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Biomedical subjects

Stanton K Shernan

Publications and source records attributed to Stanton K Shernan.

At least 19 recordsLinked to original sources
PubMed2006

Effect of pexelizumab on mortality in patients with acute myocardial infarction or undergoing coronary artery bypass surgery: a systematic overview.

BACKGROUND: Recent trials evaluating the C5 complement inhibitor, pexelizumab, have shown that modulation of inflammation during ischemia/reperfusion in patients with acute myocardial infarction (MI) or undergoing coronary artery bypass graft (CABG) surgery may improve clinical outcomes. METHODS: We performed a systematic overview of individual patient data from all completed randomized controlled trials of pexelizumab to evaluate the effect on all-cause mortality at 30 and 180 days after treatment. We used a random effects model and included all 5916 patients randomized in 4 clinical trials. Patients received placebo, pexelizumab bolus only or pexelizumab bolus followed by a 24-hour infusion. RESULTS: A significant reduction in mortality at 30 days was observed in patients treated with bolus plus infusion (n = 2476) compared with placebo (n = 2492) (2.9% vs 4.2%; relative risk [RR], 0.70; 95% confidence interval [CI], 0.52-0.95; P = .02), with no interaction according to disease state of CABG or acute MI (P for interaction .33). A trend toward a reduction in mortality was observed in patients who received bolus plus infusion or bolus only (n = 3429) compared with placebo (n = 2476) (3.5% vs 4.2%; RR, 0.85; 95% CI, 0.66-1.0975; P = .215), but not in patients who received bolus only (n = 937) compared with placebo (n = 937) (5.2% vs 5.4%; RR, 0.96; 95% CI, 0.66-1.41; P = .918). The mortality benefit with bolus plus infusion compared with placebo persisted through 180 days (P = .05). CONCLUSIONS: Pexelizumab reduced 30-day mortality in this systematic evaluation. Bolus plus infusion dose is being studied in ongoing trials in acute MI and CABG populations.

Adult↗
PubMed2006

Pexelizumab reduces death and myocardial infarction in higher risk cardiac surgical patients.

BACKGROUND: Morbidity and mortality after coronary artery bypass graft surgery are directly related to specific preoperative risk factors. We assessed the influence of preoperative risk factors on the effect of pexelizumab, a C5 complement inhibitor, to reduce postoperative morbidity and mortality in this post hoc analysis of the Pexelizumab for Reduction in Myocardial Infarction and MOrtality in Coronary Artery Bypass Graft surgery (PRIMO-CABG) trial, a phase III double-blind, placebo-controlled study of 3,099 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. METHODS: The composite endpoint of death or myocardial infarction or both through postoperative day 30 was examined in subpopulations of patients with pre-specified risk factors, which included diabetes mellitus, prior coronary artery bypass graft, urgent intervention, female sex, history of neurologic event, history of congestive heart failure, and two or more previous myocardial infarctions or a recent myocardial infarction. Stratified post hoc analyses were also performed on patients presenting with two or more and three or more of those risk factors. RESULTS: Pexelizumab significantly reduced the incidence of the composite endpoint of death or myocardial infarction through postoperative day 30 by 28% in patients with two or more risk factors (p = 0.004) and 44% in patients with three or more risk factors (p < 0.001). CONCLUSIONS: The C5 complement inhibitor, pexelizumab, reduced morbidity and mortality among high-risk patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

Antibodies, Monoclonal↗
PubMed2006

Effect of pexelizumab in coronary artery bypass graft surgery with extended aortic cross-clamp time.

BACKGROUND: Prolonged cross-clamp time during cardiac surgery increases the risk of postoperative mortality and myocardial injury. This subanalysis from the pexelizumab for reduction of infarction and mortality in coronary artery bypass grafting surgery (PRIMO-CABG) trial, a phase III double-blind, placebo-controlled study of 3,099 patients undergoing on-pump coronary artery bypass graft surgery with or without valve surgery, assessed the impact of pexelizumab, an investigational C5 complement inhibitor, on postoperative outcomes after prolonged aortic cross-clamp time. METHODS: The composite endpoint of death or myocardial infarction through postoperative day 30 and death alone through days 30, 90, and 180 were examined in subpopulations of patients across different cross-clamp times. RESULTS: After prolonged cross-clamping (> or = 90 minutes), death, or myocardial infarction through day 30 and death through days 30, 90, and 180 were significantly increased in the intent-to-treat population and were even higher in patients with two or more prespecified risk factors, compared with all patients cross-clamped less than 90 minutes. Pexelizumab significantly reduced the incidence of death or myocardial infarction through day 30, and significantly reduced the incidence of mortality through day 180, in patients with two or more risk factors that required prolonged cross-clamp time. Pexelizumab also significantly reduced perioperative myocardial injury in all patients requiring prolonged cross-clamp time. CONCLUSIONS: In this retrospective, subgroup analysis, pexelizumab reduced postoperative morbidity and myocardial injury in patients with multiple risk factors who underwent prolonged cross-clamp time during coronary artery bypass surgery. The clinical benefit of pexelizumab may be related to the effect of complement inhibition in the presence of potential ischemic-reperfusion injury associated with prolonged aortic cross-clamp time.

Antibodies, Monoclonal↗
PubMed2006

Preoperative statin therapy is associated with reduced cardiac mortality after coronary artery bypass graft surgery.

OBJECTIVE: Statin therapy in ambulatory populations is associated with a significant reduction in adverse cardiovascular events, including death and myocardial infarction. Much less is known about the beneficial effects of statins on acute perioperative cardiovascular events. The purpose of this study was to determine whether preoperative statin therapy is associated with a reduced risk of early cardiac death or nonfatal, in-hospital postoperative myocardial infarction after primary, elective coronary artery bypass graft surgery requiring cardiopulmonary bypass. METHODS: The Multicenter Study of Perioperative Ischemia (McSPI) Epidemiology II Study was a prospective, longitudinal study of 5436 patients undergoing coronary artery bypass graft surgery between November 1996 and June 2000 at 70 centers in 17 countries. The present study consisted of a pre-specified subset of these subjects divided into patients receiving (n = 1352) and not receiving (n = 1314) preoperative statin therapy. To control for potential bias related to use of statin therapy, the study estimated propensity scores by logistic regression to determine the predicted probability of inclusion in the "statin" group. Multivariate, stepwise logistic regression was then performed, controlling for patient demographics, medical history, operative characteristics, and propensity score to determine whether preoperative statin therapy was independently associated with a reduction in the risk of early (DOS-POD3) cardiac death and/or nonfatal, in-hospital postoperative myocardial infarction. RESULTS: Preoperative statin therapy was independently associated with a significant reduction (adjusted odds ratio [OR] 0.25; 95% confidence intervals [CI] 0.07-0.87) in the risk of early cardiac death after primary, elective coronary bypass surgery (0.3% vs 1.4%; P < .03), but was not associated with a reduced risk of postoperative nonfatal, in-hospital myocardial infarction (7.9% vs 6.2%; P = not significant). Discontinuation of statin therapy after surgery was independently associated with a significant increase in late (POD4-discharge) all-cause mortality (adjusted OR 2.64; 95% CI 1.32-5.26) compared with continuation of statin therapy (2.64% vs 0.60%; P < .01). This was true even when controlling for the postoperative discontinuation of aspirin, beta-blocker, or angiotensin-converting enzyme inhibitor therapy. Discontinuation of statin therapy after surgery was also independently associated with a significant increase in late cardiac mortality (adjusted OR 2.95; 95% CI 1.31-6.66) compared with continuation of statin therapy (1.91% vs 0.45%; P < 0.01). CONCLUSIONS: Preoperative statin use is associated with reduced cardiac mortality after primary, elective coronary artery bypass grafting. Postoperative statin discontinuation is associated with increased in-hospital mortality. Although further randomized trials are needed to confirm these findings, these data suggest the importance of perioperative statin administration.

Cardiopulmonary Bypass↗
PubMed2006

Acute hemodynamic collapse after induction of general anesthesia for emergent pulmonary embolectomy.

Patients undergoing pulmonary embolectomy often experience hemodynamic deterioration during induction of general anesthesia (GA). Therefore, we studied the incidence and possible risk factors for hemodynamic deterioration during GA induction. Fifty-two consecutive patients undergoing emergent pulmonary embolectomy at our institution were included. Hemodynamic collapse after GA induction was defined as hypotension refractory to vasopressor, inotrope, or fluid administration, requiring cardiopulmonary resuscitation followed by urgent institution of cardiopulmonary bypass (CPB). Demographic variables, comorbidities, specific location of thromboemboli, preoperative inotropic support, and anesthetic drugs used for GA induction were evaluated as possible risk factors. After GA induction, hemodynamic collapse occurred in 19% of patients (n = 10). However, the occurrence of hemodynamic instability was not predicted by any of the evaluated risk factors. In addition, the incidence of in-hospital mortality did not differ between hemodynamically stable or unstable patients (10%; 4 of 42 versus 10%; 1 of 10 patients, respectively). In conclusion, hemodynamic deterioration after GA induction develops frequently during emergent pulmonary embolectomy. On the basis of our experience from this study and the unpredictable nature of hemodynamic deterioration, we suggest that patients undergoing pulmonary embolectomy should be prepared and draped before GA induction, and a cardiac surgical team should immediately be available for emergent institution of cardiopulmonary bypass.

Acute Disease↗
PubMed2006

The usefulness of transesophageal echocardiography during intraoperative cardiac arrest in noncardiac surgery.

According to guidelines established by the American Society of Anesthesiologists and the Society of Cardiovascular Anesthesiologists, life-threatening hemodynamic disturbances are classified as a category I indication for the intraoperative use of transesophageal echocardiography (TEE). However, the usefulness of TEE during intraoperative cardiac arrest and its impact on patient management have not been rigorously investigated. Using our departmental TEE database, we identified a population of 22 patients who underwent noncardiac surgical procedures and experienced unexpected intraoperative hemodynamic collapse requiring the initiation of Advanced Cardiac Life Support procedures between the time of induction of general anesthesia and the termination of the surgical procedure. Results of TEE examinations, patient records, detailed operative records, and outcome of patients were reviewed for the utility of TEE to diagnose the etiology of the hemodynamic collapse. Furthermore, the impact on subsequent patient management was evaluated. A primary suspected diagnosis of the underlying pathological process was established in 19 of 22 patients with TEE, including 9 with thromboembolic events, 6 with acute myocardial ischemia, 2 with hypovolemia, and 2 patients with pericardial tamponade. A definitive diagnosis could not be made in 3 patients with TEE. In 18 patients, TEE guided specific management beyond implementation of Advanced Cardiac Life Support protocols, including the addition of surgical procedures in 12 patients. Fourteen patients survived to leave the operating room, and 7 of these patients were eventually discharged from the hospital. Thus, TEE may provide additional diagnostic information in patients with intraoperative cardiac arrest and may directly guide specific, potentially life-saving therapy.

Adult↗
PubMed2005

Role of transesophageal echocardiography in patients with suspected aortic dissection.

Patients with acute aortic dissection of the ascending aorta benefit from rapid surgical intervention. We report a patient with suspected acute aortic dissection based on history and transthoracic echocardiography findings. This patient was taken to the operating room without further workup, where transesophageal echocardiography (TEE) revealed acute myocardial infarction and mitral regurgitation due to papillary muscle rupture. The patient underwent coronary bypass grafting and mitral valve replacement. This case demonstrates that intraoperative TEE can be used as a primary diagnostic modality to rule out aortic dissection, and can provide a definitive etiology for cardiogenic shock before a planned surgical intervention.

Aged↗
PubMed2005

Pharmacogenetics of anesthetic and analgesic agents.

Predicting a patient's response to a particular drug has long been a goal of clinicians. Rapid advances in molecular biology have enabled researchers to identify associations between an individual's genetic profile and drug response. Pharmacogenetics is the study of the molecular mechanisms that underlie individual differences in drug metabolism, efficacy, and side effects. The pharmacogenetics of commonly used anesthetic and analgesic agents are reviewed.

Analgesics↗
PubMed2004

Preliminary report of the effects of complement suppression with pexelizumab on neurocognitive decline after coronary artery bypass graft surgery.

BACKGROUND AND PURPOSE: Pharmacological modulation of complement activation recently has been postulated as a therapeutic target in the treatment of neurological injury. We hypothesized that pexelizumab, a humanized scFv monoclonal antibody directed against the C5 complement component, would limit deficits in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. METHODS: The Phase II Pexelizumab study was a 914-patient, double-blind, placebo-controlled, 65-center study of patients undergoing coronary artery bypass graft surgery. Patients were randomized to pexelizumab bolus, bolus plus infusion, or placebo. Neurological and neurocognitive functions were assessed as secondary endpoints at baseline and on postoperative days (POD) 4 and 30. Cognitive deficits were assessed with multivariable tests accounting for baseline cognition, age, diabetes, years of education, sex, elevated creatinine, history of myocardial infarction, neurological disorder or congestive heart failure, and cardiopulmonary bypass time. RESULTS: Pexelizumab had no statistically significant effect on the primary composite endpoint or on overall cognition. When domain specific effects were examined, a decline of at least 10% in the visuo-spatial domain was observed on POD 4 in 56% of patients receiving placebo compared with 40% receiving pexelizumab by bolus and infusion (P=0.003). Similarly, on POD 30, a 10% decline was present in 21% of patients in the placebo group versus only 12% of the drug bolus plus infusion group (P=0.016). No differences were seen between treatment groups in any of the other domains. CONCLUSIONS: Pexelizumab administration for 24 hours perioperatively had no effect on global measures of cognition but may reduce dysfunction in the visuo-spatial domain.

Aged↗