A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly

Background. Postoperative cognitive dysfunction (POCD) after coronary artery bypass graft surgery is a common complication for which, despite many clinical investigations, no definitive etiology has been found. The current use of both high and low-dose fentanyl as anesthetic techniques allowed us to investigate the effect of fentanyl on the incidence of POCD. Methods. Three hundred fifty patients scheduled to undergo elective coronary artery bypass graft surgery were randomized to receive either high-dose fentanyl (50 mu g/kg) or low-dose fentanyl (10 mu g/kg) as the basis of the anesthetic. All patients underwent neuropsychological testing before surgery and at 1 week, 3 months, and 12 months after surgery. Results. One hundred sixty-eight patients in the low-dose group and 158 patients in the high-dose group were included in the final analysis. Neuropsychological testing was performed on 88%, 93%, and 92% of patients at 1 week, 3 months, and 12 months, respectively. There was no difference between group mean scores at any of the three testing times. Analysis of individual patients by the 20% rule did not detect any differences between groups. The one SD rule, which has fewer false-positive results, detected significantly more patients with POCD in the low-dose group than in the high-dose group at 1 week (23.6% vs. 13.7%; P = 0.03) but not at the other testing times. Patients with POCD spent an average of 1.2 days longer in the hospital than those without POCD (P = 0.021). Conclusions: High-dose fentanyl is not associated with a difference in the incidence of POCD at 3 or 12 months after surgery. Low-dose fentanyl leads to shorter postoperative ventilation times and may be associated with a greater incidence of POCD 1 week after surgery. Early POCD is associated with an increased duration of stay in the hospital.

Asymptomatic long-term survivors of coronary artery bypass surgery enjoy a quality of life equal to the general population

Background Health-related quality of life (HRQOL) among long-term survivors of coronary artery bypass surgery is an important outcome that has been little studied at the population level. Methods A postal survey was conducted in 1999 to 2000 in patients 6 to 20 years after coronary artery bypass graft (CABG) surgery in Western-Australia. A random stratified sample of 2500 was drawn from 8910 patients who had their first CABG surgery in 1980 to 1993. Health-related quality of life was measured with Short Form 36 and EuroQol visual analogue scale. Results Response was 82% (n = 2061). Health-related quality of life declined with age and was similar for men and women, although scores for women were worse for physical functioning. Compared with Australian population norms, the age- and sex-standardized scores of survivors of CABG were generally worse, mainly in the physical domain. Reported angina at the time of follow-up (33%), symptoms of heart failure equivalent to New York Heart Association (NYHA) classes II to IV (34%), and comorbidities such as diabetes and hypertension were associated with poorer HRQOL. For both men and women without angina or heart failure at follow-up, HRQOL was no different from that of the general population. Conclusion Overall, the quality of life among long-term survivors of CABG is worse than that of the general population, the difference being mainly attributable to recurrent symptoms and comorbidities. Quality of life for those without angina or heart failure at follow-up was equivalent to the population norms, providing an incentive to maximize efforts to abolish angina and ameliorate heart failure symptoms.

Assessment of statistical change criteria used to define significant change in neuropsychological test performance following cardiac surgery

Objective: This paper compares four techniques used to assess change in neuropsychological test scores before and after coronary artery bypass graft surgery (CABG), and includes a rationale for the classification of a patient as overall impaired. Methods: A total of 55 patients were tested before and after surgery on the MicroCog neuropsychological test battery. A matched control group underwent the same testing regime to generate test–retest reliabilities and practice effects. Two techniques designed to assess statistical change were used: the Reliable Change Index (RCI), modified for practice, and the Standardised Regression-based (SRB) technique. These were compared against two fixed cutoff techniques (standard deviation and 20% change methods). Results: The incidence of decline across test scores varied markedly depending on which technique was used to describe change. The SRB method identified more patients as declined on most measures. In comparison, the two fixed cutoff techniques displayed relatively reduced sensitivity in the detection of change. Conclusions: Overall change in an individual can be described provided the investigators choose a rational cutoff based on likely spread of scores due to chance. A cutoff value of ≥20% of test scores used provided acceptable probability based on the number of tests commonly encountered. Investigators must also choose a test battery that minimises shared variance among test scores.

A cost-effectiveness analysis of fluvastatin in patients with diabetes after successful percutaneous coronary intervention

Background: The Lescol Intervention Prevention Study (LIPS) was a multinational randomized controlled trial that showed a 47% reduction in the relative risk of cardiac death and a 22% reduction in major adverse cardiac events (MACEs) from the routine use of fluvastatin, compared with controls, in patients undergoing percutaneous coronary intervention (PCI, defined as angioplasty with or without stents). In this study, MACEs included cardiac death, nonfatal myocardial infarction, and subsequent PCI and coronary artery bypass graft. Diabetes was the greatest risk factor for MACEs. Objective: This study estimated the cost-effectiveness of fluvastatin when used for secondary prevention of MACEs after PCI in people with diabetes. Methods: A post hoc subgroup analysis of patients with diabetes from the LIPS was used to estimate the effectiveness of fluvastatin in reducing myocardial infarction, revascularization, and cardiac death. A probabilistic Markov model was developed using United Kingdom resource and cost data to estimate the additional costs and quality-adjusted life-years (QALYs) gained over 10 years from the perspective of the British National Health Service. The model contained 6 health states, and the transition probabilities were derived from the LIPS data. Crossover from fluvastatin to other lipid-lowering drugs, withdrawal from fluvastatin, and the use of lipid-lowering drugs in the control group were included. Results: In the subgroup of 202 patients with diabetes in the LIPS trial, 18 (15.0%) of 120 fluvastatin patients and 21 (25.6%) of 82 control participants were insulin dependent (P = NS). Compared with the control group, patients treated with fluvastatin can expect to gain an additional mean (SD) of 0.196 (0.139) QALY per patient over 10 years (P < 0.001) and will cost the health service an additional mean (SD) of 10 (E448) (P = NS) (mean [SD] US $16 [$689]). The additional cost per QALY gained was;(51 (US $78). The key determinants of cost-effectiveness included the probabilities of repeat interventions, cardiac death, the cost of fluvastatin, and the time horizon used for the evaluation. Conclusion: Fluvastatin was an economically efficient treatment to prevent MACEs in these patients with diabetes undergoing PCI.

Endothelin A receptor localization in the internal mammary artery

Introduction: The vasoconstricting peptide endothelin-1 (ET-1) binds two G-protein-coupled receptor subtypes, the Endothelin A (ETA) and Endothelin B (ETB) receptors. The ETB receptor subtype has been predominantly localised to the arterial and venous endothelial cells both in-vivo and in culture. Stimulation of ET-1 through this receptor subtype can modulate the expression of endothelial nitric oxide and accelerate endothelial cell wound healing. In comparison the ETA receptor is abundantly expressed in medial vascular smooth muscle cells and mediates the vasoconstrictor action of ET-1 and is thought to play a key role in angiogenesis. Aims: To determine the levels of ETA receptor expression and localisation in the internal mammary artery (IMA). Methods: Twenty-four IMA sections were examined from patients undergoing coronary artery bypass (CABG) surgery (5F; 19M; mean age 67 years). And 14 organ donor IMA specimens were used as controls (7M; 7F; mean age 45 years. The tissue was fixed in formalin and processed for histology. Immunohistochemistry was performed on cross-sections of the left distal IMA to assess the areas of ETA receptor staining. The percentage are of ETA receptor staining in the media was calculated using image analysis software connected to an optical microscope and semiquantitative assessment was used to grade staining intensity, that is, mild (+), moderate (++) and strong (+++). Results: ETA receptor staining was significantly elevated in the media of the CABG specimens compared with the donor controls (46.88+/11.52% Vs 18.58+/7.65%, P = .0001). Interestingly, the endothelium (++) of the IMA, as well as the small microvessels in the adventitia (+++) stained positive for ETA receptor expression. Without using a haematoxylin counterstain, the nuclei of the cell stained more intensely (+++) with respect to the cytoplasm in both the medial smooth muscle (++) and endothelial cells (++). Fibroblasts in the medial adventitia junction were also positive for ETA receptor expression (+++). Further, this receptor subtype was also strongly expressed by inflammatory cells (monocytes and macrophages). Conclusions: These results demonstrate that the ETA receptor expression is increased in the medial SMC layer of the CABG IMA specimens and also present in the endothelium, vasa vasorum, fibroblasts and inflammatory cell types. Thus it is possible that in addition to affecting vascular tone, ET-1 may play an important role in IMA remodelling.

Clinical decision-making and myocardial viability: current perspectives

Not all myocardium involved in a myocardial infarction is dead or irreversibly damaged. The balance between the amount of scar and live tissue, and the nature of the live tissue, determine the likelihood that contractile function will improve after revascularisation. This improvement (which defines viability) may be predicted with about 80% accuracy using several techniques. This review examines the determinants of functional recovery and how they may be integrated in making decisions regarding revascularisation. (Intern Med J 2005; 35: 118–125)

Incremental benefit of myocardial contrast to combined dipyridamole-exercise stress echocardiography for the assessment of coronary artery disease

Background-Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD). Methods and Results-MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity. Conclusions-The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent.

Comparison of specificity of quantitative myocardial contrast echocardiography for diagnosis of coronary artery disease in patients with versus without diabetes mellitus

Impaired coronary flow reserve is widely reported in diabetes mellitus (DM) but its effect on myocardial contrast echocardiography (MCE) is unclear. We sought to identify whether DM influences the accuracy of qualitative and quantitative assessment of coronary artery disease (CAD) using MCE in 83 patients who underwent coronary angiography (60 men, 27 with DM; 56 +/- 11 years;). Destruction replenishment imaging was performed at rest and after combined dipyridamole-exercise stress testing. Ischemia was identified by the development of new wall motion abnormalities, qualitative MCE (new perfusion defects apparent 1 second after flash during hyperemia), and quantitative MCE (myocardial blood flow reserve < 2.0 in the anterior circulation). Qualitative and quantitative assessment of perfusion was feasible in 100% and 92% of patients, respectively. Significant left anterior descending coronary stenosis (> 50% by quantitative angiography) was present in 28 patients (including 8 with DM); 55 patients had no CAD (including 19 with DM). The myocardial blood flow reserve was reduced in patients with coronary stenosis compared with those with no CAD (1.6 +/- 1.1 vs 3.8 +/- 2.5, p < 0.001). Among patients with no CAD, those with DM had an impaired flow reserve compared with control patients without DM (2.4 +/- 1.0 vs 4.5 +/- 2.8, p = 0.003). In conclusion, DM significantly influenced the quantitative, but not the qualitative, assessment of MCE, with a marked reduction in specificity in patients with DM. (c) 2005 Elsevier Inc. All rights reserved.

Inhibitors of cholesteryl ester transfer protein - a step forward in the treatment of coronary artery disease?

Although the LDL cholesterol-lowering statins have reduced the mortality and morbidity associated with coronary artery disease (CAD), considerable mortality and morbidity remains. Increasing HDL cholesterol levels is associated with reduced CAD mortality and morbidity. In healthy subjects with mild dyslipidemia, treatment with JTT-705 decreased cholesteryl ester transfer protein (CETP) activity, increased HDL cholesterol and decreased LDL cholesterol. Similarly, another CETP inhibitor, torcetrapib, has recently been shown to increase HDL cholesterol by 46%, decrease LDL cholesterol by 8% and have no effect on triglycerides in subjects with HDL cholesterol levels below 1.0 mmol/l. Increasing HDL cholesterol with inhibitors of CETP represents a new approach to dyslipidemia that requires further investigation, especially in patients with CAD.

Inflammation, complement activation and endothelial function in stable and unstable coronary artery disease

Background: Endothelial dysfunction plays an important role in the pathogenesis of coronary artery disease (CAD). Apart from traditional risk factors complement activation and inflammation may trigger and sustain endothelial dysfunction. We sought to assess the association between endothelial function, high sensitivity C-reactive protein (hs-CRP) and markers of complement activation in patients with either stable or unstable coronary artery disease. Methods: We prospectively recruited 78 patients, 35 patients with stable angina pectoris (SAP) and 43 patients with unstable angina pectoris (UAP). Endothelial function was assessed as brachial artery reactivity (BAR). Hs-CRP, C3a, C5a, and C1-Inhibitor (C1 inh.) were measured enzymatically. Results: Patients with IJAP showed higher median levels of hs-CRP and C3a compared to patients with SAP, while BAR was not significantly different between patient groups. In UAP patients, hs-CRP was significantly correlated with cholesterol (r = 0.27, p < 0.02), C3a (r = 0.32, p < 0.001) and C1 INH.(r = 0.41, p < 0.003), but not with flow mediated dilatation (r = 0.09, P = 0.41). Hs-CRP and C1 INH.were found to be independant predictors of IJAP in a backward stepwise logistic regression model. Conclusions: We conclude that both hs-CRP, a marker of inflammation and C3a, a marker of complement activation are elevated in patients with UAP, but not in patients with SAP. (c) 2005 Elsevier B.V. All rights reserved.