Prone Positioning and Neuromuscular Blocking Agents as Adjunctive Therapies in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome

Abstract

Neuromuscular blocking agents (NMBAs) and prone position (PP) are two major adjunctive therapies that can improve outcome in moderate-to-severe acute respiratory distress syndrome. NMBA should be used once lung-protective mechanical ventilation has been set, for 48 hours or less and as a continuous intravenous infusion. PP should be used as early as possible for long sessions; in COVID-19 its use has exploded. In nonintubated patients, PP might reduce the rate of intubation but not mortality. The goal of this article is to perform a narrative review on the pathophysiological rationale, the clinical effects, and the clinical use and recommendations of both NMBA and PP.

Keywords

acute respiratory distress syndrome - prone position - neuromuscular blocking agents - lung protective ventilation - COVID-19

Publication History

Article published online:
29 May 2022

• References

• 1 Gainnier M, Roch A, Forel JM. et al. Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome. Crit Care Med 2004; 32 (01) 113-119
• 2 Forel JM, Roch A, Marin V. et al. Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome. Crit Care Med 2006; 34 (11) 2749-2757
• 3 Papazian L, Forel JM, Gacouin A. et al. ACURASYS Study Investigators. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010; 363 (12) 1107-1116
• 4 Slutsky AS. Neuromuscular blocking agents in ARDS. N Engl J Med 2010; 363 (12) 1176-1180
• 5 Akoumianaki E, Lyazidi A, Rey N. et al. Mechanical ventilation-induced reverse-triggered breaths: a frequently unrecognized form of neuromechanical coupling. Chest 2013; 143 (04) 927-938
• 6 Goligher EC, Dres M, Patel BK. et al. Lung- and diaphragm-protective ventilation. Am J Respir Crit Care Med 2020; 202 (07) 950-961
• 7 Goligher EC, Fan E. Editorial: Lung and diaphragm-protective ventilation: setting new concepts in historical context. Curr Opin Crit Care 2020; 26 (01) 1-2
• 8 Goligher EC, Jonkman AH, Dianti J. et al. Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and excessive effort. Intensive Care Med 2020; 46 (12) 2314-2326
• 9 Guervilly C, Bisbal M, Forel JM. et al. Effects of neuromuscular blockers on transpulmonary pressures in moderate to severe acute respiratory distress syndrome. Intensive Care Med 2017; 43 (03) 408-418
• 10 Ranieri VM, Rubenfeld GD, Thompson BT. et al. ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012; 307 (23) 2526-2533
• 11 Moss M, Huang DT, Brower RG. et al. National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early neuromuscular blockade in the acute respiratory distress syndrome. N Engl J Med 2019; 380 (21) 1997-2008
• 12 Papazian L, Aubron C, Brochard L. et al. Formal guidelines: management of acute respiratory distress syndrome. Ann Intensive Care 2019; 9 (01) 69
• 13 Alhazzani W, Belley-Cote E, Møller MH. et al. Neuromuscular blockade in patients with ARDS: a rapid practice guideline. Intensive Care Med 2020; 46 (11) 1977-1986
• 14 Nasa P, Azoulay E, Khanna AK. et al. Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method. Crit Care 2021; 25 (01) 106
• 15 Bellani G, Laffey JG, Pham T. et al. LUNG SAFE Investigators, ESICM Trials Group. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA 2016; 315 (08) 788-800
• 16 COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators. Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med 2021; 47 (01) 60-73
• 17 Esnault P, Cardinale M, Hraiech S. et al. High respiratory drive and excessive respiratory efforts predict relapse of respiratory failure in critically ill patients with COVID-19. Am J Respir Crit Care Med 2020; 202 (08) 1173-1178
• 18 Courcelle R, Gaudry S, Serck N, Blonz G, Lascarrou JB, Grimaldi D. on behalf the COVADIS study group. Neuromuscular blocking agents (NMBA) for COVID-19 acute respiratory distress syndrome: a multicenter observational study. Crit Care 2020; 24 (01) 446
• 19 Alhazzani W, Evans L, Alshamsi F. et al. Surviving sepsis campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med 2021; 49 (03) e219-e234
• 20 Chanques G, Constantin JM, Devlin JW. et al. Analgesia and sedation in patients with ARDS. Intensive Care Med 2020; 46 (12) 2342-2356
• 21 Bouju P, Tadié JM, Barbarot N. et al. Clinical assessment and train-of-four measurements in critically ill patients treated with recommended doses of cisatracurium or atracurium for neuromuscular blockade: a prospective descriptive study. Ann Intensive Care 2017; 7 (01) 10
• 22 Hraiech S, Forel JM, Guervilly C. et al. How to reduce cisatracurium consumption in ARDS patients: the TOF-ARDS study. Ann Intensive Care 2017; 7 (01) 79
• 23 Rezaiguia-Delclaux S, Laverdure F, Genty T. et al. Neuromuscular blockade monitoring in acute respiratory distress syndrome: randomized controlled trial of clinical assessment alone or with peripheral nerve stimulation. Anesth Analg 2021; 132 (04) 1051-1059
• 24 Guérin C, Albert RK, Beitler J. et al. Prone position in ARDS patients: why, when, how and for whom. Intensive Care Med 2020; 46 (12) 2385-2396
• 25 Mure M, Martling CR, Lindahl SG. Dramatic effect on oxygenation in patients with severe acute lung insufficiency treated in the prone position. Crit Care Med 1997; 25 (09) 1539-1544
• 26 Johnson NJ, Luks AM, Glenny RW. Gas exchange in the prone posture. Respir Care 2017; 62 (08) 1097-1110
• 27 Richter T, Bellani G, Scott Harris R. et al. Effect of prone position on regional shunt, aeration, and perfusion in experimental acute lung injury. Am J Respir Crit Care Med 2005; 172 (04) 480-487
• 28 Glenny RW. Determinants of regional ventilation and blood flow in the lung. Intensive Care Med 2009; 35 (11) 1833-1842
• 29 Pappert D, Rossaint R, Slama K, Grüning T, Falke KJ. Influence of positioning on ventilation-perfusion relationships in severe adult respiratory distress syndrome. Chest 1994; 106 (05) 1511-1516
• 30 Gattinoni L, Chiumello D, Rossi S. COVID-19 pneumonia: ARDS or not?. Crit Care 2020; 24 (01) 154
• 31 Gattinoni L, Coppola S, Cressoni M, Busana M, Rossi S, Chiumello D. COVID-19 does not lead to a “typical” acute respiratory distress syndrome. Am J Respir Crit Care Med 2020; 201 (10) 1299-1300
• 32 Grasselli G, Tonetti T, Protti A. et al. collaborators. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med 2020; 8 (12) 1201-1208
• 33 Gattinoni L, Chiumello D, Caironi P. et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes?. Intensive Care Med 2020; 46 (06) 1099-1102
• 34 Chiumello D, Busana M, Coppola S. et al. Physiological and quantitative CT-scan characterization of COVID-19 and typical ARDS: a matched cohort study. Intensive Care Med 2020; 46 (12) 2187-2196
• 35 Sinha P, Fauvel NJ, Singh S, Soni N. Ventilatory ratio: a simple bedside measure of ventilation. Br J Anaesth 2009; 102 (05) 692-697
• 36 Ball L, Robba C, Herrmann J. et al. Collaborators of the GECOVID Group. Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study. Crit Care 2021; 25 (01) 214
• 37 Broccard A, Shapiro RS, Schmitz LL, Adams AB, Nahum A, Marini JJ. Prone positioning attenuates and redistributes ventilator-induced lung injury in dogs. Crit Care Med 2000; 28 (02) 295-303
• 38 Mutoh T, Guest RJ, Lamm WJ, Albert RK. Prone position alters the effect of volume overload on regional pleural pressures and improves hypoxemia in pigs in vivo. Am Rev Respir Dis 1992; 146 (02) 300-306
• 39 Terzi N, Bayat S, Noury N. et al. Comparison of pleural and esophageal pressure in supine and prone positions in a porcine model of acute respiratory distress syndrome. J Appl Physiol (1985) 2020; 128 (06) 1617-1625
• 40 Morais CCA, Koyama Y, Yoshida T. et al. High positive end-expiratory pressure renders spontaneous effort noninjurious. Am J Respir Crit Care Med 2018; 197 (10) 1285-1296
• 41 Amato MB, Meade MO, Slutsky AS. et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 2015; 372 (08) 747-755
• 42 Scaramuzzo G, Ball L, Pino F. et al. Influence of positive end-expiratory pressure titration on the effects of pronation in acute respiratory distress syndrome: a comprehensive experimental study. Front Physiol 2020; 11: 179
• 43 Gattinoni L, Pelosi P, Vitale G, Pesenti A, D'Andrea L, Mascheroni D. Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure. Anesthesiology 1991; 74 (01) 15-23
• 44 Gattinoni L, Pesenti A, Carlesso E. Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure: impact and clinical fallout through the following 20 years. Intensive Care Med 2013; 39 (11) 1909-1915
• 45 Mentzelopoulos SD, Roussos C, Zakynthinos SG. Prone position reduces lung stress and strain in severe acute respiratory distress syndrome. Eur Respir J 2005; 25 (03) 534-544
• 46 Papazian L, Gainnier M, Marin V. et al. Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome. Crit Care Med 2005; 33 (10) 2162-2171
• 47 Galiatsou E, Kostanti E, Svarna E. et al. Prone position augments recruitment and prevents alveolar overinflation in acute lung injury. Am J Respir Crit Care Med 2006; 174 (02) 187-197
• 48 Cornejo RA, Díaz JC, Tobar EA. et al. Effects of prone positioning on lung protection in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2013; 188 (04) 440-448
• 49 Coppola S, Chiumello D, Busana M. et al. Role of total lung stress on the progression of early COVID-19 pneumonia. Intensive Care Med 2021; 47 (10) 1130-1139
• 50 Rossi S, Palumbo MM, Sverzellati N. et al. Mechanisms of oxygenation responses to proning and recruitment in COVID-19 pneumonia. Intensive Care Med 2021
• 51 Gaussorgues P, Chazot C, Vedrinne C, Piperno D, Boyer F, Robert D. Improvement of diffuse pneumopathies by ventilation in prone position [in French]. Presse Med 1987; 16 (24) 1200
• 52 Vieillard-Baron A, Charron C, Caille V, Belliard G, Page B, Jardin F. Prone positioning unloads the right ventricle in severe ARDS. Chest 2007; 132 (05) 1440-1446
• 53 Jozwiak M, Teboul JL, Anguel N. et al. Beneficial hemodynamic effects of prone positioning in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2013; 188 (12) 1428-1433
• 54 Lai C, Adda I, Teboul JL. et al. Effects of prone positioning on venous return in patients with acute respiratory distress syndrome. Crit Care Med 2021; 49 (05) 781-789
• 55 Roccia H, Argaud L, Le Goïc M, Guérin C, Cour M. Electrocardiogram monitoring in the prone position in coronavirus disease 2019 acute respiratory distress syndrome. Eur J Cardiovasc Nurs 2021; 20 (08) 792-796
• 56 Gattinoni L, Tognoni G, Pesenti A. et al. Prone-Supine Study Group. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001; 345 (08) 568-573
• 57 Guerin C, Gaillard S, Lemasson S. et al. Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial. JAMA 2004; 292 (19) 2379-2387
• 58 Mancebo J, Fernández R, Blanch L. et al. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med 2006; 173 (11) 1233-1239
• 59 Taccone P, Pesenti A, Latini R. et al. Prone-Supine II Study Group. Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. JAMA 2009; 302 (18) 1977-1984
• 60 Gattinoni L, Carlesso E, Taccone P, Polli F, Guérin C, Mancebo J. Prone positioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis. Minerva Anestesiol 2010; 76 (06) 448-454
• 61 Guérin C, Reignier J, Richard J-C. et al. PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368 (23) 2159-2168
• 62 Camporota L, Sanderson B, Chiumello D. et al. Prone position in coronavirus disease 2019 and noncoronavirus disease 2019 acute respiratory distress syndrome: an international multicenter observational comparative study. Crit Care Med 2022; 50 (04) 633-643
• 63 Cour M, Bussy D, Stevic N, Argaud L, Guérin C. Differential effects of prone position in COVID-19-related ARDS in low and high recruiters. Intensive Care Med 2021; 47 (09) 1044-1046
• 64 Fan E, Del Sorbo L, Goligher EC. et al. American Thoracic Society, European Society of Intensive Care Medicine, and Society of Critical Care Medicine. An official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 2017; 195 (09) 1253-1263
• 65 Guérin C, Beuret P, Constantin JM. et al. Investigators of the APRONET Study Group, the REVA Network, the Réseau recherche de la Société Française d'Anesthésie-Réanimation (SFAR-recherche) and the ESICM Trials Group. A prospective international observational prevalence study on prone positioning of ARDS patients: the APRONET (ARDS Prone Position Network) study. Intensive Care Med 2018; 44 (01) 22-37
• 66 Albert RK, Keniston A, Baboi L, Ayzac L, Guérin C. Proseva Investigators. Prone position-induced improvement in gas exchange does not predict improved survival in the acute respiratory distress syndrome. Am J Respir Crit Care Med 2014; 189 (04) 494-496
• 67 Gattinoni L, Vagginelli F, Carlesso E. et al. Prone-Supine Study Group. Decrease in PaCO2 with prone position is predictive of improved outcome in acute respiratory distress syndrome. Crit Care Med 2003; 31 (12) 2727-2733
• 68 Ferrando C, Suarez-Sipmann F, Mellado-Artigas R. et al. COVID-19 Spanish ICU Network. Clinical features, ventilatory management, and outcome of ARDS caused by COVID-19 are similar to other causes of ARDS. Intensive Care Med 2020; 46 (12) 2200-2211
• 69 Barbaro RP, MacLaren G, Boonstra PS. et al. Extracorporeal Life Support Organization. Extracorporeal membrane oxygenation for COVID-19: evolving outcomes from the international Extracorporeal Life Support Organization Registry. Lancet 2021; 398 (10307): 1230-1238
• 70 Combes A, Hajage D, Capellier G. et al. EOLIA Trial Group, REVA, and ECMONet. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med 2018; 378 (21) 1965-1975
• 71 Mathews KS, Soh H, Shaefi S. et al. STOP-COVID Investigators. Prone positioning and survival in mechanically ventilated patients with coronavirus disease 2019-related respiratory failure. Crit Care Med 2021; 49 (07) 1026-1037
• 72 Xin Y, Martin K, Morais CCA. et al. Diminishing efficacy of prone positioning with late application in evolving lung injury. Crit Care Med 2021; 49 (10) e1015-e1024
• 73 Carsetti A, Damia Paciarini A, Marini B, Pantanetti S, Adrario E, Donati A. Prolonged prone position ventilation for SARS-CoV-2 patients is feasible and effective. Crit Care 2020; 24 (01) 225
• 74 Page DB, Vijaykumar K, Russell DW. et al. Prolonged prone positioning for COVID-19-induced acute respiratory distress syndrome: a randomized pilot study. Ann Am Thorac Soc 2021;
• 75 Parker EM, Bittner EA, Berra L, Pino RM. Efficiency of prolonged prone positioning for mechanically ventilated patients infected with COVID-19. J Clin Med 2021; 10 (13) 2969
• 76 Langer T, Brioni M, Guzzardella A. et al. PRONA-COVID Group. Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients. Crit Care 2021; 25 (01) 128
• 77 Scaramuzzo G, Gamberini L, Tonetti T. et al. ICU-RER COVID-19 Collaboration. Sustained oxygenation improvement after first prone positioning is associated with liberation from mechanical ventilation and mortality in critically ill COVID-19 patients: a cohort study. Ann Intensive Care 2021; 11 (01) 63
• 78 Coppo A, Bellani G, Winterton D. et al. Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study. Lancet Respir Med 2020; 8 (08) 765-774
• 79 Elharrar X, Trigui Y, Dols AM. et al. Use of prone positioning in nonintubated patients with COVID-19 and hypoxemic acute respiratory failure. JAMA 2020; 323 (22) 2336-2338
• 80 Ehrmann S, Li J, Ibarra-Estrada M. et al. Awake Prone Positioning Meta-Trial Group. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. Lancet Respir Med 2021; 9 (12) 1387-1395