Christophe Lelubre

Association between duration of storage of transfused red blood cells and morbidity and mortality in adult patients: myth or reality?

BACKGROUND: The duration of red blood cell (RBC) storage before transfusion may alter RBC function and, therefore, influence the incidence of complications.

Relationship between red cell storage duration and outcomes in adults receiving red cell transfusions: a systematic review

IntroductionThe duration of red blood cell (RBC) storage before transfusion may alter RBC function and supernatant and, therefore, influence the incidence of complications or even mortality.MethodsA MEDLINE search from 1983 to December 2012 was performed to identify studies reporting age of transfused RBCs and mortality or morbidity in adult patients.ResultsFifty-five studies were identified; most were single-center (93%) and retrospective (64%), with only a few, small randomized studies (eight studies, 14.5%). The numbers of subjects included ranged from eight to 364,037. Morbidity outcomes included hospital and intensive care unit (ICU) length of stay (LOS), infections, multiple organ failure, microcirculatory alterations, cancer recurrence, thrombosis, bleeding, vasospasm after subarachnoid hemorrhage, and cognitive dysfunction. Overall, half of the studies showed no deleterious effects of aged compared to fresh blood on any endpoint. Eleven of twenty-two (50%) studies reported no increased mortality, three of nine (33%) showed no increased LOS with older RBCs and eight of twelve (66%) studies showed no increased risks of organ failure. Ten of eighteen (55%) studies showed increased infections with transfusion of older RBCs. The considerable heterogeneity among studies and numerous methodological flaws precluded a formal meta-analysis.ConclusionsIn this systematic review, we could find no definitive argument to support the superiority of fresh over older RBCs for transfusion.

Red blood cell transfusion in the critically ill patient

Red blood cell (RBC) transfusion is a common intervention in intensive care unit (ICU) patients. Anemia is frequent in this population and is associated with poor outcomes, especially in patients with ischemic heart disease. Although blood transfusions are generally given to improve tissue oxygenation, they do not systematically increase oxygen consumption and effects on oxygen delivery are not always very impressive. Blood transfusion may be lifesaving in some circumstances, but many studies have reported increased morbidity and mortality in transfused patients. This review focuses on some important aspects of RBC transfusion in the ICU, including physiologic considerations, a brief description of serious infectious and noninfectious hazards of transfusion, and the effects of RBC storage lesions. Emphasis is placed on the importance of personalizing blood transfusion according to physiological endpoints rather than arbitrary thresholds.

A spatio-temporal model for spontaneous thrombus formation in cerebral aneurysms.

We propose a new numerical model to describe thrombus formation in cerebral aneurysms. This model combines CFD simulations with a set of bio-mechanical processes identified as being the most important to describe the phenomena at a large space and time scales. The hypotheses of the model are based on in vitro experiments and clinical observations. We document that we can reproduce very well the shape and volume of patient specific thrombus segmented in giant aneurysms.

The future of observational research and randomized controlled trials in red blood cell transfusion medicine

ABSTRACT Red blood cell (RBC) transfusions are commonplace in the intensive care unit (ICU) with at least 30% of ICU patients receiving a RBC transfusion at some point during their ICU stay. However, which patients should be transfused and what transfusion trigger(s) should be used remains unclear. RBC transfusion can be associated with adverse effects, but anemia is also associated with worse outcomes. Observational studies and randomized controlled trials (RCTs) have been conducted to try and answer some of the questions surrounding blood transfusion in critically ill patients. The need for blood transfusion and the benefit/risk ratio vary according to individual patient characteristics, including age and comorbidities, so large-scale RCTs in heterogeneous groups of patients may not be the most appropriate tool to investigate these issues; smaller RCTs in carefully defined patient groups may provide more useful information. Rigorous statistical analysis of large, carefully conducted observational studies will also help enhance our evidence-base in this field.

Preoperative Transfusions to Limit the Deleterious Effects of Blood Transfusions

O N a nearly daily basis, anesthesiologists are confronted with the practical dilemma that although anemia increases perioperative risk, transfusion of red blood cells is also associated with increased morbidity and mortality rates. Major complications of blood transfusion include errors in the type and cross-matching process, fluid overload, immunosuppressive effects, and infectious risks. These transfusion-associated problems may be particularly relevant in patients with cardiovascular comorbidities, and thus greater in patients undergoing cardiac surgery than in those undergoing other types of surgery. In cardiac surgical patients, preoperative anemia and perioperative transfusions are both risk factors for renal dysfunction, and anemia and blood transfusion are both associated with worse outcomes. The recent TRACS study, which randomized patients undergoing cardiac surgery to a liberal (target hematocrit 30%) or restrictive (target hematocrit 24%) perioperative transfusion strategy, demonstrated that blood transfusions could be restricted in cardiac surgery without impairing outcomes. In this issue of ANESTHESIOLOGY, Karkouti et al. propose an alternative paradigm of prophylactic erythrocyte transfusion as a means of reducing perioperative anemia, adding another dimension to the current debate of how to manage the anemia versus transfusion quandary in patients undergoing cardiac surgery. In the study by Karkouti et al. from their center in Toronto, 60 patients with moderate anemia (hemoglobin concentration 10–12 g/dl) were randomized to receive a blood transfusion 1 to 2 days before cardiac surgery with cardiopulmonary bypass, or to receive intraoperative transfusions as indicated. As expected, patients in the intervention arm became less severely anemic than control patients, and also received fewer blood transfusions. The rationale for the approach proposed by Karkouti et al. is that blood transfusions may increase the amount of circulating free iron, which could exacerbate the stress injury during surgery. Free iron catalyzes various oxidative reactions, such as the Haber-Weiss and Fenton reactions, resulting in generation of hydroxyl radicals and oxidative stress, which have been associated with organ damage. Cardiac surgery is associated with damaged erythrocytes in the cardiopulmonary bypass system, which are phagocytosed and the iron extracted by macrophages, resulting in increased iron load. Blood transfusions, especially if the transfused erythrocytes are old and damaged, provide an additional burden for the macrophages, further increasing the iron load. Normally, iron is bound to transferrin in the plasma, but with transferrin levels already decreased after major surgery and iron load increased, the capacity of transferrins to bind iron may be overwhelmed, so that more free iron is available. Moreover, the ability of macrophages to sequester iron is promoted by the hormone hepcidin, the metabolism of which is modified during cardiac surgery so that less hepcidin may be available, thus further increasing iron load. Intriguingly, increased urinary levels of hepcidin are associated with a lower risk of developing renal dysfunction after cardiac surgery. An excellent review of hepcidin’s role in iron metabolism has been published recently in ANESTHESIOLOGY. Transfusing patients 1 or 2 days before surgery may allow time for iron metabolism to stabilize before the effects of surgery come into play, thus keeping free iron levels at more acceptable, less damaging levels. This hypothesis is supported by results from the subgroup of 35 patients in the Karkouti study in whom iron studies were performed: Postoperative

Acute paraplegia and pulmonary edema after benzathine penicillin injection

Accidental intra-arterial injection is a potentially devastating complication of the intragluteal injection of benzathine penicillin. A 35-year-old woman developed after intramuscular injection of benzathine penicillin G acute paraplegia and noncardiogenic pulmonary edema. Noninvasive positive pressure ventilation was initiated with furosemide and corticosteroids. A magnetic resonance imaging scan showed findings consistent with syringomyelia and spinal cord ischemia at T9 through T10. Vascular injury may be the result of microemboli of the injected crystals of the penicillin salts. The mechanism of noncardiogenic pulmonary edema is perhaps an immunogically mediated one. At 2-year follow-up, she had no improvement in neurologic status. The deficit is considered permanent.

Host response biomarkers in sepsis: the role of procalcitonin.

Procalcitonin is the prohormone of calcitonin and present in minute quantities in health. However, during infection, its levels rise considerably and are correlated with the severity of the infection. Several assays have been developed for measurement of procalcitonin levels; in this article, we will briefly present the PCT-sensitive Kryptor(®) test (Brahms, Hennigsdorf, Germany), one of the most widely used assays for procalcitonin in recent studies. Many studies have demonstrated the value of procalcitonin levels for diagnosing sepsis and assessing disease severity. Procalcitonin levels have also been successfully used to guide antibiotic administration. However, procalcitonin is not specific for sepsis, and values need to be interpreted in the context of a full clinical examination and the presence of other signs and symptoms of sepsis.

Mechanisms and treatment of organ failure in sepsis

Sepsis is a dysregulated immune response to an infection that leads to organ dysfunction. Knowledge of the pathophysiology of organ failure in sepsis is crucial for optimizing the management and treatment of patients and for the development of potential new therapies. In clinical practice, six major organ systems — the cardiovascular (including the microcirculation), respiratory, renal, neurological, haematological and hepatic systems — can be assessed and monitored, whereas others, such as the gut, are less accessible. Over the past 2 decades, considerable amounts of new data have helped improve our understanding of sepsis pathophysiology, including the regulation of inflammatory pathways and the role played by immune suppression during sepsis. The effects of impaired cellular function, including mitochondrial dysfunction and altered cell death mechanisms, on the development of organ dysfunction are also being unravelled. Insights have been gained into interactions between key organs (such as the kidneys and the gut) and organ–organ crosstalk during sepsis. The important role of the microcirculation in sepsis is increasingly apparent, and new techniques have been developed that make it possible to visualize the microcirculation at the bedside, although these techniques are only research tools at present.Dysfunction of one or more organs is a common occurrence in patients with sepsis owing to microcirculatory alterations and cellular dysfunction. In this Review, the authors summarize knowledge of the mechanisms that underlie organ failure in sepsis and discuss how these insights are providing targets for the treatment of sepsis.Key pointsOrgan dysfunction is an integral part of sepsis, and the presence of unexplained organ dysfunction in a patient who is acutely ill should raise suspicion of the possible presence of sepsis and encourage an appropriate diagnostic examination.The pathophysiology of organ dysfunction in sepsis is similar for all organs and involves complex haemodynamic and cellular mechanisms.The first goal in the prevention of organ dysfunction in sepsis is to restore and maintain adequate oxygen delivery to cells.Single-organ dysfunction in sepsis is rare, and several organs are usually affected; mortality in patients with sepsis correlates with the number of organs that are affected.Most organ dysfunction in sepsis is reversible.Current treatment for sepsis aims to limit the development of organ dysfunction by providing rapid control of infection, haemodynamic stabilization and organ support when possible to ensure recovery of organ function.

Relationship between oxidative stress and erectile function.

Abstract The aim of this study was to investigate markers of inflammation and oxidative stress in the corpus cavernosum (CC) and to compare levels of inflammatory markers recorded in CC to venous blood from the arm to examine the potential impact of inflammatory parameters on erectile function and endothelial dysfunction in vitro. Ninety-seven patients with no complaint of erectile dysfunction (ED) at inclusion were prospectively included and completed the Erectile Function domain of the IIEF questionnaire. Several parameters, including lipids, MPO-dependent oxidised LDL (Mox-LDL), IL-8, IL-18, were measured. After RNA extraction, the expression of eNOS was analysed. A paired t-test was used for comparisons between arm and CC blood results. A two-way ANOVA was used to estimate the effects of IL-18 and IL-8 on the IIEF score. Mean patient age was 59 ± 14.5 years. IL-18, Mox-LDL, and Mox-LDL/ApoB levels were significantly increased in CC compared to arm blood. The IIEF score was correlated with IL-18 levels in the venous blood (R = −0.31, p = .003) and in the CC (R = −0.37, p = .004) and with IL-8 (R = −0.31, p = .009 and R = −0.28, respectively, p = .02). There was a significant effect with the IL-18 on IIEF potentiated by high serum IL-8 concentrations. IL-18 and Mox-LDL significantly decreased eNOS mRNA expression in human aortic endothelial cell line (HAEC). These preliminary results address the importance of inflammation in the CC and highlight a difference in marker concentrations between venous and CC blood. However, they do not show any difference in terms of clinical erectile score predictivity. Involvement of inflammatory cytokines isolated in CC in the genesis of ED requires further studies.