Although mechanical ventilation is a lifesaving intervention, it can have a deleterious effect on the diaphragm. Depending on the mechanical support provided, the diaphragm can be either underloaded, leading to atrophy, or overloaded, leading to load-induced dysfunction. Because of the multifactorial etiology of diaphragmatic dysfunction in critical care, it is difficult to evaluate the dysfunction caused by mechanical ventilation or assess the resulting clinical outcomes. Goligher et al (Am J Respir Crit Care Med. 2018;197:204-213) performed a prospective study of adult patients receiving mechanical ventilation to assess whether diaphragmatic atrophy led to prolonged ventilator dependence and associated complications.
One hundred ninety-one patients who had been mechanically ventilated for < 36 hours at the time of enrollment had at least two ultrasound measurements of diaphragm thickness (Tdi), and were available for primary analysis. Along with daily Tdi measurements, inspiratory effort was estimated by the diaphragm thickening fraction (percentage change in Tdi in the zone of apposition from end-expiration to end-inspiration). The primary outcome studied was time to liberation from ventilation; secondary outcomes included ventilator complications such as reintubation, tracheostomy, prolonged ventilation, and death.
Alterations in Tdi with mechanical ventilation were common, with significant diaphragmatic atrophy (≥ 10% decrease in Tdi) in 41% of patients within a median of 4 days of mechanical ventilation (interquartile range, 3–5) and significant diaphragmatic hypertrophy (≥ 10% increase in Tdi) in 24% of patients.
Decreased Tdi was associated with a lower daily probability of liberation from ventilation (adjusted hazard ratio 0.69 per 10% decrease in Tdi; 95% CI, 0.54–0.87), prolonged ICU admission (adjusted duration ratio, 1.71; 95% CI, 1.29–2.27), and a higher risk of complications (adjusted odds ratio, 3.00; 95% CI, 1.34–6.72). However, an increase in Tdi (n = 47; 24%) was also predictive of prolonged (≥ 3 weeks) mechanical ventilation (adjusted duration ratio, 1.38; 95% CI, 1.00–1.90). Decreased Tdi was related to abnormally low inspiratory effort, and increased Tdi was related to grossly excessive effort. Notably, the duration of ventilation was shortest in patients with inspiratory efforts most similar to breathing at rest (between 15% and 30%) during the first 3 days of ventilation.
This study confirms prior findings of mechanical ventilation-induced diaphragmatic dysfunction seen in animal models. However, this study has some limitations, including possible unmeasured patient or illness characteristics that could have confounded the results, an absence of diaphragm muscle biopsies to provide histologic confirmation, some missing Tdi measurements, technical challenges and limitations in measurements, and no post-hospital outcomes.
Despite its limitations, there are important conclusions that should be drawn from this study, namely, that the development of either diaphragmatic atrophy or hypertrophy is associated with prolonged ventilator dependence, and that patients with inspiratory efforts most similar to those of healthy people at rest experienced the shortest duration of mechanical ventilation.
Some intriguing questions now present themselves, among them: What is the best way to prevent diaphragm atrophy/hypertrophy? What is the best ventilator strategy to approximate normal breathing at rest? Do conventional lung-protective strategies protect or injure the diaphragm? What is the optimal ventilator strategy for both lung and diaphragm?
Coauthors of this installment of Concise Critical Appraisal:
Parag Chaudhari, MD, is a pulmonary and critical care fellow at Tulane University School of Medicine.
Inderpal Thethi, MD, is a pulmonary and critical care fellow at Tulane University School of Medicine.
Nathan D. Nielsen, MD, MSc, is an associate professor in the Section of Pulmonary Disease, Critical Care, and Environmental Medicine at Tulane University School of Medicine. Dr. Nielsen is an editor of Concise Critical Appraisal.