Limits...
Strategies to optimize respiratory muscle function in ICU patients.

Schellekens WJ, van Hees HW, Doorduin J, Roesthuis LH, Scheffer GJ, van der Hoeven JG, Heunks LM - Crit Care (2016)

Bottom Line: Respiratory muscle dysfunction may develop rapidly in critically ill ventilated patients and is associated with increased morbidity, length of intensive care unit stay, costs, and mortality.This review briefly discusses the pathophysiology of respiratory muscle dysfunction in intensive care unit patients and then focuses on strategies that prevent the development of muscle weakness or, if weakness has developed, how respiratory muscle function may be improved.We propose a simple strategy for how these can be implemented in clinical care.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Radboud University Medical Centre, Nijmegen, 6500 HB, The Netherlands.

ABSTRACT
Respiratory muscle dysfunction may develop rapidly in critically ill ventilated patients and is associated with increased morbidity, length of intensive care unit stay, costs, and mortality. This review briefly discusses the pathophysiology of respiratory muscle dysfunction in intensive care unit patients and then focuses on strategies that prevent the development of muscle weakness or, if weakness has developed, how respiratory muscle function may be improved. We propose a simple strategy for how these can be implemented in clinical care.

No MeSH data available.


Related in: MedlinePlus

Proposed scheme of pathophysiologic pathways in the development of respiratory muscle weakness during critical illness. Oxidative stress [89], inflammation [71, 74], increased nuclear factor (NF)-κB activity [90], and mechanical unloading [10, 11] have been proposed to initiate respiratory muscle weakness. These initiators can result in contractile protein becoming dysfunctional [4], decreased synthesis [14, 15], or muscular autophagy [12]. Oxidative stress and inflammatory pathways can activate caspases and calpains [89, 91], thereby delivering substrates for the ubiquitin-proteasome [10, 11, 92], which further degrades contractile proteins
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4835880&req=5

Fig1: Proposed scheme of pathophysiologic pathways in the development of respiratory muscle weakness during critical illness. Oxidative stress [89], inflammation [71, 74], increased nuclear factor (NF)-κB activity [90], and mechanical unloading [10, 11] have been proposed to initiate respiratory muscle weakness. These initiators can result in contractile protein becoming dysfunctional [4], decreased synthesis [14, 15], or muscular autophagy [12]. Oxidative stress and inflammatory pathways can activate caspases and calpains [89, 91], thereby delivering substrates for the ubiquitin-proteasome [10, 11, 92], which further degrades contractile proteins

Mentions: Contractile dysfunction of the respiratory muscles in ICU patients may result from the loss of muscle mass (atrophy) and/or dysfunction of the remaining contractile proteins. In a landmark paper, Levine and colleagues [10] demonstrated the rapid development of diaphragm muscle atrophy in ventilated brain-dead patients. More recently, Hooijman and colleagues [11] performed in-depth functional and structural analysis of diaphragm biopsies in critically ill patients on the ventilator. In that study, muscle fiber cross-sectional area was reduced by ±25 % after an average of 7 days of mechanical ventilation. Muscle atrophy is the final result of an imbalance between protein synthesis and degradation. Upregulation of several proteolytic pathways has been demonstrated in the respiratory muscles of ICU patients [11]. For instance, key regulators of the ubiquitin-proteasome pathway are upregulated in the diaphragm of these patients [10, 11]. Other pathways such as lysosomal protein degradation and autophagy may play a role as well (Fig. 1) [12, 13]. In addition to enhanced proteolysis, decreased protein synthesis has been reported in the diaphragm of rodents subjected to controlled mechanical ventilation [14, 15]. Besides atrophy, diaphragm weakness may be the result of contractile protein dysfunction. Even when corrected for loss of protein, muscle fibers in ICU patients develop less force [4]. Furthermore, the sensitivity of the contractile proteins for calcium is reduced [4]. The pathophysiology of contractile protein dysfunction in these patients is incompletely understood, but animal models of mechanical ventilation and endotoxemia indicate that phosphorylation and oxidative modifications of the sarcomeric proteins and mitochondrial proteins play a role in dysfunction and injury [16–19]. For an extensive background on the pathophysiology of muscle dysfunction in the critically ill, we refer to a recent excellent review on this subject [20].Fig. 1


Strategies to optimize respiratory muscle function in ICU patients.

Schellekens WJ, van Hees HW, Doorduin J, Roesthuis LH, Scheffer GJ, van der Hoeven JG, Heunks LM - Crit Care (2016)

Proposed scheme of pathophysiologic pathways in the development of respiratory muscle weakness during critical illness. Oxidative stress [89], inflammation [71, 74], increased nuclear factor (NF)-κB activity [90], and mechanical unloading [10, 11] have been proposed to initiate respiratory muscle weakness. These initiators can result in contractile protein becoming dysfunctional [4], decreased synthesis [14, 15], or muscular autophagy [12]. Oxidative stress and inflammatory pathways can activate caspases and calpains [89, 91], thereby delivering substrates for the ubiquitin-proteasome [10, 11, 92], which further degrades contractile proteins
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835880&req=5

Fig1: Proposed scheme of pathophysiologic pathways in the development of respiratory muscle weakness during critical illness. Oxidative stress [89], inflammation [71, 74], increased nuclear factor (NF)-κB activity [90], and mechanical unloading [10, 11] have been proposed to initiate respiratory muscle weakness. These initiators can result in contractile protein becoming dysfunctional [4], decreased synthesis [14, 15], or muscular autophagy [12]. Oxidative stress and inflammatory pathways can activate caspases and calpains [89, 91], thereby delivering substrates for the ubiquitin-proteasome [10, 11, 92], which further degrades contractile proteins
Mentions: Contractile dysfunction of the respiratory muscles in ICU patients may result from the loss of muscle mass (atrophy) and/or dysfunction of the remaining contractile proteins. In a landmark paper, Levine and colleagues [10] demonstrated the rapid development of diaphragm muscle atrophy in ventilated brain-dead patients. More recently, Hooijman and colleagues [11] performed in-depth functional and structural analysis of diaphragm biopsies in critically ill patients on the ventilator. In that study, muscle fiber cross-sectional area was reduced by ±25 % after an average of 7 days of mechanical ventilation. Muscle atrophy is the final result of an imbalance between protein synthesis and degradation. Upregulation of several proteolytic pathways has been demonstrated in the respiratory muscles of ICU patients [11]. For instance, key regulators of the ubiquitin-proteasome pathway are upregulated in the diaphragm of these patients [10, 11]. Other pathways such as lysosomal protein degradation and autophagy may play a role as well (Fig. 1) [12, 13]. In addition to enhanced proteolysis, decreased protein synthesis has been reported in the diaphragm of rodents subjected to controlled mechanical ventilation [14, 15]. Besides atrophy, diaphragm weakness may be the result of contractile protein dysfunction. Even when corrected for loss of protein, muscle fibers in ICU patients develop less force [4]. Furthermore, the sensitivity of the contractile proteins for calcium is reduced [4]. The pathophysiology of contractile protein dysfunction in these patients is incompletely understood, but animal models of mechanical ventilation and endotoxemia indicate that phosphorylation and oxidative modifications of the sarcomeric proteins and mitochondrial proteins play a role in dysfunction and injury [16–19]. For an extensive background on the pathophysiology of muscle dysfunction in the critically ill, we refer to a recent excellent review on this subject [20].Fig. 1

Bottom Line: Respiratory muscle dysfunction may develop rapidly in critically ill ventilated patients and is associated with increased morbidity, length of intensive care unit stay, costs, and mortality.This review briefly discusses the pathophysiology of respiratory muscle dysfunction in intensive care unit patients and then focuses on strategies that prevent the development of muscle weakness or, if weakness has developed, how respiratory muscle function may be improved.We propose a simple strategy for how these can be implemented in clinical care.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Radboud University Medical Centre, Nijmegen, 6500 HB, The Netherlands.

ABSTRACT
Respiratory muscle dysfunction may develop rapidly in critically ill ventilated patients and is associated with increased morbidity, length of intensive care unit stay, costs, and mortality. This review briefly discusses the pathophysiology of respiratory muscle dysfunction in intensive care unit patients and then focuses on strategies that prevent the development of muscle weakness or, if weakness has developed, how respiratory muscle function may be improved. We propose a simple strategy for how these can be implemented in clinical care.

No MeSH data available.


Related in: MedlinePlus