Positive end-expiratory pressure affects geometry and function of the human diaphragm

Diana Jansen, Annemijn H. Jonkman, Heder J. De Vries, Myrte Wennen, Judith Elshof, Maud A. Hoofs, Marloes Van Den Berg, Angélique M.E. De Man, Christiaan Keijzer, Gert Jan Scheffer, Johannes G. Van Der Hoeven, Armand Girbes, Pieter Roel Tuinman, J. Tim Marcus, Coen A.C. Ottenheijm, Leo Heunks

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Positive end-expiratory pressure (PEEP) is routinely applied in mechanically ventilated patients to improve gas exchange and respiratory mechanics by increasing end-expiratory lung volume (EELV). In a recent experimental study in rats, we demonstrated that prolonged application of PEEP causes diaphragm remodeling, especially longitudinal muscle fiber atrophy. This is of potential clinical importance, as the acute withdrawal of PEEP during ventilator weaning decreases EELV and thereby stretches the adapted, longitudinally atrophied diaphragm fibers to excessive sarcomere lengths, having a detrimental effect on force generation. Whether this series of events occurs in the human diaphragm is unknown. In the current study, we investigated if shortterm application of PEEP affects diaphragm geometry and function, which are prerequisites for the development of longitudinal atrophy with prolonged PEEP application. Nineteen healthy volunteers were noninvasively ventilated with PEEP levels of 2, 5, 10, and 15 cmH2O. Magnetic resonance imaging was performed to investigate PEEP-induced changes in diaphragm geometry. Subjects were instrumented with nasogastric catheters to measure diaphragm neuromechanical efficiency (i.e., diaphragm pressure normalized to its electrical activity) during tidal breathing with different PEEP levels. We found that increasing PEEP from 2 to 15 cmH2O resulted in a caudal diaphragm displacement (19 [14-26] mm, P < 0.001), muscle shortening in the zones of apposition (20.6% anterior and 32.7% posterior, P < 0.001), increase in diaphragm thickness (36.4% [0.9%-44.1%], P < 0.001) and reduction in neuromechanical efficiency (48% [37.6%-56.6%], P < 0.001). These findings demonstrate that conditions required to develop longitudinal atrophy in the human diaphragm are present with the application of PEEP.

Original languageEnglish (US)
Pages (from-to)1328-1339
Number of pages12
JournalJournal of Applied Physiology
Issue number4
StatePublished - Oct 2021
Externally publishedYes


  • Diaphragm contractile function
  • Diaphragm geometry
  • Positive end-expiratory pressure

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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