Impact of delayed initiation of erythropoietin in critically ill patients

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the impact of recombinant human erythropoietin (rHuEPO) use for anemia of critical illness at a practice site where delayed initiation is common.</p> <p>Methods</p> <p>Retrospective medical record review involving patients treated with rHuEPO for anemia of critical illness. Those patients given rHuEPO or diagnosed with end-stage renal disease (ESRD) prior to ICU admission were excluded. The primary endpoints were rHuEPO use and RBC transfusion patterns.</p> <p>Results</p> <p>Complete data were collected for consecutive admissions of 126 patients. Average age (SD) and APACHE II score were 56.5 (18.6) years and 25 (7.8), respectively. The median ICU (IQR) and hospital length of stay (LOS) were 24 (11.25, 39) and 29 (17, 44.75) days, respectively. Treatment with rHuEPO was started an average of 12.5 +/- 10.5 days after ICU admission and given for 3.8 +/- 3.8 doses. Eighty percent of patients were transfused with an average total of 5.42 +/- 5.08 units received. RBC exposure inversely correlated with a lower mean hemoglobin response to rHuEPO. ICU LOS (p < 0.0001), hemoglobin at 24 hours (p = 0.055), transfusion within 48 hours of admit (p < 0.0001), and postoperative status (p = 0.019) were the best predictors of transfusion requirements (r²= 0.37).</p> <p>Conclusion</p> <p>Delayed initiation of rHuEPO for anemia of critical illness resulted in comparable hemoglobin and transfusion benefits. Future studies are needed to establish clinical benefit and role in therapy. RBC exposure may blunt the erythropoietic effects of rHuEPO, potentially frustrating benefits to those of greatest apparent need.</p

Does blood transfusion harm cardiac surgery patients?

Over recent years there has been a substantial body of evidence demonstrating strong associations between transfusion and adverse outcomes, including myocardial, neurological and renal injury, in a range of clinical settings where transfusion is administered for reasons other than life-threatening bleeding. The strength of these associations across a range of clinical settings suggests that confounding and bias, the chief limitations of all observational studies, are unlikely to account for all of these observations. Given the wide range in transfusion rates in cardiac centres, with up to 100% of patients in some centres exposed to allogenic blood components, this evidence, albeit circumstantial, presents a strong argument for prospective randomised trials to attempt to determine, firstly, if transfusion causes adverse outcomes, and secondly, in which patient groups does the benefit of transfusion outweigh these risks? These issues are discussed in the context of an article published this month in BMC Medicine

Major surgery in an osteosarcoma patient refusing blood transfusion: case report

We describe an unusual case of osteosarcoma in a Jehovah's Witness patient who underwent chemotherapy and major surgery without the need for blood transfusion. This 16-year-old girl presented with osteosarcoma of the right proximal tibia requiring proximal tibia resection, followed by endoprosthesis replacement. She was successfully treated with neoadjuvant chemotherapy and surgery with the support of haematinics, granulocyte colony-stimulating factor, recombinant erythropoietin and intraoperative normovolaemic haemodilution. This case illustrates the importance of maintaining effective, open communication and exploring acceptable therapeutic alternative in the management of these patients, whilst still respecting their beliefs

The prevalence of anemia and its association with 90-day mortality in hospitalized community-acquired pneumonia

<p>Abstract</p> <p>Background</p> <p>The prevalence of anemia in the intensive care unit is well-described. Less is known, however, of the prevalence of anemia in hospitalized patients with lesser illness severity or without organ dysfunction. Community-acquired pneumonia (CAP) is one of the most frequent reasons for hospitalization in the United States (US), affecting both healthy patients and those with comorbid illness, and is typically not associated with acute blood loss. Our objective was to examine the development and progression of anemia and its association with 90d mortality in 1893 subjects with CAP presenting to the emergency departments of 28 US academic and community hospitals.</p> <p>Methods</p> <p>We utilized hemoglobin values obtained for clinical purposes, classifying subjects into categories consisting of no anemia (hemoglobin >13 g/dL), at least borderline (≤ 13 g/dL), at least mild (≤ 12 g/dL), at least moderate (≤ 10 g/dL), and severe (≤ 8 g/dL) anemia. We stratified our results by gender, comorbidity, ICU admission, and development of severe sepsis. We used multivariable logistic regression to determine factors independently associated with the development of moderate to severe anemia and to examine the relationship between anemia and 90d mortality.</p> <p>Results</p> <p>A total of 8240 daily hemoglobin values were measured in 1893 subjects. Mean (SD) number of hemoglobin values per patient was 4.4 (4.0). One in three subjects (33.9%) had at least mild anemia at presentation, 3 in 5 (62.1%) were anemic at some point during their hospital stay, and 1 in 2 (54.5%) survivors were discharged from the hospital anemic. Anemia increased with illness severity and was more common in those with comorbid illnesses, female gender, and poor outcomes. Yet, even among men and in those with no comorbidity or only mild illness, anemia during hospitalization was common (~55% of subjects). When anemia was moderate to severe (≤ 10 g/dL), its development was independently associated with increased 90d mortality, even among hospital survivors.</p> <p>Conclusions</p> <p>Anemia was common in hospitalized CAP and independently associated with 90d mortality when hemoglobin values were 10 g/dL or less. Whether prevention or treatment of CAP-associated anemia would improve clinical outcomes remains to be seen.</p

Erythropoietin in the intensive care unit: beyond treatment of anemia

Erythropoietin (EPO) is the major hormone stimulating the production and differentiation of red blood cells. EPO is used widely for treating anemia of critical illness or anemia induced by chemotherapy. EPO at pharmacological doses is used in this setting to raise hemoglobin levels (by preventing the apoptosis of erythroid progenitor cells) and is designed to reduce patient exposure to allogenic blood through transfusions. Stroke, heart failure, and acute kidney injury are a frequently encountered clinical problem. Unfortunately, in the intensive care unit advances in supportive interventions have done little to reduce the high mortality associated with these conditions. Tissue protection with EPO at high, nonpharmacological doses after injury has been found in the brain, heart, and kidney of several animal models. It is now well known that EPO has anti-apoptotic effects in cells other than erythroid progenitor cells, which is considered to be independent of EPOs erythropoietic activities. This review article summarizes what is known in preclinical models of critical illness and discusses why this does not correlate with randomized, controlled clinical trials

Outcome based subgroup analysis: a neglected concern

A subgroup of clinical trial subjects identified by baseline characteristics is a proper subgroup while a subgroup determined by post randomization events or measures is an improper subgroup. Both types of subgroups are often analyzed in clinical trial papers. Yet, the extensive scrutiny of subgroup analyses has almost exclusively attended to the former. The analysis of improper subgroups thereby not only flourishes in numerous disguised ways but also does so without a corresponding awareness of its pitfalls. Comparisons of the grade of angina in a heart disease trial, for example, usually include only the survivors. This paper highlights some of the distinct ways in which outcome based subgroup analysis occurs, describes the hazards associated with it, and proposes a simple alternative approach to counter its analytic bias. Data from six published trials show that outcome based subgroup analysis, like proper subgroup analysis, may be performed in a post-hoc fashion, overdone, selectively reported, and over interpreted. Six hypothetical trial scenarios illustrate the forms of hidden bias related to it. That bias can, however, be addressed by assigning clinically appropriate scores to the usually excluded subjects and performing an analysis that includes all the randomized subjects. A greater level of awareness about the practice and pitfalls of outcome based subgroup analysis is needed. When required, such an analysis should maintain the integrity of randomization. This issue needs greater practical and methodologic attention than has been accorded to it thus far

Prediction of arterial pressure increase after fluid challenge

<p>Abstract</p> <p>Background</p> <p>Mean arterial pressure above 65 mmHg is recommended for critically ill hypotensive patients whereas they do not benefit from supranormal cardiac output values. In this study we investigated if the increase of mean arterial pressure after volume expansion could be predicted by cardiovascular and renal variables. This is a relevant topic because unnecessary positive fluid balance increases mortality, organ dysfunction and Intensive Care Unit length of stay.</p> <p>Methods</p> <p>Thirty-six hypotensive patients (mean arterial pressure < 65 mmH) received a fluid challenge with hydroxyethyl starch. Patients were excluded if they had active bleeding and/or required changes in vasoactive agents infusion rate in the previous 30 minutes. Responders were defined by the increase of mean arterial pressure value to over 65 mmHg or by more than 20% with respect to the value recorded before fluid challenge. Measurements were performed before and at one hour after the end of fluid challenge.</p> <p>Results</p> <p>Twenty-two patients (61%) increased arterial pressure after volume expansion. Baseline heart rate, arterial pressure, central venous pressure, central venous saturation, central venous to arterial PCO₂difference, lactate, urinary output, fractional excretion of sodium and urinary sodium/potassium ratio were similar between responder and non-responder. Only 7 out of 36 patients had valuable dynamic indices and then we excluded them from analysis. When the variables were tested as predictors of responders, they showed values of areas under the ROC curve ranging between 0.502 and 0.604. Logistic regression did not reveal any association between variables and responder definition.</p> <p>Conclusions</p> <p>Fluid challenge did not improve arterial pressure in about one third of hypotensive critically ill patients. Cardiovascular and renal variables did not enable us to predict the individual response to volume administration.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00721604">NCT00721604</a>.</p

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0