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

nonsteroidal anti-inflammatory drug ketorolac as a substitute
for opioids may decrease the incidence and
severity of postoperative nausea and vomiting.
Other Emergence and Postoperative Phenomena. Hypertension and
tachycardia are common as the sympathetic nervous system regains its
tone and is enhanced by pain. Myocardial ischemia can appear or
markedly worsen during emergence in patients with coronary artery
disease. Emergence excitement occurs in 5-30% of patients and is
characterized by tachycardia, restlessness, crying, moaning, and
thrashing. A variety of neurologic signs, including delirium, spasticity,
hyperreflexia, and Babinski sign, are often manifest in the patient
emerging from anesthesia. Postanesthesia shivering occurs frequently
because of core hypothermia. A small dose of meperidine (12.5 mg)
lowers the shivering trigger temperature and effectively stops the activity.
The incidence of all of these emergence phenomena is greatly
reduced when opioids and α 2
agonists (dexmedetomidine) are
employed as part of the intraoperative regimen.
Airway obstruction may occur during the postoperative
period because residual anesthetic effects continue to partially
obtund consciousness and reflexes (especially in patients who
normally snore or who have sleep apnea). Strong inspiratory
efforts against a closed glottis can lead to negative-pressure pulmonary
edema. Pulmonary function is reduced postoperatively
following all types of anesthesia and surgery, and hypoxemia may
occur. Hypertension can be prodigious, often requiring aggressive
treatment.
Pain control can be complicated in the immediate postoperative
period. The respiratory suppression associated with opioids can
be problematic among postoperative patients who still have a substantial
residual anesthetic effect. Patients can alternate between
states of excruciating pain to somnolence with airway obstruction, all
in a matter of moments. The nonsteroidal anti-inflammatory agent
ketorolac (30-60 mg intravenously) frequently is effective, and the
development of injectable cyclooxygenase-2 inhibitors (Chapter 34)
holds promise for analgesia without respiratory depression. In addition,
regional anesthetic techniques are an important part of a perioperative
multimodal approach that employs local anesthetic wound
infiltration; epidural, spinal, and plexus blocks; and nonsteroidal
anti-inflammatory drugs, opioids, α 2
adrenergic receptor agonists,
and NMDA-receptor antagonists. Patient-controlled administration
of intravenous and epidural analgesics makes use of small, computerized
pumps activated on demand but programmed with safety limits
to prevent overdose. The agents used are opioids (frequently
morphine) by the intravenous route, and an opioid, local anesthetic,
or both by the epidural route. These techniques have revolutionized
postoperative pain management, can be continued for hours or days,
and promote ambulation and improved bowel function until oral pain
medications are initiated.
ACTIONS AND MECHANISMS
OF GENERAL ANESTHETICS
The Anesthetic State
General anesthetics are a structurally diverse class of
drugs that produce a common end point—a behavioral
state referred to as general anesthesia. In the broadest
sense, general anesthesia can be defined as a global but
reversible depression of CNS function resulting in the
loss of response to and perception of all external stimuli.
While this definition is appealing in its simplicity,
it is not useful for two reasons: First, it is inadequate
because anesthesia is not simply a deafferented state;
e.g., amnesia is an important aspect of the anesthetic
state. Second, not all general anesthetics produce identical
patterns of deafferentation. Barbiturates, e.g., are
very effective at producing amnesia and loss of consciousness,
but are not effective as analgesics.
An alternative way of defining the anesthetic state is to consider
it as a collection of “component” changes in behavior or perception.
The components of the anesthetic state include:
• amnesia
• immobility in response to noxious stimulation
• attenuation of autonomic responses to noxious stimulation
• analgesia
• unconsciousness
It is important to remember that general anesthesia is useful only
insofar as it facilitates the performance of surgery or other noxious
procedures. The performance of surgery usually requires an immobilized
patient who does not have an excessive autonomic response
to surgery (blood pressure and heart rate) and who has amnesia for
the procedure. Indeed, if an anesthetic produces profound amnesia,
it can be difficult in principle to determine if it also produces either
analgesia or unconsciousness.
Measurement of Anesthetic Potency
The potency of general anesthetic agents usually is
measured by determining the concentration of general
anesthetic that prevents movement in response to surgical
stimulation. For inhalational anesthetics, anesthetic
potency is measured in MAC units, with 1 MAC
defined as the minimum alveolar concentration that prevents
movement in response to surgical stimulation in
50% of subjects.
The strengths of MAC as a measurement are that:
• alveolar concentrations can be monitored continuously by
measuring end-tidal anesthetic concentration using infrared
spectroscopy or mass spectrometry
• it provides a direct correlate of the free concentration of the anesthetic
at its site(s) of action in the CNS
• it is a simple-to-measure end point that reflects an important clinical
goal
End points other than immobilization also can be used to measure
anesthetic potency. For example, the ability to respond to verbal commands
(MAC awake
) and the ability to form memories also have been
correlated with alveolar anesthetic concentration. Interestingly, verbal
response and memory formation both are suppressed at a fraction
529
CHAPTER 19
GENERAL ANESTHETICS AND THERAPEUTIC GASES