1/ Can't love this enough!💕 Sharing a few thoughts:
(i) Personally, I like IV bumetenide for pharmacodynamic reasons: mg-for-mg, bumetenide is 5x more ototoxic than furosemide but 40x more potent = resulting in an ototoxic potential of 1/8th that of furosemide. (PMID: 7338574)
(i) Personally, I like IV bumetenide for pharmacodynamic reasons: mg-for-mg, bumetenide is 5x more ototoxic than furosemide but 40x more potent = resulting in an ototoxic potential of 1/8th that of furosemide. (PMID: 7338574)
2/ This is perhaps why *conventional* maximum doses of bumetenide are twice as potent (e.g. 2mg/hour of bumetenide vs. 40mg/hour of lasix). So the loop diuretic dosage can be maximized with lower potential for ototoxicity.
(ii) The term "contraction alkalosis" is a troublesome.
(ii) The term "contraction alkalosis" is a troublesome.
3/ I've often seen alkalosis being equated to hypovolemia. Most likely, the generation of alkalosis is more dependent on Cl-HCO3 balance than the volume status, the proposed term being "chloride depletion alkalosis (CDA)": PMID: 22223876.
Volume independent mechanisms of CDA -
Volume independent mechanisms of CDA -
4/ (a)Concentration effect: Loss of HCO3-less/Cl-rich fluid from ECF (e.g. vomiting HCl or chloruresis with lasix) simply concentrates the HCO3 in the remaining ECF.
(b) ⬇️ chloride delivery to distal nephron reduces apical Cl/HCO3 transport (via pendrin) --> ⬇️ HCO3 secretion.
(b) ⬇️ chloride delivery to distal nephron reduces apical Cl/HCO3 transport (via pendrin) --> ⬇️ HCO3 secretion.
5/ Indeed, there are a couple mechanisms by which intravascular depletion can cause alkalosis:
(a) ⬇️ peritubular Pc in PCT promotes HCO3 reabsorption
(b) Stimulation of RAAS
However, these are often superseded by other factors. E.g. Secretory diarrhea causes acidosis instead!
(a) ⬇️ peritubular Pc in PCT promotes HCO3 reabsorption
(b) Stimulation of RAAS
However, these are often superseded by other factors. E.g. Secretory diarrhea causes acidosis instead!
6/ Therefore, hypovolemia is NOT required for generation of CDA.
E.g. A previously hypervolemic patient can develop CDA with chloruresis (by the two aforementioned mechanisms), while the ECF volume is still high.
Hint: perform *intravascular* volume status assessment (#pocus)
E.g. A previously hypervolemic patient can develop CDA with chloruresis (by the two aforementioned mechanisms), while the ECF volume is still high.
Hint: perform *intravascular* volume status assessment (#pocus)
7/ Diuretics can cause CDA due to chloruresis; but they can also do it by an independent mechanism:
⬆️ Na delivery to distal nephron --> ⬆️ Na reabsorption through the ENaC channel --> more negative luminal potential in distal nephron --> ⬆️ H+ secretion by α-intercalated cells.
⬆️ Na delivery to distal nephron --> ⬆️ Na reabsorption through the ENaC channel --> more negative luminal potential in distal nephron --> ⬆️ H+ secretion by α-intercalated cells.
8/ Summary -
1. CDA can develop without hypovolemia
2. Lasix can cause alkalosis irrespective of CDA (alternate mechanism)
1. + 2. = alkalosis while on lasix does NOT mean "the patient is dry". It is, however, an opportunity to use acetazolamide for sequential nephron blockade.
1. CDA can develop without hypovolemia
2. Lasix can cause alkalosis irrespective of CDA (alternate mechanism)
1. + 2. = alkalosis while on lasix does NOT mean "the patient is dry". It is, however, an opportunity to use acetazolamide for sequential nephron blockade.
