A brief reflection into the mechanism of Hyperdiuresis (3% saline + Lasix) in patients with with acute decompensated heart failure sparked by this excellent review by @PulmCrit emcrit.org/pulmcrit/pulmc… and emcrit.org/pulmcrit/hyper… #DiuresisJedi (1/13)
Here are the possible mechanisms that explain the effect:
1⃣Reversal of Hypochloremia
2⃣Pull fluid into the intravascular space
3⃣Reducing neurohormonal sodium retention (e.g. renin/angiotensin/aldosterone and sympathetic nervous system stimulation)
(2/13)
1⃣Reversal of Hypochloremia
2⃣Pull fluid into the intravascular space
3⃣Reducing neurohormonal sodium retention (e.g. renin/angiotensin/aldosterone and sympathetic nervous system stimulation)
(2/13)
1⃣ Certainly hypochloremia causes diuretic resistance, and Cl supplementation (lysine chloride) augments diuretic efficacy (read @PulmCrit blog). What is the mechanism behind hypochloremia induced diuretic resistance? (3/13)
As reviewed by @dhekidney (PMID: 29141174), increased NaCl reabsorption in the Distal Convoluted Tubule plays a very important role in Diuretic Resistance. In this regard, it is important to know that the DCT is heavily regulated by intracellular cl. (4/13) 
The kinase regulating NaCl transport in the DCT (WNK4) has a Cl binding site that regulates its kinase activity. (NaCl transport in the DCT is mediated by the NCC co-transporter which increases its activity when phosphorylated). This work was lead by my best friend @SilvanaBazua!
The DCT has a constant permeability to Cl and K, so changes in extracellular Cl or K directly affect NCC function. Both ⬆️K and ⬆️Cl inhibit NCC function (PMID 25565204). Here is an animation explaining the mechanism of hyperkalemia induced NCC inhibition: (6/13)
Obviously the reverse is also true: ⬇️K and ⬇️Cl increase NCC activity. So, hypochloremia most likely results in increased NCC activity thus inducing Diuretic Resistance. However, one could easily overcome this with Thiazides + higher Lasix dose (7/13)
The fact that Hyperdiuresis works in pts already treated with Thiazide and high Furosemide dose suggests other mechanisms are involved. (8/13)
So what about 2⃣Pull fluid into the intravascular space? .........Given that this pts must be around the flat portion of the starling curve, I'm not convinced this actually increases renal perfusion. So we are left with 3⃣Reducing neurohormonal sodium retention (9/13)
Neurohormonal response to hyperdiuresis could very well be the mechanism. However I would like to point out that one of the most robust neurohormonal responses to 3% saline must be an increase in Vasopressin. Could this actually be playing a role? (10/13)
In this study, an acute NaCl load increased BP. BP rise was blunted when NaCL load was accompanied by water. Increase in BP correlated with copeptin secretion. Suggesting that acute NaCL load can increase ADH secretion and have significant hemodynamic effects (11/13)
So if Hyperdiuresis were to increase Vasopressin secretion, could this possibly improve renal perfusion? I think It definitely can! Here is some work being done by @khaycock2 on the effects of Vasopressin on RRI (Renal Resistive Index): (12/13)
@khaycock2 has seen many cases were RRI improves when Norepinephrine is switched to Vasopressin. So, VERY SPECULATIVE, but plausible that Hyperdiuresis could induce increased Vasopressin secretion and this could improve renal perfusion therefore facilitating diuresis! (13/13)
