Beware of the Nottingham sheriff when manipulating cerebral blood flow in subarachnoid hemorrhage.

In the Sherwood forest, while Robin Hood was busy stealing from the rich to support the poor, the Nottingham sheriff fought tirelessly against him, further oppressing the starving people. In some ways during subarachnoid hemorrhage (SAH), the brain replicates a scenario of starvation, with areas of inadequate delivery due to the initial bleeding and additional delayed ischemia, in part related to vasospasm. Increasing cerebral blood flow (CBF) could therefore be extremely helpful for the starving brain. The efficacy of the standard approach to increase CBF by Triple H therapy is often inadequate and probably limited to induced arterial hypertension (1, 2). In this issue of Critical Care Medicine, Villa et al (3) pose the intriguing hypothesis that inhalation sedation with isoflurane may be beneficial in the intensive care unit setting for patients with SAH, as this approach combines the effects of depressing metabolic rate with an increase in CBF. This would be particularly relevant to the management of SAH as patients with a poor-grade World Federation of Neurosurgical Societies score are at increased risk for developing delayed cerebral ischemia (4). In an elegantly conducted open-label double cross-over study (before-afterbefore), they demonstrate that administration of isoflurane increases both local CBF, as assessed by a thermal probe, and jugular hemoglobin saturation (SjO2) in 13 patients with SAH. These findings are interpreted, in principle, as beneficial, either locally or in global terms. However, more detailed information is needed to rule out that isoflurane might play the role of the cruel sheriff, while CBF appears increased, oxygenation and metabolism may be compromised in three different ways: by decreasing arterial pressure and consequently cerebral perfusion pressure, by increasing intracranial pressure because of increased cerebral blood volume, and by diverting flow. The first two side effects have been carefully addressed in the study. The cerebral perfusion pressure drop has been avoided using titrated vasopressors, and the risk of increasing intracranial pressure has been minimized by restricting the inclusion to patients without intracranial pressure problems. These prudent choices have protected the study population but preclude the easy generalization of this intervention to the overall population. The third potential problem, however, remains of concern. Vascular effects of isoflurane in a heterogeneous vascular bed, as in SAH, may be variable and counterproductive. Even in healthy humans, isoflurane may cause a redistribution of flow, increasing flow in subcortical regions (5). It is possible that in pathologic circumstances, such as in SAH, vasodilatation induced by isoflurane may occur in intact, rather than in damaged intracranial vessels, as in case of vasospasm. In this scenario, flow could be diverted from areas suffering from vasospasm (where vascular resistance is high) to areas already well perfused, where vasodilatation would further decrease resistance. In this scenario, unaffected vessels then “steal” the flow, potentially increasing ischemia in areas at risk: the rich will become richer at the expense of the poor, as in the stereotype of the Nottingham sheriff. The risk of dangerous flow diversion, in case of vasospasm, would seem to be substantial. Further investigation of this issue is therefore necessary, perhaps by positron emission tomography or other techniques simultaneously quantifying CBF in different areas of the brain. Contrary to expectations, Villa et al (3) found that the velocity of the blood flow in the right and left middle cerebral artery measured by transcranial Doppler did not change during isoflurane administration. There is the possibility that with isoflurane not only blood may be shunted from damaged to healthy regions but also that shunting of blood through short capillaries, which are less effective in oxygen and glucose transfer than the long capillaries, may occur. The increased flow through short capillaries may then increase thermal convection, which forms the basis for measurements of CBF by thermal diffusion flowmetry. As a consequence, local CBF may appear increased, while tissue oxygenation and metabolism are actually compromised. Support for this concept is given by the observation that SjO2 was higher during isoflurane administration, indicating decreased oxygen extraction relative to perfusion. The observed increase in regional CBF may, in this case, be artifactual; even if real, however, no inference can be made from the present data concerning its usefulness. Additional limitations with regard to the generalizability of study findings exist. The study tests were performed relatively early after SAH, at a time when delayed ischemia is not yet such a prominent feature. Further studies are required to explore if the findings also hold in patients with active vasospasm. The study explored the effects of short-term isoflurane inhalation (1 hr). However, the possibility that the long-term use of isoflurane may be neurotoxic should be recognized (6). We therefore are reluctant to uncritically accept the statement that “isoflurane could be used as a sedative agent in SAH patients not affected by elevated intracranial pressure, increasing CBF. ” Obtaining these results has required a great investment of time and effort by the investigators and their clinical department for a rigorous protocol for cerebral perfusion pressure maintenance while using a specific volatile agent delivery system (AnaConDa) in the intensive care unit. Such an effort requires a highly technological and expert environment on which the investigators are to be congratulated. *See also p. 2797.