Evaluating Hemoglobin Thresholds for Blood Transfusions in Oncology Patients Admitted to the Intensive Care Unit.

BackgroundImmunoassays are crucial in the work-up of patients with suspected heparin-induced thrombocytopenia (HIT) and rapid tests have been recently developed. However, comparative data on diagnostic accuracy, reproducibility, and analytical costs of different immunoassays in clinical practice are limited.MethodsSamples of 179 consecutive patients evaluated for suspected HIT in clinical practice using a polyspecific enzyme-linked immunoabsorbent assay (GTI diagnostics; ELISA) and a rapid particle gel immunoassay (PaGIA), were additionally analysed with a IgG-specific chemiluminescent immunoassay (AcuStar HIT-IgG). Presence of HIT was defined as a positive functional heparin-induced platelet aggregation test. Diagnostic accuracy was determined for low, intermediate and high thresholds as previously established (ELISA: optical density 0.4, 1.3, and 2.0 respectively; PaGIA: positive/negative, titre of 4, titre of 32; AcuStar HIT-IgG: 1.0 U/ml, 2.8, 9.4) and reproducibility was assessed by repeated measurements. Costs of test determination were calculated taking reagents, controls, and working time of technicians according to Swiss health care system into account.ResultsData on PaGIA results were available for 171 patients (95.5%), ELISA for 144 patients (80.4%), and AcuStar HIT-IgG for 179 patients (100%). Sensitivity was above 95% for all assays at low and intermediate thresholds. Specificity increased with higher thresholds and was above 90% for all assays with intermediate and high thresholds. Specificity of AcuStar HIT-IgG (92.8%; 95% CI 87.7, 96.2) was significantly higher than PaGIA (83.0%; 95% CI 76.3, 88.5) and higher than ELISA (81.8%, 95% CI 74.2, 88.0) at low threshold (p<0.05). Reproducibility was adequate for all assays. Total costs per test were CHF 51.02 for ELISA, 117.70 for AcuStar HIT-IgG, and 83.13 for PaGIA.ConclusionsWe observed favourable diagnostic accuracy measures and a high reproducibility for PaGIA and AcuStar HIT-IgG. Implementation into 24-hours-service might improve patient care but the results must be confirmed in other settings and larger populations as well.

BackgroundBlood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established.MethodsIn this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization.ResultsWe analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups.ConclusionsAmong patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.)

Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis

BackgroundPlasma phosphorylated tau (p‐tau) has been used as a pre‐screening tool in clinical trials. Using plasma p‐tau for pre‐screening may help identify individuals more likely to be Aβ‐PET positive, reducing the number of PET scans needed at enrollment and decreasing recruitment costs. This study aims to evaluate the cost‐effectiveness of plasma p‐tau using liberal, intermediate, and conservative thresholds as pre‐screening tools in clinical trials across the AD spectrum.MethodWe studied 1,673 individuals across the AD spectrum from five cohorts: 707 cognitively unimpaired(CU) and 966 cognitively impaired(CI) with plasma p‐tau217 measures and Aβ‐PET. We tested three threshold methods:liberal(95% sensitivity), intermediate (Youden index), and conservative(95% specificity). The recruitment sample size was calculated based on p‐tau217 assay sensitivity, specificity, and Aβ positivity prevalence for a final sample size of 1,000 based on recent phase 3 trials.ResultThe intermediate threshold was the most cost‐effective, followed by the conservative. Surprisingly, the liberal threshold did not outperform the strategy of screening only with Aβ‐PET (Figure 1). Sample Size: In CU, pre‐screening with the intermediate threshold increased the initial sample size by 30% compared to the non‐pre‐screened group (n=5,000), while in CI, it increased by 28%(n=2,128). The number of Aβ‐PET scans was reduced by 64% in CU and 46% in CI. Trial Cost: In CU, the intermediate threshold reduced costs by 59% compared to no pre‐screening ($24M). In CI, costs were reduced by 39% compared to no pre‐screening ($9.4M). We tested the pre‐screening method using other p‐tau217 assays and epitopes and observed reductions in Aβ‐PET scans and recruitment costs for all p‐tau assays (Figure 2). Using our models and data, we developed a free online tool that allows users to calculate the sample size needed when using plasma p‐tau as a pre‐screening method for recruiting individuals for clinical trials. This tool will be released with our publication at AAIC (Figure 3).ConclusionOur study demonstrates that plasma p‐tau217 is an effective pre‐screening tool for clinical trials, with the intermediate threshold being the most cost‐effective for both CU and CI. This approach reduces the need for Aβ‐PET scans and optimizes recruitment time and costs, potentially enhancing the efficiency of clinical trial designs within the AD spectrum.

BackgroundPlasma phosphorylated tau (p‐tau) has been used as a pre‐screening tool in clinical trials. Using plasma p‐tau for pre‐screening may help identify individuals more likely to be Aβ‐PET positive, reducing the number of PET scans needed at enrollment and decreasing recruitment costs. This study aims to evaluate the cost‐effectiveness of plasma p‐tau using liberal, intermediate, and conservative thresholds as pre‐screening tools in clinical trials across the AD spectrum.MethodWe studied 1,673 individuals across the AD spectrum from five cohorts: 707 cognitively unimpaired(CU) and 966 cognitively impaired(CI) with plasma p‐tau217 measures and Aβ‐PET. We tested three threshold methods:liberal(95% sensitivity), intermediate(Youden index), and conservative(95% specificity). The recruitment sample size was calculated based on p‐tau217 assay sensitivity, specificity, and Aβ positivity prevalence for a final sample size of 1,000 based on recent phase 3 trials.ResultThe intermediate threshold was the most cost‐effective, followed by the conservative. Surprisingly, the liberal threshold did not outperform the strategy of screening only with Aβ‐PET (Figure 1). Sample Size: In CU, pre‐screening with the intermediate threshold increased the initial sample size by 30% compared to the non‐pre‐screened group (n = 5,000), while in CI, it increased by 28%(n = 2,128). The number of Aβ‐PET scans was reduced by 64% in CU and 46% in CI. Trial Cost: In CU, the intermediate threshold reduced costs by 59% compared to no pre‐screening($24M). In CI, costs were reduced by 39% compared to no pre‐screening($9.4M). We tested the pre‐screening method using other p‐tau217 assays and epitopes and observed reductions in Aβ‐PET scans and recruitment costs for all p‐tau assays (Figure 2). Using our models and data, we developed a free online tool that allows users to calculate the sample size needed when using plasma p‐tau as a pre‐screening method for recruiting individuals for clinical trials. This tool will be released with our publication at AAIC (Figure 3).ConclusionOur study demonstrates that plasma p‐tau217 is an effective pre‐screening tool for clinical trials, with the intermediate threshold being the most cost‐effective for both CU and CI. This approach reduces the need for Aβ‐PET scans and optimizes recruitment time and costs, potentially enhancing the efficiency of clinical trial designs within the AD spectrum.

To examine the accuracy of the World Health Organization immunological criteria for virological failure of antiretroviral treatment. Analysis of 10 treatment programmes in Africa and South America that monitor both CD4 cell counts and HIV-1 viral load. Adult patients with at least two CD4 counts and viral load measurements between month 6 and 18 after starting a non-nucleoside reverse transcriptase inhibitor-based regimen were included. WHO immunological criteria include CD4 counts persistently <100 cells/microl, a fall below the baseline CD4 count, or a fall of >50% from the peak value. Virological failure was defined as two measurements > or =10 0000 copies/ml (higher threshold) or > or =500 copies/ml (lower threshold). Measures of accuracy with exact binomial 95% confidence intervals (CI) were calculated. A total of 2009 patients were included. During 1856 person-years of follow up 63 patients met the immunological criteria and 35 patients (higher threshold) and 95 patients (lower threshold) met the virological criteria. Sensitivity [95% confidence interval (CI)] was 17.1% (6.6-33.6%) for the higher and 12.6% (6.7-21.0%) for the lower threshold. Corresponding results for specificity were 97.1% (96.3-97.8%) and 97.3% (96.5-98.0%), for positive predictive value 9.5% (3.6-19.6%) and 19.0% (10.2-30.9%) and for negative predictive value 98.5% (97.9-99.0%) and 95.7% (94.7-96.6%). The positive predictive value of the WHO immunological criteria for virological failure of antiretroviral treatment in resource-limited settings is poor, but the negative predictive value is high. Immunological criteria are more appropriate for ruling out than for ruling in virological failure in resource-limited settings.

The experiments analyze different forms of learning and 24-h retention in the field and in the laboratory in bees that accept sucrose with either low (≤3%) or high (≥30% or ≥50%) concentrations. In the field we studied color learning at a food site and at the hive entrance. In the laboratory olfactory conditioning of the proboscis extension response (PER) was examined. In the color learning protocol at a feeder, bees with low sucrose acceptance thresholds (≤3%) show significantly faster and better acquisition than bees with high thresholds (≥50%). Retention after 24 h is significantly different between the two groups of bees and the choice reactions converge. Bees with low and high acceptance thresholds in the field show no differences in the sucrose sensitivity PER tests in the laboratory. Acceptance thresholds in the field are thus a more sensitive behavioral measure than PER responsiveness in the laboratory. Bees with low acceptance thresholds show significantly better acquisition and 24-h retention in olfactory learning in the laboratory compared to bees with high thresholds. In the learning protocol at the hive entrance bees learn without sucrose reward that a color cue signals an open entrance. In this experiment, bees with high sucrose acceptance thresholds showed significantly better learning and reversal learning than bees with low thresholds. These results demonstrate that sucrose acceptance thresholds affect only those forms of learning in which sucrose serves as the reward. The results also show that foraging behavior in the field is a good predictor for learning behavior in the field and in the laboratory.

Objective:To investigate the prevalence of key endodontic pathogens and their association with the clinical features and the cause of apical periodontitis.Methods:The study population included patients referred to Khartoum Dental teaching Hospital, Sudan for endodontic treatment. Samples were collected from single-rooted teeth carious or traumatised teeth with clinical and radiographic evidence of apical periodontitis. The endodontic pathogens Porphyromonas endodontalis, Fusobacterium nucleatum and Treponema denticola were quantified by real time polymerase chain reaction (qPCR). The prevalence of each species was identified at both a low detection threshold (>50 bacteria) and a high detection threshold (>1000 bacteria).Results:75 patients (mean age 30.1 yrs SD 10.1) were included in the analysis. The most prevalent bacterium at both the low and high threshold was F. nucleatum followed by T. denticola at the low threshold and P. endodontalis at the high threshold. There was no association with symptoms at the low detection threshold, but at high threshold P. endodontalis was associated with swelling, adjusted odds ratio (OR), 9.32 95%CI 1.11- 78.66, P=0.04. All species were more prevalent in apical periodontitis due to caries only at the low detection threshold, OR=5.01 (P=0.006) for T. denticola; 4.84 (P=0.01) for F. nucleatum; and 3.62 (P=0.03) for P. endodontalis.Conclusion:There was a high prevalence of the F. nucleatum, T. denticola and P. endodontalis in apical periodontitis associated with caries. None of these bacterial were associated with pain but the presence of P. endodontalis at high levels was associated with swelling.

Infants of very low birthweight frequently receive red blood cell transfusions during their primary hospital stay. Generally, this is guided by predetermined haemoglobin or haematocrit thresholds according to a protocol or as prompted by clinical situations, including critical illness or surgery. Recommendations advocate maintaining higher thresholds in the early weeks when the risk of major morbidity is highest, while permitting lower thresholds after this time. In truth, clinicians worry about the potential effect of chronic anaemia on neurodevelopmental outcomes, as well as the risk of transfusion-related complications in the immature host. Clinical trials have reflected this practice by comparing haemoglobin levels adjusted for critical illness, comparing transfusion algorithms that use fixed differences between haemoglobin thresholds, with both thresholds progressively lowered across postnatal age. This is an update of a review first published in 2011. To evaluate the effect of lower (restrictive) compared with higher (liberal) haemoglobin thresholds for transfusion, with or without adjustment for age and critical illness with either fixed or variable transfusion volume, on mortality or later neurodevelopmental outcomes assessed in later infancy at approximately two years postmenstrual age, or the number of transfusions in very low birthweight infants. Searches were conducted in January 2024 in CENTRAL, MEDLINE, Embase, CINAHL, Epistemonikos, and trial registries. We searched the reference lists of related systematic reviews and trials. We selected randomised controlled trials (RCTs) of lower or restrictive haemoglobin/haematocrit thresholds compared with liberal or higher haemoglobin/haematocrit thresholds for transfusion in low birthweight infants within three days of birth. We used standard Cochrane methods. Our main outcomes were a combined outcome of death or neurodevelopmental impairment, all-cause mortality, and the number of transfusions per infant. We expressed our results using mean difference (MD), standardised mean difference (SMD), risk ratio (RR), and risk difference (RD) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence. Six trials, enrolling 3451 infants, compared transfusion strategies utilising a lower (restrictive) haemoglobin threshold compared to a higher (liberal) haemoglobin threshold. The transfusion thresholds used in these trials reflected prevailing clinical practice at the time of study design. For comparative purposes, they have been labelled as 'restrictive' and 'liberal'. The trials were similar in design, although each used slightly different transfusion algorithms and intervention thresholds. The three larger trials also conducted later neurosensory assessments. The number of infants included in outcome calculations varies across in-hospital versus post-discharge outcomes, assessment methods, and exclusion criteria, and our analysis uses the denominators reported in the original publications. Overall, utilising a lower compared to a higher haemoglobin transfusion threshold results in little or no difference in the combined outcome of death or neurodevelopmental impairment at 18 to 26 months postmenstrual age (RR 1.02, 95% CI 0.95 to 1.09; I2 = 55%; RD 0.01, 95% CI -0.03 to 0.04; 3 studies, 3041 infants; high-certainty evidence). Mortality at 18 to 26 months was also not different (RR 0.99, 95% CI 0.83 to 1.17; I2 = 0%; RD -0.00, 95% CI -0.03 to 0.02; I2 = 0%; 3 studies, 3186 infants; high-certainty evidence). Infants allocated to the restrictive threshold may receive fewer transfusions during the primary hospital stay (mean difference in transfusion number per infant -1.05, 95% CI -1.26 to -0.84; I2 = 84%; 6 studies, 3451 infants; low-certainty evidence). The trials comparing lower or restrictive versus higher or liberal haemoglobin thresholds for transfusion show little to no difference in important outcomes at hospital discharge and at the time of later neurodevelopmental follow-up. The use of restrictive, as compared to liberal, haemoglobin or haematocrit transfusion thresholds in these trials in infants of very low birthweight results in modest reductions in transfusion exposure and haemoglobin levels. The safety of haemoglobin levels below these lower limits has not been evaluated and should only be considered in the context of randomised controlled trials.

In this paper, we present a novel approach to obtain any desired intermediate threshold voltage in a dual V/sub T/ process. The intermediate threshold voltages are achieved by combining low and high threshold voltages in a device. We show that this combination can be easily implemented in layouts with negligible design and manufacturing overhead. Our results show that power-delay characteristics of the achieved intermediate thresholds match well with the ideal (but impractical) scenario that assumes that all intermediate thresholds are available in the technology.

In this paper, we present a novel approach to obtain any desired intermediate threshold voltage in a dual VT process. The intermediate threshold voltages are achieved by combining low and high threshold voltages in a device. We show that this combination can be easily implemented in layouts with negligible design and manufacturing overhead. Our results show that power-delay characteristics of the achieved intermediate thresholds match well with the ideal (but impractical) scenario that assumes that all intermediate thresholds are available in the technology.

HIGH AND LOW THRESHOLD FOR STARTLE REACTIVITY ASSOCIATED WITH PTSD SYMPTOMS BUT NOT PTSD RISK: EVIDENCE FROM A PROSPECTIVE STUDY OF ACTIVE DUTY MARINES.

Studies in alert preparations have demonstrated that ocular motoneurons exhibit a phasic–tonic firing rate related to eye velocity and position, respectively. The slopes of these relationships are higher in motoneurons with higher recruitment threshold and have been proposed to depend upon synaptic input. To investigate this hypothesis, motoneurons of the rat oculomotor nucleus were recorded in a brain slice preparation in control conditions and during glutamate (5 μm) application to the bath. Glutamate did not affect membrane potential or input resistance, but produced a decrease in rheobase and depolarization voltage as a function of the current needed for generating a maintained repetitive discharge (recruitment threshold current). In addition, glutamate compressed the range of recruitment threshold current (0.1–0.4 nA) as compared to the control (0.15–0.7 nA). Glutamate exposed motoneurons showed an increase in the tonic frequency gain and the peak frequency. Such increments depended on the recruitment threshold current and the last recruited motoneurons almost doubled the tonic frequency gain (35.2 vs. 57.9 spikes s(−1) nA(−1)) and the peak frequency (52.4 vs. 102.6 spikes s(−1)). Finally, glutamate increased the spike frequency adaptation due to a significant increase in the phasic firing component as compared to the tonic one. In conclusion, glutamate modulates tonic and phasic discharge properties as a function of the recruitment threshold current and, presumably, motoneuron size. These findings contribute to understand the link between cellular functions and motoneuron discharge during oculomotor behaviour.

This document aims to summarize the current literature guiding the use of red cell transfusion in critically ill patients and provides recommendations to support clinicians in their day-to-day practice. Critically ill patients differ in their age, diagnosis, co-morbidities, and severity of illness. These factors influence their tolerance of anaemia and alter the risk to benefit ratio of transfusion. The optimal management for an individual may not fall clearly within our recommendations and each decision requires a synthesis of the available evidence and the clinical judgment of the treating physician. This guideline relates to the use of red cells to manage anaemia during critical illness when major haemorrhage is not present. A previous British Committee for Standards in Haematology (BCSH) guideline has been published on massive haemorrhage (Stainsby et al, 2006), but this is a rapidly changing field. We recommend readers consult recent guidelines specifically addressing the management of major haemorrhage for evidence-based guidance. A subsequent BCSH guideline will specifically cover the use of plasma components in critically ill patients. The World Health Organization (WHO) defines anaemia in men and women as a haemoglobin (Hb) <130 and <120 g/l, respectively, (Beutler & Waalen, 2006; WHO, 2011) and severe anaemia as <80 g/l (Guralnik et al, 2004; WHO, 2011). Anaemia is highly prevalent among the critically ill; 60% of patients admitted to intensive care units (ICU) are anaemic and 20–30% have a first haemoglobin concentration (Hb) <90 g/l (Hebert et al, 2001a; Vincent et al, 2002; Corwin, 2004; Walsh et al, 2004a, 2006a). After 7 d 80% of ICU patients have an Hb <90 g/l. Cohort studies indicate a strong association between anaemia and inferior outcomes, especially amongst those with cardiovascular disease (Carson et al, 1996; Hebert et al, 1997; Kulier et al, 2007; Wu et al, 2007). Haemodilution, blood loss and blood sampling are the most important initial contributors to anaemia in critical care. Impaired erythropoiesis secondary to inflammation is increasingly important with prolonged illness (Walsh & Saleh, 2006). Depending upon casemix, 30–50% of ICU patients receive red cell (RBC) transfusions (Walsh et al, 2004b; Walsh & Saleh, 2006). Ten percent of all RBCs transfused nationally are given in general ICUs (Walsh et al, 2004a). Studies suggest that only 20% of transfusions are to treat haemorrhage (Vincent et al, 2002); the majority are given for anaemia. Mean blood consumption ranges from 2 to 4 units per admission. The writing group was selected by the BCSH Transfusion Task Force with input from the Intensive Care Society to provide expertise in relevant physiology, pathophysiology, general intensive care and specific subgroups of critically ill patients. We did not undertake a formal systematic literature review. We agreed a priori a range of issues relating to general intensive care patients, and specific sub-groups of patients with relevant co-morbidities. These were subcategories relating to general intensive care, weaning from mechanical ventilation, ischaemic heart disease (IHD), sepsis, and neurocritical care. A MEDLINE database search was conducted from its inception to December 2011 using a range of broad search terms relating to red cell transfusion, critical care, and intensive care. The search strategy is available from the authors on request. The search yielded 4856 papers. These were sub-divided according to the pre-defined subcategories and reviewed by sub-group members allocated to each part of the guideline. At least two group members contributed to each subcategory section. Using this approach a total of 508 relevant papers were extracted and reviewed in full. Recent systematic reviews and guidelines produced by other groups were also reviewed where available. The quality of evidence was judged by predefined Grades of Recommendation, Assessment, Development and Evaluation (GRADE) criteria (Jaeschke et al, 2008). Strong recommendations, grade 1, are made when the group was confident that the benefits do or do not outweigh the harm and burden of cost of a treatment. Where the magnitude of benefit is less certain, grade 2, or suggested recommendations are made. The quality of evidence is rated as A – high quality randomized control trials, B – moderate, C – low, D – expert opinion only. The GRADE system is summarized in Table 1. Global oxygen delivery (DO2) from the heart to tissues is the product of arterial O2 content and cardiac output (Barcroft, 1920). Arterial O2 content is calculated by the O2 carried by haemoglobin plus the dissolved O2; in health >99% of O2 is transported bound to haemoglobin. Tissue hypoxia can occur during critical illness as a result of problems at all stages in the O2 cascade, including airway and pulmonary disease, inadequate cardiac function and reduced or maldistributed microvascular flow. Anaemia reduces O2 carrying capacity and there is strong biological plausibility in the belief that it causes tissue hypoxia. When tissue DO2 falls, O2 supply is maintained by compensatory mechanisms that increase O2 extraction. However, there is a critical DO2 at which these compensatory mechanisms are overwhelmed and O2 transport becomes directly proportional to O2 supply. In such circumstances, severe tissue hypoxia is much more likely to occur. Studies using normovolaemic haemodilution indicate that young adults can maintain an O2 supply at Hb concentrations of 40–50 g/l by increasing cardiac output and O2 extraction (Weiskopf et al, 2006). The heart and brain have high O2 extraction ratios, which limits these compensatory mechanisms. In addition, O2 consumption is increased in the critically ill. Therefore anaemia may be less well tolerated during critical illness. An assessment of the risk to benefit ratio of transfusion to improve O2 carrying capacity is a key consideration to optimise patient outcomes. The strongest evidence guiding transfusion policy in adult critically ill patients comes from the Transfusion Requirements In Critical Care (TRICC) study (Hebert et al, 1999). Patients with a Hb ≤90 g/l were randomized to either a relatively high Hb transfusion trigger of <100 g/l with a target of 100–120 g/l, the ‘liberal’ group, or a lower trigger of <70 g/l with a target of 70–90 g/l (the ‘restrictive’ group). Mortality was compared at 30 and 60 d, and a range of secondary outcomes compared. The restrictive group received 54% fewer units of blood and 33% received no blood transfusions in the ICU, whereas all of the liberal group were transfused. Thirty-day mortality in the liberal group was typical of general ICU populations (23·3%), but there was a non-significant trend towards lower mortality for the restrictive group (18·7%, P = 0·11). In two pre-defined subgroups, younger patients (aged < 55 years) and patients with lower illness severity [Acute Physiology and Chronic Health Evaluation (APACHE) II score < 20], the risk of death during 30-d follow up was significantly lower with the restrictive strategy. For patients aged <55 years those in the restrictive group had a 5·7% mortality vs. 13·0% for those in the liberal group [95% confidence interval (CI) for the absolute difference 1·1–13·5%; P = 0·028]. Similarly, for patients with an APACHE II score < 20, those in the restrictive group had an 8·7% mortality vs. 16·1% for the liberal group (95% CI for the absolute difference: 1·0–13·6%; P = 0·03). These differences represented a number needed to treat to benefit from restrictive over liberal transfusion of about 13 patients for these sub-groups. Overall, there were also lower rates of new organ failures in the restrictive group and a trend towards higher rates of Acute Respiratory Distress Syndrome in the liberal group (7·7% vs. 11·4%). These findings support using transfusions to maintain a Hb of 70–90 g/l. Concerns about the applicability of these results include the introduction of leucodepletion of red blood cells (RBCs), the storage age of RBCs, and risk of selection bias; few patients with cardiac disease were enrolled and there was a high clinician refusal rate. The results of the TRICC study have been corroborated by two recent studies. The Transfusion Requirements After Cardiac Surgery (TRACS) study found no difference in a composite end-point of 30-d mortality and severe comorbidity in cardiac patients prospectively randomized to a liberal or restrictive transfusion strategy (Hajjar et al, 2010). Most recently the ‘FOCUS’ (Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair) study of liberal or restrictive transfusion in high-risk patients after hip surgery showed no difference in mortality or mobility in the group assigned to the restrictive transfusion strategy (Carson et al, 2011). Importantly, although patients in the FOCUS trial were not critically ill, they were elderly and had a high prevalence of cardiovascular disease. Taken together the recent literature consistently shows no clear advantage with a liberal transfusion strategy. A suggested approach to transfusion in critical care is summarised in Fig 1. Critically ill patients do not generate a physiological increase in erythropoietin concentration in response to anaemia (Corwin et al, 1999, 2002, 2007; Hobisch-Hagen et al, 2001; Corwin, 2004; Shander, 2004; Hebert & Fergusson, 2006; Belova & Kanna, 2007; Arroliga et al, 2009; Bateman et al, 2009). Several trials have evaluated the efficacy and effectiveness of erythropoietin administration in critically ill patients. Methodological variations including different patient populations, and varying dosage regimens of both erythropoietin and iron therapy makes interpretation of these trials complicated. It appears on balance that a combination of iron supplementation and erythropoietin therapy can modestly decrease transfusion requirements, but the benefits become negligible when a transfusion trigger of 70 g/l is used (Corwin et al, 2007). No difference in patient outcomes has been demonstrated, except for a possible decrease in mortality among trauma patients. Erythropoietin therapy increases deep vein thrombosis, especially when prophylaxis is not used. Erythropoietin is not licenced for use in anaemic critically ill patients. The inflammatory response complicates the interpretation of iron indices in critical illness (Walsh & Saleh, 2006). Tests of iron status typically demonstrate an increased ferritin concentration whilst transferrin levels, the serum iron-to-iron binding ratio and transferrin saturation are decreased. Iron is shifted into macrophages resulting in a functional iron deficiency similar to the anaemia of chronic disease. Evidence of absolute iron deficiency is absent in most patients, and patients do not respond to iron supplementation alone (Walsh et al, 2006b; Munoz et al, 2008). There are no large randomized trials of iron monotherapy in critically ill patients, and excess iron may increase susceptibility to infection (Maynor & Brophy, 2007). The biochemical characteristics of anaemia in the critically ill are summarized in Table 2. Blood sampling contributes substantially to iatrogenic anaemia during critical illness (Smoller & Kruskall, 1986; Corwin et al, 1995; Zimmerman et al, 1997). Studies examining the magnitude of blood loss associated with routine phlebotomy indicate typical daily blood loss of approximately 40 ml (Foulke & Harlow, 1989; Fowler & Berenson, 2003; MacIsaac et al, 2003; Corwin, 2005; Chant et al, 2006; Harber et al, 2006; Sanchez-Giron & Alvarez-Mora, 2008). Available evidence suggests that blood conservation devices are infrequently used in the ICU, although few recent studies or surveys have been published (O'Hare & Chilvers, 2001). Several studies have assessed the impact of these devices. Two showed a significant reduction in blood loss, but without an effect on anaemia or RBC use (Foulke & Harlow, 1989; MacIsaac et al, 2003; Mukhopadhyay et al, 2010). One study (Mukhopadhyay et al, 2010) showed a reduction in the severity of anaemia and reduced RBC use with the Venous Arterial blood Management Protection (VAMP) system (Edwards Lifesciences, Irvine, CA, USA). Use of this device was associated with decreased requirements for RBC transfusion (control group 0·131 units vs. active group 0·068 units RBC/patient/d, P = 0·02). The intervention group also had a smaller reduction in Hb during ICU stay, 14·4 ± 20·8 vs. 21·3 ± 23·2 g/l; P = 0·02 (Mukhopadhyay et al, 2010). No cost-effectiveness evaluations of these systems in routine practice have been published. The use of small volume paediatric sampling bottles has also been consistently associated with reduced phlebotomy-related blood loss, without affecting assay quality (Harber et al, 2006; Sanchez-Giron & Alvarez-Mora, 2008). The need to ensure RBC transfusion is used only where appropriate is emphasized by concerns about adverse consequences (Fig 1). An increasing body of laboratory and clinical research has raised the possibility that stored RBCs have harmful effects, although the clinical consequences remain to be defined. Most cohort studies show associations between transfusion and adverse patient outcomes, including death, organ infection and prolonged & Corwin, 2008). However, the of in these studies is The of transfusion in the critically ill include those to all blood transfusions in and those more specific to individual blood components in The key of administration of blood are summarized in the BCSH for the of Blood et al, 2009). In critically ill patients, and are relevant et al, 2005; et al, et al, et al, 2007). adverse or to transfusion be and to risk the of Transfusion group and the and the Blood and defines as with pulmonary increased blood and evidence of a balance after a blood transfusion et al, 2010). the of is to the of a A large study the of in critically ill patients, the as the of pulmonary within of transfusion with a ratio of or of on on a in the of et al, The different criteria used in these studies may for the differences in varying from in units of RBCs to the et al, which of to RBCs, but only as highly is as the of pulmonary within of transfusion with a ratio of in on a in the of was first in but did not receive more transfusion support et al, It is to and can occur after transfusion of or et the of as in in Blood in are typically women have during Blood Transfusion have a policy of plasma from which has reduced the of et al, 2009). When be a suggested is summarized in Table Cohort studies have the between the age of blood and clinical outcomes, including and of these studies is of the problems of and also of control of the RBC storage but not studies have found associations between the transfusion of RBCs and adverse clinical outcomes et al, & 2001; et al, 2002; et al, et al, 2011). There are no randomized trials RBCs with either RBCs or are in et al, 2011). storage are on RBCs function within of transfusion into the The of storage from to d between ICU patients receive RBCs stored for in part blood RBCs as they to be transfused after RBC storage results in that O2 and decreased increased to of in the also have adverse effects, especially in RBCs et al, 2006). is the for to the ICU in the for of et al, 2006), with mortality from to et al, 2001). is associated with tissue DO2 a range of including cardiac function and of microvascular flow. The physiological for using blood transfusions is to in capacity in anaemic patients. Tissue hypoxia is during the stages of include and cardiovascular The is to a DO2 and tissue O2 Evidence of benefit from RBC transfusion in comes from a study of et al, 2001). groups in the study received and to a and arterial The therapy group were during the first of by the oxygen saturation In where the was patients received blood transfusions to maintain a of to increase cardiac output et al, 2001). This intervention decreased the absolute risk of death in by vs. One major difference between the groups was the use of blood vs. this was a intervention it is to clinical benefit to a However, when patients are anaemic and there is evidence of inadequate DO2 during sepsis, a target Hb of g/l is In sepsis, oxygen saturation or concentration are with the of tissue hypoxia although this may not be the for patients with more clinical trials are the of therapy in The evidence for RBC transfusions in patients during the stages of critical illness resulting from is The use of RBC transfusion and to for DO2 has been et al, et al, evidence suggests that using RBC transfusions to a Hb higher 70–90 g/l has no clinical benefit the patient has organ the A of patients with severe infection in the TRICC trial to show benefit from liberal transfusion, with more in the transfused group restrictive group vs. liberal group Hebert et al, 1999). Cohort studies have also the association between RBC transfusion and clinical outcomes in patients. Studies carried the introduction of leucodepletion associations between RBC transfusion and higher whereas those after leucodepletion have lower the possibility that this may influence the risk to benefit of transfusion in these patients (Hebert et al, Vincent et al, 2002, Corwin et al, trials are restrictive liberal transfusion practice for patients with transfusion practice when a patient with critical illness a of severe during an ICU stay, such as or is – no trials are available to management in this these clinicians use in available physiological of O2 such as and together with clinical to transfusion practice. evidence not support transfusion to a Hb g/l. DO2 is from the blood and the arterial O2 brain factors to including raised of and of The tissues for a fall in DO2 by increasing their oxygen extraction ratio but this compensatory has limits and brain tissue with a high is to and secondary of brain tissue O2 that is consistently associated with outcomes brain and DO2 to is to the management of critically ill patients. anaemia is in patients admitted to the ICU brain the of the to maintain DO2 increasing the increases O2 carrying there is an between and blood and high have been to and may to et al, 2006). There are few studies that have to the optimal in critically ill patients and current is from studies and expert the use of a restrictive transfusion strategy may improve outcomes in most critically ill it these findings can be to neurocritical care patients (Hebert et al, Vincent et al, 2002; Corwin et al, There is evidence that blood transfusion in anaemic patients with brain and transfusion appears to be associated with outcomes in studies. The evidence is in the of brain haemorrhage and ischaemic is a major of secondary et al, 2009). of are of in these patients et al, et al, et al, of DO2 and of is et al, 2002; et al, 2002; et al, 2008). to maintain on and the of raised The has published guidelines on the management of the 2007). These guidelines no on the optimal Hb target to A number of studies suggest that anaemia is associated with outcomes et al, 2001; et al, 2001; et al, 2004; et al, 2006; et al, Sanchez-Giron & Alvarez-Mora, et al, but the association of anaemia with mortality is not a et al, 2006; et al, 2007). RBC transfusion in most anaemic patients with the is small and appears to decrease in patients transfusion et al, 2005; et al, 2006; et al, 2009). It has been that this in clinical effect may be to the storage age of but this et al, 2008). The influence of RBC transfusion on the of is Transfusion is associated with but in cohort studies this be to et al, 2006; et al, 2008). A of the TRICC which patients with to severe suggested no significant in mortality in patients randomized to a liberal 100–120 as compared to restrictive 70–90 transfusion strategy (Hebert et al, et al, 2006). this suggests a restrictive transfusion strategy may be in this group of patients. The approach to the management of a combination of to the and the blood brain including RBC transfusion to maintain a Hb g/l; a small study has suggested outcomes using this but the use of this et al, In there is evidence to an evidence-based on the optimal Hb Anaemia is consistently associated with in patients with and it is transfusion et al, 2007; et al, 2006; et al, 2008). transfusion DO2 in anaemic patients with it may decrease brain tissue in et al, Transfusion has been associated with reduced mortality in two studies et al, 2009; et al, 2011). A small randomized in which patients with were randomized to a Hb target of either or g/l, has suggested only a trend towards secondary outcomes, reduced and rates of functional with restrictive transfusion, but large randomized studies are studies have suggested an association between RBC transfusion and et al, 2004; et al, 2005; et al, et al, 2008). a of approximately has been used in combination with and in the and of et al, 2006). studies the efficacy of therapy are and it is reduced blood reduced Hb are for the benefits et al, 2010). The optimal Hb in patients with has not been defined. It the use of RBC transfusion outcomes. studies in patients with ischaemic suggest that the effect of on is with both high and Hb associated with et al, 2003; et al, 2008). high to and reduced have to show significant benefit from haemodilution 2002; et al, An study examining in patients with ischaemic suggests that DO2 is with a of a similar range to that in et al, & study of patients with ischaemic that the most outcomes in patients with of approximately et al, The impact of transfusion in anaemic patients admitted to the ICU ischaemic has not been There is evidence to recommend a specific lower Hb target transfusion in patients admitted to neurocritical care ischaemic Anaemia is a risk for adverse cardiovascular and death for patients with and chronic (Hajjar et al, et al, 2011). It is RBC transfusion this during especially to the which has O2 The of the system is that the increased O2 requires an increase in blood flow. Anaemia the O2 content of blood per volume and disease blood these factors increase the risk of critical cardiac can also be significantly increased as a result of the increased O2 requirements, and may blood flow. There biological plausibility that anaemia is tolerated by patients with Two cohort studies of and critically ill patients found an association between anaemia and mortality in patients with (Carson et al, 1996; Hebert et al, 1997). In both studies a Hb g/l was associated with excess These were corroborated by associations between anaemia and higher mortality in general populations, among patients et al, 2001; Kulier et al, 2007). In the TRICC there were no excess adverse cardiac in the patients with a restrictive transfusion strategy. The of patients a was higher in the liberal group vs. P = and cardiac adverse were also higher vs. P < In a of patients were as from at there was a non-significant trend towards lower 30-d mortality among patients with the liberal strategy in 30-d (95% CI to these suggested possible benefit from liberal blood use in patients with but the sub-group was In the recently published FOCUS study in elderly patients hip which compared a liberal strategy < with a restrictive strategy anaemia or Hb < found no difference in mortality or cardiovascular of patients (Carson et al, 2011). Similarly, the study compared similar liberal and restrictive transfusion in patients cardiac surgery and found no differences in 30-d mortality or severe between the groups (Hajjar et al, 2010). these trials were not in critically ill patients, both patients at high risk of There are no large randomized trials of transfusion for patients with A recent small study in patients compared liberal and transfusion in patients with an et al, 2011). The of death, or of cardiac in patients in the liberal group and in the vs. P = The majority of our current evidence is on the physiological for a higher blood O2 and from cohort studies. patients an have outcomes (Guralnik et al, An the use of together with blood loss during have increased the prevalence of anaemia among patients with Wu et approximately patients in the database aged years with After for transfusion 30-d mortality for patients with a < the benefit of transfusion among those patients with most severe anaemia et al, 2001). In cohort were from trials of for et al, 2004; et al, anaemia was associated with patient outcomes, these studies found no benefit from transfusion at lower and transfusion was associated with outcomes. Wu et compared the impact of transfusion in patients with and In this anaemia < was associated with increased mortality in and RBC transfusions were associated with decreased for anaemia was associated with increased but RBC transfusions were associated with increased recent cohort studies also did not clinical benefit from transfusion when the Hb was g/l et al, et al, 2009). cohort studies are by and the quality of evidence is of from mechanical and to improve the and of weaning are of they are likely to be both and cost Depending on up to of patients and to at 30 d 1995; et al, is associated with a increase in mortality et al, 1997; & 1997). can be associated with an in O2 supply and weaning DO2 reduced by a lower Hb and a lower cardiac output increases in O2 occur to the of (Walsh & 2009). Two studies have an association between anaemia and a to 2005; DO2 by increasing the Hb using transfusion arterial O2 content and is the physiological of using RBC transfusion to et and chronic pulmonary disease patients and that transfusion reduced the of in the A patient by the suggested transfusion may be in weaning anaemic patients et al, However, studies in a more group of patients have either no benefit from transfusion, or suggested that it is associated with a et al, Hebert et al, & 2002; et al, The two studies are of other studies – TRICC and Hebert et al, Corwin et al, provide evidence they were not to weaning or the effect of RBC transfusion on weaning and suggested that transfusion was associated with an increased of mechanical Available evidence not strong recommendations specific to transfusion and weaning from mechanical ventilation, but do not support the use of a liberal transfusion strategy. Anaemia is prevalent in the critically ill and is associated with adverse outcomes. At there are no or to RBC transfusion for rapidly increasing the Hb and O2 carrying The and that is available consistently suggests that transfusion of RBCs when the Hb is within the 70–90 g/l range has no effect on clinical outcomes either in the general critical care or in specific patient sub-groups for a physiological for reduced anaemia tolerance Importantly, it is the of effectiveness of blood transfusions in this is anaemia not outcomes or the associated with current stored red cell transfusions physiological In the large well randomized control trials are to the risk to benefit balance of RBC transfusion in a range of resulting in critical illness. the and in these guidelines is to be and at the of to the the British Society for Haematology the for the content of these of the literature used to the guideline and provide the key recommendations cohort patients blood randomized control patients Patients randomized to either units d or units d Hb <90 g/l randomized patients Patients randomized to receive RBCs d therapy patients study patients received blood d patients received blood d patients Transfusion of 2 units RBCs in patients on a ICU patients to of two transfusion – Hb maintained g/l – Hb maintained at 70–90 g/l randomized control patients of including patients Transfusion of units of RBCs patients Patients received of RBCs for each g/l that their Hb was g/l

e23319 Background: Current guidelines recommend transfusing at a hemoglobin (Hb) threshold of 7g/dl. There is a lack of evidence to support a specific threshold for transfusion in patients with active malignancy admitted to the Intensive Care Unit (ICU). This study attempts to determine an evidence-based threshold for blood transfusions in cancer. Methods: A retrospective study was done to study 561 patients with an active cancer diagnosis admitted to Northeast Georgia Medical Center ICU between 2017 and 2023 that received at least one unit of blood transfusion. Chi-Square test of association with Bonferoni correction was applied to the top five common cancers seen in ICU: Leukemia, Lymphoma, Brain tumors, Lung cancers, and GI cancers. It compared three thresholds of transfusion and looked for any change in mortality risk, readmissions, need for multiple transfusions, prevalence of new onset or recurrent heart failure, development of altered mental status, or cardiac arrest. The three thresholds for transfusions that were studied were &lt; 7g/dL, &lt; 8 g/dL, and &gt; 8 g/dL. The studied cancer types were further divided into either hematologic or solid tumors. Results: There was a decrease in overall cancer readmissions compared to expected over 30 days by 64%, 60 days by 44%, and 90 days by 47.5% when transfused for a Hb threshold of &lt;8 g/dL compared to an increase of 22.8%, 18.2%, and 18.8% in 30-, 60-, and 90-day readmissions when transfused for a Hb threshold of &lt;7 g/dL. When divided by cancer types, there was a significant decrease from expected by 30%, 47.5%, and 56% in 30-, 60-, and 90-day readmissions for patients with solid tumors for a Hb threshold of &lt; 8 g/dL. Mortality risk decreased by 50% and the need for multiple transfusions decreased by 21% when transfused for a Hb threshold of &lt; 8 g/dl. Of note, there was no significant association between transfusion levels and associated reactions. There was a decrease of 82% in altered mental status when transfused for threshold of Hb &lt;8 g/dL. Finally, significant association was not found with AKI, cardiac arrest, or heart failure and any Hb transfusion thresholds. Conclusions: Based on these results, there is a significant mortality benefit and decreased length of stay for cancer patients admitted to ICU when blood transfusion is undertaken at a hemoglobin threshold of &lt;8g/dL. These results should be further investigated in a randomized controlled trial.