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Perioperative transfusion and long-term mortality after cardiac surgery: a meta-analysis
Woldendorp K, Manuel L, Srivastava A, Doane M, Bassin L, Marshman D
General thoracic and cardiovascular surgery. 2023
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Editor's Choice
Abstract
OBJECTIVES Cardiac surgical procedures are associated with a high incidence of periprocedural blood loss and blood transfusion. Although both may be associated with a range of postoperative complications there is disagreement on the impact of blood transfusion on long-term mortality. This study aims to provide a comprehensive review of the published outcomes of perioperative blood transfusion, examined as a whole and by index procedure. METHODS A systematic review of perioperative blood transfusion cardiac surgical patients was conducted. Outcomes related to blood transfusion were analysed in a meta-analysis and aggregate survival data were derived to examine long-term survival. RESULTS Thirty-nine studies with 180,074 patients were identified, the majority (61.2%) undergoing coronary artery bypass surgery. Perioperative blood transfusions were noted in 42.2% of patients and was associated with significantly higher early mortality (OR 3.87, p < 0.001). After a median of 6.4 years (range 1-15), mortality remained significantly higher for those who received a perioperative transfusion (OR 2.01, p < 0.001). Pooled hazard ratio for long-term mortality similar for patients who underwent coronary surgery compared to isolated valve surgery. Differences in long-term mortality for all comers remained true when corrected for early mortality and when only including propensity matched studies. CONCLUSIONS Perioperative red blood transfusion appears to be associated with a significant reduction in long-term survival for patients after cardiac surgery. Strategies such as preoperative optimisation, intraoperative blood conservation, judicious use of postoperative transfusions, and professional development into minimally invasive techniques should be utilised where appropriate to minimise the need for perioperative transfusions.
PICO Summary
Population
Patients undergoing cardiac surgery (39 studies, n= 180,074).
Intervention
Red blood cell (RBC) transfusion.
Comparison
No RBC transfusion.
Outcome
The meta-analysis identified 180,074 patients with follow-up data ranging from 1 to 15 years. The majority (61.2%) of patients underwent coronary artery bypass surgery. Perioperative blood transfusions were noted in 42.2% of patients and was associated with significantly higher early mortality (OR= 3.87). After a median of 6.4 years (range 1, 15), mortality remained significantly higher for those who received a perioperative transfusion (OR= 2.01). Pooled hazard ratio for long-term mortality was similar for patients who underwent coronary surgery compared to isolated valve surgery. Differences in long-term mortality for all comers remained true when corrected for early mortality and when only including propensity matched studies.
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Transfusion Guidelines in Brain Tumor Surgery: A Systematic Review and Critical Summary of Currently Available Evidence
Rail B, Hicks WH, Oduguwa E, Barrie U, Pernik MN, Montgomery E, Tao J, Kenfack YJ, Mofor P, Adeyemo E, et al
World neurosurgery. 2022
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Editor's Choice
Abstract
OBJECTIVE Red blood cell (RBC) transfusion is commonly indicated in brain tumor surgery due to risk of blood loss. Current transfusion guidelines are based on evidence derived from critically ill patients and may not be optimal for brain tumor surgeries. Our study is the first to synthesize available evidence to suggest RBC transfusion thresholds in brain tumor patients undergoing surgery. METHODS A systematic review was conducted using PubMed, EMBASE, and Google Scholar databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to critically assess RBC transfusion thresholds in adult patients with brain tumors and complications secondary to transfusion following blood loss in the operating room (OR) or the perioperative period. RESULTS Seven (7) articles meeting our search criteria were reviewed. Brain tumor patients who received blood transfusions were older, had greater rates of ASA class 3 or 4, and presented with increased number of comorbidities including diabetes, hypertension, and cardiovascular diseases. In addition, transfused patients had a prolonged surgical time. Transfusions were associated with multiple postoperative major and minor complications, including longer hospital length of stay (LOS), increased return to the OR, and elevated 30-day mortality. Analysis of transfusion thresholds showed that a restrictive hemoglobin (Hb) threshold of 8 g/dL is safe in patients, as evidenced by a reduction in LOS, mortality, and complications (Level C Class IIa). CONCLUSIONS A restrictive Hb threshold of 8 g/dL appears to be safe and minimizes potential complications of transfusion in brain tumor patients. LEVEL OF EVIDENCE Class C Level IIa.
PICO Summary
Population
Brain tumor patients undergoing surgery (7 studies).
Intervention
Systematic review assessing red blood cell transfusion thresholds.
Comparison
Outcome
Patients who received blood transfusions were older, had greater rates of American Society of Anesthesiologists class 3 or 4, and presented with increased number of comorbidities including diabetes, hypertension, and cardiovascular diseases. Transfused patients had a prolonged surgical time. Transfusions were associated with multiple postoperative major and minor complications, including longer hospital length of stay (LOS), increased return to the operating room, and elevated 30-day mortality. Analysis of transfusion thresholds showed that a restrictive haemoglobin (Hb) threshold of 8 g/dL was safe in patients, as evidenced by a reduction in LOS, mortality, and complications.
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Transfusion Guidelines in Adult Spine Surgery: A Systematic Review and Critical Summary of Currently Available Evidence
Barrie U, Youssef CA, Pernik MN, Adeyemo E, Elguindy M, Johnson ZD, Ahmadieh TYE, Akbik OS, Bagley CA, Aoun SG
The spine journal : official journal of the North American Spine Society. 2021
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Editor's Choice
Abstract
BACKGROUND CONTEXT Red blood cell transfusion can be associated with complications in medical and surgical patients. Acute anemia in ambulatory patients undergoing surgery can also impede wound healing and independent self-care. Current transfusion threshold guidelines are still based on evidence derived from critically-ill intensive care unit medical patients and may not apply to spine surgery candidates. PURPOSE We aimed to provide the reader with a synthesis of the best available evidence to recommend transfusion trigger thresholds and guidelines in adult patients undergoing spine surgery. STUDY DESIGN/SETTING This is a systematic review. OUTCOME MEASURES Physiological measure: Blood transfusion thresholds and associated posttransfusion complications (morbidity, mortality, length of stay, infections, etc…) of the published articles. PATIENT SAMPLE Adult spine surgery patients. METHODS A systematic review of the literature using the PubMed, Google Scholar, and Web of Science electronic databases was made according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Focus was set on papers discussing thresholds for blood transfusion in adult surgical spine patients, as well as complications associated with transfusion after acute surgical blood loss in the operating room or postoperative period. Publications discussing pediatric cases, blood type analyses, blood loss prevention strategies and protocols, systematic reviews and letters to the editor were excluded. RESULTS A total of 22 articles fitting our search criteria were reviewed. Patients who received blood transfusion in these studies were older, of female gender, had more severe comorbidities except for smoking, and had prolonged surgical time. Blood transfusion was associated with multiple adverse postoperative complications, including a higher rate of superficial or deep surgical site infections, sepsis, urinary and pulmonary infections, cardiovascular complications, return to the operating room, and increased postoperative length of stay and 30-day readmission. Analysis of transfusion thresholds from these studies showed that a pre-operative hemoglobin (Hb) of > 13 g/dL, and an intraoperative and post-operative Hb nadir above 9 and 8 g/dL, respectively, were associated with better outcomes and fewer wound infections than lower thresholds (Level B Class III). Additionally, it was generally recommended to transfuse autologous blood that was < 28 days old, if possible, with a limit of 2 to 3 units to minimize patient morbidity and mortality. CONCLUSION Blood transfusion thresholds in surgical patients may be specialty-specific and different than those used for critically-ill medical patients. For adult spine surgery patients, red blood cell transfusion should be avoided if Hb numbers remain > 9 and 8 g/dL in the intraoperative and direct post-operative periods, respectively.
PICO Summary
Population
Adult spine surgery patients (22 studies).
Intervention
Systematic review of studies on recommended thresholds for blood transfusion, and its associated complications.
Comparison
Outcome
Patients who received blood transfusion in the studies reviewed were older, female, had more severe comorbidities except for smoking, and had prolonged surgical time. Blood transfusion was associated with multiple adverse postoperative complications, including a higher rate of superficial or deep surgical site infections, sepsis, urinary and pulmonary infections, cardiovascular complications, return to the operating room, and increased postoperative length of stay and 30-day readmission. Analysis of transfusion thresholds showed that a pre-operative haemoglobin (Hb) of > 13 g/dL, and an intraoperative and post-operative Hb nadir above 9 and 8 g/dL, respectively, were associated with better outcomes and fewer wound infections than lower thresholds. Additionally, it was generally recommended to transfuse autologous blood that was < 28 days old, if possible, with a limit of 2 to 3 units to minimize patient morbidity and mortality.
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A Systematic Review and Meta-analysis of Randomized Controlled Trials Comparing Intraoperative Red Blood Cell Transfusion Strategies
Lenet T, Baker L, Park L, Vered M, Zahrai A, Shorr R, Davis A, McIsaac DI, Tinmouth A, Fergusson DA, et al
Annals of surgery. 2021
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Editor's Choice
Abstract
OBJECTIVE The objective of this work was to carry out a meta-analysis of RCTs comparing intraoperative RBC transfusion strategies to determine their impact on postoperative morbidity, mortality, and blood product use. SUMMARY OF BACKGROUND DATA RBC transfusions are common in surgery and associated with widespread variability despite adjustment for casemix. Evidence-based recommendations guiding RBC transfusion in the operative setting are limited. METHODS The search strategy was adapted from a previous Cochrane Review. Electronic databases were searched from January 2016 to February 2021. Included studies from the previous Cochrane Review were considered for eligibility from before 2016. RCTs comparing intraoperative transfusion strategies were considered for inclusion. Co-primary outcomes were 30-day mortality and morbidity. Secondary outcomes included intraoperative and perioperative RBC transfusion. Meta-analysis was carried out using random-effects models. RESULTS Fourteen trials (8641 patients) were included. One cardiac surgery trial accounted for 56% of patients. There was no difference in 30-day mortality [relative risk (RR) 0.96, 95% confidence interval (CI) 0.71-1.29] and pooled postoperative morbidity among the studied outcomes when comparing restrictive and liberal protocols. Two trials reported worse composite outcomes with restrictive triggers. Intraoperative (RR 0.53, 95% CI 0.43-0.64) and perioperative (RR 0.70, 95% CI 0.62-0.79) blood transfusions were significantly lower in the restrictive group compared to the liberal group. CONCLUSIONS Intraoperative restrictive transfusion strategies decreased perioperative transfusions without added postoperative morbidity and mortality in 12/14 trials. Two trials reported worse outcomes. Given trial design and generalizability limitations, uncertainty remains regarding the safety of broad application of restrictive transfusion triggers in the operating room. Trials specifically designed to address intraoperative transfusions are urgently needed.
PICO Summary
Population
Adult patients undergoing surgery (14 studies, n= 8,641).
Intervention
Restrictive blood transfusion strategy.
Comparison
Liberal blood transfusion strategy.
Outcome
There was no difference in 30-day mortality relative risk (RR) 0.96, and pooled postoperative morbidity among the studied outcomes when comparing restrictive and liberal protocols. Two trials reported worse composite outcomes with restrictive triggers. Intraoperative (RR 0.53) and perioperative (RR 0.70) blood transfusions were significantly lower in the restrictive group compared to the liberal group.
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The effect of restrictive versus liberal transfusion strategies on longer-term outcomes after cardiac surgery: a systematic review and meta-analysis with trial sequential analysis
Kashani HH, Lodewyks C, Kavosh MS, Jeyaraman MM, Neilson C, Okoli G, Rabbani R, Abou-Setta AM, Zarychanski R, Grocott HP
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2020
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Editor's Choice
Abstract
PURPOSE Blood transfusions are frequently administered in cardiac surgery. Despite a large number of published studies comparing a "restrictive" strategy with a "liberal" strategy, no clear consensus has emerged to guide blood transfusion practice in cardiac surgery patients. The purpose of this study was to identify, critically appraise, and summarize the evidence on the overall effect of restrictive transfusion strategies compared with liberal transfusion strategies on mortality, other clinical outcomes, and transfusion-related outcomes in adult patients undergoing cardiac surgery. SOURCE We searched MEDLINE (OvidSP), EMBASE (OvidSP) and Cochrane CENTRAL (Wiley) from inception to 1 December 2017 and queried clinical trial registries and conference proceedings for randomized-controlled trials of liberal vs restrictive transfusion strategies in cardiac surgery. PRINCIPAL FINDINGS From 7,908 citations, we included ten trials (9,101 patients) and eight companion publications. Overall, we found no significant difference in mortality between restrictive and liberal transfusion strategies (risk ratio [RR], 1.08; 95% confidence interval [CI], 0.76 to 1.54; I(2) = 33%; seven trials; 8,661 patients). The use of a restrictive transfusion strategy did not appear to adversely impact any of the secondary clinical outcomes. As expected, the proportion of patients who received red blood cells (RBCs) in the restrictive group was significantly lower than in the liberal group (RR, 0.68; 95% CI, 0.64 to 0.73; I(2) = 56%; 5 trials; 8,534 patients). Among transfused patients, a restrictive transfusion strategy was associated with fewer transfused RBC units per patient than a liberal transfusion strategy. CONCLUSIONS In adult patients undergoing cardiac surgery, a restrictive transfusion strategy reduces RBC transfusion without impacting mortality rate or the incidence of other perioperative complications. Nevertheless, further large trials in subgroups of patients, potentially of differing age, are needed to establish firm evidence to guide transfusion in cardiac surgery. TRIAL REGISTRATION PROSPERO (CRD42017071440); registered 20 April, 2018.
PICO Summary
Population
Adult patients undergoing cardiac surgery (10 studies, n= 9101).
Intervention
Restrictive transfusion strategies.
Comparison
Liberal transfusion strategies.
Outcome
No significant difference was found in mortality between restrictive and liberal transfusion strategies (risk ratio [RR], 1.08; I2 (2) = 33%. The proportion of patients who received red blood cells (RBCs) in the restrictive group was significantly lower than in the liberal group (RR, 0.68; I2 (2) = 56%. Among transfused patients, a restrictive transfusion strategy was associated with fewer transfused RBC units per patient than a liberal transfusion strategy.
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A systematic review and meta-analysis of traumatic intracranial hemorrhage in patients taking prehospital antiplatelet therapy: Is there a role for platelet transfusions?
Alvikas J, Myers SP, Wessel CB, Okonkwo DO, Joseph B, Pelaez C, Doberstein C, Guillotte AR, Rosengart MR, Neal MD
The journal of trauma and acute care surgery. 2020
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Editor's Choice
Abstract
BACKGROUND Platelet transfusion has been utilized to reverse platelet dysfunction in patients on pre-injury antiplatelets who have sustained a traumatic intracranial hemorrhage (tICH); however, there is little evidence to substantiate this practice. The objective of this study was to perform a systematic review on the impact of platelet transfusion on survival, hemorrhage progression and need for neurosurgical intervention in patients with tICH on prehospital antiplatelet medication. METHODS Controlled, observational and randomized, prospective and retrospective studies describing tICH, pre-injury antiplatelet use, and platelet transfusion reported in PubMed, Embase, Cochrane Reviews, Cochrane Trials and Cochrane DARE databases between January 1987 and March 2019 were included. Investigations of concomitant anticoagulant use were excluded. Risk of bias was assessed using the Newcastle-Ottawa scale. We calculated pooled estimates of relative effect of platelet transfusion on the risk of death, hemorrhage progression and need for neurosurgical intervention using the methods of Dersimonian-Laird random-effects meta-analysis. Sensitivity analysis established whether study size contributed to heterogeneity. Subgroup analyses determined whether antiplatelet type, additional blood products/reversal agents, or platelet function assays impacted effect size using meta-regression. RESULTS Twelve articles out of 18609 screened references were applicable to our PICOS questions were qualitatively and quantitatively analyzed. We found no association between platelet transfusion and the risk of death in patients with tICH taking prehospital antiplatelets (OR 1.29; 95% CI 0.76-2.18; p=0.346; I=32.5%). There was no significant reduction in hemorrhage progression (OR 0.88; 95% CI 0.34-2.28; p=0.788; I=78.1%). There was no significant reduction in the need for neurosurgical intervention (OR 1.00, 95% CI 0.53-1.90, p=0.996, I=59.1%, p=0.032). CONCLUSIONS Current evidence does not support the use of platelet transfusion in patients with tICH on prehospital antiplatelets highlighting the need for a prospective evaluation of this practice. LEVEL OF EVIDENCE level III, Systematic Reviews and Meta-Analyses.
PICO Summary
Population
Patients with traumatic intracranial hemorrhage (tICH) on prehospital antiplatelet medication, (12 studies).
Intervention
Platelet transfusion to reverse platelet dysfunction.
Comparison
Outcome
No association was found between platelet transfusion and the risk of death in patients with tICH taking prehospital antiplatelets (OR 1.29, I2= 32.5%). There was no significant reduction in hemorrhage progression (OR 0.88, I2= 78.1%). There was no significant reduction in the need for neurosurgical intervention (OR 1.00, I2= 59.1%).
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Association between preoperative blood transfusion and postoperative venous thromboembolism: Review meta-analysis
Wang C, Kou H, Li X, Lan J
Annals of vascular surgery. 2020
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Editor's Choice
Abstract
OBJECTIVES Several studies have shown that preoperative blood transfusion is associated with postoperative venous thromboembolism (VTE). In this study, a meta-analysis was performed to explore the relationship between preoperative blood transfusion and postoperative VTE. METHODS Published articles were identified through a comprehensive review of PUBMED and EMBASE. Data from studies reporting relative risks, odds ratios, or hazard ratios comparing the risk of postoperative VTE among participants who had preoperative blood transfusion versus those without preoperative blood transfusion were analyzed. A random-effect model was used to calculate pooled odds ratios and 95% confident intervals (CI). RESULTS Eight studies, which included 3,504,778 participants, aligned with our inclusion criteria, and were included in the meta-analysis. Pooled analysis showed an association between preoperative blood transfusion and postoperative VTE, with an odds ratio of 2.95 (95%CI, 1.65, 5.30; I(2) = 89.1%). In subgroup analyses, the positive association between preoperative blood transfusion and postoperative VTE were still exist in studies with confounders adjustment. Sensitivity analysis by one-study removed analysis confirmed the robustness of our results. CONCLUSIONS Our study indicated that preoperative blood transfusion was associated with higher odds of postoperative VTE. Further large-scale prospective cohort studies are needed to investigate the causality between preoperative blood transfusion and postoperative VTE.
PICO Summary
Population
Patients undergoing surgery (8 studies, n= 3,504,778).
Intervention
Preoperative blood transfusion.
Comparison
Without preoperative blood transfusion.
Outcome
Pooled analysis showed an association between preoperative blood transfusion and postoperative venous thromboembolism (VTE). In subgroup analyses, the positive association between preoperative blood transfusion and postoperative VTE still existed in studies with confounders adjustment.
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The Effect of Perioperative Intravenous Iron on Hemoglobin in Surgical Patients: A Meta-Analysis
Koo CH, Shin HJ, Cho H, Ryu JH
The Journal of surgical research. 2019;246:42-51
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Editor's Choice
Abstract
BACKGROUND Patient blood management aims to maintain hemoglobin level, minimize blood loss, and avoid unnecessary blood transfusion. Ferric carboxymaltose, an intravenous iron agent, was included as a part of surgical patient blood management strategy. However, it is still controversial that ferric carboxymaltose can reduce transfusion requirements. The purpose of this systematic review and meta-analysis is to evaluate the benefits of perioperative ferric carboxymaltose on the postoperative hematological parameters and transfusion requirements. METHODS Randomized controlled trials evaluating the effects of ferric carboxymaltose were searched through databases: MEDLINE, EMBASE, CENTRAL, CINAHL, Scopus, Web of Science, and KoreaMed. Meta-analysis was performed using random effect models. RESULTS A total of 8 studies (n = 471) were included in the final analysis. Postoperative hemoglobin was higher in the ferric carboxymaltose group than in the control group (mean difference [MD], 0.58 g/dL; 95% confidence interval [CI], 0.36 to 0.80; P < 0.00001). Postoperative serum ferritin and transferrin saturation were also higher in the ferric carboxymaltose group (MD, 373.85 mug/L; 95% CI, 298.13 to 449.56; P < 0.00001; MD, 10.35%; 95% CI, 4.59 to 16.10; P < 0.00001, respectively). However, there were no significant differences in the number of transfused patients, length of hospital stay, and adverse events between groups. Subgroup analysis revealed that adverse events were lower in the ferric carboxymaltose group than the oral iron group. CONCLUSIONS This study supports that ferric carboxymaltose may increase the postoperative hemoglobin level in surgical patients. However, transfusion requirements could not be reduced by ferric carboxymaltose. Optimal dose and time should be further analyzed.
PICO Summary
Population
Surgical patients (n=471, 8 studies).
Intervention
Intravenous perioperative ferric carboxymaltose.
Comparison
Control (placebo or no intervention).
Outcome
Postoperative hemoglobin was higher in the ferric carboxymaltose group than in the control group (mean difference [MD], 0.58 g/dL). Postoperative serum ferritin and transferrin saturation were also higher in the ferric carboxymaltose group (MD, 373.85 mug/L; MD, 10.35%, respectively). However, there were no significant differences in the number of transfused patients, length of hospital stay, and adverse events between groups. Subgroup analysis revealed that adverse events were lower in the ferric carboxymaltose group than the oral iron group.
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Fresh frozen plasma and platelet concentrate storage duration not associated with in hospital mortality risk
Ng MSY, Hay K, Choy J, Middelburg RA, Tung JP, Fraser JF
Vox sanguinis. 2019
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Editor's Choice
Abstract
BACKGROUND AND OBJECTIVES To date, the effects of FFP and PC storage duration on mortality have only been studied in a few studies in limited patient subpopulations. The aim of the current study was to determine whether FFP and PC storage duration is associated with increased in hospital mortality risk across cardiac surgery, acute medicine, ICU and orthopaedic surgery patients. MATERIALS AND METHODS Two-stage individual patient data meta-analyses were performed to determine the effects of FFP and PC storage duration on in hospital mortality. Preset random effects models were used to determine pooled unadjusted and adjusted (adjusted for age, gender and units of product transfused) effect estimates. RESULTS The FFP storage duration analysis included 3625 patients across four studies. No significant association was observed between duration of storage and in hospital mortality in unadjusted analysis, but after adjusting for patient age, gender and units of product a small increased risk of in hospital mortality was observed for each additional month of storage (OR: 1.05, 95% CI: 1.01-1.08). This effect was no longer statistically significant when donor ABO blood group was incorporated into the random effects model on post hoc analyses. A total of 547 patients across five studies were incorporated in the PC storage duration analysis. No association was observed between PC storage duration and odds of in hospital morality (adjusted OR: 0.94, 95% CI: 0.79-1.11). CONCLUSIONS There is insufficient evidence to support shortening FFP or PC shelf life based on in hospital mortality.
PICO Summary
Population
The FFP storage duration analysis included (n=3625) patients across four studies. A total of (n=547) patients across five studies were incorporated in the PC storage duration analysis. Patients receiving fresh frozen plasma (FFP) and platelet concentrate (PC) in cardiac surgery, acute medicine, ICU or orthopaedic surgery.
Intervention
FFP and PC with shorter storage duration.
Comparison
FFP and PC with longer storage duration.
Outcome
No significant association was observed between duration of storage and in hospital mortality in unadjusted analysis, but after adjusting for patient age, gender and units of product a small increased risk of in hospital mortality was observed for each additional month of storage. This effect was no longer statistically significant when donor ABO blood group was incorporated into the random effects model on post hoc analyses. No association was observed between PC storage duration and odds of in hospital mortality.