Desflurane and Surgery Exposure During Pregnancy Decrease Synaptic Integrity and Induce Functional Deficits in Juvenile Offspring Mice.

Anesthesia in pregnant women may cause adverse effects in the hippocampus of unborn babies and fetal brain development. The mechanisms underlying pathological changes resulting from anesthetics are unclear. This study tested the hypothesis that exposure to desflurane during pregnancy may impair cognition and memory functions of juvenile offspring. Pregnant mice (at gestational day 14) were administered 10% desflurane for 3 h and compared to sham control and sciatic nerve hemi-transection surgery. Hippocampal tissues of both fetal (G14) and offspring mice (postnatal day 31) were collected and analyzed by real-time qPCR and Western blot. Functional tests were performed to assess fear and memory functions in offspring mice. Primary hippocampal neuronal cultures from postnatal day 0 (without desflurane exposure) were examined for neuronal and synaptic development under desflurane treatment in vitro. In this acute experiment, we showed that neuronal cultures exposed to desflurane significantly increased interleukin (IL)-6 expression and apoptotic gene caspase-3 activation. Desflurane exposure significantly reduced PSD-95 expression in hippocampal neurons. Similar changes were observed in hippocampal tissues from juvenile offspring mice. Inhaled desflurane impaired memory functions in offspring mice compared to sham control. These mice displayed higher sensitivity to fear conditioning. Neurons isolated from the mice exposed to desflurane exhibited significantly lower levels of synaptophysin expression. These results suggest that anesthetic exposure together with surgery during pregnancy may induce detrimental effects in juvenile offspring mice via the induction of cell death and disruption of synaptic integrity.

Exploratory analyses of postanesthetic effects of desflurane using behavioral test battery of mice.

Halogenated ethers, such as desflurane, sevoflurane, and isoflurane, are known to exert an array of effects besides sedation. However, the postanesthetic effects of desflurane remain undiscovered as no study has explored these effects systematically. Phenotypic screening using behavioral test batteries is a powerful method to identify such effects. In the present study, we behaviorally phenotyped desflurane-treated mice to investigate postanesthetic effects. We applied comprehensive behavioral test batteries measuring sensorimotor functions, anxiety, depression, sociability, attention, and learning abilities, starting 7 days after anesthesia performed with 8.0% desflurane for 6 h. Although our previous study revealed postanesthetic effects of isoflurane in adult mice, in the current study, desflurane-treated mice exhibited no such effects in any behavioral test. To further examine whether desflurane affect behavior in more early time point, we built up a new additional test battery, which carried out 1 day or 3 days after exposure to desflurane. Mice treated with desflurane 1 day before testing showed more slips than other two groups in the first trial, suggesting mild acute side effects of desflurane on motor coordination. These results suggest the safety of desflurane in clinical settings and imply that postanesthetic effects are unique to each halogenated ether.

Dexmedetomidine prevents desflurane-induced motor neuron death through NF-KappaB pathway.

Desflurane is one of the commonly used general anaesthetics. Recently, it was reported that desflurane caused neurotoxicity, raising concerns in clinical use. In this study, we found desflurane could affect viability and maturation in motor neurons. Dexmedetomidine, a α2-adrenergic receptor agonist, could attenuate the effect of desflurane on motor neurons. This process was mediated by NF-KappaB signalling. Interestingly, we also found that dexmedetomidine could recover the lesion in motor function and memory impaired by desflurane. Collectively, our results showed the neurotoxic effect of desflurane in motor neurons. More importantly, this process was alleviated by dexmedetomidine, potentially showing its application in protecting motor neuron from neurotoxic agents. Significance of the study: This work provides the evidence to support the protective role of dexmedetomidine in desflurane-induced motor neuron death. Since desflurane is a widely used anaesthetic in surgery and leads to neuron death, the neuroprotective effect of dexmedetomidine holds promising clinical application.

The negative effect of desflurane on reproductive capacity in female rats.

AIM: The aim of this study was to determine the effect of desflurane on reproductive capacity in female rats through a study of biochemical evaluations. METHOD: After experimental procedure, the blood samples of female rats were collected, and the malondialdehyde, interleukin­1­beta, total glutathione and superoxide dismutase levels were measured to evaluate oxidative stress. In addition to biochemical evaluations, the reproductive performance of the experimental groups was also examined. RESULTS: The results of our study demonstrated that in blood samples of desflurane­treated groups of rats, the parameters indicating oxidative stress and inflammation increased, and antioxidant parameters decreased (p < 0.05). It was also proven that repeated desflurane doses caused infertility in female rats, prolonged the gestation period and reduced the number of offspring. CONCLUSIONS: This study showed that recurrent desflurane application can cause infertility problems through oxidative stress in female rats (Tab. 3, Fig. 1, Ref. 25).

In vitro assessment of the direct hemolytic effect of the volatile halogenated anesthetics sevoflurane, isoflurane, and desflurane.

Sevoflurane is being repurposed as a topical analgesic for painful wounds. Providing pre-charged sevoflurane syringes to irrigate wounds implies a potential risk of accidental intravenous injections. We assessed the potential of two concentrations (33% and 50% v/v) of three anesthetics, isoflurane, desflurane and sevoflurane, to produce hemolysis in vitro. Spectrophotometric absorbance was read at 576 nm. For both concentrations, the percentage of hemolysis (mean ± SD) was higher for isoflurane (29.7 ± 3.4% and 39.5 ± 5.3%), mild for desflurane (8.0 ± 0.5% and 6.5 ± 0.9%) and negligible for sevoflurane (0.7 ± 0.0% and 0.6 ± 0.1%), respectively. In conclusion, in contrast to isoflurane and desflurane, sevoflurane did not display hemolytic potential in vitro. However, the use of syringes preloaded with sevoflurane may still be problematic if it increases the possibility of inadvertent intravenous administration through increased risk of gas embolism and severe central nervous system depression.

Inflammation and DNA damage induction in surgical patients maintained with desflurane anesthesia.

The use of anesthetics during surgical interventions may contribute to disorders in the perioperative period. Desflurane is the newest volatile halogenated anesthetic to be introduced in clinical practice. Considering that inflammation and genotoxicity are linked events, and that little is known regarding possible genetic and inflammatory effects of desflurane in surgical patients, this study evaluated DNA damage, systemic inflammatory cytokines and related gene expression in adult patients without comorbidities who underwent minor otorhinological surgeries under general anesthesia maintained with the inhalational anesthetic desflurane. This study involved a self-controlled design in which venous blood samples were collected from subjects before anesthesia administration and after the surgical procedure. The comet assay was applied to assess DNA lesions, while the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-17A and TNF-α were evaluated by flow cytometry. A genotoxic effect was observed (p = 0.027), and pro-inflammatory IL-6 and IL-8 levels were significantly increased after surgery (p = 0.001 and p = 0.02, respectively), whereas the levels of the other cytokines did not significantly change. Considering that serum IL-6 and IL-8 were increased, we further evaluated IL-6 and IL-8 gene expression by quantitative real-time polymerase chain reaction (qPCR). However, IL-6 and IL-8 gene expression was unaltered (p >  0.05). In conclusion, anesthetic maintenance with the modern agent desflurane during minor surgeries led to genotoxic and inflammatory effects without altering the expression of inflammation related-genes the day after surgery in patients without comorbidities.