Critical Illness Myopathy (CIM) and Ventilator‐Induced Diaphragm Muscle Dysfunction (VIDD): Acquired Myopathies Affecting Contractile Proteins

Abstract

Critical care and intensive care units (ICUs) have undergone dramatic changes and improvements in recent years, and critical care is today one of the fastest growing hospital disciplines. Significant improvements in treatments, removal of inefficient and harmful interventions, and introduction of advanced technological support systems have improved survival among critically ill ICU patients. However, the improved survival is associated with an increased number of patients with complications related to modern critical care. Severe muscle wasting and impaired muscle function are frequently observed in immobilized and mechanically ventilated ICU patients. Approximately 30% of mechanically ventilated and immobilized ICU patients for durations of five days and longer develop generalized muscle paralysis of all limb and trunk muscles. These patients typically have intact sensory and cognitive functions, a condition known as critical illness myopathy (CIM). Mechanical ventilation is a lifesaving treatment in critically ill ICU patients; however, the being on a ventilator creates dependence, and the weaning process occupies as much as 40% of the total time of mechanical ventilation. Furthermore, 20% to 30% of patients require prolonged intensive care due to ventilator-induced diaphragm dysfunction (VIDD), resulting in poorer outcomes, and greatly increased costs to health care providers. Our understanding of the mechanisms underlying both CIM and VIDD has increased significantly in the past decade and intervention strategies are presently being evaluated in different experimental models. This short review is restricted CIM and VIDD pathophysiology rather than giving a comprehensive review of all acquired muscle wasting conditions associated with modern critical care. © 2017 American Physiological Society. Compr Physiol 7:105-112, 2017.

Weak by the machines: muscle motor protein dysfunction – a side effect of intensive care unit treatment

“…However, its prevalence can exceed 70% in certain subgroups with a rising prevalence with ICU treatment duration . Symptoms of muscle weakness in CIM can be as severe as presenting with complete quadriplegia, are generally symmetric with a focus on distal muscle groups but can, in principle, affect all muscle types, fast‐ and slow‐twitch muscles and the diaphragm, with interesting exceptions, for example craniofacial and maxillary muscles . A hallmark in the diagnosis of CIM is the presence of severe weakness associated with a preferential myosin loss over an otherwise general myofibrillar breakdown, as, for example, seen in experimental sepsis models …”

“…This degree of atrophy is also reflected already at the single fibre level. For instance, tibialis anterior muscle fibres from CIM patients showed a roughly 20–30% smaller CSD . When typing single fibres according to their myosin heavy chain (MyHC) isoform expression, atrophy was about equal in fast type IIA MyHC expressing fibres (~75% reduction in cross‐sectional area, CSA) compared with slow type I MyHC expressing fibres (~70% reduction in CSA) in a group of four patients with preferential myosin loss and muscle weakness .…”

“…This was mainly triggered by MV and did not further decline by inclusion of steroids, NMBAs or sepsis . The differential effects of ICU treatment on diaphragm resulting in so‐called ‘ventilator‐induced diaphragm muscle dysfunction (VIDD)’ are reviewed in Ref …”

“…2 A specific group of myopathy that is not strictly related to an underlying systemic disease, but more generally associated with critical illness and intensive care unit treatment 'per se', has emerged in clinical awareness during the last decade due to its very common nature, its relevance to national health budgets worldwide and its consequences for patient morbidity and mortality. [3][4][5] This so-called critical illness myopathy (CIM), a potentially lethal condition, can be found in more than 30% of ICU populations. However, its prevalence can exceed 70% in certain subgroups with a rising prevalence with ICU treatment duration.…”

“…6 Symptoms of muscle weakness in CIM can be as severe as presenting with complete quadriplegia, are generally symmetric with a focus on distal muscle groups but can, in principle, affect all muscle types, fast-and slow-twitch muscles and the diaphragm, with interesting exceptions, for example craniofacial and maxillary muscles. 3,[7][8][9][10] A hallmark in the diagnosis of CIM is the presence of severe weakness associated with a preferential myosin loss [9][10][11] over an otherwise general myofibrillar breakdown, as, for example, seen in experimental sepsis models. 12,13 From bedside to bench Due to the complicating situation in critically ill patients with various confounding and contributing co-morbidities to the intensive care treatment, studies on pathophysiological mechanisms of CIM have long been obscured and blurred by not being able to dissect different contributions to muscle weakness.…”