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Low-dose theophylline increases urine output in diuretic-dependent critically ill children
1Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh, PA, USA.
Insights
Low-dose theophylline significantly increased urine output in critically ill children. This diuretic effect may be enhanced by dopamine, suggesting adenosine receptor antagonism as a potential mechanism.
Area of Science:
- Pediatric Intensive Care
- Pharmacology
- Nephrology
Background:
- Critically ill children often experience diuretic resistance.
- Theophylline's phosphodiesterase inhibitory effects are well-documented.
- Its role in augmenting diuresis in pediatric critical care requires further elucidation.
Purpose of the Study:
- To investigate the impact of low-dose theophylline on urine output in diuretic-dependent critically ill children.
- To assess theophylline's effect on the urinary adenosine:cyclic adenosine monophosphate (cAMP) excretion ratio as a marker of phosphodiesterase inhibition.
- To explore potential synergistic effects with dopamine.
Main Methods:
- An observational clinical case series in a pediatric intensive care unit.
- An accompanying animal laboratory experiment using rats.
- Monitoring of urine output, fluid intake, and concomitant medications in 10 oliguric children before and after theophylline administration.
- Measurement of urinary adenosine and cAMP excretion rates.
Main Results:
- Theophylline administration significantly increased urine output (1.58 to 3.75 ml/kg/h, p=0.008).
- No significant changes were observed in fluid intake or other diuretic dosages.
- Theophylline did not alter the adenosine:cAMP excretion ratio in children, but phosphodiesterase inhibition reduced this ratio in rats.
- Concurrent dopamine therapy potentiated theophylline's diuretic effect (p=0.03).
Conclusions:
- Low-dose theophylline effectively increases urine output in diuretic-dependent critically ill children.
- The mechanism is likely related to adenosine receptor antagonism rather than phosphodiesterase inhibition.
- Dopamine may enhance theophylline's diuretic efficacy in this patient population.
Objective:
Determine the effect of low-dose theophylline on urine output and the urinary adenosine: cAMP (cyclic adenosine monophosphate) excretion ratio (a measure of phosphodiesterase inhibition) in diuretic-dependent critically ill children.
Design:
Observational clinical case series and animal laboratory experiment.
Setting:
A university pediatric intensive care unit and a pharmacology research laboratory.
Patients:
10 consecutive oliguric patients treated with theophylline for diuresis.
Interventions:
Urine output, fluid intake, diuretic dosages, and number of pressors (including dopamine) were monitored over the 24-h period prior to and the 24-h period immediately after theophylline was 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 Results:
Mean theophylline level in the children was 5.0 microg/ml. Urine output 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 significant change in fluid intake, vasoactive agents, or dosages of other diuretics during the study periods. Intrarenal infusion of the IC50 concentration of isobutylmethylxanthine for phosphodiesterase activity resulted in a reduction of the adenosine: cAMP urinary excretion ratio in rats (p < 0.05). Low-dose theophylline had no effect on the adenosine: cAMP urinary excretion ratio in children. Concurrent therapy with dopamine was associated with an enhanced diuretic effect of theophylline (with dopamine, 1.30 +/- 0.30 to 5.07 +/- 0.77 ml/kg per h vs without 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-dose theophylline on the urinary adenosine: cAMP excretion ratio (p = 0.56, two-way ANOVA).
Conclusions:
Theophylline increased urine output in diuretic-dependent critically ill children and the diuretic effect may have been potentiated by concurrent use of dopamine. Adenosine receptor antagonism may be a more likely mechanism for the diuretic effect of theophylline than phosphodiesterase inhibition.