Atrial fibrillation (AF) contributes significantly to morbidity and mortality in as many as one-t... more Atrial fibrillation (AF) contributes significantly to morbidity and mortality in as many as one-third of patients after cardiac surgery that requires cardiopulmonary bypass (CPB). Recent data suggest that inflammatory infiltration of the myocardium may predispose to AF. We conducted an exploratory pilot study to determine if there was an association between the perioperative leukocyte inflammatory response to cardiac surgery/ CPB and postoperative AF. We enrolled 72 patients undergoing cardiac surgery with CPB; all patients were in sinus rhythm before surgery. Leukocyte activation (CD11b upregulation) was perioperatively measured in monocytes and neutrophils (PMN). Preoperative C-reactive protein (CRP) and perioperative neutrophil myeloperoxidase (MPO) were also monitored for inflammation, and troponin I was assayed for perioperative cardiac muscle damage. All markers were evaluated for differences between the subset of patients who developed AF versus those who remained in normal sinus rhythm after surgery. All 72 patients completed the study. Postoperative AF developed in 26 (36%) patients. Perioperative monocyte CD11b upregulation was significantly increased in patients who developed AF (P ϭ 0.01), but increases in PMN CD11b were not significantly associated with AF (P ϭ 0.057). The increase in both monocyte and PMN counts after aortic cross-clamp release was significantly associated with postoperative AF (P ϭ 0.007 and P ϭ 0.005, respectively). By contrast, preoperative CRP and perioperative MPO did not differ between AF and normal rhythm patients. Similarly, the peak value of troponin I did not differ between groups. In this pilot study of cardiac surgery/CPB patients, perioperative upregulation of the monocyte adhesion receptor, CD11b, and higher circulating monocyte and PMN numbers were associated with postoperative AF, suggesting that the induction of cellular inflammation during cardiac surgery/ CPB may contribute to this pathophysiology.
To determine the accuracy of conventional hemodynamic assessment using pulmonary artery catheter-... more To determine the accuracy of conventional hemodynamic assessment using pulmonary artery catheter-derived data in critically ill patients. Cohort study. Kaiser Permanente and Veterans Affairs Medical Centers. Twenty-five consecutive patients who had undergone elective aortocoronary bypass surgery. In the intensive care unit, conventional assessment (CA) was performed hourly by clinicians using conventional (radial artery and pulmonary artery) hemodynamic measurements from which left ventricular (LV) function and intracardiac volume were estimated. Simultaneously, transesophageal echocardiography (TEE) data were recorded on videotape, blinded to the clinicians, and quantitatively analyzed off-line. TEE-determined LV function was classified as either normal (ejection fraction > or =40%) or abnormal (ejection fraction <40%) and intracardiac volume as normal (end-diastolic area = 8 to 22 cm2), low (end-diastolic area <8 cm2), or high (end-diastolic area >22 cm2). Evaluable da...
Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital, 2005
In postmenopausal women, hormone replacement therapy (HRT) does not substantially reduce the inci... more In postmenopausal women, hormone replacement therapy (HRT) does not substantially reduce the incidence of cardiovascular disease and may produce a short-term increase in risk. Therefore, we investigated whether HRT increased risk in patients with severe coronary artery disease necessitating surgery We prospectively studied 4,782 patients undergoing coronary artery bypass grafting at 70 centers in 17 countries from November 1996 through June 2000. Patients were selected using a systematic sampling technique. Mortality, major morbidity, and transfusion requirements were compared among 3 groups: men (n=3,840), women receiving HRT (n= 144), and women not receiving HRT (n=798). Women actively receiving HRT, compared with women not receiving HRT or with men, were at no greater risk of developing the following fatal or non-fatal complications: death (2.8% vs 4.4% vs 2.8%, respectively; P=0.05), myocardial infarction (6.3% vs 7.0% vs 7.7%; P=0.67), central nervous system complication (2.1% ...
We hypothesized that genetic variations in the adrenergic signaling pathway and cytochrome P450 2... more We hypothesized that genetic variations in the adrenergic signaling pathway and cytochrome P450 2D6 enzyme are associated with new-onset atrial fibrillation (AF) in patients who underwent coronary artery bypass grafting and were treated with perioperative β-blockers (BBs). Two cohorts of patients who underwent coronary artery bypass grafting and received perioperative BBs at Duke University Medical Center were studied. In a discovery cohort of 563 individuals from the Perioperative Genetics and Safety Outcomes Study (PEGASUS), using a covariate-adjusted logistic regression analysis, we tested 492 single-nucleotide polymorphisms (SNPs) in 10 candidate genes of the adrenergic signaling pathway and cytochrome P450 2D6 for association with postoperative AF despite perioperative BB therapy. SNPs meeting a false discovery rate ≤0.20 (P<0.002) were then tested in the replication cohort of 245 individuals from the Catheterization Genetics biorepository. Of the 492 SNPs examined, 4 intron...
To examine the impact of intravenous antihypertensive selection on hospital health resource utili... more To examine the impact of intravenous antihypertensive selection on hospital health resource utilization using data from the Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events (ECLIPSE) trials. Analysis of ECLIPSE trial data comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine and unit costs based on the Premier Hospital database to assess surgery duration, time to extubation, and length of stay (LOS) with the associated cost. A total of 1414 patients from the ECLIPSE trials and the Premier hospital database were included for analysis. The duration of surgery and postoperative LOS were similar across groups. The time from chest closure to extubation was shorter in patients receiving clevidipine group compared with the pooled comparator group (median 7.0 vs 7.6 hours, P = 0.04). There was shorter intensive care unit (ICU) LOS in the clevidipine group versus the nitroglycerin group (median 27.2 vs 33.0 hours, P = 0.03). A trend toward reduced ICU LOS was also seen in the clevidipine compared with the pooled comparator group (median 32.3 vs 43.5 hours, P = 0.06). The costs for ICU LOS and time to extubation were lower with clevidipine than with the comparators, with median cost savings of $887 and $34, respectively, compared with the pooled comparator group, for a median cost savings of $921 per patient. Health resource utilization across therapeutic alternatives can be derived from an analysis of standard costs from hospital financial data to matched utilization metrics as part of a randomized controlled trial. In cardiac surgical patients, intravenous antihypertensive selection was associated with a shorter time to extubation in the ICU and a shorter ICU stay compared with pooled comparators, which in turn may decrease total costs.
Background. Postoperative acute kidney injury (AKI) is associated with high mortality and substan... more Background. Postoperative acute kidney injury (AKI) is associated with high mortality and substantial cost after aortocoronary bypass graft (CABG) surgery. We tested the hypothesis that intraoperative systolic blood pressure variation is associated with postoperative AKI. Methods. We gathered demographic, procedural, blood pressure, and renal outcome data for 7,247 CABG surgeries at a single institution between 1996 and 2005. A development/validation cohort methodology was randomly divided (66% and 33%, resp.). Peak postoperative serum creatinine rise relative to baseline (%ΔCr) was the primary AKI outcome variable. Markers reflective of intraoperative systolic blood pressure variation were derived for each patient including (1) peak and nadir values (absolute and relative to baseline) and (2) excursion episodes beyond selected thresholds (by duration, frequency, and duration × degree). Each marker of systolic blood pressure variation was then separately evaluated for association with AKI using linear regression models with adjustment for several known risk factors (age, aprotinin use, congestive heart failure, previous myocardial infarction, baseline creatinine, bypass time, diabetes, weight, concomitant valve surgery, gender, and preoperative pulse pressure). Results. An association was identified between systolic blood pressure relative to baseline and postoperative AKI ( < 0.006). Conclusions. In CABG surgery patients, intraoperative systolic blood pressure decrease relative to baseline systolic blood pressure is independently associated with postoperative AKI.
Neurocognitive decline occurs frequently after cardiac surgery and persists in a significant numb... more Neurocognitive decline occurs frequently after cardiac surgery and persists in a significant number of patients. Magnesium is thought to provide neuroprotection by preservation of cellular energy metabolism, blockade of the N-methyl-D-aspartate receptor, diminution of the inflammatory response, and inhibition of platelet activation. We therefore hypothesized that intraoperative magnesium administration would decrease postoperative cognitive impairment. After approval by the Duke University Health System Institutional Review Board, 389 patients undergoing cardiac surgery were enrolled in this prospective, randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive magnesium as a 50 mg/kg bolus followed by another 50 mg/kg infusion for 3 hours or placebo bolus and infusion. Cognitive function was assessed preoperatively and again at 6 weeks postoperatively using a standardized test battery. Mean CD11b fluorescence and percentage of platelets expressing CD62P, which are markers of leukocyte and platelet activation, respectively, were assessed by flow cytometry as a secondary outcome. The effect of magnesium on postoperative cognition was tested using multivariable regression modeling, adjusting for age, years of education, baseline cognition, sex, race, and weight. Among the 389 allocated subjects (magnesium: n=198; placebo: n=191), the incidence of cognitive deficit in the magnesium group was 44.4% compared with 44.9% in the placebo group (P=0.93). The cognitive change score and platelet and leukocyte activation were also not different between the groups. Multivariable analysis revealed a marginal interaction between treatment group and weight such that heavier subjects receiving magnesium were less likely to have cognitive deficit (P=0.06). Magnesium administered intravenously during cardiac surgery does not reduce postoperative cognitive dysfunction. http://www.clinicaltrials.gov. Unique identifier: NCT00041392.
The Journal of Thoracic and Cardiovascular Surgery, 2014
Recently, the role of β-blockers (BBs) in reducing perioperative mortality has been challenged. T... more Recently, the role of β-blockers (BBs) in reducing perioperative mortality has been challenged. The conflicting results might have resulted from the extent of BB metabolism by the cytochrome P-450 (CYP2D6) isoenzyme. The purpose of the present study was to assess the association between the preoperative use of BBs dependent on metabolism of the CYP2D6 isoenzyme with operative mortality after coronary artery bypass grafting surgery. We performed a retrospective study of 5248 patients who had undergone coronary bypass grafting surgery from January 1, 2001 to November 30, 2009 at Duke University Medical Center. The cohorts were defined by the preoperative use of BBs and BB type (non-CYP2D6_BBs, CYP2D6_BBs, or no BBs). Operative mortality was analyzed using inverse probability-weighted estimators with propensity score adjustment. Of the 5248 patients, 14% received non-CYP2D6_BBs, 43%, CYP2D6_BBs, and 43%, no BBs. The incidence of operative mortality was 0.8%, 2.1%, and 3.7% in the non-CYP2D6_BB, CYP2D6_BB, and no BB groups, respectively. Multivariable inverse probability-weighted-adjusted analyses showed that non-CYP2D6_BBs were associated with a lower incidence of operative mortality (odds ratio, 0.33; 95% confidence interval, 0.13-0.83; P = .02) compared with no BB use and a trend toward lower operative mortality (odds ratio, 0.44; 95% confidence interval, 0.16-1.07; P = .06) compared with CYP2D6_BBs. No significant decrease occurred in the risk of operative mortality between the CYP2D6_BB and no BB groups (odds ratio, 0.85; 95% confidence interval, 0.54-1.34; P = .48). Among these patients, preoperative non-CYP2D6_BB use, but not CYP2D6_BB use, was associated with a decreased risk of operative mortality.
Journal of Cardiothoracic and Vascular Anesthesia, 1999
To determine the accuracy of conventional hemodynamic assessment using pulmonary artery catheter-... more To determine the accuracy of conventional hemodynamic assessment using pulmonary artery catheter-derived data in critically ill patients. Cohort study. Kaiser Permanente and Veterans Affairs Medical Centers. Twenty-five consecutive patients who had undergone elective aortocoronary bypass surgery. In the intensive care unit, conventional assessment (CA) was performed hourly by clinicians using conventional (radial artery and pulmonary artery) hemodynamic measurements from which left ventricular (LV) function and intracardiac volume were estimated. Simultaneously, transesophageal echocardiography (TEE) data were recorded on videotape, blinded to the clinicians, and quantitatively analyzed off-line. TEE-determined LV function was classified as either normal (ejection fraction &gt; or =40%) or abnormal (ejection fraction &lt;40%) and intracardiac volume as normal (end-diastolic area = 8 to 22 cm2), low (end-diastolic area &lt;8 cm2), or high (end-diastolic area &gt;22 cm2). Evaluable data included 130 of 150 (87%) observations of simultaneously collected CA and TEE data, averaging 5.6+/-4.4 observations per patient. The overall predictive probability for conventional clinical assessment of normal ventricular function was 98% (118/121), whereas for abnormal ventricular function it was 0% (0/9). For CA of volume, the overall predictive probabilities for hypovolemia, normovolemia, and hypervolemia were 50% (3/6), 60% (69/115), and 22% (2/9). Although conventional clinical assessment of normal LV function in the intensive care unit correlates well with echocardiographic assessment, both LV dysfunction and extremes of preload (hypovolemia or hypervolemia) are assessed poorly by clinicians using conventional clinical monitoring with pulmonary artery catheterization.
Journal of Cardiothoracic and Vascular Anesthesia, 2014
To examine the impact of blood pressure control on hospital health resource utilization using dat... more To examine the impact of blood pressure control on hospital health resource utilization using data from the ECLIPSE trials. Post-hoc analysis of data from 3 prospective, open-label, randomized clinical trials (ECLIPSE trials). Sixty-one medical centers in the United States. Patients 18 years or older undergoing cardiac surgery. Clevidipine was compared with nitroglycerin, sodium nitroprusside, and nicardipine. The ECLIPSE trials included 3 individual randomized open-label studies comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine. Blood pressure control was assessed as the integral of the cumulative area under the curve (AUC) outside specified systolic blood pressure ranges, such that lower AUC represents less variability. This analysis examined surgery duration, time to extubation, as well as intensive care unit (ICU) and hospital length of stay (LOS) in patients with AUC≤10 mmHg×min/h compared to patients with AUC&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10 mmHg×min/h. One thousand four hundred ten patients were included for analysis; 736 patients (52%) had an AUC≤10 mmHg×min/h, and 674 (48%) had an AUC&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10 mmHg×min/h. The duration of surgery and ICU LOS were similar between groups. Time to extubation and postoperative LOS were both significantly shorter (p = 0.05 and p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001, respectively) in patients with AUC≤10. Multivariate analysis demonstrates AUC≤10 was significantly and independently associated with decreased time to extubation (hazard ratio 1.132, p = 0.0261) and postoperative LOS (hazard ratio 1.221, p = 0.0006). Based on data derived from the ECLIPSE studies, increased perioperative BP variability is associated with delayed time to extubation and increased postoperative LOS.
This review reports the specific impact that hypertension, identified by its component subtype cl... more This review reports the specific impact that hypertension, identified by its component subtype classification, has on perioperative outcomes. Most importantly, we review the risk of systolic hypertension and pulse pressure hypertension independent of elevated diastolic blood pressure on patients undergoing cardiac surgery.
Despite proven benefit in ambulatory patients with ischemic heart disease, the pattern of use of ... more Despite proven benefit in ambulatory patients with ischemic heart disease, the pattern of use of angiotensin-converting enzyme inhibitors (ACEIs) in coronary artery bypass graft surgery has been erratic and controversial. This is a prospective observational study of 4224 patients undergoing coronary artery bypass graft surgery. The cohort included 1838 patients receiving ACEI therapy before surgery and 2386 (56.5%) without ACEI exposure. Postoperatively, the pattern of ACEI use yielded 4 groups: continuation, 915 (21.7%); withdrawal, 923 (21.8%); addition, 343 (8.1%); and no ACEI, 2043 (48.4%). Continuous treatment with ACEI versus no ACEI was associated with substantive reductions of risk of nonfatal events (adjusted odds ratio for the composite outcome, 0.69; 95% confidence interval, 0.52-0.91; P=0.009) and a cardiovascular event (odds ratio, 0.64; 95% confidence interval, 0.46-0.88; P=0.006). Addition of ACEI de novo postoperatively compared with no ACEI therapy was also associated with a significant reduction of risk of composite outcome (odds ratio, 0.56; 95% confidence interval, 0.38-0.84; P=0.004) and a cardiovascular event (odds ratio, 0.63; 95% confidence interval, 0.40-0.97; P=0.04). On the other hand, continuous treatment of ACEI versus withdrawal of ACEI was associated with decreased risk of the composite outcome (odds ratio, 0.50; 95% confidence interval, 0.38-0.66; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), as well as a decrease in cardiac and renal events (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001 and P=0.005, respectively). No differences in in-hospital mortality and cerebral events were noted. Our study suggests that withdrawal of ACEI treatment after coronary artery bypass graft surgery is associated with nonfatal in-hospital ischemic events. Furthermore, continuation of ACEI or de novo ACEI therapy early after cardiac surgery is associated with improved in-hospital outcomes.
Atrial fibrillation (AF) contributes significantly to morbidity and mortality in as many as one-t... more Atrial fibrillation (AF) contributes significantly to morbidity and mortality in as many as one-third of patients after cardiac surgery that requires cardiopulmonary bypass (CPB). Recent data suggest that inflammatory infiltration of the myocardium may predispose to AF. We conducted an exploratory pilot study to determine if there was an association between the perioperative leukocyte inflammatory response to cardiac surgery/ CPB and postoperative AF. We enrolled 72 patients undergoing cardiac surgery with CPB; all patients were in sinus rhythm before surgery. Leukocyte activation (CD11b upregulation) was perioperatively measured in monocytes and neutrophils (PMN). Preoperative C-reactive protein (CRP) and perioperative neutrophil myeloperoxidase (MPO) were also monitored for inflammation, and troponin I was assayed for perioperative cardiac muscle damage. All markers were evaluated for differences between the subset of patients who developed AF versus those who remained in normal sinus rhythm after surgery. All 72 patients completed the study. Postoperative AF developed in 26 (36%) patients. Perioperative monocyte CD11b upregulation was significantly increased in patients who developed AF (P ϭ 0.01), but increases in PMN CD11b were not significantly associated with AF (P ϭ 0.057). The increase in both monocyte and PMN counts after aortic cross-clamp release was significantly associated with postoperative AF (P ϭ 0.007 and P ϭ 0.005, respectively). By contrast, preoperative CRP and perioperative MPO did not differ between AF and normal rhythm patients. Similarly, the peak value of troponin I did not differ between groups. In this pilot study of cardiac surgery/CPB patients, perioperative upregulation of the monocyte adhesion receptor, CD11b, and higher circulating monocyte and PMN numbers were associated with postoperative AF, suggesting that the induction of cellular inflammation during cardiac surgery/ CPB may contribute to this pathophysiology.
To determine the accuracy of conventional hemodynamic assessment using pulmonary artery catheter-... more To determine the accuracy of conventional hemodynamic assessment using pulmonary artery catheter-derived data in critically ill patients. Cohort study. Kaiser Permanente and Veterans Affairs Medical Centers. Twenty-five consecutive patients who had undergone elective aortocoronary bypass surgery. In the intensive care unit, conventional assessment (CA) was performed hourly by clinicians using conventional (radial artery and pulmonary artery) hemodynamic measurements from which left ventricular (LV) function and intracardiac volume were estimated. Simultaneously, transesophageal echocardiography (TEE) data were recorded on videotape, blinded to the clinicians, and quantitatively analyzed off-line. TEE-determined LV function was classified as either normal (ejection fraction > or =40%) or abnormal (ejection fraction <40%) and intracardiac volume as normal (end-diastolic area = 8 to 22 cm2), low (end-diastolic area <8 cm2), or high (end-diastolic area >22 cm2). Evaluable da...
Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital, 2005
In postmenopausal women, hormone replacement therapy (HRT) does not substantially reduce the inci... more In postmenopausal women, hormone replacement therapy (HRT) does not substantially reduce the incidence of cardiovascular disease and may produce a short-term increase in risk. Therefore, we investigated whether HRT increased risk in patients with severe coronary artery disease necessitating surgery We prospectively studied 4,782 patients undergoing coronary artery bypass grafting at 70 centers in 17 countries from November 1996 through June 2000. Patients were selected using a systematic sampling technique. Mortality, major morbidity, and transfusion requirements were compared among 3 groups: men (n=3,840), women receiving HRT (n= 144), and women not receiving HRT (n=798). Women actively receiving HRT, compared with women not receiving HRT or with men, were at no greater risk of developing the following fatal or non-fatal complications: death (2.8% vs 4.4% vs 2.8%, respectively; P=0.05), myocardial infarction (6.3% vs 7.0% vs 7.7%; P=0.67), central nervous system complication (2.1% ...
We hypothesized that genetic variations in the adrenergic signaling pathway and cytochrome P450 2... more We hypothesized that genetic variations in the adrenergic signaling pathway and cytochrome P450 2D6 enzyme are associated with new-onset atrial fibrillation (AF) in patients who underwent coronary artery bypass grafting and were treated with perioperative β-blockers (BBs). Two cohorts of patients who underwent coronary artery bypass grafting and received perioperative BBs at Duke University Medical Center were studied. In a discovery cohort of 563 individuals from the Perioperative Genetics and Safety Outcomes Study (PEGASUS), using a covariate-adjusted logistic regression analysis, we tested 492 single-nucleotide polymorphisms (SNPs) in 10 candidate genes of the adrenergic signaling pathway and cytochrome P450 2D6 for association with postoperative AF despite perioperative BB therapy. SNPs meeting a false discovery rate ≤0.20 (P<0.002) were then tested in the replication cohort of 245 individuals from the Catheterization Genetics biorepository. Of the 492 SNPs examined, 4 intron...
To examine the impact of intravenous antihypertensive selection on hospital health resource utili... more To examine the impact of intravenous antihypertensive selection on hospital health resource utilization using data from the Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events (ECLIPSE) trials. Analysis of ECLIPSE trial data comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine and unit costs based on the Premier Hospital database to assess surgery duration, time to extubation, and length of stay (LOS) with the associated cost. A total of 1414 patients from the ECLIPSE trials and the Premier hospital database were included for analysis. The duration of surgery and postoperative LOS were similar across groups. The time from chest closure to extubation was shorter in patients receiving clevidipine group compared with the pooled comparator group (median 7.0 vs 7.6 hours, P = 0.04). There was shorter intensive care unit (ICU) LOS in the clevidipine group versus the nitroglycerin group (median 27.2 vs 33.0 hours, P = 0.03). A trend toward reduced ICU LOS was also seen in the clevidipine compared with the pooled comparator group (median 32.3 vs 43.5 hours, P = 0.06). The costs for ICU LOS and time to extubation were lower with clevidipine than with the comparators, with median cost savings of $887 and $34, respectively, compared with the pooled comparator group, for a median cost savings of $921 per patient. Health resource utilization across therapeutic alternatives can be derived from an analysis of standard costs from hospital financial data to matched utilization metrics as part of a randomized controlled trial. In cardiac surgical patients, intravenous antihypertensive selection was associated with a shorter time to extubation in the ICU and a shorter ICU stay compared with pooled comparators, which in turn may decrease total costs.
Background. Postoperative acute kidney injury (AKI) is associated with high mortality and substan... more Background. Postoperative acute kidney injury (AKI) is associated with high mortality and substantial cost after aortocoronary bypass graft (CABG) surgery. We tested the hypothesis that intraoperative systolic blood pressure variation is associated with postoperative AKI. Methods. We gathered demographic, procedural, blood pressure, and renal outcome data for 7,247 CABG surgeries at a single institution between 1996 and 2005. A development/validation cohort methodology was randomly divided (66% and 33%, resp.). Peak postoperative serum creatinine rise relative to baseline (%ΔCr) was the primary AKI outcome variable. Markers reflective of intraoperative systolic blood pressure variation were derived for each patient including (1) peak and nadir values (absolute and relative to baseline) and (2) excursion episodes beyond selected thresholds (by duration, frequency, and duration × degree). Each marker of systolic blood pressure variation was then separately evaluated for association with AKI using linear regression models with adjustment for several known risk factors (age, aprotinin use, congestive heart failure, previous myocardial infarction, baseline creatinine, bypass time, diabetes, weight, concomitant valve surgery, gender, and preoperative pulse pressure). Results. An association was identified between systolic blood pressure relative to baseline and postoperative AKI ( < 0.006). Conclusions. In CABG surgery patients, intraoperative systolic blood pressure decrease relative to baseline systolic blood pressure is independently associated with postoperative AKI.
Neurocognitive decline occurs frequently after cardiac surgery and persists in a significant numb... more Neurocognitive decline occurs frequently after cardiac surgery and persists in a significant number of patients. Magnesium is thought to provide neuroprotection by preservation of cellular energy metabolism, blockade of the N-methyl-D-aspartate receptor, diminution of the inflammatory response, and inhibition of platelet activation. We therefore hypothesized that intraoperative magnesium administration would decrease postoperative cognitive impairment. After approval by the Duke University Health System Institutional Review Board, 389 patients undergoing cardiac surgery were enrolled in this prospective, randomized, double-blind, placebo-controlled clinical trial. Subjects were randomized to receive magnesium as a 50 mg/kg bolus followed by another 50 mg/kg infusion for 3 hours or placebo bolus and infusion. Cognitive function was assessed preoperatively and again at 6 weeks postoperatively using a standardized test battery. Mean CD11b fluorescence and percentage of platelets expressing CD62P, which are markers of leukocyte and platelet activation, respectively, were assessed by flow cytometry as a secondary outcome. The effect of magnesium on postoperative cognition was tested using multivariable regression modeling, adjusting for age, years of education, baseline cognition, sex, race, and weight. Among the 389 allocated subjects (magnesium: n=198; placebo: n=191), the incidence of cognitive deficit in the magnesium group was 44.4% compared with 44.9% in the placebo group (P=0.93). The cognitive change score and platelet and leukocyte activation were also not different between the groups. Multivariable analysis revealed a marginal interaction between treatment group and weight such that heavier subjects receiving magnesium were less likely to have cognitive deficit (P=0.06). Magnesium administered intravenously during cardiac surgery does not reduce postoperative cognitive dysfunction. http://www.clinicaltrials.gov. Unique identifier: NCT00041392.
The Journal of Thoracic and Cardiovascular Surgery, 2014
Recently, the role of β-blockers (BBs) in reducing perioperative mortality has been challenged. T... more Recently, the role of β-blockers (BBs) in reducing perioperative mortality has been challenged. The conflicting results might have resulted from the extent of BB metabolism by the cytochrome P-450 (CYP2D6) isoenzyme. The purpose of the present study was to assess the association between the preoperative use of BBs dependent on metabolism of the CYP2D6 isoenzyme with operative mortality after coronary artery bypass grafting surgery. We performed a retrospective study of 5248 patients who had undergone coronary bypass grafting surgery from January 1, 2001 to November 30, 2009 at Duke University Medical Center. The cohorts were defined by the preoperative use of BBs and BB type (non-CYP2D6_BBs, CYP2D6_BBs, or no BBs). Operative mortality was analyzed using inverse probability-weighted estimators with propensity score adjustment. Of the 5248 patients, 14% received non-CYP2D6_BBs, 43%, CYP2D6_BBs, and 43%, no BBs. The incidence of operative mortality was 0.8%, 2.1%, and 3.7% in the non-CYP2D6_BB, CYP2D6_BB, and no BB groups, respectively. Multivariable inverse probability-weighted-adjusted analyses showed that non-CYP2D6_BBs were associated with a lower incidence of operative mortality (odds ratio, 0.33; 95% confidence interval, 0.13-0.83; P = .02) compared with no BB use and a trend toward lower operative mortality (odds ratio, 0.44; 95% confidence interval, 0.16-1.07; P = .06) compared with CYP2D6_BBs. No significant decrease occurred in the risk of operative mortality between the CYP2D6_BB and no BB groups (odds ratio, 0.85; 95% confidence interval, 0.54-1.34; P = .48). Among these patients, preoperative non-CYP2D6_BB use, but not CYP2D6_BB use, was associated with a decreased risk of operative mortality.
Journal of Cardiothoracic and Vascular Anesthesia, 1999
To determine the accuracy of conventional hemodynamic assessment using pulmonary artery catheter-... more To determine the accuracy of conventional hemodynamic assessment using pulmonary artery catheter-derived data in critically ill patients. Cohort study. Kaiser Permanente and Veterans Affairs Medical Centers. Twenty-five consecutive patients who had undergone elective aortocoronary bypass surgery. In the intensive care unit, conventional assessment (CA) was performed hourly by clinicians using conventional (radial artery and pulmonary artery) hemodynamic measurements from which left ventricular (LV) function and intracardiac volume were estimated. Simultaneously, transesophageal echocardiography (TEE) data were recorded on videotape, blinded to the clinicians, and quantitatively analyzed off-line. TEE-determined LV function was classified as either normal (ejection fraction &gt; or =40%) or abnormal (ejection fraction &lt;40%) and intracardiac volume as normal (end-diastolic area = 8 to 22 cm2), low (end-diastolic area &lt;8 cm2), or high (end-diastolic area &gt;22 cm2). Evaluable data included 130 of 150 (87%) observations of simultaneously collected CA and TEE data, averaging 5.6+/-4.4 observations per patient. The overall predictive probability for conventional clinical assessment of normal ventricular function was 98% (118/121), whereas for abnormal ventricular function it was 0% (0/9). For CA of volume, the overall predictive probabilities for hypovolemia, normovolemia, and hypervolemia were 50% (3/6), 60% (69/115), and 22% (2/9). Although conventional clinical assessment of normal LV function in the intensive care unit correlates well with echocardiographic assessment, both LV dysfunction and extremes of preload (hypovolemia or hypervolemia) are assessed poorly by clinicians using conventional clinical monitoring with pulmonary artery catheterization.
Journal of Cardiothoracic and Vascular Anesthesia, 2014
To examine the impact of blood pressure control on hospital health resource utilization using dat... more To examine the impact of blood pressure control on hospital health resource utilization using data from the ECLIPSE trials. Post-hoc analysis of data from 3 prospective, open-label, randomized clinical trials (ECLIPSE trials). Sixty-one medical centers in the United States. Patients 18 years or older undergoing cardiac surgery. Clevidipine was compared with nitroglycerin, sodium nitroprusside, and nicardipine. The ECLIPSE trials included 3 individual randomized open-label studies comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine. Blood pressure control was assessed as the integral of the cumulative area under the curve (AUC) outside specified systolic blood pressure ranges, such that lower AUC represents less variability. This analysis examined surgery duration, time to extubation, as well as intensive care unit (ICU) and hospital length of stay (LOS) in patients with AUC≤10 mmHg×min/h compared to patients with AUC&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10 mmHg×min/h. One thousand four hundred ten patients were included for analysis; 736 patients (52%) had an AUC≤10 mmHg×min/h, and 674 (48%) had an AUC&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;10 mmHg×min/h. The duration of surgery and ICU LOS were similar between groups. Time to extubation and postoperative LOS were both significantly shorter (p = 0.05 and p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001, respectively) in patients with AUC≤10. Multivariate analysis demonstrates AUC≤10 was significantly and independently associated with decreased time to extubation (hazard ratio 1.132, p = 0.0261) and postoperative LOS (hazard ratio 1.221, p = 0.0006). Based on data derived from the ECLIPSE studies, increased perioperative BP variability is associated with delayed time to extubation and increased postoperative LOS.
This review reports the specific impact that hypertension, identified by its component subtype cl... more This review reports the specific impact that hypertension, identified by its component subtype classification, has on perioperative outcomes. Most importantly, we review the risk of systolic hypertension and pulse pressure hypertension independent of elevated diastolic blood pressure on patients undergoing cardiac surgery.
Despite proven benefit in ambulatory patients with ischemic heart disease, the pattern of use of ... more Despite proven benefit in ambulatory patients with ischemic heart disease, the pattern of use of angiotensin-converting enzyme inhibitors (ACEIs) in coronary artery bypass graft surgery has been erratic and controversial. This is a prospective observational study of 4224 patients undergoing coronary artery bypass graft surgery. The cohort included 1838 patients receiving ACEI therapy before surgery and 2386 (56.5%) without ACEI exposure. Postoperatively, the pattern of ACEI use yielded 4 groups: continuation, 915 (21.7%); withdrawal, 923 (21.8%); addition, 343 (8.1%); and no ACEI, 2043 (48.4%). Continuous treatment with ACEI versus no ACEI was associated with substantive reductions of risk of nonfatal events (adjusted odds ratio for the composite outcome, 0.69; 95% confidence interval, 0.52-0.91; P=0.009) and a cardiovascular event (odds ratio, 0.64; 95% confidence interval, 0.46-0.88; P=0.006). Addition of ACEI de novo postoperatively compared with no ACEI therapy was also associated with a significant reduction of risk of composite outcome (odds ratio, 0.56; 95% confidence interval, 0.38-0.84; P=0.004) and a cardiovascular event (odds ratio, 0.63; 95% confidence interval, 0.40-0.97; P=0.04). On the other hand, continuous treatment of ACEI versus withdrawal of ACEI was associated with decreased risk of the composite outcome (odds ratio, 0.50; 95% confidence interval, 0.38-0.66; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), as well as a decrease in cardiac and renal events (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001 and P=0.005, respectively). No differences in in-hospital mortality and cerebral events were noted. Our study suggests that withdrawal of ACEI treatment after coronary artery bypass graft surgery is associated with nonfatal in-hospital ischemic events. Furthermore, continuation of ACEI or de novo ACEI therapy early after cardiac surgery is associated with improved in-hospital outcomes.
Uploads
Papers by Manuel Fontes