Martin Soehle

Continuous Monitoring of Cerebrovascular Autoregulation After Subarachnoid Hemorrhage by Brain Tissue Oxygen Pressure Reactivity and Its Relation to Delayed Cerebral Infarction

Background and Purpose— Disturbances of cerebrovascular autoregulation are thought to be involved in delayed cerebral ischemia and infarction after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that the continuous monitoring of brain tissue oxygen (PtiO2) pressure reactivity enables the detection of impaired autoregulation after SAH and that impaired autoregulation is associated with delayed infarction. Methods— In 67 patients after severe SAH, continuous monitoring of cerebral perfusion pressure (CPP) and PtiO2 was performed for an average of 7.4 days. For assessment of autoregulation, the index of PtiO2 pressure reactivity (ORx) was calculated as a moving correlation coefficient between values of CPP and PtiO2. Higher ORx values indicate disturbed autoregulation, whereas lower ORx values signify intact autoregulation. Results— Twenty patients developed delayed cerebral infarction, and 47 did not. Mean ORx was significantly higher in the infarction group compared with the noninfarction group (0.43±0.09 vs 0.23±0.14, respectively; P<0.0001). In a day-by-day analysis, ORx did not differ between groups from days 1 to 4 after SAH but was significantly higher from day 5 onward in the infarction group, indicating a deficit of autoregulatory capacity. In a logistic-regression model, ORx values from days 5 and 6 after SAH carried predictive value for the occurrence of delayed infarction but before this event ultimately occurred (P=0.003). Conclusions— ORx indicates impaired autoregulation in patients who develop delayed infarction after SAH. Furthermore, this index may distinguish between patients who finally develop delayed infarction and those who do not.

Continuous assessment of cerebrovascular autoregulation after traumatic brain injury using brain tissue oxygen pressure reactivity.

Objective:To evaluate whether two newly developed indexes of brain tissue oxygen pressure reactivity (ORx and bPtio2) provide information on the status of cerebrovascular autoregulation after traumatic brain injury. This was accomplished by analyzing the relationship between these indexes and an index of cerebrovascular pressure reactivity (PRx). PRx is an established parameter for estimation of cerebrovascular autoregulation. Design:Retrospective analysis of prospectively collected data. Setting:Neurosurgical intensive care unit of a university hospital. Patients:Twenty-seven patients suffering from severe traumatic brain injury. Interventions:Continuous monitoring of mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, and partial pressure of brain tissue oxygen (Ptio2) was performed for an average of 6.5 days. ORx was calculated as a moving correlation coefficient between values of cerebral perfusion pressure and Ptio2. The bPtio2 was calculated as a moving value of the slope of the linear regression function between cerebral perfusion pressure and Ptio2. PRx was calculated as a moving correlation coefficient between values for intracranial pressure and mean arterial blood pressure. Outcome was assessed at 6 months after traumatic brain injury (Glasgow Outcome Scale). Measurements and Main Results:Both ORx and bPtio2 correlated significantly with PRx (r = .55 for ORx, r = .52 for bPtio2, p < .01). PRx and ORx showed a significantly negative correlation to the monitored Ptio2 values (r = −.42 for PRx, r = −.41 for ORx, p < .05) and outcome (r = −.52 for PRx, r = −.62 for ORx, p < .01), whereas bPtio2 did not. Conclusions:ORx and, to a lesser extent, bPtio2 correlated with the autoregulatory marker PRx and provide additional information about the status of cerebrovascular autoregulation after traumatic brain injury. The data also suggested that patients with impaired autoregulation are at increased risk for secondary cerebral hypoxia.

Correlation of continuously monitored regional cerebral blood flow and brain tissue oxygen

SummaryBackground. The purpose of this study was to investigate the relationship between continuously monitored regional cerebral blood flow (CBF) and brain tissue oxygen (PtiO2).Methods. Continuous advanced multimodal neuromonitoring including monitoring of PtiO2 (Licox, GMS) and CBF (QFlow, Hemedex) was performed in eight patients after severe subarachnoid haemorrhage (n=5) and traumatic brain injury (n=3) for an average of 9.6 days. Parameters were measured using a flexible polarographic PtiO2-probe and a thermal diffusion CBF-microprobe.Findings. Regarding the whole monitoring period in all patients, the data indicated a significant correlation between CBF and PtiO2 (r=0.36). In 72% of 400 analysed intervals of 30 minutes duration with PtiO2 changes larger than 5 mmHg, a strong correlation between CBF and PtiO2 existed (r > 0.6). In 19% of intervals a still statistically significant correlation was observed (0.3 < r < 0.6). During the remaining 9% no correlation was found (r < 0.3). Regarding the clinical stability of the monitoring devices, the CBF monitoring system allowed monitoring of CBF in 64% of the time when PtiO2 monitoring was possible only. Phases of non-monitoring were mostly due to fever of the patient, when the system does not allow monitoring to avoid overheating of the cerebral tissue.Conclusions. This study suggests a correlation between CBF and PtiO2. The level of PtiO2 seems to be predominately determined by regional CBF, since changes in PtiO2 were correlated in 90% of episodes to simultaneous changes of CBF.

Clinical Significance of Impaired Cerebrovascular Autoregulation After Severe Aneurysmal Subarachnoid Hemorrhage

Background and Purpose— The purpose of this study was to investigate the relationship between cerebrovascular autoregulation and outcome after aneurysmal subarachnoid hemorrhage. Methods— In a prospective observational study, 80 patients after severe subarachnoid hemorrhage were continuously monitored for cerebral perfusion pressure and partial pressure of brain tissue oxygen for an average of 7.9 days (range, 1.9–14.9 days). Autoregulation was assessed using the index of brain tissue oxygen pressure reactivity (ORx), a moving correlation coefficient between cerebral perfusion pressure and partial pressure of brain tissue oxygen. High ORx indicates impaired autoregulation; low ORx signifies intact autoregulation. Outcome was determined at 6 months and dichotomized into favorable (Glasgow Outcome Scale 4–5) and unfavorable outcome (Glasgow Outcome Scale 1–3). Results— Twenty-four patients had a favorable and 56 an unfavorable outcome. In a univariate analysis, there were significant differences in autoregulation (ORx 0.19±0.10 versus 0.37±0.11, P<0.001, for favorable versus unfavorable outcome, respectively), age (44.1±11.0 years versus 54.2±12.1 years, P=0.001), occurrence of delayed cerebral infarction (8% versus 46%, P<0.001), use of coiling (25% versus 54%, P=0.02), partial pressure of brain tissue oxygen (24.9±6.6 mm Hg versus 21.8±6.3 mm Hg, P=0.048), and Fisher grade (P=0.03). In a multivariate analysis, ORx (P<0.001) and age (P=0.003) retained an independent predictive value for outcome. ORx correlated with Glasgow Outcome Scale (r=−0.70, P<0.001). Conclusions— The status of cerebrovascular autoregulation might be an important pathophysiological factor in the disease process after subarachnoid hemorrhage, because impaired autoregulation was independently associated with an unfavorable outcome.

Predictive value of initial clinical status, intracranial pressure and transcranial Doppler pulsatility after subarachnoid haemorrhage

SummaryBackground. We examined the predictive value of initial clinical status, mean arterial blood pressure (MABP), intracranial pressure (ICP) and transcranial Doppler (TCD)-derived pulsatility and resistance indices for outcome and quality of life one year following aneurysmal subarachnoid haemorrhage (SAH). Method. Neuromonitoring was performed in 29 patients following clipping or coiling of an aneurysm. Mean arterial blood pressure was measured in the radial artery and intracranial pressure was assessed via a closed external ventricular drainage. Based on transcranial Doppler-recordings of the middle cerebral artery, Gosling’s pulsatility (PI) and Pourcelot’s resistance (RI) index were calculated. Glasgow outcome score (GOS) and short form-36 (SF-36) scores were determined one year after SAH. Findings. An unfavourable outcome (GOS 1–3) was observed in 34% of patients and correlated significantly (p < 0.05) with a poor initial clinical status, as determined by Glasgow Coma Scale (r = 0.55), Hunt and Hess (r = −0.62), World Federation of Neurosurgical Societies (WFNS) (r = −0.48) and Fisher (r = −0.58) score. Poor outcome was significantly associated with high mean arterial blood pressure (r = −0.44) and intracranial pressure (r = −0.48) as well as increased pulsatility (r = −0.46) and resistance (r = −0.43) indices. Hunt and Hess grade ≥4 (OR 12.4, 5–95% CI: 1.9–82.3), mean arterial blood pressure > 95 mmHg (19.5, 2.9–132.3), Gosling’s pulsatility >0.8 (6.5, 1.6–27.1) and Pourcelot’s resistance >0.57 (15.4, 2.3–103.4) were predictive for unfavourable outcome in logistic regression, however TCD-diagnosed vasospasm was not. Except for mental health, significantly reduced scores were observed in all short form-36 domains. Initial clinical status correlated significantly with the physical functioning, role physical, bodily pain, social functioning and physical component summary of short form-36. Conclusions. Mortality and morbidity following SAH remains high, especially in poor-grade patients. Outcome is mainly correlated with initial clinical status, mean arterial blood pressure, intracranial pressure, pulsatility and resistance indices. Those factors seem to be stronger than the influence of vasospasm.

Spectral entropy and bispectral index as measures of the electroencephalographic effects of propofol

Recently, Datex-Ohmeda introduced the Entropy Module™ for measuring depth of anesthesia. Based on the Shannon entropy of the electroencephalogram, state entropy (SE) and response entropy (RE) are computed. We investigated the dose-response relationship of SE and RE during propofol anesthesia in comparison with the Bispectral Index™ (BIS). Twenty patients were studied without surgical stimulus. Anesthesia was induced by a constant propofol infusion of 2000 mg/h (451 ± 77 &mgr;g·min−1·kg−1) via a large forearm vein. Propofol was infused until substantial burst suppression occurred (more than 50%) or mean arterial blood pressure decreased to <60 mm Hg. Hereafter, infusions were stopped until recovery of BIS values up to 60 was reached. Subsequently, the constant propofol infusion of 2000 mg/h was restarted to increase depth of anesthesia and again decreased (infusion was stopped) within the BIS value range of 40–60. The coefficient of determination (R2) and the prediction probability (PK) were calculated to evaluate the performance of SE, RE, and BIS to predict changing propofol effect-site concentrations. R2 values for SE, RE, and BIS of 0.88 ± 0.08, 0.89 ± 0.07, and 0.92 ± 0.06, respectively, were similar. The calculated PK values, however, revealed a significant difference between SE and RE compared with BIS, with PK = 0.77 ± 0.09, 0.76 ± 0.10, and 0.84 ± 0.06, respectively. BIS seems to show slight advantages in predicting propofol effect-site concentrations compared with SE and RE, as measured by PK but not as measured by R2.

Improvement of brain tissue oxygen and intracranial pressure during and after surgical decompression for diffuse brain oedema and space occupying infarction

BACKGROUND We evaluated the perioperative and intraoperative changes of intracranial pressure (ICP) and partial pressure of brain tissue oxygen (PtiO2) after decompressive craniectomy in patients with diffuse brain oedema and space occupying infarction. METHODS Ten patients suffering from medically intractable raised intracranial pressure (ICP) were included. The underlying diseases and causes for elevated ICP were diffuse brain oedema after subarachnoid haemorrhage (n = 3) and head injury (n = 3), or space occupying infarction of the middle cerebral artery territory due to vasospasm after SAH (n = 4). Continuous perioperative and intraoperative monitoring of PtiO2 and ICP was performed at the side of decompression. FINDINGS ICP and PtiO2 improved significantly in a uniform pattern during bone flap removal and dura opening, irrespective of the underlying disease (mean ICP from 52 mmHg to 8 mmHg, mean PtiO2 from 9 mmHg to 25 mmHg). ICP, PtiO2, and cerebral perfusion pressure were further improved in the subsequent 12 hours after surgery, as compared to the preoperative 12 hours. CONCLUSIONS Decompressive craniectomy seems to be a successful option in the treatment of intractable intracranial hypertension with associated cerebral hypoxia. These positive effects may last for several hours after the procedure irrespective of the underlying disease.

Comparison between Bispectral Index and Patient State Index as Measures of the Electroencephalographic Effects of Sevoflurane

Background: The Bispectral Index (BIS) and the Patient State Index (PSI) quantify depth of anesthesia by analyzing the electroencephalogram. The authors examined the response of BIS and PSI to sevoflurane anesthesia. Methods: In 22 patients, sevoflurane anesthesia was induced by inhalation with a tight-fitting facemask and was maintained via a laryngeal mask. Sevoflurane concentrations were increased until burst suppression occurred and subsequently decreased until BIS recovered to values above 60. This procedure was repeated twice until patients underwent intubation for subsequent surgery. End-tidal sevoflurane concentrations, BIS, and PSI were recorded simultaneously. The performance of PSI and BIS to predict the estimated sevoflurane effect site concentration, as derived from simultaneous pharmacokinetic and pharmacodynamic modeling, was compared by determination coefficients (&rgr;2) and prediction probabilities (PK). Results: A significant (P < 0.001) correlation between BIS and PSI was found (r2 = 0.75), and a close sigmoid relation between sevoflurane effect site concentration and both BIS (&rgr;2 = 0.84 ± 0.09) and PSI (&rgr;2 = 0.85 ± 0.15) was observed. The maximum sevoflurane electroencephalographic effect resulted in PSI values (1.3 ± 4.3) that were significantly (P = 0.019) lower than BIS values (7.9 ± 12.1), and the effect site efflux constant ke0 was significantly smaller (P = 0.001) for PSI (0.13 ± 0.08 min−1) than for BIS (0.24 ± 0.15 min−1). The probability of BIS (PK = 0.80 ± 0.11) to predict sevoflurane effect site concentration did not differ (P = 0.76) from that of PSI (PK = 0.79 ± 0.09). Conclusions: The BIS reacted faster to changes in sevoflurane concentrations, whereas the PSI made better use of the predefined index range. However, despite major differences in their algorithms and minor differences in their dose–response relations, both PSI and BIS predicted depth of sevoflurane anesthesia equally well.

Continuous assessment of cerebral autoregulation: clinical and laboratory experience.

The method for the continuous assessment of cerebral autoregulation using slow waves of MCA blood flow velocity (FV) and cerebral perfusion pressure (CPP) or arterial pressure (ABP) has been introduced seven years ago. We intend to review its clinical applications in various scenarios. Moving correlation coefficient (3-6 min window), named Mx, is calculated between low-pass filtered (0.05 Hz) signals of FV and CPP or ABP (when ICP is not measured directly). Data from ventilated 243 head injuries and 15 patients after poor grade subarachnoid haemorrhage, 38 patients with Carotid Artery stenosis, 35 patients with hydrocephalus and fourteen healthy volunteers is presented. Good agreement between the leg-cuff test and Mx has been confirmed in healthy volunteers (r = 0.81). Mx also correlated significantly with the static rate of autoregulation and transient hyperaemic response test. Autoregulation was disturbed (p < 0.021) by vasospasm after SAH and worse in patients with hydrocephalus in whom CSF circulation was normal (p < 0.02). In head injury, Mx indicated disturbed autoregulation with low CPP (< 55 mmHg) and too high CPP (> 95 mmHg). Mx strongly discriminated between patients with favourable and unfavourable outcome (p < 0.00002). This method can be used in many clinical scenarios for continuous monitoring of cerebral autoregulation, predicting outcome and optimising treatment strategies.

The response of the composite variability index to a standardized noxious stimulus during propofol-remifentanil anesthesia.

BACKGROUND:Recently the Composite Variability Index (CVI) was developed to quantify nociception. This index is derived from the standard deviations (s) of the Bispectral Index (sBIS) and the electromyogram (sEMG). The primary aim of our study was to compare CVI before and after a noxious stimulus. As secondary end points, we investigated the influence of remifentanil on the CVI and tested the ability of the CVI to indicate patient movement after a noxious stimulus under changing remifentanil concentrations. Furthermore, we measured the increase in CVI after a noxious stimulus in comparison to other clinical variables (BIS, sBIS, sEMG, heart rate [HR], and systolic blood pressure [BPsys]). METHODS:Twenty-four patients without a history of cardiac disease were investigated. Anesthesia was induced with propofol administered by target-controlled infusion. A standardized noxious electrical stimulus was applied (50 Hz, 70 mA, 30 seconds) to the ulnar nerve at increasing or decreasing remifentanil effect-compartment concentrations (Ceremi). Changes in baseline and poststimulus CVI, BIS, sBIS, sEMG, HR, and BPsys were investigated. Parameters’ ability to indicate movement after a noxious stimulus was evaluated with the prediction probability (PK). RESULTS:All investigated parameters (except BPsys) increased significantly after a noxious stimulus at 0, 1, 2, or 3 ng·mL−1 Ceremi. The association between poststimulus maximal parameters and movement were PK = 0.81 for HR, PK = 0.78 for sEMG, and PK = 0.72 for CVI (pairwise difference to CVI statistically nonsignificant). The association between &Dgr;sEMG or &Dgr;CVI (poststimulus value minus baseline value) and movement was significantly higher (PK = 0.76 and 0.75, respectively) compared with &Dgr;HR (PK = 0.53) (P = 0.008 and P = 0.01, respectively). Receiver operating characteristic analysis revealed a threshold value for movement for &Dgr;CVI of >0.39 (sensitivity of 0.71, specificity of 0.74) and for &Dgr;sEMG of >0.31 (sensitivity of 0.68, specificity of 0.78). CONCLUSION:In paralyzed patients, &Dgr;sEMG and &Dgr;CVI might help identify inadequately low levels of analgesia with an acceptable sensitivity and specificity. The impact of profound neuromuscular block on the CVI should be investigated in further studies.