The DDAVP clamp technique has considerably simplified the management of severe hyponatremia. The fundamentals of the technique are as follows:
- Before the use of the DDAVP clamp, the primary cause of sodium overcorrection was endogenous free water excretion by the kidneys. For example, patients would present to the hospital with retention of free water due to endogenous ADH production as a result of hypovolemia. Following volume resuscitation, ADH levels would plummet and the patient would promptly excrete a ton of free water – causing dangerously rapid correction of their sodium.
- The DDAVP clamp involves the administration of exogenous, scheduled DDAVP that blocks endogenous water excretion. By blocking renal water excretion, the DDAVP clamp eliminates the largest source of variability in a patient’s response to therapy. The sodium may subsequently be raised in a controlled fashion using titrated doses of 3% NaCl or hypertonic bicarbonate.
- Further explanation of the DDAVP clamp is here.
The DDAVP clamp was a substantial step forwards in the management of severe hyponatremia. It eliminated a lot of the variability and excitement of managing these patients.
The only drawback to the DDAVP clamp technique is that this requires the use of a continuous infusion of 3% saline to bring up the sodium concentration. Hypertonic saline infusions are safe and reasonably easy to use (contrary to widespread dogma, 3% saline does not require infusion via a central line). However, 3% saline infusions do have a few minor drawbacks:
- Gradual 3% saline infusions take a long time to work. This makes it impossible to institute any tight, closed-loop feedback system to achieve control of the sodium. For example, the results of a 3% saline infusion won’t be seen for 5-10 hours – this makes it nearly impossible to achieve very precise control of the sodium. Instead, the sodium may tend to gradually drift out of control, with intermittent nudges in the right direction.
- If the treatment team gets distracted, then the 3% saline infusion may be left running for too long or at too high a rate.
The solution to these issues is relatively obvious – the use of small, intermittent boluses of fluid to achieve the desired sodium level.
The concept is very simple. The ideal sodium curve is plotted out a priori (e.g., 6 mEq rise per 24 hours). Sodium levels are then checked q4hr or q6hrs. The volume of 3% saline or water needed to push the patient back onto the desired curve is calculated and administered. This prevents the patient from ever deviating significantly from the desired sodium curve.
These adjustments may be achieved using an iterative process as follows:
- Check the sodium level and determine how far off the sodium is from the target sodium. (If managing the sodium closely and appropriately, this shouldn’t be too much – usually within +/- 3 mM).
- Calculate the volume of 3% saline or free water that is needed to bring the sodium back to target (more on this below).
- Administer the full amount of free water or 3% saline that is predicted to bring the sodium back to target over ~2 hours.
- Recheck the sodium level after the patient has received the full volume of fluid needed to correct their sodium level back to target. Typically, sodium levels may be checked q4hr or q6hr. Completing therapy prior to repeating the sodium allows the therapeutic effect of the bolus to be accurately assessed, with subsequent action as needed (go back to step #1 and repeat the cycle).
Calculating the amount of 3% saline or water required to administer can easily be done using online calculators:
- Calculate the volume of 3% saline needed to increase the sodium using this calculator on MDCalc. The calculator can be set to determine the volume of 3% saline needed to increase the sodium by 1 mM; this may be scaled up to match the desired increase in sodium. It’s probably inadvisable to bolus more than ~250 ml 3% saline at a time.
- If the patient is developing a non-anion gap metabolic acidosis, hypertonic bicarbonate (ampules of bicarbonate with a concentration of 1 mEq/ml) may be substituted for 3% saline. Hypertonic bicarbonate has a tonicity equivalent to 6% saline. Thus, the volume of hypertonic bicarbonate can be determined by finding the appropriate volume of 3% saline that would be needed (as described above) and dividing that by two. More on this here.
- Calculate the volume of free water needed to decrease the sodium using this calculator on MDCalc (simply set the “desired sodium” to the sodium level that you are targeting).
Administering boluses of fluid may seem dangerous. However, the risk of osmotic demyelination doesn’t relate to the change in sodium over small periods of time – but rather to the overall average rate of sodium change over a day (or days). Consequently, aggressively using small boluses of 3% saline and water to achieve the desired sodium should reduce the risk of osmotic demyelination as compared to a more casual approach to sodium management.
One advantage of a DDAVP clamp-bolus technique is that it is extremely simple. The entire protocol could be automated and performed with nearly no physician input. This could be especially useful now that ICU beds are very tight (e.g., a patient with critical hyponatremia could be safely managed at a small hospital where practitioners lack experience managing hyponatremia, without requiring transfer to a tertiary center).
The SALSA multicenter RCT recently compared continuous infusions versus boluses of hypertonic saline for the management of hyponatremia. Both strategies were safe and clinically effective. However, the use of boluses showed some signs of benefit (more rapid initial correction, with reduced risk of overcorrection that required lowing of the sodium). This trial didn’t utilize DDAVP or adjust the bolus size based on sodium level, so it’s not a trial of the DDAVP clamp-bolus technique. However, it provides some evidence supporting the safety and efficacy of a strategy involving repeated boluses of hypertonic saline as needed.
There is not currently any direct evidence supporting the DDAVP clamp-bolus technique. An interesting debate would be exactly how much evidence is needed to support this. Ultimately this boils down to giving a drug (3% saline) in a different administration schedule (intermittent infusions over two hours rather than a continuous infusion). This is analogous to the use of labetalol as PRN IV boluses rather than as a continuous infusion (figure below, discussed further here). As with many things in critical care, there is no prospective RCT comparing a labetalol infusion versus PRN boluses of labetalol. Rather, practitioners will chose a dosing strategy which makes sense in the context of their logistics. Given that 3% saline has rather sluggish pharmacokinetics, I would question the wisdom of giving it as a continuous infusion in the first place (continuous infusions make pharmacokinetic sense for drugs with short half-lives).
Is the DDAVP clamp-bolus technique necessary? Certainly not. The DDAVP clamp combined with a slow infusion of hypertonic saline gets the job done fine. The DDAVP clamp-bolus technique is merely one more tool in the toolbox of managing critical hyponatremia. I believe that the DDAVP clamp-bolus technique may provide more precise control over sodium, in a more easily protocoled fashion. However, it’s unlikely that this would have measurable effects on patient-centered outcomes.
Related
- DDAVP clamp (PulmCrit blog)
- Hyponatremia (IBCC chapter)
- SALSA trial – I didn't do a deep dive on this study because other have already, see the links below:
- Original manuscript
- SALSA trial – RebelEM by Salim Rezaie
- SALSA trial – SGEM 326 with Casey Parker
- Pulmcrit wee: The cutoff razor - April 15, 2024
- PulmCrit Blogitorial – Use of ECGs for management of (sub)massive PE - March 24, 2024
- PulmCrit Wee: Propofol induced eyelid opening apraxia – the struggle is real - March 20, 2024
love it Josh. these “wee’s” can take as much time as the EMCrit posts. is there a way to get CME for these as well?
many thanks
saan
My comment
Do you think it might be useful to administer thiamine rutinely when correcting hyponatriemia, especially in the elderly, even if they are not alcoholics, thinking that they may have a slight malnutrition anyway? It certainly wouldn’t be harmful.
I use desmopressin-clamps for symptomatic (hypovolemic) hyponatremia successfully; but only on the ICU. But to my knowledge there is no exact recommendation for the dosage of Dextrose 5%i.v. if overcorrection ocurrs. In SALSA: Relowering treatment (dextrose, 5%, infusion of 10 mL/kg over 1 hour and/or intravenous desmopressin 2μg if sNa level increase was≥10 mmol/L within the first 24 hours or ≥18 mmol/Lwithin 48 hours – or tretament “as you like it” with/without desmopressin. First, I think the infusion of D5% 10ml/kg over 1h is much too fast: if dextrose is not metabolized rapidly it can induce osmotic diuresis and loss… Read more »
Thanks Josh. How do you use the ddAVP clamp in a hypovolaemic patient who requires a significant volume of fluid resuscitation?