Chapter 14 Fluids, electrolytes & acid-base

14.1 Hyponatraemia

Chung et al. (1987): - UNa discriminates between hypovolaemic (UNa ~18 mM) and eu-volaemic (UNa ~72 mM) hyponatraemia.

SALT-1 & SALT-2 (2006): - tolvaptan vs. placebo for eu- or hyper-volaemia hyponatraemia. Tolvaptan was effective at raising serum Na⁺ in the short term (up to 30 days).

EVEREST Outcome (2007): - tolvaptan vs. placebo for patients hospitalised with heart failure. Tolvaptan had beneficial effects on short-term fluid-electrolyte status but no effect on long-term mortality or heart-failure morbidity outcomes.
SGLT2i in SIAD (2022): - empagliflozin vs. placebo in chronic SIAD (n = 14, cross-over, blind RCT). Baseline Na 130 mM. After 4 weeks, improvements in serum Na and cognitive function scores in this small study.

14.2 Hyperkalaemia

OPAL-HK (2015): - patiromer vs. placebo in patients with CKD on RASi. Patiromer was effective at preventing hyperkalaemia.

Packham et al. (2015): - ZS-9 (zirconium cyclosilicate) vs. placebo in hyperkalaemia. ZS-9 was effective at lowering potassium levels.

AMBER (2019): - patiromer vs. placebo in patients with CKD and resistant HTN being treated with open-label spironolactone. At 12 weeks, more patients in the patiromer group remained on spironolactone (86 vs. 66 %). Differences in blood pressure / proteinuria not determined.

14.3 IV fluid therapy

SAFE (2004): - 4% HAS vs. 0.9% NaCl in ITU. No difference in mortality at 28 days.

FACCT: fluids and catheters treatment trial (2006): - conservative vs. liberal fluid strategy in acute lung injury. Primary outcome was death at 60 days. No difference between groups in primary outcome but conservative strategy shortened duration of ventilation / ITU stay.

FEAST (2011): – IV fluid bolus vs. no fluid bolus in children with severe febrile illness in East Africa (57% malaria). 48-hr mortality was higher in the fluid bolus group.

SMART (2018): - balanced crystalloids vs. 0.9% NaCl in critically ill adults. Primary outcome was composite of death, RRT or persistant SCr > 200% baseline. Balanced crystalloid group fared better.

SALT-ED (2018): - balanced crystalloids vs. 0.9% NaCl in non-critically ill adults. Primary outcome was composite of in-hospital mortality and length-of-stay to 28 days. No difference between groups (but less AKI in the balanced crystalloids group). Median volume of fluids was only ~1L.

RELIEF (2018): - restrictive vs. liberal peri-operative fluid strategy. No difference in the primary outcome (disability-free survival at 1 yr); more AKI in the restrictive group.

14.4 Diuretic therapy

Dikshit et al (1973): - haemodynamic parameters studied in 20 patients given IV furosemide for LV failure after acute MI. Within 15 mins, there was a 50% increase in peripheral venous capacitance and a 25% fall in LV filling pressure (PCWP), preceding any increase in urine output. Therefore the immediate beneficial effects of furosemide are mediated by venodilatation.

CARESS-HF (2012): - diuretics vs. ultrafiltration in acute decompensated heart failure. No difference in weight loss at 96 hrs; UF group had worse renal function and more adverse events.

DOSE (2011): with factorial design: bolus vs. infusion furosemide and low- vs. high- dose in acute decompensated heart failure. No significant differences in symptoms or SCr at 72 hrs in any group.

14.5 Metabolic acidosis

14.5.1 Acidosis of CKD

de Brito-Ashurst et al. (2009): - oral NaHCO₃ vs. standard care for 2 yrs in acidaemic CKD IV. NaHCO₃ slowed rate of CrCl decline.

Mahajan et al. (2010): - oral NaHCO₃ vs. placebo for 5 yrs in hypertensive CKD III. NaHCO₃ slowed rate of eGFR decline.

14.5.2 Renal tubular acidosis

FF test (2007): - furosemide-fludrocortisone test to diagnose dRTA.

14.5.3 Severe metabolic acidosis

BICAR-ICU (2018): - IV 4.2% NaHCO₃ vs placebo in severe metabolic acidaemia (pH <7.2). No effect on composite primary outcome overall - but NaHCO₃ did improve 28-day survival in (pre-specified) subgroup with AKI.