Optimal cerebral perfusion pressure in patients with intracerebral hemorrhage: an observational case series

Introduction

Current guidelines for spontaneous intracerebral hemorrhage (ICH) recommend maintaining cerebral perfusion pressure (CPP) between 50 and 70 mmHg, depending on the state of autoregulation. We continuously assessed dynamic cerebral autoregulation and the possibility of determination of an optimal CPP (CPPopt) in ICH patients. Associations between autoregulation, CPPopt and functional outcome were explored.

Methods

Intracranial pressure (ICP), mean arterial pressure (MAP) and CPP were continuously recorded in 55 patients, with 38 patients included in the analysis. The pressure reactivity index (PRx) was calculated as moving correlation between MAP and ICP. CPPopt was defined as the CPP associated with the lowest PRx values. CPPopt was calculated using hourly updated of 4 hour windows. The modified Rankin Scale (mRS) was assessed at 3 months and associations between PRx, CPPopt and outcomes were explored using Pearson correlation and Fisher’s exact test. Multivariate stepwise logistic regression models were calculated including standard outcome predictors along with percentage of time with PRx >0.2 and percentage of time within the CPPopt range.

Results

An overall PRx indicating impairment of pressure reactivity was found in 47% of patients (n = 18). The mean PRx and the time spent with a PRx > 0.2 significantly correlated with mRS at 3 months (r = 0.50, P = 0.002; r = 0.46, P = 0.004). CPPopt was calculable during 57% of the monitoring time. The median CPP was 78 mmHg, the median CPPopt 83 mmHg. Mortality was lowest in the group of patients with a CPP close to their CPPopt. However, for none of the CPPopt variables a significant association to outcome was found. The percentage of time with impaired autoregulation and hemorrhage volume were independent predictors for acceptable outcome (mRS 1 to 4) at three months.

Conclusions

Failure of pressure reactivity seems common following severe ICH and is associated with unfavorable outcome. Real-time assessment of CPPopt is feasible in ICH and might provide a tool for an autoregulation-oriented CPP management. A larger trial is needed to explore if a CPPopt management results in better functional outcomes.     

Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury

OBJECTIVES: To define optimal cerebral perfusion pressure (CPPOPT) in individual head-injured patients using continuous monitoring of cerebrovascular pressure reactivity. To test the hypothesis that patients with poor outcome were managed at a cerebral perfusion pressure (CPP) differing more from their CPPOPT than were patients with good outcome. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Neurosciences critical care unit of a university hospital. PATIENTS: A total of 114 head-injured patients admitted between January 1997 and August 2000 with continuous monitoring of mean arterial blood pressure (MAP) and intracranial pressure (ICP). MEASUREMENTS AND MAIN RESULTS: MAP, ICP, and CPP were continuously recorded and a pressure reactivity index (PRx) was calculated online. PRx is the moving correlation coefficient recorded over 4-min periods between averaged values (6-sec periods) of MAP and ICP representing cerebrovascular pressure reactivity. When cerebrovascular reactivity is intact, PRx has negative or zero values, otherwise PRx is positive. Outcome was assessed at 6 months using the Glasgow Outcome Scale. A total of 13,633 hrs of data were recorded. CPPOPT was defined as the CPP where PRx reaches its minimum value when plotted against CPP. Identification of CPPOPT was possible in 68 patients (60%). In 22 patients (27%), CPPOPT was not found because it presumably lay outside the studied range of CPP. Patients' outcome correlated with the difference between CPP and CPPOPT for patients who were managed on average below CPPOPT (r =.53, p <.001) and for patients whose mean CPP was above CPPOPT (r = -.40, p <.05). CONCLUSIONS: CPPOPT could be identified in a majority of patients. Patients with a mean CPP close to CPPOPT were more likely to have a favorable outcome than those whose mean CPP was more different from CPPOPT. We propose use of the criterion of minimal achievable PRx to guide future trials of CPP oriented treatment in head injured patients.     

Cerebral blood flow and metabolism in severe brain injury: the role of pressure autoregulation during cerebral perfusion pressure management

Objective: To ascertain if norepinephrine can be used as part of the cerebral perfusion pressure (CPP) management to increase arterial blood pressure (MAP) without causing cerebral hyperemia after severe head injury (HI).¶Design: Prospective, interventional study.¶Setting: Intensive care unit in a university hospital.¶Patients: Twelve severely HI patients; median Glasgow Coma Scale was 6 (range 3–8).¶Interventions: CPP management ( = 70 mmHg). Pressure autoregulation (assessed by norepinephrine infusion) was defined intact if %CPP/%CVR ≤ 2.¶Results: Cerebral blood flow (CBF: Xe¹³³ inhalation technique), jugular bulb oxygen saturation (SjO₂) and transcranial Doppler (TCD) were recorded during the test. Norepinephrine increased CPP by 33 % ( ± 4). Autoregulation was found to be intact in ten patients and defective in two. In the ten patients with preserved autoregulation, CBF decreased from 31 ± 3 to 28 ± 3 ml/100 g/min; in the two patients with impaired autoregulation CBF increased respectively from 16 to 35 and from 21 to 70 ml/100 g/min. SjO₂ did not change significantly from baseline. TCD remained within the normal range.¶Conclusions: During CPP management norepinephrine can be used to increase MAP without potentiating hyperemia if pressure autoregulation is preserved. The assessment of pressure autoregulation should be considered as a guide for arterial pressure-oriented therapy after HI.     

Impact of positive end-expiratory pressure on cerebral injury patients with hypoxemia

Background

Traumatic brain injury or intracranial hemorrhage patients with acute lung injury/acute respiratory distress syndrome need mechanical ventilation. The use of positive end-expiratory pressure (PEEP) in this situation remains controversial. This study explored the impact of PEEP on intracranial pressure (ICP), cerebral perfusion pressure (CPP), central venous pressure (CVP), and mean arterial pressure (MAP) in cerebral injury patients.

Methods

Nine cerebral injury patients with lung injury who needed mechanical ventilation and met the criteria for ICP monitoring were included in this study. Intraventricular catheters were positioned in 1 of the bilateral ventricles and connected to pressure transducers. Invasive arterial pressure and CVP were monitored continuously. Pressure control ventilation was applied during this clinical trial in a stepwise recruitment maneuver (RM) with 3 cm H₂O intermittent increments and decrements of PEEP.

Results

A total of 28 RMs were completed in 9 patients. Mean values of MAP, CVP, ICP, and CPP 5 minutes after RMs showed no significant differences compared with baseline (P > 0.05). Correlation analysis of all the mean values of MAP, CVP, ICP, and CPP showed significant correlation between MAP and CPP, PEEP and CVP, PEEP and ICP, and PEEP and CPP with all P values less than 0.05.

Conclusion

The impact of PEEP on blood pressure, ICP, and CPP varies greatly in cerebral injury patients. Mean arterial pressure and ICP monitoring is of benefit when using PEEP in cerebral injury patients with hypoxemia.     

Indices to quantify changes in intracranial and cerebral perfusion pressure by assessing agreement between hourly and semi-continuous recordings

Objectives Little published data exists on whether nurse-recorded end-hour values of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are representative of continuous monitoring during the hour. There is also no standard method of quantifying the observed perturbations in cerebral hemodynamics. This study compared the level of agreement between end-hour values and computer downloaded observations of ICP and CPP at 15-min intervals. We also developed the intracranial hypertension index and the cerebral hypoperfusion index to quantify perturbations in cerebral hemodynamics. Each of these indices relates the number of abnormal observations to the total number of observations taken.Methods Prospective, non-interventional study.Results The bias and precision between the two methods for ICP and CPP were –0.002±2.6 mmHg and –1.1±6.2 mmHg, respectively. A strong correlation existed between the hourly mean calculated from the 15-min and the end-hour values for both ICP (r²=0.95, p<0.0001) and CPP (r²=0.78, p<0.001). The intracranial hypertension index was 40% from the 15-min measurements and 41% from the hourly observations (p= NS). The cerebral hypoperfusion indices were 13.4% and 13.1% with the 15-min and end-hour values, respectively (p= NS).Conclusions The end-hour values of ICP and CPP are as accurate as more frequent measurements during the hour and are adequate for purposes of epidemiological research and medico-legal audit. The intracranial hypertension and cerebral hypoperfusion indices may be useful in describing cerebral hemodynamics for future interventional studies and for assessing quality in the delivery of neuro-critical care.     

Autoregulation in a Simulator-Based Educational Model of Intracranial Physiology

Objective.To implement a realistic autoregulation mechanism toenhance an existing educational brain model that displays in real-time thecerebral metabolic rate (CMRO₂), cerebral blood flow (CBF),cerebral blood volume (CBV), intracranial pressure (ICP), and cerebralperfusion pressure (CPP). Methods.A dynamic cerebrovascular resistance(CVR) feedback loop adjusts automatically to maintain CBF within a range ofthe CPP and defines autoregulation. The model obtains physiologic parametersfrom a full-scale patient simulator. We assumed that oxygen demand andarterial partial pressure of carbon dioxide (CO₂ responsivity) arethe two major factors involved in determining CBF. In addition, our brainmodel increases oxygen extraction up to 70% once CBF becomes insufficient tosupport CMRO₂. The model was validated against data from theliterature. Results.The model's response varied less than 9%from the literature data. Similarly, based on correlation coefficients betweenthe brain model and experimental data, a good fit was obtained for curvesdescribing the relationship between CBF and PaCO₂ at a meanarterial blood pressure of 150 mm Hg (R² = 0.92) and 100 mm Hg(R² = 0.70). Discussion.The autoregulated brain model, withincorporated CO₂ responsivity and a variable oxygen extraction,automatically produces changes in CVR, CBF, CBV, and ICP consistent withliterature reports, when run concurrently with a METI full-scale patientsimulator (Medical Education Technologies, Inc., Sarasota, Florida). Once themodel is enhanced to include herniation, vasospasm, and drug effects, itsutility will be expanded beyond demonstrating only basic neuroanesthesiaconcepts.     

The role of endothelin-1 in pressure autoregulation of cerebral blood flow in rats

Objective: To investigate the role of the endothelin system in pressure autoregulation of cerebral blood flow (CBF) in rats.¶Design: We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure–intracranial pressure) with norepinephrine (0.08 μg · kg^?1· min^?1 for 30 min) twice in ten anesthetized normocapnic rats. The first test was performed without (control test) and the second test after administration of the combined endothelin ET_A/B receptor antagonist, bosentan, i. v. (30 mg/kg; drug test). CBF was measured by the hydrogen clearance technique.¶Results: During the control test, norepinephrine infusion increased CPP by 21 ± 2 (23 ± 2 %) mmHg (mean ± SEM; p < 0.001) and CBF by 3.6 ± 3.1 (6 ± 8 %) ml/100 g/min (p = 0.5, Fig. 1); during the drug test, norepinephrine infusion increased CPP by 18 ± 1 (20 ± 2 %) mmHg (p < 0.001) and CBF by 15.8 ± 4.1 (46 ± 13 %) ml/100 g/min (p = 0.004). Mean arterial pressure was not affected by bosentan infusion (p = 0.2). PaC0₂ levels were stable during the tests (40.2 ± 1.4 mmHg).¶Conclusions: The endothelin system is involved in cerebral pressure autoregulation in a rodent model in vivo. The role of this system under pathophysiologic conditions such as subarachnoid hemorrhage, where basal vascular tone and its regulation may be altered, remains to be defined.     

Comparison of Local Measurement of Cerebral Metabolism and to Cerebral PvO2 during Alterations in Intracranial Pressure, PaCO2 and Arterial Pressure – An Experimental Study in Goat

Objective.to assess the changes in local brain PO₂, PCO₂, pH (PO₂br, PCO₂br, pHbr) measured by a intraparenchymal probe (Neurotrend^TM, Codeman) and compare them to simultaneous recording of cerebral PvO₂ and blood flow (CBF). Methods.Arterial, venous longitudinal sinus blood samples and CBF were analyzed in 8 adult anesthetized, ventilated goats. Three step increase of intracranial pressure (ICP) (16, 22, 29 mm Hg) were performed by inflation of an epidural balloon. At each ICP level, similar changes in MAP and in PaCO₂ were performed. Results.At constant PaCO₂ and MAP, balloon inflation induced a fast response: a decrease of PO₂br, PCO₂br and pHbr (starting 14 ± 12 sec, 45 ± 23 sec and 55 ± 19 sec after the peak ICP, respectively). Since the second inflation level, PO₂br decreased (p< 0.05) despite an ICP returning at 22 mm Hg and a cerebral perfusion pressure (CPP) larger than 90 mmHg. During changes in PaCO₂, PO₂br paralleled CBF and PvO₂ before the second balloon inflation but diverged at higher ICP. In the same time pH-pHbr gradient rose. Hypotension did not induce sizeable changes. Conclusions.The direct metabolic monitoring of cerebral tissue locally compressed show fast response. At steady state, it shows alterations which are not detected by the measurement of the oxygen saturation in the longitudinal sinus or that of CBF. It confirms that the threshold for ICP which may require therapy in presence of focal brain compression is around 20 mm Hg even in the presence of a CPP > 90 mm Hg.     

Cerebral autoregulation testing after aneurysmal subarachnoid hemorrhage: the phase relationship between arterial blood pressure and cerebral blood flow velocity

OBJECTIVE: Impairment of cerebral autoregulation (CA) appears to be an important cause for secondary ischemia after subarachnoid hemorrhage (SAH). It has been shown that graded CA impairment is predictive of outcome. Little is known about whether such impairment is present, what causes CA impairment, whether it precedes vasospasm, and whether it is predictive of outcome in patients with severe aneurysmal SAH. DESIGN: Prospective, controlled study. SETTING: Neurosurgical intensive care unit. PATIENTS: Twelve patients after aneurysmal subarachnoid hemorrhage, 40 controls. INTERVENTIONS: Recording of cerebral blood flow velocities and continuous measurement of arterial blood pressure at a controlled ventilatory frequency of six per minute to standardize the influence of intrathoracic pressure changes on blood pressure. MEASUREMENTS AND MAIN RESULTS: We calculated the phase shift angles (deltaphidegrees) between slow (0.1 Hz) arterial blood pressure and cerebral blood flow velocity waves measured by transcranial Doppler ultrasound in the middle cerebral artery during a) posthemorrhage days (PHD) 1-6 (early or prevasospasm phase), and b) during PHD 7-13 (late or vasospasm phase) using a 6/min ventilation protocol, and in 40 controls spontaneously ventilating at the same rate. deltaphi <30 degrees indicated lost CA. Mean flow velocities >100 cm/sec were considered vasospasm. We combined early and late measurements to assess the CA relationship with low cerebral perfusion pressure (CPP) and/or vasospasm. We assessed the Glasgow Outcome Scale (GOS) score at discharge (1 = worst, 5 = best). The admission Hunt and Hess score was 3.6 +/- 0.7. GOS scores were n = 3 (GOS 1), n = 2 (GOS 2), n = 5 (GOS 3), n = 1 (GOS 4), and n = 1 (GOS 5). In the early phase, deltaphi was 40.4 +/- 19.8 degrees (left), and 40.4 +/- 19.2 degrees (right). CPP was 69.4 +/- 10.9, intracranial pressure (ICP) was 6.7 +/- 2.8 mm Hg. In the late phase, deltaphi worsened in six patients and none improved: 32.1 +/- 21 degrees (left), and 26.9 +/- 17.2 degrees (right); CPP was 68.1 +/- 12.1, ICP was 7.5 +/- 3.7 mm Hg. CA was significantly impaired in both phases when compared with normal subjects (deltaphi: 65.7 +/- 24.5 degrees; p < .01 for early, p < .001 for late phase). In the early phase, seven of eight patients in whom autoregulation was intact had a GOS >2 at discharge and disturbed CA on at least one side was predictive of either vegetative condition at discharge or death (p < .01). In the late phase, deltaphi was no longer predictive of outcome. Spasm was present in 8 of 17 vessels (47%) in which CA was lost; no spasm was found in 25 of 28 vessels (89%) in which CA was intact (p < .01). A low CPP was present in 6 of 17 vessels (35%) in which CA was lost; a normal CPP was found in 21 of 27 vessels (78%) in which CA was intact (p > .05, NS). However, 14 of 17 vessels (82%) with lost CA showed spasm and/or low CPP while only 8 of 27 cases (30%) with intact CA had either spasm or low CPP (p < .001). CONCLUSIONS: CA can be assessed in a graded fashion in SAH patients. CA impairment precedes vasospasm; ongoing vasospasm worsens CA. CA assessment early after subarachnoid hemorrhage, within PHD 1-6, is predictive of outcome whereas late assessment is not. CA impairment is associated with cerebral vasospasm and low CPP.     

Early SjvO2 monitoring in patients with severe brain trauma

Objective: To investigate early cerebral variables after minimal resuscitation and to compare the adequacy of a cerebral perfusion pressure (CPP) guideline above 70 mmHg, with jugular bulb venous oxygen saturation (SjvO₂) monitoring in a patient with traumatic brain injury (TBI). Design: Prospective, observational study. Setting: Anesthesiological intensive care unit. Patients: 27 TBI patients with a postresuscitation Glasgow Coma Scale score less than 8. Intervention: After initial resuscitation, cerebral monitoring was performed and CPP increased to 70 mmHg by an increase in mean arterial pressure (MAP) with volume expansion and vasopressors as needed. Measurements and results: MAP, intracranial pressure (ICP), CPP, and simultaneous arterial and venous blood gases were measured at baseline and after treatment. Before treatment, 37 % of patients had an SjvO₂ below 55 %, and SjvO₂ was significantly correlated with CPP (r = 0.73, p < 0.0001). After treatment, we observed a significant increase (p < 0,0001) in CPP (78 ± 10 vs 53 ± 15 mmHg), MAP (103 ± 10 vs 79 ± 9 mmHg) and SvjO₂ (72 ± 7 vs 56 ± 12), without a significant change in ICP (25 ± 14 vs 25 ± 11 mmHg). Conclusion: The present study shows that early cerebral monitoring with SjvO₂ is critical to assess cerebral ischemic risk and that MAP monitoring alone is not sensitive enough to determine the state of oxygenation of the brain. SjvO₂ monitoring permits the early identification of patients with low CPP and high risk of cerebral ischemia. In emergency situations it can be used alone when ICP monitoring is contraindicated or not readily available. However, ICP monitoring gives complementary information necessary to adapt treatment. Received: 10 July 1998 Final revision received: 5 January 1999 Accepted: 20 January 1999     

Comparison of the cerebral effects of dopamine and norepinephrine in severely head-injured patients

OBJECTIVE: To compare the cerebral effects of dopamine and norepinephrine after severe head injury. DESIGN: Prospective, clinical study. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Nineteen patients with severe head-injuries already requiring vasopressor therapy. Group 1: patients receiving dopamine (n = 9); group 2: patients receiving norepinephrine (n = 10). INTERVENTION: Vasopressor therapy was switched from dopamine to norepinephrine in group 1 and from norepinephrine to dopamine in group 2, maintaining the same mean arterial pressure (MAP). MEASUREMENTS AND RESULTS: MAP, intracranial pressure (ICP), jugular venous oxygen saturation (SjvO2), transcranial Doppler mean velocity in the middle cerebral artery (Vm), and transoesophagal Doppler aortic output (AO) were evaluated under dopamine and norepinephrine. Means for each group were compared with the paired Student's t-test. For the same MAP, ICP was significantly higher with dopamine than norepinephrine in both groups (respectively, group 1: 26 +/- 11 vs 23 +/- 11 mmHg, P < 0.005; group 2: 39 +/- 13 vs 31 +/- 9 mmHg, P < 0.005). SjvO2, Vm, and AO did not change significantly between treatments. The ICP variation between treatments was not correlated with the variation of any other measured parameter. The ICP variation between treatments was significantly higher in group 2 than group 1, which could be explained by autoregulation mechanisms. CONCLUSIONS: For the same MAP, ICP was significantly higher with dopamine than norepinephrine with no argument supporting an increase of cerebral blood flow.     

Volatile isoflurane sedation in cerebrovascular intensive care patients using AnaConDa?: effects on cerebral oxygenation, circulation, and pressure

Purpose

The anesthetic-conserving device AnaConDa^?, a miniature vaporizer, allows volatile sedation in the intensive care unit (ICU). We investigated the effects of isoflurane sedation on cerebral and systemic physiology parameters in neuromonitored ICU stroke patients.

Methods

Included in the study were 19 consecutive ventilated patients with intracerebral hemorrhage (12), subarachnoid hemorrhage (4), and ischemic stroke (3) who were switched from intravenous propofol or midazolam to inhalative isoflurane sedation for an average of 3.5?days. During the sedation transition, the following parameters were assessed: mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), middle cerebral artery mean flow velocity (MFV) and cerebral fractional tissue oxygen extraction (FTOE), as well as systemic cardiopulmonary parameters and administered drugs.

Results

After the first hour, mean ICP showed an increase of 2.1?mmHg that was not clinically relevant. Likewise, MFV did not change. MAP and CPP, however, decreased by 6.5 and 6.3?mmHg, respectively. FTOE was reduced slightly from 0.24 to 0.21 (p?=?0.03). Over an observation period of 12?h, ICP remained stable, while MAP and thus CPP showed distinct decreases (CPP: ?10?mmHg at 6?h, p?<?0.001; ?7.5?mmHg at 12?h, p?=?0.005, when compared to preswitch levels) despite a 1.5-fold increase in vasopressor administration.

Conclusions

We suggest that that it is possible to reach sufficient sedation levels in cerebrovascular ICU patients by applying volatile isoflurane long-term without a relevant increase in ICP, if baseline ICP values are low or only moderately elevated. However, caution should be exercised in view of isoflurane’s decreasing effect on MAP and CPP. Multimodal neuromonitoring is strongly recommended when applying this off-label sedation method.     

The effects of inverse ratio ventilation on intracranial pressure: a preliminary report

Objective: To determine the effects of pressure control inverse ratio ventilation [PC-IRV], as compared with volume controlled normal ratio ventilation [VC], on the intracranial pressure [ICP] of patients with severe head injury. Design: A prospective study with unblinded intervention. Setting: The Intensive Therapy Unit of a base hospital. Patients and participants: Nine cases of head injury requiring mechanical ventilation and intracranial pressure monitoring were studied. Interventions: Patients were twice transferred from VC (I:E ratio 1:2) to PC-IRV (I:E ratio 2:1). Firstly, tidal volume was maintained at an equal value. Secondly, end tidal CO₂ was maintained at an equal value. No other changes were made to ventilation, vasopressor therapy or ICP control. Measurements and results: Measurements were taken of ICP, mean arterial pressure (MAP) end tidal CO₂ and respiratory parameters. In the first observation, there were significant changes in peak inspiratory pressure (PIP), mean airway pressure (Paw) and intrinsic positive end expiratory pressure (PEEP) but not for ICP, end tidal CO₂, MAP and cerebral perfusion pressure (CPP). The correlation between change in ICP and change in end tidal CO₂ was r=–0.74. In the second observation there were significant changes in tidal volume, PIP, Paw and intrinsic PEEP but not for ICP, MAP and CPP. The correlation between the change in ICP and the change in Paw was insignificant. Conclusions: PC-IRV has a minimal net effect on ICP. Changes in ICP correlate more strongly with changes in CO₂ than changes in Paw. Received: 16 January 1996 Accepted: 2 September 1996     

The first experience in monitoring the cerebral vascular autoregulation in the acute period of severe brain injury

The paper presents the first experience in monitoring the pressure reactivity index (Prx) of cerebral vascular autoregulation in a group of patients with severe brain injury. This autoregulation index along with the monitored parameters of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) allows the outcome to be predicted in brain injury: the outcome is poor at a Prx of > 0.2. The continuous estimation of the autoregulation index makes it possible to determine the optimum CPP value for each patient and to timely diagnose decompensation of cerebral vascular autoregulation, which is of importance in selecting treatment policy.     

The influence of urapidil,a new antihypertensive agent,on cerebral perfusion pressure in dogs with and without intracranial hypertension

The influence of urapidil, an arylpiperazinederivate, on intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) was investigated in dogs with (group II) and without (group I) intracranial hypertension. After i.v. administration of urapidil, intracranial pressure remained unchanged and cerebral perfusion pressure decreased to the same extent as mean arterial pressure (20%). As in neurosurgical patients, autoregulation of cerebral blood flow is often lost; a sudden increase in blood pressure may lead to an increase in cerebral blood flow and to a damage of the blood bain barrier with consequent cerebral edema. Urapidil seems to be suitable for treating hypertensive episodes perioperatively in neurosurgical patients.     

Age-dependent effects of gradual decreases in cerebral perfusion pressure on the neurochemical response in swine

Objective  

There is still a lack of knowledge on the age-dependent relation between a reduction in cerebral perfusion pressure (CPP) and compromised brain perfusion leading to excessive transmitter release and brain damage cascades. The hypothesis is that an age-dependent lower threshold of cerebral blood flow (CBF) autoregulation determines the amount and time course of transmitter accumulation.     

Dependency of cerebral blood flow on mean arterial pressure in patients with acute bacterial meningitis

OBJECTIVE: Patients with acute bacterial meningitis are often treated with sympathomimetics to maintain an adequate mean arterial pressure (MAP). We studied the influence of such therapy on cerebral blood flow (CBF). DESIGN: Prospective physiologic trial. SETTING: The Department of Infectious Diseases, Copenhagen University Hospital, Denmark. PATIENTS: Sixteen adult patients with acute bacterial meningitis. INTERVENTION: Infusion of norepinephrine to increase MAP. MEASUREMENTS: During a rise in MAP induced by norepinephrine infusion, we measured relative changes in CBF by transcranial Doppler ultrasonography of the middle cerebral artery, recording mean flow velocity (Vmean), and by the arterial to jugular oxygen saturation difference. In 10 out of 16 patients, serial measurements were performed until recovery or death. Individual autoregulation curves were analyzed by a computer program. Autoregulation was classified as impaired if Vmean increased by >10% per 30 mm Hg increase in MAP and if no lower limit of autoregulation was identified by the computer program; otherwise, autoregulation was classified as preserved. MAIN RESULTS: Initially, Vmean increased from a median value of 46 cm/sec (range, 30-87 cm/sec) to 63 cm/sec (33-105 cm/sec) (p < .0001), and arterial to jugular oxygen saturation difference decreased from 0.28 (0.16-0.51) to 0.21 (0.08-0.39) (p < .001) when MAP was raised from 69 mm Hg (55-102 mm Hg) to 110 mm Hg (93-129 mm Hg). CBF autoregulation was restored in eight of ten patients undergoing serial examination after 7 (range, 2-10) days. Six of these patients had an uncomplicated course, one had a protracted recovery, and one died. Autoregulation was not restored in two patients; one died and one had a protracted recovery. CONCLUSION: In patients in the early phase of acute bacterial meningitis, CBF autoregulation is impaired. With recovery from meningitis, the cerebral vasculature regains the ability to maintain cerebral perfusion at a constant level despite variations in MAP.     

不同呼气末正压水平对肺复张患者脑灌注压及血流动力学的影响

目的 观察肺复张(RM)对颅内压(ICP)、脑灌注压(CPP)及平均动脉压(MAP)的影响.方法 选择因严重颅脑疾患伴肺损伤需要进行机械通气的6例患者,在进行RM的同时进行持续ICP、MAP、中心静脉压(CVP)、脉搏血氧饱和度(SpO2)等监测.RM采用压力控制通气模式,逐步提升呼气末正压(PEEP)的方法.结果 6例患者共进行22例次RM,2例次分别在3 cm H2O(1 cm H2O=0.098 kPa)和6 cm H2O PEEP水平出现MAP、CPP显著降低而终止.其余20例次RM中不同PEEP水平相应的MAP、CVP、ICP、CPP平均值与基础值相比差异均无统计学意义(P均>0.05);MAP与CPP呈高度相关性(r=0.706,P=0.000).20例次RM中,单次RM内参数间呈高度相关性的比例:MAP与CPP占85%(17/20);PEEP与CVP占75%(15/20);PEEP与ICP占75%(15/20);PEEP与CPP占40%(8/20).22例次RM中MAP随PEEP变化有6种趋势:8例次相对稳定;6例次随PEEP增加而降低,然后随PEEP降低而逐渐回升;2例次随PEEP增加而升高,随PEEP降低逐渐回到基础值;2例次随PEEP增加而降低,PEEP降低后MAP不能相应升高;2例次随PEEP增加而增加,在PEEP降到基础值后MAP仍维持在高水平;2例次随PEEP增加MAP急剧降低而终止RM.11例次RM中ICP随PEEP升高而升高,随PEEP降低而降低;6例次在RM过程中无明显变化;3例次RM后ICP处于高值末回到基线.12例次RM中CPP随PEEP升高而降低,随PEEP降低而增加,并随PEEP回到基线时恢复到基础值;6例次无明显变化;2例次CPP维持在低值,分别在PEEP回到基线后10 min、20 min恢复到基础值.结论 RM对MAP、ICP、CPP的影响存在明显的个体差异.ICP监测有助于保障脑部疾患合并肺损伤患者RM实施的安全性.     

Assessment of dynamic cerebral autoregulation based on spontaneous fluctuations in arterial blood pressure and intracranial pressure

Assessments of dynamic cerebral autoregulation usually measure the cerebral blood flow velocity (CBFV) response to changes in arterial blood pressure (ABP). We studied the effect of substituting ABP by cerebral perfusion pressure (CPP), expressed as the difference between ABP and intracranial pressure (ICP), in estimates of dynamic autoregulation obtained by transfer function analysis. CBFV, ABP and ICP were recorded during periods of physiological stability in 30 patients with severe head injury. Transfer function analysis was performed using the following combinations of input-output variables: ABP-CBFV, CPP-CBFV and CBFV-ICP. Frequency and time-domain (step response) functions were averaged for recordings with mean ICP < 20 mmHg (group A) and mean ICP > or = 20 mmHg (group B). The ABP-CBFV transfer function parameters and step response for group A were similar to previous studies in normal subjects, but group B showed deterioration of dynamic autoregulation. Radically different step responses were obtained from both groups for the CPP-CBFV transfer function and the coherence was not significantly improved. The CBFV-ICP transfer function had the highest values of coherence and indicates that changes in CBFV are the cause of spontaneous fluctuations in ICP. Furthermore, the ICP step response plateau was significantly higher for group B than for group A. An alternative calculation of the CBFV step response to changes in CPP resembled the corresponding responses for the ABP input. For spontaneous fluctuations in ABP, ICP and CBFV, it is not possible to calculate the CPP-CBFV transfer function directly due to the high positive correlation between ICP and CBFV, but an alternative estimate can be obtained by using the CBFV-ICP transfer function. The latter could also be useful as a method to assess intracranial compliance in head injury patients.     

Loss of cerebrovascular autoregulation in experimental meningitis in rabbits.

The present study was designed to determine whether cerebrovascular autoregulation is intact in experimental meningitis and to examine the relationship between fluctuations in cerebral blood flow (CBF) and increased intracranial pressure (ICP). Measurements of CBF were determined by the radionuclide microsphere technique in rabbits with experimental Streptococcus pneumoniae meningitis with simultaneous ICP monitoring via an implanted epidural catheter. CBF and ICP measurements were determined at baseline and when mean arterial blood pressure (MABP) was artificially manipulated by either pharmacologic or mechanical means. CBF was pressure passive with MABP through a range of 30-120 torr, and ICP directly correlated with CBF. These findings indicate that autoregulation of the cerebral circulation is lost during bacterial meningitis, resulting in a critical dependency of cerebral perfusion on systemic blood pressure, and that the parallel changes in ICP and in CBF suggest that fluctuations in CBF may influence intracranial hypertension in this disease.