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Anesth Analg 2000;90:372
© 2000 International Anesthesia Research Society

NEUROSURGICAL ANESTHESIA

Changes in Cerebral Blood Volume with Changes in Position in Awake and Anesthetized Subjects

A. Timothy Lovell, MB, BS, FRCA*, Alan C. Marshall, MB, BS, FRCA{dagger}, Clare E. Elwell, PhD{ddagger}, Martin Smith, MB, BS, FRCA{dagger}, and John C. Goldstone, MD, FRCA*

*Division of Academic Anaesthesia, Department of Surgery, University College London Medical School, The Middlesex Hospital; {dagger}Department of Neuroanaesthesia, The National Hospital for Neurology and Neurosurgery; {ddagger}Department of Medical Physics and Bioengineering, University College London, London, United Kingdom

Address correspondence and reprint requests to Dr. J. C. Goldstone, Division of Academic Anaesthesia, UCL Medical School, Room 103, The Middlesex Hospital, Mortimer St., London W1N 8AA, UK.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Changes in posture affect cerebral blood volume (CBV), and moderate head-up tilt is used as a therapeutic maneuver to reduce CBV and intracranial pressure. However, CBV is rarely measured in the clinical setting. Near-infrared spectroscopy allows real-time bedside monitoring of cerebral hemodynamics, and we have used this technique to measure changes in CBV with changes in posture in 10 normal subjects and 10 propofol-anesthetized patients. In the awake subjects, changes in CBV were correlated with the degree of table tilt. CBV decreased with 18° head-up tilt and increased with 18° head-down tilt (P < 0.0001, r = -0.924). In anesthetized patients, there were differences between head-up and head-down tilt. In the head-down position, CBV was also correlated with the degree of table tilt (P < 0.001, r = -0.782), whereas there was a clinically insignificant reduction in CBV in the head-up position. Near-infrared spectroscopy allows continuous, real time measurement of changes in CBV at the bedside.

Implications: Near-infrared spectroscopy, a bedside technique, has been used to measure changes in cerebral blood volume in normal subjects. We have used the same technique in anesthetized patients and have shown that, when a patient is placed in the head up position, the decrease in cerebral blood volume is attenuated, relative to normal subjects.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
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.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
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): Go


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.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
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).


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  		Table 1. Demographics and Details of Anesthesia Before Measurement of Change in Cerebral Blood Volume
 

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  		Table 2. Changes in Mean Arterial Blood Pressure (mm Hg) with Change in Posture
 
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).



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  		Figure 1. Typical changes in total hemoglobin concentration ({Delta}HbT) in an awake, healthy volunteer with changes in posture during an abrupt 18°-head-down tilt and during sequential 6°-tilts. The {blacktriangleup} indicates the times at which the table position was altered.

 
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.



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  		Figure 2. Typical changes in total hemoglobin concentration ({Delta}HbT) in a patient anesthetized with propofol with changes in posture. The {blacktriangleup} indicates the times at which the table position was altered.

 
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).



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  		Figure 3. Changes in cerebral blood volume ({Delta}CBV) with change in table position. {blacksquare} = awake subjects, • = propofol-anesthetized patients. The solid line represents the multiple linear regression equation for the awake volunteers. The dashed line represents the multiple linear regression equations for the propofol-anesthetized group.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
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.


   Footnotes
 
ATL is supported by a training fellowship from the Wellcome Trust.

This work was presented in part at the 1997 annual meeting of the Neuroanaesthesia Society, Plymouth, UK, and has appeared in part in Journal of Neurosurgical Anesthesiology 1997;9:405.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication October 13, 1999.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press