Iposodiemia: diagnosi e trattamento

Transcription

1 Iposodiemia: diagnosi e trattamento Enrico Fiaccadori Unita di Fisiopatologia dell Insufficienza Renale Acuta e Cronica Dipartimento di Medicina Clinica e Sperimentale Universita degli Studi di Parma

2 Hyponatremia Epidemiology and outcome Pathophysiology as the basis for diagnosis and treatment The role of pharmacologic and non pharmacologic treatment

3 Hyponatremia: a disturbing clinical problem

4 Hyponatremia: the most frequent electrolyte disorder

5 2014

6

7 Making prompt diagnosis, relieving acute CNSrelated symptoms (cerebral edema), avoiding the possible harmful effects of the treatment itself (overcorrection)

8 Know the pathophysiology The best path to patient safety in when approaching hyponatremia

9 Hyponatremia is mainly a problem of water (relative or absolute excess of water on sodium)

10 Mechanisms of hyponatremia a) Loss of sodium (more Na than H 2 O) b) Gain of water Excess drinking hypotonic fluids, or excess parenteral hypotonic fluids and/or Reduced/inappropriate water excretion

11 The body response to water load: what is to be expected from physiology Urinary output rapidly increases: > 80% of a 20 ml/kg water load (15 ) should be eliminated in 4 hours Urine should be maximally diluted (urinary osmolality low, mosm/l) U osm /P osm < 1 No clinically relevant changes in serum sodium levels (venous blood) AVP (Antidiuretic hormone) should be totally suppressed water reabsorption in the kidney is reduced

12 Pathophysiological questions Is it possible to have hyponatremia only by increasing water (or hypotonic fluid) intake? If free water excretion cannot be adequately increased, what are the possible mechanisms?

13 Is it possible to have hyponatremia only by water gain? Yes, if one is able to drink water at a rate faster than the maximum water excretion capacity of the normal kidney (at least 750 mls/hour or 16 liters/day)

14 Large input of water in patients with hyponatremia Psycogenic polydipsia Halperin ML 2010

15 Is it possible to have hyponatremia only by water gain? Yes, if one is able to drink water at a rate faster than the maximum water excretion capacity of the normal kidney (at least 750 mls/hour) Yes, if there are interfering factors on the kidney ability to normally excrete a water load Reduced distal delivery of fluid (limited amount of water available for excretion): renal failure, volume depletion AVP activity is not totally suppressed (inappropriate secretion and/or activity of AVP)

16

17 There are 4 major mechanisms of inappropriate secretion of/or activity of AVP Volume depletion/hypotension, nausea, pain inflammation, drugs neoplasia drugs Genetic alterations of the ADH receptor

18 Syndrome of inappropriate secretion of ADH (SIADH): inappropriate for the presence of hypotonicity

19 Algorhytm for the differential diagnosis of hyponatremia (1) ERBP Guidelines 2014

20 Algorhytm for the differential diagnosis of hyponatremia (2) ERBP Guidelines 2014

21

22

23 What is the best rate for correction of hyponatremia? No «best» rate can be defined a priori: it depends from the severity of symptoms, the type of hyponatremia (acute vs chronic), the underlying comorbidities, the accompanying electrolyte disorders

24 The main problem with therapy in hyponatremia The difficult equilibrium in brain cells between how much correction is enough and how much is too much CNS complications of acute hyponatremia (brain edema) CNS complications of chronic hyponatremia therapy (ODS)

25 Acute hyponatremia is always associated with cell swelling (brain edema)

26 Rapid correction of chronic hyponatremia risk of brain cell dehydration ODS 48 hours Chronic hyponatremia

27 Osmotic Demielynation Syndrome Delayed, gradual neurologic deterioration (up to vegetative state, coma and death) appearing one to several days after a rapid correction of chronic hyponatremia Clinically defined, since imaging not always positive in the early phases Definite diagnosis by CT scan or MR

28 Hoorn EJ et al., Q J Med 2005; 98:

29 Simple goals for the treatment of severe chronic hyponatremia Sterns RH et al., Am J Kidney Dis 2010; 56:

30 Treatment of acute/symptomatic hyponatremia: practical aspects First of all define the target and the rate of correction in meq/hour for how many hours, then calculate how much of the saline solution available should be infused With 3% NaCl: to induce a correction rate of 1 meq/l/h using 3% saline, one should infuse the body weight as millilitres/hour a man with a BW of 70 Kg will increase serum Na by approximately 1 meq/hour when infused with 3% NaCl at a rate of 70 ml/hour With NaCl vials (20 meq/10 ml): to induce a correction rate of 1 meq/l/h using NaCl vials, one should infuse 20 ml/hour (i.e. 40 meq) in a subject with a BW of 70 Kg and a total body water of 42 L, serum Na will increase by approximately 1 meq/hour Potassium: if K is needed (hypokalemia and K depletion), take it into account : if K is co-administered calculate it as sodium Avoid fixed algorythms, be careful with formulas

31 Are formulas useful for the correction of hyponatremia? Adrogue HJ, Madias N Engl J Med 2000; 342:

32 Problems with formulas for hyponatremia correction Underestimation of correction in case of volume depletion or if the kidney regains spontaneously its water excretion ability Formulas may be useful to set the start of therapy, Ongoing urinary but losses they of do water, not Na and K not considered completely avoid the risk of overcorrection K intake not always considered

33 Hyponatremia correction and the risk for overcorrection Is there any risk that spontaneous correction of hyponatremia may increase the planned rate of correction, leading to unanticipated overcorrection? How to avoid too rapid spontaneous correction of hyponatremia?

34 Correcting acute/symptomatic hyponatremia Add osmoles to the numerator Serum Na + = Subtract water from the denominator Na + E + K + E Total body water The excretion of 1 L/hour of maximally diluted urine will increase serum Na by 2-3 meq/l/hour

35 Confucius The wiseman should reflect carefully, anticipating the possibility that the kidney may become an overcorrection factor, especially when temporary causes of hyponatremia are acting «Apart from doctors, the main cause of overcorrection in hyponatremia is the kidney itself, if it regains rapidly the ability to excrete water»

36 The critical issue in acute/symptomatic hyponatremia is to anticipate the possible causes of rapid correction Causes of temporary hyponatremia risk for rapid, unanticipated correction

37 Desmopressin and free water administration to slow an excessively rapid correction of hyponatremia

38 Hoorn EJ et al., Q J Med 2005; 98:

39 Conventional treatments for chronic hyponatremia

40 Vaptans are the antagonists of vasopressin receptors

41 Vasopressin antagonists (vaptans)

42

43

44 Serum sodium (SNa) values during treatment with vaptans and urea. Each point is the mean value of serum sodium for the 12 patients (mean + SD)

45 - SNa increased more than 12 mmol/l the first day in 12/35 patients (37%) and in 13 patients the increase in SNa was higher than 18 mol/l/48 hr - In two of these patients the intensivist lowered the SNa again by giving desmopressin (DDAVP) and water - No cases of clinical osmotic demyelination syndrome (ODS) developed

46

47

48

49 Maximum dose 120 mg/day

50 In hyponatremic patients tolvaptan is highly effective without significantly increasing liver enzymes Berl T et al., J Am Soc Nephrol 2010; 21:

51 Take home messages In acute symptomatic hyponatremia rapid, partial increase in serum Na levels to limit cerebral edema In chronic symptomatic hyponatremia slow correction to avoid iatrogenic neurologic injury (ODS) Take into account the kidney as a cause of unanticipated hypercorrection (look at temporary causes of hyponatremia) In-depth knowledge of pathophysiology the base for a safe approach