Multicentre randomized clinical trial to investigate the cost-effectiveness of an allogeneic single-donor fibrin sealant after coronary artery bypass grafting (FIBER Study).

BACKGROUND: Reduction of blood transfusion in cardiac surgery is an important target. The aim of this study was to investigate the cost-effectiveness of the use of CryoSeal®, an allogeneic single-donor fibrin sealant, in patients undergoing coronary artery bypass grafting (CABG). METHODS: This randomized clinical study involved seven cardiac surgery centres in the Netherlands. Patients undergoing elective isolated CABG with the use of at least one internal thoracic artery (ITA) graft were assigned randomly to receive either CryoSeal® (5 ml per ITA bed) or no CryoSeal®. Primary efficacy endpoints were units of transfused red blood cells, fresh frozen plasma and platelet concentrates, and duration of intensive care unit stay. Secondary efficacy endpoints were 48-h blood loss, reoperation for bleeding, mediastinitis, 30-day mortality and duration of hospital stay. RESULTS: Between March 2009 and January 2012, 1445 patients were randomized. The intention-to-treat (ITT) population comprised 1436 patients; the per-protocol (PP) population 1292. In both the ITT and the PP analysis, no significant difference between the treatment groups was observed for any of the primary and secondary efficacy endpoints. In addition, no significant difference between the groups was seen in the proportion of transfused patients. Estimated CryoSeal® costs were €822 (95 per cent c.i. €808 to €836) per patient, which translated to €72,000 per avoided transfusion (unbounded 95 per cent c.i.). CONCLUSION: The use of the fibrin sealant CryoSeal® did not result in health benefits. Combined with the high cost per avoided transfusion, this study does not support the implementation of routine CryoSeal® use in elective isolated CABG. REGISTRATION NUMBER: NTR1386 ( http://www.trialregister.nl).

Cognitive dysfunction after cardiac surgery: Pathophysiological mechanisms and preventive strategies.

Despite improvements in surgical techniques and the implementation of effective brain protection strategies, the incidence of brain injury after cardiac surgery has remained relatively constant over the years as patients have become older and sicker. Cognitive dysfunction is the most common clinical manifestation of brain injury after cardiac surgery. Its occurrence is related to a combination of three factors that are often associated with cardiopulmonary bypass (CPB): embolism, hypoperfusion, and the inflammatory response. However, such factors and their potential cerebral consequences are not exclusive to CPB. Postoperative cognitive dysfunction also afflicts patients who undergo cardiac surgery without CPB as well as nonsurgery patients who undergo transcatheter interventions. There is growing evidence that patient-related factors such as the presence of (cerebro)vascular risk factors play an important role in both early and late postoperative cognitive dysfunction.

A comparative study of the immune modulating properties of antifibrinolytics in cardiac surgery.

PURPOSE: Antifibrinolytics, used in cardiac surgery to abate postoperative blood loss, share anti-inflammatory properties by suppression of pro-inflammatory D-dimer and plasmin levels. Additional drug specific immune modulating qualities are often mentioned in the discussion on which antifibrinolytic can best be used. To determine the extent and relevance of these effects, we investigated cytokine and growth factor plasma levels in cardiac surgery patients randomized to receive either tranexamic acid, aprotinin, or placebo. Corticosteroid-treated patients served to put the effects in perspective. METHODS: Using a biochip immunoassay, plasma of 36 cardiac surgery patients was quantified for 12 cytokines and growth factors, assessed preoperatively and 6, 12, 24, and 48 h after the start of cardiopulmonary bypass. Eight patients were treated with tranexamic acid, nine with aprotinin, and nine received placebo. Ten placebo-treated patients received corticosteroids. RESULTS: IL-1ß, IL-6, IL-8, IL-10, IFN-γ, TNF-α, VEGF, MCP-1, and EGF plasma concentrations significantly changed over time across all patients. Aprotinin-treated patients showed decreased pro-inflammatory TNF-α and peak MCP-1 plasma levels when compared with placebo. However, corticosteroids attenuated the inflammatory response to a much larger extent, lowering postoperative IL-6, IL-10, IFN-γ, and VEGF concentrations also. CONCLUSIONS: Aprotinin attenuates postoperative pro-inflammatory levels TNF-α and MCP-1 whereas tranexamic acid does not. The majority of plasma proteins studied, however, were not affected by the use of antifibrinolytics when compared with placebo. A clinically relevant common anti-inflammatory effect through inhibition of fibrinolysis seems therefore unlikely.

Feasibility and reliability of on-line automated microemboli detection after carotid endarterectomy. A transcranial Doppler study.

OBJECTIVES: recently, a new algorithm for transcranial Doppler (TCD) ultrasound detection of microembolic signals (MES) was developed. In the present study, we investigated its on-line performance in TCD monitoring after carotid endarterectomy (CEA) and assessed off-line its accuracy in detecting MES. MATERIALS AND METHODS: first, the feasibility of MES detection in TCD monitoring after CEA in a routine clinical setting was evaluated in 50 patients. Second, to test the reliability of the software a 2-h digital audio study tape was made and analysed by the algorithm and five human experts. The "gold standard" was defined as the agreement between human experts: a MES was considered to be present if at least three human observers agreed. RESULTS: TCD monitoring for emboli detection after CEA was well tolerated by the patients and could be performed reliably. In the study tape, the human gold standard detected 107 MES, with 93 MES having an intensity of > or =7 dB. The software detected 81 and 77 MES, respectively. Using the 7 dB intensity threshold, the software had no false positives and 16 false negatives. The kappa value between the human gold standard and the software was 0.91, the proportion of specific agreement was 0.83. CONCLUSIONS: the tested algorithm provides a reliable method for automated on-line microemboli detection after CEA. This makes monitoring of the effectiveness of antiplatelet agents in the prevention of stroke after CEA more practicable.

Assessment of cognitive deterioration in individual patients following cardiac surgery: correcting for measurement error and practice effects.

Assessment of cognitive change in individual patients may be confounded by unreliability of test scores and effects of repeated testing. An index correcting for both problems is proposed and compared with change indices that do not or do not adequately deal with measurement error and practice effects. These indices were used to examine cognitive deterioration in a sample of 63 patients undergoing cardiac surgery. It was demonstrated that for test measures with a low reliability, failure to correct for measurement error resulted in overestimation of deterioration rates. For test measures with a high reliability, but showing substantial practice effects, failure to correct for practice effects resulted in underestimation of deterioration rates. With the proposed index, cognitive deterioration shortly after cardiac surgery was most frequently observed for attention and psychomotor speed, less frequently for verbal fluency, and only occasionally for learning and memory.

Residual cognitive dysfunctioning at 6 months following coronary artery bypass graft surgery.

Neuropsychological testing is a sensitive method for quantitative assessment of cognitive dysfunctioning following cardiopulmonary bypass (CPB). However, the methodological problems associated with this method, such as learning effects due to repeated testing and the effects of distress on test performance, have often been underestimated. In this study, these confounding effects were controlled for by including the spouses of patients, exposed to the same potential stress effects associated with the operation, as a nonsurgical control group. The experimental group consisted of 63 patients (40-75 years) undergoing elective coronary artery bypass graft (CABG) surgery. A battery of standardized neuropsychological tests was administered to both groups 2 weeks preoperatively and 1 week, 1 month, and 6 months postoperatively. Statistical testing of inter-group differences in preoperative to postoperative changes in test performance revealed the following results: (1) For immediate memory and learning, in general test scores showed the same time course for both groups. (2) For recent memory, patients' scores showed a significant deterioration at 1 month after CABG surgery compared with the scores of spouses. This effect had not completely disappeared at 6 months postoperatively. (3) For attention and psychomotor speed as well as verbal fluency, patients' scores had deteriorated significantly at 1 week after surgery, with incomplete recovery at 6 months. These negative cognitive effects were not related to the patients' ages or CPB parameters (duration of CPB, aortic cross-clamp time, mean flow and arterial pressure during CPB and aortic cross-clamping, and minimum nasopharyngeal temperature). No differences in self-ratings of mood over time were found between the patients and spouses. The results indicate that, when adequately controlling for the effects of learning and distress, some cognitive functions are still impaired at 6 months after CABG surgery.