Decrease In Cerebral Perfusion Pressure Research Articles

Elevation of extracellular glutamate in the final, ischemic stage of progressive epidural mass lesion in cats.

Epidural mass lesions may cause ischemia due to progressive intracranial hypertension. In order to investigate the impact of intracranial pressure on accumulation of neuroactive substances, we gradually raised intracranial pressure in five halothane anesthetized cats by inflation of an epidural balloon. We evaluated in the parietal cortex contralateral to the site of balloon inflation, alterations of extracellular glutamate and purine catabolites and of the lactate/pyruvate ratio in relation to changes of intracranial, cerebral perfusion and mean arterial blood pressure. In a complementary experiment, regional cerebral blood flow was assessed by sequential positron emission tomography. In this simplified mass lesion model, extracellular glutamate increased in all cats at a late, critical stage after tentorial herniation, when intracranial pressure had increased to more than 90 mm Hg, cerebral perfusion pressure had decreased below 40-50 mm Hg. Positron emission tomography assessments revealed that the ischemic threshold for glutamate accumulation was in the range of 15-20 mL/100 g/min. Purine catabolites and the lactate/pyruvate ratio increased somewhat earlier than glutamate, but also after reaching the critical, terminal stage. We conclude that in this model of progressive epidural compression, glutamate-mediated excitotoxic processes at sites remote from the initial focal lesion depend on processes such as delayed ischemia in combination with tentorial herniation and systemic hypotension. These processes seem to be initiated by a decrease of cerebral perfusion pressure below a threshold of 40-50 mm Hg.

Management of cerebral perfusion pressure after traumatic brain injury.

IN 1996, the Brain Trauma Foundation sponsored the development of guidelines for the management of severe traumatic brain injury (TBI). The method used for development of the guidelines was evidence based, and probably the most significant contribution of the guidelines has been to highlight the remarkable lack of class I evidence available for many current management practices. Recently, revisions to the guidelines were published, and little has been changed in the recommendations. 1 From all of the aspects of management that were reviewed for the guidelines, the authors were only able to provide three standards based on class I evidence (randomized clinical trials) and only eight guidelines based on class II evidence (table 1). Furthermore, the randomized clinical trials that have supported the three guideline standards showed ineffectiveness of certain long-standing management practices (prophylactic hyperventilation, steroid administration, prophylactic anticonvulsants) rather than showing that any practices are

Impact of the renin-angiotensin system on cerebral perfusion following subarachnoid haemorrhage in the rat.

1. This study investigated the effects of blocking the AT1 angiotensin receptors with irbesartan, either peripherally or centrally, on systemic blood pressure, intracranial pressure and cerebral perfusion pressure following experimental subarachnoid haemorrhage (SAH) in urethane-anaesthetized rats. Sympathetic nervous activation was determined by measuring plasma noradrenaline levels. 2. In untreated animals, SAH induced a sustained increased in intracranial pressure from 2.1 +/- 0.3 to 16 +/- 2 mmHg (3 h, P < 0.001). Cerebral perfusion pressure was reduced by 20 % (P < 0.001), this reduction being maintained for 3 h. Sympathetic activation was evident in the high level of plasma noradrenaline measured 3 h post-SAH (751 +/- 104 vs. 405 +/- 33 pg ml(-1), P < 0.05). 3. Acute peripheral pretreatment with irbesartan (3 mg kg(-1), I.V.) prevented the rise in plasma noradrenaline and further aggravated the decrease in cerebral perfusion pressure by producing transient systemic hypotension (blood pressure was 85 +/- 6 mmHg at 2 h post-SAH vs. 100 +/- 3 mmHg, P < 0.01). 4. Intracisternal pretreatment with irbesartan (0.035 mg) did not prevent the rise in plasma noradrenaline post-SAH but enhanced the rise in intracranial pressure by 75 % compared with untreated animals. 5. This study demonstrates that peripheral endogenous angiotensin II interacts with the sympathetic nervous system in order to maintain an adequate cerebral perfusion following SAH. Endogenous angiotensin II in the brain seems to exert a protective effect by counteracting the elevation in intracranial pressure that occurs following experimental SAH.

Brain energy metabolism during controlled reduction of cerebral perfusion pressure in severe head injuries.

To study cerebral biochemical markers with intracerebral microdialysis and bedside analysis in patients with severe head injuries treated with a controlled reduction of cerebral perfusion pressure (CPP). Prospective observational study. Neurological intensive care unit in a university hospital. A consecutive series of 48 patients with severe head injuries and intracranial pressure (ICP) above 20 mmHg after conventional treatment. Reduction of CPP was attained with i. v. infusion of beta1-antagonist (metoprolol) and an alpha2-agonist (clonidine). One microdialysis catheter was inserted via a burr hole frontally to that used for the intraventricular catheter ("better" position). In 27 patients one or more catheters were inserted into cerebral cortex surrounding an evacuated focal contusion or underlying an evacuated haematoma ("worse" position). Perfusion rate was 0.3 microl/min and samples were taken every 30 or 60 min. The levels of glucose, pyruvate, lactate, glycerol and glutamate were analysed and displayed bedside. After initiation of treatment mean CPP decreased from 73 to 62 mmHg. During the first 96 h CPP was less than 60 mmHg and less than 50 mmHg during 30% and 8% of the time, respectively. The treatment was associated with a gradual normalisation of all biochemical markers in the "better" as well as the "worse" catheter position. The study shows that pharmacological decrease in CPP according to the "Lund concept" is associated with a normalisation of cerebral metabolism. The study also indicates that intracerebral microdialysis can be used for evaluation of new treatment strategies.

Hemodynamic characterization of intracranial pressure plateau waves in head-injury patients.

Plateau waves of intracranial pressure (ICP) are often recorded during intensive care monitoring of severely head injured patients. They are traditionally interpreted as meaningful secondary brain insults because of the dramatic decrease in cerebral perfusion pressure (CPP). The aim of this study was to investigate both the hemodynamic profile and the clinical consequences of plateau waves. One hundred sixty head-injured patients were studied using continuous monitoring of ICP; almost 20% of these patients exhibited plateau waves. In 96 patients arterial pressure, ICP, and transcranial Doppler (TCD) blood flow velocity were studied daily for 20 minutes to 3 hours. Sixteen episodes of plateau waves in eight patients were recorded and analyzed. The dramatic increase in ICP was followed by a profound fall in CPP (by 45%). In contrast, flow velocity fell by only 20%. Autoregulation was documented to be intact both before and after plateau but was disturbed during the wave (p < 0.05). Pressure-volume compensatory reserve was always depleted before the wave. Cerebrovascular resistance decreased during the wave by 60% (p < 0.05) and TCD pulsatility increased (p < 0.05). Plateau waves did not increase the probability of an unfavorable outcome following injury. The authors have confirmed that the plateau waves are a hemodynamic phenomenon associated with cerebrovascular vasodilation. They are observed in patients with preserved cerebral autoregulation but reduced pressure-volume compensatory reserve.

A Piglet Model for Evaluation of Cerebral Blood Flow and Brain Oxidative Metabolism during Gradual Cerebral Perfusion Pressure Decrease

A piglet model was developed to study the effect of epidural volume expansion on cerebral perfusion pressure (CPP) by stepwise elevating intracranial pressure (ICP). Mean arterial blood pressure (ABP) was strictly maintained using an extracorporeal ABP controller. Two-week-old piglets (n = 10) were studied by surgically placing an epidural balloon over the right parietal region and gradually increasing the inflation to increase ICP to 25, 35 and 45 mm Hg, maintaining each pressure level for 30 min. Regional cerebral blood flow was measured using the colored microsphere technique, and cerebral oxygen delivery and cerebral metabolic rate of oxygen were calculated at baseline conditions and after reaching ICP levels of 25, 35 and 45 mm Hg. The results showed that this model of epidural volume expansion reproducibly reduces CPP to 70, 50 and 33% of baseline CPP values with elevation of ICP, and that the physiological variables remained stable throughout each increase in ICP. We conclude that the model simulates the effects of an acute intracranial focal mass expansion and is well suited for the evaluation of different therapeutical strategies for increased ICP in newborns and infants.

Cerebrovascular effects of high intracranial pressure after moderate hemorrhage.

Patients with head injuries often develop increased intracranial pressure after hemorrhage. The authors studied the effect of moderate hemorrhage followed by elevated intracranial pressure on cerebrovascular variables. Cerebral blood flow in 13 pigs was measured with laser Doppler flowmetry, and cerebral venous blood gases were taken from the sagittal sinus. High intracranial pressure (80% of mean arterial pressure) was induced by infusion of artificial cerebrospinal fluid into the cisterna magna, and blood pressure was reduced by bleeding to a mean of 78% of the prebleeding values in eight pigs. Five pigs served as secondary controls. High intracranial pressure before hemorrhage caused a decrease in cerebral blood flow to 34% of the baseline values, a decrease in sagittal sinus oxygen saturation to 46%, and a decrease in cerebral perfusion pressure to 36%, but did not change cerebrovascular resistance. High intracranial pressure after hemorrhage decreased cerebral blood flow to 14% of baseline values. Sagittal sinus oxygen saturation decreased to 22%, cerebral perfusion pressure decreased to 30%, and the cerebrovascular resistance increased by 355%. The moderate hypotension after hemorrhage caused a considerable enhancement of the effects of high intracranial pressure on cerebral hemodynamics.

Does Spinal Anesthesia Affect Cerebral Oxygenation During Transurethral Prostatectomy?

Background and ObjectivesTransurethral resection of the prostate (TURP) is associated with the unique complication of transurethral resection of prostate syndrome (TURS), which is attributed to the absorption of irrigating fluid. This study was initiated to investigate the effects of spinal anesthesia and TURP on cerebral oxygen balance.MethodsThirty patients scheduled for TURP were included. Jugular bulb oxygen saturation (SjbO2) was measured via retrograde cannulation of jugular venous bulb. Spinal anesthesia was initiated by 3 mL hyperbaric 0.5% bupivacaine injected at L3-L4 in the sitting position, producing a block to the T10 dermatome. Hemodynamic measurements and arterial and jugular bulb blood gasometry were performed before and after spinal anesthesia, throughout surgery, and during the postoperative period.ResultsA significant decrease of cerebral perfusion pressure after spinal anesthesia was accompanied by a significant decrease of SjbO2 below a preoperative value of 61% ± 1. Eight patients developed yawning, irritability, restlessness, and nausea toward the end of surgery, and these were considered to be early signs of TURS. These patients demonstrated SjbO2 below 55% and 50% in 63% and 42% of respective data set points.ConclusionThe neurologic symptoms in patients undergoing TURP during spinal anesthesia might not only be caused by absorption of irrigating fluid but also by impairment of cerebral oxygenation.

Does spinal anesthesia affect cerebral oxygenation during transurethral prostatectomy?

Transurethral resection of the prostate (TURP) is associated with the unique complication of transurethral resection of prostate syndrome (TURS), which is attributed to the absorption of irrigating fluid. This study was initiated to investigate the effects of spinal anesthesia and TURP on cerebral oxygen balance. Thirty patients scheduled for TURP were included. Jugular bulb oxygen saturation (SjbO2) was measured via retrograde cannulation of jugular venous bulb. Spinal anesthesia was initiated by 3 mL hyperbaric 0.5% bupivacaine injected at L3-L4 in the sitting position, producing a block to the T10 dermatome. Hemodynamic measurements and arterial and jugular bulb blood gasometry were performed before and after spinal anesthesia, throughout surgery, and during the postoperative period. A significant decrease of cerebral perfusion pressure after spinal anesthesia was accompanied by a significant decrease of SjbO2 below a preoperative value of 61% +/- 1. Eight patients developed yawning, irritability, restlessness, and nausea toward the end of surgery, and these were considered to be early signs of TURS. These patients demonstrated SjbO2 below 55% and 50% in 63% and 42% of respective data set points. The neurologic symptoms in patients undergoing TURP during spinal anesthesia might not only be caused by absorption of irrigating fluid but also by impairment of cerebral oxygenation.

Can cerebrovascular reactivity be assessed by dynamic susceptibility contrast-enhanced MRI?

The acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure (CPP) by investigation of vasomotor reactivity (VMR). Our aim was to study cerebral blood flow and blood volume changes induced by the ACZ test in healthy control subjects using dynamic susceptibility contrast-enhanced gradient-echo MRI (DSC-MRI). A FLASH sequence was used to produce susceptibility-weighted images during an intravenous injection of 0.1 mmol/kg gadopentetate dimeglumine (Gd-DTPA). After the first dynamic study, 1 g acetazolamide was given intravenously and 10 min later a second bolus of Gd-DTPA was injected. Using the indicator-dilution theory, relative cerebral blood volume and relative cerebral blood flow were estimated. In healthy subjects the ACZ test induced a significant increase in relative blood volume (from 80.5 +/- 10.7 to 113.4 +/- 11.9) and relative blood flow (from 5.73 +/- 0.96 to 7.5 +/- 0.97), symmetrically in the cerebral hemispheres. This approach might be promising in the understanding of cerebral haemodynamics in patients with vascular disorders.

Traumatic brain injury in the developing rat pup: studies of ICP, PVI and neurological response.

Diffuse brain swelling is a common complication in young victims of a seven head injury but, there is a lack of data on relevant models of injury. We produced diffuse brain injury in 21 day old Lewis rat pups (N = 33) by modifying a recently established weight-drop-model. The trauma threshold, neurological response, histological changes, intracranial pressure (ICP), and arterial blood pressure (ABP) were determined. In addition, the pressure-volume-index (PVI) was measured 15 min before, 2 min, and 1 h after brain injury. In the 1 m/100 g group 4 of 5 rats died, whereas in the 0.5 m/100 g only 4 of 28 died. The PVI increased at 2 min after traumatic brain injury (TBI) but ICP was unchanged, except for a minor increase immediately after injury. Histological studies revealed diffuse neuronal death, predominantly involving the cortex and hippocampus. The results of the present study indicate that determination of ICP in the developing rat pup during and after diffuse brain injury is possible. A 0.5 m/100 g weight-drop-trauma results in a morphologically severe injury but with low mortality. The increase in PVI can be attributed to a decrease of cerebral perfusion pressure (CPP) after injury. However, the absence of a further increase of ICP after injury in the developing rat indicates that this may not be a primary consequence of injury in paediatric patients.

Low brain tissue oxygen pressure: Incidence and corrective therapies

In 16 head injured patients, the monitoring ofbrain tissue oxygen pressure (ti-pO2) show 22 episodes oflow ti-pO2 (≤12 mmHg). Mean episode duration was 16 h. At time of the lowest ti-pO2 value, cerebral perfusion pressure (CPP), was<60 mmHg in 5 cases, 4 of them with impending brain death. Oxygen saturation values of the jugular venous blood (SVjO2) remained in the normal range (55-85 mmHg) in 12 cases and exceeded 85 mmHg in 3 cases, 2 of them with impending brain death. Lactate-oxygen index (LOI) was normal (<0.08) in 7/10 cases and at very high level ( > 0.60) in 3 cases in.cluding 2 cases of impending brain death. A first group of low ti-pO2 episodes was clearly related to an insufficient CPP level (n = 13), comprising 4 cases of parallel decrease in CPP and ti-pO2 until brain death, and 9 cases in which ti-pO2 was restored along with a significant increase in CPP (p<0.001). In 5 patients, low ti-pO2 episodes were due to another cause: vasospasm (2 cases), hypoxemia, anemia and premature interruption of anesthesia. Appropriate treatments were effective in restoring ti-pO2 with no change in CPP. In 4 patients, the cause of low ti-pO2 was not identifiable and episodes resolved spontaneously. The results confirm the critical influence ofCPP and ti-pO2 Patients in whom elevation of CPP improved ti-pO2 have normal range cpp during the episode. Optimal CPP should therefore be sometimes higher than recommended. ti-pO2 monitoring appears a good method to define the optimal CPP level in individual patient. The duration of the artefactual period after catheter placement is to clarify. [Neural Res 1998; 20 (Suppl 1): 548-551]

Contribution of mathematical modelling to the interpretation of bedside tests of cerebrovascular autoregulation

OBJECTIVESCerebral haemodynamic responses to short and longlasting episodes of decreased cerebral perfusion pressure contain information about the state of autoregulation of cerebral blood flow. Mathematical simulation may help to elucidate...

Assessment of cerebrovascular reactivity by dynamic susceptibility contrast-enhanced MR imaging

In patients with cerebrovascular disease the acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure (CPP) through the investigation of the vasomotor reactivity (VMR). This latter is currently assessed with ACZ with several methods. Recently, magnetic resonance imaging (MRI) techniques have been developed that are sensitive to stimulus-induced changes in blood flow. Dynamic susceptibility contrast material-enhanced gradient-echo MRI techniques (DSC-MRI) might be an attractive tool to assess VMR. We aimed to test the ability of DSC-MRI in the assessment of VMR. Relative hemodynamic parameters rCBV, MTT, and rCBF were evaluated at baseline after the first injection of gadopentetate dimeglumine and 10 min after the intravenous administration of ACZ (1 g) with a second bolus of contrast agent. Assessment of hemodynamic parameters was performed over the whole hemisphere and also within regions of interest. The significances of the mean differences, before and after ACZ, were assessed with repeated-measures ANOVA with two within factors: laterality (right–left) and ACZ. DSC-MRI with ACZ test was performed in ten healthy controls (aged 51.4±16.2 years). The cerebral hemispheric ratio for the three parameters (cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF)) ranged between 1.01 and 1.03. The mean gray matter-to-white matter ratio for CBV, CBF and MTT were 2.44, 2.41 and 1.05, respectively. As the laterality effect was not significant, left and right hemispheric values were averaged. A significant increase of all hemodynamic parameters was observed after ACZ ( P<0.01–0.001). The same changes for CBV, CBF and MTT were observed after ACZ according to the regions of interest ( P<0.006–0.015). DSC-MRI is a non-invasive method which enables the assessment of VMR. This technique may be added to any conventional MRI in order to detect a hemodynamic impact of an ICA stenosis. Therefore, it might be useful in determining the appropriate management when the indication for surgical versus medical therapy is in question.

MR imaging of experimental subdural bleeding. Correlates of brain deformation and tissue water content, and changes in vital physiological parameters.

To evaluate morphological and physiological changes during acute lethal subdural bleeding in 2 models of anaesthetized dogs. In model I, blood from the aorta was led into a collapsed subdural rubber balloon while in model II, the blood was directed into the subdural compartment over the left cerebral frontoparietal lobe. Eight vital physiological parameters were continuously registered. MR imaging visualized the compression and displacement of cerebral tissue, and assessed the dynamic changes in cerebral tissue water. In model I, tissue herniation and compression of cerebral ventricles led to death at a haematoma volume corresponding to 8% of the intracranial volume. In model II, the extravasated blood progressed infratentorially and into the spinal sac with a volume that was 3 times larger than that of the lethal haematoma. Tissue water increased almost linearly during bleeding in both models. The high level of mortality after acute subdural haematoma is caused by a reduction in intracranial volume tolerance with a critical decrease in cerebral perfusion pressure, resulting in a fatal cerebral ischaemia.

A proposed relationship between increased intra-abdominal, intrathoracic, and intracranial pressure.

To determine the effect of acutely increased intra-abdominal pressure on pleural pressure, intracranial pressure, and cerebral perfusion pressure, and to clarify the relationship between these parameters. Nonrandomized, controlled study. Laboratory at a university medical center. Yorkshire swine, weighing 15 to 20 kg. Anesthetized, ventilated swine had a balloon inserted into the peritoneal cavity and catheters placed for measurement of intracranial pressure, pleural pressure, central venous pressure, pulmonary artery occlusion pressure, and mean arterial pressure. Following baseline measurements, intra-abdominal pressure was increased by incrementally inflating the intraperitoneal balloon. All parameters were remeasured 30 mins after each increase in intra-abdominal pressure. Two groups were studied: a) group 1 (n = 9) animals had intra-abdominal pressure increased to 25 mm Hg above baseline, then released; b) group 2 (n = 3) animals underwent sternotomy and pleuropericardotomy to prevent an increase in pleural pressure with increasing intra-abdominal pressure. Increase of intra-abdominal pressure to 25 mm Hg above baseline caused significant (p < .05) increases in intracranial pressure (7.3 +/- 0.6 [SEM] to 16.4 +/- 1.9 mm Hg), pleural pressure (4.3 +/- 1.3 to 11.8 +/- 1.9 mm Hg), pulmonary artery occlusion pressure (9.0 +/- 0.6 to 14.3 +/- 0.8 mm Hg), and central venous pressure (6.6 +/- 0.7 to 10.7 +/- 0.9 mm Hg). The cardiac index (3.4 +/- 0.3 to 1.6 +/- 0.1 L/min/m2) and cerebral perfusion pressure (75.6 +/- 3.6 to 62.0 +/- 6.8 mm Hg) deceased significantly (p < .05), whereas mean arterial pressure (82.8 +/- 3.2 to 78.4 +/- 6.6 mm Hg) remained essentially constant. Sternotomy and pleuro-pericardotomy negated all effects of increased intra-abdominal pressure except the decreased cardiac index (1.6 +/- 0.1 to 2.5 +/- 0.2 L/min/m2). Acutely increased intra-abdominal pressure causes a significant increase in intracranial pressure and a decrease in cerebral perfusion pressure. Increased intra-abdominal pressure appears to produce this effect by augmenting pleural and other intrathoracic pressures and causing a functional obstruction to cerebral venous outflow via the jugular venous system. It is possible that the same phenomenon may be why persons with chronically increased intra-abdominal pressure, such as the morbidly obese, suffer from a high frequency rate of idiopathic intracranial hypertension.

Management of intracranial hemodynamics in the adult: a research analysis of head positioning and recommendations for clinical practice and future research.

Head elevation is a conventional nursing intervention used to control raised intracranial pressure and avoid complications in patients with neurotrauma or other conditions requiring management of intracranial hemodynamics. This therapy, however, provides a particular dilemma for health care providers. While elevating the head of the bed does decrease intracranial pressure, it may put some patients at risk for intracranial hypertension and cerebral ischemia due to decreases in cerebral perfusion pressure. This article analyzes research on head positioning that provides individual outcome measurements versus group means in adult patients with various conditions. The risk/benefit method of analysis used in this review revealed that in addition to only monitoring and controlling for ICP, we must also monitor and control CPP with a greater emphasis on this particular measurement. This analysis also revealed that optimal head positioning to manage intracranial hemodynamics should be decided upon on an individual basis using both ICP and CPP measurements.

Course of Vasomotor Reactivity Using Dynamic Susceptibility Contrast-Enhanced MRI in a Patient with High-Grade Internal Carotid Artery Stenosis: Pre-and Post-Surgical Findings

In patients with cerebrovascular disease the acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure through the investigation of the vasomotor reactivity (VMR). The latter is currently assessed with ACZ using several methods. Dynamic susceptibility contrast-enhanced gradient echo MRI techniques (DSC-MRI) might be an attractive tool to assess VMR. We described the course of VMR in a patient with high-grade internal carotid artery stenosis before and after surgery using DSC-MRI.

Treatment of acute intracranial hypertension with RU 51599, a selective kappa opioid agonist.

RU 51599, a selective kappa opioid agonist which is a potent aquaretic, was studied for its effect on acute intracranial hypertension. In ketamine anesthetized cats acute intracranial hypertension was induced by progressive inflation of an epidural balloon with physiological saline at a constant rate of 0.5 ml/hr for three hours. In the control group (n = 8), the balloon was maintained inflated for another an hour after which it was deflated. In the post deflation period monitoring was continued for one hour. In the treatment group (n = 8), cats were treated by an intravenous (i.v.) injection of RU 51599, at a dose of 1 mg/kg every hour at the beginning of balloon inflation, during balloon inflation, at the completion of inflation, and after deflation. Changes in intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), blood gases, serum electrolytes and osmolality, and brain water content water content were studied in both groups. In the control group, epidural brain compression resulted in significant increases in the mean ICP up to 80.7 +/- 9.8 mmHg at 3 hrs (during balloon inflation), 68.6 +/- 8.3 after complete inflation, and 62.1 +/- 11.4 mmHg after deflation (P < 0.01), and significant decreases in CPP to 55.5 +/- 14.0 mmHg at 3 hrs (during balloon inflation), 43.0 +/- 11.2 mmHg after inflation, and 36.3 +/- 9.9 mmHg after deflation (P < 0.01). In the treatment group there were significant decreases in the mean ICP to 35.2 +/- 6.8 mmHg at 3 hrs (during balloon inflation), 32.3 +/- 7.9 after inflation, and 16.1 +/- 3.6 mmHg after deflation (P < 0.01), and significant increases in CPP to 103.2 +/- 6.1 mmHg at 3 hrs (during balloon inflation), 109.0 +/- 8.8 mmHg after inflation, and 102.7 +/- 8.2 mmHg after deflation (P < 0.01). Brain water content was also significantly reduced (P < 0.05). There were no significant changes in the serum electrolytes and osmolality throughout the experiments. Our results suggest that, the mechanism by which RU 51599 reduces ICP is related to reduction in the brain water content.

Monitoring of cerebral oxygenation in patients with severe head injuries: brain tissue PO2 versus jugular vein oxygen saturation.

Monitoring of cerebral oxygenation is considered to be of great importance in minimizing secondary hypoxic and ischemic brain damage following severe head injury. Although the threshold for cerebral hypoxia in jugular bulb oximetry (measurement of O2 saturation in the jugular vein (SjvO2)) is generally accepted to be 50% oxygen saturation, a comparable value in brain tissue PO2 (PtiO2) monitoring, a new method for direct assessment of PO2 in the cerebral white matter, has not yet been established. Hence, the purpose of this study was to compare brain PtiO2 with SjvO2 in severely head injured patients during phases of reduced cerebral perfusion pressure (CPP) to define a threshold in brain PtiO2 monitoring. In addition, the safety and data quality of both SjvO2 and brain PtiO2 monitoring were studied. In 15 patients with severe head injuries, SjvO2 and brain PtiO2 were monitored simultaneously. For brain PtiO2 monitoring a polarographic microcatheter was inserted in the frontal cerebral white matter, whereas for SjvO2 measurements were obtained by using a fiberoptic catheter placed in the jugular bulb. Intracranial pressure was monitored by means of an intraparenchymal catheter. Mean arterial blood pressure, CPP, end-tidal CO2, and arterial oxygen saturation (pulse oximetry) were continuously recorded. All data were simultaneously stored and analyzed using a multimodal computer system. For specific analysis, phases of marked deterioration in systemic blood pressure and consecutive reductions in CPP were investigated. There were no complications that could be attributed to the PtiO2 catheters, that is, no intracranial bleeding or infection. The "time of good data quality" was 95% in brain PtiO2 compared to 43% in SjvO2; PtiO2 monitoring could be performed twice as long as SjvO2 monitoring. During marked decreases in CPP, SjvO2 and brain PtiO2 correlated closely. A significant second-order regression curve of SjvO2 versus brain PtiO2 (p < 0.01) was plotted. At a threshold of 50% in SjvO2, brain PtiO2 was found to be within the range of 3 to 12 mm Hg, with a regression curve "best fit" value of 8.5 mm Hg. There was a close correlation between CPP and oxygenation parameters (PtiO2 and SjvO2) when CPP fell below a breakpoint of 60 mm Hg, suggesting intact cerebral autoregulation in most patients. This study demonstrates that monitoring brain PtiO2 is a safe, reliable, and sensitive diagnostic method to follow cerebral oxygenation. In comparison to SjvO2, PtiO2 is more suitable for long-term monitoring. It can be used to minimize episodes of secondary cerebral maloxygenation after severe head injury and may, hopefully, improve the outcome in severely head injured patients.