ability of the blood-brain barrier, higher body water content, less mature hepatic microsomal enzyme systems, and lower albumin concentrations—affect the pharmacodynamics and pharmacokinetics of analgesic and anesthetic drugs (Thurmon et al., 1996).

In summary, although there is not enough evidence to determine whether neonatal animals perceive pain, some stimuli that are noxious to adult animals have been shown to trigger reflexive behavior in neonates, and this suggests that neonates would benefit from the administration of analgesics.

ANESTHESIA AND ANALGESIA

Fetus

Available evidence suggests that the late-term fetus (E19–E20 in the rat) is responsive to noxious stimulation, as is the late-term fetal lamb and 26-week human fetus. Therefore, provision of anesthesia for potentially painful procedures is advised for late-term fetuses. For fetal manipulations in utero, anesthetics used to prevent pain in the mother are probably adequate to prevent pain in the fetus. Most drugs used for anesthesia in mammals—including barbiturates, ketamine, opioids, and inhalant anesthetics—readily cross the placenta. Therefore, the primary consideration should be adequate anesthesia, analgesia, and supportive care for the dam.

Anesthetic agents widely accepted for use in fetal surgical procedures include such inhalants as halothane, isoflurane, and desflurane (Abboud et al., 1995; Sabik et al., 1993). Balanced anesthesia with isoflurane and thiobarbiturates has been successfully used for late-term fetal pigs (Sims et al., 1997), whereas methoxyflurane and xylazine are associated with postnatal mortality in puppies delivered by caesarean section when those drugs were used for anesthesia in the dam (Moon et al., 2000).

Monitoring of anesthesia in fetal animals presents several challenges. Electrocardiographic monitoring can be used to easily monitor heart rhythm and electrical activity in fetuses of larger mammals, though bradycardia is a poor indicator of fetal distress. Pulse oximetry is noninvasive and effective for fetal lambs. It has a rapid response and is simple to use on the exposed fetus of larger mammals (Luks et al., 1998b). Direct monitoring of blood pressure and intravascular oximetry can quickly and accurately indicate fetal distress but are generally considered impractical because of their invasiveness.

In some studies, consideration of the potential effect of in utero drug exposure on physiologic and behavioral development of the animal may be appropriate (e.g., Belcheva et al., 1994; Niesink et al., 1999; Rodier et al., 1986). Non-opioid analgesics such as acetylsalicylic acid and acetaminophen, are potent inhibitors of prostaglandin synthesis, and their use in a fetus may result in unintended physiologic effects (Peterson, 1985). Prenatal administration of meperi-



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