Controlled mechanical ventilation (CMV) is a ventilator mode where the respiratory muscles are not contracting, and the ventilator takes full responsibility for inflating the respiratory system. Evidence accumulating over the past two decades has shown that CMV can induce dysfunction of the diaphragm, mainly consisting of atrophy, oxidative stress, and ultrastructural injury, resulting in decreased diaphragmatic contractility. This is called ventilator-induced diaphragmatic dysfunction (VIDD).1
The frequency with which CMV is used cannot be determined with certainty. An international survey revealed that 13% of mechanically ventilated patients receive a neuromuscular blocker for 8% of the total days of ventilator support.2 In these patients, full ventilator support is mandatory. Moreover, it was recently shown that the use of neuromuscular blockers during the first 2 days of ventilator support improves the survival of patients with severe acute respiratory distress syndrome,3 a finding that may lead to increased use of CMV. Other patient groups not receiving neuromuscular blockers also receive full ventilator support, such as patients with traumatic brain injury, postoperative neurosurgical patients, comatose patients, patients with status epilepticus on barbiturate coma to suppress seizure activity, and so on. Thus, a considerable percentage of ventilated patients are at risk of developing VIDD.
The mechanisms of this dysfunction and the clinical relevance for mechanically ventilated patients is the subject of this chapter.
The first human evidence for the existence of VIDD came from retrospective analysis of postmortem data obtained in neonates who received ventilatory assistance for 12 days or more immediately before death. This study revealed diffuse diaphragmatic myofiber atrophy (small myofibers with rounded outlines), not present in extradiaphragmatic muscles or diaphragms of infants ventilated for 7 days or less.4
Recently, direct evidence came from studies of brain-dead organ donors (with an intact circulation) who underwent CMV and who developed biopsy-proven atrophy5,6 and decline in the contractility of their diaphragm.6
Ventilator-induced atrophy7 is usually measured by the reduction of the cross-sectional area of myocytes in histologic sections. Atrophy has been observed in both slow-twitch and fast-twitch human diaphragmatic fibers and is quite significant (Fig. 43-1), its magnitude amounting to 40% to 50% after quite variable periods of CMV (range: 15 to 276 hours.)5,6,8 Atrophy preferentially affects the diaphragm because it was not observed in the pectoralis major muscle of the same patients.5 The longer the duration of CMV, the greater the observed atrophy (Fig. 43-2).6
Atrophy in the human diaphragm after CMV. The slow-twitch and fast-twitch fibers in the case specimens (Panels A, C, and E) are smaller than those in the control diaphragms (Panels B, D, and F). Panels A and B (hematoxylin and eosin) show that neither inflammatory infiltrate nor necrosis is ...