Aprotinin reduces cardiac troponin I release and inhibits apoptosis of polymorphonuclear cells during off-pump coronary artery bypass surgery.

OBJECTIVES: In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. DESIGN: A prospective randomized clinical trial. SETTING: University hospital. PARTICIPANTS: Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. INTERVENTIONS: Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. MEASUREMENTS AND MAIN RESULTS: Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor alpha; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (p = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. CONCLUSIONS: The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery.

Performance analysis of interactive multimodal CME retraining on attitude toward and application of OPCAB.

OBJECTIVE: The transfer of tacit and codified knowledge on a surgical technique is studied in a consecutive cohort of teams participating in interactive multimodal continuing medical education (CME) retraining in off-pump coronary artery bypass (OPCAB). METHODS: Fifty teams of 1.3 +/- 0.5 surgeons and 1.1 +/- 1.9 anesthetists visited 2.2 +/- 0.7 days. Variables describe the pre-visit cardiac activity and OPCAB attitude, complexity score (10 frequently cited complexity criteria), application, and conversion rate. The multimodal approach to knowledge transfer included interactive discussions (commitment; resistances; levers and process of change; methods; outcome; resource optimization), active participation in 3.8 +/- 1.3 unselected cases (anchor-stitch, enucleation techniques), low-fidelity bench model (shunt placement, anastomotic technique), and CD-ROM. Exit end points included OPCAB attitude and complexity score. Late end points (3 months) included OPCAB attitude, complexity score, and application rate. RESULTS: OPCAB was considered, upon exit, beneficial for all patients by 90% of the teams (versus 29 % pre-visit), but by only 62 % of the teams at 3 months. The complexity score downgraded at exit from 3.6 +/- 2 (pre-visit) to 1.2 +/- 1 (P <.001) but increased again at 3 months to 1.6 +/- 1 (P =.001 versus pre-visit and P =.001 versus exit). The 3-month OPCAB rate of the surgeons was 49% +/- 32% versus 23% +/- 28% pre-visit (P <.0001). This was influenced by the pre-visit OPCAB rate and education, as well as by the post-visit changes in complexity scores and attitude. The conversion rate toward cardiopulmonary bypass improved from 3.5% +/- 5% (pre-visit) to 1.3% +/- 3% (3 months, P =.006). CONCLUSIONS: The multimodal OPCAB re-training resulted in a substantial increase of the application, concomitant with a decrease in conversion. The positive impact on attitude and complexity score, at exit, was somewhat reduced in the following clinical confrontation.

OPCAB versus early mortality and morbidity: an issue between clinical relevance and statistical significance.

OBJECTIVE: To evaluate the impact of OPCAB on major postoperative events in a large consecutive cohort of patients, covering the complete spectrum of risk. METHODS: A consecutive series of 3333 CABG patients operated in a single institution (Jan/97-Jan/03) is analyzed after a complete (98%) midterm reengineering towards off-pump surgery (Oct/99). Patients in cardiogenic shock are excluded. The on- (N=1593) or off-pump (N=1740) datasets are comparable for most demographic and non-cardiac variability. The studied events are early mortality, early stroke, early infarct, early dialysis and hospital stay. Three methods adjust for possible patient selection: similar datasets, forced inclusion of a saturated OPCAB propensity score and finally multivariate correction. RESULTS: Non-risk adjusted. The 3-month survival was 96.7+/-0.4% (OPCAB) and 95.9+/-0.5% (ECC) (P=0.2). The 8-day freedom from stroke was 99.4+/-0.2% (OPCAB) and 98.5+/-0.3% (ECC) (P=0.004). The prevalence of dialysis was 1.67% in OPCAB and 2.27% in ECC (P=0.2). The 8-day freedom from infarct was 98.4+/-0.2% (OPCAB) and 98.3+/-0.2% (ECC) (P=0.7). The freedom from hospital discharge day 15 was 17.6+/-0.9% (OPCAB) and 18.4+/-0.8% (ECC) (P=0.001). Propensity score corrected and adjusted for event-related variability. The survival effect remained non-significant (P=0.3), also for patients with a EuroSCORE>8 (P=0.9). The stroke effect became non-significant (P=0.2), but stayed significant for patients with severe internal carotid artery stenosis (P=0.02). The dialysis-effect remained non-significant (P=0.6), also for patients with an elevated creatinine (P=0.7). The early infarct-effect remained non-significant (P=0.8), also for the female patients (P=0.8). The hospital discharge was significantly influenced by the OPCAB approach for the total group (P=0.02) as well as for the patients with EuroSCORE>8 (P=0.01). CONCLUSIONS: The observed 20% reduction of mortality, 60% reduction of stroke and 20% reduction of dialysis were partly neutralized by the adjusting methods and demand, at least, larger datasets to obtain statistical significance. Subdatasets with fewer patients but higher risk identified risk-reducing effects for stroke. Hospital stay was shortened by the OPCAB approach. The interactions between risk, number of patients and the risk-reducing effect are the cornerstones of evidence generation for the OPCAB approach. These results were obtained through a very strict reengineering and cannot be extended to all OPCAB programs.