Cerebral blood volume (CBV) is manipulated therapeutically during neuroanesthesia and intensive care. For example, moderate head-up tilt is often applied to reduce cerebral venous volume and intracranial pressure. However, CBV is rarely measured in the clinical setting. Volume measurements in vivo are complex, and measurements of CBV are further complicated by technical difficulties.
Early attempts at the measurement of CBV relied on the radiolabeling of blood cells or plasma proteins (1), which are difficult and unreliable bedside techniques. Subsequently, these radiolabeling techniques were refined to produce values for regional CBV (2). More recently, tomographic methods have been used. Single-photon emission tomography (3) or positron emission (4) are reliable and accurate techniques but require the use of radioisotopes in a remote imaging suite. There has been increasing interest in the use of magnetic resonance imaging for the measurement of CBV (5), and while this avoids use of ionizing radiation, the issue of transferring a critically ill patient to a remote imaging suite remains.
Changes in posture are known to affect intracranial pressure (6,7), and these changes may, in part, be associated with changes in CBV (6). However, the exact relationship between CBV and changes in posture is unclear, because equipment design does not allow dynamic measurements of CBV to be made when using established techniques.
Near-infrared spectroscopy (NIRS) is a continuous, noninvasive bedside monitor that has been used to measure changes in cerebral hemodynamics. NIRS exploits the relative transparency of biological tissues to near-infrared light and the differential absorption of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb). When fiberoptic bundles are applied to the scalp, it is possible to make measurements on the intact head (8,9). NIRS can measure real-time changes in HbO2 and Hb concentrations, and the sum of these changes is equal to the change in the concentration of the total amount of hemoglobin (HbT) within the field of view. A change in HbT concentration implies a change in CBV, assuming the whole blood hemoglobin concentration and the cerebral large to small vessel hematocrit ratio remain constant for the duration of the measurement or series of measurements (10–12).
This study investigates the use of NIRS to investigate changes in HbT concentration associated with changes in posture in normal awake subjects and in patients anesthetized with propofol.
After institutional ethics committee approval and with written informed consent, 10 healthy volunteers and 10 patients scheduled to undergo elective spinal surgery (single-level microdiscectomy), with total IV anesthesia with propofol and morphine, were enrolled into this study.
Electrocardiogram, noninvasive blood pressure, and arterial oxygen saturation were monitored in all volunteers and anesthetized patients by using a Hewlett Packard Merlin monitor (Hewlett Packard Corp., Berkshire, UK) and recorded by using custom software. PETCO2 was also monitored and recorded in the anesthetized patients.
Changes in HbO2 and Hb were continuously recorded by using a NIRO 500 spectrophotometer (Hamamatsu Photonics, Hamamatsu City, Japan) (13). It incorporates four pulsed semiconductor laser diodes using wavelengths of 775, 826, 850, and 909 nm with a frequency of 1.9 kHz and is capable of detecting intracranial events (14,15). The optodes were located in the right frontal region, avoiding the sinuses just below the hairline, with an interoptode spacing of 4 cm. A sampling interval of 0.5 s was used, and changes in HbO2 and Hb were calculated by using a previously established algorithm (16,17) incorporating a differential path length factor of 6.26 (18). The concentration change of HbT was calculated as the sum of the changes in HbO2 and Hb concentrations. The results of real-time changes were presented as changes in HbT referenced to an arbitrary baseline. Comparative data between changes in posture have been converted to changes in CBV by using the following equation (10,11):MATH
Anesthesia was induced with 0.1 mg/kg morphine and 2–3 mg/kg propofol. Neuromuscular block was established with 0.6 mg/kg atracurium, the trachea was intubated, and ventilation was controlled by using an oxygen-enriched air mixture to maintain PETCO2 between 30 and 34 mm Hg. Anesthesia was maintained by using a continuous infusion of propofol at a rate of 5–12 mg · kg−1 · hr−1 and incremental morphine.
The awake volunteers and anesthetized patients lay supine on an operating table fitted with a spirit level to facilitate positioning. After application of the NIRS optodes, baseline measurements of HbT were recorded for 10 min. The table was then abruptly tilted 6° head-down and maintained in this position for 2 min. This maneuver was repeated twice, producing tilts of 12° and 18° head-down before a return to the horizontal position. After a further 2-min period of equilibration, the table was abruptly tilted 6° head-up and maintained in this position for 2 min before further tilts to 12° and 18° head-up. In addition, in the awake volunteer group, abrupt one-step 18° head-down and head-up tilts, maintained for 2 mins, were performed before each set of step-wise maneuvers.
The mean value for HbT for the final 30 s of each tilt position was taken as the equilibrium value for that body position and the value against which changes were recorded. The effects of changes in body position on change in CBV were analyzed by analysis of covariance and multiple linear regression (19,20). Statistical analysis was performed by using SAS 6.11 (SAS Institute Inc., Cary, NC). Comparison of the effects of stepwise as opposed to a single step maneuver was by using t-tests. A P value < 0.05 was taken as significant. All results are expressed as mean ± SD.
The demographics and clinical details of the anesthetized patients are shown in Table 1. In the anesthetized patients, the rate of propofol administration had been constant for at least 30 min before the start of the study. Arterial oxygen saturation and PETCO2 were unaffected by changes in posture. Changes in mean arterial blood pressure were clinically insignificant (Table 2).
A recording of the changes during head-down tilting in an awake subject is shown in Figure 1. Of note is the observation that the change in HbT concentration occurs immediately after the change in body position. There was no significant difference in the changes in HbT concentration when volunteers were tipped head-down in one or three steps, being 4.06 ± 1.39 μmol/L for a single 18°-change and 3.57 ± 1.35 μMolar for the total of the three sequential 6°-steps. Similarly for the head-up tilt, there was no significant difference between a single 18°-tilt (−2.08 ± 1.35 μmol/L) and the total for three 6°-steps (−2.28 ± 1.45 μmol/L).
A recording of the changes in HbT concentration during head-down and head-up tilt in an anesthetized patient is shown in Figure 2. There are changes similar to those observed in the awake volunteers with head-down tilt, being 3.51 ± 2.68 μmol/L for the total of three sequential 6°-steps, but little change in HbT concentration with head-up tilt, being only −0.70 ± 0.99 μmol/L for the total of three 6°-steps.
The differences between the awake volunteers and anesthetized patients during head-up tilt and the similarities between the two groups during head-down tilt are shown in Figure 3. Analysis of covariance demonstrated a significant correlation between degree of table tilt and changes in HbT concentration (P < 0.0001) for the awake volunteers with a corrected correlation coefficient of −0.913. Multiple linear regression in the awake volunteers yielded a slope for the regression for both head-down and head-up tilts of 0.164 μmol/L per degree of tilt. In the anesthetized patients, there was a significant correlation between the degree of table tilt and change in HbT concentration in the head-down (P < 0.001) and head-up (P < 0.002) positions with corrected correlation coefficients of −0.78 and −0.54, respectively. Multiple regression analysis in the anesthetized subjects revealed a slope for the regression of −0.196 μmol/L per degree of tilt for the head-down tilt and −0.038 μmol/L per degree of tilt for head-up tilt. The head-down changes were similar to those in the awake volunteers, but the head-up changes were significantly reduced (P < 0.0001).
This study demonstrates the ability of NIRS to monitor, in real time, the effects of changes in body position on HbT and, therefore, on CBV. The observed changes are small and, assuming a normal cerebral HbT concentration of 85 μmol/L (3), account for ±6% of total CBV.
It is difficult to compare our findings with those of other investigators because this is the first attempt to measure dynamic posture-related CBV changes by using NIRS. Other groups have used changes in arterial blood CO2 tensions to alter CBV and confirmed that NIRS is capable of measuring changes under such circumstances (21–23). However, two distinct NIRS methods can be used to measure CBV, and it is possible that these might produce different results. We have chosen to use changes in HbT concentration as the method of CBV measurement in this study. HbT concentration changes in proportion to CBV if hemoglobin concentration and the cerebral large to small vessel hematocrit ratio remain constant during the measurement period (10–12). Although this technique does not allow measurement of absolute CBV, its advantage lie in the ability to make continuous real-time measurements of changes in CBV. Such dynamic measurements might be useful in a variety of clinical settings. Another NIRS method allows quantification of CBV by using graded arterial hypoxemia and has been described in detail elsewhere (12,24). This technique allows measurement of absolute CBV which is clearly also advantageous under certain circumstances. However, the limitations include the intermittent nature of the technique and the use of arterial hypoxemia, which may limit its clinical applicability. Some studies have used both techniques simultaneously and supplemented the continuous measurement of changes in CBV derived from changes in HbT concentration with intermittent measurements of absolute CBV calculated from graded hypoxemia techniques (21,23). Discrepancies between the two methods have been noted, and it has been suggested that the HbT technique is less reliable (23). Gupta et al. (22) confirmed that CBV varied directly with PETCO2 when calculated from the regression line of and HbO2/SpO2, but they were unable to demonstrate a systematic relationship between changes in HbT concentration and PETCO2. However, Wyatt et al. (12) successfully used changes in HbT to measure changes in CBV in response to alterations in PaCO2 in neonates. Clearly, these differences require explanation and may be related to the different ways in which changes in PaCO2 and posture affect CBV, as much as to the NIRS techniques themselves. Domination of NIRS measurements of CBV by one part of the cerebral vasculature might explain how different methods of changing CBV would produce different results with the two NIRS techniques. Consider the situation if NIRS measurements were affected more by changes in the cerebral venous system than by changes in the arterial circulation: It is likely that, under such circumstances, NIRS-derived changes in CBV would be greater for changes in posture that affect the passive venous system than for changes in PaCO2, which have greater impact on the arterial system. This hypothesis cannot be answered by the present study but clearly requires further investigation.
Although NIRS samples from arterial, venous, and capillary compartments, the relative contribution of each to the signal has not yet been clearly defined. It is therefore not possible to determine whether the observed changes in CBV occurred equally in all compartments. We hypothesize that, in the awake volunteers, head-down tilt was associated with a small increase in venous blood volume because this is a valveless compartment and would be expected to expand as a result of the increase in venous pressure associated with head-down tilt. Similarly, during head-up tilt in the awake volunteers, it is likely that the reduction in CBV was caused by a reduction in the volume of the venous and/or capillary compartments. We feel that the change in CBV is unlikely to be a result of an increase in the arterial compartment, because arterial blood pressure did not change during tilting.
We are left to explain the striking differences between awake and anesthetized patients during head-up tilt. We deliberately chose to make our measurements at the end of surgery in order to make them, as much as possible, under steady-state conditions and not immediately after the induction of anesthesia, at a time when blood pressure and cerebral oxygenation may be rapidly changing (25). Propofol reduces cerebral metabolism (26), which is associated with a degree of cerebral vasoconstriction. Additionally, the anesthetized patients were ventilated to a modest level of hypocapnia, which may also have been associated with cerebral vasoconstriction. During the head-down tilt, cerebral vasoconstriction would not alter the behavior of the venous system and CBV would still increase as a result of passive hydrostatic filling of this compartment. It is possible that during head-up tilt, because the volume of blood in the brain was already reduced, compensatory mechanisms prevented reductions in CBV to the same extent seen in the awake volunteers. This might affect the use of posture as a therapeutic strategy to reduce CBV in patients anesthetized with propofol.
We have shown that it is possible to monitor real-time changes in HbT concentration associated with changes in posture by using NIRS, which reacts promptly when posture is changed in a time scale suitable for clinical use at the bedside. Notwithstanding the inherent difficulties in the technique, we believe that the changes in HbT reflect changes in CBV. The ability of NIRS to measure changes in CBV may have implications for the monitoring and management of brain-injured patients and should be investigated further.
1. Sklar FH, Burke EF Jr, Langfitt TW. Cerebral blood volume: values obtained with 51
Cr-labelled red blood cells and RISA. J Appl Physiol 1968; 24:79–82.
2. Risberg J, Lundberg N, Ingvar DH. Regional cerebral blood volume during acute transient rises of the intracranial pressure (plateau waves). J Neurosurg 1969; 31:303–10.
3. Sakai F, Nakazawa K, Tazaki Y, et al. Regional cerebral blood volume and hematocrit measured in normal human volunteers by single-photon emission computed tomography. J Cereb Blood Flow Metab 1985; 5:207–13.
4. Ter-Pogossian MM, Herscovitch P. Radioactive oxygen-15 in the study of cerebral blood flow, blood volume, and oxygen metabolism. Semin Nucl Med 1985; 15:377–94.
5. Jezzard P, Song AW. Technical foundations and pitfalls of clinical fMRI. Neuroimage 1996; 4:S63–75.
6. Magnaes B. Body position and cerebrospinal fluid pressure. Part 1. Clinical studies on the effect of rapid postural changes. J Neurosurg 1976; 44:687–97.
7. Schneider GH, von Helden A, Franke R, et al. Influence of body position on jugular venous oxygen saturation, intracranial pressure and cerebral perfusion pressure. Acta Neurochir Wein 1993; 59:107–12.
8. Wyatt JS, Cope M, Delpy DT, et al. Quantification of cerebral oxygenation and haemodynamics in sick newborn infants by near infrared spectrophotometry. Lancet 1986; 2:1063–6.
9. Reynolds EOR, McCormick DC, Roth SC, et al. New non-invasive methods for the investigation of cerebral oxidative metabolism and haemodynamics in newborn infants. Ann Med 1991; 23:681–6.
10. Wyatt JS, Edwards AD, Cope M, et al. Response of cerebral blood volume to changes in arterial carbon dioxide tension in preterm and term infants. Pediatr Res 1991; 29:553–7.
11. Edwards AD, McCormick DC, Roth SC, et al. Cerebral hemodynamic effects of treatment with modified natural surfactant investigated by near infrared spectroscopy. Pediatr Res 1992; 32:532–6.
12. Wyatt JS, Cope M, Delpy DT, et al. Quantitation of cerebral blood volume in newborn infants by near-infrared spectroscopy. J Appl Physiol 1990; 68:1086–91.
13. Cope M, Delpy DT. System for long-term measurement of cerebral blood and tissue oxygenation on newborn infants by near infra-red transillumination. Med Biol Engl Comput 1988; 26:289–94.
14. Villringer A, Planck J, Hock C, et al. Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. Neurosci Lett 1993; 154:101–4.
15. Owen-Reece H, Elwell CE, Wyatt JS, Delpy DT. The effect of scalp ischaemia on measurement of cerebral blood volume by near-infrared spectroscopy. Physiol Meas 1996; 17:279–86.
16. Wray S, Cope M, Delpy DT, et al. Characterization of the near infrared absorption spectra of cytochrome aa3
and haemoglobin for the non-invasive monitoring of cerebral oxygenation. Biochim Biophys Acta 1988; 933:184–92.
17. Essenpreis M, Elwell CE, Cope M, et al. Spectral dependence of temporal point spread functions in human tissues. Appl Opt 1993; 32:418–25.
18. Duncan A, Meek JH, Clemence M, et al. Optical pathlength measurements on the adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy. Phys Med Biol 1995; 40:295–304.
19. Bland JM, Altman DG. Calculating correlation coefficients with repeated observations. Part 1. Correlation within subjects. BMJ 1995; 310:446.
20. Kleinbaum DG, Kupper LL, Muller KE, Nizam A, eds. Applied regression analysis and multivariable methods. 3rd ed. Pacific Grove: Duxbury Press, 1998.
21. Owen-Reece H, Elwell CE, Goldstone J, et al. Investigation of the effects of hypocapnia upon cerebral haemodynamics in normal volunteers and anaesthetised subjects by near infrared spectroscopy (NIRS). Adv Exp Med Biol 1994; 361:475–82.
22. Gupta AK, Menon DK, Czosnyka M, et al. Non-invasive measurement of cerebral blood volume in volunteers. Br J Anaesth 1997; 78:39–43.
23. Brun NC, Greisen G. Cerebrovascular responses to carbon dioxide as detected by near-infrared spectroscopy: a comparison of three different measures. Pediatr Res 1994; 36:20–4.
24. Elwell CE, Cope M, Edwards AD, et al. Quantification of adult cerebral hemodynamics by near-infrared spectroscopy. J Appl Physiol 1994; 77:2753–60.
25. Lovell AT, Owen-Reece H, Elwell CE, et al. Continuous measurement of cerebral oxygenation by near infrared spectroscopy during induction of anesthesia. Anesth Analg 1999; 88:554–8.
© 2000 International Anesthesia Research Society
26. Alkire MT, Haier RJ, Barker SJ, et al. Cerebral metabolism during propofol anesthesia in humans studied with positron emission tomography. Anesthesiology 1995; 82:393–403.