Respiratory Drive and Inspiratory Effort in COVID-19 Associated ARDS

Mechanical Ventilation Complication Clinical Trial

Official title:

Respiratory Drive and Inspiratory Effort in COVID-19 Associated ARDS: a Multicentric Prospective Observational Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06224010
• Other study ID #: CE 0084148
• Status: Completed
• Start date: November 21, 2020
• Est. completion date: June 20, 2023

Study information

• Verified date: January 2024
• Source: University of Turin, Italy
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Data comparing respiratory drive and effort in critically ill patients with acute respiratory distress syndrome associated to different severity of COVID-19 penumonia (CARDS) and to other risk factors are lacking. Objectives: To assess respiratory drive and effort of CARDS patients at the first transition from controlled to assisted spontaneous breathing. The second aim was the rate of a composite outcome including the need of higher level of sedation

Description:

Multicenter cohort study in four Italian ICU including adults with moderate and severe CARDS (PaO2/FiO2 <100 mmHg) at ICU admission. An historical cohort of patients with ARDS from various etiologies used for comparison. Respiratory drive (P0.1), diaphragm electrical activity (EAdi), inspiratory effort derived from EAdi (∆PmusEAdi) and from deflection in airway pressure occluded (ΔPocc) (PmusΔPocc), dynamic transpulmonary driving pressure (ΔPL,dyn, the difference between peak and end-expiratory transpulmonary pressure) measured under assisted ventilation. The main ventilatory pattern variables: - Airway Occlusion Pressure (P0.1): Measurement of the decrease in airway pressure during an end-expiratory occlusion. - Pmus-EAdi-derived (∆Pmus, EAdi): Measurement of the pressure generated by the respiratory muscles during inspiration derived by electrical activity of the diaphragm measurements. - Transpulmonary pressure EAdi-derived (∆Plung,dyn): difference between peak and end-expiratory transpulmonary pressure . - Occlusive Pressure Difference (∆Pocc): Evaluation of the pressure difference between the initial and final airway opening during inspiration. - Pmus-∆Pocc-derived (∆Pmus, ∆Pocc): Measurement of the pressure generated by the respiratory muscles during inspiration derived by ∆Pocc (∆Pocc*0.75) - Transpulmonary driving pressure ∆Pocc derived (∆Plung, ∆Pocc): calculated as (Peak airway pressure -PEEP) - 2/3 * ∆Pocc - Diaphragmatic Electrical Activity (EAdi): Recording of the electrical activity of the diaphragm. - Peak EAdi (EAdiPEAK): Determination of the highest recorded value of diaphragmatic electrical activity. - Pressure time product of the trans-diaphragmatic pressure per breath and per minute(PTP/min): the integral of Pmusc-EAdi-derived during inspiration per breath. - Inspiratory Delay (ID): Assessment of the time delay between the start of neural inspiration and the onset of mechanical ventilation. - Neuro-ventilatory Efficiency (NVE): Measurement of the efficiency of the neural drive to the respiratory muscles. - Peak Airway Opening Pressure (PawPEAK): Measurement of the peak pressure in the airway during inspiration. - Inspiratory Pressure-Time Product (PmusEAdi/b): Calculation of the work of breathing by integrating the product of diaphragmatic electrical activity and the change in airway pressure during inspiration. - Tidal Volume (VT): Measurement of the volume of air inspired and expired during each breath. - Respiratory Rate: Calculation of the number of breaths per minute delivered by the mechanical ventilator. - Inspiratory and Expiratory Time (Ti,MECH and Te,MECH): Determination of the duration of mechanical inspiration and expiration. - Inspiratory Duty Cycle (TI/TTOT-neur): Calculation of the ratio of inspiratory time to total respiratory cycle time based on neural inspiration.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: June 20, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with a diagnosis of acute respiratory distress syndrome based on the Berlin criteria.
• Patients with ARDS due to confirmed COVID-19 through real-time RT-PCR on nasopharyngeal swabs or lower respiratory tract aspirates.
• Patients who had received invasive mechanical ventilation for more than 72 hours.
• Patients who were candidates for assisted ventilation.

Readiness for assisted ventilation, which was defined by the following criteria:

1. Improvement of the condition leading to acute respiratory failure.

2. Positive end-expiratory pressure lower than 10 cmH2O and inspiratory oxygen fraction lower than 0.5.

3. Richmond agitation sedation scale score between 0 and -3.

4. Ability to trigger the ventilator, i.e., decrease pressure airway opening by more than 3-4 cmH2O during a brief (5-10 seconds) end-expiratory occlusion test.

• Hemodynamic stability without vasopressor or inotropes, except for dobutamine and norepinephrine infusion below certain thresholds (dobutamine <5 gamma/Kg/min and norepinephrine <0.3 gamma/Kg/min).
• Normothermia.

Exclusion Criteria:

• Patients affected by neurological or neuromuscular pathology and/or known phrenic nerve dysfunction.
• Patients with any contraindication to the insertion of a nasogastric tube, such as recent upper gastrointestinal surgery or esophageal varices.
• Patients < 18 years old

Related Conditions & MeSH terms

• Acute Lung Injury
• ARDS, Human
• COVID-19
• Mechanical Ventilation Complication
• Respiratory Aspiration
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency
• Respiratory Tract Infections
• Weaning Failure

Intervention

Other:
• Respiratory drive and effort assessment
The use of a neurally-adjusted ventilatory assist catheter, the measurement of electrical activity of the diaphragm, ?Pocc, P0.1, and other ventilatory parameters to assess respiratory drive and effort in three cohorts of patients

Locations

Country	Name	City	State
Italy	S.C. Anestesia e Rianimazione 1U A.O.U.- Città della Salute e della Scienza, P.O. Molinette Corso Bramante 88-90	Turin

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Bellani G, Bronco A, Arrigoni Marocco S, Pozzi M, Sala V, Eronia N, Villa G, Foti G, Tagliabue G, Eger M, Pesenti A. Measurement of Diaphragmatic Electrical Activity by Surface Electromyography in Intubated Subjects and Its Relationship With Inspiratory Effort. Respir Care. 2018 Nov;63(11):1341-1349. doi: 10.4187/respcare.06176. — View Citation

Bertoni M, Telias I, Urner M, Long M, Del Sorbo L, Fan E, Sinderby C, Beck J, Liu L, Qiu H, Wong J, Slutsky AS, Ferguson ND, Brochard LJ, Goligher EC. A novel non-invasive method to detect excessively high respiratory effort and dynamic transpulmonary driving pressure during mechanical ventilation. Crit Care. 2019 Nov 6;23(1):346. doi: 10.1186/s13054-019-2617-0. — View Citation

Di Mussi R, Spadaro S, Mirabella L, Volta CA, Serio G, Staffieri F, Dambrosio M, Cinnella G, Bruno F, Grasso S. Impact of prolonged assisted ventilation on diaphragmatic efficiency: NAVA versus PSV. Crit Care. 2016 Jan 5;20:1. doi: 10.1186/s13054-015-1178-0. — View Citation

Di Mussi R, Spadaro S, Volta CA, Bartolomeo N, Trerotoli P, Staffieri F, Pisani L, Iannuzziello R, Dalfino L, Murgolo F, Grasso S. Continuous assessment of neuro-ventilatory drive during 12 h of pressure support ventilation in critically ill patients. Crit Care. 2020 Nov 20;24(1):652. doi: 10.1186/s13054-020-03357-9. — View Citation

Vaschetto R, Cammarota G, Colombo D, Longhini F, Grossi F, Giovanniello A, Della Corte F, Navalesi P. Effects of propofol on patient-ventilator synchrony and interaction during pressure support ventilation and neurally adjusted ventilatory assist. Crit Care Med. 2014 Jan;42(1):74-82. doi: 10.1097/CCM.0b013e31829e53dc. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Respiratory drive	Evaluation of respiratory drive using P0.1	90 breaths
Primary	Neuroventilatory coupling	Evaluation of respiratory drive using EAdi PEAK	90 breaths
Primary	Respiratory effort	Evaluation of respiratory drive using ?Pmus-EAdi derived, ?Pmus-?Pocc derived, PTP/min	90 breaths
Primary	Transpulmonary driving pressure	Evaluation of respiratory drive using ?Plung, dynamic	90 breaths
Secondary	Composite outcome	Transition from light to deep sedation (Richmond agitation sedation scale from 0/-3 to -4/-5) or from assisted to controlled ventilation within 48 hours of spontaneous assisted breathing	within forty eight hour from assisted spontaneous breathing
Secondary	Intensive care unit mortality	Mortality	Intensive care unit stay
Secondary	Mortality	Mortality	60 days after measurement