Side Effects and Contraindications
The effects of barbiturates on various organ systems have been
studied extensively. Some side effects occur in unpredictable, varying proportions
of patients, whereas the cardiovascular and pulmonary effects are dose related.[336]
[337]
[338]
No
important
differences have been found between the barbiturates with regard to their effects
on the various organ systems (respiratory, cardiovascular, gastrointestinal, hepatic,
and renal), but there are differences in other complications with these drugs. Complications
of injecting barbiturates include a garlic or onion taste (40% of patients), allergic
reactions, local tissue irritation, and rarely, tissue necrosis. An urticarial rash
that lasts a few minutes may develop on the head, neck, and trunk. More severe reactions
such as facial edema, hives, bronchospasm, and anaphylaxis can also occur. Treatment
of anaphylaxis is 1-mL increments of 1:10,000 epinephrine with intravenous fluids.
Aminophylline can be given for bronchospasm.
Thiopental and thiamylal produce fewer excitatory symptoms with
induction than methohexital does; cough, hiccough, tremors, and twitching are produced
approximately five times more often with methohexital. Tissue irritation and local
complications may occur more frequently with the use of thiopental and thiamylal
than with methohexital. In comparative studies, pain on injection was shown to be
greater with methohexital (12%) than with thiopental (9%). Results also show that
phlebitis occurs more frequently with methohexital (8%) than with thiopental (1%).
[339]
Tissue and venous irritation is more common
if a 5% solution is used rather than the standard 2% solution.
Rarely, accidental intra-arterial injection can occur, the consequences
of which may be severe. The degree of injury is related to the concentration of
the drug. Treatment consists of (1) dilution of the drug by the administration of
saline into the artery, (2) heparinization to prevent thrombosis, and (3) brachial
plexus block.[340]
Overall, proper intravenous
administration of thiopental is remarkably free of local toxicity.
Cardiovascular System
Cardiovascular depression from barbiturates is a result of both
central and peripheral (direct vascular and cardiac) effects.[341]
The hemodynamic changes produced by barbiturates have been studied in healthy subjects
and patients with heart disease.[342]
[343]
The primary cardiovascular effect of barbiturate induction is peripheral vasodilation
resulting in pooling of blood in the venous system.[344]
A decrease in contractility is another effect and is related to reduced availability
of calcium to myofibrils. In addition, the heart rate is increased.[343]
Mechanisms for the decrease in cardiac output include (1) direct negative inotropic
action, (2) decreased ventricular filling because
of increased capacitance, and (3) transiently decreased sympathetic outflow from
the CNS.[332]
[345]
The increase in heart rate (10% to 36%) that accompanies thiopental administration
probably results from baroreceptor-mediated sympathetic reflex stimulation of the
heart in response to the drop in output and pressure. Thiopental produces dose-related
negative inotropic effects that appear to result from a decrease in calcium influx
into the cells with a resultant diminished amount of calcium at sarcolemma sites.
The cardiac index is unchanged or reduced, and mean arterial pressure is maintained
or slightly reduced. Thiopental infusions and lower doses tend to be accompanied
by smaller hemodynamic changes than those noted with rapid bolus injections. In
the dose ranges studied, no relationship between plasma thiopental level and hemodynamic
effect has been found. A sympathetic discharge in response to intubation increases
the heart rate and blood pressure and can be attenuated by the administration of
fentanyl (1 to 3 µg/kg).
Little difference is seen in responses after administration of
thiopental and methohexital to heart disease patients. The increase in heart rate
(11% to 36%) encountered in patients with coronary artery disease who are anesthetized
with thiopental (1 to 4 mg/kg) is potentially deleterious because of the obligatory
increase in myocardial oxygen consumption (MVO2
)
that accompanies the increased heart rate. Patients who have normal coronary arteries
have no difficulty maintaining adequate coronary blood flow to meet the increased
MVO2
.[346]
When thiopental is given to hypovolemic patients, there is a significant reduction
in cardiac output (69%), as well as an important decrease in blood pressure.[347]
Patients without adequate compensatory mechanisms may therefore have serious hemodynamic
depression with thiopental induction.
Respiratory System
Barbiturates produce dose-related central respiratory depression.
In addition, a significant incidence of transient apnea occurs after the administration
of barbiturates for induction of anesthesia. The evidence for central depression
is a correlation between EEG suppression and minute ventilation. With increased
anesthetic effect, minute ventilation is diminished. The time course of respiratory
depression has not been fully studied, but it appears that peak respiratory depression
(as measured by the slope of CO2
concentration in blood) and minute ventilation
after delivery of thiopental (3.5 mg/kg) occurs 1 to 1.5 minutes after administration.
These parameters return to predrug levels rapidly, and within 15 minutes the drug
effects are barely detectable.[348]
Patients with
chronic lung disease are slightly more susceptible to the respiratory depression
associated with thiopental. Apnea occurs during induction of anesthesia with thiopental
in at least 20% of cases, but the duration of apnea is short, approximately 25 seconds.
[349]
The usual ventilatory pattern with thiopental
induction has been described as "double apnea." The initial apnea that occurs during
drug administration lasts a few seconds and is succeeded by a few breaths of reasonably
adequate tidal volume, followed by a more lengthy apneic period. During induction
of anesthesia with thiopental, ventilation must be assisted or controlled to provide
adequate respiratory exchange.
Like other barbiturates, methohexital is a central respiratory
system depressant. Induction doses (1.5 mg/kg) significantly decrease the slope
of the ventilatory response to carbon dioxide (VRCO2
).[350]
Maximal reduction in VRCO2
occurred 30 seconds after drug administration
and began to approach normal levels within 15 minutes. The peak decrease in tidal
volume occurred 60 seconds after methohexital delivery and also returned to baseline
within 15 minutes. In contrast to the effects on ventilation, patients were awake
within about 5 minutes after the administration of methohexital (1.5 mg/kg). No
difference in the duration of ventilatory depression is seen after methohexital or
thiopental delivery when the drugs are studied in a similar manner.[348]
Contraindications
Wood has listed the contraindications to intravenous barbiturate
use.[351]
First, in patients with respiratory obstruction
or an inadequate airway, thiopental may worsen respiratory depression. Second, severe
cardiovascular instability or shock may preclude its use. Third, status asthmaticus
is a condition in which airway control and ventilation may be further worsened by
thiopental. Fourth, porphyria may be precipitated or acute attacks may be accentuated
by the administration of thiopental. Fifth, without proper equipment for administration
(intravenous instrumentation) and airway equipment (means of artificial ventilation),
thiopental should not be administered.
