Diaphragm weakness and mechanical ventilation - what's the critical issue?

While animal studies indicate that controlled mechanical ventilation (MV) induces diaphragm weakness and myofiber atrophy, there are no data in humans that confirm MV per se produces diaphragm weakness. Whether or not diaphragm weakness results from MV, sepsis, corticosteroids, hyperglycemia, or a combination of these factors, however, is not the most important issue raised by the recent study from Hermans and colleagues. This study makes an important contribution by providing additional evidence that many critically ill patients have profound diaphragm weakness. If diaphragm weakness of this magnitude is present in most mechanically ventilated patients, a strong argument can be made that respiratory muscle weakness is a major contributor to respiratory failure.     

膈肌超声在危重症中的临床应用

膈肌是人体最重要的呼吸肌,而脓毒症、机械通气、营养不良等因素可导致膈肌功能障碍。超声因具有安全、无创、可重复性强等优点,近几年已被广泛应用于危重症患者的诊断及治疗。膈肌超声通过对膈肌结构和功能的评估,起到预测机械通气患者撤机结果、鉴别膈肌萎缩和膈肌麻痹、判断慢性阻塞性肺病严重程度以及评估人机同步性等多种作用,可用于临床危重患者膈肌功能障碍的诊断及治疗效果评估。     

Clinical review: Early patient mobilization in the ICU

Early mobilization (EM) of ICU patients is a physiologically logical intervention to attenuate critical illness-associated muscle weakness. However, its long-term value remains controversial. We performed a detailed analytical review of the literature using multiple relevant key terms in order to provide a comprehensive assessment of current knowledge on EM in critically ill patients. We found that the term EM remains undefined and encompasses a range of heterogeneous interventions that have been used alone or in combination. Nonetheless, several studies suggest that different forms of EM may be both safe and feasible in ICU patients, including those receiving mechanical ventilation. Unfortunately, these studies of EM are mostly single center in design, have limited external validity and have highly variable control treatments. In addition, new technology to facilitate EM such as cycle ergometry, transcutaneous electrical muscle stimulation and video therapy are increasingly being used to achieve such EM despite limited evidence of efficacy. We conclude that although preliminary low-level evidence suggests that EM in the ICU is safe, feasible and may yield clinical benefits, EM is also labor-intensive and requires appropriate staffing models and equipment. More research is thus required to identify current standard practice, optimal EM techniques and appropriate outcome measures before EM can be introduced into the routine care of critically ill patients.     

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.     

Bench-to-bedside review: Diaphragm muscle function in disuse and acute high-dose corticosteroid treatment

Critically ill patients may require mechanical ventilatory support and short-term high-dose corticosteroid to treat some specific underlying disease processes. Diaphragm muscle inactivity induced by controlled mechanical ventilation produces dramatic alterations in diaphragm muscle structure and significant losses in function. Although the exact mechanisms responsible for losses in diaphragm muscle function are still unknown, recent studies have highlighted the importance of proteolysis and oxidative stress. In experimental animals, short-term strategies that maintain partial diaphragm muscle neuromechanical activation mitigate diaphragmatic force loss. In animal models, studies on the influence of combined controlled mechanical ventilation and short-term high-dose methylprednisolone have given inconsistent results in regard to the effects on diaphragm muscle function. In the critically ill patient, further research is needed to establish the prevalence and mechanisms of ventilator-induced diaphragm muscle dysfunction, and the possible interaction between mechanical ventilation and the administration of high-dose corticosteroid. Until then, in caring for these patients, it is imperative to allow partial activation of the diaphragm, and to administer the lowest dose of corticosteroid for the shortest duration possible.     

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.     

Effects of levosimendan on respiratory muscle function in patients weaning from mechanical ventilation

Respiratory muscle weakness frequently develops in critically ill patients and is associated with adverse outcome, including difficult weaning from mechanical ventilation. Today, no drug is approved to improve respiratory muscle function in these patients. Previously, we have shown that the calcium sensitizer levosimendan improves calcium sensitivity of human diaphragm muscle fibers in vitro and contractile efficiency of the diaphragm in healthy subjects. The main purpose of this study is to investigate the effects of levosimendan on diaphragm contractile efficiency in mechanically ventilated patients. In a double-blind randomized placebo-controlled trial, mechanically ventilated patients performed two 30-min continuous positive airway pressure (CPAP) trials with 5-h interval. After the first CPAP trial, study medication (levosimendan 0.2 µg/kg/min continuous infusion or placebo) was administered. During the CPAP trials, electrical activity of the diaphragm (EAdi), transdiaphragmatic pressure (Pdi), and flow were measured. Neuromechanical efficiency (primary outcome parameter) was calculated. Thirty-nine patients were included in the study. Neuromechanical efficiency was not different during the CPAP trial after levosimendan administration compared to the CPAP trial before study medication. Tidal volume and minute ventilation were higher after levosimendan administration (11 and 21%, respectively), whereas EAdi and Pdi were higher in both groups in the CPAP trial after study medication compared to the CPAP trial before study medication. Levosimendan does not improve diaphragm contractile efficiency.     

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.     

Diaphragm weakness in mechanically ventilated critically ill patients

Introduction

Studies indicate that mechanically ventilated patients develop significant diaphragm muscle weakness, but the etiology of weakness and its clinical impact remain incompletely understood. We assessed diaphragm strength in mechanically ventilated medical ICU patients, correlated the development of diaphragm weakness with multiple clinical parameters, and examined the relationship between the level of diaphragm weakness and patient outcomes.

Methods

Transdiaphragmatic twitch pressure (PdiTw) in response to bilateral magnetic stimulation of the phrenic nerves was measured. Diaphragm weakness was correlated with the presence of infection, blood urea nitrogen, albumin, and glucose levels. The relationship of diaphragm strength to patient outcomes, including mortality and the duration of mechanical ventilation for successfully weaned patients, was also assessed.

Results

We found that infection is a major risk factor for diaphragm weakness in mechanically ventilated medical ICU patients. Outcomes for patients with severe diaphragm weakness (PdiTw <10 cmH₂O) were poor, with a markedly increased mortality (49%) compared to patients with PdiTw ≥10 cmH₂O (7% mortality, P = 0.022). In addition, survivors with PdiTw <10 cmH₂O required a significantly longer duration of mechanical ventilation (12.3 ± 1.7 days) than those with PdiTw ≥10 cmH₂O (5.5 ± 2.0 days, P = 0.016).

Conclusions

Infection is a major cause of severe diaphragm weakness in mechanically ventilated patients. Moreover, diaphragm weakness is an important determinant of poor outcomes in this patient population.     

Critical illness neuromuscular syndromes

Critical illness neuromyopathy (CINM) is the most common peripheral neuromuscular disorder encountered in the ICU. Bilateral diffuse weakness predominant in the proximal part of the limbs after improvement of the acute phase of the critical illness is highly suggestive of CINM. Although muscle and peripheral nerve are often involved in combination, muscle involvement alone is increasingly identified on electrophysiologic investigation, including direct muscle stimulation. Respiratory weakness results in delayed weaning and prolonged mechanical ventilation. Besides muscle immobilization and prolonged sepsis-induced multiorgan failure, which are risk factors for CINM, hyperglycemia and use of corticosteroids might have a deleterious effect on the neuromuscular system in critically ill patients.     

基于4E模式的ICU早期康复方案在机械通气患者中的应用

目的:分析基于4E模式的ICU早期康复方案在机械通气患者中的应用效果。方法:采用便利抽样法,选取某医院2个ICU病区收治的74例患者为研究对象,ICU一区患者为实验组(n=38),ICU二区患者为对照组(n=36)。对照组接受常规康复护理,实验组接受基于4E模式的ICU早期康复方案。结果:两组患者在ICU谵妄发生率、谵妄持续时间、医学研究理事会肌力评分、ICU获得性衰弱(ICU-AW)发生率、机械通气时间、ICU住院时间、总住院时间等方面差异均有统计学意义(P<0.05)。在实施过程中,实验组患者未发生早期康复相关的严重不良事件。结论:对机械通气患者实施基于4E模式的ICU早期康复方案安全可行且有效,可改善患者肌力,降低ICU-AW及ICU谵妄发生率,缩短ICU谵妄持续时间、机械通气时间、ICU住院时间与总住院时间。     

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.

     

Cytomegalovirus infection in critically ill patients: a systematic review

Introduction

The precise role of cytomegalovirus (CMV) infection in contributing to outcomes in critically ill immunocompetent patients has not been fully defined.

Methods

Studies in which critically ill immunocompetent adults were monitored for CMV infection in the intensive care unit (ICU) were reviewed.

Results

CMV infection occurs in 0 to 36% of critically ill patients, mostly between 4 and 12 days after ICU admission. Potential risk factors for CMV infection include sepsis, requirement of mechanical ventilation, and transfusions. Prolonged mechanical ventilation (21 to 39 days vs. 13 to 24 days) and duration of ICU stay (33 to 69 days vs. 22 to 48 days) correlated significantly with a higher risk of CMV infection. Mortality rates in patients with CMV infection were higher in some but not all studies. Whether CMV produces febrile syndrome or end-organ disease directly in these patients is not known.

Conclusions

CMV infection frequently occurs in critically ill immunocompetent patients and may be associated with poor outcomes. Further studies are warranted to identify subsets of patients who are likely to develop CMV infection and to determine the impact of antiviral agents on clinically meaningful outcomes in these patients.     

Clinical review: Respiratory failure in HIV-infected patients - a changing picture

Respiratory failure in HIV-infected patients is a relatively common presentation to ICU. The debate on ICU treatment of HIV-infected patients goes on despite an overall decline in mortality amongst these patients since the AIDS epidemic. Many intensive care physicians feel that ICU treatment of critically ill HIV patients is likely to be futile. This is mainly due to the unfavourable outcome of HIV patients with Pneumocystis jirovecii pneumonia who need mechanical ventilation. However, the changing spectrum of respiratory illness in HIV-infected patients and improved outcome from critical illness remain under-recognised. Also, the awareness of certain factors that can affect their outcome remains low. As there are important ethical and practical implications for intensive care clinicians while making decisions to provide ICU support to HIV-infected patients, a review of literature was undertaken. It is notable that the respiratory illnesses that are not directly related to underlying HIV disease are now commonly encountered in the highly active antiretroviral therapy (HAART) era. The overall incidence of P. jirovecii as a cause of respiratory failure has declined since the AIDS epidemic and sepsis including bacterial pneumonia has emerged as a frequent cause of hospital and ICU admission amongst HIV patients. The improved overall outcome of HIV patients needing ICU admission is related to advancement in general ICU care, including adoption of improved ventilation strategies. An awareness of respiratory illnesses in HIV-infected patients along with an appropriate diagnostic and treatment strategy may obviate the need for invasive ventilation and improve outcome further. HIV-infected patients presenting with respiratory failure will benefit from early admission to critical care for treatment and support. There is evidence to suggest that continuing or starting HAART in critically ill HIV patients is beneficial and hence should be considered after multidisciplinary discussion. As a very high percentage (up to 40%) of HIV patients are not known to be HIV infected at the time of ICU admission, the clinicians should keep a low threshold for requesting HIV testing for patients with recurrent pneumonia.     

Definitions and epidemiology of the chronically critically ill

Patients who are chronically critically ill constitute 5-10% of patients with acute respiratory failure but demand a disproportionate share of ICU resources. Epidemiologic studies and clinical trials require definitions for enrollment, and a uniform definition would be ideal to allow comparisons between studies. While a consensus definition exists (≥ 21 consecutive days of mechanical ventilation for ≥ 6 h/d), many study designs have required alternative definitions that include requirement for a tracheostomy, a different period of mechanical ventilation, or admission to a weaning facility. Regardless of definition, studies have indicated that the incidence of chronic critical illness has doubled in recent decades and may double again in the next decade. The overall 1-year survival for chronically critically ill patients is between 40% and 50%, depending on the cohort studied. New clinical prediction rules have been developed to better identify patients who are at high risk and low risk of death. These models could be enhanced by data on functional outcomes for survivors. The healthcare system has been adapting to the increase in chronic critical illness by increasing critical beds in short-term and long-term acute care hospitals, but continued monitoring of resources will be necessary, since the prevalence of chronic critical illness is expected to increase further.     

Frailty in the critically ill: a novel concept

The concept of frailty has been defined as a multidimensional syndrome characterized by the loss of physical and cognitive reserve that predisposes to the accumulation of deficits and increased vulnerability to adverse events. Frailty is strongly correlated with age, and overlaps with and extends aspects of a patient's disability status (that is, functional limitation) and/or burden of comorbid disease. The frail phenotype has more specifically been characterized by adverse changes to a patient's mobility, muscle mass, nutritional status, strength and endurance. We contend that, in selected circumstances, the critically ill patient may be analogous to the frail geriatric patient. The prevalence of frailty amongst critically ill patients is currently unknown; however, it is probably increasing, based on data showing that the utilization of intensive care unit (ICU) resources by older people is rising. Owing to the theoretical similarities in frailty between geriatric and critically ill patients, this concept may have clinical relevance and may be predictive of outcomes, along with showing important interaction with several factors including illness severity, comorbid disease, and the social and structural environment. We believe studies of frailty in critically ill patients are needed to evaluate how it correlates with outcomes such as survival and quality of life, and how it relates to resource utilization, such as length of mechanical ventilation, ICU stay and duration of hospitalization. We hypothesize that the objective measurement of frailty may provide additional support and reinforcement to clinicians confronted with end-of-life decisions on the appropriateness of ICU support and/or withholding of life-sustaining therapies.     

ICU-based rehabilitation and its appropriate metrics

PURPOSE OF REVIEW: Survival of critically ill patients is frequently associated with significant functional impairment and reduced health-related quality of life. Early rehabilitation of ICU patients has recently been identified as an important focus for interdisciplinary ICU teams. However, the amount of rehabilitation performed in ICUs is often inadequate. The scope of the review is to discuss recent developments in application of assessment tools and rehabilitation in critically ill patients within an interdisciplinary approach. RECENT FINDINGS: ICU-based rehabilitation has become an important evidence-based component in the management of patients with critical illness. The assessment and evidence-based treatment of these patients should include a focus on prevention and treatment of deconditioning (muscle weakness, joint stiffness, impaired functional performance) and weaning failure (respiratory muscle weakness) to identify targets for rehabilitation. A variety of modalities for assessment and early ICU rehabilitation are supported by emerging clinical research and must be implemented according to the stage of critical illness, comorbidities, and consciousness and cooperation of the patient. SUMMARY: Daily evaluation of every critically ill patient should include evaluation of the need for bedrest and immobility, and assessment of the potential for early rehabilitation interventions. Early ICU rehabilitation is an interdisciplinary team responsibility, involving physical therapists, occupational therapists, nurses and medical staff.     

Intensive-care-unit-acquired muscle weakness

Neuromuscular abnormalities culminating in skeletal-muscle weakness occur very commonly in critically ill patients. Intensive-care-unit (ICU) acquired neuromuscular abnormalities are typically divided into 2 discrete classes: polyneuropathy and myopathy. However, it is likely that these 2 entities commonly coexist, with myopathy being the most common cause of weakness. Major risk factors for ICU-acquired neuromuscular abnormalities include sepsis, corticosteroid administration, and hyperglycemia, with other associated factors including neuromuscular blockade and increasing severity of illness. The pathogenesis of these disorders is not well defined, but probably involves inflammatory injury of nerve and/or muscle that is potentiated by functional denervation and corticosteroids. ICU-acquired neuromuscular abnormalities are associated with multiple adverse outcomes, including higher mortality, prolonged duration of mechanical ventilation, and increased length of stay. The only intervention proven to reduce the incidence of ICU-acquired neuromuscular abnormalities is intensive insulin therapy. Additional research is necessary to better delineate the causes and pathogenesis of these disorders and to identify potential preventive and therapeutic strategies. In addition, consensus guidelines for its classification and diagnosis are needed.     

Études cliniques

The prognosis of critically ill patients has changed considerably in recent years. Admission to the intensive care unit is nevertheless a source of complications that can result in difficult weaning from mechanical ventilation. Peripheral neuromuscular impairments and respiratory muscle weakness are among these complications. Although these events are common and known to have adverse effects in the more or less long term, their evaluation is complex and continues to generate debate. Assessing them in the most objective possible manner is a crucial prerequisite to develop an effective therapeutic strategy. The objective of this review is to describe the specific available methods for assessing cough ability and peripheral muscle strength, and to discuss published data on the use of these methods during weaning from mechanical ventilation.