Predictive Factors for High Flow Nasal Cannula Failure in Acute Hypoxemic Respiratory Failure in an Intensive Care Unit

    

    

    Figure 2: ROC curves predicting HFNC success.
The sensitivity and specificity would be 0.88 and 0.41 if cut-off value for ROX
12 hours would be 5.626.
    

Discussion

Acute Hypoxemic Respiratory Failure (AHRF) is a fatal complication of many diseases and it contributes to 30% of ICU admissions [13,14]. It has been increasingly recognized that mechanical ventilation is associated with various adverse events and the hospital mortality remained as high as 30% [15,16]. NIV is an established treatment to improve gas exchange and to decrease intubation rate and mortality in Chronic Obstructive Pulmonary Disease (COPD) and Congestive Heart Failure (CHF) [17,18]. However, the use of NIV in acute hypoxemic respiratory failure is debatable and is even shown to be detrimental in some studies.

High flow nasal cannula appears to be a good alternative to avoid mechanical ventilation in acute hypoxemic respiratory failure. Patients were found to have a higher PF ratio, and a lower respiratory rate, work of breathing and Thoraco-Abdominal Asynchrony (TAA), when they were receiving HFNC [10,19,20]. Sztrymf et al. reported a significant decrease in TAA at 1 hr in patients receiving HFNC (p=0.0007),10 and found that patients exhibiting higher percentage of TAA as early as 30 minutes after HFNC initiation were more likely to require endotracheal intubation.

Frat, in the FLORALI trial, [11] found lower ICU mortality and 90-day mortality rates, and longer ventilator-free days in the patients receiving HFNC, compared to patients receiving standard oxygen therapy or NIV. In the post hoc analysis of the subgroup of patients with P/F ratio <200, intubation rate was significantly lower in the patients receiving HFNC. Compared to standard oxygen therapy, HFNC was associated with significant reduction in the intubation rate (OR 0.52, 95% CI 0.34-0.79, P=0.002) in a meta-analysis by Zhao, [21] despite no difference in mortality (OR 1.01, 95% CI 0.67-1.53, P=0.96).

Heart rate, respiratory rate, SOFA score, APACHE II score, oxygenation, delirium, and thoraco-abdominal asynchrony have been inconsistently identified as predictive factors for HFNC failure in different studies [9,10,22-25].

In our study, the only factor associated with HFNC failure by multivariate analysis is the ROX index at 12 hours after HFNC commencement (OR 0.802, p= 0.012). The ROX index, a ratio of pulse oximetry (SpO₂)/fraction of inspired oxygen (FiO₂) to respiratory rate, was proposed by Roca to predict the HFNC failure [26]. In his 4-year observational cohort study, ROX index demonstrated the best prediction accuracy (AUROC, 0.74) at 12 hours after HFNC initiation, with the best cut-off value for the ROX index estimated to be 4.88. It was also better than other physiological parameters to predict failure when measured at 18 hours and 24 hours after HFNC initiation. Compared to other clinical parameters, our study showed the greatest Area under Receiver Operating Characteristics Curve (AUROC=0.659) if ROX at 12 hours with the sensitivity and specificity of 0.88 and 0.41 if cut-off value was set at 5.626. Our study shared similar findings with Roca’s study that the ROX index at 12 hours was better than other physiological parameters to predict HFNC failure. ROX index appears to be a useful tool and can be easily incorporated in routine clinical monitoring in patients using HFNC. We would also like to point out that the ROX index at 1 hour after HFNC was significantly lower in patients with HFNC failure (p=0.014). Although the ROX index at 1 hour only has an AUROC of 0.605 only, it may be still worthy of calculating the ROX index as early as 1 hour after HFNC.

According to our study, heart rates before and 1 hour after HFNC were predictive of HFNC failure. Apart from being a haemodynamic parameter, patient heart rate also reflects the degree of stress and the dosage of vasopressors. Interestingly, Frat also found the heart rate one hour after HFNC commencement was the only factor associated with intubation in the post-hoc analysis of the FLORALI study [25].

We found that HFNC failure patients had significant higher APACHE IV Scores and lower GCS scores upon ICU admission (p=0.002, 0.024). Obviously, a higher APACHE score signifies higher illness severity, and it has been identified as a factor for failure in previous studies. Imai, in his retrospective cohort, found delirium as a predictor of failure in high flow nasal cannula in 106 patients with acute respiratory failure [22]. Impaired consciousness in ICU patients may lead to a lower threshold for endotracheal intubation, and on the other hand it may reflect the severity of underlying illnesses.

The failure rate of 55.65% in our study seems to be high when compared to the intubation rate of 38% in the FLORALI study [11]. However, the definition of failure of HFNC differed in the two studies. Apart from intubation, we also regard escalation to NIV and 28-day mortality as HFNC failure. After excluding these patients, 43 patients (34.7%) required mechanical ventilation and the intubation rate was comparable to that in the FLORALI study. Interestingly, among 21 patients with escalation to non-invasive ventilation, a majority of 15 patients (71.4%) did not need escalation to mechanical ventilation. The role of non-invasive ventilation as escalation of support after failure of HFNC has never been investigated and may warrant further studies.

In our study, patients with higher APACHE IV scores, more deranged physical parameters including high heart rates & respiratory rates and blood parameters of low platelet counts, sodium levels and higher pH were at higher risk of HFNC failure. Close monitoring of clinical response is deemed important in patients receiving HFNC. As early as 1 hour after HFNC initiation, the heart rate can provide additional information to predict treatment failure. ROX index at 12 hours has a valuable role in clinical monitoring. As supported by findings from Roca’s cohort 26 and our study, escalation of treatment has to be considered if ROX index is lower than the cutoff value or patient condition deteriorates. Because HFNC has an advantage of improving patient comfort and patients probably may tolerate for long period of time, physicians should beware of delaying endotracheal intubation.

Our study had several limitations. Firstly, it is a retrospective study without predetermined protocol for the indication, initiation and cessation of HFNC. Secondly, patients’ comfort, dyspnoea and TAA were not assessed as they were not routinely documented in the medical record. Thirdly, the ROX index at 12 hours, as a tool to predict failure, is unable to identify patients failing HFNC within 12 hours. Fourthly, our study has a small sample size and is prone to be under-powered. Finally, there is heterogeneity in the causes of acute hypoxemic respiratory failure, though no relationship was found in our study between HFNC failure and the etiology of the respiratory failure.

Conclusion

HFNC is an excellent modality of respiratory support with advantages of simplicity and excellent tolerance, with proven benefit in terms of patient physiological parameters and clinical outcome. Close monitoring of the physical parameters is crucial. The ROX index has a predictive role in treatment failure and can be easily employed as a routine monitoring parameter for patients on HFNC. Physicians should beware of delayed intubation which was shown to have worse clinical outcome.

Authorship Statement

Dr. Chung-tat Lun designed, analysed the data and wrote the paper; Dr. Chi-kin Leung collected data and wrote the paper; Dr Hoiping Shum collected and analysed the data and Dr. Sheung-on So designed and supervised the writing.

Disclosure Statement

All the authors did not have any conflicts of interest. The study is not funded by any organization.

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