# Effect of decreasing respiratory rate on the mechanical power of ventilation and lung injury biomarkers: a randomized cross-over clinical study in COVID-19 ARDS patients

## TL;DR

This study found that lowering the breathing rate in ventilated COVID-19 ARDS patients reduces mechanical power but does not lower lung injury biomarkers.

## Contribution

The study is the first to investigate the effect of reduced respiratory rate on mechanical power and lung injury biomarkers in a randomized cross-over design in COVID-19 ARDS patients.

## Key findings

- Lower respiratory rate significantly reduced mechanical power of ventilation in ARDS patients.
- No significant differences were observed in inflammatory or lung injury biomarkers between lower and higher respiratory rates.
- Cardiac function and respiratory mechanics were unaffected by changes in respiratory rate.

## Abstract

The respiratory rate (RR) is a key determinant of the mechanical power of ventilation (MP). The effect of reducing the RR on MP and its potential to mitigate ventilator-induced lung injury remains unclear.

To compare invasive ventilation using a lower versus a higher RR with respect to MP and plasma biomarkers of lung injury in COVID-19 ARDS patients.

In a randomized cross-over clinical study in COVID-19 ARDS patients, we compared ventilation using a lower versus a higher RR in time blocks of 12 h. Patients were ventilated with tidal volumes of 6 ml/kg predicted body weight, and positive-end-expiratory pressure and fraction of inspired oxygen according to an ARDS network table. Respiratory mechanics and hemodynamics were assessed at the end of each period, and blood samples were drawn for measurements of inflammatory cytokines, epithelial and endothelial lung injury markers. In a subgroup of patients, we performed echocardiography and esophageal pressure measurements.

We enrolled a total of 32 patients (26 males [81%], aged 52 [44–64] years). The median respiratory rate during ventilation with a lower and a higher RR was 20 [16–22] vs. 30 [26–32] breaths/min (p < 0.001), associated with a lower median minute ventilation (7.3 [6.5–8.5] vs. 11.6 [10–13] L/min [p < 0.001]) and a lower median MP (15 [11–18] vs. 25 [21–32] J/min [p < 0.001]). No differences were observed in any inflammatory (IL-6, IL-8, and TNF-R1), epithelial (s-RAGE and SP-D), endothelial (Angiopoietin-2), or pro-fibrotic activity (TGF-ß) marker between high or low RR. Cardiac function by echocardiography, and respiratory mechanics using esophageal pressure measurements were also not different.

Reducing the respiratory rate decreases mechanical power in COVID-19 ARDS patients but does not reduce plasma lung injury biomarkers levels in this cross-over study.

Study registration This study is registered at clinicaltrials.gov (study identifier NCT04641897)

The online version contains supplementary material available at 10.1186/s40635-025-00782-4.