Hyponatremia Guidelines Part 4

Chronic Hyponatremia without severe or moderately severe symptoms              

**Stop non essential offending agents
**Cause specific treatment
**If mild, suggest against treatment with the sole aim to increase the Na( excellent point)
**If moderate to profound, to treat to not more than 10mmol/L over first 24 hours
**Diagnostic workup
**If cause is fluid overload- Fluid restriction is only recommended. They recommend against V2 receptor antagonist and demeclocycline.
**If SIADH, FW restriction as first line treatment.  If profound, suggestion to increase solute intake with 0.25-0.5g/kg/day of urea or a combination of loop diuretics and oral sodium chloride
**If moderate or severe- against demeclocycline.
**If SIADH and moderate, recommend against V2 receptor antagonists( same goes for severe SAIDH)

**If low circulating volume related chronic low Na, use of .9% saline or balanced solutions recommended.

Why V2 receptor antagonists were not recommended in above Volume overload and SAIDH scenerios?

The reviewers of this committee looked at two systematic reviews that compared V2 receptor antagonists to placebo in chronic hyponatremia. The first review had 15 randomized trials and found no significant difference in risk of death and other adverse events although Na did increase by 5mmol/L.  More rapid increases were noted in the V2 arms. The first systematic review did conclude that vasopressin antagonist treatment significantly increased response rate both early (RR, 3.15; 95% CI, 2.27-4.37; 11 trials) and late (RR, 2.27; 95% CI, 1.79-2.89; 4 trials). Response rates were high in trials assessing mostly euvolemic patients and those assessing mostly hypervolemic patients, with greater effect estimate in the former.

The second review was in 2011, eleven trials were identified (1094 patients). Short-term use of VRAs in treating hyponatremia was successful at raising [Na(+)](serum). Additional experience is required to guide their optimal use and minimize safety concerns. There was no change in deaths. 

So if the above two reviews showed positive response- why did they not recommend use of these agents? The authors feel that the quality of evidence was generally reduced by risk of bias due to difficulties with blinding participants, potentially unbalanced use of FW restriction and incomplete outcome reporting in addition to industry sponsorship.  There is also mention in the discussion re the liver toxicities associated with higher doses of these agents when they were studied in ADPKD.  Drug doses administered are lower in hypoantremia management.  Overall, besides all that, the review committee felt that there is a good risk of overly rapid correction of hyponatremia with these agents.  

Interesting thoughts and I commend the reviewers on looking at these agents with an eye of scrutiny. Although the most randomized trials in hyponatremia are with these agents.   

For full review
http://www.ncbi.nlm.nih.gov/pubmed/24569496