Page 482 - Clinical Application of Mechanical Ventilation

448 Chapter 13

Mechanism of Action. Barbiturates are capable of producing all levels of CNS
depression, ranging from mild sedation to hypnosis to deep coma to death. As
previously discussed in the benzodiazepine section, GABA is the most common
CNS inhibitory neurotransmitter. The GABA receptor exists as a complex involv-
ing the benzodiazepine receptor, the barbiturate receptor, and the GABA receptor
and its associated chloride ion channel (Figure 13-7) (Olson, 1988). Drug bind-
ing to this receptor complex facilitates GABA-mediated hyperpolarization of the
GABA-mediated hyper- neuron via an increase in chloride ion entry into the cell. This hyperpolarization
polarization of the neuron makes the neuron more resistant to depolarization, causing depression of CNS
makes the neuron more
resistant to depolarization, function. The importance of this cellular mechanism in producing the clinical
causing depression of CNS
function. effects of barbiturates is unclear.
Higher doses of barbiturates may directly activate the chloride ion channel in-
dependent of the barbiturate-GABA receptor complex (Levine, 1994). This results
in a progressive depression of central nervous system function ranging from deep
sedation to coma. When coma is induced, these agents are capable of decreasing ce-
rebral metabolic oxygen consumption. Through autoregulation, the brain decreases
cerebral blood flow, thereby lowering intracranial pressure.

Adverse Effects. These once widely used agents now have limited applications in
Venodilation with
peripheral pooling of blood, critically ill patients because of dose-dependent cardiovascular and respiratory
tachycardia, and depressed depression (Price-Roberts, 1984). Venodilation with peripheral pooling of blood,
myocardial contractility
may result in hypotension in tachycardia, and depressed myocardial contractility may result in hypotension,
patients with poor cardiac especially in elderly patients with poor cardiac function.
function.
Respiratory adverse effects to barbiturates include blunted ventilatory response
to hypoxia and hypercapnia, and reduced tidal volume and respiratory rate. Other
adverse effects attributed to barbiturates include rashes and gastrointestinal upset.

Drug Interactions. Barbiturates may induce tolerance as well as physical and
psychologic dependence. These concepts have been discussed at length in the
Barbiturates increase the section on opioid therapy. Another problem complicating barbiturate therapy is
clearance of those drugs that
are metabolized by the liver. the potential for numerous drug interactions. When barbiturates are in use, liver
metabolism of other drugs may be enhanced, thus decreasing their effects. Cau-
tion should be exercised when adding to or deleting a drug from a therapeutic
regimen containing a barbiturate, giving consideration to the possible need for
Barbiturates do not dosage adjustment.
relieve pain and may Barbiturates do not relieve pain and may paradoxically heighten pain intensity
paradoxically heighten the
sensation of pain. (Dundee et al., 1988). Therefore it is necessary to reassess analgesic efficacy when
these drugs are used in patients requiring analgesia.

OTHER AGENTS USED IN MECHANICAL VENTILATION

Other agents used in mechanical ventilation include propofol (for sedation and
maintenance of anesthesia), haloperidol (for treatment of delirium), dexmedetomi-
dine (for sedation of mechanically ventilated patients), and nitric oxide (for dilation
of pulmonary vessels).

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