Raimund Helbok

Cerebral Perfusion Pressure Thresholds for Brain Tissue Hypoxia and Metabolic Crisis After Poor-Grade Subarachnoid Hemorrhage

Background and Purpose— To identify a minimally acceptable cerebral perfusion pressure threshold above which the risks of brain tissue hypoxia (BTH) and oxidative metabolic crisis are reduced for patients with subarachnoid hemorrhage (SAH). Methods— We studied 30 poor-grade SAH patients who underwent brain multimodality monitoring (3042 hours). Physiological measures were averaged over 60 minutes for each collected microdialysis sample. Metabolic crisis was defined as a lactate/pyruvate ratio >40 with a brain glucose concentration ⩽0.7 mmol/L. BTH was defined as PbtO2 <20 mm Hg. Outcome was assessed at 3 months with the Modified Rankin Scale. Results— Multivariable analyses adjusting for admission Hunt-Hess grade, intraventricular hemorrhage, systemic glucose, and end-tidal CO2 revealed that cerebral perfusion pressure ⩽70 mm Hg was significantly associated with an increased risk of BTH (OR, 2.0; 95% CI, 1.2–3.3; P=0.007) and metabolic crisis (OR, 2.1; 95% CI, 1.2–3.7; P=0.007). Death or severe disability at 3 months was significantly associated with metabolic crisis (OR, 5.4; 95% CI, 1.8–16; P=0.002) and BTH (OR, 5.1; 95% CI, 1.2–23; P=0.03) after adjusting for admission Hunt-Hess grade. Conclusions— Metabolic crisis and BTH are associated with mortality and poor functional recovery after SAH. Cerebral perfusion pressure levels <70 mm Hg was associated with metabolic crisis and BTH, and may increase the risk of secondary brain injury in poor-grade SAH patients.

Intracranial multimodal monitoring for acute brain injury: A single institution review of current practices

BackgroundCritical care management of patients with severe acute brain injury has undergone tremendous advances. Neurosurgeons and neurointensivists have a large armamentarium of invasive monitoring devices available to help detect secondary brain injury and guide therapy. No consensus exists regarding patient specific selection of monitoring devices, the placement of devices in relation to injured brain tissue, or the preferred insertion technique. Here we review our experience in a consecutive series of acutely brain injured patients who underwent multimodality monitoring.MethodsSixty-one patients admitted to the Neurological Intensive Care Unit underwent multimodality intracranial monitoring between January 2005 and October 2008. Patient demographics, hospital length of stay, types of monitoring devices and modalities monitored, insertion techniques, device placement location relative to injury, and complications are reported.ResultsMonitored modalities included brain tissue oxygen (PbtO2) in 97% (Nxa0=xa059), microdialysis (MD) in 79% (Nxa0=xa048), intracranial electroencephalography in 31% (Nxa0=xa019), brain temperature in 18% (Nxa0=xa011), and cerebral blood flow in 11% (Nxa0=xa07). On average, monitoring started within 2 days (0–8) of admission and was continued for 7 days (1–17). The majority of probes (56%; Nxa0=xa035) were placed into patients with focal brain injuries, while in 43% Nxa0=xa026 the injury was diffuse. Among those with focal injury, probe placement was categorized as peri-lesional in 46% (Nxa0=xa016), and within a clot or infarct in 17% (Nxa0=xa06). The most frequent complication of multimodality brain monitoring was device malfunction or dislodgement (43%; Nxa0=xa026). Rates of hematoma and infection were 3 and 5%, respectively. Average NICU length of stay was 17 days (3–48) and 26% (Nxa0=xa016) of patients were dead at discharge.ConclusionsCollaboration among institutions is necessary to establish practice guidelines for the choice and placement of multimodal monitors. Further advancement in device technology is needed to improve insertion techniques, inter-device compatibility, and device durability. Multimodality data needs to be analyzed to determine the preferable device location.

Systemic glucose and brain energy metabolism after subarachnoid hemorrhage.

BackgroundBrain energy metabolic crisis (MC) and lactate–pyruvate ratio (LPR) elevations have been linked to poor outcome in comatose patients. We sought to determine if MC and LPR elevations after subarachnoid hemorrhage (SAH) are associated with acute reductions in serum glucose.MethodsTwenty-eight consecutive comatose SAH patients that underwent multimodality monitoring with intracranial pressure and microdialysis were studied. MC was defined as lactate/pyruvate ratio (LPR)xa0≥xa040 and brain glucosexa0<xa00.7xa0mmol/l. Time-series data were analyzed using a multivariable general linear model with a logistic link function for dichotomized outcomes.ResultsMultimodality monitoring included 3,178xa0h of observation (mean 114xa0±xa065xa0h per patient). In exploratory analysis, serum glucose significantly decreased from 8.2xa0±xa01.8xa0mmol/l (148xa0mg/dl) 2xa0h before to 6.9xa0±xa01.9xa0mmol/l (124xa0mg/dl) at the onset of MC (Pxa0<xa00.001). Reductions in serum glucose of 25% or more were significantly associated with new onset MC (adjusted odds ratio [OR] 3.6, 95% confidence interval [CI] 2.2–6.0). Acute reductions in serum glucose of 25% or more were also significantly associated with an LPR rise of 25% or more (adjusted OR 1.6, 95% CI 1.1–2.4). All analyses were adjusted for significant covariates including Glasgow Coma Scale and cerebral perfusion pressure.ConclusionsAcute reductions in serum glucose, even to levels within the normal range, may be associated with brain energy metabolic crisis and LPR elevation in poor-grade SAH patients.

Effects of the neurological wake-up test on clinical examination, intracranial pressure, brain metabolism and brain tissue oxygenation in severely brain-injured patients

IntroductionDaily interruption of sedation (IS) has been implemented in 30 to 40% of intensive care units worldwide and may improve outcome in medical intensive care patients. Little is known about the benefit of IS in acutely brain-injured patients.MethodsThis prospective observational study was performed in a neuroscience intensive care unit in a tertiary-care academic center. Twenty consecutive severely brain-injured patients with multimodal neuromonitoring were analyzed for levels of brain lactate, pyruvate and glucose, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and brain tissue oxygen tension (PbtO2) during IS trials.ResultsOf the 82 trial days, 54 IS-trials were performed as interruption of sedation and analgesics were not considered safe on 28 days (34%). An increase in the FOUR Score (Full Outline of UnResponsiveness score) was observed in 50% of IS-trials by a median of three (two to four) points. Detection of a new neurologic deficit occurred in one trial (2%), and in one-third of IS-trials the trial had to be stopped due to an ICP-crisis (> 20 mmHg), agitation or systemic desaturation. In IS-trials that had to be aborted, a significant increase in ICP and decrease in PbtO2 (P < 0.05), including 67% with critical values of PbtO2 < 20 mmHg, a tendency to brain metabolic distress (P < 0.07) was observed.ConclusionsInterruption of sedation revealed new relevant clinical information in only one trial and a large number of trials could not be performed or had to be stopped due to safety issues. Weighing pros and cons of IS-trials in patients with acute brain injury seems important as related side effects may overcome the clinical benefit.

Anemia is Associated with Metabolic Distress and Brain Tissue Hypoxia After Subarachnoid Hemorrhage

BackgroundAnemia is frequently encountered in critically ill patients and adversely affects cerebral oxygen delivery and brain tissue oxygen (PbtO2). The objective of this study is to assess whether there is an association between anemia and metabolic distress or brain tissue hypoxia in patients with subarachnoid hemorrhage.MethodsRetrospective study was conducted in a neurological intensive care unit in a university hospital. Patients with subarachnoid hemorrhage that underwent multimodality monitoring with intracranial pressure, PbtO2 and microdialysis were analyzed. The relationships between hemoglobin (Hb) concentrations and brain tissue hypoxia (PbtO2 ≤xa015xa0mmHg) and metabolic distress (lactate/pyruvate ratio ≥40) were analyzed with general linear models of logistic function for dichotomized outcomes utilizing generalized estimating equations.ResultsA total of 359 matched neuromonitoring hours and Hb measurements were analyzed from 34 consecutive patients. The median hemoglobin was 9.7xa0g/dl (interquartile range 8.8–10.5). After adjusting for significant covariates, reduced hemoglobin concentration was associated with a progressively increased risk of brain tissue hypoxia (adjusted OR 1.7 [1.1–2.4]; Pxa0=xa00.01 for every unit decrease). Also after adjusting for significant covariates, hemoglobin concentrations below 9xa0g/dl and between 9.1 and 10 g/dl were associated with an increased risk of metabolic distress as compared to concentrations between 10.1 and 11 g/dl (adjusted OR 3.7 [1.5–9.4]; Pxa0=xa00.004 for Hbxa0≤xa09xa0g/dl and adjusted OR 1.9 [1.1–3.3]; Pxa0=xa00.03 for Hb 9.1–10xa0g/dl).ConclusionsAnemia is associated with a progressively increased risk of cerebral metabolic distress and brain tissue hypoxia after subarachnoid hemorrhage.

Global Cerebral Edema and Brain Metabolism After Subarachnoid Hemorrhage

Background and Purpose— Global cerebral edema is common among patients with poor-grade subarachnoid hemorrhage and is associated with poor outcome. Currently no targeted therapy exists largely due to an incomplete understanding of the underlying mechanisms. Methods— This is a prospective observational study including 39 consecutive patients with poor-grade subarachnoid hemorrhage with multimodal neuromonitoring. Levels of microdialysate lactate–pyruvate ratio, episodes of cerebral metabolic crisis (lactate-pyruvate ratio >40 and brain glucose <0.7 mmol/L), brain tissue oxygen tension, cerebral perfusion pressure, and transcranial Doppler sonography flow velocities were analyzed. Results— Median age was 54 years (range, 45 to 61 years) and 62% were female. Patients with global cerebral edema on admission (n=24 [62%]) had a higher incidence of metabolic crisis in the first 12 hours of monitoring (n=15 [15% versus 2%], P<0.05) and during the total time of neuromonitoring (20% versus 3%, P<0.001) when compared to those without global cerebral edema. There was no difference in brain tissue oxygen tension or cerebral perfusion pressure between the groups; however, in patients with global cerebral edema, a higher cerebral perfusion pressure was associated with lower lactate–pyruvate ratio (P<0.05). Episodes of metabolic crisis were associated with poor outcome (modified Rankin Scale score 5 or 6, P<0.05). Conclusions— In patients with poor-grade subarachnoid hemorrhage, global cerebral edema is associated with early brain metabolic distress.

Intracortical EEG for the Detection of Vasospasm in Patients with Poor-Grade Subarachnoid Hemorrhage

BackgroundTo study the feasibility of utilizing intracortical electroencephalography (ICE) including quantitative EEG (qEEG) analysis for the detection of vasospasm in five consecutive poor-grade SAH patients.MethodsIntracortical electroencephalography (ICE) was obtained via a single miniature parenchymal 8-contact depth electrode placed at the bedside. Quantitative EEG parameters, calculated on surface EEG and ICE, included alpha/delta ratio (ADR), mean amplitude, suppression percent, and total power. Percent changes between averaged values over 4–6xa0h of baseline EEG and EEG prior to angiography were calculated. The entire continuous qEEG recording for each patient was then reviewed to determine optimal automated alarm criteria.ResultsICE ADR was the most accurate for predicting angiographic vasospasm (5/5). ICE ADR decreased between baseline and follow-up by 42% (from 0.56xa0±xa00.07 to 0.32xa0±xa00.03) for those with vasospasm (Nxa0=xa03) compared to 17% (0.62xa0±xa00.06 to 0.51xa0±xa00.03) for those without (Nxa0=xa02). A sustained decrease in the ICE ADR from baseline (>25% for ≥4xa0h) occurred in all three patients with angiographically confirmed vasospasm and not in the two without; this decline occurred 1–3xa0days prior to angiographic confirmation.ConclusionsIntracortical EEG is promising for detecting ischemia from vasospasm in poor-grade SAH patients, may be superior to scalp EEG, and allow automated detection, particularly using the ADR. Larger studies are needed to better define the effectiveness of this approach.

Early neurological deterioration after subarachnoid haemorrhage: risk factors and impact on outcome

Background Early neurological deterioration occurs frequently after subarachnoid haemorrhage (SAH). The impact on hospital course and outcome remains poorly defined. Methods We identified risk factors for worsening on the Hunt–Hess grading scale within the first 24u2005h after admission in 609 consecutively admitted aneurysmal SAH patients. Admission risk factors and the impact of early worsening on outcome was evaluated using multivariable analysis adjusting for age, gender, admission clinical grade, admission year and procedure type. Outcome was evaluated at 12u2005months using the modified Rankin Scale (mRS). Results 211 patients worsened within the first 24u2005h of admission (35%). In a multivariate adjusted model, early worsening was associated with older age (OR 1.02, 95% CI 1.001 to 1.03; p=0.04), the presence of intracerebral haematoma on initial CT scan (OR 2.0, 95% CI 1.2 to 3.5; p=0.01) and higher SAH and intraventricular haemorrhage sum scores (OR 1.05, 95% CI 1.03 to 1.08 and 1.1, 95% CI 1.01 to 1.2; p<0.001 and 0.03, respectively). Early worsening was associated with more hospital complications and prolonged length of hospital stay and was an independent predictor of death (OR 12.1, 95% CI 5.7 to 26.1; p<0.001) and death or moderate to severe disability (mRS 4–6, OR 8.4, 95% CI 4.9 to 14.5; p=0.01) at 1u2005year. Conclusions Early worsening after SAH occurs in 35% of patients, is predicted by clot burden and is associated with mortality and poor functional outcome at 1u2005year.

Intracerebral Monitoring of Silent Infarcts After Subarachnoid Hemorrhage

BackgroundSilent infarction is common in poor-grade subarachnoid hemorrhage (SAH) patients and associated with poor outcome. Invasive neuromonitoring devices may detect changes in cerebral metabolism and oxygenation.MethodsFrom a consecutive series of 32 poor-grade SAH patients we identified all CT-scans obtained during multimodal neuromonitoring and analyzed microdialysis parameters and brain tissue oxygen tension (PbtO2) preceding CT-scanning.ResultsEighteen percent of the reviewed head-CTs (12/67) revealed new infarcts. Of the eight infarcts in the vascular territory of the neuromonitoring, seven were clinically silent. Neuromonitoring changes preceding radiological evidence of infarction included lactate-pyruvate-ratio elevation and brain glucose decreases when compared to those with distant or no ischemia (Pxa0≤xa00.03, respectively). PbtO2 was lower, but this did not reach statistical significance.ConclusionsThese data suggest that there may be distinct changes in brain metabolism and oxygenation associated with the development of silent infarction within the monitored vascular territory in poor-grade SAH patients. Larger prospective studies are needed to determine whether treatment triggered by neuromonitoring data has an impact on outcome.

High-dose intra-arterial verapamil for the treatment of cerebral vasospasm after subarachnoid hemorrhage: Prolonged effects on hemodynamic parameters and brain metabolism

BACKGROUND: Studies attempting to establish the safety and efficacy of standard and high-dose intra-arterial infusions of calcium channel blockers for treatment of cerebral vasospasm have focused on hemodynamic changes during the angiographic procedure. OBJECTIVE: To evaluate longer-term drug effects over the hours following infusion and the effects on brain tissue oxygen tension or cerebral metabolism. METHODS: We studied 11 patients with poor-grade aneurysmal subarachnoid hemorrhages who underwent multimodality brain monitoring and angiography with infusion of high-dose intra-arterial verapamil (≥15 mg total dose). Hourly intracerebral microdialysis measurements and continuously recorded mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Pbto2 were analyzed for 6 hours before and 12 hours following treatment. RESULTS: A median dose of 23 mg (range, 15-55 mg) of intra-arterial verapamil was given. Compared with baseline values, reductions in CPP and MAP were maximal at 3 hours postangiography (from 105 ± 13 mm Hg to 95 ± 15 mm Hg and from 116 ± 12 mm Hg to 106 ± 16 mm Hg, P < .01) and persisted for up to 6 hours (P < .04); increases in vasopressor therapy were required in 8 procedures (53%). ICP significantly increased during the first 3 hours post angiography (P < .03). Brain glucose increased by 33% by hour 9 (P < .001). There were no significant changes in Pbto2 or the lactate/pyruvate ratio. CONCLUSION: High-dose intra-arterial verapamil causes increases in ICP and reductions in CPP, followed by an increase in brain glucose levels, without altering brain oxygen tension or oxidative metabolism. Patients undergoing high-dose intra-arterial verapamil therapy warrant close hemodynamic and ICP monitoring for at least 12 hours following treatment.