Review question
Are high-flow nasal cannulae (HFNC) a helpful treatment option for adult patients in the intensive care unit (ICU) who need breathing support?
Background
People in the ICU may need support to breathe and HFNC are one option for this. HFNC deliver warm air and oxygen through small plastic tubes that sit inside the nostrils. The airflow is at a higher rate each minute than standard oxygen therapy (which is not always warmed and may be delivered through a plastic face mask or nasal cannulae). Other support options include non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV). These approaches use mild pressure to push air into the lungs through tightly-fitting face masks or a helmet covering the entire head. Invasive mechanical ventilation provides the highest level of support, using a ventilator (artificial breathing machine) to push air in and out of the lungs through a plastic tube inserted into the windpipe.
Search date
The evidence is current to April 2020.
Study characteristics
All participants were adults (16 years or older) requiring support to breathe in an ICU. Most participants had respiratory failure (in which the lungs are unable to get enough oxygen into the blood) or had just been taken off a ventilator and needed support to transition to independent breathing.
We searched for randomized controlled trials; these trials give participants an equal chance to be in either trial group and provide the best evidence. We included trials that compared HFNC with standard oxygen therapy or NIV or NIPPV. We included 31 studies with 5136 participants, 51 ongoing studies and 19 studies awaiting classification. Fourteen studies were funded by manufacturers of breathing equipment.
Key results
HFNC compared to standard oxygen therapy
We found that using HFNC may reduce the need for patients to change to another type of breathing support (treatment failure). We found no evidence of a difference between the two interventions for: hospital deaths, length of ICU stay, pneumonia (lung infection), skin damage caused by tubes or masks in contact with the face, comfort while patients received breathing support, or in how well either treatment provided oxygen to the blood.
HFNC compared to NIV or NIPPV
We found no evidence of a difference in treatment failure between using HFNC and NIV or NIPPV. We also found no evidence of a difference for hospital deaths, length of ICU stay, pneumonia, or barotrauma (damage to the body caused by differences in pressure inside and outside the body). NIV or NIPPV may improve how well oxygen gets into the blood. We are uncertain whether HFNC could be more comfortable for patients in the first 24 hours of use. No studies reported skin damage.
Quality of evidence
We used a rating scale to decide the quality of the evidence in these trials. When we rate evidence as very low-certainty, it means that we are very uncertain about the reliability of the results. High-certainty means that we are very confident about the results.
We did not always have evidence from enough studies to give us confidence in the key results. Sometimes our findings changed if we removed studies that were less well reported (e.g. regarding how participants were allocated to a treatment). We also found some variation between study results for some outcomes. We are moderately certain in our findings that HFNC did not influence hospital deaths and pneumonia when compared to standard oxygen therapy, but for all other outcomes, we judged the evidence to be of low or very low certainty. This means that our confidence in these results is limited or very limited, and the real effect may be very different.
Conclusion
HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably makes little or no difference when compared to NIV or NIPPV. For most other review outcomes, we found no reliable evidence of a difference in effect. However, we identified another 51 ongoing trials and we plan to include these in future updates of the review. When these trials are incorporated, we may reach different conclusions about whether HFNC is helpful for breathing support in adult ICU patients.
HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably makes little or no difference to treatment failure when compared to NIV or NIPPV. For most other review outcomes, we found no evidence of a difference in effect. However, the evidence was often of low or very low certainty. We found a large number of ongoing studies; including these in future updates could increase the certainty or may alter the direction of these effects.
High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adults experiencing acute respiratory failure, or at risk of acute respiratory failure, in the intensive care unit (ICU). This is an update of an earlier version of the review.
To assess the effectiveness of HFNC compared to standard oxygen therapy, or non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU.
We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (17 April 2020), clinical trial registers (6 April 2020) and conducted forward and backward citation searches.
We included randomized controlled studies (RCTs) with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask; or NIV or NIPPV which included continuous positive airway pressure and bilevel positive airway pressure) in adults admitted to the ICU.
We used standard methodological procedures as expected by Cochrane.
We included 31 studies (22 parallel-group and nine cross-over designs) with 5136 participants; this update included 20 new studies. Twenty-one studies compared HFNC with standard oxygen therapy, and 13 compared HFNC with NIV or NIPPV; three studies included both comparisons. We found 51 ongoing studies (estimated 12,807 participants), and 19 studies awaiting classification for which we could not ascertain study eligibility information.
In 18 studies, treatment was initiated after extubation. In the remaining studies, participants were not previously mechanically ventilated.
HFNC versus standard oxygen therapy
HFNC may lead to less treatment failure as indicated by escalation to alternative types of oxygen therapy (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.45 to 0.86; 15 studies, 3044 participants; low-certainty evidence). HFNC probably makes little or no difference in mortality when compared with standard oxygen therapy (RR 0.96, 95% CI 0.82 to 1.11; 11 studies, 2673 participants; moderate-certainty evidence). HFNC probably results in little or no difference to cases of pneumonia (RR 0.72, 95% CI 0.48 to 1.09; 4 studies, 1057 participants; moderate-certainty evidence), and we were uncertain of its effect on nasal mucosa or skin trauma (RR 3.66, 95% CI 0.43 to 31.48; 2 studies, 617 participants; very low-certainty evidence). We found low-certainty evidence that HFNC may make little or no difference to the length of ICU stay according to the type of respiratory support used (MD 0.12 days, 95% CI -0.03 to 0.27; 7 studies, 1014 participants). We are uncertain whether HFNC made any difference to the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) within 24 hours of treatment (MD 10.34 mmHg, 95% CI -17.31 to 38; 5 studies, 600 participants; very low-certainty evidence). We are uncertain whether HFNC made any difference to short-term comfort (MD 0.31, 95% CI -0.60 to 1.22; 4 studies, 662 participants, very low-certainty evidence), or to long-term comfort (MD 0.59, 95% CI -2.29 to 3.47; 2 studies, 445 participants, very low-certainty evidence).
HFNC versus NIV or NIPPV
We found no evidence of a difference between groups in treatment failure when HFNC were used post-extubation or without prior use of mechanical ventilation (RR 0.98, 95% CI 0.78 to 1.22; 5 studies, 1758 participants; low-certainty evidence), or in-hospital mortality (RR 0.92, 95% CI 0.64 to 1.31; 5 studies, 1758 participants; low-certainty evidence). We are very uncertain about the effect of using HFNC on incidence of pneumonia (RR 0.51, 95% CI 0.17 to 1.52; 3 studies, 1750 participants; very low-certainty evidence), and HFNC may result in little or no difference to barotrauma (RR 1.15, 95% CI 0.42 to 3.14; 1 study, 830 participants; low-certainty evidence). HFNC may make little or no difference to the length of ICU stay (MD -0.72 days, 95% CI -2.85 to 1.42; 2 studies, 246 participants; low-certainty evidence). The ratio of PaO2/FiO2 may be lower up to 24 hours with HFNC use (MD -58.10 mmHg, 95% CI -71.68 to -44.51; 3 studies, 1086 participants; low-certainty evidence). We are uncertain whether HFNC improved short-term comfort when measured using comfort scores (MD 1.33, 95% CI 0.74 to 1.92; 2 studies, 258 participants) and responses to questionnaires (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 168 participants); evidence for short-term comfort was very low certainty. No studies reported on nasal mucosa or skin trauma.