RApid Fluid Volume EXpansion in Patients in Shock After the Initial Phase of Resuscitation.

Not Applicable

Recruiting

• Conditions: Shock; Hypovolemia
• Interventions: Drug: fluid bolus; Device: Vascular pressure transducers (Edwards Life Science, USA); Device: PiCCO system (Pulsion, Germany); Other: Passive Leg Raising test

• Registration Number: NCT02645851
• Lead Sponsor: Centre Hospitalier Régional d'Orléans

Brief Summary

Rapid volume expansion using repeated intravenous fluid boluses is a very common intervention performed in the intensive care unit (ICU) in the early days of resuscitation of patients with shock. Once passed the initial phase of resuscitation, the fluid boluses administered fail to effectively increase the patients' cardiac output in about 50% of cases. Pulse pressure changes or stroke volume changes induced by a Passive Leg Raising (PLR) test have acceptable/good ability to predict fluid responsiveness (in terms of cardiac output change) and may be systematically used in patients with persistent shock with the aim of limiting the total amount of fluid administered to patients by avoiding undue fluid boluses. One may suppose that such a volume expansion management policy could impact morbidity and mortality of shocked patients. Among the predictive indices available in clinical practice, the PLR test has the advantages of being usable regardless of the patients' respiratory status and cardiac rhythm. Changes in left ventricular stroke volume during the PLR test perform better that changes in pulse pressure to predict fluid responsiveness. However, in counterpart, pulse pressure changes during PLR can be assessed without the need of other hemodynamic exploration such central venous pressure measurement or cardiac output monitoring. The investigators hypothesized that strategies using either stroke volume changes or pulse pressure changes induced by the PLR test to decide wether a fluid bolus clinically deemed indicated should or should not be administered, may limit the amount of fluid received by the patients during the first 5 days of shock, improve their oxygenation index, and shorten the time passed under mechanical ventilation, as compared to a "liberal" strategy (usual care) that does not use predictive indices of fluid responsiveness.

Detailed Description

A pilot, single-center, randomized, open-label, 3 parallel groups clinical trial with 1:1:1 assignment of interventions, comparing outcomes between patients with persistent shock assigned to either 1) the "Volume expansion guided by PLR-induced changes in Stroke Volume" strategy, or 2) the "Volume expansion guided by PLR-induced changes in Pulse Pressure" strategy, or 3) to usual care (i.e., without the use of any predictive index of fluid responsiveness). Patients in shock (either of septic, cardiac or other origin) will be included once passed the first hours of resuscitation. The time window for inclusion will be from 6 to 24 hours after the beginning of resuscitation, a delay necessary to ensure that initial hypovolemia has been fully compensated.

The randomization will be stratified according to the presumed origin of shock (cardiac, septic, or other) and according to the PaO2/FiO2 ratio (\<200 or ≥ 200 mmHg).

The randomly assigned intervention will be used during the first 5 days of shock (120 hours).

Study Timeline

• Study First Submitted: 2015-12-27
• Study First Submitted QC: 2016-01-04
• Study First Posted: 2016-01-05
• Study Start: 2016-01-16
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-08
• Last Update Posted: 2024-01-10
• Primary Completion: 2025-12-06
• Study Completion: 2025-12-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 141

Inclusion Criteria

• Patients will be eligible for inclusion if 6 hours after H0 (and before H24) all the following conditions are present:
• Informed consent obtained (or emergency inclusion possible when legal representatives and patient's family are not present, as allowed by the Ethic Committee and by the French Law)
• Persistence of arterial hypotension (as defined above) or continuous iv infusion of norepinephrine
• Patient under invasive mechanical ventilation
• At least one of the following conditions is present
• Alteration of consciousness
• Mottling skin
• Cyanosis of the extremities despite SaO2>90%
• Oliguria defined as urine output below 0.5ml/kg of actual body weight over at least 1 hour
• Arterial lactate > 2 mmol/L
• ScvO2 < 70%
• Central venous (internal jugular or subclavian) or femoral venous catheter in place
• Arterial catheter in place

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Exclusion Criteria

1. Shock began more than 24 hours ago

2. Age < 18 yrs.

3. Pregnancy

4. Uncontrolled haemorrhage

5. Intra-aortic balloon counterpulsation in place

6. Patient under veno-arterial extracorporeal membrane oxygenation (V-A ECMO)

7. Cardiogenic pulmonary oedema during the past 24 hours

8. Patient equipped with a cardiac output monitoring device

9. Brain death

10. Moribund patient

11. Traction of a lower limb

12. Amputated lower limb above the ankle level

13. Documented intra-abdominal hypertension

14. Cardiac arrest motivating ICU admission or cardiac arrest since admission 14. Patient without social security number 15. Consent refusal

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
"PLR-induced SV changes" based strategy	fluid bolus	During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the final decision to administer or not the fluid bolus will be determined by the percentage changes in Stroke Volume (SV) observed during a 1-min Passive Leg Raising test: Administration of the fluid bolus if SV changes ≥10%, or no administration otherwise. Measurement of beat-to-beat stroke volume by intraarterial pulse contour analysis using the PiCCO system (Pulsion, Germany) will be used to assess stroke volume changes. Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
"PLR-induced PP changes" based strategy	Vascular pressure transducers (Edwards Life Science, USA)	During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the final decision to administer or not the fluid bolus will be determined by the percentage changes in Pulse Pressure (PP) observed during a 1-min Passive Leg Raising test: Administration of the fluid bolus if PP changes ≥10%, or no administration otherwise. We will perform measurement of intraarterial blood pressure using vascular pressure transducers (Edwards Life Science, USA). Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
Usual Care	fluid bolus	During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the fluid bolus will be administered without measurement of any predictive index of fluid responsiveness. Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
"PLR-induced SV changes" based strategy	Passive Leg Raising test	During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the final decision to administer or not the fluid bolus will be determined by the percentage changes in Stroke Volume (SV) observed during a 1-min Passive Leg Raising test: Administration of the fluid bolus if SV changes ≥10%, or no administration otherwise. Measurement of beat-to-beat stroke volume by intraarterial pulse contour analysis using the PiCCO system (Pulsion, Germany) will be used to assess stroke volume changes. Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
"PLR-induced SV changes" based strategy	PiCCO system (Pulsion, Germany)	During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the final decision to administer or not the fluid bolus will be determined by the percentage changes in Stroke Volume (SV) observed during a 1-min Passive Leg Raising test: Administration of the fluid bolus if SV changes ≥10%, or no administration otherwise. Measurement of beat-to-beat stroke volume by intraarterial pulse contour analysis using the PiCCO system (Pulsion, Germany) will be used to assess stroke volume changes. Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
"PLR-induced PP changes" based strategy	fluid bolus	During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the final decision to administer or not the fluid bolus will be determined by the percentage changes in Pulse Pressure (PP) observed during a 1-min Passive Leg Raising test: Administration of the fluid bolus if PP changes ≥10%, or no administration otherwise. We will perform measurement of intraarterial blood pressure using vascular pressure transducers (Edwards Life Science, USA). Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
Usual Care	Vascular pressure transducers (Edwards Life Science, USA)	During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the fluid bolus will be administered without measurement of any predictive index of fluid responsiveness. Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
"PLR-induced SV changes" based strategy	Vascular pressure transducers (Edwards Life Science, USA)	During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the final decision to administer or not the fluid bolus will be determined by the percentage changes in Stroke Volume (SV) observed during a 1-min Passive Leg Raising test: Administration of the fluid bolus if SV changes ≥10%, or no administration otherwise. Measurement of beat-to-beat stroke volume by intraarterial pulse contour analysis using the PiCCO system (Pulsion, Germany) will be used to assess stroke volume changes. Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.
"PLR-induced PP changes" based strategy	Passive Leg Raising test	During the intervention period (i.e., within 120 hrs following inclusion), every time a fluid bolus is deemed necessary to improve the patient's cardiac output, the final decision to administer or not the fluid bolus will be determined by the percentage changes in Pulse Pressure (PP) observed during a 1-min Passive Leg Raising test: Administration of the fluid bolus if PP changes ≥10%, or no administration otherwise. We will perform measurement of intraarterial blood pressure using vascular pressure transducers (Edwards Life Science, USA). Per protocol inclusion criteria, patients will be carrying central venous and artery catheters.

Primary Outcome Measures

Name	Time	Method
PaO2/FiO2 ratio changes	from inclusion to the 24th hour after inclusion

Secondary Outcome Measures

Name	Time	Method
Fluid balance	from inclusion to the 7th day
Immediate respiratory tolerance of fluid bolus (Yes or No)	at each fluid bolus administered during the intervention period (from inclusion to 120 hours later)	Definition of immediate respiratory tolerance: SpO2 drops by less than 3% AND respiratory rate increase by less than 20% between before and after fluid bolus AND no occurrence of clinical pulmonary edema.
ventilator free days	ventilator free days between inclusion and the 28th day	Every complication related to intravenous or arterial catheters inserted during the intensive care unit stay will be recorded
mortality rate	at 28 days
Catheter-related complications	from inclusion to the date of intensive care unit discharge, an average of 10 days	Every complication related to intravenous or arterial catheters inserted during the intensive care unit stay will be recorded

Trial Locations

Locations (1)

Centre Hospitalier Régional d'Orléans, France; 🇫🇷 Orléans, France