Volemic status estimation in clinical practice

Transcription

1 Volemic status estimation in clinical practice Marion VALLET, Pierre-Yves CHARLES, Acil JAAFAR, Françoise PRADDAUDE, Ivan TACK Service des Explorations Fonctionnelles Physiologiques ; Hôpital de Rangueil, C.H.U. de TOULOUSE Laboratoire de Physiologie, Facultés de Médecine de Toulouse, Université Paul Sabatier ANJH Hôpital Necker, avril 218

2 Extracellular fluid volume / volemia / effective blood volume Extracellular volume Effective arterial blood volume Interstitial volume Plasma volume Not measurable, Equilibrium between: Cardiac output Parallel alterations unless capillary hyperpermeability Blood Volume Vascular resistance

3 When is it useful to determine volemia / extracellular fluid volume?

4 Chronic hyponatremia Hypo-osmotic hyponatremia Low urinary osmolality Excessive water intakes Inadapted urinary osmolality Relative excess of AVP Hypovolemia SIAD (slight volemic expansion)

5 «Clinical assessment of extracellular fluid volume in hyponatremia» 58 patients Hyponatremia < 13 mmol/l Absence of edema and ascites Clinical examination: cardiac parameters, jugular venous pressure, orthostatic changes in pulse and blood pressure, skin turgor, moisture in the axillae, and hydration of mucous membranes Contracted ECFV = «saline responders» Clinical assessment correctly identified less than 5% of hypovolemic patients Chung HM, The American Journal of Medicine, 1987

6 Biological assessment of ECFV/volemia during hyponatremia Plasma renin Urinary sodium concentration Chung HM, The American Journal of Medicine, 1987

7 Néphrologie, 7 ème édition, Collège Universitaire des Enseignants de Néphrologie, 216

8 J Clin Endocrinol Metab, August 28, 93(8): jcem.endojournals.org patients Hyponatremia <13 mmol/l SIAD vs non SIAD TABLE 2. Biochemical and clinical data before treatment in four etiological categories of hyponatremic patients SIAD group (n 31) Salt depletion (n 27) Non-SIAD group (n 55) ECFV expansion (n 21) Diuretics (n 7) P value Serum Na (mmol/liter) (5) (6) (4) (5).38 Potassium (mmol/liter) 4.1 (.4) 4.2 (.9) 4.3 (.5) 3.7 (.5).241 Creatinine (mg/dl).8 (.3) 1.3 (1) 1.2 (.6) 1.3 (.8).3 Urea (mg/dl) 31.2 (16) 54.4 (38) 81.1 (6) 56.3 (5).1 UA (mg/dl) 3.3 (1) 6.4 (2) a 8.2 (3) a 6.2 (4) a.1 Hematocrit (%) 33.2 (5) 36.9 (4) 34.8 (5) 33.9 (4).29 Osmolality (mosm/kg) 252 (13) 256 (14) 269 (19) 255 (16).4 Renin (ng/liter) 9.6 (5 23) 31. (15 98) 33.1 (54 731) 14.8 (5 257).1 Aldosterone (ng/liter) 72 (24 145) 94 (48 291) 21 (78 492) 65 (32 24).7 Urinary Na excretion (mmol/liter) 96 (5) 29 (13) a 44 (21) a 64 (32) a.1 Potassium excretion (mmol/liter) 42 (26) 45 (22) 45 (17) 27 (15).72 Osmolality (mosm/kg) 478 (17) 463 (218) 383 (127) 283 (13).4 Clearance ratio FE-Na (%).9 (.5 1.8).3 (.1.6) a.5 (.2 1.1) a 1.6 (.4 4).1 FE-urea (%) 5 (18) 31 (15) a 32 (18) a 39 (12).1 FE-UA (%) 17 (11 23) 6 (4 9) a 6 (2 8) a 7 (4 1).1 FE-potassium (%) 12 (7 19) 14 (5 21) 17 (9 27) 16 (8 65).351 Vital signs BP in supine position (mm Hg) 124/74 (21/12) 115/69 (19/9) 111/64 (21/11) 129/71 (18/8).42 Heart rate in supine position (Bpm) 74.4 (13) 78.8 (15) 71.5 (12) 75.7 (15).452 Orthostatic decrease in systolic BP (%) 3. ( 9) 22. (16 25) a 2.5 (13 27) a 6. (4 1).1 Orthostatic increase in heart rate (%) 1. (6 14) 25. (2 34) a 34.5 (25 45) a 6. ( 14).1 Data are mean (SD) or median (25th-75th percentile), respectively. BP, Blood pressure; Bpm, beats per minute. a P Biological assessment of ECFV/volemia during hyponatremia.5 compared with the SIAD group. Fenske W, JCEM, 28

9 The patient characteristics and respective causes of hyponatremia are shown in Table 1. A total of 45 patients received a test aldosterone (Diagnostic infusion Products of isotonic Corp., Los N acl Angeles, (SIAD CA); nand 24, reninnon-siad n 21). A concentration (Cis-Bio Intl., M arcoule, France). final diagnosis of SIAD was made in 31 patients (36%). There Data analysis were15 SIAD patients(48%) who received diuretics. N eoplastic Characteristics disease, of studyespecially participants carcinoma are presented of asthe means lung, withwas the dominant unthe non-siad gro werealso significa salt-depleted and E Biological assessment Result of secfv/volemia during no difference in S sampleswere analyzed using ion-selective electrodes for Na, potassium, and chloride. Osmolality was measured directly via determination of freezing point depression. Cortisol, ACTH, and TSH were measured by immunoassay (IM M ULITE 2; SiemensM edical Solution Diagnostic GmbH, Bad Nauheim, Germany). Plasma aldosterone and renin measurements were performed by RIA using commercially available assays: BPin supine position (mm Hg) 124/74 (21/12) 115/69 (19/9) 111/64 (21/11) 129/71 (18/8).42 Heart rate in supine position (Bpm) 74.4 (13) 78.8 (15) 71.5 (12) 75.7 (15).452 Orthostatic decrease in systolic BP (%) 3. ( 9) 22. (16 25) a 2.5 (13 27) a 6. (4 1).1 Orthostatic increase in heart rate (%) 1. (6 14) 25. (2 34) a 34.5 (25 45) a 6. ( 14).1 Data are mean (SD) or median (25th-75th percentile), respectively. BP, Blood pressure; Bpm, beats per minute. a P.5 compared with the SIAD group. UNa U-Na (mmol/l) FE-Na (%) FE-Urea (%) S-UA (mg/dl) FE-UA (%) # * FE urea * their SD values for normally distributed variables, medians with 25th to 75th percentile for nonnormally distributed variables, and frequencies for categorical variables. M ean values were compared by the Kruskal-Wallis test among different groups. Group comparisons between patients with and without SIAD were made using the Student s t test after testing for equality of variances by Levene s test. Categorical variableswerecompared bythefisher s ex- between patients expansion. The values of presented in box p patients with and 1). In general, the tween the SIAD an act test and 2 test. To describe the diagnostic A Patients on diuretics utility of the different biomarkers, standard diagnostic 15 performancemeasureswerecalculated * 4 * * with their 95% confidence intervals (CIs), and 6 3 receiver operating characteristics (ROCs) were 3 1 plotted. The area under the curve (AUC) was calculated by the nonparametric trapezoidal 2 rule, with itsse and 95% CI (1).Differences in the diagnostic utility between biomarkers were 1 B Patients estimated by differences in the ROC area, considering the correlation between models be- without diuretics Yes No Yes No Yes No Yes No Yes No cause they were based on the same cases (1, SIAD SIAD SIAD SIAD SIAD 11). Toaccount for multiplecomparisonsof the FIG. 1. Levels of U-Na, FE-Na, FE-urea, S-UA, and FE-UA in patients with SIAD (light boxes) and without 1 diagnostic variables, a simplebonferroni adjustment SIAD (dark boxes), and with (A) and without (B) diuretic therapy. Boxes show median and interquartile was made, and statistical significance range, and whiskers indicate 5th to 95th percentile. *, Bonferroni-adjusted Pvalue.5 for wasaccepted at.5 (i.e..5/1).for the comparison 86 patients between SIAD and non-siad groups. #, Bonferroni-adjusted Pvalue.2 for comparison comparisons between ROC curves, theconventional Comparison P value of the.5diagnostic was accepted. utility Statistical (ROC analysis) of FE-UA, S-UA, and FE-urea to differentiate between SIAD and non SIAD groups., Bonferroni-adjusted Pvalue.5 for comparison between FIG. 3. patients with and without diuretic treatment. Hyponatremia <13 mmol/l between SIAD and EABV depleted hyponatremia in patients with (A) and without (B) diuretic treatment. The diagonal line indicates the area of.5, corresponding to no informative discrimination. Pvalues are for the differences between areas (see Patients and Methods). SIAD vs non SIAD With/without diuretics Uric acid hyponatremia The Endocrine Society. Downloaded from press.endocrine.org by [${individualuser.displayname}] on 18 May 216. at 2:31 For personal use only. No other uses without permission.. All rights reserved. Uric Acid Fractional Excretion The Endocrine Society. Downloaded from press.endocrine.org by [${individualuser.displayname}] on 18 May 216. at 2:31 For personal Fenske W, JCEM, 28

10 Chronic hyponatremia in our Department SIAD Hypovolemic SBP, mmhg 145 ± 19 (22) 161 ± 13 (7) DBP, mmhg 81 ± 12 (22) 89 ± 19 (7) Plasma sodium, mmol/l 128 ± 6 (22) 133 ± 2 (7) Plasma proteins, g/l 69 ± 6 (22) 69 ± 4 (7) egfr, ml/min/1.73m 2 1 ± 22 (22) 83 ± 18 (7) 24h sodium excretion, mmol/24h 111 (79-144) (2) 114 (6-172) (7) Plasma uric acid, mol/l 17 ± 63 (22) 281 ± 5 (7)* FEUA, % 17 (11-21) (22) 8 (6-11) (7)* Plasma renin, µui/l 4.1 ( ) (21) 44.7 (9-51.8) (7)* Grellier J, et al., Osteoporos Int, 217

11 Chronic hyponatremia in our Department SIAD Hypovolemic SBP, mmhg 145 ± 19 (22) 161 ± 13 (7) DBP, mmhg 81 ± 12 (22) 89 ± 19 (7) Plasma sodium, mmol/l 128 ± 6 (22) 133 ± 2 (7) Plasma proteins, g/l 69 ± 6 (22) 69 ± 4 (7) egfr, ml/min/1.73m 2 1 ± 22 (22) 83 ± 18 (7) 24h sodium excretion, mmol/24h 111 (79-144) (2) 114 (6-172) (7) Plasma uric acid, mol/l 17 ± 63 (22) 281 ± 5 (7)* FEUA, % 17 (11-21) (22) 8 (6-11) (7)* Plasma renin, µui/l 4.1 ( ) (21) 44.7 (9-51.8) (7)* ECFV, ml/kg 257 ± 57 (22) 169 ± 28 (5)* Grellier J, et al., Osteoporos Int, 217

12 When is it useful to determine volemia / extracellular fluid volume?

13 Hypokalemia Néphrologie, 7 ème édition, Collège Universitaire des Enseignants de Néphrologie, 216

14 Patients explored after unilateral adrenalectomy for primary aldosteronism Indication: mild hyperkalemia or labile blood pressure Normal blood pressure or persistent hypertension Normal plasma renin and aldosterone (no persistent hyperaldosteronism) Median (min-max) n=6 SBP, mmhg 129 ( ) DBP, mmhg 78 (71-13) Plasma potassium, mmol/l 4.8 ( ) Usual values Plasma renin, mui/l 8. ( ) Plasma aldosterone, ng/l 18.5 (1-77) 1-15 FEUA, % 7.6 ( ) No orthostatic increase in plasma renin and aldosterone Vallet et al, AACE Clinical Case Report, 216

15 Patients explored after unilateral adrenalectomy for primary aldosteronism Indication: mild hyperkalemia or labile blood pressure Normal blood pressure or persistent hypertension Normal plasma renin and aldosterone (no persistent hyperaldosteronism) Median (min-max) n=6 SBP, mmhg 129 ( ) DBP, mmhg 78 (71-13) Plasma potassium, mmol/l 4.8 ( ) Usual values Plasma renin, mui/l 8. ( ) Plasma aldosterone, ng/l 18.5 (1-77) 1-15 FEUA, % 7.6 ( ) ECFV, ml/kg 163 (18-167) Renin-aldosterone axis deficiency Vallet et al, AACE Clinical Case Report, 216

16 In search for ECFV surrogate marker?

17 Which biological parameters for volemic status estimation? Retrospective study, January 211 to January 218 Patients having ECFV determination Inulin distribution volume, using the Peters corrected Brochner- Mortensen model Exclusion : Edema, cardiac or liver insufficiencies BMI>35 kg/m 2

18 General characteristics 1 patients Indication: Hyponatremia n=33 Hyperkalemia n=24 Hypokalemia n=27 Others (refractory hypertension, orthostatic hypotension, ) All (n=1) Age, yr 56±17 Female/Male 64/36 BMI, kg/m 2 24±5

19 General characteristics Hypovolemic (n=39) Normovolemic (n=42) Hypervolemic (n=19) Overall p ECFV, ml/kg 161 (15-167) 192 (184-21)* 232 (22-246)*$ <.1 Age, yr 54±15 59±17 55±18 NS Female/Male 25/14 29/13 1/9 BMI, kg/m 2 24±4 24±5 21±4 NS egfr, ml/min/1.73m 2 89 (72-96) 92 (75-15) 13 (93-112)*.8 mgfr, ml/min/1.73m 2 72 (57-83) 84 (69-96) 12 (84-19)*$ <.1 Treatments ACEi or ARB treatment, % Beta-blockers, % Diuretics, % 15 5

20 Fasting FENa, % «Classical» estimation of volemic status Hypovolemic (n=39) Normovolemic (n=42) Hypervolemic (n=19) Overall p SBP, mmhg 138±31 144±22 145±22 NS DBP, mmhg 77±14 8±12 85±14 NS Cardiac frequency, bpm 67±1 7±11 66±13 NS Plasma proteins, g/l 7±5 7±5 71±3 NS 24h sodium excretion, mmol/24h 18 (69-151) 11 (65-161) 122 (76-168) NS Fasting FENa, %.72 ( ) 1.11 ( ) 1.17 ( ) NS 6 r=.27; p= ECFV, ml/kg

21 Fasting FEUA, % Fasting FEUA, % Plasma renin, mui/ml Plasma renin, mui/ml «Classical» estimation of volemic status 4 * Basal plasma renin 1 r=-.38; p= Hypo Hyper ECFV, ml/kg 3 * FE uric acid r=.43; p< Hypo Hyper FE urea: r=.3 ; p= ECFV, ml/kg

22 Fasting calciuria (mmol/mmol creat) Fasting calciuria (mmol/mmol creat) Calcium homeostasis 3 * Calciuria 3 r=.54; p< Hypo Hyper ECFV, ml/kg Ionized plasma calcium, mmol/l Plasma phosphorus, mmol/l Hypovolemic (n=39) Normovolemic (n=42) Hypervolemic (n=19) 1.21± ±.5 1.2±.5 1.4±.18 1.± ±.13 TmPO 4, mmol/l.99 ( ).95 ( ).92 ( ) PTH, pg/ml 42 (31-53) 41 (31-59) 41 (23-63) 25OH vitamin D, ng/ml 19 (15-26) 17 (12-29) 16 (9-32)

23 Fasting citraturia, mg/mmol creat Fasting citraturia, mg/mmol creat Fasting urinary ph Fasting urinary ph Acid-base status Hypovolemic (n=39) Normovolemic (n=42) Hypervolemic (n=19) Plasma bicarbonate, mmol/l 24.9± ± ±2.9 Fasting urinary ph * 1 8 r=.41; p<.1 FE bicarbonate r=.45; p< Hypo Fasting citraturia Hyper ECFV, ml/kg r=.34; p=.7 No difference for: Titrable acidity NH No difference for 24h citraturia. Hypo Hyper ECFV, ml/kg

24 Parameters well correlated with ECFV (r>.4) Fasting calciuria FEUA Fasting urinary ph/fe bicarbonate Parameters «moderatly» correlated with ECFV Plasma renin (but not always measured in optimal conditions) Fasting citraturia FE urea FE sodium Parameters not correlated with ECFV Blood pressure, heart rate Protidemia

25 Sensitivity% Diagnostic utility of calciuria to differentiate between hypo and hypervolemia ROC curve fasting calciuria 1 AUC=.85 8 Cutoff :.37 mmol/mmol % - Specificity% Cutoff for Sp >85%: <.37 for hypovolemia; >.45 for hypervolemia

26 Sensitivity% Diagnostic utility of FEUA to differentiate between hypo and hypervolemia ROC curve FEUA AUC= % - Specificity% Cutoff : 11,3% Cutoff for Sp >85%: <9% for hypovolemia; >12% for hypervolemia

27 Sensitivity% Diagnostic utility of fasting urinary ph to differentiate between hypo and hypervolemia ROC curve fasting urinary ph AUC= Cutoff : % - Specificity% Cutoff for Sp >85%: <6. for hypovolemia; >7. for hypervolemia

28 Conclusion ECFV measurement is useful in chronic mild ECFV abnomality Volemic status can also be easily estimated by biological parameters Fasting calciuria, FEUA, and urinary ph are useful to discriminate between hypo and hyper volemia Protidemia and urinary sodium are less relevant Clinical examination Protidemia Urinary sodium FE urea Calciuria FEUA Urinary ph ECFV measurement Using these parameters altogether to improve volemic status prediction