Thoracic Fluid Content During Stabilization and Therapeutic De-escalation in Septic Shock (TFC-SEPSIS)

Assessment of Intra-thoracic Water by Bio Reactance During Stabilization and Therapeutic De-escalation in Septic Shock: A Prospective, Multicenter, Observational Study

In ICU, fluid challenge represents one of the cornerstones of hemodynamic care. However, fluid overload due to an excessive and/or inappropriate fluid administration could be associated with morbidity or mortality. Unfortunately, there is currently no continuous non-invasive devices to monitor fluid content at bedside. Bio reactance is a non-invasive, rapid and continuous technology developed in order to measure body fluid compartment. Monitoring devices functioning with such technology are promising to evaluate fluid overload in ICU.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock; Fluid Overload; Hemodynamic Instability

Detailed Description

During the resuscitation phase of shock, fluid administration represents one of the cornerstones of care in order to increase cardiac output and improve microvascular blood flow. However, inappropriate fluid administration can increase tissue edema which compromises recovery after the resolution of shock state. Recently, Sakr et al. demonstrated that a higher fluid balance at 72 hours was associated with hospital mortality after septic shock. Furthermore, an administration of more than 5 liters of fluid during the first ICU stay was independently associated with an increase in mortality and hospital costs. Therefore, treating fluid removal appears to be a key component of the de-escalation phase of shock. Thus, all valuable parameters which potentially reflect tissue edema may help clinicians to individualized the necessity of fluid removal during the stabilization and de-escalation phase of shock. Among them, extra-vascular lung water (EVLW) measured with trans-pulmonary thermodilution is able to detect changes in thoracic fluid content but needs to be monitored invasively and only sequential values are recorded (each thermodilution measure). On the other hand, lung ultrasonography may help clinicians to assess fluid overload but its ability to quantify thoracic fluid content is difficult and subjective.

Bio reactance is a non-invasive, rapid and continuous method to measure body fluid compartment. All measures can be performed at bedside. Bio reactance monitoring devices allow measurement of hemodynamic parameters such as cardiac index or stroke volume but also Thoracic Fluid Content (TFC). TFC is measured through the changes in impedance of thoracic tissue to the electrical current. This parameter represents the whole fluid content in the thorax (intravascular, extravascular and intra-pleural). TFC has already been evaluated in several context. During hemodialysis, TFC is correlated to the amount of fluid removal and might help clinician to improve hemodialysis session management in ICU. In cardiac surgery, electrical impedance is correlated with changes in fluid balance. In ICU, TFC is able to predict a mechanical ventilation weaning failure with a moderate accuracy (AUC 0.69 [0.57 - 0.8], bet cut-off value > 50 k.Ω-1) in patients with moderate to severe alteration of left ventricular ejection fraction.

The main objective of the current study will evaluated correlation between thoracic fluid content (TFC) measurement and other valuable indices of fluid overload used at bedside. Secondary objectives will be to evaluate association between TFC and other clinical outcomes (organ dysfunction, mortality and quality of life after hospital living).

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Xavier Chapalain, MD; Phone Number: +33230337893; Email: xavier.chapalain@chu-brest.fr
• Study Contact Backup: Name: Dauphou Eddi; Email: dauphou.eddi@chu-brest.fr

Study Locations

• France
  • Brest, France, 29200
    • Recruiting
    • CHU Brest
    • Contact: Xavier CHAPALAIN
    • Contact: Email: xavier.chapalain@chu-brest.fr
  • Paris, France, 75015
    • Not yet recruiting
    • Hegp - Aphp
    • Contact: Bernard Cholley
    • Contact: Email: bernard.cholley@aphp.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult patients admitted in ICU for septic shock

Description

Inclusion Criteria:

• Adult (Age >18 years old)

• Septic shock according to Sepsis-3 definition:

  • A suspected or confirmed infection
  • Persisting hypotension, despite adequate fluid resuscitation, requiring vasopressor to maintain a Mean Arterial Pressure (MAP) ≥ 65 mmHg
  • Lactate level > 2 mmol/l
• Predictive ICU length of stay > 3 days

Exclusion Criteria:

• Admission in ICU for more than 3 days
• Refusal to participate
• Moribund patients
• Decision of therapeutic withdrawal
• Curators

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in daily body weight	Evaluation of correlation between daily body weight and thoracic fluid content	Daily, during the first 10 days
Changes in extra vascular lung water	Evaluation of correlation between extra vascular lung water and thoracic fluid content	Daily, during the first 10 days
Changes in daily fluid balance	Evaluation of correlation between fluid balance and thoracic fluid content	Daily, during the first 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of ICU stay	Number of day from admission to ICU leaving	during ICU stay (up to 10 days)
Length of hospital stay	Number of day from admission to hospital leaving	during hospital stay (up to 10 days)
Ventilator free days at Day 28	Number of day alive without mechanical from ICU admission to Day 28	Day 28
Mortality at Day 28	Survival (Yes/No)	Day 28
Short Form-12	Quality of life will measured by Short-Form 12 questionnaire. This validated scale contains sub-scale which explore eight domains: physical activities, social activities, usual role in activities, pain, mental health, emotional problem, vitality, general health perceptions. A higher Short Form-12 score is associated with a better quality of life, a lower Short Form-12 score is associated with a lower quality of life. The minimum score is 10 and the maximum is 60.	3 months
Percentage of patients who return at home	Evaluation of rehabilitation with the proportion of patients able to return at home	3 months
Percentage of patients who have professional activities	Evaluation of rehabilitation with the proportion of patients able to return at professional activities	3 months

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Investigators: Principal Investigator: Xavier Chapalain, MD, University Hospital, Brest

Publications and helpful links

General Publications

• Bouhemad B, Zhang M, Lu Q, Rouby JJ. Clinical review: Bedside lung ultrasound in critical care practice. Crit Care. 2007;11(1):205. doi: 10.1186/cc5668.
• Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307.
• Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D; Sepsis Occurrence in Acutely Ill Patients Investigators. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006 Feb;34(2):344-53. doi: 10.1097/01.ccm.0000194725.48928.3a.
• Vincent JL, De Backer D. Circulatory shock. N Engl J Med. 2013 Oct 31;369(18):1726-34. doi: 10.1056/NEJMra1208943. No abstract available.
• Marik PE, Linde-Zwirble WT, Bittner EA, Sahatjian J, Hansell D. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med. 2017 May;43(5):625-632. doi: 10.1007/s00134-016-4675-y. Epub 2017 Jan 27.
• Sakr Y, Rubatto Birri PN, Kotfis K, Nanchal R, Shah B, Kluge S, Schroeder ME, Marshall JC, Vincent JL; Intensive Care Over Nations Investigators. Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit. Crit Care Med. 2017 Mar;45(3):386-394. doi: 10.1097/CCM.0000000000002189.
• Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL; Sepsis Occurrence in Acutely Ill Patients (SOAP) Investigators. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care. 2008;12(3):R74. doi: 10.1186/cc6916. Epub 2008 Jun 4.
• Vaara ST, Korhonen AM, Kaukonen KM, Nisula S, Inkinen O, Hoppu S, Laurila JJ, Mildh L, Reinikainen M, Lund V, Parviainen I, Pettila V; FINNAKI Study Group. Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study. Crit Care. 2012 Oct 17;16(5):R197. doi: 10.1186/cc11682.
• Jozwiak M, Silva S, Persichini R, Anguel N, Osman D, Richard C, Teboul JL, Monnet X. Extravascular lung water is an independent prognostic factor in patients with acute respiratory distress syndrome. Crit Care Med. 2013 Feb;41(2):472-80. doi: 10.1097/CCM.0b013e31826ab377.
• Sakka SG, Klein M, Reinhart K, Meier-Hellmann A. Prognostic value of extravascular lung water in critically ill patients. Chest. 2002 Dec;122(6):2080-6. doi: 10.1378/chest.122.6.2080.
• Malbrain ML, Huygh J, Dabrowski W, De Waele JJ, Staelens A, Wauters J. The use of bio-electrical impedance analysis (BIA) to guide fluid management, resuscitation and deresuscitation in critically ill patients: a bench-to-bedside review. Anaesthesiol Intensive Ther. 2014 Nov-Dec;46(5):381-91. doi: 10.5603/AIT.2014.0061.
• Kossari N, Hufnagel G, Squara P. Bioreactance: a new tool for cardiac output and thoracic fluid content monitoring during hemodialysis. Hemodial Int. 2009 Oct;13(4):512-7. doi: 10.1111/j.1542-4758.2009.00386.x. Epub 2009 Sep 16.
• Perko MJ, Jarnvig IL, Hojgaard-Rasmussen N, Eliasen K, Arendrup H. Electric impedance for evaluation of body fluid balance in cardiac surgical patients. J Cardiothorac Vasc Anesth. 2001 Feb;15(1):44-8. doi: 10.1053/jcan.2001.20272.
• Fathy S, Hasanin AM, Raafat M, Mostafa MMA, Fetouh AM, Elsayed M, Badr EM, Kamal HM, Fouad AZ. Thoracic fluid content: a novel parameter for predicting failed weaning from mechanical ventilation. J Intensive Care. 2020 Mar 5;8:20. doi: 10.1186/s40560-020-00439-2. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 27, 2024

Study Record Updates

• Last Update Posted (Actual): August 27, 2024
• Last Update Submitted That Met QC Criteria: August 26, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: 29BRC22.0275_TFC-SEPSIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available beginning three years and ending fifteen years following the final study report completion
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest University Hospital. Requestors will be required to sign and complete a data access agreement
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No