Mid-regional pro-adrenomedullin (MR-proADM), a marker of positive fluid balance in critically ill patients: results of the ENVOL study.

BACKGROUND: The optimal control of blood volume without fluid overload is a main challenge in the daily care of intensive care unit (ICU) patients. Accordingly this study focused on the identification of biomarkers to help characterize fluid overload status. METHODS: Sixty-seven patients were studied from ICU admission to day 7 (D7). Blood and urine samples were taken daily and sodium and water balance strictly calculated resulting in a total cumulative assessment of ∆Na+ and ∆H2O. Furthermore, plasmatic biomarkers (cortisol, epinephrine, norepinephrine, renin, angiotensin II, aldosterone, pro-endothelin, copeptine, atrial natriuretic peptide, erythropoietin, mid-regional pro-adrenomedullin (MR-proADM)) and Sequential Organ Failure Assessment (SOFA) scores were measured at D2, D5 and D7. Blood volumes were measured with 51Cr fixed on red blood cells at D2 and D7. RESULTS: The ∆Na+ or ∆H2O were increased in all patients but never related to blood volumes at D2 nor D7. Total blood volumes were at normal values with constantly low red blood cell volumes and normal or decreased plasmatic volume. Weight, plasmatic proteins, and hemoglobin were weakly related to ∆Na+ or ∆H2O. Amongst all tested biomarkers, only MR-proADM was related to sodium and fluid overload. This biomarker was also a predictor of SOFA scores. CONCLUSIONS: Plasmatic concentration in MR-proADM seems to be a good surrogate for evaluation of ∆Na+ or ∆H2O and predicts sodium and extracellular fluid overload. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01858675 in May 13, 2013.

Should immunoglobulin therapy be used in allogeneic stem-cell transplantation? A randomized, double-blind, dose effect, placebo-controlled, multicenter trial.

BACKGROUND: The universal use of prophylactic immunoglobulin in stem-cell transplantation has not been supported by strong evidence of benefit. Results of most trials were reported before effective drugs for cytomegalovirus infection and disease were available, and no trial was placebo controlled. OBJECTIVE: To assess the role and the dose-effect relationship of immunoglobulin in the prophylaxis of complications after allogeneic stem-cell transplantation. DESIGN: Multicenter randomized, double-blind, dose effect placebo-controlled study. SETTING: 19 stem-cell transplantation centers in France. PATIENTS: 200 patients who had allogeneic stem-cell transplantation from HLA-identical sibling donors between 1998 and 2000. INTERVENTION: Immunoglobulin at doses of 50 mg/kg of body weight, 250 mg/kg, or 500 mg/kg weekly from day -7 to day 100 after transplantation or placebo. MEASUREMENTS: Cumulative incidence of infection, graft-versus-host disease, veno-occlusive disease, interstitial pneumonia, and transplantation-related mortality at 6 months; overall survival at 2 years after transplantation. RESULTS: Immunoglobulin had no benefit over placebo; 92% of patients in the pooled immunoglobulin group and 90% of patients in the placebo group had one or more infections (difference, 2 percentage points [95% CI, -8 to 12 percentage points]). Cumulative incidences of interstitial pneumonia, graft-versus-host disease, transplantation-related mortality, and overall survival were similar in patients receiving placebo and those receiving immunoglobulin; no dose-effect relationships were evident. Grade 3 (severe) veno-occlusive disease occurred more frequently as the immunoglobulin dose increased (P = 0.01). CONCLUSIONS: Use of prophylactic immunoglobulin in allogeneic recipients of stem-cell transplant from HLA-identical sibling donors is not recommended.