Beat-to-Beat Measurement of Cardiovascular Effects of a Single Subcutaneous Dose of Terbutaline in Healthy Subjects.

Abstract

To evaluate the cardiovascular effects over time of a single subcutaneous (SC) dose of terbutaline 0.75mg in young healthy volunteers using continuous, beat-to-beat monitoring of cardiovascular effects. Nine healthy young volunteers were administered a SC dose of terbutaline sulphate 0.75mg. Cardiovascular effects were continuously monitored over 2 hours using Finapres and Modelflow technology. Blood was drawn at several timepoints for determination of the plasma terbutaline concentration. The peak plasma concentration of terbutaline was 17.3 ± 4.5 (µg/L at 28.9 ± 12.5 minutes after SC administration. Changes in cardiovascular parameters were observed very quickly, with increases in stroke volume (16.7 ±8.9%), cardiac output (46.0 ± 22.6%), systolic blood pressure (15.1 ± 11.6%) and heart rate (48.1 ± 15.7%) at 9.3 ± 3.8, 16.9 ± 4.8, 21.3 ± 8.9 and 49.7 ± 16.4 minutes, respectively. In five of eight subjects a very rapid (at 9.6 ± 3.7 minutes) drop in diastolic blood pressure (9.8 ± 5.1 %) was observed, while total peripheral resistance decreased maximally by 33.5 ± 7.9% at 18.9 ± 7.1 minutes. The magnitude of the cardiovascular effects again stresses the need for cautious use of SC terbutaline in patients with a history of cardiovascular disease. The time-course of some of the cardiovascular effects of a SC dose of terbutaline in relation to terbutaline plasma concentrations was unexpected and suggests direct β2-adrenoreceptor-mediated effects on the heart. Further investigations using both selective and nonselective β-receptor antagonists are needed to unravel the complex interactions of β2-receptor-mediated terbutaline-induced effects and cardiovascular reflex mechanisms.