Monro-Kellie Doctrine

In 1783, Alexander Monro stated that the cranium was a “rigid box” filled with a “nearly incompressible brain.” The cranium and its constituents (blood, cerebrospinal fluid, and brain tissue) create a state of volume equilibrium, such that any increase in volume of one of the components must be offset by a decrease in volume of another. In 1824, George Kellie confirmed many of Monro’s early observations.

This compensatory mechanism as described in the Monro-Kellie doctrine is a limited one. Because the cranium is by nature a noncompliant vault, once the compensatory mechanisms have been exhausted, a given increase in the volume of one factor will result in a dramatic increase in intracranial pressure. The relationship between intracranial pressure and volume is shown in Figure 38-1. It should be noted that patients with a space-occupying lesion may be situated more to the right on the compliance curve shown in Figure 38-1 than those without such a lesion. This means that although small increases in intracranial volume may be tolerated in healthy patients, individuals situated toward the right of this curve may decompensate as a result of further increments in intracranial volume.

Cerebral Perfusion Pressure

Cerebral perfusion pressure (CPP) is defined as the difference between the force driving blood into the brain (mean arterial pressure [MAP]) and the force resisting movement of blood into the brain (intracranial pressure [ICP] or central venous pressure [CVP], whichever is the highest).

Cerebral perfusion pressure therefore can be reduced by decreases in mean arterial pressure (hypotension) or increases in intracranial pressure (see next section) or central venous pressure (caused by coughing or vomiting). In a study by McPherson et al.³⁹ with two groups of beagle dogs anesthetized with thiopental and maintained on isoflurane, cerebral perfusion pressure was 82 ± 5 mm Hg (10.9 ± 0.7 kPa) (mean ± standard error of the mean [SEM]).

A number of studies on human patients with severe head injuries have shown an increase in mortality and poor outcome when cerebral perfusion pressure is less than 60 mm Hg (8 kPa) for a sustained period of time.⁷³

Intracranial Pressure

Intracranial pressure (ICP) is the pressure exerted by tissues and fluids within the skull. Under normal circumstances, intracranial pressure ranges from 5 to 12 mm Hg (0.7 to 1.6 kPa).⁴³ In a study by Mazzoni et al.³⁷ with eight mongrel dogs anesthetized with acepromazine and pentobarbital and mechanically ventilated with 70% N₂O in oxygen to maintain arterial carbon dioxide tension at approximately 35 mm Hg (4.7 kPa), intracranial pressure was 8 ± 0.5 mm Hg (1.1 ± 0.07 kPa) (mean ± SEM). Intracranial hypertension (elevated intracranial pressure) may result from an expanding tissue or fluid mass, depressed skull fracture, interference with normal absorption of cerebrospinal fluid, or systemic disturbances promoting brain edema.

Cerebral Blood Flow

Cerebral blood flow (CBF) is dependent on cerebral perfusion pressure. Cerebral blood flow is defined as follows:

Normal cerebral blood flow in the dog is 75.9 ± 10.4 mL/min/100 g (mean ± SEM).³⁵

Autoregulatory mechanisms maintain a relatively constant cerebral blood flow despite changes in systemic arterial pressure (Figure 38-2). However, this autoregulation fails if systemic mean arterial pressure falls below 60 mm Hg.^35,46 From this point on, cerebral blood flow declines linearly with systemic arterial pressure. This implies that these patients are more susceptible to cerebral ischemia resulting from low mean arterial pressure. Similarly, at systemic mean arterial pressures higher than ≈180 mm Hg, cerebral perfusion pressure can augment linearly with arterial pressure.⁴⁶ In such cases, an abrupt increase in systemic arterial pressure can result in a dangerous elevation of intracranial pressure. It is worth noting that this autoregulation can become impaired or abolished by a variety of insults, including trauma, hypoxemia, hypercapnia (Figure 38-3), and large-dose volatile anesthetics (Figure 38-4). Moreover, some patients with traumatic brain injury have a rightward shifted lower limit of autoregulation, necessitating the maintenance of a higher mean arterial pressure than normal.⁷³

Cerebral Metabolic Rate for Oxygen

Cerebral metabolic rate for oxygen (CMRO₂) is the volume of O₂ metabolized by the brain per unit of time. Published normal values in the dog are on the order of 3.5 ± 0.3 mL/min/100 g.³⁹ When considered with respect to total body oxygen consumption, the brain accounts for approximately 20% of the total body oxygen requirement. Sixty percent of the CMRO₂ is used in generating adenosine triphosphate (ATP) to support neuronal activity, and 40% is used for maintaining cellular integrity.

CMRO₂ can be increased in conditions such as pyrexia and seizures, and may increase with the use of certain drugs. To preserve cerebral oxygenation, oxygen supply should exceed cerebral oxygen demand. Thus, a reduction in CMRO₂ is desirable. Pharmacologic (e.g., benzodiazepines, barbiturates, propofol) and nonpharmacologic (e.g., hypothermia) maneuvers can be used to decrease CMRO₂.

Cushing’s Response

When intracranial pressure is high, cerebral perfusion pressure is low. When cerebral perfusion pressure is low, cerebral blood flow (i.e., perfusion of the brain with arterial blood) decreases, reducing delivery of oxygen to the brain. Reduced delivery of oxygen to the brain stimulates release of catecholamines, which results in an increase in mean arterial pressure. However, this increase in mean arterial pressure stimulates pressure receptors in the aortic arch and carotid bodies, causing the heart rate to decrease, giving rise to the Cushing’s response. The response therefore is characterized by systemic hypertension and bradycardia, which occur secondary to intracranial hypertension. If the Cushing’s response develops, therapy should be directed toward reducing intracranial pressure rather than treating the hemodynamic changes observed.

Glycemia

Syring et al.⁶⁴ found correlation in dogs and cats presented with head trauma between blood glucose concentrations on admission and severity of their neurologic condition. However, in this study, the degree of hyperglycemia could not be associated with outcome. Adverse metabolic and cerebral ischemic effects of high blood glucose concentrations are well documented. The influence of hyperglycemic ischemia on tissue damage and cerebral blood flow was studied in rats subjected to short-lasting transient middle cerebral artery occlusion.¹⁷ Brief focal cerebral ischemia combined with hyperglycemia led to larger and more severe tissue damage. The mechanistic basis for this remains unclear. The most persistent hypothesis is that glucose, in the absence of oxygen, undergoes anaerobic glycolysis, resulting in intracellular acidosis, which amplifies the severity of other deleterious cascades initiated by the ischemic insult.

Intravenous Agents

The drugs most frequently employed for craniotomy in human patients include local anesthetics, the opioids sufentanil and remifentanil, propofol, and the alpha-2 agonist dexmedetomidine and clonidine.²⁰ However, a number of agents can be safely and successfully used to anesthetize patients for neurosurgery.

Short-acting drugs are advantageous in neuroanesthesia; rapid, high-quality recoveries, as well as the ability to titrate effects, are more easily achieved with such agents. As a result, the use of constant rate infusion (CRI) is common practice during these procedures because this offers more rapid moment-to-moment control should physiologic changes occur.