Current studies show that hypoeosinophilia is a predictor in some infectious diseases (sepsis, systemic inflammatory response syndrome) and non-infectious diseases (acute coronary syndrome, chronic obstructive emphysema, stroke).
The inflammatory response, particularly the acute inflammatory response, can cause significant EOS changes 16, and hypoeosinophilia is one of the reference diagnostic indicators of infectious and non-infectious diseases. Similar to C-reactive protein and procalcitonin, the EOS count is a serological diagnostic indicator of sepsis in the intensive care unit8. For non-infectious diseases, hypoeosinophilia is also positively related to the severity of acute ACS-induced myocardial injury; in other words, a greater myocardial infarct area corresponds to more severe peripheral hypoeosinophilia7. Hypoeosinophilia is also associated with the severity of chronic obstructive pulmonary disease. Mortality is significantly higher in patients with hypoeosinophilia at admission versus patients with normal EOS levels at admission, suggesting that EOS levels may reflect the severity of chronic obstructive pulmonary disease to some extent3. Moreover, hypoeosinophilia is a new predictor of adverse prognosis in patients with hemorrhagic or ischemic stroke, which may be associated with stroke-induced immunosuppression 5,9,10.
Currently, researchers believe that anesthesia methods and anesthetics affect the immune inflammatory response to varying degrees 11-13. However, no studies have investigated the effects of anesthesia methods on EOS levels. In this study, we retrospectively analyzed the clinical data of patients undergoing hip fracture surgery under different anesthesia methods to investigate the relationship between postoperative EOS changes and postoperative hospital stay.
According to the hypothesis and literature reports, this study included some measurements that might affect the association between postoperative hypoeosinophilia and postoperative hospital stay. We investigated demographic data of all participants and in subgroups stratified by anesthesia method. Preoperative EOS showed no difference between the general anesthesia group and the spinal anesthesia group, while postoperative day 1 EOS was lower in the general anesthesia group than that in the spinal anesthesia group. Because multiple drugs with varying doses were used during general anesthesia, we thought that complex medication affected patients’ inflammatory immune response and lowered postoperative EOS levels. On the other hand, fewer drugs were used during spinal anesthesia, resulting in less interference with inflammatory immune responses and thus facilitating discernment of the effect of surgical stress on postoperative day 1 EOS levels. Besides, some other variables had significant difference between two groups, such as age, intraoperative blood loss and RBC transfusion, postoperative day 1 HCT (Table 1). These differences in two groups are understandable. First, Anesthesiologists tend to choose spinal anesthesia for aged and high-risk patients. That is the reason why age was lower in the general anesthesia group than that in the spinal anesthesia group. Second, intraoperative data indicated that blood loss and RBC transfusion volume were higher in the general anesthesia group than those in the spinal anesthesia group. And consequently, postoperative day 1 HCT was found lower in the general anesthesia group than that in the spinal anesthesia group, which was considered to be related to greater intraoperative blood loss in the general anesthesia group. Similar to other literature reports, we considered that the between-group difference in blood loss in this study may be related to the anesthesia method17.
Length of postoperative hospital stay usually associates with patient age, gender, comorbidity, general physical condition, severity of surgical strikes and complications. In this study, ASA physical status as a well recognized evaluation of patient general condition was enrolled. It is also widely recognized by doctors that the severity of surgical strikes can be represent by the amount of intraoperative blood loss and transfusion. Therefore, variables related to blood loss need to be included in covariate screening. Since EOS is a subtype of WBC, perioperative WBC data should also be included in the covariates. The above variables were considered as potential confounding factors and included in univariate analysis. Variables showed significance (P<0.05) in univariate analysis or in the comparison of two groups were included in the multivariate analysis as covariables (Table 1 and 2).
Multivariate analysis failed to find association between post operative day 1 EOS and postoperative hospital stay in total patients ([EOS 1× 107/L increase] b=-0.08, 95%CI -0.21, 0.04), after adjusting age, gender, ASA, intraoperative blood loss, intraoperative RBC transfusion, postoperative day 1 HCT and WBC, and postoperative complications (Table 3). Considering anesthesia method might be an effect modifier, we further conducted subgroup analysis and interaction test stratified by anesthesia method. After adjusting the same confounders as in total patients and the interaction term for ASA, intraoperative blood loss, intraoperative RBC transfusion and postoperative complications, we found that the correlation between postoperative day 1 EOS and postoperative hospital stay ([EOS 1× 107/L increase] b=-0.39, 95%CI -0.74, -0.05) was significant in the general anesthesia, but was not ([EOS 1× 107/L increase] b=-0.02, 95%CI -0.15, 0.1) in the spinal anesthesia group. Also, the interaction of anesthesia method on postoperative hospital stay related to postoperative day 1 EOS was significant (P for interaction=0.0347)(Table4). Therefore, combined with EOS comparison between groups, it can be considered that general anesthesia reduces postoperative EOS and hypoeosinophilia is negatively correlated with length of postoperative hospitalization.
Literatures reported that different anesthesia methods cause different postoperative inflammatory immune responses, but the detailed mechanisms are unknown 18-21. In this study, the between-group difference of postoperative EOS may be related to the degree of interference with the inflammatory immune response between different anesthesia methods and drugs. Fewer drugs were used during spinal anesthesia versus general anesthesia. In this study, various regimens were used for general anesthesia, including total intravenous anesthesia and intravenous induction followed inhalation maintenance with multiple drugs, including midazolam, propofol, sufentanil, remifentanil, and sevoflurane, which exhibit varying degrees of interference with postoperative immune function; this may be the cause of postoperative hypoeosinophilia and the negative correlation between postoperative EOS level and postoperative hospital stay in the general anesthesia group. Taken together, this study suggests that patients undergoing general anesthesia should be closely monitored for hypoeosinophilia to enable early detection and intervention.
As a retrospective study, this study has some limitations. First, the sample size in the general anesthesia group was small, further subgroup analysis (e.g., inhalational anesthesia vs. intravenous anesthesia) couldn’t be conduct because of the limited sample size. Second, not all patients underwent blood tests on postoperative day 2; therefore, comparing longer-term postoperative EOS levels was impossible. In the future, larger studies, preferably multicenter and prospective studies, are needed to further validate the results.