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

Bernard Vigué, Pierre-Etienne Leblanc, Frédérique Moati, Eric Pussard, Hussam Foufa, Aurore Rodrigues, Samy Figueiredo, Anatole Harrois, Jean-Xavier Mazoit, Homa Rafi, Jacques Duranteau, Bernard Vigué, Pierre-Etienne Leblanc, Frédérique Moati, Eric Pussard, Hussam Foufa, Aurore Rodrigues, Samy Figueiredo, Anatole Harrois, Jean-Xavier Mazoit, Homa Rafi, Jacques Duranteau

Abstract

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.

Keywords: Adrenomedullin; Fluid balance; Fluid overload; Intensive care unit; MR-proADM; Plasma biomarker; Sodium overload.

Figures

Fig. 1
Fig. 1
a Cumulative sodium balance (∆Na+, g) on day 2 (D2) and D7 in the 67 patients studied. b Cumulative fluid balance (∆H2O, L) on D2 and D7. Thresholds of 36 g for sodium and 4 L for water, corresponding to 4 L of saline and described as a tolerable fluid overload, are marked as shaded zone around equilibrate balances. SBT severe brain trauma, SAH aneurysmal subarachnoid hemorrhage, NCT severe non-cerebral trauma, PPS postoperative peritonitis with shock
Fig. 2
Fig. 2
Total blood volume (TBV, mL/Kg) (a), red blood cell volume (RBCV, mL/Kg) (b) and plasmatic volume (PV, mL/Kg) (c) on day 2 (D2) and D7. Thresholds of 20 % around normal values are marked as shaded zones. SBT severe brain trauma, SAH aneurysmal subarachnoid hemorrhage, NCT severe non-cerebral trauma, PPS postoperative peritonitis with shock
Fig. 3
Fig. 3
ROC curves to describe the relationship between the plasmatic concentration of mid-regional pro-adrenomedullin (MR-proADM) and fluid overload of 4 L for ∆H2O and 36 g for ∆Na+. Area under the curve (AUC) is 0.838 (0.780–0.888) for ∆H2O and 0.823 (0.764–0.880) for ∆Na+ determining the relationship between dangerous fluid overload and plasmatic MR-proADM. The Youden index indicates a threshold for plasmatic MR-proADM (0.865 nmol/L (specificity 0.625/sensitivity 0.865) for ∆Na+ >36 g and 1.125 nmol/L (specificity 0.900/sensitivity 0.604) for ∆H2O >4 L) to predict fluid overload

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