© 2003 American Thoracic Society
Weaning Failure, Muscle Injury, and FatigueTo the Editor:Dr. Laghi (1) and colleagues have made some interesting measurements in patients undergoing weaning trials in the intensive care unit. They have attempted to avoid any of the inherent problems with measuring twitch pressure including twitch potentiation (2) and changes in geometry of the chest wall. The subjects who failed the weaning trial did not show a drop in twitch pressure, which suggested to the authors that low frequency fatigue, which the authors equate with injury of the diaphragm, is not responsible for the subjects' weaning failure. These subjects did reach a pressure–time index where the diaphragm would be anticipated to be contracting at fatiguing levels—i.e., pressure–time index of 0.17 to 0.22. This pressure–time index was maintained for 44 minutes. The weaning trials were stopped because the patients developed signs of distress, which, according to the authors' calculations, may have occurred before fatigue developed. Although these patients may have been put back on mechanical ventilation before developing fatigue, fatigue as evidenced by reduced force immediately after exertion should not be taken as an indication to exclude muscle injury. Injured muscles do not develop immediate evidence of force loss (3). Indeed, the injurious contraction initiates a process of inflammation and repair that takes place over days to weeks. The force loss with muscle injury can be detected with both high and low frequency electrical stimulation. After injurious muscle contraction, the maximum force loss occurs at a time when muscle enzyme release peaks, as does the symptom of muscle soreness, usually three days after the injury (3–6). Indeed, we have found negligible drops in transdiaphragmatic pressure generation (force–frequency curves) in an animal model of diaphragmatic injury immediately after the inspiratory loading protocol (3). However, three days later, there is quite marked force loss at both high and low frequencies that approximates 40%, but we found no difference in twitch force until after the second IRL on Day 3 (3). These values are obtained during supramaximal epiphrenic stimulation. Muscle biopsies in this animal model reveal muscle fiber necrosis and inflammation. Recovery from muscle injury takes at least two weeks, is well documented in human limb muscles (4, 5), and has been shown to occur in the diaphragm (6). Thus, although diaphragm function as measured by twitch Pdi is not reduced after weaning failure in these patients, this does not exclude the possibility of diaphragm injury.
a Department of Medicine University of British Columbia Vancouver, British Columbia, Canada REFERENCES
From the Authors: Dr. Road and colleagues ask a critical question about the pathophysiology of weaning failure: Is the load on the respiratory muscles sufficient to cause respiratory muscle damage? Their question is of fundamental importance. Were patients to develop respiratory muscle injury during a failed weaning trial, this new injury could become the ultimate determinant of whether the ventilator is discontinued. Excessive mechanical load on muscles can cause short-lasting, high-frequency fatigue, long-lasting, low-frequency fatigue (1), and early (2) and delayed muscle injury (3). An inspiratory load that induces visible injury on light microscopy of the diaphragm has to be extremely large (3). Even loads sufficient to cause acute hypercapnic respiratory failure (arterial carbon dioxide tension of 95 mm Hg and pH of 7.14) did not cause visible diaphragmatic injury in the study of Jiang and collaborators (3). None of our weaning failure patients (4) developed that degree of respiratory acidosis (3). It is thus unlikely, and perhaps impossible, that a failed weaning trial can in itself cause sufficient stress to inflict diaphragmatic damage (4). If low-frequency fatigue and muscle damage are not responsible for weaning failure, what is? We can only speculate. The massive recruitment of ribcage and expiratory muscles in weaning failure patients (4) probably represents an integrated response by the respiratory centers to prevent the type of muscle damage to which Dr. Road and colleagues are referring. Another vital aspect, often overlooked in research on respiratory muscle failure, is the presence of an intensivist who reinstitutes mechanical ventilation before a patient reaches respiratory extremis. That fundamental intervention is not replicated in most (if not all) animal studies of severe respiratory loading, which often continue to respiratory arrest. What is the direction for future research on respiratory muscles in weaning? At least three aspects need to be addressed. First, could insults to the respiratory muscles before the first weaning trial—such as sepsis (5) or ventilator-associated muscle injury (6)—influence weaning outcome? Second, does high-frequency fatigue play a role in causing weaning failure? Third, can we identify treatments that improve respiratory muscle function and therefore improve outcome in the difficult-to-wean patient?
Division of Pulmonary and Critical Care Medicine Edward Hines Jr. Veterans Administration Hospital Loyola University of Chicago Stritch School of Medicine Hines, Illinois FOOTNOTES Conflict of Interest Statement: F.L. has no declared conflict of interest; M.J.T. has no declared conflict of interest. REFERENCES
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