Ritodrine- and terbutaline-induced hypokalemia in preterm labor: Mechanisms and consequences

Abstract

The effects of ritodrine and terbutaline on potassium homeostasis, renal function, and cardiac rhythm were assessed in women treated with these drugs for preterm labor. Timed blood and urine samples were obtained for two hours before and during six hours of intravenous ritodrine (N = 5) and terbutaline (N = 5) administered in pharmacologically equivalent doses. No differences were found in any parameters affecting potassium homeostasis or renal function between these drugs. A decrease in mean plasma potassium of 0.9 mEq/liter occurred after 30 minutes of drug infusion (4.2 ± 0.1 to 3.3 ± 0.1 mEq/liter, P < 0.005) before any significant changes in plasma glucose (75.0 ± 4.7 to 93.7 ± 6.1 mg/dl, P = NS) or plasma insulin (12.4 ± 6.0 to 28.4 ± 5.1 mU/ml, P = NS). The mean plasma potassium after four hours of drug infusion was 2.5 ± 0.1 mEq/liter. Plasma insulin rose to a level known to induce cellular potassium uptake (39.2 ± 7.7 mU/ml) after 60 minutes of drug therapy and remained at this level for four hours. Hyperlactatemia occurred at four hours (4.7 ± 0.8 mmol/liter) and the plasma lactate/pyruvate ratio increased in a 10:1 ratio. Both drugs significantly reduced glomerular filtration rate, sodium, potassium, and chloride excretion and urinary flow rate. Changes in acid-base homeostasis, plasma aldosterone, or renal potassium excretion did not contribute to ritodrine- or terbutaline-induced hypokalemia. In 83 women with preterm labor randomly assigned to ritodrine (N = 42) or terbutaline (N = 41), the maximum decrease in plasma potassium occurred after six hours of drug infusion. During Holter monitoring, 3 of 14 women treated with ritodrine or terbutaline developed symptomatic cardiac arrhythmias at the lowest plasma potassium, while no women treated with saline and morphine (N = 12) developed cardiac arrhythmias (P = 0.14). We conclude that ritodrine and terbutaline induce profound hypokalemia by stimulating cellular potassium uptake and both drugs cause significant renal sodium and fluid retention and cardiac arrhythmias. Careful monitoring of electrolytes, fluid balance, and cardiac rhythm should occur during tocolytic therapy with ritodrine or terbutaline.