RESUMEN
BACKGROUND: An estimated one-quarter to one-half of people diagnosed with haematological malignancies experience anaemia. There are different strategies for red blood cell (RBC) transfusions to treat anaemia. A restrictive transfusion strategy permits a lower haemoglobin (Hb) level whereas a liberal transfusion strategy aims to maintain a higher Hb. The most effective and safest strategy is unknown. OBJECTIVES: To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). SEARCH METHODS: We searched for randomised controlled trials (RCTs) and non-randomised studies (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2023, Issue 2), and eight other databases (including three trial registries) to 21 March 2023. We also searched grey literature and contacted experts in transfusion for additional trials. There were no language, date or publication status restrictions. SELECTION CRITERIA: We included RCTs and prospective NRS that evaluated restrictive versus liberal RBC transfusion strategies in children or adults with malignant haematological disorders receiving intensive chemotherapy or radiotherapy, or both, with or without HSCT. DATA COLLECTION AND ANALYSIS: Two authors independently screened references, full-text reports of potentially relevant studies, extracted data from the studies, and assessed the risk of bias. Any disagreement was discussed and resolved with a third review author. Dichotomous outcomes were presented as a risk ratio (RR) with a 95% confidence interval (CI). Narrative syntheses were used for heterogeneous outcome measures. Review Manager Web was used to meta-analyse the data. Main outcomes of interest included: all-cause mortality at 31 to 100 days, quality of life, number of participants with any bleeding, number of participants with clinically significant bleeding, serious infections, length of hospital admission (days) and hospital readmission at 0 to 3 months. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: Nine studies met eligibility; eight RCTs and one NRS. Six hundred and forty-four participants were included from six completed RCTs (n = 560) and one completed NRS (n = 84), with two ongoing RCTs consisting of 294 participants (260 adult and 34 paediatric) pending inclusion. Only one completed RCT included children receiving HSCT (n = 6); the other five RCTs only included adults: 239 with acute leukaemia receiving chemotherapy and 315 receiving HSCT (166 allogeneic and 149 autologous). The transfusion threshold ranged from 70 g/L to 80 g/L for restrictive and from 80 g/L to 120 g/L for liberal strategies. Effects were reported in the summary of findings tables only for the trials that included adults to reduce indirectness due to the limited evidence contributed by the prematurely terminated paediatric trial. Evidence from RCTs Overall, there may be little to no difference in the number of participants who die within 31 to 100 days using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 451 participants; RR 1.00, 95% CI 0.27 to 3.70, P=0.99; very low-certainty evidence). There may be little to no difference in quality of life at 0 to 3 months using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 431 participants; analysis unable to be completed due to heterogeneity; very low-certainty evidence). There may be little to no difference in the number of participants who suffer from any bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies; 448 participants; RR 0.91, 95% CI 0.78 to 1.06, P = 0.22; low-certainty evidence). There may be little to no difference in the number of participants who suffer from clinically significant bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (four studies; 511 participants; RR: 0.94, 95% CI 0.74 to 1.19, P = 0.60; low-certainty evidence). There may be little to no difference in the number of participants who experience serious infections at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies, 451 participants; RR: 1.20, 95% CI 0.93 to 1.55, P = 0.17; low-certainty evidence). A restrictive transfusion strategy likely results in little to no difference in the length of hospital admission at 0 to 3 months compared to a liberal strategy (two studies; 388 participants; analysis unable to be completed due to heterogeneity in reporting; moderate-certainty evidence). There may be little to no difference between hospital readmission using a restrictive transfusion strategy compared to a liberal transfusion strategy (one study, 299 participants; RR: 0.89, 95% CI 0.52 to 1.50; P = 0.65; low-certainty evidence). Evidence from NRS The evidence is very uncertain whether a restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-certainty evidence); or decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-certainty evidence). No NRS reported on the other eligible outcomes. AUTHORS' CONCLUSIONS: Findings from this review were based on seven studies and 644 participants. Definite conclusions are challenging given the relatively few included studies, low number of included participants, heterogeneity of intervention and outcome reporting, and overall certainty of evidence. To increase the certainty of the true effect of a restrictive RBC transfusion strategy on clinical outcomes, there is a need for rigorously designed and executed studies. The evidence is largely based on two populations: adults with acute leukaemia receiving intensive chemotherapy and adults with haematologic malignancy requiring HSCT. Despite the addition of 405 participants from three RCTs to the previous review's results, there is still insufficient evidence to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days, we would need a total of 1492 participants to have an 80% chance of detecting, at a 5% level of significance, an increase in all-cause mortality from 3% to 6%. Further RCTs are needed overall, particularly in children.
Asunto(s)
Anemia , Transfusión de Eritrocitos , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Transfusión de Eritrocitos/estadística & datos numéricos , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Anemia/terapia , Adulto , Niño , Sesgo , Calidad de Vida , Hemoglobina A/análisis , Ensayos Clínicos Controlados no Aleatorios como Asunto , Hemoglobinas/análisisRESUMEN
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.
Asunto(s)
Procedimientos Ortopédicos , Accidente Cerebrovascular , Ácido Tranexámico , Masculino , Femenino , Adulto , Humanos , Ácido Tranexámico/uso terapéutico , Aprotinina/uso terapéutico , Desamino Arginina Vasopresina , Metaanálisis en Red , Hemorragia/etiología , Ácido Aminocaproico/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Procedimientos Ortopédicos/efectos adversos , FibrinaRESUMEN
BACKGROUND: Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT. METHODS: We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure. RESULTS: Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3-5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5). CONCLUSIONS: Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a 'one-size-fits-all' approach should be used across different clinical settings.
Asunto(s)
Hemorragia , Hemostáticos , Adulto , Humanos , Hemorragia/tratamiento farmacológico , Hemostáticos/uso terapéutico , Transfusión Sanguínea , Plaquetas , Transfusión de EritrocitosRESUMEN
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.
Asunto(s)
Artroplastia de Reemplazo , Fracturas Óseas , Hemostáticos , Infarto del Miocardio , Embolia Pulmonar , Accidente Cerebrovascular , Ácido Tranexámico , Reacción a la Transfusión , Trombosis de la Vena , Humanos , Ácido Tranexámico/uso terapéutico , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Hemostáticos/uso terapéutico , Fibrinógeno , Trombosis de la Vena/tratamiento farmacológico , Accidente Cerebrovascular/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Fracturas Óseas/cirugíaRESUMEN
BACKGROUND: Concerns regarding the safety and availability of transfused donor blood have prompted research into a range of techniques to minimise allogeneic transfusion requirements. Cell salvage (CS) describes the recovery of blood from the surgical field, either during or after surgery, for reinfusion back to the patient. OBJECTIVES: To examine the effectiveness of CS in minimising perioperative allogeneic red blood cell transfusion and on other clinical outcomes in adults undergoing elective or non-urgent surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases and two clinical trials registers for randomised controlled trials (RCTs) and systematic reviews from 2009 (date of previous search) to 19 January 2023, without restrictions on language or publication status. SELECTION CRITERIA: We included RCTs assessing the use of CS compared to no CS in adults (participants aged 18 or over, or using the study's definition of adult) undergoing elective (non-urgent) surgery only. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 106 RCTs, incorporating data from 14,528 participants, reported in studies conducted in 24 countries. Results were published between 1978 and 2021. We analysed all data according to a single comparison: CS versus no CS. We separated analyses by type of surgery. The certainty of the evidence varied from very low certainty to high certainty. Reasons for downgrading the certainty included imprecision (small sample sizes below the optimal information size required to detect a difference, and wide confidence intervals), inconsistency (high statistical heterogeneity), and risk of bias (high risk from domains including sequence generation, blinding, and baseline imbalances). Aggregate analysis (all surgeries combined: primary outcome only) Very low-certainty evidence means we are uncertain if there is a reduction in the risk of allogeneic transfusion with CS (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.59 to 0.72; 82 RCTs, 12,520 participants). Cancer: 2 RCTs (79 participants) Very low-certainty evidence means we are uncertain whether there is a difference for mortality, blood loss, infection, or deep vein thrombosis (DVT). There were no analysable data reported for the remaining outcomes. Cardiovascular (vascular): 6 RCTs (384 participants) Very low- to low-certainty evidence means we are uncertain whether there is a difference for most outcomes. No data were reported for major adverse cardiovascular events (MACE). Cardiovascular (no bypass): 6 RCTs (372 participants) Moderate-certainty evidence suggests there is probably a reduction in risk of allogeneic transfusion with CS (RR 0.82, 95% CI 0.69 to 0.97; 3 RCTs, 169 participants). Very low- to low-certainty evidence means we are uncertain whether there is a difference for volume transfused, blood loss, mortality, re-operation for bleeding, infection, wound complication, myocardial infarction (MI), stroke, and hospital length of stay (LOS). There were no analysable data reported for thrombosis, DVT, pulmonary embolism (PE), and MACE. Cardiovascular (with bypass): 29 RCTs (2936 participants) Low-certainty evidence suggests there may be a reduction in the risk of allogeneic transfusion with CS, and suggests there may be no difference in risk of infection and hospital LOS. Very low- to moderate-certainty evidence means we are uncertain whether there is a reduction in volume transfused because of CS, or if there is any difference for mortality, blood loss, re-operation for bleeding, wound complication, thrombosis, DVT, PE, MACE, and MI, and probably no difference in risk of stroke. Obstetrics: 1 RCT (1356 participants) High-certainty evidence shows there is no difference between groups for mean volume of allogeneic blood transfused (mean difference (MD) -0.02 units, 95% CI -0.08 to 0.04; 1 RCT, 1349 participants). Low-certainty evidence suggests there may be no difference for risk of allogeneic transfusion. There were no analysable data reported for the remaining outcomes. Orthopaedic (hip only): 17 RCTs (2055 participants) Very low-certainty evidence means we are uncertain if CS reduces the risk of allogeneic transfusion, and the volume transfused, or if there is any difference between groups for mortality, blood loss, re-operation for bleeding, infection, wound complication, prosthetic joint infection (PJI), thrombosis, DVT, PE, stroke, and hospital LOS. There were no analysable data reported for MACE and MI. Orthopaedic (knee only): 26 RCTs (2568 participants) Very low- to low-certainty evidence means we are uncertain if CS reduces the risk of allogeneic transfusion, and the volume transfused, and whether there is a difference for blood loss, re-operation for bleeding, infection, wound complication, PJI, DVT, PE, MI, MACE, stroke, and hospital LOS. There were no analysable data reported for mortality and thrombosis. Orthopaedic (spine only): 6 RCTs (404 participants) Moderate-certainty evidence suggests there is probably a reduction in the need for allogeneic transfusion with CS (RR 0.44, 95% CI 0.31 to 0.63; 3 RCTs, 194 participants). Very low- to moderate-certainty evidence suggests there may be no difference for volume transfused, blood loss, infection, wound complication, and PE. There were no analysable data reported for mortality, re-operation for bleeding, PJI, thrombosis, DVT, MACE, MI, stroke, and hospital LOS. Orthopaedic (mixed): 14 RCTs (4374 participants) Very low- to low-certainty evidence means we are uncertain if there is a reduction in the need for allogeneic transfusion with CS, or if there is any difference between groups for volume transfused, mortality, blood loss, infection, wound complication, PJI, thrombosis, DVT, MI, and hospital LOS. There were no analysable data reported for re-operation for bleeding, MACE, and stroke. AUTHORS' CONCLUSIONS: In some types of elective surgery, cell salvage may reduce the need for and volume of allogeneic transfusion, alongside evidence of no difference in adverse events, when compared to no cell salvage. Further research is required to establish why other surgeries show no benefit from CS, through further analysis of the current evidence. More large RCTs in under-reported specialities are needed to expand the evidence base for exploring the impact of CS.
Asunto(s)
Artritis Infecciosa , Trasplante de Células Madre Hematopoyéticas , Infarto del Miocardio , Embolia Pulmonar , Accidente Cerebrovascular , Infección de Heridas , Femenino , Embarazo , Adulto , Humanos , Procedimientos Quirúrgicos Electivos , Transfusión SanguíneaRESUMEN
OBJECTIVE: The aim of this systematic scoping review is to identify and categorize the outcome measures that have been reported in clinical studies, where therapeutic plasma exchange (TPE) has been used as an intervention in any clinical settings, excluding thrombotic thrombocytopenic purpura (TTP). METHODS: We searched electronic databases using a predefined search strategy from inception to October 9, 2020. Two reviewers independently screened and extracted data. RESULTS: We included 42 studies (37 RCTs and 5 prospective cohort studies) grouped into six main categories (neurology, immunology, renal, rheumatology, hematology, and dermatology). Primary outcomes were defined in eight studies (19%, 8/42) and were categorized as efficacy (five studies) or patient reported outcomes (three studies). A power calculation was reported in six studies (75%, 6/8): five neurology studies (mainly patient reported outcomes) and a single immunological study (efficacy outcome). Disease-specific efficacy outcomes were dependent on the clinical setting of the population receiving TPE. Most of the trials (43%, 18/42) were undertaken in patients with neurology conditions where clear, disease-specific, clinical outcome measures were used, including neurological disability scales (11/18, 61%), change in neurological examination (9/18, 50%), and functional improvement scores (7/18, 39%). For other conditions, the reporting of disease-specific outcomes was poorly reported. Safety outcomes were mainly related to replacement fluid type rather than being disease-specific. The most common outcome reported was hypotension (19%, 8/42), and this was primarily in patients exchanged with albumin. CONCLUSION: Future clinical studies to determine which fluid replacement option is most efficacious and safe should use disease-specific outcomes, as a trial in one therapeutic area may not necessarily translate to another therapeutic area. Patient reported outcomes are not universally reported for all disease areas. Safety measures focused primarily on fluid safety.
Asunto(s)
Intercambio Plasmático , Púrpura Trombocitopénica Trombótica , Albúminas , Humanos , Evaluación de Resultado en la Atención de Salud , Intercambio Plasmático/efectos adversos , Estudios Prospectivos , Púrpura Trombocitopénica Trombótica/terapiaRESUMEN
Donor-transmitted cancer (DTC) has major implications for the affected patient as well as other recipients of organs from the same donor. Unlike heterotopic transplant recipients, there may be limited treatment options for orthotopic transplant recipients with DTC. We systematically reviewed the evidence on DTC in orthotopic solid organ transplant recipients (SOTRs). We searched MEDLINE, EMBASE, PubMed, Scopus, and Web of Science in January 2020. We included cases where the outcome was reported and excluded donor-derived cancers. We assessed study quality using published checklists. Our domains of interest were presentation, time to diagnosis, cancer extent, management, and survival. There were 73 DTC cases in liver (n = 51), heart (n = 10), lung (n = 10) and multi-organ (n = 2) recipients from 58 publications. Study quality was variable. Median time to diagnosis was 8 months; 42% were widespread at diagnosis. Of 13 cases that underwent re-transplantation, three tumours recurred. Mortality was 75%; median survival 7 months. Survival was worst in transmitted melanoma and central nervous system tumours. The prognosis of DTC in orthotopic SOTRs is poor. Although re-transplantation offers the best chance of cure, some tumours still recur. Publication bias and clinical heterogeneity limit the available evidence. From our findings, we suggest refinements to clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020165001, Prospero Registration Number: CRD42020165001.
Asunto(s)
Trasplante de Órganos , Trasplantes , Humanos , Recurrencia Local de Neoplasia , Trasplante de Órganos/efectos adversos , Donantes de Tejidos , Receptores de TrasplantesRESUMEN
BACKGROUND: How do we decide which topics should be prioritized for research? The need for a robust process for prioritization by key stakeholders, and not just the researchers themselves, was recognized by the James Lind Alliance. A methodology has been established to enable clinicians, patients, and caregivers to identify and prioritize important uncertainties for research in different health areas. This methodology was applied to transfusion medicine to help focus the research agenda in this field. STUDY DESIGN AND METHODS: A steering group was formed in 2015 comprising four donor/patient/caregiver representatives and six clinicians and was supported by an information scientist and James Lind Alliance representatives. The scope of the priority-setting partnership included uncertainties from blood donation through transfusion but excluded laboratory aspects of transfusion and specialist blood products. Three methods were used to identify the top 10 research priorities: two widely disseminated online surveys, a search of existing literature, and a final prioritization workshop. RESULTS: There were 408 respondents to the first survey contributing 817 questions, which were refined into 54 indicative questions that had not already been answered by previous research. Respondents to a second survey were asked to select the three questions they believed to be the most important. The 30 most popular research questions were then brought to a workshop of donors, patients, and caregivers to produce the "top 10." CONCLUSION: This prioritized list should be of considerable value to both researchers and funding bodies when considering what research should be conducted in transfusion medicine.
Asunto(s)
Investigación Biomédica , Donantes de Sangre , Transfusión Sanguínea , Personal de Salud , Encuestas y Cuestionarios , Incertidumbre , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Recipients of allogeneic haematopoietic stem cell transplants (HSCT) can develop acute or chronic, or both forms of graft-versus-host disease (a/cGvHD), whereby immune cells of the donor attack host tissues. Steroids are the primary treatment, but patients with severe, refractory disease have limited options and a poor prognosis. Mesenchymal stromal cells (MSCs) exhibit immunosuppressive properties and are being tested in clinical trials for their safety and efficacy in treating many immune-mediated disorders. GvHD is one of the first areas in which MSCs were clinically applied, and it is important that the accumulating evidence is systematically reviewed to assess whether their use is favoured. OBJECTIVES: To determine the evidence for the safety and efficacy of MSCs for treating immune-mediated inflammation post-transplantation of haematopoietic stem cells. SEARCH METHODS: We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library 2018, Issue 12), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (from 1990) and ongoing trial databases to 6 December 2018. No constraints were placed on language or publication status. SELECTION CRITERIA: We included RCTs of participants with a haematological condition who have undergone an HSCT as treatment for their condition and were randomised to MSCs (intervention arm) or no MSCs (comparator arm), to prevent or treat GvHD. We also included RCTs which compared different doses of MSCs or MSCs of different sources (e.g. bone marrow versus cord). We included MSCs co-transplanted with haematopoietic stem cells as well as MSCs administered post-transplantation of haematopoietic stem cells. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane.We employed a random-effects model for all analyses due to expected clinical heterogeneity arising from differences in participant characteristics and interventions. MAIN RESULTS: We identified 12 completed RCTs (879 participants), and 13 ongoing trials (1532 enrolled participants planned). Of 12 completed trials, 10 compared MSCs versus no MSCs and two compared different doses of MSCs. One trial was in people with thalassaemia major, the remaining trials were for haematological malignancies. Seven trials administered MSCs to prevent GvHD, whereas five trials gave MSCs to treat GvHD.In the comparison of MSCs with no MSCs, cells were administered at a dose of between 105 and 107 cells/kg in either a single dose (six trials) or in multiple doses (four trials) over a period of three days to four months. The dose-comparison trials compared 2 x 106 cells/kg with 8 x 106 cells/kg in two infusions, or 1 x 106 cells/kg with 3 x 106 cells/kg in a single infusion.The median duration of follow-up in seven trials which administered MSCs prophylactically ranged from 10 to 60 months. In three trials of MSCs as treatment for aGvHD, participants were followed up for 90 or 100 days. In two trials of MSCs as treatment for cGvHD, the mean duration of follow-up was 13.4 months (MSC group) and 23.6 months (control group) in one trial, and 56 weeks in the second trial. Five trials included adults only, six trials included adults and children, and one trial included children only. In eight trials which reported the gender distribution, the percentage of females ranged from 20% to 59% (median 35.8%).The overall quality of the included studies was low: randomisation methods were poorly reported and several of the included studies were subject to a high risk of performance bias and reporting bias. One trial which started in 2008 has not been published and the progress of this trial in unknown, leading to potential publication bias. The quality of evidence was therefore low or very low for all outcomes due to a high risk of bias as well as imprecision due to the low number of overall participants, and in some cases evidence based on a single study. We found that MSCs may make little or no difference in the risk of all-cause mortality in either prophylactic trials (HR 0.85, 95% CI 0.50 to 1.42; participants = 301; studies = 5; I2 = 34% ; low-quality evidence) or therapeutic trials (HR 1.12, 95% CI 0.80 to 1.56; participants = 244; studies = 1; very low-quality evidence), and no difference in the risk of relapse of malignant disease (prophylactic trials: RR 1.08, 95% CI 0.73 to 1.59; participants = 323; studies = 6; I2 = 0%; low-quality evidence) compared with no MSCs. MSCs were well-tolerated, no infusion-related toxicity or ectopic tissue formation was reported. No study reported health-related quality of life. In prophylactic trials, MSCs may reduce the risk of chronic GvHD (RR 0.66, 95% CI 0.49 to 0.89; participants = 283; studies = 6; I2 = 0%; low-quality evidence). This means that only 310 (95% CI 230 to 418) in every 1000 patients in the MSC arm are expected to develop chronic GvHD compared to 469 in the control arm. However, MSCs may make little or no difference to the risk of aGvHD (RR 0.86, 95% CI 0.63 to 1.17; participants = 247; studies = 6; I2 = 0%; low-quality evidence). In GvHD therapeutic trials, we are very uncertain whether MSCs improve complete response of either aGvHD (RR 1.16, 95% CI 0.79 to 1.70, participants = 260, studies = 1; very low-quality evidence) or cGvHD (RR 5.00, 95%CI 0.75 to 33.21, participants = 40, studies = 1; very low-quality evidence).In two trials which compared different doses of MSCs, we found no evidence of any differences in outcomes. AUTHORS' CONCLUSIONS: MSCs are an area of intense research activity, and an increasing number of trials have been undertaken or are planned. Despite a number of reports of positive outcomes from the use of MSCs for treating acute GvHD, the evidence to date from RCTs has not supported the conclusion that they are an effective therapy. There is low-quality evidence that MSCs may reduce the risk of cGvHD. New trial evidence will be incorporated into future updates of this review, which may better establish a role for MSCs in the prevention or treatment of GvHD.
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Enfermedad Injerto contra Huésped/terapia , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Mesenquimatosas , Talasemia beta/terapia , Enfermedad Aguda , Enfermedad Crónica , Enfermedad Injerto contra Huésped/epidemiología , Neoplasias Hematológicas/mortalidad , Humanos , Incidencia , Trasplante de Células Madre Mesenquimatosas/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , RecurrenciaRESUMEN
BACKGROUND: In the absence of bleeding, plasma is commonly transfused to people prophylactically to prevent bleeding. In this context, it is transfused before operative or invasive procedures (such as liver biopsy or chest drainage tube insertion) in those considered at increased risk of bleeding, typically defined by abnormalities of laboratory tests of coagulation. As plasma contains procoagulant factors, plasma transfusion may reduce perioperative bleeding risk. This outcome has clinical importance given that perioperative bleeding and blood transfusion have been associated with increased morbidity and mortality. Plasma is expensive, and some countries have experienced issues with blood product shortages, donor pool reliability, and incomplete screening for transmissible infections. Thus, although the benefit of prophylactic plasma transfusion has not been well established, plasma transfusion does carry potentially life-threatening risks. OBJECTIVES: To determine the clinical effectiveness and safety of prophylactic plasma transfusion for people with coagulation test abnormalities (in the absence of inherited bleeding disorders or use of anticoagulant medication) requiring non-cardiac surgery or invasive procedures. SEARCH METHODS: We searched for randomised controlled trials (RCTs), without language or publication status restrictions in: Cochrane Central Register of Controlled Trials (CENTRAL; 2017 Issue 7); Ovid MEDLINE (from 1946); Ovid Embase (from 1974); Cumulative Index to Nursing and Allied Health Literature (CINAHL; EBSCOHost) (from 1937); PubMed (e-publications and in-process citations ahead of print only); Transfusion Evidence Library (from 1950); Latin American Caribbean Health Sciences Literature (LILACS) (from 1982); Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) (Thomson Reuters, from 1990); ClinicalTrials.gov; and World Health Organization (WHO) International Clinical Trials Registry Search Platform (ICTRP) to 28 January 2019. SELECTION CRITERIA: We included RCTs comparing: prophylactic plasma transfusion to placebo, intravenous fluid, or no intervention; prophylactic plasma transfusion to alternative pro-haemostatic agents; or different haemostatic thresholds for prophylactic plasma transfusion. We included participants of any age, and we excluded trials incorporating individuals with previous active bleeding, with inherited bleeding disorders, or taking anticoagulant medication before enrolment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included five trials in this review, all were conducted in high-income countries. Three additional trials are ongoing. One trial compared fresh frozen plasma (FFP) transfusion with no transfusion given. One trial compared FFP or platelet transfusion or both with neither FFP nor platelet transfusion given. One trial compared FFP transfusion with administration of alternative pro-haemostatic agents (factors II, IX, and X followed by VII). One trial compared the use of different transfusion triggers using the international normalised ratio measurement. One trial compared the use of a thromboelastographic-guided transfusion trigger using standard laboratory measurements of coagulation. Four trials enrolled only adults, whereas the fifth trial did not specify participant age. Four trials included only minor procedures that could be performed by the bedside. Only one trial included some participants undergoing major surgical operations. Two trials included only participants in intensive care. Two trials included only participants with liver disease. Three trials did not recruit sufficient participants to meet their pre-calculated sample size. Overall, the quality of evidence was low to very low across different outcomes according to GRADE methodology, due to risk of bias, indirectness, and imprecision. One trial was stopped after recruiting two participants, therefore this review's findings are based on the remaining four trials (234 participants). When plasma transfusion was compared with no transfusion given, we are very uncertain whether there was a difference in 30-day mortality (1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; risk ratio (RR) 0.38, 95% confidence interval (CI) 0.13 to 1.10; very low-quality evidence). We are very uncertain whether there was a difference in major bleeding within 24 hours (1 trial comparing FFP transfusion vs no transfusion, 76 participants; RR 0.33, 95% CI 0.01 to 7.93; very low-quality evidence; 1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; RR 1.59, 95% CI 0.28 to 8.93; very low-quality evidence). We are very uncertain whether there was a difference in the number of blood product transfusions per person (1 trial, 76 participants; study authors reported no difference; very low-quality evidence) or in the number of people requiring transfusion (1 trial comparing FFP or platelet transfusion or both with neither FFP nor platelet transfusion, 72 participants; study authors reported no blood transfusion given; very low-quality evidence) or in the risk of transfusion-related adverse events (acute lung injury) (1 trial, 76 participants; study authors reported no difference; very low-quality evidence). When plasma transfusion was compared with other pro-haemostatic agents, we are very uncertain whether there was a difference in major bleeding (1 trial; 21 participants; no events; very low-quality evidence) or in transfusion-related adverse events (febrile or allergic reactions) (1 trial, 21 participants; RR 9.82, 95% CI 0.59 to 162.24; very low-quality evidence). When different triggers for FFP transfusion were compared, the number of people requiring transfusion may have been reduced (for overall blood products) when a thromboelastographic-guided transfusion trigger was compared with standard laboratory tests (1 trial, 60 participants; RR 0.18, 95% CI 0.08 to 0.39; low-quality evidence). We are very uncertain whether there was a difference in major bleeding (1 trial, 60 participants; RR 0.33, 95% CI 0.01 to 7.87; very low-quality evidence) or in transfusion-related adverse events (allergic reactions) (1 trial; 60 participants; RR 0.33, 95% CI 0.01 to 7.87; very low-quality evidence). Only one trial reported 30-day mortality. No trials reported procedure-related harmful events (excluding bleeding) or quality of life. AUTHORS' CONCLUSIONS: Review findings show uncertainty for the utility and safety of prophylactic FFP use. This is due to predominantly very low-quality evidence that is available for its use over a range of clinically important outcomes, together with lack of confidence in the wider applicability of study findings, given the paucity or absence of study data in settings such as major body cavity surgery, extensive soft tissue surgery, orthopaedic surgery, or neurosurgery. Therefore, from the limited RCT evidence, we can neither support nor oppose the use of prophylactic FFP in clinical practice.
Asunto(s)
Anticoagulantes/uso terapéutico , Transfusión de Componentes Sanguíneos/métodos , Hemorragia/prevención & control , Procedimientos Quirúrgicos Operativos , Anticoagulantes/efectos adversos , Hemostáticos/uso terapéutico , Humanos , Plasma , Cuidados Preoperatorios , Ensayos Clínicos Controlados Aleatorios como Asunto , TromboelastografíaRESUMEN
BACKGROUND: Some hospital patients may be at risk of or may present with major bleeding. Abnormalities of clotting (coagulation) are often recorded in these people, and the traditional management has been with transfusions of blood components, either to prevent bleeding (prophylactic) or to treat bleeding (therapeutic). There is growing interest in the use of targeted therapies with specific pro-coagulant haemostatic (causing bleeding to stop and to keep blood within a damaged blood vessel) factor concentrates in place of plasma. OBJECTIVES: To assess the effects and safety of pro-coagulant haemostatic factors and factor concentrates in the prevention and treatment of bleeding in people without haemophilia. SEARCH METHODS: We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (2018, issue 3), MEDLINE (from 1948), Embase (from 1974), CINAHL (from 1938), PubMed (publications in process to 18 April 2018), PROSPERO, Transfusion Evidence Library (from 1950), LILACS (from 1980), IndMED (from 1985), KoreaMed (from 1934), Web of Science Conference Proceedings Citation Index (from 1990) and ongoing trial databases to 18 April 2018. SELECTION CRITERIA: We included RCTs that compared intravenous administration of a pro-coagulant haemostatic factor concentrate, either with placebo, current best or standard treatment, or another pro-coagulant haemostatic factor concentrate for prevention or treatment of bleeding. There was no restriction on the types of participants. We excluded studies of desmopressin, tranexamic acid and aminocaproic acid and use of pro-coagulant haemostatic factors for vitamin K over-anticoagulation. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodological procedures. MAIN RESULTS: We identified 31 RCTs with 2392 participants and 22 ongoing trials. There were 13 therapeutic RCTs that randomised 1057 participants (range from 20 to 249 participants) and 18 prophylactic trials that randomised 1335 participants (range 20 to 479 participants). The pro-coagulant haemostatic factor concentrate was fibrinogen in 23 trials, Factor XIII in seven trials and pro-thrombin complex concentrates (PCC) in one trial.Seventeen trials had industrial funding or support, eight studies either did not declare their funding or were unclear about their source of funding and six studies declared non-industrial funding sources.Certainty in the evidence and included study biasOur certainty in the evidence, using GRADE criteria, ranged from very low to high across all outcomes. We assessed most outcomes as being of low certainty. Risks of bias were a concern in many of the RCTs; randomisation methodology was unclear in 15 RCTs, with allocation concealment unclear in 14 RCTs and at high risk of bias in five RCTs. The blinding status of outcome assessors was unclear in 13 RCTs and at high risk of bias in five RCTs, although most outcomes in these trials were objective and not prone to observer bias. Study personnel were often unblinded or insufficient information was available to assess their level of blinding (five RCTs were at unclear risk and seven at high risk of bias).Primary outcomesAll-cause mortality was reported by 21 RCTs, arterial thromboembolic events by 22 RCTs, and venous thromboembolic events by 21 RCTs.Fibrinogen concentrate: prophylactic trials with inactive comparator (nine RCTs)The trials had heterogeneous clinical settings and outcome time points, so we did not pool the data. Compared to placebo, there was no evidence that prophylactic fibrinogen concentrate reduced all-cause mortality (4 RCTs; 248 participants). Compared to inactive comparators there was low- to moderate-quality evidence that prophylactic fibrinogen concentrate did not increase the risk of arterial or venous thromboembolic complications (7 RCTs; 398 participants).Fibrinogen concentrate: prophylactic trials with active comparator (two RCTs)There was no mortality or incidence of thromboembolic events in these two RCTs (with 57 participants).Fibrinogen concentrate: therapeutic trials with inactive comparator (eight RCTs)The trials had heterogeneous surgical settings and outcome time points, so we pooled data for subgroups only. Compared to an inactive comparator, there was no evidence (quality ranging from low to high) that fibrinogen concentrate reduced all-cause mortality in actively bleeding participants (7 RCTs; 724 participants). Compared to inactive comparators there was no evidence that the use of fibrinogen concentrate in active bleeding increased arterial (7 RCTs; 607 participants) or venous (6 RCTs; 562 participants) thromboembolic events.Fibrinogen concentrate: therapeutic trials with active comparator (four RCTs)We did not pool the outcome data, as they were not measured at comparable time points. Compared to other active pro-coagulant agents, there was no evidence (very low to moderate quality) that fibrinogen concentrate reduced all-cause mortality in actively bleeding participants (4 RCTs; 220 participants). There was no evidence that fibrinogen concentrate increased the risk of arterial (3 RCTs; 126 participants) or venous (4 RCTs; 220 participants) thromboembolic events.FactorXIII: Prophylactic trials with inactive comparator (six trials)The trials were heterogeneous in their surgical settings and time points for outcome analysis, so we pooled data for subgroups only. Compared to an inactive comparator, there was no evidence that prophylactic Factor XIII reduced all-cause mortality (5 RCTs; 414 participants). There was no evidence (very low to low quality) of a difference in the arterial or venous event rate between Factor XIII and inactive comparators (4 trials; 354 participants).FactorXIII: therapeutic trials with inactive comparator (one trial)There was no mortality or incidence of thromboembolic events in this trial.Prothrombin complex concentrate (PCC): prophylactic trials with inactive comparator (one trial)There was no evidence (moderate quality) that PCC reduced all-cause mortality (1 trial; 78 participants). No thromboembolic complications were reported in this trial. AUTHORS' CONCLUSIONS: The paucity of good-quality comparable evidence precludes the drawing of conclusions for clinical practice. Further research is required to determine the risk-to-benefit ratio of these interventions. The sample sizes of future RCTs would need to be greatly increased to detect a reduction in mortality or thromboembolic events between treatment arms. To improve consistency in outcome reporting, the development of core outcome sets is essential and may help address a number of the limitations identified in this review.
Asunto(s)
Factores de Coagulación Sanguínea/uso terapéutico , Factor XIII/uso terapéutico , Fibrinógeno/uso terapéutico , Hemorragia/terapia , Hemostáticos/uso terapéutico , Causas de Muerte , Hemorragia/mortalidad , Hemorragia/prevención & control , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Red blood cell (RBC) transfusion is a common treatment for anaemia in many conditions. The safety and efficacy of transfusing RBC units that have been stored for different durations before a transfusion is a current concern. The duration of storage for a RBC unit can be up to 42 days. If evidence from randomised controlled trials (RCT) were to indicate that clinical outcomes are affected by storage duration, the implications for inventory management and clinical practice would be significant. OBJECTIVES: To assess the effects of using red blood cells (RBCs) stored for a shorter versus a longer duration, or versus RBCs stored for standard practice duration, in people requiring a RBC transfusion. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PubMed (for epublications), LILACS, Transfusion Evidence Library, Web of Science CPCI-S and four international clinical trial registries on 20 November 2017. SELECTION CRITERIA: We included RCTs that compared transfusion of RBCs of shorter versus longer storage duration, or versus standard practice storage duration. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. MAIN RESULTS: We included 22 trials (42,835 participants) in this review.The GRADE quality of evidence ranged from very low to moderate for our primary outcome of in-hospital and short-term mortality reported at different time points.Transfusion of RBCs of shorter versus longer storage duration Eleven trials (2249 participants) compared transfusion of RBCs of shorter versus longer storage duration. Two trials enrolled low birth weight neonates, two enrolled children with severe anaemia secondary to malaria or sickle cell disease, and eight enrolled adults across a range of clinical settings (intensive care, cardiac surgery, major elective surgery, hospitalised in-patients, haematology outpatients). We judged only two trials to be at low risk of bias across all domains; most trials had an unclear risk for multiple domains.Transfusion of RBCs of shorter versus longer storage duration probably leads to little or no difference in mortality at seven-day follow-up (risk ratio (RR) 1.42, 95% confidence interval (CI) 0.66 to 3.06; 1 trial, 3098 participants; moderate quality evidence) or 30-day follow-up (RR 0.85, 95%CI 0.50 to 1.45; 2 trials, 1121 participants; moderate quality evidence) in adults undergoing major elective cardiac or non-cardiac surgery.For neonates, no studies reported on the primary outcome of in-hospital or short-term mortality. At 40 weeks gestational age, the effect of RBCs of shorter versus longer storage duration on the risk of death was uncertain, as the quality of evidence is very low (RR 0.90, 95% CI 0.41 to 1.85; 1 trial, 52 participants).The effect of RBCs of shorter versus longer storage duration on the risk of death in children with severe anaemia was also uncertain within 24 hours of transfusion (RR 1.50, 95% CI 0.43 to 5.25; 2 trials, 364 participants; very low quality evidence), or at 30-day follow-up (RR 1.40, 95% CI 0.45 to 4.31; 1 trial, 290 participants; low quality evidence).Only one trial, in children with severe anaemia (290 participants), reported adverse transfusion reactions. Only one child in each arm experienced an adverse reaction within 24 hours of transfusion.Transfusion of RBCs of shorter versus standard practice storage duration Eleven trials (40,588 participants) compared transfusion of RBCs of shorter versus standard practice storage duration. Three trials enrolled critically ill term neonates; two of these enrolled very low birth weight neonates. There were no trials in children. Eight trials enrolled critically ill and non-critically ill adults, with most being hospitalised. We judged four trials to be at low risk of bias across all domains with the others having an unclear risk of bias across multiple domains.Transfusion of RBCs of shorter versus standard practice storage duration probably leads to little or no difference in adult in-hospital mortality (RR 1.05, 95% CI 0.97 to 1.14; 4 trials, 25,704 participants; moderate quality evidence), ICU mortality (RR 1.06, 95% CI 0.98 to 1.15; 3 trials, 13,066 participants; moderate quality evidence), or 30-day mortality (RR 1.04, 95% CI 0.96 to 1.13; 4 trials, 7510 participants;moderate quality evidence).Two of the three trials that enrolled neonates reported that there were no adverse transfusion reactions. One trial reported an isolated case of cytomegalovirus infection in participants assigned to the standard practice storage duration group. Two trials in critically ill adults reported data on transfusion reactions: one observed no difference in acute transfusion reactions between arms (RR 0.67, 95% CI 0.19 to 2.36, 2413 participants), but the other observed more febrile nonhaemolytic reactions in the shorter storage duration arm (RR 1.48, 95% CI 1.13 to 1.95, 4919 participants).Trial sequential analysis showed that we may now have sufficient evidence to reject a 5% relative risk increase or decrease of death within 30 days when transfusing RBCs of shorter versus longer storage duration across all patient groups. AUTHORS' CONCLUSIONS: The effect of storage duration on clinically important outcomes has now been investigated in large, high quality RCTs, predominantly in adults. There appears to be no evidence of an effect on mortality that is related to length of storage of transfused RBCs. However, the quality of evidence in neonates and children is low. The current practice in blood banks of using the oldest available RBCs can be continued safely. Additional RCTs are not required, but research using alternative study designs, should focus on particular subgroups (e.g. those requiring multiple RBC units) and on factors affecting RBC quality.
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Anemia/terapia , Conservación de la Sangre , Transfusión de Eritrocitos , Eritrocitos , Adulto , Anemia/etiología , Anemia/mortalidad , Anemia de Células Falciformes/complicaciones , Conservación de la Sangre/efectos adversos , Conservación de la Sangre/mortalidad , Seguridad de la Sangre , Niño , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/mortalidad , Guías como Asunto , Mortalidad Hospitalaria , Humanos , Recién Nacido , Recién Nacido de muy Bajo Peso , Malaria/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Tamaño de la Muestra , Factores de TiempoRESUMEN
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the clinical effectiveness and safety of prophylactic plasma transfusion for people with confirmed or presumed coagulopathy requiring non-cardiac surgery.
RESUMEN
PURPOSE OF REVIEW: Red blood cell transfusion is a common treatment for anaemia worldwide, but concerns continue to be raised about adverse effects of cellular blood components, which are biological products. One hypothesis for the adverse effects associated with blood transfusion is the harmful effects of storage on red cells that have been demonstrated in laboratory and animal studies. Over the past few years, a number of more significant randomized controlled trials comparing 'fresh' versus 'older' blood have been published in an attempt to address the clinical consequences of storage age, with two further large trials ongoing. RECENT FINDINGS: These recent trials enrolled approximately 4000 participants across a variety of populations - cardiac surgical, critically ill, paediatric and acute hospitalized in-patients. All trials achieved statistically significant separation of red cell storage duration between both groups. The results of all these trials have found no clinical benefit to using fresher red cells when compared with older or standard-issue red cells. However, certain subgroups of patients either receiving red cells stored at more extreme ages of storage or those with additional risks for impaired microcirculations (critically ill elderly, severe sepsis and major haemorrhage) were either underrepresented or not included in these trials. SUMMARY: At present, on the basis of recent trials, there is no indication for blood transfusion services to implement preferential utilization of fresher red cell units.
Asunto(s)
Conservación de la Sangre , Transfusión de Eritrocitos , Manejo de Especímenes , Ensayos Clínicos como Asunto , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/métodos , Eritrocitos/fisiología , Humanos , Evaluación del Resultado de la Atención al Paciente , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013. OBJECTIVES: To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. SEARCH METHODS: We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016. SELECTION CRITERIA: We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration's 'Risk of bias' tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data. MAIN RESULTS: We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA.Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology.Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity.We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) -0.37 to 3.77: consolidation; 18 participants; MD -1.50 bleeding events, 95% CI -3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies.Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence).All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD -5.60 platelet units, 95% CI -9.02 to -2.18: induction; 38 participants, MD -1.00 platelet units, 95% CI -9.11 to 7.11; very low-quality evidence).Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence).None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL). AUTHORS' CONCLUSIONS: Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020.
Asunto(s)
Ácido Aminocaproico/uso terapéutico , Antifibrinolíticos/uso terapéutico , Enfermedades Hematológicas/complicaciones , Hemorragia/prevención & control , Ácido Tranexámico/uso terapéutico , Transfusión de Eritrocitos/estadística & datos numéricos , Enfermedades Hematológicas/tratamiento farmacológico , Hemorragia/etiología , Humanos , Lisina/análogos & derivados , Transfusión de Plaquetas/efectos adversos , Trombocitopenia/etiología , Trombocitopenia/terapia , TromboemboliaRESUMEN
BACKGROUND: Red blood cell transfusion is a common treatment for anaemia in many clinical conditions. One current concern is uncertainty as to the clinical consequences (notably efficacy and safety) of transfusing red blood cell units that have been stored for different durations of time before a transfusion. If evidence from randomised controlled trials were to indicate that clinical outcomes are affected by storage age, the implications for inventory management and clinical practice would be significant. OBJECTIVES: To assess the effects of using fresher versus older red blood cells in people requiring a red blood cell transfusion. SEARCH METHODS: We ran the search on 29th September 2014. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO), PubMed (for e-publications), three other databases and trial registers. SELECTION CRITERIA: We included randomised controlled trials comparing fresher red blood cell transfusion versus active transfusion of older red blood cells, and comparing fresher red blood cell transfusion versus current standard practice. All definitions of 'fresher' and 'older'/'standard practice' red blood cells were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted from the trial report data on adverse red blood cell transfusion reactions, when reported. MAIN RESULTS: We included 16 trials (1864 participants) in the review. Eight trials (279 participants) compared transfusion of fresher red blood cells versus transfusion of older stored red blood cells ('fresher' vs 'older'). Eight trials (1585 participants) compared the transfusion of fresher red blood cells versus current standard practice ('fresher' vs 'standard practice'). Five trials enrolled neonates, one trial enrolled children and 12 trials enrolled adults. Overall sample sizes were small: only two trials randomly assigned more than 100 participants.We performed no meta-analyses for a variety of reasons: no uniform definition of 'fresher' or 'older' red blood cell storage; overlap in the distribution of the age of red blood cells; and heterogeneity in measurements and reporting of outcomes of interest to this review. We tabulated and reported results by individual trial. Overall risk of bias was low or unclear, with four incidences of high risk of bias: in allocation concealment (three trials) and in incomplete outcome data (one trial).No trial measured all of the outcomes of interest in this review. Four trials comparing 'fresher' with 'older' red blood cells reported the primary outcome: mortality within seven days (one study; 74 participants) and at 30 days (three trials; 62 participants). Six trials comparing 'fresher' with 'standard practice' red blood cells reported the primary outcome: mortality within seven days (three studies; 159 participants) and at 30 days (three trials; 1018 participants). All 10 trials reported no clear differences in mortality at either time point between intervention arms.Three trials comparing 'fresher' with 'standard practice' red blood cells reported red blood cell transfusion-associated adverse events. No adverse reactions were reported in two trials, and one incidence of cytomegalovirus (CMV) infection was described in the 'standard practice' arm in one trial.Overall the trials reported no clear difference between either of the intervention comparisons in long-term mortality (three trials; 478 participants); clinically accepted measures of multiple organ dysfunction (two trials: 399 participants); incidence of in-hospital infection (two trials; 429 participants); duration of mechanical ventilation (three trials: 95 participants); and number of participants requiring respiratory organ support (five trials; 528 participants) or renal support (one trial; 57 participants). The outcome 'physiological markers of oxygen consumption or alterations in microcirculation' was reported by 11 studies, but the measures used were highly varied, and no formal statistical analysis was undertaken. AUTHORS' CONCLUSIONS: Several factors precluded firm conclusions about the clinical outcomes of transfusing red blood cell units that have been stored for different periods of time before transfusion, including differences in clinical population and setting, diversity in the interventions used, methodological limitations and differences in how outcomes were measured and reported.No clear differences in the primary outcome - death - were noted between 'fresher' and 'older' or 'standard practice' red blood cells in trials that reported this outcome. Findings of a large number of ongoing trials will be incorporated into this review when they are published.Updates of this review will explore the degree of overlap in trials between 'fresher', 'older' and 'standard practice' storage ages of red blood cells and will consider whether the size of any observed effects is dependent on recipient factors such as clinical background, patient age or clinical presentation.
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Conservación de la Sangre , Transfusión de Eritrocitos , Adulto , Conservación de la Sangre/efectos adversos , Conservación de la Sangre/mortalidad , Niño , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/mortalidad , Guías como Asunto , Humanos , Recién Nacido , Recién Nacido de muy Bajo Peso , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de TiempoRESUMEN
BACKGROUND: The incidence of hip fracture is increasing and it is more common with increasing age. Surgery is used for almost all hip fractures. Blood loss occurs as a consequence of both the fracture and the surgery and thus red blood cell transfusion is frequently used. However, red blood cell transfusion is not without risks. Therefore, it is important to identify the evidence for the effective and safe use of red blood cell transfusion in people with hip fracture. OBJECTIVES: To assess the effects (benefits and harms) of red blood cell transfusion in people undergoing surgery for hip fracture. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (31 October 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014, Issue 10), MEDLINE (January 1946 to 20 November 2014), EMBASE (January 1974 to 20 November 2014), CINAHL (January 1982 to 20 November 2014), British Nursing Index Database (January 1992 to 20 November 2014), the Systematic Review Initiative's Transfusion Evidence Library, PubMed for e-publications, various other databases and ongoing trial registers. SELECTION CRITERIA: Randomised controlled trials comparing red blood cell transfusion versus no transfusion or an alternative to transfusion, different transfusion protocols or different transfusion thresholds in people undergoing surgery for hip fracture. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed each study's risk of bias and extracted data using a study-specific form. We pooled data where there was homogeneity in the trial comparisons and the timing of outcome measurement. We used GRADE criteria to assess the quality (low, moderate or high) of the evidence for each outcome. MAIN RESULTS: We included six trials (2722 participants): all compared two thresholds for red blood cell transfusion: a 'liberal' strategy to maintain a haemoglobin concentration of usually 10 g/dL versus a more 'restrictive' strategy based on symptoms of anaemia or a lower haemoglobin concentration, usually 8 g/dL. The exact nature of the transfusion interventions, types of surgery and participants varied between trials. The mean age of participants ranged from 81 to 87 years and approximately 24% of participants were men. The largest trial enrolled 2016 participants, over 60% of whom had a history of cardiovascular disease. The percentage of participants receiving a red blood cell transfusion ranged from 74% to 100% in the liberal transfusion threshold group and from 11% to 45% in the restrictive transfusion threshold group. There were no results available for the smallest trial (18 participants). All studies were at some risk of bias, in particular performance bias relating to the absence of blinding of personnel. We judged the evidence for all outcomes, except myocardial infarction, was low quality reflecting risk of bias primarily from imbalances in protocol violations in the largest trial and imprecision, often because of insufficient events. Thus, further research is likely to have an important impact on these results.There was no evidence of a difference between a liberal versus restricted threshold transfusion in mortality, at 30 days post hip fracture surgery (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.67 to 1.26; five trials; 2683 participants; low quality evidence) or at 60 days post surgery (RR 1.08, 95% CI 0.80 to 1.44; three trials; 2283 participants; low quality evidence). Assuming an illustrative baseline risk of 50 deaths per 1000 participants in the restricted threshold group at 30 days, these data equate to four fewer (95% CI 17 fewer to 14 more) deaths per 1000 in the liberal threshold group at 30 days.There was no evidence of a difference between a liberal versus restricted threshold transfusion in functional recovery at 60 days, assessed in terms of the inability to walk 10 feet (3 m) without human assistance (RR 1.00, 95% CI 0.87 to 1.15; two trials; 2083 participants; low quality evidence).There was low quality evidence of no difference between the transfusion thresholds in postoperative morbidity for the following complications: thromboembolism (RR 1.15 favouring a restrictive threshold, 95% CI 0.56 to 2.37; four trials; 2416 participants), stroke (RR 2.40 favouring a restrictive threshold, 95% CI 0.85 to 6.79; four trials; 2416 participants), wound infection (RR 1.61 favouring a restrictive threshold, 95% CI 0.77 to 3.35; three trials; 2332 participants), respiratory infection (pneumonia) (RR 1.35 favouring a restrictive threshold, 95% CI 0.95 to 1.92; four trials; 2416 participants) and new diagnosis of congestive heart failure (RR 0.77 favouring a liberal threshold, 95% CI 0.48 to 1.23; three trials; 2332 participants). There was very low quality evidence of a lower risk of myocardial infarction in the liberal compared with the restrictive transfusion threshold group (RR 0.59, 95% CI 0.36 to 0.96; three trials; 2217 participants). Assuming an illustrative baseline risk of myocardial infarction of 24 per 1000 participants in the restricted threshold group, this result was compatible with between one and 15 fewer myocardial infarctions in the liberal threshold group. AUTHORS' CONCLUSIONS: We found low quality evidence of no difference in mortality, functional recovery or postoperative morbidity between 'liberal' versus 'restrictive' thresholds for red blood cell transfusion in people undergoing surgery for hip fracture. Although further research may change the estimates of effect, the currently available evidence does not support the use of liberal red blood cell transfusion thresholds based on a 10 g/dL haemoglobin trigger in preference to more restrictive transfusion thresholds based on lower haemoglobin levels or symptoms of anaemia in these people. Future research needs to address the effectiveness of red blood cell transfusions at different time points in the surgical pathway, whether pre-operative, peri-operative or postoperative. In particular, such research would need to consider people who are symptomatic or haemodynamically unstable who were excluded from most of these trials.
Asunto(s)
Transfusión de Eritrocitos/métodos , Fracturas de Cadera/cirugía , Anciano de 80 o más Años , Anemia/terapia , Transfusión de Eritrocitos/efectos adversos , Transfusión de Eritrocitos/mortalidad , Hemoglobina A/análisis , Fracturas de Cadera/sangre , Fracturas de Cadera/mortalidad , Humanos , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la FunciónRESUMEN
BACKGROUND: Fresh frozen plasma (FFP) is a blood component containing procoagulant factors, which is sometimes used in cardiovascular surgery with the aim of reducing the risk of bleeding. The purpose of this review is to assess the risk of mortality for patients undergoing cardiovascular surgery who receive FFP. OBJECTIVES: To evaluate the risk to benefit ratio of FFP transfusion in cardiovascular surgery for the treatment of bleeding patients or for prophylaxis against bleeding. SEARCH METHODS: We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2015), MEDLINE (OvidSP, 1946 to 21 April 2015), EMBASE (OvidSP, 1974 to 21 April 2015), PubMed (e-publications only: searched 21 April 2015), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 21 April 2015). We also searched the references of all identified trials and relevant review articles. We did not limit the searches by language or publication status. SELECTION CRITERIA: We included randomised controlled trials in patients undergoing major cardiac or vascular surgery who were allocated to a FFP group or a comparator (no plasma or an active comparator, either clinical plasma (any type) or a plasma-derived blood product). We included participants of any age (neonates, children and adults). We excluded studies of plasmapheresis and plasma exchange. DATA COLLECTION AND ANALYSIS: Two authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two authors assessed risk of bias in the included studies and extracted data independently. We took care to note whether FFP was used therapeutically or prophylactically within each trial. MAIN RESULTS: We included 15 trials, with a total of 755 participants for analysis in the review. Fourteen trials compared prophylactic use of FFP against no FFP. One study compared therapeutic use of two types of plasma. The timing of intervention varied, including FFP transfusion at the time of heparin neutralisation and stopping cardiopulmonary bypass (CPB) (seven trials), with CPB priming (four trials), after anaesthesia induction (one trial) and postoperatively (two trials). Twelve trials excluded patients having emergency surgery and nine excluded patients with coagulopathies.Overall the trials were small, with only four reporting an a priori sample size calculation. No trial was powered to determine changes in mortality as a primary outcome. There was either high risk of bias, or unclear risk, in the majority of trials included in this review.There was no difference in the number of deaths between the intervention arms in the six trials (with 287 patients) reporting mortality (very low quality evidence). There was also no difference in blood loss in the first 24 hours for neonatal/paediatric patients (four trials with 138 patients; low quality evidence): mean difference (MD) -1.46 ml/kg (95% confidence interval (CI) -4.7 to 1.78 ml/kg); or adult patients (one trial with 120 patients): MD -12.00 ml (95% CI -101.16 to 77.16 ml).Transfusion with FFP was inferior to control for preventing patients receiving any red cell transfusion: Peto odds ratio (OR) 2.57 (95% CI 1.30 to 5.08; moderate quality evidence). There was a difference in prothrombin time within two hours of FFP transfusion in eight trials (with 210 patients; moderate quality evidence) favouring the FFP arm: MD -0.71 seconds (95% CI -1.28 to -0.13 seconds). There was no difference in the risk of returning to theatre for reoperation (eight trials with 398 patients; moderate quality evidence): Peto OR 0.81 (95% CI 0.26 to 2.57). Only one included study reported adverse events as an outcome and reported no significant adverse events following FFP transfusion. AUTHORS' CONCLUSIONS: This review has found no evidence to support the prophylactic administration of FFP to patients without coagulopathy undergoing elective cardiac surgery. There was insufficient evidence about treatment of patients with coagulopathies or those who are undergoing emergency surgery. There were no reported adverse events attributable to FFP transfusion, although there was a significant increase in the number of patients requiring red cell transfusion who were randomised to FFP. Variability in outcome reporting between trials precluded meta-analysis for many outcomes across all trials, and there was evidence of a high risk of bias in most of the studies. Further adequately powered studies of FFP, or comparable pro-haemostatic agents, are required to assess whether larger reductions in prothrombin time translate into clinical benefits. Overall the evidence from randomised controlled trials for the safety and efficacy of prophylactic transfusion of FFP for cardiac surgery is insufficient.
Asunto(s)
Procedimientos Quirúrgicos Cardiovasculares/mortalidad , Hemostasis Quirúrgica , Plasma , Adulto , Pérdida de Sangre Quirúrgica/prevención & control , Niño , Procedimientos Quirúrgicos Electivos/mortalidad , Transfusión de Eritrocitos , Humanos , Recién Nacido , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de RiesgoRESUMEN
BACKGROUND: A promising approach to the treatment of chronic ischaemic heart disease (IHD) and heart failure is the use of stem cells. The last decade has seen a plethora of randomised controlled trials (RCTs) developed worldwide which have generated conflicting results. OBJECTIVES: The critical evaluation of clinical evidence on the safety and efficacy of autologous adult bone marrow-derived stem cells (BMSC) as a treatment for chronic ischaemic heart disease (IHD) and heart failure. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013, Issue 3), MEDLINE (from 1950), EMBASE (from 1974), CINAHL (from 1982) and the Transfusion Evidence Library (from 1980), together with ongoing trial databases, for relevant trials up to 31st March 2013. SELECTION CRITERIA: Eligible studies included RCTs comparing autologous adult stem/progenitor cells with no autologous stem/progenitor cells in participants with chronic IHD and heart failure. Co-interventions such as primary angioplasty, surgery or administration of stem cell mobilising agents, were included where administered to treatment and control arms equally. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references for eligibility, assessed trial quality and extracted data. We undertook a quantitative evaluation of data using fixed-effect meta-analyses. We evaluated heterogeneity using the I² statistic; we explored considerable heterogeneity (I² > 75%) using a random-effects model and subgroup analyses. MAIN RESULTS: We include 23 RCTs involving 1255 participants in this review. Risk of bias was generally low, with the majority of studies reporting appropriate methods of randomisation and blinding, Autologous bone marrow stem cell treatment reduced the incidence of mortality (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.14 to 0.53, P = 0.0001, 8 studies, 494 participants, low quality evidence) and rehospitalisation due to heart failure (RR 0.26, 95% CI 0.07 to 0.94, P = 0.04, 2 studies, 198 participants, low quality evidence) in the long term (≥12 months). The treatment had no clear effect on mortality (RR 0.68, 95% CI 0.32 to 1.41, P = 0.30, 21 studies, 1138 participants, low quality evidence) or rehospitalisation due to heart failure (RR 0.36, 95% CI 0.12 to 1.06, P = 0.06, 4 studies, 236 participants, low quality evidence) in the short term (< 12 months), which is compatible with benefit, no difference or harm. The treatment was also associated with a reduction in left ventricular end systolic volume (LVESV) (mean difference (MD) -14.64 ml, 95% CI -20.88 ml to -8.39 ml, P < 0.00001, 3 studies, 153 participants, moderate quality evidence) and stroke volume index (MD 6.52, 95% CI 1.51 to 11.54, P = 0.01, 2 studies, 62 participants, moderate quality evidence), and an improvement in left ventricular ejection fraction (LVEF) (MD 2.62%, 95% CI 0.50% to 4.73%, P = 0.02, 6 studies, 254 participants, moderate quality evidence), all at long-term follow-up. Overall, we observed a reduction in functional class (New York Heart Association (NYHA) class) in favour of BMSC treatment during short-term follow-up (MD -0.63, 95% CI -1.08 to -0.19, P = 0.005, 11 studies, 486 participants, moderate quality evidence) and long-term follow-up (MD -0.91, 95% CI -1.38 to -0.44, P = 0.0002, 4 studies, 196 participants, moderate quality evidence), as well as a difference in Canadian Cardiovascular Society score in favour of BMSC (MD -0.81, 95% CI -1.55 to -0.07, P = 0.03, 8 studies, 379 participants, moderate quality evidence). Of 19 trials in which adverse events were reported, adverse events relating to the BMSC treatment or procedure occurred in only four individuals. No long-term adverse events were reported. Subgroup analyses conducted for outcomes such as LVEF and NYHA class revealed that (i) route of administration, (ii) baseline LVEF, (iii) cell type, and (iv) clinical condition are important factors that may influence treatment effect. AUTHORS' CONCLUSIONS: This systematic review and meta-analysis found moderate quality evidence that BMSC treatment improves LVEF. Unlike in trials where BMSC were administered following acute myocardial infarction (AMI), we found some evidence for a potential beneficial clinical effect in terms of mortality and performance status in the long term (after at least one year) in people who suffer from chronic IHD and heart failure, although the quality of evidence was low.
Asunto(s)
Insuficiencia Cardíaca/cirugía , Isquemia Miocárdica/cirugía , Trasplante de Células Madre/métodos , Células de la Médula Ósea/citología , Enfermedad Crónica , Insuficiencia Cardíaca/mortalidad , Hospitalización/estadística & datos numéricos , Humanos , Isquemia Miocárdica/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Trasplante de Células Madre/efectos adversos , Trasplante de Células Madre/mortalidad , Volumen Sistólico/fisiologíaRESUMEN
BACKGROUND: Congenital heart disease is the most commonly diagnosed neonatal congenital condition. Without surgery, only 30% to 40% of patients affected will survive to 10 years old. Mortality has fallen since the 1990s with 2006 to 2007 figures showing surgical survival at one year of 95%. Patients with congenital heart disease are potentially exposed to red cell transfusion at many points in the surgical pathway. There are a number of risks associated with red cell transfusion that may be translated into increased patient morbidity and mortality. OBJECTIVES: To evaluate the effects of red cell transfusion on mortality and morbidity on patients with congenital heart disease at the time of cardiac surgery. SEARCH METHODS: We searched 11 bibliographic databases and three ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2013), MEDLINE (Ovid, 1950 to 11 June 2013), EMBASE (Ovid, 1980 to 11 June 2013), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (to June 2013). We also searched references of all identified trials, relevant review articles and abstracts from between 2006 and 2010 of the most relevant conferences. We did not limit the searches by language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing red cell transfusion interventions in patients undergoing cardiac surgery for congenital heart disease. We included participants of any age (neonates, paediatrics and adults) and with any type of congenital heart disease (cyanotic or acyanotic). We excluded patients with congenital heart disease undergoing non-cardiac surgery. No co-morbidities were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: We identified 11 trials (862 participants). All trials were in neonatal or paediatric populations. The trials covered only three areas of interest: restrictive versus liberal transfusion triggers (two trials), leukoreduction versus non-leukoreduction (two trials) and standard versus non-standard cardiopulmonary bypass (CPB) prime (seven trials). Owing to the clinical diversity in the participant groups (cyanotic (three trials), acyanotic (four trials) or mixed (four trials)) and the intervention groups, it was not appropriate to pool data in a meta-analysis. No study reported data for all the outcomes of interest to this review. Risk of bias was mixed across the included trials, with only attrition bias being low across all trials. Blinding of study personnel and participants was not always possible, depending on the intervention being used.Five trials (628 participants) reported the primary outcome: 30-day mortality. In three trials (a trial evaluating restrictive and liberal transfusion (125 participants), a trial of cell salvage during CPB (309 participants) and a trial of washed red blood cells during CPB (128 participants)), there was no clear difference in mortality at 30 days between the intervention arms. In two trials comparing standard and non-standard CPB prime, there were no deaths in either randomised group. Long-term mortality was similar between randomised groups in one trial each comparing restrictive and liberal transfusion or standard and non-standard CPB prime.Four trials explored a range of adverse effects following red cell transfusion. Kidney failure was the only adverse event that was significantly different: patients receiving cell salvaged red blood cells during CPB were less likely to have renal failure than patients not exposed to cell salvage (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.09 to 0.79, 1 study, 309 participants). There was insufficient evidence to determine whether there was a difference between transfusion strategies for any other severe adverse events.The duration of mechanical ventilation was measured in seven trials (768 participants). Overall, there was no consistent difference in the duration of mechanical ventilation between the intervention and control arms.The duration of intensive care unit (ICU) stay was measured in six trials (459 participants). There was no clear difference in the duration of ICU stay between the intervention arms in the transfusion trigger and leukoreduction trials. In the standard versus non-standard CPB prime trials, one trial examining the impact of washing transfused bypass prime red blood cells showed no clear difference in duration of ICU stay between the intervention arms, while the trial assessing ultrafiltration of the priming blood showed a shorter duration of ICU stay in the ultrafiltration group. AUTHORS' CONCLUSIONS: There are only a small number of small and heterogeneous trials so there is insufficient evidence to assess the impact of red cell transfusion on patients with congenital heart disease undergoing cardiac surgery accurately. It is possible that the presence or absence of cyanosis impacts on trial outcomes, which would necessitate different clinical management of two groups. Further adequately powered, specific, high-quality trials are warranted to assess this fully.