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Cerebral Hyperemia, Systemic Hypertension, and Perioperative Intracranial Morbidity: Is There a Smoking Gun?

Schubert, Armin, MD

doi: 10.1097/00000539-200203000-00002
Editorials: Editorial

Department of General Anesthesiology, Cleveland Clinic Foundation, Cleveland, Ohio

November 20, 2001.

Address correspondence to Armin Schubert, MD, Department of General Anesthesiology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.

Emergence from anesthesia for intracranial surgery may be accompanied by coughing, ventilatory insufficiency and hypertension. Anesthesiologists and surgeons share a concern that this may cause intracranial complications such as bleeding and brain edema. Early intracranial hypertension after elective craniotomy occurs in nearly 20% of patients. Intracranial hemorrhage (ICH) accounts for a substantial portion of this incidence (1). ICH can be a devastating complication of surgery, occurring in 0.9%–3.5% of cranial surgery cases (2–4). Compared with extensive study of intraoperative cerebrovascular pathophysiology, little work has been done to define the cerebral circulatory state after craniotomy and to relate it to the occurrence of postoperative complications. The contribution by Bruder et al. (5) in this month’s issue of Anesthesia & Analgesia is particularly welcome because it expands our understanding in an underinvestigated area.

More than a decade ago it was appreciated that the cerebral arterio-venous oxygen content difference (AVDO2) is depressed immediately after craniotomy, a finding taken to be suggestive of a state of luxury perfusion (6,7). However, cerebral AVDO2 is determined by both cerebral blood flow (CBF) and cerebral metabolic rate (CMR). Changes in AVDO2 are difficult to interpret unless either is known.

In a two-part prospective clinical trial of elective craniotomy patients, Bruder et al. (5) report transcranial Doppler (TCD) data confirming the occurrence of cerebral hyperemia on anesthetic emergence. This observation held true whether patients had operations for brain tumor or unruptured cerebral aneurysm clipping. It occurred whether patients were anesthetized with propofol or isoflurane. There was a 60%–80% increase in cerebral blood flow velocity (CBFV) from preinduction baseline on extubation that persisted at a lower level (20%–40% increase) for at least 1 h.

The authors’ speculation that “stress” is likely to have accounted for the hyperemic response bears comment. Certainly, stimulation is high during tracheal extubation and peripheral sensory afferent traffic is likely increased during this time, manifesting in increased CMR and CBF. Stimulation from the endotracheal tube increases CBF (8), an effect that can be ablated by sufficient anesthetic dose (9). Although plasma norepinephrine levels increase during tracheal intubation (10), norepinephrine administration is actually associated with reduction in CBF (11). Circulating catecholamines, therefore, could not account for the occurrence of cerebral hyperemia. This leaves us with metabolic stress from brain activation. In the Bruder et al. study (5), CMR was not measured directly, leaving open the possibility that it was unchanged, depressed, or somewhat, but not proportionally, increased in relation to CBF. The latter would be necessary to invoke a cerebral metabolic stress response with secondary blood flow increases. Interestingly, this pattern of partial uncoupling between CBF and CMR also occurs on return to normocarbia after prolonged hypocarbia (12).

The investigators dismiss factors other than stress, such as hemodilution, anesthetic-induced autoregulation failure, and recovery from prolonged hyperventilation, as confounders that could have accounted for the observed short-lived cerebral hyperemia. Despite their arguments, a CBF effect from return to normocapnia after prolonged hypocapnia cannot be as easily discounted as the investigators are ready to do. They rely heavily on previously reported CBF increments per mm Hg Paco2 and the absence of a correlation of Paco2 with their CBFV data. Such data and correlations are not necessarily relevant considering that, on return to normocapnia after prolonged hypocapnia, CBF increases in response to perivascular pH. Because of a slow but substantial loss in cerebrospinal fluid (CSF) bicarbonate, perivascular pH is likely depressed more than is appreciated from the increase in Paco2 and therefore may lead to a substantial hyperemia (12) despite a nearly normal Paco2. CSF pH-related cerebral hyperemia would be expected to occur independent of anesthetic regimens and to follow a transient course.

These considerations leave return from hypocapnia, albeit mild to moderate, as an important plausible explanation for the observed hyperemic changes in the Bruder et al. (5) study. Before embarking on a search for the mechanism responsible for early postoperative cerebral luxury perfusion, future investigators would do well to examine the influence of prolonged hyperventilation more closely.

Does blood pressure drive CBF and the resultant transcranial Doppler-measurable hyperemia, putting patients at risk for intracerebral bleeding? A link between blood pressure and cerebral hyperemia is, at least in theory, easily explained. Almost all patients exhibit some degree of hypertension in the early postoperative period after cranial surgery (13). Blood pressure may increase too rapidly for cerebral autoregulatory control to be effective. Furthermore, brain areas near the operative site may not autoregulate well because of retractor ischemia or residual tumor. Abrupt increases in blood pressure would readily overwhelm autoregulatory mechanisms, causing cerebral luxury perfusion instantly, which may then continue because of postoperative autoregulatory dysfunction.

Let us examine whether such theoretical explanations are substantiated by fact. In Bruder et al.’s (5) patients, hyperemic responses occurred despite good blood pressure control. This is consistent with other observations. Felding et al. reported metoprolol (14) and ketanserin (15) to control blood pressure without affecting the transient hyperemia manifested by low AVDO2 after craniotomy. Blood pressure control after carotid endarterectomy likewise did not prevent hyperemic responses (16). Available evidence indicates that although blood pressure control may be a desirable and achievable goal after intracranial surgery, it cannot rationally be expected to prevent cerebral hyperperfusion.

It is now possible to control blood pressure quite well during emergence from craniotomy without affecting CBF. Much less certain is whether blood pressure control can avert or even reduce the risk of intracranial bleeding after craniotomy, the occurrence of which substantially increases length of hospital stay, mortality, and, by implication, the cost of care (2). Postoperative hypertension has been implicated as a risk factor for intracranial bleeding. Our group reported a strong association between intraoperative or immediate (12-h) postoperative hypertension with the development of subsequent ICH (2). Others reported ICH related to systemic hypertension in anticoagulated patients (17,18) and those with normal coagulation status (3,19).

Despite the plethora of data pointing to a “smoking gun,” there are no prospective randomized controlled trials showing a reduction of intracranial bleeding episodes with postoperative blood pressure control at any level. It is tempting to speculate that blood pressure control cannot result in better bleeding outcomes because control of hypertension does not affect the occurrence of hyperemia.

To convert speculation to fact, additional investigative work is needed to find the missing link between the occurrence of perioperative hypertension and the development of postcraniotomy ICH. Much effort has been expended to achieve safe and effective blood pressure control for craniotomy patients.

The time is now ripe to understand whether blood pressure control improves neurological outcome. The large expenditure of national health care resources on postoperative blood pressure control (20) should alone justify the performance of a randomized, controlled, multicenter trial aimed at investigating the benefits of blood pressure control. It is quite possible that its benefits are more pronounced in certain higher-risk populations. This is well illustrated by the observation that glioblastoma, craniotomy revision, and long surgical duration represent risk factors for early postoperative intracranial hypertension (1).

If hyperemia occurs despite good blood pressure control, are there other potential pathophysiologic mechanisms that could account for its development and independently also put patients at risk for intracranial bleeding? Radiologic evaluation of brain tumors after resection shows intravascular contrast enhancement 3 days postoperatively within residual tumor, attributed to the absence of a blood-brain barrier, and at 7–14 days, attributed to neovascularization (21). These observations point to other mechanisms besides hyperemia that could contribute to the development of intracranial bleeding after brain tumor resection.

The study of Bruder et al. (5), by demonstrating increased CBFV concurrent with the previously known reduced cerebral AVDO2, proves the existence of transient cerebral hyperemia during the first hour after craniotomy for elective intracranial surgery. By describing CBFV, the investigators contributed significantly to our knowledge of the cerebral circulatory physiology of emergence from anesthesia after craniotomy. However, cerebral hyperemia after emergence from craniotomy appears to be a short-lived phenomenon whose etiology and importance to surgical patient outcome is unclear. The investigators speculate about a number of potential pathophysiologic mechanisms, but their study design cannot distinguish among them. Although they have certainly revived interest in a “smoking gun,” they have not yet found it.

The clinical importance of an hour’s worth of asymptomatic cerebral hyperemia is far from certain. But other questions need answering as well: Do cerebral hyperemic episodes happen after the first postoperative hour and return from prolonged hypocapnia? If so, is their etiology different from that of immediate postoperative luxury perfusion? Are later episodes related to the development of bleeding and cerebral edema? Can long acting drugs or other interventions, administered before and during anesthesia, modify the risk of bleeding and edema formation after cranial surgery through identifiable mechanisms? As is readily apparent, there is fertile ground for further study and Dr. Bruder’s team should be congratulated for providing encouragement to proceed productively along these lines of investigation.

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