BACKGROUND: Diaphragm atrophy and dysfunction is a major problem among critically ill patients on mechanical ventilation. Ventilator-induced diaphragmatic dysfunction is thought to play a major role, resulting in a failure of weaning. Stimulation of the phrenic nerves and resulting diaphragm contraction could potentially prevent or treat this atrophy. The subject of this study is to determine the effectiveness of diaphragm stimulation in preventing atrophy by measuring changes in its thickness. METHODS: A total of 12 patients in the intervention group and 10 patients in the control group were enrolled. Diaphragm thickness was measured by ultrasound in both groups at the beginning of study enrollment (hour 0), after 24 hours, and at study completion (hour 48). The obtained data were then statistically analyzed and both groups were compared. RESULTS: The results showed that the baseline diaphragm thickness in the interventional group was (1.98 ± 0.52) mm and after 48 hours of phrenic nerve stimulation increased to (2.20 ± 0.45) mm (p=0.001). The baseline diaphragm thickness of (2.00 ± 0.33) mm decreased in the control group after 48 hours of mechanical ventilation to (1.72 ± 0.20) mm (p<0.001). CONCLUSIONS: Our study demonstrates that induced contraction of the diaphragm by pacing the phrenic nerve not only reduces the rate of its atrophy during mechanical ventilation but also leads to an increase in its thickness - the main determinant of the muscle strength required for spontaneous ventilation and successful ventilator weaning. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (18/06/2018, NCT03559933, https://clinicaltrials.gov/ct2/show/NCT03559933 ).

Department of Anesthesiology and Intensive Care 1st Faculty of Medicine Charles University and Military University Hospital U Vojenské nemocnice 1200 Prague 169 02 Czech Republic

Department of Biomedical Technology Faculty of Biomedical Engineering Czech Technical University Prague Czech Republic

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Esteban A, Anzueto A, Alia I, et al. How is mechanical ventilation employed in the intensive care unit? An international utilization review. Am J Respir Crit Care Med. 2000;161:1450–1458. doi: 10.1164/ajrccm.161.5.9902018. PubMed DOI

Pfuntner A, Wier LM, Stocks C. Most frequent procedures performed in U.S. hospitals, 2011: Statistical Brief #165. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. Rockville: Agency for Healthcare Research and Quality; 2013. PubMed

Wunsch H, Kramer A, Gershengorn HB. Validation of intensive care and mechanical ventilation codes in Medicare data. Crit Care Med. 2017;45(7):e711–e714. doi: 10.1097/CCM.0000000000002316. PubMed DOI PMC

Timsit JF, Esaied W, Neuville M, Bouadma L, Mourvllier B. Update on ventilator-associated pneumonia. F1000Res. 2017;6:2061. PubMed PMC

Zilberberg MD, de Wit M, Shorr AF. Accuracy of previous estimates for adult prolonged acute mechanical ventilation volume in 2020: update using 2000–2008 data. Crit Care Med. 2012;40(1):18–20. doi: 10.1097/CCM.0b013e31822e9ffd. PubMed DOI

Beduneau G, Pham T, Schortgen F, Piquilloud L, Zogheib E, Jonas M, et al. Epidemiology of Weaning Outcome according to a New Definition. The WIND study. Am J Respir Crit Care Med. 2017;195(6):772–83 PubMed

Dres M, Goligher EC, Heunks LMA, Brochard LJ. Critical illness-associated diaphragm weakness. Intensive Care Med. 2017;43(10):1441–1452. doi: 10.1007/s00134-017-4928-4. PubMed DOI

Petrof BJ, Hussain SN. Ventilator-induced diaphragmatic dysfunction: what have we learned? Curr Opin Crit Care. 2016;22(1):67–72. doi: 10.1097/MCC.0000000000000272. PubMed DOI

Dasta JF, McLaughlin TP, Mody SH, et al. Daily cost of an intensive care unit day: the contribution of mechanical ventilation. Crit Care Med. 2005;33:1266–1271. doi: 10.1097/01.CCM.0000164543.14619.00. PubMed DOI

Esteban A, Ferguson ND, Meade MO, et al. Evolution of mechanical ventilation in response to clinical research. Am J Respir Crit Care Med. 2008;177:170–177. doi: 10.1164/rccm.200706-893OC. PubMed DOI

Schweickert WD. ICU-acquired weakness. Chest. 2007;131:1541. doi: 10.1378/chest.06-2065. PubMed DOI

Jaber S, Petrof BJ, Jung B, Chanques G, Berthet J, Rabuel C, Bouyabrine H, Courouble P, Koechlin-Ramonatxo C, Sebbane M, Similowski T, Scheuermann V, Mebazaa A, Capdevila X, Mornet D, Mercier J, Lacampagne A, Philips A, Matecki S. Rapidly Progressive Diaphragmatic Weakness and Injury during Mechanical Ventilation in Humans. Am J Respir Crit Care Med. 2011;183:364–371. doi: 10.1164/rccm.201004-0670OC. PubMed DOI

Gruther W, Benesch T, Zorn C, Paternostro-Sluga T, Quittan M, Fialka- Moser V, et al. Muscle wasting in intensive care patients: ultrasound observation of the M. quadriceps femoris muscle layer. Acta DermVenereol. 2008;40:185–9. PubMed

Gilbert R, Auchincloss JH, Peppi D. Relationship of rib cage and abdomen motion to diaphragm function during quiet breathing. Chest. 1981;80:607–612. doi: 10.1378/chest.80.5.607. PubMed DOI

Demoule A, Jung B, Prodanovic H, Molinari N, Chanques G, Coirault C, et al. Diaphragm dysfunction on admission to ICU: prevalence, risk factors and prognostic impact - a prospective study. Am J Respir Crit Care Med. 2013;188:213–219. doi: 10.1164/rccm.201209-1668OC. PubMed DOI

Hermans G, Casaer MP, Clerckx B, Güiza F, Vanhullebusch T, Derde S, et al. Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. Lancet Respir Med. 2013;1:621–629. doi: 10.1016/S2213-2600(13)70183-8. PubMed DOI

Peñuelas O, Keough E, López-Rodríguez L, Carriedo D, Gonçalves G, Barreiro E, Lorente JÁ. Ventilator-induced diaphragm dysfunction: translational mechanisms lead to therapeutical alternatives in the critically ill. Intensive Care Med Exp. 2019;7(Suppl 1):48. doi: 10.1186/s40635-019-0259-9.PMID:31346802;PMCID:PMC6658639. PubMed DOI PMC

Testelmans D, Maes K, Wouters P, Powers SK, Decramer M, Gayan-Ramirez G. Infusions of rocuronium and cisatracurium exert different effects on rat diaphragm function. Intensive Care Med. 2007;33:872–879. doi: 10.1007/s00134-007-0584-4. PubMed DOI

Maes K, Testelmans D, Cadot P, Deruisseau K, Powers SK, Decramer M, et al. Effects of acute administration of corticosteroids during mechanical ventilation on rat diaphragm. Am J Respir Crit Care Med. 2008;178:1219–1226. doi: 10.1164/rccm.200702-296OC. PubMed DOI PMC

Levine S, Nguyen T, Taylor N, Friscia ME, Budak MT, Rothenberg P, et al. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 2008;358:1327–1335. doi: 10.1056/NEJMoa070447. PubMed DOI

Manno E, Navarra M, Faccio L, Motevallian M, Bertolaccini L, Mfochivè A, et al. Deep impact of ultrasound in the intensive care unit: the “ICU-sound” protocol. Anesthesiology. 2012;117:801–809. doi: 10.1097/ALN.0b013e318264c621. PubMed DOI

Zambon M, Greco M, Bocchino S, Cabrini L, Beccaria PF, Zangrillo A. Assessment of diaphragmatic dysfunction in the critically ill patient with ultrasound: a systematic review. Intensive Care Med. 2017;43(1):29–38. doi: 10.1007/s00134-016-4524-z. PubMed DOI

Le Pimpec-Barthes F, Legras A, Arame A, Pricopi C, Boucherie JC, Badia A, et al. Diaphragm pacing: the state of the art. J Thorac Dis. 2016;8(Suppl 4):S376–S386. doi: 10.21037/jtd.2016.03.97. PubMed DOI PMC

Evans D, Shure D, Clark L, et al. Temporary transvenous diaphragm pacing vs. standard of care for weaning from mechanical ventilation: study protocol for a randomized trial. Trials. 2019;20(1):60. Published 2019 Jan 17. doi:10.1186/s13063-018-3171-9 PubMed PMC

Reynolds S, Ebner A, Meffen T, Thakkar V, Gani M, Taylor K, Clark L, Sadarangani G, Meyyappan R, Sandoval R, Rohrs E, Hoffer JA. Diaphragm Activation in Ventilated Patients Using a Novel Transvenous Phrenic Nerve Pacing Catheter. Crit Care Med. 2017;45(7):e691–e694. doi: 10.1097/CCM.0000000000002366. PubMed DOI

Adler D, Gottfried SB, Bautin N, Mirkovic T, Schmidt M, Raux M, et al. Repetitive magnetic stimulation of the phrenic nerves for diaphragm conditioning: a normative study of feasibility and optimal settings. Appl Physiol Nutr Metab. 2011;36(6):1001–1008. doi: 10.1139/h11-095. PubMed DOI

O'Rourke J, Soták M, Curley GF, Doolan A, Henlín T, Mullins G, Tyll T, Omlie W, Ranieri MV. Initial Assessment of the Percutaneous Electrical Phrenic Nerve Stimulation System in Patients on Mechanical Ventilation. Crit Care Med. 2020;48(5):e362–e370. doi: 10.1097/CCM.0000000000004256.PMID:32191413;PMCID:PMC7161723. PubMed DOI PMC

Cohn D, Benditt JO, Eveloff S, McCool FD. Diaphragm thickening during inspiration. J Appl Physiol. 1997;83(1):291–296. doi: 10.1152/jappl.1997.83.1.291. PubMed DOI

Ueki J, De Bruin PF, Pride NB. In vivo assessment of diaphragm contraction by ultrasound in normal subjects. Thorax. 1995;50:1157–1161. doi: 10.1136/thx.50.11.1157. PubMed DOI PMC

Francis CA, Hoffer JA, Reynolds S. Ultrasonographic Evaluation of Diaphragm Thickness During Mechanical Ventilation in Intensive Care Patients. AJCC. 2016;25(1):e1–e8. PubMed

Grosu HB, Lee YI, Lee J, Eden E, Eikermann M, Rose KM. Diaphragm muscle thinning in patients who are mechanically ventilated. Chest. 2012;142(6):1455–1460. doi: 10.1378/chest.11-1638. PubMed DOI

Neumann P, Rothen HU, Berglund JE, Valtysson J, Magnusson A, Hedenstierna G. Positive end-expiratory pressure prevents atelectasis during general anaesthesia even in the presence of a high inspired oxygen concentration. Acta Anaesthesiol Scand. 1999;43(3):295–301. doi: 10.1034/j.1399-6576.1999.430309.x. PubMed DOI

SONIX Touch Q Extended User Manual, 00.040.708, Revision B, Ultrasonix Medical Corporation, 130 - 4311 Viking Way, Richmond, BC V6V 2K9, Canada

Goligher EC, Fan E, Herridge MS, Murray A, Vorona S, Brace D, Rittayamai N, Lanys A, Tomlinson G, Singh JM, Bolz SS, Rubenfeld GD, Kavanagh BP, Brochard LJ, Ferguson ND. Evolution of Diaphragm Thickness during Mechanical Ventilation. Impact of Inspiratory Effort. Am J Respir Crit Care Med. 2015 Nov 1;192(9):1080-8. doi: 10.1164/rccm.201503-0620OC. PMID: 26167730. PubMed

Nevins ML, Epstein SK. Predictors of outcome for patients with COPD requiring invasive mechanical ventilation. Chest. 2001;119:1840–1849. doi: 10.1378/chest.119.6.1840. PubMed DOI

See more in PubMed

ClinicalTrials.gov
NCT03559933