Different strategies for mechanical VENTilation during CardioPulmonary Bypass (CPBVENT 2014): study protocol for a randomized controlled trial

Elena Bignami, Marcello Guarnieri, Francesco Saglietti, Enivarco Massimo Maglioni, Sabino Scolletta, Stefano Romagnoli, Stefano De Paulis, Gianluca Paternoster, Cinzia Trumello, Roberta Meroni, Antonio Scognamiglio, Alessandro Maria Budillon, Vincenzo Pota, Alberto Zangrillo, Ottavio Alfieri, Elena Bignami, Marcello Guarnieri, Francesco Saglietti, Enivarco Massimo Maglioni, Sabino Scolletta, Stefano Romagnoli, Stefano De Paulis, Gianluca Paternoster, Cinzia Trumello, Roberta Meroni, Antonio Scognamiglio, Alessandro Maria Budillon, Vincenzo Pota, Alberto Zangrillo, Ottavio Alfieri

Abstract

Background: There is no consensus on which lung-protective strategies should be used in cardiac surgery patients. Sparse and small randomized clinical and animal trials suggest that maintaining mechanical ventilation during cardiopulmonary bypass is protective on the lungs. Unfortunately, such evidence is weak as it comes from surrogate and minor clinical endpoints mainly limited to elective coronary surgery. According to the available data in the academic literature, an unquestionable standardized strategy of lung protection during cardiopulmonary bypass cannot be recommended. The purpose of the CPBVENT study is to investigate the effectiveness of different strategies of mechanical ventilation during cardiopulmonary bypass on postoperative pulmonary function and complications.

Methods/design: The CPBVENT study is a single-blind, multicenter, randomized controlled trial. We are going to enroll 870 patients undergoing elective cardiac surgery with planned use of cardiopulmonary bypass. Patients will be randomized into three groups: (1) no mechanical ventilation during cardiopulmonary bypass, (2) continuous positive airway pressure of 5 cmH2O during cardiopulmonary bypass, (3) respiratory rate of 5 acts/min with a tidal volume of 2-3 ml/Kg of ideal body weight and positive end-expiratory pressure of 3-5 cmH2O during cardiopulmonary bypass. The primary endpoint will be the incidence of a PaO2/FiO2 ratio <200 until the time of discharge from the intensive care unit. The secondary endpoints will be the incidence of postoperative pulmonary complications and 30-day mortality. Patients will be followed-up for 12 months after the date of randomization.

Discussion: The CPBVENT trial will establish whether, and how, different ventilator strategies during cardiopulmonary bypass will have an impact on postoperative pulmonary complications and outcomes of patients undergoing cardiac surgery.

Trial registration: ClinicalTrials.gov, ID: NCT02090205 . Registered on 8 March 2014.

Keywords: CPAP; Cardiopulmonary bypass; Low tidal volume; Postoperative pulmonary complications; Protective ventilation; Respiratory insufficiency; Systemic inflammatory response.

Figures

Fig. 1
Fig. 1
The SPIRIT figure of this trial
Fig. 2
Fig. 2
Ventilation flowchart. Description of the ventilatory strategies used before, during and after cardiopulmonary bypass. Abbreviations: CPB cardiopulmonary bypass, VC-CMV volume-controlled continuous mandatory ventilation, TV tidal volume, IBW ideal body weight, PEEP positive end-expiratory pressure, FiO2 inspired oxygen fraction

References

    1. Ball L, Costantino F, Pelosi P. Postoperative complications of patients undergoing cardiac surgery. Curr Opin Crit Care. 2016;22(4):386–92. doi: 10.1097/MCC.0000000000000319.
    1. Magnusson L, Zemgulis V, Wicky S, Tydén H, Thelin S, Hedenstierna G. Atelectasis is a major cause of hypoxemia and shunt after cardiopulmonary bypass: an experimental study. Anesthesiology. 1997;87:1153–63. doi: 10.1097/00000542-199711000-00020.
    1. Reber A, Budmiger B, Wenk M, Haefeli WE, Wolff T, Bein T, et al. Inspired oxygen fraction after cardiopulmonary bypass: effects on pulmonary function with regard to endothelin-1 concentrations and venous admixture. Br J Anaesth. 2000;84:565–70. doi: 10.1093/bja/84.5.565.
    1. Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002;97:215–52. doi: 10.1097/00000542-200207000-00030.
    1. Allou N, Bronchard R, Guglielminotti J, Dilly MP, Provenchere S, Lucet JC, et al. Risk factors for postoperative pneumonia after cardiac surgery and development of a preoperative risk score. Crit Care Med. 2014;42:1150–6. doi: 10.1097/CCM.0000000000000143.
    1. Apostolakis EE, Koletsis EN, Baikoussis NG, Siminelakis SN, Papadopoulos GS. Strategies to prevent intraoperative lung injury during cardiopulmonary bypass. J Cardiothorac Surg. 2010;5:1. doi: 10.1186/1749-8090-5-1.
    1. García-Delgado M, Navarrete-Sánchez I, Colmenero M. Preventing and managing perioperative pulmonary complications following cardiac surgery. Curr Opin Anaesthesiol. 2014;27:146–52. doi: 10.1097/ACO.0000000000000059.
    1. Warren O, Alexiou C, Massey R, Leff D, Purkayastha S, Kinross J, et al. The effects of various leukocyte filtration strategies in cardiac surgery. Eur J Cardiothorac Surg. 2007;31:665–76. doi: 10.1016/j.ejcts.2006.12.034.
    1. Tassani P, Richter JA, Barankay A, Braun SL, Haehnel C, Spaeth P, et al. Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures? J Cardiothorac Vasc Anesth. 1999;13:165–72. doi: 10.1016/S1053-0770(99)90081-2.
    1. Vohra HA, Levine A, Dunning J. Can ventilation while on cardiopulmonary bypass improve post-operative lung function for patients undergoing cardiac surgery? Interact Cardiovasc Thorac Surg. 2005;4:442–6. doi: 10.1510/icvts.2005.114710.
    1. Schreiber JU, Lancé MD, de Korte M, Artmann T, Aleksic I, Kranke P. The effect of different lung-protective strategies in patients during cardiopulmonary bypass: a meta-analysis and semiquantitative review of randomized trials. J Cardiothorac Vasc Anesth. 2012;26:448–54. doi: 10.1053/j.jvca.2012.01.034.
    1. Loeckinger A, Kleinsasser A, Lindner KH, Margreiter J, Keller C, Hoermann C. Continuous positive airway pressure at 10 cm H(2)O during cardiopulmonary bypass improves postoperative gas exchange. Anesth Analg. 2000;91:522–7. doi: 10.1213/00000539-200009000-00004.
    1. Oczenski W, Schwarz S, Fitzgerald RD. Vital capacity manoeuvre in general anaesthesia: useful or useless? Eur J Anaesthesiol. 2004;21:253–9. doi: 10.1097/00003643-200404000-00001.
    1. Imura H, Caputo M, Lim K, Ochi M, Suleiman MS, Shimizu K, et al. Pulmonary injury after cardiopulmonary bypass: beneficial effects of low-frequency mechanical ventilation. J Thorac Cardiovasc Surg. 2009;137:1530–7. doi: 10.1016/j.jtcvs.2008.11.014.
    1. Ng CS, Arifi AA, Wan S, Ho AM, Wan IY, Wong EM, et al. Ventilation during cardiopulmonary bypass: impact on cytokine response and cardiopulmonary function. Ann Thorac Surg. 2008;85:154–62. doi: 10.1016/j.athoracsur.2007.07.068.
    1. Zupancich E, Paparella D, Turani F, Munch C, Rossi A, Massaccesi S, et al. Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: a randomized clinical trial. J Thorac Cardiovasc Surg. 2005;130:378–83. doi: 10.1016/j.jtcvs.2004.11.061.
    1. Celebi S, Köner O, Menda F, Korkut K, Suzer K, Cakar N. The pulmonary and hemodynamic effects of two different recruitment maneuvers after cardiac surgery. Anesth Analg. 2007;104:384–90. doi: 10.1213/01.ane.0000252967.33414.44.
    1. Celebi S, Köner O, Menda F, Omay O, Günay I, Suzer K, et al. Pulmonary effects of noninvasive ventilation combined with the recruitment maneuver after cardiac surgery. Anesth Analg. 2008;107:614–9. doi: 10.1213/ane.0b013e31817e65a1.
    1. Dobbinson TL, Miller JR. Respiratory and cardiovascular responses to PEEP in artificially ventilated patients after cardiopulmonary bypass surgery. Anaesth Intensive Care. 1981;9:307–13.
    1. Coppola S, Froio S, Chiumello D. Protective lung ventilation during general anesthesia: is there any evidence? Crit Care. 2014;18:210. doi: 10.1186/cc13777.
    1. Ferrando C, Soro M, Belda FJ. Protection strategies during cardiopulmonary bypass: ventilation, anesthetics and oxygen. Curr Opin Anaesthesiol. 2015;28:73–80. doi: 10.1097/ACO.0000000000000143.
    1. Badenes R, Lozano A, Belda FJ. Postoperative pulmonary dysfunction and mechanical ventilation in cardiac surgery. Crit Care Res Pract. 2015;2015:420513.
    1. Lellouche F, Delorme M, Bussières J, Ouattara A. Perioperative ventilatory strategies in cardiac surgery. Best Pract Res Clin Anaesthesiol. 2015;29(3):381–95. doi: 10.1016/j.bpa.2015.08.006.
    1. Fischer MO, Courteille B, Guinot PG, Dupont H, Gérard JL, Hanouz JL, et al. Perioperative ventilatory management in cardiac surgery: a French nationwide survey. Medicine (Baltimore) 2016;95(9):e2655. doi: 10.1097/MD.0000000000002655.
    1. Definition Task Force ARDS, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307:2526–33.
    1. Ranucci M, Ballotta A, La Rovere MT, Castelvecchio S, Surgical and Clinical Outcome Research (SCORE) Group Postoperative hypoxia and length of intensive care unit stay after cardiac surgery: the underweight paradox? PLoS One. 2014;9(4):e93992. doi: 10.1371/journal.pone.0093992.
    1. Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet. 2014;384(9942):495–503. doi: 10.1016/S0140-6736(14)60416-5.
    1. Weiss YG, Merin G, Koganov E, Ribo A, Oppenheim-Eden A, Medalion B, et al. Postcardiopulmonary bypass hypoxemia: a prospective study on incidence, risk factors, and clinical significance. J Cardiothorac Vasc Anesth. 2000;14(5):506–13. doi: 10.1053/jcan.2000.9488.
    1. Esteve F, Lopez-Delgado JC, Javierre C, Skaltsa K, Carrio ML, Rodríguez-Castro D, et al. Evaluation of the PaO2/FiO2 ratio after cardiac surgery as a predictor of outcome during hospital stay. BMC Anesthesiol. 2014;14:83. doi: 10.1186/1471-2253-14-83.
    1. Futier E, Constantin JM, Paugam-Burtz C, Pascal J, Eurin M, Neuschwander A, et al. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013;369:428–37. doi: 10.1056/NEJMoa1301082.
    1. Lellouche F, Dionne S, Simard S, Bussières J, Dagenais F. High tidal volumes in mechanically ventilated patients increase organ dysfunction after cardiac surgery. Anesthesiology. 2012;116:1072–82. doi: 10.1097/ALN.0b013e3182522df5.
    1. Ladha K, Vidal Melo MF, McLean DJ, Wanderer JP, Grabitz SD, Kurth T, et al. Intraoperative protective mechanical ventilation and risk of postoperative respiratory complications: hospital based registry study. BMJ. 2015;351:h3646. doi: 10.1136/bmj.h3646.
    1. Young RW. Hyperoxia: a review of the risks and benefits in adult cardiac surgery. J Extra Corpor Technol. 2012;44:241–9.
    1. Ranucci M, Castelvecchio S, Ditta A, Brozzi S, Boncilli A, Baryshnikova E. Transfusions during cardiopulmonary bypass: better when triggered by venous oxygen saturation and oxygen extraction rate. Perfusion. 2011;26:327–33. doi: 10.1177/0267659111407539.
    1. Puls A, Pollok-Kopp B, Wrigge H, Quintel M, Neumann P. Effects of a single-lung recruitment maneuver on the systemic release of inflammatory mediators. Intensive Care Med. 2006;32:1080–5. doi: 10.1007/s00134-006-0174-x.
    1. Pizov R, Weiss YG, Oppenheim-Eden A, Glickman H, Goodman S, Koganov Y, et al. High oxygen concentration exacerbates cardiopulmonary bypass-induced lung injury. J Cardiothorac Vasc Anesth. 2000;14(5):519–23. doi: 10.1053/jcan.2000.9486.
    1. Ranucci M, Castelvecchio S, Conte M, Megliola G, Speziale G, Fiore F, et al. The easier, the better: age, creatinine, ejection fraction score for operative mortality risk stratification in a series of 29,659 patients undergoing elective cardiac surgery. J Thorac Cardiovasc Surg. 2011;142:581–6. doi: 10.1016/j.jtcvs.2010.11.064.
    1. Canet J, Gallart L, Gomar C, Paluzie G, Vallès J, Castillo J, et al. Prediction of postoperative pulmonary complications in a population-based surgical cohort. Anesthesiology. 2010;113:1338–50. doi: 10.1097/ALN.0b013e3181fc6e0a.
    1. De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. N Engl J Med. 2004;351:1250–1. doi: 10.1056/NEJMe048225.
    1. International Conference on Harmonization. ICH Harmonized Tripartite Guideline. Good Clinical Practice. 1996.
    1. World Medical Association. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. 52nd WMA General Assembly, Edinburgh, Scotland, October 2000. Last Amended October 2008.
    1. Apostolakis E, Filos KS, Koletsis E, Dougenis D. Lung dysfunction following cardiopulmonary bypass. J Card Surg. 2010;25:47–55. doi: 10.1111/j.1540-8191.2009.00823.x.
    1. Paparella D, Yau TM, Young E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg. 2002;21:232–44. doi: 10.1016/S1010-7940(01)01099-5.
    1. Müller H, Hügel W, Reifschneider HJ, Horpacsy G, Hannekum A, Dalichau H. Lysosomal enzyme activity influenced by various types of respiration during extracorporeal circulation. Thorac Cardiovasc Surg. 1989;37:65–71. doi: 10.1055/s-2007-1013909.
    1. Gaudriot B, Uhel F, Gregoire M, Gacouin A, Biedermann S, Roisne A, et al. Immune dysfunction after cardiac surgery with cardiopulmonary bypass: beneficial effects of maintaining mechanical ventilation. Shock. 2015;44(3):228–33. doi: 10.1097/SHK.0000000000000416.
    1. Bignami E, Guarnieri M, Saglietti F, Belletti A, Trumello C, Giambuzzi I, et al. Mechanical ventilation during cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2016;30(6):1668–75. doi: 10.1053/j.jvca.2016.03.015.
    1. Ibañez J, Riera M, Amezaga R, Herrero J, Colomar A, Campillo-Artero C, et al. Long-term mortality after pneumonia in cardiac surgery patients: a propensity-matched analysis. J Intensive Care Med. 2016;31(1):34-40.
    1. He S, Chen B, Li W, Yan J, Chen L, Wang X, et al. Ventilator-associated pneumonia after cardiac surgery: a meta-analysis and systematic review. J Thorac Cardiovasc Surg. 2014;148:3148–55. doi: 10.1016/j.jtcvs.2014.07.107.
    1. Beer L, Szerafin T, Mitterbauer A, Debreceni T, Maros T, Dworschak M, et al. Low tidal volume ventilation during cardiopulmonary bypass reduces postoperative chemokine serum concentrations. Thorac Cardiovasc Surg. 2014;62:677–82. doi: 10.1055/s-0034-1387824.
    1. Durukan AB, Gurbuz HA, Salman N, Unal EU, Ucar HI, Yorgancioglu CE. Ventilation during cardiopulmonary bypass did not attenuate inflammatory response or affect postoperative outcomes. Cardiovasc J Afr. 2013;24:224–30. doi: 10.5830/CVJA-2013-041.
    1. Beer L, Szerafin T, Mitterbauer A, Kasiri MM, Debreceni T, Palotás L, et al. Ventilation during cardiopulmonary bypass: impact on heat shock protein release. J Cardiovasc Surg. 2014;55:849–56.
    1. Beer L, Szerafin T, Mitterbauer A, Debreceni T, Maros T, Dworschak M, et al. Continued mechanical ventilation during coronary artery bypass graft operation attenuates the systemic immune response. Eur J Cardiothorac Surg. 2013;44:282–7. doi: 10.1093/ejcts/ezs659.
    1. Gagnon J, Laporta D, Béïque F, Langlois Y, Morin JF. Clinical relevance of ventilation during cardiopulmonary bypass in the prevention of postoperative lung dysfunction. Perfusion. 2010;25:205–10. doi: 10.1177/0267659110373839.
    1. Davoudi M, Farhanchi A, Moradi A, Bakhshaei MH, Safarpour G. The effect of low tidal volume ventilation during cardiopulmonary bypass on postoperative pulmonary function. J Tehran Heart Cent. 2010;5:128–31.
    1. Scherer M, Dettmer S, Meininger D, Deschka H, Geyer G, Regulla C, et al. Alveolar recruitment strategy during cardiopulmonary bypass does not improve postoperative gas exchange and lung function. Cardiovasc Eng. 2009;9:1–5. doi: 10.1007/s10558-009-9063-6.
    1. John LC, Ervine IM. A study assessing the potential benefit of continued ventilation during cardiopulmonary bypass. Interact Cardiovasc Thorac Surg. 2008;7:14–7. doi: 10.1510/icvts.2007.158451.
    1. Altmay E, Karaca P, Yurtseven N, Ozkul V, Aksoy T, Ozler A, et al. Continuous positive airway pressure does not improve lung function after cardiac surgery. Can J Anaesth. 2006;53:919–25. doi: 10.1007/BF03022835.
    1. Ayad AE, Hamed HF. Continuous positive airway pressure (CPAP) during cardiopulmonary bypass attenuates postoperative pulmonary dysfunction and complications. Egypt J Anaesth. 2003;19:345–51.
    1. Claxton BA, Morgan P, McKeague H, Mulpur A, Berridge J. Alveolar recruitment strategy improves arterial oxygenation after cardiopulmonary bypass. Anaesthesia. 2003;58:111–6. doi: 10.1046/j.1365-2044.2003.02892.x.
    1. Zabeeda D, Gefen R, Medalion B, Khazin V, Shachner A, Ezri T. The effect of high-frequency ventilation of the lungs on postbypass oxygenation: a comparison with other ventilation methods applied during cardiopulmonary bypass. J Cardiothorac Vasc Anesth. 2003;17:40–4. doi: 10.1053/jcan.2003.8.
    1. Beer L, Warszawska JM, Schenk P, Debreceni T, Dworschak M, Roth GA, et al. Intraoperative ventilation strategy during cardiopulmonary bypass attenuates the release of matrix metalloproteinases and improves oxygenation. J Surg Res. 2015;195:294–302. doi: 10.1016/j.jss.2014.12.022.
    1. Figueiredo LC, Araújo S, Abdala RC, Abdala A, Guedes CA. CPAP at 10 cm H2O during cardiopulmonary bypass does not improve postoperative gas exchange. Rev Bras Cir Cardiovasc. 2008;23:209–15. doi: 10.1590/S0102-76382008000200010.
    1. Macedo FI, Gologorsky E, Costa AC, Pham SM, Salerno TA. Beating heart surgery with pulmonary perfusion and ventilation during cardiopulmonary bypass: target organs’ perfusion without plegia. Semin Thorac Cardiovasc Surg. 2012;24:308–10. doi: 10.1053/j.semtcvs.2012.08.002.
    1. Lim CH, Nam MJ, Lee JS, Kim HJ, Kim JY, Shin HW, et al. A meta-analysis of pulmonary function with pulsatile perfusion in cardiac surgery. Artif Organs. 2015;39(2):110–7. doi: 10.1111/aor.12312.

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