The Systemic and Regional Hemodynamic Effects of Phenylephrine in Sheep Under Normal Conditions and During Early Hyperdynamic Sepsis

Department of Intensive Care, Austin Health, Melbourne, Victoria, Heidelberg, Victoria 3084, Australia.
Anesthesia and analgesia (Impact Factor: 3.42). 05/2012; 115(2):330-42. DOI: 10.1213/ANE.0b013e31825681ab
Source: PubMed

ABSTRACT Phenylephrine treatment of hypotension in sepsis raises concern because it may decrease vital organ bloodflow. Accordingly, we investigated the effects of phenylephrine on systemic and regional bloodflow in normal and septic sheep.
Responses to phenylephrine or vehicle infusion for 6 hours were determined in conscious normal sheep and sheep with early sepsis induced by administration of live Escherichia coli. Cardiac output and coronary, mesenteric, and renal bloodflow were measured with implanted flow probes.
In normal sheep, phenylephrine decreased cardiac output and heart rate (HR) but increased stroke volume and mean arterial blood pressure (MAP) (84 ± 6 to 108 ± 6 mm Hg, magnitude of mean difference [diff.] 19 [22.6%]; 95% confidence intervals [CI], 17-21). There were significant decreases in regional conductance values with a transient decrease in mesenteric bloodflow, no change in coronary bloodflow, and increased renal bloodflow (222 ± 53 to 271 ± 55 mL/min; diff. 31 [13.9%]; 95% CI, 26-36). During hyperdynamic sepsis, vasodilatation and increased bloodflow occurred in all vascular beds. Phenylephrine restored MAP and stroke volume to baseline values, but HR, cardiac output, and total peripheral conductance progressively decreased. Phenylephrine decreased mesenteric and coronary conductance, with no sustained reduction in flows, but renal conductance was significantly decreased and overall renal bloodflow increased (293 ± 22 vs 347 ± 100 mL/min; diff. 55 [18.8%]; 95% CI, 47-65).
In sheep with early hyperdynamic sepsis, phenylephrine, at a dose that restored MAP, increased stroke volume and renal bloodflow while decreasing HR and coronary bloodflow but not mesenteric bloodflow. Similar responses were seen in normal animals.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Traditionally, renal ischemia has been regarded as central to the pathogenesis of sepsis-associated acute kidney injury (SA-AKI). Accordingly, hemodynamic management of SA-AKI has emphasized restoration of renal perfusion, whereas, experimentally, ischemia reperfusion models have been emphasized. However, in human beings, SA-AKI usually is accompanied by hyperdynamic circulation. Moreover, clinical and experimental evidence now suggests the importance of inflammatory mechanisms in the development of AKI and microcirculatory dysfunction more than systemic alteration in renal perfusion. In this review, we examine systemic, regional, and microcirculatory hemodynamics in SA-AKI, and attempt to rationalize the hemodynamic management of this condition. Copyright © 2015 Elsevier Inc. All rights reserved.
    Seminars in Nephrology 01/2015; 35(1):64-74. DOI:10.1016/j.semnephrol.2015.01.007 · 2.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: La dysfonction endothéliale est à l’origine de la vasodilatation et de l’hypotension qui caractérisent le choc septique. Elle est responsable par des mécanismes nombreux et complexes de perturbations majeures de la perfusion microcirculatoire qui devient hétérogène et insuffisante. Les molécules vasoconstrictrices capables de cibler les mécanismes de la vasoplégie septique sont en cours d’expérimentation animale et sont loin d’une utilisation possible en clinique. Les vasopresseurs utilisés actuellement en clinique, la vasopressine, son analogue la terlipressine, ainsi que les amines α-adrénergiques (noradrénaline, adrénaline) sont des vasoconstricteurs non sélectifs qui ne ciblent pas la vasoplégie septique là où elle est prépondérante. Leurs effets d’augmentation de la pression artérielle et de la pression de perfusion des organes sont très similaires. Leurs effets sur les circulations régionales et sur la microcirculation dépendent du rapport entre l’effet macro-hémodynamique obtenu (débit cardiaque, pression artérielle), facilement mesurable, et l’effet de vasoconstriction de la microcirculation, plus difficile à évaluer en clinique. Dans cette mini-revue, nous discutons des effets macro- et microcirculatoires des différents vasopresseurs au cours du choc septique et examinons les essais cliniques comparatifs pour tenter de répondre aux questions pratiques suivantes: quel vasopresseur utiliser, pour quel objectif tensionnel et comment surveiller ses effets ? Abstract Endothelial dysfunction causes vasodilation and hypotension that characterize septic shock. Many complex molecular pathways lead to major alterations and heterogeneity of the microcirculation. Molecules capable of targeting the mechanisms of the septic vasoplegia are currently in development or under animal experimentation and are still far from a possible clinical use. The vasopressors currently used in clinical practice, vasopressin and its analogue terlipressin and α-adrenergic agonists (norepinephrine, epinephrine) are “blind” vasoconstrictors that do not target vasoplegia where it is dominant. Their effects on blood pressure and organ perfusion pressure are very similar. Their impact on the regional and microcirculation depends on the ratio between the obtained easily measurable macro-hemodynamic effects (cardiac output, blood pressure) and the effect of vasoconstriction on the microcirculation, more difficult to monitor clinically. In this mini-review we discuss the macro- and microcirculatory effects of the different vasopressors in septic shock and examine the published comparative clinical trials to address the following practical questions: what vasopressor should we use, which blood pressure level should we target, and how to monitor its effects?
    Réanimation 03/2014; 23(2):135-147. DOI:10.1007/s13546-014-0850-8
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the past decade, analysis of the urinary proteome (urinary proteomics) has intensified in response to the need for novel biomarkers that support early diagnosis of kidney diseases. In particular, this also applies to acute kidney injury, which is a heterogeneous complex syndrome with a still-increasing incidence at the intensive care unit. Unfortunately, this major need remains largely unmet to date. The current report aims to explain why attempts to implement urinary proteomic-discovered acute kidney injury diagnostic candidates in the intensive care unit setting have not yet led to success. Subsequently, some key notes are provided that should enhance the chance of translating selected urinary proteomic candidates to valuable tools for the nephrologist and intensivist in the near future.
    Expert Review of Proteomics 06/2014; DOI:10.1586/14789450.2014.932252 · 3.54 Impact Factor