Nimotop

Monitoring of brain tissue oxygenation (p^sub ti^O^sub 2^) enables early diagnosis of secondary cerebral ischemia and may guide a cerebral perfusion pressure (CPP) orientated therapy. The purpose of our study was to explain the concept of p^sub ti^O^sub 2^-autoregulation, defined as the ability of the brain to maintain p^sub ti^O^sub 2^ despite changes in CPP, and to show the different slates of p^sub ti^O^sub 2^-autoregulation we found. Microcatheters to assess p^sub ti^O^sub 2^ and intracranial pressure were implanted into cerebral 'tissue at risk' of patients suffering from traumatic brain injury or subarachnoid hemorrhage. By using a multimodal neuromonitoring setup and in-house built software we assessed and displayed online the relationship between p^sub ti^O^sub 2^ and CPP based on a data buffer consisting of 12 h. Depending on the linear regression slope (bp^sub ti^O^sub 2^ = [Delta]P^sub ti^O^sub 2^/[Delta]CPP), we defined the state of p^sub 2^O^sub 2^-autoregulation as present (0 bp^sub ti^O^sub 2^1/3) or inverse (bp^sub ti^O^sub 2^

Keywords: Brain tissue oxygenation; cerebral autoregulation; traumatic brain injury; subarachnoid hemorrhage; cerebral perfusion pressure; multimodal cerebral monitoring

INTRODUCTION

Following traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH), patients are at a considerable risk of suffering secondary brain injury1,2 due to brain edema or cerebral vasospasm, respectively. In TBI, a decrease in arterial blood pressure (ABP) or an increase in intracranial pressure (ICP) may critically reduce cerebral perfusion pressure (CPP) thus leading to cerebral ischemia. Therefore the necessity to monitor ICP and to maintain a sufficient CPP has been stressed3 and implemented into guidelines for the management of TBI4. However, cerebral ischemia may occur even at a sufficient CPP5,6 and the subsequent cerebral hypoxia results in a worsening of outcome following TBI7-10. Hence, the monitoring of brain oxygenation has been advocated and techniques such as the jugular bulb oximetry11 and brain tissue oxygen partial pressure measurement12,13 have been applied.

Recently, the effect of a 'p^sub ti^O^sub 2^ guided, CPPorientated therapy', tailored to achieve a p^sub ti^O^sub 2^>10mmHg by manipulation in CPP, has been evaluated in comparison to a standard CPP orientated (>70mmHg) therapy in 93 TBI-patients14: The p^sub ti^O^sub 2^ guided group exhibited significantly less hypoxic events and snowed a trend towards an improvement in outcome. Subsequently the question arose on what CPP is necessary to achieve a p^sub ti^O^sub 2^ > 10 mmHg in a given patient at a given time. Hence we evaluated online the influence of CPP on p^sub ti^O^sub 2^ and developed the concept of p^sub ti^O^sub 2^-autoregulation, defined as the ability of the brain to maintain p^sub ti^O^sub 2^ despite changes in CPP.

This study was performed to elucidate this concept, to show different patterns of p^sub ti^O^sub 2^-autoregulation, and to explain their therapeutical implications in patients suffering from TBI or SAH.

MATERIALS AND METHODS

Patients and treatment

This study was approved by the local ethics committee, and written consent was obtained from patients' relatives. Patients suffering from severe TBI or SAH were investigated in this study. TBI patients received treatment according to the European Brain Injury Consortium guidelines (EBIC)4 including initial CT scan, evacuation of intracranial hematoma and use of vasopressors (dopamine, noradrenaline) and/or mannitol if needed. Cerebral angiography was performed in SAH patients, and aneurysms were subsequently clipped surgically or coiled interventionally. In addition, SAH patients received nimodipine (6 x 60 mg p.o.) (Nimotop S, Bayer AG, Leverkusen, Germany) and were treated with triple-H therapy if vasospasm was present based on transcranial Doppler criteria. All patients were ventilated (Servo 300 A, Siemens-Elema, (Solna, Sweden) with parameters adjusted to maintain an arterial pO^sub 2^ of 95-1 30 mmHg and pCO^sub 2^ of 30-35 mmHg (TBI) or 35-45 mmHg (SAH).

Both TBI and SAH patients were monitored on our neurosurgical intensive care unit using advanced multimodal neuromonitoring: P^sub ti^O^sub 2^ was assessed using flexible polarographic microcatheters (Licox Revoxode CC1 .SB, CMS, Kiel-Mielkendorf, Germany) with a probe diameter of 0.6 mm and an oxygen sensitive area of 13mm^sup 2^. lntracranial pressure (ICP) was measured by an intraparenchymal microsensor transducer (Codman MicroSensor, Codman, Raynham, MA, USA). Both p^sub ti^O^sub 2^ and ICP sensor were inserted via a double lumen skull bolt kit (Licox IM2, CMS) into a depth of 22-27 mm (p^sub ti^O^sub 2^) or 10-1 5 mm (ICP) subdural, respectively. Attention was drawn to implant the catheters into CT-normal tissue which was considered to be at risk of cerebral edema or to be affected by vasospasm: In TBI the hemisphere of the focal lesion and in SAH the territory supplied by the aneurysm carrying artery was chosen. Arterial blood pressure (ABP) was assessed invasively from a radial artery catheter and referenced to the Foramen of Monroi. Neuromonitoring was started as early as possible after initial surgery and finished during respirator weaning.

Data collection and assessment of p^sub ti^O^sub 2^-autoregulation

Analog data of ABP, ICP and p^sub ti^O^sub 2^ were sampled (50 Hz) and digitised using an analog-to-digital converter (Licox MMM, CMS). Running software which was developed by one of the authors (MS), data were fitted to a personal computer and analysed online: ABP, ICP and p^sub ti^O^sub 2^ were averaged for each subsequent 5 sec interval to obtain mean values and to filter out heartbeat related changes. Then cerebral perfusion pressure (CPP) was calculated and together with ABP, ICP and p^sub ti^O^sub 2^ data stored in a first-in-first-out buffer, so that it contained the data of the last 12 h (n = 8640 data per parameter) at any time. The software displayed the time course of ABP, ICP, CPP and p^sub ti^O^sub 2^ , and stored the data on hard disc. In addition, it showed the actual state of the p^sub ti^O^sub 2^autoregulation by displaying all (8640) p^sub ti^O^sub 2^ data versus its related CPP-values resulting in a 'cloud of points' representing the state of p^sub ti^O^sub 2^-autoregulation during the past 12 h (Figures 1-4A).

To analyse this 'cloud of points', p^sub ti^O^sub 2^ data were divided into CPP-classes with a classwidth of IOmmHg and the mean p^sub ti^O^sub 2^ of each class was calculated and displayed as bars (Figures 1-4A). Other graphs, for example showing ICP versus its related ABP data, or p^sub ti^O^sub 2^ versus ICP (Figure 4B) were constructed in the same fashion.

Data artefacts occurred, for instance in CPP when arterial blood gas analysis was drawn. They were suppressed by two mechanisms: First, for calculation of mean p^sub ti^O^sub 2^-values and linear regression slope, rare and extreme CPP data were automatically excluded if their related CPP-class contained less than 60 data, corresponding to a monitoring time of less then 5 min. Second, artificial changes in p^sub ti^O^sub 2^, for instance when FiO^sub 2^ was set to 1.0 for a short period of time during endotracheal suction, had only minimal influence on bp^sub ti^O^sub 2^ since they were outnumbered by nonartificial values in the calculation of the mean p^sub ti^O^sub 2^ and the linear regression slope, as long as those changes were short in duration. However, distorted and nonrepresentative mean p^sub ti^O^sub 2^ and bp^sub ti^O^sub 2^ values are likely to be obtained if the FiO^sub 2^ is changed for a longer period or in general set to another level or if there are major changes in cerebral metabolism, e.g. induction of barbiturate coma. In such circumstances, the 12 h data buffer should be erased and a new analysis should be started as soon as conditions have stabilised.

The state of p^sub ti^O^sub 2^-autoregulation was defined depending on the slope (bp^sub ti^O^sub 2^) of the linear regression of p^sub ti^O^sub 2^ on CPP as present (01/3) or inverse (bp^sub ti^O^sub 2^

CPP was adjusted by vasoactive drugs (dopamine, noradrenaline) to fulfil standard protocols for TBI and SAH therapy. However no additional CPP therapy was performed to artificially enlarge the CPP range.

Regional cerebral hypoxia was assumed at a mean P^sub ti^O^sub 2^ of less than 10 mmHg8,15. The figures presented were taken as hardcopies from the above described online p^sub ti^O^sub 2^-autoregulation graphs. Information on arterial paO^sub 2^, the inspired fraction of oxygen (FiO^sub 2^) and the slope of linear regression were added to the hardcopies later on, based on patients' records and calculated data, respectively.

RESULTS

Present p^sub ti^O^sub 2^-autoregulation (0

An example of a present p^sub ti^O^sub 2^-autoregulation in a 19-year-old male patient is shown in Figure 1A. He had suffered a severe TBI with a combined epidural and subdural hematoma, which was evacuated immediately after admission. The mean p^sub ti^O^sub 2^ on day 12 changed as little as from 22.4 to 23.9 mmHg, shown as bars in Figure 1A, despite changes in CPP from 50 to 90 mmHg. As a consequence, the bp^sub ti^O^sub 2^ was found to be as low as 0.067 + or - 0.005 (mean + or - standard error, p

A 36-year-old woman showed regional cerebral hypoxia (p^sub ti^O2

Moderate p^sub ti^O^sub 2^-autoregulation (1/6

A typical example of a moderate p^sub ti^O^sub 2^-autoregulation with a bp^sub ti^O^sub 2^ of 0.202 + or -0.006, p

Figure 2B was obtained from a 64-year-old gentleman on the day following severe TBI with multiple brain contusions. It displays a moderate p^sub ti^O^sub 2^-autoregulation (bp^sub ti^O^sub 2^ =0.285 + or -0.006, p

Impaired p^sub ti^O^sub 2^-autoregulation (b^sub p^sub ti^^O^sub 2^>1/3)

Figure 3A was obtained from a 60-year-old woman showing an impaired p^sub ti^O^sub 2^-autoregulation (b^sub p^sub ti^O^sub 2^^= 0.401 + or -0.006, p

Inverse p^sub ti^O^sub 2^-autoregulation (b^sub p^sub ti^0^sub 2^^

An inverse state of p^sub ti^O^sub 2^-autoregulation is characterised by a negative linear regression slope: Unlike the previous reported examples, an increase in CPP (from 50 to 90 mmHg) is associated with a drop in p^sub ti^O^sub 2^ (from 34.6 to 23.2 mmHg) as shown in Figure 4A (b^sub p^sub ti^O^sub 2^^ = "0.539 + or -0.018, p

DISCUSSION

Definition of p^sub ti^O^sub 2^-autoregulation

Following the definition of pressure autoregulation as the ability of the brain to maintain CBF despite changes in CPP17, we defined p^sub ti^O^sub 2^-autoregulation as the ability to maintain p^sub ti^O^sub 2^ despite changes in CPP. In fact, there is a connection between both kinds of autoregulation: The p^sub ti^O^sub 2^ itself results from the balance between local microvascular O2 delivery and the local cellular O2 consumption. With CBF being one of the major factors affecting O2 delivery, changes in p^sub ti^O^sub 2^ are correlated to changes in CBF18,19. However, since O2 delivery, O2 consumption and therefore p^sub ti^O^sub 2^ are influenced by other local factors, such as P^sub ti^O^sub 2^, PaCO^sub 2^, temperature and metabolism13, p^sub ti^O^sub 2^-autoregulation is not to be taken as a substitute for pressure autoregulation. In addition, p^sub ti^O^sub 2^-autoregulation is different from the regulatory mechanism for local p^sub ti^O^sub 2^ during changes in PaO^sub 2^, that we have postulated earlier13. P^sub ti^O^sub 2^-autoregulation is rather used to examine whether hypoxic p^sub ti^O^sub 2^ values can be affected by an increase in CPP in a given patient at a given time.

Interpretation of p^sub ti^O^sub 2^-autoregulation

There is an ongoing discussion on which CPP should be achieved to maintain a sufficient brain oxygenation following head injury. Authors propose a CPP of 60 mmHg5,15, 70 mmHg3,20 or 80 mmHg21, whereas the 'Lund concept' even suggests a reduction in CPP22. In addition, there is a controversy whether an increase in CPP is effective14,23 or not24 to elevate p^sub ti^O^sub 2^. In our opinion, the optimal CPP depends on the current state of p^sub ti^O^sub 2^-autoregulation. Based on our data from TBI and SAH patients, we propose four different states of p^sub ti^O^sub 2^-autoregulation, which we called present, moderate, impaired and inverse p^sub ti^O^sub 2^-autoregulation. To distinguish between the different states, we determined the slope b^sub p^sub ti^O^sub 2^^ = [Delta]p^sub ti^O^sub 2^/[Delta]CPP of the linear regression between the two parameters.

During present p^sub ti^O^sub 2^-autoregulation, p^sub ti^O^sub 2^ is maintained despite changes in CPP. Therefore in this particular state of p^sub ti^O^sub 2^-autoregulation, an increase in CPP is ineffective in raising a hypoxic p^sub ti^O^sub 2^ as shown in the example of Figure IB. In contrast, in moderate or impaired p^sub ti^O^sub 2^-autoregulation, p^sub ti^O^sub 2^ can be raised by an increase in CPP. Due to the steeper linear regression slope in impaired p^sub ti^O^sub 2^-autoregulation, a lesser elevation in CPP is necessary to do so, as compared to moderate p^sub ti^O^sub 2^-autoregulation. To stress this fact, we distinguished between those two states of (nonpresent) p^sub ti^O^sub 2^-autoregulation, however it should be noted that the thresholds between the different states were arbitrarily chosen based on clinical considerations: The vast majority of our patients showed CPP variations of at least 30 mmHg during the investigated 12 h intervals and depending on the p^sub ti^O^sub 2^ variations within this 30 mmHg CPP interval, the states of p^sub ti^O^sub 2^-autoregulation were at first considered as present (b^sub p^sub ti^O^sub 2^^ or = 10 mmHg) (Table 1). To enable comparison with patients that have larger CPP variations than 30 mmHg, the linear regression slope b^sub p^sub ti^O^sub 2^^ =[Delta]p^sub ti^O^sub 2^/[Delta]CPP was finally chosen as the determining parameter, instead (Table 1).

The reason why different states of p^sub ti^O^sub 2^-autoregulation exist are not completely understood so far. Based on the concept, that p^sub ti^O^sub 2^ is determined by the balance between O2 supply and consumption and that CBF is a major determinant of tissue O2 supply, we hypothesise as follows:

In impaired pressure autoregulation, a decrease in CPP will result in a reduction of both CBF and O2 delivery. Therefore p^sub ti^O^sub 2^ will decline on condition that O2 consumption is unchanged. Depending on how close the relationship between CPP and CBF is, either the pattern of moderate or impaired p^sub ti^O^sub 2^autoregulation will develop.

The pattern of present p^sub ti^O^sub 2^-autoregulation could arise from two very different conditions: First, under circumstances of a preserved pressure autoregulation, CBF and therefore O2 supply would be unaffected by changes in CPP, resulting in unchanged, normoxic p^sub ti^O^sub 2^ values. Second, in a situation where O2 demand exceeds O2 supply, e.g. in cerebral ischemia, a rise in CPP might induce an increase in CBF and O2 delivery, however not enough to satisfy O2 demand. Again, p^sub ti^O^sub 2^ would remain unchanged, however on a hypoxic level. Since we defined the different states of p^sub ti^O^sub 2^-autoregulation based on the clinical question whether an increase in CPP is effective to raise p^sub ti^O^sub 2^, it makes sense to summarise those two conditions into the same pattern of (present) p^sub ti^O^sub 2^-autoregulation despite their different underlying pathophysiology. The absolute value of p^sub ti^O^sub 2^ itself will distinguish between those two conditions.

To our knowledge, the pattern of inverse p^sub ti^O^sub 2^autoregulation, e.g. a drop in p^sub ti^O^sub 2^ despite an increase in CPP (Figure 4A), has not been described so far. Furthermore, the higher the ICP, the higher the p^sub ti^O^sub 2^ was found (Figure 4B). We hypothesise that a regional cerebral vasodilatation occurred. This would result in an increase in ICP and in O2-supply, while CPP decreases. As a consequence, p^sub ti^O^sub 2^ would rise on condition that O2 consumption remains unchanged.

To elucidate the underlying pathophysiology of the different p^sub ti^O^sub 2^-autoreguiation patterns, further studies need to be performed, which should include CBF assessment particularly.

Advantages and limitations of the technique

Examinations of a p^sub ti^O^sub 2^/CPP relationship have already been performed before revealing a correlation between parameters12,15 or not24,25. They were based on data mixed either from the entire examination period or from different patients. However the status of p^sub ti^O^sub 2^-autoregulation changes considerably over time within the same patient and between different patients. Therefore the main advantage of our technique is that it enables individual and online information on the current state of p^sub ti^O^sub 2^-autoregulation, which can be used to decide whether and how CPP should be manipulated in case of hypoxic p^sub ti^O^sub 2^values. Furthermore, it is mainly based on spontaneous changes in CPP and requires no artificial CPPmanipulation, besides those to fulfil the EBIC guidelines. A 12-hours data collection period was chosen to allow for sufficient changes in CPP. Even when a CPP of 70 mmHg should be achieved in TBI due to this protocol, considerable drops and changes occurred caused by positioning and manipulations on the patient.

The online analysis of the p^sub ti^O^sub 2^/CPP relationship is only feasible since the p^sub ti^O^sub 2^ probe reacts quickly to changes in tissue oxygenation12 and errors due to a desynchronisation of parameters in time are therefore marginal. In addition, changes too fast were filtered out due to the 5 sec averaging of parameters.

The examples demonstrate a linear relationship between p^sub ti^O^sub 2^ and CPP without the existence of a lower or upper CPP-threshold, at least not in the investigated CPP range. Outside this range, thresholds might exist when considering the connection between pressure and p^sub ti^O^sub 2^-autoregulation. From a technical point of view, the software would reveal these thresholds, however we did not enlarge the range of CPP values to search for them: ABP was not decreased artificially to prevent the patients from ischemia. On the other hand, CPP was not raised beyond the level suggested for TBI therapy, since major rises in CPP might induce vasogenic brain edema under circumstances of a blood-brain barrier disruption22. To detect such a situation early, we plotted the ICP values versus its related ABP values using the same algorithm as for determination of p^sub ti^O^sub 2^-autoregulation. Thus, it can be identified whether an threshold in ABP exists, upon which ICP rises.

We have taken together examples of patients suffering from different entities such as TBI and SAH, since the different patterns of p^sub ti^O^sub 2^-autoregulation were found to exist in both. However the frequency of those patterns may differ in TBI and SAH, and a study has already been started regarding this issue.

Before using the p^sub ti^O^sub 2^ readings to guide therapy it must be considered that they were obtained by a focal measurement technique and are hence not representative for the entire brain. Since it is the therapeutic goal to prevent or detect tissue hypoxia, we implanted the probes into tissue considered to be at risk of secondary ischemia. To be sure about the location of the p^sub ti^O^sub 2^ catheter tip, we strongly recommend radiological imaging, e.g. computed tomography, after probe implantation.

CONCLUSION

To our knowledge, this is the first study based on an online assessment of the relationship between CPP and p^sub ti^O^sub 2^ in patients suffering from TBI or SAH. We defined this relationship as p^sub ti^O^sub 2^-autoregulation and found four different patterns named as present, moderate, impaired and inverse p^sub ti^O^sub 2^-autoregulation, depending on the linear regression slope b^sub p^sub ti^O^sub 2^^ = [Delta]p^sub ti^O^sub 2^/[Delta]CPP. Assessment of p^sub ti^O^sub 2^-autoregulation enables valuable online information whether low p^sub ti^O^sub 2^ values could be affected by an increase in CPP and about which CPP is necessary to do so. In addition, it is a powerful tool to assess temporal as well as interindividual changes of the p^sub ti^O^sub 2^/CPP relationship. It reflects the next step in the development from a CPP-orientated towards a p^sub ti^O^sub 2^-guided CPP therapy of secondary cerebral ischemia. Further studies need to be performed in order to elucidate the pathophysiology of changes in the pattern of p^sub ti^O^sub 2^autoregulation and whether those changes may be affected therapeutically.

ACKNOWLEDGEMENTS

This study was supported by the Deutsche Forschungsgemeinschaft (DFC), grant Me-1020/3-2.

REFERENCES

1 Kassel NF, Sasaki T, Colohan ART, Nazar G. Cerebral vasospasm following subarachnoid hemorrhage. Stroke 1985; 16: 562-572

2 Bouma GJ, Muizelaar JP, Choi SC, Newlon PG, Young HF. Cerebral circulation and metabolism after severe traumatic brain injury: The elusive role of ischemia. J Neurosurg 1991; 75: 685-693

3 Rosner MJ, Rosner SD, Johnson AH. Cerebral perfusion pressure: Management protocol and clinical results. J Neurosurg 1995; 83: 949-962

4 Maas AIR, Dearden M, Teasdale GM, Braakman R, Cohadon F, lannotti F, Karimi A, Lapierre F, Murray G, Ohman J, Persson L, Servadei F, Stochetti N, Unterberg A. EBIC-Guidelines for management of severe head injury in adults. Acta Neurochir (Wien) 1997; 139: 286-294

5 Cruz J, Jaggi JL, Hoffstad OJ. Cerebral blood flow, vascular resistance, and oxygen metabolism in acute brain trauma: Redifining the role of cerebral perfusion pressure? Crit Care Med 1995; 23: 1412-1417

6 Meixensberger J. Xenon 133-CBF measurements in severe head injury and subarachnoid hemorrhage. Acta Neurochir (Wien) 1993; 59 (Suppl): 28-33

7 Gopinath SP, Robertson CS, Contant CF, Hayes C, Feldman Z, Narayan RK, Grossman RG. Jugular venous desaturation and outcome after head injury. J Neurol Neurosurg Psychiatry 1994; 57: 717-723

8 Dings J, Jager A, Meixensberger J, Roosen K. Brain tissue pO^sub 2^ and outcome after severe head injury. Neurol Res 1998; 20 (Suppl 1): S71-S75

9 van den Brink WA, van Santbrink H, Steyerberg EW, Avezaat CJJ, Suazo JAC, Hogesteeger C, Jansen WJ, Kloos LMH, Vermeulen J, Maas AIR. Brain oxygen tension in severe head injury. Neumsurgery 2000; 46: 868-878

10 Valadka AB, Gopinath SP, Contant CF, Uzura M, Robertson CS. Relationship of brain tissue pO^sub 2^ to outcome after severe head injury. Crit Care Med 1998; 26: 1576-1581

11 Sheinberg M, Kanter MJ, Robertson CS, Contant CF, Narayan RK, Grossman RG. Continuous monitoring of jugular venous oxygen saturation in head injured patients. J Neurosurg 1992; 76: 212-217

12 Maas AIR, Fleckenstein W, de Jong DA, van Santbrink H. Monitoring cerebral oxygenation: Experimental studies and preliminary clinical results of continuous monitoring of cerebrospinal fluid and brain tissue oxygen tension. Acta Neurochir (Suppl.) 1993; 59: 50-57

13 Meixensberger J, Dings J, Kuhnigk H, Roosen K. Studies of tissue pO^sub 2^ in normal and pathological human brain cortex. Acta Neurochir (Suppl.) 1993; 59: 58-63

14 Meixensberger J, Jaeger M, Vath A, Dings J, Kunze E, Roosen K. Brain tissue oxygen guided therapy supplementing ICP/CPP-therapy after traumatic brain injury. J Neurol Neurosurg Psychiatry 2003; 74: 760-764

15 Kiening KL, Unterberg AW, Bardt TF, Schneider CH, Lanksch WR. Monitoring of cerebral oxygenation in patients with severe head injuries: Brain tissue pO^sub 2^ versus jugular vein oxygen saturation. J Neurosurg 1996; 85: 751-757

16 Drake CG. Report of World Federation of Neurological Surgeons Committee on a universal subarchnoid hemorrhage grading scale. J Neurosurg 1988; 68: 985-986

17 Harper AM. Autoregulation of cerebral blood flow: Influence of the arterial blood pressure on the blood flow through the cerebral cortex. J Neurol Neurosurg Psychiatry 1966; 29:398-403

18 Doppenberg EMR, Zauner A, Bullock R, Ward JD, Fatouros PP, Young HF. Correlations between brain tissue oxygen tension, carbon dioxide tension, pH, and cerebral blood flow - A better way of monitoring the severely injured brain? Surg Neurol 1998; 49: 650-654

19 Zauner A, Bullock R, Di X, Young HF. Brain oxygen, CO2, pH, and temperature monitoring: Evaluation in the feline brain. Neurosurgery 1995; 37: 11 68-1177

20 Chan KH, Miller JD, Dearden NM, Andrews PJ, Midgley S. The effect of changes in cerebral perfusion pressure upon middle cerebral artery blood flow velocity and jugular bulb venous oxygen saturation after severe brain injury. J Neurosurg 1992; 77: 55-61

21 McGraw CP. A cerebral perfusion pressure greater then 80 mmHg is more beneficial. In: Hoff JT, Betz AL, eds. lntracranial Pressure VII, Berlin: Springer-Verlag, 1989: pp. 839-841

22 Asgeirsson B, Grande PO, Nordstrom CH. A new therapy of post-trauma brain oedema based on haemodynamic principles for brain volume regulation. Intensive Care Med 1994; 20:260-267

23 Stochetti N, Chieregato A, De Marchi M, Croci M, Benti R, Grimoldi N. High cerebral perfusion pressure improves low values of local brain tissue O2 tension (P^sub ti^O^sub 2^) in focal lesions. Acta Neurochir (Suppl.) 1998; 71: 162-165

24 Sahuquillo J, Amoros S, Santos A, Poca MA, Panzardo H, Dominguez L, Pedraza S. Does an increase in cerebral perfusion pressure always mean a better oxygenated brain? A study in head-injured patients. Acta Neurochir (Suppl.) 2000; 76: 457-462

25 van Santbrink H, Maas AIR, Avezaat CJJ. Continuous monitoring of partial pressure of brain tissue oxygen in patients with severe head injury. Neurosurgery 1996; 38: 21-31

Martin Soehle, Matthias Jaeger and Jurgen Meixensberger

Department of Neurosurgery, University of Leipzig, Germany

Correspondence and reprint requests to: Prof. Dr J. Meixensberger, Department of Neurosurgery, University of Leipzig, Johannisallee 34, 04103 Leipzig, Germany, [meix@medizin.uni-leipzig.de] Accepted for publication December 2002.

Copyright Forefront Publishing Group Jun 2003
Provided by ProQuest Information and Learning Company. All rights Reserved