Mark E. Comunale

Precardiopulmonary Bypass Right Ventricular Function Is Associated with Poor Outcome After Coronary Artery Bypass Grafting in Patients with Severe Left Ventricular Systolic Dysfunction

Patients with severe left ventricular systolic dysfunction (LVSD) undergoing coronary artery bypass grafting (CABG) have an increased risk for morbidity and mortality. The purpose of this study was to assess the association of pre-CABG right ventricular (RV) function with outcome for patients with severe LVSD. We performed a retrospective evaluation of 41 patients with severe LVSD (left ventricular ejection fraction [LVEF] ≤25%) scheduled for nonemergent CABG. Data were obtained from review of medical records, transesophageal echocardiography tapes, and phone interview. The pre- and post-cardiopulmonary bypass (CPB) LVEF and the RV fractional area of contraction (RVFAC) were calculated by using intraoperative transesophageal echocardiography. Group 1 patients had an RVFAC ≤35% (n = 7), whereas Group 2 patients had RVFAC >35% (n = 34). The durations of mechanical ventilation and of intensive care unit and hospital stays are presented as the median. Pre-CABG LVEF was similar between Groups 1 and 2 (15.8% ± 3.3% versus 17.8% ± 3.9%). Compared with Group 2, Group 1 patients required greater duration of mechanical ventilation (12 days versus 1 day;P < 0.01), longer intensive care unit (14 versus 2 days;P < 0.01) and hospital (14 versus 7 days;P = 0.02) stays, had a more frequent incidence and severity of LV diastolic dysfunction, and had a smaller change in LVEF immediately after CPB (4.1% ± 8.3% versus 12.5% ± 9.2%;P = 0.03). All Group 1 patients died of cardiac causes within 2 yr of surgery; five died during the same hospital admission. Three Group 2 patients died: one of colon cancer at 18 mo after CABG and two of cardiac causes 24 and 48 mo after surgery. A fourth patient was awaiting cardiac transplantation 4 yr after surgery. The remaining Group 2 patients were New York Heart Association Classification I or II. For patients with severe LVSD undergoing CABG, pre-CPB RV dysfunction was associated with poor outcome. Patients with RVFAC >35% had a relatively uneventful perioperative course and good long-term survival, whereas patients with RVFAC ≤35% had a poor early and late outcome. Assessment of RV function is useful to further assess the risk of CABG.

Electrocardiographic and hemodynamic changes and their association with myocardial infarction during coronary artery bypass surgery : A multicenter study

Background Electrocardiographic (ECG) changes during coronary artery bypass graft surgery have not been described in detail in a large multicenter population. The authors describe these ECG changes and evaluate them, along with demographic and clinical characteristics and intraoperative hemodynamic alterations, as predictors of myocardial infarction (MI) as defined by two sets of criteria. Methods Data from 566 patients at 20 clinical sites, collected as part of a clinical trial to evaluate the efficacy of acadesine for reducing MI, were analyzed at core laboratories. Perioperative ECG changes were identified using continuous three‐lead Holter ECG. Systolic blood pressure, diastolic blood pressure, and heart rate were recorded each minute during operation. The occurrence of MI by Q wave or myocardial fraction of creatine kinase (CK‐MB) or autopsy criteria, and by (Q wave and CK‐MB) or autopsy criteria was determined. Results During perioperative Holter monitoring, episodes of ST segment deviation, major cardiac conduction changes greater or equal to 30 min, or use of ventricular pacing greater or equal to 30 min occurred in 58% patients, primarily in the first 8 h after release of aortic occlusion. Of the 25% patients who met the Q wave or CK‐MB or autopsy criteria for MI, 19% had increased CK‐MB as well as ECG changes. (Q wave and CK‐MB) or autopsy criteria for MI were met by 4% of patients. The CK‐MB concentration generally peaked by 16 h after release of aortic occlusion. In patients with (n = 187) and without a perioperative episode of ST segment deviation, the incidence of MI was 36% and 19%, respectively (P < 0.01), by Q wave or CK‐MB or autopsy criteria, and 6% and 3%, respectively (P = 0.055), by (Q wave and CK‐MB) or autopsy criteria. Multiple logistic regression analysis showed that intraoperative ST segment deviation, intraventricular conduction defect, left bundle branch block, duration of hypotension (systolic blood pressure < 90 mmHg) after cardiopulmonary bypass, and duration of cardiopulmonary bypass are independent predictors of Q wave or CK‐MB or autopsy MI. The independent predictors of (Q wave and CK‐MB) or autopsy MI are intraoperative ST segment deviation and duration of aortic occlusion. Conclusions Major ECG changes occurred in 58% of patients during coronary artery bypass graft surgery, primarily within 8 h after release of aortic occlusion. Multicenter data collection revealed a substantial variation in the incidence of MI and an overall incidence of up to 25%, with most MI occurring within 16 h after release of aortic occlusion. Intraoperative monitoring of ECG and hemodynamics has incremental value for predicting MI.

The concordance of intraoperative left ventricular wall-motion abnormalities and electrocardiographic S-T segment changes: Association with outcome after coronary revascularization

BACKGROUND Transesophageal echocardiography (TEE) and Holter electrocardiography (ECG) are used to detect intraoperative ischemia during coronary artery bypass graft surgery (CABG). Concordance of these modalities and sensitivity as indicators of adverse perioperative cardiac outcomes are poorly defined. The authors tried to determine whether routine use of Holter ECG and TEE in patients with CABGs has clinical value in identifying those patients in whom myocardial infarction (MI) is likely to develop. METHODS A total of 351 patients with CABG and both ECG- and TEE-evaluable data were examined for the occurrence of ischemia and infarction. The TEE and five-lead Holter ECGs were performed continuously during cardiac surgery. The incidence of MI (creatine kinase-MB > or = 100 ng/ml) within 12 h of arrival in the intensive care [ICU] unit, new ECG Q wave on ICU admission or on the morning of postoperative day 1, or both, were recorded. RESULTS Electrocardiographic or TEE evidence of intraoperative ischemia was present in 126 (36%) patients. The concordance between modalities was poor (positive concordance = 17%; Kappa statistic = 0.13). Myocardial infarction occurred in 62 (17%) patients, and 32 (52%) of them had previous intraoperative ischemia. Of these, 28 (88%) were identified by TEE, whereas 13 (41%) were identified by ECG. Prediction of MI was greater for TEE compared with ECG. CONCLUSIONS Wall-motion abnormalities detected by TEE are more common than S-T segment changes detected by ECG, and concordance between the two modalities is low. One half of patients with MI had preceding ECG or TEE ischemia. Logistic regression revealed that TEE is twice as predictive as ECG in identifying patients who have MI.

Microvascular endothelial dysfunction and its mechanism in a rat model of subarachnoid hemorrhage

After subarachnoid hemorrhage (SAH), large cerebral arteries are prone to vasospasm. Using a rat model of SAH, we examined whether cortical microvessels demonstrate vasomotor changes that may make them prone to spasm and whether endothelial dysfunction may account for any observed changes. Two days after percutaneous catheterization into the cisterna magna, 0.3 mL of autologous blood was injected into the subarachnoid space. The brain tissue was harvested 20 min later, and microvessels were dissected from the parietal cortex. Vasomotor responses to the thromboxane analog U46619, the protein kinase C agonist phorbol acetate, endothelin-1, adenosine diphosphate, nitroprusside, and isoproterenol were examined in vitro in cerebral arterioles from the control, sham-operated, and SAH animals. Endothelial nitric oxide synthase (NOS3) messenger RNA and protein concentration was measured by northern and western blotting, respectively. Arterioles from the SAH animals demonstrated attenuated dilation to the endothelium-dependent dilator adenosine diphosphate and accentuated constriction to endothelin-1, while responses to the other agents tested were unchanged. NOS3 protein concentration was decreased, but NOS3 messenger RNA was increased after SAH. After SAH, cortical arterioles demonstrate endothelial dysfunction, which may be the basis for microvascular spasm. This is in part related to decreased NOS3, which occurs despite an increase in its transcription.

Pulsed wave Doppler measurement of cardiac output from the right ventricular outflow tract.

Doppler ultrasound can be used to measure cardiac output (CO).Intraoperative Doppler cardiac output (DCO) by transesophageal echocardiography (TEE) has been studied using blood flow velocity from the left ventricular outflow tract (LVOT), the mitral valve (MV), and the main pulmonary artery (MPA). The purpose of this study was to compare DCO, measured from a relatively new TEE view of the right ventricular outflow tract (RVOT), with thermodilution cardiac output (TDCO). We also compared changes in DCO from the RVOT to changes in TDCO. A 5.0/3.7 MHz multiplane TEE probe was placed in 45 adult cardiac surgical patients undergoing general anesthesia. Patients were excluded if there was greater than mild tricuspid valve insufficiency. From the transgastric view, at approximately 110-140 degrees, the RVOT was imaged. DCO was calculated from 1) the time-velocity integral (TVI) using pulse wave (PW) Doppler, 2) the area of the RVOT (measured in early systole using the diameter (pi (D/2)2) of the RVOT at the level of the PW Doppler sample volume), and 3) the heart rate. Simultaneous TDCO was performed by a separate examiner. The RVOT was imaged satisfactorily in 84% of patients (38/45). The mean bias between DCO and TDCO was -0.01 L/min (2 SD +/- 0.45 L/min; n = 38). There was good correlation between DCO and TDCO (R2 = 0.97). Changes in TDCO and changes in DCO were compared in 15 patients. The mean bias between changes in DCO and changes in TDCO was 0.04 L/min (2 SD +/- 0.66 L/min). Analysis of the changes in DCO and TDCO showed good correlation (R2 = 0.96). We conclude that there is a good correlation between DCO measured from the RVOT and TDCO. This technique permits cardiac output measurement without the necessity of placing a pulmonary artery catheter, and it also provides a method of evaluating RVOT blood flow. (Anesth Analg 1996;83:466-71)

Management of cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia using prostaglandin E1 and aspirin

P ATIENTS WITH heparin-induced thrombocytopenia (HIT) who require anticoagulation for cardiopulmonary bypass (CPB) present a difficult management problem. The therapeutic options available are limited, particularly if the indication for surgery requiring CPB is urgent. A case is presented of a patient with HIT and unstable angina who underwent urgent coronary artery bypass grafting (CABG) without thrombotic or hemorrhagic complications. The patient was anticoagulated with heparin. 400 U/kg (4 mg/kg); preoperative aspirin and an intraoperative infusion of prostaglandin E, were administered as inhibitors of platelet aggregation.

Attenuation of Endothelium-Dependent Dilation of Pig Pulmonary Arterioles After Cardiopulmonary Bypass Is Prevented by Monoclonal Antibody to Complement C5a

UNLABELLED We examined whether pulmonary endothelial dysfunction associated with cardiopulmonary bypass (CPB) may be mediated by complement C5a in pigs. Pigs were placed on normothermic CPB for 1 h with or without a previous administration of 1.6 mg/kg anti-C5a monoclonal antibody (MAb), then reperfused for 2 h. Pulmonary tissue myeloperoxidase activity was measured. Expression of nitric oxide synthase (NOS) was measured by reverse transcriptase polymerase chain reaction and Western blotting. Pulmonary arterioles approximately 100 microm in diameter were preconstricted with the thromboxane analog U46619 1 microM, and relaxation responses to adenosine diphosphate 10(-9)-10(-4) M, substance P 10(-12)-10(-6) M, and sodium nitroprusside 10(-9)-10(-4) M were examined in vitro by videomicroscopy. Relaxation to the endothelium-dependent dilators adenosine diphosphate and substance P was attenuated after CPB; this attenuation was prevented by the previous administration of MAb. Relaxation to sodium nitroprusside was not affected by CPB. Neutrophil sequestration, as measured by MPO activity, increased after CPB, either with or without MAb. Transcription of NOS was unchanged by CPB, but translation of constitutive NOS was decreased after CPB, and this decrease was prevented by a previous administration of MAb. We conclude that pig pulmonary endothelial dysfunction associated with CPB may be mediated by C5a. The mechanism may involve changes in NOS translation. IMPLICATIONS In pigs, pulmonary endothelial dysfunction may occur after cardiopulmonary bypass due to product(s) of complement activation.

Management of cardiopulmonary bypass in a patient with congenital factor XII deficiency

ACTOR XII, also known as Hagemann factor, is the F first enzyme in the intrinsic pathway of the clotting cascade. Patients with a congenital Factor XII deficiency demonstrate laboratory abnormalities but are not at risk for bleeding diatheses.’ The activated coagulation time (ACT) is prolonged in these patients and is, thus, of little value for monitoring the adequacy of anticoagulation during cardiopulmonary bypass (CPB). This report describes the management of a patient with a congenital deficiency of Factor XII who presented for coronary artery bypass grafting (CABG). All three bypass grafts thrombosed shortly after separation from CPB and heparin reversal, suggesting a Factor XII associated hypercoagulability. Further complicating this patient’s management was prolonged preoperative heparin therapy and the potential for heparin resistance, making estimation of anticoagulation requirements even more problematic.

Significance of D-dimer concentrations during and after cardiopulmonary bypass

OBJECTIVE To determine whether D-dimer fragments predictably increase during cardiopulmonary bypass (CPB), and if so, whether increases correlate with postoperative blood loss or predict postoperative coagulopathy. DESIGN Prospective observational study of 65 consecutive patients undergoing first-time coronary artery bypass graft (CABG) or first-time valve replacement. SETTING Single center University teaching hospital. PARTICIPANTS Male and female patients between the ages of 30 and 90 years undergoing first-time CABG or valve replacement surgery using CPB. Patients were excluded from study for prolonged preoperative bleeding time, preoperative warfarin therapy, perioperative intra-aortic balloon pump support, thrombolytic therapy in the week preceding operation, reoperation, and emergency operation. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Blood sampling for platelet count, prothrombin time, partial thromboplastin time, thrombin time, fibrinogen, activated coagulation time (ACT) and D-dimer concentrations was obtained at four times during each case; (1) preoperatively, after insertion of the internal jugular introducer, before insertion of pulmonary artery catheter; (2) during CPB at 28 degrees C, immediately before rewarming; (3) after heparin neutralization (20 minutes after initial protamine dose); (4) 12 to 24 hours postoperatively. Blood loss in the intensive care unit was calculated by measuring total mediastinal drainage output at 1 and 4 hours after arrival from the operating room. An initial decrease in fibrinogen was noted during bypass, but no increase in D-dimer was identified. A few patients developed a modest increase in D-dimer after heparin neutralization, but none greater than 2.0 ug/mL. Postoperatively, fibrinogen concentration increased toward baseline levels. However, this is when six patients developed significant (> 2.0 ug/mL) D-dimer formation. Results suggest appropriate physiologic response-normalization of fibrinogen with new synthesis and remodeling of clot in the operative site causing D-dimer formation. Patients with highest D-dimer levels at 12 to 24 hours postoperatively had the highest blood loss at 4 hours postoperatively, suggesting that early postoperative excess bleeding predisposed to increased clot formation and subsequent clot remodeling causing elevated D-dimer concentrations. CONCLUSIONS D-dimer concentration is not usually elevated in patients undergoing CPB when adequately anticoagulated as monitored using the ACT. When mild elevation of D-dimer occurs, it is most often after heparin neutralization and/or in the postoperative period and is not predictive of increased postoperative blood loss. Elevations of D-dimer concentrations in the postoperative period without corresponding decreases in fibrinogen concentrations may occur and do not signify coagulopathy.

Potassium concentrations and ventricular ectopy: a prospective, observational study in post-cardiac surgery patients.

OBJECTIVE To determine whether a correlation exists between concentrations of intracellular and extracellular potassium and to determine the frequency of ventricular ectopy in patients after cardiac operations. DESIGN Prospective, observational clinical evaluation. SETTING Surgical-respiratory intensive care unit of a university-affiliated tertiary care center. PATIENTS Continuous 24-hr electrocardiographic monitoring was performed, and serum (extracellular) and erythrocyte (intracellular) potassium concentrations ([K+]e and [K+]i) were determined, before cardiopulmonary bypass, immediately postoperatively, and at 2, 4, 12, and 20 hrs after elective coronary bypass grafting in 31 patients. INTERVENTIONS None. Potassium replacement was left to the discretion of the attending physicians. MEASUREMENTS AND MAIN RESULTS Although the mean [K+]e varied significantly during the postoperative 24-hr period (p<.0001), the [K+]i did not (p = .953). No significant correlations were found between premature ventricular beats and [K+]i, [K+]e, or [K+]i/[K+]e (all p>.05). However, among the few patients who had one or more episodes of ventricular tachycardia (VT) within 30 mins of a study K+ sample, the mean [K+]e was significantly lower during the episode(s) of VT compared with the mean [K+]e in the absence of VT (p<.01). CONCLUSIONS Although it is clear that over the clinically acceptable range of [K+]e and [K+]i concentrations seen in this population, there is no correlation between potassium concentrations and the occurrence of premature ventricular beats, the infrequent association of more serious ventricular ectopy, VT, with lower [K+]e concentrations supports the practice of using serum potassium to guide potassium replacement in patients after cardiac operations.