Atrophy of Diaphragm Muscle Fibers in Mechanically Ventilated Patients
July 1, 2008 3 minutes read
Atrophy of Diaphragm Muscle Fibers in Mechanically Ventilated Patients
Abstract & Commentary
By Richard J. Wall, MD, MPH, Pulmonary Critical Care & Sleep Disorders Medicine, Southlake Clinic, Valley Medical Center, Renton, WA, is Associate Editor for Critical Care Alert.
Dr. Wall reports no financial responsibility to this field of study.
Synopsis: In this small case series, the authors showed that the combination of complete diaphragm inactivity and mechanical ventilation leads to disuse atrophy of diaphragm muscle fibers.
Source: Levine S, et al. N Engl J Med. 2008;358(13): 1327-1335.
Clinicians generally believe that mechanical ventilation rests and restores the respiratory muscles in acute respiratory failure. However, animal studies have challenged this notion by showing that the combination of complete diaphragmatic inactivity and prolonged mechanical ventilation may lead to atrophy of diaphragm muscle fibers. In the current study, Levine and colleagues sought to determine whether such changes occur in the human diaphragm.
The authors compared diaphragm biopsies from 14 brain-dead organ donors (case subjects) and 8 living control subjects. The biopsies were obtained from the donors before harvest and from the controls as they underwent lung resection for a benign lesion or stage 1 cancer. The brain-dead cases had received full ventilatory support (ie, no diaphragm activity) for 18-69 hours whereas the control subjects had received only 2-3 hours of mechanical ventilation. The biopsy specimens were examined using histologic, biochemical, and gene-expression techniques. This included measuring muscle fiber size, markers of oxidative stress, and muscle degradation.
Overall, the cases showed marked diaphragm muscle atrophy. The slow-twitch fibers in the cases were 57% smaller (p = 0.001) and the fast-twitch fibers were 53% smaller (p = 0.01). Total glutathione concentrations were 23% lower in cases (p = 0.01), consistent with increased oxidative stress. Caspase expression was higher in cases (p = 0.03), consistent with increased muscle proteolysis. Finally, cases had higher levels of atrogin-1 and MuRF-1 (0 values, 0.002 and 0.001, respectively), two mRNA markers of muscle degradation.
Commentary
It is widely accepted that respiratory muscle weakness is one of many factors leading to respiratory failure. Twenty years ago, this concept encouraged the use of ventilator modes such as continuous mandatory ventilation (CMV). In CMV, volume-cycled breaths are delivered at preset intervals, regardless of patient effort. Because CMV is uncomfortable for patients with spontaneous respiratory efforts, it has given way to assist-control (AC). In fact, CMV is rarely used except in paralyzed or apneic patients. In the current study, cases were placed on CMV because they were brain dead.
To understand the historical context of this study, one must recognize that the original ventilators were designed for patients who developed nonparenchymal respiratory failure (eg, polio). As ICUs became more commonplace, the principles of those early ventilators were applied to patients with respiratory failure from parenchymal disorders such as COPD, pneumonia, and ARDS. In the absence of adequate research, mode selection was often based upon the available machine, operator experience, or tradition. For many years, CMV was a predominant mode in ICUs.
In medical-surgical ICUs today, patients are rarely placed on CMV. For example, in my institution, our newly purchased ventilators don't even have this option. We typically use volume-targeted AC, airway pressure-release ventilation (APRV), pressure-controlled ventilation (PCV), intermittent mandatory ventilation (IMV), or pressure support. All of these modes permit spontaneous breathing by the patient. In other words, my ICU patients almost never have complete diaphragm inactivity. Given the trend towards lighter sedation and daily awakening, even patients receiving "full support" for ARDS are exhibiting some spontaneous breaths.
Thus, while the current study is thought provoking, I am uncertain whether it really applies to current practice because it does not provide answers to key questions such as: Is one ventilator mode better for the diaphragm than another? How often does a patient need to spontaneously breathe in order to avoid diaphragm atrophy? How do the various ventilator modes interact with other factors such as neuromuscular blockade and corticosteroids? Hopefully, we will start unraveling these questions in the next few years.
Clinicians generally believe that mechanical ventilation rests and restores the respiratory muscles in acute respiratory failure.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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