Hyponatraemia: frusemide was more effective than chlorothiazide in producing free water clearance in oedema.

Clinical bottom line (level 2b)

  1. Compared to a thiazide, frusemide reduced urine/plasma osmolality more effectively in patients with oedema and hyponatraemia.
  2. This effect was maintained in the presence of exogenous vasopressin.
Szatalowicz et al: Clinical Science 1982; 62: 235-238
Expires July 2005

The study

Unblinded ?concealed un-randomised trial with intention-to-treat
Setting: university hospital, USA

19 patients (aged mean 45 years, 84% male) stable patients with heart disease, liver disease or nephrotic syndrome and peripheral oedema, who had:
  • plasma sodium concentrations <135 mmol/l
  • creatinine clearances >50 ml/min
  • urine/plasma osmolality ratios >1

Control Group: (n = 9, 9 analysed): chlorothiazide either 10 mg/kg or 20 mg/kg (see below for regimen)
Experimental Group: (n = 10, 10 analysed): frusemide 0.25-5 mg/kg or 1 mg/kg vs 2 control groups
Patients were nil by mouth for 8 hours prior to and during the study. Patients were either given an infusion of insulin and PAH (120 ml/hr) or a glucose solution (50 g/d). During the last two hours, all patients were given 100 m-units of vasopressin/hr.
100% followed for 4 hours

The evidence

Outcome Control Group
(SD)		 Experimental Group
(SD)		 Mean Difference
(95% CI)
reduction in urine/plasma osmolality ratio: 10 mg/kg chlorothiazide 0.20
() 		0.80
() 		p<0.01
( to )
reduction in urine/plasma osmolality ratio: 20 mg/g chlorothiazide 0.49
() 		1.2
() 		p<0.01
( to )

  • Addition of vasopressin increased urea/plasma osmolality ratio in patients on chlorothiazide by 0.30 but had no effect on patients on frusemide.
  • Plasma sodium and osmolality results are not given.

    • Comments

    1. Selection criteria of patients are not given.
    2. The investigators initially compared the higher dose frusemide regime to the lower dose chlorothiazide (patient numbers not given) and then studied further nine patients with the alternative doses.

    Citation

    1. Szatalowicz VL, Miller PD, Lacher JW, et al: Comparative effect of diuretics on renal water excretion in hyponatraemic oedematous disorders. Clinical Science 1982; 62: 235-238
    Search Terms: hyponatremia, diuretics and therapy in Medline
    Contributor: Tim Ringrose and Clare Wotton, July 2000
    Reviewer:

    Clinical Question.
    Patient hyponatraemia
    Intervention or Exposure frusemide
    Comparison chlorothiazide
    Outcome renal water excretion