Introduction
Materials and methods
1 | Formulation of a clear question | Which procedures support the implementation of blood management in fast-track total joint arthroplasty? |
---|---|---|
2 | Exhaustive and reproducible research of all relevant information (published and unpublished studies) concerning the question | Partly reproducible, non-exhaustive. |
3 | Systematic selection of eligible studies on the basis of pre-defined inclusion criteria | All papers had to be related to fast-track pathways or accelerated procedures, and had to be written in English at least in the abstract. Detailed information is reported in the PRISMA diagram before the end of introduction. |
4 | Analysis of the methodological quality of included studies | No. |
5 | Quantitative or qualitative synthesis of the information according to the nature, complexity of the question and availability of data | To facilitate reading, qualitative and quantitative information is synthesized and summarized in tables. Information about fast-track procedures is matched with every single step of the general orthopedic blood management strategy. |
6 | Discussion of the reasons for agreement and inconsistency between the results of the different studies | Yes. |
Results
Preoperative blood management
Content | Conventional studies, guidelines, and recommendations | Fast-track setting |
---|---|---|
Anemia and iron deficiency treatment Since preoperative and postoperative anemia are generally related, we refer to the latter in the present section. | Anemia standards and detection | |
Patients undergoing TKA should meet standard criteria regarding the minimum preoperative Hb [28‐30]. Otherwise, surgery should be postponed [29]. Recent guidelines recommend preoperative correction of anemia and iron deficiency in all patients with a Hb < 13 g/dL [30]. | Pre- and postoperative Hb levels (together with the subsequent need for transfusions) play a role on fast-track TJA postoperative outcomes, Length of Stay (LOS) and patient satisfaction [15, 35]. Preoperative anemia is frequently associated with prolonged LOS, 90-day re-admission and blood transfusions, preventing fast-track TJA to express full value both in THA and TKA procedures [31, 36] (*). 549 fast-track TJA procedures on patients aged ≥ 85 years revealed blood-related issues such as postoperative anemia, blood transfusions, and mobilization to be the most relevant medical cause of more than 4 days LOS (27.3%), where preoperative anemia had no significant impact. Preoperative anemia was instead one of the main medical causes of readmissions within 90 days, together with suspected but disproved thromboembolic events. Authors concluded that fast-track TJA aiming at 3 days median LOS and discharge to home is feasible in most patients aged ≥ 85 years, provided attention to pre- and post-operative anemia [16]. With regard to THA, authors show a weak but significant correlation between post-operative Hb and early functional recovery (6-min walk test) in 65 year-old patients, while they did not find any influence between the former and other functional criteria nor quality of life [37]. | |
Iron deficiency treatment | ||
This is why preoperative iron supplementation is highly suggested in orthopedic procedures, alone or together with intraoperative tranexamic acid (TXA) [40, 41]. (*) Studies report intravenous (IV) iron therapy to be safe and dominate on oral, in particular with patients with malabsorption such as coeliac disease [32, 42, 43]. When using oral supplements for iron storage, a daily dose of 100 mg elemental iron is recommended for 2 to 6 weeks before surgery. When using IV iron supplementation, requirements can be estimated using the Ganzoni equation [44]. | Studies on 882 unselected fast-track THA/TKA patients confirmed anemia to be prevalent in elderly patients and to be associated with increased transfusion risk and postoperative morbidity. Iron deficiency is confirmed to be the most common and reversible cause [45]. Fast-track THA non-anemic patients with iron deficiency were supplemented with oral highly absorbable Sideral® Forte (at least) 4 weeks before surgery. They had a smaller decline in post-operative Hb, shorter hospital stay and reduced blood transfusions, generating a saving of 1763.25 € per patient. Therefore, preoperative sucrosomial iron® is a cost-effective solution for fast-track THA surgery [46]. (*) | |
Blood thinners (antiplatelet, anticoagulant, antithrombotic agents) | These drugs have a key role in preventing cardiac and vascular events [47]. To normalize bleeding, they are usually stopped a few days before surgery [8]... ... But patients at high cardiovascular risk should not stop aspirin in the perioperative period [48]. Given that cardiovascular disease is common in patients planning to undergo to TKA, both the continuation and the discontinuation of antiplatelet therapy can be associated with major risks, depending on patient characteristics, severity of the procedure and estimated time of immobilization [8, 49, 50]. The management of these medications in the perioperative setting should be adapted to the single patient according to cardiologist, orthopedic surgeon, and anesthesiologist [18]. | Preoperative use of anticoagulant agents needs important evaluations in fast-track TJA too [51, 52]. (*) A study on the incidence of stroke within 30-days after 24.682 fast-track TJA found preoperative use of anticoagulant treatment to be the most important risk factor, together with age ≥ 85. Anemia was also included, but not significant. It is therefore important to check for the use of preoperative anticoagulants, and anemia, to avoid cardiovascular perioperative events in elderly patients [53]. (*) |
Transfusion protocol agreement Although transfusion is a postoperative intervention, establishing the trigger must be done before surgery. | Reasons to variate transfusion practice in orthopedic surgery are not well understood. In case of elective surgery, the need for allogenic transfusion was said to predictable in 97.4% of the cases, according to (i) preoperative anemia, (ii) perioperative blood loss, (iii) transfusion trigger [54]. A survey on clinicians and hospitals in the UK showed transfusion triggers after TJA to variate between 6 to 11 g/dL, calling for shared evidence-based guidelines to improve practice and avoid waste [55]. This is consistent with results from a previous international survey, according to which transfusion triggers vary significantly among different clinicians, hospitals and countries [56]. Systematic review on transfusion drivers in orthopedic surgery shows low Hb and old age to be the main predictors for the need of transfusion, followed by surgical complexity, low body weight, additional comorbidities (rheumatoid arthritis, history of anemia, diabetes, cardiovascular disease, renal failure, or metastasis), and female sex [57]. Studies on restrictive triggers in major orthopedic patients show transfusion rate and deep wound infections to be respectively reduced from 34 to 17%, and from 2.6 to 1.5% [58]. This is confirmed by a prospective study on unilateral knee arthroplasty (UKA), which adopted a postoperative trigger < 8.5 g/dL (or greater in case of a symptomatic patient): transfusion rates were reduced from 31 to 11.9%, blood waste from 60 to 1%, with no adverse outcomes [59]. Current evidence confirms that a restrictive trigger (Hb < 8 g/dL) is safe and cheaper3 ... which is supported by the National Institute for Health and Clinical Excellence even more restrictive recommendations [60]. | A study on fast-track TJA predictors of LOS and patient satisfaction found: The need for blood transfusion to be the main predictor of a longer stay (> 3 days) Blood transfusion to occur in 22% and 12% of THA and TKA respectively, although it does not compromise a high satisfaction rank (9.4 and 9.3 up to 10) Transfusions were administered when postoperative hematocrit level (at the first day) was 25% less than preoperative. Transfusions were associated with age, lack of mobility during the first day after surgery, co-morbidities, low Hb and increased ASA score [15]. The need for blood transfusion is a predictor that produces significant value in accelerated pathways such as fast-track surgery, since they provide caregivers with useful information to plan for treatments and beds. |
Erythropoietin (EPO) | EPO reduces post-operative transfusions [63] both in THA and TKA [64‐67], even in rheumatoid arthritis patients [67], but it is associated with adverse events such as deep venous thrombosis (DVT), pulmonary embolism (PE), fever, hypokalemia, urinary tract infection, nausea, hypoxia, and vomiting in up to 5% of the population [68‐70]. Moreover, it is unclear whether benefits are not offset by costs [71]. | |
Preoperative autologous blood donation (PAD) |
Intraoperative blood management
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 [81‐85]. 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. |
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]. | 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]. | 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) [106‐108]. 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 [110‐112]. 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, 115‐120]. 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]. 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]. |
Topical fibrin sealants (TFS) | 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]. | 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 [149‐155]. 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]. | 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]. | 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 | 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. |
Postoperative blood management
Content | Conventional studies, guide lines, and recommendations | Fast-track setting |
---|---|---|
Postoperative anemia | See Table 2. | |
Compression | Intermittent pneumatic compression to reduce bleeding in (fast-track) high risk patients is considered later, together with thromboprophylaxis. | |
Cryotherapy | Systematic review on 13 RCTs proved cryotherapy to be effective in reducing blood loss after TKA selected patients, while its benefits remained controversial after THA [172]. Previous systematic review and meta-analysis over 11 TKA studies show only slight short-lasting benefit of cryotherapy in routine procedures [173]. | Cryotherapy has been advocated as a safe and effective strategy to improve fast-track TKA postoperative results, acting on pain, edema, and blood loss. Continuous cold flow device in the acute postoperative setting did not show superiority in comparison with traditional icing regimen. Thus, due to the costs, it should be reserved to selected cases [174]. |
Limb position | Different knee flexion positions (e.g., hip elevation by 60° combined with 60° knee flexion) have been reported to have promising results with respect to reducing perioperative blood loss [175‐177]. Postoperative knee flexion is therefore an easy, inexpensive, and effective method in blood loss reduction [18]. | There seems to be no reason to opt for a limb position according to the pathway. Searching the literature for #limb(-)position, #blood and #fast(-)track gave 2 results, none of which consistent with orthopedics. |
Postoperative cell savage | PCS effectiveness and cost-effectiveness seem to be maximized in patients with pre-operative Hb 12–15 g/dL, while in patients with pre-operative Hb less than 12 g/dL it should be combined with other techniques [178]. | The use of TXA has almost eliminated the need for other blood conservation strategies [73, 74], included postoperative blood salvation, and is therefore a valuable innovation to be applied under a fast-track pathway [75]. Postoperative cell salvage is still useful to those patients who cannot be administered TXA. |
Drainage clamping and removal | The introduction of drainage clamping in bilateral total joint arthroplasty proved effective and cost-effective in pioneer studies on TKA and THA [179, 180]. More recent studies on TKA proved its effectiveness to be debatable [181‐183], and when effective, proved debatable intervals of administration [184‐186]. Today, 3-h interval clamping proved effective in reducing TKA postoperative Hb drop with no increase in thromboembolic episodes and wound complications [187], and proved to be even more effective in combination with TXA, even if there is still need of a major focus on duration and intervals [188, 189]. With regard to THA, 4-h drainage clamping proved potential for routine implementation, for it reduced blood loss and the following need of transfusion with no significant difference on other clinical outcomes [190]. According to a RCT on 224 THA patients, intra-articular soaking of high concentration of TXA with 2-h clamping drainage can reduce the total blood loss and transfusion rates in primary THA without significant increase in postoperative thrombotic complications [191]. | A prospective cohort study evaluated the safety and feasibility of early removal of drainage tube in primary fast-track TKA. Wound drainage was removed within 6–12 h after surgery. The procedure could drain the haematocele and reduce the risk of infection, without increasing the sense of pain, inflammatory reaction, limb swelling, and total blood loss. Removal of drainage tube was therefore safe and feasible within 6–12 h after surgery [192]. According to clinical expertise, drains can be avoided in selected cases, when local conditions free of obvious bleeding following re-established pressure ensure the absence of the risk of hematoma. |
Is the incidence of readmissions resulting from VTE and bleeding complications higher with LMWH or with mobile compression plus ASA? | In THA, there was no difference in the frequency or readmissions for bleeding complication (wound or systemic) between the treatments. In TKA, patients treated with LMWH had higher readmission rates within 6 weeks after surgery, because of bleeding complications, wound infection, or VTE. |
Is the incidence of wound bleeding complications higher with LMWHG or with mobile compression plus ASA? | In THA, there was higher wound bleeding complication frequency with LMWH. In TKA, patients treated with LMWH had a higher frequency of wound bleeding complications or infection. |
In TKA, is the frequency of systemic bleeding events and complications related to chemoprophylaxis higher with LMWH or with mechanical compression plus ASA? | Patients treated with LMWH had higher rates of systemic bleeding or complications. |
Is there a difference in symptomatic VTEs between LMWH and mechanical compression plus ASA? | There was no difference between the rate of symptomatic VTEs between the groups. |
Low VTE risk procedure | High VTE risk procedure | |
---|---|---|
Low VTE risk patient | GT PT only in case they have to rest in bed for more than two days, due to particular reasons | GT + PT (LMWH/AAS) and/or MT |
High VTE risk patient | GT + PT (LMWH/AAS) and/or MT | GT + PT (LMWH) + MT |