High flow nasal cannula (HFNC) with Heliox decreases diaphragmatic injury in a newborn porcine lung injury model

Abstract

Background: High flow nasal cannula (HFNC) improves ventilation by washing out nasopharyngeal dead space while delivering oxygen. Heliox (helium-oxygen gas mixture), a low-density gas mixture, decreases resistance to airflow, reduces the work of breathing, and facilitates distribution of inspired gas. Excessive lung work and potential injury increases the workload on the immature diaphragm predisposing the muscle to fatigue, and can lead to inflammatory and oxidative stress, thereby contributing to impaired diaphragmatic function. We tested the hypothesis that HFNC with Heliox will decrease the work of breathing thereby unloading the neonatal diaphragm, and potentially reducing diaphragmatic injury.

Methods: Spontaneously breathing neonatal pigs were randomized to Nitrox (nitrogen-oxygen gas mixture) or Heliox, and studied over 4 hr following oleic acid injury. Gas exchange, pulmonary mechanics indices, and systemic markers of inflammation were measured serially. Diaphragm inflammation biomarkers and histology for muscle injury were assessed at termination.

Results: Heliox breathing animals demonstrated decreased respiratory load and work of breathing with lower pressure-rate product, lower labored breathing index, and lower levels of diaphragmatic inflammatory markers, and muscle injury score as compared to Nitrox.

Conclusion: These results suggest that HFNC with Heliox is a useful adjunct to attenuate diaphragmatic fatigue in the presence of lung injury by unloading the diaphragm, resulting in a more efficient breathing pattern, and decreased diaphragm injury.

Keywords: diaphragm injury; helium-oxygen (Heliox); high flow nasal cannula (HFNC); lung injury.

© 2014 Wiley Periodicals, Inc.

Figures

Figure 1

Lung physiological profile (mean ± SEM) in Heliox group (solid line with open triangles) vs Nitrox group (dashed line with open squares) from post lung injury and over 1 through 4 hours. (a) No significant difference in pH between the two groups (P = 0.21). (b) PaCO2 was lower for Heliox group, though over time did not reach statistical significance (P = 0.34). (c) PaO2 level was higher for Heliox group at all time points from hour 1 through 4, though not statistically significant (P = 0.64). (d) FIO2 requirement was similar between both groups (P = 0.43).

Figure 2

Pressure rate product (PRP) and percentage change of this parameter from baseline injury (BI) over time (post injury-50% FIO2 and over hour 1 through 4) in Heliox group (solid line with open triangles) vs Nitrox group (dashed line with open squares). (a) Pressure rate product values trended lower in the heliox group (P = 0.06). (b) Percentage change in PRP normalized to baseline injury on y-axis plotted against post injury and over 4 hours of spontaneous breathing. Heliox group has significantly greater percentage drop in pressure rate product over time (* P < 0.01).

Figure 3

Labored Breathing Index (LBI) and percentage change of this parameter from baseline injury (BI) over time (post injury-50% FIO2 and over hour 1 through 4) in Heliox group (solid line with open triangles) vs Nitrox group (dashed line with open squares). (a) Heliox group compared to Nitrox group had significantly lower LBI values over time (* P < 0.01). (b) Percentage change in LBI normalized to baseline injury on y-axis plotted against time from post injury and over 4 hours of spontaneous breathing. Heliox group has significantly greater percentage drop in LBI over time (* P < 0.01).

Figure 4

Diaphragm Myeloperoxidase (MPO) and interleukin 8 (IL-8) levels after 4 hours of oleic acid injury in Heliox and Nitrox groups are presented as normalized for total protein concentration in the diaphragm. (a) MPO trended lower in the Heliox group compared to Nitrox group, not statistically significant (P 0.07). (b) IL-8 levels were significantly lower in the Heliox group after 4 hours of spontaneous breathing, post oleic acid injury (* P

Figure 5

Diaphragm muscle injury score (MIS), cross-sectional muscle fiber diameter and H & E stained cross-sections of diaphragm. (Clear bars are Nitrox breathing animals and dashed bars are Heliox breathing). (a) Muscle injury Score comparing nitrox to heliox sections. Muscle Injury was attenuated in heliox breathing pigs compared to nitrox group (* P 0.05). (c & d) H&E stained cross-sections of diaphragm (magnification 400x) obtained from one newborn pig in each group. (c) Nitrox section, arrows points to uneven staining and fragmented fibers. (d) Heliox section showing more uniform staining and less fragmentation.