Monitoring of brain tissue oxygenation following severe subarachnoid hemorrhage

Monitoring of brain tissue oxygenation following severe subarachnoid hemorrhage

Meixensberger, Jurgen

The purpose of this prospective observational study was to investigate the relation between the frequency of critical neuromonitoring parameters (brain tissue pO^sub 2^, (P^sub ti^O^sub 2^) 20 mmHg, cerebral perfusion pressure (CPP) 20 mmHg (n = 25) and CPP 20 mmHg was significantly more frequent during the second last day (p

Keywords: Cerebral oxygenation; cerebral perfusion pressure; intracranial pressure; subarachnoid hemorrhage; outcome

INTRODUCTION

Secondary ischemia and vasospasm in patients suffering from subarachnoid hemorrhage (SAH) are known to worsen outcome1-4. Early detection of ischemia and guidance of the widely used hypervolemic hypertensive hemodilution therapy (HHH) are major demands in intensive care unit (ICU) treatment of these patients2,5. Therefore, monitoring of cerebral blood flow (CBF) by SPECT and transcranial Doppler (TCD) measurements6 are regularly performed to complement neurological examinations. In addition, monitoring of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral oxygenation offer the possibility of continuous bedside observation in these critically ill patients. The monitoring of jugular venous oxygen saturation7 (SJvO2) and partial pressure of brain tissue oxygen8-14 (P^sub ti^O^sub 2^) are well established in acute traumatic brain injury. In case of developing vasospasm after SAH, monitoring of regional PtjO2 in the area at risk theoretically is more sensitive to hypoxic events than monitoring of global cerebral oxygenation by SjvO^sub 2^. Therefore, in a prospective observational study, we included monitoring of PtiO2 into our ICU setup. The aim was to evaluate the value of advanced neuromonitoring, including P^sub ti^O^sub 2^, ICP, and CPP for the prediction of outcome after SAH.

PATIENTS AND METHODS

Neuromonitoring of ICP, CPP, and P^sub ti^O^sub 2^ was performed in patients suffering from aneurysmal SAH if they secondarily deteriorated to Hunt and Hess grade 4 due to neurological worsening caused by development of vasospasm or had an initial Hunt and Hess grade 4(15), according to a protocol approved by the local ethics committee. For each patient, records of age, initial Hunt and Hess grade, and the presence of initial pupillary disturbances were made. The severity of SAH was classified from initial CT scans using the Fisher Score16. The location of the aneurysm was determined by cerebral angiography. The arterial territory of CT visible hypodensities, occurring during the time course of neuromonitoring, were recorded. Outcome was classified according to the Glasgow outcome scale (GOS)17 after six months. All patients were intubated, artificially ventilated, and managed according to the same protocol. The major targets of the protocol were

1.Maintenance of P^sub a^O^sub 2^ [asymptotically =] 100 mmHg and P^sub a^CO^sub 2^ [asymptotically =] 35-40 mmHg.

2. Early surgery of the aneurysm.

3. Prevention of increased ICP > 20 mmHg and hydrocephalus by CSF drainage/decompression.

4. HHH therapy to reduce hypoxia due to vasospasm.

Ca2+ antagonists (intravenous nimodipine) were only administered if blood pressure was not affected. One of the targets in CPP adjustment was to avoid critical levels of tissue oxygenation (P^sub ti^O^sub 2^

Monitoring of P^sub ti^O^sub 2^ was performed using a Clark-type sensor (Licox, GMS, Kiel-Mielkendorf, Germany) which was inserted in the vascular territory considered to be at risk of ischemia. This was usually the vascular territory of the aneurysm carrying artery. Details of catheter implementation were already given elsewhere10,14. To rule out artificial readings of the P^sub ti^O^sub 2^ catheter, the reactivity to an increase of the inspired oxygen fraction to 1.0 was checked. CT scans were performed to rule out bleeding or a hypodensity around the catheter14. Mean arterial blood pressure (MAP) was measured in the radial artery referenced to the Foramen of Monro. Monitoring of ICP was done either by a Camino sensor (Camino Laboratories, San Diego, CA, USA) or by a ventriculostomy and CPP was calculated from MAP-ICP.

Neuromonitoring signals of MAP, ICP and P^sub ti^O^sub 2^ were digitized at a rate of 4 min^sup -1^, and data were automatically stored on a computer (Neurox/Licox system, GMS).

Further data handling and statistical analyses were performed on a computer, using self-made software (SCILAB, INRIA, Paris, Visual C++, Microsoft Corp.) and a commercial statistic package (STATISTICA, StatSoft, Inc., Tulsa, OK, USA). Artifacts, due to nursing and interruptions of the monitoring, were manually removed from individual data sets. Additionally, the first hour after insertion of the P^sub ti^O^sub 2^ catheter was eliminated, as this time is needed for equilibration14. For patients who died from herniation the P^sub ti^O^sub 2^ data was cut off as soon as it reached zero (Figure 1B).

For each patient, relative proportions of pathologic ICP (> 20 mmHg), CPP (

1. Total monitoring time.

2. Total time without last two days of monitoring.

3. Second last day of monitoring.

4. Last day of monitoring.

The decision to analyze not only the total time of monitoring, but separately the last day, the second last day, and the total time of monitoring without the last two days, was based on a preliminary data analysis. This revealed, that a simple analysis of the whole monitoring period did not sufficiently reflect the sequential changes of parameters between both groups, occurring specially towards the critical end of monitoring in the nonsurvivor group. The choice for using relative values was made as the comparison of absolute durations of critical values over the whole time period would have been biased by the fact that the average monitoring times were different between the outcome groups.

The patients were divided into a nonsurvivor group (GOS = D and a survivor group (GOS = 3-5). Patients with GOS = 2 at six months after SAH were not present in our cohort. Clinical and neuromonitoring data were expressed as median values and lower/upper quartiles or as frequency of patients per category. Differences between both outcome groups were tested using Mann-Whitney U-nest and Chi-square test. Variations of monitoring data during the different time periods were analyzed using Friedmans ANOVA test.

RESULTS

Our study included 42 patients. Clinical data are presented in Table 1. No significant differences for age and Fisher grade were found between both outcome groups. Although the relative proportion of patients initially presenting with a Hunt and Hess grade of 4 and pupillary impairment was increased in the nonsurvivor group, the differences did not reach significance. The cause of death in the nonsurvivor group was in all cases development of uncontrollable raised intracranial pressure due to brain edema and fulminant vasospasm. The average time delay between SAH and surgery of the aneurysm did not differ between both outcome groups, but two patients within the nonsurvivor group could not be operated due to their clinical condition. No difference was found for the delay between SAH and the onset of monitoring whereas the duration of monitoring was significantly shorter in the nonsurvivor group.

Due to the low number of patients for each category of aneurysm location no significant differences could be observed between both outcome groups. All basilar artery aneurysms were coiled. Regarding the distribution of CT visible hypodensities, significant differences between both outcome groups were only observed for the presence of multiple hypodensities. The elevated frequency of no CT-hypodensities in the survivor group compared to the nonsurvivor group did not reach significance level.

Data sets of unilateral P^sub ti^O^sub 2^ monitoring were available for all patients. Eleven of the 42 patients had bilateral P^sub ti^O^sub 2^ monitoring. In these cases only the data from the probe that would have been inserted in case of unilateral monitoring were used for analyses. Considering unilateral P^sub ti^O^sub 2^ monitoring, 23 of the 42 probes were inserted ipsilaterally to a cortical hypodensity as detected on follow-up CT scans, four of the probes were inserted contralaterally to the side where the hypodensity appeared and 15 of the patients had no hypodensity in the territory of the middle or anterior cerebral artery.

An example of a patient with bilateral monitoring of PtiO2 is shown in Figure 1A. Probe 1 was inserted into CT normal tissue in the frontal right hemisphere contralateral to the developing hypodensity in the territory of the middle cerebral artery (MCA). Probe 2 was inserted on the ipsilateral side close to the hypodensity. Figure 1B shows the neuromonitoring data of this patient. For none of the monitored parameters, prolonged episodes of critical values could be detected before the last day of monitoring, when brain herniation due to uncontrollable ICP occurred. However, the P^sub ti^O>^sub 2^ values of probe 2, located close to the hypodensity, are lower compared to the values of probe 1 and show an earlier decrease below the critical threshold of 10 mmHg.

Relative proportions of critical values for P^sub ti^O^sub 2^, ICP, and CPP over the total monitoring time for both outcome groups are presented in Table 2. Considering all 42 PtjO2 probes the median value for the occurrence of hypoxic values of P^sub ti^O^sub 2^ 20 mmHg occur over eight times more frequently in the nonsurvivor than in the survivor group. The corresponding ratio for critical CPP values (

The variations of relative proportions of critical monitoring parameters during the time periods (1) whole monitoring time without two last days, (2) second last day and (3) last day of monitoring are shown in Figure 2. Critical values of P^sub ti^O^sub 2^, ICP, and CPP are significantly more frequent in the nonsurvivor group during the last day of monitoring. Increased ICP values reveal the most pronounced differences and highly significant correlation to outcome for the last two days of monitoring. For CPP and P^sub ti^O^sub 2^ no significant differences between both outcome groups were observed before the last day of monitoring.

In the survivor group, the median values of relative proportions of all three monitoring parameters dropped from 2%-3% in the first time interval to almost 0% on the last day of monitoring. In the nonsurvivor group, the relative proportion of critical ICP values continuously rose from 1% to 68% during time course, while the proportions of critical CPP and P^sub ti^O^sub 2^ decreased on the second last day of monitoring and strongly increased on the last day of monitoring.

DISCUSSION

Monitoring of P^sub ti^O^sub 2^ in patients suffering from severe SAH is used in our neurointensive care management as a complementary tool besides ICP and CPP monitoring, in order to detect secondary brain hypoxia leading to cerebral infarction, events which are known to worsen the outcome of these patients1″4. The major goal of therapy is to avoid critical values of ICP, CPP, and Pt,O2. Avoidance of P^sub ti^O^sub 2^

If the total monitoring time is considered, proportions of critical values of P^sub ti^O^sub 2^, ICP, and CPP in the nonsurvivor group are significantly increased. However, a more detailed analysis of different time periods indicates that the largest and most significant differences occur on the last day of monitoring only. Clinically, at this stage cerebral infarction with massive brain swelling, brain herniation, and brain death was already present. At the second last day, only critical ICP values show significant differences between both outcome groups, whereas the proportions of critical CPP and P^sub ti^O^sub 2^ values do not differ. During the earlier monitoring periods the frequency of critical parameters did not differ between outcome groups. These findings are indicative, that P^sub ti^O^sub 2^ monitoring may not serve as an early prognostic marker after severe SAH. As previously described by Kett-White ef a/.19, P^sub ti^O^sub 2^-monitoring allows detection of cerebral infarction, but fails to predict impending symptomatic ischemia. Although in our study the lack of early prognostic significance may be partly due to the small number of patients, it may also be a consequence of the HHH therapy that was successful in avoiding critical values of CPP and P^sub ti^O^sub 2^, while not preventing patients from death. A reduction of critical P^sub ti^O^sub 2^ values during HHH therapy may be expected, as Darby et al.20 were able to show that induced hypertension successfully normalized CBF values from below the ischemic threshold.

For a further interpretation it is necessary to remember that the regional P^sub ti^O^sub 2^ reflects the balance between local oxygen delivery (CBF, P^sub ti^O^sub 2^) and tissue oxygen consumption. Several studies have shown that CBF after SAH is reduced21-25 and that the extent of CBF reduction correlates with the severity of SAH and with the degree of vasospasm26,27. Simultaneously with the CBF reduction, the oxygen consumption of cerebral tissue, expressed by the cerebral metabolic rate of oxygen (CMRO^sub 2^) is reduced after SAH24’26’27. Voldby et al.27 reported that CMRO^sub 2^ is more reduced than CBF indicating a relative luxury perfusion. In the case of a simultaneous reduction of CBF and CMRO^sub 2^ the reduction of P^sub ti^O^sub 2^ may thus be less pronounced compared to a reduction of CBF solely. In the case of luxury perfusion, even an increase of P^sub ti^O^sub 2^ may occur. This could further explain why differences in the proportion of critical P^sub ti^O^sub 2^ values are small between the investigated outcome groups.

Additionally, for interpretation of local P^sub ti^O^sub 2^ values, the positioning of the microcatheter must be taken into consideration. Further analysis (unpublished data, not shown) demonstrated a clear tendency to detect more hypoxic values, if the P^sub ti^O^sub 2^ probe is positioned close to a hypodensity in the vascular territory of interest. Therefore it is mandatory to check positioning of the probe to minimize misinterpretation of the data during time course of monitoring10.

A comparison of the prognostic value of the different neuromonitoring parameters reveal critical ICP to have the highest significance levels, as compared to hypoxic P^sub ti^O^sub 2^. Some reasons might argue for the increased prognostic significance of critical ICP values. While ICP is directly measured, CPP is calculated from two measured parameters, MAP-ICP, making it susceptible to noise coming from both contributing parameters. Furthermore, the HHH therapy might still be successful in preventing critical CPP values in case of moderately increased ICP values. A recent study28 performed on head injured patients also indicated a highly predictive value of increased ICP values, while high CPP values (> 60 mmHg) did not significantly improve outcome.

The increased significance of ICP compared to P^sub ti^O^sub 2^ monitoring may be a consequence of the points discussed above. Furthermore, ICP is a parameter which reflects rather global properties, whereas P^sub ti^O^sub 2^ depends on regional hemodynamics and metabolism.

CONCLUSION

Our results show the limited value of the investigated parameters as early predictors of outcome. Larger patient collectives are necessary to increase statistical significance of the results and also allow better separation of patient groups with respect to severity of initial injury and final outcome.

But even in the case of large patient collectives, the obtained relations between critical neuromonitoring values and outcome have to be interpreted within the scope that therapy is intended to avoid critical values. A possible improvement in outcome, that might be achieved by therapy, would only be accessible with a randomized study which is unacceptable as it would withhold monitoring to about half of the patients.

Further improvements are also necessary to optimize positioning of P^sub ti^O^sub 2^ catheters with respect to ischemic regions and to investigate the role of other parameters like regional tissue pH and concentration of metabolites as assessed by microdialysis.

ACKNOWLEDGEMENTS

This work was supported by the Vera and Volker Doppelfeld Stiftung.

REFERENCES

1 Kassel NF, Torner JC, Haley EC, Jane JA, Adams HP, Kongable GL. The internal cooperative study on timing of aneurysm surgery. Part 1: Overall management results. J Neurosurg 1990; 73: 18-36

2 Dorsch NWC, King MT. A review of cerebral vasospasm in aneurysmal subarachnoic hemorrhage. Part 1: Incidence and effects. J Clin Neurosci 1994; 1: 19-26

3 Solenski NJ, Haley EC, Kassel NF, Kongable G, Germanson T, Trukowski L, Torner JC and the participants of the multicenter cooperative aneurysm study. Medical complications of aneurysmal subarachnoid hemorrhage: A report of the multicenter, cooperatuve aneurysm study. Crit Care Med 1995; 23: 1001-1017

4 Lee JH, Martin NA, Alsina G, McArthur DL, Zaucha K, Hovda DA, Becker DP. Hemodynamically significant vasospasm and outcome after head injury: A prospective study. J Neurosurg 1997; 87: 221-233

5 Dorsch NWC. A review of cerebral vasospasm in aneurysmal subarachnoid hemorrhage. Part 2: Management. J Clin Neurosci 1994; 1: 78-92

6 Wardlaw JW, Offin R, Teasdale GM, Teasdale EM. Is routine transcranial Doppler ultrasound monitoring useful in the management of subarachnoid hemorrhage? J Neurosurg 1998; 88: 272-276

7 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

8 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 (Wien) Suppl 1993; 59: 50-57

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

10 Dings J, Meixensberger J, Roosen K. Brain tissue pO^sub 2^-monitoring catheterstability and complications. Neurol Res 1997; 19: 241-245

11 Kiening KL, Hartl R, Unterberg AW, Schneider GH, Bardt T, Lanksch WR. Brain tissue pO^sub 2^-monitoring in comatose patients: Implications for therapy. Neural Res 1997; 19: 233-240

12 Zauner A, Doppenberg E, Woodward JJ, Allen C, Jebraili S, Young HF, Bullock R. Multiparametric continuous monitoring of brain metabolism and substrate delivery in neurosurgical patients. Neural Res 1997; 19: 265-273

13 van den Brink WA, van Santbrink H, Avezaat CJ, Hogesteeger C, Jansen W, Kloos LM, Vermeulen J, Mass AJ. Monitoring brain oxygen tension in severe head injury: The Rotterdam experience. Acts Neurochir (Wien) Suppl 1998; 71: 190-194

14 Dings J, Meixensberger J, Jager A, Roosen K. Clinical experience with 118 brain oxygen partial pressure catheter probes. Neurosurgery 1998; 43: 1082-1094

15 Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968; 28: 14-20

16 Fisher CM, Kistler JP, David JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980; 6: 468-483

17 Jennett B, Bond M. Assessment of outcome after severe brain damage: A practical scale. Lancet 1975; 1: 480-484

18 Kiening KL, Unterberg AW, Bardt TF, Schneider GH, 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

19 Kelt-White R, Hutchinson PJ, Al-Rawi PG, Gupta AK, Pickard JD, Kirkpatrick PJ. Adverse cerebral events detected after subarachnoid hemorrhage using brain oxygen and microdialysis probes. Neurosurgery 2002; 50: 1213-1222

20 Darby JM, Yonas H, Marks EC, Durham S, Snyder RW, Nemoto EM. Acute cerebral blood flow response to dopamine-induced hypertension after subarachnoid hemorrhage. J Neurosurg 1994; 80: 857-864

21 Glemers Hj, Beks JWF, journee HL. Regional cerebral blood flow in patients with subarachnoid hemorrhage. Acta Neurochir 1979; 47: 245-251

22 Ishii R. Regional cerebral blood flow in patients with ruptured intracranial aneurysms. J Neurosurg 1979; 50: 587-594

23 Meyer CHA, Lowe D, Meyer M, Richardson PL, Neil-Dwyer G. Progressive changes in cerebral blood flow during the first three weeks after subarachnoid hemorrhage. Neurosurgery 1983; 12: 58-76

24 Jakobson M, Skjodt T, Enevoldsen E. Cerebral blood flow and metabolism following subarachnoid hemorrhage: Effect of subarachnoid blood. Acta Neurol Scand 1991; 83: 226-233

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

26 Grubb RL, Raichle ME, Eichung JO, Gado MH. Effects of subarachnoid hemorrhage on cerebral blood volume, blood flow and oxygen utilization in humans. J Neurosurg 1977; 46: 446-453

27 Voldby B, Enevoldsen EM, Jensen FT. Regional CBF, intraventricular pressure and cerebral metabolism in patients with ruptured intracranial aneurysms. J Neurosurg 1985; 62: 48-58

28 Juul N, Morris GF, Marshall SB, Marshall LF. Intracranial hypertension and cerebral perfusion pressure: Influence on neurological deterioration and outcome in severe head injury. J Neurosurg 2000; 92: 1-6

Jurgen Meixensberger*, Albert Vath[dagger], Matthias Jaeger*, Ekkehard Kunze[dagger], Jim Dings[double dagger] and Klaus Roosen[dagger]

*Department of Neurosurgery, University of Leipzig, Leipzig

[dagger]Department of Neumsurgery, University of Wurzburg, Wurzburg, Germany

[double dagger] Department of Neurosurgery, Academisch Ziekenhuis Maastricht, The Netherlands

Correspondence and reprint requests to: Prof. Dr Jurgen Meixensberger, Department of Neurosurgery, University of Leipzig, Johannisallee 34, D-04103 Leipzig, Germany.

[meix@medizin.uni-leipzig.de] Accepted for publication March 2003.

Copyright Forefront Publishing Group Jul 2003

Provided by ProQuest Information and Learning Company. All rights Reserved