Cardiospecific sevoflurane treatment quenches inflammation but does not attenuate myocardial cell damage markers: a proof-of-concept study in patients undergoing mitral valve repair

Inflammation is considered a key mediator of complications after cardiac surgery. Sevoflurane has been shown to quench inflammation and to provide cardioprotection in preclinical studies. Clinical studies using sevoflurane confirm this effect on inflammation but do not consistently show clinical ben...

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Bibliographic Details
Published in:	British journal of anaesthesia : BJA Vol. 112; no. 6; pp. 1005 - 1014
Main Authors:	Kortekaas, K.A., van der Baan, A., Aarts, L.P.H.J., Palmen, M., Cobbaert, C.M., Verhagen, J.C.M., Engbers, F.H.M., Klautz, R.J.M., Lindeman, J.H.N.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-06-2014 Oxford University Press
Subjects:	Adult Aged Aged, 80 and over anaesthetics volatile, sevoflurane Anesthetics, Inhalation - administration & dosage Anesthetics, Inhalation - blood Anesthetics, Inhalation - therapeutic use Biomarkers - blood C-Reactive Protein - drug effects Cardiac Surgical Procedures - methods cardiopulmonary bypass Cardiopulmonary Bypass - methods Cardiotonic Agents - administration & dosage Cardiotonic Agents - blood Cardiotonic Agents - therapeutic use Female Humans immune response Interleukin-6 - blood Interleukin-8 - blood Interleukin-8 - drug effects Male Methyl Ethers - blood Methyl Ethers - therapeutic use Middle Aged Mitral Valve - surgery myocardial damage Myocarditis - blood Myocarditis - drug therapy Postoperative Complications - blood Postoperative Complications - drug therapy Prospective Studies reperfusion injury Single-Blind Method anaesthetics volatile, sevoflurane cardiopulmonary bypass myocardial damage reperfusion injury immune response
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Summary:	Inflammation is considered a key mediator of complications after cardiac surgery. Sevoflurane has been shown to quench inflammation and to provide cardioprotection in preclinical studies. Clinical studies using sevoflurane confirm this effect on inflammation but do not consistently show clinical benefits. This paradox may indicate that the contribution of inflammation to postoperative sequalae is less than commonly thought or that systemic doses are too low in their local concentration. To test the latter, we evaluated the effects of intramyocardial sevoflurane delivery. Selective myocardial sevoflurane delivery was performed during aortic cross-clamping in patients undergoing valve surgery (n=11). Results were compared with a control group not receiving sevoflurane (n=10). A reference group (n=5) was added to evaluate the effects of systemic sevoflurane delivery. Paired arterial and myocardial venous blood samples were collected at various time points post-reperfusion. Inflammatory mediators and myocardial cell damage were studied. Intramyocardial delivery was superior to systemic delivery in attenuation of interleukin-6 and interleukin-8 (−44% and −25%, respectively; both P=0.001). Myocardial and systemic sevoflurane delivery effectively suppressed surgery-related inflammatory responses including postoperative C-reactive protein levels when compared with controls [63 (47–99) (P=0.01) and 58 (56–81) (P=0.04) compared with 107 (79–144) mg litre−1]. Sevoflurane treatment did not reduce postoperative troponin T, creatine kinase, and creatine kinase-MB values. This proof-of-concept study suggests that intramyocardial delivery compared with the systemic delivery of sevoflurane more strongly attenuates the systemic inflammatory response after cardiopulmonary bypass without reducing postoperative markers of myocardial cell damage. Nederlands Trial Register NTR2089.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-News-1 ObjectType-Feature-3 content type line 23
ISSN:	0007-0912 1471-6771
DOI:	10.1093/bja/aet588