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Pharmacotherapy for Mechanical Ventilation 441

Excretion. Benzodiazepines are metabolized in the liver to active and inactive me-
tabolites that are excreted mainly in the urine. Although the pharmacokinetics of
drugs are often used to explain correlations between plasma concentrations and
effect, benzodiazepines do not exhibit this relationship. Furthermore, carefully
controlled clinical trials have not shown the superiority of one agent over another
for various ICU indications (Dasta et al., 1994). Therefore, the choice of benzodi-
azepine is often based on cost.
Adverse Effects. Dose-dependent adverse central nervous system effects are very
Dose-dependent adverse
CNS effects include confusion, common with benzodiazepines. They are an extension of the pharmacologic ac-
weakness, dizziness, drowsi- tions of the drugs and include confusion, weakness, dizziness, drowsiness, ataxia,
ness, ataxia, syncope, vertigo,
and amnesia. syncope, vertigo, and amnesia (McEvoy, 1995). Central nervous system stimula-
tion occurs occasionally in patients with underlying psychiatric disorders. These
patients present with restlessness, mania, euphoria, acute rage reactions, and sleep
disorders (McCartney et al., 1993). A withdrawal syndrome may occur if these
Withdrawal syndrome
(anxiety, tachycardia, dia- drugs are abruptly discontinued in patients on prolonged therapy or high doses.
phoresis, hypertension, and, This may be manifested by severe anxiety, tachycardia, diaphoresis, hypertension,
occasionally, seizures) may
occur if benzodiazepines are and, occasionally, seizures (McCartney et al., 1994).
abruptly discontinued. Parenteral administration of benzodiazepines may result in a dose-dependent re-

spiratory depression (Forster et al., 1980) which is additive to that produced by opi-
oids. Elderly and COPD patients are at the greatest risk (Levine, 1994). Although
depression of the respiratory drive is not usually as great with benzodiazepines as
with other sedative agents, apnea may occur. Careful dosing of these agents is also
necessary to avoid prolonged mechanical ventilation.
Benzodiazepines may also have direct effects on cardiovascular hemodynamics.
Benzodiazepines may They have been shown to decrease mean arterial pressure, stroke volume, cardiac
decrease the mean arte-
rial pressure, stroke volume, output, and systemic vascular resistance (Reves et al., 1990). Additive decreases in
cardiac output, and systemic blood pressure may occur when opioids are administered concurrently. Table 13-12
vascular resistance.
outlines the cardiovascular effects of benzodiazepines.
Assessment of Sedation. The indication for benzodiazepines and the estimated du-
ration of therapy may be helpful in deciding whether to administer these drugs
intermittently or continuously. Sedation and analgesia protocols are recommended
along with daily sedation holidays to avoid prolonging a patient’s requirement for

TABLE 13-12 Cardiovascular Effects of Benzodiazepines

1. T Mean arterial pressure

2. T Stroke volume
3. T Cardiac output

4. T Systemic vascular resistance

5. T Blood pressure
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