Passive leg raising in brain injury patients within the neurointensive care unit. A prospective trial.

INTRODUCTION: In critically ill brain-injured patients maintaining balanced fluid management is a crucial part of critical care. Many factors influence the relationship between fluid management, cerebral blood flow and cerebral oxygenation. Passive leg raising (PLR)-induced changes predict fluid responsiveness in the majority of non-neurological ICU patients. In patients with intracranial lesions, PLR testing has been hypothesized to increase intracranial pressure (ICP), although data are lacking. We wanted to investigate the feasibility of PLR with expected intracranial pressure increase, according to the higher cerebral blood volume. This should be self-limiting in patients with intact cerebral autoregulation. MATERIAL AND METHODS: We prospectively included patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (aSAH) in this pilot trial. PLR was performed within 48 hours after the initial diagnosis and on days 5-8. All patients had ICP monitoring. Absence of intracranial hypertension (defined as ICP < 25 mm Hg) was considered a positive test result. RESULTS: Ten patients were recruited for this study. The cohort consisted of 6 male patients with TBI and 4 female patients with aSAH. Mean patient age was 55.6 years (range 35-76). Overall, 18 tests could be performed, of which only one had to be terminated due to temporarily elevated ICP. 9 out of 10 patients had no intracranial hypertension during the acute (mean ICP increase 8.45 mm Hg, range 4-16) or during the subacute phase (mean ICP increase 9.12 mm Hg, range 3-18). CONCLUSIONS: PLR is feasible in patients with intracranial pathology to assess fluid responsiveness and provide optimized patient volume management without increasing the risk of persistent intracranial hypertension.

Delayed cerebral ischemia and spreading depolarization in absence of angiographic vasospasm after subarachnoid hemorrhage.

It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we tested whether SDs and DCI are abolished when vasospasm is reduced or abolished by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal intracranial vessels. The SDs were recorded using a subdural electrode strip. Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs were recorded in 10 of 13 patients (77%). Digital subtraction angiography revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate vasospasm in the remaining. Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.

Feasibility of intraventricular nicardipine prolonged release implants in patients following aneurysmal subarachnoid haemorrhage.

OBJECTIVE: Intracisternal nicardipine prolonged release implants (NPRI) have been shown to be effective in the prophylaxis of cerebral vasospasm (VS). However, they cannot be used in patients following coil occlusion of the aneurysm. As a certain dissemination of nicardipine within the cerebrospinal fluid (CSF) has been described, we examined the feasibility of intraventricular use of NPRI in patients that underwent clip and coil occlusion of their aneurysms following aneurysmal subarachnoid haemorrhage (aSAH). By comparison with an historical control group, an estimation of their effectivity in regard to angiographic vasospasm and the development of cerebral infarction has been performed. METHODS: Thirty-one patients suffering from aSAH were prospectively included in this trial. Study participants received prior to clipping (n = 17) or coiling (n = 14) 6 (n = 15) or 10 NPRI (n = 16) into the lateral ventricles. Physiological data were collected, proximal and global VS were determined using pre-operative and day 8 ± 1 angiography, and incidence of hydrocephalus and VS related infarcts were evaluated and compared to a historical control group consisting of 16 operated patients without NPRI implantation. RESULTS: Intraventricular NPRI were tolerated well. There were no adverse side effects detectable, physiological variables such as heart rate (HR), mean arterial blood pressure (MAP), intracranial pressure (ICP) and electrolytes showed no difference compared to control. There was no difference in the proportion of patients that required CSF shunting. A significant positive angiographic effect could only be observed in clipped patients (proximal vessel diameters: control, 80 ± 30%; NPRI 90 ± 24%; incidence of moderate/severe global VS: control, 73%; NPRI, 41%). CONCLUSIONS: The use of intraventricular NPRI seems to be safe and tolerated well. There is preliminary evidence for effectivity on angiographic VS for clipped patients only. A further increase of the effective dose might also exert efficacy in the subset of patients following coil occlusion.

Correlation of clinical outcome with pressure-, oxygen-, and flow-related indices of cerebrovascular reactivity in patients following aneurysmal SAH.

BACKGROUND: Impaired cerebrovascular reactivity (CR) has been reported to be associated with adverse outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, CR may be determined using different paradigms and it is unclear, which measurement method most suitable reflects the clinical course or is able to predict clinical deterioration. METHODS: Twenty-one aSAH patients were included in this study. Following occlusion of the aneurysms with or without implantation of nicardipine prolonged release implants (NPRIs), mean arterial and mean intracranial pressure, regional tissue oxygenation, and regional cerebral blood flow was determined. Based on these data, pressure-, oxygen-, and flow-related autoregulatory indices (PRx, ORx, FRx) were simultaneously calculated and correlated with outcome parameters including the Glasgow outcome score (GOS) and the modified Rankin (mRankin) scale. RESULTS: Eight patients showed newly developed cerebral infarcts. Low values of GOS and mRankin scale highly correlated with the incidence of cerebral infarcts (GOS, P = 0.001; mRankin, P = 0.003). However, indices of CR did not differ significantly between the infarction (I) and the noninfarction group (NI) (PRx, I, 0.058 +/- 0.096, NI, 0.097 +/- 0.203, P = 0.538; ORx, I, 0.162 +/- 0.316, NI, 0.094 +/- 0.176, P = 0.690; FRx, I, 0.395 +/- 0.200, NI, 0.265 +/- 0.177, P = 0.119). No correlation was found between indices and clinical outcome parameters (all not significant). However, ORx and FRx correlated well (P = 0.016). CONCLUSIONS: Due to the low number of included subjects, the obtained results are preliminary. However, they indicate that either the present technique of index-determination is not sensitive enough or that there is no strong relation between the measured indices and clinical outcome. Future verification is required of continuous against already established non-continuous monitoring techniques of CR in order to relate both to clinical outcome.

Clinical evaluation of the safety and efficacy of lumbar cerebrospinal fluid drainage for the treatment of refractory increased intracranial pressure.

OBJECT: Several approaches have been established for the treatment of intracranial hypertension; however, a considerable number of patients remain unresponsive to even aggressive therapeutic strategies. Lumbar CSF drainage has been contraindicated in the setting of increased intracranial pressure (ICP) because of possible cerebral herniation. The authors of this study investigated the efficacy and safety of controlled lumbar CSF drainage in patients suffering from intracranial hypertension following severe traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH). METHODS: The authors prospectively evaluated 100 patients-45 with TBI and 55 with SAH-having a mean age of 43.7 +/- 15.7 years (mean +/- SD) and suffering from refractory intracranial hypertension (ICP > 20 mm Hg). Intracranial pressure and cerebral perfusion pressure (CPP) before and after the initiation of lumbar CSF drainage as well as related complications were documented. Patient outcomes were assessed 6 months after injury. RESULTS: The application of lumbar CSF drainage led to a significant reduction in ICP from 32.7 +/- 10.9 to 13.4 +/- 5.9 mm Hg (p < 0.05) and an increase in CPP from 70.6 +/- 18.2 to 86.2 +/- 15.4 mm Hg (p < 0.05). Cerebral herniation with a lethal outcome occurred in 6% of patients. Thirty-six patients had a favorable outcome, 12 were severely disabled, 7 remained in a persistent vegetative state, and 45 died. CONCLUSIONS: Lumbar drainage of CSF led to a significant and clinically relevant reduction in ICP. The risk of cerebral herniation can be minimized by performing lumbar drainage only in cases with discernible basal cisterns.

Effects of fentanyl and S(+)-ketamine on cerebral hemodynamics, gastrointestinal motility, and need of vasopressors in patients with intracranial pathologies: a pilot study.

In neurosurgical patients, opioids are administered to prevent secondary cerebral damage. Complications often related to the administration of opioids are a decrease in blood pressure affording the use of vasopressors and intestinal atonia. One alternative approach to opioids is the application of S(+)-ketamine. However, owing to a suspected elevation of intracranial pressure (ICP), the administration of S(+)-ketamine has questioned for a long time. The aim of the present study was to evaluate ICP, gastrointestinal motility, and catecholamine consumption in neurosurgical patients undergoing 2 different protocols of anesthesia using fentanyl or S(+)-ketamine. Twenty-four patients sustaining traumatic brain injury or aneurysmal subarachnoid hemorrhage received methohexitone plus either fentanyl or S(+)-ketamine to establish a comparable level of sedation. To reach an adequate cerebral perfusion pressure (CPP), the norepinephrine dosage was adapted successively. Enteral nutrition and gastrointestinal stimulation were started directly after admission on the critical care unit. ICP, CPP, and norepinephrine dosage were recorded over 5 days and also the time intervals to full enteral nutrition and first defecation. There was no difference regarding ICP, CPP, and the time period until full enteral nutrition or first defecation between both groups. Patients who underwent analgesia with S(+)-ketamine showed a trend to a lower demand of norepinephrine compared with the fentanyl group. Our results indicate that S(+)-ketamine does not increase ICP and that its use in neurosurgical patients should not be discouraged on the basis of ICP-related concerns.

The use of the excimer laser-assisted anastomosis technique alleviates neuroanesthesia during cerebral high-flow revascularization.

In patients with complex intracranial aneurysms or skull base tumors, parent vessel occlusion and flow replacement by high-flow bypass surgery is a demanding therapy, both for the neurosurgeon and the neuroanesthesiologist. One reason for this is the need for prolonged temporary occlusion of a major cerebral artery, which carries a high risk of perioperative ischemia and necessitates versatile neuroprotective measures during anesthesia. Recently, a novel excimer laser-assisted nonocclusive anastomosis (ELANA) technique has been introduced, circumventing the need for temporary occlusion of cerebral vessels. We hypothesized that the use of this ELANA technique would facilitate also the neuroanesthesiologic management of these patients. To test this, we reviewed the details of the neuroanesthesiologic management of patients undergoing ELANA high-flow bypass surgery at our institution. Twenty-nine patients with giant aneurysms (n=27) or skull base tumor (n=2) who were undergoing parent vessel occlusion and permanent flow replacement by high-flow bypass surgery using the ELANA technique were investigated retrospectively. The records of the patients were analyzed for induction and maintenance of anesthesia, fluid therapy, transfusion requirements, hemodynamic parameters, and brain protective strategies. Although we are not able to provide a sufficient body of cohort data to compare the neuroanesthesiologic management of patients undergoing the conventional anastomosis technique with management using the ELANA technique, in each of our reported cases the conventional anastomosis technique would have entailed a high probability of prolonged temporary occlusion that would, in turn, have warranted intensive brain-protective strategies. The observation that use of the ELANA technique precluded the necessity of brain-protective strategies without entailing perioperative cerebral infarction suggests that the ELANA technique supports the neurosurgeon in creating difficult permanent intracranial anastomoses and also facilitates neuroanesthesiologic management of patients undergoing cerebral high-flow revascularization procedures.

Effects of hypervolemia and hypertension on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation after subarachnoid hemorrhage.

OBJECTIVE: Hypertensive, hypervolemic, hemodilution therapy (triple-H therapy) is a generally accepted treatment for cerebral vasospasm after subarachnoid hemorrhage. However, the particular role of the three components of triple-H therapy remains controversial. The aim of the study was to investigate the influence of the three arms of triple-H therapy on regional cerebral blood flow and brain tissue oxygenation. DESIGN: Animal research and clinical intervention study. SETTING: Surgical intensive care unit of a university hospital. SUBJECTS AND PATIENTS: Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients with subarachnoid hemorrhage. INTERVENTIONS: First, we investigated the effect of the three components of triple-H therapy under physiologic conditions in an experimental pig model. In the next step we applied the same study protocol to patients following aneurysmal subarachnoid hemorrhage. Mean arterial pressure, intracranial pressure, cerebral perfusion pressure, cardiac output, regional cerebral blood flow, and brain tissue oxygenation were continuously recorded. Intrathoracic blood volume and central venous pressure were measured intermittently. Vasopressors and/or colloids and crystalloids were administered to stepwise establish the three components of triple-H therapy. MEASUREMENTS AND MAIN RESULTS: In the animals, neither induced hypertension nor hypervolemia had an effect on intracranial pressure, brain tissue oxygenation, or regional cerebral blood flow. In the patient population, induction of hypertension (mean arterial pressure 143 +/- 10 mm Hg) resulted in a significant (p < .05) increase of regional cerebral blood flow and brain tissue oxygenation at all observation time points. In contrast, hypervolemia/hemodilution (intrathoracic blood volume index 1123 +/- 152 mL/m) induced only a slight increase of regional cerebral blood flow while brain tissue oxygenation did not improve. Finally, triple-H therapy failed to improve regional cerebral blood flow more than hypertension alone and was characterized by the drawback that the hypervolemia/hemodilution component reversed the effect of induced hypertension on brain tissue oxygenation. CONCLUSIONS: Vasopressor-induced elevation of mean arterial pressure caused a significant increase of regional cerebral blood flow and brain tissue oxygenation in all patients with subarachnoid hemorrhage. Volume expansion resulted in a slight effect on regional cerebral blood flow only but reversed the effect on brain tissue oxygenation. In view of the questionable benefit of hypervolemia on regional cerebral blood flow and the negative consequences on brain tissue oxygenation together with the increased risk of complications, hypervolemic therapy as a part of triple-H therapy should be applied with utmost caution.

Predictors of mortality in ARDS patients referred to a tertiary care centre: a pilot study.

BACKGROUND AND OBJECTIVE: In order to identify parameters predicting intensive care unit mortality in patients transferred to a specialized tertiary centre because of progressive acute respiratory distress syndrome, an observational pilot study was carried out involving 94 patients. METHODS AND RESULTS: Forty-one patients (43.6%) died. Survival was defined as intensive care unit discharge. Survivors were younger (32.0 +/- 11.8 vs. 39.1 +/- 12.4 yr, P = 0.008), at admission they had a lower acute physiology and chronic health evaluation (APACHE) II score (21.7 +/- 5.4 vs. 25.4 +/- 5.2, P = 0.0009), higher PaO2/FiO2 (122 +/- 79 vs. 79 +/- 42 mmHg, P = 0.002), lower positive end-expiratory pressure (10.6 +/- 3.1 vs. 12.5 +/- 3.7 cmH2O, P = 0.02) and a lower Murray score (2.8 +/- 0.63 vs. 3.0 +/- 0.62, P = 0.04). No differences were observed for tidal volumes and peak inspiratory pressures. Days of hospitalization and mechanical ventilation prior to transferral were not related to survival. Multivariate analysis of variables assessed on admission detected only differences for age (P = 0.014) and APACHE II (P = 0.005). Odds ratio was 1.06 (95% confidence interval (CI): 1.013-1.119) for age and 1.21 (CI: 1.059-1.381) for APACHE II. Multivariate analysis of changes in respiratory parameters, APACHE II and Murray score during the first 3 days after transferral revealed a significant difference only for positive end-expiratory pressure (P < 0.008). Corresponding odds ratio was 2.40 (CI: 1.25-4.58) for an increase of 1 cmH2O/24 h. CONCLUSION: Age-related mortality in this small, but highly selected group of patients with established ARDS increased early in life even in a population with an overall mean age of 35.1 yr. APACHE II was the only clinical predictor for mortality on admission. The need for a substantial increase in positive end-expiratory pressure after transferral markedly reduced the chance to survive.

Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation.

OBJECTIVE: Acute respiratory dysfunction frequently occurs following severe aneurysmal subarachnoid hemorrhage requiring positive end-expiratory pressure (PEEP) ventilation to maintain adequate oxygenation. High PEEP levels, however, may negatively affect cerebral perfusion. The goal of this study was, to examine the influence of various PEEP levels on intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, and systemic hemodynamic variables. DESIGN: Animal research and clinical intervention study. SETTING: Surgical intensive care unit of a university hospital. SUBJECTS AND PATIENTS: Experiments were carried out in five healthy pigs, followed by a clinical investigation of ten patients suffering subarachnoid hemorrhage. INTERVENTIONS: Under continuous monitoring of intracranial pressure, brain tissue oxygen tension, regional cerebral blood flow, mean arterial pressure, and cardiac output, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O in the experimental part and from baseline to 20 cm H2O in the clinical part. MEASUREMENTS AND MAIN RESULTS: In animals, high PEEP levels had no adverse effect on intracranial pressure, brain tissue oxygen tension, or regional cerebral blood flow. In patients with severe subarachnoid hemorrhage, stepwise elevation of PEEP resulted in a significant decrease of mean arterial pressure and regional cerebral blood flow. Analyses of covariance revealed that these changes of regional cerebral blood flow depended on mean arterial pressure changes as a result of a disturbed cerebrovascular autoregulation. Consequently, normalization of mean arterial pressure restored regional cerebral blood flow to baseline values. CONCLUSIONS: Application of high PEEP does not impair intracranial pressure or regional cerebral blood flow per se but may indirectly affect cerebral perfusion via its negative effect on macrohemodynamic variables in case of a disturbed cerebrovascular autoregulation. Therefore, following severe subarachnoid hemorrhage, a PEEP-induced decrease of mean arterial pressure should be reversed to maintain cerebral perfusion.