Effect of isotonic versus hypotonic maintenance fluid therapy on urine output, fluid balance, and electrolyte homeostasis: a crossover study in fasting adult volunteers
From the heart of the International Fluid Academy in Antwerp comes this study on the kinetics of two different intravenous infusions in healthy volunteers. So many things to consider, let’s get straight in there.
Let’s start in Pedantry corner. Both of the solutions investigated are hyperosmolar and rarely if ever used in British practice. Moreover, the “isotonic” solution is actually a little hypertonic. I can put these points to one side, however, because what the study really answers is a comparison of a 2 day ‘maintenance’ dose of Na+ and Cl- v a 2 day 3x the ‘maintenance’ dose. In the overdose group you’d expect the plasma [Na+] to rise a bit, the plasma [Cl-] to rise a bit, and the ECF volume to rise a bit. And that is exactly what the researchers demonstrated. The anticipated fall in plasma aldosterone concentration with an excess of sodium and chloride was impressively demonstrated, but we should not rush to claim that this will be a significant physiological benefit. Plasma [albumin] also fell, plausible mechanisms include ECF dilution or displacement of albumin to the extravascular space (increased Jv). Inhibition of synthesis less likely as the increase in plasma osmolarity did not reach statistical significance. In the hypotonic maintenance group there was a fall in plasma [Na+], suggesting that 90 mmol/ day is not quite enough for a healthy subject. Though this fall in plasma [Na+] would be dangerous to a patient with raised ICP and poor intracranial compliance, it is perfectly safe for a research subject.
What do we learn that we did not know before? Let’s start with Belgian research subjects (trainees?) They will happily fast for forty eight hours TWICE in a month! This I find almost unbelievable. UK trainees have to be offered coffee, pastries (Danish) and chocolates (Belgian) q2h or their performance significantly degrades. Perhaps this accounts for the Belgian reputation for producing excellent cyclists. Sir Bradley Wiggins, do you want an ICU job?
The researchers are very keen to ascertain which would be the superior ‘maintenance fluid’ for surgical patients. The second experiment therefore must be to repeat the protocol on the same accommodating volunteers while inflicting severe pain (grade 5+) on them. The third experiment (if they are still game) would be pain + non-steroidal analgesic (well-known for causing water retention), then pain + opiate, a well-established ADH stimulant.
Finally, and for me one of the most important learning points from this project: one of the subjects responded idiosyncratically to salt challenge. He is labelled an Outlier, and his data expunged from the analysis. This serves as a reminder that there are patients out there who respond to intravenous fluid therapy in ways we just don’t expect. They are rare, but having witnessed the tragic demise of a young woman from acute hyponatraemia after uncomplicated gynaecologic surgery, 2 litres post-op maintenance and 10 mg Morphine Sulphate analgesia, I will never forget that there are stressed and oestrogenised women who just can’t handle an intravenous hypotonic load. She would not have died if given isotonic (normal) saline maintenance. Doubters, note that no number of RCTs can disprove this assertion. (Management of hyponatraemia. Ariel Arieff)