Thursday, August 7, 2014

Managing Overcorrection of Hyponatremia with DDAVP

So you have a patient who presents to your emergency department after being brought in by EMS with a three-day history of nausea and vomiting. The patient has had what he describes as a “pretty rough weekend” and admits to have consumed large quantities of alcoholic beverages. While you are examining the patient, the patient has two episodes of tonic-clonic seizures, both episodes subsiding with administration of benzodiazepines. Labs are collected, and the complete metabolic panel reveals a serum sodium concentration of 117 mEq/L. As the clinician, you are very diligent in correcting this patient’s acute episode of symptomatic hyponatremia and you perform the necessary calculations to determine the infusion rate for correcting the serum sodium with your fluid of choice (or you may even decide to go ahead and simply administer a 100 mL bolus of 3% sodium chloride).  The patient is not experiencing any further neurological deficits, but the patient is admitted for further monitoring and is on a relatively strict fluid restriction. Labs are drawn a couple of hours later, and results of the complete metabolic panel now reveal a serum sodium concentration of 131 mEq/L.

A few choice expletives are flying through your head now. What in the world happened? Here you are, with the best of intentions in correcting the sodium, but for some reason, you overshot and swung the sodium pendulum a bit too aggressively. For the time being, the patient is neurologically intact, but you are fearful that the patient may be at great risk of osmotic demyelination syndrome. So what are you going to do now?

There are some treatment options that you can initiate at this point, but bear in mind that they should be performed in conjunction with a nephrology consult. The nephrologist may recommend initiation of desmopressin (DDAVP).  DDAVP is a synthetic analog of vasopressin that binds to the V2 receptors within the collecting ducts of the kidneys to prevent the production of dilute urine and essentially increase water reabsorption. The mantra of “sodium follows water” applies here, and in doing so, the rate of correction of the serum sodium can become a bit more predictable and stable. With one exception (1), much of the evidence surrounding the use of DDAVP for treating the overcorrection of serum sodium in the setting of hyponatremia stems from research by Stern and colleagues (2, 3, 4).


With this, you may ask the question of whether we should be preemptively administering DDAVP in conjunction with our fluid of choice in managing hyponatremia to prevent overcorrection of serum sodium. In a study published in the American Journal of Kidney Disease (5), this very question was posed and a retrospective review of 25 patients was undertaken to determine the rate of sodium correction and related outcomes following concomitant administration of both hypertonic saline and DDAVP in patients who presented with hyponatremia. The administration of both agents was aimed to maintain the increase in serum sodium concentrations by no more than 6 mEq/L in a 24-hour period. At 24 and 48 hours, the rate of increase in serum sodium concentrations was 5.8 ± 2.8mEq/L and 4.5 ± 2.2mEq/L, respectively. In addition, at the 24 and 48-hour time points, serum sodium concentrations did not increase by more than 12 mEq/L and 18 mEq/L, respectively, and none of the patients experienced any complications associated with this treatment strategy. The investigators do state that though this treatment strategy is seemingly successful, it may not be appropriate to utilize in all patients, and evaluation of the underlying cause of they hyponatremia is necessary to determine whether the patient may be able to tolerate this regimen.

In terms of dosing and administration of DDAVP, it generally ranges anywhere from 1 to 2 mcg intravenously or subcutaneously administered every 6 to 8 hours until you are comfortable with the level of correction in the serum sodium. Some folks may also advocate for concomitant administration of a weight-based fluid bolus of 5% dextrose in water (a dose of 6 mL/kg) infused over one to two hours, and this may help reduce the sodium concentration by 2 mEq/L. Again, much caution is advised when this technique is employed and nephrology should be on board to help guide the course of treatment.

Going back to our patient above, prompt recognition of the overcorrection in serum sodium leads you to consult nephrology, and both DDAVP and 5% dextrose in water are administered intermittently at 8-hour intervals over a 24-hour period. Serum sodium concentrations hover in the 133 to 137 mEq/L range during that time period. Sodium concentrations over the next couple of days stabilize back to normal, and with no further complications experienced during the course of the hospital stay, the patient is able to be safely discharged three days later.

Done and done.

References:
  1. Tomlin SC, Williams R, Riley S. Preventing overcorrection of hyponatraemia with desmopressin. BMJ Case Rep 2011 Nov 8 (doi: 10.1136/bcr.07.2011.4512).
  2. Perianayagam A, Sterns RH, Silver SM, et al. DDAVP is effective in preventing and reversing inadvertent overcorrection of hyponatremia. Clin J Am Soc Nephrol 2008; 3:331-336.
  3. Mohmand HK, Issa D, Ahmad Z, Cappuccio JD, Kouides RW, Sterns RH. Hypertonic saline for hyponatremia: risk of inadvertent overcorrection. Clin J Am Soc Nephrol 2007; 2:1110-1117.
  4. Sterns RH, Hix JK, Silver S. Treating profound hyponatremia: a strategy for controlled correction. Am J Kidney Dis 2010; 56:774-779.
  5. Sood L, Sterns RH, Hix JK, Silver SM, Chen L. Hypertonic saline and desmopressin: a simple strategy for safe correction of severe hyponatremia. Am J Kidney Dis 2013; 61:571-578.