Page 460 - Basic _ Clinical Pharmacology ( PDFDrive )

446 SECTION V Drugs That Act in the Central Nervous System

The duration of exposure to the anesthetic can have a signifi- blood flow within the brain. However, volatile anesthetics may also
cant effect on the speed of emergence from anesthesia, especially produce cerebral vasodilation, which can increase cerebral blood
in the case of the more soluble anesthetics. Accumulation of flow. The net effect on cerebral blood flow (increase, decrease, or
anesthetics in muscle, skin, and fat increases with prolonged no change) depends on the concentration of anesthetic delivered.
exposure (especially in obese patients), and blood concentra- At 0.5 MAC, the reduction in CMR is greater than the vasodila-
tion may decline slowly after discontinuation as the anesthetic tion caused by anesthetics, so cerebral blood flow is decreased.
is slowly eliminated from these tissues. Although recovery after Conversely, at 1.5 MAC, vasodilation by the anesthetic is greater
a short exposure to anesthesia may be rapid even with the more than the reduction in CMR, so cerebral blood flow is increased. In
soluble agents, recovery is slow after prolonged administration of between, at 1.0 MAC, the effects are balanced and cerebral blood
halothane or isoflurane. flow is unchanged. An increase in cerebral blood flow is clinically
undesirable in patients who have increased intracranial pressure
1. Ventilation—Two parameters that can be manipulated by because of brain tumor, intracranial hemorrhage, or head injury.
the anesthesiologist are useful in controlling the speed of induc- Therefore, administration of high concentrations of volatile
tion of and recovery from inhaled anesthesia: (1) concentration anesthetics is best avoided in patients with increased intracranial
of anesthetic in the inspired gas and (2) alveolar ventilation. As pressure. Hyperventilation can be used to attenuate this response;
stated above, since the concentration of anesthetic in the inspired decreasing the Paco (the partial pressure of carbon dioxide in
2
gas cannot be reduced below zero, hyperventilation is the only way arterial blood) through hyperventilation causes cerebral vasocon-
to speed recovery. striction. If the patient is hyperventilated before the volatile agent
is started, the increase in intracranial pressure can be minimized.
2. Metabolism—Modern inhaled anesthetics are eliminated Nitrous oxide can increase cerebral blood flow and cause
mainly by ventilation and are only metabolized to a very small increased intracranial pressure. This effect is most likely caused by
extent; thus, metabolism of these drugs does not play a significant activation of the sympathetic nervous system (as described below).
role in the termination of their effect. However, metabolism may Therefore, nitrous oxide may be combined with other agents
have important implications for their toxicity (see Toxicity of (intravenous anesthetics) or techniques (hyperventilation) that
Anesthetic Agents). Hepatic metabolism may also contribute to reduce cerebral blood flow in patients with increased intracranial
the elimination of and recovery from some older volatile anesthet- pressure.
ics. For example, halothane is eliminated more rapidly during Potent inhaled anesthetics produce a basic pattern of change to
recovery than enflurane, which would not be predicted from brain electrical activity as recorded by standard electroencephalog-
their respective tissue solubility. This increased elimination occurs raphy (EEG). Isoflurane, desflurane, sevoflurane, halothane, and
because over 40% of inspired halothane is metabolized during an enflurane produce initial activation of the EEG at low doses and
average anesthetic procedure, whereas less than 10% of enflurane then slowing of electrical activity up to doses of 1.0–1.5 MAC.
is metabolized over the same period. At higher concentrations, EEG suppression increases to the point
In terms of the extent of hepatic metabolism, the rank order of electrical silence with isoflurane at 2.0–2.5 MAC. Isolated
for the inhaled anesthetics is halothane > enflurane > sevoflurane > epileptic-like patterns may also be seen between 1.0 and 2.0
isoflurane > desflurane > nitrous oxide (Table 25–1). Nitrous MAC, especially with sevoflurane and enflurane, but frank clini-
oxide is not metabolized by human tissues. However, bacteria in cal seizure activity has been observed only with enflurane. Nitrous
the gastrointestinal tract may be able to break down the nitrous oxide used alone causes fast electrical oscillations emanating from
oxide molecule. the frontal cortex at doses associated with analgesia and depressed
consciousness.
PHARMACODYNAMICS Traditionally, anesthetic effects on the brain produce four
stages or levels of increasing depth of CNS depression (Guedel’s
Organ System Effects of Inhaled signs, derived from observations of the effects of inhaled diethyl
Anesthetics ether): Stage I—analgesia: The patient initially experiences
analgesia without amnesia. Later in stage I, both analgesia and
A. CNS Effects amnesia are produced. Stage II—excitement: During this stage,
Anesthetic potency is currently described by the minimal alveolar the patient appears delirious and may vocalize but is completely
concentration (MAC) required to prevent a response to a surgi- amnesic. Respiration is rapid, and heart rate and blood pressure
cal incision (see Box: What Does Anesthesia Represent & Where increase. Duration and severity of this light stage of anesthesia are
Does It Work?). This parameter was first described by investiga- shortened by rapidly increasing the concentration of the agent.
tors in the 1960s and remains the best clinical guide for admin- Stage III—surgical anesthesia: This stage begins with slowing
istering inhaled anesthetics, especially since improved medical of respiration and heart rate and extends to complete cessation
technology can now provide instantaneous, accurate determina- of spontaneous respiration (apnea). Four planes of stage III are
tion of gas concentrations. described based on changes in ocular movements, eye reflexes, and
Inhaled anesthetics (and intravenous anesthetics, discussed pupil size, indicating increasing depth of anesthesia. Stage IV—
later) decrease the metabolic activity of the brain. A decreased medullary depression: This deep stage of anesthesia represents
cerebral metabolic rate (CMR) generally causes a reduction in severe depression of the CNS, including the vasomotor center