Introduction with a case
Physiology of sodium over-correction
Managing sodium over-correction: DDAVP vs. D5W
Rescue DDAVP strategy
Reactive DDAVP strategy
Proactive DDAVP strategy
- DDAVP (2 micrograms IV q8hr) is started immediately and continued until the sodium is close to normal.
- Sodium is corrected by infusing hypertonic solutions, primarily 3% saline. Of course, hypertonic bicarbonate could also be used, as discussed last week. For a patient requiring volume resuscitation, a large volume of normal saline could be used as well. The key point is that the sodium is increased by a direct effect of the infused solutions. This differs from approaches based on treatment of the underlying problem and waiting for the kidneys to excrete free water.
- Oral fluid intake must be restricted while on DDAVP.
- Potassium supplementation should be taken into account as this is osmotically equivalent to sodium (e.g. 40 mEq KCl tablet is roughly equivalent to ~80ml of 3% NaCl).
- Medications formulated in D5W should be avoided if possible, or otherwise taken into account (e.g. 100 ml of D5W will negate the effect of ~30ml of 3% NaCl)
- If volume overload occurs, this may be managed with furosemide.
An example of how this strategy would work for a patient with severe symptomatic hyponatremia is shown below. DDAVP is started immediately to block renal free water excretion. Boluses of hypertonic therapy are provided initially to improve symptoms and raise the sodium by ~5 mM. Given that the target rise in sodium over the first day is ~6 mM, after the initial increase in sodium, fluid intake is stopped for one day causing the sodium to be stable. Subsequently, an infusion of hypertonic saline is started to gradually increase the sodium to normal.
Contraindications to proactive DDAVP
Evidence supporting the proactive DDAVP strategy
Vaptans = The opposite of DDAVP
- Over-correction of sodium is usually due to recovery of normal renal physiology with excretion of water.
- DDAVP blocks renal excretion of water, allowing the sodium to be predictably manipulated using the Adrogue-Madias equation. This can be accomplished using three strategies:
- Rescue DDAVP strategy: If the sodium has already over-corrected, DDAVP may be combined with D5W to decrease the sodium.
- Reactive DDAVP strategy: If the sodium is rising at a dangerous rate, this may be temporarily halted with a combination of DDAVP and fluid restriction. This stops free water input and excretion, causing the sodium to be relatively stable over time.
- Proactive DDAVP strategy: For patients at high risk for osmotic demyelination syndrome, it may be safest to start DDAVP immediately. With this strategy, DDAVP prevents water excretion from the kidneys, so hyponatremia must be treated directly by infusing hypertonic fluids.
- Conivaptan and Tolvaptan may cause uncontrolled water excretion and over-correction of the sodium. This is not recommended.
- Hyponatremia in general
- Proactive DDAVP strategy
- 2014 European Consensus Guideline on Hyponatremia
- Sterns 2010: Explanation & example of proactive DDAVP strategy
- Sood 2013 : Largest case series of proactive DDAVP strategy.
- MacMillan 2015: Fresh systematic review of DDAVP in hyponatremia
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(1) A jump in urine output may signal a drop in endogenous vasopressin level with an impending over-correction of sodium – so that may be a signal to consider DDAVP use, I'm with you there.
(2) As far as the urine osm, I think perhaps you mean using osm<100 as a signal to consider DDAVP use? Most patients with hyponatremia will have a urine osm>100. It is when the urine osm *decreases* that endogenous vasopressin levels are falling, which would be a signal for possible impending over-correction of the sodium.
Thanks a lot! I wish I had known this stuff when I was a fellow.
Amazing article thanks so much! Some nephrologists suggest the following as an approach: you should measure UOP, if >100cc/hr test the urine, if >100 osm then ddavp should be administered as overcorrection in this setting is more likely, not sure what the evidence for this is but it makes sense though.
As a hospitalist, I love reading this blog. As usual, great graphics, great teaching, innovative and practice changing ideas.
I'm a pulmonary/ccm fellow, and I just wanted to say thanks for maintaining this blog. I've been reading your posts for awhile now, and I find them very informative. I've been spreading the word to some of my colleagues. Keep up the great work!
One question I have with this DDAVP “clamp” strategy is that what to do when it is not just the sodium that’s a serious issue but the volume as well? For example, a patient with septic shock in the ER who also has Na < 115. How do you balance fluid resuscitation?
Hey josh since it appears that this article is speaking to hyponatremia in the setting of hypovolemia and hence the reason for tx with DDAVP and the avoidance of conivapten would it be safe to assume that low dose conivapten would be appropriate in the intravascularly overloaded patients such as heart failure patients? hope this question makes sense and as an aside I just starting reading your articles tonight on my fourth one already fascinating stuff keep up the good work!!!
This approach is very innovative but limited to hypovolemic cases only
The delta sodium predicting equations are not helpful per multiple papers
They all have deficiencies most centered on static nature of inputs. I think Dr stearns who is cited here is foremost authority on use of ddavp to clamp sodium rise pre emptively.
I would only suggest checking sodium early and often
In future an accurate istat Na will be helpful in monitoring sNa very closely much like we monitor glucose on an insulin drip
This may make reactive ddavp strategy more successful.
For more info on sodium Predicting equations see Dr stearns review in CKj (NDT+)
I was wondering if you could apply the opposite reasoning for severe hypernatraemia.
Apply a vaptan clamp and then titrate in 5% dextrose or sterile water.
Great article. @ Derek Louey. I wouldn’t think about using a Vaptan clamp in hypernatremia. Given it blocks the vasopressin receptors causing the kidneys to release free water… it will cause the Na to Increase. If you gave hypotonic solutions with this (D5w) you would only chase your tail. Now, the use of a DDAVP clamp in the setting of judicious use of D5w may be a more physiologically sound approach to severe Hypernatremia.
As a transport RN without access to DDAVP, would you suggest starting vasopressin in the presence of diuresis after initial treatment for hyponatremia? I found an article comparing dilute Vaso boluses to ddavp in DI. What would be the recommended dosing in this situation?
I want to give a comment on the study by Rafat 2014: Using DDVAP as a rescue therapy to avoid overcorrection lead to only a small increase in urine osmolality (mean 200 mosmol/kg), but a great decline in urine volume. Compared to healthy individuals (Baumgarten R Nephrol Dialysis Transplantation 2010, p 1155: – urine osmolality rise form 100 to 800mosmol/kg after DDVAP) the rise in urine osmolality is very small in hyponatremic patients.
How could this be explained?
Hi.. nice review… Can we use vasopressin if DDAVP isnt available? thanks
Hi Josh, Thanks for the interesting post. I’m an internist in Tel Aviv, Israel, and I find many of your posts comprehensive, interesting and thought provoking. I’ve sent several to my residents as the best source for covering some topics. I especially appreciate the EBM approach. I’ve been wondering about some of the strategies you mention regarding severe hyponatremia. The DDAVP clamp is a strategy based on great physiological logic. I don’t recall seeing any patient-relevant benefit. I think the same goes even for managing over correction of sodium for severe hyponatremia. Sure, sodium levels will normalize more slowly. Do… Read more »
Hi, I am an administrator for the Facebook Page, Got Diabetes Insipidus. We have over 4700 international members. I am a retired teacher with a Ph.D and my husband is a biochemist Ph.D. I have been collecting and posting documents about DI, UK hospital warning notices and and medical journal articles for members to present to physicians, particularly upon hospitalization. For multiple reasons hyponatremia is one of the potential challenges of DI as many patients are not coached on how to manage DI and desmopressin in addition to desmo interacting with so many other medications. One of the biggest challenges… Read more »