Editorial Comment: High Frequency Ventilation and Extracorporeal Membrane Oxygenation: A Winning Combination?
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lthough high frequency oscillatory ventilation (HFOV) was first used in humans >40 years ago,1 no clear indication has emerged to date. The theory underlying HFOV use follows logically from an extensive body of animal2 and human3 research finding increased lung injury and damage from large tidal volume ventilation in the setting of acute respiratory distress syndrome (ARDS). By decreasing tidal volume to “subtidal” breaths well below 1 mL/kg and titrating respiratory rate to mean airway pressure and CO2 removal (~600 breaths/min), alveolar collapse and overdistension injury could be minimized. Enthusiasm for HFV has remained sufficiently high that modern commercial ventilators4 and protocols5 exist for its use, and variants such as high frequency percussive ventilation (HFPV) have been developed. Although a full discussion of the theoretical and practical differences between HFOV variants is beyond this commentary, HFOV uses only subtidal volumes at high frequencies, whereas HFPV layers high frequency (~10 Hz) subtidal volumes on top of regular frequency breaths.6 Unfortunately, multiple clinical trials have repeatedly failed to find benefit for HFOV in patients with ARDS. Two recent high profile randomized trials7,8 and 2 large metaanalyses9,10 concur that HFOV confers minimal survival benefit in ARDS patients. Although mechanisms explaining why HFOV is clinically ineffective range from detrimental effects on preload, hypercapnic acidosis from inadequate CO2 removal, and challenges in managing complex ventilator modes, none have been clinically proven. In addition, the use of smaller tidal volumes in conventional ventilation11 and the increasing use of extracorporeal support with oxygenation (ECMO) for severe ARDS12 complicate real-world comparisons between HFOV and conventional ventilation. In this issue of A&A Case Reports, Boscolo et al.13 report an unusual use of HFPV: to facilitate separation from ECMO support. In a 48-year woman with Klebsiella pneumonia, sepsis, and ARDS, the authors initiated arterial-venous ECMO when conventional ventilator and hemodynamic support strategies had failed. After 16 days, they had successfully treated the infection but were left with persistent oxygenation failure and increasing ECMO-related complications. To accelerate separation from ECMO, Boscolo et al. initiated a 4-hour HFPV trial. They noted dramatically improved clearance of pulmonary secretions, an improved chest radiograph appearance, and a reduced requirement for ECMO and were able to successfully separate the patient Copyright © 2015 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000133
April 1, 2015 • Volume 4 • Number 7
from ECMO the next day. They continued HFPV trials for the next 3 days, each time finding improved secretion clearance. The patient made a full recovery and was discharged from the intensive care unit 3 months after admission. As is appropriate for a case report, Boscolo et al. raise more questions than they answer. Was the mechanism of improved lung function better recruitment or secretion clearance? How did they decide on a 4- and not 6- (or 8-) hour trial? Could the patient have separated from ECMO sooner with earlier use of high frequency strategies? Would HFOV have worked as well as HFPV? And, for the skeptical, might not separation from ECMO have occurred without ever needing a high frequency approach? While none of these questions can be answered, they provide rich material for future clinical trials. Even less well understood than the role of ECMO in patients with refractory ARDS is how to manage the lungs during ECMO support. Should clinicians rest the lungs completely or ventilate occasionally to prevent atelectasis and/or pulmonary vascular thrombosis, and if so, what tidal volume and rates should they use? Intriguingly, the intersection of ECMO and HFV makes theoretical sense. By clearing CO2 and supporting the circulation, ECMO mitigates 2 harmful effects of HFOV. Perhaps such synergy permits HFOV to facilitate frequent suctioning and aggressive clearance of pulmonary secretions. Boscolo et al. considered improved secretion clearance the key to their successful care of this patient. In addition to unusual observations and rare complications, a goal of A&A Case Reports is to stimulate future investigation. This case report falls squarely into that hypothesis-generating category and will stimulate future investigation into the complex world of refractory ARDS. E Avery Tung, MD, FCCM Department of Anesthesia & Critical Care University of Chicago Chicago, Illinois [email protected] REFERENCES 1. Heijman K, Heijman L, Jonzon A, Sedin G, Sjöstrand U, Widman B. High frequency positive pressure ventilation during anaesthesia and routine surgery in man. Acta Anaesthesiol Scand 1972;16:176–87 2. Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 1998;157:294–323 3. Girard TD, Bernard GR. Mechanical ventilation in ARDS: a state-of-the-art review. Chest 2007;131:921–9 cases-anesthesia-analgesia.org
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4. Harcourt ER, John J, Dargaville PA, Zannin E, Davis PG, Tingay DG. Pressure and flow waveform characteristics of eight highfrequency oscillators. Pediatr Crit Care Med 2014;15:e234–40 5. Fessler HE, Derdak S, Ferguson ND, Hager DN, Kacmarek RM, Thompson BT, Brower RG. A protocol for high-frequency oscillatory ventilation in adults: results from a roundtable discussion. Crit Care Med 2007;35:1649–54 6. Lucangelo U, Fontanesi L, Antonaglia V, Pellis T, Berlot G, Liguori G, Bird FM, Gullo A. High frequency percussive ventilation (HFPV). Principles and technique. Minerva Anestesiol 2003;69:841–8, 848–51 7. Young D, Lamb SE, Shah S, MacKenzie I, Tunnicliffe W, Lall R, Rowan K, Cuthbertson BH; OSCAR Study Group. Highfrequency oscillation for acute respiratory distress syndrome. N Engl J Med 2013;368:806–13 8. Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, Zhou Q, Matte A, Walter SD, Lamontagne F, Granton JT, Arabi YM, Arroliga AC, Stewart TE, Slutsky AS, Meade MO; OSCILLATE Trial Investigators; Canadian Critical Care Trials Group. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med 2013;368:795–805
86 cases-anesthesia-analgesia.org
9. Gu XL, Wu GN, Yao YW, Shi DH, Song Y. Is high-frequency oscillatory ventilation more effective and safer than conventional protective ventilation in adult acute respiratory distress syndrome patients? A meta-analysis of randomized controlled trials. Crit Care 2014;18:R111 10. Maitra S, Das D, Ghosh P, Hajra S, Roy SS, Bhattacharya S. High cAMP attenuation of insulin-stimulated meiotic G2-M1 transition in zebrafish oocytes: interaction between the cAMPdependent protein kinase (PKA) and the MAPK3/1 pathways. Mol Cell Endocrinol 2014;393:109–19 11. Checkley W, Brower R, Korpak A, Thompson BT; Acute Respiratory Distress Syndrome Network Investigators. Effects of a clinical trial on mechanical ventilation practices in patients with acute lung injury. Am J Respir Crit Care Med 2008;177:1215–22 12. Ventetuolo CE, Muratore CS. Extracorporeal life support in critically ill adults. Am J Respir Crit Care Med 2014;190:497–508 13. Boscolo A, Peralta A, Baratto F, Rossi S, Carlo O. High frequency percussive ventilation: a new strategy for separation from extracorporeal membrane oxygenation. A&A Case Reports 2015;4:79–84
A & A case reports
A
lthough high frequency oscillatory ventilation (HFOV) was first used in humans >40 years ago,1 no clear indication has emerged to date. The theory underlying HFOV use follows logically from an extensive body of animal2 and human3 research finding increased lung injury and damage from large tidal volume ventilation in the setting of acute respiratory distress syndrome (ARDS). By decreasing tidal volume to “subtidal” breaths well below 1 mL/kg and titrating respiratory rate to mean airway pressure and CO2 removal (~600 breaths/min), alveolar collapse and overdistension injury could be minimized. Enthusiasm for HFV has remained sufficiently high that modern commercial ventilators4 and protocols5 exist for its use, and variants such as high frequency percussive ventilation (HFPV) have been developed. Although a full discussion of the theoretical and practical differences between HFOV variants is beyond this commentary, HFOV uses only subtidal volumes at high frequencies, whereas HFPV layers high frequency (~10 Hz) subtidal volumes on top of regular frequency breaths.6 Unfortunately, multiple clinical trials have repeatedly failed to find benefit for HFOV in patients with ARDS. Two recent high profile randomized trials7,8 and 2 large metaanalyses9,10 concur that HFOV confers minimal survival benefit in ARDS patients. Although mechanisms explaining why HFOV is clinically ineffective range from detrimental effects on preload, hypercapnic acidosis from inadequate CO2 removal, and challenges in managing complex ventilator modes, none have been clinically proven. In addition, the use of smaller tidal volumes in conventional ventilation11 and the increasing use of extracorporeal support with oxygenation (ECMO) for severe ARDS12 complicate real-world comparisons between HFOV and conventional ventilation. In this issue of A&A Case Reports, Boscolo et al.13 report an unusual use of HFPV: to facilitate separation from ECMO support. In a 48-year woman with Klebsiella pneumonia, sepsis, and ARDS, the authors initiated arterial-venous ECMO when conventional ventilator and hemodynamic support strategies had failed. After 16 days, they had successfully treated the infection but were left with persistent oxygenation failure and increasing ECMO-related complications. To accelerate separation from ECMO, Boscolo et al. initiated a 4-hour HFPV trial. They noted dramatically improved clearance of pulmonary secretions, an improved chest radiograph appearance, and a reduced requirement for ECMO and were able to successfully separate the patient Copyright © 2015 International Anesthesia Research Society DOI: 10.1213/XAA.0000000000000133
April 1, 2015 • Volume 4 • Number 7
from ECMO the next day. They continued HFPV trials for the next 3 days, each time finding improved secretion clearance. The patient made a full recovery and was discharged from the intensive care unit 3 months after admission. As is appropriate for a case report, Boscolo et al. raise more questions than they answer. Was the mechanism of improved lung function better recruitment or secretion clearance? How did they decide on a 4- and not 6- (or 8-) hour trial? Could the patient have separated from ECMO sooner with earlier use of high frequency strategies? Would HFOV have worked as well as HFPV? And, for the skeptical, might not separation from ECMO have occurred without ever needing a high frequency approach? While none of these questions can be answered, they provide rich material for future clinical trials. Even less well understood than the role of ECMO in patients with refractory ARDS is how to manage the lungs during ECMO support. Should clinicians rest the lungs completely or ventilate occasionally to prevent atelectasis and/or pulmonary vascular thrombosis, and if so, what tidal volume and rates should they use? Intriguingly, the intersection of ECMO and HFV makes theoretical sense. By clearing CO2 and supporting the circulation, ECMO mitigates 2 harmful effects of HFOV. Perhaps such synergy permits HFOV to facilitate frequent suctioning and aggressive clearance of pulmonary secretions. Boscolo et al. considered improved secretion clearance the key to their successful care of this patient. In addition to unusual observations and rare complications, a goal of A&A Case Reports is to stimulate future investigation. This case report falls squarely into that hypothesis-generating category and will stimulate future investigation into the complex world of refractory ARDS. E Avery Tung, MD, FCCM Department of Anesthesia & Critical Care University of Chicago Chicago, Illinois [email protected] REFERENCES 1. Heijman K, Heijman L, Jonzon A, Sedin G, Sjöstrand U, Widman B. High frequency positive pressure ventilation during anaesthesia and routine surgery in man. Acta Anaesthesiol Scand 1972;16:176–87 2. Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 1998;157:294–323 3. Girard TD, Bernard GR. Mechanical ventilation in ARDS: a state-of-the-art review. Chest 2007;131:921–9 cases-anesthesia-analgesia.org
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4. Harcourt ER, John J, Dargaville PA, Zannin E, Davis PG, Tingay DG. Pressure and flow waveform characteristics of eight highfrequency oscillators. Pediatr Crit Care Med 2014;15:e234–40 5. Fessler HE, Derdak S, Ferguson ND, Hager DN, Kacmarek RM, Thompson BT, Brower RG. A protocol for high-frequency oscillatory ventilation in adults: results from a roundtable discussion. Crit Care Med 2007;35:1649–54 6. Lucangelo U, Fontanesi L, Antonaglia V, Pellis T, Berlot G, Liguori G, Bird FM, Gullo A. High frequency percussive ventilation (HFPV). Principles and technique. Minerva Anestesiol 2003;69:841–8, 848–51 7. Young D, Lamb SE, Shah S, MacKenzie I, Tunnicliffe W, Lall R, Rowan K, Cuthbertson BH; OSCAR Study Group. Highfrequency oscillation for acute respiratory distress syndrome. N Engl J Med 2013;368:806–13 8. Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, Zhou Q, Matte A, Walter SD, Lamontagne F, Granton JT, Arabi YM, Arroliga AC, Stewart TE, Slutsky AS, Meade MO; OSCILLATE Trial Investigators; Canadian Critical Care Trials Group. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med 2013;368:795–805
86 cases-anesthesia-analgesia.org
9. Gu XL, Wu GN, Yao YW, Shi DH, Song Y. Is high-frequency oscillatory ventilation more effective and safer than conventional protective ventilation in adult acute respiratory distress syndrome patients? A meta-analysis of randomized controlled trials. Crit Care 2014;18:R111 10. Maitra S, Das D, Ghosh P, Hajra S, Roy SS, Bhattacharya S. High cAMP attenuation of insulin-stimulated meiotic G2-M1 transition in zebrafish oocytes: interaction between the cAMPdependent protein kinase (PKA) and the MAPK3/1 pathways. Mol Cell Endocrinol 2014;393:109–19 11. Checkley W, Brower R, Korpak A, Thompson BT; Acute Respiratory Distress Syndrome Network Investigators. Effects of a clinical trial on mechanical ventilation practices in patients with acute lung injury. Am J Respir Crit Care Med 2008;177:1215–22 12. Ventetuolo CE, Muratore CS. Extracorporeal life support in critically ill adults. Am J Respir Crit Care Med 2014;190:497–508 13. Boscolo A, Peralta A, Baratto F, Rossi S, Carlo O. High frequency percussive ventilation: a new strategy for separation from extracorporeal membrane oxygenation. A&A Case Reports 2015;4:79–84
A & A case reports
