Experimental and pilot clinical data suggest that spontaneously breathing patients with sepsis and septic shock may present increased respiratory drive and effort, even in the absence of pulmonary infection. The study hypothesis was that respiratory drive and effort may be increased in septic patients and correlated with extrapulmonary determinant and that high-flow nasal cannula may modulate drive and effort.


Twenty-five nonintubated patients with extrapulmonary sepsis or septic shock were enrolled. Each patient underwent three consecutive steps: low-flow oxygen at baseline, high-flow nasal cannula, and then low-flow oxygen again. Arterial blood gases, esophageal pressure, and electrical impedance tomography data were recorded toward the end of each step. Respiratory effort was measured as the negative swing of esophageal pressure (ΔPes); drive was quantified as the change in esophageal pressure during the first 500 ms from start of inspiration (P0.5). Dynamic lung compliance was calculated as the tidal volume measured by electrical impedance tomography, divided by ΔPes. The results are presented as medians [25th to 75th percentile].


Thirteen patients (52%) were in septic shock. The Sequential Organ Failure Assessment score was 5 [4 to 9]. During low-flow oxygen at baseline, respiratory drive and effort were elevated and significantly correlated with arterial lactate (r = 0.46, P = 0.034) and inversely with dynamic lung compliance (r = –0.735, P < 0.001). Noninvasive support by high-flow nasal cannula induced a significant decrease of respiratory drive (P0.5: 6.0 [4.4 to 9.0] vs. 4.3 [3.5 to 6.6] vs. 6.6 [4.9 to 10.7] cm H2O, P < 0.001) and effort (ΔPes: 8.0 [6.0 to 11.5] vs. 5.5 [4.5 to 8.0] vs. 7.5 [6.0 to 12.6] cm H2O, P < 0.001). Oxygenation and arterial carbon dioxide levels remained stable during all study phases.


Patients with sepsis and septic shock of extrapulmonary origin present elevated respiratory drive and effort, which can be effectively reduced by high-flow nasal cannula.

Editor’s Perspective
What We Already Know about This Topic
  • Increases in respiratory drive and effort in critically ill patients may place the patient at higher risk for respiratory failure and intubation.
  • The authors have previously shown that respiratory drive and effort are significantly increased in patients with pulmonary infection and that support by high-flow nasal cannula significantly reduces this increase relative to low-flow oxygen therapy.
  • Whether respiratory drive is increased and the effect of high-flow nasal cannula in patients with extrapulmonary sepsis remain unknown.
What This Article Tells Us That Is New
  • Respiratory drive and effort and dynamic lung compliance were evaluated in 25 nonintubated patients with extrapulmonary sepsis or septic shock using arterial blood gases, esophageal pressure monitoring, and electrical impedance tomography at baseline with low flow nasal oxygen therapy during high-flow nasal cannula support and again with low-flow nasal oxygen therapy. Patient comfort was evaluated using a 10-point visual analog scale at each step.
  • High-flow nasal oxygen therapy significantly reduced elevated respiratory drive and effort.
  • There was no correlation between patient perceived comfort and measures of drive and effort.
  • The impact of the findings from this physiologic study on patient outcome remain to be determined.