What we already know
Weaning from mechanical ventilation represents a challenge for clinicians. A dedicated ERS task force focused some fundamental aspects that clinicians should consider before extubation [1]. The assessment of readiness to wean must consider cardiorespiratory load (adequate gas exchange and hemodynamic stability) neuromuscular aspect (consciousness, sedation, delirium, peripheral disfunction, critical illness neuromuscular abnormalities) metabolic disorders, absence of anemia and nutritional status. Candidates to extubation should attempt a spontaneous breathing trial (SBT), defined as the assessment of the patient’s ability to breathe spontaneously, which can be performed by different methods (T-tube, low levels of pressure support and PEEP or zero PEEP).  Extubation failure is defined as the inability to sustain spontaneous breathing after removal of the endotracheal tube and need for reintubation.  The incidence of extubation failure varies between 6 and 47% and is associated with a high mortality rate [2]. While the weaning steps before extubation are exhaustively reported, there is not definite consensus about respiratory support after extubation.

2021 ERS guidelines about the use of high flow nasal cannula (HFNC) oxygen therapy splits post extubation acute respiratory failure (ARF) in postoperative and non-surgical patients [3]. Surgical patients are classified according to the risk to develop postoperative pulmonary complications (surgery procedures and timing, type of anesthesia and ventilation settings, patient’s characteristic as comorbidities and lifestyle). HFNC or conventional oxygen therapy (COT) can be both used as respiratory support in post operative low-risk patients; while ERS guidelines suggest the use of either HFNC or non-invasive ventilation (NIV) for high risk patients.  High risk non-surgical patients are defined as those who develop hypercapnia during SBT, those with chronic cardiac and respiratory disorders, elderly patients, and those with airway obstruction. For this group of patients ERS guidelines suggest the use of NIV over HFNC after extubation, while for low or moderate risk of extubation failure patients should receive HFNC over COT.

Introduction
High-Flow Versus Venturi Mask Oxygen Therapy to Prevent Re-Intubation in Hypoxemic Patients After Extubation is a sponsored, multicenter, randomized, two-arms open label clinical trial, conducted from January 2014 to October 2016 in 13 European intensive care unit (ICU). This study compared the use of COT (delivered by venturi mask) to HFNC in post extubation ARF in both surgical and non-surgical patients.

Methods
Adult intubated patients mechanically ventilated for at least 48 hours who met spontaneous breathing trial criteria (reported in the main text) were considered eligible for undergoing a SBT trial, which was conducted according to clinical practice at each center. SBT was defined as successfully completed by the presence of all the following criteria during and at the end of the trial: respiratory rate < 35/min; arterial oxygen saturation ≥ 90%; heart rate < 120/min; systolic blood pressure > 90 and < 160 mmHg, adequate cough. The inclusion criterion was hypoxemia within 120 minutes after extubation, defined as arterial oxygen partial pressure to nominal inspired oxygen fraction ratio (PaO2/FiO2) equal to or lower than 300 mmHg, or by a peripheral oxygen saturation (SpO2) to nominal FiO2 ratio equal or lower 300% (with SpO2<98%) while receiving oxygen therapy via Venturi Mask 31%. Patients with tracheostomy, pregnancy and those who received prophylactic NIV immediately after extubation (more than 3 consecutive failures of an SBT or arterial carbon dioxide partial pressure (PaCO2) greater than 45 mmHg and respiratory acidosis (pH < 7,35) or respiratory rate higher than 25 breaths per minute before the SBT) were excluded.

Enrolled patients were randomized 1:1 to receive COT with venturi mask or HFNC.  Randomization was stratified according to the presence of hypercapnia, age, and cause of admission in ICU. The primary outcome was extubation failure, defined as the need for endotracheal re-intubation within 72 hours after extubation. Criteria for intubations were previously defined and reported in the main text.

Among patients experiencing respiratory failure during the assigned treatment, a trial of rescue NIV before re-intubation was allowed if subsequent criteria were met: respiratory acidosis (defined as an arterial pH below 7.35 with PaCO2>45 mm Hg), clinical signs suggestive of respiratory-muscle fatigue or increased respiratory effort (i.e., use of accessory muscles, intercostal indrawing, or paradoxical motion of the abdomen); respiratory rate > 35 breaths/minute for one hour; hypoxemia (defined as an arterial oxygen saturation < 90% or PaO2 < 80 mmHg with FiO2 >50%). Non-invasive ventilation settings and interfaces were chosen by the attending physician.

Secondary outcomes were the rate of endotracheal re-intubation within 72 hours in the intention-to-treat population, need for endotracheal intubation up to 28 days from randomization, need for NIV within 72 hours and up to 28 days from enrolment, length of ICU and hospital length of stay, the need for ICU re-admission, ICU and in-hospital mortality.

Study population
494 patients were randomly assigned to receive HFNC or Venturi Mask oxygen, reaching the calculated sample size. The most common reason for intubation was acute respiratory failure (41% in Venturi mask group and 49% in HFNC group).

Results
No statistical differences between HFNC group and Venturi Mask group were found in re-intubation rate at 72 hours (primary outcome) and 28 days (secondary outcome). In particular, the rate of intubation was 13% vs 11% and 21% vs 23% at 72 hours and 28 days respectively. No statistical differences were found for others secondary outcome except for the need for rescue NIV, which was significantly lower in the HFNC group than in the Venturi Mask group both at 72 hours and 28 days (8% vs. 17%, p=0.002; 12% vs. 21%, p=0.007, respectively). The reintubation rate of patients who received rescue NIV within 28 days from enrolment did not differ between the two groups. Upon patients who required NIV rescue use, patients who received Venturi mask more frequently met the criteria of tachypnea and respiratory fatigue/distress than patients supported by HFNC (p < 0.001 and p = 0.017 respectively).  Post-hoc exploratory analyses were performed in subgroups according to age (≥65 years); mechanical ventilation duration≥7 days; SAPSII≥40 at ICU admission; SOFA score≥ 4 at enrolment; compensated hypercapnia (PaCO2 > 45 mmHg with pH equal or greater than 7.35 at study inclusion). No statistical differences between any subgroups were founded.

Conclusion
HFNC does not reduce the rate of endotracheal re-intubation compared to Venturi Mask oxygen therapy in hypoxemic patients after scheduled extubation.  HFNC is associated with less frequent need for rescue NIV.

Food for thought

• The main result of this study is that HFNC may prevent the use of rescue NIV in post extubation acute respiratory failure.
• The less frequent use of rescue NIV in the HFNC group appear to be related to the lower incidence of tachypnea and respiratory fatigue during the treatment. These effects are in line with previous physiological data [4]. Avoiding rescue use of NIV, HFNC may permit to improve patients’ comfort, reduce health care personnel workload, and reduce the use of ventilator equipment.
• Non-invasive ventilation settings, duration, and interfaces (chosen by the attending physicians) are not reported in the text, as well as the respiratory support used between NIV cycles (HFNC vs. Venturi mask).
• According to the results of this study, NIV failure seems to be not influenced by previous use of HFNC or Venturi mask in post-extubation ARF.

References
[1] 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. PMID: 17470624.
[2] Kulkarni AP, Agarwal V. Extubation failure in intensive care unit: predictors and management. Indian J Crit Care Med. 2008 Jan;12(1):1-9. doi: 10.4103/0972-5229.40942. PMID: 19826583; PMCID: PMC2760915.
[3] Oczkowski S, Ergan B, Bos L, Chatwin M, Ferrer M, Gregoretti C, Heunks L, Frat JP, Longhini F, Nava S, Navalesi P, Ozsancak Uğurlu A, Pisani L, Renda T, Thille AW, Winck JC, Windisch W, Tonia T, Boyd J, Sotgiu G, Scala R. ERS clinical practice guidelines: high-flow nasal cannula in acute respiratory failure. Eur Respir J. 2022 Apr 14;59(4):2101574. doi: 10.1183/13993003.01574-2021. PMID: 34649974.
[4] Mauri T, Turrini C, Eronia N, Grasselli G, Volta CA, Bellani G, Pesenti A. Physiologic Effects of High-Flow Nasal Cannula in Acute Hypoxemic Respiratory Failure. Am J Respir Crit Care Med. 2017 May 1;195(9):1207-1215. doi: 10.1164/rccm.201605-0916OC. PMID: 27997805.