Sigh35 and End-expiratory Occlusion Test (EEOT) for Assessing flUid Responsiveness in Critically Ill Patients Undergoing Pressure Support Ventilation (SETUP)

The application of a brief SIGH of 4 seconds at 35 cmH20 has shown to reliably predict fluid responsiveness in critically ill patients undergoing pressure support ventilation.

The end-expiratory occlusion test (EEOT) has been also used in the same type of patients, with the same purpose, but in a limited amount of studies.

The aim of this study is to compare the reliability of the the two test in assessing fluid responsiveness.

Study Overview

• Status: Recruiting
• Conditions: Critically Ill Patients; Hemodynamic Instability; Mechanical Ventilation Pressure High
• Intervention / Treatment: Diagnostic test: SIGH; Diagnostic test: EEOT; Diagnostic test: Fluid challenge

Detailed Description

Assessing preload dependence in critically ill patients is a challenge for the Intensive Care Unit (ICU) physicians. During controlled mechanical ventilation, dynamic indexes can be applied in non-arrhythmic patients with sufficiently high tidal volume (VT), i.e., >8 ml/kg and non-severely impaired lung compliance. The interplay between mechanical ventilation and hemodynamic is more complex in patients with a spontaneous breathing activity, whose respiratory efforts affect intrathoracic pressure and venous return to the right ventricle (RV).

To overcome these limitations, functional hemodynamic assessment, consisting in maneuvers determining a sudden change in cardiac preload, such as Passive leg raising (PLR) or end-expiratory occlusion test (EEO), represents a valuable means for assessment of fluid responsiveness.

Both PLR and EEO have been successfully utilized for assessing fluid responsiveness, regardless of ventilatory assistance and mode of ventilation. Unfortunately, however, some drawbacks limit the extensive use of these maneuvers in clinical practice. One the one hand, PLR cannot be applied in some clinical situations, such as traumatisms of the hip, legs or lumbar spine, deep venous thrombosis, intracranial or abdominal hypertension. Indeed, a recent large observational study showed PLR to be the most common form of assessment of fluid responsiveness, being used, nonetheless, in only 10.7% of the patients necessitating the assessment of fluid responsiveness. On the other hand, rates of EEO failure as high as 22.5 % have been reported, consequent to visible patient's effort against the occluded airway.

It has been recently successfully tested a new approach for assessing fluid responsiveness in patients undergoing partial ventilatory assistance. It has been proposed that the changes from baseline of systolic arterial pressure (SAP), pulse pressure (PP) and stroke volume index (SVI) in relationship to the airway pressure (Paw) generated during a "sigh" maneuver can predict fluid responsiveness in ICU patients undergoing pressure support ventilation (PSV) In the first "proof of concept" study (performed in 40 hemodynamically unstable ICU patients) three sighs has been tested, in a computer-generated random order, at either 15 (SIGH15), 25 (SIGH25) and 35 (SIGH35) cmH2O of total inspiratory Paw (PEEP + PSV). The results showed that only the variation of the pulse pressure recorded after SIGH35 application successfully predicted fluid responsiveness. [AUC of PP after SIGH35 = 0.91 (0.82 - 0.99); sensitivity 75% (47.6%-92.7%) and specificity 91.6 (73.0%- 98.9%); best threshold value of the ROC curve was -35% from baseline].

Hemodynamic Measurements. All patients will be equipped with a continuous hemodynamic monitoring of arterial waveform.

The primary end point will be assessed by means comparison of the areas (AUC) under receiver operating characteristic (ROC) curves: considering the data reported in the literature, we assumed that the AUC of the SIGH35 should be of at least 0.85 to be clinically relevant. This value was compared to the null hypothesis (AUC = 0.65; ratio of samples sizes in negative and positive groups of 1:1): the calculated sample size is 50 patients. Considering the possibility of the occurrence extrasystoles during the beat-to-beat evaluation of the EEOT and the SIGH, the sample size is inflated by the 20% to account for the rate of loss of patients during the post-hoc data analysis. The final sample size is 60 patients.

Fluid responsiveness is defined as a CI increase ≥ 10% after FC infusion.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Recruiting
      • Humanitas Research Hospital
      • Contact: Antonio Messina, MD; Phone Number: +390282241; Email: antonio.messina@humanitas.it
      • Contact: Antonio Messina, MD; Phone Number: +3902822414131; Email: mess81rc@gmail.com
    • Rozzano, Milano, Italy
      • Recruiting
      • Humanitas Research Hospital
      • Contact: Antonio Messina, PhD; Phone Number: +390282241; Email: antonio.messina@humanitas.it

Participation Criteria

Eligibility Criteria

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

Description

• Adult (>18 yo) ICU patients undergoing PSV ventilation
• Inspiratory support level (PS) between 8 and 15 cmH2O and positive end-expiratory pressure (PEEP) between 5 and 12 cmH2O,

• Presence of acute circulatory failure defined as:

  • Systolic blood pressure (SBP) ≤90 mmHg or mean arterial pressure (MAP) ≤70 mmHg or requiring vasopressors to maintain SBP >90 mmHg or MAP >70 mmHg or decline of SBP > 50 mm Hg in known hypertensive patients, along with one or more of the following:
  • urinary flow ≤0.5 mL/kg/min for ≥2 hours
  • heart rate ≥100 beats per minute
  • presence of skin mottling and 4) blood lactate concentration ≥4 mmol/L.

Exclusion criteria

• left ventricular ejection fraction <30% or severe valvular dysfunction
• atrial fibrillation
• severe acute respiratory distress syndrome (ARDS)
• abdominal compartment syndrome
• air leakage through chest drains
• artifacts in arterial waveform
• pathological respiratory patterns due to neurological diseases
• signs of fatigue or respiratory distress

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention EEO_SIGH; Single arm intervention. All the patients will receive the two tests (SIGH and EEOT) in 1:1 random sequence order

Diagnostic test: SIGH; To add the Sigh35 to PSV, the ventilator is set in pressure controlled synchronized intermittent mandatory ventilation plus PSV [SIMV (PC) + PS mode], with SIMV rate set a 1/min and inspiratory time of 4 seconds. SIMV (PC) = 35 cmH20 of total inspiratory support (PEEP + PS).; Diagnostic test: EEOT; • The EEOT is performed by interrupting the mechanical ventilation for 15 seconds, by using and end-expiratory hold on the ventilator. The ventilator trigger is set at 2 L/min.; Diagnostic test: Fluid challenge; Bolus of fluids of 4 ml/kg given within 10 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulse pressure prediction of fluid responsiveness	Pulse pressure changes after SIGH35 application	Evaluated before and after SIGH35 (within 1 minute from SIGH35 application)
Stroke volume prediction of fluid responsiveness	Stroke Volume changes after SIGH35 application	Evaluated before and after SIGH35 (within 1 minute from SIGH35 application)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulse pressure prediction of fluid responsiveness	Pulse pressure changes after EEOT application	Evaluated before and after EEOT (within 1 minute from EEOT application)
Stroke volume prediction of fluid responsiveness	Stroke Volume changes after EEOT application	Evaluated before and after EEOT (within 1 minute from EEOT application)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of failure of SIGH test	Presence of cough	During the test execution
Rate of failure of EEOT test	Trigger of the ventilator	During the test execution

Collaborators and Investigators

• Sponsor: Humanitas Clinical and Research Center

Publications and helpful links

General Publications

• Monnet X, Osman D, Ridel C, Lamia B, Richard C, Teboul JL. Predicting volume responsiveness by using the end-expiratory occlusion in mechanically ventilated intensive care unit patients. Crit Care Med. 2009 Mar;37(3):951-6. doi: 10.1097/CCM.0b013e3181968fe1.
• Patroniti N, Foti G, Cortinovis B, Maggioni E, Bigatello LM, Cereda M, Pesenti A. Sigh improves gas exchange and lung volume in patients with acute respiratory distress syndrome undergoing pressure support ventilation. Anesthesiology. 2002 Apr;96(4):788-94. doi: 10.1097/00000542-200204000-00004.
• Messina A, Colombo D, Barra FL, Cammarota G, De Mattei G, Longhini F, Romagnoli S, DellaCorte F, De Backer D, Cecconi M, Navalesi P. Sigh maneuver to enhance assessment of fluid responsiveness during pressure support ventilation. Crit Care. 2019 Jan 28;23(1):31. doi: 10.1186/s13054-018-2294-4.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 11, 2021
• First Posted (Actual): June 14, 2021

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness
• Other Study ID Numbers: SIGH_EEOT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.

Drug and device information, study documents

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