To the Editor: 

I read with interest (and concern for those gestating) the article by Palanisamy et al.  analyzing adult Sprague-Dawley rats exposed to isoflurane in utero .1This was clearly a well-done study demonstrating reduced spatial memory and reduced anxiety in those animals exposed to isoflurane in utero  during a time of critical brain development. The question arises as to how this may apply clinically to humans. The gestational length described in this study was 22 days, or 528 h. The study exposed subjects to 4 h of isoflurane. Therefore, the intrauterine exposure to isoflurane accounted for 0.758% of the total gestational period. This seems miniscule, but when placed in perspective, is a significantly long period of time. In humans, a term gestation is 40 weeks, or 6,720 h, meaning a similar exposure in pregnant women would total 50 h, 55 min, and 48 s. It should not be surprising that exposing the developing fetal brain to isoflurane for more than 2 days might cause a reduction in spatial memory. After all, the effect of isoflurane on plastic water traps is well described.2,3Although the effect of volatile anesthetics on the developing brain is a fascinating and important topic, further study should include exposures that are clinically relevant to the human developing brain. In the meantime, it can be recommended that we avoid general anesthesia in pregnant women undergoing operations lasting longer than 50 h.

Palanisamy A, Baxter MG, Keel PK, Xie Z, Crosby G, Culley DJ: Rats exposed to isoflurane in utero  during early gestation are behaviorally abnormal as adults. ANESTHESIOLOGY 2011; 114:521–8
Abraham C, Deshpande SK: Isoflurane damage to a Draeger Primus water trap. Eur J Anaesthesiol 2006; 23:531–2
McAllister RK, Payne MN, Bittenbinder TM: Disruption of water trap from leak of isoflurane during the vaporizer filling process in the Dräger Apollo. ANESTHESIOLOGY 2007; 107:514