Marked regional endothelial dysfunction in mottled skin area in patients with severe infections

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Abstract

Background

Mottling around the knee, reflecting a reduced skin blood flow, is predictive of mortality in patients with septic shock. However, the causative pathophysiology of mottling remains unknown. We hypothesized that the cutaneous hypoperfusion observed in the mottled area is related to regional endothelial dysfunction.

Methods

This was a prospective, observational study in a medical ICU in a tertiary teaching hospital. Consecutive adult patients with sepsis admitted to ICU were included. After resuscitation, endothelium-dependent vasodilation in the skin circulation was measured before and after iontophoresis of acetylcholine (Ach) in the forearm and the knee area. We analyzed the patterns of induced vasodilatation according to the presence or absence of mottling and vital status at 14 days.

Results

We evaluated 37 septic patients, including 11 without and 26 with septic shock. Overall 14-day mortality was 22%. Ten patients had mottling around the knee (10/37, 27%). In the knee area, the increased skin blood flow following iontophoresis of Ach was lower in patients with mottled skin as compared to patients without mottled skin (area under curve (AUC) 3280 (2643–6440) vs. 7980 (4233–19,707), both P < 0.05). In the forearm area, the increased skin blood flow following iontophoresis of Ach was similar in patients with and without mottled skin. Among patients with septic shock, the increased skin blood flow following iontophoresis of Ach in the knee area was significantly lower in non-survivors as compared to survivors at 14 days (AUC 3256 (2600–4426) vs. 7704 (4539–15,011), P < 0.01). In patients with septic shock, the increased skin blood flow in the forearm area following iontophoresis of Ach was similar in survivors and non-survivors at 14 days.

Conclusion

Mottling is associated with regional endothelial dysfunction in patients with septic shock. Endothelial dysfunction in the knee skin area was more pronounced in non-survivors than in survivors.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-017-1742-x) contains supplementary material, which is available to authorized users.

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Most cited references 20

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Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure.

F Michard, S Boussat, D Chemla … (2000)

In mechanically ventilated patients with acute circulatory failure related to sepsis, we investigated whether the respiratory changes in arterial pressure could be related to the effects of volume expansion (VE) on cardiac index (CI). Forty patients instrumented with indwelling systemic and pulmonary artery catheters were studied before and after VE. Maximal and minimal values of pulse pressure (Pp(max) and Pp(min)) and systolic pressure (Ps(max) and Ps(min)) were determined over one respiratory cycle. The respiratory changes in pulse pressure (DeltaPp) were calculated as the difference between Pp(max) and Pp(min) divided by the mean of the two values and were expressed as a percentage. The respiratory changes in systolic pressure (DeltaPs) were calculated using a similar formula. The VE-induced increase in CI was >/= 15% in 16 patients (responders) and < 15% in 24 patients (nonresponders). Before VE, DeltaPp (24 +/- 9 versus 7 +/- 3%, p < 0.001) and DeltaPs (15 +/- 5 versus 6 +/- 3%, p < 0.001) were higher in responders than in nonresponders. Receiver operating characteristic (ROC) curves analysis showed that DeltaPp was a more accurate indicator of fluid responsiveness than DeltaPs. Before VE, a DeltaPp value of 13% allowed discrimination between responders and nonresponders with a sensitivity of 94% and a specificity of 96%. VE-induced changes in CI closely correlated with DeltaPp before volume expansion (r(2) = 0. 85, p < 0.001). VE decreased DeltaPp from 14 +/- 10 to 7 +/- 5% (p < 0.001) and VE-induced changes in DeltaPp correlated with VE-induced changes in CI (r(2) = 0.72, p < 0.001). It was concluded that in mechanically ventilated patients with acute circulatory failure related to sepsis, analysis of DeltaPp is a simple method for predicting and assessing the hemodynamic effects of VE, and that DeltaPp is a more reliable indicator of fluid responsiveness than DeltaPs.

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The respiratory variation in inferior vena cava diameter as a guide to fluid therapy.

Marc Feissel, Frederic Michard, Jean-Pierre Faller … (2004)

To investigate whether the respiratory variation in inferior vena cava diameter (DeltaD(IVC)) could be related to fluid responsiveness in mechanically ventilated patients. Prospective clinical study. Medical ICU of a non-university hospital. Mechanically ventilated patients with septic shock (n=39). Volume loading with 8 mL/kg of 6% hydroxyethylstarch over 20 min. Cardiac output and DeltaD(IVC) were assessed by echography before and immediately after the standardized volume load. Volume loading induced an increase in cardiac output from 5.7+/-2.0 to 6.4+/-1.9 L/min (P or =15% (responders). Before volume loading, the DeltaD(IVC) was greater in responders than in non-responders (25+/-15 vs 6+/-4%, P<0.001), closely correlated with the increase in cardiac output (r=0.82, P<0.001), and a 12% DeltaD(IVC) cut-off value allowed identification of responders with positive and negative predictive values of 93% and 92%, respectively. Analysis of DeltaD(IVC) is a simple and non-invasive method to detect fluid responsiveness in mechanically ventilated patients with septic shock.

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Author and article information

Contributors

Simon Bourcier: Simon_bourcier@hotmail.com

Jérémie Joffre: jeremiejoffre@yahoo.fr

Vincent Dubée: vdubee@gmail.com

Gabriel Preda: gabropreda@gmail.com

Jean-Luc Baudel: jean-luc.baudel@aphp.fr

Naïke Bigé: naikebige@gmail.com

Guillaume Leblanc: guillaume.leblanc.1@gmail.com

Bernard I. Levy: bernard.levy@inserm.fr

Bertrand Guidet: bertrand.guidet@aphp.fr

Eric Maury: eric.maury@aphp.fr

Hafid Ait-Oufella: hafid.aitoufella@aphp.fr

Journal

Journal ID (nlm-ta): Crit Care

Title: Critical Care

Publisher: BioMed Central (London )

ISSN (Print): 1364-8535

ISSN (Electronic): 1466-609X

Publication date (Electronic): 23 June 2017

Publication date PMC-release: 23 June 2017

Publication date Collection: 2017

Volume: 21

Electronic Location Identifier: 155

Affiliations

[1 ]Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Saint-Antoine, Service de réanimation médicale, 184 rue du Faubourg Saint-Antoine, 75571 Paris, Cedex 12 France

[2 ]ISNI 0000 0001 1955 3500, GRID grid.5805.8, , Université Pierre-et-Marie Curie, ; Paris 6, France

[3 ]Inserm U1136, Paris, F-75012 France

[4 ]ISNI 0000 0004 0495 1460, GRID grid.462416.3, Inserm U970, , Centre de Recherche Cardiovasculaire de Paris (PARCC), ; Paris, France

[5 ]ISNI 0000 0004 1936 8390, GRID grid.23856.3a, Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, , Université Laval, ; Québec, QC Canada

Article

Publisher ID: 1742

DOI: 10.1186/s13054-017-1742-x

PMC ID: 5481873

PubMed ID: 28641580

SO-VID: b1b40519-bf8e-4320-8433-d1e1e8dfd5e4

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 29 December 2016

Date accepted : 26 May 2017

Custom metadata

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: infection,mottling,tissue perfusion,mortality,endothelial function

Data availability:

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: infection, mottling, tissue perfusion, mortality, endothelial function

Marked regional endothelial dysfunction in mottled skin area in patients with severe infections

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JAMA Network: Coronavirus

Most cited references 20

A New Simplified Acute Physiology Score (SAPS II) Based on a European/North American Multicenter Study

Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure.

The respiratory variation in inferior vena cava diameter as a guide to fluid therapy.

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