Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.

Despite numerous guidelines on the management of anaemia in surgical patients, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in the postoperative period. A number of experienced researchers and clinicians took part in a two-day expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the postoperative period. These statements include: a diagnostic approach to iron deficiency and anaemia in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up that is easy to implement. Available data allow the fulfilment of the requirements of Pillar 1 of Patient Blood Management. We urge national and international research funding bodies to take note of these recommendations, particularly in terms of funding large-scale prospective, randomised clinical trials that can most effectively address the important clinical questions and this clearly unmet medical need.

Objectives: To determine whether a multidisciplinary, multimodal Patient Blood Management (PBM) program for patients undergoing surgery is effective in reducing perioperative complication rate, and thereby is effective in improving clinical outcome. Background: PBM is a medical concept with the focus on a comprehensive anemia management, to minimize iatrogenic (unnecessary) blood loss, and to harness and optimize patient-specific physiological tolerance of anemia. Methods: A systematic review and meta-analysis was performed. Eligible studies had to address each of the 3 PBM pillars with at least 1 measure per pillar, for example, preoperative anemia management plus cell salvage plus rational transfusion strategy. The study protocol has been registered with PROSPERO (CRD42017079217). Results: Seventeen studies comprising 235,779 surgical patients were included in this meta-analysis (100,886 pre-PBM group and 134,893 PBM group). Implementation of PBM significantly reduced transfusion rates by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.55–0.68, P < 0.00001], 0.43 red blood cell units per patient (mean difference −0.43, 95% CI −0.54 to −0.31, P < 0.00001), hospital length of stay (mean difference −0.45, 95% CI −0.65 to −0.25, P < 0,00001), total number of complications (RR 0.80, 95% CI 0.74–0.88, P <0.00001), and mortality rate (RR 0.89, 95% CI 0.80–0.98, P = 0.02). Conclusions: Overall, a comprehensive PBM program addressing all 3 PBM pillars is associated with reduced transfusion need of red blood cell units, lower complication and mortality rate, and thereby improving clinical outcome. Thus, this first meta-analysis investigating a multimodal approach should motivate all executives and health care providers to support further PBM activities.

IMPORTANCEAlthough current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses.OBJECTIVE To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. DESIGN, SETTING, AND PARTICIPANTSA parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. INTERVENTIONSPatients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. MAIN OUTCOMES AND MEASURESCoprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. RESULTS Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002).CONCLUSIONS AND RELEVANCE Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality.

An International Consensus Conference (ICC) on PBM was held in 2018 to develop evidence‐based clinical and research recommendations for preoperative anaemia, red blood cell (RBC) transfusion thresholds for adults and implementation of PBM programmes. An international scientific committee (SC) defined 17 Population‐Intervention‐Comparison‐Outcome (PICO) questions for the three topics preoperative anaemia, red blood cell (RBC) transfusion thresholds for adults and PBM implementation. Based on these questions, an extensive literature search was conducted in four biomedical databases. The GRADE framework (= grading of recommendations, assessment, development and evaluation) was used to develop a systematic approach to the presentation of evidence summaries and for making clinical recommendations. Three expert panels (EP) consisting of clinicians, scientists, nurses, patient representatives and methodologists were established and used these methods to develop recommendations driven by published evidence. Out of more than 17 500 literature citations, data from 145 studies were incorporated. The expert panel for preoperative anaemia developed 4 clinical and 3 research recommendations. A strong recommendation advices early detection and management of preoperative anaemia before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations have been formulated. Two strong clinical recommendations for RBC transfusion thresholds comprise a haemoglobin concentration of <7 g/dl for critically ill, but clinical stable adult intensive care patients independent of septic shock and <7·5 g/dl for adults undergoing cardiac surgery. For the implementation of PBM programmes, 2 clinical and 3 research recommendations were developed. Research recommendations were formulated as encouragement of new studies to answer open questions. Due to the relative paucity of strong evidence‐based answers in current publications to the 17 PICO questions, additional research, an international consensus for accepted definitions and Hb thresholds as well as clinically meaningful end‐points for clinical studies are necessary. The 2018 PBM ICC defined the current status of PBM evidence and established 10 clinical and 12 research recommendations for preoperative anaemia, RBC transfusion thresholds for adults and implementation of PBM programmes.

Background The COVID-19 pandemic has led highly developed healthcare systems to the brink of collapse due to the large numbers of patients being admitted into hospitals. One of the potential prognostic indicators in patients with COVID-19 is frailty. The degree of frailty could be used to assist both the triage into intensive care, and decisions regarding treatment limitations. Our study sought to determine the interaction of frailty and age in elderly COVID-19 ICU patients. Methods A prospective multicentre study of COVID-19 patients ≥ 70 years admitted to intensive care in 138 ICUs from 28 countries was conducted. The primary endpoint was 30-day mortality. Frailty was assessed using the clinical frailty scale. Additionally, comorbidities, management strategies and treatment limitations were recorded. Results The study included 1346 patients (28% female) with a median age of 75 years (IQR 72–78, range 70–96), 16.3% were older than 80 years, and 21% of the patients were frail. The overall survival at 30 days was 59% (95% CI 56–62), with 66% (63–69) in fit, 53% (47–61) in vulnerable and 41% (35–47) in frail patients (p < 0.001). In frail patients, there was no difference in 30-day survival between different age categories. Frailty was linked to an increased use of treatment limitations and less use of mechanical ventilation. In a model controlling for age, disease severity, sex, treatment limitations and comorbidities, frailty was independently associated with lower survival. Conclusion Frailty provides relevant prognostic information in elderly COVID-19 patients in addition to age and comorbidities. Trial registration Clinicaltrials.gov: NCT04321265, registered 19 March 2020.

IMPORTANCE Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs. OBJECTIVE To develop a set of evidence-based recommendations for patient blood management (PBM) and for research. EVIDENCE REVIEWThe scientific committee developed 17 Population/Intervention/ Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018.FINDINGS From 17 607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23 143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration <7 g/dL) as well as for patients undergoing cardiac surgery (recommended threshold for RBC transfusion, hemoglobin concentration <7.5 g/dL). For implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and to use electronic decision support systems (both conditional recommendations) to improve appropriate RBC utilization. CONCLUSIONS AND RELEVANCEThe 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.

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