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There are so few prospective randomized trials in hyponatremia that we cherish every one, even the quirky, underpowered ones. So let’s take our hats off and salute the Royal Thai Air Force for putting the DDAVP clamp under the RCT microscope.
Safety and efficacy of proactive versus reactive administration of desmopressin in severe symptomatic hyponatremia: a randomized controlled trial
https://www.nature.com/articles/s41598-024-57657-z
The trial is underpowered: their power calculation called for 66 patients, but they enrolled 49. Still, I love that they had the courage to test something many of us, including me, have accepted without prospective data. Given the scarcity of trials, this is very much the hyponatremia way.
The investigators randomized patients to a proactive strategy (a DDAVP clamp) versus reactive DDAVP.
And they had the courage to enroll people who were actually sick. Many hyponatremia trials enroll patients with relatively mild disease, but this cohort had an average sodium of 115 mEq/L, which is impressive. Just look at the High risk of osmotic demyelination syndrome and the Clinical presentation in this population. These are the bad actors in hyponatremia—the patients who actually need randomized trials.
The HIT trial would have benefited from enrolling a cohort like this.
The results though, were similar to the HIT. There was no difference in overcorrection, 24-hour sodium change, or length of stay. The sodium rose more in the proactive group at 48 hours, but given multiple comparisons in a small trial, that signal should be ignored.
The overcorrection rate was 16.7% in the proactive group vs 28% in the reactive group (P = 0.54).
That’s remarkably consistent with MacMillan’s Toronto data, where about 18% of all comers overcorrected. It’s also far better than the 40% overcorrection rate reported by George Et al in Western Pennsylvania.
Interestingly, Pakchotanon enrolled patients with Na <125 mEq/L, neatly splitting the difference between the <130 threshold used by MacMillan and the <120 used by George.
Honestly, I expected better sodium control than they achieved. My suspicion is that the 3% saline dosing protocol in this trial was relatively aggressive. I know I tend to be more conservative with hypertonic saline when managing severe hyponatremia.
Still, this study is welcome. It’s part of a growing trend in hyponatremia research toward prospective data rather than retrospective dogma.
And in hyponatremia, every randomized trial moves the field forward.