The findings of the study would appear to have more relevance for non-U.S. anesthesiologists, but further study under conditions likely to be found in the United States may nonetheless be necessary.

“It is well known that medical residents are exposed to inhalational anesthetics, since they spend several hours per day and several days each week in the surgical center,” said Mariana G. Braz, PhD, a researcher at Universidade Estadual Paulista in Botucatu, Brazil. “Given that genetic instability is the first step in the development of chronic disease—including cancer—and no study yet has evaluated genetic damage in medical residents, this investigation sought to compare and evaluate markers of DNA damage, cell proliferation and cell death at the end of residency.”

“They were exposed for three years to inhalational anesthetics such as isoflurane and sevoflurane, and also nitrous oxide,” Braz said. The exposed group was age- and sex-matched with the unexposed group; the groups were demographically comparable. Residents ranged from 25 to 33 years of age.

As part of the genetic analysis, exfoliated buccal cells were collected from each resident and then freshly prepared. The coded slides were stained using the Feulgen fast-green method, and various cell types were scored to evaluate genetic instability, cytotoxicity and changes in the proliferation index using the buccal micronucleus cytome assay, a minimally invasive assay widely used for biomonitoring of inhalation exposure. The researchers also estimated exposure to inhalational anesthetics using ambient air measurements through a portable infrared spectrophotometer; values were expressed in parts per million (ppm).

As reported at the 2018 annual meeting of the American Society of Anesthesiologists (abstract A1049), anesthesiology residents spent approximately 60 hours per week (dubbed “high exposure”) in the OR and PACU, compared with approximately 18 hours per week in the OR for their surgical counterparts (“low exposure”).

“We found very high concentrations of anesthetics,” Braz explained. Indeed, the exposure assessment revealed that mean values were approximately 150 ppm for nitrous oxide, 5 ppm for isoflurane and 10 ppm for sevoflurane.

“Considering that Brazil doesn’t have any recommendations/limits for professional exposure, we followed the criteria from the U.S. National Institute for Occupational Safety and Health,” Braz said, “which limits nitrous oxide exposure to 25 ppm and halogenated anesthetics to 2 ppm.”

As the Table illustrates, anesthesiology residents showed lower frequencies of basal cells (P=0.001), and higher frequencies of micronuclei (P=0.038), karyorrhexis (P=0.001) and pyknosis (P=0.03) than unexposed residents. (Karyorrhexis refers to fragmented nuclei of cells that spread chromatin throughout the cytoplasm; pyknosis is the condensation of chromatin in the nucleus during necrosis or apoptosis.) Karyolytic cells were also significantly increased in anesthesiology residents compared with both surgery residents and controls (P=0.0009).

Table. Buccal Micronucleus Cytome Assay Markersa
Unexposed, % Anesthesiology, % Surgery, % P Value
Basal cells 54±23 31±13 40±15 0.001
Binucleated cells 9.3±6.7 12.4±8.8 13.1±5.2 0.1
Condensed chromatin 18.7±13.2 33.3±30.7 23.1±20.1 0.1
Karyolysis 5.1±4.3 24.9±23.4 12.5±14.6 0.0009
Karyorrhexis 22.4±16.1 55.1±37.7 38.9±23.5 0.001
Micronuclei 0.3±0.6 0.7±1.1 0.6±0.9 0.038
Nuclear buds 1.3±1.9 1.7±2.5 1.5±2.4 0.5
Pyknosis 3.1±4.7 9.6±9.7 5.0±5.2 0.03
a Data expressed as mean ± standard deviation.

“So we can say that by the end of the medical residency, the physicians were highly exposed to anesthetics,” Braz said. “Consequently, they have genetic damage. This is especially true for anesthesiology residents, who have increased genetic instability and cell death biomarkers, and reduced cell-proliferative potential.

“This means these individuals are at a genetically higher risk of developing some diseases in the future,” Braz noted. “So this exposure can have a real impact on their health.”

Levels Much Higher Than Allowed by OSHA

Yet as Stuart A. Forman, MD, PhD, a professor of anesthesia at Harvard Medical School, in Boston, told Anesthesiology News, the findings may have limited applicability to U.S. institutions. “The most striking aspect of the article is that the anesthetic exposure levels at the Brazilian site where this study took place are extremely high,” Dr. Forman said. “In particular, the nitrous oxide levels are sixfold higher than OSHA [the Occupational Safety and Health Administration] allows in the U.S., and the anesthesia residents worked long hours (60 hours per week) in this environment. Nitrous oxide inactivation of vitamin B12 might explain the significant findings, but other factors cannot be ruled out.

“Because of the extreme waste-gas exposures reported in this study, its findings may not be generalizable to most other settings,” Dr. Forman continued. “A similar study under more typical operating room ventilation conditions conforming to OSHA standards is needed before deciding whether the results are of concern to a significant fraction of anesthesia providers.”

Braz agreed that while the findings may have limited applicability in the United States, ORs in the developing and underdeveloped countries may not share this reality. “I agree with Dr. Forman that more research is needed under conditions conforming to OSHA standards,” she said. “It would be important and interesting to conduct such a study.”