Assisted or Controlled Ventilation in Ards (Ascovent)

Not Applicable

• Conditions: ARDS; Ventilator-Induced Lung Injury; Mechanical Ventilation Complication; Inflammatory Response
• Interventions: Diagnostic Test: assessment of inflammatory response during PSV

• Registration Number: NCT03245684
• Lead Sponsor: University of Roma La Sapienza

Brief Summary

The present pilot randomized controlled clinical trial will test the hypothesis that in patients with ARDS, fixing ventilator settings to the conventional protective ventilatory strategy (VT 6 ml/kg ideal body weight and Pplat ≤ 30 cmH2O, PEEP according the PEEP/FiO2 table), control modes of mechanical ventilation will be associated to a concentration of pulmonary and systemic inflammatory mediators lower than the concentration of inflammatory mediators observed during assisted modes of mechanical ventilation.

Detailed Description

All patients will be treated according to the sedation protocols and standards of care. Sedation will be guaranteed by continuous infusion of Propofol 2-4 ml / Kg / h, Remifentanil 0.05-0.1 mcg / Kg / min to obtain a RASS scale level of -5 of the RASS. Mio-resolution eventually obtained by a loading dose of 15 mg e.v. followed by a continuous infusion of 37.5 mg / h of besylated Cisatracury, will be reserved for patients with P/F \<150.

During a 48 hrs pre-randomization period, control mechanical ventilation will be set with a Tidal Volume (VT) of 6 ml / kg (for ideal weight) and a Pplat limited to 30 cm H2O; inspiratory flow 50-70 l / min with end-of-breath pause of 0.2-0.5 sec, ratio I: E from 1: 1 to 1: 3, respiratory frequency of 20-35 steps to maintain 7.3 \<pH \<7.5. If the pH is \<7.30 the respiratory frequency will increase up to 35 / min; If the pH is\> 7.5, the respiratory rate will be progressively reduced to the target pH range. FiO2 and The PEEP will be set according to the ARDSnet table (33)

After 48 hours, the patient will be randomized through one of the following two groups:

Control Mechanical ventilation (CMV): patient's spontaneous activity will be shut done by sedation and/or respiratory muscles paralysis. Volume (during volume control) or pressure (during pressure control), PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol (33).

Pressure Support Ventilation (PSV): patient's spontaneous activity will maintained and sedation will be maintained at a level of Richmond Assessment Sedation Scale (RASS) between -2 and -3. The level of pressure support (including PEEP) will be limited to ≤ 30 cmH2O; the pressure support level will ensure a tidal volume of 6 ml / Kg ideal body weight. PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol (33)

Study Timeline

• Status Verified: 2017-08
• Study First Submitted: 2017-08-04
• Study First Submitted QC: 2017-08-09
• Last Update Submitted: 2017-08-09
• Study First Posted: 2017-08-10
• Last Update Posted: 2017-08-10
• Study Start: 2017-09-01
• Primary Completion: 2019-09-01
• Study Completion: 2019-09-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Patients > 18 years of age who:

  1. Are intubated less than 24 hours since meeting the Berlin definition criteria for ARDS.
  2. Have a commitment to full support;
  3. Have no exclusion criteria

Exclusion Criteria

1. Intubation and mechanical ventilation (any form) for > 24 hours;
2. Acute brain injury with Glasgow coma scale (GCS) <7;
3. Body mass index > 40;
4. Age < 18 years;
5. Neuromuscular disease that impairs ability to ventilate without assistance;
6. Severe chronic respiratory disease;
7. Burns > 40% total body surface area;
8. Malignancy or other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%;
9. Allogeneic bone marrow transplant within the last 5 years;
10. Chronic respiratory condition making patient respirator dependent;
11. Patient, surrogate, or physician not committed to full support;
12. Acute myocardial infarction or acute coronary syndrome within 30 days;
13. Moribund patient: not expected to survive 24 hours;
14. No consent/inability to obtain consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pressure Support Ventilation	assessment of inflammatory response during PSV	after 48h of controlled ventilation the patient randomised in this arm will desedated and switched on Pressure Support Ventilation (PSV): patient's spontaneous activity will maintained and sedation will be maintained at a level of Richmond Assessment Sedation Scale (RASS) between -2 and -3. The level of pressure support (including PEEP) will be limited to ≤ 30 cmH2O; the pressure support level will ensure a tidal volume of 6 ml / Kg ideal body weight. PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol. assessment of inflammatory response during PSV
Controlled Mechanical Ventilation	assessment of inflammatory response during PSV	patient's spontaneous activity will be shut done by sedation and/or respiratory muscles paralysis. Volume (during volume control) or pressure (during pressure control), PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol

Primary Outcome Measures

Name	Time	Method
Pulmonary concentration of inflammation mediators (broncho-alveolar lavage: BAL)	96 hours	Dosage of inflammatory mediators (tumor necrosis factor-α soluble receptors, interleukin-6, interleukin-8 and interleukin-1β and interleukin-1 receptor antagonist)

Secondary Outcome Measures

Name	Time	Method
Systemic concentration of inflammation mediators (plasma)	96 hours	The concentrations of the same mediators (tumor necrosis factor-α soluble receptors, interleukin-6, interleukin-8 and interleukin-1β and interleukin-1 receptor antagonist) in a sample of 10 ml of blood taken from a central venous line will be analyzed