General Anesthetic
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Desflurane is not teratogenic in two animal species, but there are no reports of its use early in human gestation. The animal data are reassuring, but the absence of human data during organogenesis precludes an estimation of the risk for structural anomalies. In addition, general anesthesia usually involves the use of several pharmacological agents. Although no teratogenicity has been observed with three other halogenated general anesthetic agents (halothane, isoflurane, and methoxyflurane), only halothane has 1st trimester human exposure data (1). The use of desflurane during cesarean section does not appear to affect the newborn any differently from other general anesthetic agents. All such agents can cause depression in the newborn that may last for 24 hours or more. The potential reproductive toxicity (spontaneous abortion and infertility) of occupational exposure to desflurane has not been studied but is a concern based on the exposure concentration found in one study. In addition, occupational exposure to nitrous oxide also was measured in that study, and indicated that the nurses were exposed to both nitrous oxide and volatile anesthetic agents at the same time.
FETAL RISK SUMMARY
Desflurane, a general inhalation anesthetic agent administered via vaporizer, is indicated for the induction and/or maintenance of anesthesia during surgery. It is a nonflammable, volatile liquid that is in the same class of halogenated agents as enflurane, halothane, isoflurane, methoxyflurane, and sevoflurane. Desflurane is closely related chemically to enflurane and isoflurane. The only difference between desflurane and isoflurane is the substitution of fluorine in desflurane for the single chlorine atom in isoflurane. This small change, however, produces marked pharmacokinetic and clinical effects. The potency of desflurane is 20% that of isoflurane, the blood–gas partition coefficient is reduced (i.e., reduced solubility in blood) (0.42 vs. 1.46) as is tissue solubility (brain–blood partition coefficient 1.3 vs. 1.6), and recovery from anesthesia is faster (2).
Three mutagenic tests with desflurane found no evidence of genotoxicity (3). No teratogenic effects were observed in reproduction tests with rats and rabbits at doses of approximately 10 and 13 cumulative minimum alveolar anesthetic concentration (MAC-hour) exposures at 1 MAC-hour/day, respectively, during organogenesis. (Note: MAC is the concentration that causes immobility in 50% of patients exposed to a noxious stimulus such as a surgical incision; it represents the ED50 [4]). However, an approximately 6% decrease in the body weight of male rat pups delivered prematurely by cesarean section was noted at this dose. No treatment-related behavioral changes or other toxicity (dystocia or decreased body weight) were observed in rat offspring exposed to desflurane 1 MAC-hour/day from gestation day 15–lactation day 21 (3).
The low molecular weight (about 168) and the presence of desflurane in the brain suggest that it will cross the placenta to the fetus. Two reviews have concluded that, in general, inhalational anesthetic agents are freely transferred to fetal tissues (1,5) and, in most cases, the maternal and fetal blood concentrations are approximately equivalent (5). The relatively low human blood–gas partition coefficient and the rapid clearance from the maternal blood also suggest that desflurane will be rapidly cleared from the fetus, thus reducing the potential for neurobehavior depression of the newborn.
A brief 1993 report compared the closely related anesthetic agents, desflurane and enflurane (10 patients in each group), during cesarean delivery (6). Uterine tone increased significantly over time (a potential risk factor for maternal bleeding), but there were no differences between the groups. The mean umbilical vein:maternal artery ratios were 0.69 and 0.51, respectively. No differences between the groups were measured in the Neurological and Adaptive Capacity Scores (NACS) at 2 and 24 hours, 1 and 5 minute Apgar scores (8.0 and 8.9 vs. 7.5 and 9.0, respectively), and cord arterial blood gases or pH (6).
Two end-tidal concentrations of desflurane (3% and 6%) were compared with enflurane (0.6%) for cesarean section delivery in a 1995 study (7). The MACs for the three groups were 0.45, 0.90, and 0.40, respectively, thus representing subanesthetic concentrations. A 50%–50% mixture of nitrous oxide and oxygen was administered with the anesthetic agents (25 patients in each group). Maternal blood loss was similar among the groups. In the newborns, the time-to-sustained-respiration was >90 seconds in one (4%), seven (28%), and five (20%), respectively. The increased incidence in the 6% desflurane group was significantly longer than in the 3% desflurane group. There were no significant differences in the NACS at 2 and 24 hours, but some depression was noted: NACS <35 at 2 hours in four (16%), seven (28%), and six (24%); and at 24 hours—one (4%), one (4%), and none, respectively. Low Apgar scores (<7) were found at 1 minute in three (12%), seven (28%), and six (24%), respectively (ns), and at 5 minutes in none, one (4%), and one (4%), respectively (ns) (7).
A 1995 study compared desflurane (1.0%–4.5%) and oxygen (N = 40) with nitrous oxide (30%–60%) in oxygen (N = 40) for analgesia during vaginal delivery (8). Maternal analgesia scores and blood loss were similar between the groups. Four (10%) of the desflurane group had an NACS < 35 at 2 hours compared with seven (18%) of those exposed to nitrous oxide (ns). At 24 hours, none of desflurane group had an NACS <35 compared with three (8%) in the nitrous oxide group (ns). Apgar scores <7 at 1 minute occurred in 13% and 8% (ns), respectively, but all Apgar scores were ≥7 at 5 minutes. However, nine patients in the desflurane group had amnesia for delivery, a potentially undesirable effect in an obstetrical patient (8).
A study published in 1998 evaluated the exposure of nine nurses in a postanesthesia care unit (PACU) to exhaled desflurane and isoflurane and compared these exposures with the National Institute of Occupational Safety and Health (NIOSH)-recommended exposure limits (9). The NIOSH recommendation for volatile anesthetics (without concomitant nitrous oxide exposure) is a maximum of 2 ppm, but it has not been adopted by the Occupational Safety and Health Administration. Moreover, the recommended limit is controversial and is thought by some to be inappropriately low. However, a potential for reproductive risk (spontaneous abortion and infertility) is thought to exist for some anesthetic agents. The study involved exposure in the PACU to exhaled anesthetic gases from 50 adult patients (desflurane N = 31, isoflurane N = 19) over an approximate 1-hour recovery time. About half the patients were extubated in the PACU. Exposure was continuously measured from the shoulders (i.e., breathing zone) of the nurses. Breathing-zone anesthetic concentrations of desflurane and isoflurane exceeded the NIOSH limits in 87% and 37% of the cases, respectively. These exposures were above the limit 49% of the time for desflurane and 12% of the time for isoflurane. The investigators listed several limitations to their study and concluded that the results might represent a “worst-case analysis” (9).
A 2004 study found a significant association between maternal occupational exposure to waste anesthetic gases during pregnancy and developmental deficits in their children, including gross and fine motor ability, inattention/hyperactivity, and IQ performance (see Nitrous Oxide).
BREASTFEEDING SUMMARY
Although desflurane has been administered during labor and delivery, the effects of this exposure on the infant that begins nursing immediately after birth have not been described. Desflurane is probably excreted into colostrum and milk as suggested by its presence in the maternal blood and its low molecular weight (about 168), but the toxic potential of this exposure for the infant is unknown. However, the risk to a nursing infant from exposure to desflurane is probably very low (10). Moreover, the concentrations in milk should be less than other halogenated anesthetic agents because of the decreased blood and tissue solubility of desflurane and its rapid washout from the mother’s system. The manufacturer states that excretion in milk was not clinically important 24 hours after anesthesia (3). Another halogenated inhalation anesthetic, halothane, is classified as compatible with breastfeeding (see Halothane).
References
1.Friedman JM. Teratogen update: anesthetic agents. Teratology 1988;37:69–77.
2.Eger EI II. Desflurane animal and human pharmacology: aspects of kinetics, safety, and MAC. Anesth Analg 1992;75:S3–9.
3.Product information. Suprane. Baxter Healthcare Corporation, Anesthesia & Critical Care, 2002.
4.Trevor AJ, Miller RD. General anesthetics. In: Katzung BG, ed. Basic and Clinical Pharmacology. 8th ed. New York, NY: McGraw-Hill, 2001:426.
5.Kanto J. Risk–benefit assessment of anaesthetic agents in the puerperium. Drug Saf 1991;6:285–301.
6.Wallace DH, Armstrong A, Darras A, Gajraj N, Gambling D, White P. The effect of desflurane or low-dose enflurane on uterine tone at cesarean delivery: placental transfer and recovery (abstract). Anesthesiology 1993;79:A1019.
7.Abboud TK, Zhu J, Richardson M, Peres Da Silva P, Donovan M. Desflurane: a new volatile anesthetic for cesarean section. Maternal and neonatal effects. Acta Anaesthesiol Scand 1995;39:723–6.
8.Abboud TK, Swart F, Zhu J, Donovan MM, Peres Da Silva E, Yakal K. Desflurane analgesia for vaginal delivery. Acta Anaethesiol Scan 1995;39:259–61.
9.Sessler DI, Badgwell JM. Exposure of postoperative nurses to exhaled anesthetic gases. Anesth Analg 1998;87:1083–8.
10.Spigset O. Anaesthetic agents and excretion in breast milk. Acta Anaesthesiol Scand 1994;38:94–103.