LOW-DOSE THEOPHYLLINE INCREASES URINE OUTPUT IN DIURETIC-DEPENDENT CRITICALLY ILL CHILDREN

Objective: Determine the effect of low-dose theophylline on urine outp ut and the urinary adenosine: cAMP (cyclic adenosine monophosphate) ex cretion ratio (a measure of phosphodiesterase inhibition) in diuretic- dependent critically ill children. Design: Observational clinical case series and animal laboratory experiment. Setting: A university pediat ric intensive care unit and a pharmacology research laboratory. Patien ts: 10 consecutive oliguric patients treated with theophylline for diu resis. Interventions: Urine output, fluid intake, diuretic dosages, an d number of pressors (including dopamine) were monitored over the 24-h period prior to and the 24-h period immediately after theophylline wa s started. Hourly collections of urine were obtained at baseline and 1 and 3 h after theophylline was started and urinary excretion rates of adenosine and cAMP were measured and calculated. Measurements and res ults: Mean theophylline level in the children was 5.0 mu g/ml. Urine o utput increased from 1.58 +/- 0.46 to 3.75 +/- 0.77 ml/kg per h (p = 0 .008, paired t-test) after theophylline administration. There was no s ignificant change in fluid intake, vasoactive agents, or dosages of ot her diuretics during the study periods. Intrarenal infusion of the IC5 0 concentration of isobutylmethylxanthine for phosphodiesterase activi ty resulted in a reduction of the adenosine: cAMP urinary excretion ra tio in rats (p < 0.05). Low-dose theophylline had no effect on the ade nosine: cAMP urinary excretion ratio in children. Concurrent therapy w ith dopamine was associated with an enhanced diuretic effect of theoph ylline (with dopamine, 1.30 +/- 0.30 to 5.07 +/- 0.77 ml/kg per h vs w ithout dopamine, 1.77 +/- 0.76 to 2.86 +/- 1.08 ml/kg per h; p = 0.03, two-way ANOVA). There was no interaction between dopamine and low-dos e theophylline on the urinary adenosine: cAMP excretion ratio (p = 0.5 6, two-way ANOVA). Conclusions: Theophylline increased urine output in diuretic-dependent critically ill children and the diuretic effect ma y have been potentiated by concurrent use of dopamine. Adenosine recep tor antagonism may be a more likely mechanism for the diuretic effect of theophylline than phosphodiesterase inhibition.