Thoracic Fluid Content During Stabilization and Therapeutic De-escalation in Septic Shock

Official title

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

Overview

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.

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).

Primary outcome measures

• Changes in daily body weight [Time frame: Daily, during the first 10 days]
• Changes in extra vascular lung water [Time frame: Daily, during the first 10 days]
• Changes in daily fluid balance [Time frame: Daily, during the first 10 days]

Secondary outcome measures (7)

• Length of ICU stay [Time frame: during ICU stay (up to 10 days)]
• Length of hospital stay [Time frame: during hospital stay (up to 10 days)]
• Ventilator free days at Day 28 [Time frame: Day 28]
• Mortality at Day 28 [Time frame: Day 28]
• Short Form-12 [Time frame: 3 months]
• Percentage of patients who return at home [Time frame: 3 months]
• Percentage of patients who have professional activities [Time frame: 3 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

France · 2 centers

• Chu Brest — Brest
• Hegp - Aphp — Paris

Publications

• 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. PMID 24171518
• 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. PMID 11794169
• 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. PMID 28130687
• 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. PMID 27922878
• 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. PMID 16424713
• 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. PMID 18533029
• 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. PMID 23075459
• 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. PMID 23263578

Identifiers

NCT: NCT06572995 · 29BRC22.0275_TFC-SEPSIS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗