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Editor's Choice
  • Nuñez JH
  • Colomina J
  • Angles F
  • Pallisó F
  • Acosta HF
  • et al.
Arch Orthop Trauma Surg. 2024 Apr;144(4):1585-1595 doi: 10.1007/s00402-024-05243-3.
POPULATION:

Patients undergoing primary total hip or knee arthroplasty (5 studies, n= 17,667).

INTERVENTION:

Systematic review and meta-analysis to assess the necessity of routine pretransfusion tests before primary total hip or knee arthroplasty.

COMPARISON:

OUTCOME:

Pooled results revealed a 96.3% over-ordering pretransfusion test rate (95% CI [0.92, 1.00]) among patients undergoing primary total hip or knee arthroplasty. The pooled prevalence of hospital transfusion rate was 3.6%. There were statistically significant differences in preoperative haemoglobin (Hb) levels between patients not requiring transfusion (Hb= 13.9 g/dl; 95% CI [12.59, 15.20]) and those needing transfusion (Hb= 11.9 g/dl; 95% CI [10.69, 13.01]).

BACKGROUND:

The excessive routine ordering of pretransfusion tests (blood typing, screening, and cross-matching) for surgical cases incurs significant unnecessary costs and places an undue burden on transfusion services. This study aims to systematically review the literature regarding the necessity of routine pretransfusion tests before total hip arthroplasty (THA) or total knee arthroplasty (TKA) and summarize their outcomes.

STUDY METHODS:

A systematic review and meta-analysis were performed. The study's characteristics, the prevalence of over-ordering pretransfusion tests, transfusion rates, and potential cost savings to the healthcare system were analyzed.

RESULTS:

The study included 17,667 patients. Pooled results revealed a 96.3% over-ordering pretransfusion test rate (95% CI: 0.92-1.00; p < 0.001) among patients undergoing primary THA or TKA. The pooled prevalence of hospital transfusion rate was 3.6%. Notably, there were statistically significant differences in preoperative hemoglobin (Hb) levels between patients not requiring transfusion (Hb = 13.9 g/dl; 95% CI 12.59-15.20; p < 0.001) and those needing transfusion (Hb = 11.9 g/dl; 95% CI 10.69-13.01; p < 0.001) (p = 0.03). The per-patient total cost savings ranged from 28.63 to 191.27 dollars.

DISCUSSION:

Our study suggests that routine pre-transfusion testing for all patients undergoing primary THA or TKA may be unnecessary. We propose limiting pretransfusion test orders to patients with preoperative hemoglobin levels below 12 g/dl in unilateral primary TKA or THA. This targeted approach can result in significant cost savings for healthcare systems and transfusion services by reducing the over-ordering of pretransfusion tests in these surgical procedures.

Editor's Choice
  • Wang M
  • Che JX
  • Chen L
  • Song TT
  • Qu JT
  • et al.
Chin Med Sci J. 2024 Mar;39(1):54-68 doi: 10.24920/004294.
POPULATION:

Patients undergoing spine surgery (21 randomised controlled trials, n= 1,388).

INTERVENTION:

Dexmedetomidine (Dex).

COMPARISON:

Saline.

OUTCOME:

This meta-analysis revealed a negative effect of Dex on haemodynamics. Dex increased the risk of hypotension and bradycardia during spine surgery, while it did not reduce intraoperative blood loss. The risk of hypotension and bradycardia was higher with the use of a loading dose in combination with a maintenance dose than using a maintenance dose alone. Dex was more likely to cause severe hypotension rather than mild hypotension. In terms of heart rate reduction, the incidence of both mild and severe bradycardia increased.

Objective Dexmedetomidine (Dex) is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate. However, its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate. This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery.Methods The Web of Science, MEDLINE, EMBASE, and the Cochrane Library were searched up to February 2023 for randomized controlled trials (RCTs) including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline. A fixed- or random-effect model was used depending on heterogeneity.Results Twenty-one RCTs, including 1388 patients, were identified. Dex added the overall risk of intraoperative hypotension (odds ratio [OR]: 2.11; 95% confidence interval [CI]: 1.24 - 3.58; P=0.006) and bradycardia (OR: 2.48; 95%CI: 1.57 - 3.93; P=0.0001). The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension (OR: 2.00; 95%CI: 1.06 - 3.79; P=0.03) and bradycardia (OR: 2.28; 95%CI: 1.42 - 3.66; P=0.0007). For patients receiving total intravenous anesthesia, there was an increased risk of hypotension (OR: 2.90; 95%CI: 1.24 - 6.82; P=0.01) and bradycardia (OR: 2.66; 95%CI: 1.53 - 4.61; P=0. 0005). For patients in the inhalation anesthesia group, only an increased risk of bradycardia (OR: 4.95; 95%CI: 1.41 - 17.37; P=0.01) was observed. No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group. The incidence of severe hypotension (OR: 2.57; 95%CI: 1.05 - 6.32; P=0.04), but not mild hypotension, was increased. Both mild (OR: 2.55; 95%CI: 1.06 - 6.15; P=0.04) and severe (OR: 2.45; 95%CI: 1.43 - 4.20; P=0.001) bradycardia were associated with a higher risk. The overall analyses did not reveal significant reduction in intraoperative blood loss. However, a significant decrease in blood loss was observed in total inhalation anesthesia subgroup (mean difference [MD]: -82.97; 95%CI: -109.04 - -56.90; P<0.001).Conclusions Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery. The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss.

Editor's Choice
  • Moulton SG
  • Hartwell MJ
  • Feeley BT
  • Moulton, S. G.
  • Hartwell, M. J.
  • et al.
Am J Sports Med. 2024 Feb 7;3635465231213039 doi: 10.1177/03635465231213039.
POPULATION:

Patients undergoing arthroscopic rotator cuff repair surgery with platelet-rich plasma (PRP) (25 studies).

INTERVENTION:

Systematic review to evaluate the presence of spin bias in the abstracts of systematic reviews and meta-analyses of PRP with rotator cuff repair surgery.

COMPARISON:

OUTCOME:

Each included study was evaluated for the 15 most common forms of spin. Correlations between spin types and study characteristics were evaluated. At least 1 form of spin bias was found in 56% (14/25) of the included studies. In regard to the 3 different categories of spin, a form of misleading interpretation was found in 56% (14/25) of the studies. A form of misleading reporting was found in 48% (12/25) of the studies. A form of inappropriate extrapolation was found in 16% (4/25) of the studies. A significant association was found between misleading interpretation and publication year (odds ratio (OR) 1.41 per year increase in publication; 95% CI [1.04, 1.92]) and misleading reporting and publication year (OR 1.41 per year increase in publication; 95% CI [1.02, 1.95]). An association was found between inappropriate extrapolation and journal impact factor (OR 0.21 per unit increase in impact factor; 95% CI [0.044, 0.99]).

BACKGROUND:

The use of platelet-rich plasma (PRP) in orthopaedics continues to increase. One common use of PRP is as an adjunct in rotator cuff repair surgery. Multiple systematic reviews and meta-analyses have summarized the data on PRP use in rotator cuff repair surgery. However, systematic reviews and meta-analyses are subject to spin bias, where authors' interpretations of results influence readers' interpretations.

PURPOSE:

To evaluate spin in the abstracts of systematic reviews and meta-analyses of PRP with rotator cuff repair surgery.

STUDY DESIGN:

Systematic review; Level of evidence, 3.

METHODS:

A PubMed and Embase search was conducted using the terms rotator cuff repair and PRP and systematic review or meta-analysis. After review of 74 initial studies, 25 studies met the inclusion criteria. Study characteristics were documented, and each study was evaluated for the 15 most common forms of spin and using the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews, Version 2) rating system. Correlations between spin types and study characteristics were evaluated using binary logistic regression for continuous independent variables and a chi-square test or Fisher exact test for categorical variables.

RESULTS:

At least 1 form of spin was found in 56% (14/25) of the included studies. In regard to the 3 different categories of spin, a form of misleading interpretation was found in 56% (14/25) of the studies. A form of misleading reporting was found in 48% (12/25) of the studies. A form of inappropriate extrapolation was found in 16% (4/25) of the studies. A significant association was found between misleading interpretation and publication year (odds ratio [OR], 1.41 per year increase in publication; 95% CI, 1.04-1.92; P = .029) and misleading reporting and publication year (OR, 1.41 per year increase in publication; 95% CI, 1.02-1.95; P = .037). An association was found between inappropriate extrapolation and journal impact factor (OR, 0.21 per unit increase in impact factor; 95% CI, 0.044-0.99; P = .048).

CONCLUSION:

A significant amount of spin was found in the abstracts of systematic reviews and meta-analyses of PRP use in rotator cuff repair surgery. Given the increasing use of PRP by clinicians and interest among patients, spin found in these studies may have a significant effect on clinical practice.

Editor's Choice
  • Skubas NJ
  • Callum J
  • Bathla A
  • Keshavarz H
  • Fergusson D
  • et al.
Br J Anaesth. 2024 Feb;132(2):237-250 doi: 10.1016/j.bja.2023.11.009.
POPULATION:

Paediatric and adult patients undergoing cardiovascular surgery (42 randomised controlled trials).

INTERVENTION:

Intravenous albumin.

COMPARISON:

Synthetic colloids and crystalloids.

OUTCOME:

Primary outcome of all-cause mortality. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use. Mortality was assessed in 15 trials (n= 2,711) and the risk difference was 0.00; 95% confidence interval (CI) [-0.01, 0.01] I(2)= 0%. Among secondary outcomes, intravenous albumin resulted in smaller fluid balance, mean difference -0.55 L; 95% CI [-1.06, -0.4], I(2)= 90% (nine studies, n= 1,975) and higher albumin concentrations, mean difference 7.77 gL(-1); 95% CI [3.73, 11.8], I(2)= 95% (six studies, n= 325). Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids.

BACKGROUND:

Intravenous albumin is commonly utilised in cardiovascular surgery for priming of the cardiopulmonary bypass circuit, volume replacement, or both, although the evidence to support this practice is uncertain. The aim was to compare i.v. albumin with synthetic colloids and crystalloids for paediatric and adult patients undergoing cardiovascular surgery for all-cause mortality and other perioperative outcomes.

METHODS:

A systematic review and meta-analysis of randomised controlled trials (RCTs) of i.v. albumin compared with synthetic colloids and crystalloids on the primary outcome of all-cause mortality was conducted. Secondary outcomes included renal failure, blood loss, duration of hospital or intensive care unit stay, cardiac index, and blood component use; subgroups were analysed by age, comparator fluid, and intended use (priming, volume, or both). We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CCRT) from 1946 to November 23, 2022.

RESULTS:

Of 42 RCTs, mortality was assessed in 15 trials (2711 cardiac surgery patients) and the risk difference was 0.00, 95% confidence interval (CI) -0.01 to 0.01, I2=0%. Among secondary outcomes, i.v. albumin resulted in smaller fluid balance, mean difference -0.55 L, 95% CI -1.06 to -0.4, I2=90% (nine studies, 1975 patients) and higher albumin concentrations, mean difference 7.77 g L-1, 95% CI 3.73-11.8, I2=95% (six studies, 325 patients).

CONCLUSIONS:

Intravenous albumin use was not associated with a difference in morbidity and mortality in patients undergoing cardiovascular surgery, when compared with comparator fluids. The lack of improvement in important outcomes with albumin and its higher cost suggests it should be used restrictively.

SYSTEMATIC REVIEW PROTOCOL:

PROSPERO; CRD42020171876.

Editor's Choice
  • Wang C
  • Lebedeva V
  • Yang J
  • Anih J
  • Park LJ
  • et al.
Perioper Med (Lond). 2024 Jan 23;13(1):5 doi: 10.1186/s13741-023-00358-4.
POPULATION:

Children or adults without known inherited bleeding disorders undergoing surgery or other invasive procedures (63 randomised controlled trials, n= 4,163).

INTERVENTION:

Desmopressin administered intravenously or subcutaneously before, during, or immediately after a surgical or interventional procedure.

COMPARISON:

Placebo, usual care, or antifibrinolytic agents.

OUTCOME:

Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95; 95% confidence interval (CI) [0.86, 1.05]) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75; 95% CI [0.47, 1.19]) when compared to placebo or usual care. However, the authors demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units; 95% CI [-0.94, -0.15]), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI [-0.56, -0.23]), and the risk of bleeding events (2 trials, RR 0.45; 95% CI [0.24, 0.84]). The certainty of evidence of these findings was generally low.

We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.

Editor's Choice
  • Wang T
  • Wang J
  • Zhang M
  • Zhang H
  • Zhang Q
  • et al.
BMC Anesthesiol. 2024 Jan 16;24(1):26 doi: 10.1186/s12871-024-02414-y.
POPULATION:

Adult patients undergoing cardiovascular surgery with cardiopulmonary bypass (10 randomised controlled trials).

INTERVENTION:

Network meta-analysis (NMA) to perform direct comparisons, including albumin vs. artificial colloid and artificial colloid vs. crystalloid, and to obtain indirect evidence for the comparisons between albumin and crystalloid priming strategies.

COMPARISON:

OUTCOME:

Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative red blood cell (RBC) transfusions (MD -0.68U; 95% CI [-1.26, -0.09U]) and intraoperative RBC transfusions (MD -0.20U; 95% CI [-0.39, -0.01U]) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant (MD -0.16U; 95% CI: [-0.45, 0.14U]). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance.

BACKGROUND:

In on-pump cardiac surgery, the albumin priming strategy could maintain colloid osmotic pressure better than crystalloid solutions and reduce excessive perioperative fluid balance. However, a high-quality meta-analysis is required to compare the safety of these approaches in perioperative red blood cell (RBC) transfusions. Owing to limited direct evidence, we conducted a network meta-analysis (NMA) to increase the pool of studies and provide indirect evidence.

METHODS:

The pre-defined primary outcomes were intraoperative and the first 24 h postoperative RBC transfusion volume in units. The pre-defined secondary outcome was postoperative blood loss (the first 24 h). We reviewed all randomized controlled trials comparing albumin, crystalloid, and artificial colloid priming strategies. Studies that only displayed pre-defined outcomes could be included. A pairwise meta-analysis was performed on studies that directly compared the pre-defined outcomes between albumin and crystalloids. Additionally, a random-effects network meta-analysis (NMA) model was employed to generate indirect evidence for the pre-defined outcomes between albumin and crystalloids.

RESULTS:

The literature search identified 830 studies,10 of which were included in the final analysis. Direct meta-analysis indicated that crystalloid priming significantly decreased total perioperative RBC transfusions (MD: -0.68U; 95%CI: -1.26, -0.09U; P = 0.02) and intraoperative RBC transfusions (MD: -0.20U; 95%CI: -0.39, -0.01U; P = 0.03) compared to albumin. Postoperative RBC transfusions showed a decreasing trend in the crystalloid group; however, the difference was not statistically significant. (MD: -0.16U; 95%CI: -0.45, 0.14U; P = 0.30). After including indirect evidence, the NMA results continued to demonstrate a higher RBC receiving with the albumin priming strategy compared to crystalloids, although the differences did not reach statistical significance. For postoperative blood loss, direct evidence showed no significant differences between albumin and crystalloid priming strategies. However, NMA evidence displayed that albumin exist higher probability of reducing postoperative blood loss than crystalloid.

CONCLUSION:

Both direct and NMA evidence indicated that the albumin priming strategy resulted in more perioperative RBC transfusions than crystalloids. Considering the additional blood management burden, the application of an albumin-priming strategy in on-pump cardiac surgery still needs more consideration.

Editor's Choice
  • Gibbs VN
  • Champaneria R
  • Sandercock J
  • Welton NJ
  • Geneen LJ
  • et al.
Cochrane Database Syst Rev. 2024 Jan 16;1(1):CD013295 doi: 10.1002/14651858.CD013295.pub2.
POPULATION:

People undergoing elective hip or knee surgery (102 randomised controlled trials).

INTERVENTION:

Antifibrinolytics (tranexamic acid, aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants.

COMPARISON:

Placebo or one of the active interventions.

OUTCOME:

The primary outcomes were the proportion of participants requiring an allogeneic blood transfusion and all‐cause mortality. Tranexamic acid was the most common drug studied. Mortality was not reported by many trials. Tranexamic acid interventions consistently ranked higher than other treatments such as aprotinin, EACA and topical fibrin sealants compared with placebo. The authors noted that mixed routes of administration (oral and intra‐articular, intravenous and intra‐articular) appear to be more effective than single routes of administration and higher doses of tranexamic acid feature higher up the treatment ranking hierarchy. The authors identified 30 ongoing studies.

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.

Editor's Choice
  • Stangl S
  • Popp M
  • Reis S
  • Sitter M
  • Saal-Bauernschubert L
  • et al.
Syst Rev. 2024 Jan 2;13(1):5 doi: 10.1186/s13643-023-02431-x.
POPULATION:

Patients with iron deficiency or iron deficiency anaemia undergoing major surgery (13 studies: 5 randomised controlled trials and 8 observational studies).

INTERVENTION:

Systematic review to identify and appraise outcomes reported for preoperative or perioperative treatment of iron deficiency, with or without anemia.

COMPARISON:

OUTCOME:

Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the 'blood and lymphatic system' domain, followed by ‘adverse event’ (77%) and ‘need for further resources’ (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting.

BACKGROUND:

Iron deficiency (ID) is the leading cause of anemia worldwide. The prevalence of preoperative ID ranges from 23 to 33%. Preoperative anemia is associated with worse outcomes, making it important to diagnose and treat ID before elective surgery. Several studies indicated the effectiveness of intravenous iron supplementation in iron deficiency with or without anemia (ID(A)). However, it remains challenging to establish reliable evidence due to heterogeneity in utilized study outcomes. The development of a core outcome set (COS) can help to reduce this heterogeneity by proposing a minimal set of meaningful and standardized outcomes. The aim of our systematic review was to identify and assess outcomes reported in randomized controlled trials (RCTs) and observational studies investigating iron supplementation in iron-deficient patients with or without anemia.

METHODS:

We searched MEDLINE, CENTRAL, and ClinicalTrials.gov systematically from 2000 to April 1, 2022. RCTs and observational studies investigating iron supplementation in patients with a preoperative diagnosis of ID(A), were included. Study characteristics and reported outcomes were extracted. Outcomes were categorized according to an established outcome taxonomy. Quality of outcome reporting was assessed with a pre-specified tool. Reported clinically relevant differences for sample size calculation were extracted.

RESULTS:

Out of 2898 records, 346 underwent full-text screening and 13 studies (five RCTs, eight observational studies) with sufficient diagnostic inclusion criteria for iron deficiency with or without anemia (ID(A)) were eligible. It is noteworthy to mention that 49 studies were excluded due to no confirmed diagnosis of ID(A). Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the 'blood and lymphatic system' domain, followed by "adverse event" (77%) and "need for further resources" (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting.

CONCLUSION:

This systematic review comprehensively depicts the heterogeneity of reported outcomes in studies investigating iron supplementation in ID(A) patients regarding exact definitions and timing. Our analysis provides a systematic base for consenting to a minimal COS.

SYSTEMATIC REVIEW REGISTRATION:

PROSPERO CRD42020214247.

Editor's Choice
  • Hariri G
  • Collet L
  • Duarte L
  • Martin GL
  • Resche-Rigon M
  • et al.
Crit Care. 2023 Sep 12;27(1):354 doi: 10.1186/s13054-023-04640-1.
POPULATION:

Adult patients undergoing cardiac surgery such as coronary artery bypass grafting and/or valve surgery (86 randomised controlled trials (RCTs) n= 25,855).

INTERVENTION:

Non-pharmacological interventions to reduce the incidence of cardiac surgery-associated acute kidney injury (CSA-AKI): Goal directed perfusion (GDP), pulsatile flow during cardiopulmonary bypass (CPB), minimally invasive extracorporeal circulation (MECC), epidural analgesia, remote ischemic preconditioning (RIPc), tight glycemic control, kidney disease improving global outcomes care bundle, hyperoxia during CPB, restrictive transfusion strategy, high target arterial pressure.

COMPARISON:

Usual care.

OUTCOME:

No intervention had high-quality evidence to reduce CSA-AKI. From the included studies, the most frequent intervention was RIPc (31 RCTs, n= 7,738), MECC, (14 RCTs, n= 1,617) and pulsatile blood flow during CPB (10 RCTs, n= 1,993). Three interventions were associated with a significantly reduced risk of CSA-AKI: GDP, RIPc and pulsatile flow during CPB.

BACKGROUND:

Cardiac surgery-associated acute kidney injury (CSA-AKI) is frequent. While two network meta-analyses assessed the impact of pharmacological interventions to prevent CSA-AKI, none focused on non-pharmacological interventions. We aim to assess the effectiveness of non-pharmacological interventions to reduce the incidence of CSA-AKI.

METHODS:

We searched PubMed, Embase, Central and clinical trial registries from January 1, 2004 (first consensus definition of AKI) to July 1, 2023. Additionally, we conducted manual screening of abstracts of major anesthesia and intensive care conferences over the last 5 years and reference lists of relevant studies. We selected all randomized controlled trials (RCTs) assessing a non-pharmacological intervention to reduce the incidence of CSA-AKI, without language restriction. We excluded RCTs of heart transplantation or involving a pediatric population. The primary outcome variable was CSA-AKI. Two reviewers independently identified trials, extracted data and assessed risk of bias. Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation to assess the quality of evidence.

RESULTS:

We included 86 trials (25,855 patients) evaluating 10 non-pharmacological interventions to reduce the incidence of CSA-AKI. No intervention had high-quality evidence to reduce CSA-AKI. Two interventions were associated with a significant reduction in CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion (RR, 0.55 [95% CI 0.40-0.76], I2 = 0%; Phet = 0.44) and remote ischemic preconditioning (RR, 0.86 [0.78-0.95]; I2 = 23%; Phet = 0.07). Pulsatile flow during cardiopulmonary bypass was associated with a significant reduction in CSA-AKI incidence but with very low quality of evidence (RR = 0.69 [0.48; 0.99]; I2 = 53%; Phet < 0.01). We found high quality of evidence for lack of effect of restrictive transfusion strategy (RR, 1.02 [95% CI 0.92; 1.12; Phet = 0.67; I2 = 3%) and tight glycemic control (RR, 0.86 [95% CI 0.55; 1.35]; Phet = 0.25; I2 = 26%).

CONCLUSIONS:

Two non-pharmacological interventions are likely to reduce CSA-AKI incidence, with moderate quality of evidence: goal-directed perfusion and remote ischemic preconditioning.

Editor's Choice
  • Kang ZY
  • Ma S
  • Liu W
  • Liu C
Transpl Immunol. 2023 Jun;78:101801 doi: 10.1016/j.trim.2023.101801.
POPULATION:

Kidney transplant recipients (11 studies, n= 19,543).

INTERVENTION:

Kidney transplantation with blood transfusion (n= 6,191).

COMPARISON:

Kidney transplantation without blood transfusion (n= 13,352).

OUTCOME:

The authors assessed the pooled associations between blood transfusion and occurrence of de novo donor-specific antibodies (dnDSA) and clinical outcomes. Blood transfusion was strongly correlated with the development of dnDSA (relative risk (RR) 1.40; 95% confidence interval (CI) [1.17, 1.67]). Patients with blood transfusion had a higher risk of developing anti-human leukocyte antigen (HLA) class I dnDSA than non-transfused patients (RR 1.75; 95% CI [1.14, 2.69]) as well as significantly higher rates of antibody-mediated rejection (RR 1.41; 95% CI [1.21, 2.35]) and graft loss (RR 1.75; 95% CI [1.30, 2.35]). There were no statistically significant differences between the two groups in the development of anti-HLA antibodies, anti-HLA class II dnDSA, and anti-HLA class I and II dnDSA; delayed graft function; T cell-mediated rejection; acute rejection; borderline rejection; or patient death.

The relationship between blood transfusion following kidney transplantation (KT) and the development of de novo donor-specific antibodies (dnDSA) is controversial. This was investigated by conducting a meta-analysis of studies on patients who underwent KT with or without blood transfusion, and by evaluating the effect of post-KT blood transfusion on clinical outcomes of kidney transplant recipients. Relevant studies in the PubMed, EMBASE, and Cochrane Library databases were identified from inception to July 1, 2022. Two reviewers independently extracted data from the selected articles and estimated study quality. A fixed effects or random effects model was used to pool data according to the heterogeneity among studies. Data included in the meta-analysis were derived from 11 studies with a total of 19,543 patients including 6191 with and 13,352 without blood transfusion post-KT. We assessed the pooled associations between blood transfusion and occurrence of dnDSA and clinical outcomes of transplant recipients. Blood transfusion was strongly correlated with the development of dnDSA (relative risk [RR] = 1.40, 95% confidence interval [CI]: 1.17-1.67; P < 0.05). Patients with blood transfusion had a higher risk of developing anti-human leukocyte antigen (HLA) class I dnDSA than non-transfused patients (RR = 1.75, 95% CI: 1.14-2.69; P < 0.05) as well as significantly higher rates of antibody-mediated rejection (AMR) (RR = 1.41, 95% CI: 1.21-2.35; P < 0.05) and graft loss (RR = 1.75, 95% CI: 1.30-2.35; P < 0.05). There were no statistically significant differences between the two groups in the development of anti-HLA antibodies, anti-HLA class II dnDSA, and anti-HLA class I and II dnDSA; delayed graft function; T cell-mediated rejection; acute rejection; borderline rejection; or patient death. Our results suggest that blood transfusion was associated with dnDSA development in KT recipients. The findings of this systematic review also suggest that post-KT blood transfusion recipients have a higher risk of AMR, and graft loss compared with non-transfused patients. Evidence from this meta-analysis indicates that the use of blood transfusion post-KT is associated with a significantly higher risk of immunological sensitization. More and higher quality results from large randomized controlled trials are still needed to inform clinical practice.