Ventriculo-arterial Coupling and Myocardial Work in Sepsis and Septic Shock

NCT06853574 | Not Yet Recruiting DMC

• 1 other identifier: 70/2025/6-1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is a term which describes an excessive response of the body to an infection and, if not promptly treated, can turn into septic shock a condition in which the organs don't receive enough oxygen to satisfy their needs. The aim of the study is to assess how the treatment of sepsis and septic shock will modify myocardial work and ventriculo-arterial coupling, that can be considered as indicators of ventricular and arterial performance efficacy respectively. Each patient will be treated according to updated guidelines for sepsis and septic shock management, they will voluntarily be enrolled and they can decide to withdraw in each moment without any consequence on their treatment. The investigators, after receiving the consent, will collect patients' data, take blood samples and perform ultrasound measurements and then will start the treatment which can be based on fluids infusion, vasopressors or both. The investigators think that a modern cardiovascular assessment approach can be used to individually set the optimal blood pressure target in sepsis and septic shock with the combined evaluation of myocardial work and ventriculo-arterial coupling.

Conditions

Sepsis; Septic Shock

Keywords

sepsis; septic shock; myocardial work; ventriculo-arterial coupling; ICU; intensive care

Outcome Measures

Primary Outcomes (2)

• Changes in ventriculo-arterial coupling

  ventricular coupling will be analyzed on admission and its changes after treatment will be observed. To analyze ventriculo-arterial coupling, invasive blood pressure through either a radial or femoral arterial line will be collected and then data will be plotted into iElastance app available on smartphones to get the also knows as single beat determination ventriculo-arterial coupling.

  From enrollment to 24 hours after treatment start

• Changes in myocardial work

  Myocardial work will be analyzed on admission and its changes after treatment will be observed. To realize this, a transthoracic cardiac ultrasound will be performed and the images will be transferred to EchoPAC from General Electrics (GE) to get the pressure-volume strain analysis also known as myocardial work.

  From enrollment to 24 hours after treatment start

Secondary Outcomes (1)

• Mean arterial pressure optimal target

  From enrollment to 24 hours after treatment start

Study Arms (2)

Fluids

ACTIVE COMPARATOR

The patients will be included in this arm on admission basing on the absence of peripheral edema, presence of apical A lines at lung ultrasound, inferior vena cava width \< 2 cm and velocity-time integral (VTI) variation \> 10%. If the fluid therapy will not be effective, patients will also receive vasopressors.

Drug: Fluid therapy; Drug: Noradrenaline infusion

No fluids

ACTIVE COMPARATOR

The patients will be included in this arm on admission basing on the presence of peripheral edema, presence of apical B lines at lung ultrasound, inferior vena cava width \> 2 cm and velocity-time integral (VTI) variation \< 10%. In this arm the patients will receive vasopressors with an initial mean arterial pressure target of 65 mmHg; then the investigators will target to 80-85 mmHg to observe tha changes in ventriculo-arterial coupling.

Drug: Noradrenaline infusion

Interventions

Fluid therapy DRUG

Infusion of 8 ml/Kg/30' or 16 ml/kg/60' of fluids.

Fluids

Noradrenaline infusion DRUG

dosage will be titrated in order to obtain mean arterial pressure target

Also known as: Vasopressin infusion

Fluids; No fluids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• or more years old
• sepsis
• septic shock

You may not qualify if:

• lack of consent
• less than 18 years old
• pregnancy
• more than moderate aortic stenosis ( aortic valve area (AVA) \< 1.4 cm2, aortic valve area indexed (AVAi) \< 0.85, doppler velocity index (DVI) \< 0.5)
• more than mild mitral regurgitation (vena contracta (VC) width \<= 3 mm, mitral regurgitation (MR) effective regurgitant orifice area (EROA) \< 20, MR regurgitant volume (RegV) \< 30 ml)
• cardiac arrythmias (e.g. atrial fibrillation/flutter, frequent ventricular and supraventricular or nodal activity)
• renal replacement therapy
• other than continous modes of mechanical ventilation

Sponsors & Collaborators

• General and Teaching Hospital Celje: lead

Study Sites (1)

General Hospital Celje

Celje, 3000, Slovenia

Location

Related Publications (12)

• Sunagawa K, Sagawa K, Maughan WL. Ventricular interaction with the loading system. Ann Biomed Eng. 1984;12(2):163-89. doi: 10.1007/BF02584229.

  PMID: 6507965 BACKGROUND

• Kakihana Y, Nishida O, Taniguchi T, Okajima M, Morimatsu H, Ogura H, Yamada Y, Nagano T, Morishima E, Matsuda N; J-Land 3S Study Group. Efficacy and safety of landiolol, an ultra-short-acting beta1-selective antagonist, for treatment of sepsis-related tachyarrhythmia (J-Land 3S): a multicentre, open-label, randomised controlled trial. Lancet Respir Med. 2020 Sep;8(9):863-872. doi: 10.1016/S2213-2600(20)30037-0. Epub 2020 Mar 31.

  PMID: 32243865 BACKGROUND

• Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, Orecchioni A, D'Egidio A, D'Ippoliti F, Raffone C, Venditti M, Guarracino F, Girardis M, Tritapepe L, Pietropaoli P, Mebazaa A, Singer M. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013 Oct 23;310(16):1683-91. doi: 10.1001/jama.2013.278477.

  PMID: 24108526 BACKGROUND

• Nasrollahi-Shirazi S, Sucic S, Yang Q, Freissmuth M, Nanoff C. Comparison of the beta-Adrenergic Receptor Antagonists Landiolol and Esmolol: Receptor Selectivity, Partial Agonism, and Pharmacochaperoning Actions. J Pharmacol Exp Ther. 2016 Oct;359(1):73-81. doi: 10.1124/jpet.116.232884. Epub 2016 Jul 22.

  PMID: 27451411 BACKGROUND

• Zhou X, Pan J, Wang Y, Wang H, Xu Z, Zhuo W. Left ventricular-arterial coupling as a predictor of stroke volume response to norepinephrine in septic shock - a prospective cohort study. BMC Anesthesiol. 2021 Feb 17;21(1):56. doi: 10.1186/s12871-021-01276-y.

  PMID: 33596822 BACKGROUND

• Chen CH, Fetics B, Nevo E, Rochitte CE, Chiou KR, Ding PA, Kawaguchi M, Kass DA. Noninvasive single-beat determination of left ventricular end-systolic elastance in humans. J Am Coll Cardiol. 2001 Dec;38(7):2028-34. doi: 10.1016/s0735-1097(01)01651-5.

  PMID: 11738311 BACKGROUND

• Zhou X, Zhang Y, Pan J, Wang Y, Wang H, Xu Z, Chen B, Hu C. Optimizing left ventricular-arterial coupling during the initial resuscitation in septic shock - a pilot prospective randomized study. BMC Anesthesiol. 2022 Jan 21;22(1):31. doi: 10.1186/s12871-021-01553-w.

  PMID: 35062874 BACKGROUND

• Antonini-Canterin F, Poli S, Vriz O, Pavan D, Bello VD, Nicolosi GL. The Ventricular-Arterial Coupling: From Basic Pathophysiology to Clinical Application in the Echocardiography Laboratory. J Cardiovasc Echogr. 2013 Oct-Dec;23(4):91-95. doi: 10.4103/2211-4122.127408.

  PMID: 28465893 BACKGROUND

• Andrei S, Bahr PA, Berthoud V, Popescu BA, Nguyen M, Bouhemad B, Guinot PG. Diuretics depletion improves cardiac output and ventriculo-arterial coupling in congestive ICU patients during hemodynamic de-escalation. J Clin Monit Comput. 2023 Aug;37(4):1035-1043. doi: 10.1007/s10877-023-01011-7. Epub 2023 Apr 25.

  PMID: 37097337 BACKGROUND

• Bischoff AR, Stanford AH, McNamara PJ. Short-term ventriculo-arterial coupling and myocardial work efficiency in preterm infants undergoing percutaneous patent ductus arteriosus closure. Physiol Rep. 2021 Nov;9(22):e15108. doi: 10.14814/phy2.15108.

  PMID: 34806325 BACKGROUND

• Demailly Z, Besnier E, Tamion F, Lesur O. Ventriculo-arterial (un)coupling in septic shock: Impact of current and upcoming hemodynamic drugs. Front Cardiovasc Med. 2023 May 30;10:1172703. doi: 10.3389/fcvm.2023.1172703. eCollection 2023.

  PMID: 37324631 BACKGROUND

• Rehn M, Chew MS, Olkkola KT, Ingi Sigurethsson M, Yli-Hankala A, Hylander Moller M. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock in adults 2021 - endorsement by the Scandinavian society of anaesthesiology and intensive care medicine. Acta Anaesthesiol Scand. 2022 May;66(5):634-635. doi: 10.1111/aas.14045. Epub 2022 Mar 6.

  PMID: 35170043 BACKGROUND

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Fluid Therapy

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Central Study Contacts

Matej Prof. Dr. Podbregar, Intensive care medicine

CONTACT

+38640215960; podbregar.matej@gmail.com

Andrea Dr. D'Angelo, Emergency medicine resident

CONTACT

+393313550085; andrea.dangelo.1092@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Matej Podbregar

Study Record Dates

• First Submitted: January 31, 2025
• First Posted: March 3, 2025
• Study Start: February 1, 2025
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: March 3, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

SL (1)