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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