P0.1 and Extubation Failure in Critically Ill Patients

Mechanical Ventilation Clinical Trial

Official title:

Airway Occlusion Pressure (P0.1) to Predict Extubation Failure in Critically Ill Patients: A Prospective Cohort Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05802745
• Other study ID #: A-2023-014
• Status: Not yet recruiting
• Start date: May 2023
• Est. completion date: August 2024

Study information

• Verified date: March 2023
• Source: Cleveland Clinic Abu Dhabi
• Contact: Jihad Mallat, MD, PhD
• Phone: +97125019000
• Email: mallatj[@]clevelandclinicabudhabi.ae
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Weaning and extubation are essential steps for the management of critically ill patients when mechanical ventilation (MV) is no longer required. Extubation failure (EF) occurs in approximately 10-30% (1,2) of all patients meeting the readiness criteria and have tolerated a spontaneous breathing trial (SBT). EF is associated with prolonged MV, as well as increased morbidity and mortality (2). Therefore, the early identification of critically ill patients who are likely to experience EF is vital for improved outcomes.

EF can result from different factors (respiratory, metabolic, neuromuscular), particularly cardiac factor, and can be caused by the inability of the respiratory muscle pump to tolerate increases in the cardiac and respiratory load (1,3).

Respiratory drive represents the intensity of the neural stimulus to breathe. In mechanically ventilated patients, it can be abnormally low (i.e., suppressed or insufficient) or abnormally high (i.e., excessive), and thus result in excessively low or high inspiratory effort, leading to potential injury to the respiratory muscles (i.e., myotrauma) (4,5) or to the lungs. A high incidence of abnormal drive (low or high) may explain the high incidence of diaphragm dysfunction at time of separation from mechanical ventilation (6).

Airway occlusion pressure (P0.1) is the drop in airway pressure (Paw) 100 milliseconds after the onset of inspiration during an end-expiratory occlusion of the airway (7). P0.1 measurement is not perceived by the patient and does not influence respiratory pattern. It is, in theory, a reliable measure of respiratory drive because the brevity of the occlusion explains that it is not affected by patient's response to the occlusion and it is independent of respiratory mechanics (8). P0.1 has also been correlated with inspiratory effort (9, 10) and it has been shown that in patients under assisted mechanical ventilation P0.1 might be able to detect potentially excessive inspiratory effort (11).

P0.1 is a non-invasive measure and clinically available at bedside since currently nearly all modern ventilators provide a means of measuring it. Originally, a high P0.1 during a spontaneous breathing trial was associated with failure, suggesting that a high respiratory drive could predict weaning failure. However, only a few and old clinical studies investigated the association between P0.1 and extubation failure (EF) and were not conclusive (12,13). We hypothesized that patients with EF would have increased P0.1 values during spontaneous breathing trial (SBT). Therefore, the aims of our study will be to (1) to evaluate the ability of changes in P0.1 (Delta-P0.1) during SBT to predict EF and (2) to assess if Delta-P0.1 is an independent predictor of EF.

Description:

Weaning protocol SBTs will be performed in semirecumbent patients on Pressure Support Ventilation (PSV) mode with inspiratory pressure of 5 cmH2O and positive-end-expiratory pressure (PEEP) of 5 cmH2O as per ICU protocol. Inspiratory oxygen fraction (FiO2) will be adjusted for the achievement of an arterial oxygen saturation value > 90%, as measured by pulse oximetry. The SBT duration will be 30 minutes as per ICU protocol. The criteria that will be used for poor SBT tolerance are: (1) diaphoresis; (2) use of accessory respiratory muscles; (3) RR > 35/min; (4) oxygen saturation by pulse oximetry < 90% with FiO2 ≥ 50%; (5) HR > 140/min or greater than a 20% increase from baseline; (6) Systolic blood pressure >180 mmHg or <90 mmHg; (7) development of cardiac arrhythmias; and/or low level of consciousness.

The decision to stop SBT will be made by the physicians. Patients who will fail SBT will be shifted to their previous ventilator mode and not be enrolled in the study.

Patients who will complete the SBT will be extubated and followed-up for 72 hours. The medical team (physician, nurse, and respiratory therapist) involved in the extubation decision will be blinded to the P0.1 results. EF will be diagnosed if the patient is extubated but required reintubation within the following 72 hours. Criteria for acute respiratory failure after extubation are the development of at least one of the following: (a) respiratory acidosis with pH < 7.32 and arterial CO2 pressure (PaCO2) > 45 mmHg; (b) arterial oxygen saturation < 90% with FiO2 > 0.5; (c) RR > 35/min; (d) clinical signs of respiratory fatigue.

The management of post-extubation respiratory failure will not be protocolized and will be left to the physician's discretion.

Ventilatory, including P0.1 and hemodynamic parameters, including EtCO2 will be recorded as the average of at least three measurements immediately before SBT, during SBT, and at 30 minutes after SBT initiation. Arterial and central venous blood gas (if central line present) will be measured immediately before SBT and at 30 minutes after SBT initiation.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: August 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All patients aged 18 years or older who received mechanical ventilation for at least 48 hours and satisfied the weaning criteria will be eligible for enrollment.

The readiness-to-wean criteria that will be employed are: (1) the resolution or improvement of the underlying cause of respiratory failure for which the patient was intubated; (2) hemodynamic stability, defined as heart rate (HR) < 140/min and systolic blood pressure between 90 and 160 mmHg with no or minimal doses of vasopressors; (3) stable respiratory status, defined as oxygen saturation > 90% with fraction of inspired oxygen (FiO2) = 0.5 and positive end expiratory-pressure (PEEP) =8 cmH2O, respiratory rate (RR) = 35/min, spontaneous tidal volume (Vt) > 5 mL/kg, and no significant respiratory acidosis; (4) adequate mental status, and (5) adequate cough.

Exclusion Criteria:

• Presence of tracheostomy

• Do-not-reintubate orders

• pregnancy

• Absence of informed consent

• Spontaneous breathing trial failure.

Related Conditions & MeSH terms

• Critical Illness
• Critically Ill
• Mechanical Ventilation
• Weaning Failure

Intervention

Other:
• Reintubation
Patients requiring re-intubation for acute respiratory failure.

Locations

Country	Name	City	State
France	Amiens University Hospital	Amiens
France	Centre Hospitalier d'Arras	Arras
France	Dijon University Hospital	Dijon

Sponsors (1)

Lead Sponsor	Collaborator
Cleveland Clinic Abu Dhabi

Country where clinical trial is conducted

France, 

References & Publications (13)

Alberti A, Gallo F, Fongaro A, Valenti S, Rossi A. P0.1 is a useful parameter in setting the level of pressure support ventilation. Intensive Care Med. 1995 Jul;21(7):547-53. doi: 10.1007/BF01700158. — View Citation

Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, Pearl R, Silverman H, Stanchina M, Vieillard-Baron A, Welte T. Weaning from mechanical ventilation. Eur Respir J. 2007 May;29(5):1033-56. doi: 10.1183/09031936.00010206. — View Citation

Dres M, Dube BP, Mayaux J, Delemazure J, Reuter D, Brochard L, Similowski T, Demoule A. Coexistence and Impact of Limb Muscle and Diaphragm Weakness at Time of Liberation from Mechanical Ventilation in Medical Intensive Care Unit Patients. Am J Respir Cri — View Citation

Fernandez R, Raurich JM, Mut T, Blanco J, Santos A, Villagra A. Extubation failure: diagnostic value of occlusion pressure (P0.1) and P0.1-derived parameters. Intensive Care Med. 2004 Feb;30(2):234-240. doi: 10.1007/s00134-003-2070-y. Epub 2003 Nov 8. — View Citation

Goligher EC, Brochard LJ, Reid WD, Fan E, Saarela O, Slutsky AS, Kavanagh BP, Rubenfeld GD, Ferguson ND. Diaphragmatic myotrauma: a mediator of prolonged ventilation and poor patient outcomes in acute respiratory failure. Lancet Respir Med. 2019 Jan;7(1): — View Citation

Goligher EC, Dres M, Fan E, Rubenfeld GD, Scales DC, Herridge MS, Vorona S, Sklar MC, Rittayamai N, Lanys A, Murray A, Brace D, Urrea C, Reid WD, Tomlinson G, Slutsky AS, Kavanagh BP, Brochard LJ, Ferguson ND. Mechanical Ventilation-induced Diaphragm Atro — View Citation

MacIntyre N. Discontinuing mechanical ventilatory support. Chest. 2007 Sep;132(3):1049-56. doi: 10.1378/chest.06-2862. — View Citation

Mancebo J, Albaladejo P, Touchard D, Bak E, Subirana M, Lemaire F, Harf A, Brochard L. Airway occlusion pressure to titrate positive end-expiratory pressure in patients with dynamic hyperinflation. Anesthesiology. 2000 Jul;93(1):81-90. doi: 10.1097/000005 — View Citation

Rittayamai N, Beloncle F, Goligher EC, Chen L, Mancebo J, Richard JM, Brochard L. Effect of inspiratory synchronization during pressure-controlled ventilation on lung distension and inspiratory effort. Ann Intensive Care. 2017 Oct 6;7(1):100. doi: 10.1186 — View Citation

Sassoon CS, Te TT, Mahutte CK, Light RW. Airway occlusion pressure. An important indicator for successful weaning in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1987 Jan;135(1):107-13. doi: 10.1164/arrd.1987.135.1.107. — View Citation

Telias I, Damiani F, Brochard L. The airway occlusion pressure (P0.1) to monitor respiratory drive during mechanical ventilation: increasing awareness of a not-so-new problem. Intensive Care Med. 2018 Sep;44(9):1532-1535. doi: 10.1007/s00134-018-5045-8. E — View Citation

Thille AW, Richard JC, Brochard L. The decision to extubate in the intensive care unit. Am J Respir Crit Care Med. 2013 Jun 15;187(12):1294-302. doi: 10.1164/rccm.201208-1523CI. — View Citation

Whitelaw WA, Derenne JP, Milic-Emili J. Occlusion pressure as a measure of respiratory center output in conscious man. Respir Physiol. 1975 Mar;23(2):181-99. doi: 10.1016/0034-5687(75)90059-6. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Extubation failure	to evaluate the ability of changes in P01 (Delta-P0.1) during SBT to predict extubation failure after 72 hours of extubation.	Within 72 hours after extubation.
Secondary	Delta-P01 as independent factor of extubation failure	To assess if Delta- P0.1 during SBT is an independent predictor of extubation failure	Within 72 hours after extubation.
Secondary	Extubation failure	Association between Delta-P0.1 and extubation failure after 7 days of extubation	7 days after extubation