Hyponatremia - Early differential diagnosis, management and prognosis

Abstract: Abstract Hyponatremia is the most common electrolyte imbalance. It is associated with increased morbidity and in-hospital mortality. An effective early management is dependent on knowledge of epidemiology in the current population, accurate assessment of patient volume status and efficient diagnostic investigation. I) Prevalence of hyponatremia was investigated in an unselected population presenting to the Emergency department. Four groups of hyponatremia severity were established: Group 1: P-Na <120mM, Group 2: 120-124mM, Group 3:125-129mM, Group 4:130-134mM and 100 patients from each group were included. (Patients in Group 2-4 matched to Group 1 for age, gender, ER visit calender month.) Hyponatremia (P-Na <135mmol/L) was identified in 3% of the entire emergency population. Leading etiologies being SIADH and thiazide diuretics. Patients in Group 1 were 3.6 times (CI95%:1.9-6.8) more likely to be on thiazide diuretics compared to Group 4. Only 31 % of patients in Group 1 was evaluated with basic laboratory investigation (P-osm, U-osm, U-Na). II) Initial treatment of hyponatremia is based on clinical evaluation of patient volume status, but an accurate assessment is difficult, particularly differentiating between hypovolemia and euvolemia. Biomarkers were evaluated in the diagnosis (MR-proANP, MR-proADM, copeptin, proET-1, NT-proBNP). A total of 81 patients were included and a well substantiated volume status could be determined in 72 patients. A significant association was observed between MR-proANP and volemic state (p=0.0001). Using logistic regression, MR-proANP was significantly related to euvolemia in multivariate backward elimination model (OR:2.45 per SD of MR-proANP, 95% CI 1.22-4.91, p=0.012.) Copeptin levels were not associated with a diagnosis of SIADH or volemic state. III) Further study on early management and differentiation between patient volume groups were performed using apelin, urine-metoxycathecholaminer and bioreactance measurement of stroke volume index (SVI) after passive leg raise test. An increase in SVI ≥ 10% was defined as a sign of volume responsiveness (i.e hypovolemia). Blood and urine samples were analysed at baseline and during infusion of isotonic sodium chloride (1000ml/10h) 4h, 12h, 24h and daily until discharge. In total 8 patients were included (4 hypovolemic, 4 euvolemic), median P-Na 120 mM, 79 years of age. Apelin was significantly higher in hypovolemic patients (299 vs 175 ng/ml, p=0.021). All hypovolemic, but no euvolemic patients had a level >250 ng/ml. All patients in the hypovolemic group increased their stroke volume after passive leg raise. IV) The aim of this study was to examine prevalence of hyponatremia in a large community-based cohort and association with future morbidity and mortality. In total, 22 267 individuals from the Malmö Preventive Project (MPP) cohort were included. Median follow-up time 34 years. Hyponatremia (S-Na<135mM) was observed in 166 subjects (0.7%). Hyponatremia was associated with increased all-cause mortality after adjusting for cardiovascular risk factors even when comparing “borderline” hyponatremia (S-Na 135-136) with normonatremia, HR 1.332 (1.184-1.499) p<0.001. There was also an association between hyponatremia and incident coronary artery disease (CAD) both with hyponatremia and borderline hyponatremia (e.g.S-Na135-136mM), HR:1.320 (1.127-1.545), p=0.001. Conclusions: The results of the papers included in this thesis, indicate that MR-proANP, apelin and bioreactance measurement may be valuable in early management of hyponatremia, especially determination of patient volume status. Hyponatremia is a risk factor for future cardiovascular disease and all-cause mortality even at mild levelsnear the reference range.