Pedro Kurtz

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.

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.

Continuous EEG monitoring: is it ready for prime time?

Purpose of reviewContinuous electroencephalography (cEEG) is being used more frequently in intensive care units to detect epileptic activity and ischemia. This review analyzes clinical applications and limitations of cEEG as a routine neuromonitoring tool. Recent findingscEEG is primarily used to detect nonconvulsive seizures, which are frequent and possibly associated with harm. Cerebral ischemia, such as that from vasospasm after subarachnoid hemorrhage, can be detected earlier by EEG and quantitative EEG (qEEG). Highly skilled technicians and subspecialty-trained physicians are needed to generate good quality EEG and to interpret these data. qEEG allows more efficient interpretation of large amounts of EEG and may trigger prespecified alarms. Currently, there is little high-quality data on cEEG to define indications, cost-saving potential, and impact on outcome. A few studies have demonstrated how cEEG can be integrated into multimodality brain monitoring of severely brain-injured patients. SummarycEEG should be considered as an integral part of multimodality monitoring of the injured brain, particularly in patients at risk for nonconvulsive seizure or ischemia. Automated alarms may help establish cEEG monitoring as an integral part of brain monitoring. All neurological ICUs that routinely care for patients with refractory status epilepticus should have the capability to perform cEEG monitoring. Further research determining the impact on outcome and making EEG monitoring more user friendly may help move this technique out of the subspecialized ICU setting into the general ICU environment. In the future, it may be possible to use specific EEG parameters as endpoints for therapeutic interventions.

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.

Brain interstitial fluid TNF-α after subarachnoid hemorrhage

OBJECTIVE TNF-alpha is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-alpha may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH). METHODS We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8h and recorded at the same point that brain interstitial fluid TNF-alpha was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations. RESULTS Each patient had a mean of 9 brain tissue TNF-alpha measurements obtained over an average of 72h of monitoring. TNF-alpha levels rose progressively over time. Predictors of elevated brain interstitial TNF-alpha included higher brain interstitial fluid glucose levels (beta=0.066, p<0.02), intraventricular hemorrhage (beta=0.085, p<0.021), and aneurysm size >6mm (beta=0.14, p<0.001). There was no relationship between TNF-alpha levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate-pyruvate ratio. INTERPRETATION Brain interstitial TNF-alpha levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels.

Clinical practices, complications, and mortality in neurological patients with acute severe hypertension: the Studying the Treatment of Acute hyperTension registry.

Objective:To determine the demographic and clinical features, hospital complications, and predictors of 90-day mortality in neurologic patients with acute severe hypertension. Design:Studying the Treatment of Acute hyperTension (STAT) was a multicenter (n = 25) observational registry of adult critical care patients with severe hypertension treated with intravenous therapy. Setting:Emergency department or intensive care unit. Patients:A qualifying blood pressure measurement >180 mm Hg systolic or >110 mm Hg diastolic (>140/90 mm Hg for subarachnoid hemorrhage) was required for inclusion in the STAT registry. Patients with a primary neurologic admission diagnosis were included in the present analysis. Interventions:All patients were treated with at least one parenteral (bolus or continuous infusion) antihypertensive agent. Measurements and Main Results:Of 1,566 patients included in the STAT registry, 432 (28%) had a primary neurologic diagnosis. The most common diagnoses were subarachnoid hemorrhage (38%), intracerebral hemorrhage (31%), and acute ischemic stroke (18%). The most common initial drug was labetalol (48%), followed by nicardipine (15%), hydralazine (15%), and sodium nitroprusside (13%). Mortality at 90 days was substantially higher in neurologic than in non-neurologic patients (24% vs. 6%, p < .0001). Median initial blood pressure was 183/95 mm Hg and did not differ between survivors and nonsurvivors. In a multivariable analysis, neurologic patients who died experienced lower minimal blood pressure values (median 103/45 vs. 118/55 mm Hg, p < .0001) and were less likely to experience recurrent hypertension requiring intravenous treatment (29% vs. 51%, p = .0001) than those who survived. Mortality was also associated with an increased frequency of neurologic deterioration (32% vs. 10%, p < .0001). Conclusion:Neurologic emergencies account for approximately 30% of hospitalized patients with severe acute hypertension, and the majority of those who die. Mortality in hypertensive neurologic patients is associated with lower minimum blood pressure values, less rebound hypertension, and a higher frequency of neurologic deterioration. Excessive blood pressure reduction may contribute to poor outcome after severe brain injury.

Spontaneous hyperventilation and brain tissue hypoxia in patients with severe brain injury

Background Hyperventilation has been shown to be associated with cerebral vasoconstriction and increased risk of infarction. Our aim was to determine whether spontaneous reduction in end-tidal CO2 (EtCO2) was associated with an increased in brain tissue hypoxia (BTH). Method We studied 21 consecutive patients (mean age 50±16 years; 15 women) undergoing continuous monitoring for brain tissue oxygenation (PbtO2), intracranial pressure (ICP), cerebral perfusion pressure (CPP) and EtCO2; mean values were recorded hourly BTH was defined as brain tissue oxygen tension (PbtO2) <15 mm Hg. Results Diagnoses included subarachnoid haemorrhage (67%), intracranial haemorrhage (24%) and traumatic brain injury (10%). Overall, BTH occurred during 22.5% of the study period (490/2179 hourly data). The frequency of BTH increased progressively from 15.7% in patients with normal EtCO2 (35–44 mm Hg) to 33.9% in patients with EtCO2<25 mm Hg (p<0.001). The mean tidal volume and minute ventilation were 7±2 ml/kg and 9±2 1/min, respectively. Hypocapnia was associated with higher measured-than-set respiratory rates and maximal minute ventilation values, suggestive of spontaneous hyperventilation. Using a generalised estimated equation (GEE) and after adjustment for GCS, ICP and core temperature, the variables independently associated with BTH events were EtCO2 (OR: 0.94; 95% CI 0.90 to 0.97; p<0.001) and CPP (OR: 0.98; 95% CI 0.97 to 0.99; p=0.004). Conclusion The risk of brain tissue hypoxia in critically brain-injured patients increases when EtCO2 values are reduced. Unintentional spontaneous hyperventilation may be a common and under-recognised cause of brain tissue hypoxia after severe brain injury.

Transcranial Doppler Ultrasound in the Acute Phase of Aneurysmal Subarachnoid Hemorrhage

Background: Angiographic studies suggest that acute vasospasm within 48 h of aneurysmal subarachnoid hemorrhage (SAH) predicts symptomatic vasospasm. However, the value of transcranial Doppler within 48 h of SAH is unknown. Methods: We analyzed 199 patients who had at least 1 middle cerebral artery (MCA) transcranial Doppler examination within 48 h of SAH onset. Abnormal MCA mean blood flow velocity (mBFV) was defined as >90 cm/s. Delayed cerebral ischemia (DCI) was defined as clinical deterioration or radiological evidence of infarction due to vasospasm. Results: Seventy-six patients (38%) had an elevation of MCA mBFV >90 cm/s within 48 h of SAH onset. The predictors of elevated mBFV included younger age (OR = 0.97 per year of age, p = 0.002), admission angiographic vasospasm (OR = 5.4, p = 0.009) and elevated white blood cell count (OR = 1.1 per 1,000 white blood cells, p = 0.003). Patients with elevated mBFV were more likely to experience a 10 cm/s fall in velocity at the first follow-up than those with normal baseline velocities (24 vs. 10%, p < 0.01), suggestive of resolving spasm. DCI developed in 19% of the patients. An elevated admission mBFV >90 cm/s during the first 48 h (adjusted OR = 2.7, p = 0.007) and a poor clinical grade (Hunt-Hess score 4 or 5, OR = 3.2, p = 0.002) were associated with a significant increase in the risk of DCI. Conclusion: Early elevations of mBFV correlate with acute angiographic vasospasm and are associated with a significantly increased risk of DCI. Transcranial Doppler ultrasound may be an early useful tool to identify patients at higher risk to develop DCI after SAH.

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 24 h 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 12 months using the modified Rankin Scale (mRS). Results 211 patients worsened within the first 24 h 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 1 year. 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 1 year.

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.