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Table 1 Most relevant studies of HFNC therapy

From: Current evidence for the effectiveness of heated and humidified high flow nasal cannula supportive therapy in adult patients with respiratory failure

  Reference Design Patients Results
Acute respiratory failure Roca et al. [33] Retrospective cohort 37 lung transplant recipients readmitted to ICU due to ARF (40 episodes) The absolute risk reduction for MV with HFNC therapy was 29.8 % and the NNT to prevent one intubation with HFNC was 3. Multivariate analysis showed that HFNC therapy was the only variable at ICU admission associated with a decreased risk of MV (odds ratio 0.11 [95 % CI 0.02–0.69]; P = 0.02)
Frat et al. [34] RCT 310 ARF patients randomly assigned to HFNC, COT, or NIV The hazard ratio for death at 90 days was 2.01 (95 % CI 1.01–3.99) with COT vs HFNC (P = 0.046) and 2.50 (95 % CI 1.31–4.78) with NIV vs HFNC (P = 0.006). In the subgroup of patients with a PaO2/FIO2 ≤ 200 mmHg, the intubation rate was significantly lower in the HFNC group
Sztrymf et al. [22]. Prospective cohort 38 ARF patients HFNC was associated with an early reduction of the RR, HR, dyspnea score, supraclavicular retraction and thoracoabdominal asynchrony, and better oxygenation. Absence of a significant decrease in the RR, lower oxygenation and persistence of thoracoabdominal asynchrony after HFNC initiation were early indicators of HFNC failure
Roca et al. [16]. Prospective cohort 20 ARF patients who first received humidified oxygen with a bubble humidifier and delivered via face mask for 30 min and then via HFNC with heated humidifier for another 30 min The HFNC was associated with less dyspnea and mouth dryness, and was more comfortable. HFNC was associated with higher and lower RR with no differences in PaCO2
Sztrymf et al. [22] Prospective cohort 20 patients with persistence of ARF despite COT HFNC was associated with better oxygenation and lower RR
Rello et al. [24] Retrospective cohort 35 patients with ARF due to H1N1v pneumonia After 6 h of HFNC O(2) therapy, non-responders presented a lower PaO2/FIO2. All eight patients on vasopressors required intubation
Lemiale et al. [51] RCT 100 immunocompromised patients with ARF randomized to a 2-h trial of HFNC vs COT No differences on NIV or invasive MV during the 2-h period were observed. No differences in secondary outcomes (RR, HR, comfort, dyspnea, and thirst) were observed
Mokart et al. [52] Retrospective propensity-score analysis 178 cancer patients admitted to the ICU due to severe ARF HFNC-NIV was associated with more VFD and less septic shock occurrence. Mortality of patients treated with HFNC was 35 % vs 57 % for patients never treated with HFNC (P = 0.008)
Hyun Cho et al. [30] Retrospective cohort 75 patients with ARF admitted to the ICU 62.7 % of patients successfully avoided intubation. APACHE II, SOFA, cardiogenic pulmonary edema, and improvement in oxygenation within 24 h were predictors of HFNC success
Gaunt et al. [50] Retrospective cohort 145 ICU patients who received HFNC Subjects with a greater length of time between ICU admission and first use of HFNC had longer ICU and hospital LOS, even after controlling for adverse events and mechanical ventilation
Nagata et al. [49] Retrospective cohort (two periods: before-after) 83 (before) vs 89 (after) ARF patients In the after period, fewer patients needed MV (NIV or MV): 100 % (before) vs 63 % (after) (P ≤ 0.01)
Jones et al. [48] RCT 303 hypoxemic and tachypneic patients admitted to the ED (165 HFNC vs 138 COT) 5.5 % of HFNC patients vs 11.6 % of COT patients required MV within 24 h of admission (P = 0.053)
Kang et al. [53] Retrospective cohort 175 patients who failed on HFNC and required intubation In propensity-adjusted and -matched analysis, early intubation (<48 h) was associated with better overall ICU mortality (adjusted OR = 0.317, P = 0.005; matched OR = 0.369, P = 0.046)
Messika et al. [55] Prospective cohort 45 very severely hypoxemic patients with bilateral infiltrates who may be considered as ARDS patients The intubation rate was 40 %. In the multivariate analysis, higher SAPS II scores were associated with HFNC failure
Cardiac surgery Corley et al [10]. Prospective cohort 20 patients post-cardiac surgery. Impedance measures, P(aw), ratio, respiratory rate, and modified Borg scores were recorded first on COT and then on HFNC HFNC significantly increased EELI. Tidal impedance variation, P(aw) and oxygenation, and reduced RR. HFNC also improved subjective dyspnea scoring
Parke et al. [46] Randomized 60 patients with mild to moderate hypoxemic ARF were randomized to receive HFNC or COT HFNC patients tended to need NIV less frequently (10 % vs 30 %; P = 0.10) and had significantly fewer desaturations (P = 0.009)
Parke et al. [47] RCT 340 patients post-cardiac surgery who were randomized to receive either HFNC vs COT from extubation to day 2 after surgery No differences in oxygenation on day 3 after surgery were observed, but did reduce the requirement for escalation of respiratory support (OR 0.47, 95 % CI 0.29–0.7, P = 0.001)
Corley et al. [45] RCT 155 patients with BMI ≥ 30 kg/m2. 74 patients received COT vs 81 patients treated with HFNC post-extubation No difference was seen between groups in atelectasis. There was no difference in mean PaO2/FIO2 ratio or RR. Five patients failed allocated treatment in the control group compared with three in the treatment group (OR 0.53, 95 % CI 0.11–2.24, P = 0.40)
Stéphan et al. [44] Randomized non-inferiority controlled trial 830 patients who had undergone cardiothoracic surgery who developed ARF (failure of a spontaneous breathing trial or successful breathing trial but failed extubation) or were deemed at risk for respiratory failure after extubation due to preexisting risk factors. HFNC vs BiPAP The treatment failed in 87 (21.0 %) of 414 patients with HFNC and 91 (21.9 %) of 416 patients with BiPAP (P = 0.003). No significant differences were found for ICU mortality (23 patients with BiPAP [5.5 %] and 28 with high-flow nasal oxygen therapy [6.8 %]; P = 0 .66)
Pre intubation Miguel-Montanes et. al [43]. Prospective quasi-experimental before-after study 101 patients who were intubated. Non-inclusion criteria were age <18 years, intubation for cardiac arrest, severe hypoxemia (defined as SpO2 < 95 % with COT), patients already receiving HFNC, and patients under NIV Median lowest SpO2 was 94 % with COT versus 100 % (95–100) with HFNC (P < 0.0001). Patients in the non-rebreathing bag reservoir facemask group experienced more episodes of severe hypoxemia (2 % vs 14 %, P = 0.03)
Vourc’h et al. [42] Randomized controlled trial 124 patients with PaO2/FIO2 ratio <300 mmHg, RR ≥30 bpm, and if they required FIO2 ≥ 0.5 to obtain a SpO2 of at least 90 %. Patients were randomized to HFNC or HFFM No differences in the lowest saturation were observed (HFNC 91.5 % vs HFFM 89.5 %, P = 0.44). There was no difference for difficult intubation, ventilation-free days, intubation-related adverse events (including desaturation <80 %), or mortality
Post-extubation Maggiore et al. [41] RCT 105 patients with PaO2/FIO2 ≤ 300 before extubation who were randomized to 48 h of COT or HFNC The PaO2/FIO2 was higher in the HFNC group (287 ± 74 vs 247 ± 81, P = 0.03). Comfort and airway dryness were also better with HFNC. HFNC patients had fewer interface displacements (32 % vs 56 %, P = 0.01) and oxygen desaturations (40 % vs 75 %; P < 0.001) and required reintubation (4 % vs 21 %, P = 0.01) or any form of ventilator support (7 % vs 35 %, P < 0.001) less frequently
Rittayamai et al. [40] Randomized crossover study 17 patients were randomized after extubation to receive either HFNC for 30 min followed by COT for another 30 min or COT for 30 min followed by HFNC for another 30 min At the end of the study, patients with HFNC reported less dyspnea and lower RR and HR. Most of the subjects (88.2 %) preferred HFNC to COT
Tiruvoipati et al. [39] Randomized crossover study 50 patients were randomized to either HFNC followed by HFFM or HFFM followed by HFNC after a stabilization period of 30 min after extubation There was no significant difference in gas exchange, RR, or hemodynamics. HFNC was better tolerated (P = 0.01) and tended to be more comfortable (P = 0.09)
Invasive procedures Lucangelo et al. [38] RCT Patients were randomly assigned to three groups: 40 L/min through a Venturi mask (V40, N = 15), nasal cannula (N40, N = 15), and 60 L/min through a nasal cannula (N60, N = 15) during bronchoscopy At the end of bronchoscopy, N60 presented higher PaO2/FIO2 and SpO2
Simon et al. [37] RCT 40 critically ill patients with hypoxaemic ARF to receive either NIV or HFNC during bronchoscopy in the ICU The NIV group presented better oxygenation. Two patients with HFNC were unable to proceed to bronchoscopy due to progressive hypoxemia
Heart failure Roca et al. [25] Prospective cohort Ten adult patients with New York Heart Association (NYHA) class III and left ventricle ejection fraction 45 % or less. Sequential echocardiographies were performed at baseline, using HFNC with 20 lpm and 40 lpm and post-HFNC Median IVC inspiratory significantly (P < 0.05) decreased from baseline (37 %) to HFNC with 20 lpm (28 %) and HFNC with 40 lpm (21 %). Changes in the IVC inspiratory collapse were reversible after HFNC withdrawal
Carratalá et al. [29] Case series Five patients with ACPE with stable dyspnea or hypoxemia following NIV All patients were successfully treated with HFNC, presenting clinical and gasometrical improvements
ED Lenglet et al. [36] Prospective cohort 17 patients with ARF admitted to ED who required oxygen >9 L/min HFNC was associated with better dyspnea scores. RR also decreased and oxygenation improved. Fewer patients with HFNC exhibited clinical signs of respiratory distress
Rittayamai et al. [54] Prospective randomized comparative study 40 hypoxemic patients were randomized to receive HFNC or conventional oxygen for 1 h HFNC improved dyspnea and comfort. No serious adverse events related with HFNC were observed
Palliative care Peters et al. [35] Prospective cohort 50 DNI patients with ARF admitted to ICU HFNC improved oxygenation and decreased RR
  1. APACHE Acute Physiology and Chronic Health Evaluation, ARDS acute respiratory distress syndrome, BiPAP bilevel positive airway pressure, BMI body mass index, bpm breaths per minute, CI confidence interval, COT conventional oxygen therapy, DNI do not intubate, ED emergency department, EELI end expiratory lung impedance, HFFM High flow face mask, HR heart rate, LOS length of stay, lpm liters per min, MV mechanical ventilation, NIV non-invasive ventilation, NNT number needed to treat, OR odds ratio, RCT randomized controlled trial, SOFA Sequential Organ Failure Assessment, SpO 2 pulse oximetry, VFD ventilator free days