Relationship Between Pulse Pressure and Stroke Volume in the Critically Ill Patients: The ANDROMEDA-PEGASUS Study

Can Pulse Pressure Assessment at the Bedside Detect Low Values or Track Changes of Stroke Volume in Critically Ill Patients? The Multicenter, Cross-sectional, Observational, ANDROMEDA-PEGASUS Study

The goal of this study is to assess the predictive capacity of pulse pressure to estimate stroke volume, as assessed by bedside echocardiography in critically ill patients.

We hypothesize that pulse pressure will be able to adequately detect low values of stroke volume, and to track changes of stroke volume during commonly used dynamic cardiovascular interventions.

Pulse pressure transduced from an arterial line will be measured simultaneously with left ventricular outflow tract velocity time integral in a broad range of critically ill patients. Ancillary clinical, hemodynamic and echocardiographic data will also be registered.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness

Detailed Description

Critically ill patients often present complex cardiovascular derangements that impair oxygen delivery to the tissues leading to progressive organ dysfunction. Monitoring tissue perfusion and identifying the predominant hemodynamic patterns are key clinical objectives to implement resuscitative strategies and revert this vicious cycle. However, in different stages of acute circulatory dysfunction at the emergency department (ED) or the intensive care unit (ICU), or resource-limited settings, initial resuscitative decisions may be taken with basic clinical information only. In addition, many therapeutic interventions in the ICU such as fluids, diuretics, vasoactive drugs, and ventilatory-related maneuvers, among others, may jeopardize stroke volume (SV) in different ways, a fact that may evolve undetected due to the absence of specific hemodynamic monitors in all patients.

Unfortunately, there is no simple, costless, and universally available clinical monitor to detect low SV. There have been, however, physiological implications to use blood pressure components as a surrogate for SV. Although pulse pressure (PP) has been observed to be largely determined by SV in experimental conditions, the key issues remain to be clarified: can PP monitoring at the bedside be useful to detect extreme values, or track changes, in underlying SV? Moreover, what are the limitations, the contexts, the technical aspects, among other factors, that can affect this relationship, and thus help clinicians to potentially use PP as an early warning signal or a trigger for initial resuscitative or therapeutic interventions?

From a clinical point of view, the most relevant question is if PP monitoring can detect a low SV so that corrective measures might be implemented, while more advanced confirmatory monitoring, including point-of-care ultrasound, is pending. In addition, what are the potential confounders for this assumption? If these questions are answered, this simple and costless tool may be used as a first-line approach for macrohemodynamic profiling and clinical decision-making, which could be especially valuable in resource-limited settings and in sites where ultrasound or advanced cardiac output monitoring is not immediately available. In this multicenter, observational, cross-sectional study, we aim at answering the following research question:

Research Question

• In critically ill patients, does pulse pressure, measured through an invasive arterial line, have an adequate predictive capacity to estimate stroke volume, as assessed by bedside echocardiography?
• We hypothesize that pulse pressure will be able to adequately detect low values of stroke volume, and to track changes of stroke volume during commonly used dynamic cardiovascular interventions.

Primary Objective

- To assess the predictive capacity of pulse pressure to detect low stroke volume, evaluated by bedside ultrasonography in critically ill patients.

Secondary Objectives

• To assess the predictive capacity of PP to detect low SV in different clinical contexts in ICU patients, such as in those with acute respiratory distress syndrome (ARDS), postoperative states, or septic shock, among others.
• To assess the impact of several demographic, clinical and technical issues on the predictive capacity of PP to estimate SV, such as mechanical ventilation, vasoactive medication, age, position of the arterial line, among others.
• To determine the capacity of PP to track changes of SV during common intensive care interventions such as passive leg raising (PLR) maneuver or fluid challenges.

• Study Type: Observational
• Enrollment (Estimated): 1500

Contacts and Locations

• Study Contact: Name: Eduardo Kattan, MD, PhD; Phone Number: +56223543292; Email: e.kattan@gmail.com
• Study Contact Backup: Name: Glenn Hernandez, MD, PhD; Phone Number: +56223543292; Email: glennguru@gmail.com

Study Locations

• Brazil
  • Sao Paulo, Brazil
    • Recruiting
    • Hospital do Coracao
    • Contact: Alexandre B Cavalcanti, MD, PhD; Email: abiasi@hcor.com.br
• Chile
  • Santiago, Chile
    • Recruiting
    • Hospital Clínico UC Christus
    • Contact: Eduardo Kattan, MD, PhD; Email: e.kattan@gmail.com
    • Principal Investigator: Eduardo Kattan, MD
• Colombia
  • Cali, Colombia
    • Recruiting
    • Fundacion Valle Del Lili
    • Contact: Gustavo Ospina-Tascón, MD, PhD; Email: gusospin@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

- During the study period (one or two weeks according to local study team), eligible patients will be identified during morning rounds. Consecutive patients which comply with inclusion and exclusion criteria and consent in participating will be included in the study. A broad range of ICU patients will be included to perform relevant subgroup analysis.

Description

Inclusion Criteria:

• 18 years
• Admitted to ICU
• Functioning arterial line in place

Exclusion Criteria:

• Pregnancy
• Inadequate arterial line transduction (see below)
• Refusal of consent
• Patient who requires extracorporeal circulation

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Left ventricular outflow tract velocity time integral	measured by bedside echocardiography	1 day
Pulse pressure	measured from invasive arterial line	1 day

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborators: Erasmus Medical Center; Hospital do Coracao; Fundacion Clinica Valle del Lili
• Investigators: Principal Investigator: Eduardo Kattan, MD, PhD, Assistant Professor; Principal Investigator: Glenn Hernandez, MD, PhD, Full Professor

Publications and helpful links

General Publications

• Marquez J, McCurry K, Severyn DA, Pinsky MR. Ability of pulse power, esophageal Doppler, and arterial pulse pressure to estimate rapid changes in stroke volume in humans. Crit Care Med. 2008 Nov;36(11):3001-7. doi: 10.1097/CCM.0b013e31818b31f0.
• Hernandez G, Ospina-Tascon GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Granda-Luna V, Cavalcanti AB, Bakker J; The ANDROMEDA SHOCK Investigators and the Latin America Intensive Care Network (LIVEN); Hernandez G, Ospina-Tascon G, Petri Damiani L, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Cavalcanti AB, Bakker J, Hernandez G, Alegria L, Ferri G, Rodriguez N, Holger P, Soto N, Pozo M, Bakker J, Cook D, Vincent JL, Rhodes A, Kavanagh BP, Dellinger P, Rietdijk W, Carpio D, Pavez N, Henriquez E, Bravo S, Valenzuela ED, Vera M, Dreyse J, Oviedo V, Cid MA, Larroulet M, Petruska E, Sarabia C, Gallardo D, Sanchez JE, Gonzalez H, Arancibia JM, Munoz A, Ramirez G, Aravena F, Aquevedo A, Zambrano F, Bozinovic M, Valle F, Ramirez M, Rossel V, Munoz P, Ceballos C, Esveile C, Carmona C, Candia E, Mendoza D, Sanchez A, Ponce D, Ponce D, Lastra J, Nahuelpan B, Fasce F, Luengo C, Medel N, Cortes C, Campassi L, Rubatto P, Horna N, Furche M, Pendino JC, Bettini L, Lovesio C, Gonzalez MC, Rodruguez J, Canales H, Caminos F, Galletti C, Minoldo E, Aramburu MJ, Olmos D, Nin N, Tenzi J, Quiroga C, Lacuesta P, Gaudin A, Pais R, Silvestre A, Olivera G, Rieppi G, Berrutti D, Ochoa M, Cobos P, Vintimilla F, Ramirez V, Tobar M, Garcia F, Picoita F, Remache N, Granda V, Paredes F, Barzallo E, Garces P, Guerrero F, Salazar S, Torres G, Tana C, Calahorrano J, Solis F, Torres P, Herrera L, Ornes A, Perez V, Delgado G, Lopez A, Espinosa E, Moreira J, Salcedo B, Villacres I, Suing J, Lopez M, Gomez L, Toctaquiza G, Cadena Zapata M, Orazabal MA, Pardo Espejo R, Jimenez J, Calderon A, Paredes G, Barberan JL, Moya T, Atehortua H, Sabogal R, Ortiz G, Lara A, Sanchez F, Hernan Portilla A, Davila H, Mora JA, Calderon LE, Alvarez I, Escobar E, Bejarano A, Bustamante LA, Aldana JL. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019 Feb 19;321(7):654-664. doi: 10.1001/jama.2019.0071.
• Bakker J, Kattan E, Annane D, Castro R, Cecconi M, De Backer D, Dubin A, Evans L, Gong MN, Hamzaoui O, Ince C, Levy B, Monnet X, Ospina Tascon GA, Ostermann M, Pinsky MR, Russell JA, Saugel B, Scheeren TWL, Teboul JL, Vieillard Baron A, Vincent JL, Zampieri FG, Hernandez G. Current practice and evolving concepts in septic shock resuscitation. Intensive Care Med. 2022 Feb;48(2):148-163. doi: 10.1007/s00134-021-06595-9. Epub 2021 Dec 15.
• Hernandez G, Messina A, Kattan E. Invasive arterial pressure monitoring: much more than mean arterial pressure! Intensive Care Med. 2022 Oct;48(10):1495-1497. doi: 10.1007/s00134-022-06798-8. Epub 2022 Jul 8. No abstract available.
• Westerhof N, Lankhaar JW, Westerhof BE. The arterial Windkessel. Med Biol Eng Comput. 2009 Feb;47(2):131-41. doi: 10.1007/s11517-008-0359-2. Epub 2008 Jun 10.
• Convertino VA, Cooke WH, Holcomb JB. Arterial pulse pressure and its association with reduced stroke volume during progressive central hypovolemia. J Trauma. 2006 Sep;61(3):629-34. doi: 10.1097/01.ta.0000196663.34175.33.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): January 30, 2026

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): December 17, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: stroke volume; pulse pressure
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: 240730006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data may be shared upon reasonable request to the principal investigators
• IPD Sharing Time Frame: after publication
• IPD Sharing Access Criteria: De-identified data may be shared upon reasonable request to the principal investigators
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No