (1498 +/- 53, 788 +/- 37, 849 +/- 36 dyne.sec/cm5.m2 at baseline, 3, and 5 hrs) followed the endotoxin bolus. Cerebral blood flow (65.4 +/- 4.3, 57.7 +/- 3.1, and 58.6 +/- 3.0 mL/100 g/min at baseline, 3, and 5 hrs), cerebral oxygen delivery (11.6 +/- 0.7, 9.8 +/- 0.6, and 9.5 +/- 0.6 mL/100 g/min at baseline, 3, and 5 hrs), cerebral metabolic rate for oxygen (3.8 +/- 0.4, 3.3 +/- 0.3, and 3.0 +/- 0.3 mL/100 g/min at baseline, 3, and 5 hrs), and cerebral vascular resistance (1.4 +/- 0.2, 1.4 +/- 0.2, and 1.3 +/- 0.2 mm Hg/mL/100 g/min at baseline, 3, and 5 hrs) were unchanged throughout the 5-hr study period. Signs of cerebral dysfunction were not apparent, although the volunteers appeared drowsy during the latter part of the study. CONCLUSION A dose of endotoxin sufficient to induce systemic vasodilation in healthy subjects does not influence cerebral blood flow or the cerebral metabolic rate for oxygen.

The 1996 Moyer Award. Effects of endotoxin on the Th1/Th2 response in humans.

Monocyte/T-cell interactions play a critical role in the systemic response to infection. Distinct patterns of cytokines are produced by two different types of T-helper cells (Th). Th1 cells secrete interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), whereas Th2 cells produce IL-4, IL-5, IL-6, IL-10, and IL-13. In volunteers systemic endotoxin administration initiates many features of gram-negative sepsis including cytokine release, but the patterns (i.e., Th1/Th2 patterns) have not yet been studied. In this institutional review board-approved study we investigated the effect of an intravenous bolus of endotoxin from Escherichia coli (4 ng/kg body weight) on the Th1/Th2 response in four female and four male volunteers (mean age 27.1 +/- 0.8 years). Plasma cytokine levels for IL-2, IL-4, IL-10, IL-12, and IFN-gamma and heart rate, mean arterial pressure, temperature, white blood cell, and differential blood count were determined before and hourly for 5 hours after endotoxin administration. All volunteers had tachycardia, decreased mean arterial pressure, fever, and leukocytosis. IL-10 was significantly (p < 0.05) elevated (9.4 +/- 3.9 pg/ml vs 60.9 +/- 19.3 pg/ml) 3 hours after endotoxin was administered, whereas IL-2 levels were decreased (69 +/- 26 U/ml vs 30.6 +/- 14.9 U/ml). IL-4 and IFN-gamma were not detectable in plasma. No changes were seen in the plasma levels of IL-12. Systemic responses did not correlate with changes in cytokine levels. Cytokine patterns found in this study suggest that after low-dose endotoxin administration the T-cell immune response is shifted towards the Th2 cell type response. This early shift towards a Th2 cell response may contribute to the depressed cell-mediated immune response associated with sepsis.

Cerebral near-infrared spectroscopy: a plea for modest expectations.

I n this issue, Saito et al. (1) report on the use of a two-wavelength near-infrared (NIR) spectroscope (INVOS 3100; Somanetics Corp., Troy, MI) to demonstrate that electroconvulsive therapy (ECT) decreases regional brain oxygen saturation (rSo,) immediately after application of the current, then increases rSo, to values exceeding those obtained before ECT. Because this monitor of cerebral oxygenation has now been approved by the U.S. Food and Drug Administration for clinical use, the report by Saito et al. provides an opportunity to briefly review what we might expect of this technology and what we should not expect. This device can very likely meet some modest expectations but certainly will fail if expected to meet unrealistic goals. It is essential to note that near-infrared spectroscopy (NIRS) cannot at present provide precise, quantitative data regarding cerebral venous saturation. Therefore, measurements of “regional brain saturation” cannot be considered equivalent to measurements of jugular venous hemoglobin oxygen saturation for routine clinical purposes, nor can data acquired with this device be considered appropriate for quantitative measurement of cerebral hemoglobin saturation for physiologic research. However, NIRS shows promise as a monitor of trends in cerebral oxygenation in patients in whom the adequacy of cerebral oxygenation cannot be predicted by knowing the key physiologic variables of systemic blood pressure, Pace, and Pao,. NIRS, first described by Jobsis in 1977 (2), is based on a modification of the Beer-Lambert law, which states that changes in absorbance as light passes through tissue are proportional to the concentration of light-absorbing pigments or chromophores (oxyand deoxyhemoglobin), the chromophore absorption coefficient constant (x), and the distance that light has traveled in tissue (mean optical path length). As biological tissues are relatively transparent to NIR light at

Left ventricular diastolic filling characteristics are not impaired but systolic performance was augmented in the early hours of experimental endotoxemia in humans

ABSTRACT This study was performed to determine whether endotoxemia causes diastolic cardiac dysfunction. Eleven healthy volunteers, 30 ± 6 years of age, underwent comprehensive transthoracic echocardiographic assessment including two-dimensional, M-mode transmitral and tissue Doppler of systolic and diastolic function at baseline and at 3 and 5 h after intravenous administration of purified Escherichia coli endotoxin (4 ng/kg). Data were analyzed by analysis of variance; P values of less than 0.05 were considered significant. Endotoxin administration resulted in a hyperdynamic state characterized by decreased mean arterial pressure and significant increase in cardiac index. This was accompanied by increases in several load-dependent systolic performance indices (3 and 5 h). Robust increases in peak systolic blood pressure/end-systolic volume index, one of the relatively load-independent contractility parameter, were also observed at 3 h after endotoxin administration. Transmitral peak early velocity (E), which represents early filling, significantly increased at 3 h after infusion. Late diastolic velocity (A), which represents atrial contraction, significantly increased at 3 and 5 h after infusion. The E/A ratio indicative of delayed relaxation significantly decreased due to increases in A (transmitral) and A (tissue Doppler) at 3 and 5 h after infusion. As expected, endotoxin infusion resulted in a hyperdynamic state associated with increases in systolic function indices including endocardial systolic velocities. The observed decreases in E/A (transmitral) and E/A (tissue Doppler) ratio were primarily due to increases in A and A. Moreover, isovolumic relaxation time and time constant for left ventricular relaxation, a load-independent parameter for ventricular relaxation, remained unchanged at 3 and 5 h after endotoxin infusion. Therefore, our findings are more likely due to enhanced atrial contractility resulting from increased sympathetic activity in response to reduction in left ventricular afterload and not due to altered diastolic filling characteristics.

Signal extraction technology: A better mousetrap?

P ulse oximetry provides a simple, continuous, noninvasive assessment of arterial blood oxygen saturation. Introduced by Nicolai (1) in 1932, oximetry did not gain widespread acceptance until the 197Os, when it was first reported that arterial hemoglobin oxygen saturation could be measured by analysis of pulsatile blood flow (2). The pulse oximeter operates by measuring the attenuation of red (660 nm) and infrared light (940 nm) as it passes through a pulsatile tissue bed. Pulsatile blood flow is essential to allow differentiation of arterial from other absorbers of light such as venous and capillary blood components, as well as overlying tissue and skin (2). Conceptually, the value of pulse oximetry is in identification and correction of hypoxemic events, which, if untreated, could result in serious complications such as brain injury, cardiac arrest, or death (3). In a review of anesthetic-related, closed malpractice claims, Tinker et al. (4) stated that 31.5% of cases with adverse outcomes could have been prevented through additional monitoring. Eichhorn (5) in a review of l,OOl,OOO ASA physical status I and II patients, found 11 major intraoperative accidents that could have been attributed solely to anesthesia; seven were deemed preventable. Unrecognized hypoventilation was the most common intraoperative event associated with severe patient injury. Other extensive clinical series document that pulse oximetry increases the identification of hypoxemic events (6,7). Although pulse oximetry is now well established, the technology has not been greatly improved since 1988 (B), and a number of limitations persist. Kestin et al. (9) reported that 75% of all auditory alarms during routine anesthesia did not originate from changes in physiological variables and only 3% represented patient risk. Freund et al. (10) reported 11,046 cases, with a 1.12% failure rate, defined as the inability to obtain any pulse oximetry reading for a cumulative period of 30 minutes or more after all mechanical problems had been eliminated. A higher rate of failure was present in elderly patients, those with ASA physical status III,

Validation of a Noninvasive Measurement of Regional Hemoglobin Oxygen Saturation

Near-infrared (NIR) spectroscopy may provide a continuous and noninvasive assessment of global brain hemoglobin oxygen saturation by measuring the differential absorption of infrared light [1–3]. As biological tissues are relatively transparent to infrared light at wavelengths between 400 and 1000 nm, infrared light may penetrate skin, subcutaneous tissue, bone, and dura to the brain [4–7], where it is absorbed by oxygenated hemoglobin, deoxygenated hemoglobin, and cytochrome aa3. Thus, the attenuation of infrared light of specific wavelengths by these chromophores may be used to measure brain oxygenation [1, 3, 8–11]. The hemoglobin oxygen saturation measured by the cerebral oximeter receives contributions from arterial, venous, and capillary blood vessels, with a predominantly venous contribution [11, 12], and may reflect the balance between cerebral oxygen consumption and delivery.