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Biomedical subjects

D P Taggart

Publications and source records attributed to D P Taggart.

At least 19 recordsLinked to original sources

Postoperative hypoxia is a contributory factor to cognitive impairment after cardiac surgery.

OBJECTIVE: Cognitive dysfunction and postoperative hypoxia are common sequelae of coronary artery bypass grafting, but there has been no study to determine whether there is any relationship between them. METHODS: Arterial blood gas measurements were performed before surgical intervention and on the second and fifth postoperative day, and neuropsychological assessments were performed before surgical intervention and 5 days and 3 months postoperatively by using a battery of 10 psychometric tests in 175 patients undergoing coronary artery bypass grafting. An estimate of overall performance on the battery at each assessment point was provided by a simple aggregate cognitive index score calculated from the mean z scores of 4 normally distributed test variables. Multiple regression analysis was performed by using the cognitive index score at day 5 as the dependent variable, with age, sex, duration of the operation, presence or absence of cardiopulmonary bypass, preoperative cognitive index score, and arterial oxygenation and percentage of saturation at day 5 as independent variables. RESULTS: The mean cognitive index score decreased significantly in 115 (66%) patients who agreed to neuropsychological test battery assessment on the fifth postoperative day but improved significantly beyond baseline at 3 months. Mean arterial oxygen tension and percentage of saturation decreased significantly 2 days after the operation and, although improving over the following 3 days, remained decreased at day 5. Decreased cognitive index scores at day 5 strongly predicted cognitive impairment at 3 months (r = 0.36). The only significant independent predictors of the day 5 cognitive index score in the multiple regression analysis were preoperative cognitive index score and arterial oxygenation tension at day 5 (r = 0.24, P <.03). CONCLUSIONS: We report a significant correlation between postoperative cognitive dysfunction and hypoxia 5 days after coronary artery bypass grafting. This finding might have therapeutic implications because early postoperative cognitive dysfunction influences long-term impairment.

Cognition Disorders↗

Neuroprotection during cardiac surgery: a randomised trial of a platelet activating factor antagonist.

OBJECTIVE: To assess platelet activating factor (PAF) antagonists, potent neuroprotective agents in experimental cerebral dysfunction, in clinical practice. DESIGN: Double blind, minimised, placebo controlled trial of low and high dose PAF antagonist (lexipafant). SETTING: Cardiac surgery unit. PATIENTS: 150 patients undergoing coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass. INTERVENTIONS: Randomisation to placebo, low dose (10 mg) or high dose (100 mg) lexipafant. MAIN OUTCOME MEASURES: Incidence of impairment on four established cognitive tests, undertaken before, five days, and three months after CABG, examined by three methods for defining impairment. RESULTS: The three groups were similar with respect to preoperative and intraoperative factors. Observed levels of cognitive impairment were less than had been predicted from previous studies. There was no difference in the groups in cognitive change scores at five days or three months. Group mean analysis showed significant time factors for all four tests but not for interactions or for the lexipafant group. A composite cognitive index, based on the aggregate of four normally distributed tests, showed a significant effect for timing of the test but not for the lexipafant group or interaction. Age, but not duration of bypass, was the most important determinant of postoperative cognitive impairment. CONCLUSIONS: The neuroprotective PAF antagonist lexipafant did not differentially reduce the level of cognitive impairment after CABG as determined by power estimates derived from published studies. The strongest predictors of cognitive impairment were age and timing of the test after operation.

Cognition Disorders↗

Total arterial revascularisation as a primary strategy for coronary artery bypass grafting.

BACKGROUND: Bilateral internal thoracic arteries confer improved survival benefit after coronary artery bypass grafting (CABG). Despite increasing evidence, the use of arterial conduits has not been accepted as a primary practice in most of the centres in the UK for various reasons. A series of patients has been analysed to assess the feasibility of total arterial revascularisation as a primary strategy in patients requiring first time CABG. METHODS: Altogether 245 patients undergoing first time CABG by one surgeon, from June 1999 to October 2000, were studied. Group 1 consisted of 165 patients undergoing total arterial revascularisation (using bilateral internal thoracic and radial arteries) and group 2 consisted of 80 patients undergoing conventional CABG (using one internal thoracic artery and supplemental veins). Thirty day mortality and early morbidity with particular reference to resternotomy for bleeding, cerebrovascular accidents, renal failure, and sternal dehiscence were the main outcome measures. RESULTS: Patients in group 1 were younger (mean (SD) 60 (10) v 65 (9) years; p<0.001), had lower Parsonnet scores (mean (SD) 5 (5) v 11 (7); p<0.001), and better left ventricular function. Both groups received a similar number of grafts. The percentage of patients undergoing total arterial revascularisation rose from 44% in the first three months to over 75% in the three latter three month periods. Overall 30 day mortality was 1.3%, one patient (0.6%) in group 1 and two patients (2.5%) in group 2. There was a similar incidence of postoperative complications and length of median postoperative stay in both groups. CONCLUSION: Total arterial revascularisation can be adopted as a primary strategy in most patients undergoing CABG with no increase in mortality or morbidity.

Aged↗

Effect of arterial revascularisation on survival: a systematic review of studies comparing bilateral and single internal mammary arteries.

BACKGROUND: Coronary artery bypass grafting (CABG) is the commonest major operation in most developed countries. A single internal mammary artery (IMA) graft has proven survival benefits, but the additional survival advantage of a second graft is unknown. We systematically reviewed published studies of bilateral versus single IMA grafts in CABG to assess any differences in survival. METHODS: We identified from Medline all studies in which single and bilateral IMA grafts were compared. We included studies in which at least 100 patients in each group had been followed up for at least 4 years. We assessed study quality on the basis of patient selection, comparability of intervention groups (especially for age, sex, ventricular function, and diabetes status), outcome assessment, and completeness of follow-up. Our primary outcome was survival. Estimates of treatment effect (single versus bilateral) expressed as hazard ratios were pooled across studies. FINDINGS: None of the studies was a randomised trial, but nine cohort studies met our inclusion criteria. Seven studies yielded survival data for meta-analysis, and included 15962 patients: 11269 single and 4693 bilateral IMA grafts. The bilateral group had significantly better survival than the single group (hazard ratio for death 0.81; 95% CI 0.70-0.94). Exclusion of methodologically weak studies improved survival rates with bilateral IMA grafts. INTERPRETATION: Because no study was a randomised trial, our results are more uncertain than is indicated by the 95% CI. Nevertheless, bilateral IMA grafts seem to give better survival rates than single grafts.

Aged↗

Effects of a platelet-activating factor antagonist on lung injury and ventilation after cardiac operation.

BACKGROUND: Platelet-activating factor is a mediator of lung injury during cardiac operation. Platelet-activating factor antagonists reduce lung injury in animal models of cardiopulmonary bypass but there is no confirmatory evidence in clinical practice. METHODS: The effect of a low or high dose of a platelet-activating factor antagonist (Lexipafant) was assessed in a single center, double-blind, placebo-controlled, parallel group study. One hundred fifty patients undergoing coronary artery bypass grafting were randomized by minimization into three groups to receive placebo infusion, 10 or 100 mg of lexipafant for over 24 hours. Serial arterial oxygen and carbon dioxide tension, alveolar arterial oxygen gradient, and percent saturation were measured before operation and at 1, 6, 24, 48 hours, and 5 days after operation. RESULTS: Patient groups were similar with respect to age, sex, body surface area, and urgency of operation. Likewise, the groups were similar with respect to duration of cardiopulmonary bypass and the number and type of grafts. Maximum lung injury occurred at 48 hours when the arterial oxygen tension and percent saturation reached a nadir (both p < 0.001) accompanied by the maximum increase in the alveolar arterial gradient (p < 0.001). All measurements demonstrated partial recovery by 5 days but remained significantly (p < 0.001) impaired in comparison to baseline values. Duration of ventilation was similar in all groups. Lexipafant, at low or high dose, did not moderate lung injury after cardiopulmonary bypass and did not influence the duration of postoperative ventilation. CONCLUSIONS: Despite experimental and clinical evidence implicating platelet-activating factor in the pathophysiology of lung injury after cardiopulmonary bypass, no beneficial effect of a platelet-activating factor antagonist on lung function or ventilation could be demonstrated in this clinical trial.

Adult↗

Phenoxybenzamine is more effective and less harmful than papaverine in the prevention of radial artery vasospasm.

OBJECTIVES: There is an increasing use of arterial conduits for coronary artery bypass grafting, and the radial artery is commonly used as the third graft. The major drawback of the radial artery is its proclivity to spasm. Both papaverine and phenoxybenzamine have been recommended as topical vasodilators in clinical practice. We compared the efficacy of both drugs to prevent radial artery spasm and their ability to preserve endothelial function. METHODS: The ability of both drugs to prevent alpha-adrenoreceptor mediated constriction was tested in vitro in an organ bath in radial artery segments obtained from 20 patients. Vessel viability was determined by potassium (K(+)) constriction, and endothelial function was assessed by observing endothelium-dependent relaxation by a synthetic analogue of acetylcholine, carbachol. RESULTS: Papaverine consistently abolished and prevented spasm for up to a maximum of 30 min in all segments. In contrast, phenoxybenzamine consistently abolished and prevented radial artery spasm in all segments for at least 6 h. Whereas papaverine damaged the endothelium of 70% of vessels, there was no evidence of endothelial damage in any arterial segments after exposure to phenoxybenzamine. CONCLUSIONS: Phenoxybenzamine more effectively prevents alpha-adrenoreceptor mediated spasm of the human radial artery than papaverine. It is also less harmful to the endothelium.

Adrenergic alpha-Antagonists↗

Neurological and cognitive disorders after coronary artery bypass grafting.

Cerebral injury is a major cause of mortality and morbidity of coronary artery bypass grafting. Stroke occurs in 3% of patients and is largely caused by embolization of atheromatous debris during manipulation of the diseased aorta. Cognitive impairment, which is predominantly caused by microembolization of gaseous and particulate matter, mainly generated by cardiotomy suction, is more common. Demonstration of similar cognitive impairment in patients operated on without cardiopulmonary bypass indicates that other pathophysiological mechanisms, such as anaesthesia and hypoperfusion, are also involved. Advances in medical, anesthetic, and surgical management have resulted in a reduction in the incidence of neurological injury in CABG patients over the past decade. On the other hand, an increasingly elderly population with more severe comorbidity, who are more prone to cerebral injury, are increasingly being referred for CABG. Possible mechanisms to reduce overt and subtle cerebral injury are discussed. The use of composite arterial grafts performed on the beating heart may be the most effective way of minimizing the risk of cerebral injury associated with CABG.

Biomarkers↗

Respiratory dysfunction after cardiac surgery: effects of avoiding cardiopulmonary bypass and the use of bilateral internal mammary arteries.

BACKGROUND: The quantitative contribution of cardiopulmonary bypass (CPB) to respiratory dysfunction after cardiac surgery is not documented and the effect of the use of bilateral internal mammary artery (IMA) grafts is not clear. METHODS: One hundred and seventy-five patients undergoing CABG with (CPB, n=150) and without (NOCPB, n=25) CPB were studied. PMN elastase (as a marker of the systemic inflammatory response) and serial arterial oxygen (paO(2)) and carbon dioxide (paCO(2)) tension, alveolar arterial oxygen (AaO(2)) gradient and percent saturation were measured. The CPB group was subdivided into three groups by the number of IMA grafts used: 0IMA (n=12), 1IMA (n=82) and 2IMA (n=51). RESULTS: The NOCPB group was younger, had significantly better preoperative blood gases, received fewer grafts and had lower PMN elastase levels than the CPB group. In both groups maximum respiratory dysfunction occurred at 48 h (paO(2), percentage saturation and Aa gradient all P<0.001 versus baseline) with partial recovery by 5 days. The percentage decline and subsequent recovery in all blood gas parameters was near identical in the CPB and NOCPB groups. Amongst the three IMA groups the percentage changes in all blood gas parameters were similar, as was the duration of postoperative ventilation and time to discharge. There was no correlation between blood gas parameters at 48 h with age, CPB time, blood loss, duration of ventilation or peak PMN elastase level. CONCLUSIONS: Changes in postoperative gas exchange are similar in patients undergoing CABG with and without CPB even although PMN elastase levels indicate that CPB produces a more marked inflammatory response. The use of 2IMA compared with 1IMA does not increase respiratory dysfunction.

Aged↗

Biochemical assessment of myocardial injury after cardiac surgery: effects of a platelet activating factor antagonist, bilateral internal thoracic artery grafts, and coronary endarterectomy.

OBJECTIVE: Platelet activating factor antagonists reduce ischemia-reperfusion injury in experiments, but there is no supportive clinical evidence. METHODS: A single-center, double-blind, minimized, placebo-controlled, randomized trial of low-dose (10 mg) or high-dose (100 mg) platelet activating factor antagonist was conducted in 150 patients undergoing coronary artery bypass grafting. Myocardial injury was determined by serial measurements of the MB isoenzyme of creatine kinase and cardiac troponin T. The effects of single or bilateral internal thoracic artery grafting and coronary endarterectomy on myocardial injury were also assessed. RESULTS: The placebo and platelet activating factor antagonist groups were similar with respect to preoperative, intraoperative, and postoperative factors. Four patients (2.7%) died before discharge, 3 from cardiac events. Thirteen patients (9%) had biochemical evidence of myocardial infarction, of whom 3 died. Stepwise multiple regression analysis demonstrated that duration of cardiopulmonary bypass was the most important determinant of elevations in creatine kinase MB isoenzyme and cardiac troponin T up to 6 hours after the operation and that the use of a platelet activating factor antagonist and the number of internal thoracic artery grafts did not influence myocardial injury at any time. Endarterectomy was performed in 11 patients (7%), of whom 6 (55%) had biochemically defined myocardial infarction and of whom 1 died (9%). Endarterectomy was the most important determinant of elevated levels of creatine kinase MB isoenzyme and cardiac troponin T 24 and 48 hours after the operation. CONCLUSION: Platelet activating factor antagonists do not reduce perioperative myocardial injury. Bilateral and single internal thoracic artery grafting results in similar levels of myocardial injury, whereas endarterectomy is frequently associated with biochemical evidence of myocardial injury.

Area Under Curve↗