Journal of Translational Critical Care Medicine

: 2022  |  Volume : 4  |  Issue : 1  |  Page : 5-

Diaphragm-Protective Mechanical Ventilation: Saving the Diaphragm from the Detrimental Effects of Mechanical Ventilation

Zhonghua Shi1, Jian-Xin Zhou2, Leo Heunks3,  
1 Department of Intensive Care Medicine, Amsterdam University Medical Centers; Amsterdam Cardiovascular Sciences Research Institute, Amsterdam University Medical Centers, Amsterdam, Netherlands; Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
2 Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
3 Department of Intensive Care, Erasmus Medical Center, Rotterdam, The Netherlands

Correspondence Address:
Prof. Leo Heunks
Erasmus Medical Center, Postbus 2040, 3015 GD, Rotterdam
The Netherlands


Diaphragm weakness develops in up to 80% of the critically ill patients, and is associated with adverse clinical outcomes. Mechanical ventilation has been proposed to play a role in the development of diaphragm weakness in critically ill patients, especially by ventilator under-assist or ventilator over-assist. Therefore, in addition to the concept of lung-protective ventilation to protect the lung, diaphragm-protective ventilation has been recently proposed to limit the development of diaphragm weakness. In this concise review, we will discuss the current evidence for diaphragm-protective ventilation and the clinical consequences.

How to cite this article:
Shi Z, Zhou JX, Heunks L. Diaphragm-Protective Mechanical Ventilation: Saving the Diaphragm from the Detrimental Effects of Mechanical Ventilation.J Transl Crit Care Med 2022;4:5-5

How to cite this URL:
Shi Z, Zhou JX, Heunks L. Diaphragm-Protective Mechanical Ventilation: Saving the Diaphragm from the Detrimental Effects of Mechanical Ventilation. J Transl Crit Care Med [serial online] 2022 [cited 2022 Sep 27 ];4:5-5
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 Critical Illness-Associated Diaphragm Weakness

The diaphragm is the most important muscle of the respiratory pump, which drives alveolar ventilation. An imbalance between the load and capacity of the respiratory pump is a potentially life-threatening condition. In severe cases, invasive mechanical ventilation is unavoidable. However, it is now recognized that mechanical ventilation, while lifesaving, may have detrimental effects on the diaphragm.[1],[2],[3] In fact, diaphragm dysfunction develops in 64% of the patients within 24 h of intubation, and increases to more than 80% during the course of intensive care unit (ICU) stay.[3],[4] Diaphragm dysfunction is associated with prolonged mechanical ventilation, higher incidence of weaning failure, and mortality.[5] Several factors have been proposed to play a role in the development of critical illness-associated diaphragm weakness including mechanical ventilation, inflammation, denutrition, and exposure to selected drugs.[3]

The impact of mechanical ventilation on the respiratory muscles depends on ventilator settings, suggesting that optimizing ventilator support may limit the impact of mechanical ventilation on the diaphragm. This has been termed “diaphragm-protective ventilation.”[6]

 Mechanisms of Ventilator-Induced Diaphragm Dysfunction

Four mechanisms for the development of diaphragm weakness that are modifiable by ventilator settings have been proposed, although with different levels of evidence.

Disuse atrophy

Development of diaphragm atrophy has been demonstrated using different techniques (e.g., histological analysis of muscle biopsies, ultrasound, and computed tomography [CT] scan).[2],[4],[7],[8],[9],[10],[11] Patients on controlled mechanical ventilation or high levels of inspiratory support appear at highest risk for the development of diaphragm atrophy. It should be noted that loss of contractile protein is a physiological response to inactivity which in case of the respiratory muscles may develop with ventilator over-assistance.[4],[7],[8] Indeed, it has been demonstrated that ±50% of patients receiving invasive mechanical ventilation develop diaphragm atrophy.[7] More recently, atrophy of the expiratory muscles has been described in selected ventilated ICU patients, although surprisingly, no correlation was found between changes in thickness of the diaphragm and expiratory muscles of these patients.[12] This indicates that the diaphragm responds differently to mechanical ventilation as compared to other respiratory muscles.

Load-induced injury

Muscle injury consistent with high loading (such as sarcolemma rupture, sarcomeric disarray, and inflammatory infiltration) has been reported in the diaphragm of ventilated animals and ICU patients.[4],[13],[14],[15],[16],[17] Load-induced injury results from excessive activity of the respiratory muscles with ventilator under-assistance. In the presence of sepsis and systematic inflammation, the diaphragm may be more susceptible to load-induced injury, and even moderate increase of respiratory effort may cause diaphragm injury and weakness.[16],[18] It should be noted that evidence of load-induced diaphragm injury is mainly derived from experimental studies, its prevalence (or even existence) and clinical impact in mechanically ventilated critically ill patients remain to be established. However, the existing physiological data support a mechanical ventilation approach that prevents very high breathing effort for prolonged periods of time in order to protect the diaphragm.

Eccentric injury

Eccentric contractions occur with diaphragm activation during the expiratory phase. Intense eccentric contractions lead to persistent diaphragm functional impairment associated with sarcomeric and sarcolemmal damage.[19] Diaphragm eccentric contractions may develop with several types of patient-ventilator asynchrony, such as premature cycling, reverse triggering, and ineffective effort during expiration.[20],[21],[22],[23],[24],[25] The diaphragm has been shown to be activated during expiration in an animal model of acute respiratory distress syndrome (ARDS),[20] and as in the presence of expiratory flow, thoracic volume decreases, any activity of the diaphragm in this phase results in eccentric contractions, although it remains to be investigated under which conditions this results in injury. Nevertheless, it should be acknowledged that the concept of eccentric injury in the diaphragm of ICU patients is based on experimental work and physiological reasoning. No data are yet available to prove this concept in humans.

Longitudinal atrophy

Mechanical ventilation with positive end-expiratory pressure (PEEP) increases end-expiratory lung volume, which flattens the diaphragm dome and shortens the zone of apposition of the diaphragm.[26] Experimental data have demonstrated that this results in structural modification of the diaphragm myofibers, in particular shortening of the muscle, so-called longitudinal atrophy.[27] PEEP-induced longitudinal atrophy is characterized by absorbing serially linked sarcomeres, the smallest contractile units in the muscle fibers. Together with the aforementioned cross-sectional atrophy, this impairs the ability of diaphragm to deal with a sudden release of PEEP and increase of the inspiratory load, for example, during a weaning trial. Although PEEP-induced diaphragm longitudinal atrophy has been demonstrated in experimental models and PEEP-induced shortening of the diaphragm in the zone of apposition in healthy subjects, the clinical impact remains to be investigated.

 Diaphragm-Protective Ventilation

On the premise of the abovementioned mechanisms for diaphragm weakness in ventilated ICU patients, the main component of diaphragm-protective ventilation is to maintain a physiological level of diaphragm effort, i.e., to limit ventilator over-assist and ventilator under-assist. Recent statements have recommended to maintain the diaphragm activity within a physiological range in ventilated patients.[28],[29] Several bedside techniques are available to monitor respiratory muscle effort. The reference values provided are based on physiological reasoning and consensus. As outlined above, inactivity has been proposed to be an important contributor to diaphragm weakness, and therefore, it is advisable to maintain some diaphragm activity while patients are mechanically ventilated. However, clinical studies have demonstrated that in the early phase of severe ARDS, 48 h of neuromuscular blockade may improve patient outcome,[30],[31] and does not increase the duration of mechanical ventilation, making it unlikely that these patients have developed clinically relevant respiratory muscle weakness due to neuromuscular blockade. The mechanisms are unclear, but it may be hypothesized that diaphragm activity during severe systemic inflammation is potentially injurious. Alternatively, the protective effect of neuromuscular blockade on the lung may outweigh the detrimental effect on the diaphragm. This remains to be investigated.

Patient-ventilator asynchrony is a common phenomenon in mechanically ventilated patients and associated with mortality.[23] When a mismatch (level of assist or timing) occurs between the patient demand and ventilator support, asynchrony may ensure. Therefore, maintaining appropriate ventilator settings in terms of level of support and time of cycling are important to limit the impact of mechanical ventilation on the diaphragm. However, the threshold for the detrimental effects of patient-ventilator asynchrony is unknown and is likely different for each patient.

In the case of longitudinal atrophy, an acute reduction or withdrawal of PEEP lengthens the diaphragm fibers and forces the diaphragm to contract at longer (stretched) sarcomere length (i.e., the descending limb of the force-length relation curve), thus contributing to the diaphragm contractile weakness. If this concept appears true, a gradual reduction of the PEEP may be beneficial, in order to let the diaphragm muscle adapt to operating at increased sarcomere lengths. However, clinical evidence for this strategy is lacking and more clinical studies are needed before this can be implemented in clinical care.

 Monitor of the Diaphragm Effort

Achieving the abovementioned targets for diaphragm-protective ventilation relies on close monitoring of diaphragm effort at the bedside [Figure 1]. Esophageal pressure (Pes) or transdiaphragmatic pressure (Pdi, i.e., gastric pressure-Pes) provides a continuous, direct measurement of diaphragm effort, which is the gold standard for respiratory muscle effort and can be used to directly guide the ventilatory settings. The Pes swing within the range of 3–15 cmH2O is close to the physiological range and could be used as a target for the ventilator setting.[28],[29],[32]{Figure 1}

The electrical activity of the diaphragm (EAdi) has been used to estimate the diaphragm effort,[33] which could be obtained using a dedicated nasogastric feeding tube equipped with miniaturized electrodes at the distal end (i.e., EAdi catheter, Maquet©, Sweden). As there are large variations in individual patients (4–29 μV in young healthy subjects), there is no so-called physiological reference of EAdi.[34] Together with the ventilator waveforms, such as flow and airway pressure, Pes or EAdi can be used to identify patient-ventilation interaction.[35],[36]

Noninvasive techniques may be used to assess respiratory muscle effort. First, airway occlusion pressure (P0.1), the pressure developed in the occluded airway 100 ms after the onset of inspiration, is a reasonable estimate of respiratory drive and inspiratory effort.[37] P0.1 is independent of the respiratory mechanics and the patient's reaction. P0.1 higher than 1–1.5 cmH2O and lower than 3.5–5 cmH2O may help to prevent disuse atrophy and loading injury, respectively.[29] Second, the maximum airway pressure generated by a patient against an end-expiratory airway occlusion may be used to detect excessive respiratory muscle pressure and identify patient-ventilation asynchrony.[38]

Diaphragm ultrasound has become increasingly popular,[39] which provides a reliable assessment for thickness and activity of both the inspiratory and expiratory muscle groups.[12],[39] Measuring the thickness of the diaphragm from the zone of position and its change over the breathing cycle (i.e., thickening fraction) provides a noninvasive estimate for contractile effort,[40] although recent reports demonstrate a rather poor correlation between ultrasound derived thickening fraction and transdiaphragmatic pressure in ICU patients.[41] Although consensus statements suggest a diaphragm thickening fraction in the range of 15%–30% is associated with the shortest duration of mechanical ventilation,[42] these recommendations should be used with caution. Clearly, more data are needed to validate ultrasound-derived variables as an estimate for diaphragm effort. In addition, when used together with ventilator waveforms, diaphragm ultrasound can be used to detect different types of patient-ventilator asynchrony.[39]

 Balance Between Diaphragm- and Lung-Protective Ventilation

Diaphragm contraction is more prominent in the dorsal lung region compared to the ventral lung region, which is beneficial for the recruitment of the dorsal lung regions (i.e., the dependent region).[43] However, activation of the diaphragm in the dorsal region may lead to markedly increase in the lung stress, the so-called patient self-inflicted lung injury,[44] especially in patients with moderate or severe ARDS. Therefore, under these circumstances, maintaining diaphragm activity may jeopardize the goal of lung protection. Given the level of evidence available, when conflicting, we should probably prioritize lung-protective ventilation over the diaphragm-protective ventilation.[29] Notably, a high respiratory drive may develop in critically ill patients and may be detrimental for both the lung and diaphragm.[45] Modulation of respiratory drive may be challenging; in this situation, extracorporeal CO2 removal may be required in addition to modulation of ventilator breathing assist to deliver lung- and diaphragm-protective ventilation.[28],[46]

 Future Research

Diaphragm-protective ventilation is a novel concept that will undoubtedly evolve with increasing knowledge. Most important is to establish the safe limits for diaphragm activity under different clinical circumstances (e.g., early ARDS, weaning phase). Furthermore, the feasibility of achieving these targets should be established, especially in patients with high respiratory drive. Third, the effect of diaphragm-protective ventilation on preventing the diaphragm dysfunction, thus improving the clinical outcomes should be evaluated in clinical trials. In addition, several cellular and molecular mechanisms which are involved in decreased protein synthesis, increased proteolysis, increased oxidative stress, and mitochondrial dysfunction have been implicated in VIDD.[2] The role of specific drugs to limit diaphragm weakness in ventilated critically ill patients remains to be investigated.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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