ABSTRACT
BACKGROUND: Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care. OBJECTIVES: To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology. SEARCH METHODS: We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants. DATA COLLECTION AND ANALYSIS: We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received. MAIN RESULTS: We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials). AUTHORS' CONCLUSIONS: We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review.
Subject(s)
Orthopedic Procedures , Stroke , Tranexamic Acid , Male , Female , Adult , Humans , Tranexamic Acid/therapeutic use , Aprotinin/therapeutic use , Deamino Arginine Vasopressin , Network Meta-Analysis , Hemorrhage/etiology , Aminocaproic Acid/therapeutic use , Stroke/drug therapy , Orthopedic Procedures/adverse effects , FibrinABSTRACT
BACKGROUND: Pelvic, hip, and long bone fractures can result in significant bleeding at the time of injury, with further blood loss if they are treated with surgical fixation. People undergoing surgery are therefore at risk of requiring a blood transfusion and may be at risk of peri-operative anaemia. Pharmacological interventions for blood conservation may reduce the risk of requiring an allogeneic blood transfusion and associated complications. OBJECTIVES: To assess the effectiveness of different pharmacological interventions for reducing blood loss in definitive surgical fixation of the hip, pelvic, and long bones. SEARCH METHODS: We used a predefined search strategy to search CENTRAL, MEDLINE, PubMed, Embase, CINAHL, Transfusion Evidence Library, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) from inception to 7 April 2022, without restrictions on language, year, or publication status. We handsearched reference lists of included trials to identify further relevant trials. We contacted authors of ongoing trials to acquire any unpublished data. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people who underwent trauma (non-elective) surgery for definitive fixation of hip, pelvic, and long bone (pelvis, tibia, femur, humerus, radius, ulna and clavicle) fractures only. There were no restrictions on gender, ethnicity, or age. We excluded planned (elective) procedures (e.g. scheduled total hip arthroplasty), and studies published since 2010 that had not been prospectively registered. Eligible interventions included: antifibrinolytics (tranexamic acid, aprotinin, epsilon-aminocaproic acid), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants, and non-fibrin sealants. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using GRADE. We did not perform a network meta-analysis due to lack of data. MAIN RESULTS: We included 13 RCTs (929 participants), published between 2005 and 2021. Three trials did not report any of our predefined outcomes and so were not included in quantitative analyses (all were tranexamic acid versus placebo). We identified three comparisons of interest: intravenous tranexamic acid versus placebo; topical tranexamic acid versus placebo; and recombinant factor VIIa versus placebo. We rated the certainty of evidence as very low to low across all outcomes. Comparison 1. Intravenous tranexamic acid versus placebo Intravenous tranexamic acid compared to placebo may reduce the risk of requiring an allogeneic blood transfusion up to 30 days (RR 0.48, 95% CI 0.34 to 0.69; 6 RCTs, 457 participants; low-certainty evidence) and may result in little to no difference in all-cause mortality (Peto odds ratio (Peto OR) 0.38, 95% CI 0.05 to 2.77; 2 RCTs, 147 participants; low-certainty evidence). It may result in little to no difference in risk of participants experiencing myocardial infarction (risk difference (RD) 0.00, 95% CI -0.03 to 0.03; 2 RCTs, 199 participants; low-certainty evidence), and cerebrovascular accident/stroke (RD 0.00, 95% CI -0.02 to 0.02; 3 RCTs, 324 participants; low-certainty evidence). We are uncertain if there is a difference between groups for risk of deep vein thrombosis (Peto OR 2.15, 95% CI 0.22 to 21.35; 4 RCTs, 329 participants, very low-certainty evidence), pulmonary embolism (Peto OR 1.08, 95% CI 0.07 to 17.66; 4 RCTs, 329 participants; very low-certainty evidence), and suspected serious drug reactions (RD 0.00, 95% CI -0.03 to 0.03; 2 RCTs, 185 participants; very low-certainty evidence). No data were available for number of red blood cell units transfused, reoperation, or acute transfusion reaction. We downgraded the certainty of the evidence for imprecision (wide confidence intervals around the estimate and small sample size, particularly for rare events), and risk of bias (unclear or high risk methods of blinding and allocation concealment in the assessment of subjective measures), and upgraded the evidence for transfusion requirement for a large effect. Comparison 2. Topical tranexamic acid versus placebo We are uncertain if there is a difference between topical tranexamic acid and placebo for risk of requiring an allogeneic blood transfusion (RR 0.31, 95% CI 0.08 to 1.22; 2 RCTs, 101 participants), all-cause mortality (RD 0.00, 95% CI -0.10 to 0.10; 1 RCT, 36 participants), risk of participants experiencing myocardial infarction (Peto OR 0.15, 95% CI 0.00 to 7.62; 1 RCT, 36 participants), cerebrovascular accident/stroke (RD 0.00, 95% CI -0.06 to 0.06; 1 RCT, 65 participants); and deep vein thrombosis (Peto OR 1.11, 95% CI 0.07 to 17.77; 2 RCTs, 101 participants). All outcomes reported were very low-certainty evidence. No data were available for number of red blood cell units transfused, reoperation, incidence of pulmonary embolism, acute transfusion reaction, or suspected serious drug reactions. We downgraded the certainty of the evidence for imprecision (wide confidence intervals around the estimate and small sample size, particularly for rare events), inconsistency (moderate heterogeneity), and risk of bias (unclear or high risk methods of blinding and allocation concealment in the assessment of subjective measures, and high risk of attrition and reporting biases in one trial). Comparison 3. Recombinant factor VIIa versus placebo Only one RCT of 48 participants reported data for recombinant factor VIIa versus placebo, so we have not presented the results here. AUTHORS' CONCLUSIONS: We cannot draw conclusions from the current evidence due to lack of data. Most published studies included in our analyses assessed the use of tranexamic acid (compared to placebo, or using different routes of administration). We identified 27 prospectively registered ongoing RCTs (total target recruitment of 4177 participants by end of 2023). The ongoing trials create six new comparisons: tranexamic acid (tablet + injection) versus placebo; intravenous tranexamic acid versus oral tranexamic acid; topical tranexamic acid versus oral tranexamic acid; different intravenous tranexamic acid dosing regimes; topical tranexamic acid versus topical fibrin glue; and fibrinogen (injection) versus placebo.
Subject(s)
Arthroplasty, Replacement , Fractures, Bone , Hemostatics , Myocardial Infarction , Pulmonary Embolism , Stroke , Tranexamic Acid , Transfusion Reaction , Venous Thrombosis , Humans , Tranexamic Acid/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Hemostatics/therapeutic use , Fibrinogen , Venous Thrombosis/drug therapy , Stroke/drug therapy , Myocardial Infarction/drug therapy , Fractures, Bone/surgeryABSTRACT
OBJECTIVE: Assess the prognostic value of pre-operative haemoglobin concentration (Hb) for identifying patients who develop severe post-operative anaemia or require blood transfusion following primary total hip or knee, or unicompartmental knee arthroplasty (THA, TKA, UKA). BACKGROUND: Pre-operative group and save (G&S), and post-operative Hb measurement may be unnecessary for many patients undergoing hip and knee arthroplasty provided individuals at greatest risk of severe post-operative anaemia can be identified. METHODS AND MATERIALS: Patients undergoing THA, TKA, or UKA between 2011 and 2018 were included. Outcomes were post-operative Hb below 70 and 80 g/L, and peri-operative blood transfusion. Logistic regression assessed the association between pre-operative Hb and each outcome. Decision curve analysis compared strategies for selecting patients for G&S and post-operative Hb measurement. RESULTS: 10 015 THA, TKA and UKA procedures were performed in 8582 patients. The incidence of blood transfusion (4.5%) decreased during the study. Using procedure specific Hb thresholds to select patients for pre-operative G&S and post-operative Hb testing had a greater net benefit than selecting all patients, no patients, or patients with pre-operative anaemia. CONCLUSIONS: Pre-operative G&S and post-operative Hb measurement may not be indicated for UKA or TKA when adopting restrictive transfusion thresholds, provided clinicians accept a 0.1% risk of patients developing severe undiagnosed post-operative anaemia (Hb < 70 g/L). The decision to perform these blood tests for THA patients should be based on local institutional data and selection of acceptable risk thresholds.
Subject(s)
Anemia , Arthroplasty, Replacement, Knee , Anemia/diagnosis , Anemia/etiology , Anemia/therapy , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Blood Transfusion , Hematologic Tests , Hemoglobins/analysis , HumansABSTRACT
BACKGROUND: Reverse total shoulder replacement (TSR) in elderly patients with primary osteoarthritis (OA) and rotator cuff pathology is increasingly being performed. The purpose of our study was to determine the medium-term results of anatomic TSR for OA in patients with established preoperative partial-thickness rotator cuff tears on magnetic resonance imaging (MRI) scans. METHODS: We reviewed a cohort of patients who had undergone anatomic TSR for OA with a preoperative MRI diagnosis of partial-thickness rotator cuff tear. Patients were assessed with preoperative and post operative Oxford Shoulder Scores, evaluation of their range-of-movement and clinical rotator cuff assessment. Anteroposterior and axillary radiographs were used to assess for any proximal humeral migration (using the Torchia classification) and any evidence of loosening. The Lazarus score was used to grade glenoid radiolucencies. RESULTS: The study comprised 36 patients (14 men and 22 women) who underwent TSR and had partial-thickness rotator cuff tears on MRI; preoperatively, all showed mild to moderate fatty infiltration. The mean age of the patients was 79.2 years (range, 75-88 years); the mean follow-up period was 5.8 years (range, 5-9 years). Significant improvements in pain and range of movement were reported in all cases. At the final follow-up, the mean Oxford Shoulder Score was 42 points (range, 32-46 points), with a minimum improvement of 14 points (P = .001). External rotation (20° vs. 40°, P = .001), forward flexion (80° vs. 140°, P = .015), abduction (45° vs. 90°, P = .015), and internal rotation also improved. Lucencies were observed in 8 glenoids, with 6 showing grade 1 Lazarus changes, 2 showing grade 2, and none showing grade 3. There were no cases of implant loosening. Clinically, 4 patients had rotator cuff weakness but only 2 showed evidence of proximal migration. One patient remained satisfied, whereas the other patient, with moderate-grade proximal migration according to the Torchia classification, underwent revision for rotator cuff failure; one further patient underwent washout and DAIR (débridement, antibiotics, and implant retention) for infection. DISCUSSION: There is a paucity of literature on whether a preoperative partial-thickness rotator cuff tear has an adverse effect on the outcome of TSR. Our results show that the presence of a partial cuff tear on preoperative MRI does not significantly affect function after anatomic TSR in the medium term. With anatomic TSR having less morbidity for patients and allowing greater potential options for revision, we believe that the use of reverse shoulder arthroplasty in this cohort of patients, with partial rotator cuff tears, may not be necessary and we advocate consideration of anatomic TSR in this patient group.
Subject(s)
Arthroplasty, Replacement, Shoulder , Rotator Cuff Injuries , Shoulder Joint , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Range of Motion, Articular , Rotator Cuff/surgery , Rotator Cuff Injuries/diagnostic imaging , Rotator Cuff Injuries/surgery , Shoulder Joint/diagnostic imaging , Shoulder Joint/surgery , Treatment OutcomeABSTRACT
BACKGROUND: Blood transfusion can be a lifesaving intervention after perioperative blood loss. Many prediction models have been developed to identify patients most likely to require blood transfusion during elective surgery, but it is unclear whether any are suitable for clinical practice. STUDY DESIGN AND SETTING: We conducted a systematic review, searching MEDLINE, Embase, PubMed, The Cochrane Library, Transfusion Evidence Library, Scopus, and Web of Science databases for studies reporting the development or validation of a blood transfusion prediction model in elective surgery patients between January 1, 2000 and June 30, 2021. We extracted study characteristics, discrimination performance (c-statistics) of final models, and data, which we used to perform risk of bias assessment using the Prediction model risk of bias assessment tool (PROBAST). RESULTS: We reviewed 66 studies (72 developed and 48 externally validated models). Pooled c-statistics of externally validated models ranged from 0.67 to 0.78. Most developed and validated models were at high risk of bias due to handling of predictors, validation methods, and too small sample sizes. CONCLUSION: Most blood transfusion prediction models are at high risk of bias and suffer from poor reporting and methodological quality, which must be addressed before they can be safely used in clinical practice.
Subject(s)
Blood Transfusion , Models, Statistical , Humans , Prognosis , Blood Transfusion/methods , HemorrhageABSTRACT
AIMS: The aim of this study was to identify modifiable risk factors associated with mortality in patients requiring revision total hip arthroplasty (THA) for periprosthetic hip fracture. METHODS: The electronic records of consecutive patients undergoing revision THA for periprosthetic hip fracture between December 2011 and October 2018 were reviewed. The data which were collected included age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, the preoperative serum level of haemoglobin, time to surgery, operating time, blood transfusion, length of hospital stay, and postoperative surgical and medical complications. Univariate and multivariate logistic regression analyses were used to determine independent modifiable factors associated with mortality at 90 days and one year postoperatively. RESULTS: A total of 203 patients were identified. Their mean age was 78 years (44 to 100), and 108 (53%) were female. The median time to surgery was three days (interquartile range (IQR) 2 to 5). The mortality rate at one year was 13.8% (n = 28). The commonest surgical complication was dislocation (n = 22, 10.8%) and the commonest medical complication within 90 days of surgery was hospital-acquired pneumonia (n = 25, 12%). Multivariate analysis showed that the rate of mortality one year postoperatively was five-fold higher in patients who sustained a dislocation (odds ratio (OR) 5.03 (95% confidence interval (CI) 1.60 to 15.83); p = 0.006). The rate of mortality was also four-fold higher in patients who developed hospital-acquired pneumonia within 90 days postoperatively (OR 4.43 (95% CI 1.55 to 12.67); p = 0.005). There was no evidence that the time to surgery was a risk factor for death at one year. CONCLUSION: Dislocation and hospital-acquired pneumonia following revision THA for a periprosthetic fracture are potentially modifiable risk factors for mortality. This study suggests that surgeons should consider increasing constraint to reduce the risk of dislocation, and the early involvement of a multidisciplinary team to reduce the risk of hospital-acquired pneumonia. We found no evidence that the time to surgery affected mortality, which may allow time for medical optimization, surgical planning, and resource allocation. Cite this article: Bone Joint J 2020;102-B(5):580-585.