Analysis of risk factors for the failure of respiratory support with high-flow nasal cannula oxygen therapy in children with acute respiratory dysfunction: A case-control study

Abstract

Background: Evidence-based clinical practice guidelines regarding high-flow nasal cannula (HFNC) use for respiratory support in critically ill children are lacking. Therefore, we aimed to determine the risk factors for early HFNC failure to reduce the failure rate and prevent adverse consequences of HFNC failure in children with acute respiratory dysfunction.

Methods: Demographic and laboratory data were compared among patients, admitted to the pediatric intensive care unit between January 2017 and December 2018, who were included in a retrospective cohort study. Univariate and multivariate analyses were performed to determine risk factors for eventual entry into the predictive model for early HFNC failure and to perform an external validation study in a prospective observational cohort study from January to February 2019. Further, the association of clinical indices and trends pre- and post-treatment with HFNC treatment success or failure in these patients was dynamically observed.

Results: In total, 348 pediatric patients were included, of these 282 (81.0%) were included in the retrospective cohort study; HFNC success was observed in 182 patients (64.5%), HFNC 0-24 h failure in 74 patients (26.2%), and HFNC 24-48 h failure in 26 patients (9.2%). HFNC 24 h failure was significantly associated with the pediatric risk of mortality (PRISM) III score [odds ratio, 1.391; 95% confidence interval (CI): 1.249-1.550], arterial partial pressure of carbon dioxide-to-arterial partial pressure of oxygen (PaCO2/PaO2) ratio (odds ratio, 38.397; 95% CI: 6.410-230.013), and respiratory rate-oxygenation (ROX) index (odds ratio, 0.751; 95% CI: 0.616-0.915). The discriminating cutoff point for the new scoring system based on the three risk factors for HFNC 24 h failure was ≥ 2.0 points, with an area under the receiver operating characteristic curve of 0.794 (95% CI, 0.729-0.859, P < 0.001), sensitivity of 68%, and specificity of 79%; similar values were noted on applying the model to the prospective observational cohort comprising 66 patients (AUC = 0.717, 95% CI, 0.675-0.758, sensitivity 83%, specificity 44%, P = 0.009). In this prospective cohort, 11 patients with HFNC failure had an upward trend in PaCO2/PaO2 ratio and downward trends in respiratory failure index (P/F ratio) and ROX index; however, opposite directions of change were observed in 55 patients with HFNC success. Furthermore, the fractional changes (FCs) in PaCO2/PaO2 ratio, P/F ratio, percutaneous oxygen saturation-to-fraction of inspired oxygen (S/F) ratio, and ROX index at 2 h post-HFNC therapy onset were statistically significant between the two groups (all, P < 0.05).

Conclusion: In the pediatric patients with acute respiratory insufficiency, pre-treatment PRISM III score, PaCO2/PaO2 ratio, and ROX index were risk factors for HFNC 24 h failure, and the direction and magnitude of changes in the PaCO2/PaO2 ratio, P/F ratio, and ROX index before and 2 h after HFNC treatment were warning indicators for HFNC 24 h failure. Further close monitoring should be considered for patients with these conditions.

Keywords: acute respiratory insufficiency; high-flow nasal cannula oxygen therapy; pediatrics; respiratory failure; risk factor.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Liu, Li, Luo, Liu, Li and Qiao.

Figures

FIGURE 1

Flow chart of the study. HFNC, high-flow nasal cannula.

FIGURE 2

Receiver operating characteristic curves for the prediction model in the patients with 24 h high-flow nasal cannula failure. Two hundred and eighty-two patients were included in the retrospective cohort (A), 66 in the prospective observational cohort (B), and no overlap was observed between the two cohorts. The discriminated cutoff point for the new scoring system to predict HFNC 24 h failure was ≥ 2 points, with an AUC of 0.794 (95% CI, 0.729–0.859, P < 0.001), sensitivity of 68%, and specificity of 79% in the retrospective cohort (A), and with an AUC of 0.752 (95% CI, 0.603–0.901, P = 0.009), sensitivity of 46%, and specificity of 86% in prospective observational cohort (B). PRISM, pediatric risk of mortality; PaCO2/PaO2, arterial partial pressure of carbon dioxide-to-arterial partial pressure of oxygen; ROX, ratio of percutaneous oxygen saturation and fraction of inspired oxygen to respiratory rate; AUC, area under the curve; CI, confidence interval.

FIGURE 3

Time-course changes of arterial blood gas analysis before and 2, 6, and 12 h after high-flow nasal cannula treatment onset as mean (SD) in the prospective cohort. CI, confidence interval; PaCO2, arterial partial pressure of carbon dioxide; PaO2, arterial partial pressure of oxygen; PaCO2/PaO2, arterial partial pressure of carbon dioxide-to-arterial partial pressure of oxygen; P/F ratio, arterial partial oxygen pressure-to-fraction of inspired oxygen ratio; S/F ratio, percutaneous oxygen saturation-to-fraction of inspired oxygen ratio; ROX, ratio of percutaneous oxygen saturation and fraction of inspired oxygen to respiratory rate. *P < 0.05; **P < 0.001.

FIGURE 4

Fractional changes in blood gas indexes prior to treatment and up to 2 h post-treatment. FC, Fractional change = (data 2 h after HFNC treatment)-(data before HFNC treatment)/data before HFNC treatment; PaCO2, arterial partial pressure of carbon dioxide; PaO2, arterial partial pressure of oxygen; PaCO2/PaO2, arterial partial pressure of carbon dioxide-to-arterial partial pressure of oxygen; P/F ratio, arterial partial oxygen pressure-to-fraction of inspired oxygen ratio; S/F ratio, percutaneous oxygen saturation-to-fraction of inspired oxygen ratio; ROX, ratio of percutaneous oxygen saturation and fraction of inspired oxygen to respiratory rate.