Utilization of epinephrine-soaked gauzes to address bleeding from osteotomy sites in non-tourniquet total knee arthroplasty: a retrospective cohort study

Utilization of epinephrine-soaked gauzes to address bleeding from osteotomy sites in non-tourniquet total knee arthroplasty: a retrospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Utilization of epinephrine-soaked gauzes to address bleeding from osteotomy sites in non-tourniquet total knee arthroplasty: a retrospective cohort study Hongzhi Liu, Zhaohui Liu, Qidong Zhang, Wanshou Guo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-23569/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Aug, 2020 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted 10 You are reading this latest preprint version Abstract Background Abandoning tourniquet was commenced because of the complications of tourniquet extensively used for the control of hemorrhage in total knee arthroplasty (TKA). Bleeding management is critical to acquire a relative bloodless arthrotomy interface for maximize cement fixation in non-tourniquet TKA. The purpose of this study was to investigate hemostatic and hemodynamic effects of epinephrine-soaked gauzes in cemented TKAs. Methods A retrospective cohort study of 101 patients in two groups was performed. The first group (n = 51) underwent unilateral TKA with our procedures of epinephrine use, the second group (n = 50) had the same protocol with tourniquet and no epinephrine utilization. Surgical field visualization was assessed by grading scale for difficulty of intraoperative visualization due to blood and number of surgical field clearances. Perioperative blood loss were recorded. Hemodynamic parameters were observed in the epinephrine group. Results There was statistically significant difference (p < 0.01) on surgeon-rated difficulty in visualization in the epinephrine group between before and after use of epinephrine, and no statistically significant differences (p = 0.96) between two groups before cementing. No statistically significantly result on numbers of surgical field clearances between two groups (p = 0.25) was reached. Significant difference in hidden blood loss, was observed in two groups (p = 0.04). The hemodynamic effects of epinephrine may be under control. Conclusion The procedure of epinephrine soaked gauzes, as a prudent adjunct, may be effective to reduce blood loss and obtain bloodless bone sections in non-tourniquet TKAs, regardless of hemodynamics. Orthopedics Epinephrine Tourniquet Total knee arthroplasty Hemostatic effects Hemodynamic Figures Figure 1 Background Epinephrine is often used in local infiltration analgesia to reduce systemic absorption of the local anesthetic and prolong the analgesic effect in total knee arthroplasty (TKA) [ 1 , 2 , 3 ], is also used to reduce perioperative blood loss [ 4 , 5 ]. Epinephrine as a procoagulant has been demonstrated key activities associated with increased fibrinogen release, activation of fibrinogen receptors, and effects on other coagulation factors whose activities are mediated via beta-adrenergic receptor. Further research has showed that platelet count increases arise from splenic autotransfusion following low-dose epinephrine infusion via alpha-adrenergic receptors [ 6 , 7 , 8 ]. In short, the whole blood clotting time significantly decreases. Administration of epinephrine is controversial in joint replacement because of a composite of major cardiopulmonary complications including ventricular tachycardia, broken-heart syndrome, pulmonary edema, and intraventricular bleeding [ 9 , 10 , 11 ]. However, there has been little discussion about its hemostatic effect as a vasoconstrictor, and hemodynamic effect when administering epinephrine in TKA procedure. A pneumatic tourniquet is commonly used in TKA to improve visualization of the operative field, decrease intraoperative blood loss, and enhance the quality of cementation [ 12 , 13 ]. Even in some no-tourniquet procedures, a tourniquet was also inflated during component cementation because some participating surgeons felt a tourniquet was necessary to minimize blood at the bone-cement interface and maximize fixation. However, acute hypotension and the ischemia-reperfusion (I-R) injury would occur when blood perfusion was re-established and release of metabolites from the ischemic limb and reduced cardiac preload after deflation of the tourniquet. And it would have a high risk of cardiac and cerebral micro emboli, a high risk of deep venous thrombosis, and an increased incidence of arterial thrombosis especially for the elderly undertaking TKA who have multiple comorbidities [ 14 ]. Therefore, for a tourniquet-free TKA protocol, our attempt was made to establish a set of intra-surgical procedures that can provide a satisfying visualization and a relatively bloodless bone interface for cementation with the topical hemostatic agent of epinephrine solution. Furthermore, epinephrine-related side effects associated with adverse cardiopulmonary complications may be fatal in rare cases and cautious hemodynamic monitoring is needed. The purpose of this study was to determine the hemostatic effect of epinephrine-soaked gauzes by comparing surgical field visualization between patients receiving epinephrine and those undergoing tourniquet. We hypothesized that epinephrine-soaked gauzes would be sufficient to reduce blood loss and obtain bloodless bone sections in patients undergoing non-tourniquet cemented TKA. Methods Patient selection This study protocol has been approved by the IRB of the authors’ affiliated institutions. This is a retrospective cohort study of 143 patients who under a primary unilateral cemented TKA from January 1, 2018 to December 31, 2019 in our hospital. From the final analysis patients with prior surgery involving the femur or tibia, prior lower extremity fracture, coagulopathy and uncontrolled hypertension, history of myocardial infarction or stroke, and bilateral total knee arthroplasty were excluded. In the final analysis, a total of 101 patients fulfilled the study inclusion criteria and were available. The patients were analyzed in 2 groups. In the first group, a tourniquet was not used but prepared for blooding out of control and gauzes soaked with a normal saline solution mixed with a dose of epinephrine (dilution 1:125,000) were utilized to cover and pressurize for hemostasis on the osteotomized surface of the distal femoral and proximal tibial bones at the finish of bone resections. In the second group, a pneumatic tourniquet placed high on the thigh was inflated to 250 mmHg before the skin incision and deflated after the cement was completely polymerized. All other aspects of perioperative care were constant throughout the groups. Perioperative management All the operations were performed with a fixed plant posterior-stabilized total knee prosthesis in a medial parapatellar approach. A general anesthetic with an adductor canal block was used for all the patients [ 15 ]. And appropriate perioperative parenteral antibiotics were administered for infection prophylaxis. High-pressure pulsatile lavage was used to clean the bone surfaces and soft tissues. Before wound closure, all knees received an intraarticular injection of a cocktail containing ropivacaine, morphine, and ketorolac to enhance postoperative analgesia without drain insertion. Elastic compressive dressing was also used. Each patient received the same perioperative regimen: tranexamic acid (TXA), pain control and rehabilitation. TXA was given at the initiation of the surgery and just before closure [ 16 ]. Multimodal postoperative pain management and accelerated physical therapy were performed as previously described. Low molecular weight heparin (enoxaparin, 3,000 IU) was administered subcutaneously 12 h after the operation and was continued for 2 weeks for thrombosis prophylaxis. After recovery from anesthesia, quadriceps femoris muscle isometric contraction was immediately started, and rehabilitation began on the first postoperative day, including muscle power training. Outcome measurement The primary outcome of the study was surgical field visualization including surgeon-rated difficulty in visualization and number of surgical field clearances. Two authors, blinded to one another's results, assessed it. Any disagreement was resolved by a consensus between all authors. Surgeon-rated difficulty in visualization was performed prior to using epinephrine in Epinephrine group and before cementing in two groups. Number of surgical field clearances was also used in two groups over the period from the finish of bone cutting through the cement hardening. Every action of surgical field clearance excluding using epinephrine-soaked gauzes was counted as the number of surgical field clearances. Perioperative blood loss was the second outcome. Volumes of intraoperative blood loss, postoperative blood loss, blood transfusion, and hidden blood loss were recorded. The blood volume of each patient was calculated by a formula that consists of patient weight, height and sex [ 17 ]. The blood loss was calculated on the basis of the validated Gross formula [ 18 ]. Hematocrit (Hct) and Hb (Hemoglobin) levels were determined preoperatively and on postoperative day 2. The intraoperative blood loss represented by the increased weight of the gauzes plus the volume in the aspirator bottle excluding rinse. The amounts of postoperative visible blood loss were calculated by weighing the dressings removed after the surgery. Intraoperative characteristics included the surgical duration (beginning at incision until emergence from anesthesia), tourniquet time were noted. Meanwhile, in the epinephrine group, incidences of hypertension, hypotension and tachycardia were evaluated. Hemodynamic parameters at 1-minute intervals for 15 minutes since timing of application of the epinephrine were recorded. The incidence of symptomatic deep vein thrombosis (DVT) was detected by a bilateral lower extremity deep venous color Doppler ultrasound examination. The development of symptomatic pulmonary embolism (PE) was identified by computed tomography pulmonary angiogram (CTPA). Other complications, such as subcutaneous hematoma, skin complications (blisters, bruises, superficial and deep wound infection), were also recorded. Statistical analyses Data were entered into an Access Case Report Form database and further analyzed by R software (version 3.6.3, The R Foundation, Vienna, Austria). Quantitative data are presented as the mean and standard deviation (SD); categorical variables are used as proportions. Differences in continuous variables between groups were evaluated with Independent-Sample T test or Mann-Whitney U test, depending on the distribution characteristics of the data. A chi-square test or Fisher exact test for difference in proportions was used to estimate the differences between groups in categorical variables. Values of p 0.05) found at baseline with regard to age, BMI, sex, ASA class, mean starting hemoglobin, or preoperative diagnosis between the groups. In this study, 101 patients were available, as shown in Table 1 : 51 in the epinephrine group, and 50 in the no epinephrine group. The tourniquet time for the tourniquet group was 61.1 min. The mean operating time for the epinephrine group (81.6 min) and the no epinephrine group (80.9 min) was not significantly different (p = 0.76). Table 1 Patient Demographic Characteristics Epinephrine group (N = 51) No epinephrine group (N = 50) P value Age* (yr) 67.1 (8.6) 66.8 (8.9) 0.88† Sex‡ 0.34# Male 4 (7.8%) 8 (16.0%) Female 47 (92.2%) 42 (84.0%) BMI* (kg/m^2) 25.8 (3.2) 26.2 (3.4) 0.55† Starting hemoglobin* (g/dL) 131.8 (12.3) 132.4 (14.3) 0.22† ASA classification‡ 0.32§ 1 (normal, healthy) 20 (39.2%) 19 (38.0%) 2 (mild, systemic disease) 30 (58.8%) 29 (58.0%) 3 (severe systemic disease) 1 (2.0%) 3 (6.0%) Preoperative diagnosis‡ 0.99** Osteoarthritis 50 (98.0%) 48 (96.0%) Rheumatoid arthritis 1 (2.0%) 2 (4.0%) Tourniquet time* (min) NA 61.1 (7.8) Operating time (min)* 81.6 (12.1) 80.9 (9.3) 0.764† *The values are given as the mean and the standard deviation. †Significance was determined with use of Independent-Sample T test. ‡The values are given as the number of patients, with the percentage in parentheses. #Significance was determined with use of the chi-square test. §Significance was determined with use of the Mann-Whitney U test. **Significance was determined with use of the Fisher exact test. In terms of surgical field visualization, there was statistically significant difference (p < 0.01) on surgeon-rated difficulty in visualization in the epinephrine group between before and after use of epinephrine, and no statistically significant differences (p = 0.96) between two groups before cementing (Table 2 ). We also found no statistically significantly result on numbers of surgical field clearances between two groups (p = 0.25) (Table 3 ). Table 2 Surgeon-rated difficulty in visualization* Before Epinephrine Before Cementing P value Epinephrine group No epinephrine group Epinephrine group No epinephrine group (N = 51) (N = 50) (N = 51) (N = 50) 0 No Difficulty 0 (0.0%) NA 42 (82.3%) 41 (82.0%) < 0.01§# 0.96§## 1 Some difficulty, but did not affect the case 6 (11.8%) NA 8 (15.7%) 8 (16.0%) 2 Moderate difficulty 12 (23.5%) NA 1 (2.0%) 1 (2.0%) 3 Severe difficulty 33 (64.7%) NA 0 (0.0%) 0 (0.0%) *The values are given as the number of patients, with the percentage in parentheses. §Significance was determined with use of the Mann-Whitney U test. # P value was calculated for difference in Epinephrine group between before and after use of epinephrine. ## P value was calculated for difference between Epinephrine and No Epinephrine groups before cementing. . Table 3 No of surgical field clearances*# Epinephrine group (N = 51) No epinephrine group (N = 50) P value None 17(33.3%) 21(55.3%) 0.25§ 1–3 cycles 29(56.9%) 27(48.2%) > 3 cycles 5(9.8%) 2(28.6%) *The values are given as the number of patients, with the percentage in parentheses. §Significance was determined with use of the Mann-Whitney U test. #Grading scale for difficulty of intraoperative visualization due to blood: 0 No Difficulty; 1 Some difficulty, but did not affect the case; 2 Moderate difficulty; 3 Severe difficulty. Table 4 shows that the epinephrine group had significantly less hidden blood loss (p = 0.04) than the no epinephrine group. There was no between-group difference in the calculated blood loss (p = 0.26), intraoperative blood loss (p = 0.87). Two patients in the no epinephrine group, and 2 patients in the epinephrine group received a blood transfusion. Table 4 Comparison of Differences in Blood Loss Epinephrine group (N = 51) No epinephrine group (N = 50) P value Calculated blood loss*# (mL) 735.9 (293.7) 847.7 (333.8) 0.26† Intraoperative blood loss* (ml) 175.3 (83.7) 170.5 (80.9) 0.87† Hidden blood loss* ## (ml) 576.6 (229.3) 693.2 (302.9) 0.04† Transfusion§ 0.99# None 49 (96.1%) 48 (96%) 2 unit 0 (0.0%) 0 (0.0%) 4 units 2 (3.9%) 2(4.0%) * The values are given as the mean and the standard deviation. † Significance was determined with use of Independent-Sample T test. § The values are given as the number of patients, with the percentage in parentheses. #Significance was determined with use of the Fisher exact test. # PBV (Patient’s blood volume) = k1 x height (m3) + k2 x weight (kg) + k3, where k1 = 0.3669, k2 = 0.03219, and k3 = 0.6041 for men; and k1 = 0.3561, k2 = 0.03308, and k3 = 0.1833 for women; Total blood loss = PBV x (preoperative Hct – postoperative Hct). ## Hidden blood loss = Total blood loss – Intraoperative blood loss + Allogeneic blood transfusion. The incidence of hemodynamic instability after application of epinephrine, including hypertension, hypotension, and tachycardia, is shown in Table 5 . Figure 1 presents the changes in hemodynamic parameters, including systolic blood pressure (SBP), mean blood pressure (MBP), and heart rate (HR), at 5-minute intervals from timing of use of the epinephrine to 15 minutes following that. Table 5 Incidences of Hemodynamic Instabilities After Application of the Epinephrine. Epinephrine group (N = 51) Systolic BP > 190 mmHg or mean BP > 140 mmHg 0 (0.0%) Systolic BP > 140 mmHg or mean BP > 110 mmHg 6 (11.8%) Systolic BP increase of 20% from baseline 4(7.8%) Systolic BP < 90 mmHg or mean BP 100 beats per minute) 1 (2.0%) Data are presented as number; BP, blood pressure. Postoperative deep venous thrombosis and other complication percentages in each group are presented in Table 6 . 2 patients in in the no epinephrine group developed skin blisters and 2 other patients did bruises. No patients had superficial or deep wound infection, aseptic loosening, myocardial infarction, or cerebrovascular accident postoperatively. Table 6 Complications Epinephrine group* (N = 51) No epinephrine group* (N = 50) P value Deep venous thrombosis or pulmonary embolism 0.24# None 51 (100%) 48 (96%) Deep venous thrombosis 0 (0%) 2 (4%) Pulmonary embolism 0 (0%) 0 (0%) Other complications† 0.52# None 49 (96.1%) 45 (90.0%) Subcutaneous hematoma 1 (1.9%) 1 (2.0%) Skin complications Blisters 0 (0.0%) 2 (4.0%) Bruises 1 (1.9%) 2 (4.0%) *The values are given as the number of patients, with the percentage in parentheses. †No patients in the data set were recorded as having superficial infection, deep infection aseptic loosening, myocardial infarction, or cerebrovascular accident as other complications. #Significance was determined with use of the Fisher exact test. Discussion We found that ideal bloodless visualization of the operative field was obtained in the epinephrine group, comparing that in epinephrine group between before and after use of epinephrine and in two groups prior to cementing. We also found that the use of epinephrine resulted in reducing postoperative hidden blood loss significantly and hemodynamic parameters fluctuated under control in patients receiving epinephrine. Vasoconstriction effect of epinephrine is complex, and vasoconstriction intensity differs depending on vessel type: arteries, arterioles, precapillary sphincters, capillaries, venules, and veins [ 19 ]. It is conceivable that the use of vasoconstrictor epinephrine might predispose to delayed intraoperative bleeding, by temporarily blocking vessels that later start bleeding when the initial vasoconstrictor effect has passed. Though epinephrine’s maximal effect on arterial vasoconstriction may work at 7 to 10 minutes, it takes considerably longer for a new local equilibrium to be obtained with regard to hemoglobin quantity. If optimal visualization and fixation are desired, the ideal time for cement hardening should be the time when local hemoglobin concentration is lowest [ 20 , 21 ]. Therefore, it is sufficient for cementing of the tibia and femur by preparing two batches of cement 6 to 9 minutes apart, then holding components carefully in place until the cement has completely polymerized. In our study, there was no evidence of any rebound bleeding in the postoperative period in any of our patients, as an indication in the nearly equal volume of intraoperative blood loss that occurred. This finding also suggests that the use of epinephrine does not increase the risk of intraoperative rebound bleeding with good hemostasis for the occurrence of the roughly same volume of intraoperative blood loss. In our study topical use of epinephrine-soaked gauzes has induced a significant reduction of perioperative hidden blood loss compared with utilization of tourniquet. Epinephrine as a platelet-stimulating agent can cause aggregation of human platelets through alpha-adrenergic mechanisms [ 8 ]. It can explain the effectiveness of this procoagulant in decreasing postoperative blood loss because of its hemostatic effect [ 22 ]. This method was characterised by the absence of complications and adverse reactions associated with epinephrine. Hemodynamic parameters in our study fluctuated under control in patients receiving epinephrine. Peak changes in HR, MBP, SBP were observed to reached 10 minutes following the beginning of the epinephrine use, and they fell to about original value at 15 minutes from start. Tissue ischemia, infection and skin necrosis were also not detected in the epinephrine group. This study had several limitations. First, the concentration and technique of epinephrine solution merits deeper considerations and further study. To our knowledge, there is not a single study with outcome measurements that epinephrine is used for hemostasis in the osteotomized sites. A body of previous studies have reported subcutaneous injection of epinephrine solutions in concentrations up to 1:50,000 with good effect in burn and hand surgery [ 23 , 24 , 25 , 26 ], and even higher concentration has been safely used in other forms of surgery [ 27 , 28 ]. We empirically prepared an epinephrine solution at a concentration of 1:125,000 which was higher than that in some orthopaedic surgery, on the basis of consideration that effective drug concentration was longer for cement hardening before it wore off. Meanwhile, the tumescent technique as it applies to suction lipectomy of plastic surgery has been more extensively studied, but these data are not directly applicable to orthopaedic cases as much of the epinephrine is used in bone cut [ 29 , 30 ]. Hence, we attempted to utilize the technique of epinephrine, soaking not infiltrating, on the osteotomized surfaces, because tumescent or infiltrating technique was abandoned for such adverse effects of epinephrine as delaying wound healing, increasing the risk of infection, and compromising flap survival. Second, the incidence of hemodynamic instability may have been obscured because we merely investigated hemodynamic parameters at 5-minute intervals only for 20 minutes since application of the epinephrine and bone cement may adversely affect hemodynamics. Third, short-, medium-, and long-term outcomes outcome following TKA is needed to evaluate whether the epinephrine procedure will compromise prothesis survival or not. Lastly, we failed to find any differences in the incidence of postoperative complications, this might be due to a relatively small sample size or lack of clinical implication. Further large-scale studies on high-risk patients are needed to assess the association between intra- and postoperative cardiovascular complications and the use of epinephrine. Conclusion The procedure of epinephrine-soaked gauzes can result in an effective form of addressing blood oozing from cut bone planes, while it does not lead to apparent hemodynamic oscillations and vigilant hemodynamic monitoring is a necessity. The utilization of epinephrine-soaked gauzes seems to have an advantage in terms of great potential for a complete tourniquet-free procedure, regardless of hemodynamics. Abbreviations ASA:American Society of Anesthesiologists; BMI:body mass index; BP:blood pressure; CTPA:computed tomography pulmonary angiogram; DVT:deep vein thrombosis; Hb:Hemoglobin; Hct:Hematocrit; HR:heart rate; MBP:mean blood pressure; PE:pulmonary embolism; SBP:systolic blood pressure; TKA:total knee arthroplasty; TXA:tranexamic acid. Declarations Availability of data and materials Not applicable. Ethics approval and consent to participate China-Japan Friendship Hospital institutional review board approved this study. Application number: 2013-SF-1. A written consent was obtained by all patients who participated in this study. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding This study was funded by National Natural Science Foundation of China (grant number 81703896, 81673776), Beijing municipal science and technology commission (grant number Z171100001017209), and the Capital Health Research and Development of Special (grant number 2016-2-4062). The Fund’s role is to provide review and publishing costs. Authors’ contributions H.L. contributed to the conception and design of the study, the acquisition of data, interpretation of the results and writing the final manuscript. Z.L. contributed to the conception and design of the study, the acquisition of data, interpretation of the results and writing the final manuscript. Q.Z. contributed to data extraction from the database and the data statistical analysis. W.G. contributed to the conception and design of the study, provided a critical revision of the manuscript. All authors read and approved the final manuscript. Acknowledgments Not applicable. References Mc Cartney CJ, Mc Leod GA. 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Cite Share Download PDF Status: Published Journal Publication published 25 Aug, 2020 Read the published version in BMC Musculoskeletal Disorders → Version 1 posted Editorial decision: Major revision 01 Jun, 2020 Review # 2 received at journal 31 May, 2020 Review # 1 received at journal 20 May, 2020 Reviewer # 2 agreed at journal 30 Apr, 2020 Editor assigned by journal 27 Apr, 2020 Reviewers invited by journal 27 Apr, 2020 Reviewer # 1 agreed at journal 27 Apr, 2020 Submission checks completed at journal 23 Apr, 2020 Editor invited by journal 23 Apr, 2020 First submitted to journal 17 Apr, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-23569","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":513160,"identity":"4e117b0e-0472-4ab5-ac03-cb7038926799","order_by":1,"name":"Hongzhi Liu","email":"","orcid":"https://orcid.org/0000-0001-5147-1660","institution":"Beijing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hongzhi","middleName":"","lastName":"Liu","suffix":""},{"id":513161,"identity":"6b00e791-7d81-43d3-8b65-0a32be1159e9","order_by":2,"name":"Zhaohui Liu","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zhaohui","middleName":"","lastName":"Liu","suffix":""},{"id":513162,"identity":"d29d050b-cb02-4f46-bf6e-67be6c35049d","order_by":3,"name":"Qidong Zhang","email":"","orcid":"","institution":"China-Japan Friendship Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qidong","middleName":"","lastName":"Zhang","suffix":""},{"id":513163,"identity":"62467b46-3c5a-499c-bcaf-da53fce8dcf4","order_by":4,"name":"Wanshou Guo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYDCCA3AWDxBXSMjJk6jljIWxYQNJWhjbKhKRRLADvuPNj1/zVByWN+c/e/Ax7zyJBMYG5oePbuDRInnmmJk1z5nDhjtn5CUb826TyGNnYDM2zsGjxeBGDpsxb9ttxg03eMykgVqKGRt42KSJ0WK/4fwZoJY5EokNBwhrYX4M1JK44UAOUEsDEVpAfmGcc+Z/8oYbOcaGc45JGBs2E/ALKMQ+vKlIswU6zPDBm5o6OXn25oeP8WkBAjYJVD4zfuVgJR8IqxkFo2AUjIIRDQA0JE1v0PJMxwAAAABJRU5ErkJggg==","orcid":"","institution":"","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Wanshou","middleName":"","lastName":"Guo","suffix":""}],"badges":[],"createdAt":"2020-04-17 11:22:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-23569/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-23569/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12891-020-03595-6","type":"published","date":"2020-08-25T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":986355,"identity":"358cf634-2457-471f-a8db-749d66103200","added_by":"auto","created_at":"2020-04-28 13:51:26","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":72021,"visible":true,"origin":"","legend":"Hemodynamic parameters at 1-minute intervals for 15 minutes since timing of application of the epinephrine. HR, heart rate; MBP, mean blood pressure; SBP, systolic blood pressure","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-23569/v1/Figure1.jpg"},{"id":13500324,"identity":"69ef4f3e-95c7-4972-b686-8d6d0adb0b7b","added_by":"auto","created_at":"2021-09-16 23:05:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":427738,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-23569/v1/76684956-50a0-4a38-a2d5-f3cc9f736b1d.pdf"}],"financialInterests":"","formattedTitle":"Utilization of epinephrine-soaked gauzes to address bleeding from osteotomy sites in non-tourniquet total knee arthroplasty: a retrospective cohort study","fulltext":[{"header":"Background","content":" \u003cp\u003eEpinephrine is often used in local infiltration analgesia to reduce systemic absorption of the local anesthetic and prolong the analgesic effect in total knee arthroplasty (TKA) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], is also used to reduce perioperative blood loss [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Epinephrine as a procoagulant has been demonstrated key activities associated with increased fibrinogen release, activation of fibrinogen receptors, and effects on other coagulation factors whose activities are mediated via beta-adrenergic receptor. Further research has showed that platelet count increases arise from splenic autotransfusion following low-dose epinephrine infusion via alpha-adrenergic receptors [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In short, the whole blood clotting time significantly decreases. Administration of epinephrine is controversial in joint replacement because of a composite of major cardiopulmonary complications including ventricular tachycardia, broken-heart syndrome, pulmonary edema, and intraventricular bleeding [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, there has been little discussion about its hemostatic effect as a vasoconstrictor, and hemodynamic effect when administering epinephrine in TKA procedure.\u003c/p\u003e \u003cp\u003eA pneumatic tourniquet is commonly used in TKA to improve visualization of the operative field, decrease intraoperative blood loss, and enhance the quality of cementation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Even in some no-tourniquet procedures, a tourniquet was also inflated during component cementation because some participating surgeons felt a tourniquet was necessary to minimize blood at the bone-cement interface and maximize fixation. However, acute hypotension and the ischemia-reperfusion (I-R) injury would occur when blood perfusion was re-established and release of metabolites from the ischemic limb and reduced cardiac preload after deflation of the tourniquet. And it would have a high risk of cardiac and cerebral micro emboli, a high risk of deep venous thrombosis, and an increased incidence of arterial thrombosis especially for the elderly undertaking TKA who have multiple comorbidities [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTherefore, for a tourniquet-free TKA protocol, our attempt was made to establish a set of intra-surgical procedures that can provide a satisfying visualization and a relatively bloodless bone interface for cementation with the topical hemostatic agent of epinephrine solution. Furthermore, epinephrine-related side effects associated with adverse cardiopulmonary complications may be fatal in rare cases and cautious hemodynamic monitoring is needed. The purpose of this study was to determine the hemostatic effect of epinephrine-soaked gauzes by comparing surgical field visualization between patients receiving epinephrine and those undergoing tourniquet. We hypothesized that epinephrine-soaked gauzes would be sufficient to reduce blood loss and obtain bloodless bone sections in patients undergoing non-tourniquet cemented TKA.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section3\"\u003e \u003ch2\u003ePatient selection\u003c/h2\u003e \u003cp\u003eThis study protocol has been approved by the IRB of the authors\u0026rsquo; affiliated institutions. This is a retrospective cohort study of 143 patients who under a primary unilateral cemented TKA from January 1, 2018 to December 31, 2019 in our hospital. From the final analysis patients with prior surgery involving the femur or tibia, prior lower extremity fracture, coagulopathy and uncontrolled hypertension, history of myocardial infarction or stroke, and bilateral total knee arthroplasty were excluded. In the final analysis, a total of 101 patients fulfilled the study inclusion criteria and were available. The patients were analyzed in 2 groups. In the first group, a tourniquet was not used but prepared for blooding out of control and gauzes soaked with a normal saline solution mixed with a dose of epinephrine (dilution 1:125,000) were utilized to cover and pressurize for hemostasis on the osteotomized surface of the distal femoral and proximal tibial bones at the finish of bone resections. In the second group, a pneumatic tourniquet placed high on the thigh was inflated to 250\u0026nbsp;mmHg before the skin incision and deflated after the cement was completely polymerized. All other aspects of perioperative care were constant throughout the groups.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePerioperative management\u003c/h2\u003e \u003cp\u003eAll the operations were performed with a fixed plant posterior-stabilized total knee prosthesis in a medial parapatellar approach. A general anesthetic with an adductor canal block was used for all the patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. And appropriate perioperative parenteral antibiotics were administered for infection prophylaxis. High-pressure pulsatile lavage was used to clean the bone surfaces and soft tissues. Before wound closure, all knees received an intraarticular injection of a cocktail containing ropivacaine, morphine, and ketorolac to enhance postoperative analgesia without drain insertion. Elastic compressive dressing was also used. Each patient received the same perioperative regimen: tranexamic acid (TXA), pain control and rehabilitation. TXA was given at the initiation of the surgery and just before closure [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Multimodal postoperative pain management and accelerated physical therapy were performed as previously described. Low molecular weight heparin (enoxaparin, 3,000\u0026nbsp;IU) was administered subcutaneously 12\u0026nbsp;h after the operation and was continued for 2 weeks for thrombosis prophylaxis. After recovery from anesthesia, quadriceps femoris muscle isometric contraction was immediately started, and rehabilitation began on the first postoperative day, including muscle power training.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcome measurement\u003c/h2\u003e \u003cp\u003eThe primary outcome of the study was surgical field visualization including surgeon-rated difficulty in visualization and number of surgical field clearances. Two authors, blinded to one another's results, assessed it. Any disagreement was resolved by a consensus between all authors. Surgeon-rated difficulty in visualization was performed prior to using epinephrine in Epinephrine group and before cementing in two groups. Number of surgical field clearances was also used in two groups over the period from the finish of bone cutting through the cement hardening. Every action of surgical field clearance excluding using epinephrine-soaked gauzes was counted as the number of surgical field clearances.\u003c/p\u003e \u003cp\u003ePerioperative blood loss was the second outcome. Volumes of intraoperative blood loss, postoperative blood loss, blood transfusion, and hidden blood loss were recorded. The blood volume of each patient was calculated by a formula that consists of patient weight, height and sex [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The blood loss was calculated on the basis of the validated Gross formula [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Hematocrit (Hct) and Hb (Hemoglobin) levels were determined preoperatively and on postoperative day 2. The intraoperative blood loss represented by the increased weight of the gauzes plus the volume in the aspirator bottle excluding rinse. The amounts of postoperative visible blood loss were calculated by weighing the dressings removed after the surgery. Intraoperative characteristics included the surgical duration (beginning at incision until emergence from anesthesia), tourniquet time were noted. Meanwhile, in the epinephrine group, incidences of hypertension, hypotension and tachycardia were evaluated. Hemodynamic parameters at 1-minute intervals for 15 minutes since timing of application of the epinephrine were recorded. The incidence of symptomatic deep vein thrombosis (DVT) was detected by a bilateral lower extremity deep venous color Doppler ultrasound examination. The development of symptomatic pulmonary embolism (PE) was identified by computed tomography pulmonary angiogram (CTPA). Other complications, such as subcutaneous hematoma, skin complications (blisters, bruises, superficial and deep wound infection), were also recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eData were entered into an Access Case Report Form database and further analyzed by R software (version 3.6.3, The R Foundation, Vienna, Austria). Quantitative data are presented as the mean and standard deviation (SD); categorical variables are used as proportions. Differences in continuous variables between groups were evaluated with Independent-Sample T test or Mann-Whitney U test, depending on the distribution characteristics of the data. A chi-square test or Fisher exact test for difference in proportions was used to estimate the differences between groups in categorical variables. Values of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered to be statistically significant.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":" \u003cp\u003eThere were no significant differences (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) found at baseline with regard to age, BMI, sex, ASA class, mean starting hemoglobin, or preoperative diagnosis between the groups. In this study, 101 patients were available, as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e: 51 in the epinephrine group, and 50 in the no epinephrine group. The tourniquet time for the tourniquet group was 61.1\u0026nbsp;min. The mean operating time for the epinephrine group (81.6\u0026nbsp;min) and the no epinephrine group (80.9\u0026nbsp;min) was not significantly different (p\u0026thinsp;=\u0026thinsp;0.76).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient Demographic Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEpinephrine group (N\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo epinephrine group (N\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge* (yr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.1 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.8 (8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.88\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eSex\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.34#\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47 (92.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (84.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI* (kg/m^2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.8 (3.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.2 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.55\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStarting hemoglobin* (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131.8 (12.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132.4 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.22\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eASA classification\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.32\u0026sect;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 (normal, healthy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (39.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (38.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2 (mild, systemic disease)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (58.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (58.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 (severe systemic disease)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (6.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003ePreoperative diagnosis\u0026Dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOsteoarthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50 (98.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (96.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRheumatoid arthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTourniquet time* (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.1 (7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperating time (min)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.6 (12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80.9 (9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.764\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*The values are given as the mean and the standard deviation. \u0026dagger;Significance was determined with use of Independent-Sample T test. \u0026Dagger;The values are given as the number of patients, with the percentage in parentheses. #Significance was determined with use of the chi-square test. \u0026sect;Significance was determined with use of the Mann-Whitney U test. **Significance was determined with use of the Fisher exact test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn terms of surgical field visualization, there was statistically significant difference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) on surgeon-rated difficulty in visualization in the epinephrine group between before and after use of epinephrine, and no statistically significant differences (p\u0026thinsp;=\u0026thinsp;0.96) between two groups before cementing (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). We also found no statistically significantly result on numbers of surgical field clearances between two groups (p\u0026thinsp;=\u0026thinsp;0.25) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSurgeon-rated difficulty in visualization*\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBefore Epinephrine\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBefore Cementing\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEpinephrine group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo epinephrine group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEpinephrine group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo epinephrine group\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0 No Difficulty\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (82.3%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41 (82.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u0026sect;#\u003c/p\u003e \u003cp\u003e0.96\u0026sect;##\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 Some difficulty, but did not affect the case\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (11.8%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (15.7%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (16.0%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2 Moderate difficulty\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (23.5%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (2.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (2.0%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3 Severe difficulty\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (64.7%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e \u003cp\u003e*The values are given as the number of patients, with the percentage in parentheses. \u0026sect;Significance was determined with use of the Mann-Whitney U test. # P value was calculated for difference in Epinephrine group between before and after use of epinephrine. ## P value was calculated for difference between Epinephrine and No Epinephrine groups before cementing.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNo of surgical field clearances*#\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEpinephrine group (N\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo epinephrine group (N\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(55.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.25\u0026sect;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;3 cycles\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29(56.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(48.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3 cycles\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(9.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e*The values are given as the number of patients, with the percentage in parentheses. \u0026sect;Significance was determined with use of the Mann-Whitney U test. #Grading scale for difficulty of intraoperative visualization due to blood: 0 No Difficulty; 1 Some difficulty, but did not affect the case; 2 Moderate difficulty; 3 Severe difficulty.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows that the epinephrine group had significantly less hidden blood loss (p\u0026thinsp;=\u0026thinsp;0.04) than the no epinephrine group. There was no between-group difference in the calculated blood loss (p\u0026thinsp;=\u0026thinsp;0.26), intraoperative blood loss (p\u0026thinsp;=\u0026thinsp;0.87). Two patients in the no epinephrine group, and 2 patients in the epinephrine group received a blood transfusion.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Differences in Blood Loss\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEpinephrine group (N\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNo epinephrine group (N\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalculated blood loss*# (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e735.9 (293.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e847.7 (333.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.26\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative blood loss* (ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e175.3 (83.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e170.5 (80.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.87\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHidden blood loss* ## (ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e576.6 (229.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e693.2 (302.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.04\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eTransfusion\u0026sect;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e0.99#\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (96.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (96%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2 unit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 units\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e* The values are given as the mean and the standard deviation. \u0026dagger; Significance was determined with use of Independent-Sample T test. \u0026sect; The values are given as the number of patients, with the percentage in parentheses. #Significance was determined with use of the Fisher exact test. # PBV (Patient\u0026rsquo;s blood volume)\u0026thinsp;=\u0026thinsp;k1 x height (m3)\u0026thinsp;+\u0026thinsp;k2 x weight (kg)\u0026thinsp;+\u0026thinsp;k3, where k1\u0026thinsp;=\u0026thinsp;0.3669, k2\u0026thinsp;=\u0026thinsp;0.03219, and k3\u0026thinsp;=\u0026thinsp;0.6041 for men; and k1\u0026thinsp;=\u0026thinsp;0.3561, k2\u0026thinsp;=\u0026thinsp;0.03308, and k3\u0026thinsp;=\u0026thinsp;0.1833 for women; Total blood loss\u0026thinsp;=\u0026thinsp;PBV x (preoperative Hct \u0026ndash; postoperative Hct). ## Hidden blood loss\u0026thinsp;=\u0026thinsp;Total blood loss \u0026ndash; Intraoperative blood loss\u0026thinsp;+\u0026thinsp;Allogeneic blood transfusion.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe incidence of hemodynamic instability after application of epinephrine, including hypertension, hypotension, and tachycardia, is shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the changes in hemodynamic parameters, including systolic blood pressure (SBP), mean blood pressure (MBP), and heart rate (HR), at 5-minute intervals from timing of use of the epinephrine to 15 minutes following that.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncidences of Hemodynamic Instabilities After Application of the Epinephrine.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEpinephrine group (N\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic BP\u0026thinsp;\u0026gt;\u0026thinsp;190\u0026nbsp;mmHg or mean BP\u0026thinsp;\u0026gt;\u0026thinsp;140\u0026nbsp;mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic BP\u0026thinsp;\u0026gt;\u0026thinsp;140\u0026nbsp;mmHg or mean BP\u0026thinsp;\u0026gt;\u0026thinsp;110\u0026nbsp;mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic BP increase of 20% from baseline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(7.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic BP\u0026thinsp;\u0026lt;\u0026thinsp;90\u0026nbsp;mmHg or mean BP\u0026thinsp;\u0026lt;\u0026thinsp;60\u0026nbsp;mmHg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (13.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTachycardia (heart rate\u0026thinsp;\u0026gt;\u0026thinsp;100 beats per minute)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eData are presented as number; BP, blood pressure.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePostoperative deep venous thrombosis and other complication percentages in each group are presented in Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. 2 patients in in the no epinephrine group developed skin blisters and 2 other patients did bruises. No patients had superficial or deep wound infection, aseptic loosening, myocardial infarction, or cerebrovascular accident postoperatively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComplications\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEpinephrine group* (N\u0026thinsp;=\u0026thinsp;51)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo epinephrine group* (N\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eDeep venous thrombosis or pulmonary embolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.24#\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48 (96%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep venous thrombosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary embolism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eOther complications\u0026dagger;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52#\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49 (96.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (90.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubcutaneous hematoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eSkin complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlisters\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBruises\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e*The values are given as the number of patients, with the percentage in parentheses. \u0026dagger;No patients in the data set were recorded as having superficial infection, deep infection aseptic loosening, myocardial infarction, or cerebrovascular accident as other complications. #Significance was determined with use of the Fisher exact test.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eWe found that ideal bloodless visualization of the operative field was obtained in the epinephrine group, comparing that in epinephrine group between before and after use of epinephrine and in two groups prior to cementing. We also found that the use of epinephrine resulted in reducing postoperative hidden blood loss significantly and hemodynamic parameters fluctuated under control in patients receiving epinephrine.\u003c/p\u003e \u003cp\u003eVasoconstriction effect of epinephrine is complex, and vasoconstriction intensity differs depending on vessel type: arteries, arterioles, precapillary sphincters, capillaries, venules, and veins [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. It is conceivable that the use of vasoconstrictor epinephrine might predispose to delayed intraoperative bleeding, by temporarily blocking vessels that later start bleeding when the initial vasoconstrictor effect has passed. Though epinephrine\u0026rsquo;s maximal effect on arterial vasoconstriction may work at 7 to 10 minutes, it takes considerably longer for a new local equilibrium to be obtained with regard to hemoglobin quantity. If optimal visualization and fixation are desired, the ideal time for cement hardening should be the time when local hemoglobin concentration is lowest [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Therefore, it is sufficient for cementing of the tibia and femur by preparing two batches of cement 6 to 9 minutes apart, then holding components carefully in place until the cement has completely polymerized. In our study, there was no evidence of any rebound bleeding in the postoperative period in any of our patients, as an indication in the nearly equal volume of intraoperative blood loss that occurred. This finding also suggests that the use of epinephrine does not increase the risk of intraoperative rebound bleeding with good hemostasis for the occurrence of the roughly same volume of intraoperative blood loss.\u003c/p\u003e \u003cp\u003eIn our study topical use of epinephrine-soaked gauzes has induced a significant reduction of perioperative hidden blood loss compared with utilization of tourniquet. Epinephrine as a platelet-stimulating agent can cause aggregation of human platelets through alpha-adrenergic mechanisms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It can explain the effectiveness of this procoagulant in decreasing postoperative blood loss because of its hemostatic effect [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis method was characterised by the absence of complications and adverse reactions associated with epinephrine. Hemodynamic parameters in our study fluctuated under control in patients receiving epinephrine. Peak changes in HR, MBP, SBP were observed to reached 10 minutes following the beginning of the epinephrine use, and they fell to about original value at 15 minutes from start. Tissue ischemia, infection and skin necrosis were also not detected in the epinephrine group.\u003c/p\u003e \u003cp\u003eThis study had several limitations. First, the concentration and technique of epinephrine solution merits deeper considerations and further study. To our knowledge, there is not a single study with outcome measurements that epinephrine is used for hemostasis in the osteotomized sites. A body of previous studies have reported subcutaneous injection of epinephrine solutions in concentrations up to 1:50,000 with good effect in burn and hand surgery [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], and even higher concentration has been safely used in other forms of surgery [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. We empirically prepared an epinephrine solution at a concentration of 1:125,000 which was higher than that in some orthopaedic surgery, on the basis of consideration that effective drug concentration was longer for cement hardening before it wore off. Meanwhile, the tumescent technique as it applies to suction lipectomy of plastic surgery has been more extensively studied, but these data are not directly applicable to orthopaedic cases as much of the epinephrine is used in bone cut [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Hence, we attempted to utilize the technique of epinephrine, soaking not infiltrating, on the osteotomized surfaces, because tumescent or infiltrating technique was abandoned for such adverse effects of epinephrine as delaying wound healing, increasing the risk of infection, and compromising flap survival. Second, the incidence of hemodynamic instability may have been obscured because we merely investigated hemodynamic parameters at 5-minute intervals only for 20 minutes since application of the epinephrine and bone cement may adversely affect hemodynamics. Third, short-, medium-, and long-term outcomes outcome following TKA is needed to evaluate whether the epinephrine procedure will compromise prothesis survival or not. Lastly, we failed to find any differences in the incidence of postoperative complications, this might be due to a relatively small sample size or lack of clinical implication. Further large-scale studies on high-risk patients are needed to assess the association between intra- and postoperative cardiovascular complications and the use of epinephrine.\u003c/p\u003e "},{"header":"Conclusion","content":" \u003cp\u003eThe procedure of epinephrine-soaked gauzes can result in an effective form of addressing blood oozing from cut bone planes, while it does not lead to apparent hemodynamic oscillations and vigilant hemodynamic monitoring is a necessity. The utilization of epinephrine-soaked gauzes seems to have an advantage in terms of great potential for a complete tourniquet-free procedure, regardless of hemodynamics.\u003c/p\u003e "},{"header":"Abbreviations","content":" \u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eASA:American Society of Anesthesiologists; BMI:body mass index; BP:blood pressure; CTPA:computed tomography pulmonary angiogram; DVT:deep vein thrombosis; Hb:Hemoglobin; Hct:Hematocrit; HR:heart rate; MBP:mean blood pressure; PE:pulmonary embolism; SBP:systolic blood pressure; TKA:total knee arthroplasty; TXA:tranexamic acid.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e "},{"header":"Declarations","content":"\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\u003cp\u003eChina-Japan Friendship Hospital institutional review board approved this study. Application number: 2013-SF-1. A written consent was obtained by all patients who participated in this study.\u003c/p\u003e\u003ch2\u003eConsent for publication\u003c/h2\u003e\u003cp\u003eNot applicable.\u003c/p\u003e \u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was funded by National Natural Science Foundation of China (grant number 81703896, 81673776), Beijing municipal science and technology commission (grant number Z171100001017209), and the Capital Health Research and Development of Special (grant number 2016-2-4062). The Fund\u0026rsquo;s role is to provide review and publishing costs.\u003c/p\u003e \u003ch2\u003eAuthors\u0026rsquo; contributions\u003c/h2\u003e \u003cp\u003eH.L. contributed to the conception and design of the study, the acquisition of data, interpretation of the results and writing the final manuscript. Z.L. contributed to the conception and design of the study, the acquisition of data, interpretation of the results and writing the final manuscript. Q.Z. contributed to data extraction from the database and the data statistical analysis. W.G. contributed to the conception and design of the study, provided a critical revision of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e \u003ch2\u003eAcknowledgments\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e "},{"header":"References","content":"\u003col\u003e\u003cli\u003e \u003cspan\u003eMc Cartney CJ, Mc Leod GA. Local infiltration analgesia for total knee arthroplasty. Br J Anaesth. 2011;107:487\u0026ndash;9.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eAndersen LO, Kehlet H. Analgesic efficacy of local infiltration analgesia in hip and knee arthroplasty: a systematic review. Br J Anaesth. 2014;113:360\u0026ndash;74.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eFenten MGE, Bakker SMK, Touw DJ, et al. Pharmacokinetics of 400 mg ropivacaine after periarticular local infiltration analgesia for total knee arthroplasty. Acta Anaesthesiol Scand. 2017;61(3):338\u0026ndash;45.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eJans \u0026Oslash;, Grevstad U, Mand\u0026oslash;e H, Kehlet H, Johansson PI. A randomized trial of the effect of low dose epinephrine infusion in addition to tranexamic acid on blood loss during total hip arthroplasty. Br J Anaesth. 2016;116(3):357\u0026ndash;62.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eGao F, Sun W, Guo W, Li Z, Wang W, Cheng L. Topical application of tranexamic acid plus diluted epinephrine reduces postoperative hidden blood loss in total hip arthroplasty. J Arthroplasty. 2015;30(12):2196\u0026ndash;200.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eBakovic D, Pivac N, Eterovic D, Breskovic T, Zubin P, Obad A, Dujic Z. The effects of low-dose epinephrine infusion on spleen size, central and hepatic circulation and circulating platelets. Clin Physiol Funct Imaging. 2013;33(1):30\u0026ndash;7.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003evon Ka ̈nel R, Dimsdale JE. Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. Eur J Haematol. 2000;65(6):357\u0026ndash;69.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eYun-Choi HS, Park KM, Pyo MK. Epinephrine induced platelet aggregation in rat platelet-rich plasma. Thromb Res. 2000;100(6):511\u0026ndash;8.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eToivonen J, Pitko VM, Rosenberg PH. Comparison between intra-articular bupivacaine with epinephrine and epinephrine alone on short-term and long-term pain after knee arthroscopic surgery under general anesthesia in day-surgery patients. Acta Anaesthesiol Scand. 2002;46:435\u0026ndash;40.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eBelkin NS, Degen RM, Liguori GA, Kelly BT. (2017) Epinephrine-induced pulmonary edema during hip arthroscopy: a report of two cases and a review of the literature. Phys Sports med. 2017;45:353-6.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eMazzocca AD, Meneghini RM, Chhablani R, et al. Epinephrine-induced pulmonary edema during arthroscopic knee surgery: a case report. J Bone Joint Surg Am. 2003;85(5):913\u0026ndash;5.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eTai TW, Lin CJ, Jou IM, Chang CW, Lai KA, Yang CY. Tourniquet use in total knee arthroplasty: a meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2011;19(7):1121\u0026ndash;30.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eChen S, Li J, Peng H, Zhou J, Fang H, Zheng H. The influence of a half-course tourniquet strategy on peri-operative blood loss and early functional recovery in primary total knee arthroplasty. Int Orthop. 2014;38:355\u0026ndash;9.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eMaradit Kremers H, Larson DR, Crowson CS, Kremers WK, Washington RE, Steiner CA, et al. Prevalence of total hip and knee replacement in the United States. J Bone Joint Surg Am. 2015;97(17):1386\u0026ndash;97.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eSeruya M, Oh AK, Rogers GF, Boyajian MJ, Myseros JS, Yaun AL, Keating RF. Controlled hypotension and blood loss during frontoorbital advancement. J Neurosurg Pediatr. 2014;9(5):491\u0026ndash;6.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eYang ZG, Chen WP, Wu LD. Effectiveness and safety of tranexamic acid in reducing blood loss in total knee arthroplasty: a meta-analysis. J Bone Joint Surg Am. 2012;94(13):1153\u0026ndash;9.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eNadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surgery. 1962;51(2):224\u0026ndash;32.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eGross JB. Estimating allowable blood loss: corrected for dilution. Anesthesiology. 1983;58(3):277\u0026ndash;80.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eLee RE, Holze EA. The peripheral vascular system in the bulbar conjunctiva of young normotensive adults at rest. J Clin Invest. 1950;29:146\u0026ndash;50.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eGibson M. Outpatient carpal tunnel decompression without tourniquet: A simple local anaesthetic technique. Ann R Coll Surg Engl. 1990;72:408\u0026ndash;9.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eMcKee DE, Lalonde DH, Thoma A, et al. Optimal time delay between epinephrine injection and incision to minimize bleeding. Plast Reconstr Surg. 2013;131:811.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eGasparini G, Papaleo P, Pola P, et al. Local infusion of norepinephrine reduces blood losses and need of transfusion in total knee arthroplasty. Int Orthop. 2006;30:253.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eBezuhly M, Sparkes GL, Higgins A, Neumeister MW, Lalonde DH. Immediate thumb extension following extensor indicis proprius to extensor pollicis longus tendon transfer using the wide-awake approach. Plast Reconstr Surg. 2007;119:1507\u0026ndash;12.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eHiggins A, Lalonde HD, Bell M, McKee D, Lalonde JF. Avoiding flexor tendon repair rupture with intraoperative total active movement examination. Plast Reconstr Surg. 2010;126:941\u0026ndash;5.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eMcKee DE, Lalonde DH, Thoma A, Dickson L. Achieving the optimal epinephrine effect in wide awake hand surgery using local anesthesia without tourniquet. Hand. 2015;10:613\u0026ndash;5.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eBashir MM, Qayyum R, Saleem MH, Siddique K, Kahn FA. Effect of time interval between tumescent local anesthesia infiltration and start of surgery on operative field visibility in hand surgery without tourniquet. J Hand Surg Am. 2015;40:1606\u0026ndash;9.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eDe Bono R, Rao GS. Vasoconstrictor infiltration in breast reduction surgery: is it harmful? Br J Plast Surg. 1997;50:260\u0026ndash;2.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eSteele MH. Three-year experience using near infrared spectroscopy tissue oximetry monitoring of free tissue transfer. Ann Plast Surg. 2011;66:540\u0026ndash;5.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eKlein JA. The tumescent technique. anesthesia and modified liposuction technique. Dermatol Clin. 1990;8:425\u0026ndash;37.\u003c/span\u003e \u003c/li\u003e \u003cli\u003e \u003cspan\u003eBudny PG, Regan PJ, Roberts AHN. The estimation of blood loss during burns surgery. Burns. 1993;19:134\u0026ndash;7.\u003c/span\u003e \u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Epinephrine, Tourniquet , Total knee arthroplasty , Hemostatic effects, Hemodynamic","lastPublishedDoi":"10.21203/rs.3.rs-23569/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-23569/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground Abandoning tourniquet was commenced because of the complications of tourniquet extensively used for the control of hemorrhage in total knee arthroplasty (TKA). Bleeding management is critical to acquire a relative bloodless arthrotomy interface for maximize cement fixation in non-tourniquet TKA. The purpose of this study was to investigate hemostatic and hemodynamic effects of epinephrine-soaked gauzes in cemented TKAs.\u003c/p\u003e \u003cp\u003eMethods A retrospective cohort study of 101 patients in two groups was performed. The first group (n\u0026thinsp;=\u0026thinsp;51) underwent unilateral TKA with our procedures of epinephrine use, the second group (n\u0026thinsp;=\u0026thinsp;50) had the same protocol with tourniquet and no epinephrine utilization. Surgical field visualization was assessed by grading scale for difficulty of intraoperative visualization due to blood and number of surgical field clearances. Perioperative blood loss were recorded. Hemodynamic parameters were observed in the epinephrine group.\u003c/p\u003e \u003cp\u003eResults There was statistically significant difference (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) on surgeon-rated difficulty in visualization in the epinephrine group between before and after use of epinephrine, and no statistically significant differences (p\u0026thinsp;=\u0026thinsp;0.96) between two groups before cementing. No statistically significantly result on numbers of surgical field clearances between two groups (p\u0026thinsp;=\u0026thinsp;0.25) was reached. Significant difference in hidden blood loss, was observed in two groups (p\u0026thinsp;=\u0026thinsp;0.04). The hemodynamic effects of epinephrine may be under control.\u003c/p\u003e \u003cp\u003eConclusion The procedure of epinephrine soaked gauzes, as a prudent adjunct, may be effective to reduce blood loss and obtain bloodless bone sections in non-tourniquet TKAs, regardless of hemodynamics.\u003c/p\u003e","manuscriptTitle":"Utilization of epinephrine-soaked gauzes to address bleeding from osteotomy sites in non-tourniquet total knee arthroplasty: a retrospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-04-28 13:51:24","doi":"10.21203/rs.3.rs-23569/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-06-01T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-05-31T12:00:00+00:00","index":2,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nDear authors, Thank you for your submission.Despite the interesting topic you worked on, I believe your study has significant defects that need to be addressed.\n1- Dictation errors, like line 77 word \"Under\" could be underwent and line 89 the word\"plant\" which could be implant..\n2-You paper needs a fully english editing and formatting\n3-Methods, a) I was not able to find the duration for follow up in your study while you are describing the level of significance for complications like aseptic loosening, wound infection, DVT and so on in your result section. b) Your primary outcome is to measure surgical field visualization, but you have not mentioned any scales or metrics for such a qualitative measure. c) Also you need to clarify the time cut off point and acuity for secondary outcomes like DVT, wound complication and infection etc. If these are measured in the hospital setting in the acute post-op period or after patients have been discharged from hospital?\n4- Control group: I believe to evaluate the effect of epinephrine(Epi) on field visualization and other outcomes you would have a group of TKA patients without a tourniquet and epinephrine both together, otherwise you have missed two important confounding factor: One is the effect of tourniquet and number two is the effect of physiological hemostasis which will take place as the procedure progresses! So in the Epi group you have compared the visualization field before and after Epi. application, hence we can not assess the net effect of Epinephrine regardless of physiological hemostasis, if any.\n5-I was mot convienced why you have used two batch of cement.(Line 171)* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I recommend additional statistical review**\n* Quality of written English: **Not suitable for publication unless extensively edited**\n* Declaration of competing interests: **'I declare that I have no competing interests'**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"editorInvitedReview","content":"","date":"2020-05-20T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nDear Editor,\nThank you for requesting a review of the manuscript titled \"Utilization of epinephrine-soaked gauze to address bleeding from osteotomy sites in non-tourniquet total knee arthroplasty: a retrospective cohort study\". The current manuscript investigated the effect of epinephrine soaked gauze on improving visibility and maintaining a relatively bloodless field during TKA without Tourniquet use. The authors outlined that the use of epinephrine soaked gauze improved visibility prior to the cementation of the components. The described methodology is sound and appropriate for the investigation at hand. Please find my specific comments below:\n\nAbstract\n\nI would recommend rewording the background in a manner that avoids generalizing the aversion to tourniquet use. Tourniquet use in TKA remains mainstream in most institutions with emphasis on minimizing the tourniquet time rather than complete avoidance.\n\nPlease provide numerical values in the results section and not just significance levels.\n\nBackground\n\nI would recommend adding \"and\" before \"is also\" in line 44\n\nPlease reword Line 57-59 to relay the message in a clearer fashion. I would also recommend against the use of the expression\"no-tourniquet\" and would suggest the use of \"non-tourniquet\" or \"tourniquet-free\" instead.\n\nMethods\n\nPlease explain how did two independent surgeons assess the surgeon-reported difficulty in visualization?\n\nIs the visualization score a validated parameter or has it been developed by the authors for the purpose of the study?\n\nResults\n\nCan the authors provide data on the safety of such method compared to the tourniquet, since the main reason behind aversion from tourniquet use are the associated complications?\n\nDiscussion\n\nWell outlined. However, I would recommend reviewing the manuscript linguistically to improve how it reads.\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"reviewerAgreed","content":"","date":"2020-04-30T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorAssigned","content":"","date":"2020-04-27T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-04-27T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-04-27T12:00:00+00:00","index":1,"fulltext":""},{"type":"checksComplete","content":"","date":"2020-04-23T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-04-23T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-04-17T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-musculoskeletal-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmsd","sideBox":"Learn more about [BMC Musculoskeletal Disorders](http://bmcmusculoskeletdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12891","title":"BMC Musculoskeletal Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"188bcb90-b7ee-4ebc-828b-3f79631a47a8","owner":[],"postedDate":"April 28th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":89937,"name":"Orthopedics"}],"tags":[],"updatedAt":"2020-09-03T15:56:29+00:00","versionOfRecord":{"articleIdentity":"rs-23569","link":"https://doi.org/10.1186/s12891-020-03595-6","journal":{"identity":"bmc-musculoskeletal-disorders","isVorOnly":false,"title":"BMC Musculoskeletal Disorders"},"publishedOn":"2020-08-25 12:00:00","publishedOnDateReadable":"August 25th, 2020"},"versionCreatedAt":"2020-04-28 13:51:24","video":"","vorDoi":"10.1186/s12891-020-03595-6","vorDoiUrl":"https://doi.org/10.1186/s12891-020-03595-6","workflowStages":[]},"version":"v1","identity":"rs-23569","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-23569","identity":"rs-23569","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}