When the most important muscle in the body fails…

 

The diaphragm is the principal muscle of respiration and is innervated by the phrenic nerves through the C3–C5 nerve roots. There is a high prevalence of diaphragmatic weakness among critically ill patients. No correlation seems to exist between weakness of the limbs and diaphragmatic weakness; in fact, diaphragmatic dysfunction may be twice as common as paresis of the limbs due to polyneuropathy or myopathy related to critical illness (1). Diaphragmatic dysfunction may be a stronger predictor of mortality than the severity of multiorgan failure among critically ill patients (2). Furthermore, weakness of the diaphragm is much harder to recognize compared to limb muscle weakness. Hence, it is important to have a high index of suspicion in patients who may be at risk of developing diaphragmatic dysfunction.

Clinical indicators

The possibility of diaphragmatic dysfunction must be considered in patients who seem to have recovered sufficiently from the underlying illness but fail repeated attempts to wean. Failure of adequate spontaneous ventilation in spite of reasonable lung mechanics and good gas exchange heightens the suspicion of diaphragmatic dysfunction. Paradoxical breathing, when the abdomen seems to get sucked in during inspiration and moves outwards during expiration is an important clinical indicator. The chest radiograph may show elevation of the diaphragm on one or both sides, depending on the extent of involvement.

The incidence of diaphragmatic dysfunction

The most sensitive test of diaphragmatic dysfunction is through magnetic stimulation of the phrenic nerves in the neck and measurement of the twitch pressure generated at the proximal end of the endotracheal tube. Using trans-diaphragmatic twitch pressure measurement, 34/43 (79%) patients developed diaphragmatic dysfunction during their stay in the ICU (3). Obviously, mild dysfunction may often be missed by clinical examination alone.

Ventilation (VIDD) and sepsis-induced diaphragmatic dysfunction (SIDD)

Both mechanical ventilation and sepsis can independently, and in combination, lead to signification diaphragmatic dysfunction. The degree of dysfunction may be closely related to the duration of mechanical ventilation. Histopathological examination of the diaphragm was carried out in brain dead organ donors who were on mechanical ventilation for 18–79 h and compared with patients who underwent 2–3 h of ventilation during thoracotomy for lung cancer. Inactivity of the diaphragm combined with mechanical ventilation resulted in marked atrophy of myofibers compared to controls (4). Activation of oxidative stress appears to be the trigger for VIDD. The generation of reactive oxygen species appears to initiate oxidative stress, resulting in DNA fragmentation and proteolysis leading to impairment of diaphragmatic contractility.

Ultrasonography- a simple bedside tool to identify diaphragmatic dysfunction

The identification of diaphragmatic dysfunction by the bedside may be reliably carried out by ultrasonography. Two parameters are used to assess diaphragmatic function: (1) diaphragmatic thickening during a maximal inspiratory effort (thickening fraction) and (2) amplitude of diaphragmatic excursion during tidal breathing.

Diaphragmatic excursion

A low frequency (2–5 MHz) curvilinear probe is placed in the subcostal region between the midclavicular and anterior axillary lines using the liver or the spleen as the acoustic window. Once the diaphragm is visualized, the M-mode cursor is positioned perpendicular to the posterior aspect of the diaphragm and the excursion is measured (Fig 1). A distance of excursion of less than 1 cm during quiet breathing or paradoxical movement (cranial movement on inspiration) is indicative of diaphragmatic weakness (5).

fig 1

Fig 1. Measurement of diaphragmatic excursion on M-mode view using a 5 MHz curvilinear transducer. The M-mode cursor is positioned perpendicular to the posterior aspect of the diaphragm. The amplitude of excursion measured in this image is 3.15 cm (double-headed arrow)

Thickening fraction

To assess thickening during inspiration, a high frequency (8–12 mHz) linear probe is used. The probe is placed between the 7–9thintercostal spaces in the midaxillary line. The diaphragm is seen as a non-echogenic zone sandwiched between the diaphragmatic pleura and the peritoneum. Thickness is measured at end-inspiration and end-expiration (Fig 2). The thickening fraction is calculated using the formula: Thickness at end-inspiration (maximal thickness) – thickness at end-expiration/thickness at end-inspiration. A thickening fraction of less than 20% is suggestive of diaphragmatic dysfunction (6).

Fig 2

Fig 2. Ultrasonographic imaging of the diaphragm using a 12 MHz linear probe. The diaphragm is seen as a hypoechoic zone between the pleura and the peritoneum, seen as hyperechoic lines. The image on the left shows thickness at end-expiration (green line); the image on the right shows thickness at end-inspiration (orange line). Thickening fraction = End-expiratory thickness – End inspiratory thickness/End-expiratory thickness

Prevention and treatment of diaphragmatic dysfunction

Maintenance of spontaneous respiratory effort during mechanical ventilation is the key to prevention of diaphragmatic dysfunction. Clearly, this strategy may be counterproductive and harmful in patients with a pronounced respiratory drive, particularly in severe acute respiratory distress syndrome. Modest use of sedatives and muscle relaxants for a limited duration is appropriate to during the initial period of mechanical ventilation. However, regular interruption of muscle relaxants and sedation should be carried out to assess the respiratory drive with a view to allowing spontaneous respiratory efforts as early as possible. Electrolyte abnormalities, including hypocalcemia, hypomagnesemia, and hypophosphatemia are well known to provoke or worsen diaphragmatic weakness; levels must be estimated regularly and maintained within the normal range. Endocrine abnormalities, especially myxedema is known to cause muscle weakness and must be considered in patients with diaphragmatic dysfunction. There is emerging interest in improving diaphragmatic function by phosphodiesterase inhibition using theophylline and with the use of levosimendan, a calcium sensitizer. Phrenic nerve stimulation and antagonization of oxidative stress using antioxidants including vitamin C and E may be therapeutic modalities for the future.

Summary

  • Diaphragmatic dysfunction is common among critically ill patients and may often be unrecognized.
  • Diaphragmatic dysfunction leads to adverse clinical outcomes including mortality.
  • Mechanical ventilation and sepsis are independent triggers of diaphragmatic dysfunction and may potentiate each other in combination.
  • It is important to have a high index of suspicion in patients at risk of diaphragmatic dysfunction.
  •  Ultrasonography is a simple and sensitive tool to diagnose diaphragmatic dysfunction by the bedside in critically ill patients.
  • Maintenance of spontaneous respiratory efforts in mechanically ventilated patients with limited use of sedatives and muscle relaxants may prevent diaphragmatic dysfunction.
  • Electrolyte and endocrine abnormalities must be sought for and corrected.

 

References

  1. Dres M, Dubé B-P, Mayaux J, Delemazure J, Reuter D, Brochard L, et al. Coexistence and Impact of Limb Muscle and Diaphragm Weakness at Time of Liberation from Mechanical Ventilation in Medical Intensive Care Unit Patients. Am J Respir Crit Care Med. 2017 01;195(1):57–66.
  2. Supinski GS, Westgate P, Callahan LA. Correlation of maximal inspiratory pressure to transdiaphragmatic twitch pressure in intensive care unit patients. Crit Care. 2016 Mar 23;20(1):77.
  3. Demoule A, Molinari N, Jung B, Prodanovic H, Chanques G, Matecki S, et al. Patterns of diaphragm function in critically ill patients receiving prolonged mechanical ventilation: a prospective longitudinal study. Ann Intensive Care. 2016;6:75. Available from: http://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-016-0179-8
  4. Levine S, Budak MT, Sonnad S, Shrager JB. Rapid Disuse Atrophy of Diaphragm Fibers in Mechanically Ventilated Humans. N Engl J Med. 2008;9.
  5. Kim WY, Suh HJ, Hong S-B, Koh Y, Lim C-M. Diaphragm dysfunction assessed by ultrasonography: influence on weaning from mechanical ventilation. Crit Care Med. 2011 Dec;39(12):2627–30.
  6. Gottesman E, McCool FD. Ultrasound evaluation of the paralyzed diaphragm. Am J Respir Crit Care Med. 1997 May;155(5):1570–4.

 

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