Bench-to-bedside review: Weaning failure – should we rest the respiratory muscles with controlled mechanical ventilation?

The use of controlled mechanical ventilation (CMV) in patients who experience weaning failure after a spontaneous breathing trial or after extubation is a strategy based on the premise that respiratory muscle fatigue (requiring rest to recover) is the cause of weaning failure. Recent evidence, however, does not support the existence of low frequency fatigue (the type of fatigue that is long-lasting) in patients who fail to wean despite the excessive respiratory muscle load. This is because physicians have adopted criteria for the definition of spontaneous breathing trial failure and thus termination of unassisted breathing, which lead them to put patients back on the ventilator before the development of low frequency respiratory muscle fatigue. Thus, no reason exists to completely unload the respiratory muscles with CMV for low frequency fatigue reversal if weaning is terminated based on widely accepted predefined criteria. This is important, since experimental evidence suggests that CMV can induce dysfunction of the diaphragm, resulting in decreased diaphragmatic force generating capacity, which has been called ventilator-induced diaphragmatic dysfunction (VIDD). The mechanisms of VIDD are not fully elucidated, but include muscle atrophy, oxidative stress and structural injury. Partial modes of ventilatory support should be used whenever possible, since these modes attenuate the deleterious effects of mechanical ventilation on respiratory muscles. When CMV is used, concurrent administration of antioxidants (which decrease oxidative stress and thus attenuate VIDD) seems justified, since antioxidants may be beneficial (and are certainly not harmful) in critical care patients.     

Bench-to-bedside review: Weaning failure – should we rest the respiratory muscles with controlled mechanical ventilation?

The use of controlled mechanical ventilation (CMV) in patients who experience weaning failure after a spontaneous breathing trial or after extubation is a strategy based on the premise that respiratory muscle fatigue (requiring rest to recover) is the cause of weaning failure. Recent evidence, however, does not support the existence of low frequency fatigue (the type of fatigue that is long-lasting) in patients who fail to wean despite the excessive respiratory muscle load. This is because physicians have adopted criteria for the definition of spontaneous breathing trial failure and thus termination of unassisted breathing, which lead them to put patients back on the ventilator before the development of low frequency respiratory muscle fatigue. Thus, no reason exists to completely unload the respiratory muscles with CMV for low frequency fatigue reversal if weaning is terminated based on widely accepted predefined criteria. This is important, since experimental evidence suggests that CMV can induce dysfunction of the diaphragm, resulting in decreased diaphragmatic force generating capacity, which has been called ventilator-induced diaphragmatic dysfunction (VIDD). The mechanisms of VIDD are not fully elucidated, but include muscle atrophy, oxidative stress and structural injury. Partial modes of ventilatory support should be used whenever possible, since these modes attenuate the deleterious effects of mechanical ventilation on respiratory muscles. When CMV is used, concurrent administration of antioxidants (which decrease oxidative stress and thus attenuate VIDD) seems justified, since antioxidants may be beneficial (and are certainly not harmful) in critical care patients.     

Bench-to-bedside review: weaning failure--should we rest the respiratory muscles with controlled mechanical ventilation?

The use of controlled mechanical ventilation (CMV) in patients who experience weaning failure after a spontaneous breathing trial or after extubation is a strategy based on the premise that respiratory muscle fatigue (requiring rest to recover) is the cause of weaning failure. Recent evidence, however, does not support the existence of low frequency fatigue (the type of fatigue that is long-lasting) in patients who fail to wean despite the excessive respiratory muscle load. This is because physicians have adopted criteria for the definition of spontaneous breathing trial failure and thus termination of unassisted breathing, which lead them to put patients back on the ventilator before the development of low frequency respiratory muscle fatigue. Thus, no reason exists to completely unload the respiratory muscles with CMV for low frequency fatigue reversal if weaning is terminated based on widely accepted predefined criteria. This is important, since experimental evidence suggests that CMV can induce dysfunction of the diaphragm, resulting in decreased diaphragmatic force generating capacity, which has been called ventilator-induced diaphragmatic dysfunction (VIDD). The mechanisms of VIDD are not fully elucidated, but include muscle atrophy, oxidative stress and structural injury. Partial modes of ventilatory support should be used whenever possible, since these modes attenuate the deleterious effects of mechanical ventilation on respiratory muscles. When CMV is used, concurrent administration of antioxidants (which decrease oxidative stress and thus attenuate VIDD) seems justified, since antioxidants may be beneficial (and are certainly not harmful) in critical care patients.     

Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm

Introduction  

Controlled mechanical ventilation (CMV) induces profound modifications of diaphragm protein metabolism, including muscle atrophy and severe ventilator-induced diaphragmatic dysfunction. Diaphragmatic modifications could be decreased by spontaneous breathing. We hypothesized that mechanical ventilation in pressure support ventilation (PSV), which preserves diaphragm muscle activity, would limit diaphragmatic protein catabolism.     

Preserving spontaneous breathing during mechanical ventilatory support: an old yet fascinating story

Facilitation of early spontaneous breathing activity is the most important measure to shorten weaning and avoid ventilator-induced lung injury and diaphragmatic injury in mechanically ventilated patients. However, the optimal degree of spontaneous muscle activity and ventilator support remains to be determined. Furthermore, effectiveness in relation to the pathophysiology of respiratory failure is unclear. In this regard the experimental study by Saddy and colleagues reveals interesting insights into the pathophysiology of ventilator-induced injury. More important, their results raise important questions that should be evaluated in further studies.In a recent issue of Critical Care, Saddy and colleagues [1] present an important article on the impact of partial ventilatory support on lung tissue inflammation and diaphragm dysfunction in mechanically ventilated rats. Their data reveal surprising results, in particular showing that the degree of diaphragmatic injury may depend not only on the amount of spontaneous respiratory activity preserved by applying specific settings of mechanical support, but also on the etiology of acute lung injury; that is, pulmonary versus extrapulmonary acute respiratory distress syndrome (ARDS). The present article reminds us that the question posed by Milic-Emili in a commentary published nearly 30 years ago as to whether weaning is an art or a science [2] is still valid, albeit a substantial body of available evidence now clearly explains several pathophysiological details of respiratory muscle failure in ICU patients [3,4].Of course, the relevance of animal models in translational research may always be questioned. This is particularly the case for rodent models, as the validity of the inflammatory response in these species as a model for human diseases has been challenged very recently [5]. Furthermore, respiratory mechanics widely differs between humans and rodents, as suggested, for example, by the different physiological respiratory rates that are relatively higher in the latter species and may, therefore, influence gas transport and exchange [6]. Nevertheless, the present study has the major merits of, firstly, having included diaphragm function and morphology (a relevant topic that still deserves fundamental research), and, secondly, having quantified diaphragmatic activity under different experimental conditions by means of the pressure–time product. This variable is calculated by tracing the esophageal pressure and is therefore particularly challenging to measure in small animals, but it is close to clinical reality as it is fairly well accessible in humans and may therefore support translating experimental results into clinical conditions [7].Taken together, the present data confirm, in principle, the well accepted notions that passive mechanical ventilation quickly damages the diaphragm [8] and promotes lung injury by atelectasis formation [9]. However, they also reveal that the impact of mechanical ventilation may be more difficult to explain, especially in extrapulmonary ARDS. In fact, under partial spontaneous breathing combined with low degree of ventilator support the authors observed an unexpected increase in diaphragmatic injury whereas atelectasis formation decreased comparable to pulmonary ARDS.These fairly surprising results may remind us that the impact of mechanical ventilation on lung tissue and the diaphragm is still far from being completely understood and merit intensive study in the future. In particular, some effort should be spent reproducing in the experimental conditions factors that potentially influence the response to mechanical ventilation in clinical settings. For example, most ICU patients are affected by co-existing diseases, especially cardiovascular diseases, diabetes, and chronic obstructive pulmonary disease, which, independent of the acute condition, also influence the muscular and diaphragmatic function and may even accentuate the impact of mechanical ventilation.Animal models mimicking conditions of co-existing chronic diseases should therefore be recommended to improve translation of experimental data into clinical situations and may be considered as the next step in studying the impact of mechanical ventilation and partial spontaneous breathing on diaphragm and lung tissue. Furthermore, most patients requiring mechanical ventilator support are affected by septic conditions leading to organ dysfunction and metabolic disorders. The utility of partial spontaneous breathing for maintaining diaphragmatic function has been well demonstrated in several experiments and nicely confirmed in the present study, but the effects of spontaneous breathing under septic conditions still need to be investigated. Finally, it is well known that not only restriction of passive movement but also muscular overload due to increased work of breathing may cause structural diaphragmatic damage that is characteristic for weaning failure. Thus, another important task of further studies is to find the perfect balance between diaphragmatic loading and unloading with regard to diaphragmatic and pulmonary function. In this context it will be interesting to see if modern spontaneous breathing modes may find their role in future concepts of lung and diaphragmatic protective ventilation strategies.In summary, the present article improves our knowledge in a fundamental topic of critical care and should encourage us to further study the influence of mechanical ventilatory support on lung tissue and diaphragm function, which is likely to be an important key to improving patient outcome in the ICU.     

Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm

Common medical conditions that require mechanical ventilation include chronic obstructive lung disease, acute lung injury, sepsis, heart failure, drug overdose, neuromuscular disorders, and surgery. Although mechanical ventilation can be a life saving measure, prolonged mechanical ventilation can also present clinical problems. Indeed, numerous well-controlled animal studies have demonstrated that prolonged mechanical ventilation results in diaphragmatic weakness due to both atrophy and contractile dysfunction. Importantly, a recent clinical investigation has confirmed that prolonged mechanical ventilation results in atrophy of the human diaphragm. This mechanical ventilation-induced diaphragmatic weakness is important because the most frequent cause of weaning difficulty is respiratory muscle failure due to inspiratory muscle weakness and/or a decline in inspiratory muscle endurance. Therefore, developing methods to protect against mechanical ventilation-induced diaphragmatic weakness is important.     

Ventilator-induced diaphragm dysfunction: the clinical relevance of animal models

Experimental evidence suggests that controlled mechanical ventilation (CMV) can induce dysfunction of the diaphragm, resulting in an early-onset and progressive decrease in diaphragmatic force-generating capacity, called ventilator-induced diaphragmatic dysfunction (VIDD). The mechanisms of VIDD are not fully elucidated, but include muscle atrophy (resulting from lysosomal, calpain, caspase and proteasome activation), oxidative stress, structural injury (disrupted myofibrils, increased numbers of lipid vacuoles, and abnormally small and disrupted mitochondria), myofiber remodeling and mitochondrial dysfunction. The major clinical implication of the VIDD is to limit the use of CMV to the extent possible. Partial (assisted) modes of ventilatory support should be used whenever feasible, since these modes attenuate the deleterious effects of mechanical ventilation on respiratory muscles. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Diaphragmatic dysfunction in the intensive care unit: caught in the cross-fire between sepsis and mechanical ventilation

Accumulating evidence indicates that diaphragmatic weakness is common and frequently severe in mechanically ventilated patients. Supinski and Callahan now report that infection is a major risk factor for diaphragmatic weakness in this patient population. Importantly, they show that patients with the greatest levels of diaphragmatic dysfunction have a much poorer prognosis in terms of more prolonged ventilation as well as higher mortality. Mechanical ventilation itself has also been found to induce diaphragmatic weakness along with cellular changes resembling those found in sepsis. Future studies should be directed at understanding the interaction between sepsis and mechanical ventilation, and to developing therapeutic approaches that target their common cellular pathways implicated in diaphragmatic weakness.Mechanical ventilation is one of the most frequently employed interventions in the intensive care unit (ICU). Although it is a life-saving measure, much time and effort is spent in trying to wean patients from the ventilator as quickly as possible, since mechanical ventilation is also a cause of numerous complications. In a recent issue of Critical Care, Supinski and Callahan [1] report that infection is a significant risk factor for diaphragmatic weakness and failure to wean patients from mechanical ventilation. The authors employed state of the art methods (transdiaphragmatic pressure measurements during bilateral magnetic stimulation of the phrenic nerves), and found that patients with evidence of infection had less than half the diaphragmatic pressure-generating ability of uninfected patients. In addition, patients with the most severe diaphragmatic weakness had a markedly worse prognosis. This consisted not only of a more prolonged need for ventilator support, but was also reflected in substantially higher mortality. Indeed, diaphragmatic function appeared to be a better prognostic indicator than other more conventional indices of critical illness severity, such as the Sequential Organ Failure Assessment score. Interestingly, the treating physicians in the ICU dramatically underestimated (in 90% of patients) the degree of diaphragmatic weakness present in their mechanically ventilated patients.These findings should be an eye opener for practicing clinicians. They point to a need for greater awareness of the very high prevalence of diaphragmatic weakness in mechanically ventilated patients. The inability to successfully wean patients from mechanical ventilation has been closely linked to an unfavorably elevated level of the respiratory muscle work load/capacity ratio [2,3]. Although great emphasis is appropriately placed upon reducing the numerator in this relationship through attempts at improving respiratory system mechanics, the denominator (reflecting respiratory muscle function) is more difficult to assess and often neglected. Nevertheless, several studies have now shown that diaphragmatic weakness is common and frequently profound in mechanically ventilated patients [4-6], although the precise reasons for this are not well understood.Based upon the fact that even uninfected patients in the study by Supinski and Callahan exhibited a large decrease (to approximately 50% of normal values) of diaphragmatic force-generating capacity, it seems clear that a major component of the diaphragmatic weakness observed in mechanically ventilated patients must be caused by additional factors other than infection. In this regard, another recent study reported that diaphragmatic weakness was present on the very first day of admission to the ICU in patients requiring mechanical ventilation for a variety of conditions, including, but not limited to, sepsis [7]. The study by Supinski and Callahan did not specifically evaluate the time course for developing diaphragmatic dysfunction, either from the time of ICU admission and initiation of mechanical ventilation, or from the onset of infection. When taken together, however, the above studies strongly suggest that diaphragmatic dysfunction constitutes a distinct, common, and under-recognized form of organ failure that occurs with many types of critical illness, and especially during sepsis.The results of these studies in ICU patients are also consistent with a large body of data from different animal models, which have consistently demonstrated impaired diaphragmatic function during sepsis [8]. There is limited information about the impact of mechanical ventilation upon sepsis-induced diaphragmatic dysfunction, but the interaction between the two appears to be complex. Although mechanical ventilation may mitigate the adverse effects of sepsis upon diaphragmatic function and oxygen demand to the muscle very early in its course [9], there are several reasons to believe that mechanical ventilation will either worsen or impede recovery from sepsis-induced diaphragmatic dysfunction over the longer term. In this regard, mechanical ventilation itself leads to diaphragmatic atrophy and weakness in non-septic animals and humans, a phenomenon referred to as ventilator-induced diaphragmatic dysfunction (VIDD) [10]. Furthermore, sepsis-induced diaphragmatic dysfunction and VIDD appear to share many of the same pathogenetic mechanisms, such as increased oxidative stress and mitochondrial dysfunction within diaphragm muscle fibers [11]. Therefore, the combination of sepsis and VIDD could create a ‘perfect storm’, with mechanical ventilation either exacerbating the magnitude of diaphragmatic weakness caused by infection or slowing the subsequent recovery of diaphragmatic function once sepsis has resolved. Further studies will be required to specifically address these questions, and there is a clear need for novel therapeutic approaches that can either reverse or limit the development of diaphragmatic weakness in mechanically ventilated patients. The presence of common cellular mechanisms implicated in sepsis-induced diaphragmatic dysfunction and VIDD raises the possibility that pharmacologic agents directed at their shared molecular targets might be effective therapies for both conditions.

Abbreviations

ICU: Intensive care unit; VIDD: Ventilator-induced diaphragmatic dysfunction.

Competing interests

The author declares that he has no competing interests.     

Increased duration of mechanical ventilation is associated with decreased diaphragmatic force: a prospective observational study

Introduction  

Respiratory muscle weakness is an important risk factor for delayed weaning. Animal data show that mechanical ventilation itself can cause atrophy and weakness of the diaphragm, called ventilator-induced diaphragmatic dysfunction (VIDD). Transdiaphragmatic pressure after magnetic stimulation (TwPdi BAMPS) allows evaluation of diaphragm strength. We aimed to evaluate the repeatability of TwPdi BAMPS in critically ill, mechanically ventilated patients and to describe the relation between TwPdi and the duration of mechanical ventilation.     

Critical illness and mechanical ventilation: effects on the diaphragm

Although life-saving, mechanical ventilation is associated with numerous complications. These include pneumonia, cardiovascular compromise, barotrauma, and ventilator-induced lung injury. Recent data from animal studies suggest that controlled mechanical ventilation can cause dysfunction of the diaphragm, decreasing its force-generating capacity--a condition referred to as ventilator-induced diaphragmatic dysfunction (VIDD). The decrease in diaphragmatic contractility is time-dependent and worsens as mechanical ventilation is prolonged. Evidence supporting the occurrence of comparable diaphragmatic dysfunction in critically ill patients is scarce, although most patients receiving mechanical ventilation display profound diaphragmatic weakness. Atrophy, fibers remodeling, oxidative stress, and structural injury have been implicated as potential mechanisms of VIDD. The decrease in diaphragmatic force that occurs during controlled mechanical ventilation is attenuated during assisted modes of ventilation. Whether the decrease in diaphragmatic contractility observed during controlled ventilation contributes to failure to wean from the ventilator is difficult to ascertain. Weaning-failure patients have reasons other than VIDD for respiratory-muscle weakness. Until we have further data, it seems prudent to avoid the use of controlled mechanical ventilation in patients with acute respiratory failure.     

Ventilation spontanée au cours du syndrome de détresse respiratoire aiguë

In patients with acute respiratory distress syndrome, lung protective ventilatory strategy usually requires heavy sedation and the use of neuromuscular blocking agents because of the risk of major asynchronies and/or excessive tidal volumes in pressure control ventilation in the case of excessive patient inspiratory effort. An original approach aiming at maintaining spontaneous breathing without increasing these risks is allowed by the Airway Pressure Release Ventilation mode. In this mode, pressure control breaths are delivered and the patient can breathe spontaneously without assistance at anytime at the two pressure levels. This ventilation mode is by design asynchronous. It might allow the improvement of alveolar recruitment, in particular, in dependant zones to decrease the risk of ventilator-induced diaphragmatic dysfunction, to reduce the dose of sedative agents and the length of stay on mechanical ventilation, and to also improve hemodynamics. However, a high spontaneous breathing activity might be associated with an excessive work of breathing and an increased risk of ventilator-induced lung injury.     

Physiological effects of noninvasive positive ventilation during acute moderate hypercapnic respiratory insufficiency in children

Introduction  A prospective physiological study was performed in 12 paediatric patients with acute moderate hypercapnic respiratory insufficiency to assess the ability of noninvasive positive pressure ventilation (NPPV) to unload the respiratory muscles and improve gas exchange. Materials and methods  Breathing pattern, gas exchange, and inspiratory muscle effort were measured during spontaneous breathing and NPPV. Results  NPPV was associated with a significant improvement in breathing pattern, gas exchange and respiratory muscle output. Tidal volume and minute ventilation increased by 33 and 17%, and oesophageal and diaphragmatic pressure time product decreased by 49 and 56%, respectively. This improvement in alveolar ventilation translated into a reduction in mean partial pressure in carbon dioxide from 48 to 40 mmHg (P = 0.01) and in respiratory rate from 48 to 41 breaths/min (P = 0.01). No difference between a clinical setting and a physiological setting of NPPV was observed. In conclusion, this study shows that NPPV is able to unload the respiratory muscles and improve clinical outcome in young patients admitted to the paediatric intensive care unit for acute moderate hypercapnic respiratory insufficiency. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Myofeedback: a new method of teaching breathing exercises in emphysematous patients.

The diaphragm of the emphysematous patient is low and limited in its excursions, producing an increased functional residual capacity and decreased pulmonary ventilation. This report describes our experiences with a new technique for 1) the training of abdominal-diaphragmatic (A-D) breathing and 2) the relaxation of accessory respiratory muscles in emphysematous patients. Abdominal muscle contraction during expiration has been shown to increase diaphragmatic excursions and, hence, pulmonary ventilation. Use of this technique has been limited, however, because of the difficulty in learning this breathing pattern. Through continuous audio and visual feedback of myoelectric potentials (myofeedback) from abdominal muscles, 12 patients learned A-D breathing. The lower rectus abdominis muscle was found to be the most suitable muscle for obtaining the myoelectric potentials. Similarly, by providing the patients with myofeedback from their accessory muscles, they decreased the use of these muscles, thus increasing their respiratory efficiency. With myofeedback, patients appear to learn new breathing patterns effectively and in fewer sessions than with conventional procedures.     

Assessment of diaphragmatic dysfunction in the critically ill patient with ultrasound: a systematic review

Purpose

Diaphragmatic dysfunction (DD) has a high incidence in critically ill patients and is an under-recognized cause of respiratory failure and prolonged weaning from mechanical ventilation. Among different methods to assess diaphragmatic function, diaphragm ultrasonography (DU) is noninvasive, rapid, and easy to perform at the bedside. We systematically reviewed the current literature assessing the usefulness and accuracy of DU in intensive care unit (ICU) patients.

Methods

Pubmed, Cochrane Database of Systematic Reviews, Embase, Scopus, and Google Scholar Databases were searched for pertinent studies. We included all original, peer-reviewed studies about the use of DU in ICU patients.

Results

Twenty studies including 875 patients were included in the final analysis. DU was performed with different techniques to measure diaphragmatic inspiratory excursion, thickness of diaphragm (Tdi), and thickening fraction (TF). DU is feasible, highly reproducible, and allows one to detect diaphragmatic dysfunction in critically ill patients. During weaning from mechanical ventilation and spontaneous breathing trials, both diaphragmatic excursion and diaphragmatic thickening measurements have been used to predict extubation success or failure. Optimal cutoffs ranged from 10 to 14 mm for excursion and 30–36 % for thickening fraction. During assisted mechanical ventilation, diaphragmatic thickening has been found to be an accurate index of respiratory muscles workload. Observational studies suggest DU as a reliable method to assess diaphragm atrophy in patients undergoing mechanical ventilation.

Conclusions

Current literature suggests that DU could be a useful and accurate tool to detect diaphragmatic dysfunction in critically ill patients, to predict extubation success or failure, to monitor respiratory workload, and to assess atrophy in patients who are mechanically ventilated.

     

A paper on the pace of recovery from diaphragmatic fatigue and its unexpected dividends

Because the diaphragm is essential for survival, we wondered if it might be less vulnerable to the long-lasting effects of fatigue than limb muscles. Using a recently introduced magnetic probe to activate the phrenic nerves, we followed the evolution of twitch transdiaphragmatic pressure after inducing fatigue in healthy volunteers. Twenty-four hours after its induction, diaphragmatic fatigue had not fully recovered. Findings from this study later served as the foundation for incorporating a once-daily, T-tube-trial arm into a randomized controlled trial of techniques for ventilator weaning in intensive care unit patients and also influenced the design of a controlled trial of the weaning of tracheostomy patients who required prolonged ventilation. The research methodology was later employed to determine whether low-frequency fatigue is responsible for weaning failure. Employing a further modification of the technique—twitch airway pressure—it became evident that respiratory muscle weakness is a greater problem than fatigue in ventilated patients. Twitch airway pressure is now being used to document the prevalence and consequences of ventilator-induced respiratory muscle weakness. Our study—which began with a circumscribed, simple question—has yielded dividends in unforeseen directions, illustrating the fruitfulness of research into basic physiological mechanisms.     

Clinical review: intensive care unit acquired weakness

A substantial number of patients admitted to the ICU because of an acute illness, complicated surgery, severe trauma, or burn injury will develop a de novo form of muscle weakness during the ICU stay that is referred to as “intensive care unit acquired weakness” (ICUAW). This ICUAW evoked by critical illness can be due to axonal neuropathy, primary myopathy, or both. Underlying pathophysiological mechanisms comprise microvascular, electrical, metabolic, and bioenergetic alterations, interacting in a complex way and culminating in loss of muscle strength and/or muscle atrophy. ICUAW is typically symmetrical and affects predominantly proximal limb muscles and respiratory muscles, whereas facial and ocular muscles are often spared. The main risk factors for ICUAW include high severity of illness upon admission, sepsis, multiple organ failure, prolonged immobilization, and hyperglycemia, and also older patients have a higher risk. The role of corticosteroids and neuromuscular blocking agents remains unclear. ICUAW is diagnosed in awake and cooperative patients by bedside manual testing of muscle strength and the severity is scored by the Medical Research Council sum score. In cases of atypical clinical presentation or evolution, additional electrophysiological testing may be required for differential diagnosis. The cornerstones of prevention are aggressive treatment of sepsis, early mobilization, preventing hyperglycemia with insulin, and avoiding the use parenteral nutrition during the first week of critical illness. Weak patients clearly have worse acute outcomes and consume more healthcare resources. Recovery usually occurs within weeks or months, although it may be incomplete with weakness persisting up to 2 years after ICU discharge. Prognosis appears compromised when the cause of ICUAW involves critical illness polyneuropathy, whereas isolated critical illness myopathy may have a better prognosis. In addition, ICUAW has shown to contribute to the risk of 1-year mortality. Future research should focus on new preventive and/or therapeutic strategies for this detrimental complication of critical illness and on clarifying how ICUAW contributes to poor longer-term prognosis.     

Music therapy as a treatment method for improving respiratory muscle strength in patients with advanced multiple sclerosis: a pilot study.

Respiratory muscle weakness, predominantly of the expiratory muscles, is characteristic of individuals with advanced multiple sclerosis and can result in difficulty in clearing secretions and repeated episodes of pneumonia. This pilot study evaluated the effectiveness of music therapy in strengthening respiratory muscles through an emphasis on diaphragmatic breathing and coordination of breath and speech. Twenty patients were randomly assigned to one of two groups: one that received music therapy or one that attended music appreciation sessions. Participants' inspiratory and expiratory muscle strength was measured by testing mouth pressure before and after the intervention. The experimental group showed some improvement in terms of expiratory muscle strength, in contrast to the control group, which showed deterioration. The results were not statistically significant, however. Patients in both groups exhibited considerable weakness in their expiratory muscles, and results for 79% of the participants were below 30% of the predicted values. Variability, a major confounding factor that resulted in reduced statistical power, led the investigators to suggest an intercenter collaboration to amass sufficient numbers of patients for a future study. Early manifestation of respiratory muscle weakness warrants inclusion of respiratory muscle testing in examination protocols and early intervention efforts.     

Respiratory insufficiency in adult-onset acid maltase deficiency

Although the adult form of acid maltase deficiency is characterized by weakness of the limb girdle muscles, weakness of the respiratory muscles out of proportion to that of the limb muscles may make the diagnosis less obvious. We present four patients aged 35 to 57 with respiratory muscle weakness associated with signs of cor pulmonale and symptoms of alveolar hypoventilation. Each had symptoms of fatigue, hypersomnolence, morning headache, and orthopnea, the cause of which was misdiagnosed. The key to diagnosis was paradoxic abdominal motion on inspiration. This finding, consistent with diaphragmatic paralysis, led to neurologic evaluation, electromyographic examination, and muscle biopsy to confirm the diagnosis. The symptoms of alveolar hypoventilation were reversed with chronic nocturnal ventilation, which assisted in rehabilitating some patients.     

Clinical review: Ventilator-induced diaphragmatic dysfunction - human studies confirm animal model findings!

Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation. However, the use of controlled mechanical ventilation in animal models results in a major reduction of diaphragmatic force-generating capacity together with structural injury and atrophy of diaphragm muscle fibers, a condition termed ventilator-induced diaphragmatic dysfunction (VIDD). Increased oxidative stress and exaggerated proteolysis in the diaphragm have been linked to the development of VIDD in animal models, but much less is known about the extent to which these phenomena occur in humans undergoing mechanical ventilation in the ICU. In the present review, we first briefly summarize the large body of evidence demonstrating the existence of VIDD in animal models, and outline the major cellular mechanisms that have been implicated in this process. We then relate these findings to very recently published data in critically ill patients, which have thus far been found to exhibit a remarkable degree of similarity with the animal model data. Hence, the human studies to date have indicated that mechanical ventilation is associated with increased oxidative stress, atrophy, and injury of diaphragmatic muscle fibers along with a rapid loss of diaphragmatic force production. These changes are, to a large extent, directly proportional to the duration of mechanical ventilation. In the context of these human data, we also review the methods that can be used in the clinical setting to diagnose and/or monitor the development of VIDD in critically ill patients. Finally, we discuss the potential for using different mechanical ventilation strategies and pharmacological approaches to prevent and/or to treat VIDD and suggest promising avenues for future research in this area.     

Clinical review: ventilator-induced diaphragmatic dysfunction--human studies confirm animal model findings!

Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation. However, the use of controlled mechanical ventilation in animal models results in a major reduction of diaphragmatic force-generating capacity together with structural injury and atrophy of diaphragm muscle fibers, a condition termed ventilator-induced diaphragmatic dysfunction (VIDD). Increased oxidative stress and exaggerated proteolysis in the diaphragm have been linked to the development of VIDD in animal models, but much less is known about the extent to which these phenomena occur in humans undergoing mechanical ventilation in the ICU. In the present review, we first briefly summarize the large body of evidence demonstrating the existence of VIDD in animal models, and outline the major cellular mechanisms that have been implicated in this process. We then relate these findings to very recently published data in critically ill patients, which have thus far been found to exhibit a remarkable degree of similarity with the animal model data. Hence, the human studies to date have indicated that mechanical ventilation is associated with increased oxidative stress, atrophy, and injury of diaphragmatic muscle fibers along with a rapid loss of diaphragmatic force production. These changes are, to a large extent, directly proportional to the duration of mechanical ventilation. In the context of these human data, we also review the methods that can be used in the clinical setting to diagnose and/or monitor the development of VIDD in critically ill patients. Finally, we discuss the potential for using different mechanical ventilation strategies and pharmacological approaches to prevent and/or to treat VIDD and suggest promising avenues for future research in this area.