The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient’s tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

https://epub.ub.uni-muenchen.de/24023/1/oa_24023.pdf

Management of severe perioperative bleeding Guidelines from the European Society of Anaesthesiology

KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update.

Context: Elderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown. Objective: To compare traditional and novel risk factors as predictors of cardiovascular mortality. Design, Setting, and Patients: A total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years. Main Outcome Measures: Cardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m2. Results: Among the participants, 1249(22%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease(all P values .05). Among the novel risk factors, only log C-reactive protein(P=.05) and log interleukin 6(P .001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 personyears; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73(95%confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74(95%confidence interval, 0.71-0.78; P for difference=.15). Conclusions: Traditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk.

Cardiovascular mortality risk in chronic kidney disease: Comparison of traditional and novel risk factors

Objective Dabigatran was recently approved for anticoagulation in patients with atrial fibrillation (AF); data regarding real-world use, comparative effectiveness and safety are sparse. Design Pharmacoepidemiological cohort study. Methods/settings From nationwide registers, we identified patients with an in-hospital or outpatient-clinic AF diagnosis who claimed a prescription of dabigatran 110 or 150 mg, or vitamin K antagonist (VKA), between 22 August and 31 December 2011. HRs of thromboembolic events (ischaemic stroke, transitory ischaemic attack and peripheral artery embolism) and bleedings were estimated using Cox regression analyses in all patients and stratified by previous VKA use. Results Overall, 1612 (3.1%) and 1114 (2.1%) patients claimed a prescription of dabigatran 110 and 150 mg, and 49640 (94.8%) of VKA. Patients treated with dabigatran 150 mg were younger with less comorbidity than those treated with dabigatran 110 mg and VKA, as were VKA naive patients compared with previous VKA users. Recommendations set by the European Medicine Agency (EMA) for dabigatran were met in 90.3% and 55.5% of patients treated with 110 and 150 mg. Patients treated with 150 mg dabigatran, who did not fulfil the recommendations by EMA, were >80 years, patients with liver or kidney disease, patients with previous bleeding. Compared with VKA, the thromboembolic risk associated with dabigatran 110 and 150 mg was HR 3.52 (1.40 to 8.84) and 5.79 (1.81 to 18.56) in previous VKA users, and HR 0.95(0.47 to 1.91) and 1.14(0.60 to 2.16) in VKA naive patients. Bleeding risk was increased in previous VKA users receiving dabigatran 110 mg, but not in patients with 150 mg dabigatran, nor in the VKA naive users. Conclusions Deviations from the recommended use of dabigatran were frequent among patients treated with 150 mg. With cautious interpretation, dabigatran use in VKA naive patients seems safe. Increased risk of thromboembolism and bleeding with dabigatran among previous VKA users was unexpected and may reflect patient selection and ‘drug switching’ practices.

https://bmjopen.bmj.com/content/bmjopen/3/5/e002758.full.pdf

Dabigatran use in Danish atrial fibrillation patients in 2011: a nationwide study.

https://www.kidney-international.org/article/S0085-2538(15)00093-9/pdf

The molecular mechanisms of hemodialysis vascular access failure

Summary Background and objectives The role of thrombophilia in failing arteriovenous fistula (AVF) among patients with ESRD undergoing hemodialysis is not established. This study aimed to assess whether AVF primary patency is associated with thrombophilia and coagulation abnormalities. Design, setting, participants, & measurements This observational study screened 219 patients between 2002 and 2004 for thrombophilia before AVF surgery. Thrombophilia included factor V Leiden and prothrombin G20210A mutations, protein C and antithrombin activities, and protein S. Coagulation abnormalities included high factor VIII:C, homocysteine, fibrinogen, and d-dimer levels; presence of antiphospholipid antibodies; and short thrombin time. We reviewed patient charts for comorbid conditions, AVF maturation and interventions, kidney transplantation, and patient survival (mean follow-up duration, 3.6 [range, 2.3–5.8] years). Primary patency from the AVF placement and functional primary patency from the first AVF cannulation were analyzed with Kaplan-Meier and Cox proportional hazards models. Results Thrombophilia was present in 9% of the patients, and coagulation abnormalities occurred in 77%. One-year primary patency was 68%; 46% of the AVF failures occurred before the initiation of hemodialysis. Female sex (hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.7–4.1) and thrombophilia (HR, 2.2; 95% CI, 1.2–4.2) were independent risk factors for loss of primary patency. Thrombophilia mutations or low antithrombin level (HR, 3.8), female sex (HR, 2.5), and diabetes (HR, 1.9) were associated with shortened functional primary patency of AVF. Conclusions Against the background of frequent coagulation abnormalities, thrombophilia and female sex predispose patients with ESRD to access failure, mostly due to thrombosis or stenosis.

Thrombophilia and Arteriovenous Fistula Survival in ESRD

Clinicians prescribing new oral anticoagulants (OACs; dabigatran, rivaroxaban, and apixaban) should be aware of the exclusion criteria related to bleeding risks defined in published clinical studies. At least a quarter of patients currently using warfarin have an exclusion criterion that may prevent easy transition to the new OACs. In the summary of product characteristics for dabigatran, as an example, the target populations appear generalized. Due to fixed dosing and predictable pharmacology, routine laboratory monitoring of new OACs is deemed unnecessary. Under special circumstances, however, understanding the extent of thrombin or factor (F) Xa inhibition may aid in evaluating compliance and handling emergency interventions, bleeding complications, or overdoses. Although commonly available global coagulation-time assessments (prothrombin time and activated partial thromboplastin time) are insensitive, they may assist clinical management by indicating a severe accumulation of OACs; moreover, a normal thrombin time (TT) excludes a thrombin-inhibitor effect. In particular circumstances, specific assays (diluted TT, Ecarin clotting time, anti-FIIa or anti-FXa activity) may quantify the anticoagulant effect, but therapeutic ranges for dose adjustment are not yet established. Laboratory results are also influenced by clinical situation: e.g. bleed (consumption of coagulation factors) versus postoperative state (activation of coagulation). Without specific antidotes and evidence-based treatment strategies, new OACs are clinically worrisome in patients with impaired renal or liver function. Postmarketing surveillance and recording of bleeding complications (ICD-10 D68.32) are therefore of major importance.

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Active online assessment of patients using new oral anticoagulants: bleeding risk, compliance, and coagulation analysis.

Background: Cancer is currently one of the most important factors affecting the long-term health and survival of heart transplant patients. Material and methods: We calculated the standardized incidence ratios (SIR) for different cancer sites and the cancer-specific standardized mortality ratio (SMR) by linking a cohort of 479 adult heart transplant recipients transplanted in 1985-2014 (4491.6 person-years of follow-up) with data from the national Finnish Cancer Registry until the end of 2015, and with the data from the Statistics Finland's national registry of causes of death. Results: A total of 267 cancers occurred in 143 patients (SIR 6.0; 95% confidence interval (CI) 5.3-6.7). The SIR for overall cancer was considerably higher for men (SIR 6.7; 95% CI 5.9-7.5) than for women (1.4; 95% CI 0.6-2.6). Most frequent cancers were non-melanoma skin cancers (basal cell carcinoma 83 cases, squamous cell skin cancer (SCC) 56 cases), followed by Non-Hodgkin lymphoma (NHL) (36 cases), lung cancer (17), cancer of prostate (16) and cancer of kidney (12). SIRs were highest for SCC (51.9; 95% CI 39.2-67.4), lip cancer (47.4; 95% CI 19.1-97.7), cancer of tongue (26.3; 95% CI 7.2-67.4), and NHL (25.7; 95% CI 18.0-35.6). For most cancers, SIRs increased steadily by time since transplantation. Cancer mortality was three times higher for heart transplant recipients than for the population (SMR 3.1; 95% CI 2.1-4.1). Conclusions: Both cancer incidence and mortality are remarkably increased after heart transplantation, with the relative incidence most elevated for SCC, lip and other oral cancers, and for NHL.

Cancer incidence and mortality after heart transplantation – A population-based national cohort study

Background:The use of venoarterial extracorporeal membrane oxygenation in cardiogenic shock keeps increasing, but its cost-utility is unknown.Methods:We studied retrospectively the cost-utility of ...

/pdf/cost-utility-of-venoarterial-extracorporeal-membrane-5gd0quw537.pdf

Cost-utility of venoarterial extracorporeal membrane oxygenation in cardiogenic shock and cardiac arrest.

OBJECTIVES Our goal was to study the outcome of patients with cardiogenic shock who were treated with venoarterial extracorporeal membrane oxygenation (VA ECMO), including the subsequent long-term health-related quality of life (HRQoL). METHODS We conducted a retrospective study of 133 consecutive patients treated in a single centre from 2007 to 2016. The HRQoL was studied using the EuroQuol-5 dimensions-3 level questionnaire and the RAND 36-Item Short Form Health Survey at a minimum of 1 year after VA ECMO. RESULTS Of all patients, 66 (49.6%) were weaned from VA ECMO and 16 (12.0%) patients were bridged directly to a transplant, 15 (11.3%) to a ventricular assist device and 1 (0.8%) to a total artificial heart. Survival to discharge was 63.9% and to 1 year, 60.9%. A higher in-hospital mortality rate was independently associated with lower HCO3 at VA ECMO implantation [odds ratio (OR) 1.2/decrease of 1 mmol/l in HCO3 (95% confidence interval 1.1-1.3, P < 0.001)] and with increased need of red blood cells transfused during intensive care [OR 1.9/unit of red blood cells needed/day (95% confidence interval 1.4-2.6, P  < 0.001)]. HRQoL measured with the EuroQuol-5 dimensions-3 level questionnaire was equal to the HRQoL of the general population. In the 36-Item Short Form questionnaire, patients reported better emotional well-being and equal energy, pain and general health perception compared to the general population. Limitations were experienced only in physical health. In total, 56% of the patients ≤ 60 years had returned to work. CONCLUSIONS VA ECMO can provide acceptable long-term survival with good HRQoL for selected patients with refractory cardiogenic shock. Timing of patient assessment and of VA ECMO implantation is essential because deeper acidosis is associated with a higher in-hospital mortality rate.

Birgitta Salmela

Papers

Thrombophilia and Arteriovenous Fistula Survival in ESRD

Active online assessment of patients using new oral anticoagulants: bleeding risk, compliance, and coagulation analysis.

Cancer incidence and mortality after heart transplantation – A population-based national cohort study

Cost-utility of venoarterial extracorporeal membrane oxygenation in cardiogenic shock and cardiac arrest.

Extracorporeal membrane oxygenation for refractory cardiogenic shock: patient survival and health-related quality of life.