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Orthopaedic Trauma and Anemia: Conservative versus Liberal Transfusion Strategy: A Prospective Randomized Study
Mullis, B. H., Mullis, L. S., Kempton, L. B., Virkus, W., Slaven, J. E., Bruggers, J.
Journal of orthopaedic trauma. 2024;38(1):18-24
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Editor's Choice
Abstract
OBJECTIVES To determine whether it is safe to use a conservative packed red blood cell transfusion hemoglobin (Hgb) threshold (5.5 g/dL) compared with a liberal transfusion threshold (7.0 g/dL) for asymptomatic musculoskeletal injured trauma patients who are no longer in the initial resuscitative period. METHODS Design: Prospective, randomized, multicenter trial. SETTING Three level 1 trauma centers. PATIENT SELECTION CRITERIA Patients aged 18-50 with an associated musculoskeletal injury with Hgb less than 9 g/dL or expected drop below 9 g/dL with planned surgery who were stable and no longer being actively resuscitated were randomized once their Hgb dropped below 7 g/dL to a conservative transfusion threshold of 5.5 g/dL versus a liberal threshold of 7.0 g/dL. OUTCOME MEASURES AND COMPARISONS Postoperative infection, other post-operative complications and Musculoskeletal Functional Assessment scores obtained at baseline, 6 months, and 1 year were compared for liberal and conservative transfusion thresholds. RESULTS Sixty-five patients completed 1 year follow-up. There was a significant association between a liberal transfusion strategy and higher rate of infection (P = 0.01), with no difference in functional outcomes at 6 months or 1 year. This study was adequately powered at 92% to detect a difference in superficial infection (7% for liberal group, 0% for conservative, P < 0.01) but underpowered to detect a difference for deep infection (14% for liberal group, 6% for conservative group, P = 0.2). CONCLUSIONS A conservative transfusion threshold of 5.5 g/dL in an asymptomatic young trauma patient with associated musculoskeletal injuries leads to a lower infection rate without an increase in adverse outcomes and no difference in functional outcomes at 6 months or 1 year. LEVEL OF EVIDENCE Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
PICO Summary
Population
Musculoskeletal trauma patients with planned surgery (n= 99).
Intervention
Liberal transfusion threshold of 7.0 g/dL (n= 49).
Comparison
Conservative transfusion threshold of 5.5 g/dL (n= 50).
Outcome
Overall, 46/49 (93.9%) of the liberal group had a transfusion versus 23/50 (46.0%) of the conservative group had a transfusion after resuscitation and after enrollment in this study. Following resuscitation and enrollment in the study, patients in the liberal group received a median of 1 unit of blood transfused (range 0–12) and patients in the conservative group received a median of 0 units of blood (range 0–14). Sixty-five patients completed 1- year follow-up. There was a significant association between a liberal transfusion strategy and higher rate of infection, with no difference in functional outcomes at 6 months or 1 year.
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Reporting Bias is Highly Prevalent in Systematic Reviews and Meta-Analyses of Platelet Rich Plasma Injections for Hip Osteoarthritis
Kim, D., Bashrum, B. S., Kotlier, J. L., Mayfield, C. K., Thompson, A. A., Abu-Zahra, M., Hwang, M., Bolia, I. K., Petrigliano, F. A., Liu, J. N.
Arthroscopy, sports medicine, and rehabilitation. 2024;6(1):100851
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Editor's Choice
Abstract
PURPOSE To describe the incidence and types of spin in systematic reviews of platelet-rich plasma (PRP) injections for hip osteoarthritis (OA) and to determine whether patterns in study characteristics could be identified among studies with identifiable spin. METHODS The PubMed, Scopus, and SPORTDiscus databases were queried. Inclusion criteria were systematic reviews or meta-analyses that included an assessment of intra-articular PRP injections as a stand-alone treatment for hip OA. Two authors independently assessed the presence of spin in the included studies and recorded general study characteristics. The prevalence of the 15 different categories of spin was quantified using descriptive statistics. RESULTS Fifteen studies met inclusion criteria for this study. All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. CONCLUSIONS Spin is highly prevalent in abstracts of systematic reviews of PRP in the treatment of hip OA. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration. When present, spin in the abstracts of reviewed studies tended to favor the use of PRP in hip osteoarthritis. CLINICAL RELEVANCE It is important to understand the prevalence of spin in published abstracts, especially in areas of great impact or interest, so authors and readers can have a greater awareness of this potential form of bias.
PICO Summary
Population
Patients with hip osteoarthritis (15 systematic reviews).
Intervention
Systematic review to describe the incidence and types of spin bias in systematic reviews of platelet-rich plasma injections for hip osteoarthritis and to determine whether patterns in study characteristics could be identified among studies with identifiable spin.
Comparison
Outcome
All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration.
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Effectiveness of care bundles for prevention and treatment of postpartum hemorrhage: a systematic review
Vogel, J. P., Nguyen, P. Y., Ramson, J., De Silva, M. S., Pham, M. D., Sultana, S., McDonald, S., Adu-Bonsaffoh, K., McDougall, A. R. A.
American journal of obstetrics and gynecology. 2024
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Editor's Choice
Abstract
OBJECTIVE Care bundles are a promising approach to reducing postpartum hemorrhage (PPH)-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for PPH prevention and/or treatment. DATA SOURCES We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to 9 June 2023) and ClinicalTrials.gov and ICTRP (last 5 years) using a phased search strategy, combining terms for PPH and care bundles. STUDY ELIGIBILITY CRITERIA Peer-review studies evaluating PPH-related care bundles. Care bundles were defined as interventions comprising three or more components implemented collectively, concurrently or in rapid succession. Randomized and non-randomized controlled trials, interrupted time series and before-after studies (controlled or uncontrolled) were eligible. STUDY APPRAISAL AND SYNTHESIS Risk of bias assessed using ROB2 (randomized trials) and ROBINS-I (non-randomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies we used effect direction tables and summarized results narratively. RESULTS Twenty-two studies were included for analysis. For prevention-only bundles (two studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization and ICU stay, and maternal wellbeing. For treatment-only bundles (nine studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (RR 0.40; 95% CI 0.32-0.50) as well as blood transfusion for bleeding, PPH, severe PPH, and mean blood loss. One non-randomized trial and seven uncontrolled studies suggest other PPH treatment bundles might reduce blood loss and severe PPH, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative (CMQCC) care bundle may reduce severe maternal morbidity (RR 0.64, 95% CI 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution. CONCLUSIONS The E-MOTIVE intervention improves PPH-related outcomes among women delivering vaginally, and the CMQCC bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated.
PICO Summary
Population
Women experiencing vaginal birth or caesarean delivery (22 studies).
Intervention
Care bundles for postpartum haemorrhage (PPH) prevention and/or treatment.
Comparison
Outcome
For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization and intensive care unit stay, and maternal wellbeing. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (RR 0.40; 95% CI [0.32, 0.50] as well as blood transfusion for bleeding, PPH, severe PPH, and mean blood loss. One non-randomized trial and seven uncontrolled studies suggest other PPH treatment bundles might reduce blood loss and severe PPH, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative (CMQCC) care bundle may reduce severe maternal morbidity (RR 0.64; 95% CI [0.57, 0.72]. Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types.
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Alveolar Hemorrhage in ANCA-associated Vasculitis: Results of an International, Randomized, Controlled Trial (PEXIVAS)
Fussner, L. A., Flores-Suárez, L. F., Cartin-Ceba, R., Specks, U., Cox, P. G., Jayne, D. R. W., Merkel, P. A., Walsh M Md, PhD
American journal of respiratory and critical care medicine. 2024
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Editor's Choice
Abstract
RATIONALE Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The Plasma Exchange (PLEX) and Glucocorticoids (GC) in Severe AAV (PEXIVAS;NCT00987389) trial was the largest in AAV and first to enroll participants with DAH requiring mechanical ventilation. OBJECTIVES Evaluate characteristics, treatment effects, outcomes for patients with AAV with and without DAH. METHODS PEXIVAS randomized 704 participants to PLEX or no-PLEX and reduced or standard-dose GC. DAH status was defined at enrollment as no-DAH, non-severe, or severe (room air SpO(2)≤85% or use of mechanical ventilation). MEASUREMENTS AND MAIN RESULTS At enrollment, 191(27.1%) participants had DAH (61 severe, including 29 ventilated) and were younger, more frequently relapsing, PR3-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH (n=513,72.9%). Among those with DAH, 8/95(8.4%) receiving PLEX died within one year vs. 15/96(15.6%) with no-PLEX (HR 0.52,CI 0.21-1.24), while 13/96(13.5%) receiving reduced-GC died vs. 10/95(10.5%) with standard-GC (HR 1.33,CI 0.57-3.13). When ventilated, ventilator-free days were similar with PLEX vs. no-PLEX (medians 25,IQR 22-26 vs. 22-27), fewer with reduced-GC (23[20-25]) vs. standard-GC (26[25-28]). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191(12.0%) with DAH died within one year vs. 34/513(6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments. CONCLUSION Patients with AAV and DAH differ from those without DAH in multiple ways. Further data are required to confirm or refute a benefit of PLEX or GC dosing on mortality. Clinical trial registration available at www. CLINICALTRIALS gov, ID: NCT00987389.
PICO Summary
Population
Patients with severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis including glomerulonephritis and/or diffuse alveolar hemorrhage (DAH), enrolled in the PEXIVAS trial (n= 704).
Intervention
Plasma exchange (PLEX) and standard glucocorticoid (GC) (n= 176). PLEX and reduced GC (n= 176).
Comparison
No PLEX and standard GC (n= 175). No PLEX and reduced GC (n= 177).
Outcome
At enrollment, 191 (27.1%) participants had DAH and were younger, more frequently relapsing, proteinase 3-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH (n= 513 (72.9%)). Among those with DAH, 8/95 (8.4%) receiving PLEX died within one year vs. 15/96 (15.6%) with no-PLEX (HR 0.52; CI [0.21, 1.24]), while 13/96 (13.5%) receiving reduced-GC died vs. 10/95 (10.5%) with standard-GC (HR 1.33; CI [0.57, 3.13]). When ventilated, ventilator-free days were similar with PLEX vs. no-PLEX (medians 25; IQR 22, 26 vs. 22, 27), fewer with reduced-GC (23 [20, 25]) vs. standard-GC (26 [25, 28]). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191 (12.0%) with DAH died within one year vs. 34/513 (6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments.
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Prevention strategies for vasovagal reaction in whole blood donors: A quadri-armed randomised control trial
Meher, R., Patidar, G. K., Chaurasia, R., Pandey, H. C., Hazarika, A.
Transfusion medicine (Oxford, England). 2024
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Editor's Choice
Abstract
INTRODUCTION Vasovagal reaction (VVR) is a frequently encountered generalised donor adverse reaction, associated with donor deterrence towards future donation. Several mitigation strategies for prevention of VVR were tried but still not standardised. This quadri-armed randomised study evaluated the utility of water ingestion, applied muscle tension (AMT) and combination of both in preventing the VVR among blood donors. METHODS A quadri-armed randomised controlled trial was performed on 4320 whole blood donors. Blood donors of 18-65 years of age were randomised into four groups based on the interventions performed i.e., control with no intervention (Group 1, n = 1081), water ingestion (Group 2, n = 1082), AMT (Group 3, n = 1070) and combined intervention (Group 4, n = 1087). VVR during and immediately after blood donation were observed along with assessment of risk factors in blood donors and the effectiveness of interventions were analysed. RESULTS The incidence of VVR observed 1.6% in our study, with the highest occurrence in the control group (2.5%) and the lowest in the combined intervention group (0.9%). Multivariable logistic regression revealed that the control group donors faced a 1.38-fold greater risk of VVR compared to those receiving interventions (OR: 1.38, 95% CI: 1.10-1.75). Other risk factors included younger age (OR: 1.5, 95% CI: 1.05-2.17), first-time donation (OR: 5.7, 95% CI: 1.66-5.74), prior history of VVR (OR: 2.5, 95% CI: 10.4-101.52). DISCUSSION/CONCLUSION The combined approach of water ingestion and AMT proved significantly more effective in VVR prevention compared to individual interventions.
PICO Summary
Population
Whole blood donors (n= 4,320).
Intervention
Water ingestion (n= 1,082). Applied muscle tension (AMT), (n= 1,070). Combination of water ingestion and AMT (combined intervention group, n= 1,087).
Comparison
No intervention (control group, n= 1,081).
Outcome
The incidence of vasovagal reaction (VVR) was 1.6%, with the highest occurrence in the control group (2.5%) and the lowest in the combined intervention group (0.9%). Multivariable logistic regression revealed that the control group donors faced a 1.38-fold greater risk of VVR compared to those receiving interventions (OR 1.38; 95% CI [1.10, 1.75]). Other risk factors included younger age (OR 1.5; 95% CI [1.05, 2.17]), first-time donation (OR 5.7; 95% CI [1.66, 5.74]), and prior history of VVR (OR 2.5; 95% CI [10.4, 101.52]).
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Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial
Donohue, J. K., Iyanna, N., Lorence, J. M., Brown, J. B., Guyette, F. X., Eastridge, B. J., Nirula, R., Vercruysse, G. A., O'Keeffe, T., Joseph, B., et al
Trauma surgery & acute care open. 2024;9(1):e001346
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Editor's Choice
Abstract
BACKGROUND Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings. METHODS We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis. RESULTS NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β=-27.6, 95% CI (-51.3 to -3.9), p=0.02). CONCLUSIONS Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity. LEVEL OF EVIDENCE Level II.
PICO Summary
Population
Patients at risk for haemorrhage receiving tranexamic acid before hospitalization, enrolled in the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport (STAAMP) Trial (n= 903).
Intervention
Prehospital tranexamic acid (TXA) (n= 447).
Comparison
Placebo (n= 456).
Outcome
This study was a secondary analysis of the STAAMP trial, comparing patients that received thromboelastography (TEG) (YES-TEG, n= 837) and patients unable to be sampled (NO-TEG, n= 66) to analyze subgroups in which to investigate TEG differences. NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs. 125 (88, 147)), lower prehospital Glascow Coma Score (14 (3, 15) vs. 15 (12, 15)), greater rates of prehospital intubation (39.4% vs. 24.4%) and greater mortality at 30 days (36.4% vs. 6.8%). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs. 1.1 (1.0, 1.2)). Within a severe prehospital shock cohort (SBP< 70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β= -27.6; 95% CI [-51.3, -3.9].
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Results of clinical effectiveness of conventional versus Mirasol-treated Apheresis Platelets in Patients with Hypoproliferative Thrombocytopenia (MiPLATE) trial
Koepsell, S. A., Stolla, M., Sedjo, R. L., Carson, J., Knudson, M., Cook, R., Fasano, R., Ngamsuntikul, S. G., Cohn, C., Gorlin, J., et al
Transfusion. 2024
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Editor's Choice
Abstract
BACKGROUND The Mirasol® Pathogen Reduction Technology System was developed to reduce transfusion-transmitted diseases in platelet (PLT) products. STUDY DESIGN AND METHODS MiPLATE trial was a prospective, multicenter, controlled, randomized, non-inferiority (NI) study of the clinical effectiveness of conventional versus Mirasol-treated Apheresis PLTs in participants with hypoproliferative thrombocytopenia. The novel primary endpoint was days of ≥Grade 2 bleeding with an NI margin of 1.6. RESULTS After 330 participants were randomized, a planned interim analysis of 297 participants (145 MIRASOL, 152 CONTROL) receiving ≥1 study transfusion found a 2.79-relative rate (RR) in the MIRASOL compared to the CONTROL in number of days with ≥Grade 2 bleeding (95% confidence interval [CI] 1.67-4.67). The proportion of subjects with ≥Grade 2 bleeding was 40.0% (n = 58) in MIRASOL and 30.3% (n = 46) in CONTROL (RR = 1.32, 95% CI 0.97-1.81, p = .08). Corrected count increments were lower (p < .01) and the number of PLT transfusion episodes per participant was higher (RR = 1.22, 95% CI 1.05-1.41) in MIRASOL. There was no difference in the days of PLT support (hazard ratio = 0.86, 95% CI 0.68-1.08) or total number of red blood cell transfusions (RR = 1.12, 95% CI 0.91-1.37) between MIRASOL versus CONTROL. Transfusion emergent adverse events were reported in 119 MIRASOL participants (84.4%) compared to 133 (82.6%) participants in CONTROL (p = NS). DISCUSSION This study did not support that MIRASOL was non-inferior compared to conventional platelets using the novel endpoint number of days with ≥Grade 2 bleeding in MIRASOL when compared to CONTROL.
PICO Summary
Population
Participants with hypoproliferative thrombocytopenia requiring platelet transfusions, enrolled in the MiPLATE trial (n= 297).
Intervention
Mirasol-treated plasma-stored apheresis platelets (Mirasol group, n= 145).
Comparison
Conventional plasma-stored apheresis platelets (Control group, n= 152).
Outcome
The novel primary endpoint was days of ≥Grade 2 bleeding with a non-inferiority margin of 1.6. Participants in the Mirasol group had more days of grade ≥2 bleeding than participants in the Control group (RR 2.74; 95% CI [1.66, 4.53]), the primary endpoint. The secondary endpoints showed a similar proportion of participants in each group with days of grade ≥2 bleeding and no difference in red blood cell transfusion despite a higher rate of participants with platelets refractoriness, platelet transfusions, and lower corrected count increments in the Mirasol group.
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Pharmacological interventions for the prevention of bleeding in people undergoing elective hip or knee surgery: a systematic review and network meta-analysis
Gibbs, V. N., Champaneria, R., Sandercock, J., Welton, N. J., Geneen, L. J., Brunskill, S. J., Dorée, C., Kimber, C., Palmer, A. J., Estcourt, L. J.
The Cochrane database of systematic reviews. 2024;1(1):Cd013295
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Editor's Choice
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.
PICO Summary
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.
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Effects of albumin and crystalloid priming strategies on red blood cell transfusions in on-pump cardiac surgery: a network meta-analysis
Wang, T., Wang, J., Zhang, M., Zhang, H., Zhang, Q., Liu, G., Dong, W., Wang, Y., Ji, B.
BMC anesthesiology. 2024;24(1):26
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Editor's Choice
Abstract
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.
PICO Summary
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.
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Desmopressin to reduce periprocedural bleeding and transfusion: a systematic review and meta-analysis
Wang, C., Lebedeva, V., Yang, J., Anih, J., Park, L. J., Paczkowski, F., Roshanov, P. S.
Perioperative medicine (London, England). 2024;13(1):5
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Editor's Choice
Abstract
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.
PICO Summary
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.