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Dubin A, Mugno M. The Effects of Dobutamine in Septic Shock: An Updated Narrative Review of Clinical and Experimental Studies. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:751. [PMID: 38792934 PMCID: PMC11123338 DOI: 10.3390/medicina60050751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 04/26/2024] [Accepted: 04/27/2024] [Indexed: 05/26/2024]
Abstract
The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.
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Affiliation(s)
- Arnaldo Dubin
- Cátedras de Terapia Intensiva y Farmacología Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120, La Plata B1902AGW, Argentina
- Sanatorio Otamendi, Azcuénaga 870, Ciudad Autónoma de Buenos Aires C1115AAB, Argentina;
| | - Matías Mugno
- Sanatorio Otamendi, Azcuénaga 870, Ciudad Autónoma de Buenos Aires C1115AAB, Argentina;
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Williams AM, Manouchehri N, Erskine E, Tauh K, So K, Shortt K, Webster M, Fisk S, Billingsley A, Munro A, Tigchelaar S, Streijger F, Kim KT, Kwon BK, West CR. Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury. Nat Commun 2020; 11:5209. [PMID: 33060602 PMCID: PMC7562705 DOI: 10.1038/s41467-020-18905-8] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 09/14/2020] [Indexed: 12/29/2022] Open
Abstract
Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left ventricular (LV) contractility. Here, we aim to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of T2 SCI, we assess LV end-systolic elastance (contractility) via invasive pressure-volume catheterization, monitor intraparenchymal SCO2 and SCBF with fiberoptic oxygen sensors and laser-Doppler flowmetry, respectively, and quantify spinal cord metabolites with microdialysis. We demonstrate that high-thoracic SCI acutely impairs cardiac contractility and substantially reduces SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that augmenting LV contractility with the β-agonist dobutamine increases SCO2 and SCBF more effectively than vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Finally, in pigs with T2 SCI survived for 12 weeks post-injury, we confirm that acute hemodynamic management with dobutamine appears to preserve cardiac function and improve hemodynamic outcomes in the chronic setting. Our data support that cardio-centric hemodynamic management represents an advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI.
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Affiliation(s)
- Alexandra M Williams
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Neda Manouchehri
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Erin Erskine
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Keerit Tauh
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Kitty So
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Katelyn Shortt
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Megan Webster
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Shera Fisk
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Avril Billingsley
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Alex Munro
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Seth Tigchelaar
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Femke Streijger
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada
| | - Kyoung-Tae Kim
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Department of Neurosurgery, School of Medicine, Kyungpook National University Hospital, Daegu, South Korea
| | - Brian K Kwon
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada.,Vancouver Spine Surgery Institute, Department of Orthopaedics, University of British Columbia, Vancouver, BC, Canada
| | - Christopher R West
- International Collaboration On Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada. .,Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
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Ospina-Tascón GA, Calderón-Tapia LE. Inodilators in septic shock: should these be used? ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:796. [PMID: 32647721 PMCID: PMC7333155 DOI: 10.21037/atm.2020.04.43] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Septic shock involves a complex interaction between abnormal vasodilation, relative and/or absolute hypovolemia, myocardial dysfunction, and altered blood flow distribution to the tissues. Fluid administration, vasopressor support and inotropes, represent fundamental pieces of quantitative resuscitation protocols directed to assist the restoration of impaired tissue perfusion during septic shock. Indeed, current recommendations on sepsis management include the use of inotropes in the case of myocardial dysfunction, as suggested by a low cardiac output, increased filling pressures, or persisting signals of tissue hypoperfusion despite an adequate correction of intravascular volume and mean arterial pressure by fluid administration and vasopressor support. Evidence supporting the use of inotropes in sepsis and septic shock is mainly based on physiological studies. Most of them suggest a beneficial effect of inotropes on macro hemodynamics especially when sepsis coexists with myocardial dysfunction; others, however, have demonstrated variable results on regional splanchnic circulation, while others suggest favorable effects on microvascular distribution independently of its impact on cardiac output. Conversely, impact of inodilators on clinical outcomes in this context has been more controversial. Use of dobutamine has not been consistently related with more favorable clinical results, while systematic administration of levosimendan in sepsis do not prevent the development of multiorgan dysfunction, even in patients with evidence of myocardial dysfunction. Nevertheless, a recent metanalysis of clinical studies suggests that cardiovascular support regimens based on inodilators in sepsis and septic shock could provide some beneficial effect on mortality, while other one corroborated such effect on mortality specially in patients with proved lower cardiac output. Thus, using or not inotropes during sepsis and septic shock remains as controversy matter that deserves more research efforts.
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Affiliation(s)
- Gustavo A Ospina-Tascón
- Department of Intensive Care, Fundación Valle del Lili-Universidad Icesi, Cali, Colombia.,Translational Medicine in Critical Care and Experimental Surgery Laboratory, Universidad Icesi, Cali, Colombia
| | - Luis E Calderón-Tapia
- Department of Intensive Care, Fundación Valle del Lili-Universidad Icesi, Cali, Colombia.,Translational Medicine in Critical Care and Experimental Surgery Laboratory, Universidad Icesi, Cali, Colombia
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Bomberg H, Bierbach B, Flache S, Novák M, Schäfers HJ, Menger MD. Dobutamine Versus Vasopressin After Mesenteric Ischemia. J Surg Res 2019; 235:410-423. [DOI: 10.1016/j.jss.2018.10.028] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 09/15/2018] [Accepted: 10/17/2018] [Indexed: 12/26/2022]
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Dubin A, Lattanzio B, Gatti L. The spectrum of cardiovascular effects of dobutamine - from healthy subjects to septic shock patients. Rev Bras Ter Intensiva 2018; 29:490-498. [PMID: 29340539 PMCID: PMC5764562 DOI: 10.5935/0103-507x.20170068] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Accepted: 03/27/2017] [Indexed: 12/13/2022] Open
Abstract
Dobutamine is the inotrope most commonly used in septic shock patients to
increase cardiac output and correct hypoperfusion. Although some experimental
and clinical studies have shown that dobutamine can improve systemic and
regional hemodynamics, other research has found that its effects are
heterogenous and unpredictable. In this review, we analyze the pharmacodynamic
properties of dobutamine and its physiologic effects. Our goal is to show that
the effects of dobutamine might differ between healthy subjects, in experimental
and clinical cardiac failure, in animal models and in patients with septic
shock. We discuss evidence supporting the claim that dobutamine, in septic
shock, frequently behaves as a chronotropic and vasodilatory drug, without
evidence of inotropic action. Since the side effects are very common, and the
therapeutic benefits are unclear, we suggest that dobutamine should be used
cautiously in septic shock. Before a definitive therapeutic decision, the
efficacy and tolerance of dobutamine should be assessed during a brief time with
close monitoring of its positive and negative side effects.
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Affiliation(s)
- Arnaldo Dubin
- Cátedra de Farmacologia Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata - Buenos Aires, Argentina.,Servicio de Terapia Intensiva, Sanatorio Otamendi y Miroli - Buenos Aires, Argentina
| | - Bernardo Lattanzio
- Cátedra de Farmacologia Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata - Buenos Aires, Argentina
| | - Luis Gatti
- Cátedra de Farmacologia Aplicada, Facultad de Ciencias Médicas, Universidad Nacional de La Plata - Buenos Aires, Argentina
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Ospina-Tascón GA, García Marin AF, Echeverri GJ, Bermudez WF, Madriñán-Navia H, Valencia JD, Quiñones E, Rodríguez F, Marulanda A, Arango-Dávila CA, Bruhn A, Hernández G, De Backer D. Effects of dobutamine on intestinal microvascular blood flow heterogeneity and O 2 extraction during septic shock. J Appl Physiol (1985) 2017; 122:1406-1417. [PMID: 28336538 PMCID: PMC5494430 DOI: 10.1152/japplphysiol.00886.2016] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 03/16/2017] [Accepted: 03/16/2017] [Indexed: 11/22/2022] Open
Abstract
Derangements of microvascular blood flow distribution might contribute to disturbing O2 extraction by peripheral tissues. We evaluated the dynamic relationships between the mesenteric O2 extraction ratio ([Formula: see text]) and the heterogeneity of microvascular blood flow at the gut and sublingual mucosa during the development and resuscitation of septic shock in a swine model of fecal peritonitis. Jejunal-villi and sublingual microcirculation were evaluated using a portable intravital-microscopy technique. Simultaneously, we obtained arterial, mixed-venous, and mesenteric blood gases, and jejunal-tonometric measurements. During resuscitation, pigs were randomly allocated to a fixed dose of dobutamine (5 µg·kg-1·min-1) or placebo while three sham models with identical monitoring served as controls. At the time of shock, we observed a significant decreased proportion of perfused intestinal-villi (villi-PPV) and sublingual percentage of perfused small vessels (SL-PPV), paralleling an increase in [Formula: see text] in both dobutamine and placebo groups. After starting resuscitation, villi-PPV and SL-PPV significantly increased in the dobutamine group with subsequent improvement of functional capillary density, whereas [Formula: see text] exhibited a corresponding significant decrease (repeated-measures ANOVA, P = 0.02 and P = 0.04 for time × group interactions and intergroup differences for villi-PPV and [Formula: see text], respectively). Variations in villi-PPV were paralleled by variations in [Formula: see text] (R2 = 0.88, P < 0.001) and these, in turn, by mesenteric lactate changes (R2 = 0.86, P < 0.001). There were no significant differences in cardiac output and systemic O2 delivery throughout the experiment. In conclusion, dynamic changes in microvascular blood flow heterogeneity at jejunal mucosa are closely related to the mesenteric O2 extraction ratio, suggesting a crucial role for microvascular blood flow distribution on O2 uptake during development and resuscitation from septic shock.NEW & NOTEWORTHY Our observations suggest that dynamic changes in the heterogeneity of microvascular blood flow at the gut mucosa are closely related to mesenteric O2 extraction, thus supporting the role of decreasing functional capillary density and increased intercapillary distances on alterations of O2 uptake during development and resuscitation from septic shock. Addition of a low-fixed dose of dobutamine might reverse such flow heterogeneity, improving microcirculatory flow distribution and tissue O2 consumption.
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Affiliation(s)
- Gustavo A Ospina-Tascón
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia; .,Universidad del Valle, Escuela de Ciencias Básicas, Cali, Colombia
| | - Alberto F García Marin
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia
| | - Gabriel J Echeverri
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia
| | - William F Bermudez
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia
| | - Humberto Madriñán-Navia
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia
| | - Juan David Valencia
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia
| | - Edgardo Quiñones
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia
| | - Fernando Rodríguez
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia
| | - Angela Marulanda
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia
| | - César A Arango-Dávila
- Department of Intensive Care Medicine, Fundación Valle del Lili, Universidad ICESI, Cali, Colombia.,Universidad del Valle, Escuela de Ciencias Básicas, Cali, Colombia
| | - Alejandro Bruhn
- Departamento de Medicina Intensiva, Pontificia Universidad Católica de Chile, Santiago, Chile; and
| | - Glenn Hernández
- Departamento de Medicina Intensiva, Pontificia Universidad Católica de Chile, Santiago, Chile; and
| | - Daniel De Backer
- Intensive Care Department, CHIREC Hospitals, Université Libre de Bruxelles, Brussels, Belgium
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Fuchs C, Ertmer C, Rehberg S. Effects of vasodilators on haemodynamic coherence. Best Pract Res Clin Anaesthesiol 2016; 30:479-489. [DOI: 10.1016/j.bpa.2016.10.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 10/24/2016] [Indexed: 12/21/2022]
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Reyad AR, Elkharboutly W, Wahba A, Elmorshedi M, Hasaneen NA. Effect of intraoperative dobutamine on splanchnic tissue perfusion and outcome after Whipple surgery. J Crit Care 2013; 28:531.e7-15. [DOI: 10.1016/j.jcrc.2013.02.017] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2011] [Revised: 12/26/2012] [Accepted: 02/24/2013] [Indexed: 01/05/2023]
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Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study. Intensive Care Med 2013; 39:1435-43. [PMID: 23740284 DOI: 10.1007/s00134-013-2982-0] [Citation(s) in RCA: 99] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Accepted: 05/23/2013] [Indexed: 12/17/2022]
Abstract
PURPOSE The role of dobutamine during septic shock resuscitation is still controversial since most clinical studies have been uncontrolled and no physiological study has unequivocally demonstrated a beneficial effect on tissue perfusion. Our objective was to determine the potential benefits of dobutamine on hemodynamic, metabolic, peripheral, hepatosplanchnic and microcirculatory perfusion parameters during early septic shock resuscitation. METHODS We designed a randomized, controlled, double-blind, crossover study comparing the effects of 2.5-h infusion of dobutamine (5 mcg/kg/min fixed-dose) or placebo in 20 septic shock patients with cardiac index ≥2.5 l/min/m(2) and hyperlactatemia. Primary outcome was sublingual perfused microvascular density. RESULTS Despite an increasing cardiac index, heart rate and left ventricular ejection fraction, dobutamine had no effect on sublingual perfused vessel density [9.0 (7.9-10.1) vs. 9.1 n/mm (7.9-9.9); p = 0.24] or microvascular flow index [2.1 (1.8-2.5) vs. 2.1 (1.9-2.5); p = 0.73] compared to placebo. No differences between dobutamine and placebo were found for the lactate levels, mixed venous-arterial pCO2 gradient, thenar muscle oxygen saturation, capillary refill time or gastric-to-arterial pCO2 gradient. The indocyanine green plasma disappearance rate [14.4 (9.5-25.6) vs. 18.8 %/min (11.7-24.6); p = 0.03] and the recovery slope of thenar muscle oxygen saturation after a vascular occlusion test [2.1 (1.1-3.1) vs. 2.5 %/s (1.2-3.4); p = 0.01] were worse with dobutamine compared to placebo. CONCLUSIONS Dobutamine failed to improve sublingual microcirculatory, metabolic, hepatosplanchnic or peripheral perfusion parameters despite inducing a significant increase in systemic hemodynamic variables in septic shock patients without low cardiac output but with persistent hypoperfusion.
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Effects of Combination Dobutamine and Vasopressin Therapy on Microcirculatory Blood Flow in a Porcine Model of Severe Endotoxic Shock. J Surg Res 2011; 171:191-8. [DOI: 10.1016/j.jss.2009.11.739] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2009] [Revised: 11/04/2009] [Accepted: 11/25/2009] [Indexed: 11/21/2022]
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Abstract
The ultimate goals of hemodynamic therapy in shock are to restore effective tissue perfusion and to normalize cellular metabolism. In sepsis, both global and regional perfusion must be considered. In addition, mediators of sepsis can perturb cellular metabolism, leading to inadequate use of oxygen and other nutrients despite adequate perfusion; one would not expect organ dysfunction mediated by such abnormalities to be corrected by hemodynamic therapy. Despite the complex pathophysiology of sepsis, an underlying approach to its hemodynamic support can be formulated that is particularly pertinent with respect to vasoactive agents. Both arterial pressure and tissue perfusion must be taken into account when choosing therapeutic interventions and the efficacy of hemodynamic therapy should be assessed by monitoring a combination of clinical and hemodynamic parameters. It is relatively easy to raise blood pressure, but somewhat harder to raise cardiac output in septic patients. How to optimize regional blood and microcirculatory blood flow remains uncertain. Specific end points for therapy are debatable and are likely to evolve. Nonetheless, the idea that clinicians should define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis remains a fundamental principle. The practice parameters were intended to emphasize the importance of such an approach so as to provide a foundation for the rational choice of vasoactive agents in the context of evolving monitoring techniques and therapeutic approaches.
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Affiliation(s)
- Steven M Hollenberg
- Divisions of Cardiovascular Disease and Critical Care Medicine, Coronary Care Unit, Cooper University Hospital, Camden, NJ 08103, USA.
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14
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Abstract
The microcirculation plays an essential role in health and disease. Microvascular perfusion can be assessed directly using laser Doppler flowmetry and various imaging techniques or indirectly using regional capnometry and measurement of indicators of mismatch between oxygen delivery and oxygen consumption or indices of disturbed cellular oxygen utilization. Assessment of microvascular oxygen availability implies measurement of oxygen pressure or measurement of hemoglobin oxygen saturation. Microvascular function is assessed using other methods, including venous plethysmography. In this paper, I review current knowledge concerning assessment of the microcirculation with special emphasis on methods that could be used at the bedside.
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Affiliation(s)
- Yasser Sakr
- Department of Anesthesiology and Intensive Care, Friedrich Schiller University Hospital, Erlanger Allee 101, Jena 07743, Germany.
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Abstract
When fluid administration fails to restore an adequate arterial pressure and organ perfusion in patients with septic shock, therapy with vasoactive agents should be initiated. The ultimate goals of such therapy in shock are to restore effective tissue perfusion and to normalize cellular metabolism. The efficacy of hemodynamic therapy in sepsis should be assessed by monitoring a combination of clinical and hemodynamic parameters. Although specific end points for therapy are debatable, and therapies will inevitably evolve as new information becomes available, the idea that clinicians should define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis remains a fundamental principle.
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Affiliation(s)
- Steven M Hollenberg
- Divisions of Cardiovascular Disease and Critical Care Medicine, Cooper University Hospital, Camden, NJ 08103, USA.
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Inotropic Support During Experimental Endotoxemic Shock: Part II. A Comparison of Levosimendan with Dobutamine. Anesth Analg 2009; 109:1576-83. [DOI: 10.1213/ane.0b013e3181af40e0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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17
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Assadi A, Desebbe O, Kaminski C, Rimmelé T, Bénatir F, Goudable J, Chassard D, Allaouchiche B. Effects of sodium nitroprusside on splanchnic microcirculation in a resuscitated porcine model of septic shock. Br J Anaesth 2008; 100:55-65. [DOI: 10.1093/bja/aem278] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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18
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Schwarte LA, Stevens MF, Ince C. Splanchnic Perfusion and Oxygenation in Critical Illness. Intensive Care Med 2007. [DOI: 10.1007/0-387-35096-9_58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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20
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Wang Z, Su F, Bruhn A, Yang X, Vincent JL. Acute hypercapnia improves indices of tissue oxygenation more than dobutamine in septic shock. Am J Respir Crit Care Med 2007; 177:178-83. [PMID: 17947612 DOI: 10.1164/rccm.200706-906oc] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
RATIONALE Hypercapnia has similar hemodynamic effects to those of a dobutamine infusion and may have relevance in the management of septic shock. OBJECTIVES To compare the effects induced by hypercapnia with those of dobutamine in a clinically relevant model of septic shock. METHODS Fecal peritonitis was induced in 21 anesthetized, invasively monitored, mechanically ventilated female sheep. A combination of Ringer's lactate and 6% hydroxyethyl starch solution was titrated to maintain constant cardiac filling throughout the experiments. Two hours after feces spillage, animals were randomized to one of three groups (each, n = 7): (1) hypercapnia: carbon dioxide given to maintain partial pressure of carbon dioxide between 55 and 65 mm Hg throughout the experiment; (2) dobutamine: dobutamine infused intravenously (7 microg/kg/min); (3) control: no treatment. In the dobutamine and control groups, the partial pressure of carbon dioxide was kept between 35 and 45 mm Hg. All animals were monitored until spontaneous death. MEASUREMENTS AND MAIN RESULTS The animals in the hypercapnia group had significantly lower arterial pH than the other two groups (P < 0.05). Hypercapnic and dobutamine-treated animals developed significantly higher heart rate, cardiac index, and oxygen delivery, and lower lactate concentrations than control animals (P < 0.05). Hypercapnic animals had lower post mortem lung wet/dry ratio than the control animals (P < 0.05). The alveolar-arterial oxygen partial pressure difference and shunt fraction were significantly lower in hypercapnic animals than in the other groups (P < 0.05). CONCLUSIONS In this clinically relevant ovine model of septic shock, hypercapnia had similar effects to dobutamine on hemodynamic variables and lactic acidosis. Hypercapnia improved tissue oxygenation and reduced lung edema formation more than dobutamine administration.
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Affiliation(s)
- Zhen Wang
- Department of Intensive Care, Erasme Hospital, Route de Lennik 808, 1070-B Brussels, Belgium.
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Dubin A, Murias G, Sottile JP, Pozo MO, Barán M, Edul VSK, Canales HS, Etcheverry G, Maskin B, Estenssoro E. Effects of levosimendan and dobutamine in experimental acute endotoxemia: a preliminary controlled study. Intensive Care Med 2007; 33:485-94. [PMID: 17262190 DOI: 10.1007/s00134-006-0519-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2006] [Accepted: 12/19/2006] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To test the hypothesis that levosimendan increases systemic and intestinal oxygen delivery (DO(2)) and prevents intramucosal acidosis in septic shock. DESIGN Prospective, controlled experimental study. SETTING University-based research laboratory. SUBJECTS Nineteen anesthetized, mechanically ventilated sheep. INTERVENTIONS Endotoxin-treated sheep were randomly assigned to three groups: control (n=7), dobutamine (10 microg/kg/min, n=6) and levosimendan (100 microg/kg over 10 min followed by 100 microg/kg/h, n=6) and treated for 120 min. MEASUREMENTS AND MAIN RESULTS After endotoxin administration, systemic and intestinal DO(2) decreased (24.6+/-5.2 vs 15.3+/-3.4 ml/kg/min and 105.0+/-28.1 vs 55.8+/-25.9 ml/kg/min, respectively; p<0.05 for both). Arterial lactate and the intramucosal-arterial PCO(2) difference (DeltaPCO(2)) increased (1.4+/-0.3 vs 3.1+/-1.5 mmHg and 9+/-6 vs 23+/-6 mmHg mmol/l, respectively; p<0.05). Systemic DO(2) was preserved in the dobutamine-treated group (22.3+/-4.7 vs 26.8+/-7.0 ml/min/kg, p=NS) but intestinal DO(2) decreased (98.9+/-0.2 vs 68.0+/-22.9 ml/min/kg, p<0.05) and DeltaPCO(2) increased (12+/-5 vs 25+/-11 mmHg, p<0.05). The administration of levosimendan prevented declines in systemic and intestinal DO(2) (25.1+/-3.0 vs 24.0+/-6.3 ml/min/kg and 111.1+/-18.0 vs 98.2+/-23.1 ml/min/kg, p=NS for both) or increases in DeltaPCO(2) (7+/-7 vs 10+/-8, p=NS). Arterial lactate increased in both the dobutamine and levosimendan groups (1.6+/-0.3 vs 2.5+/-0.7 and 1.4+/-0.4 vs. 2.9+/-1.1 mmol/l, p=NS between groups). CONCLUSIONS Compared with dobutamine, levosimendan increased intestinal blood flow and diminished intramucosal acidosis in this experimental model of sepsis.
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Affiliation(s)
- Arnaldo Dubin
- Cátedra de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 42 No 577, 1900, La Plata, Argentina.
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Creteur J, De Backer D, Sakr Y, Koch M, Vincent JL. Sublingual capnometry tracks microcirculatory changes in septic patients. Intensive Care Med 2006; 32:516-23. [PMID: 16485092 DOI: 10.1007/s00134-006-0070-4] [Citation(s) in RCA: 133] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2005] [Accepted: 11/28/2005] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To test the hypothesis that microcirculatory blood flow is the main determinant of sublingual carbon dioxide pressure in patients with septic shock. DESIGN Prospective, open-label study. SETTING A 31-bed medico-surgical department of intensive care. PATIENTS Eighteen consecutive mechanically ventilated patients with septic shock. INTERVENTIONS A 5 microg/kg x min dobutamine infusion was used to increase blood flow. METHODS Sublingual carbon dioxide pressure was monitored using a microelectrode sensor, and sublingual microcirculation was assessed using orthogonal polarization spectral imaging. The sublingual carbon dioxide pressure gap was calculated as the difference between sublingual and arterial carbon dioxide pressures. In each patient, a nasogastric tonometry catheter was inserted for gastric mucosal carbon dioxide pressure measurement. The gastric carbon dioxide pressure gap was calculated as the difference between gastric mucosal and arterial carbon dioxide pressures. MEASUREMENTS AND RESULTS Dobutamine infusion was associated with increases cardiac index and mixed venous blood oxygen saturation. Dobutamine infusion resulted in decreases in sublingual carbon dioxide pressure gap from 40+/-15 to 17+/-8 mmHg (p<0.01). There was a significant correlation between sublingual and gastric mucosal carbon dioxide pressures (r 2=0.61, p<0.05). At baseline, sublingual carbon dioxide pressure gap correlated with the proportion of well-perfused capillaries (r 2=0.80). The decrease in sublingual carbon dioxide pressure gap paralleled the increase in the proportion of well-perfused capillaries in each patient. CONCLUSIONS Regional microcirculatory blood flow is the main determinant of sublingual carbon dioxide pressure. Sublingual capnometry could represent a simple, non-invasive method to monitor these microcirculatory alterations in septic patients.
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Affiliation(s)
- Jacques Creteur
- Department of Intensive Care, Erasme University Hospital, Route de Lennik 808, 1070, Brussels, Belgium
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Abstract
PURPOSE OF REVIEW Tissue dysoxia is now widely regarded as the major factor leading to organ dysfunction in critically ill patients. Recent data suggests that early aggressive resuscitation of critically ill patients, which limits and/or reverses tissue dysoxia may prevent progression to organ dysfunction and improve outcome. The traditional clinical and laboratory markers used to assess tissue dysoxia are, however, insensitive and have numerous limitations. Regional carbon dioxide monitoring appears to be ideally suited to monitoring the adequacy of resuscitation. This review provides an update on this evolving technology. RECENT FINDINGS Gastric intramucosal carbon dioxide as measured by gastric tonometry has proven to be useful as a prognostic marker, in evaluating the response to specific therapeutic interventions and as an end point of resuscitation. Gastric tonometry is, however, cumbersome and has a number of limitations that may have prevented its widespread adoption. The measurement of carbon dioxide in the sublingual mucosa by sublingual capnometry is technically simple, noninvasive, and provides near instantaneous information. Clinical studies have demonstrated a good correlation between gastric intramucosal carbon dioxide and sublingual mucosa carbon dioxide. Sublingual mucosa carbon dioxide responds more rapidly to therapeutic interventions than does gastric intramucosal carbon dioxide and may be a better prognostic marker. SUMMARY Sublingual capnometry may be the ideal technology for guiding early goal directed therapy. This technology may be useful for monitoring tissue oxygenation, titrating therapeutic interventions, and as an end point for resuscitation in critically ill and injured patients.
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Affiliation(s)
- Paul E Marik
- Pulmonary and Critical Care Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
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Matejovic M, Krouzecky A, Martinkova V, Rokyta R, Radej J, Kralova H, Treska V, Radermacher P, Novak I. Effects of tempol, a free radical scavenger, on long-term hyperdynamic porcine bacteremia*. Crit Care Med 2005; 33:1057-63. [PMID: 15891336 DOI: 10.1097/01.ccm.0000162927.94753.63] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVES Pretreatment with tempol, a membrane-permeable radical scavenger, has been shown to be protective in rodent models of endotoxic and Gram-positive shock. However, neither the pretreatment design nor hypodynamic endotoxic shock in rodents mimics the clinical scenario. Therefore, we investigated the effects of tempol in a posttreatment model of long-term, volume-resuscitated, hyperdynamic porcine bacteremia. DESIGN Prospective, randomized, controlled experimental study. SETTING University animal laboratory. SUBJECTS Sixteen anesthetized, mechanically ventilated, and instrumented pigs. INTERVENTIONS Sepsis was induced and maintained for 24 hrs with continuous infusion of live Pseudomonas aeruginosa. After 12 hrs of hyperdynamic sepsis, animals were randomized to receive either vehicle (control, n = 8) or continuous infusion of tempol (n = 8, 30 mg/kg/hr). MEASUREMENTS AND MAIN RESULTS Systemic and hepatosplanchnic hemodynamics, oxygen exchange, metabolism, ileal mucosal microcirculation, and tonometry as well as oxidative stress and coagulation variables were assessed before and after 12, 18, and 24 hrs of P. aeruginosa infusion. Tempol significantly attenuated reduction in mean arterial pressure. Despite comparable mesenteric macrocirculation, tempol attenuated the otherwise progressive deterioration in ileal mucosal microcirculation and prevented mucosal acidosis. By contrast, treatment with tempol failed to influence the P. aeruginosa-induced derangements of hepatosplanchnic redox state, liver lactate clearance, and regional acidosis but prevented the development of renal dysfunction. In addition, tempol reduced nitrosative stress without significant effect on the gradual increase in plasma 8-isoprostanes. Finally, tempol attenuated sepsis-induced endothelial (von Willebrand factor) and hemostatic dysfunction (thrombin-antithrombin complexes, plasminogen activator inhibitor-type 1). CONCLUSIONS The radical scavenger tempol partially prevented live bacteria from causing key features of hemodynamic and metabolic derangements in porcine hyperdynamic sepsis and beneficially affected surrogate markers of sepsis-induced endothelial and coagulation dysfunction. Incomplete reduction of oxidative stress because of dilutional effects and/or missed optimal therapeutic window for antioxidant treatment when used in posttreatment approach may account for the only partial protection by tempol in this model.
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Affiliation(s)
- Martin Matejovic
- Intensive Care Unit, First Medical Department, Charles University Medical School and Teaching Hospital, Plzen, Czech Republic
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Schwarte LA, Picker O, Bornstein SR, Fournell A, Scheeren TWL. Levosimendan is superior to milrinone and dobutamine in selectively increasing microvascular gastric mucosal oxygenation in dogs*. Crit Care Med 2005; 33:135-42; discussion 246-7. [PMID: 15644660 DOI: 10.1097/01.ccm.0000150653.89451.6f] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The effect of levosimendan, a novel inotropic vasodilator (inodilator), on the microvascular gastric mucosal hemoglobin oxygenation (muHbo(2)) is unknown. A possible effect could thereby be selective for the splanchnic region or could primarily reflect changes in systemic oxygen transport (Do(2)) and/or oxygen consumption (Vo(2). We compared systemic and regional effects of levosimendan with those of established inotropes, milrinone and dobutamine. DESIGN Laboratory experiment. SETTING University animal research laboratory of experimental anesthesiology. SUBJECTS Chronically instrumented dogs with flow probes for cardiac output measurement. INTERVENTIONS Anesthetized, mechanically ventilated dogs (each group n = 6) on different days randomly received levosimendan (10 microg.kg, followed by four infusion steps: 0.125-1.0 microg.kg.min), milrinone (5.0 microg.kg, followed by 1.25-10 microg.kg.min), or dobutamine (2.5-10.0 microg.kg.min). Since these drugs may modify regional or systemic responses to fluid load, an additional predefined volume challenge was subsequently performed with hydroxyethyl starch 6% (10 mL.kg). MEASUREMENTS AND MAIN RESULTS We measured muHbo(2) (reflectance spectrophotometry), Do(2), Vo(2), and systemic hemodynamics. Levosimendan significantly increased muHbo(2) from baseline (approximately 55% for all groups) to 64 +/- 4% and further to 69 +/- 2% with volume challenge (mean +/- sem). At the systemic level, levosimendan alone only slightly increased Do(2) at a Vo(2). Milrinone elicited similar systemic effects (Do(2), Vo(2), hemodynamics) but failed to increase muHbo(2). Dobutamine, conversely, increased muHbo(2) to a similar extent as levosimendan; however, this was accompanied by marked increases in Do(2) and Vo(2). The gastric mucosa selectivity of these interventions, expressed as slope of the muHbo(2)/Do2 relation, was highest for levosimendan (+1.89 and +1.14, without and with volume challenge), compared with milrinone (+0.45 and + 0.47) and dobutamine (+0.48 and + 0.33). CONCLUSIONS Levosimendan is superior to milrinone (no significant regional effects) and dobutamine (marked systemic effects) in increasing gastric mucosal oxygenation selectively (i.e., at only moderately increased Do(2) and stable Vo(2). If our experimental data apply to the clinical setting, levosimendan may serve as an option to selectively increase gastrointestinal mucosa oxygenation in patients at risk to develop splanchnic ischemia.
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Affiliation(s)
- Lothar A Schwarte
- Department of Anesthesiology, University Hospital of Düsseldorf, Germany
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Hollenberg SM, Ahrens TS, Annane D, Astiz ME, Chalfin DB, Dasta JF, Heard SO, Martin C, Napolitano LM, Susla GM, Totaro R, Vincent JL, Zanotti-Cavazzoni S. Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med 2004; 32:1928-48. [PMID: 15343024 DOI: 10.1097/01.ccm.0000139761.05492.d6] [Citation(s) in RCA: 313] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To provide the American College of Critical Care Medicine with updated guidelines for hemodynamic support of adult patients with sepsis. DATA SOURCE Publications relevant to hemodynamic support of septic patients were obtained from the medical literature, supplemented by the expertise and experience of members of an international task force convened from the membership of the Society of Critical Care Medicine. STUDY SELECTION Both human studies and relevant animal studies were considered. DATA SYNTHESIS The experts articles reviewed the literature and classified the strength of evidence of human studies according to study design and scientific value. Recommendations were drafted and graded levels based on an evidence-based rating system described in the text. The recommendations were debated, and the task force chairman modified the document until <10% of the experts disagreed with the recommendations. CONCLUSIONS An organized approach to the hemodynamic support of sepsis was formulated. The fundamental principle is that clinicians using hemodynamic therapies should define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis by monitoring a combination of variables of global and regional perfusion. Using this approach, specific recommendations for fluid resuscitation, vasopressor therapy, and inotropic therapy of septic in adult patients were promulgated.
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Martikainen TJ, Uusaro A, Tenhunen JJ, Ruokonen E. Dobutamine compensates deleterious hemodynamic and metabolic effects of vasopressin in the splanchnic region in endotoxin shock. Acta Anaesthesiol Scand 2004; 48:935-43. [PMID: 15315609 DOI: 10.1111/j.0001-5172.2004.00435.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Vasopressin is a potent vasopressor in septic shock, but it may impair splanchnic perfusion. We compared the effects of vasopressin alone and in combination with dobutamine on systemic and splanchnic circulation and metabolism in porcine endotoxin shock. METHODS Twelve pigs were randomized to receive either vasopressin (VASO, n = 6) or vasopressin in combination with dobutamine (DOBU, n = 6) during endotoxin shock (E. coli endotoxin infusion). Endotoxin infusion rate was increased to induce hypotension after which vasoactive drugs were started. We aimed to keep systemic mean arterial pressure (MAP) >70 mmHg by vasopressin; the goal of dobutamine infusion was to prevent decrease in cardiac output often associated with vasopressin infusion. Regional blood flows, oxygen delivery and consumption, arterial and regional lactate concentrations were measured. RESULTS Mean arterial pressure >70 mmHg was achieved in both the VASO and DOBU groups. After the primary decrease of cardiac output by vasopressin, systemic blood flow remained stable in vasopressin-treated animals. However, vasopressin as a monotherapy decreased portal venous blood flow. This was prevented by dobutamine. Vasopressin also induced splanchnic lactate release and arterial hyperlactatemia, which were not observed when dobutamine was combined with vasopressin. CONCLUSION Dobutamine prevents adverse hemodynamic and metabolic effects of vasopressin in septic shock.
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Affiliation(s)
- T J Martikainen
- Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Finland
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Matejovic M, Krouzecky A, Martinkova V, Rokyta R, Kralova H, Treska V, Radermacher P, Novak I. SELECTIVE INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITION DURING LONG-TERM HYPERDYNAMIC PORCINE BACTEREMIA. Shock 2004; 21:458-65. [PMID: 15087823 DOI: 10.1097/00024382-200405000-00010] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
We have recently demonstrated that selective inducible nitric oxide (NO) synthase (iNOS) inhibition with 1400W attenuated the hemodynamic and metabolic alterations affiliated with hyperdynamic porcine endotoxemia. In contrast to endotoxemia, limited evidence is available to document a relationship between NO and organ dysfunction in large animal bacteremic models. Therefore, using the same experimental setup, we investigated the role of selective iNOS blockade in porcine bacteremia induced and maintained for 24 h with a continuous infusion of live Pseudomonas aeruginosa. After 12 h of sepsis, animals received either vehicle (Control, n = 8) or continuous infusion of selective iNOS inhibitor, L-N6-(1-iminoethyl)-lysine (L-NIL; n = 8). Measurements were performed before, and 12, 18, and 24 h after P. aeruginosa infusion. L-NIL inhibited sepsis-induced increase in plasma nitrate/nitrite concentrations and prevented hypotension without affecting cardiac output. Despite comparable hepatosplanchnic macrocirculation, L-NIL blunted the progressive deterioration in ileal mucosal microcirculation and prevented mucosal acidosis. L-NIL largely attenuated mesenteric and hepatic venous acidosis, significantly improved P. aeruginosa-induced impairment of hepatosplanchnic redox state, and mitigated the decline in liver lactate clearance. Furthermore, the administration of L-NIL reduced the hepatocellular injury and prevented the development of renal dysfunction. Finally, treatment with L-NIL significantly attenuated the formation of 8-isoprostane concentrations, a direct marker of lipid peroxidation. Thus, selective iNOS inhibition with L-NIL prevented live bacteria from causing key features of metabolic derangements in porcine hyperdynamic sepsis. Underlying mechanisms probably include reduced oxidative stress with improved microcirculatory perfusion and restoration of cellular respiration.
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Affiliation(s)
- Martin Matejovic
- Intensive Care Unit, 1st Medical Department, Charles University, Plzen, Czech Republic.
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Kozar RA, Holcomb JB, Hassoun HT, Macaitis J, DeSoignie R, Moore FA. Superior mesenteric artery occlusion models shock-induced gut ischemia-reperfusion. J Surg Res 2004; 116:145-50. [PMID: 14732361 DOI: 10.1016/s0022-4804(03)00301-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Superior mesenteric artery occlusion (SMAO) is a simple and reproducible model of shock-induced gut ischemia/reperfusion, but some argue that it is not clinically relevant. The purpose of the current study was to compare SMAO to a standard model of controlled hemorrhage (CH) and uncontrolled hemorrhage (UH). METHODS Rats had femoral lines and a jejunal mucosal laser Doppler placed followed by SMAO (60 min of ischemia, no resuscitation), controlled hemorrhage (40 mm Hg for 60 min, 2:1 resuscitation shed blood and lactated Ringers), or uncontrolled hemorrhage (liver injury, 3:1 resuscitation with lactated Ringers). Base deficit, lactate, and jejunal mucosal flow (as a percentage of baseline) were recorded during ischemia and for 120 min after reperfusion. Jejunal tissue was harvested for morphological evaluation. Comparison among groups was by analysis of variance (ANOVA), and significance was set at P < 0.05. RESULTS Mucosal blood flow was similar among groups at the onset of reperfusion (CH, 16.9 +/- 5.0% versus UH, 10.9 +/- 3.1% versus SMAO, 13.9 +/- 6.2%) and during the initial period of reperfusion. By 120 min, however, flow in CH (75.4 +/- 2.5%) was significantly higher that in either UH (36.4 +/- 13.1%) or SMAO (31.7 +/- 8.4%). Histological injury was less with CH, while base deficit was significantly higher in CH at the onset of reperfusion (-24 +/- 2 versus UH, -10 +/- 3 and SMAO, -6 +/- 3 mM/L) but comparable by the end (CH, -17 +/- 4 versus UH, -16 +/- 3 and SMAO, -17 +/- 2 mM/L). CONCLUSIONS SMAO is a clinically relevant model of shock-induced gut ischemia/reperfusion.
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Affiliation(s)
- Rosemary A Kozar
- Department of Surgery, University of Texas-Houston, Houston, TX 77030, USA.
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Schwarte LA, Picker O, Schindler AW, Fournell A, Scheeren TWL. Dopamine under α1-blockade, but not dopamine alone or fenoldopam, increases depressed gastric mucosal oxygenation*. Crit Care Med 2004; 32:150-6. [PMID: 14707574 DOI: 10.1097/01.ccm.0000099340.53754.5b] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To compare the effects of dopamine, both in the presence and absence of alpha1-blockade, and fenoldopam on microvascular gastric mucosal oxygenation and systemic oxygen transport under compromised circulatory conditions, both without and with fluid resuscitation. DESIGN Randomized controlled animal study. SETTING University department of anesthesiology. SUBJECTS Eight anesthetized dogs with chronically implanted ultrasound flow probes around the pulmonary artery for continuous measurement of cardiac output. INTERVENTIONS On different days, the dogs received in random order either dopamine (2.5 and 5.0 microg.kg(-1).min(-1), with or without alpha1-blocker pretreatment), the selective DA1-agonist fenoldopam (0.1 and 1.0 microg.kg(-1).min(-1), with and without DA1-blocker pretreatment), or saline (control). These interventions were performed under compromised cardiocirculatory conditions (induced by ventilation with positive end-expiratory pressure [PEEP] of 10 cm H2O), both without and with fluid resuscitation. MEASUREMENTS AND MAIN RESULTS We continuously measured regional microvascular hemoglobin saturation (microHbO2) in gastric mucosa by reflectance spectrophotometry and systemic oxygen transport ([U1E0A]O2). Ventilation with PEEP significantly decreased [U1E0A]O2 (from 19 +/- 2 to 9 +/- 1 mL.kg(-1).min(-1), mean +/- sem) and gastric mucosal microHbO2 (from 57 +/- 2% to 37 +/- 3%). Fluid resuscitation restored [U1E0A]O2 back to baseline (from 9 +/- 1 to 19 +/- 2 mL.kg(-1).min(-1)) but only partially restored microHbO2 (from 37 +/- 3% to 50 +/- 4%). Under both conditions, dopamine with and without alpha1-blockade significantly increased [U1E0A]O2 (by about 5 mL.kg-1.min-1 in the nonresuscitated state and 10 mL.kg-1.min-1 in the fluid resuscitated state, respectively), but only dopamine in the presence of alpha1-blockade also significantly increased gastric mucosal microHbO2 (by 5 +/- 1% and 7 +/- 2% in the nonresuscitated and fluid resuscitated states, respectively). Fenoldopam under all study conditions did not significantly affect [U1E0A]O2 or microHbO2, either in the presence or absence of DA1-blockade. CONCLUSIONS During compromised cardiocirculatory conditions, alpha1-receptor activation during dopamine infusion prevented an increase in gastric mucosal oxygenation. Furthermore, selective DA1-stimulation (by fenoldopam) was insufficient to overcome the PEEP-induced depression of microHbO2. The responses of gastric mucosal oxygenation did not parallel changes in systemic oxygen transport. These findings were independent of fluid resuscitation.
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Affiliation(s)
- Lothar A Schwarte
- Department of Anesthesiology, University Hospital of Duesseldorf, Germany.
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Claesson J, Lehtipalo S, Winsö O. Do lung recruitment maneuvers decrease gastric mucosal perfusion? Intensive Care Med 2003; 29:1314-21. [PMID: 12851763 DOI: 10.1007/s00134-003-1830-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2002] [Accepted: 04/29/2003] [Indexed: 11/30/2022]
Abstract
OBJECTIVE To evaluate effects of lung recruitment maneuvers on gastric mucosal perfusion, systemic circulation, and lung mechanics in patients with acute lung injury. DESIGN Prospective observational clinical study. SETTING. General intensive care unit of university hospital. PATIENTS AND PARTICIPANTS Fourteen patients with acute lung injury (ten in the main study group and four in a validation group). INTERVENTIONS. Three 2-min-long recruitment maneuvers (RM) with transient increases in mean airway pressure to 35 cmH(2)O (RM1 and RM2) and 44 cmH(2)O (RM3). MEASUREMENTS AND RESULTS Measurements of systemic hemodynamics, gastric mucosal perfusion (laser Doppler flowmetry), and lung mechanics were performed immediately before, at the end of, and 3 min after each RM. Cardiac index decreased during all RMs while mean arterial pressure decreased only during RM3. Gastric mucosal perfusion was not significantly changed during any of the RMs. When comparing values obtained before the first RM with values after the third RM there was a significant decrease in cardiac index ( P=0.043) and a non-significant ( P=0.051) decrease in gastric mucosal perfusion. There were no significant changes in systemic oxygenation or lung mechanics after three RMs, even though four patients showed marked transient increases in systemic oxygenation during RMs. CONCLUSIONS In this study of ten patients there were no significant changes in gastric mucosal perfusion during lung recruitment maneuvers. There was, however, a trend towards gradual decreases in gastric mucosal perfusion.
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Affiliation(s)
- J Claesson
- Department of Surgical and Perioperative Sciences, Anesthesiology and Intensive Care, Umeå University Hospital, 90185, Umeå, Sweden.
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Schwarte LA, Picker O, Schindler AW, Fournell A, Scheeren TWL. Fenoldopam--but not dopamine--selectively increases gastric mucosal oxygenation in dogs. Crit Care Med 2003; 31:1999-2005. [PMID: 12847395 DOI: 10.1097/01.ccm.0000074718.04034.bf] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To compare the effects of fenoldopam and dopamine on gastric mucosal and systemic oxygenation, and to identify the receptors involved. DESIGN Randomized controlled animal study. SETTING University research department of experimental anesthesiology. SUBJECTS Seven anesthetized dogs with chronically implanted ultrasound flow probes around the pulmonary artery for continuous measurement of cardiac output. INTERVENTIONS On different days, the dogs received in random order either the selective DA(1)-agonist fenoldopam (0.1 and 1.0 microg x kg-1.= x min-1, with or without DA(1)-blocker pretreatment), dopamine (2.5 and 5.0 microg.kg-1 x min-1, with or without alpha(1)-blocker pretreatment), or saline (control). MEASUREMENTS AND MAIN RESULTS We continuously measured regional microvascular hemoglobin oxygen saturation (muHbO(2)) in gastric mucosa by reflectance spectrophotometry, and systemic oxygen delivery. Fenoldopam increased gastric mucosal muHbO(2) by approximately 20%, and this effect was prevented by selective DA(1)-receptor blockade. In contrast, dopamine neither alone nor during alpha(1)-blockade altered muHbO(2). With respect to systemic measures of oxygen transport, fenoldopam had negligible effects, whereas dopamine (with and without alpha(1)-blocker pretreatment) dose-dependently increased cardiac output and systemic oxygen delivery by approximately 30%. CONCLUSIONS Fenoldopam dose-dependently increased microvascular oxygenation of the gastric mucosa without changing systemic oxygen transport, i.e., this drug acted selectively on the splanchnic mucosa. The increase in gastric mucosal oxygenation was mediated by DA(1)-receptors. In contrast, dopamine markedly increased systemic oxygen transport, but did not affect microvascular oxygenation of gastric mucosa. This lacking effect on gastric mucosal oxygenation was not caused by alpha(1)-mediated vasoconstriction. The regional effects of both catecholamines could not be deduced from systemic hemodynamics and oxygenation.
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Affiliation(s)
- Lothar A Schwarte
- Department of Anesthesiology, University Hospital of Dusseldorf, Germany
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Figueiredo LFPD, Silva E, Cruz Jr RJ, Silva MRE. Gas tonometry for evaluation of gastrointestinal mucosal perfusion: experimental models of trauma, shock and complex surgical maneuvers - Part 1. Acta Cir Bras 2002. [DOI: 10.1590/s0102-86502002000400003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Substantial clinical and animal evidences indicate that the mesenteric circulatory bed, particularly the gut mucosa, is highly vulnerable to reductions in oxygen supply and prone to early injury in the course of hemodynamic changes induced by trauma, shock, sepsis and several complex surgical maneuvers. Gut hypoxia or ischemia is one possible contributing factor to gastrointestinal tract barrier dysfunction that may be associated with the development of systemic inflammatory response and multiple organ dysfunction syndrome, a common cause of death after trauma, sepsis or major surgeries. Monitoring gut perfusion during experiments may provide valuable insights over new interventions and therapies highly needed to reduce trauma and sepsis-related morbidity and mortality. We present our experience with gas tonometry as a monitor of the adequacy of gastrointestinal mucosal perfusion in clinical and experimental models of trauma, shock and surgical maneuvers associated with abrupt hemodynamic changes, such as aortic occlusion and hepatic vascular exclusion. Next issue we will be presenting our experience with gas tonometry in experimental and clinical sepsis.
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Hu S, Sheng ZY. The effects of anisodamine and dobutamine on gut mucosal blood flow during gut ischemia/reperfusion. World J Gastroenterol 2002; 8:555-7. [PMID: 12046091 PMCID: PMC4656442 DOI: 10.3748/wjg.v8.i3.555] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine if anisodamine is able to augment mucosal perfusion during gut I/R ischemia-reperfusion.
METHODS: A jejunal sac was formed in Sprague Dawley rat. A Laser Doppler probe and a tonometer were inserted into the sac which was filled with saline. The superior mesenteric artery was occluded (SMAO) for 60 minutes followed by 90 minutes of reperfusion. At the end of 60 minutes of SMAO, either 0.2 mg/kg of anisodmine or dobutamine was injected into the jejunal sac. Laser Doppler mucosal blood flow and regional PCO2 (PrCO2) measurements were made.
RESULTS: Mucosal blood flow was significantly increased at 30, 60 and 90 minutes of reperfusion (R30, R60, R90) when intraluminal anisodamine or dobutamine was present compared to intraluminal saline only (44 ± 3.3% or 48 ± 4.1% vs 37 ± 2.6% at R30, 57 ± 5.0% or 56 ± 4.7% vs 45 ± 2.7% at R60, 64 ± 3.3% or 56 ± 4.2% vs 48 ± 3.4% at R90, respectively P < 0.05). Blood flow changes were also reflected by lowering of jejunal PrCO2 measurements after intraluminal anisodamine or dobutamine compared with that of the saline controls (41 ± 3.1 mmHg or 44 ± 3.0 mmHg vs 49 ± 3.7 mmHg at R30, 38 ± 3.7 mmHg or 40 ± 2.1 mmHg vs 47 ± 3.8 mmHg at R60, 34 ± 2.1 mmHg or 39 ± 3.0 mmHg vs 46 ± 3.4 mmHg at R90, respectively, P < 0.05). Most interesting finding was that there were significantly higher mucosal blood flow and lower jejunal PrCO2 in anisodamine group than those in dobutamine group at 90 minutes of reperfusion (64 ± 3.3% vs 56 ± 4.2% for blood flow or 34 ± 2.1 mmHg vs 39 ± 3.0 mmHg for PrCO2, respectively, P < 0.05), suggesting that anisodamine had a more lasting effect on mucosal perfusion than dobutamine.
CONCLUSION: Intraluminal anisodamine and dobutamine can augment mucosal blood flow during gut I/R and alleviate mucosal acidosis. The results provided benificial effects on the treatment of splanchnic hypoperfusion following traumatic or burn shock.
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Affiliation(s)
- Sen Hu
- Burns Institute, 304th Hospital of PLA, 51 Fu Cheng Road, Beijing 100037, China
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Scheeren TWL, Schwarte LA, Loer SA, Picker O, Fournell A. Dopexamine but not dopamine increases gastric mucosal oxygenation during mechanical ventilation in dogs. Crit Care Med 2002; 30:881-7. [PMID: 11940763 DOI: 10.1097/00003246-200204000-00028] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To compare the effects of dopamine and dopexamine on gastric mucosal oxygenation during mechanical ventilation without and with positive end-expiratory airway pressure (PEEP) and after compensation of the PEEP-induced hemodynamic suppression. DESIGN Randomized controlled animal study. SETTING University research department of experimental anesthesiology. SUBJECTS Ten anesthetized dogs with chronically implanted ultrasound flow probes around the pulmonary artery for continuous measurement of cardiac output. INTERVENTIONS On different days, the dogs randomly received dopamine (2.5 and 5.0 microg x kg(-1) x min(-1), n = 10), dopexamine (0.5 and 1.0 microg x kg(-1) x min(-1)) without (n = 8) or with pretreatment with a selective beta2-adrenoceptor antagonist (ICI 118,551, n = 7), or saline (control, n = 7). To simulate common clinical situations, these interventions were performed during different ventilation modes: during mechanical ventilation without and with high levels of PEEP, and after compensation of the PEEP-induced systemic hemodynamic suppression by titrated volume resuscitation with hydroxyethyl starch. MEASUREMENTS AND MAIN RESULTS We continuously measured microvascular hemoglobin saturation (mu-Hbo2) by light-guide spectrophotometry in the gastric mucosa. Dopexamine, but not dopamine, significantly increased gastric mucosal mu-Hbo2 by about 20%, regardless of the dose and the ventilation mode. Both catecholamines dose-dependently increased cardiac output and oxygen delivery by up to 75% without effects on systemic oxygen saturation. The effects of dopexamine on mu-Hbo2 as well as on cardiac output and oxygen delivery were prevented by selective beta2-adrenoceptor-blockade. CONCLUSIONS Dopexamine but not dopamine improved gastric mucosal oxygenation in dogs. This effect was independent of the dosage and the ventilation mode. Thus, dopexamine may reverse a decrease in splanchnic oxygenation induced by ventilation with PEEP. The dopexamine-induced increase in gastric mucosal oxygenation was mediated by beta2-adrenoceptors, which explains the superior effects of dopexamine to dopamine on mu-Hbo2. The regional effects of both catecholamines were not mirrored by systemic hemodynamics.
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Affiliation(s)
- Thomas W L Scheeren
- Department of Anesthesiology, Heinrich-Heine-University, Düsseldorf, Germany
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Abstract
A clinically feasible method for assessing regional splanchnic perfusion is still lacking. Methods used for research purposes demonstrate that the effects of current therapies on splanchnic perfusion are not predictable in intensive care patients with and without ARDS. Tonometry, laser Doppler flowmetry, and spectrophotometry have been used to assess splanchnic perfusion. Combining the available methods in different parts of the gastrointestinal tract may help assess splanchnic perfusion more accurately in the near future.
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Affiliation(s)
- Stephan M Jakob
- Department of Intensive Care Medicine, University Hospital Inselspital, Bern, Switzerland.
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Affiliation(s)
- P E Marik
- Trauma Life Support Center, Mercy Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Holzer P, Painsipp E. Differential effects of clonidine, dopamine, dobutamine, and dopexamine on basal and acid-stimulated mucosal blood flow in the rat stomach. Crit Care Med 2001; 29:335-43. [PMID: 11246314 DOI: 10.1097/00003246-200102000-00021] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To analyze the effects of clonidine, dopamine, dobutamine, and dopexamine on gastric mucosal blood flow (GMBF) at baseline and after stimulation by acid back diffusion through a disrupted gastric mucosal barrier. DESIGN Prospective, randomized, unblinded study. SETTING University research laboratory. SUBJECTS Adult Sprague-Dawley rats. INTERVENTIONS Mean arterial blood pressure (MAP) and heart rate (HR) were recorded from a carotid artery of the phenobarbital-anesthetized animals. A jugular vein was cannulated for continuous infusion of saline and intravenous drug administration. The stomach was prepared for luminal perfusion and for recording GMBF with the hydrogen gas clearance technique. Gastric mucosal vascular conductance (GMVC) was calculated as GMBF divided by MAP. MEASUREMENTS AND MAIN RESULTS Clonidine (37.5 and 112.5 nmol x kg(-1)) lowered MAP and HR and caused gastric vasodilation as shown by a rise of GMVC. The 2.5-fold increase in GMVC elicited by gastric perfusion with HCl (0.15 M) plus ethanol (25%) was depressed by clonidine. All cardiovascular effects of clonidine were prevented by the alpha2-adrenoceptor antagonist idazoxan (2 micromol x kg(-1)). Infusion of dopamine (15 and 45 micromol x kg(-1) x hr(-1)), dobutamine, or dopexamine (each at 5 and 15 micromol x kg(-1) x hr(-1)) caused tachycardia. GMVC at baseline was attenuated by the higher dose of dopamine and dopexamine, but not dobutamine. In contrast, the acid-induced vasodilation in the gastric mucosa was depressed by dobutamine and dopexamine, but not dopamine. CONCLUSIONS Clonidine, dobutamine, and dopexamine at high dosage suppress the gastric mucosal vasodilator response to acid back diffusion, which is an important defense mechanism. Although the dose equivalence between rats and humans is not known, the antivasodilator effects highlight an adverse action whereby large doses of dobutamine, dopexamine, and clonidine may compromise gastric mucosal homeostasis and facilitate stress ulcer formation. Dopamine lacks this detrimental activity.
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Affiliation(s)
- P Holzer
- Department of Experimental and Clinical Pharmacology, University of Graz, Graz, Austria.
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Heino A, Hartikainen J, Merasto ME, Koski EM, Tenhunen J, Alhava E, Takala J. Effects of dobutamine on splanchnic tissue perfusion during partial superior mesenteric artery occlusion. Crit Care Med 2000; 28:3484-90. [PMID: 11057805 DOI: 10.1097/00003246-200010000-00020] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To evaluate the effects of dobutamine and fluid treatment on splanchnic hemodynamics and tissue oxygenation during partial superior mesenteric artery occlusion. DESIGN Prospective, open randomized, full-factorial design. SETTING University research laboratory. SUBJECTS Forty-eight female pigs. INTERVENTIONS In 24 anesthetized pigs (ischemic group), superior mesenteric artery (SMA) blood flow was reduced to 30% from the baseline for 120 mins; 24 pigs (sham group) served as nonischemic controls. The animals were further assigned into four treatment arms. In the control arm, the animals were administered only basic fluid therapy. In the fluid therapy arm, pulmonary artery occlusion pressure was maintained at 10 mm Hg with fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arm, dobutamine at 10 microg/min/kg was administered and pulmonary artery occlusion pressure was maintained at 10 mm Hg with fluids. MEASUREMENTS AND MAIN RESULTS Systemic and regional hemodynamics and oxygen transport, as well as jejunal intramucosal pH, intramucosal-arterial PCO2 gradient, and portal venous-arterial lactate gradient were measured. Ischemia did not modify the effects of fluids or dobutamine on systemic hemodynamics and oxygen transport. Dobutamine-treated animals had a higher cardiac index compared with control animals (218 +/- 22 vs. 135 +/- 13 mL/min/kg; p = .012), and the effect was enhanced when dobutamine was combined with fluid treatment (365 +/- 23 mL/ min/kg; p = .019). Fluid treatment alone did not influence cardiac index, whereas it increased SMA blood flow compared with control groups (15 +/- 2 vs. 12 +/- 2 mL/min/kg; p = .023). Dobutamine also decreased the proportion of SMA blood flow of cardiac output compared with control groups (6 +/- 1 vs. 9% +/- 1%; p = .024). Other treatments had no effect on SMA blood flow. Ischemia increased intramucosal-arterial Pco2 gradient to 54.8 +/- 10.7 torr (7.31 +/- 1.43 kPa) (p = .002 vs. sham control) and decreased intramucosal pH to 7.13 +/- 0.06 (p = .028 vs. sham control). In the ischemic animals, dobutamine without fluid therapy reduced intramucosal pH further to 7.00 +/- 0.09 (p = .023 vs. ischemic control) and increased portal venous-arterial lactate gradient (p = .033). CONCLUSIONS Dobutamine alone worsened splanchnic tissue perfusion during partial superior mesenteric artery occlusion. As compared with fluid treatment alone, the combination of fluid and dobutamine therapy did not improve tissue perfusion.
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Affiliation(s)
- A Heino
- Department of Surgery, Kuopio University Hospital, Finland
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Hiltebrand LB, Krejci V, Banic A, Erni D, Wheatley AM, Sigurdsson GH. Dynamic study of the distribution of microcirculatory blood flow in multiple splanchnic organs in septic shock. Crit Care Med 2000; 28:3233-41. [PMID: 11008987 DOI: 10.1097/00003246-200009000-00019] [Citation(s) in RCA: 96] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To study dynamic distribution of microcirculatory blood flow in multiple splanchnic organs during septic shock; to test the hypothesis that changes in microcirculatory blood flow in splanchnic organs correlate with changes in regional flow during septic shock. DESIGN A prospective, controlled, animal study. SETTING Animal laboratory in a university medical center. SUBJECTS Nine anesthetized and mechanically ventilated domestic pigs. INTERVENTIONS Systemic flow (cardiac output) was measured with thermodilution and regional (superior mesenteric artery) flow with transit time flowmetry. Local blood flow (microcirculatory flow) was continuously measured in splanchnic organs (gastric, jejunal, and colon mucosa, liver, and pancreas) and the kidney with multichannel laser Doppler flowmetry. Septic shock was induced with fecal peritonitis. After 240 mins of sepsis, intravenous fluids were administered to alter hypodynamic shock to hyperdynamic septic shock. MEASUREMENTS AND MAIN RESULTS In this severe septic shock model, systemic and regional flows decreased by approximately 50% during the first 240 mins. Similar reductions were recorded in microcirculatory flow in the mucosa of the stomach (-41%; p < .001) and colon (-47%; p < .001). In the jejunal mucosa, on the other hand, flow remained virtually unchanged. Microcirculatory flow was also significantly decreased in the liver (-49%; p < .001), pancreas (-56%; p < .001), and kidney (-44%; p < .001). Administration of intravenous fluids at 240 mins was followed by three-fold increases in systemic and regional flows (approximately 70% above baseline). In the jejunal mucosa, flow also increased significantly above baseline (42%; p < .001), whereas in the stomach and the colon, it barely reached baseline. Kidney blood flow increased to baseline, whereas pancreas and liver flows remained 26% (p < .05) and 34% (p < .001), respectively, below baseline. CONCLUSION Changes in microcirculatory blood flow in the splanchnic organs are heterogeneous, both in early hypodynamic and in hyperdynamic septic shock, and cannot be predicted from changes in systemic or regional flows. Microcirculatory blood flow in the jejunal mucosa remains constant during early septic shock, whereas pancreatic blood flow decreases significantly more than regional flow.
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Affiliation(s)
- L B Hiltebrand
- Department of Anaesthesia and Intensive Care, University of Berne, Switzerland
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Abstract
Derangements in tissue perfusion occur during critical illness, and the resulting deficit in oxygen delivery may play an important role in the pathogenesis of hemorrhagic and septic shock. Cells and organisms have developed a variety of adaptive strategies to maintain adequate energy production to maintain normal cellular function under hypoxic conditions. Recent studies from our laboratory suggest that certain proinflammatory cytokines, which are likely to be elaborated during or after shock, can interfere with the ability of cells to adapt to hypoxia, and thereby contribute to the development of organ system dysfunction.
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Affiliation(s)
- D J Bertges
- Department of Surgery, University of Pittsburgh Medical School, PA, USA
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Agustí M, Elizalde JI, Adàlia R, Cifuentes A, Fontanals J, Taurà P. Dobutamine restores intestinal mucosal blood flow in a porcine model of intra-abdominal hyperpressure. Crit Care Med 2000; 28:467-72. [PMID: 10708185 DOI: 10.1097/00003246-200002000-00030] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To assess the effects of dopamine and dobutamine administration on the systemic and mesenteric (macro- and microvascular) circulatory disturbances induced by intra-abdominal hyperpressure. DESIGN Prospective, randomized study. SETTING Animal research laboratory in a university hospital. SUBJECTS Twenty-five pigs of either gender, weighing 30-35 kg. INTERVENTIONS Animals were anesthetized, and their lungs were mechanically ventilated. Pulmonary artery flotation and carotid artery catheters were inserted for hemodynamic monitoring and blood sampling. A perivascular flow probe was placed around the superior mesenteric artery, and a laser Doppler probe was positioned in the lumen of the ileum to measure arterial and intestinal mucosal blood flows, respectively. CO2 was insufflated into the peritoneal cavity to reach an intra-abdominal pressure of 15 mm Hg, and 60 mins later, animals received dopamine (5 microg/kg/min; n = 10), dobutamine (5 microg/kg/min; n = 10), or saline (n = 5) for 30 mins. MEASUREMENTS AND MAIN RESULTS Peritoneal CO2 insufflation induced significant increases in heart rate, arterial pressure, and systemic vascular resistance with concomitant decreases in cardiac output and superior mesenteric arterial and intestinal mucosal blood flows. Although dobutamine infusion reversed the decrease in cardiac output, it failed to restore superior mesenteric artery blood flow; however, intestinal mucosal blood flow returned to baseline levels. Dopamine also attenuated the decrease in cardiac output, but it had no beneficial effect on splanchnic hemodynamic variables. CONCLUSIONS Low-dose infusion of dobutamine, but not dopamine, corrects the intestinal mucosal perfusion impairment induced by moderate increases in intra-abdominal pressure.
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Affiliation(s)
- M Agustí
- Department of Anesthesia, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
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Joly LM, Monchi M, Cariou A, Chiche JD, Bellenfant F, Brunet F, Dhainaut JF. Effects of dobutamine on gastric mucosal perfusion and hepatic metabolism in patients with septic shock. Am J Respir Crit Care Med 1999; 160:1983-6. [PMID: 10588617 DOI: 10.1164/ajrccm.160.6.9708113] [Citation(s) in RCA: 37] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We prospectively evaluated the effects of dobutamine on gastric mucosal perfusion and hepatocytic clearance in patients with septic shock. After resuscitation with volume expansion and norepinephrine (12 patients) as needed, 14 hemodynamically stable patients (median age: 60 yr, median SAPS II score: 47) were given an infusion of 7.5 microg/kg/min dobutamine for 1 h. Gastric mucosal perfusion and hepatocytic clearance were assessed with tonometry and indocyanine green (ICG) elimination, respectively. All measurements were made before dobutamine infusion, after 1 h of dobutamine infusion, and 1 h after the infusion ended. Cardiac output (thermodilution technique) increased with dobutamine from a baseline median level of 4.0 L/min/m(2) (range: 1.7 to 7.4 L/min/m(2)) to 5.0 L/min/m(2) (range: 3.5 to 8.9 L/min/m(2)) (p = 0.004) and returned to baseline levels after dobutamine infusion ended. The gastric-arterial PCO(2) difference decreased from a baseline median level of 13 mm Hg (range: 5 to 54 mm Hg) to 7 mm Hg (range: 5 to 48 mm Hg) (p = 0.005). ICG elimination was low in all patients at baseline (median plasma disappearance rate: 12.2%; range: 7.6 to 16.2%) and did not change significantly during or after dobutamine infusion. In summary, dobutamine increases gastric mucosal perfusion but does not alter hepatocytic clearance in patients with septic shock. The absence of a beneficial effect of dobutamine on hepatocytic clearance may be related to profound alterations in hepatocellular metabolism during septic shock.
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Affiliation(s)
- L M Joly
- Medical Intensive Care Unit, Cochin Port Royal University Hospital, Paris, France
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Oriowo MA. Alpha1-adrenoceptor antagonist effect of (+/-)-dobutamine in rat isolated gastric artery preparation. J Cardiovasc Pharmacol 1999; 34:728-33. [PMID: 10547090 DOI: 10.1097/00005344-199911000-00015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
(+/-)-Dobutamine at concentrations < or =10(-5) M did not evoke contractions of rat gastric artery segments. However, when the tissues were contracted with methoxamine, (+/-)-dobutamine evoked concentration-dependent relaxation. The relaxant responses were not significantly affected by propranolol. In the same preparation, propranolol competitively antagonized isoprenaline-induced relaxation with a -log K(B) value of 7.90+/-0.26. (+/-)-Dobutamine did not relax arterial ring segments precontracted with vasopressin (10(-7) M). (+/-)-Dobutamine antagonized noradrenaline-induced contractions of the gastric artery segments. The pA2 value was 6.93+/-0.20, and the slope of the Schild regression line was 1.22+/-0.14. This value (slope) was not significantly different from 1, indicating competitive antagonism. Pretreatment of gastric artery segments with dobutamine before phenoxybenzamine (PBZ) protected against inactivation of alpha1-adrenoceptors by PBZ. The dose ratio of prazosin (3x10(-9) M) and (+/-)-dobutamine (10(-5) M) in combination was close to the expected sum of their individual dose ratios minus 1, indicating interaction with a common site. It was therefore concluded that (+/-)-dobutamine evoked relaxation of rat gastric artery segments by an action not involving beta-adrenoceptor activation but by blocking alpha1-adrenoceptors.
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Affiliation(s)
- M A Oriowo
- Department of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, Safat.
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Global Goals of Oxygen Metabolism and Intestinal Integrity. Crit Care Med 1999. [DOI: 10.1097/00003246-199910000-00067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Creteur J, De Backer D, Vincent JL. A dobutamine test can disclose hepatosplanchnic hypoperfusion in septic patients. Am J Respir Crit Care Med 1999; 160:839-45. [PMID: 10471606 DOI: 10.1164/ajrccm.160.3.9807029] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
In 36 hemodynamically stable septic patients, we explored whether changes in gastric mucosal-arterial PCO(2) gradient (PCO(2)gap) induced by a short-term dobutamine infusion may reveal hepatosplanchnic hypoperfusion. Hepatosplanchnic blood flow (HSBF) was determined by the continuous indocyanine green infusion technique and gastric mucosal PCO(2) (Pg(CO(2))) by saline tonometry. In each patient, hemodynamic measurements, blood samples, and Pg(CO(2)) determinations were performed three times: first at baseline (DOB 0), second during a dobutamine infusion at a dose of 5 microgram/kg/min (DOB 5), and third at a dose of 10 microgram/kg/min (DOB 10). The results were analyzed by Wilcoxon's matched-pairs signed rank test and are presented as medians with ranges. The PCO(2)gap decreased preferentially in groups of patients with inadequate hepatosplanchnic perfusion, i.e., with a low fractional HSBF (HSBF/CI), defined as the ratio of the HSBF to the simultaneous cardiac index, or a high gradient between the mixed venous blood and the suprahepatic blood O(2) saturations (DSvh(O(2))). In the 11 patients with a DSvh(O(2)) above 20% at baseline, PCO(2)gap decreased from 12.1 (6.3 to 19.5) mm Hg at DOB 0 to 6.2 (2.5 to 19. 3) mm Hg at DOB 5 (p < 0.001 versus DOB 0), and to 4.2 (0.1 to 35.9) mm Hg at DOB 10 (p < 0.05 versus DOB 5), whereas in the 25 patients with a DSvh(O(2)) below 20% at baseline, PCO(2)gap did not change significantly. At no time was the PCO(2)gap correlated with HSBF/CI or DSvh(O(2)). We conclude that although the PCO(2)gap does not correlate well with global indexes of gut oxygenation, such a simple dobutamine infusion test could identify patients with inadequate hepatosplanchnic perfusion.
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Affiliation(s)
- J Creteur
- Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Brussels, Belgium
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Ichai C, Levraut J, Baruch I, Samat-Long C, Leverve X, Grimaud D. Hypocapnia does not alter hepatic blood flow or oxygen consumption in patients with head injury. Crit Care Med 1998; 26:1725-30. [PMID: 9781731 DOI: 10.1097/00003246-199810000-00030] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE To evaluate the effects of hypocapnia on the systemic and hepatic circulations and oxygenation values in patients with head injury. DESIGN Open-label, prospective study. SETTING University hospital, department of anesthesiology and intensive care unit. PATIENTS Eleven mechanically ventilated patients with isolated head trauma and stable hemodynamic status. INTERVENTIONS At the beginning of the study, each patient presented with normocapnic ventilation. Mechanical hyperventilation was then adjusted to obtain stable hypocapnia over an interval of 24 hrs. Cardiac output and other systemic hemodynamic parameters were measured, using a pulmonary artery catheter. Hepatic parameters were measured via a catheter inserted into the hepatic vein. Total hepatic blood flow was determined by the Fick principle using a continuous infusion of indocyanine green. Arterial and hepatic venous blood gases were sampled to determine systemic and hepatic-splanchnic oxygenation. Measurements were done at the end of the four phases: a) 30 mins of normocapnia (N); b) 30 mins of hypocapnia (H0); c) 3 hrs of hypocapnia (H3); and d) 24 hrs of hypocapnia (H24). Intracranial pressure and cerebral perfusion pressure were hourly monitored throughout the study. MEASUREMENTS AND MAIN RESULTS There were no significant changes in systemic hemodynamic parameters. The hepatic blood flow index did not differ from normocapnia (N 1.8 +/- 0.4 L/min/m2) to hypocapnia (H0 1.6 +/- 0.3 L/min/m2; H3 1.7 +/- 0.4 L/min/m2; H24 1.7 +/- 0.4 L/min/m2). The ratio of hepatic blood flow index to cardiac index remained stable throughout the study. Hypocapnia did not affect hepatic-splanchnic oxygen delivery and consumption. CONCLUSIONS Hypocapnic hyperventilation does not alter hepatic hemodynamic parameters in patients with head injury. This result may be related to the lack of changes in cardiac output or in the hepatic vasoreactivity. Moreover, hypocapnia does not modify hepatic-splanchnic oxygenation. Thus, in case of intracranial hypertension, hypocapnia might be used without undesirable effect on the hepatic-splanchnic perfusion.
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Affiliation(s)
- C Ichai
- Department of Anesthesiology and Intensive Care, University of Nice School of Medicine, Hôpital Saint-Roch, France
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