GUIDELINES FOR THE CARE AND USE OF MAMMALS IN NEUROSCIENCE AND BEHAVIORAL RESEARCH by National Research Council of the National Academies

Author:National Research Council of the National Academies
Language: eng
Format: epub
Tags: Biology and Life Sciences : Lab Animal Research
Publisher: NATIONAL ACADEMY PRESS
Published: 2003-08-22T00:00:00+00:00

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 meperidine or bupivacaine to primates may influence behavioral maturation (Golub, 1996). In higher mammals, such as nonhuman primates, appropriate postoperative analgesia for the dam is an important precaution in preventing premature labor after intrauterine surgery (Tame et al., 1999).

For experimental protocols that require the manipulation of late-term rodent fetuses after their removal from nonanesthetized mothers (such as a dam euthanized by decapitation or cervical dislocation), guidelines for anesthesia and analgesia in neonates should be followed.

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