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      Nitroglycerin challenge identifies microcirculatory target for improved resuscitation in patients with circulatory shock

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          Abstract

          Background

          Circulatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCD NG, RBCv NG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target.

          Methods

          Sublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock.

          Results

          54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m 2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCv NG. Heart rate ( p < 0.001), central venous pressure ( p = 0.02), lactate ( p < 0.001), capillary refill time ( p < 0.01), and Mottling score ( p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCD NG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCD NG similar to baseline FCD found in patients without shock.

          Conclusion

          Critically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40635-024-00662-3.

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          Most cited references42

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          Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock

          To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012."
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            Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine

            Objective Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. Methods The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575–590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit? (2) Should we monitor preload and fluid responsiveness in shock? (3) How and when should we monitor stroke volume or cardiac output in shock? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock? Four types of statements were used: definition, recommendation, best practice and statement of fact. Results Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. Conclusions This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock.
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              Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine

              Hand-held vital microscopes (HVMs) were introduced to observe sublingual microcirculatory alterations at the bedside in different shock states in critically ill patients. This consensus aims to provide clinicians with guidelines for practical use and interpretation of the sublingual microcirculation. Furthermore, it aims to promote the integration of routine application of HVM microcirculatory monitoring in conventional hemodynamic monitoring of systemic hemodynamic variables.
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                Author and article information

                Contributors
                matthias.hilty@usz.ch
                Journal
                Intensive Care Med Exp
                Intensive Care Med Exp
                Intensive Care Medicine Experimental
                Springer International Publishing (Cham )
                2197-425X
                2 September 2024
                2 September 2024
                December 2024
                : 12
                : 76
                Affiliations
                [1 ]Institute of Intensive Care Medicine, University Hospital of Zurich, ( https://ror.org/01462r250) Zurich, Switzerland
                [2 ]Laboratory of Translational Intensive Care, Department of Intensive Care, Erasmus MC, University Medical Center, ( https://ror.org/018906e22) Rotterdam, The Netherlands
                Author information
                http://orcid.org/0000-0001-5861-4505
                http://orcid.org/0000-0001-7775-3279
                http://orcid.org/0000-0001-8180-2117
                http://orcid.org/0000-0002-2765-881X
                Article
                662
                10.1186/s40635-024-00662-3
                11369126
                39222259
                7eec1f93-8f6e-455c-a37f-ef8b11c27515
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 5 October 2023
                : 21 August 2024
                Funding
                Funded by: University of Zurich Walter und Gertrud Siegenthaler Foundation
                Categories
                Research Articles
                Custom metadata
                © European Society of Intensive Care Medicine and Springer Nature Switzerland AG 2024

                microcirculation,critical care,sublingual microcirculatory assessment,microcirculatory reserve capacity,capillary recruitment,resuscitation

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