Therapeutic benefits of proning to improve pulmonary gas exchange in severe respiratory failure: focus on fundamentals of physiology.

NEW FINDINGS: What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its 'natural' posture, and thus optimises the ventilation-perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life-threatening hypoxaemia in COVID-19 and other types of critical illness with respiratory failure. ABSTRACT: The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID-19-associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation-perfusion ( V ̇ A -- Q ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ ) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral-to-dorsal) V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient is present in both postures, but with better V ̇ A -- Q ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ matching in the prone position. In ARDS and CARDS, the vertical V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life-threatening hypoxaemia in patients with ARDS and CARDS.

Protective potential of high-intensity interval training on cardiac structure and function after COVID-19: protocol and statistical analysis plan for an investigator-blinded randomised controlled trial.

INTRODUCTION: COVID-19 is associated with a marked systemic inflammatory response with concomitant cardiac injury and remodelling, but it is currently unknown whether the latter is reversible. Given that high-intensity interval training (HIIT) is a powerful stimulus to improve cardiorespiratory fitness while also eliciting marked anti-inflammatory effects, it may be an important countermeasure of reducing cardiopulmonary morbidity following COVID-19. METHODS AND ANALYSIS: 40 COVID-19 survivors who have been discharged from hospital will be included in this investigator-blinded randomised study with a 12-week HIIT intervention. Patients will be 1:1 block-randomised by sex to either a supervised HIIT exercise group or standard care (control group). The main hypothesis is that a 12-week HIIT scheme is a safe way to improve loss of cardiac mass and associated cardiorespiratory fitness, despite hypothesised limited HIIT-induced changes in conventional lung function indices per se. Ultimately, we hypothesise that the HIIT scheme will reduce post-COVID-19 symptoms and improve quality of life. ETHICS AND DISSEMINATION: This study is approved by the Scientific Ethical Committee at the Capital Region of Denmark (H-20033733, including amendments 75068 and 75799) and registered at ClinicalTrials.gov (NCT04647734, pre-results). The findings will be published in a peer-reviewed journal, including cases of positive, negative and inconclusive results.Trial registration number NCT04549337.

Fidelity, tolerability and safety of acute high-intensity interval training after hospitalisation for COVID-19: a randomised cross-over trial.

OBJECTIVES: Many patients with COVID-19 suffer from persistent symptoms, many of which may potentially be reversed by high-intensity interval training (HIIT). Yet, the safety and tolerability of HIIT after COVID-19 is controversial. This study aimed to investigate the fidelity, tolerability and safety of three different HIIT protocols in individuals that had recently been hospitalised due to COVID-19. METHODS: The study was a randomised cross-over trial. We compared three supervised HIIT protocols (4×4, 6×1, 10-20-30) in 10 individuals recently discharged after hospitalisation for severe COVID-19. Each HIIT protocol had a duration of 38 min and was performed with a 1-week washout between them. Outcomes included adverse events, exercise training intensity and tolerability assessed by the Likert scale (1-10). RESULTS: All 10 participants aged 61 (mean, SD 8) years (5 males) completed all three HIIT protocols with no adverse events. High intensities were achieved in all three protocols, although they differed in terms of time spent with a heart rate ≥85% of maximum (mean (SD); 4×4: 13.7 (6.4) min; 10-20-30: 12.1 (3.8) min; 6×1: 6.1 (5.6) min; p=0.03). The three protocols were all well tolerated with similar Likert scale scores (mean (SD); 4×4: 8 (2), 10-20-30: 8 (2), 6×1: 9 (2), p=0.72). CONCLUSION: Our findings indicate that recently hospitalised individuals for severe COVID-19 may safely tolerate acute bouts of supervised HIIT as per protocol. This warrants future studies testing the potential of regular HIIT as a rehabilitation strategy in this context.