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Table 3 Intraoperative blood management

From: Blood management in fast-track orthopedic surgery: an evidence-based narrative review

Content Conventional studies, guide lines, and recommendations Fast-track setting
Minimally invasive surgery (with or without navigation) MIS techniques are believed to reduce blood loss in TJA procedures, included the so-called tissue sparing surgery [81,82,83,84,85]. Blood loss after minimally invasive TKA was compared between using or not imageless navigation, together with intraoperative tourniquet but no postoperative drainage. Blood loss was not significantly affected by the use of imageless navigation, following which time of surgery was a bit longer but Hb reduction and amount of blood were similar [86]. Blood loss reduction is included in the benefits of MIS TJA surgery. However, a survey on fast-track TJA procedures concludes that MIS benefits on blood loss are still unclear [87], and more studies should be conducted to assess whether its use in fast-track THA affects overall patient satisfaction [88] (*).
Tourniquet Although the majority of orthopedic surgeons still widely use it, its role remains controversial. If tourniquet reduces intraoperative blood loss, this gain can be offset by the amount of blood lost after its release [89]. A meta-analysis on 30 RCTs seems to confirm its lack of effectiveness in TKA for better clinical outcomes, less complications and better early post-operative ROM achieved without a tourniquet [90]. The benefits of tourniquet in TKA are also questioned in fast-track surgery. An RCT found knee-extension 48 h after surgery to be reduced in 90% patients regardless to its use. Moreover, tourniquet reduced bleeding during surgery, but had no benefits on postoperative Hb levels, pain, nausea, OS, or periarticular swelling. Finally, using or not a tourniquet had no difference in early postoperative outcomes after surgery [91]. A study on 151 fast-track TKA verified the effectiveness of a tourniquet on post-operative bleeding and rehabilitation together with suction drainage application. Suction drain was associated to lower Hb levels, higher transfusion rate, higher pain and slower functional recovery, while short-term tourniquet did not influence postoperative bleeding and rehabilitation program [92]. (*) However, a protocol for another RCT aims to verify the effectiveness of a tourniquet on patient’s recovery after fast-track TKA, in association to the anaesthetic regimen. Primary outcome is cumulative intravenous oxycodone consumption by patient-controlled analgesia during the first 24 postoperative hours. Secondary outcomes include postoperative nausea and vomiting, the length of hospital stay, the duration of the surgery, blood loss, demand for surgical unit resources, complications, readmissions, postoperative knee function, range of motion, health-related quality of life, prolonged pain, and mortality [93].
Anesthesia In order to provide guidelines for fast-track TKA, it was conducted a survey on anaesthetic techniques [94]. With regard to blood management, it was found that blood loss is not affected by administering regional (RA) or general anesthesia (GA), while RA is associated with other outcomes such as reduced post-operative pain, length of stay and better rehabilitation [95]. RA is associated with lower thromboembolic complications, even if—after performing a subgroup analysis—anticoagulants were the precaution who made the difference [96]. RA is suggested for TKA patients with comorbidities [97], while there is no evidence enough about their benefits on cardiovascular morbidity, DVT, and PE in association with pharmacological thromboprophylaxis [95]. In case of THK, the same authors did not find evidence enough to compare the benefits of GA or RA on blood loss [98], while others found RA to be better after adjusting for patients’ specific comorbidities and/or when combined with accurate transfusion prevention [99, 100]. With regard to intraoperative blood loss, no difference was found in performing GA (through propofol and remifentanil) or spinal anesthesia (SA) (through intrathecal bupivacaine) However, GA is confirmed to dominate on SA on relevant outcomes for a fast-track pathway, such as early mobilization, less opioid consumption, and reduced pain scores 6h after surgery [101].
Hypotensive epidural anesthesia (HEA) HEA was developed to combine the advantages of epidural anesthesia (airway problems, reduced rate of DVT) with the benefits of induced hypotension [102]. Although HEA’s use seems to be safe and effective, it’s not a first line method in TKA, while it is more spread in THA [103,104,105]. There seems to be no reason to choose or not for HEA according to the pathway. Searching the literature for #hipothensive epidural anaeshtesia, #hea, #arthroplasty and #fast(-)track gave no results.
Antifibrinolytic agents The most common antifibrinolytic agents in use are Tranexamic Acid (TXA) and ε-aminocaproic acid (EACA) [106,107,108]. TXA is more cost-effective than EACA on reducing perioperative bleeding and transfusions [109]. Apoproptine is more effective at decreasing blood loss, but increase the risk of cardiovascular complications. Therefore, it has been removed from the market [110,111,112]. TXA seems therefore to be the best solution. Indeed, meta-analysis show the use of TXA in TKA to be and effective and safe solution in reducing blood loss [113]. A RCT proved TXA to dominate on post-operative cell salvage both in primary THA and TKA [114], which is confirmed by several studies, even if the ideal regime remains controversial, and variates according to topical (intra-articular), general (intra-venous), and amount of administration [73, 74, 115,116,117,118,119,120]. Multiple intravenous boluses injections (pre-, intra-, postoperatively) proved to dominate on a single intravenous dose [121], as well as a bolus of tranexamic acid followed by infusion was found to be more useful than a single dose in decreasing perioperative blood loss in patients undergoing hip surgeries: it reduced allogenic blood transfusions without increasing risk of thromboembolic events [122]. Intra-articular administration is a safe alternative for TKA patients at risk for intravenous administration [123]: moreover, one intra-articular administration is as effective as three doses regimen in preventing blood loss with no difference in thromboembolic complications [124, 125]. According to another study, mixing IV and IA administration is better than administering them alone [126, 127]. RCTs show the high effectiveness of TXA, both with tourniquet and without [117, 118]. Finally, there is no contraindication for its use in patients with a history of venous thromboembolism [128]. Tranexamic acid has been recognized as a valuable innovation under a bundled payment model [11] (*). Fast-track TJA was soon declared to produce no more complications than conventional procedures, including thromboembolic episodes [129]. TXA is shown to reduce perioperative blood loss (and the following need for allogenic blood transfusion) also in accelerated recoveries and clinical pathways, without increasing the rate of thromboembolism [14, 92, 130, 131]. (*) Combined intra-articular (IA) and intravenous TXA reduced blood loss in 60 fast-track TKA patients [132]. Adding low-dose epinephrine to TXA on 100 fast-track THA patients did not reduce blood loss during surgery, but reduced it of 180 mL within 24 h [133]. (*) Tranexamic acid is recognized as a valuable innovation under a fast-track THA pathway [75]. Its effectiveness in conventional TKA had also been largely demonstrated [114, 134], supporting it to be a valuable innovation in fast-track TKA too.
Topical fibrin sealants (TFS) A meta-analysis on TKA suggests the administration of intravenous TXA to dominate on TFS [135], whose effectiveness and cost-effectiveness are debatable [136, 137]. The eventual use of TFS in revision surgery makes them irrelevant for fast-track pathways, which are dedicated to primary intervention.
(Intraoperative) cell salvage A meta-analysis on 43 trials show perioperative (intra- and post-) cell salvage to reduce blood loss in both THA and TKA [138]. However, the study points out how more recent trials show blood salvage benefit to be overwhelmed by more effective innovations [139,140,141]. The use of TXA has almost eliminated the need for other blood conservation strategies [73, 74], included intraoperative blood salvation, and is therefore a valuable innovation to be applied under a fast-track pathway [75]. Intraoperative cell salvage is still useful to those patients who cannot be administered TXA.
Peri/intra-articular injections Topical hemostatic vasoconstriction
Epinephrine is the agent of choice for its topical hemostatic vasoconstriction [142]. Injections of epinephrine together with bupivacaine just before wound closure reduced 32% of drain output, but showed no significant reduction in transfusion rate [143]. Moreover, a recent study denies the effective hemostatic role of intra-articular epinephrine in TKA [144]. However, the combined administration of low-dose epinephrine and tranexamic acid reduced perioperative blood loss and inflammatory response compared with tranexamic acid alone, with no apparent increase in thromboembolic and other complications [145]. A synthesis on fast-track TJA clinical and organizational aspects questioned the value of adding epinephrine during anesthesia [129]. Adding epinephrine to TXA on 100 fast-track THA patients did not reduce intraoperative blood loss, but reduced it of 180 mL within 24 h [133] (*), confirming perioperative blood loss to be reduced by the combination between intravenous low-dose epinephrine and tranexamic acid.
Local infiltration analgesia (LIA)
A review over 11 RCTs shows LIA to be a safe and efficient technique for TJA [146]. A systematic review over 27 RCTs confirmed LIA to provide effective analgesia in TKA, either combined or not with multimodal systemic analgesia; in contrast, LIA provided limited additional benefit in THA when combined with a multimodal regimen [147]. The introduction of intraoperative LIA is consistent with blood management for its combination with TXA proved significant benefits on postoperative Hb levels, reduced LOS, no increase in transfusion and, therefore, better cost-effectiveness (when compared to perioperative autologous blood salvage and preoperative EPO) [148]. Postoperative pain treatment is a fundamental step in achieving early rehabilitation and reduced hospital LOS, therefore the use of LIA is ideal in fast-track pathways [147] (*), even more in combination with TXA, whose benefits were discussed in the dedicated section.
Bipolar and monopolar sealants Bipolar sealant is a novel approach in TKA, but it provides no significant difference in postoperative drain output, Hb level and transfusion requirement when compared to monopolar sealant [149,150,151,152,153,154,155]. As long as the cost-effectiveness of bipolar sealants remains controversial, there is no reason to adopt them in routine care [156]. A synthesis on fast-track TJA clinical and organizational aspects included bipolar sealants as a means to minimize blood loss and transfusions [129]. However, there seems to be no particular reason to choose or not for bipolar or monopolar sealants according to the pathway. Searching the literature for #bipolar sealant, #monopolar sealant and #fast(-)track gave no results.
Platelet-rich plasma (PRP) Intra-operative adoption of PRP is shown to reduce TKA post-operative blood loss [157]. PRP is effective in wound healing, but controversial in haemostasis [158, 159]. There seems to be no reason to choose or not for PRP according to the pathway. Searching the literature for #platelet rich plasma, #PRP, #blood and #fast(-)track gave no results.
Bone wax Bone wax helps to control bleeding from bone surface during surgical procedures [160]. Despite its recent use in TKA to reduce total blood loss while maintaining higher Hb levels, more studies are needed to verify its safety with regard to allergic reactions, inflammation and foreign bodies formation [161, 162]. There seems to be no reason to choose or not for bone wax according to the pathway. Searching the literature for #bone wax, #arthroplasty, #orthopedics and #fast(-)track gave no results.
Sealing femoral tunnel A meta-analysis over 4 TKA RCTs concludes that the use of extramedullary (EM) guide results in less blood loss—given similar operation time—in comparison with the intramedullary (IM) one [163]. However, IM seems to dominate EM on TKA survivorship [164]. There seems to be no reason to choose or not for sealing femoral tunnel according to the pathway. Searching the literature for #sealing femoral tunnel, # arthroplasty and #fast(-)track gave no results.