German Patient Blood Management Network: effectiveness and safety analysis in 1.2 million patients.

BACKGROUND: Patient Blood Management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood whilst promoting patient safety and empowerment. The effectiveness and safety of PBM over a longer period have not yet been investigated. METHODS: We performed a prospectively designed, multicentre follow-up study with non-inferiority design. Data were retrospectively extracted case-based from electronic hospital information systems. All in-hospital patients (≥18 yr) undergoing surgery and discharged between January 1, 2010 and December 31, 2019 were included in the analysis. The PBM programme focused on three domains: preoperative optimisation of haemoglobin concentrations, blood-sparing techniques, and guideline adherence/standardisation of allogeneic blood product transfusions. The outcomes were utilisation of blood products, composite endpoint of in-hospital mortality and postoperative complications (myocardial infarction/ischaemic stroke/acute renal failure with renal replacement therapy/sepsis/pneumonia), anaemia rate at admission and discharge, and hospital length of stay. RESULTS: A total of 1 201 817 (pre-PBM: n=441 082 vs PBM: n=760 735) patients from 14 (five university/nine non-university) hospitals were analysed. Implementation of PBM resulted in a substantial reduction of red blood cell utilisation. The mean number of red blood cell units transfused per 1000 patients was 547 in the PBM cohort vs 635 in the pre-PBM cohort (relative reduction of 13.9%). The red blood cell transfusion rate was significantly lower (P<0.001) with odds ratio 0.86 (0.85-0.87). The composite endpoint was 5.8% in the PBM vs 5.6% in the pre-PBM cohort. The non-inferiority aim (safety of PBM) was achieved (P<0.001). CONCLUSIONS: Analysis of >1 million surgical patients showed that the non-inferiority condition (safety of Patient Blood Management) was fulfilled, and PBM was superior with respect to red blood cell transfusion. CLINICAL TRIAL REGISTRATION: NCT02147795.

Preoperative anaemia and red blood cell transfusion in patients with aneurysmal subarachnoid and intracerebral haemorrhage - a multicentre subanalysis of the German PBM Network Registry.

PURPOSE: Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period. METHODS: This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH. RESULTS: A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications. CONCLUSIONS: Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02147795, https://clinicaltrials.gov/ct2/show/NCT02147795.

Effectiveness of Preoperative Iron Supplementation in Major Surgical Patients With Iron Deficiency: A Prospective Observational Study.

OBJECTIVE: To evaluate the effectiveness of routine intravenous iron in surgical patients with iron deficiency anemia (IDA). BACKGROUND: Anemia is the most common medical disease in the world and is an independent risk factor for morbidity and mortality. Iron deficiency (ID) is the main cause for anemia and constitutes a potentially preventable condition with great impact on surgical outcome. METHODS: In this prospective single-center observational study, surgical patients were screened for the presence of anemia and ID. Patients were assigned to 1 of 4 study groups: A- (no anemia); A-, ID+, T+ (no anemia, iron-deficient, iron supplementation); A+ (anemia); and A+, ID+, T+ (anemia, iron-deficient, iron supplementation) according to hemoglobin level, iron status, and supplementation with iron. RESULTS: Among 1728 patients, 1028 were assigned to A-; 55 to A-, ID+, T+; 461 to A+; and 184 to A+, ID+, T+. While all iron-supplemented IDA patients required less red blood cell (RBC) transfusion during the postoperative period (A+ 42.5% vs A+, ID+, T+ 31.5%), a reduced intraoperative transfusion rate was observed for ID and IDA patients only if iron was supplemented >7 days before surgery. Hospital stay was significantly reduced by 2.8 days in iron-supplemented patients (P < 0.01 comparing 13.9 ±â€Š0.8 days for A+, ID+, T+ vs. 16.7 ±â€Š0.7 days for A+). CONCLUSION: Preoperative IDA management with intravenous iron is effective in improving hemoglobin level, thereby reducing intraoperative RBC transfusion rate particular if iron is administrated >7 days before surgery. Hospital length of stay was reduced in all preoperatively iron-supplemented IDA patients.

Screening for iron deficiency in surgical patients based on noninvasive zinc protoporphyrin measurements.

BACKGROUND: Approximately every third surgical patient is anemic. The most common form, iron deficiency anemia, results from persisting iron-deficient erythropoiesis (IDE). Zinc protoporphyrin (ZnPP) is a promising parameter for diagnosing IDE, hitherto requiring blood drawing and laboratory workup. STUDY DESIGN AND METHODS: Noninvasive ZnPP (ZnPP-NI) measurements are compared to ZnPP reference determination of the ZnPP/heme ratio by high-performance liquid chromatography (ZnPP-HPLC) and the analytical performance in detecting IDE is evaluated against traditional iron status parameters (ferritin, transferrin saturation [TSAT], soluble transferrin receptor-ferritin index [sTfR-F], soluble transferrin receptor [sTfR]), likewise measured in blood. The study was conducted at the University Hospitals of Frankfurt and Zurich. RESULTS: Limits of agreement between ZnPP-NI and ZnPP-HPLC measurements for 584 cardiac and noncardiac surgical patients equaled 19.7 µmol/mol heme (95% confidence interval, 18.0-21.3; acceptance criteria, 23.2 µmol/mol heme; absolute bias, 0 µmol/mol heme). Analytical performance for detecting IDE (inferred from area under the curve receiver operating characteristics) of parameters measured in blood was: ZnPP-HPLC (0.95), sTfR (0.92), sTfR-F (0.89), TSAT (0.87), and ferritin (0.67). Noninvasively measured ZnPP-NI yielded results of 0.90. CONCLUSION: ZnPP-NI appears well suited for an initial IDE screening, informing on the state of erythropoiesis at the point of care without blood drawing and laboratory analysis. Comparison with a multiparameter IDE test revealed that ZnPP-NI values of 40 µmol/mol heme or less allows exclusion of IDE, whereas for 65 µmol/mol heme or greater, IDE is very likely if other causes of increased values are excluded. In these cases (77% of our patients) ZnPP-NI may suffice for a diagnosis, while values in between require analyses of additional iron status parameters.

In-line filtration of intravenous infusion may reduce organ dysfunction of adult critical patients.

BACKGROUND: The potential harmful effects of particle-contaminated infusions for critically ill adult patients are yet unclear. So far, only significant improved outcome in critically ill children and new-borns was demonstrated when using in-line filters, but for adult patients, evidence is still missing. METHODS: This single-centre, retrospective controlled cohort study assessed the effect of in-line filtration of intravenous fluids with finer 0.2 or 1.2 µm vs 5.0 µm filters in critically ill adult patients. From a total of n = 3215 adult patients, n = 3012 patients were selected by propensity score matching (adjusting for sex, age, and surgery group) and assigned to either a fine filter cohort (with 0.2/1.2 µm filters, n = 1506, time period from February 2013 to January 2014) or a control filter cohort (with 5.0 µm filters, n = 1506, time period from April 2014 to March 2015). The cohorts were compared regarding the occurrence of severe vasoplegia, organ dysfunctions (lung, kidney, and brain), inflammation, in-hospital complications (myocardial infarction, ischemic stroke, pneumonia, and sepsis), in-hospital mortality, and length of ICU and hospital stay. RESULTS: Comparing fine filter vs control filter cohort, respiratory dysfunction (Horowitz index 206 (119-290) vs 191 (104.75-280); P = 0.04), pneumonia (11.4% vs 14.4%; P = 0.02), sepsis (9.6% vs 12.2%; P = 0.03), interleukin-6 (471.5 (258.8-1062.8) ng/l vs 540.5 (284.5-1147.5) ng/l; P = 0.01), and length of ICU (1.2 (0.6-4.9) vs 1.7 (0.8-6.9) days; P <  0.01) and hospital stay (14.0 (9.2-22.2) vs 14.8 (10.0-26.8) days; P = 0.01) were reduced. Rate of severe vasoplegia (21.0% vs 19.6%; P > 0.20) and acute kidney injury (11.8% vs 13.7%; P = 0.11) was not significantly different between the cohorts. CONCLUSIONS: In-line filtration with finer 0.2 and 1.2 µm filters may be associated with less organ dysfunction and less inflammation in critically ill adult patients. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (number: NCT02281604).

Evaluation of a Clinical Decision Support System for the most evidence-based approach to managing perioperative anticoagulation.

STUDY OBJECTIVE: We explored the feasibility of a Clinical Decision Support System (CDSS) to guide evidence-based perioperative anticoagulation. DESIGN: Prospective randomised clinical management simulation multicentre study. SETTING: Five University and 11 general hospitals in Germany. PARTICIPANTS: We enrolled physicians (anaesthesiologist (n = 73), trauma surgeons (n = 2), unknown (n = 1)) with different professional experience. INTERVENTIONS: A CDSS based on a multiple-choice test was developed and validated at the University Hospital of Frankfurt (phase-I). The CDSS comprised European guidelines for the management of anticoagulation in cardiology, cardio-thoracic, non-cardio-thoracic surgery and anaesthesiology. Phase-II compared the efficiency of physicians in identifying evidence-based approach of managing perioperative anticoagulation. In total 168 physicians were randomised to CDSS (PERI-KOAG) or CONTROL. MEASUREMENTS: Overall mean score and association of processing time and professional experience were analysed. The multiple-choice test consists of 11 cases and two correct answers per question were required to gain 100% success rate (=22 points). MAIN RESULTS: In total 76 physicians completed the questionnaire (n = 42 PERI-KOAG; n = 34 CONTROL; attrition rate 54%). Overall mean score (max. 100% = 22 points) was significantly higher in PERI-KOAG compared to CONTROL (82 ± 15% vs. 70 ± 10%; 18 ± 3 vs. 15 ± 2 points; P = 0.0003). A longer processing time is associated with significantly increased overall mean scores in PERI-KOAG (≥33 min. 89 ± 10% (20 ± 2 points) vs. <33 min. 73 ± 15% (16 ± 3 points), P = 0.0005) but not in CONTROL (≥33 min. 74 ± 13% (16 ± 3 points) vs. <33 min. 69 ± 9% (15 ± 2 points), P = 0.11). Within PERI-KOAG, there is a tendency towards higher results within the more experienced group (>5 years), but no significant difference to less (≤5 years) experienced colleagues (87 ± 10% (19 ± 2 points) vs. 78 ± 17% (17 ± 4 points), P = 0.08). However, an association between professional experience and success rate in CONTROL has not been shown (71 ± 8% vs. 70 ± 13%, 16 ± 2 vs. 15 ± 3 points; P = 0.66). CONCLUSIONS: CDSS significantly improved the identification of evidence-based treatment approaches. A precise usage of CDSS is mandatory to maximise efficiency.

Association of anaemia, co-morbidities and red blood cell transfusion according to age groups: multicentre sub-analysis of the German Patient Blood Management Network Registry.

BACKGROUND: Blood transfusions are common medical procedures and every age group requires detailed insights and treatment bundles. The aim of this study was to examine the association of anaemia, co-morbidities, complications, in-hospital mortality, and transfusion according to age groups to identify patient groups who are particularly at risk when undergoing surgery. METHODS: Data from 21 Hospitals of the Patient Blood Management Network Registry were analysed. Patients were divided into age subgroups. The incidence of preoperative anaemia, co-morbidities, surgical disciplines, hospital length of stay, complications, in-hospital mortality rate, and transfusions were analysed by descriptive and multivariate regression analysis. RESULTS: A total of 1 117 919 patients aged 18-108 years were included. With increasing age, the number of co-morbidities and incidence of preoperative anaemia increased. Complications, hospital length of stay, and in-hospital mortality increased with age and were higher in patients with preoperative anaemia. The mean number of transfused red blood cells (RBCs) peaked, whereas the transfusion rate increased continuously. Multivariate regression analysis showed that increasing age, co-morbidities, and preoperative anaemia were independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion. CONCLUSION: Increasing age, co-morbidities, and preoperative anaemia are independent risk factors for complications, longer hospital length of stay, in-hospital mortality, and the need for RBC transfusion. Anaemia diagnosis and treatment should be established in all patients.

Independent Risk Factors for RBC Transfusion in Children Undergoing Surgery. Analysis of 14,248 Cases at a German University Hospital.

BACKGROUND: paediatric patients are vulnerable to blood loss and even a small loss of blood can be associated with severe shock. In emergency situations, a red blood cell (RBC) transfusion may become unavoidable, although it is associated with various risks. The aim of this trial was to identify independent risk factors for perioperative RBC transfusion in children undergoing surgery. METHODS: to identify independent risk factors for perioperative RBC transfusion in children undergoing surgery and to access RBC transfusion rates and in-hospital outcomes (e.g., length of stay, mortality, and typical postoperative complication rates), a monocentric, retrospective, and observational study was conducted. Descriptive, univariate, and multivariate analyses were performed. RESULTS: between 1 January 2010 and 31 December 2019, data from n = 14,248 cases were identified at the centre. Analysis revealed an RBC transfusion rate of 10.1% (n = 1439) in the entire cohort. The independent predictors of RBC transfusion were the presence of preoperative anaemia (p < 0.001; OR = 15.10 with preoperative anaemia and OR = 2.40 without preoperative anaemia), younger age (p < 0.001; ORs between 0.14 and 0.28 for children older than 0 years), female gender (p = 0.036; OR = 1.19 compared to male gender), certain types of surgery (e.g., neuro surgery (p < 0.001; OR = 10.14), vascular surgery (p < 0.001; OR = 9.93), cardiac surgery (p < 0.001; OR = 4.79), gynaecology (p = 0.014; OR = 3.64), visceral surgery (p < 0.001; OR = 2.48), and the presence of postoperative complications (e.g., sepsis (p < 0.001; OR = 10.16), respiratory dysfunction (p < 0.001; OR = 7.56), cardiovascular dysfunction (p < 0.001; OR = 4.68), neurological dysfunction (p = 0.029; OR = 1.77), and renal dysfunction (p < 0.001; OR = 16.17)). CONCLUSION: preoperative anaemia, younger age, female gender, certain types of surgery, and postoperative complications are independent predictors for RBC transfusion in children undergoing surgery. Future prospective studies are urgently required to identify, in detail, the potential risk factors and impact of RBC transfusion in children.

The Reticulocyte Hemoglobin Equivalent as a Screening Marker for Iron Deficiency and Iron Deficiency Anemia in Children.

BACKGROUND: Iron deficiency (ID) is one of the most common nutritional deficiencies in children worldwide and may result in iron deficiency anemia (IDA). The reticulocyte hemoglobin equivalent (Ret-He) provides information about the current availability of iron in erythropoiesis. This study aims to examine the validation of Ret-He as a screening marker for ID and IDA in children. METHODS: Blood samples were retrospectively obtained from medical records. Anemia was defined according to the definition provided by the World Health Organization (WHO) for children. ID was defined by transferrin saturation (TSAT) < 20% and ferritin < 100 ng/mL. Children were classified into four groups: IDA, non-anemia iron deficiency (NAID), control and others. RESULTS: Out of 970 children, 332 (34.2%) had NAID and 278 (28.7%) presented with IDA. Analysis revealed that Ret-He significantly correlates with ferritin (rho = 0.41; p < 0.001), TSAT (rho = 0.66; p < 0.001) and soluble transferrin receptor (sTfR) (rho = -0.72; p < 0.001). For ROC analysis, the area under the curve (AUC) was 0.771 for Ret-He detecting ID and 0.845 for detecting IDA. The cut-off value for Ret-He to diagnose ID was 33.5 pg (sensitivity 90.7%; specificity 35.8%) and 31.6 pg (sensitivity 90.6%; specificity 50.4%) to diagnose IDA. CONCLUSIONS: The present study demonstrates Ret-He to be a screening marker for ID and IDA in children. Furthermore, Ret-He can be used as a single screening parameter for ID and IDA in children without considering other iron parameters. Economically, the use of Ret-He is highly relevant, as it can save one blood tube per patient and additional costs.

Quantification of Intraoperative Blood Loss in a Simulated Scenario Using a Novel Device.

BACKGROUND: Particularly for protracted bleeding situations, the realization of a relevant blood loss is necessary for early initiation of therapy to avoid hemodynamic instability and shock. The frequently used visual assessment of blood loss is known to be incorrect. An innovative option to address this problem is a mobile application using colorimetric image correction and analysis. METHODS: The objective of this study was to evaluate the clinical applicability and accuracy of a novel mobile device application using colorimetric image correction and analysis for blood loss estimation. Scenarios of blood-filled surgical sponges were created to evaluate the accuracy of colorimetric-based blood loss estimation and visual and gravimetric blood loss estimation. RESULTS: Fifty-three anesthesiologists ran through the scenarios. The estimated blood loss correlated the least with the reference blood loss in the visual technique (Rho: 0.52; P < 3.7×10-16), followed by the gravimetric technique (Rho: 0.73; P = 2.8×10-05). The best correlation was found in the colorimetric blood loss measurement (Rho: 0.77; P = 3.53×10-06). A median overestimation per scenario of 133.0 mL (interquartile range [IQR] 33.0 mL-283.0 mL) was observed when using the visual method, whereas 32.5 mL (IQR 10.8 mL-44.0 mL) was overestimated with the gravimetric method and 31 mL (IQR 17.0 mL-42.8 mL) with the colorimetric method. Especially in the case of blood loss underestimation, the application has the least deviation from the reference. CONCLUSION: The blood loss measured in the sponges correlated strong with the reference blood loss, showing the smallest median overestimation and the smallest deviation in underestimation. The visual estimation shows serious errors, where the gravimetric method is prone to errors, especially in dilution. The colorimetric method offers an easily implementable possibility to monitor blood loss in real time and to initiate early diagnostic and therapeutic measures in case of persistent blood loss. The influence of real-time estimation of colorimetric blood loss on transfusion decisions should be the subject of future studies.

Do we visually estimate intra-operative blood loss better with white or green sponges and is the deviation from the real blood loss clinically acceptable? Results from a simulated scenario study.

BACKGROUND: The intraoperative blood loss is estimated daily in the operating room and is mainly done by visual techniques. Due to local standards, the surgical sponge colours can vary (e.g. white in US, green in Germany). The influence of sponge colour on accuracy of estimation has not been in the focus of research yet. MATERIAL AND METHODS: A blood loss simulation study containing four "bleeding" scenarios each per sponge colour were created by using expired whole blood donation samples. The blood donations were applied to white and green surgical sponges after dilution with full electrolyte solution. Study participants had to estimate the absorbed blood loss in sponges in all scenarios. The difference to the reference blood loss was analysed. Multivariate linear regression analysis was performed to investigate other influence factors such as staff experience and sponge colour. RESULTS: A total of 53 anaesthesists participated in the study. Visual estimation correlated moderately with reference blood loss in white (Spearman's rho: 0.521; p = 3.748*10-16) and green sponges (Spearman's rho: 0.452; p = 4.683*10-12). The median visually estimated blood loss was higher in white sponges (250ml IRQ 150-412.5ml) than in green sponges (150ml IQR 100-300ml), compared to reference blood loss (103ml IQR 86-162.8). For both colour types of sponges, major under- and overestimation was observed. The multivariate statistics demonstrates that fabric colours have a significant influence on estimation (p = 3.04*10-10), as well as clinician's qualification level (p = 2.20*10-10, p = 1.54*10-08) and amount of RBL to be estimated (p < 2*10-16). CONCLUSION: The deviation of correct blood loss estimation was smaller with white surgical sponges compared to green sponges. In general, deviations were so severe for both types of sponges, that it appears to be advisable to refrain from visually estimating blood loss whenever possible and instead to use other techniques such as e.g. colorimetric estimation.

Preoperative Anaemia in Primary Hip and Knee Arthroplasty. / Präoperative Anämie in der Hüft- und Kniegelenkendoprothetik.

INTRODUCTION: Approximately one in three patients has untreated preoperative anaemia, which in turn is associated with an increased need for transfusion of allogenic red blood cell concentrates (RBC) and complications in the context of a surgical intervention. Here, the prevalence of preoperative and postoperative anaemia as well as their effects on transfusion rate, hospital length of stay and hospital mortality in primary hip and knee arthroplasty has been analysed. METHODS: From January 2012 to September 2018, 378,069 adult inpatients from 13 German hospitals were analysed on the basis of an anonymized registry. Of these, n = 10,017 patients had a hip and knee joint primary arthroplasty. The primary endpoint was the incidence of preoperative anaemia, which was analysed by the first available preoperative haemoglobin value according to the WHO definition. Secondary endpoints included in-hospital length of stay, number of patients with red blood cell concentrate transfusion, incidence of hospital-acquired anaemia, number of deceased patients, and postoperative complications. RESULTS: The preoperative anaemia rate was 14.8% for elective knee joint arthroplasty, 22.9% for elective hip joint arthroplasty and 45.0% for duo-prosthesis implantation. Preoperative anaemia led to a significantly higher transfusion rate (knee: 8.3 vs. 1.8%; hip: 34.5 vs. 8.1%; duo-prosthesis: 42.3 vs. 17.4%), an increased red blood cell concentrate consumption (knee: 256 ± 107 vs. 29 ± 5 RBC/1000 patients; hip: 929 ± 60 vs. 190 ± 16 RBC/1000 patients; duo-prosthesis: 1411 ± 98 vs. 453 ± 42 RBC/1000 patients). Pre-operative anaemia was associated with prolonged hospital stay (12.0 [10.0; 17.0] d vs. 11.0 [9.0; 13.0] d; p < 0.001) and increased mortality (5.5% [4.6 - 6.5%] vs. 0.9% [0.7 - 1.2%]; Fisher p < 0.001) compared to non-anaemic patients. In patients aged 80 years and older, the incidence of preoperative anaemia and thus the transfusion rate was almost twice as high as in patients under 80 years of age. SUMMARY: Preoperative anaemia is common in knee and hip primary arthroplasty and was associated with a relevant increase in red blood cell concentrate consumption. In the context of patient blood management, a relevant potential arises, especially in elective orthopaedic surgery, to better prepare elective patients, to avoid unnecessary transfusions and thus to conserve the valuable resource blood.

Track-structure simulations of energy deposition patterns to mitochondria and damage to their DNA.

PURPOSE: Mitochondria have been implicated in initiating and/or amplifying the biological effects of ionizing radiation not mediated via damage to nuclear DNA. To help elucidate the underlying mechanisms, energy deposition patterns to mitochondria and radiation damage to their DNA have been modelled. METHODS: Track-structure simulations have been performed with PARTRAC biophysical tool for 60Co γ-rays and 5 MeV α-particles. Energy deposition to the cell's mitochondria has been analyzed. A model of mitochondrial DNA reflecting experimental information on its structure has been developed and used to assess its radiation-induced damage. RESULTS: Energy deposition to mitochondria is highly inhomogeneous, especially at low doses. Although a dose-dependent fraction of mitochondria sees no energy deposition at all, the hit ones receive rather high amounts of energy. Nevertheless, only little damage to mitochondrial DNA occurs, even at large doses. CONCLUSION: Mitochondrial DNA does not represent a critical target for radiation effects. Likely, the key role of mitochondria in radiation-induced biological effects arises from the communication between mitochondria and/or with the nucleus. Through this signaling, initial modifications in a few heavily hit mitochondria seem to be amplified to a massive long-term effect manifested in the whole cell or even tissue.