311Page 2research is needed but it is plausible that benefits/risks of hyperoxia may be dependent upon the type of ischemic/hypoxic insult being treated and upon the timing of therapy. With lack of better evidence, use of pulseoximetry to optimize hemoglobin saturation may provide the safest compromise when deciding upon oxygen doseduring resuscitation.
Carbon Dioxide
One of the brain’s most primitive and resilient mechanisms of blood flow regulation is responsivity toarterial carbon dioxide concentration (PaCO
2
). Because reduced PaCO
2
is associated with reduced cerebral bloodflow (CBF), and because reduced CBF is associated with reduced intracranial pressure (ICP), it had been common practice to treat intracranial hypertension with hypocapnia. This was extended to the operating room, particularly inthe place of space-occupying lesions. Further, some drugs such as volatile anesthetics can increase ICP, but this isattenuated with hyperventilation.
10
Although these points of logic appear to provide sound rationale for employinghyperventilation in brain-injured patients, the logic ignores a potentially important issue. If the dilemma presented by intracranial hypertension is decreased perfusion pressure, potentially severe enough to render tissue ischemic,does it make sense to treat ischemia with a vasoconstrictive intervention such as hyperventilation? This plausiblycould, in fact, exacerbate ischemia. This question remained unresolved until recently when proton emissiontomography was used to study patients with TBI. Reducing PaCO
2
from 35-40 mm Hg to only 30 mm Hg caused a2.5-fold increase in the volume of brain having flow values <10 ml/100gm/min.
11
This is consistent with the only prospective trial of hyperventilation on TBI outcome which observed a decreased number of patients with resultantgood or moderate disability when chronic hyperventilation was employed.
12
Information such as this has causedthe Brain Trauma Foundation (American Association of Neurological Surgeons) to advise that use of hyperventilation “should be avoided during the first 5 days after severe TBI and particularly during the first 24hours”.
13
It remains unresolved whether acute hyperventilation provides improved outcome value for pendingtranstentorial herniation or when rapid surgical decompression of a hematoma (e.g., epidural) is anticipated. Withinthe context of focal ischemic stroke, clinical trials have found no benefit from induced hypocapnia,
14,15
althoughhyperventilation is still sometimes employed in cases of refractory brain edema. Use of hyperventilation duringcardiopulmonary resuscitation may serve to increase mean intrathoracic pressure thereby decreasing perfusion pressure and is not advocated.
16
Overall, hyperventilation appears to offer greater opportunity to worsen rather than improve outcome froma cerebral ischemic insult. Monitoring end-tidal CO
2
and PaCO
2
can provide information necessary to maintainnormocapnia.
Blood Glucose
Critical substrates for aerobic glycolysis include oxygen and glucose, neither of which the brain maintainsin meaningful reserve. In the face of oxygen deprivation, the brain converts to aerobic glycolysis. Althoughincreased glucose concentrations would seem advantageous to support this survival mechanism of ATP production,many laboratory and clinical studies have found this not to be true. The mechanism by which hyperglycemiaaugments ischemic brain injury remains controversial. Substantial evidence indicates that intracellular lacticacidosis inhibits ionic balance and enzymatic function. Hyperglycemia also promotes recruitment of inflammatorycells, free radical formation, and endothelial cell dysfunction.
In vitro
research has suggested that hyperglycemia-induced glucocorticoid release contributes to injury although this has been questioned with
in vivo
studies.
17
Regardless of mechanism, even modest increases in blood glucose prior to or during an ischemic insult persistentlyworsen outcome in humans and laboratory models. There is increasing evidence that treatment with insulin to provide euglycemia improves clinical outcome in adult stroke.
18
The threshold values that would trigger suchintervention have not been adequately defined. In rats, a plasma glucose threshold of approximately 180 mg/dl wasnecessary to induce an adverse effect in ischemic brain.
19
In contrast, Lanier et al.
20
found intravenous glucose, inan amount insufficient to cause appreciable changes in plasma glucose concentration, was sufficient to markedlyworsen outcome from complete cerebral ischemia in primates. It has been documented that regulation of plasmaglucose below 140 mg/dl
21
or blood glucose within 90-100 mg/dl
22
substantially reduced mortality in critical care patients. Thus, different targets for insulin-induced glucose regulation could be argued for in patients withischemic/hypoxic injury. Of note, in rats overtreated with insulin following a focal ischemic insult, hypoglycemiaworsened outcome.
23
The above data, while not specific to the perioperative patient, provide sufficient evidence that blood or plasma glucose should be monitored in the acute phase of brain injury. Evidence also suggests thattreatment of hyperglycemia with insulin to establish a euglycemic state may improve outcome.
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