Venkatesh Aiyagari

Hypoperfusion Without Ischemia Surrounding Acute Intracerebral Hemorrhage

A zone of hypoperfusion surrounding acute intracerebral hemorrhage (ICH) has been interpreted as regional ischemia. To determine if ischemia is present in the periclot area, the authors measured cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), and oxygen extraction fraction (OEF) with positron emission tomography (PET) in 19 patients 5 to 22 hours after hemorrhage onset. Periclot CBF, CMRO2, and OEF were determined in a 1-cm-wide area around the clot. In the 16 patients without midline shift, periclot data were compared with mirror contralateral regions. All PET images were masked to exclude noncerebral structures, and all PET measurements were corrected for partial volume effect due to clot and ventricles. Both periclot CBF and CMRO2 were significantly reduced compared with contralateral values (CBF: 20.9 ± 7.6 vs. 37.0 ± 13.9 mL 100 g−1 min−1, P = 0.0004; CMRO2: 1.4 ± 0.5 vs. 2.9 ± 0.9 mL 100 g−1 min−1, P = 0.00001). Periclot OEF was less than both hemispheric OEF (0.42 ± 0.15 vs. 0.47 ± 0.13, P = 0.05; n = 19) and contralateral regional OEF (0.44 ± 0.16 vs. 0.51 ± 0.13, P = 0.05; n = 16). In conclusion, CMRO2 was reduced to a greater degree than CBF in the periclot region in acute ICH, resulting in reduced OEF rather than the increased OEF that occurs in ischemia. Thus, the authors found no evidence for ischemia in the periclot zone of hypoperfusion in acute ICH patients studied 5 to 22 hours after hemorrhage onset.

Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage

Background: Arterial hypertension is common in the first 24 hours after acute intracerebral hemorrhage (ICH). Although increased blood pressure usually declines to baseline values within several days, the appropriate treatment during the acute period has remained controversial. Arguments against treatment of hypertension in patients with acute ICH are based primarily on the concern that reducing arterial blood pressure will reduce cerebral blood flow (CBF). The authors undertook this study to provide further information on the changes in whole-brain and periclot regional CBF that occur with pharmacologic reductions in mean arterial pressure (MAP) in patients with acute ICH. Methods: Fourteen patients with acute supratentorial ICH 1 to 45 mL in size were studied 6 to 22 hours after onset. CBF was measured with PET and 15O-water. After completion of the first CBF measurement, patients were randomized to receive either nicardipine or labetalol to reduce MAP by 15%, and the CBF study was repeated. Results: MAP was lowered by −16.7 ± 5.4% from 143 ± 10 to 119 ± 11 mm Hg. There was no significant change in either global CBF or periclot CBF. Calculation of the 95% CI demonstrated that there is less than a 5% chance that global or periclot CBF fell by more than −2.7 mL 100 g−1 min−1. Conclusion: In patients with small- to medium-sized acute ICH, autoregulation of CBF was preserved with arterial blood pressure reductions in the range studied.

Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage

AbstractIntroduction: Warfarin-associated intracranial hemorrhage (ICH) requires rapid normalization of clotting function. Current therapies are associated with significant complications and/or prolonged time to correction of coagulopathy. Recombinant factor VIIa (FVIIa) might allow faster and safer correction of coagulopathy. Methods: This article presents a retrospective chart review of all patients with warfarin-associated ICH treated in a neurology/neurosurgery intensive care unit over an 11-month period. Results: All patients were treated to rapidly reverse the warfarin effect. Fifteen patients received vitamin K and fresh frozen plasma (FFP) alone (FFP group). Twelve patients also received FVIIa (FVIIa group). The median times from presentation to an international normalization ratio (INR) of less than 1.3 were 32.2 and 8.8 hours in the FFP the FVIIa groups, respectively (p=0.016). INR normalized slowly (at 110 and 130 hours, respectively) in two patients with end-stage renal failure who were given FVIIa, one of whom developed disseminated intravascular coagulation after three doses of FVIIa. No other complications occurred from FVIIa administration. One patient in the FFP group developed severe pulmonary edema. Conclusion: FVIIa may be an effective adjunct to FFP in warfarin-related ICH, facilitating faster correction of INR and decreasing FFP requirements. A prospective, randomized trial is needed to confirm these preliminary findings and to determine whether there is a clinical benefit.

Factors associated with withdrawal of mechanical ventilation in a neurology/neurosurgery intensive care unit.

ObjectiveThe objective of this study was to identify factors associated with the decision to withdraw mechanical ventilation from patients in a neurology/neurosurgery intensive care unit. Specifically, the following factors were considered: the severity of the neurologic illness, the healthcare delivery system, and social factors. DesignRetrospective analysis of prospectively collected clinical database. SettingNeurology/neurosurgery intensive care unit of a large academic tertiary care hospital. PatientsPatients were 2,109 nonelective admissions to the neurology/neurosurgery intensive care unit who received mechanical ventilation over a period of 82 months. InterventionsNone. Measurements and Main Results The average age was 56 ± 19.7 yrs, 53% were male, and 81% were functionally normal before admission. The median Glasgow Coma Scale score was 14, the average Acute Physiology and Chronic Health Evaluation II severity of illness score was 13.5 ± 8.3, and probability of death was 18.2 ± 22.0%. Mechanical ventilation was withdrawn from 284 (13.5%). Factors that were independently associated with withdrawal of mechanical ventilation were as follows: more severe neurologic injury [admission Glasgow Coma Scale score (odds ratio 0.86/point, confidence interval 0.82–0.90), diagnosis of subarachnoid hemorrhage (odds ratio 2.44, confidence interval 1.50–3.99), or ischemic stroke (odds ratio 1.72, confidence interval 1.13–2.60)], older age (odds ratio 1.04/yr, confidence interval 1.03–1.05), and higher Acute Physiology and Chronic Health Evaluation II probability of death (odds ratio 1.03/%, confidence interval 1.02–1.04). Mechanical ventilation was less likely to be withdrawn if patients were African-American (odds ratio 0.50, confidence interval 0.36–0.68) or had undergone surgery (odds ratio 0.44, confidence interval 0.2– 0.67). Marital status, premorbid functional status, clinical service (neurology vs. neurosurgery), attending status (private vs. academic), and type of health insurance were not associated with decisions to withdraw mechanical ventilation. ConclusionsWe conclude that decisions to withdraw mechanical ventilation in the neurology/neurosurgery intensive care unit are based primarily on the severity of the acute neurologic condition and age but not on characteristics of the healthcare delivery system. Care is less likely to be withdrawn from African-American patients or those who had surgery.

Early mortality following spontaneous intracerebral hemorrhage

The authors reviewed the charts of 1,421 patients with cerebral hemorrhage to determine the cause of death. Limitation or withdrawal of life-sustaining interventions was the most common cause of death (68%) followed by brain death (28%). Neurologic reasons were the most common cause of delayed decisions to withdraw or limit therapy. Brain death was more common in African Americans, whereas life-sustaining interventions were withdrawn or limited early more often in whites.

Management of Blood Pressure for Acute and Recurrent Stroke

Marc Fisher MD Kennedy Lees MD Section Editors: Hypertension is the most important modifiable risk factor for stroke.1,2 It is estimated that 25% or more of strokes may be attributable to hypertension. Because many patients with stroke have mild hypertension or prehypertension, we have shifted our focus and now think of stroke on a continuum of risk based on blood pressure (BP) level rather than on a threshold effect.3 Because high BP may not exist in isolation, a wider definition of hypertension has been proposed that also takes into account the absolute risk of cardiovascular events and associated metabolic factors or early disease markers.3 Lowering BP reduces the risk of stroke. Epidemiological studies have shown that for each 10 mm Hg lower systolic blood pressure (SBP), there is a decrease in risk of stroke of approximately one third in persons aged 60 to 79 years. This association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, stroke subtypes, and for fatal and nonfatal events.4 Lowering diastolic blood pressure (DBP) was once the main target to achieve stroke and other cardiovascular event reduction, but SBP has now become the target.3 As recently shown, even the elderly with sustained SBP elevation may gain from BP reduction in relation to less fatal or nonfatal stroke, death, and heart failure.5 Although the role of longer-term BP control to improve outcomes in patients with stroke is undisputed, BP management immediately after a stroke remains controversial. In an effort to resolve this controversy, several pilot clinical trials have been initiated. In this review, we discuss the results of some of these trials and available evidence-based guidelines for BP control in the settings of acute ischemic and hemorrhagic stroke (excluding subarachnoid hemorrhage) and …

Cerebral Autoregulation and Blood Pressure Lowering

Despite its comparatively small size, the brain receives a disproportionate amount of blood flow compared with most other organ systems. Cerebral blood flow is closely coupled to brain metabolism and can be affected by respiratory-induced CO2 changes and arterial blood pressure. Autoregulation is the intrinsic capacity of resistance vessels in end organs, such as heart, kidney, and brain, to dilate and constrict in response to dynamic perfusion pressure changes, maintaining blood flow relatively constant (Figure). This rapid vascular response occurs within seconds of arterial pressure fluctuations. The exact mediators of cerebral autoregulation are not completely understood. However, neurogenic stimuli; metabolic factors, such as adenosine accumulation during low perfusion; and direct intravascular pressure effects on smooth muscle or mediated via endothelial-derived relaxation factor (ie, NO) and constriction factor (ie, endothelin-1) have been implicated.1 Autoregulation maintains cerebral blood flow relatively constant between 50 and 150 mm Hg mean arterial pressure. The range is right shifted in chronically hypertensive patients. The cerebral resistance vessels in normotensive individuals are known to autoregulate across a broad range of mean arterial pressures. Perfusion pressures below the lower limit result in initially increased oxygen extraction …

Reversible left ventricular dysfunction associated with raised troponin I after subarachnoid haemorrhage does not preclude successful heart transplantation

Transient abnormalities in ECGs, echocardiograms, and cardiac enzymes have been described in the acute setting of subarachnoid haemorrhage. In addition, left ventricular dysfunction has been reported at the time of brain death. A patient with an acute subarachnoid haemorrhage who presented with raised troponin I (TnI) concentrations and diffuse left ventricular dysfunction is described. After declaration of brain death 32 hours later, the heart was felt initially not suitable for transplantation. A normal cardiac catheterisation, however, lead to successful transplantation of the donor heart. Raised catecholamine concentrations and metabolic perturbations have been proposed as the mechanisms leading to the cardiac dysfunction seen with brain death. This may be a biphasic process, allowing time for myocardial recovery and reversal of the left ventricular dysfunction. Awareness of this phenomenon in the acutely ill neurologic population needs to be raised in order to prevent the unnecessary rejection of donor hearts.

Correction of coagulopathy in warfarin associated cerebral hemorrhage

Purpose of reviewWarfarin is the most commonly used oral anticoagulant. Intracranial hemorrhage is the most serious complication of anticoagulation and the anticoagulant effect of warfarin has to be urgently reversed in this situation. Traditional methods of reversal of the anticoagulant effect of warfarin involving the use of vitamin K and fresh frozen plasma are slow and relatively ineffective and there is a need for alternative treatment approaches. Recent findingsAgents such as prothrombin complex conjugates and recombinant activated factor VII are being increasingly used to emergently correct warfarin-associated coagulopathy. Over the last decade, several small case series have suggested that these agents may lead to more rapid correction of the INR, however, improved clinical outcome is yet to be proven. A recent small prospective trial has also demonstrated the safety of a prothrombin complex conjugate and its efficacy in rapidly correcting an elevated INR in these patients. SummaryThere is a need for well designed randomized clinical trials aimed at evaluating the efficacy of these agents in improving the outcome of patients with anticoagulant associated intracranial hemorrhage.

Autoregulation after ischaemic stroke.

Objectives Absent outcome data from randomized clinical trials, management of hypertension in acute ischaemic stroke remains controversial. Data from human participants have failed to resolve the question whether cerebral blood flow (CBF) in the peri-infarct region will decrease due to impaired autoregulation when systemic mean arterial pressure (MAP) is rapidly reduced. Methods Nine participants, 1–11 days after hemispheric ischaemic stroke, with systolic blood pressure more than 145 mmHg, underwent baseline PET measurements of regional CBF. Intravenous nicardipine infusion was then used to rapidly reduce mean arterial pressure 16 ± 7 mmHg and CBF measurement was repeated. Results Compared with the contralateral hemisphere, there were no significant differences in the percent change in CBF in the infarct (P = 0.43), peri-infarct region (P = 1.00) or remainder of the ipsilateral hemisphere (P = 0.50). Two participants showed CBF reductions of greater than 19% in both hemispheres. Conclusion In this study, selective regional impairment of CBF autoregulation in the infarcted hemisohere to reduced systemic blood pressure was not a characteristic of acute cerebral infarction. Reductions in CBF did occur in some individuals, but it was bihemispheric phenomenon that likely was due to an upward shift of the autoregulatory curve as a consequence of chronic hypertension. These results indicate individual monitoring of changes in global CBF, such as with bedside transcranial Doppler, may be useful to determine individual safe limits when MAP is lowered in the setting of acute ischaemic stroke. The benefit of such an approach can only be demonstrated by clinical trials demonstrating improved patient outcome.