We compared the extubation time in patients with and without obstructive respiratory dysfunction after orthopedic lower limb surgery under general anesthesia with desflurane. Patients with obstructive respiratory dysfunction showed significantly longer extubation time than patients without obstructive respiratory dysfunction. Cox regression analysis showed that male sex and obstructive respiratory dysfunction are independent risk factors for prolonged extubation. This is the first known report to evaluate the early recovery from desflurane in patients with obstructive respiratory dysfunction. In contrast, age, operation time, and BMI were not the risk factors for prolonged extubation.
Desflurane is characterized by its low blood/gas partition coefficients, which promote its rapid elimination from the body. An experimental study in an animal model showed that drug-induced bronchoconstriction delayed desflurane elimination [5]. In this animal model, the investigators elucidated that the elimination of desflurane was affected by ventilation-perfusion (V/Q) scatter caused by the shift of ventilation distribution and perfusion dispersion. Furthermore, in the animal model of bronchoconstriction, the elimination of desflurane was more affected due to its low solubility than isoflurane, which is more soluble [7]. These data are consistent with the principle that uptake and elimination of less soluble agents rely more on gas exchange in lower V/Q lung ratios than more soluble agents. In addition, recent clinical studies reported that V/Q scatter caused by general anesthesia is large especially with desflurane, due to its low blood/gas partition coefficient [8]. Therefore, the delay of emergence could be more prominent with desflurane than with other inhalational anesthetics because of the larger V/Q mismatch. A clinical study in patients with COPD indicated that V/Q mismatch was more prominent than expected, even in patients at stage I before FEV1 decline [6]. They also showed that low V/Q areas are more prominent than high V/Q areas at the early stages of the disease. These data suggested the possibility that the elimination of desflurane could be delayed due to V/Q mismatch even in patients with slightly decreased FEV1/FVC.
The effect of desflurane on respiratory resistance could also affect its elimination. Volatile anesthetics are known to have bronchodilating properties, although recent literature reports conflicting evidence about the effects of desflurane on respiratory resistance. A recent randomized control trial showed that desflurane did not affect respiratory resistance at 1MAC as much as sevoflurane and isoflurane, although 1.5 MAC caused significant increases in respiratory resistance [9]. Conversely, experimental studies on human bronchial tissue showed that desflurane exerted similar relaxant effects on proximal airway smooth muscle as halothane, whereas desflurane was significantly less effective on distal bronchi [10]. The primary region affected in patients with COPD is found in the distal bronchi, which causes expiratory flow limitation. Thus, the obstruction of distal airways, which are less susceptible to the bronchodilating effect of desflurane, may delay the elimination of desflurane. Although the effect of desflurane on respiratory resistance in patients with COPD is still unclear, desflurane was reported to increase the respiratory resistance in patients who smoke [11]. On the other hand, sevoflurane was reported to decrease respiratory resistance in patients with COPD as well as with patients without COPD [12]. However, some patients did not respond to sevoflurane inhalation, with the percentage of those being higher in patients with COPD. These data suggest the possibility that volatile anesthetics including desflurane may not exert bronchodilating effects or even may increase the respiratory resistance in patients with COPD or in smokers. Although the proportion of current smokers was similar between the two groups in this study, desflurane may not show bronchodilating effects or increase respiratory resistance in patients with obstructive respiratory dysfunction, leading to delayed emergence.
Several studies reported that age, BMI, and operation time were associated with prolonged extubation after general anesthesia including general anesthesia induced by volatile agents [13, 14]. It has been shown that emergence and/or recovery from anesthesia are faster with desflurane than with sevoflurane, even in obese patients or elderly patients who are at higher risk for prolonged extubation [3, 4, 15]. However, it is unknown whether the emergence from general anesthesia with desflurane was affected by obesity or older age. Our data indicated that age, BMI, and surgery duration were not associated with extubation time after desflurane anesthesia. The prevalence of COPD is higher in the elderly, and the patients with obstructive respiratory function were older than the control patients in our study. Although maintenance concentration of desflurane was lower in the obstructive respiratory dysfunction group due to the reduced amount of inhalational anesthetic agents required in older patients, age-adjusted MAC was similar between the two groups. Additionally, logistic regression analysis showed that age was not associated with prolonged extubation, indicating that older age of patients in the obstructive respiratory dysfunction group was not the cause of the delay in extubation time.
We also found that male sex was an independent risk factor for prolonged extubation. Previous reports showed that emergence was significantly faster in women after general anesthesia with propofol and volatile anesthetics, including desflurane [16, 17]. An experimental study revealed that females had lower propofol plasma levels and less time to wakening during constant propofol infusion than males [18]. Conversely, it has been reported that there are no pharmacological differences related to sex in the effects of volatile anesthetics on the bispectral index of electroencephalography [19]. Although the underlying mechanisms are still unclear, our data support previous reports showing that the emergence from volatile anesthesia tends to be slower in male patients than in female patients.
Unlike other volatile anesthetics, desflurane has airway-irritating properties at concentrations that exceed 1MAC, which increases the risk of coughing, breath holding, and laryngospasm. Despite these properties of desflurane, studies comparing desflurane with sevoflurane found no differences in the incidence of such respiratory complications [20]. Conversely, these complications were more frequently observed in smokers than in nonsmokers regardless of anesthetic agent. In our study, the proportion of smokers was similar between the two groups, and it is unlikely that the airway-irritating properties of desflurane caused the delay in extubation time.
The clinical relevance of a 2-min slower emergence on outcome in patients with obstructive respiratory dysfunction is debatable. It would only have clinical relevance if it were associated with differences in patient outcomes or resource utilization. Recently, a meta-analysis comparing the early recovery from desflurane and sevoflurane in elderly patients revealed that time to open eyes and extubation was faster in the desflurane group, whereas no significant differences were observed in time to discharge from the recovery room. These data suggest that faster extubation time does not translate to faster recovery. Conversely, patients with obstructive respiratory dysfunction are at risk for airway complications and postoperative pulmonary complications. For such patients, faster emergence and extubation with a secure airway may confer several benefits; thus, it is important to understand the recovery profile from general anesthesia in patients with obstructive respiratory dysfunction. This study suggests the need for additional investigation of recovery profiles after the use of volatile anesthetics in patients with obstructive respiratory dysfunction.
This study has some limitations. First, the study used a retrospective design, and the treatment strategy was not controlled. We did not confirm ventilatory conditions after discontinuation of desflurane, such as the flow rate of fresh gas, respiratory rate, or partial pressure of end-expiratory carbon dioxide, which could affect the elimination of volatile anesthetics. Second, we did not evaluate the actual elimination of desflurane. Thus, longer extubation time in patients with obstructive respiratory dysfunction may not be due to the delay in desflurane elimination. Because the end-tidal volatile agent partial pressure in the presence of V/Q mismatch may not a reliable measure for the arterial blood level, partial pressure in the arterial blood should be measured to assess the elimination of desflurane [8]. Third, it should be considered that in our study, patients with obstructive respiratory dysfunction were not necessarily diagnosed with COPD. All except three patients in the obstructive respiratory dysfunction group were classified as moderate COPD based on the Global Initiative for Chronic Obstructive Lung Disease criteria. Thus, the generalization of our findings may not apply to patients with severe COPD. Fourth, in our study, the patients with obstructive respiratory dysfunction were older than patients in the control group, suggesting they may have comorbidities that would not be expected in the general population. We could not exclude the possibility that some comorbidities could affect the emergence from general anesthesia, although our multivariate analysis showed no association between age and extubation time.
