Elevation Of Cerebral Perfusion Pressure Research Articles

Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER-TBI Study

BackgroundAfter traumatic brain injury (TBI), fever is frequent. Brain temperature (BT), which is directly linked to body temperature, may influence brain physiology. Increased body and/or BT may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome.MethodsCollaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI), a prospective multicenter longitudinal study on TBI in Europe and Israel, includes a high resolution cohort of patients with data sampled at a high frequency (from 100 to 500 Hz). In this study, simultaneous BT, ICP, and CPP recordings were investigated. A mixed-effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes in ICP and CPP during the episodes of BT changes (Δ BT ≥ 0.5 °C lasting from 15 min to 3 h) up or downward. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test (also known as Wilcoxon signed-rank test).ResultsTwenty-one patients with 2,435 h of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38 °C and experienced at least one episode of ICP above 20 mm Hg. The linear mixed-effects model revealed an association between BT above 37.5 °C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n = 79) ICP increased, whereas CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n = 70). All these changes were of moderate clinical relevance (increase of ICP of 4.5 and CPP decrease of 7.5 mm Hg for BT rise, and ICP reduction of 1.7 and CPP elevation of 3.7 mm Hg during BT defervescence), even if statistically significant (p < 0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes.ConclusionsPatients after TBI usually develop BT > 38 °C soon after the injury. BT may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5 °C and a higher ICP was identified but not confirmed for lower BT ranges. The relationship between BT, ICP, and CPP become clearer during rapid temperature changes. During episodes of temperature elevation, BT seems to have a significant impact on ICP and CPP.

Randomized Clinical Trial of 20% Mannitol Versus 3% Hypertonic Saline in Children With Raised Intracranial Pressure Due to Acute CNS Infections.

Mannitol is a commonly used osmotherapy agent in raised intracranial pressure. However, the side effects of mannitol are significant. In traumatic brain injury (adult and pediatric), hypertonic saline (3%) shows varied results in comparison with 20% mannitol. We compared the effect of 3% hypertonic saline versus 20% mannitol (using common dosing strategies) on raised intracranial pressure in pediatric acute CNS infections. Open-label randomized controlled trial. PICU of a quaternary care academic institute. Children 1-12 years old, with raised intracranial pressure and modified-Glasgow Coma Scale scores less than or equal to 8, were enrolled. Patients were randomly assigned to 20%-mannitol (n = 28), 0.5 gram/kg/dose versus 3%-hypertonic saline (n = 29), 10 mL/kg loading followed by 0.5-1 mL/kg/hr infusion. An intraparenchymal catheter was used to monitor the intracranial pressure. The primary outcome was the proportion of patients achieved target average intracranial pressure less than 20 mm Hg during 72 hours. Secondary outcomes were interventions, morbidity, and mortality. The proportion of patients with target average intracranial pressure (< 20 mm Hg) was higher in hypertonic saline-group as compared to mannitol-group (79.3% vs 53.6%; adjusted hazard ratio 2.63; 95% CI: 1.23-5.61). Mean (± SE) reduction of intracranial pressure (-14.3 ± 1.7 vs -5.4 ± 1.7 mm Hg; p ≤ 0.001) and elevation of cerebral perfusion pressure (15.4 ± 2.4 vs 6 ± 2.4 mm Hg; p = 0.007) from baseline were significant in hypertonic saline-group. Mean (± SE) intracranial pressure over 72 hours was lower (14 ± 2 vs 22 ± 2 mm Hg; p = 0.009), and cerebral perfusion pressure was higher (65 ± 2.2 vs 58 ± 2.2; p = 0.032) in hypertonic saline-group. Hypertonic saline-group had higher modified-Glasgow Coma Scale score at 72 hours (median, interquartile range 10; 7-11 vs 7; 3-9; p = 0.003), lower mortality (20.7% vs 35.7%; p = 0.21), shorter duration of mechanical ventilation (5 vs 15 d; p = 0.002), and PICU stay (11 vs 19 d; p = 0.016) and less severe neurodisability at discharge (31% vs 61%; p = 0.049). In pediatric acute CNS infections, 3%-hypertonic saline was associated with a greater reduction of intracranial pressure as compared to 20% mannitol.

Vasopressin Increases Cerebral Perfusion Pressure but not Cerebral Blood Flow in Neurosurgical Patients with Catecholamine-Refractory Hypotension: A Preliminary Evaluation Using the Non-Invasive Quantix ND in Comparison to the Literature

The maintenance of sufficient mean arterial pressure (MAP) is important for all patients in intensive care but for neurosurgical patients after SAH or TBI it is essential to avoid secondary brain damage or delayed ischemia. So far most neurosurgical intensive care units use intracranial pressure (ICP) and cerebral perfusion pressure (CPP) as therapy guidance for those patients. Use of fluid resuscitation and catecholamines is standard to achieve CPP between 50-70 mmHg. But sometimes catecholamine-refractory hypotension occurs. In those cases, arginin-vasopressin (AVP) might be the drug of choice. AVP and its synthetic analogies are widely used in modern medicine and gained interest in treatment of septic shock or refractory hypotension after cardiac surgery or hypovolemic shock. Recent papers also showed a significant impact of AVP in resuscitation after traumatic brain injury (TBI) and influence on CPP in TBI patients during ICU treatment. But litttle is known about the effects of AVP on cerebral perfusion and oxygenation. The present preliminary study was carried out to examine the influence of AVP administration on cerebral blood flow by using the non invasive Quantix ND device. We found significantly increased MAP and CPP but no concomitant elevation in CBF. In contrast, in two patients the CBF even decreased despite elevation of CPP. We conclude that AVP is an alternative drug to maintain MAP and CPP but has to be used with care in patiens with already compromised cerebral perfusion.

Editorial: Decompressive craniectomy

The accompanying article by Bor-Seng-Shu et al.1 attempts to address a rather straightforward question: Does decompressive craniectomy reduce intracranial pressure (ICP) and increase cerebral perfusion pressure (CPP) in the setting of traumatic brain injury? While conventional wisdom would hold this as a foregone conclusion, studies that have included this information have not been entirely conclusive. Moreover, most studies on the topic have been rather small and have not had sufficient power to arrive at a conclusion. The authors of this pooled analysis attempt to address the issue of statistical power by pooling available studies. The outcomes examined by Bor-Seng-Shu are rather straightforward, but the method does illustrate some of the limitations of doing a meta-analysis of widely heterogeneous studies. As the authors themselves indicate, there is wide variability in almost every aspect of the studies utilized in the meta-analysis—from patient inclusion criteria, to ICP measurement techniques, to medical treatment intensity, to surgical timing, to surgical technique. In fact, in a true meta-analysis, such important sources of variability are typically incorporated in the inclusion/ exclusion criteria. While the authors of this meta-analysis excluded some analyses (such as case reports, reviews, nonhuman studies, non-English studies, and so forth), very important sources of variability remain in the included studies. We should always exercise caution when interpreting the results of this type of pooled analysis. The assumption that pooling patient data from multiple studies will result in a valid pooled comparison is not always a reliable one. Disparity in patient numbers between studies with confounding variables will not infrequently lead to a contradictory conclusion (Yule-Simpson effect). Given that there is wide variation in patient accrual in the present pooled analysis (4–100 patients in the included studies) as well as a number of likely confounders, the possibility of a Simpson paradox should not be discounted. Because of the study heterogeneity in this pooled analysis, it is difficult to have much confidence in the degree of ICP reduction or CPP elevation afforded by decompressive craniectomy. However, the conclusion of the analysis—that cranial decompression reduces ICP and increases CPP—is believable. It remains to be seen whether the degree of ICP reduction and its durability hold up as more studies on the topic are published. (http://thejns.org/doi/abs/10.3171/2012.1.JNS1283)

Comparison of Effects of Equiosmolar Doses of Mannitol and Hypertonic Saline on Cerebral Blood Flow and Metabolism in Traumatic Brain Injury

The potential superiority of hypertonic saline (HTS) over mannitol (MTL) for control of intracranial pressure (ICP) following traumatic brain injury (TBI) is still debated. Forty-seven severe TBI patients with increased ICP were prospectively recruited in two university hospitals and randomly treated with equiosmolar infusions of either MTL 20% (4 mL/kg; n=25 patients) or HTS 7.5% (2 mL/kg; n=22 patients). Serum sodium, hematocrit, ICP, arterial blood pressure, cerebral perfusion pressure (CPP), shear rate, global indices of cerebral blood flow (CBF) and metabolism were measured before, and 30 and 120 min following each infusion during the course of illness. Outcome was assessed at 6 months. Both HTS and MTL effectively and equally reduced ICP levels with subsequent elevation of CPP and CBF, although this effect was significantly stronger and of longer duration after HTS and correlated with improved rheological blood properties induced by HTS. Further, effect of HTS on ICP appeared to be more robust in patients with diffuse brain injury. In contrast, oxygen and glucose metabolic rates were left equally unaffected by both solutions. Accordingly, there was no significant difference in neurological outcome between the two groups. In conclusion, MTL was as effective as HTS in decreasing ICP in TBI patients although both solutions failed to improved cerebral metabolism. HTS showed an additional and stronger effect on cerebral perfusion of potential benefit in the presence of cerebral ischemia. Treatment selection should therefore be individually based on sodium level and cerebral hemodynamics.

Impaired cerebral blood flow autoregulation during posttraumatic arterial hypotension after fluid percussion brain injury is prevented by phenylephrine in female but exacerbated in male piglets by extracellular signal-related kinase mitogen-activated protein kinase upregulation.

Traumatic brain injury contributes to morbidity and mortality in children and boys are disproportionately represented. Hypotension is common and worsens outcome after traumatic brain injury. Extracellular signal-related kinase mitogen-activated protein kinase is upregulated and reduces cerebral blood flow after fluid percussion brain injury in piglets. We hypothesized that increased cerebral perfusion pressure through phenylephrine sex dependently reduces impairment of cerebral autoregulation during hypotension after fluid percussion brain injury through modulation of extracellular signal-related kinase mitogen-activated protein kinase. Prospective, randomized animal study. University laboratory. Newborn (1- to 5-day-old) pigs. Cerebral blood flow, pial artery diameter, intracranial pressure, and autoregulatory index were determined before and after fluid percussion brain injury in untreated, preinjury, and postinjury phenylephrine (1 microg/kg/min intravenously) treated male and female pigs during normotension and hemorrhagic hypotension. Cerebrospinal fluid extracellular signal-related kinase mitogen-activated protein kinase was determined by enzyme-linked immunosorbent assay. Reductions in pial artery diameter, cerebral blood flow, cerebral perfusion pressure, and elevated intracranial pressure after fluid percussion brain injury were greater in males, which were blunted by phenylephrine pre- or postfluid percussion brain injury. During hypotension and fluid percussion brain injury, pial artery dilation was impaired more in males. Phenylephrine decreased impairment of hypotensive pial artery dilation after fluid percussion brain injury in females, but paradoxically caused vasoconstriction after fluid percussion brain injury in males. Papaverine-induced pial artery vasodilation was unchanged by fluid percussion brain injury and phenylephrine. Cerebral blood flow, cerebral perfusion pressure, and autoregulatory index decreased markedly during hypotension and fluid percussion brain injury in males but less in females. Phenylephrine prevented reductions in cerebral blood flow, cerebral perfusion pressure, and autoregulatory index during hypotension in females but increased reductions in males. Cerebrospinal fluid extracellular signal-related kinase mitogen-activated protein kinase was increased more in males than females after fluid percussion brain injury. Phenylephrine blunted extracellular signal-related kinase mitogen-activated protein kinase upregulation in females but increased extracellular signal-related kinase mitogen-activated protein kinase upregulation in males after fluid percussion brain injury. These data indicate that elevation of cerebral perfusion pressure with phenylephrine sex dependently prevents impairment of cerebral autoregulation during hypotension after fluid percussion brain injury through modulation of extracellular signal-related kinase mitogen-activated protein kinase. These data suggest the potential role for sex-dependent mechanisms in cerebral autoregulation after pediatric traumatic brain injury.

NOREPINEPHRINE AND CEREBRAL BLOOD FLOW REGULATION IN PATIENTS WITH ARTERIOVENOUS MALFORMATIONS

To test the hypothesis that the sympathetic nervous system plays a role in cerebral blood flow regulation in patients with arteriovenous malformations (AVM). Cortical interstitial norepinephrine was measured by means of microdialysis, regional cerebral blood flow was measured by a thermal diffusion technique, and regional oxygen saturation (SO2) was measured by microspectrophotometry in 12 patients harboring cerebral AVMs (AVM group) and in 15 patients with deep-seated nonvascular lesions (control group) before and after resection. Measurements were compared according to groups and times of measurements. All values are given as means +/- standard deviation. Cortical regional SO2 increased significantly (P < 0.05) in both groups after surgery (AVM group: presurgery 52.4 +/- 12.5% SO2, postsurgery 71.4 +/- 7.4% SO2; control group: presurgery 57.1 +/- 8.4% SO2, postsurgery 69.9 +/- 8.7% SO2), whereas regional cerebral blood flow increased only in the AVM group (AVM group: presurgery 18.9 +/- 6.6 ml/100 g/min, postsurgery 26.2 +/- 6.9 ml/100 g/min; control group: presurgery 20.1 +/- 7.6 ml/100 g/min, postsurgery 19.4 +/- 7.8 ml/100 g/min). Norepinephrine concentrations were significantly lower in the AVM group as compared with the control group before surgery. Although there was no significant difference between pre- and postsurgery conditions in the AVM group, the norepinephrine level of the control group was significantly lower after surgery (AVM group: presurgery 3.3 +/- 1.2 nmol/L, postsurgery 2.9 +/- 1.7 nmol/L; control group: presurgery 5.4 +/- 1.4 nmol/L, postsurgery 4.2 +/- 1.1 nmol/L). Chronically lowered perfusion pressure seems to induce the hypothesized adaptive down-regulation of sympathetic nervous system activity, yet protective up-regulation after a sudden elevation of cerebral perfusion pressure after AVM excision could not be shown in this study.

Hypertensive encephalopathy and the blood-brain barrier: is δPKC a gatekeeper?

Hypertensive encephalopathy is a life-threatening condition due to elevation of cerebral perfusion pressure beyond the limits of autoregulation. Breakdown of the blood-brain barrier (BBB) leads to cerebral edema and reduced blood flow. In this issue of the JCI, Mochly-Rosen and colleagues demonstrate a novel molecular strategy for preserving the BBB in a model of hypertension-induced encephalopathy (see the related article beginning on page 173). Using a rationally designed peptide inhibitor of deltaPKC, they stabilized the BBB and improved mortality in hypertensive rats. This study highlights the therapeutic potential of deltaPKC inhibitors in hypertensive encephalopathy and provides incentive to elucidate deltaPKC signaling pathways that mediate BBB dysfunction in other disease states.

CEREBRAL BLOOD FLOW IN TRAUMATIC CONTUSIONS IS PREDOMINANTLY REDUCEDAFTER AN INDUCED ACUTE ELEVATION OF CEREBRAL PERFUSION PRESSURE

To evaluate the response to an acute elevation of cerebral perfusion pressure (CPP) of the regional cerebral blood flow (rCBF) measured in the edematous area of traumatic contusions. rCBF was measured in the intracontusional low-density area, in the pericontusional healthy-appearing brain tissue surrounding the contusion, in a healthy-appearing area in the contralateral hemisphere, in 16 head-injured patients with 16 traumatic contusions larger than 2 cm at baseline, and after 20 minutes of norepinephrine-induced 20-mmHg elevation of CPP levels. After an induced acute elevation of CPP from baseline values of 65.8 ml/100 g/min (standard deviation, 8.6) to final values of 88.7 ml/100 g/min (standard deviation, 8.9; P < or = 0.0001), we found that rCBF mean levels decreased in the intracontusional low-density area (P = 0.0278), and change in rCBF was inversely associated to the baseline values. After grouping contusions according to the rCBF response to induced acute CPP elevation, rCBF mean values recorded at baseline were significantly lower in lesions with "rCBF improvement" than in those with "rCBF reduction" in the intracontusional low-density area (P = 0.0435). Our findings suggest that CPP elevation induced by norepinephrine is effective in improving contusional rCBF only in selected cases, which are represented by a subset of contusions with critical perfusion, which can be identified by rCBF measurements. Conversely, in contusions with rCBF higher than critical low values, the CPP elevation could probably induce a temporary breakdown of the blood brain barrier, and the norepinephrine leads to a vasoconstriction with a worsening of regional perfusion.

Cerebral response to norepinephrine compared with fluid resuscitation in ovine traumatic brain injury and systemic inflammation*

Traumatic brain injury is frequently accompanied by a systemic inflammatory response. Systemic inflammation was associated with cerebral hyperperfusion uncoupled to global oxygen metabolism in ovine head trauma. The present study investigated the cerebral effects of cerebral perfusion pressure (CPP) management performed by either fluid resuscitation or vasopressor treatment of low CPP induced by systemic inflammation. Nonrandomized experimental study. University hospital laboratory. A total of 12 adult sheep. Sheep were anesthetized and ventilated throughout the experimental period (13 hrs). After baseline measurements (hour 0), blunt head trauma was induced by a nonpenetrating stunner. After postinjury measurements (hour 2), all animals received continuous endotoxin infusion. At hour 10, one group (n = 6) was infused with hydroxyethyl starch until CPP reached 60-70 mm Hg. A second group (n = 6) received norepinephrine for CPP elevation. In the norepinephrine group, blood was isovolemically exchanged by hydroxyethyl starch to achieve comparable hematocrit levels. Head trauma increased intracranial pressure and decreased brain tissue oxygen tension. Endotoxemia induced a hyperdynamic cardiovascular response with increased internal carotid blood flow in the presence of systemic hypotension and decreased CPP. Hydroxyethyl starch infusion further increased internal carotid blood flow from (mean +/- sd) 247 +/- 26 (hour 10) to 342 +/- 42 mL/min (hour 13) and intracranial pressure from 20 +/- 4 (hour 10) to a maximum of 25 +/- 3 mm Hg (hour 12) but did not significantly affect brain tissue oxygen tension, sinus venous oxygen saturation and oxygen extraction fraction. Norepinephrine increased internal carotid blood flow from 268 +/- 19 to 342 +/- 58 mL/min and intracranial pressure from 22 +/- 11 to 24 +/- 11 mm Hg (hour 10 vs. hour 13) but significantly increased sinus venous oxygen saturation from 49 +/- 4 (hour 10) to a maximum of 59 +/- 6 mm Hg (hour 12) and decreased oxygen extraction fraction. The increase in brain tissue oxygen tension during norepinephrine treatment was not significant. We conclude that despite identical carotid blood flows, only CPP management with norepinephrine reduced the cerebral oxygen deficit in this model.

Does induced hypertension reduce cerebral ischaemia within the traumatized human brain?

Recent changes in published guidelines for the management of patients with severe head injury are based on data showing that aggressive maintenance of cerebral perfusion pressure (CPP) can worsen outcome due to extracranial complications of therapy. However, it remains unclear whether CPP augmentation could reduce cerebral ischaemia, a finding which might prompt the search for CPP augmentation protocols that avoid these extracranial complications. We studied 10 healthy volunteers and 20 patients within 6 days of closed head injury. All subjects underwent imaging of cerebral blood flow (CBF), blood volume (CBV), oxygen metabolism (CMRO2) and oxygen extraction fraction (OEF) using 15O PET. In addition, for patients, the EEG power ratio index (PRI), burst suppression ratio and somatosensory evoked potentials (SEP) were obtained and CPP was increased from 68 +/- 4 to 90 +/- 4 mmHg using an infusion of norepinephrine and measurements were repeated. Following elevation of CPP, CBF and CBV were increased and CMRO2 and OEF were reduced (P < 0.001 for all comparisons). Regions with a reduction in CMRO2 were associated with the greatest reduction in OEF (r2 = 0.3; P < 0.0001). Although CPP elevation produced a significant fall in the ischaemic brain volume (IBV) (from 15 +/- 16 to 5 +/- 4 ml; P < 0.01) and improved flow metabolism coupling, the IBV was small and clinically insignificant in the majority of these patients. However, the reduction in IBV was directly related to the baseline IBV (r2 = 0.97; P < 0.001) and patients with large baseline IBV showed substantial and clinically significant reductions. CPP augmentation increased the EEG PRI (5.0 +/- 1.5 versus 4.3 +/- 1.4, P < 0.01), implying an overall decrease in neural activity, but these changes did not correlate with the reduction in CMRO2 and there was no change in SEP cortical amplitude (N20-P27). These data provide support for recent changes in recommended CPP levels for head injury management across populations of patients with significant head injury. However, they do not provide guidance on whether the intervention may be more appropriate at earlier stages after injury, or in patients selected because of high baseline IBV. It also remains unclear whether CPP values below 65 mmHg can be safely used in this population. Clarification of the significance of a reduction in CMRO2 and neuronal electrical function will require further study.

Therapeutic hypertension: principles and methods

While the beneficial effects of hypertension in treating cerebral vasospasm and the artificial elevation of cerebral perfusion pressure are controversial, this paper provides an excellent basic primer on cardiovascular physiology. It is well for all of us to be reminded of the variables, which may be therapeutically manipulated, as we institute various targeted therapies for these disorders. Returning to the basics is always worthwhile, as we strive to provide the best available neurological critical care for our patients.

Cerebral perfusion pressure elevation with oxygen-carrying pressor after traumatic brain injury and hypotension in Swine.

Previously, we had shown that elevation of cerebral perfusion pressure, using pressors, improved short-term outcomes after traumatic brain injury and hemorrhagic shock in swine. The current study evaluates outcomes after resuscitation with diaspirin cross-linked hemoglobin (DCLHb)--a hemoglobin-based oxygen carrier with pressor activity--in the same swine model of traumatic brain injury and hemorrhagic shock. Anesthetized and ventilated swine received traumatic brain injury via cortical fluid percussion (6-8 atm) followed by 45% blood volume hemorrhage. One hour later, animals were randomized to either a control group (SAL) resuscitated with normal saline equal to three times shed blood volume or to one of two experimental groups resuscitated with DCLHb. The two experimental groups consisted of a low-dose group, resuscitated with 250 mL of DCLHb (Hb1), and a high-dose group, resuscitated with 500 mL of DCLHb (Hb2). Animals were observed for 210 minutes postresuscitation. Outcomes evaluated were cerebral oxygenation by measuring partial pressure and saturation of oxygen in cerebrovenous blood; cerebral function by evaluating the preservation and magnitude of cerebrovascular carbon dioxide reactivity; and brain structural damage by semiquantitatively assessing beta amyloid precursor protein positive axons. Postresuscitation, cerebral perfusion pressure was higher in the DCLHb groups (p < 0.05, Hb1 and Hb2 vs. SAL), and intracranial pressure was lower in the Hb2 group (p < 0.05 vs. SAL). Cerebrovenous oxygen level was similar in all groups (p > 0.05). At baseline, 5% carbon dioxide evoked a 16 +/- 1% increase in cerebrovenous oxygen saturation, indicating vasodilatation. At 210 minutes, this response was nearly absent in SAL (4 +/- 4%) (p < 0.05 vs. baseline) and Hb1 (1 +/- 5%), but was partially preserved in Hb2 (9 +/- 5%). There was no intergroup difference in beta amyloid precursor protein positive axons. Five of 20 SAL and 0 of 13 DCLHb animals developed brain death (flat electroencephalogram) (p = 0.05, SAL vs. DCLHb). Postresuscitation, DCLHb animals maintained higher mean pulmonary arterial pressure (28 +/- 1 mm Hg, SAL; 42 +/- 1 mm Hg, Hb1; 45 +/- 1 mm Hg, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL) and lower cardiac output (3.9 +/- 1.6 L/min, SAL; 2.6 +/- 0.1 L/min, Hb1; 2.7 +/- 0.1 L/min, Hb2) (p < 0.05, Hb1 and Hb2 vs. SAL). Three Hb2 animals died as a result of cardiac failure, and one SAL animal died as a result of irreversible shock. In this swine model of traumatic brain injury and hemorrhagic shock, resuscitation with DCLHb maintained a higher cerebral perfusion pressure. Low-dose DCLHb (minimal increase in oxygen carriage) failed to significantly improve short-term outcome. With high-dose DCLHb (significant improvement in oxygen carriage), intracranial pressure was lower and cerebrovascular carbon dioxide reactivity was partially preserved; however, this was at the cost of poorer cardiac performance secondary to high afterload.

Responses of Posttraumatic Pericontusional Cerebral Blood Flow and Blood Volume to an Increase in Cerebral Perfusion Pressure

In and around traumatic contusions, cerebral blood flow (CBF) is often near or below the threshold for ischemia. Increasing cerebral perfusion pressure (CPP) in patients with head injuries may improve CBF in these regions. However, the pericontusional response to this intervention has not been studied. Using positron emission tomography (PET), we have quantified the response to an increase in CPP in and around contusions in 18 contusions in 18 patients. Regional CBF and cerebral blood volume (CBV) were measured with PET at CPPs of 70 and 90 mmHg using norepinephrine to control CPP. Based upon computed tomography, regions of interest (ROIs) were placed as two concentric ellipsoids, each of 1-cm width, around the core of the contusions. Measurements were compared with a control ROI in tissue with normal anatomic appearance. Baseline CBF and CBV increased significantly with increasing distance from the core of the lesion. The increase in CPP led to small increases in CBF in all ROIs except the core. The largest absolute CBF increase was found in the control ROI. Relative CBF increases did not differ between ROIs so that ischemic areas remained ischemic. Pericontusional oedema on computed tomography was associated with lower absolute values of CBF and CBV but did not differ from nonoedematous tissue in the relative response to CPP elevation.

Intracranial hypertension and cerebral ischemia after severe traumatic brain injury

Arterial hypotension and intracranial hypertension are detrimental to the injured brain. Although artificial elevation of cerebral perfusion pressure (CPP) has been advocated as a means to maintain an adequate cerebral blood flow (CBF), the optimal CPP for the treatment of severe traumatic brain injury (TBI) remains unclear. In addition, CBF evolves significantly over time after TBI, and CBF may vary considerably in patient to patient. For these reasons, a more useful approach may be to consider the optimal CPP in an individual patient at any given time, rather than having an arbitrary goal applied uniformly to all patients. Important information for optimizing CBF is provided by monitoring intracranial pressure in combination with assessment of the adequacy of CBF by using global indicators (for example, jugular oximetry), supplemented when appropriate by local data, such as brain tissue oxygen tension.

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]

Brain tissue pO2-monitoring in comatose patients: Implications for therapy

Monitoring of brain tissue partial pressure of O2 (ti-pO2) is a promising new technique that allows early detection of impending cerebral ischemia in brain-injured patients. The purpose of this study was to investigate the effects of standard therapeutic interventions .used in the treatment of intracranial hypertension in comatose patients on cerebral oxygenation. In the neurosurgical intensive care unit ti-p02 arterial blood pressure, intracranial pressure OCP), cerebral perfusion pressure (CPP) and jugula'r bulb oxygen saturation (SjV02) were prospectively studied (0.1 Hz acquisition rate) in 23 comatose patients (21 with sever~ traumatic brain injury, 2 with intracerebral hematoma) during various treatment modalities: elevation of CPP with dop~mine (n = 35), lowering of the head (n = 22), induced arterial hypocapnia (n = 13), mannitol infusion (n = 16), and decompressive craniotomy (n = 1). Ischemic episodes (‘IE’ = ti-p02< 10 mmHg for > 15 min) within the first week after the insult were always associated with unfavorable neurological outcome. Elevation of CPP from 32 ± 2 to 67 ± 4 mmHg significantly improved ti-p02 by 62% (13 ± 2 to 21 ± 1 mmHg) and reduced ICP indicating intact cerebral autoregulation. Further raising CPP from 68 ± 2 to 84 ± 2 mmHg did not alter ti-p02' Mannitol-induced ICP reduction from 23 ± 1 to 16 ± 2 mmHg did not affect ti-p02 nor did lowering of the head from 3rY to (Y. Hyperventilation from an endtidal pC02 of 29± 3 to 21 ± 3 mmHg normalized ICP and CPP, but significantly reduced ti-p02 from 31 ± 2 to 14 ± 3 nimHg. Decompressive craniotomy in· a 15-year old patient with refractory intracranial hypertension instantly restored ti-p02 Based on the present data, our understanding of many interventions previously believed to improve brain oxygenation might have to be. re-evaluated. A CPP > 60 mmHg emerges as the most important factor determining sufficient brain tissue p02' Any intervention used to further elevate CPP does-not improve ti-p02, to the contrary, hyperventilation even bears the risk of inducing brain ischemia. [Neural Res 1997; 19: 233-240]