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Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022
Kietaibl, S., Ahmed, A., Afshari, A., Albaladejo, P., Aldecoa, C., Barauskas, G., De Robertis, E., Faraoni, D., Filipescu, D. C., Fries, D., et al
European Journal of Anaesthesiology. 2023;40(4):226-304
Abstract
BACKGROUND Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.
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Optimizing Safety and Success: The Advantages of Bloodless Cardiac Surgery. A Systematic Review and Meta-Analysis of Outcomes in Jehovah's Witnesses
Gemelli, M., Italiano, E. G., Geatti, V., Addonizio, M., Cao, I., Dimagli, A., Dokollari, A., Tarzia, V., Gallo, M., Ferrari, E., et al
Current problems in cardiology. 2023;:102078
Abstract
OBJECTIVE Transfusions are extremely frequent after cardiac surgery, and they have a considerable economic burden and impact on outcomes. Optimal patient blood management (PBM) could play a fundamental role in reducing the rate of transfusion and Jehovah's Witnesses (JW) represent the ideal surrogate study population. This meta-analysis compares outcomes of JWs and non-JWs' patients undergoing cardiac surgery, assessing the safety of a bloodless cardiac surgery. METHODS A scoping review was conducted using a search strategy for studies assessing outcomes of JW undergoing cardiac surgery. The primary outcome was perioperative mortality, and a random-effects meta-analysis was performed. RESULTS Ten studies were included in our meta-analysis, involving 780 JW patients refusing any type of transfusion ("JW") and 1182 patients accepting transfusion if needed ("non-JW"). 86% of non-JW patients received at least 1 transfusion. There was no significant difference in terms of perioperative mortality (OR 0.91; 95% CI 0.55 - 1.52; p = 0.72). The volume blood loss was significantly less in the JW (p = 0.001), while the rate of reoperation for bleeding was also lower, but not statistically significative, in the JW (p = 0.16). Both pre-operative and post-operative hemoglobin and hematocrit were significantly higher in the JW. CONCLUSIONS Bloodless cardiac surgery is safe and early outcomes are similar between JW and non-JW patients: optimal patient blood management is fundamental in guarantying these results. Further studies are needed to assess if a limitation of transfusion could have a positive long-term impact on outcomes.
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Systematic review highlights high risk of bias of clinical prediction models for blood transfusion in patients undergoing elective surgery
Dhiman P, Ma J, Gibbs VN, Rampotas A, Kamal H, Arshad SS, Kirtley S, Doree C, Murphy MF, Collins GS, et al
Journal of clinical epidemiology. 2023
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Editor's Choice
Abstract
BACKGROUND Blood transfusion can be a lifesaving intervention after perioperative blood loss. Many prediction models have been developed to identify patients most likely to require blood transfusion during elective surgery, but it is unclear whether any are suitable for clinical practice. STUDY DESIGN AND SETTING We conducted a systematic review, searching MEDLINE, Embase, PubMed, The Cochrane Library, Transfusion Evidence Library, Scopus, and Web of Science databases for studies reporting the development or validation of a blood transfusion prediction model in elective surgery patients between 01/01/2000 to 30/06/2021. We extracted study characteristics, discrimination performance (c-statistics) of final models and data which we used to perform risk of bias assessment using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS We reviewed 66 studies (72 developed and 48 externally validated models). Pooled c-statistics of externally validated models ranged from 0.67 to 0.78. Most developed and validated models were at high risk of bias due to handling of predictors, validation methods, and too small sample sizes. CONCLUSION Most blood transfusion prediction models are at high risk of bias and suffer from poor reporting and methodological quality, which must be addressed before they can be safely used in clinical practice.
PICO Summary
Population
Patients undergoing elective surgery (66 studies).
Intervention
Blood transfusion prediction models used perioperatively.
Comparison
Outcome
This systematic review appraised 120 prediction models developed or validated for predicting blood transfusion in elective surgery (72 developed and 48 externally validated models). Pooled c-statistics of externally validated models ranged from 0.67 to 0.78. Most developed and validated models were at high risk of bias due to handling of predictors, validation methods, and too small sample sizes.
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Preoperative fibrinogen level and blood transfusions in liver transplantation: A systematic review
Thibeault, F., Plourde, G., Fellouah, M., Ziegler, D., Carrier, F. M.
Transplantation reviews (Orlando, Fla.). 2023;37(4):100797
Abstract
BACKGROUND Orthotopic liver transplantation (OLT) is a major surgery often associated with significant bleeding. We conducted a systematic review to explore the association between preoperative fibrinogen level and intraoperative blood products transfusion, blood loss and clinical outcomes in patients undergoing OLT. METHODS We included observational studies conducted in patients undergoing an OLT mostly for end-stage liver disease that reported an association between the preoperative fibrinogen level and our outcomes of interest. Our primary outcome was the intraoperative red blood cell (RBC) transfusion requirements. Our secondary outcomes were intraoperative blood loss, intraoperative transfusion of any blood product, postoperative RBC transfusion, postoperative thrombotic or hemorrhagic complications, and mortality. We used a standardized search strategy. We reported our results mostly descriptively but conducted meta-analyses using random-effect models when judged feasible. RESULTS We selected 24 cohort studies reporting at least one of our outcomes. We found that a high preoperative fibrinogen level was associated with fewer intraoperative RBC and other blood products transfusions, and lower blood loss. We also found a lower overall survival in patients with a higher fibrinogen level (pooled hazard ratio [95% CI] of 1.50 [1.23 to 1.84]; 5 studies, n = 1012, I(2) = 48%). Only one study formally explored a fibrinogen level threshold effect. Overall, reporting was heterogeneous, and risk of bias was variable mostly because of uncontrolled confounding. CONCLUSION A higher preoperative fibrinogen level was associated with fewer intraoperative RBC and other blood products transfusions, lower blood loss, and higher mortality. Further studies may help clarify observed associations and inform guidelines.
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Cardiac surgery in Jehovah's Witnesses patients and association with peri-operative outcomes: a systematic review and meta-analysis
Vitolo M, Mei DA, Cimato P, Bonini N, Imberti JF, Cataldo P, Menozzi M, Filippini T, Vinceti M, Boriani G
Current problems in cardiology. 2023;:101789
Abstract
BACKGROUND Strategies for blood conservation, coupled with a careful preoperative assessment, may be applied to Jehovah's Witnesses (JW) patients who are candidates for cardiac surgery interventions. There is a need to assess clinical outcomes and safety of bloodless surgery in JW patients undergoing cardiac surgery. METHODS We performed a systematic review and meta-analysis of studies comparing JW patients with controls undergoing cardiac surgery. The primary endpoint was short-term mortality (in-hospital or 30-day mortality). Peri-procedural myocardial infarction, re-exploration for bleeding, pre-and post-operative Hb levels and cardiopulmonary bypass (CPB) time were also analyzed. RESULTS A total of 10 studies including 2,302 patients were included. The pooled analysis showed no substantial differences in terms of short-term mortality among the two groups (OR 1.13, 95% CI 0.74-1.73, I(2)=0%). There were no differences in peri-operative outcomes among JW patients and controls (OR 0.97, 95% CI 0.39-2.41, I(2)=18% for myocardial infarction; OR 0.80, 95% CI 0.51-1.25, I(2)=0% for re-exploration for bleeding). JW patients had a higher level of pre-operative Hb (Standardized Mean Difference [SMD] 0.32, 95% CI 0.06-0.57) and a trend toward a higher level of post-operative Hb (SMD 0.44, 95% CI -0.01-0.90). A slightly lower CPB time emerged in JWs compared with controls (SMD -0.11, 95% CI -0.30-0.07). CONCLUSIONS JW patients undergoing cardiac surgery, with avoidance of blood transfusions, did not have substantially different peri-operative outcomes compared with controls, with specific reference to mortality, myocardial infarction, and re-exploration for bleeding. Our results support the safety and feasibility of bloodless cardiac surgery, applying patient blood management strategies.
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What is the optimal management of thromboprophylaxis after liver transplantation regarding prevention of bleeding, hepatic artery or portal vein thrombosis? A systematic review of the literature and expert panel recommendations
Kirchner VA, O'Farrell B, Imber C, McCormack L, Northup PG, Song GW, Spiro M, Raptis DA, Durand F
Clinical transplantation. 2022;:e14629
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Abstract
BACKGROUND A key tenet of clinical management of patients post liver transplantation (LT) is the prevention of thrombotic and bleeding complications. This systematic review investigated the optimal management of thromboprophylaxis after LT regarding portal vein thrombosis (PVT) or hepatic artery thrombosis (HAT) and prevention of bleeding. METHODS Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Seven databases were used to conduct extensive literature searches focusing on the use of anticoagulation in LT and its impact on the following outcomes: PVT, HAT, and bleeding. (CRD42021244288) RESULTS Of the 2,478 articles/abstracts screened, 16 studies were included in the final review. All articles were critically appraised by a panel of independent reviewers. There was wide variation regarding the anticoagulation protocols used. Thromboprophylaxis with therapeutic doses of heparin/Vitamin K antagonist combination did not decrease the risk of de novo or the recurrence of PVT but was associated with an increased risk of bleeding in some studies. Only the use of aspirin resulted in a small but significant decrease in the incidence of HAT post-LT, yet it did not increase the risk of bleeding. CONCLUSIONS Based on existing data and expert opinion, thromboprophylaxis at therapeutic or prophylactic dose is not recommended for prevention of de novo PVT following LT in patients not at high risk. Aspirin should be considered as the standard of care following LT to prevent HAT. Thromboprophylaxis should be strongly considered in recipients at risk of HAT and PVT following LT. This article is protected by copyright. All rights reserved.
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Time to surgery and complications in hip fracture patients on novel oral anticoagulants: a systematic review
Cheung, Z. B., Xiao, R., Forsh, D. A.
Archives of Orthopaedic and Trauma Surgery. 2022;142(4):633-640
Abstract
BACKGROUND Early surgery has been consistently demonstrated to reduce complications and mortality in hip fracture patients. There remains no general consensus, however, regarding the optimal time to surgery for hip fracture patients who are on novel oral anticoagulants (NOAC) on admission and its effect on clinical outcomes after surgery. The objective of this review was to assess the effect of preoperative NOAC therapy on time to surgery and postoperative complications in hip fracture patients. METHODS We performed a systematic review of the literature using the PubMed, Embase, and Cochrane Library electronic databases. Relevant articles were identified and included if they: (i) included patients on NOAC therapy on admission who did not undergo reversal; (ii) included a control group of patients not on any anticoagulation; (iii) included time from admission to surgery; and (iv) included one of the following outcomes: blood transfusion, venous thromboembolism (VTE), stroke, readmission, and mortality. RESULTS Nine studies were included with a total of 4,419 patients. There were 414 NOAC patients and 4,005 non-anticoagulated patients. Six of the nine studies found a significant increase in time to surgery for patients on NOAC therapy. Three of the seven studies that reported rates of blood transfusion found a significantly higher incidence of transfusion in patients on NOACs. None of the studies found a significant difference in VTE and stroke. One of the two studies that reported readmissions showed a higher risk of readmission for patients on NOACs. Eight of the nine included studies found no significant difference in postoperative mortality rates between the NOAC and control groups, with the remaining study finding a higher mortality rate only in patients on NOAC therapy who underwent fixation and not those who underwent arthroplasty. CONCLUSIONS These mixed findings suggest that delay to surgery may not be warranted in the urgent surgical setting of patients on NOAC therapy who sustain hip fractures.
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Impact on Mortality and Major Bleeding of Radial Versus Femoral Artery Access for Coronary Angiography or Percutaneous Coronary Intervention: a Meta-analysis of Individual Patient Data from Seven Multicenter Randomized Clinical Trials
Gargiulo G, Giacoppo D, Jolly SS, Cairns J, Le May M, Bernat I, Romagnoli E, Rao SV, van Leeuwen MAH, Mehta SR, et al
Circulation. 2022
Abstract
BACKGROUND In some randomized controlled trials (RCTs), transradial (TRA) compared with transfemoral access (TFA) was associated with lower mortality in coronary artery disease patients undergoing invasive management. We analyzed the effects of TRA versus TFA across multicenter RCTs and whether these associations are modified by patient or operator characteristics. METHODS We performed an individual patient data meta-analysis of multicenter RCTs comparing TRA versus TFA among patients undergoing coronary angiography with or without percutaneous coronary intervention (PCI) (PROSPERO; CRD42018109664). The primary outcome was all-cause mortality and the co-primary outcome was major bleeding at 30 days. The primary analysis was conducted by one-stage mixed-effects models based on the intention-to-treat cohort. The impact of access-site on mortality and major bleeding was further assessed by multivariable analysis. The relationship among access-site, bleeding, and mortality was investigated by natural effect model mediation analysis with multivariable adjustment. RESULTS A total of 21,600 patients (TRA=10,775 vs. TFA=10,825) from 7 RCTs were included. Median age was 63.9 years, 31.9% were female, 95% presented with acute coronary syndrome (ACS), and 75.2% underwent PCI. All-cause mortality (1.6% vs. 2.1%; HR 0.77, 95% CI 0.63-0.95, p=0.012) and major bleeding (1.5% vs. 2.7%; OR 0.55, 95% CI 0.45- 0.67, p<0.001) were lower with TRA. Subgroup analyses for mortality showed consistent results, except for baseline hemoglobin ((pinteraction)=0.033), indicating that the benefit of TRA was substantial in patients with significant anemia, while it was not significant in patients with milder or no baseline anemia. After adjustment, TRA remained associated with 24% and 51% relative risk reduction of all-cause mortality and major bleeding. A mediation analysis showed that the benefit of TRA on mortality was only partially driven by major bleeding prevention, and ancillary mechanisms are required to fully explain the causal association. CONCLUSIONS TRA is associated with lower all-cause mortality and major bleeding at 30 days, compared with TFA. The effect on mortality was driven by patients with anemia. The reduction in major bleeding only partially explains the mortality benefit.
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Point-of-care platelet function testing for guided transfusion in neurosurgical management of intracranial hemorrhage: a systematic review
Xu FWX, Lim NA, Sim MA, Lean LL, Loh NW, Ng KT, Chua VTY, Chew STH, Ti LK
European journal of medical research. 2022;27(1):191
Abstract
Given the rising prevalence of antiplatelet therapy, rapid preoperative identification of patients with bleeding diathesis is necessary for the guidance of blood product administration. This is especially relevant in neurosurgery for intracranial hemorrhage (ICH), where indiscriminate transfusions may lead to further hemorrhagic or thromboembolic injury. Point-of-care (POC) testing of platelet function is a promising solution to this dilemma, as it has been proven effective in cardiac surgery. However, to date, POC platelet function testing in neurosurgery has not been extensively evaluated. This systematic review appraises the use of POC platelet function test (PFT) in emergency neurosurgery in terms of its impact on patient outcomes.A comprehensive search was conducted on four electronic databases (Pubmed, MEDLINE, Embase, and Cochrane) for relevant English language articles from their respective inceptions until 1 June 2022. We included all randomized controlled trials and cohort studies that met the following inclusion criteria: (i) involved adult patients undergoing neurosurgery for ICH; (ii) evaluated platelet function via POC PFT; (iii) reported a change in perioperative blood loss; and/or (iv) reported data on treatment-related adverse events and mortality. Assessment of study quality was conducted using the Newcastle Ottawa Quality Assessment Scale for Cohort Studies and Case-Control Studies, and the JBI Critical Appraisal Checklist for Case Series.The search yielded 2,835 studies, of which seven observational studies comprising 849 patients met the inclusion criteria for this review. Overall, there is evidence that the use of POC PFT to assess bleeding risk reduced bleeding events, thromboembolic adverse outcomes, and the length of hospitalization. However, there is currently insufficient evidence to suggest that using POC PFT improves blood product use, functional outcomes or mortality.
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Viscoelastic versus conventional coagulation tests to reduce blood product transfusion in patients undergoing liver transplantation: A systematic review and meta-analysis
Aceto P, Punzo G, Di Franco V, Teofili L, Gaspari R, Wolfango Avolio A, Del Tedesco F, Posa D, Lai C, Sollazzi L
European journal of anaesthesiology. 2022
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Editor's Choice
Abstract
BACKGROUND Recent literature suggests viscoelastic test (VET)-guided transfusion management could be associated with reduced blood product administration in patients undergoing liver transplantation. OBJECTIVES To assess the effectiveness of coagulation management guided by VETs compared with conventional coagulation tests (CCTs) in reducing blood product transfusion in patients undergoing liver transplantation. DESIGN Systematic review and meta-analysis of randomised (RCTs) and nonrandomised clinical trials performed according to PRISMA guidelines. The protocol was previously published (PROSPERO CRD42021230213). DATA SOURCES The Cochrane Central Library, PubMed/MEDLINE, Embase and the Transfusion Evidence Library were searched up to 30th January 2022. ELIGIBILITY CRITERIA Setting: operating room. Patients: liver transplantation recipients. Intervention: use of VETs versus CCTs. Main outcome measures: the primary outcome was the mean number of transfused units for each blood product including red blood cells (RBCs), fresh frozen plasma (FFP), platelets (PLTs) and cryoprecipitate. Secondary outcomes included mortality rate, intensive care unit (ICU) and hospital length of stay (LOS). RESULTS Seventeen studies (n = 5345 patients), 15 observational and two RCTs, were included in this review. There was a mean difference reduction in RBCs [mean difference: -1.40, 95% confidence interval (95% CI), -1.87 to -0.92; P < 0.001, I2 = 61%) and FFP units (mean difference: -2.98, 95% CI, -4.61 to -1.35; P = < 0.001; I2 = 98%) transfused in the VETs group compared with the CCTs one. A greater amount of cryoprecipitate was administered in the VETs group (mean difference: 2.71, 95% CI, 0.84 to 4.58; P = 0.005; I2 = 91%). There was no significant difference in the mean number of PLT units, mortality, hospital and ICU-LOS. CONCLUSION Our meta-analysis demonstrated that VETs implementation was associated with reduced RBC and FFP consumption in liver transplantation patients without effects on mortality and hospital and ICU-LOS. The certainty of evidence ranged from moderate to very low. Further well conducted RCTs are needed to improve the certainty of evidence.
PICO Summary
Population
Patients undergoing liver transplantation (17 studies, n= 5,345).
Intervention
Coagulation management guided by viscoelastic tests (VETs group).
Comparison
Conventional coagulation tests (CCTs group).
Outcome
There was a mean difference reduction in red blood cells (mean difference: -1.40, 95% confidence interval (95% CI) -1.87 to -0.92, I2 = 61%) and fresh frozen plasma units (mean difference: -2.98, 95% CI -4.61 to -1.35; I2 = 98%) transfused in the VETs group compared with the CCTs group. A greater amount of cryoprecipitate was administered in the VETs group (mean difference: 2.71, 95% CI, 0.84 to 4.58; I2 = 91%). There was no significant difference in the mean number of platelets units, mortality, hospital and intensive care unit (ICU) and hospital length of stay (LOS).