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01.04.2016 | Reports of Original Investigations | Ausgabe 4/2016

Canadian Journal of Anesthesia/Journal canadien d'anesthésie 4/2016

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

Canadian Journal of Anesthesia/Journal canadien d'anesthésie > Ausgabe 4/2016
MD David M. Ansley, PhD Koen Raedschelders, MD Peter T. Choi, PhD Baohua Wang, MD Richard C. Cook, PhD David D. Y. Chen
Wichtige Hinweise
This article is accompanied by an editorial. Please see Can J Anesth 2016; 63: this issue.
This project was funded with peer-reviewed awards and grants from the International Anesthesia Research Society, Canadian Anesthesia Research Foundation, and the Canadian Institutes of Health Research (#82757). These organizations had no role in the study design, conduct, analysis or reporting. Koen Raedschelders was supported by a CIHR Canada Graduate Student Scholarship and CIHR Postdoctoral Fellowship.

Author contributions

David Ansley, Koen Raedschelders, David Chen, and Peter Choi designed the study. David Ansley, Peter Choi, Koen Raedschelders, and Baohua Wang coordinated the study. David Ansley, Baohua Wang, and Koen Raedschelders analyzed the data. Koen Raedschelders and David Chen conducted drug measurements and blood bioanalysis. Richard Cook helped with data acquisition. David Ansley was the principal investigator. Baohua Wang conducted tissue analysis. All authors contributed to critical revision of article content.



The efficacy of myocardial conditioning strategies is compromised in patients with advanced age, diabetes, or low ejection fraction. We conducted a single-centre parallel-arm blinded randomized-controlled trial to determine whether propofol provides perioperative myocardial protection.


Patients enrolled in this study were scheduled for primary aortocoronary bypass surgery utilizing normothermic cardiopulmonary bypass (CPB) with blood cardioplegia. The participants were stratified by diabetic status and left ventricular ejection fraction and randomly assigned to receive either an elevated dose of propofol –previously associated with experimental cardioprotection– or an isoflurane preconditioning regime. The primary endpoint was the coronary sinus (CS) concentration of 15-F2t-isoprostane (isoP). Secondary endpoints included in-hospital low cardiac output syndrome (LCOS) and major adverse cardiac events, 12- and 24-hr CS cardiac troponin I (cTnI) release, and myocardial B-cell lymphoma 2 (Bcl-2) protein expression.


Data were analyzed from 125 of 137 randomized participants. Participants receiving propofol experienced a greater mean (SD) increase from baseline in CS 15-F2t-isoP levels compared with those receiving isoflurane [26.9 (10.9) pg·mL−1 vs 12.1 (10.4) pg·mL−1, respectively; mean difference, 14.8; 95% confidence interval (CI), 11.0 to 18.6; P < 0.001] but a decreased incidence of LCOS (20.9% vs 57.1%, respectively; relative risk [RR],0.37; 95% CI, 0.22 to 0.62; P < 0.001). The incidence of LCOS was similar between groups in participants without type 2 diabetes mellitus (DM2) (P = 0.382) but significantly decreased in the propofol DM2 subgroup compared with the isoflurane DM2 subgroup (17.9% vs 70.3%, respectively; RR, 0.26; 95% CI, 0.13 to 0.52; P < 0.001). Propofol was associated with an increase in myocardial Bcl-2 protein expression (P = 0.005), a lower incidence of a CS cTnI threshold for myocardial infarction (P = 0.014), and fewer heart failure events (P < 0.001).


Propofol may be a preemptive intraoperative cardioprotectant for patients with DM2 under conditions of normothermic CPB and blood cardioplegic arrest. The study is registered at (NCT00734383) and (ISRCTN70879185).

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