Comparison of changes in jugular venous bulb oxygen saturation and cerebral oxygen saturation during variations of haemoglobin concentration under propofol and sevoflurane anaesthesia

K. Yoshitani1,*, M. Kawaguchi1, M. Iwata1, N. Sasaoka1, S. Inoue1, N. Kurumatani2 and H. Furuya1

Departments of 1 Anaesthesiology and 2 Hygiene, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan

* Corresponding author. Present address: Department of Anaesthesiology, National Cardiovascular Centre, Fujishirodai 5-7-1, Suita, Osaka, 565-8565, Japan. E-mail: nkenji{at}mva.biglobe.ne.jp

Accepted for publication October 22, 2004.


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. A severe reduction in haemoglobin concentration can lead to a decrease in jugular venous bulb oxygen saturation (). However, recent evidences suggests that cerebral oxygen saturation () measured by near infrared spectroscopy decreased during even mild haemodilution. We therefore tested the hypothesis that the changes in may not be parallel to those in during haemodilution. In addition, as cerebral oxygen balance during the operation can vary depending on the anaesthetics used, the changes in and during haemodilution were compared between patients under propofol and isoflurane/nitrous oxide anaesthesia.

Methods. Forty-two patients with pre-donated autologous blood were randomly assigned to receive propofol (Group P) or sevoflurane/nitrous oxide (Group S) anaesthesia. A fibreoptic catheter was placed in the jugular bulb to measure . A cerebral oximeter, INVOS 4100S was used to monitor . Arterial and jugular bulb blood samples were drawn simultaneously at: (i) 10 min after the start of operation, (ii) after 400 ml of blood loss, (iii) after 800 ml of blood loss, (iv) just before the transfusion of pre-donated autologous blood, and (v) after 400 ml transfusion.

Results. Mean (SD) control values of in Group P were significantly lower than those in Group S (55 (8)% vs 71 (10)%, respectively; P<0.05), whereas there was no significant difference in control values of between the two groups. During the operation, haemoglobin (Hb) concentrations significantly deceased in the both groups compared with control values (from 9.8 to 7.6 g dl–1 in Group P and from 9.9 to 8.0 g dl–1 in Group S). During a reduction in Hb concentration, values remained unchanged in both groups, whereas values significantly decreased in both groups (from 57 to 51% in Group P and from 59 to 52% in Group S).

Conclusion. The results indicated that, although the changes in and during a reduction in haemoglobin concentration were similar under propofol and sevoflurane/nitrous oxide anaesthesia, the changes in were not parallel to those in . The discrepancy of the results in and may make the interpretation of their values difficult during haemodilution.

Keywords: circulation, haemodilution ; monitoring, jugular venous bulb oxygen saturation ; monitoring, near infrared spectroscopy


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Jugular venous bulb oxygen saturation () has been used as an indirect assessment of global cerebral oxygen use to guide physiologic managements in a variety of clinical settings. During haemodilution, cerebral blood flow (CBF) and oxygen extraction are known to increase to compensate for the decreased oxygen transport in both human and experimental animals.13 CBF has been shown to change to keep oxygen transport to the brain tissue constant.4 When cerebral hyperaemic compensation cannot meet oxygen demand, significant increase in oxygen extraction and decrease in can be observed. During mild to moderate haemodilution to a haematocrit of 20%, values remained unchanged in patients undergoing orthopaedic surgery.5 During severe haemodilution, began to decrease significantly at a mean haematocrit of 7.6% in a pig model.6 These suggested that a critical level of haematocrit and haemoglobin (Hb) concentration, in which can decrease because of a failure to compensate a reduction in oxygen transport, is relatively low compared with those, which we encounter occasionally in clinical situations with mild to moderate haemodilution.

Near infrared spectroscopy (NIRS) provides a non-invasive optical monitoring technique assessing regional cerebral oxygen saturation (). Several studies have proven the efficacy of NIRS during neurosurgical and cardiac surgical areas.713 Recent evidences have indicated that can decrease as haemoglobin concentration decreased during haemodilution. Torella and colleagues14 have demonstrated that values decreased significantly during normovolemic haemodilution to a target Hb concentration of 11 g dl–1 and had a significant positive correlation with Hb concentrations. Lassnigg and colleagues15 also reported that a decrease in Hb concentration (from 11.7 to 8.5 g dl–1) during the onset of cardiopulmonary bypass (CPB) induced a significant reduction in oxyhemoglobin (O2Hb) measured by NIRS. These data suggested that can decrease even during mild haemodilution and changes in may differ from those in during haemodilution. In the present study we therefore tested the hypothesis that the changes in may not be parallel to those in during haemodilution. In addition, recent data suggested that cerebral oxygen balance during the operation could vary depending on the anaesthetics used. values have been shown to be lower under propofol compared with isoflurane or sevoflurane anaesthesia.1619 We therefore compared the changes in and during changes in haemoglobin concentration between patients under propofol and isoflurane/nitrous oxide anaesthesia.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
After institutional approval and informed consent, 42 patients scheduled for elective total hip arthroplasty with pre-deposited autologous blood were enrolled in this study. Autologous blood donation of two units (800 ml) was performed 2 weeks before the day of the surgery. The donation volume was replaced simultaneously with 6% hydroxyethylated starch in a 1:1 ratio. The patients were randomly allocated into two groups: Group P (n=21) receiving propofol/fentanyl and Group S (n=21) receiving sevoflurane/nitrous oxide/fentanyl. No drug was given for preanaesthetic medication. Anaesthesia was induced with fentanyl (4 µg kg–1) and propofol (2 mg kg–1) and tracheal intubation was facilitated with vecuronium 0.2 mg kg–1. In Group P, anaesthesia was maintained with propofol 5 mg kg h–1 and the lungs were mechanically ventilated with an air/oxygen mixture (). In Group S, anaesthesia was maintained with sevoflurane (1%, end-tidal concentration) and the lungs were mechanically ventilated with an oxygen nitrous oxide mixture (). Additional fentanyl was administered if necessary. Pre-donated autologous blood was returned when Hb concentration decreased to <7 g dl–1 or the femoral prosthesis was inserted into the femoral canal.

Routine monitoring equipment included a radial artery catheter for direct arterial blood pressure measurement, a pulse oximeter, and an electrocardiograph. End-tidal carbon dioxide () tension and end-tidal concentration of sevoflurane were measured using a CAPNOMAC multi-gas analyser (Hewlett-Packard, Andover, MA, USA). The tympanic membrane temperature was also continuously monitored by Mon-a-Therm (Mallinckrodt Co., St Louis, MO, USA) and maintained between 35.5°C and 36.5°C using a warming blanket.

Cerebral oximeter, INVOS 4100S (Somanetics, Troy, MI, USA) was used to monitor cerebral oxygen saturation. For the measurements, the cerebral oximeter probe was placed on the right forehead, with the caudal border ~1 cm above the eyebrow with the medial edge at the midline. This position places the light source and sensors away from the frontal sinus. To measure for the assessment of the ratio of cerebral oxygen delivery to demand, a fibreoptic catheter (U 440, Oximetrix, Abbott Critical Care System, Abbott Laboratory, North Chicago, IL, USA) was placed in the right jugular venous bulb. Catheter position was verified by radiography in the anterior–posterior projection. Measurements were performed at the following 5 points: (i) 10 min after the start of operation, (ii) after 400 ml of blood loss, (iii) after 800 ml of blood loss, (iv) just before the transfusion of pre-donated autologous blood, and (v) after 400 ml transfusion. At each measurement, arterial and jugular venous bulb bloods were collected and cerebral oxygenation data were simultaneously measured. During the operation, blood loss was calculated from swab weights and discard suction volumes every 10 min and the calculated blood loss was replaced by the same amount of 6% hydroxyethylated starch to avoid hypovolaemia.

For estimation, cerebral oxygenation state and cerebral oxygen extraction ratio (COER) were calculated using the following equations:




where and are the arterial and jugular venous bulb oxygen contents.

Statistics
Data are expressed as mean (SD). Demographic variables between the groups were compared using un-paired t-test or {chi}2-test. Haemodynamic variables and cerebral oxygen parameters were analysed using two-way ANOVA with repeated measurement (intergroup comparison) and one-way ANOVA with repeated measurement (intragroup comparison). Post-hoc analysis using multiple independent sample t-tests with Bonferroni correction was performed where significant differences occurred. A preliminary estimate of sample size was based on an expected 10% reduction in . With a type I error of 0.05 and a type II error of 0.2, the required sample size was 17–19 patients in each group. We estimated dropout rate as 10%. Therefore we assigned 21 patients randomly to Groups P and S, respectively. During measurements, patients who required vasodilator drugs were excluded from the study. Sample size was determined by ‘G power’ (the software is freely available from the website: http://www.psycho.uni-duesseldorf.de/aap/projects/gpower/index.html). Data were analysed using the SPSS-PC statistical software program (Version 11.0.1: SPSS, Inc., Chicago, IL, USA).


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Of the 42 patients who were enrolled into the study, five patients were excluded because of unsuccessful cannulation of internal jugular vein or treatment with vasodilator. Patient characteristics are shown in Table 1. There were no significant differences in patient characteristics between the two groups. Physiological data are shown in Table 2. There was no significant difference in physiological variables between the two groups.


View this table:
[in this window]
[in a new window]
 
Table 1 Patient characteristics (n=37). Data are presented as mean (SD) unless indicated. There were no statistically significant differences between the two groups

 

View this table:
[in this window]
[in a new window]
 
Table 2 Physiological data (n=37).

 
Changes in Hb concentrations and cerebral hemodynamic values are shown in Figure 1. There was no significant difference in Hb concentrations of control values between the two groups (Group P, 9.8 (1.0) g dl–1; Group S, 9.9 (1.3) g dl–1). During the operation, Hb concentrations gradually decreased and Hb concentrations just before transfusion of pre-donated blood were significantly lower than control values in both groups (Group P, 7.6 (1.0) g dl–1; Group S, 8.0 (1.2) g dl–1).



View larger version (22K):
[in this window]
[in a new window]
 
Fig 1 The time course of changes in (A) Hb concentrations, (B) jugular venous bulb oxygen saturation (), (C) cerebral oxygen saturation (), and (D) cerebral oxygen extraction ratio (COER) in the two experimental groups. Patients in Group P received propofol/fentanyl anaesthesia and those in Group S received nitrous oxide/sevoflurane/fentanyl anaesthesia. Measurements were performed at: (i) 10 min after the start of operation (control values), (ii) at 400 ml of blood loss, (iii) at 800 ml of blood loss, (iv) just before the transfusion of pre-donated autologous blood, and (v) after 400 ml transfusion. Data are expressed as mean (SD). *P<0.05 vs control values; {dagger}P<0.05 vs time (iv), #P<0.05 vs Group P.

 
Changes in cerebral haemodynamic values are shown in Figure 1. Control values in Group P were significantly lower than those in Group S (55 (8)% vs 71 (10)%, respectively; P<0.05). Control values of COER in Group P were significantly higher compared with those in Group S (32 (8)% vs 47 (10)%, respectively; P<0.05). During a reduction in Hb concentration, values did not change significantly in both groups. After the transfusion of pre-donated blood, values were significantly increased compared with those just before the transfusion in Group P (from 55 (8) to 62 (5)%, P<0.05), but not in S. After the transfusion of predonated blood, COER values were significantly decreased compared with those just before transfusion in Group P (from 48 (8) to 43 (9)%, P<0.05), but not in Group S.

In contrast to the results of , there was no significant difference in control values of between the two groups (Group P, 57 (10)%; Group S, 59 (9)%). During a reduction in Hb concentration, values were gradually decreased in both groups. values just before the transfusion of pre-donated blood (Group P, 51 (8)%; Group S, 52 (10)%) were significantly lower compared with control values in both groups (P<0.05).

Figure 2 shows the relationship between values and Hb concentrations, and between values and Hb concentrations. There is a significant positive correlation between values and Hb concentrations (Group P, r=0.37, P<0.001; Group S, r=0.46, P<0.001), whereas there are no significant correlation between values and Hb concentrations (Group P, r=0.12, P=0.26; Group S, r=0.19, P=0.07).



View larger version (22K):
[in this window]
[in a new window]
 
Fig 2 Relationship between Hb concentrations and cerebral oxygen saturation () values in (A) Group P and (B) Group S. There were significant positive correlations between values and Hb concentrations (Group P, r=0.37, P<0.001; Group S, r=0.46, P<0.001). Relationship between Hb concentrations and jugular venous bulb oxygen saturation () in (C) Group P and (D) Group S. There were no significant correlations between values and Hb concentrations (Group P, r=0.12, P=0.26; Group S, r=0.19, P=0.07).

 

    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The results in the present study showed that values remained unchanged during mild to moderate haemodilution, whereas values significantly decreased as Hb concentration decreased. This suggests that the changes in were not parallel to those in during haemodilution. The changes in and values were not modified by the background anaesthetics used, although values, but not values, were significantly lower under propofol anaesthesia compared with those under sevoflurane/nitrous oxide anaesthesia.

Although available data on changes in and during mild to moderate haemodilution are limited in humans, previous data are consistent with the results obtained in the present study, in which the reduction in mean Hb concentrations from 9.8 to 7.6 g dl–1 in Group P and from 9.9 to 8.0 g dl–1 in Group S did not affect values, but significantly reduced values. Shapira and colleagues5 evaluated the safety of haemodilution combined with induced hypotension with in patients under isoflurane anaesthesia and demonstrated that values remained unchanged during mild to moderate haemodilution with a haematocrit: from 35.6 to 20%. In contrast, Torella and colleagues14 have demonstrated that values decreased significantly during acute normovolaemic haemodilution to a target haemoglobin of 11 g dl–1 in aortic surgery and a significant positive correlation between Hb concentrations and values were noted. Lassnigg and colleagues15 also reported that O2Hb measured by NIRS significantly decreased during the onset of CPB, in which Hb concentrations were decreased from 11.7 to 8.5 g dl–1.

The reasons of discrepancy in changes of and during haemodilution are unknown. However, possible explanations are as follows. First, is an indirect indicator of global cerebral oxygen use and has high specificity and low sensitivity of cerebral ischaemia. Normal values may not reflect focal areas of ischaemia, although low values were indicative of low flow.20 In contrast, monitoring to detect cerebral ischaemia had high sensitivity and specificity.8 Therefore, it seems likely that changes might reflect regional oxygen imbalance during mild to moderate haemodilution, although did not detect any changes in global cerebral oxygen balance. In fact, Hino and colleagues21 demonstrated that regional cerebral oxygen extraction fraction (OEF) of cortical grey matter significantly increased (41.7 to 43.3%) during a mild reduction in Hb concentration (14.3 to 12.6 g dl–1) using positron emission tomography in human volunteers. Morimoto and colleagues22 also reported that brain tissue oxygen tension gradually decreased as Hb concentration decreased, as the increases in CBF and oxygen extraction could only partially compensate for the decreased oxygen transport during haemodilution.

Second, the algorithm to estimate might lead to an overestimated reduction in values during haemodilution. A modified Beer–Lambert law has been used to estimate and O2Hb in NIRS and contains a factor of pathlength. Lassnigg and colleagues15 suggested that low arterial Hb concentration leads to an increase in optical pathlength and an overestimation of the decrease in cerebral O2Hb. In fact, Kurth and colleagues23 demonstrated that optical pathlength increased linearly with decreasing Hb concentration in the perfusate to the brain. As pathlength factors are assumed to be constant in the Beer–Lambert law, the increase in pathlength factors may lead overestimation of changes in .

Although the control values of were significantly lower under propofol than sevoflurane anaesthesia, values did not change significantly in either group during haemodilution in the present study. Previous studies1619 have reported that values were lower under propofol anaesthesia compared with isoflurane or sevoflurane anaesthesia. Our results were compatible with those in previous studies. Different effects of these anaesthetics on cerebral blood flow might have caused the differences of values between the two groups.16 However, any differences in absolute values between the two groups were not observed. Previous studies showed that there was a significant correlation between percentage changes in and values, but there was a wide limit of agreement between absolute and values.14 24 These were consistent with the result of our study. However, we previously reported that tissue oxygen index (TOI), one of , that use the algorithm independent of pathlength factors, were significantly lower under propofol anaesthesia than under isoflurane anesthesia.25 Although exact mechanisms are unknown, pathlength factors might affect the absolute values of .

There are several limitations in the present study to merit comments. First, we did not measure CBF and CMRO2, which may limit the interpretation of the results because we could not differentiate between the changes of flow and oxygen consumption. Second, although we tried to maintain normovolaemia, we did not have haemodynamic parameters including pulmonary artery pressure and central venous pressure proving that we achieved this goal. In fact, inaccuracy of calculating blood loss may have prevented us to achieve this goal. Third, all patients in this study were free from cerebral pathology. It remains therefore unknown how and would have responded during haemodilution in patients with a cerebral pathology. Fourth, only mild haemodilution was assessed in the present study. During severe haemodilution, the changes in and may be different from those obtained in the present study. To clarify these points, further studies will be necessary.

In summary, we compared the changes in and values during a mild changes in Hb concentration under propofol and sevoflurane/nitrous oxide anaesthesia. Although values remained unchanged, values significantly decreased as Hb concentration decreased and positive correlation between values and Hb concentrations was observed. These results suggest that the changes in were not parallel to those in during haemodilution and retransfusion. In clinical situations, the discrepancy between the results of and makes their interpretation difficult. Further studies will be necessary to clarify this point.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Hudak ML, Koehler RC, Rosenberg AA, Traystman RJ, Jones MD Jr. Effect of haematocrit on cerebral blood flow. Am J Physiol 1986; 251: H63–70[ISI][Medline]

2 Hudetz AG, Wood JD, Biswal BB, Krolo I, Kampine JP. Effect of haemodilution on RBC velocity, supply rate, and haematocrit in the cerebral capillary network. J Appl Physiol 1999; 87: 505–9[Abstract/Free Full Text]

3 Todd MM, Weeks JB, Warner DS. Cerebral blood flow, blood volume, and brain tissue haematocrit during isovolemic haemodilution with hetastarch in rats. Am J Physiol 1992; 263: H75–82[ISI][Medline]

4 Todd MM, Wu B, Maktabi M, Hindman BJ, Warner DS. Cerebral blood flow and oxygen delivery during hypoxemia and haemodilution: role of arterial oxygen content. Am J Physiol 1994; 267: H2025–31[ISI][Medline]

5 Shapira Y, Gurman G, Artru AA, et al. Combined haemodilution and hypotension monitored with jugular bulb oxygen saturation, EEG, and ECG decreases transfusion volume and length of ICU stay for major orthopaedic surgery. J Clin Anesth 1997; 9: 643–9[CrossRef][ISI][Medline]

6 van Bommel J, Trouwborst A, Schwarte L, Siegemund M, Ince C, Henny ChP. Intestinal and cerebral oxygenation during severe isovolemic haemodilution and subsequent hyperoxic ventilation in a pig model. Anesthesiology 2002; 97: 660–70[CrossRef][ISI][Medline]

7 Williams IM, Picton AJ, Hardy SC, Mortimer AJ, McCollum CN. Cerebral hypoxia detected by near infrared spectroscopy. Anaesthesia 1994; 49: 762–6[ISI][Medline]

8 Samra SK, Dy EA, Welch K, Dorje P, Zelenock GB, Stanley JC. Evaluation of a cerebral oximeter as a monitor of cerebral ischemia during carotid endarterectomy. Anesthesiology 2000; 93: 964–70[CrossRef][ISI][Medline]

9 Carlin RE, McGraw DJ, Calimlim JR, Mascia MF. The use of near-infrared cerebral oximetry in awake carotid endarterectomy. J Clin Anesth 1998; 10: 109–13[CrossRef][ISI][Medline]

10 Abdul-Khaliq H, Troitzsch D, Schubert S, et al. Cerebral oxygen monitoring during neonatal cardiopulmonary bypass and deep hypothermic circulatory arrest. Thorac Cardiovasc Surg 2002; 50: 77–81[CrossRef][ISI][Medline]

11 Abdul-Khaliq H, Schubert S, Troitzsch D, et al. Dynamic changes in cerebral oxygenation related to deep hypothermia and circulatory arrest evaluated by near-infrared spectroscopy. Acta Anaesthesiol Scand 2001; 45: 696–701[CrossRef][ISI][Medline]

12 Terborg C, Gora F, Weiller C, Rother J. Reduced vasomotor reactivity in cerebral microangiopathy: a study with near-infrared spectroscopy and transcranial Doppler sonography. Stroke 2000; 31: 924–9[Abstract/Free Full Text]

13 Yoshitani K, Kawaguchi M, Tatsumi K, Kitaguchi K, Furuya H. A comparison of the INVOS 4100 and the NIRO 300 near-infrared spectrophotometers. Anesth Analg 2002; 94: 586–90[Abstract/Free Full Text]

14 Torella F, Haynes SL, McCollum CN. Cerebral and peripheral near-infrared spectroscopy: an alternative transfusion trigger? Vox Sang 2002; 83: 254–7[CrossRef][ISI][Medline]

15 Lassnigg A, Hiesmayr M, Keznickl P, Mullner T, Ehrlich M, Grubhofer G. Cerebral oxygenation during cardiopulmonary bypass measured by near-infrared spectroscopy: effects of haemodilution, temperature, and flow. J Cardiothorac Vasc Anesth 1999; 13: 544–8[CrossRef][ISI][Medline]

16 Kaisti KK, Metsahonkala L, Teras M, et al. Effects of surgical levels of propofol and sevoflurane anaesthesia on cerebral blood flow in healthy subjects studied with positron emission tomography. Anesthesiolgy 2002; 96: 1358–70[CrossRef][ISI][Medline]

17 Jansen GFA, van Praagh BH, Kedaria MB, Odoom JA. Jugular bulb oxygen saturation during propofol and isoflurane/nitrous oxide anaesthesia in patients undergoing brain tumours. Anesth Analg 1999; 89: 358–63[Abstract/Free Full Text]

18 Kawano Y, Kawaguchi M, Inoue S, et al. Jugular bulb oxygen saturation under propofol or sevoflurane/nitrous oxide anaesthesia during deliberate mild hypothermia in neurosurgical patients. J Neurosurg Anesthesiol 2004; 16: 6–10[CrossRef][ISI][Medline]

19 Petersen KD, Landsfeldt U, Cold GE, et al. Intracranial pressure and cerebral hemodynamic in patients with cerebral tumors: a randomized prospective study of patients subjected to craniotomy in propofol–fentanyl, isoflurane–fentanyl, or sevoflurane–fentanyl anaesthesia. Anesthesiology 2003; 98: 329–36[CrossRef][ISI][Medline]

20 Schell RM, Cole DJ. Cerebral monitoring: jugular venous oximetry. Anesth Analg 2000; 90: 559–66[Free Full Text]

21 Hino A, Ueda S, Mizukawa N, Imahori Y, Tenjin H. Effect of haemodilution on cerebral hemodynamics and oxygen metabolism. Stroke 1992; 23: 423–6[Abstract]

22 Morimoto Y, Mathru M, Martinez-Tica JF, Zornow MH. Effects of profound anemia on brain tissue oxygen tension, carbon dioxide tension, and pH in rabbits. J Neurosurg Anesthesiol 2001; 13: 33–9[CrossRef][ISI][Medline]

23 Kurth CD, Uher B. Cerebral haemoglobin and optical pathlength influence near-infrared spectroscopy measurement of cerebral oxygen saturation. Anesth Analg 1997; 84: 1297–305[Abstract]

24 Henson LC, Calalang C, Temp JA, Ward DS. Accuracy of a cerebral oximeter in healthy volunteers under conditions of isocapunic hypoxia. Anesthesiology 1998; 88: 58–65[ISI][Medline]

25 Yoshitani K, Kawaguchi M, Tatsumi K, Sasaoka N, Kurumatani N, Furuya H. Intravenous administration of flurbiprofen does not affect cerebral blood flow velocity and cerebral oxygenation under isoflurane and propofol anaesthesia. Anesth Analg 2004; 98: 471–6[Abstract/Free Full Text]