Page 467 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 25 General Anesthetics 453

The dose should be reduced by 25% in patients older than methohexital, barbiturates decrease electrical activity on the EEG
65 years and in those with an American Society of Anesthesiolo- and can be used as anticonvulsants. In contrast, methohexital
gists status of 3 or 4. activates epileptic foci and may therefore be useful to facilitate
electroconvulsive therapy or during the identification of epileptic
foci during surgery.
BARBITURATES
B. Cardiovascular Effects
This section focuses on the use of thiopental and methohexital
for induction of general anesthesia; however, these barbiturate The decrease in systemic blood pressure associated with admin-
hypnotics have been largely replaced as induction agents by pro- istration of barbiturates for induction of anesthesia is primarily
pofol. Other barbiturates and general barbiturate pharmacology due to peripheral vasodilation and is usually smaller than the
are discussed in Chapter 22. blood pressure decrease associated with propofol. There are also
The anesthetic effect of barbiturates presumably involves a direct negative inotropic effects on the heart. However, inhibi-
combination of enhancement of inhibitory transmission and inhi- tion of the baroreceptor reflex is less pronounced than with
bition of excitatory neurotransmission (Figure 25–1). Although propofol; thus, compensatory increases in heart rate limit the
the effects on inhibitory transmission probably result from activa- decrease in blood pressure and make it transient. The depressant
tion of the GABA receptor complex, the effects on excitatory effects on systemic blood pressure are increased in patients with
A
transmission are less well understood. hypovolemia, cardiac tamponade, cardiomyopathy, coronary
artery disease, or cardiac valvular disease because such patients
Pharmacokinetics are less able to compensate for the effects of peripheral vasodi-
lation. Hemodynamic effects are also more pronounced with
Thiopental and methohexital undergo hepatic metabolism, larger doses and rapid injection.
mostly by oxidation but also by N-dealkylation, desulfuration,
and destruction of the barbituric acid ring structure. Bar- C. Respiratory Effects
biturates should not be administered to patients with acute Barbiturates are respiratory depressants, and a usual induction
intermittent porphyria because they increase the production dose of thiopental or methohexital typically produces transient
of porphyrins through stimulation of aminolevulinic acid syn- apnea, which will be more pronounced if other respiratory depres-
thetase. Methohexital has a shorter elimination half-time than sants are also administered. Barbiturates lead to decreased minute
thiopental due to its larger plasma clearance (Table 25–2), lead- ventilation through reduced tidal volumes and respiratory rate
ing to a faster and more complete recovery after bolus injection. and also decrease the ventilatory responses to hypercapnia and
Although thiopental is metabolized more slowly and has a long hypoxia. Resumption of spontaneous breathing after an anesthetic
elimination half-time, recovery after a single bolus injection induction dose of a barbiturate is characterized by a slow breath-
is comparable to that of methohexital and propofol because it ing rate and decreased tidal volume. Suppression of laryngeal
depends on redistribution to inactive tissue sites rather than on reflexes and cough reflexes is probably not as profound as after an
metabolism (Figure 25–7). However, if administered through equianesthetic propofol administration, which makes barbiturates
repeated bolus injections or continuous infusion, recovery will an inferior choice for airway instrumentation in the absence of
be markedly prolonged because elimination will depend on neuromuscular blocking drugs. Furthermore, stimulation of the
metabolism under these circumstances (see also context-sensitive upper airway or trachea (eg, by secretions, laryngeal mask air-
half-time, Figure 25–8).
way, direct laryngoscopy, tracheal intubation) during inadequate
depression of airway reflexes may result in laryngospasm or bron-
Organ System Effects chospasm. This phenomenon is not unique to barbiturates but is
A. CNS Effects true whenever the drug dose is inadequate to suppress the airway
Barbiturates produce dose-dependent CNS depression ranging reflexes.
from sedation to general anesthesia when administered as bolus
injections. They do not produce analgesia; instead, some evidence D. Other Effects
suggests they may reduce the pain threshold, causing hyperalgesia. Accidental intra-arterial injection of barbiturates results in
Barbiturates are potent cerebral vasoconstrictors and produce excruciating pain and intense vasoconstriction, often leading
predictable decreases in cerebral blood flow, cerebral blood vol- to severe tissue injury involving gangrene. Approaches to treat-
ume, and ICP. As a result, they decrease CMRO consumption ment include blockade of the sympathetic nervous system (eg,
2
in a dose-dependent manner up to a dose at which they suppress stellate ganglion block) in the involved extremity. If extravasa-
all EEG activity. The ability of barbiturates to decrease ICP and tion occurs, some authorities recommend local injection of the
CMRO makes these drugs useful in the management of patients area with 0.5% lidocaine (5–10 mL) in an attempt to dilute the
2
with space-occupying intracranial lesions. They may provide neu- barbiturate concentration. Life-threatening allergic reactions
roprotection from focal cerebral ischemia (stroke, surgical retrac- to barbiturates are rare, with an estimated occurrence of 1 in
tion, temporary clips during aneurysm surgery), but probably not 30,000 patients. However, barbiturate-induced histamine release
from global cerebral ischemia (eg, from cardiac arrest). Except for occasionally is seen.