Comparison of Two Extubation Techniques in Critically Ill Adult Patients (ExtubAR Trial): Randomized Clinical Trial
Phase: NA
Conditions: Weaning Failure, Mechanical Ventilation Complication
Sponsor: Hospital Donación Francisco Santojanni

 
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Title: 
Comparison of Two Extubation Techniques in Critically Ill Adult Patients (ExtubAR trial): 
Randomized Clinical Trial 
 
Evaluated and approved by the Research Ethics Committee (#12-2018-05, approved on February 28, 
2019) and registered on ClinicalTrials.gov (NCT03918811, April 18, 2019).   
 
Authors:  
Mauro Andreu a,b; Matías Bertozzi a,b,h ; Marco Bezzi b; Silvina Borello b ; Daniela Castro b ; Victoria Di 
Giorgio b,h ; Mariana Aguirre b ; Karina Miralles c ; Diego Noval c ; Sebastián Fredes c,g ; Eliana Wilhelm d 
; Mauricio Zakimchuk d ; Julián Buffarini Cignoli d ; Mariana Bernardini e ; Leticia Rey e ; Valeria Pieroni e 
; Pablo D´Annunzio f ; Gustavo Plotnikow f ; Romina Prato f ; Matías Lompizano g ; María Guaymas g ; 
Matías Accoce h ; Javier Dorado h,k ; Gimena Cardoso h,b ; Patricia Torres i,b ; Vanesa Pavlotsky j,b ; 
Emiliano Navarro k,h ; Eliana Markman l ; Paula Di Nardo l ; Ivonne Kunzi Steyer l ; Carolina Thomsen m,b  
; Cecilia Palacios m ; Mariela Davies m ; Mercedes Ruffo n ; Victoria Leon n ; Fernando Tapia n .  
 
a) Universidad Nacional de la Matanza, Florencio Varela 1903, B1754, San Justo, Province of Buenos Aires, Argentina. 
b) Hospital Donación Francisco Santojanni, Pilar 950, C1408, Autonomous City of Buenos Aires, Argentina. 
c) Sanatorio Mitre, Bartolomé Mitre 2553, C1039, Autonomous City of Buenos Aires, Argentina. 
d) Sanatorio Colegiales, Conde 851, C1426, Autonomous City of Buenos Aires, Argentina. 
e) Hospital El Cruce, Av. Calchaquí 5401, B1888, Florencio Varela, Province of Buenos Aires, Argentina. 
f) 
Sanatorio Anchorena Recoleta, Dr. Tomás Manuel de Anchorena 1872, C1425, Autonomous City of Buenos Aires, Argentina. 
g) Hospital Churruca Visca, Uspallata 3400, C1437, Autonomous City of Buenos Aires, Argentina. 
h) Sanatorio Anchorena San Martín, Perdriel 4189, B1672, Villa Lynch, Province of Buenos Aires, Argentina. 
i) 
Sanatorio ITOIZ, Alsina 174, B1870, Avellaneda, Province of Buenos Aires, Argentina. 
j) 
Clínica Bazterrica, Juncal 3002, C1425, Autonomous City of Buenos Aires, Argentina. 
k) Hospital Carlos G. Durand, Av. Díaz Vélez 5044, C1405, Autonomous City of Buenos Aires, Argentina. 
l) 
Clínica Santa Isabel, Av. Directorio 2037, C1406, Autonomous City of Buenos Aires, Argentina.  
m) Sanatorio San Cayetano, Av. Directorio 4743, C1407, Autonomous City of Buenos Aires, Argentina.  

 
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n) Hospital Dr. Guillermo Rawson, Sta Fe Este 972, J5402, San Juan, Argentina.  
 
Introduction 
 
Extubation is the removal of the endotracheal tube (ETT) when it is no longer required [1]. This 
procedure may be associated with complications, such as desaturation, stridor, bronchospasm, and 
severe cough [2,3]. The complication rates reported in the literature range from 6.6% to 100% [4–6]. In 
some cases, these complications may lead to extubation failure [7]. 
Two orotracheal extubation (OTE) techniques are described in the literature [8]. The traditional 
extubation technique consists of introducing a suction catheter into the ETT and trachea, deflating the 
cuff, and removing the ETT by applying continuous endotracheal suctioning during the entire 
procedure. The positive pressure extubation technique, on the other hand, involves applying positive 
pressure through the airway during cuff deflation and extubation. Thus, the air flow passing between 
the ETT and the larynx pushes pooled subglottic secretions towards the oropharynx so that they can 
be expelled through the oral cavity. Both techniques intend to minimize the leakage of the 
oropharyngeal content into the distal airway. However, according to several authors, the negative 
pressure generated by suctioning during the traditional technique may promote rather than prevent 
leakage [9,10]. 
A noninferiority clinical trial showed that the positive pressure extubation technique was safe and 
noninferior to the traditional technique in terms of the incidence of immediate postextubation 
complications, postextubation pneumonia (PEP), OTE failure, and reintubation [11]. Although prior 
studies reported better clinical outcomes with the positive pressure extubation technique [6,12], its 
superiority has not been deeply studied yet. Therefore, the objective of our study is to determine 
whether the positive pressure OTE technique, compared with the traditional OTE technique, reduces 
the incidence of major postextubation complications (up to 60 minutes) in critically ill adult patients.  
 
 

 
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Methods  
 
Design 
 
A multicenter randomized clinical trial was conducted in 13 centers from Argentina. Patients admitted 
to the intensive care units (ICU) between April 1, 2019, and March 26, 2020, were included in the 
analysis. Our study was evaluated and approved by the Research Ethics Committee (#12-2018-05, 
approved on February 28, 2019) and registered on ClinicalTrials.gov (NCT03918811, April 18, 2019).  
The results were reported according to the CONSORT Statement for reporting randomized clinical trials 
[13]. 
 
Participants 
 
We included patients aged > 18 years, requiring invasive mechanical ventilation (IMV) through an ETT, 
who had successfully completed a spontaneous breathing trial (SBT) [14] and met the following OTE 
criteria: an adequate level of consciousness (Glasgow Coma Scale score ≥ 8/15) [15] and effective 
cough (cough at order and/or at endotracheal suctioning) [16,17]. The participants' or their legal 
representatives' informed consent was also required. Patients with a history of upper airway (UA) injury 
or surgery, with a limited therapeutic effort, who had previously been extubated or tracheostomized, 
or who had required noninvasive mechanical ventilation (NIMV) as a weaning method were excluded 
from our study.  
 
 
Procedure and Interventions 
 
Patients who met the eligibility criteria and successfully completed the SBT were immediately 
randomized.  Once OTE was performed by two operators, assessment of outcome measures within 60 

 
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min after extubation was done by a third operator (blinded). Daily monitoring of outcome measures 
within 72 h after extubation was performed by this same operator. If preventive NIMV or high flow nasal 
cannula (HFNC) had been decided, they were initiated 15 min after OTE in order not to influence 
monitoring of outcome measures. Extubation maneuvers were performed in accordance with the 
procedure reported in the literature [11]. The traditional OTE technique consisted of deflating the cuff 
and removing the ETT by applying continuous endotracheal suctioning during the entire procedure. In 
positive pressure extubation, ventilator parameters were set at 15/10 cmH2O, in PC-CSV mode. The 
cuff was deflated, and a suction catheter was introduced through the mouth to suction secretions from 
the oropharyngeal cavity [11,18,19] while the ETT was removed without endotracheal suctioning (see 
supplementary material).  
 
Outcome measures 
 
Postextubation overall complications:[11] clinical evidence of desaturation [3,5,6,20], hypertension 
[1,3,4,20], tachycardia [1,3,4,20], tachypnea [1,21], or poor respiratory mechanics [21] (at least one 
within 15 min after extubation), or clinical evidence of UA obstruction [4,22], postobstructive pulmonary 
edema [2,22], vomiting [3,5], bronchospasm [3,5], or severe cough [3,5,23] (at least one within 60 min 
after extubation). 
Postextubation major complications:[11] clinical evidence of desaturation (within 15 min after 
extubation), or clinical evidence of UA obstruction or vomiting (at least one within 60 min after 
extubation).  
Postextubation minor complications:[11] clinical evidence of hypertension, tachycardia, tachypnea, or 
poor respiratory mechanics (at least one within 15 min after extubation), or clinical evidence of 
postobstructive pulmonary edema, bronchospasm, or severe cough (at least one within 60 min after 
extubation). 
Postextubation pneumonia (PEP) was defined as the presence of new or increased pulmonary infiltrate 
on chest radiography before OTE, in addition to the presence of fever, leukocytosis (> 10,000/mm3), or 

 
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leukopenia (< 4,000/mm3) compared with preextubation values and/or increase of tracheobronchial 
secretions or change in their quality (within 72 h after extubation) [16]. 
Extubation failure was defined as the need for NIMV or HFNC to treat the failure or reintubation within 
72 h after extubation [1,24]. Reintubation was defined as the need for a new introduction of the ETT 
within 72 h after extubation [1,25]. 
 
Randomization  
 
Randomization was performed in blocks and stratified by participating center and by the risk of 
extubation failure (high or low), as reported in prior studies [16,26]. Randomization assignment was 
blinded to the operators in charge of the procedures through an online platform (see supplementary 
material).  
 
Blinding 
 
Due to the nature of the intervention, blinding of patients and operators performing OTE was not 
possible. The evaluator who recorded measures of interest after extubation was blinded to the assigned 
extubation technique. The database was monitored by third parties with no direct participation in the 
study and no interest in its outcomes. The data were analyzed pursuant to the statistical analysis plan 
devised before the study, and the person in charge of data statistical analysis was blinded to the 
technique used. 
 
Sample size 
 
Based on a major complication rate of 37.6%, reported in a prior study [11], 778 patients (389 per 
group) were required to have an 80% chance of detecting, as significant at the 5% level, a decrease in 

 
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the incidence of major complications from 37.6% in the control group (traditional technique) to 28.2% 
in the experimental group (positive pressure technique) (relative difference of 25%). 
 
Statistical analysis 
 
The primary analysis of outcomes was a per-protocol analysis. An intention-to-treat analysis was also 
performed. Thus, a “worst case scenario” method was adopted, assigning the event of interest to the 
patients lost to follow-up who were randomly assigned to the positive pressure group and not allocating 
the event of interest to the patients lost to follow-up who were randomly assigned to the traditional 
group.  No interim analyses were planned. Chi-square test or Fisher exact test were used for the 
comparison categorical variables. Continuous variables with normal distribution were presented as 
mean and standard deviation (SD) and were compared with the Student's t test for independent 
samples. Non-normally distributed variables were presented as median with 25% and 75% percentiles. 
For outcome measures (primary and secondary), relative risks (RR) and 95% confidence intervals (CI) 
were calculated. Effect estimates were also reported with their absolute risk differences (ARD) and their 
corresponding 95% confidence intervals (95% CI). Tests were two-tailed, and a p-value <0.05 was 
considered significant. Statistical analysis was performed using SPSS version 25.0; SPSS Inc, Chicago, 
IL, USA. 
 
References 
 
Supplementary Material 
 
Spontaneous breathing trial 
 

 
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Patients who met the eligibility criteria and successfully completed the spontaneous breathing trial 
(SBT) were immediately randomized. It was conducted with a T-tube, by applying continuous positive 
airway pressure (continuous positive pressure in the airway) at 5 cm H2O, or by applying pressure 
support (PS) from 5 to 8 cm H2O for a period ranging from 30 to 120 minutes. The oxygen flow rate or 
FiO2 was regulated to keep an oxygen saturation over 90%. After extubation, supplementary oxygen 
was administered with the same FiO2 used at the end of the successful SBT. All variables were 
collected and recorded in specific forms.  
 
 
Interventions 
 
Both procedures were performed by two operators. In the traditional orotracheal traditional extubation 
(OTE), a closed suction system catheter was placed into the endotracheal tube (ETT) by the first 
operator, and endotracheal suctioning (ES) was initiated. The cuff was immediately deflated by the 
second operator, and the ETT was removed with continuous ES during the entire procedure. In the 
positive pressure OTE, the first operator set the ventilator parameters to PS ventilation mode, with an 
inspiratory pressure of 15 cm H2O and a positive end expiratory pressure (PEEP) of 10 cm H2O. Then, 
the cuff was deflated by the second operator, and the suction catheter was introduced through the 
mouth to suction secretions drawn to the oropharynx while the ETT was removed by the first operator 
without applying ES. Before the study, the participating centers were trained in both OTE procedures 
by means of videos. 
 
Procedure  
 
Patients were included in the study once they had successfully completed the SBT and met the OTE 
criteria. The blinded evaluator followed a preextubation checklist. It entailed discontinuing enteral 
nutrition, adjusting the head of the bed to 45o, suctioning oropharyngeal and tracheobronchial 

 
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secretions, and recording preextubation monitoring on the pertaining sheet. Regardless of the 
procedure, the alarms were silenced, and the ventilator parameters were set at PS 15/10 cmH20 by 
one operator, so that the blinded evaluator could not hear the maneuver or read the ventilator 
parameters. The blinded evaluator left and was replaced by the operators, who knew about the 
technique assigned. They initiated the randomization through http://extubar.ajrpt.com and were in 
charge of the OTE and postextubation oxygen delivery. Regardless of the OTE technique, the patients 
received supplemental oxygen through a nasal cannula placed before ETT removal to keep the oxygen 
flow used in the SBT. 
Once the OTE was completed, the blinded evaluator assessed the outcome measures recorded within 
60 min after extubation. Daily monitoring of outcome measures within 72 h after extubation was carried 
out.  
 
The decision to perform OTE and to use NIMV or HFNC to prevent OTE failure, follow-up, and treatment 
was taken by the blinded evaluator, or the respiratory therapist on duty, who was blinded to 
randomization assignment. If preventive NIMV or HFNC had previously been decided, it was 
implemented 15 min after OTE so as not to affect monitoring of outcome measures.  
 
 
Randomization 
 
 
The randomization sequence was generated before the study by using the web site 
(https://www.sealedenvelope.com/) in blocks of 6 and stratified by participating center and by the risk 
of extubation failure (high or low). High risk of extubation failure was defined as the presence of at least 
one of the following criteria: age ≥66 years, moderate or severe chronic obstructive pulmonary disease 
(COPD), ≥2 comorbidities (COPD, peripheral artery disease, immune deficiency, liver disease, 
hypertension, diabetes, neurological disease, heart failure, chronic renal failure), body mass index (BMI) 
≥31, congestive heart failure as main reason from IMV, difficult intubation, IMV ≥8 days, a requirement 
of suctioning respiratory secretions (≥3 suctions within 4 h before the OTE), difficult or prolonged 

 
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weaning and/or APACHE II (Acute Physiology and Chronic Health disease Classification System II) a 
day before the OTE ≥13. Randomization assignment was blinded to researchers in charge of recruiting 
patients through an online platform (http://extubar.ajrpt.com).