Abstract
IntroductionRecent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements.MethodsWe enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 μg·kg-1·h-1), vasopressin (.03 U·min-1) or norepinephrine (15 μg·min-1; n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA.ResultsThere were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of .03 U of vasopressin or 15 μg·min-1 of norepinephrine, 1.3 μg·kg-1·h-1 of terlipressin allowed a marked reduction in catecholamine requirements (0.8 ± 1.3 and 1.2 ± 1.4 vs. 0.2 ± 0.4 μg·kg-1·min-1 at 48 hours; each P < 0.05) and was associated with less rebound hypotension (P < 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 ± 2.8 and 2.8 ± 2.5 vs. 0.9 ± 0.3 mg·dL-1; each P < 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P < 0.001 48 hours vs. BL).ConclusionsThe present study provides evidence that continuous infusion of low-dose terlipressin – when given as first-line vasopressor agent in septic shock – is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements.Trial registrationClinicalTrial.gov NCT00481572.
Highlights
Recent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy
The present study provides evidence that continuous infusion of low-dose terlipressin – when given as first-line vasopressor agent in septic shock – is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements
In the past few years, it has become evident that the efficacy of hemodynamic optimization by fluids and vasopressor agents critically depends on the urgency of therapy [1,2,3,4]
Summary
Recent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. It is still unknown whether vasopressin and terlipressin are effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements. The potential problem, is that TP bolus infusion may contribute to excessive vasoconstriction and a reflectory decrease in cardiac output with a proportional depression in oxygen delivery [10] This may be especially problematic in a condition of increased oxygen demand, such as early sepsis [1,3]. The optimal time of therapy, remains to be determined
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
