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

548 anesthesia (Rasmussen et al., 2006). Xenon is well tolerated
in patients of advanced age. No long-term side
effects from xenon anesthesia have been reported.
SECTION II
NEUROPHARMACOLOGY
Effects on Organ Systems
Cardiovascular System. Xenon has minimal effects on cardiovascular
function. Arterial pressure, unlike the situation with other
anesthetic agents, is well maintained. Left ventricular contractility
is not affected and heart rate and systemic vascular resistance
are essentially unchanged. Autonomic function is better maintained
under xenon anesthesia than under anesthesia with propofol and
inhaled anesthetics (Hanss et al., 2006). Even in patients with significant
cardiac disease, xenon maintains a favorable profile
(Lockwood et al., 2006).
Respiratory System. Under xenon anesthesia, respiratory rate is
reduced slightly. However, an increase in tidal volume maintains
minute ventilation, indicating that there is minimal respiratory
depression. An increase in airway pressure does occur; this has been
attributed to the greater density and viscosity of xenon (compared
to oxygen) and not due to changes in bronchomotor tone (Baumert
et al., 2002).
Central Nervous System. Like other anesthetic agents, xenon
reduces cerebral metabolism by 25-30%. This reduction in metabolism
is accompanied by a corresponding reduction in cerebral
blood flow. Consequently, xenon is not expected to increase
intracranial pressure.
Liver, Kidney, and GI Tract. Xenon is an inert agent and does not
undergo metabolism. Hepatic or renal toxicity with its use have not
been reported.
ANESTHETIC ADJUNCTS
A general anesthetic is rarely given as the sole agent.
Anesthetic adjuncts usually are used to augment specific
components of anesthesia, permitting lower doses
of general anesthetics with fewer side effects. Because
they are such an integral part of general anesthetic drug
regimens, their use as anesthetic adjuncts is described
briefly here. The detailed pharmacology of each drug is
covered in other chapters.
Benzodiazepines
While benzodiazepines (Chapter 17) can produce anesthesia
similar to that of barbiturates, they are more commonly
used for sedation rather than general anesthesia
because prolonged amnesia and sedation may result
from anesthetizing doses. As adjuncts, benzodiazepines
are used for anxiolysis, amnesia, and sedation prior to
induction of anesthesia or for sedation during procedures
not requiring general anesthesia. The benzodiazepine
most frequently used in the perioperative
period is midazolam followed distantly by diazepam
(VALIUM, others), and lorazepam (ATIVAN, others).
Midazolam is water soluble and typically is administered
intravenously but also can be given orally, intramuscularly, or rectally;
oral midazolam is particularly useful for sedation of young
children. Midazolam produces minimal venous irritation as
opposed to diazepam and lorazepam, which are formulated in
propylene glycol and are painful on injection, sometimes producing
thrombophlebitis. Midazolam has the pharmacokinetic advantage,
particularly over lorazepam, of being more rapid in onset
and shorter in duration of effect. Sedative doses of midazolam
(0.01-0.05 mg/kg intravenously) reach peak effect in ~2 minutes
and provide sedation for ~30 minutes. Elderly patients tend to be
more sensitive to and have a slower recovery from benzodiazepines
(Jacobs et al., 1995); thus, titration to the desired effect of smaller
doses in this age group is prudent. Midazolam is hepatically
metabolized with a clearance (6-11 mL/min per kg), similar to
that of methohexital and ~20 and 7 times higher than those of
diazepam and lorazepam, respectively. Either for prolonged sedation
or for general anesthetic maintenance, midazolam is more suitable
for infusion than are other benzodiazepines, although its
duration of action does significantly increase with prolonged infusions
(Figure 19–3). Benzodiazepines reduce both cerebral blood
flow and metabolism but at equi-anesthetic doses are less potent in
this respect than are barbiturates. They are effective anticonvulsants
and sometimes are given to treat status epilepticus.
Benzodiazepines modestly decrease blood pressure and respiratory
drive, occasionally resulting in apnea. Thus, blood pressure and
respiratory rate should be monitored in patients sedated with intravenous
benzodiazepines.
α 2
Adrenergic Agonists. Dexmedetomidine (PRECEDEX)
is an imidazole derivative that is a highly selective α 2
adrenergic receptor agonist (Kamibayashi and Maze,
2000). Dexmedetomidine is FDA-approved for shortterm
(< 24 hours) sedation of critically ill adults and
sedation prior to and/or during surgical or other medical
procedures in non-intubated patients. Activation of the
α 2A
adrenergic receptor by dexmedetomidine produces
both sedation and analgesia, but does not reliably provide
general anesthesia, even at maximal doses
(Lakhlani et al., 1997).
Dexmedetomidine is a sedative-hypnotic that provides
analgesia with little respiratory depression and,
in most patients, a tolerable decrease in blood pressure
and heart rate. The drug is likely to be increasingly used
for sedation and as an anesthetic adjunct.
The most common side effects of dexmedetomidine include
hypotension and bradycardia, both of which are attributed to
decreased catecholamine release by activation peripherally and in
the CNS of the α 2A
receptor (Lakhlani et al., 1997). Nausea and dry
mouth also are common untoward reactions. At higher drug concentrations,
the α 2B
subtype is activated, resulting in hypertension and
a further decrease in heart rate and cardiac output. Dexmedetomidine
has the very useful property of producing sedation and analgesia with
minimal respiratory depression (Belleville et al., 1992); thus, it is particularly
valuable in sedation of patients who are not endotracheally