Current use of vasopressors in septic shock

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Abstract

Background

Vasopressors are commonly applied to restore and maintain blood pressure in patients with sepsis. We aimed to evaluate the current practice and therapeutic goals regarding vasopressor use in septic shock as a basis for future studies and to provide some recommendations on their use.

Methods

From November 2016 to April 2017, an anonymous web-based survey on the use of vasoactive drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM). A total of 17 questions focused on the profile of respondents, triggering factors, first choice agent, dosing, timing, targets, additional treatments, and effects of vasopressors. We investigated whether the answers complied with current guidelines. In addition, a group of 34 international ESICM experts was asked to formulate recommendations for the use of vasopressors based on 6 questions with sub-questions (total 14).

Results

A total of 839 physicians from 82 countries (65% main specialty/activity intensive care) responded. The main trigger for vasopressor use was an insufficient mean arterial pressure (MAP) response to initial fluid resuscitation (83%). The first-line vasopressor was norepinephrine (97%), targeting predominantly a MAP > 60–65 mmHg (70%), with higher targets in patients with chronic arterial hypertension (79%). The experts agreed on 10 recommendations, 9 of which were based on unanimous or strong (≥ 80%) agreement. They recommended not to delay vasopressor treatment until fluid resuscitation is completed but rather to start with norepinephrine early to achieve a target MAP of ≥ 65 mmHg.

Conclusion

Reported vasopressor use in septic shock is compliant with contemporary guidelines. Future studies should focus on individualized treatment targets including earlier use of vasopressors.

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Most cited references 42

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Fluid challenges in intensive care: the FENICE study

Maurizio Cecconi, Christoph Hofer, Jean-Louis Teboul … (2015)

Background Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC. Methods This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC. Results 2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500–1000). The median time was 24 min (40–60 min), and the median rate of FC was 1000 [500–1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57–61 %). In 43 % (CI 41–45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34–37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20–24 %). No safety variable for the FC was used in 72 % (CI 70–74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response. Conclusions The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account. Electronic supplementary material The online version of this article (doi:10.1007/s00134-015-3850-x) contains supplementary material, which is available to authorized users.

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Effects of perfusion pressure on tissue perfusion in septic shock.

M Astiz, C M Carpati, E C Rackow … (2000)

To measure the effects of increasing mean arterial pressure (MAP) on systemic oxygen metabolism and regional tissue perfusion in septic shock. Prospective study. Medical and surgical intensive care units of a tertiary care teaching hospital. Ten patients with the diagnosis of septic shock who required pressor agents to maintain a MAP > or = 60 mm Hg after fluid resuscitation to a pulmonary artery occlusion pressure (PAOP) > or = 12 mm Hg. Norepinephrine was titrated to MAPs of 65, 75, and 85 mm Hg in 10 patients with septic shock. At each level of MAP, hemodynamic parameters (heart rate, PAOP, cardiac index, left ventricular stroke work index, and systemic vascular resistance index), metabolic parameters (oxygen delivery, oxygen consumption, arterial lactate), and regional perfusion parameters (gastric mucosal Pco2, skin capillary blood flow and red blood cell velocity, urine output) were measured. Increasing the MAP from 65 to 85 mm Hg with norepinephrine resulted in increases in cardiac index from 4.7+/-0.5 L/min/m2 to 5.5+/-0.6 L/min/m2 (p < 0.03). Arterial lactate was 3.1+/-0.9 mEq/L at a MAP of 65 mm Hg and 3.0+/-0.9 mEq/L at 85 mm Hg (NS). The gradient between arterial P(CO2) and gastric intramucosal Pco2 was 13+/-3 mm Hg (1.7+/-0.4 kPa) at a MAP of 65 mm Hg and 16+/-3 at 85 mm Hg (2.1+/-0.4 kPa) (NS). Urine output at 65 mm Hg was 49+/-18 mL/hr and was 43+/-13 mL/hr at 85 mm Hg (NS). As the MAP was raised, there were no significant changes in skin capillary blood flow or red blood cell velocity. Increasing the MAP from 65 mm Hg to 85 mm Hg with norepinephrine does not significantly affect systemic oxygen metabolism, skin microcirculatory blood flow, urine output, or splanchnic perfusion.

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The relationship between ICU hypotension and in-hospital mortality and morbidity in septic patients

Kamal Maheshwari, Brian H Nathanson, Sibyl Munson … (2018)

Purpose Current guidelines recommend maintaining a mean arterial pressure (MAP) ≥ 65 mmHg in septic patients. However, the relationship between hypotension and major complications in septic patients remains unclear. We, therefore, evaluated associations of MAPs below various thresholds and in-hospital mortality, acute kidney injury (AKI), and myocardial injury. Methods We conducted a retrospective analysis using electronic health records from 110 US hospitals. We evaluated septic adults with intensive care unit (ICU) stays ≥ 24 h from 2010 to 2016. Patients were excluded with inadequate blood pressure recordings, poorly documented potential confounding factors, or renal or myocardial histories documented within 6 months of ICU admission. Hypotension exposure was defined by time-weighted average mean arterial pressure (TWA-MAP) and cumulative time below 55, 65, 75, and 85 mmHg thresholds. Multivariable logistic regressions determined the associations between hypotension exposure and in-hospital mortality, AKI, and myocardial injury. Results In total, 8,782 patients met study criteria. For every one unit increase in TWA-MAP < 65 mmHg, the odds of in-hospital mortality increased 11.4% (95% CI 7.8%, 15.1%, p < 0.001); the odds of AKI increased 7.0% (4.7, 9.5%, p < 0.001); and the odds of myocardial injury increased 4.5% (0.4, 8.7%, p = 0.03). For mortality and AKI, odds progressively increased as thresholds decreased from 85 to 55 mmHg. Conclusions Risks for mortality, AKI, and myocardial injury were apparent at 85 mmHg, and for mortality and AKI risk progressively worsened at lower thresholds. Maintaining MAP well above 65 mmHg may be prudent in septic ICU patients. Electronic supplementary material The online version of this article (10.1007/s00134-018-5218-5) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

Thomas W. L. Scheeren:

ORCID: http://orcid.org/0000-0002-9184-4190

+31 50 3616161 , t.w.l.scheeren@umcg.nl

Jan Bakker: jan.bakker@erasmusmc.nl

Daniel De Backer: ddebacke@ulb.ac.be

Djillali Annane: djillali.annane@aphp.fr

Pierre Asfar: piasfar@chu-angers.fr

E. Christiaan Boerma: christiaan.boerma@znb.nl

Maurizio Cecconi: maurizio.cecconi@hunimed.eu

Arnaldo Dubin: arnaldodubin@gmail.com

Martin W. Dünser: Martin.Duenser@i-med.ac.at

Jacques Duranteau: jacques.duranteau@aphp.fr

Anthony C. Gordon: anthony.gordon@imperial.ac.uk

Olfa Hamzaoui: olfa.hamzaoui@aphp.fr

Glenn Hernández: glennguru@gmail.com

Marc Leone: marc.leone@ap-hm.fr

Bruno Levy: blevy5463@gmail.com

Claude Martin: ClaudeDenis.MARTIN@ap-hm.fr

Alexandre Mebazaa: alexandre.mebazaa@aphp.fr

Xavier Monnet: xavier.monnet@aphp.fr

Andrea Morelli: andrea.morelli@uniroma1.it

Didier Payen: dpayen1234@orange.fr

Rupert Pearse: r.pearse@qmul.ac.uk

Michael R. Pinsky: pinsky@pitt.edu

Peter Radermacher: peter.radermacher@uni-ulm.de

Daniel Reuter: Daniel.Reuter@med.uni-rostock.de

Bernd Saugel: bcs.muc@gmx.de , bernd.saugel@gmx.de , b.saugel@uke.de

Yasser Sakr: yasser.sakr@med.uni-jena.de

Mervyn Singer: m.singer@ucl.ac.uk

Pierre Squara: pierre.squara@orange.fr

Antoine Vieillard-Baron: antoine.vieillard-baron@aphp.fr

Philippe Vignon: philippe.vignon@unilim.fr

Simon T. Vistisen: vistisen@clin.au.dk

Iwan C. C. van der Horst:

ORCID: http://orcid.org/0000-0003-3891-8522

i.c.c.van.der.horst@umcg.nl

Jean-Louis Vincent: jlvincent@intensive.org

Jean-Louis Teboul: jean-louis.teboul@aphp.fr

Journal

Journal ID (nlm-ta): Ann Intensive Care

Journal ID (iso-abbrev): Ann Intensive Care

Title: Annals of Intensive Care

Publisher: Springer International Publishing (Cham )

ISSN (Electronic): 2110-5820

Publication date (Electronic): 30 January 2019

Publication date PMC-release: 30 January 2019

Publication date Collection: 2019

Volume: 9

Electronic Location Identifier: 20

Affiliations

[1 ]ISNI 0000 0004 0407 1981, GRID grid.4830.f, Department of Anesthesiology, University Medical Center Groningen, , University of Groningen, ; Hanzeplein 1, P.O. Box 30.001, 9700RB Groningen, The Netherlands

[2 ]ISNI 0000 0001 2109 4251, GRID grid.240324.3, New York University Medical Center, ; New York, USA

[3 ]ISNI 0000 0001 2285 2675, GRID grid.239585.0, Columbia University Medical Center, ; New York, USA

[4 ]ISNI 000000040459992X, GRID grid.5645.2, Erasmus MC University Medical Center, ; Rotterdam, Netherlands

[5 ]ISNI 0000 0001 2157 0406, GRID grid.7870.8, Pontificia Universidad Católica de Chile, ; Santiago, Chile

[6 ]ISNI 0000 0001 2348 0746, GRID grid.4989.c, Department of Intensive Care, CHIREC Hospitals, , Université Libre de Bruxelles, ; Brussels, Belgium

[7 ]ISNI 0000 0001 2323 0229, GRID grid.12832.3a, Department of Intensive Care Medicine, School of Medicine Simone Veil, Raymond Poincaré Hospital (APHP), , University of Versailles-University Paris Saclay, ; 104 boulevard Raymond Poincaré, 92380 Garches, France

[8 ]ISNI 0000 0001 2248 3363, GRID grid.7252.2, Département de Médecine Intensive-Réanimation et de Médecine Hyperbare, Centre Hospitalier Universitaire Angers, Institut MITOVASC, CNRS, UMR 6214, INSERM U1083, , Angers University, ; Angers, France

[9 ]ISNI 0000 0004 0419 3743, GRID grid.414846.b, Department of Intensive Care, , Medical Centre Leeuwarden, ; Leeuwarden, The Netherlands

[10 ]Department of Anaesthesia and Intensive Care Units, Humanitas Research Hospital and Humanitas University, Milan, Italy

[11 ]ISNI 0000 0001 2097 3940, GRID grid.9499.d, Cátedra de Farmacología Aplicada, Facultad de Ciencias Médicas, , Universidad Nacional de La Plata y Servicio de Terapia Intensiva, ; Sanatorio Otamendi, Buenos Aires, Argentina

[12 ]ISNI 0000 0001 1941 5140, GRID grid.9970.7, Department of Anesthesiology and Intensive Care Medicine, , Kepler University Hospital and Johannes Kepler University Linz, ; Linz, Austria

[13 ]ISNI 0000 0001 2181 7253, GRID grid.413784.d, Assistance Publique des Hopitaux de Paris, Department of Anaesthesia and Intensive Care, , Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Hôpital de Bicêtre, ; Le Kremlin-Bicêtre, France

[14 ]ISNI 0000 0001 2113 8111, GRID grid.7445.2, Section of Anaesthetics, Pain Medicine and Intensive Care, , Imperial College London, ; London, UK

[15 ]ISNI 0000 0000 9454 4367, GRID grid.413738.a, Assistance Publique-Hôpitaux de Paris Paris-Sud University Hospitals, Intensive Care Unit, , Antoine Béclère Hospital, ; Clamart, France

[16 ]ISNI 0000 0001 2157 0406, GRID grid.7870.8, Departamento de Medicina Intensiva, Facultad de Medicina, , Pontificia Universidad Católica de Chile, ; Santiago, Chile

[17 ]ISNI 0000 0001 2176 4817, GRID grid.5399.6, Assistance Publique Hôpitaux de Marseille, Service d’Anesthésie et de Réanimation CHU Nord, , Aix Marseille Université, ; Marseille, France

[18 ]ISNI 0000 0001 2194 6418, GRID grid.29172.3f, Service de Réanimation Médicale Brabois et pôle cardio-médico-chirurgical, CHRU, INSERM U1116, , Université de Lorraine, ; Brabois, 54500 Vandoeuvre les Nancy, France

[19 ]ISNI 0000 0001 2217 0017, GRID grid.7452.4, Department of Anesthesia, Burn and Critical Care, APHP Hôpitaux Universitaires Saint Louis Lariboisière, U942 Inserm, , Université Paris Diderot, ; Paris, France

[20 ]ISNI 0000 0001 2181 7253, GRID grid.413784.d, Assistance Publique-Hôpitaux de Paris, Paris-Sud University Hospitals, Medical Intensive Care Unit, , Bicêtre Hospital, ; Le Kremlin-Bicêtre, France

[21 ]INSERM UMR_S 999, Paris-Saclay University, Le Plessis-Robinson, France

[22 ]GRID grid.7841.a, Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, , University of Rome “La Sapienza”, ; Rome, Italy

[23 ]ISNI 0000 0001 2217 0017, GRID grid.7452.4, INSERM 1160 and Hôpital Lariboisière, APHP, , University Paris 7 Denis Diderot, ; Paris, France

[24 ]ISNI 0000 0001 2171 1133, GRID grid.4868.2, Queen Mary University of London, ; London, UK

[25 ]ISNI 0000 0004 1936 9000, GRID grid.21925.3d, Department of Critical Care Medicine, , University of Pittsburgh, ; Pittsburgh, USA

[26 ]GRID grid.410712.1, Institut für Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, ; Ulm, Germany

[27 ]ISNI 0000000121858338, GRID grid.10493.3f, Department of Anesthesiology and Intensive Care Medicine, , Rostock University Medical Centre, ; Rostock, Germany

[28 ]ISNI 0000 0001 2180 3484, GRID grid.13648.38, Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, , University Medical Center Hamburg-Eppendorf, ; Hamburg, Germany

[29 ]ISNI 0000 0000 8517 6224, GRID grid.275559.9, Department of Anesthesiology and Intensive Care, , Uniklinikum Jena, ; Jena, Germany

[30 ]ISNI 0000000121901201, GRID grid.83440.3b, Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, , University College London, ; London, UK

[31 ]GRID grid.477172.0, ICU Department, Réanimation CERIC, , Clinique Ambroise Paré, ; Neuilly, France

[32 ]Assistance Publique-Hôpitaux de Paris, Intensive Care Unit, University Hospital Ambroise Paré, Boulogne-Billancourt, France

[33 ]INSERM U-1018, CESP, Team 5, University of Versailles Saint-Quentin en Yvelines, Villejuif, France

[34 ]ISNI 0000 0001 2165 4861, GRID grid.9966.0, Medical-Surgical Intensive Care Unit, INSERM CIC-1435, Teaching Hospital of Limoges, , University of Limoges, ; Limoges, France

[35 ]ISNI 0000 0001 1956 2722, GRID grid.7048.b, Institute of Clinical Medicine, , Aarhus University, ; Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark

[36 ]ISNI 0000 0004 0407 1981, GRID grid.4830.f, Department of Critical Care, University Medical Center Groningen, , University of Groningen, ; Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands

[37 ]ISNI 0000 0001 2348 0746, GRID grid.4989.c, Department of Intensive Care, Erasme University Hospital, , Université Libre de Bruxelles, ; Brussels, Belgium

[38 ]ISNI 0000 0001 2171 2558, GRID grid.5842.b, Service de Réanimation Médicale, Hôpital de Bicêtre, , Hôpitaux Universitaires Paris-Sud, ; Le Kremlin-Bicêtre, France

Author information

Thomas W. L. Scheeren http://orcid.org/0000-0002-9184-4190

Iwan C. C. van der Horst http://orcid.org/0000-0003-3891-8522

Article

Publisher ID: 498

DOI: 10.1186/s13613-019-0498-7

PMC ID: 6353977

PubMed ID: 30701448

SO-VID: 78cdf56a-407c-4048-8ba1-565a352c1c04

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.

History

Date received : 25 October 2018

Date accepted : 22 January 2019

Custom metadata

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: shock,sepsis,septic shock,resuscitation,vasopressor,vasoactive agonists,norepinephrine,arterial blood pressure

Data availability:

ScienceOpen disciplines: Emergency medicine & Trauma

Keywords: shock, sepsis, septic shock, resuscitation, vasopressor, vasoactive agonists, norepinephrine, arterial blood pressure

Current use of vasopressors in septic shock

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Abstract

Background

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UCL: UN SDG 03 Good Health and Well-Being

Most cited references 42

Fluid challenges in intensive care: the FENICE study

Effects of perfusion pressure on tissue perfusion in septic shock.

The relationship between ICU hypotension and in-hospital mortality and morbidity in septic patients

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