Improved Outcome in an Animal Model of Prolonged Cardiac Arrest Through Pulsatile High Pressure Controlled Automated Reperfusion of the Whole Body
Maximilian Kreibich
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorGeorg Trummer
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorFriedhelm Beyersdorf
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorChristian Scherer
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorKatharina Förster
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorItumeleng Taunyane
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorCorresponding Author
Christoph Benk
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Address correspondence and reprint requests to Christoph Benk, PhD, Department of Cardiovascular Surgery, University Heart Centre Freiburg, Hugstetter Str. 55,79106 Freiburg, Germany. E-mail: [email protected]Search for more papers by this authorMaximilian Kreibich
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorGeorg Trummer
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorFriedhelm Beyersdorf
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorChristian Scherer
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorKatharina Förster
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorItumeleng Taunyane
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Search for more papers by this authorCorresponding Author
Christoph Benk
Faculty of Medicine, Department of Cardiovascular Surgery, Heart Centre Freiburg University, University of Freiburg, Freiburg, Germany
Address correspondence and reprint requests to Christoph Benk, PhD, Department of Cardiovascular Surgery, University Heart Centre Freiburg, Hugstetter Str. 55,79106 Freiburg, Germany. E-mail: [email protected]Search for more papers by this authorAbstract
The reperfusion period after extracorporeal cardiopulmonary resuscitation has been recognized as a key player in improving the outcome after cardiac arrest (CA). Our aim was to evaluate the effects of high mean arterial pressure (MAP) and pulsatile flow during controlled automated reperfusion of the whole body. Following 20 min of normothermic CA, high MAP, and pulsatile blood flow (pulsatile group, n = 10) or low MAP and nonpulsatile flow (nonpulsatile group, n = 6) controlled automated reperfusion of the whole body was commenced through the femoral vessels of German landrace pigs for 60 min. Afterwards, animals were observed for eight days. Blood samples were analyzed throughout the experiment and a species-specific neurologic disability score (NDS) was used for neurologic evaluation. In the pulsatile group, nine animals finished the study protocol, while no animal survived postoperative day four in the nonpulsatile group. NDS were significantly better at any given time in the pulsatile group and reached overall satisfactory outcome values. In addition, blood analyses revealed lower levels of lactate in the pulsatile group compared to the nonpulsatile group. This study demonstrates superior survival and neurologic outcome when using pulsatile high pressure automated reperfusion following 20 min of normothermic CA compared to nonpulsatile flow and low MAP. This study strongly supports regulating the reperfusion period after prolonged periods of CA.
Conflict of Interest
MK, CS, KF, and IT have no conflict of interest to declare. GT, FB, and CB are shareholders of Resuscitec Ltd.
REFERENCES
- 1Berdowski J, Berg RA, Tijssen JG, Koster RW. Global incidences of out-of-hospital cardiac arrest and survival rates: systematic review of 67 prospective studies. Resuscitation 2010; 81: 1479–87.
- 2Ehlenbach WJ, Barnato AE, Curtis JR, Kreuter W, Koepsell TD, Deyo RA. Epidemiologic study of in-hospital cardiopulmonary resuscitation in the elderly. N Engl J Med 2009; 361: 22–31.
- 3Chen YS, Lin JW, Yu HY, et al. Cardiopulmonary resuscitation with assisted extracorporeal life-support versus conventional cardiopulmonary resuscitation in adults with in-hospital cardiac arrest: an observational study and propensity analysis. Lancet 2008; 372: 554–61.
- 4Richardson AS, Schmidt M, Bailey M, Pellegrino VA, Rycus PT, Pilcher DV. ECMO Cardio-Pulmonary Resuscitation (ECPR), trends in survival from an international multicentre cohort study over 12-years. Resuscitation 2017; 112: 34–40.
- 5Alghamdi AA, Latter DA. Pulsatile versus nonpulsatile cardiopulmonary bypass flow: an evidence-based approach. J Card Surg 2006; 21: 347–54.
- 6Alkan T, Akçevin A, Undar A, Türkoğlu H, Paker T, Aytaç A. Benefits of pulsatile perfusion on vital organ recovery during and after pediatric open heart surgery. ASAIO J 2007; 53: 651–4.
- 7Milano AD, Dodonov M, Van Oeveren W, Onorati F, Gu YJ, Tessari M. Pulsatile cardiopulmonary bypass and renal function in elderly patients undergoing aortic valve surgerydagger. Eur J Cardiothorac Surg 2015; 47: 291–8. discussion 8.
- 8Trummer G, Foerster K, Buckberg GD, et al. Superior neurologic recovery after 15 minutes of normothermic cardiac arrest using an extracorporeal life support system for optimized blood pressure and flow. Perfusion 2014; 29: 130–8.
- 9Trummer G, Foerster K, Buckberg GD, et al. Successful resuscitation after prolonged periods of cardiac arrest: a new field in cardiac surgery. J Thorac Cardiovasc Surg 2010; 139: 1325–32, 1332.e1–2.
- 10Beyersdorf F. The use of controlled reperfusion strategies in cardiac surgery to minimize ischaemia/reperfusion damage. Cardiovasc Res 2009; 83: 262–8.
- 11Buckberg GD. When is cardiac muscle damaged irreversibly? J Thorac Cardiovasc Surg 1986; 92: 483–7.
- 12Taunyane IC, Benk C, Beyersdorf F, et al. Preserved brain morphology after controlled automated reperfusion of the whole body following normothermic circulatory arrest time of up to 20 minutes. Eur J Cardiothorac Surg 2016; 50: 1025–4.
- 13Trummer G, Supady A, Beyersdorf F, et al. Controlled automated reperfusion of the whole body after 120 minutes of Cardiopulmonary resuscitation: first clinical report. Scand J Trauma Resusc Emerg Med 2017; 25: 66.
- 14Mancini ME, Diekema DS, Hoadley TA, et al. Part 3: Ethical Issues: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132: S383–96.
- 15Kim SJ, Kim HJ, Lee HY, Ahn HS, Lee SW. Comparing extracorporeal cardiopulmonary resuscitation with conventional cardiopulmonary resuscitation: a meta-analysis. Resuscitation 2016; 103: 106–16.
- 16Abu-Omar Y, Ratnatunga C. Cardiopulmonary bypass and renal injury. Perfusion 2006; 21: 209–13.
- 17Taylor KM, Bain WH, Davidson KG, Turner MA. Comparative clinical study of pulsatile and non-pulsatile perfusion in 350 consecutive patients. Thorax 1982; 37: 324–30.
- 18Gold JP, Charlson ME, Williams-Russo P, et al. Improvement of outcomes after coronary artery bypass. A randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg 1995; 110: 1302–11. discussion 11-4.
- 19Singh RK, Barratt-Boyes BG, Harris EA. Does pulsatile flow improve perfusion during hypothermic cardiopulmonary bypass?. J Thorac Cardiovasc Surg 1980; 79: 827–32.
- 20Louagie YA, Gonzalez M, Collard E, et al. Does flow character of cardiopulmonary bypass make a difference?. J Thorac Cardiovasc Surg 1992; 104: 1628–38.
- 21Goto M,
Kudoh K,
Minami S, et al. The renin-angiotensin-aldosterone system and hematologic changes during pulsatile and nonpulsatile cardiopulmonary bypass. Artif Organs 2008; 17: 318–22.
10.1111/j.1525-1594.1993.tb00587.x Google Scholar
- 22Murkin JM, Martzke JS, Buchan AM, Bentley C, Wong CJ. A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. I. Mortality and cardiovascular morbidity. J Thorac Cardiovasc Surg 1995; 110: 340–8.
- 23Siepe M, Pfeiffer T, Gieringer A, et al. Increased systemic perfusion pressure during cardiopulmonary bypass is associated with less early postoperative cognitive dysfunction and delirium. Eur J Cardiothorac Surg 2011; 40: 200–7.
- 24Strandgaard S, Paulson OB. Regulation of cerebral blood flow in health and disease. J Cardiovasc Pharmacol 1992; 19: S89–93.
- 25Colak Z, Borojevic M, Bogovic A, Ivancan V, Biocina B, Majeric-Kogler V. Influence of intraoperative cerebral oximetry monitoring on neurocognitive function after coronary artery bypass surgery: a randomized, prospective study. Eur J Cardiothorac Surg 2015; 47: 447–54.
- 26Siepe M, Goebel U, Mecklenburg A, et al. Pulsatile pulmonary perfusion during cardiopulmonary bypass reduces the pulmonary inflammatory response. Ann Thorac Surg 2008; 86: 115–22.
- 27Petroni T, Harrois A, Amour J, et al. Intra-aortic balloon pump effects on macrocirculation and microcirculation in cardiogenic shock patients supported by venoarterial extracorporeal membrane oxygenation*. Crit Care Med 2014; 42: 2075–82.
- 28Onorati F, Santarpino G, Tangredi G, et al. Intra-aortic balloon pump induced pulsatile perfusion reduces endothelial activation and inflammatory response following cardiopulmonary bypass. Eur J Cardiothorac Surg 2009; 35: 1012–9. discussion 9.
- 29Wang S, Izer JM, Clark JB, et al. In vivo hemodynamic performance evaluation of novel electrocardiogram-synchronized pulsatile and nonpulsatile extracorporeal life support systems in an adult swine model. Artif Organs 2015; 39: E90–101.
- 30Itoh H, Ichiba S, Ujike Y, et al. Effect of the pulsatile extracorporeal membrane oxygenation on hemodynamic energy and systemic microcirculation in a piglet model of acute cardiac failure. Artif Organs 2016; 40: 19–26.
- 31Weiser C, Weihs W, Holzer M, et al. Feasibility of profound hypothermia as part of extracorporeal life support in a pig model. J Thorac Cardiovasc Surg 2017; 154: 867–74.
- 32Ekmektzoglou KA, Xanthos T, Papadimitriou L. Biochemical markers (NSE, S-100, IL-8) as predictors of neurological outcome in patients after cardiac arrest and return of spontaneous circulation. Resuscitation 2007; 75: 219–28.
- 33Geisen U, Benk C, Beyersdorf F, et al. Neuron-specific enolase correlates to laboratory markers of haemolysis in patients on long-term circulatory support. Eur J Cardiothorac Surg 2015; 48: 416–20. discussion 20.
