Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical...

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Severe sepsis and septic shock

New therapeutic strategies have emerged along with our understanding that disturbances of iron homeostasis, impaired proliferation of erythroid progenitor cells, and blunted erythropoietin response occur in anemia of chronic disease. This review discusses advances in our knowledge of the causes and management of the condition.

https://www.nejm.org/doi/pdf/10.1056/NEJMra041809

Anemia of Chronic Disease

Methods We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes. Results A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P = 0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup. Conclusions In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. (ClinicalTrials.gov number, NCT00597077.)

https://www.nejm.org/doi/pdf/10.1056/NEJMoa0708789

Rhythm control versus rate control for atrial fibrillation and heart failure

ObjectiveTo quantify the incidence of anemia and red blood cell (RBC) transfusion practice in critically ill patients and to examine the relationship of anemia and RBC transfusion to clinical outcomes.DesignProspective, multiple center, observational cohort study of intensive care unit (ICU) patient

http://www.nimbot.com/Med/Articles/Journal%20Clubs/2006-10/The%20CRIT%20Study-%20Anemia%20and%20blood%20transfusion%20in%20the%20critically%20ill%20in%20the%20US.pdf

The CRIT Study: Anemia and blood transfusion in the critically ill--current clinical practice in the United States.

Propensity-score methods are increasingly being used to reduce the impact of treatment-selection bias in the estimation of treatment effects using observational data. Commonly used propensity-score methods include covariate adjustment using the propensity score, stratification on the propensity score, and propensity-score matching. Empirical and theoretical research has demonstrated that matching on the propensity score eliminates a greater proportion of baseline differences between treated and untreated subjects than does stratification on the propensity score. However, the analysis of propensity-score-matched samples requires statistical methods appropriate for matched-pairs data. We critically evaluated 47 articles that were published between 1996 and 2003 in the medical literature and that employed propensity-score matching. We found that only two of the articles reported the balance of baseline characteristics between treated and untreated subjects in the matched sample and used correct statistical methods to assess the degree of imbalance. Thirteen (28 per cent) of the articles explicitly used statistical methods appropriate for the analysis of matched data when estimating the treatment effect and its statistical significance. Common errors included using the log-rank test to compare Kaplan-Meier survival curves in the matched sample, using Cox regression, logistic regression, chi-squared tests, t-tests, and Wilcoxon rank sum tests in the matched sample, thereby failing to account for the matched nature of the data. We provide guidelines for the analysis and reporting of studies that employ propensity-score matching.

https://www.epi.msu.edu/janthony/requests/propensity/Austin_A%20critical%20appraisal%20of%20propensity%20score.pdf

A critical appraisal of propensity-score matching in the medical literature between 1996 and 2003

Context Anemia is a common problem in critically ill patients admitted to intensive care units (ICUs), but the consequences of anemia on morbidity and mortality in the. critically ill is poorly defined. Objectives To prospectively define the incidence of anemia and use of red blood cell (RBC) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU. Design Prospective observational study conducted November 1999, with 2. components: a blood sampling study and an, anemia and blood transfusion study. Setting and Patients The blood sampling study included 1136 patients from 145 western European ICUs, and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs. Patients were followed up for 28 days or until hospital discharge, interinstitutional transfer, or death. Main Outcome Measures Frequency of blood drawing and associated volume of blood drawn, collected over a 24-hour period; hemoglobin levels, transfusion rate, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), and mortality, collected throughout a 2-week period. Results The mean (SD) volume per blood draw was 10.3 (6.6) mL, with an average total volume of 41.1 (39.7) mL during the 24-hour period. There was a positive correlation between organ dysfunction and the number of blood draws (r=0.34; P<.001) and total volume drawn (r=0.28; P<.001). The mean hemoglobin concentration at ICU admission was 11.3 (2.3) g/dL, with 29% (963/3295) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0% (1307/3534). Older patients and those with a longer ICU length of stay were more commonly transfused. Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion (ICU rates: 18.5% vs 10.1%, respectively; chi(2)=50.1; P<.001; overall rates: 29.0% vs 14.9%, respectively; chi(2) =88.1; P<.001). For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P=.02); the Kaplan-Meier log-rank test confirmed this difference. Conclusions This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients. Additionally, this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality.

https://jamanetwork.com/journals/jama/articlepdf/195310/jce10054.pdf

Anemia and blood transfusion in critically ill patients.

Objectives
To determine CO and gastric mucosal perfusion in patients during elective major surgery; to seek a relationship with subsequent outcome.

Intra-operative gut mucosal hypoperfusion is associated with increased post-operative complications and cost

Objective: The gastrointestinal tonometer, which allows measurement of gastrointestinal mucosal CO2 and subsequent derivation of gut intramucosal pH (pHi), has been demonstrated to be a sensitive predictor of outcome following major surgery. Current theory suggests that the origin of the low pH may be hypovolaemia. This study was designed to compare the temporal sequence of changes in tonometric readings with invasive blood pressure, stroke volume, heart rate, lactate and arterial blood gas measurements during progressive haemorrhage. Design: Observational healthy volunteer study. Setting: Intensive care unit at University College London Hospitals. Subjects: Six healthy, medically qualified volunteers. Interventions: After obtaining baseline measurements, the subjects were progressively bled 25 % (range = 21–31 %) of their blood volume over a period of 1 h in two approximately equal aliquots. Equilibration was allowed for 30 min following the bleed, after which further measurements were made and the blood was then retransfused over 30 min. Measurements and main results: There was no consistent change in any of the haemodynamic variables other than gastric intramucosal CO2 : arterial CO2 gap (PiCO2− PaCO2) after removal of the first aliquot of blood, although five of the six subjects also demonstrated a fall in pHi. After removal of the second aliquot of blood, PiCO2− PaCO2 gap and pHi continued to indicate a worsening gastric intramucosal acidosis; stroke volume, as measured by suprasternal Doppler, demonstrated a marked fall, while all other variables measured had not altered consistently or to such a degree as to elicit a clinical response or cause suspicion of a hypovolaemic state. On retransfusion, all variables returned towards baseline. Conclusions: This study demonstrates the value of tonometry as an early monitor of hypovolaemia and highlights the shortcomings of other more commonly measured clinical variables.

Comparison of commonly used clinical indicators of hypovolaemia with gastrointestinal tonometry.

In the quest for an absolute monitor of tissue oxygen utilisation the tonometer is, unfortunately, not the Holy Grail. However, the tonometer is commercially available and a practical monitor of gut mucosal perfusion for use in the peri-operative period. As the tonometer is not yet in general use we are faced with an ideal opportunity to audit its introduction, something we have failed to do for other clinical monitors.

The role of gut mucosal hypoperfusion in the pathogenesis of post-operative organ dysfunction.

Hextend® is a new plasma volume expander containing 6% hydroxyethyl starch (HES) in a physiologically balanced medium of electrolytes, glucose, and lactate (weight average, molecular weight 670 kDa, molar substitution 0.75). This open-label study was designed to investigate the pharmacokinetic and p

/pdf/hydroxyethyl-starch-in-balanced-electrolyte-solution-hextend-1qf973fsl0.pdf

A. R. Webb

Papers

Anemia and blood transfusion in critically ill patients.

Intra-operative gut mucosal hypoperfusion is associated with increased post-operative complications and cost

Comparison of commonly used clinical indicators of hypovolaemia with gastrointestinal tonometry.

The role of gut mucosal hypoperfusion in the pathogenesis of post-operative organ dysfunction.

Hydroxyethyl starch in balanced electrolyte solution (Hextend)--pharmacokinetic and pharmacodynamic profiles in healthy volunteers.