The Efficacy of P0.1-guided Sedation Protocol in Critically Ill Patients Receiving Invasive Mechanical Ventilation: A Randomized Controlled Trial

Summary

This clinical trial aims to assess the efficacy of sedation protocol targeting optimal respiratory drive using P0.1 and arousal level compared with conventional sedation strategy (targeting arousal level alone) in patients requiring mechanical ventilation in the medical intensive care unit.

Timeline

Start

2023-12-22

Primary completion

2026-03-31

Completion

2026-06-30

Publications

• Background Brochard L, Slutsky A, Pesenti A. Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure. Am J Respir Crit Care Med. 2017 Feb 15;195(4):438-442. doi: 10.1164/rccm.201605-1081CP.
• Background Sklienka P, Frelich M, Bursa F. Patient Self-Inflicted Lung Injury-A Narrative Review of Pathophysiology, Early Recognition, and Management Options. J Pers Med. 2023 Mar 28;13(4):593. doi: 10.3390/jpm13040593.
• Background Carteaux G, Parfait M, Combet M, Haudebourg AF, Tuffet S, Mekontso Dessap A. Patient-Self Inflicted Lung Injury: A Practical Review. J Clin Med. 2021 Jun 21;10(12):2738. doi: 10.3390/jcm10122738.
• Background Spinelli E, Mauri T, Beitler JR, Pesenti A, Brodie D. Respiratory drive in the acute respiratory distress syndrome: pathophysiology, monitoring, and therapeutic interventions. Intensive Care Med. 2020 Apr;46(4):606-618. doi: 10.1007/s00134-020-05942-6. Epub 2020 Feb 3.
• Background Spinelli E, Pesenti A, Slobod D, Fornari C, Fumagalli R, Grasselli G, Volta CA, Foti G, Navalesi P, Knafelj R, Pelosi P, Mancebo J, Brochard L, Mauri T. Clinical risk factors for increased respiratory drive in intubated hypoxemic patients. Crit Care. 2023 Apr 11;27(1):138. doi: 10.1186/s13054-023-04402-z.
• Background Chanques G, Constantin JM, Devlin JW, Ely EW, Fraser GL, Gelinas C, Girard TD, Guerin C, Jabaudon M, Jaber S, Mehta S, Langer T, Murray MJ, Pandharipande P, Patel B, Payen JF, Puntillo K, Rochwerg B, Shehabi Y, Strom T, Olsen HT, Kress JP. Analgesia and sedation in patients with ARDS. Intensive Care Med. 2020 Dec;46(12):2342-2356. doi: 10.1007/s00134-020-06307-9. Epub 2020 Nov 10.
• Background Goligher EC, Jonkman AH, Dianti J, Vaporidi K, Beitler JR, Patel BK, Yoshida T, Jaber S, Dres M, Mauri T, Bellani G, Demoule A, Brochard L, Heunks L. Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and excessive effort. Intensive Care Med. 2020 Dec;46(12):2314-2326. doi: 10.1007/s00134-020-06288-9. Epub 2020 Nov 2.
• Background Dzierba AL, Khalil AM, Derry KL, Madahar P, Beitler JR. Discordance Between Respiratory Drive and Sedation Depth in Critically Ill Patients Receiving Mechanical Ventilation. Crit Care Med. 2021 Dec 1;49(12):2090-2101. doi: 10.1097/CCM.0000000000005113.
• Background Wongtangman K, Grabitz SD, Hammer M, Wachtendorf LJ, Xu X, Schaefer MS, Fassbender P, Santer P, Kassis EB, Talmor D, Eikermann M; SICU Optimal Mobilization Team (SOMT) Group. Optimal Sedation in Patients Who Receive Neuromuscular Blocking Agent Infusions for Treatment of Acute Respiratory Distress Syndrome-A Retrospective Cohort Study From a New England Health Care Network. Crit Care Med. 2021 Jul 1;49(7):1137-1148. doi: 10.1097/CCM.0000000000004951.
• Background Jackson DL, Proudfoot CW, Cann KF, Walsh TS. The incidence of sub-optimal sedation in the ICU: a systematic review. Crit Care. 2009;13(6):R204. doi: 10.1186/cc8212. Epub 2009 Dec 16.
• Background Kassis EB, Beitler JR, Talmor D. Lung-protective sedation: moving toward a new paradigm of precision sedation. Intensive Care Med. 2023 Jan;49(1):91-94. doi: 10.1007/s00134-022-06901-z. Epub 2022 Oct 14. No abstract available.
• Background Bertoni M, Spadaro S, Goligher EC. Monitoring Patient Respiratory Effort During Mechanical Ventilation: Lung and Diaphragm-Protective Ventilation. Crit Care. 2020 Mar 24;24(1):106. doi: 10.1186/s13054-020-2777-y.
• Background Rittayamai N, Beloncle F, Goligher EC, Chen L, Mancebo J, Richard JM, Brochard L. Effect of inspiratory synchronization during pressure-controlled ventilation on lung distension and inspiratory effort. Ann Intensive Care. 2017 Oct 6;7(1):100. doi: 10.1186/s13613-017-0324-z.
• Background Telias I, Junhasavasdikul D, Rittayamai N, Piquilloud L, Chen L, Ferguson ND, Goligher EC, Brochard L. Airway Occlusion Pressure As an Estimate of Respiratory Drive and Inspiratory Effort during Assisted Ventilation. Am J Respir Crit Care Med. 2020 May 1;201(9):1086-1098. doi: 10.1164/rccm.201907-1425OC.
• Background Beloncle F, Piquilloud L, Olivier PY, Vuillermoz A, Yvin E, Mercat A, Richard JC. Accuracy of P0.1 measurements performed by ICU ventilators: a bench study. Ann Intensive Care. 2019 Sep 13;9(1):104. doi: 10.1186/s13613-019-0576-x.
• Background de Vries HJ, Tuinman PR, Jonkman AH, Liu L, Qiu H, Girbes ARJ, Zhang Y, de Man AME, de Grooth HJ, Heunks L. Performance of Noninvasive Airway Occlusion Maneuvers to Assess Lung Stress and Diaphragm Effort in Mechanically Ventilated Critically Ill Patients. Anesthesiology. 2023 Mar 1;138(3):274-288. doi: 10.1097/ALN.0000000000004467.
• Background Writing Group for the PReVENT Investigators; Simonis FD, Serpa Neto A, Binnekade JM, Braber A, Bruin KCM, Determann RM, Goekoop GJ, Heidt J, Horn J, Innemee G, de Jonge E, Juffermans NP, Spronk PE, Steuten LM, Tuinman PR, de Wilde RBP, Vriends M, Gama de Abreu M, Pelosi P, Schultz MJ. Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial. JAMA. 2018 Nov 13;320(18):1872-1880. doi: 10.1001/jama.2018.14280.
• Background Grasselli G, Calfee CS, Camporota L, Poole D, Amato MBP, Antonelli M, Arabi YM, Baroncelli F, Beitler JR, Bellani G, Bellingan G, Blackwood B, Bos LDJ, Brochard L, Brodie D, Burns KEA, Combes A, D'Arrigo S, De Backer D, Demoule A, Einav S, Fan E, Ferguson ND, Frat JP, Gattinoni L, Guerin C, Herridge MS, Hodgson C, Hough CL, Jaber S, Juffermans NP, Karagiannidis C, Kesecioglu J, Kwizera A, Laffey JG, Mancebo J, Matthay MA, McAuley DF, Mercat A, Meyer NJ, Moss M, Munshi L, Myatra SN, Ng Gong M, Papazian L, Patel BK, Pellegrini M, Perner A, Pesenti A, Piquilloud L, Qiu H, Ranieri MV, Riviello E, Slutsky AS, Stapleton RD, Summers C, Thompson TB, Valente Barbas CS, Villar J, Ware LB, Weiss B, Zampieri FG, Azoulay E, Cecconi M; European Society of Intensive Care Medicine Taskforce on ARDS. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies. Intensive Care Med. 2023 Jul;49(7):727-759. doi: 10.1007/s00134-023-07050-7. Epub 2023 Jun 16.
• Background Brenner M, Mukai DS, Russell JE, Spiritus EM, Wilson AF. A new method for measurement of airway occlusion pressure. Chest. 1990 Aug;98(2):421-7. doi: 10.1378/chest.98.2.421.
• Background Devlin JW, Skrobik Y, Gelinas C, Needham DM, Slooter AJC, Pandharipande PP, Watson PL, Weinhouse GL, Nunnally ME, Rochwerg B, Balas MC, van den Boogaard M, Bosma KJ, Brummel NE, Chanques G, Denehy L, Drouot X, Fraser GL, Harris JE, Joffe AM, Kho ME, Kress JP, Lanphere JA, McKinley S, Neufeld KJ, Pisani MA, Payen JF, Pun BT, Puntillo KA, Riker RR, Robinson BRH, Shehabi Y, Szumita PM, Winkelman C, Centofanti JE, Price C, Nikayin S, Misak CJ, Flood PD, Kiedrowski K, Alhazzani W. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018 Sep;46(9):e825-e873. doi: 10.1097/CCM.0000000000003299.
• Background Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. doi: 10.1097/CCM.0b013e3182783b72.
• Background Seo Y, Lee HJ, Ha EJ, Ha TS. 2021 KSCCM clinical practice guidelines for pain, agitation, delirium, immobility, and sleep disturbance in the intensive care unit. Acute Crit Care. 2022 Feb;37(1):1-25. doi: 10.4266/acc.2022.00094. Epub 2022 Feb 28.
• Background National Heart, Lung, and Blood Institute PETAL Clinical Trials Network; Moss M, Huang DT, Brower RG, Ferguson ND, Ginde AA, Gong MN, Grissom CK, Gundel S, Hayden D, Hite RD, Hou PC, Hough CL, Iwashyna TJ, Khan A, Liu KD, Talmor D, Thompson BT, Ulysse CA, Yealy DM, Angus DC. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019 May 23;380(21):1997-2008. doi: 10.1056/NEJMoa1901686. Epub 2019 May 19.
• Background Marra A, Ely EW, Pandharipande PP, Patel MB. The ABCDEF Bundle in Critical Care. Crit Care Clin. 2017 Apr;33(2):225-243. doi: 10.1016/j.ccc.2016.12.005.
• Background Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, Pearl R, Silverman H, Stanchina M, Vieillard-Baron A, Welte T. Weaning from mechanical ventilation. Eur Respir J. 2007 May;29(5):1033-56. doi: 10.1183/09031936.00010206.
• Background Tongyoo S, Tantibundit P, Daorattanachai K, Viarasilpa T, Permpikul C, Udompanturak S. High-flow nasal oxygen cannula vs. noninvasive mechanical ventilation to prevent reintubation in sepsis: a randomized controlled trial. Ann Intensive Care. 2021 Sep 14;11(1):135. doi: 10.1186/s13613-021-00922-5.
• Background Sandhu RS, Pasquale MD, Miller K, Wasser TE. Measurement of endotracheal tube cuff leak to predict postextubation stridor and need for reintubation. J Am Coll Surg. 2000 Jun;190(6):682-7. doi: 10.1016/s1072-7515(00)00269-6.
• Background Cheng KC, Hou CC, Huang HC, Lin SC, Zhang H. Intravenous injection of methylprednisolone reduces the incidence of postextubation stridor in intensive care unit patients. Crit Care Med. 2006 May;34(5):1345-50. doi: 10.1097/01.CCM.0000214678.92134.BD.
• Background Fan T, Wang G, Mao B, Xiong Z, Zhang Y, Liu X, Wang L, Yang S. Prophylactic administration of parenteral steroids for preventing airway complications after extubation in adults: meta-analysis of randomised placebo controlled trials. BMJ. 2008 Oct 20;337:a1841. doi: 10.1136/bmj.a1841.
• Background Pluijms WA, van Mook WN, Wittekamp BH, Bergmans DC. Postextubation laryngeal edema and stridor resulting in respiratory failure in critically ill adult patients: updated review. Crit Care. 2015 Sep 23;19(1):295. doi: 10.1186/s13054-015-1018-2.
• Background Lee CH, Peng MJ, Wu CL. Dexamethasone to prevent postextubation airway obstruction in adults: a prospective, randomized, double-blind, placebo-controlled study. Crit Care. 2007;11(4):R72. doi: 10.1186/cc5957.
• Background Hernandez G, Vaquero C, Colinas L, Cuena R, Gonzalez P, Canabal A, Sanchez S, Rodriguez ML, Villasclaras A, Fernandez R. Effect of Postextubation High-Flow Nasal Cannula vs Noninvasive Ventilation on Reintubation and Postextubation Respiratory Failure in High-Risk Patients: A Randomized Clinical Trial. JAMA. 2016 Oct 18;316(15):1565-1574. doi: 10.1001/jama.2016.14194.
• Background Papazian L, Klompas M, Luyt CE. Ventilator-associated pneumonia in adults: a narrative review. Intensive Care Med. 2020 May;46(5):888-906. doi: 10.1007/s00134-020-05980-0. Epub 2020 Mar 10.
• Background Klompas M, Branson R, Cawcutt K, Crist M, Eichenwald EC, Greene LR, Lee G, Maragakis LL, Powell K, Priebe GP, Speck K, Yokoe DS, Berenholtz SM. Strategies to prevent ventilator-associated pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in acute-care hospitals: 2022 Update. Infect Control Hosp Epidemiol. 2022 Jun;43(6):687-713. doi: 10.1017/ice.2022.88. Epub 2022 May 20.
• Background Singh A, Anjankar AP. Propofol-Related Infusion Syndrome: A Clinical Review. Cureus. 2022 Oct 17;14(10):e30383. doi: 10.7759/cureus.30383. eCollection 2022 Oct.
• Background Murray JF, Matthay MA, Luce JM, Flick MR. An expanded definition of the adult respiratory distress syndrome. Am Rev Respir Dis. 1988 Sep;138(3):720-3. doi: 10.1164/ajrccm/138.3.720. No abstract available.
• Background Matthay MA, Arabi Y, Arroliga AC, Bernard G, Bersten AD, Brochard LJ, Calfee CS, Combes A, Daniel BM, Ferguson ND, Gong MN, Gotts JE, Herridge MS, Laffey JG, Liu KD, Machado FR, Martin TR, McAuley DF, Mercat A, Moss M, Mularski RA, Pesenti A, Qiu H, Ramakrishnan N, Ranieri VM, Riviello ED, Rubin E, Slutsky AS, Thompson BT, Twagirumugabe T, Ware LB, Wick KD. A New Global Definition of Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2024 Jan 1;209(1):37-47. doi: 10.1164/rccm.202303-0558WS.

Drugs

Indications