Sedative-Tranquilizers (also see
Chapter 10
)
Sedative-tranquilizers, including barbiturates, phenothiazines,
hydroxyzine, and benzodiazepines, have been used for sedation, anxiolysis, or both
during early labor and before cesarean delivery. Although barbiturates such as secobarbital
were once popular, they are currently unfashionable because of antianalgesic effects
in the mother and prolonged depressant effects in the neonate. Even with small doses
of barbiturates that result in no depression of the Apgar score, the newborn's attention
span may be depressed for upward of 4 days.[92]
Promethazine is the most commonly administered phenothiazine in
obstetrics. Used together with meperidine, it can be given in doses of 25 to 50
mg to prevent emesis. Its ability to potentiate the analgesic effects of opioids,
however, is in doubt.[93]
Promethazine appears
in fetal blood within 1 to 2 minutes after intravenous injection in the mother and
reaches equilibrium within 15 minutes.[94]
Ketamine is an N-methyl-D-aspartate
(NMDA) receptor antagonist that produces dissociative anesthesia and has been used
in pregnant patients. As a phenylcyclidine derivative, its mechanism of action may
be mediated by an interaction with phencyclidine receptors located in the limbic
and corticothalamic areas of the brain. Some evidence, however, suggests that NMDA
antagonism is central to the effects of ketamine. Ketamine has been used in subanesthetic
doses (0.5 to 1 mg/kg or 10 mg every 2 to 5 minutes to a total of 1 mg/kg in 30 minutes)
during labor.[95]
In addition to its use in labor,
ketamine in a dose of 25 to 50 µg can be used to supplement an incomplete neuraxial
blockade for cesarean section. Its main disadvantages are the potential for hypertension
and emergence reactions. High doses (greater than 2 mg/kg) can produce psychomimetic
effects and increased uterine tone, which may cause low Apgar scores and abnormalities
in neonatal muscle tone.[96]
Benzodiazepines such as diazepam (Valium), lorazepam (Ativan),
and midazolam (Versed) can be used as sedatives and anxiolytics in labor. However,
these drugs readily cross the placenta, with elimination half-lives as long as 48
hours for diazepam and upward of 120 hours for its main metabolite N-desmethyldiazepam.
[97]
Anecdotal evidence suggests that exposure
to
benzodiazepines early in utero may result in malformations such as cleft lip.[98]
Closer analysis involving first-trimester administration of benzodiazepines shows
that most infants were normal at birth and had normal postnatal development.[97]
The use of these drugs during labor will obviously have no effect
on fetal malformations, but they may be associated with other problems in the neonate,
including sedation, hypotonia, cyanosis, and impaired metabolic responses to stress.
In addition, because these drugs are potent amnestic agents, a parturient may not
be able to remember her birthing experience.[99]
Many of the adverse effects can be reversed by the administration of flumazenil,
which is a competitive benzodiazepine receptor antagonist.
