SEVERE CHRONIC HYPONATREMIA: A Pathophysiological Rumination.

PART 4: CONTROL ISSUES

1. Losing Control: In the preceding posts, I explained how sudden emergence of water diuresis as the predominant mechanism by which rapid overcorrection of serum sodium happens in cases of severe chronic hyponatremia.  Few situations or more stressful in nephrology than when we suddenly find that serum sodium has increased by 12 mmol or more within a few hours. The usual scurried response is the immediate administration of 5% dextrose water, DDAVP are both. There has recently been some evidence that using DDAVP with D5W rapidly re-lower the sodium is well tolerated. But, as it was illustrated in this  paper, the response to these therapies is very unpredictable with the usual clinical course being a rather erratic series of rises and falls in serum sodium.

Two mechanisms are responsible for the vast majority of cases of overcorrection due to emergence of water diuresis.  (1) a sudden drop in plasma ADH/AVP levels due either to resolution of a transient source of ADH secretion or repletion of subclinical hypovolemia and (2) in cases of solute depletion hyponatremia, the sudden availability of solute (in the form of saline solutions or protein load) in the setting of an appropriately suppressed ADH. The common feature of both these phenomena is the very low level of plasma ADH which allows water diuresis.

2. Gaining Back the Control:  So how can we prevent the sudden water diuresis which is the hallmark of serum sodium overcorrection? We’ve argued above that the lack of sufficient ADH or sudden turning off of the ADH secretion is responsible for the sudden loss of free water in the urine. To address this issue specifically, in this paper by Sood et al, the Rochester group tested a very simple yet brilliant idea: why not keep the SIADH state from turning off by creating a robust iatrogenic state of SIADH? This was achieved by giving IV DDAVP 2mg every 8 hours (1 mg was tried as well but there was some breakthrough diuresis; also q6hr schedule was also tried). What this does is, by greatly reducing urine output, stabilize the denominator in Edelman’s equation (i.e. almost eliminated changes in TBW, see figure in previous post) and turn the patient into the proverbial beaker, into which now sodium, potassium and water can be added as needed to control the rate of sodium correction. In their series of 25 patients with starting serum sodium of less than 120 mEq/L, quoting directly from the abstract, “Mean changes in serum sodium levels during the first and second 24 hours of therapy were 5.8 +/- 2.8 (SD) and 4.5 +/- 2.2 mEq/L, respectively, without correction by >12 mEq/L in 24 hours or >18 mEq/L in 48 hours and without a decrease during therapy.” There was no difference in the predicted and actual correction of sodium and there were no adverse effects associated with the treatment.

Essentially, by converting the patients into human "beakers" by inducing iatrogenic SIADH and then infusing 3% saline at the desired rate allow for safe and predictable rise in serum sodium without any complications.

Our experience with this protocol has been extremely gratifying.  When this protocol was used very carefully, the serum sodium correction graph was almost invariably an almost straight line: Something that we almost never see with the traditional method of treatment of severe hyponatremia.

Once a serum sodium is between 125 and 130 mmol/L DDAVP can be discontinued while closely watching the patient.

There are a few important points that need to be mentioned here.

#1 --- It has to be clarified to the nursing staff that the DDAVP needs to be given exactly every 8 hours and the dose cannot be missed.  If the dose is missed, there can be breakthrough large volume diuresis in about 10-12 hours from the last dose which can cause overcorrection.

#2 --- The water content of all fluids given/ingested will be retained.  Therefore a very strict fluid restriction needs to be enforced.  In the IV fluids being given to the patient's in the form of infusions with antibiotics etc. need to be accounted for by calculation.

#3 --- in patients with congestive heart failure lasix can be used if it seems like fluid overload is becoming a problem.

#4 --- if a double-lumen PICC line is being used for 3% saline infusion and for drawing labs, the hypertonic infusion should be held for a few minutes before a drawing serum sodium level.  Recirculation can give a falsely elevated sodium level.  An important clue in this situation would be that there would be no large change in urine output that would be expected with a true sudden rise in serum sodium.

This protocol is somewhat opposite of what we have traditionally been taught regarding treatment of severe hyponatremia.  Given how stress-free and easy the management of severe hyponatremia has become with this for me and other colleagues, I expect this protocol to gain more widespread acceptance over the next few years.  I would also like to know if anybody has had experience with this protocol, good or bad.

Hyponatremia remains a clinical challenge but is also fun and stimulating at the same time.  A little time spent on determining the physiology at work and using more quantitative methods of choosing the doses of 3% saline coupled with good results for the patient make it very rewarding as well.

Posted by Hashim Mohmand