Effect of using smaller blood volume tubes and closed blood collection devices on total blood loss in patients undergoing major cardiac and vascular surgery.

BACKGROUND: Diagnostic laboratory tests are an integral part of managing hospitalized patients. In particular, patients in the intensive care units (ICUs) can experience a concerning amount of blood loss due to diagnostic testing, which can increase the risk developing iatrogenic anemia. Several interventions exist to curtail avoidable blood loss, for example computerized decision support, smaller phlebotomy tubes, and other blood conservation devices. Nevertheless, use of these interventions is not standardized. Therefore, the objective of our study was to quantify the daily phlebotomy volume taken from patients who had undergone major cardiac or vascular surgery. METHODS: We estimated the number of blood analyses and volumes of drawn blood of 400 consecutive patients (≥ 18 yr) undergoing major cardiac or vascular surgery. The amount of blood saved using small-volume tubes and in combination with blood conservation device rather than standard-volume tubes was estimated for serum chemistry (serum), ethylenediaminetetraacetic acid (EDTA) tubes, sodium citrate coagulation (SCC) tubes, and arterial blood gas (ABG) analysis. RESULTS: The mean total blood loss due to phlebotomy drawing using standard-volume tubes during hospitalization was 167.9 mL (95% confidence interval [CI], 158.0 to 177.8), 255.6 mL (95% CI, 226.5 to 284.6), and 695.3 mL (95% CI, 544.1 to 846.4) for patients undergoing cardiac surgery with a hospital length of stay (LOS) of 0-10, 11-20, and ≥ 21 days, respectively. The mean total blood loss due to phlebotomy during hospitalization was 80.5 mL (95% CI, 70.5 to 90.6), 225.0 mL (95% CI, 135.1 to 314.8 mL) and 470.3 mL (95% CI, 333.5 to 607.1) for vascular surgery patients with LOS 0-10, 11-20, and ≥ 21 days, respectively. Patients with at least a two-day stay at the ICU had a mean blood loss of 146.6 mL (95% CI, 134.6 to 158.6 mL) and those with ≥ 11 days incurred a loss of 1,428 mL (95% CI, 1,117.8 to 1,739.2). The use of closed blood collection device and small-volume tubes (serum, EDTA, SCC, and ABG) reduced blood loss by 82.8 mL for patients with an ICU stay of 2 days and up to 824.0 mL for patients with a ICU stay of ≥ 11 days. CONCLUSION: Diagnostic laboratory tests are associated with significant patient blood loss, but are a modifiable risk factor. The use of small-volume tubes and closed blood collection devices decreases the volume of patient blood drawn for analysis and prevents blood waste.

RéSUMé: CONTEXTE: Les tests diagnostiques de laboratoire font partie intégrante de la prise en charge des personnes hospitalisées. Plus spécifiquement, la patientèle des unités de soins intensifs (USI) peut perdre une quantité inquiétante de sang en raison des tests de diagnostic, ce qui peut augmenter le risque d'anémie iatrogène. Plusieurs interventions existent pour réduire les pertes de sang évitables, par exemple une aide à la décision informatisée, des tubes de phlébotomie plus petits et d'autres dispositifs de conservation du sang. Néanmoins, le recours à ces interventions n'est pas normalisé. Par conséquent, l'objectif de notre étude était de quantifier le volume quotidien de phlébotomie prélevée chez des patient·es ayant bénéficié d'une chirurgie cardiaque ou vasculaire majeure. MéTHODE: Nous avons estimé le nombre d'analyses sanguines et les volumes de sang prélevés de 400 personnes consécutives (≥ 18 ans) bénéficiant d'une chirurgie cardiaque ou vasculaire majeure. La quantité de sang économisée à l'aide de tubes de petit volume et en combinaison avec un dispositif de conservation du sang plutôt que des tubes de volume standard a été estimée pour la chimie sérique (sérum), les tubes d'acide éthylène-diamine-tétra-acétique (EDTA), les tubes de coagulation au citrate de sodium (CCS) et l'analyse des gaz du sang artériel (GSA). RéSULTATS: La perte sanguine totale moyenne due au prélèvement de phlébotomie à l'aide de tubes de volume standard pendant l'hospitalisation était de 167,9 mL (intervalle de confiance [IC] à 95 %, 158,0 à 177,8), 255,6 mL (IC 95 %, 226,5 à 284,6) et 695,3 mL (IC 95 %, 544,1 à 846,4) chez les patient·es bénéficiant d'une chirurgie cardiaque avec une durée de séjour à l'hôpital de 0 à 10, 11 à 20, et ≥ 21 jours, respectivement. La perte sanguine totale moyenne due à la phlébotomie pendant l'hospitalisation était de 80,5 mL (IC 95 %, 70,5 à 90,6), 225,0 mL (IC 95 %, 135,1 à 314,8 mL) et 470,3 mL (IC 95 %, 333,5 à 607,1) chez les patient·es ayant bénéficié d'une chirurgie vasculaire avec des durées de séjour de 0-10, 11-20 et ≥ 21 jours, respectivement. Les patient·es ayant séjourné au moins deux jours à l'USI ont eu une perte de sang moyenne de 146,6 mL (IC 95 %, 134,6 à 158,6 mL) et celles et ceux ayant séjourné ≥ 11 jours ont subi une perte de 1428 mL (IC 95 %, 1117,8 à 1739,2). L'utilisation d'un dispositif de prélèvement sanguin fermé et de tubes de petit volume (sérum, EDTA, SCC et gsa) a réduit la perte de sang de 82,8 mL pour les patient·es ayant séjourné à l'USI 2 jours et jusqu'à 824,0 mL pour les patient·es ayant séjourné en USI ≥ 11 jours. CONCLUSION: Les tests de laboratoire diagnostiques sont associés à une perte de sang importante chez les patient·es, mais constituent un facteur de risque modifiable. L'utilisation de tubes de petit volume et de dispositifs fermés de prélèvement sanguin diminue le volume de sang prélevé pour analyse et prévient le gaspillage de sang.

Current concepts in postpartum anemia management.

PURPOSE OF REVIEW: Postpartum anemia (PPA) is common in women after childbirth and affects about 50-80% of all women worldwide. Iron deficiency (ID) is the main cause for anemia and constitutes a potentially preventable condition with great impact on the mother's physical and mental condition after delivery. In most cases, PPA is associated with antenatal ID and peripartum blood losses. Numerous published studies confirmed the positive effect of PPA diagnosis and treatment. RECENT FINDINGS: Iron deficiency as well as iron deficiency anemia (IDA) are common in the postpartum period and represent significant health problems in women of reproductive age. SUMMARY: Important movements towards early detection and therapy of postpartum anemia have been observed. However, postpartum anemia management is not implemented on a large scale as many healthcare professionals are not aware of the most recent findings in the field. Diagnosis and therapy of PPA, particularly iron supplementation in ID and IDA, has proven to be highly effective with a tremendous effect on women's wellbeing and outcome.

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.

Is a Patient Blood Management programme economically reasonable?

PURPOSE OF REVIEW: The value of healthcare is defined as the achieved health outcome in relation to the incurred costs. Patient Blood Management (PBM) is a multidisciplinary, evidence-based and patient-centred concept to optimize the patients' red blood cell mass, minimize blood loss and bleeding and to secure the physiological reserve, including the promotion of evidence-based transfusion strategies. This review describes the healthcare value and the cost effectiveness of single PBM measures as well as the implementation of comprehensive PBM programmes. RECENT FINDINGS: Overall, measures improving surgical outcome and reducing hospital length of stay, such as intravenous iron supplementation in iron deficient anaemic patients, the use of antifibrinolytic agents for the treatment of bleeding, the use of cell salvage and adherence to an evidence-based transfusion strategy, are associated with cost savings. SUMMARY: Although several single PBM measures have been shown to be effective and cost-efficient, it remains challenging to compare the results among differing healthcare systems.

[Implementation of Patient Blood Management as Standard-of-Care]. / Etablierung eines Patient Blood Managements als Behandlungsstandard.

Anaemia is among the most common co-morbidity in surgical patients. However, it often remains unrecognized and untreated, which results in an increased requirement for allogeneic blood products and complications. Patient Blood Management offers patient-centred and evidence-based therapies and preventive measures for anaemia. Patient Blood Management is composed of 3 main pillars: pre-operative anaemia management, blood loss reduction and the rational use of allogeneic blood products. The World Health Organization demands the implementation of Patient Blood Management measures since 2010. However, a comprehensive implementation of Patient Blood Management as a standard-of-care is still not achieved. Here, we describe the need for a comprehensive Patient Blood Management implementation and highlight several specific Patient Blood Management measures.

The impact of intravenous iron supplementation in elderly patients undergoing major surgery.

BACKGROUND: Age and preoperative anaemia are risk factors for poor surgical outcome and blood transfusion. The aim of this study was to examine the effect of iron supplementation in iron-deficient (ID) elderly patients undergoing major surgery. METHOD: In this single-centre observational study, patients ≥ 65 years undergoing major surgery were screened for anaemia and ID. Patients were assigned to the following groups: A- (no anaemia); A-,ID+,T+ (no anaemia, iron-deficient, intravenous iron supplementation); A+ (anaemia); and A+,ID+,T+ (anaemia, iron-deficient, intravenous iron supplementation). RESULTS: Of 4,381 patients screened at the anaemia walk-in clinic, 2,381 (54%) patients were ≥ 65 years old and 2,191 cases were included in analysis. The ID prevalence was 63% in patients with haemoglobin (Hb) < 8 g/dl, 47.2% in patients with Hb from 8.0 to 8.9 g/dl, and 44.3% in patients with Hb from 9 to 9.9 g/dl. In severely anaemic patients, an Hb increase of 0.6 (0.4; 1.2) and 1.2 (0.7; 1.6) g/dl was detected with iron supplementation 6-10 and > 10 days before surgery, respectively. Hb increased by 0 (-0.1; 0) g/dl with iron supplementation 1-5 days before surgery, 0.2 (-0.1; 0.5) g/dl with iron supplementation 6-10 days before surgery, and 0.2 (-0.2; 1.1) g/dl with supplementation > 10 days before surgery (p < 0.001 for 1-5 vs. 6-10 days). Overall, 58% of A+,ID+,T+ patients showed an Hb increase of > 0.5 g/dl. The number of transfused red blood cell units was significantly lower in patients supplemented with iron (0 (0; 3)) compared to non-treated anaemic patients (1 (0; 4)) (p = 0.03). Patients with iron supplementation > 6 days before surgery achieved mobility 2 days earlier than patients with iron supplementation < 6 days. CONCLUSIONS: Intravenous iron supplementation increases Hb level and thereby reduces blood transfusion rate in elderly surgical patients with ID anaemia.

Long-term live imaging and multiscale analysis identify heterogeneity and core principles of epithelial organoid morphogenesis.

BACKGROUND: Organoids are morphologically heterogeneous three-dimensional cell culture systems and serve as an ideal model for understanding the principles of collective cell behaviour in mammalian organs during development, homeostasis, regeneration, and pathogenesis. To investigate the underlying cell organisation principles of organoids, we imaged hundreds of pancreas and cholangiocarcinoma organoids in parallel using light sheet and bright-field microscopy for up to 7 days. RESULTS: We quantified organoid behaviour at single-cell (microscale), individual-organoid (mesoscale), and entire-culture (macroscale) levels. At single-cell resolution, we monitored formation, monolayer polarisation, and degeneration and identified diverse behaviours, including lumen expansion and decline (size oscillation), migration, rotation, and multi-organoid fusion. Detailed individual organoid quantifications lead to a mechanical 3D agent-based model. A derived scaling law and simulations support the hypotheses that size oscillations depend on organoid properties and cell division dynamics, which is confirmed by bright-field microscopy analysis of entire cultures. CONCLUSION: Our multiscale analysis provides a systematic picture of the diversity of cell organisation in organoids by identifying and quantifying the core regulatory principles of organoid morphogenesis.

Patient Blood Management in intensive care patients.

PURPOSE OF REVIEW: Patients admitted to ICUs are a heterogeneous group, displaying multiple anaemia risk factors and comorbidities. Clinicians should therefore take all possible measures to identify modifiable risks. Patient Blood Management (PBM) is an approach promoting the timely application of evidence-based interventions designed to maintain patients own blood mass. RECENT FINDINGS: Within ICU-patients, anaemia is highly prevalent. Generally, anaemia is associated with impaired outcome and need of blood transfusion. Currently, with ICUs working at full capacity and the global blood reserves exhausted, the SARS-CoV-2 pandemic reinforces the need for PBM implementation. For instance, implementation of a comprehensive coagulation management and measures to avoid iatrogenic blood loss may prevent bleeding-associated complications and adherence to blood transfusion guidelines may reduce adverse events associated with transfusion. SUMMARY: Critically ill patients display various morbidities often requiring individualized treatment. PBM offers patient-centred measures to improve outcome any time during hospital stay.

Adjusting Current Hemoglobin Thresholds: A Way to Improve Outcome in Women Undergoing Major Surgery.

Background/Objective: In the perioperative setting, a suboptimal total hemoglobin (Hb) mass puts women and men at an unreasonable disadvantage. Anemia is an independent risk factor for transfusion, postoperative complications, and mortality. The Hb cut-off value for women was set at <12.0 g/dL by the World Health Organization (WHO) and has been rigorously debated for decades. The aim of this study was to elucidate the risk for postoperative complications in female patients with Hb levels < 12.0, 12.0-12.9, and ≥13.0 g/dL. Material and Methods: Single-center retrospective analysis of female patients undergoing major surgery. Results: In total, 6,516 patients ≥18 years of age had major surgery between 2018 and 2019 and 2,446 female patients were included in analysis. Mean age was 67.4 ± 16.6, 66.4 ± 15.6, and 64.5 ± 15.5 years in female patients with preoperative Hb levels <12.0, 12.0-12.9 and ≥13.0 g/dL, respectively. The transfusion rate of red blood cells (RBCs) was significantly higher in female patients with Hb <12.0 g/dL (53%) and with Hb 12.0-12.9 g/dL (31%) compared to female patients ≥13.0 g/dL (22%). Rates of pneumonia, acute kidney injury, and sepsis were significantly higher in patients with Hb <12.0 and 12.0-12.9 g/dL compared to patients with Hb ≥13.0 g/dL. Total length of hospital stay was significantly longer in female patients with Hb <12.0 g/dL than patients with Hb 12.0-12.9 g/dL and Hb ≥13.0 g/dL (10 days vs. 8 days). Conclusion: Taken together, our data show that Hb values below 12.9 g/dL are associated with increased probability of RBC transfusions and increased risk of postoperative complications. In addition, our results indicate that postoperative outcomes for women might be optimized by increasing cut-off values for anemia. The call to revise the anemia threshold for women by the WHO can no longer be disregarded.

Preoperative hemoglobin thresholds for survival equity in women and men.

Anemia affects humans throughout life, and is linked to higher morbidity and mortality. Unclear is whether hemoglobin values are equivalent between women and men. This study evaluates the association of preoperative hemoglobin levels with in-hospital mortality and estimates thresholds for survival equity between men and women. All adult patients undergoing surgery between 2010 and 2019 from 14 German hospitals were included in the study. Thresholds for survival equity were determined with generalized additive models. In total, 842,130 patients with a median in-hospital follow-up time of 7 days were analyzed. During follow-up 20,370 deaths occurred. Preoperative hemoglobin stratified in-hospital mortality (log-rank test p < 0.001) and was associated with mortality independently of demographic risk, surgical risk and health status. For each 1 g/dL reduction in preoperative hemoglobin, the odds of mortality increased by a factor of 1.22 (95% CI 1.21-1.23, p < 0.001). A preoperative hemoglobin threshold of 10.5 g/dL reflected equivalent risk for both male and female patients. Hemoglobin levels below 10.5 g/dL had higher risk of mortality for women than for men. The findings from this study aid evidence-based thresholds, inform anemia management and promote equitable care, thus enhancing patient outcomes.

How do I/we forecast tomorrow's transfusion? A focus on recipients' profiles.

Red blood cell (RBC) transfusion is a life-saving medical intervention and has an essential role in the management of surgical patients. However, blood donations and supply levels are decreasing, therefore there is an unmet need for the accurate prediction of the transfusion probability for surgical patients. Multiple methods have been established to predict the need for RBC transfusion. Maximum surgical blood order schedules are widely used in the clinical setting. However, these lists are not designed to accurately predict RBC utilization for an individual case as factors such as preoperative haemoglobin level, total body blood volume, comedications are not considered. Artificial intelligence and related technologies based on machine learning modelling are valuable alternatives to predict transfusion probability taking into account patient individual risk factors including among others comorbidities, laboratory parameters, use of oral anticoagulation, ASA score, surgeon's ID or applied blood saving measures. Overall, forecasting the need for a RBC transfusion can facilitate personalized medicine, quality assurance, decrease blood wastage, decrease costs, and increase patient safety. Furthermore, transfusion prediction models could facilitate blood management strategies before surgery.

Ultra-thin fluorocarbon foils optimise multiscale imaging of three-dimensional native and optically cleared specimens.

In three-dimensional light microscopy, the heterogeneity of the optical density in a specimen ultimately limits the achievable penetration depth and hence the three-dimensional resolution. The most direct approach to reduce aberrations, improve the contrast and achieve an optimal resolution is to minimise the impact of changes of the refractive index along an optical path. Many implementations of light sheet fluorescence microscopy operate with a large chamber filled with an aqueous immersion medium and a further inner container with the specimen embedded in a possibly entirely different non-aqueous medium. In order to minimise the impact of the latter on the optical quality of the images, we use multi-facetted cuvettes fabricated from vacuum-formed ultra-thin fluorocarbon (FEP) foils. The ultra-thin FEP-foil cuvettes have a wall thickness of about 10-12 µm. They are impermeable to liquids, but not to gases, inert, durable, mechanically stable and flexible. Importantly, the usually fragile specimen can remain in the same cuvette from seeding to fixation, clearing and observation, without the need to remove or remount it during any of these steps. We confirm the improved imaging performance of ultra-thin FEP-foil cuvettes with excellent quality images of whole organs such us mouse oocytes, of thick tissue sections from mouse brain and kidney as well as of dense pancreas and liver organoid clusters. Our ultra-thin FEP-foil cuvettes outperform many other sample-mounting techniques in terms of a full separation of the specimen from the immersion medium, compatibility with aqueous and organic clearing media, quick specimen mounting without hydrogel embedding and their applicability for multiple-view imaging and automated image segmentation. Additionally, we show that ultra-thin FEP foil cuvettes are suitable for seeding and growing organoids over a time period of at least ten days. The new cuvettes allow the fixation and staining of specimens inside the holder, preserving the delicate morphology of e.g. fragile, mono-layered three-dimensional organoids.