Two Types of Anesthesia and Hemodynamic Changes in Patients Over 60 Years of Age Who Need Articial Femoral Head Replacement: A Retrospective Cohort Study

Background:Articial femoral head replacement is one of the most effective methods for treatment of severe diseases of femoral joint in the elderly. The ideal anesthetic effect is one of the key elements for the success of the operation because it brings fast recovery. However, the multiple comorbidities of the elder patients make them too weak to tolerate the hemodynamic changes after anesthesia. In this case, the most suitable anesthesia method for patients undergoing femoral head replacement surgery is of great signicance. Objective:To compare the post-anesthetic hemodynamic changes between combined lumbar plexus and sciatic nerve block(CLPSB) and combined spinal and epidural anesthesia(CSEA) in elderly patients undergoing unilateral articial femoral head replacement. Methods:We reviewed records of the patients who aged over 60 years old (age 62-103 years) and received unilateral articial femoral head replacement between January 2015 and December 2020 in the rst aliated hospital of Shantou University Medical College. After adjustment according to the inclusion criteria, 477 patients were included and divided into CLPSB group (n=90) and CSEA group (n=387). The primary outcome was comparison of the hemodynamic changes after anesthesia, including the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR). The second outcome was the comparison of the vasopressor used during the surgery. Results:We established three models to compare the two anesthesia methods on hemodynamic changes. Crude model included all variates for analysis, while model I adjusted age and gender. Model II adjusted other comorbidities in addition to model I. All three models exhibit that changes of MAP ( ∆ MAP) after CSEA were higher than that after CLPSB(β= 6.88, 95% CI: 4.33 - 9.42, P < 0.0001), with signicant difference, which indicated that CSEA causes higher uctuation of MAP. Concurrently, the use of vasopressors increased by 137% (OR=2.37, 95%CI: 1.24-4.53, P=0.0091) in the CSEA group, which is statistically signicant. However, the changes of HR ( ∆ HR) between the CLPSB and CSEA was not signicant(β= 0.50, 95% CI: 1.62 - 2.62, P = 0.6427). Conclusions:Both CLPSB and CSEA are ideal anesthesia methods for patients receiving femoral head eplacement, though CLPSB is more suitable for elderly patients with advanced hemodynamic stability.


Introduction
Arti cial femoral head replacement refers to the human femoral head necrosis caused by a variety of factors, the use of arti cial femoral head instead of femoral head function of the operation. Elderly people are more prone to femoral head lesions due to calcium loss and decreased body function. With the aggravation of population aging, the number of elderly patients receiving arti cial femoral head replacement is also increasing gradually. Since arti cial femoral head replacement is a large surgical operation, patients need to be operated under anesthesia, and elderly patients often have a variety of chronic underlying diseases, and the risk of anesthesia is signi cantly increased compared with the younger group. [1] Combined spinal-epidural anesthesia (CSEA) is characterized with rapid onset, full muscle relaxation, longer duration of anesthesia effect, and it is convenient for postoperative analgesia.However, for elderly patients, the anesthesiologists face greater challenges because of compulsive position of the patients and leading to greater failure rate comparing with combined lumbar plexus-sciatic nerve blockage (CLPSB). What's more, it disturbs the stability of the circulatory system.
Combined lumbar plexus-sciatic nerve block(CLPSB) is an effective anesthesia method for unilateral lower limb surgery, [2] which has little effect on the general physiological state of the patients. Also, it is an optional option when patients are taking antiplatelet and/or anticoagulant drugs.
In this study, we evaluated the role of CSEA and CLPSB in hemodynamics during arti cial femoral head replacement in elderly patients. [3] 2. Participants And Methods

Study Design
In this study, conducted a retrospective cohort study, with the relationship between the two types of anesthesia and hemodynamics.Target independent variables are two modes of anesthesia and dependent variables are hemodynamic changes (including ∆MAP=post-MAP-pre-MAP, ∆HR=post-HR-pre-HR, as well as the application of intraoperative vasopressors)

Study population
The data of participants of chinese patients with newly-diagnosed patients requiring arti cial femoral head replacement were nonselectively and consecutively collected from Department of Anesthesiology, The First A liated Hospital of Shantou University Medical College, Shantou, Guangdong Province city, China. Our data did not include identi able participants data for the purpose of safeguarding patient privacy. Data were compiled from Hospital electronic medical record system. Participants informed consent is not required in this study because of the nature of retrospective cohort study. The study protocol was approved by the Medical Ethics Committee of the First A liated Hospital of Shantou University Medical College.The data are anonymous, and the requirement for informed consent was therefore waived.Written informed consents were waived by the Medical Ethics Committee of the First A liated Hospital of Shantou University Medical College, because our study did't involve privacy and treatment of patients.
We reviewed the surgical records of 530 ASA grade I-III elderly patients who underwent unilateral arti cial femoral head replacement in our hospital from January 2015 to December 2020. We excluded 4 patients younger than 60 years old, 39 patients who chose endotracheal intubation general anesthesia, and 10 patients who switched to epidural anesthesia only after CSEA puncture failure. A total of 477 patients aged 62 to 103 years (male: female =122:355) were included and divided into CSEA group (n=387) and CLPSB group (n=90) according to different anesthesia methods.The patient selection process is shown in Fig. 1.

Variables
We recorded the two types of anesthesia as categorical variables. The procedure is described as follows: We were divided into two groups according to the two types of anesthesia.
According to published guidelines and studies, we obtain the nal result variables (∆MAP, ∆HR as continuous variables and Vasopressor as classi cation variables). The detailed procedure for measuring hemodynamic changes was described as follows: baseline mean arterial pressure was subtracted from the mean arterial pressure measured 10 minutes after occlusion, and baseline heart rate was subtracted from the heart rate measured 10 minutes after occlusion.
In this study, we included the following covariables, which can be summarized as follows :(1) Demographic data; (2) Variables that can affect hemodynamic changes reported in previous literature; (3) According to our clinical experience. Therefore, the following variables were used to construct a fully adjusted model :(1) continuous variables: age, baseline systolic blood pressure, baseline diastolic blood pressure, and baseline heart rate (obtained at baseline); (2) Classi cation variables: gender, hypertension, diabetes, heart disease, lung disease, central nervous system disease.

Methods
Premedication was not performed for any of patient. After arrival in the operating room, noninvasive blood pressure, electrocardiogram (ECG) and oxygen saturation (SpO2) were performed. Before anesthesia, intravenous access was established through 18G intravenous cannula in the upper arm and Ringer solution 10ml/kg was administered as prehydration. Oxygen, at the rate of 5L/min was delivered through a facial mask as well.
For CSEA group, the patient was placed in the lateral recumbent position and epidural space puncture was performed in L2-3 or L3-4 with needle-through-needle technique. Tuohy 18-gauge needle was in ltrated into epidural space at the point 1-1.5cm lateral to the midline with saline resistant loss technique. And then pencil point spinal needle 26-gauge passed through Touhy needle and reached to subarachnoid space. Isobaric 0.5% ropivacaine 15mg was administered intrathecally after observing free leakage of cerebrospinal uid. After all, spinal needle was withdrew and epidural catheter 20-gauge was placed cephalically 4cm in the epidural space, and 0.5% ropivacaine solution was injected 3-4ml if necessary. The patient was then placed in supine position.
For CLPSB group, combined lumbar plexus-sciatic nerve blockage was performed guiding by nerve stimulator (Stimuplex HNS 12 nerve stimulator, Stimuplex D B. Braum nerve-stimulator-guided needle). Psoas compartment block technique was used in lumbar plexus nerve blockage. [4,5] The patient was placed in lateral decubitus position with his neck, back and hips exed, and posterior iliac spine was identi ed. The nerve-stimulator-guided needle was inserted vertically at the intersection point of the posterior iliac spine and the line 4cm lateral and parallel to the midline along the intercristal line. The nerve stimulator delivered a current of 1.0mA at a frequency of 1MHz at the very beginning, and once appropriate movement was induced, the current was progressively decreased at 0.4mA, and 10ml 1.5% chloroprocaine and 20ml 0.4% ropivacaine were administered when ipsilateral contraction of the quadriceps muscle was still induced, indicating that the tip of the needle is close to the lumbar plexus. Next, the patients' positions were not changed, and sciatic nerve blockage was performed as follows: the greater trochanter and posterior iliac spine were identi ed and 4cm caudally on the midperpendicular line of this two landmarks was marked as the puncture point. The nerve-stimulator-guided needle was inserted vertically at this point and the nerve stimulator delivered a current of 1.0mA at a frequency of 1MHz, and the stimulation current was reduced to 0.2-0.4mA until dorsi exion motion on foot became visible. Following negative aspiration with the injector, 10ml 1.5% chloroprocaine and 20ml 0.4% ropivacaine were The patient's non-invasive blood pressure and heart rate were recorded at baseline and 10 minutes after anesthesia. The application of intraoperative vasopressors was also recorded. [7,8] All methods were performed in accordance with the relevant guidelines and regulations.

Statistical Analysis
We expressed continuous variables with normal distribution as mean ± standard deviation. Categorical variables were expressed in frequency or as a percentage. We used χ2 (categorical variables), Student T test (normal distribution), or Mann-Whitney U test (skewed distribution) to test for differences among different anesthesia groups. The data analysis process of this study was based on three criteria: (1) what is the relationship between anesthesia and hemodynamics (∆MAP, ∆HR, vasopressor); (2) which factors modify or interfere with the relationship between anesthesia and hemodynamics; and (3) adjust the interference factors or After the strati ed analysis, what is the true relationship between anesthesia and hemodynamics? Therefore, data analysis can be summarized in three steps.
Step 1: Univariate and multivariate linear regression were employed. We constructed three models: crude model, no covariates were adjusted; model 1, only adjusted for sociodemographic data age and gender ; model 2, model 1+other covariates presented in table 1. [9] Step 2: The subgroup analyses were performed using strati ed linear regression models. For continuous variable, we rst converted it to a categorical variable according to the clinical cut point or tertile, and then performed an interaction test. Tests for effect modi cation for those of subgroup indicators were followed by the likelihood ration test. [10]To ensure the robustness of data analysis, we did a sensitivity analysis. All the analyses were performed with the statistical software packages R (http://www.R-project.org, The R Foundation) and EmpowerStats (http://www.empowerstats.com, X&Y Solutions, Inc, Boston, MA). P values less than 0.05 (two-sided) were considered statistically signi cant. [11] 4. Results

Baseline characteristics of selected participants
A total of 477 participants were selected for the nal data analysis after screening by inclusion and exclusion criteria (see Figure 1 for a ow chart). We showed baseline characteristics of these selected participants in table 1 according to two types of anesthesia. In general, the average age of the 477 selected participants was 80.17± 7.671 years old and about 0.25577% of them were male. No statistically signi cant differences were detected in age,gender,no complications,hypertension,diabetes,heart disease,central nervous system disease among different anesthesia groups (P > 0.05).There were statistical differences in pulmonary diseases among different anesthesia groups (P <0.05).
In Table 2, we show baseline and post-block hemodynamic values for these selected participants, as well as differences in mean arterial pressure and heart rate between the two groups, and the use of vasoactive drugs.There were no signi cant differences in baseline systolic blood pressure, baseline diastolic blood pressure, baseline mean arterial blood pressure and baseline heart rate between the two groups (P>0.05).The systolic blood pressure after block, diastolic blood pressure after block, mean arterial pressure after block and heart rate after block in the CSEA group were all lower than those in the CLPSB group, and the difference was statistically signi cant (P <0.05).The difference between baseline mean arterial pressure and post-block mean arterial pressure was statistically signi cant between the two groups (P<0.05), and the CSEA group was signi cantly lower than the CLPSB group. There was no statistical difference between baseline heart rate and post-block heart rate between the two groups (P>0.05). The proportion of vasoactive drugs used in the CSEA group was higher than that in the CLPSB group, and the difference was statistically signi cant (P<0.05).

Unvariate analysis
We listed the results of univariate analyses in Table 3. By univariate linear regression. First of all,we found that age,gender,diabetes,heart disease,lung disease,central nervous system disease were not associated with ∆MAP and ∆HR(P>0.05);univariate analysis showed that hypertension were positively correlated with ∆MAP and ∆HR (P<0.05). [12]Then,we found that age,gender,diabetes,hypertension,lung disease,central nervous system disease were not associated with vasopressor (P>0.05);univariate analysis showed that heart disease were positively correlated with vasopressor (P<0.05).

Results of unadjusted and adjusted linear regression
In this study, we constructed three models to analyze the independent effects of two types of anesthesia on ∆MAP,∆HR,vasopressor (unvariate and multivariate linear regression ). The effect sizes (β and OR,β for ∆MAP and ∆HR,OR for vasopressor) and 95% con dence intervals were listed in Table 4-6. In the unadjusted model (crude model),the effect size of 6.80mmHg for ∆MAP in unadjusted model means that mean arterial pressure change was higher in CSEA group than in CLPSB group(6.80, 95%CI (4.27, 9.34)),the difference was statistically signi cant (P < 0.05). In the minimum-adjusted model (model 1), mean arterial pressure change was higher in CSEA group than in CLPSB group (7.02,95% CI (4.47, 9.56)),the difference was statistically signi cant (P < 0.05). In the fully-adjusted model (model 2) (adjusted all covariates presented in table 1), mean arterial pressure change was higher in CSEA group than in CLPSB group (6.88, 95% CI (4.33, 9.42)),the difference was statistically signi cant (P < 0.05).In the unadjusted model (crude model),the effect size of 0.71bmp for ∆HR in unadjusted model means that heart rate change was higher in CSEA group than in CLPSB group(0.71, 95%CI (-1.39, 2.81)),the difference was not statistically signi cant (P > 0.05). In the minimum-adjusted model (model 1), heart rate change was higher in CSEA group than in CLPSB group (0.59,95% CI (-1.51, 2.70)),the difference was not statistically signi cant (P > 0.05). In the fully-adjusted model (model 2) (adjusted all covariates presented in table 1), heart rate change was higher in CSEA group than in CLPSB group (0.50, 95% CI (-1.62, 2.62)),the difference was not statistically signi cant (P > 0.05).In the unadjusted model (crude model),the effect size of 2.29 for vasopressor in unadjusted model means that use of vasopressor was higher in CSEA group than in CLPSB group 129%(2.29, 95%CI (1.22, 4.30)),the difference was statistically signi cant (P < 0.05). In the minimum-adjusted model (model 1), use of vasopressor was higher in CSEA group than in CLPSB group 141%(2.41,95% CI (1.28, 4.54)),the difference was statistically signi cant (P < 0.05). In the fully-adjusted model (model 2) (adjusted all covariates presented in table 1), use of vasopressor was higher in CSEA group than in CLPSB group 137% (2.37, 95% CI (1.24, 4.53)),the difference was statistically signi cant (P < 0.05).

Subgroup analysis
We used age,gender,no complications,hypertension,diabetes,heart disease,lung diseases,central diseases as the strati cation variables to observe the trend of effect sizes in these variables (Figure 2-4). No signi cant heterogeneity was found in all subgroups (P>0.05).Found that central disease patients who applied probability increase use of vasopressor(OR 6.44,95%CI (1.46, 28.47),P=0.0662). Other results of the subgroup analysis were consistent with the preliminary results.

Discussion
The present study was a retrospective cohort study comparing the hemodynamic effects of combined lumbar plexus-sciatic nerve block with combined lumbar epidural anesthesia in elderly patients undergoing arti cial femoral head replacement. [13] The earliest recorded attempts at hip replacement were performed in Germany by Themistocles Gluck in 1891. [14] And an American surgeon, Dr. Austin T. Moore carried out the rst metallic hip replacement surgery on September 28, 1940 at Columbia Hospital in Columbia, South Carolina. [15] Most of the patients suffered from hip fracture and receiving femoral head arthroplasty are elderly patients. And multisystematic diseases, such as hypertension, diabetes mellitus, coronary artery diseases, cerebral infarction, and chronic obstructive pulmonary diseases, often exist as well. They bring great risks to the patients and big changes to the anesthesiologists.[16, 17] So, it is a big task for us to choose a most suitable anesthetic technique for the patients. [24]However, our results showed that CSEA signi cantly reduced blood pressure in patients undergoing arti cial femoral head replacement.The decrease value was 17.20 ± 11.37mmHg.We analyzed these studies that were inconsistent with our results, and we speculated that the reasons for the different results might be caused by the following factors :(1) the study population was different. (2) The number of study cases was small.
Combined lumbar plexus-sciatic nerve blockage technique can be the alternative choice for femoral head arthroplasty in elderly patients. It can provide full anesthesia blockage in unilateral lower limb. And it has less in uence on cardiovascular system and respiratory system. It is more suitable for elderly patients and especially those suffering from cardiac dysfunction and pulmonary dysfunction.Similar to us, Marcel A. de Leeuw, MD et al. found that peripheral nerve block did not cause clinically signi cant hemodynamic changes.
[25] Leonardo Teixeira Domingues Duarte has similar results to ours, and has also shown that the addition of sciatic nerve block to lumbar plexus block promotes complete blockade of the injurious nerve innervation of the hip, but the dose of local anesthetic is also signi cantly increased. [26] In our study, the probability of intraoperative application of vasoactive drugs in the CSEA group was higher than that in the CLPSB group.
CSEA technique causes hypotension through peripheral vasodilation due to sympathetic efferent block.
[27]CLPSB technique has less effect on hemodynamics and is more suitable for elderly patients.Mehmet Aksoy et al. 's study reached a similar conclusion. [28] In our study, combined lumbar plexus-sciatic nerve blockage and combined spinal-epidural anesthesia are both suitable for elderly patients receiving arti cial femoral head replacement. Combined lumbar plexus-sciatic nerve blockage anesthesia method has an advantage in hemodynamic stability, and it has less in uence on physical status. Combined spinal-epidural anesthesia method has more reliable clinical effects and faster onset of action. However, it may cause cardiovascular disturbance and affect respiratory system due to high block level.
[29] Guang Han et al. studied that sitting CSEA was more stable than lying CSEA in terms of hemodynamics.
suggested that a low dose of high-density bupivacaine (7.5 mg) in combination with sufentanil (5 mg) could provide reliable lumbar anesthesia for the repair of hip fractures in elderly patients with fewer hypotensive events and no need for vasopressant support. [31] The limitations of this study include: (1) in this study, we research object is mainly over 60 patients with femoral head replacement is required, the results do not apply to patients younger than 60 years of age, and other patients (2) the surgical procedure of this study is the single center of regional level, so the results do not necessarily apply to other region or ethnic group. Combined with the above two points, the universality and extrapolation of the research have some de ciencies. (3) we are not listed in the study of the operation of the hemodynamic situation, because we know that in the operation because different surgery, surgeons in surgical bleeding, operation time, auxiliary opioid analgesia, etc, there will be a lot of confounding factors, block after the longer results is unreliable, so we have no intraoperative and postoperative data list. In future studies, we will design prospective studies to explore intraoperative and postoperative hemodynamic changes through randomization and blind methods.
From what has been discussed above,we should choose a most suitable anesthesia approach according to the patient conditions. The datasets generated during and analysed during the current study are not publicly available due to our data is still undergoing other analysis, we cannot share it at present, but are available from the corresponding author on reasonable request.

-Competing interests
The authors declare that they have no competing interests.

-Funding
Not applicable -Authors' contributions Weiqi Ke was responsible for the overall implementation of the study and paper writing, Yuting Wang was responsible for the data analysis, Xukeng Guo was responsible for the data collection and paper writing, Ronghua Huang, Xiangdong Zhang, Weikai Wang and Xuan Ji were responsible for the data collection, and Shaohui Zhuang was responsible for the overall guidance.All authors reviewed the manuscript.

-Acknowledgements
We appreciated Ms. Xinglin Chen and Ms. Linlin Jiang for their guidance in data analysis.    Abbreviations: CI, con dence interval.
Model adjusted for age and gender.
Model adjusted for age, gender, hypertension, diabetes, heart diseases, lung diseases, Central diseases.  Effect size of two types of anesthesia on ∆HR in prespeci ed and exploratory subgroups in Each Subgroup