Cargando…

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock

INTRODUCTION: The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20%...

Descripción completa

Detalles Bibliográficos
Autores principales: Morelli, Andrea, Donati, Abele, Ertmer, Christian, Rehberg, Sebastian, Kampmeier, Tim, Orecchioni, Alessandra, Di Russo, Alessandro, D'Egidio, Annalia, Landoni, Giovanni, Lombrano, Maria Rita, Botticelli, Laura, Valentini, Agnese, Zangrillo, Alberto, Pietropaoli, Paolo, Westphal, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334762/
https://www.ncbi.nlm.nih.gov/pubmed/21929764
http://dx.doi.org/10.1186/cc10453
_version_ 1782230680952897536
author Morelli, Andrea
Donati, Abele
Ertmer, Christian
Rehberg, Sebastian
Kampmeier, Tim
Orecchioni, Alessandra
Di Russo, Alessandro
D'Egidio, Annalia
Landoni, Giovanni
Lombrano, Maria Rita
Botticelli, Laura
Valentini, Agnese
Zangrillo, Alberto
Pietropaoli, Paolo
Westphal, Martin
author_facet Morelli, Andrea
Donati, Abele
Ertmer, Christian
Rehberg, Sebastian
Kampmeier, Tim
Orecchioni, Alessandra
Di Russo, Alessandro
D'Egidio, Annalia
Landoni, Giovanni
Lombrano, Maria Rita
Botticelli, Laura
Valentini, Agnese
Zangrillo, Alberto
Pietropaoli, Paolo
Westphal, Martin
author_sort Morelli, Andrea
collection PubMed
description INTRODUCTION: The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20% in the microvascular flow index of small vessels among groups. METHODS: The design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 μg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization. RESULTS: TP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 μg/kg/minute (0.29 to 1.04) vs. 0.16 μg/kg/minute (0.03 to 0.37) for TP and 0.40 μg/kg/minute (0.20 to 1.05) vs. 0.23 μg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7% (2.6 to 19.8) for TP, 8.9% (0.0 to 17.8) for AVP, and 6.9% (3.5 to 10.1) for placebo (P < 0.05 vs. baseline for each comparison), as well as perfused vessel density 18.6% (8.6 to 36.9) for TP, 20.2% (-3.0 to 37.2) for AVP, and 11.4% (-3.0 to 19.4) for placebo (P < 0.05 vs. baseline for each comparison). CONCLUSIONS: The present study suggests that to achieve a MAP of 65 to 75 mmHg in septic patients treated with NE, the addition of continuously infused low-dose TP or AVP does not affect sublingual microcirculatory blood flow. In addition, our results suggest that microcirculatory flow abnormalities are mainly related to other factors (for example, volume status, timing, hemodynamics and progression of the disease) rather than to the vasopressor per se. TRIAL REGISTRATION: ClinicalTrial.gov NCT00995839
format Online
Article
Text
id pubmed-3334762
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-33347622012-04-27 Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock Morelli, Andrea Donati, Abele Ertmer, Christian Rehberg, Sebastian Kampmeier, Tim Orecchioni, Alessandra Di Russo, Alessandro D'Egidio, Annalia Landoni, Giovanni Lombrano, Maria Rita Botticelli, Laura Valentini, Agnese Zangrillo, Alberto Pietropaoli, Paolo Westphal, Martin Crit Care Research INTRODUCTION: The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20% in the microvascular flow index of small vessels among groups. METHODS: The design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 μg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization. RESULTS: TP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 μg/kg/minute (0.29 to 1.04) vs. 0.16 μg/kg/minute (0.03 to 0.37) for TP and 0.40 μg/kg/minute (0.20 to 1.05) vs. 0.23 μg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7% (2.6 to 19.8) for TP, 8.9% (0.0 to 17.8) for AVP, and 6.9% (3.5 to 10.1) for placebo (P < 0.05 vs. baseline for each comparison), as well as perfused vessel density 18.6% (8.6 to 36.9) for TP, 20.2% (-3.0 to 37.2) for AVP, and 11.4% (-3.0 to 19.4) for placebo (P < 0.05 vs. baseline for each comparison). CONCLUSIONS: The present study suggests that to achieve a MAP of 65 to 75 mmHg in septic patients treated with NE, the addition of continuously infused low-dose TP or AVP does not affect sublingual microcirculatory blood flow. In addition, our results suggest that microcirculatory flow abnormalities are mainly related to other factors (for example, volume status, timing, hemodynamics and progression of the disease) rather than to the vasopressor per se. TRIAL REGISTRATION: ClinicalTrial.gov NCT00995839 BioMed Central 2011 2011-09-19 /pmc/articles/PMC3334762/ /pubmed/21929764 http://dx.doi.org/10.1186/cc10453 Text en Copyright ©2011 Morelli et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Morelli, Andrea
Donati, Abele
Ertmer, Christian
Rehberg, Sebastian
Kampmeier, Tim
Orecchioni, Alessandra
Di Russo, Alessandro
D'Egidio, Annalia
Landoni, Giovanni
Lombrano, Maria Rita
Botticelli, Laura
Valentini, Agnese
Zangrillo, Alberto
Pietropaoli, Paolo
Westphal, Martin
Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock
title Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock
title_full Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock
title_fullStr Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock
title_full_unstemmed Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock
title_short Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock
title_sort effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334762/
https://www.ncbi.nlm.nih.gov/pubmed/21929764
http://dx.doi.org/10.1186/cc10453
work_keys_str_mv AT morelliandrea effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT donatiabele effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT ertmerchristian effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT rehbergsebastian effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT kampmeiertim effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT orecchionialessandra effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT dirussoalessandro effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT degidioannalia effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT landonigiovanni effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT lombranomariarita effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT botticellilaura effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT valentiniagnese effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT zangrilloalberto effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT pietropaolipaolo effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock
AT westphalmartin effectsofvasopressinergicreceptoragonistsonsublingualmicrocirculationinnorepinephrinedependentsepticshock