Clinical trial NCT05950178: Validation of the Apnea Test Performed by High-flow Oxygen Therapy in Patients With Clinical Brain Death
Official title: Validation of Apnea Test Conducted Using High-flow Oxygen Therapy in Patients With Clinical Brain Death
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Brain Death
Keywords: Clinical brain death
Apnea test
High-flow oxygenation
Standard oxygen therapy
High-flow oxygen therapy
Lead sponsor: Centre Hospitalier Régional d'Orléans
Sponsor class: OTHER
First posted: 2023-07-18
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Non-randomized controlled single-center trial.
Primary purpose: DIAGNOSTIC

Brief summary: Brain death is a clinical and paraclinical diagnosis established in a known etiological context. It involves the irreversible destruction of cerebral functions in a beating-heart individual.

In the context of organ and tissue donation from a critically ill patient, the clinical diagnosis of brain death is confirmed through a mandatory apnea test. This test is conducted by disconnecting the patient from the ventilator for a duration of 8 to 10 minutes. The test is considered validated when there is no spontaneous respiratory movement and the presence of hypercapnia. Hypercapnia is defined as a PaCO2 (carbon dioxide partial pressure) greater than 60 mmHg or an increase of more than 20 mmHg compared to the pre-ventilator disconnection capnia. These thresholds are meant to provide a strong stimulus to the respiratory centers, objectively confirming the absence of spontaneous ventilation.

In practice, the apnea test is performed under CPAP (Continuous Positive Airway Pressure) or by administering oxygen at 6-10L/min through the endotracheal tube.

High-flow oxygenation could be a simple alternative for the apnea test during the validation of the clinical diagnosis of brain death while reducing the risk of lung derecruitment and compromising organ viability and/or lung donation.

However, due to the high gas flow used (60 L/min), high-flow oxygenation can lead to a "washout" effect in the anatomical dead space, which may lower the carbon dioxide partial pressure. Consequently, even in a patient in a state of brain death, where spontaneous ventilation is absent by definition, it is not certain that the carbon dioxide partial pressure will increase to the threshold of 60 mmHg or more than 20 mmHg in 10 minutes during an apnea test conducted with high-flow oxygenation.

The purpose of this study is, therefore, to examine the feasibility of clinically diagnosing brain death through an apnea test performed with high-flow oxygenation.

To determine whether the validation criterion which involves observing an arterial capnia \> 60 mmHg or an increase \> 20 mmHg (compared to the capnia at the beginning of the test) after 10 minutes can be achieved during an apnea test conducted under high-flow oxygen therapy in patients with clinically confirmed brain death by standard apnea test (under standard oxygen therapy)

Detailed description: The protocol is based on performing two consecutive apnea tests on a patient in clinical brain death in intensive care unit. The first apnea test will be conducted under standard oxygen therapy and confirms clinical brain death (standard procedure). The second apnea test (for the study) will be conducted under high-flow oxygen therapy. Only patients whose apnea test is initially validated under standard oxygen therapy will have the second apnea test under high-flow oxygen therapy.

After a standardized preoxygenation, the 1st apnea test will be performed under standard oxygen therapy through the endotracheal tube (flow at 8L/min) for 10 minutes. An arterial blood gas sampling will be sampled every 2 minutes during the1st apnea test.

The confirmation of clinical brain death by validating the apnea test under standard oxygen therapy will be done if the following two conditions are met: 1) absence of a spontaneous respiratory movements AND 2) an arterial capnia \> 60 mmHg or an increase \> 20 mmHg (compared to the capnia at the end of preoxygenation).

Then the patient will be reconnected to the ventilator for 15 minutes. A second standardized preoxygenation will be performed before the 2nd apnea test. The second apnea test will be performed under high-flow oxygen therapy through the endotracheal tube (flow at 50L/min, FiO2 100%) for 10 minutes. An arterial blood gas sampling will be sampled every 2 minutes during the1st apnea test.

Then the patient will be reconnected to the ventilator with the same settings before the start of the study.

Eligibility criteria: Inclusion Criteria:

* All patients in critical care with clinical brain death and potential organ and tissue donors for whom an apnea test is indicated.

Exclusion Criteria:

* Minor patients.
* Person under guardianship
* Protected Majors
* Not affiliated to French social security
* Pregnant women.
* Patients with a history of Chronic Obstructive Pulmonary Disease with a GOLD score of III or IV.
* Patients with at least one absolute contraindication to organ donation.
* Patients whose relatives have spontaneously expressed the patient's refusal to donate organs for therapeutic purposes.
* Patients on VA ECMO and, in general, any patient with a contraindication to performing the apnea test (DV, significant hemodynamic instability...).
* Patients whose relatives have refused the patient's participation in the study.

Primary outcomes:
measure: Percentage of patients exceeding the hypercapnia threshold
timeFrame: 48 hours
Secondary outcomes:
measure: Time required after ventilator disconnection to exceed 60mmHg of PaCO2 or for which PaCO2 increases by more than 20mmHg compared to the PaCO2 before disconnection.
timeFrame: 48 hours
measure: Recording of PaO2 and PaCO2 values measured in 2-minute intervals during the standard apnea test and apnea test under high-flow oxygen therapy.
timeFrame: 48 hours
measure: Recording of the PaO2/FiO2 ratio before and after each apnea test.
timeFrame: 48 hours
measure: Recording of systolic blood pressure, measured every minute during the two apnea tests
timeFrame: 48 hours
measure: Recording of diastolic blood pressure, measured every minute during the two apnea tests
timeFrame: 48 hours
measure: Recording of heart rate,measured every minute during the two apnea tests
timeFrame: 48 hours
measure: Recording of pulse oximetry, measured every minute during the two apnea tests
timeFrame: 48 hours
Other outcomes:
Locations:
city: Orléans
country: France
facility: CHR d'ORLEANS
Study officials:
affiliation: CHR d'Orléans
name: Damien BARRIER
role: PRINCIPAL_INVESTIGATOR
References:
citation: Greer DM, Shemie SD, Lewis A, Torrance S, Varelas P, Goldenberg FD, Bernat JL, Souter M, Topcuoglu MA, Alexandrov AW, Baldisseri M, Bleck T, Citerio G, Dawson R, Hoppe A, Jacobe S, Manara A, Nakagawa TA, Pope TM, Silvester W, Thomson D, Al Rahma H, Badenes R, Baker AJ, Cerny V, Chang C, Chang TR, Gnedovskaya E, Han MK, Honeybul S, Jimenez E, Kuroda Y, Liu G, Mallick UK, Marquevich V, Mejia-Mantilla J, Piradov M, Quayyum S, Shrestha GS, Su YY, Timmons SD, Teitelbaum J, Videtta W, Zirpe K, Sung G. Determination of Brain Death/Death by Neurologic Criteria: The World Brain Death Project. JAMA. 2020 Sep 15;324(11):1078-1097. doi: 10.1001/jama.2020.11586.
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citation: Vogelmeier CF, Criner GJ, Martinez FJ, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, Chen R, Decramer M, Fabbri LM, Frith P, Halpin DM, Lopez Varela MV, Nishimura M, Roche N, Rodriguez-Roisin R, Sin DD, Singh D, Stockley R, Vestbo J, Wedzicha JA, Agusti A. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary. Am J Respir Crit Care Med. 2017 Mar 1;195(5):557-582. doi: 10.1164/rccm.201701-0218PP.
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