Blood management in intensive care medicine: CRIT and ABC – what can we learn?

In 284 US intensive care units the CRIT study (Anemia and blood transfusion in the critically ill – Current clinical practice in the United States) assessed allogeneic red blood cell (RBC) transfusion and outcome in 4892 patients. As in the former European ABC study (Anemia and blood transfusion in the critically ill), the mean pretransfusion hemoglobin was approximately 8.5 g/dl and RBC transfusions were independently associated with an increased mortality. These studies were purely observational and, therefore, despite the finest statistical models indicating that RBC transfusions were independently associated with a higher mortality, it remains possible that this adverse outcome is not due to a harmful effect of RBC transfusion in itself, but merely reflects the fact that transfused patients were sicker to start with. The definitive call is still out, but one mechanism by which RBC transfusion might be harmful now appears less likely; namely, storage lesion. In the CRIT study, mortality was not increased in patients receiving 'old' RBCs (>14 days stored) versus 'fresh' RBCs. The effect of leukoreduction could not be assessed since mainly nonleukoreduced RBCs were transfused. The evidence is mounting, however, that RBC transfusions are efficacious only when oxygen delivery is compromised. What can be done to diminish the use of RBC transfusions, its costs and side effects in intensive care medicine? There are two important options available today: decreasing blood loss for diagnostic purposes using pediatric sampling tubes, and establishing restrictive multidisciplinary transfusion guidelines and implementing them in daily clinical practice

Allogeneic blood transfusions: benefit, risks and clinical indications in countries with a low or high human development index

The risks associated with allogeneic red blood cell (RBC) transfusions differ significantly between countries with low and high human development indexes (HDIs). In countries with a low HDI, the risk of infection (HIV, HBV, HCV and malaria) is elevated. In contrast, in countries with a high HDI, immunological reactions (haemolytic transfusion reactions, alloimmunization and immunosuppression) are predominant. Therefore the overall risk associated with RBC transfusions in low HDI countries is much more significant than that in high HDI countries. In view of these risks, the limited efficacy of RBC transfusion and its high costs, this procedure should be used sparingly and rationally. Therefore RBC transfusion protocols adapted to the local situation are essential. Such protocols should distinguish between physiological and haemoglobin-based transfusion triggers. In countries with a high HDI, relative tachycardia and hypotension, despite normovolaemia, ST-segment changes suggestive of myocardial ischaemia and an Hb level 80 years and those with coronary artery or cerebrovascular disease. In countries with a low HDI, clinical signs of circulatory failure or myocardial ischaemia and an Hb level <5 g/dl can serve as transfusion guideline

Interactive Regulation of Dissolved Copper Toxicity by an Estuarine Microbial Community

Cultured marine microorganisms under copper stress produce extracellular compounds having a high affinity for copper (copper-complexing ligands). These ligands are similar in binding strength to those found in natural waters, but few studies have examined the relationship between copper, copper-complexing ligand concentrations, and natural microbial populations. A series of in situ experiments in the Elizabeth River, Virginia, revealed that an intact estuarine microbial community responded to copper stress by production of extracellular, high-affinity copper-complexing ligands. The rate of ligand production was dependent on copper concentration and resulted in a reduction of the concentration of free cupric ions, Cu2+, by more than three orders of magnitude during a 2-week period in one experiment. We believe that this interactive response to copper stress represents a feedback system through which microbial communities can potentially buffer dissolved Cu2+ ion concentrations, thereby regulating copper bioavailability and toxicity

Clinical effectiveness of fresh frozen plasma compared with fibrinogen concentrate: a systematic review

ABSTRACT: INTRODUCTION: Haemostatic therapy in surgical and/or massive trauma patients typically involves transfusion of fresh frozen plasma (FFP). Purified human fibrinogen concentrate may offer an alternative to FFP in some instances. In this systematic review, we investigated the current evidence for the use of FFP and fibrinogen concentrate in the perioperative or massive trauma setting. METHODS: Studies reporting the outcome (blood loss, transfusion requirement, length of stay, survival and plasma fibrinogen level) of FFP or fibrinogen concentrate administration to patients in a perioperative or massive trauma setting were identified in electronic databases (1995 to 2010). Studies were included regardless of type, patient age, sample size or duration of patient follow-up. Studies of patients with congenital clotting factor deficiencies or other haematological disorders were excluded. Studies were assessed for eligibility, and data were extracted and tabulated. RESULTS: Ninety-one eligible studies (70 FFP and 21 fibrinogen concentrate) reported outcomes of interest. Few were high-quality prospective studies. Evidence for the efficacy of FFP was inconsistent across all assessed outcomes. Overall, FFP showed a positive effect for 28% of outcomes and a negative effect for 22% of outcomes. There was limited evidence that FFP reduced mortality: 50% of outcomes associated FFP with reduced mortality (typically trauma and/or massive bleeding), and 20% were associated with increased mortality (typically surgical and/or nonmassive bleeding). Five studies reported the outcome of fibrinogen concentrate versus a comparator. The evidence was consistently positive (70% of all outcomes), with no negative effects reported (0% of all outcomes). Fibrinogen concentrate was compared directly with FFP in three high-quality studies and was found to be superior for > 50% of outcomes in terms of reducing blood loss, allogeneic transfusion requirements, length of intensive care unit and hospital stay and increasing plasma fibrinogen levels. We found no fibrinogen concentrate comparator studies in patients with haemorrhage due to massive trauma, although efficacy across all assessed outcomes was reported in a number of noncomparator trauma studies. CONCLUSIONS: The weight of evidence does not appear to support the clinical effectiveness of FFP for surgical and/or massive trauma patients and suggests it can be detrimental. Perioperatively, fibrinogen concentrate was generally associated with improved outcome measures, although more high-quality, prospective studies are required before any definitive conclusions can be drawn

Fluxes of Copper-Complexing Ligands from Estuarine Sediments

Most studies of the organic complexation of Cu in natural waters have focused on distributions and processes in the water column, where a significant fraction of Cu-complexing ligands may be biologically produced. We present direct evidence for a flux of Cu-complexing ligands from estuarine sediments, demonstrating that sediments are a significant, yet previously unrecognized source of the ligands. Fluxes of Cu-complexing ligands from Chesapeake Bay sediments range from 300 to 1,200 nmol m-2 d-1, exceeding fluxes of total dissolved Cu by 3-\u3e40-fold, suggesting that any Cu fluxing from the sediments is likely to be organically complexed. Our results indicate that benthic fluxes may supply from 10 to 50% of the standing stock of Cu-complexing ligands in Chesapeake Bay and suggest that such fluxes may strongly influence the biogeochemistry of Cu in shallow water environments and potentially in the ocean as a whole

Digital accessible knowledge: Mobilizing legacy data and the future of taxonomic publishing

No abstract available

Propofol decreases the axonal excitability in rat primary sensory afferents

AIMS: The aim of this present study was to investigate the changes of peripheral sensory nerve excitability produced by propofol. MAIN METHODS: In a recently described in vitro model of rodent saphenous nerve we used the technique of threshold tracking (QTRAC®) to measure changes of axonal nerve excitability of Aβ-fibres caused by propofol. Concentrations of 10μMol, 100μMol and 1000μMol were tested. Latency, peak response, strength-duration time constant (τSD) and recovery cycle of the sensory neuronal action potential (SNAP) were recorded. KEY FINDINGS: Our results have shown that propofol decreases nerve excitability of rat primary sensory afferents in vitro. Latency increased with increasing concentrations (0μMol: 0.96±0.07ms; 1000μMol 1.10±0.06ms, P<0.01). Also, propofol prolonged the relative refractory period (0μMol: 1.79±1.13ms; 100μMol: 2.53±1.38ms, P<0.01), and reduced superexcitability (0 μMol: -14.0±4.0%; 100μMol: -9.5±5.5%) and subexcitability (0μMol: 7.5±1.2%; 1000μMol: 3.6±1.2) significantly during the recovery cycle (P<0.01). SIGNIFICANCE: Our results have shown that propofol decreases nerve excitability of primary sensory afferents. The technique of threshold tracking revealed that axonal voltage-gated ion channels are significantly affected by propofol and therefore might be at least partially responsible for earlier described analgesic effects

Clinical review: Prothrombin complex concentrates - evaluation of safety and thrombogenicity (vol 15, pg 201, 2011)

Prothrombin complex concentrates (PCCs) are used mainly for emergency reversal of vitamin K antagonist therapy. Historically, the major drawback with PCCs has been the risk of thrombotic complications. The aims of the present review are to examine thrombotic complications reported with PCCs, and to compare the safety of PCCs with human fresh frozen plasma. The risk of thrombotic complications may be increased by underlying disease, high or frequent PCC dosing, and poorly balanced PCC constituents. The causes of PCC thrombogenicity remain uncertain but accumulating evidence indicates the importance of factor II (prothrombin). With the inclusion of coagulation inhibitors and other manufacturing improvements, today's PCCs may be considered safer than earlier products. PCCs may be considered preferable to fresh frozen plasma for emergency anticoagulant reversal, and this is reflected in the latest British and American guidelines. Care should be taken to avoid excessive substitution with prothrombin, however, and accurate monitoring of patients' coagulation status may allow thrombotic risk to be reduced. The risk of a thrombotic complication due to treatment with PCCs should be weighed against the need for rapid and effective correction of coagulopathy