Resuscitation Strategies in Septic Shock (ReSSeS)

Resuscitation Strategies in Septic Shock. A Randomized Controlled Trial of Two Different Fluid Loading Strategies in ICU Patients With Early Septic Shock

The purpose of this study, in mechanically ventilated septic shock patients, is to determine whether a fluid loading strategy based on parameters derived from the transpulmonary thermodilution technique may lead to more ventilator free days compared to a fluid loading strategy based on the surviving sepsis guidelines.

Study Overview

• Status: Unknown
• Conditions: Septic Shock; Critically Ill
• Intervention / Treatment: Device: Transpulmonary Thermodilution; Device: Surviving Sepsis Guidelines (SSG)

Detailed Description

Rationale: Fluid loading is an important intervention in patients with severe sepsis and septic shock in order to prevent development of multi organ failure and mortality. The Surviving Sepsis Guidelines recommend during the first 6 hours of resuscitation a central venous pressure (CVP) based fluid loading approach, targeting to 12-15 mmHg in mechanically ventilated patients. CVP however has proven to be a poor indicator for preload and preload dependency, while dynamic parameters as stroke volume variation (SVV) derived from the transpulmonary thermodilution technique (TPTD) are superior. Together with the ability to measure the extravascular lung water (EVLW), the TPTD technique may guide fluid management more accurately and may prevent deleterious fluid overloading.

Objective: The risk of fluid overloading in mechanically ventilated patients with septic shock is less when fluid administration is based on a fluid loading protocol using SVV together with EVLW measurements than applying the Surviving Sepsis Guidelines targeting CVP to 12-15 mmHg, in at least the first 6 hours of resuscitation, translating in more ventilator free days (VFDs) Study design: This is a prospective, randomized, non-blinded, single-center, controlled clinical trial comparing two different fluid resuscitation strategies in patients with septic shock. Patients will be randomized for fluid management based on the Surviving Sepsis Guidelines (SSG) or based transpulmonary thermodilution (TPTD) derived SVV and EVLW in at least the first 6 hours of resuscitation.

Study population: All patients of ≥18 years admitted to the ICU because of septic shock together with the need for mechanical ventilation are eligible for randomization Intervention: During at least the first 6 hours of resuscitation, the standard group (SSG guided therapy) follows a fluid resuscitation protocol based on the Surviving Sepsis Campaign recommendations. Initial trigger for fluid loading when circulatory insufficiency is present will be the CVP (target ≥12 mmHg). The intervention group (TPTD guided therapy) follows a fluid resuscitation protocol based on SVV and EVLW. Initial trigger for fluid loading when circulatory insufficiency is present will be SVV. The study protocol will be applied up to a maximum of 72 hours.

Main study parameters/endpoints: VFDs on day 28. Benefit and risks associated with participation: Since inclusion criteria include a TPTD (5F fiber optic, femoral artery) catheter, the inconvenience as compared to standard treatment is minimal. Current routine hospital policy involves TPTD catheter insertion in most of the patients meeting the inclusion criteria specified above.

• Study Type: Interventional
• Enrollment (Anticipated): 170
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: RJ Trof, MD PhD; Phone Number: 0031-53-4872000; Email: r.trof@mst.nl
• Study Contact Backup: Name: M Burgmeijer; Phone Number: 0053-4872000; Email: researchIC@mst.nl

Study Locations

• Netherlands
  • Enschede, Netherlands
    • Recruiting
    • Medisch Spectrum Twente
    • Contact: RJ Trof, MD PhD; Email: r.trof@mst.nl
    • Contact: Research IC; Email: researchIC@mst.nl
    • Principal Investigator: RJ Trof, MD PhD
    • Sub-Investigator: A Beishuizen, MD PhD
    • Sub-Investigator: JW Vermeijden, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 18 years
2. Clinical evidence of sepsis (microbiology confirmation, radiological or direct view (pus in biological fluid) or direct surgical view).

3. ≥ 2 SIRS criteria:

   1. Temperature < 36.0°C or > 38.0°C
   2. Heart rate > 90 bpm
   3. Respiratory rate > 20 rpm or PaCO2 < 4.2 kPa or need of mechanical ventilation.
   4. Leukocytes > 12.0 x109/L or < 4.0 x109/L or >10% bands
4. Circulatory shock defined as sustained systemic hypotension (systolic arterial pressure <90 mmHg or MAP <65 mmHg (<75 mmHg in a hypertensive patient) despite a 1,000 ml IV fluid challenge over 30 min (including IV fluids administered pre-ICU) or the need for vasopressor therapy. Hypertensive patients are patients with a history of confirmed hypertension treated with antihypertensive agents.
5. Mechanical ventilation by endotracheal tube (any form)

Exclusion Criteria:

1. Pregnancy
2. Pre-terminal illness with life expectancy <28 days
3. Duration of circulatory shock >6 hours
4. Severe peripheral arterial vascular occlusion disease (Fontaine level III-IV)
5. Inability for femoral artery canulation
6. No informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transpulmonary thermodilution (TPTD); The intervention group (TPTD guided therapy) follows a fluid resuscitation protocol based on stroke volume variation (SVV) and extravascular lung water (EVLW). Initial trigger for fluid loading when circulatory insufficiency is present will be SVV.	Device: Transpulmonary Thermodilution; Initial trigger for fluid loading when circulatory insufficiency is present will be SVV. If SVV ≤10% in patients on controlled mechanical ventilation with tidal volumes of ≥8 ml/kg, fluid loading will not be performed. If SVV >10% or spontaneous breathing efforts are present, a fluid challenge should be performed. Also if patients are on controlled mechanical ventilation with tidal volumes of ≤7 ml/kg, a fluid challenge should be performed. If fluid responsiveness is present and SVV decreases to ≤10%, further fluid loading should be stopped. If SVV is still >10%, the increase in EVLW will decide whether to continue fluid loading or not; if EVLW is ≥12 mL/kg PBW and EVLW increases upon fluid loading, further fluid loading should be stopped.; Other Names: PiCCO, Pulsion Medical Systems, Germany
Active Comparator: Surviving Sepsis Guidelines (SSG); The standard group (SSG guided therapy) follows a fluid resuscitation protocol based on the Surviving Sepsis Campaign recommendations. Initial trigger for fluid loading when circulatory insufficiency is present will be the CVP (target ≥12 mmHg).	Device: Surviving Sepsis Guidelines (SSG); Initial trigger for fluid loading when circulatory insufficiency is present will be the CVP (target ≥12 mmHg). If circulatory insufficiency is absent, fluid loading will not be initiated or stopped independently of the actual CVP level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ventilator free days (VFDs)	VFDs from enrolment to extubation until day 28	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of circulatory shock (hours)	Duration of circulatory shock, defined as the amount of consecutive hours on vasopressor therapy	72 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality	ICU mortality plus 30-days and 90-days mortality	30 days and 90 days
RIFLE-F score	Evolution of renal function (RIFLE-F score) during the first 5 days after inclusion and use of renal replacement therapy (RRT)	5 days
fluid balance	Fluid balances during the first 5 days after inclusion	5 days
length of stay in the ICU	Length of stay in the ICU	28 days

Collaborators and Investigators

• Sponsor: Medisch Spectrum Twente
• Investigators: Principal Investigator: RJ Trof, MD PhD, Medisch Spectrum Twente, Department of Intensive Care; Study Director: A Beishuizen, MD PhD, Medisch Spectrum Twente, Department of Intensive Care

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: May 19, 2014
• First Submitted That Met QC Criteria: May 29, 2014
• First Posted (Estimate): May 30, 2014

Study Record Updates

• Last Update Posted (Estimate): November 21, 2014
• Last Update Submitted That Met QC Criteria: November 20, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Septic shock; Fluid resuscitation; Critically ill patients; Transpulmonary thermodilution
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Shock, Septic; Shock; Critical Illness
• Other Study ID Numbers: ReSSeS-2014