Common subjective assessments of olfactory performance include the Sniffin' Sticks test, CCCRC olfactory function test, and Brief Smell Identification Test. Among these, the CCCRC olfactory function test (also known as the cross-cultural odor identification test) is a rapid and effective measure of olfactory function [14]. It also takes into account differences in local and regional food cultures, as well as the fact that tested odors are easy to spot and distinguish by most people due to their simple features and comparatively stable intensity and nature. The present study assessed the effects of 6% desflurane (a common clinical dose) on short-term olfactory memory. Our results suggested that the inhaled anesthetic did not affect post-operative short-term olfactory memory. These findings are consistent with the study by Yildiz et al. [15], which determined that γ-aminobutyric acid (GABA), glutamate, and adrenergic neurotransmitter systems are known targets of anesthetics and may be correlated with olfactory memory [16–17]. However, the mechanisms of action were not further clarified. Little is known about the influences of anesthetics and anesthesia methods on olfactory memory. Multiple studies have found that isoflurane, a commonly used inhalation anesthetic, may induce neurotoxicity associated with cognitive impairment or learning/memory impairment [18]. Desflurane, in contrast, was not found to have this negative effect [15]. Conversely, another clinical study demonstrated that inhalation of 1.2% isoflurane had no obvious impact on olfactory memory [19].
Perioperative neurocognitive disorder is a recently developed overarching term for cognitive impairment developed during the preoperative or post-operative period. It has been observed in patients from across different age groups and undergoing various operations. Currently, there is a lack of agreement about the diagnostic criteria for PND. Advanced age, low education level, pre-existing cognitive impairment, alcoholism, and severity of coexisting diseases are considered to be major risk factors. Nevertheless, the pathogenesis of PND remains unelucidated, and growing evidence suggests that neuroinflammation and blood-brain barrier (BBB) dysfunction are the key contributors to PND [6, 20].
Neuron-specific enolase is a marker of cerebral ischemia and hypoxia injury, while S-100β protein is related to the severity of nervous system injury. Both of these indices may reflect nerve cell injury, and their fluctuating concentrations during the perioperative period are predictive of PND [21]. When brain neurons are damaged, the peripheral blood concentrations of S-100β and NSE increase. Most studies on POCD and post-operative delirium have also found increased plasma S-100β and NSE levels, which are considered to be evidence of increased BBB permeability [22]. In the present study, no significant differences were observed in S-100β protein and NSE concentrations before and after surgery. This suggests that desflurane does not affect patients’ short-term olfactory memory after surgery.
The role of melatonin in memory has recently become a popular research topic. It has been reported that melatonin is conducive to short-term memory and short-term olfactory memory [23, 24]. Animal researches have demonstrated that melatonin is related to the strength of associations in memory, especially in stressful situations. This association may depend on high concentrations of melatonin binding sites, which are important in matching odors with appropriate memories in the entorhinal cortex and hippocampal CA1 region [25, 26]. The role of melatonin in consolidating memory has also been confirmed in other studies. Meanwhile, the role of anesthetics (such as sevoflurane) in reducing melatonin levels and subsequently leading to post-operative olfactory memory impairment has been demonstrated in other studies[3]. Arai et al. [26]found that isoflurane may increase the concentration of melatonin in the blood, while sevoflurane may reduce it. GABA is a common major inhibitory neurotransmitter found in general anesthetics and olfactory bulb synapses. Our previous study [13] revealed that sevoflurane may reduce the concentrations of melatonin in the blood by inhibiting the binding of GABA to the corresponding receptors in the central nervous system, resulting in olfactory neuroepithelial damage and olfactory memory impairment. The present study found that inhalation of 6% desflurane did not change plasma melatonin levels, likely because desflurane does not have an impact on post-operative short-term olfactory memory.
This is the first study to assess changes in short-term olfactory memory and S-100β protein, NSE, and melatonin levels after desflurane anesthesia. However, it has some limitations. The sample size was small, the effects of long-term inhalation and inhalation of different concentrations of desflurane were not investigated, and changes in olfactory memory were not followed long-term. Further, clinical studies have confirmed that advanced age, infection, and previous cognitive impairment are risk factors for PND. However, it is unclear whether desflurane has an effect on the olfactory memory of elderly patients and patients with schizophrenia, dementia, or depression. Hence, the influences of anesthetics on post-operative olfactory memory should be further investigated in these patient subgroups. Finally, although previous studies have verified the role of melatonin in olfactory memory, there is a lack of data to confirm the direct relations between plasma s-100β protein, NSE, and olfactory memory. These measures may only reflect a parallel relationship among post-operative changes, and not necessarily indicate causality. Consequently, future research on post-operative olfactory memory should also include measurements of cognitive function.
In sum, the current study found that undergoing general anesthesia with the inhaled anesthetic desflurane did not affect the short-term olfactory memory of patients undergoing laparoscopic surgery. This may be explained by the proposition that desflurane maintains plasma S-100β protein, NSE, and melatonin levels. However, further research is needed to clarify whether varying degrees of olfactory memory impairment are associated with PND.