General Anesthesia

All inhalational anesthetics suppress central nervous system neuronal activity, producing unconsciousness through potentiation of gamma-aminobutyric acid type A receptor-mediated inhibition and, for nitrous oxide, N-methyl-D-aspartate receptor antagonism. This suppression produces characteristic dose-dependent electroencephalographic changes: progressive slowing, increasing amplitude, burst suppression, and ultimately an isoelectric tracing at supratherapeutic concentrations. Isoflurane most readily produces burst suppression at 1.5 to 2 minimum alveolar concentration — a property exploited to provide maximal metabolic protection during brief periods of deliberate vascular occlusion in neurosurgery.

Two central nervous system effects exist in clinical tension with each other. All volatile agents reduce the cerebral metabolic rate for oxygen — a desirable property that reduces the brain's vulnerability to ischemia. At the same time, all volatile agents cause cerebral vasodilation and increase cerebral blood flow, which raises intracranial blood volume and can elevate intracranial pressure in patients with reduced intracranial compliance. Managing this tension — maximizing metabolic protection while controlling intracranial pressure — is the defining challenge of neuroanesthesia.

All volatile halogenated anesthetics cause dose-dependent cerebral vasodilation, increasing cerebral blood flow at concentrations above approximately 0.5 minimum alveolar concentration. This effect is a direct action on cerebrovascular smooth muscle, independent of changes in cerebral metabolic rate. The magnitude differs among agents: halothane produces the greatest cerebral blood flow increase at equivalent doses, while isoflurane and sevoflurane produce more modest increases. Desflurane is intermediate and similar to isoflurane.

Critically, this vasodilation can be substantially counteracted by controlled hyperventilation. Reducing the arterial carbon dioxide partial pressure through deliberate hyperventilation causes cerebral vasoconstriction via carbon dioxide-mediated changes in perivascular pH, largely offsetting the anesthetic-induced vasodilation. This is the pharmacological rationale for mild hyperventilation in neurosurgical patients — it blunts the anesthetic-induced rise in cerebral blood flow and intracranial pressure. The carbon dioxide vasomotor reactivity of cerebral vessels is preserved during inhalational anesthesia, making this a reliable and rapid intervention.

Cerebral autoregulation is the ability of the cerebral vasculature to maintain relatively constant blood flow across a range of cerebral perfusion pressures (approximately 50 to 150 mmHg in healthy adults) by adjusting cerebrovascular resistance. Below the lower limit, vasodilation is maximal and blood flow falls passively with further pressure decreases, risking ischemia. Above the upper limit, forced vasodilation occurs with risk of hypertensive encephalopathy.

Volatile anesthetic agents impair cerebral autoregulation in a dose-dependent fashion. At concentrations of 1 minimum alveolar concentration or above, all volatile agents substantially reduce autoregulatory capacity, making cerebral blood flow more directly dependent on mean arterial pressure. Under deep volatile anesthesia, hypotension causes proportional reductions in cerebral blood flow, while hypertension causes proportional increases and potentially elevated intracranial pressure. This has direct implications for hemodynamic management in neurosurgical patients, where maintaining mean arterial pressure within a range that supports adequate cerebral perfusion pressure is a primary goal. Propofol, at clinical doses, preserves cerebral autoregulation better than volatile agents — one rationale for preferring total intravenous anesthesia in patients with compromised intracranial compliance.

All inhalational anesthetics reduce mean arterial pressure in a dose-dependent fashion, but the mechanism differs importantly among agents and determines which patients tolerate each agent better.

Halothane reduces blood pressure primarily through direct myocardial depression — it reduces cardiac output by depressing contractility and suppressing sinoatrial node automaticity, causing bradycardia. Systemic vascular resistance is relatively maintained. Patients with impaired myocardial function tolerate this mechanism poorly.

Isoflurane, sevoflurane, and desflurane (at stable concentrations) reduce blood pressure primarily through peripheral vasodilation, lowering systemic vascular resistance. Cardiac output is relatively preserved because reduced afterload maintains stroke volume, and baroreceptor reflexes increase heart rate to compensate for vasodilation. This mechanism is better tolerated in patients with impaired myocardial function compared to halothane, because cardiac output is maintained despite falling blood pressure.

Halothane causes bradycardia through direct depression of sinoatrial node automaticity and sensitization to vagal tone — this is distinct from all modern agents. Isoflurane, sevoflurane, and nitrous oxide maintain or mildly increase heart rate through baroreceptor-mediated sympathetic reflexes in response to vasodilation. Desflurane at stable concentrations has a similar profile to isoflurane, but when the inspired concentration is rapidly increased, a marked transient sympathetic discharge produces tachycardia and hypertension — a property unique to desflurane and clinically important in patients with coronary artery disease.

Hypoxic pulmonary vasoconstriction is the physiological mechanism by which pulmonary blood flow is diverted away from poorly ventilated lung segments, maintaining ventilation-perfusion matching and oxygenation. All volatile halogenated agents inhibit hypoxic pulmonary vasoconstriction in a dose-dependent manner, worsening intrapulmonary shunting and contributing to intraoperative hypoxemia — this is particularly relevant during one-lung ventilation for thoracic surgery. Propofol does not inhibit hypoxic pulmonary vasoconstriction, making total intravenous anesthesia with propofol the preferred technique when oxygenation is marginal during one-lung ventilation.