Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry

an observational study

J DAVIS, Tsin Yeo, J THOMAS, M McMillan, C DARCY, Yvette McNeil, A CHENG, D CELERMAJER, D STEPHENS, Nicholas Anstey

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Introduction: Sepsis has a high mortality despite advances in management. Microcirculatory and endothelial dysfunction contribute to organ failure, and better tools are needed to assess microcirculatory responses to adjunctive therapies. We hypothesised that peripheral arterial tonometry (PAT), a novel user-independent measure of endothelium-dependent microvascular reactivity, would be impaired in proportion to sepsis severity and related to endothelial activation and plasma arginine concentrations.Methods: Observational cohort study in a 350-bed teaching hospital in tropical Australia. Bedside microvascular reactivity was measured in 85 adults with sepsis and 45 controls at baseline and 2-4 days later by peripheral arterial tonometry. Microvascular reactivity was related to measures of disease severity, plasma concentrations of L-arginine (the substrate for nitric oxide synthase), and biomarkers of endothelial activation.Results: Baseline reactive hyperaemia index (RH-PAT index), measuring endothelium-dependent microvascular reactivity; (mean [95% CI]) was lowest in severe sepsis (1.57 [1.43-1.70]), intermediate in sepsis without organ failure (1.85 [1.67-2.03]) and highest in controls (2.05 [1.91-2.19]); P < 0.00001. Independent predictors of baseline RH-PAT index in sepsis were APACHE II score and mean arterial pressure, but not plasma L-arginine or markers of endothelial activation. Low baseline RH-PAT index was significantly correlated with an increase in SOFA score over the first 2-4 days (r = -0.37, P = 0.02).Conclusions: Endothelium-dependent microvascular reactivity is impaired in proportion to sepsis severity and suggests decreased endothelial nitric oxide bioavailability in sepsis. Peripheral arterial tonometry may have a role as a user-independent method of monitoring responses to novel adjunctive therapies targeting endothelial dysfunction in sepsis. � 2009 Davis et al.; licensee BioMed Central Ltd.
    Original languageEnglish
    Pages (from-to)R155-
    JournalCritical Care
    Volume13
    Issue number5
    Publication statusPublished - 2009

    Fingerprint

    Manometry
    Observational Studies
    Sepsis
    Endothelium
    Arginine
    APACHE
    Nitric Oxide Synthase Type III
    Hyperemia
    Teaching Hospitals
    Biological Availability
    Arterial Pressure
    Nitric Oxide
    Cohort Studies
    Biomarkers
    Mortality
    Therapeutics

    Cite this

    DAVIS, J ; Yeo, Tsin ; THOMAS, J ; McMillan, M ; DARCY, C ; McNeil, Yvette ; CHENG, A ; CELERMAJER, D ; STEPHENS, D ; Anstey, Nicholas. / Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry : an observational study. In: Critical Care. 2009 ; Vol. 13, No. 5. pp. R155-.
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    title = "Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry: an observational study",
    abstract = "Introduction: Sepsis has a high mortality despite advances in management. Microcirculatory and endothelial dysfunction contribute to organ failure, and better tools are needed to assess microcirculatory responses to adjunctive therapies. We hypothesised that peripheral arterial tonometry (PAT), a novel user-independent measure of endothelium-dependent microvascular reactivity, would be impaired in proportion to sepsis severity and related to endothelial activation and plasma arginine concentrations.Methods: Observational cohort study in a 350-bed teaching hospital in tropical Australia. Bedside microvascular reactivity was measured in 85 adults with sepsis and 45 controls at baseline and 2-4 days later by peripheral arterial tonometry. Microvascular reactivity was related to measures of disease severity, plasma concentrations of L-arginine (the substrate for nitric oxide synthase), and biomarkers of endothelial activation.Results: Baseline reactive hyperaemia index (RH-PAT index), measuring endothelium-dependent microvascular reactivity; (mean [95{\%} CI]) was lowest in severe sepsis (1.57 [1.43-1.70]), intermediate in sepsis without organ failure (1.85 [1.67-2.03]) and highest in controls (2.05 [1.91-2.19]); P < 0.00001. Independent predictors of baseline RH-PAT index in sepsis were APACHE II score and mean arterial pressure, but not plasma L-arginine or markers of endothelial activation. Low baseline RH-PAT index was significantly correlated with an increase in SOFA score over the first 2-4 days (r = -0.37, P = 0.02).Conclusions: Endothelium-dependent microvascular reactivity is impaired in proportion to sepsis severity and suggests decreased endothelial nitric oxide bioavailability in sepsis. Peripheral arterial tonometry may have a role as a user-independent method of monitoring responses to novel adjunctive therapies targeting endothelial dysfunction in sepsis. � 2009 Davis et al.; licensee BioMed Central Ltd.",
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    author = "J DAVIS and Tsin Yeo and J THOMAS and M McMillan and C DARCY and Yvette McNeil and A CHENG and D CELERMAJER and D STEPHENS and Nicholas Anstey",
    year = "2009",
    language = "English",
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    DAVIS, J, Yeo, T, THOMAS, J, McMillan, M, DARCY, C, McNeil, Y, CHENG, A, CELERMAJER, D, STEPHENS, D & Anstey, N 2009, 'Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry: an observational study', Critical Care, vol. 13, no. 5, pp. R155-.

    Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry : an observational study. / DAVIS, J; Yeo, Tsin; THOMAS, J; McMillan, M; DARCY, C; McNeil, Yvette; CHENG, A; CELERMAJER, D; STEPHENS, D; Anstey, Nicholas.

    In: Critical Care, Vol. 13, No. 5, 2009, p. R155-.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Sepsis-associated microvascular dysfunction measured by peripheral arterial tonometry

    T2 - an observational study

    AU - DAVIS, J

    AU - Yeo, Tsin

    AU - THOMAS, J

    AU - McMillan, M

    AU - DARCY, C

    AU - McNeil, Yvette

    AU - CHENG, A

    AU - CELERMAJER, D

    AU - STEPHENS, D

    AU - Anstey, Nicholas

    PY - 2009

    Y1 - 2009

    N2 - Introduction: Sepsis has a high mortality despite advances in management. Microcirculatory and endothelial dysfunction contribute to organ failure, and better tools are needed to assess microcirculatory responses to adjunctive therapies. We hypothesised that peripheral arterial tonometry (PAT), a novel user-independent measure of endothelium-dependent microvascular reactivity, would be impaired in proportion to sepsis severity and related to endothelial activation and plasma arginine concentrations.Methods: Observational cohort study in a 350-bed teaching hospital in tropical Australia. Bedside microvascular reactivity was measured in 85 adults with sepsis and 45 controls at baseline and 2-4 days later by peripheral arterial tonometry. Microvascular reactivity was related to measures of disease severity, plasma concentrations of L-arginine (the substrate for nitric oxide synthase), and biomarkers of endothelial activation.Results: Baseline reactive hyperaemia index (RH-PAT index), measuring endothelium-dependent microvascular reactivity; (mean [95% CI]) was lowest in severe sepsis (1.57 [1.43-1.70]), intermediate in sepsis without organ failure (1.85 [1.67-2.03]) and highest in controls (2.05 [1.91-2.19]); P < 0.00001. Independent predictors of baseline RH-PAT index in sepsis were APACHE II score and mean arterial pressure, but not plasma L-arginine or markers of endothelial activation. Low baseline RH-PAT index was significantly correlated with an increase in SOFA score over the first 2-4 days (r = -0.37, P = 0.02).Conclusions: Endothelium-dependent microvascular reactivity is impaired in proportion to sepsis severity and suggests decreased endothelial nitric oxide bioavailability in sepsis. Peripheral arterial tonometry may have a role as a user-independent method of monitoring responses to novel adjunctive therapies targeting endothelial dysfunction in sepsis. � 2009 Davis et al.; licensee BioMed Central Ltd.

    AB - Introduction: Sepsis has a high mortality despite advances in management. Microcirculatory and endothelial dysfunction contribute to organ failure, and better tools are needed to assess microcirculatory responses to adjunctive therapies. We hypothesised that peripheral arterial tonometry (PAT), a novel user-independent measure of endothelium-dependent microvascular reactivity, would be impaired in proportion to sepsis severity and related to endothelial activation and plasma arginine concentrations.Methods: Observational cohort study in a 350-bed teaching hospital in tropical Australia. Bedside microvascular reactivity was measured in 85 adults with sepsis and 45 controls at baseline and 2-4 days later by peripheral arterial tonometry. Microvascular reactivity was related to measures of disease severity, plasma concentrations of L-arginine (the substrate for nitric oxide synthase), and biomarkers of endothelial activation.Results: Baseline reactive hyperaemia index (RH-PAT index), measuring endothelium-dependent microvascular reactivity; (mean [95% CI]) was lowest in severe sepsis (1.57 [1.43-1.70]), intermediate in sepsis without organ failure (1.85 [1.67-2.03]) and highest in controls (2.05 [1.91-2.19]); P < 0.00001. Independent predictors of baseline RH-PAT index in sepsis were APACHE II score and mean arterial pressure, but not plasma L-arginine or markers of endothelial activation. Low baseline RH-PAT index was significantly correlated with an increase in SOFA score over the first 2-4 days (r = -0.37, P = 0.02).Conclusions: Endothelium-dependent microvascular reactivity is impaired in proportion to sepsis severity and suggests decreased endothelial nitric oxide bioavailability in sepsis. Peripheral arterial tonometry may have a role as a user-independent method of monitoring responses to novel adjunctive therapies targeting endothelial dysfunction in sepsis. � 2009 Davis et al.; licensee BioMed Central Ltd.

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