DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

528 asthmaticus with halothane and intractable angina with
epidural local anesthetics, should not obscure this critical
point that permeates the training and practice of the
specialty. Hence, administration of general anesthesia,
as well as the development of new anesthetic agents and
physiologic monitoring technology, has been driven by
three general objectives:
SECTION II
NEUROPHARMACOLOGY
1. Minimizing the potentially deleterious direct and
indirect effects of anesthetic agents and techniques.
2. Sustaining physiologic homeostasis during surgical
procedures that may involve major blood loss,
tissue ischemia, reperfusion of ischemic tissue,
fluid shifts, exposure to a cold environment, and
impaired coagulation.
3. Improving postoperative outcomes by choosing
techniques that block or treat components of the
surgical stress response, which may lead to shortor
long-term sequelae.
Hemodynamic Effects of General Anesthesia. The most
prominent physiological effect of anesthesia induction,
associated with the majority of both intravenous and
inhalational agents, is a decrease in systemic arterial
blood pressure. The causes include direct vasodilation,
myocardial depression, or both; a blunting of baroreceptor
control; and a generalized decrease in central
sympathetic tone. Agents vary in the magnitude of their
specific effects (described later in the chapter), but in all
cases the hypotensive response is enhanced by underlying
volume depletion or preexisting myocardial dysfunction.
Even anesthetics that show minimal
hypotensive tendencies under normal conditions (e.g.,
etomidate and ketamine) must be used with caution in
trauma victims, in whom intravascular volume depletion
is being compensated by intense sympathetic discharge.
Smaller-than-normal anesthetic dosages are
employed in patients presumed to be sensitive to hemodynamic
effects of anesthetics.
Respiratory Effects of General Anesthesia. Airway
maintenance is essential following induction of anesthesia,
as nearly all general anesthetics reduce or eliminate
both ventilatory drive and the reflexes that
maintain airway patency. Therefore, ventilation generally
must be assisted or controlled for at least some period
during surgery. The gag reflex is lost, and the stimulus
to cough is blunted. Lower esophageal sphincter tone
also is reduced, so both passive and active regurgitation
may occur. Endotracheal intubation, introduced by
Kuhn in the early 1900s, has been a major reason for a
decline in the number of aspiration deaths during general
anesthesia. Muscle relaxation is valuable during
the induction of general anesthesia where it facilitates
management of the airway, including endotracheal intubation.
Neuromuscular blocking agents commonly are
used to effect such relaxation (Chapter 11), reducing the
risk of coughing or gagging during laryngoscopicassisted
instrumentation of the airway, and thus reducing
the risk of aspiration prior to secure placement of an
endotracheal tube. Alternatives to an endotracheal tube
include a facemask and a laryngeal mask, an inflatable
mask placed in the oropharynx forming a seal around
the glottis. The choice of airway management is based
on the type of procedure and characteristics of the
patient.
Hypothermia. Patients commonly develop hypothermia
(body temperature < 36°C) during surgery. The reasons
for the hypothermia include low ambient temperature,
exposed body cavities, cold intravenous fluids, altered
thermoregulatory control, and reduced metabolic rate.
General anesthetics lower the core temperature set point
at which thermoregulatory vasoconstriction is activated
to defend against heat loss. Furthermore, vasodilation
produced by both general and regional anesthesia offsets
cold-induced peripheral vasoconstriction, thereby
redistributing heat from central to peripheral body compartments,
leading to a decline in core temperature
(Sessler, 2000). Metabolic rate and total body oxygen
consumption decrease with general anesthesia by
~30%, reducing heat generation.
Even small drops in body temperatures may lead to an
increase in perioperative morbidity, including cardiac complications,
wound infections, and impaired coagulation. Prevention of hypothermia
has emerged as a major goal of anesthetic care. Modalities to
maintain normothermia include using warm intravenous fluids, heat
exchangers in the anesthesia circuit, forced-warm-air covers, and
new technology involving water-filled garments with microprocessor
feedback control to a core temperature set point.
Nausea and Vomiting. Nausea and vomiting in the postoperative
period continue to be significant problems
following general anesthesia and are caused by an
action of anesthetics on the chemoreceptor trigger zone
and the brainstem vomiting center, which are modulated
by serotonin (5-HT), histamine, acetylcholine
(ACh), and dopamine (DA). The 5-HT 3
-receptor antagonists,
ondansetron and dolasetron (Chapters 13 and
46), are very effective in suppressing nausea and vomiting.
Common treatments also include droperidol,
metoclopramide, dexamethasone, and avoidance of
N 2
O. The use of propofol as an induction agent and the