Uses
Barbiturates are used clinically in the practice of anesthesia
for induction and maintenance of anesthesia, as well as for premedication. Less
frequently, barbiturates are used to provide cerebral protection to patients at risk
for incomplete ischemia. The three barbiturates that are used most commonly in the
United States for intravenous anesthesia and maintenance of anesthesia are thiopental,
thiamylal, and methohexital.
Thiopental is an excellent hypnotic for use as an intravenous
induction agent. The prompt onset (15 to 30 seconds) of action and smooth induction
noted with its use make thiopental superior to most other available drugs. The relatively
rapid emergence, particularly after single use for induction, was also a reason for
the widespread use of thiopental in this setting. Thiopental does not possess analgesic
properties and must therefore be supplemented with other analgesic drugs to obtund
the reflex responses to noxious stimuli during anesthesia and surgical procedures.
Thiopental can be used to maintain general anesthesia because repeated doses reliably
sustain unconsciousness and contribute to amnesia. Thiopental is not a perfect choice,
however, for use as the hypnotic component during balanced anesthesia.[330]
Probably because of thiopental's antanalgesic properties as plasma levels of the
drug decrease, analgesic supplementation is required more often with thiopental than
with midazolam when used during balanced anesthesia.[331]
Methohexital is the only intravenous barbiturate used for induction
that offers a serious challenge to thiopental. At a dose of 1 to 2 mg/kg, induction
is swift and so is emergence. Methohexital may also be used as the hypnotic component
to maintain anesthesia. Like thiopental, it is not an analgesic. Therefore, additional
opioids or volatile anesthetics are required to provide a balanced technique satisfactory
for general anesthesia during surgery. Methohexital is cleared more rapidly than
thiopental, so
it is superior to thiopental for maintenance of anesthesia because accumulation and
saturation of peripheral sites take longer. For brief infusion (<60 minutes),
recovery from a methohexital infusion titrated to maintain hypnosis (50 to 150 µg/kg/min)
is similar to that provided by propofol. The upper limits of safe infusion doses
have probably not yet been defined, but seizures have occurred in neurosurgical patients
after large doses of methohexital (24 mg/kg).[332]
Finally, some clinicians advocate the use of methohexital in pediatric patients
as a rectal premedication agent. Methohexital may be given rectally and is absorbed
rapidly. Mean peak plasma levels occur within 14 minutes after rectal administration
and are associated with a rapid hypnotic effect. The dose recommended for this use
is 25 mg/kg by rectal instillation (10% solution through a 14 French catheter, 7
cm into the rectum).[333]
[334]
With this method of administration, onset of sleep is rapid.
Dosing
Doses for the two most commonly used barbiturates are listed in
Table 10-6
. The usual dose
of thiopental (3 to 4 mg/kg) and thiamylal (3 to 4 mg/kg) is about twice that of
methohexital (1.0 to 2.0 mg/kg). In dose-response studies, the ED50
for
thiopental ranged from 2.2 to 2.7 mg/kg, and that for methohexital was 1.1 mg/kg.
[324]
Because the ED50
induces anesthesia
in only 50% of a given group of patients, higher doses are needed to reliably induce
anesthesia in all patients. Thus, the usual dose of thiopental is 3 to 4 mg/kg given
intravenously over a period of 5 to 15 seconds. There is less interpatient variability
in the dose response to barbiturates than to benzodiazepines when used for induction
of anesthesia, but there is still significant variability in the doses of thiopental
required to induce anesthesia.[324]
In one large
study, the induction dose for healthy patients varied from 2.8 to 9.7 mg/kg.[335]
Interpatient dose variability is related to the presence of hemorrhagic shock, the
level of cardiac output, lean body mass, obesity, sex, and age. Hemorrhagic shock,
lean body mass, age, and obesity contribute to the variability in patient response
by decreasing the central volume of distribution. Thus, less blood volume (shock,
dehydration) or less lean body mass (obesity, common in the elderly and lower in
females than males) decreases the volume in
*Adult
and pediatric intravenous doses are roughly the same in milligrams per kilogram.
†Methohexital can be given rectally
in pediatric patients at 20 to 25 mg/kg per dose.
which the drug is diluted or the volume into which it is quickly redistributed, respectively.
Finally, patients who have severe anemia or burns, malnutrition, widespread malignant
disease, uremia, and ulcerative colitis or intestinal obstruction also require lower
induction doses of barbiturate.
