Manuel L. Fontes

Risk Index for Perioperative Renal Dysfunction/Failure Critical Dependence on Pulse Pressure Hypertension

Background— An acute renal event after coronary bypass graft surgery is associated with high mortality and substantial additive cost. Methods and Results— This prospective and descriptive study of 4801 patients having coronary bypass graft surgery with cardiopulmonary bypass from November 1996 to June 2000 at 70 centers in 16 countries established associations between predictor variables and postoperative renal composite (renal dysfunction and/or renal failure) from a cohort of 2381 patients and developed a risk index assessed in a validation cohort of 2420 patients. Postoperative renal composite occurred in 231 patients (4.8%). Independent and significant risk factors were age >75 years (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.23 to 3.37; P=0.006), preoperative congestive heart failure (OR, 2.38; CI, 1.55 to 3.64; P<0.001), prior myocardial infarction (OR, 1.75; CI, 1.08 to 2.83; P=0.023), preexisting renal disease (OR, 3.71; CI, 2.41 to 5.70; P<0.001), intraoperative multiple inotrope use (OR, 2.75; CI, 1.75 to 4.31; P<0.001), intraoperative intra-aortic balloon pump insertion (OR, 4.41; CI, 2.21 to 8.80; P<0.001), cardiopulmonary bypass >2 hours (OR, 1.78; CI, 1.15 to 2.74; P=0.01), and preoperative pulse pressure such that for every additional 20–mm Hg increment in pulse pressure >40 mm Hg, there was an OR of 1.49 (CI, 1.17 to 1.89; P=0.001). Patients with pulse pressure hypertension >80 mm Hg were 3 times more likely to die a renal-related death compared with those without (3.7% versus 1.1%). Conclusions— Beside established risk factors, pulse pressure is independently and significantly associated with increased renal composite.

Atrial fibrillation after cardiac surgery/cardiopulmonary bypass is associated with monocyte activation

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 = 0.01), but increases in PMN CD11b were not significantly associated with AF (P = 0.057). The increase in both monocyte and PMN counts after aortic cross-clamp release was significantly associated with postoperative AF (P = 0.007 and P = 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.

Assessment of ventricular function in critically III patients: Limitations of pulmonary artery catheterization☆

Abstract Objective: To determine the accuracy of conventional hemodynamic assessment using pulmonary artery catheterderived data in critically ill patients. Design: Cohort study. Setting: Kaiser Permanente and Veterans Affairs Medical Centers. Participants: Twenty-five consecutive patients who had undergone elective aortocoronary bypass surgery. Measurements and Main Results: 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 ≥40%) or abnormal (ejection fraction 22 cm2). Conclusion: 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.

Neutrophil CD11b upregulation during cardiopulmonary bypass is associated with postoperative renal injury

BACKGROUND Renal injury remains a persistent complication of cardiopulmonary bypass (CPB) that, when sufficient to require dialysis, increases mortality eight-fold. The high prevalence of renal failure in sepsis and adult respiratory distress syndrome has been linked to the systemic inflammatory response associated with those disorders. We hypothesized that components of the inflammatory response to CPB may similarly contribute to post-CPB acute renal injury. METHODS Markers of leukocyte and platelet activation peri-CPB were measured in 75 patients undergoing cardiac operation with CPB and were correlated with acute renal injury, defined as an increase (> or = 50%) in peak serum creatinine post-CPB. RESULTS Eleven patients sustained post-CPB acute renal injury. This subset of patients demonstrated significantly greater increases in neutrophil CD11b density (p = 0.01), as well as higher total neutrophil counts (p = 0.045), compared with patients with preserved renal function. Hemodynamic instability sufficient to require postoperative hemodynamic support also predicted an increased risk of acute renal injury. However, neutrophil CD11b upregulation did not correlate with this or any other clinical variables associated with renal risk, suggesting that this marker of the neutrophil inflammatory response may independently predict renal injury. By contrast other inflammatory markers, neutrophil myeloperoxidase levels, monocyte CD11b, base line C-reactive protein, and platelet CD62P expression did not differ between the two patient groups. CONCLUSIONS Upregulation of the neutrophil adhesion receptor CD11b and high circulating neutrophil numbers are associated with acute renal injury after CPB, suggesting a contribution by activated neutrophils to the pathophysiology of this complication.

Platelet PlA2 polymorphism enhances risk of neurocognitive decline after cardiopulmonary bypass

BACKGROUND Neurocognitive decline, often produced by atherosclerotic plaque embolization, remains a frequent complication of cardiopulmonary bypass. Plaque fragments may initiate local thrombosis, which, in turn, aggravates the embolic insult. Prothrombotic genetic factors may exacerbate this process. We investigated whether the PlA2 polymorphism of platelet GPIIIa, a prothrombotic risk factor in other cardiovascular settings, is associated with early neurocognitive decline after cardiopulmonary bypass. METHODS Neurocognitive changes were evaluated by the Mini-Mental State Examination administered preoperatively and on postoperative day 4 and the PlA genotype determined in 70 patients undergoing cardiopulmonary bypass. RESULTS Forty-nine patients were PlA1/A1, and 21 were PlA1/A2 or PlA2/A2. Fifty-two patients (74%) demonstrated post-cardiopulmonary bypass neurocognitive decline, of which 34 were PlA1/A1 and 18 were PlA1/A2 or PlA2/A2 Multivariate analysis revealed that the PlA2 genotype and baseline Mini-Mental State Examination were significantly associated with greater neurocognitive decline (decreased Mini-Mental State Examination scores, p = 0.036 and 0.024, respectively). CONCLUSIONS This study demonstrates a link between the PlA2 allele of platelet GPIIIa and more severe neurocognitive decline after cardiopulmonary bypass. Although the mechanism is unknown, it could represent exacerbation of platelet-dependent thrombotic processes associated with plaque embolism.

Patterns of Use of Perioperative Angiotensin-Converting Enzyme Inhibitors in Coronary Artery Bypass Graft Surgery With Cardiopulmonary Bypass Effects on In-Hospital Morbidity and Mortality

Background— 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. Methods and Results— 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<0.001), as well as a decrease in cardiac and renal events (P<0.001 and P=0.005, respectively). No differences in in-hospital mortality and cerebral events were noted. Conclusions— 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.

Pulse Pressure and Risk of Adverse Outcome in Coronary Bypass Surgery

BACKGROUND: Among ambulatory patients, an increase in pulse pressure (PP) is a well-established determinant of vascular risk. The relationship of PP and acute perioperative vascular outcome among patients having coronary artery bypass graft (CABG) surgery is less well known. METHODS: We conducted a prospective observational study involving 5436 patients having elective CABG surgery requiring cardiopulmonary bypass. Of these, 4801 met final inclusion criteria. Comprehensive data were captured for medical history, intraoperative and postoperative physiologic and laboratory measures, diagnostic testing, and clinical events. The relationship between preoperative hypertension (systolic, diastolic, PP) and ischemic cardiac and cerebral outcomes and death was assessed using multivariable logistic regression; P < 0.05 was considered significant. RESULTS: Nine hundred and seventeen patients (19.1%) had fatal and nonfatal vascular complications, including 146 patients (3.0%) with cerebral and 715 patients (14.9%) with cardiac events. In-hospital mortality occurred in 147 patients (3.1%). Among all blood pressure variables measured preoperatively, PP was most strongly associated with an increased risk of postoperative complications. PP increments of 10 mm Hg (above a threshold of 40 mm Hg) were associated with an increased risk of cerebral events (adjusted odds ratio: 1.12; 95% CI [1.002–1.28]; P = 0.026). The incidence of a cerebral event and/or death from neurologic complications nearly doubled for patients with PP >80 mm Hg versus ≤80 mm Hg (5.5% vs 2.8%; P = 0.004). PP more than 80 mm Hg was also found to be associated with cardiac complications, increasing the incidence of congestive heart failure by 52%, and death from cardiac cause by nearly 100% (P = 0.003 and 0.006, respectively). CONCLUSION: An increase in PP was independently and significantly associated with greater fatal and nonfatal adverse cerebral and cardiac outcomes in patients having CABG surgery. These findings highlight the associated risks of preoperative PP on acute postoperative vascular outcomes.

Patterns of Use of Perioperative ACE Inhibitors in CABG Surgery with Cardiopulmonary Bypass: Effects on In-Hospital Morbidity and Mortality

Background— 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. Methods and Results— 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<0.001), as well as a decrease in cardiac and renal events (P<0.001 and P=0.005, respectively). No differences in in-hospital mortality and cerebral events were noted. Conclusions— 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.

Platelet PlA2 polymorphism and platelet activation are associated with increased troponin I release after cardiopulmonary bypass.

Background The PlA2 polymorphism of platelet glycoprotein IIIa has been identified as a prothrombotic risk factor in a number of cardiovascular settings. The aim of this study was to determine whether the PlA2 polymorphism of platelet glycoprotein IIIa and degree of platelet activation were associated with more severe myocardial injury as indicated by troponin I release following cardiopulmonary bypass. Methods The PlA genotype was determined in 66 patients undergoing elective coronary artery bypass grafting requiring cardiopulmonary bypass. Troponin I concentrations and the percentage of circulating, activated (CD62P+) platelets were measured at predetermined intervals perioperatively. Results Forty-six patients were PlA1,A1, and 20 were PlA1,A2 or PlA2,A2. Patients with at least one PlA2 allele had significantly greater postoperative troponin I concentrations than PlA1 homozygotes (P = 0.006, analysis of variance). Peak troponin I concentrations also correlated significantly with the increase in circulating, activated platelets (P = 0.02, Spearman rank correlation). Conclusions The PlA2 allele of platelet glycoprotein IIIa is associated with higher troponin I concentrations following cardiopulmonary bypass surgery, suggesting that this platelet polymorphism contributes to perioperative myocardial injury.

Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery

Background:Cardiac surgery requiring cardiopulmonary bypass is associated with platelet activation. Because platelets are increasingly recognized as important effectors of ischemia and end-organ inflammatory injury, the authors explored whether postoperative nadir platelet counts are associated with acute kidney injury (AKI) and mortality after coronary artery bypass grafting (CABG) surgery. Methods:The authors evaluated 4,217 adult patients who underwent CABG surgery. Postoperative nadir platelet counts were defined as the lowest in-hospital values and were used as a continuous predictor of postoperative AKI and mortality. Nadir values in the lowest 10th percentile were also used as a categorical predictor. Multivariable logistic regression and Cox proportional hazard models examined the association between postoperative platelet counts, postoperative AKI, and mortality. Results:The median postoperative nadir platelet count was 121 × 109/l. The incidence of postoperative AKI was 54%, including 9.5% (215 patients) and 3.4% (76 patients) who experienced stages II and III AKI, respectively. For every 30 × 109/l decrease in platelet counts, the risk for postoperative AKI increased by 14% (adjusted odds ratio, 1.14; 95% CI, 1.09 to 1.20; P < 0.0001). Patients with platelet counts in the lowest 10th percentile were three times more likely to progress to a higher severity of postoperative AKI (adjusted proportional odds ratio, 3.04; 95% CI, 2.26 to 4.07; P < 0.0001) and had associated increased risk for mortality immediately after surgery (adjusted hazard ratio, 5.46; 95% CI, 3.79 to 7.89; P < 0.0001). Conclusion:The authors found a significant association between postoperative nadir platelet counts and AKI and short-term mortality after CABG surgery.