Effects of hemodynamic monitoring using a single-use transesophageal echocardiography probe in critically ill patients - study protocol for a randomized controlled trial

Abstract

Background: Hemodynamic instability is one of the leading causes of intensive care unit (ICU) admission. Early stabilization of hemodynamics is associated with improved outcome. The monitoring used to guide hemodynamic support may influence the time needed to achieve stable hemodynamics. Visualization of the heart using echocardiography offers the advantage of direct measurement of cardiac volumes and ventricular function. A miniaturized monoplane transesophageal echocardiography (TEE) probe was developed, allowing for almost continuous qualitative hemodynamic TEE assessment (hTEE) after brief bedside training. The primary objective of the study is to assess whether hemodynamic monitoring using the hTEE technology shortens time to resolution of shock in ICU patients in comparison to standard monitoring using a central venous catheter, pulmonary artery catheter, or conventional echocardiography.

Methods: Five hundred consecutive subjects with circulatory shock (low mean arterial blood pressure (MAP) and signs of organ hypoperfusion) at the time of ICU admission are included in the study. The subjects are randomly assigned to one of four groups using a 2 × 2 factorial design stratified by method of hemodynamic monitoring (hTEE vs standard hemodynamic monitoring) and frequency of hemodynamic assessments (minimum every 4 h vs standard of care). The primary study outcome is the time from study inclusion to resolution of circulatory shock, defined as MAP > 60 mmHg for ≥ 4 h after discontinuation of vasopressors and inotropes. The hTEE monitoring consists of the acquisition of three defined echocardiography views: Transgastric mid-esophageal short axis with measurement of fractional area change of left ventricle, mid-esophageal four-chamber view with measurement of the ratio of right to left ventricular area, and mid-esophageal ascending aortic short-axis view with measurement of the superior vena cava collapsibility index. In the control groups, monitoring modalities, including conventional TTE and TEE but not hTEE, are at the discretion of the treating physician. The interpretation of hemodynamic monitoring and the subsequent changes in patient management are recorded after each hemodynamic assessment. Differences in the primary and further secondary time-to-event outcomes will be assessed using a competing risk model accounting for the competing risk of death.

Discussion: The effect of using echocardiography as a monitoring modality on relevant patient outcomes has not been established so far. The study at hand may be one of the first trials to provide detailed data on effectiveness and safety of echocardiography to guide treatment in patients with circulatory shock.

Trial registration: ClinicalTrials.gov, ID: NCT02048566. Registered on January 29, 2014.

Keywords: Circulatory shock; Echocardiography; Hemodynamic monitoring; Intensive care unit.

Conflict of interest statement

Ethics approval and consent to participate

This study is carried out in accordance with the protocol and conducted according to international standards of Good Clinical Practice, applicable government regulations and Institutional research policies and procedures. The study has been approved by the Institutional Review Board (IRB) of the Canton of Bern (Kantonale Ethikkommission des Kantons Bern). Any important protocol modifications are reported to the IRB.

Most eligible patients are unable to give consent for the study at the time of ICU admission because of mental incapacity due to the underlying medical condition and treatment (mechanical ventilation). The study is based on assessing parameters during the initial stabilization period immediately after ICU admission; therefore, randomization and study inclusion must occur as soon as possible. Before a patient is enrolled, a physician who is not participating in study must confirm that the interests of the patient are safeguarded and that all inclusion criteria and no exclusion criteria are present. Thereafter, deferred consent involving study inclusion according to the stated criteria in this protocol, followed by the request for a representative’s (deferred proxy consent, within 72 h) and patient’s informed consent (deferred subject consent, as soon as patient’s conditions allows) in a later phase, is used. All subjects for this study and their designed representatives receive a consent form describing this study and providing sufficient information for subjects to make an informed decision about their participation in this study. The consent form must be signed by the subject or legally acceptable surrogate, and the investigator-designated research professional obtaining the consent. In cases where the patient’s representative’s consent to the study and the patient’s consent cannot be obtained due to the patient’s condition (death, neurological compromise) after provisional study inclusion by proxy consent, the data are used for further analysis. In cases where it is not possible to contact relatives, or if no relatives exist and the patient’s consent cannot be obtained due to the patient’s condition (death, neurological compromise) after provisional study inclusion by deferred consent, the data are used for further analysis. In the event that a study patient dies before being able to come to an informed decision on study participation and no relatives are available for deferred proxy consent, the collected data are used for analysis [21, 22]. If the patient or relatives deny consent for study inclusion or if the patient or relatives withdraw consent at any time after provisional study inclusion by deferred consent, data are not used for further analysis.

Competing interests

The authors declare that no support from any organization was received for the submitted work. The Department of Intensive Care Medicine of the University Hospital Bern, Switzerland has, or has had in the past, research contracts with Orion Corporation, Abbott Nutrition International, B. Braun Medical AG, CSEM SA, Edwards Lifesciences Services GmbH, Kenta Biotech Ltd., Maquet Critical Care AB, Omnicare Clinical Research AG and research and development/consulting contracts with Edwards Lifesciences SA, Maquet Critical Care AB, and Nestlé. The Department has received unrestricted educational grants from the following organizations for organizing a quarterly postgraduate educational symposium, the Berner Forum for Intensive Care (until 2015): Fresenius Kabi, gsk, MSD, Lilly, Baxter, astellas, AstraZeneca, B Braun, CSL Behring, Maquet, Novartis, Covidien, Nycomed, Pierre Fabre Pharma AG (formerly known as RobaPharm), Pfizer, Orion Pharma, Bard Medica S.A., Abbott AG, Anandic Medical Systems. The Department has received unrestricted educational grants from the following organizations for organizing bi-annual postgraduate courses in the fields of critical care ultrasound, management of ECMO and mechanical ventilation: Pierre Fabre Pharma AG (formerly known as RobaPharm), Pfizer AG, Bard Medica S.A., Abbott AG, Anandic Medical Systems, PanGas AG Healthcare, Orion Pharma, Bracco, Edwards Lifesciences AG, Hamilton Medical AG, Fresenius Kabi (Schweiz) AG, Getinge Group Maquet AG, Dräger Schweiz AG.

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Figures

Fig. 1

Participant timeline