Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery - A randomized trial.

Van Dijk et al. - The Octopus Study Group. JAMA 2002;287;1405-1412

Reviewer: Christos Koutentis, MB, ChB
VAMC, West Palm Beach, FL

Intellectual and neurocognitive dysfunction as a complication after CABG surgery has received increasing attention over the last few years. Cognitive decline may affect as many as 50% of all cardiac surgical patients. The financial burden of neurological complications associated with cardiac surgery in the U.S. alone has been estimated at greater than $4 billion a year. The presumption that cardiopulmonary bypass (CPB) is a major cause of cerebral morbidity is a factor driving the increased use of off-pump CABG surgery. However, two small trials showed conflicting results on the effect of off-pump CABG surgery on cognitive outcome. One study by Diegler et al. (n = 40)1 demonstrated improvement in cognitive outcome after off-pump CABG while the other study by Lloyd et al. (n = 60)2 showed no difference in cognitive outcome. To address this controversy, Van Dijk et al. conducted a randomized clinical trial of sufficient size comparing the effect of on-pump and off-pump technique on cognitive outcome among patients undergoing CABG in the Netherlands.

The number of subjects for the study was determined by assuming a 21% incidence of cognitive decline after on-pump CABG at 3 months and that off-pump CABG would reduce this incidence by 2/3. Patient inclusion criteria were first-time isolated CABG, no Q wave MI within 6 months, preserved LV function, and compliance with neuropsychological testing during a 1 year follow up. A total of 281 patients were enrolled and randomized to off-pump CABG surgery (n = 131) or on-pump CABG surgery (n = 134).

Cardiac surgeons experienced in both off- and on-pump CABG performed all operations using the Octopus device. In the off-pump group, 54% had thoracic epidural anesthesia combined with low dose opioids. In the on-pump group, 99% had total intravenous anesthesia with high dose opioids. Bypass was managed using -stat, a minimum nasopharyngeal temperature of 32UC, non-pulsatile perfusion at 2.0-2.4 L/m2/min, a crystalloid-colloid CPB prime, a maximum blood temperature of 39UC for rewarming, and a maximum temperature gradient between blood and water of 5UC. Blood was salvaged through a suction cardiotomy reservoir without a filter in the on-pump group. A cell saver was used in the on-pump group.

The primary endpoint of the study was cognitive outcome at 3 months after surgery. Secondary endpoints were cognitive outcome at 12 months after surgery, differences in quality of life at 3 and 12 months, stroke rate and all-cause mortality at 3 and 12 months.

Cognitive outcome was quantified before surgery and at 3 and 12 months post-surgery on the basis of 10 neuropsychologic tests administered by psychologists who were blinded for randomization. The tests assessed motor skill, memory, attention, visuospatial capacity, and information processing.

At 3 months after operation, cognitive decline occurred in 21.1% of off-pump patients and 29.2% in on-pump patients (RR=0.65; 95% CI, 0.36 - 1.16; P=0.15). The incidence of cognitive decline was not affected by adjustments for patient characteristics or anesthetic technique. At 12 months, cognitive decline occurred in 30.8% of off-pump patients and 33.6% of on-pump patients (RR=0.88; 95% CI, 0.52-1.49; P=0.69). Among individual tests, only verbal memory was different and improved twice as much in the off-pump group (p=0.01). No differences were observed at 3 and 12 months in quality of life, stroke rate, and all-cause mortality.

This large, well-conceived and carefully conducted trial failed to demonstrate a significant benefit of off-pump over the on-pump technique for CABG in terms of neurologic morbidity. It was possible that the study was under powered to detect a difference between groups. Sample size calculations may not have fully incorporated measurement varibility associated with psychological testing. The assumption that the off-pump technique would reduce the incidence of cognitive dysfunction by 2/3 compared to the on-pump technique also turned out to be incorrect. The authors postulated that factors other than CPB might have accounted for the less than expected difference between the groups, but adjustment for demographic variables, number of bypass grafts performed, or anesthetic technique did not change the results. Because a 10% cognitive decline has been observed after noncardiac surgery independent of anesthetic technique, surgical trauma alone may explain the reduction in neurocognitive performance.

Another explanation for the failure to detect differences between the two groups was the enrollment of only relatively young patients with less advanced disease and comorbidity. It remains possible that the benefits of the off-pump technique can only be demonstrated in older and sicker patients. It was also possible that the off-pump technique caused additional unexpected sources for cognitive decline. The hemodynamic consequences of exposing the posterior wall of the heart for bypass grafting may temporarily decrease cerebral perfusion pressure. It was also possible that a longer follow up period was required to detect differences attributed to off-pump surgery. In the study performed by Newman,3 CABG patients showed a progression in cognitive dysfunction from 24% at 6 months to 42% after 5 years. Data from this present study may also indicate that the severity of cognitive decline after CABG surgery in the present setting is less than what has been previously reported.

References
1. Diegler A et al. Neuromonitoring and neurocognitive outcome in off pump versus conventional coronary bypass operation. Ann Thorac Surg 2000;69:1162-1166
2. Lloyd CT et al. Serum S100 protein release and neuropsychologic outcome during coronary revascularization on the beating heart: a prospective randomized study. J Thorac Cardiovasc Surg 2000;119:148-154
3. Newman MF et al. Longitudinal assessment of neurocognitive function after coronary artery bypass surgery. N Engl. J Med, 2001;344:395-402

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