Effects of simultaneously infused terlipressin and dobutamine in septic shock

Abstract

Terlipressin is increasingly used in the treatment of sepsis-associated hypotension. However, terlipressin may reduce cardiac output and global oxygen supply. Methods We performed a prospective, randomized, controlled clinical study to determine whether dobutamine may counterbalance the depressions in cardiac index and mixed-venous oxygen saturation resulting from sole terlipressin infusion. We enrolled 60 septic shock patients requiring high doses of norepinephrine (0.9 �g/kg/min) to maintain mean arterial pressure at 70 � 5 mmHg. Patients were randomly allocated to be treated either with (a) 1 mg terlipressin, (b) 1 mg terlipressin followed by incremental dobutamine doses to reverse the anticipated reductions in mixed-venous oxygen saturation, or (c) sole norepinephrine infusion (control; each n = 20). Results Data from right heart catheterization, thermo-dye dilution catheter, gastric tonometry, as well as organ function and coagulation were obtained at baseline and after 2 and 4 hours. Terlipressin (with and without dobutamine) infusion preserved the mean arterial pressure at threshold values of 70 � 5 mmHg, while allowing one to reduce norepinephrine doses to 0.18 � 0.04 and 0.2 � 0.05 �g/kg/min, respectively (vs 1.4 � 0.07 �g/kg/min in controls at 4 hours; each P < 0.01). The terlipressin-linked decrease in mixed-venous oxygen saturation was reversed by dobutamine (at 4 hours: 59 � 2 vs 69 � 3%, P = 0.023). No statistically significant differences were found intra-group and between groups in terms of differences between gastric mucosal and arterial carbon dioxide partial pressure, blood clearance of indocyanine green, as well as the plasma disappearance rate of indocyanine green Conclusions In catecholamine-dependent human septic shock, terlipressin (with and without concomitant dobutamine) stabilizes hemodynamics and reduces norepinephrine requirements. Dobutamine is a useful inotropic agent to reverse the depression in global oxygen transport resulting from sole terlipressin infusion without obvious side effects.