Postoperative pneumonia is a major cause of morbidity and mortality following cardiac surgery. The inflammatory response to cardiac surgery has been widely studied, but specific mechanisms for postoperative pneumonia have not been determined. Tranexamic acid is renowned for its effect on bleeding but can also modulate inflammatory processes. Cardiac surgery is known to release mitochondrial DAMPs (mtDAMPs) and is linked to postoperative inflammation and atrial fibrillation. We speculated that mtDAMPs might be related to postoperative pneumonia and that this might be modulated by tranexamic acid.
Forty-one (41) patients from the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial were studied. Levels of mitochondrial DNA, matrix metallopeptidase 9 (MMP-9) and neutrophil elastase (NE) were determined in plasma preoperatively, at 24 and 72 hours post-surgery and correlated with clinical outcome.
mtDNA was significantly elevated postoperatively in the placebo and tranexamic acid (TXA) groups. Neutrophil elastase increased immediately postoperatively and at 24 hours. MMP-9 was elevated in the placebo group early postoperatively and in the TXA group at the immediate postoperative time point and after 24 hours. Six (6) of the 41 (14.6%) patients subsequently developed pneumonia. mtDNA levels were significantly increased at the early postoperative period and the 24-hour time point in patients with pneumonia.
Cardiac surgery releases mtDNA, increases MMP-9 and NE and this was not influenced by TXA. Inflammation postoperatively might be linked to pneumonia since mtDNA was further elevated in these patients. Due to the low number of individuals developing pneumonia, further studies are warranted to clearly identify whether TXA impacts on the inflammatory response in postoperative pneumonia.
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- Postoperative pneumonia following cardiac surgery in non-ventilated patients versus mechanically ventilated patients: is there any difference?.Crit Care. 2015; 19: 116
- Risk factors for the development of pneumonia post cardiac surgery.Cardiovasc J Afr. 2012; 23: 212-215
- The impact of nosocomial infections on patient outcomes following cardiac surgery.Chest. 1997; 112: 666-675
- Homologous blood transfusion as a risk factor for postoperative infection after coronary artery bypass graft operations.J Thorac Cardiovasc Surg. 1992; 104: 1092-1099
- Risk factors for severe bacterial infections after valve replacement and aortocoronary bypass operations analysis of 246 cases by logistic regression.Ann Thorac Surg. 1985; 40: 224-228
- Risk factor analysis of pneumonias developing after open heart surgery.Crit Care. 2005; 9: 10
- Nosocomial pneumonia in elderly patients following cardiac surgery.Respir Med. 2006; 100: 729-736
- Incidence and risk factors for ventilator-associated pneumonia after major heart surgery.Intensive Care Med. 2009; 35: 1518-1525
- Identification of inflammatory mediators and their modulation by strategies for the management of the systemic inflammatory response during cardiac surgery.J Cardiothorac Vasc Anesth. 2013; 27: 983-1033
- The inflammatory response to cardiopulmonary bypass: Part 1-mechanisms of pathogenesis.J Cardiothorac Vasc Anesth. 2008; 23: 223-231
- Circulating mitochondrial DAMPS cause inflammatory responses to injury.Nature. 2010; 464: 104-107
- Mitochondrial damage-associated molecular patterns from fractures suppress pulmonary immune responses via formyl peptide receptors 1 and 2.J Trauma Acute Care Surg. 2015; 78: 272-279
- Tranexamic acid: a review of its use in the treatment of hyperfibrinolysis.Drugs. 2012; 72: 585-617
- Early tranexamic acid administration ameliorates the endotheliopathy of trauma and shock in an in vitro model.J Trauma Acute Care Surg. 2017; 82: 1080-1086
- Tranexamic acid attenuates inflammatory response in cardiopulmonary bypass surgery through blockade of fibrinolysis: a case control study followed by a randomized double-blind controlled trial.Crit Care. 2007; 11: R117
- Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery.J Thorac Cardiovasc. 2013; 145: 1611-1616
- Neutrophil extracellular traps kill bacteria.Science. 2004; 303: 1532-1535
- Mitochondrial DNA released by trauma induces neutrophil extracellular traps.PLoS One. 2015; 10: e0120549
- Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery.J Crit Care. 2014; 29: 1133.e1-1133.e5
- Mitochondrial damps are released during cardiopulmonary bypass surgery and associated with post-operative atrial fibrillation.Heart Lung Circ. 2017; (pii: S1443-9506(17)30118-X)
- Aspirin and tranexamic acid for coronary artery surgery (ATACAS) trial: rationale and design.Am Heart J. 2008; 155: 224-230
- The tissue-type plasminogen activator-plasminogen activator inhibitor 1 complex promotes neurovascular injury in brain trauma: evidence from mice and humans.Brain. 2012; 135: 3251-3264
- Matrix metalloproteinases: regulators of the tumor microenvironment.Cell. 2010; 141: 52-67
- Matrix metalloproteinase-9: many shades of function in cardiovascular disease.Physiology (Bethesda). 2013; 28: 391-403
- Neutrophil-mediated secretion and activation of matrix metalloproteinase-9 during cardiac surgery with cardiopulmonary bypass.Anesth Analg. 2005; 100: 1554-1560
- Netting neutrophils in autoimmune small-vessel vasculitis.Nat Med. 2009; 15: 623-625
- NETS are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis.Sci Transl Med. 2013; 5: 178ra40
Published online: October 06, 2021
Accepted: August 4, 2021
Received in revised form: June 3, 2021
Received: May 16, 2018
© 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.