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The Effects of Sevoflurane Exposure on Ventilator-Induced Diaphragmatic Dysfunction in a Rat Model: Interconnectedness of Basic Science, Clinical Science, and Clinical Practice

De Lima, Luiz Germano Reblin MD*; Hollmann, Markus W. MD, PhD, DEAA

doi: 10.1213/ANE.0000000000000730
Editorials: Editorial

From the *Department of Anesthesiology, University of Mississippi Medical Center, Jackson, Mississippi; and Department of Anesthesiology, Academic Medical Center Amsterdam, Amsterdam, the Netherlands.

Accepted for publication February 10, 2015.

Funding: None.

The authors declare no conflicts of interest.

Reprints will not be available from the authors.

Address correspondence to Luiz Germano Reblin De Lima, MD, Department of Anesthesiology, University of Mississippi Medical Center, 2500 N State St., Jackson, MS 39216. Address e-mail to ldelima@umc.edu.

The subject of ventilator-induced diaphragmatic dysfunction is important because hundreds of thousands of patients receive prolonged mechanical ventilation in intensive care units (ICUs). Many of these patients require difficult and prolonged weaning, accounting for 40% to 60% of the total time on mechanical ventilation. Difficulty weaning from ventilation increases ICU stay and health care costs. There is some evidence that ventilator-induced diaphragmatic dysfunction may develop after 6 hours or less of mechanical ventilation. If so, then patients undergoing long surgeries might be at risk. Perhaps subsets of patients undergoing cancer resection, trauma reconstruction, or complex cardiovascular operations bear a higher inflammatory burden from ventilator-induced diaphragmatic dysfunction.

Ventilator-induced diaphragmatic dysfunction is multifactorial. Diaphragm inactivity is obviously one major contributor. In this issue of Anesthesia & Analgesia, Breuer et al.1 present evidence that sevoflurane exposure prevents oxidative stress of the inactive diaphragm but decreases protein synthesis, increases proteolysis, and leads to force reduction in both mechanically ventilated and spontaneously breathing rats. This is important because current ventilator-induced diaphragmatic dysfunction prevention strategies call for periods of spontaneous ventilation or other interventions that decrease ventilator support. If patients receive sevoflurane, such strategies may fail. The same research group recently showed that propofol, commonly used for sedation in mechanically ventilated patients, does not protect against oxidative injury and induces similar diaphragm dysfunction and atrophy during spontaneous breathing and mechanical ventilation in rats.2 The implication is that sedation with propofol or sevoflurane may impair weaning in patients requiring ventilator support.

Sevoflurane has been used for sedation of mechanically ventilated patients. This use is facilitated by disposable anesthetic-conserving devices such as the AnaConDa (Sedana Medical, Uppsala, Sweden).3 However, because of its rapid washin and washout, sevoflurane might be advantageous if it is used judiciously for short periods.

Animal studies have the advantage of simplicity. In the study by Breuer and colleagues, the rats only received sevoflurane. This cannot be readily translated to the clinical setting because mechanically ventilated patients receive many drugs and interventions. Clinical studies on the influence of sevoflurane on ventilator-induced diaphragmatic dysfunction will have to control for many variables to attribute the findings to sevoflurane and not to something else. However, let us assume that the animal results apply perfectly to humans. This is suggested by a 2011 review from Jaber et al.4 The authors examined the effects of drugs, drug interactions, mechanical ventilation, sepsis, and other factors on ventilator-induced diaphragmatic dysfunction. Their review demonstrated that data from animal models are applicable to humans.

Finding that animal data extrapolate to humans does not necessarily guide clinical practice. If not sevoflurane or propofol, then what are the options for ventilated patients? Dexmedetomidine? It may reduce length of ventilation, but does not reduce delirium, and may increase the risk of bradycardia.5 Propofol? Perhaps, but propofol ICU syndrome is always a worry. Benzodiazepines? They increase the risk of posttraumatic stress disorder in mechanically ventilated patients.6 No sedation? This may be effective in some settings,7 but it seems unnecessarily stressful, particularly if the patient is agitated. Even if sevoflurane affects the human diaphragm exactly the same way it affects the rat diaphragm, this information does not inform our clinical practice.

The expansion of scientific knowledge opens new venues for research such as the effects on the diaphragm of drugs used in anesthesia and intensive care, potential protective measures, and possible associations between ventilator-induced diaphragmatic dysfunction and ventilator-induced lung injury. These are interesting and worthwhile subjects for future research. From a clinician’s perspective, the interconnectedness of basic science, clinical science, and clinical practice reminds us that clinical anesthesiology is a craft, and sometimes an art, rooted in science. Our scientific foundations guide our practice, inform our decisions, standardize our approaches, and improve our outcomes.

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DISCLOSURES

Name: Luiz Germano Reblin De Lima, MD.

Contribution: This author helped write this manuscript.

Attestation: Luiz Germano Reblin De Lima approved the final manuscript.

Name: Markus W. Hollmann, MD, PhD, DEAA.

Contribution: This author helped write this manuscript.

Attestation: Markus W. Hollmann approved the final manuscript.

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RECUSE NOTE

Dr. Markus W. Hollmann is the Section Editor for Preclinical Pharmacology for the Journal. This manuscript was handled by Dr. Steven L. Shafer, Editor-in-Chief, and Dr. Hollmann was not involved in any way with the editorial process or decision.

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REFERENCES

1. Breuer T, Maes K, Rossaint R, Marx G, Scheers H, Bergs I, Bleilevens C, Gayan-Ramirez G, Bruells CS. Sevoflurane exposure prevents diaphragmatic oxidative stress during mechanical ventilation but reduces force and affects protein metabolism even during spontaneous breathing in a rat model. Anesth Analg. 2015;121:73–80
2. Bruells CS, Maes K, Rossaint R, Thomas D, Cielen N, Bergs I, Bleilevens C, Weis J, Gayan-Ramirez G. Sedation using propofol induces similar diaphragm dysfunction and atrophy during spontaneous breathing and mechanical ventilation in rats. Anesthesiology. 2014;120:665–72
3. Berton J, Sargentini C, Nguyen JL, Belii A, Beydon L. AnaConDa reflection filter: bench and patient evaluation of safety and volatile anesthetic conservation. Anesth Analg. 2007;104:130–4
4. Jaber S, Jung B, Matecki S, Petrof BJ. Clinical review: ventilator-induced diaphragmatic dysfunction—human studies confirm animal model findings! Crit Care. 2011;15:206
5. Chen K1, Lu Z, Xin YC, Cai Y, Chen Y, Pan SM. Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients. Cochrane Database Syst Rev. 2015:CD010269
6. Wade DM, Howell DC, Weinman JA, Hardy RJ, Mythen MG, Brewin CR, Borja-Boluda S, Matejowsky CF, Raine RA. Investigating risk factors for psychological morbidity three months after intensive care: a prospective cohort study. Crit Care. 2012;16:R192
7. Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375:475–80
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