Perioperative myocardial ischemia in patients undergoing noncardiac surgery--II: Incidence and severity during the 1st week after surgery. The Study of Perioperative Ischemia (SPI) Research Group.

Because of the importance of postoperative myocardial ischemia and because substantial physiologic changes can occur for prolonged periods postoperatively, the incidence, severity and temporal course of myocardial ischemia were studied in 100 high risk patients during the 1st week after major noncardiac surgery. Electrocardiographic (ECG) changes consistent with ischemia were continuously monitored using ambulatory solid state ECG in the 100 patients with or at risk for coronary artery disease. Ischemic episodes were defined as reversible ST segment depression greater than or equal to 1 mm or elevation greater than or equal to 2 mm above the baseline value, with the baseline adjusted for respiratory and positional variation and temporal drift. All ischemic episodes were confirmed by three independent blinded investigators using hard-copy recordings. Total ECG monitoring time was 10,445 h. Twenty-seven patients (27%) developed 437 episodes of ischemia during the 1st week after surgery. The total duration of ischemia was 18,658 min, or 1.8 min of ischemia/h monitored. Ischemia was most severe during the early (days 0 to 3) versus late (days 4 to 7) postoperative period: 284 versus 153 episodes; 2.2 versus 1.2 min of ischemia/h. The greatest severity occurred on postoperative day 3: 109 episodes, 3.4 min of ischemia/h monitored, 1.5 mm mean ST change and 130 min mean duration. However, in 8% of patients, severe episodes also occurred late: postoperative day 6 = 44 episodes, 1.7 min of ischemia/h monitored, 1.3 mm mean ST change (59% greater than or equal to 2 mm) and 92 min mean duration. Most ischemic episodes (57%) were associated with tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of steal-prone anatomy on intraoperative myocardial ischemia. The SPI Research Group.

OBJECTIVES: Our study objective was to determine whether the presence of steal-prone anatomy conferred an increased risk in the development of intraoperative myocardial ischemia. BACKGROUND: Coronary artery steal of collateral blood flow has been demonstrated for many vasodilators, including isoflurane, the most commonly used inhalational anesthetic agent in the United States. It has been postulated that patients with steal-prone anatomy (total occlusion of one coronary artery that is supplied distally by collateral flow from another coronary artery with a > or = 50% stenosis) may be particularly at risk for the development of intraoperative myocardial ischemia when an anesthetic with a vasodilator property is being administered. METHODS: We evaluated the risk of myocardial ischemia under isoflurane anesthesia (vs. a high dose narcotic technique using sufentanil) using continuous intraoperative electrocardiography and transesophageal echocardiography in patients with and without steal-prone anatomy undergoing coronary artery bypass graft surgery. RESULTS: Sixty-two (33%) of the 186 patients had steal-prone anatomy: in 5 (8%) the collateral-supplying vessel was > or = 50% to 69% stenosed, in 24 (39%) it was > or = 70% to 89% stenosed and in 33 (53%) it was > or = 90% stenosed. The incidence of ischemia (transesophageal echocardiography or intraoperative electrocardiography, or both) was similar in patients with and without steal-prone coronary anatomy (18 [29%] of 62 patients vs. 39 [31%] of 124 patients, p = 0.87, 95% confidence interval = -0.13 to 0.17). The incidence of intraoperative ischemia was similar in patients who received isoflurane or sufentanil anesthesia (20 [32%] of 62 patients vs. 37 [30%] of 124 patients, p = 0.87). The incidence of tachycardia and hypotension was low (increases in heart rate = 9.8%, and decreases in systolic blood pressure = 10.8% of total monitoring time during the prebypass period compared with preoperative baseline values). The incidence of adverse cardiac outcome was similar in patients with and without preoperative steal-prone coronary anatomy (4 [7%] of 62 patients vs. 14 [11%] of 124 patients, p = 0.53). CONCLUSIONS: These findings demonstrate that under strict hemodynamic control the presence of steal-prone anatomy does not confer an increased risk in the development of intraoperative myocardial ischemia.

Significance of the pericardium in human subjects: effects on left ventricular volume, pressure and ejection.

To assess the effect of the pericardium, left ventricular systolic function and diastolic compliance were studied in 15 patients before and after pericardiotomy during coronary artery surgery. Using first pass radionuclide angiography, curves for left ventricular systolic function (stroke work versus end-diastolic volume) and a measure of diastolic compliance (pulmonary capillary wedge pressure versus end-diastolic volume) were generated by changing body position to alter venous return. Left ventricular end-diastolic volume ranged from 41 to 111 ml/m2 and pulmonary capillary wedge pressure from 0 to 24 mm Hg. No significant changes were found in blood pressure (150/83 to 148/82 mm Hg), heart rate (66.7 to 67.1 beats/min), cardiac index (2.38 to 2.41 liters/min per m2), ejection fraction (0.56 to 0.54), end-systolic volume index (31.4 to 32.2 ml/m2), end-diastolic volume index (65.9 to 69.5 ml/m2) or pulmonary capillary wedge pressure (7.5 to 7.3 mm Hg). The pericardium did not affect the curves relating stroke work and end-diastolic volume or those relating pulmonary capillary wedge pressure and end-diastolic volume. Thus, when filling pressure and volume are normal or only moderately elevated, the pericardium does not appear to affect left ventricular systolic function or diastolic compliance in patients.

Perioperative myocardial ischemia in patients undergoing noncardiac surgery--I: Incidence and severity during the 4 day perioperative period. The Study of Perioperative Ischemia (SPI) Research Group.

To determine the incidence and characteristics of perioperative myocardial ischemia, the electrocardiographic (ECG) changes consistent with ischemia during the 4 day perioperative period were documented and characterized in 100 patients with or at risk for coronary artery disease undergoing noncardiac surgery. Using continuous two channel ECG monitoring (leads CC5 and CM5), the frequency and severity of ECG ischemic episodes defined by ST segment depression greater than or equal to 1 mm or elevation greater than or equal to 2 mm during the preoperative (up to 2 days), intraoperative and early postoperative (first 2 days) periods were compared. Preoperatively, 28 patients (28%) exhibited 105 episodes of ischemia; intraoperatively, 27 patients exhibited 39 episodes and postoperatively, 42 patients exhibited 187 episodes. There was no difference between the pre- and intraoperative episode characteristics. However, postoperative ischemic episodes were the most severe. The mean ST change was 1.5, 2 and 2.6 mm for pre-, intra- and postoperative episodes, respectively (p less than 0.0001 postoperative versus pre- or intraoperative); duration of ischemic episodes was 69, 45 and 207 min, respectively (p less than 0.005 postoperative versus preoperative, p less than 0.001 versus intraoperative) and area under the ST curve was 88, 74 and 383 mm.min (p less than 0.009 postoperative versus preoperative, p less than 0.005 versus intraoperative). Ninety-four percent of all postoperative ischemic episodes were silent; 80% of all episodes occurred without acute change (+/- 20% of control) in heart rate and 77% of intraoperative episodes occurred without acute change in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic approaches to postoperative ischemia. The Study of Perioperative Ischemia Research Group.

Previous attempts to identify predictors of cardiac complications, an important cause of postoperative morbidity and mortality following non-cardiac surgery, have focused mainly on the patient's preoperative state. Our research group, however, has found that adverse cardiac outcome correlates most highly with the appearance of at least 1 ischemic episode determined by continuous ambulatory electrocardiographic monitoring (AEM) in the early postoperative period. Such early postoperative ischemia conferred (1) a greater than 9-fold increased risk of experiencing in-hospital cardiac death, nonfatal myocardial infarction, or postoperative unstable angina, and (2) a greater than 2-fold increased long-term (2-year) risk of cardiac death, myocardial infarction, or angina requiring coronary angioplasty or coronary artery bypass grafting (CABG). Additionally, 5 predictors of such postoperative ischemia were identified: left ventricular hypertrophy, diabetes mellitus, hypertension, definite coronary artery disease, and preoperative digoxin use. These findings suggest that patients who are at high risk for postoperative myocardial ischemia warrant more intensive postoperative monitoring. Moreover, since such ischemia is potentially reversible, the testing of strategies designed to prevent or manage postoperative ischemia appears warranted and is discussed. Our group also has established the usefulness of AEM for identifying ischemic episodes in patients undergoing CABG. However, patients who require cardiopulmonary bypass present unique problems regarding the interpretation of AEM recordings. We describe guidelines for the interpretation of AEM results obtained under these conditions and suggest criteria based on the degree of interpretability for patient inclusion in future studies.

Protection of myocardial function not enhanced by high concentrations of potassium during cardioplegic arrest.

Myocardial performance was evaluated intraoperatively in 20 patients undergoing myocardial revascularization when hypothermic potassium cardioplegic arrest was used. High concentrations of potassium (20 mEq/L) were compared to normal concentrations of potassium (5 mEq/L) in hypothermic cardioplegic solutions. The cardioplegic arrest period averaged 53 +/- 3 minutes in the high potassium group and 54 +/- 4 minutes in the low potassium group, Intraoperative calculation of ejection fraction and end-diastolic volume was accomplished by the technique of radiocardiography. All data were grouped according to end-diastolic volume index (EDVI) for both high (HK) and low (LK) potassium comparisons. Comparisons between high and low potassium groups demonstrated no significant differences in ejection fraction (HK = 66%, LK = 61%), cardiac index (HK = 2.74 L/min/m2, LK = 3.0 L/min/m2), stroke work (HK = 36 gm.m/m2, LK = 30 gm.m/m2), oxygen consumption as measured by left heart double product (HK = 9,438; LK = 9,209), and myocardial compliance (HK = 2.8 cc/torr, LK = 4.2 cc/torr at the post-cardioplegic arrest period). The role potassium plays in producing a rapid cardiac arrest is well accepted. Its protective effect on the preservation of high-energy phosphate stores is postulated, but its addition to perfusion hypothermia does not appear to enhance the protective effect observed with perfusion hypothermia alone.

The safety and efficacy of ten percent pentastarch as a cardiopulmonary bypass priming solution. A randomized clinical trial.

Ten percent pentastarch is a low-molecular-weight hydroxyethyl starch with greater oncotic pressure and shorter intravascular persistence than 6% hetastarch. To evaluate its safety and efficacy as a component of cardiopulmonary bypass priming solution, we prospectively studied 90 patients undergoing coronary artery bypass grafting or valve replacement necessitating cardiopulmonary bypass (bubble oxygenator and moderate systemic hypothermia). Sixty patients were randomized to receive 75 gm of either 10% pentastarch (group P) or 25% albumin (group A), and 30 patients received lactated Ringer's solution alone (group C). Intravascular colloid osmotic pressure during cardiopulmonary bypass was highest with either of the colloid primes (15-minute measurement: group P, 15.7 +/- 2.2 mm Hg (mean +/- standard deviation); group A, 15.2 +/- 2.0 mm Hg; group C, 11.3 +/- 1.7 mm Hg; p less than 0.05, groups P and A compared with group C). This was associated with a lower volume requirement during cardiopulmonary bypass to maintain the venous reservoir (group P, 333 +/- 318 ml; group A, 483 +/- 472 ml; group C, 1332 +/- 1013 ml; p less than 0.05, groups P and A compared with group C). Urine output during cardiopulmonary bypass was similar in each group. Net intraoperative fluid balance was lowest in the colloid groups (groups P and A, 5.7 +/- 1.4 L; group C, 6.9 +/- 1.3 L; p less than 0.05, groups P and A compared with group C). Cardiac index shortly after weaning from cardiopulmonary bypass was greatest in group P (group P, 3.2 +/- 0.9; group A, 2.8 +/- 0.8; group C, 2.7 +/- 0.6 dyne.sec.cm-5; p less than 0.05, group P compared with group C). Changes in alveolar-arterial oxygen gradients, shunt fraction, and effective compliance were similar in all groups. During cardiopulmonary bypass, pentastarch appeared to cause the greatest degree of hemodilution, as suggested by the lowest hemoglobin, factor VII and IX levels and platelet count. The activated partial thromboplastin time was significantly prolonged during and immediately after cardiopulmonary bypass in group P relative to groups A and C (p less than 0.05), although there were no significant differences in the activated clotting time before cardiopulmonary bypass, during cardiopulmonary bypass, or after heparin neutralization. As well, clinical indices of hemostasis, including mediastinal drainage, red cell, platelet, and fresh frozen plasma requirements, and reoperation for excessive postoperative bleeding, were similar. We conclude that pentastarch, when used in cardiopulmonary bypass prime, is as safe as either albumin or Ringer's solution alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization.

The proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. We tested the hypothesis that cytokine levels are elevated after uncomplicated coronary artery bypass grafting and associated with episodes of postoperative myocardial ischemia and dysfunction. Coronary artery bypass grafting was performed under general anesthesia with moderate systemic hypothermia and cold-blood potassium cardioplegic solution. Tumor necrosis factor-alpha and interleukin-6 levels were determined by bioassays, and interleukin-8 levels were measured by a sandwich enzyme-linked immunosorbent assay. Myocardial function and ischemic episodes were assessed by intraoperative transesophageal echocardiography and perioperative 12-channel Holter monitoring. A total of 22 patients were studied, with no deaths or complications. Arterial tumor necrosis factor-alpha rose in a bimodal distribution, peaking at 2 and 18 to 24 hours after the operation (at 20.2 +/- 6.4 pg/ml, [mean +/- standard error of the mean]) and 5.8 +/- 1.6 pg/ml, respectively; before cardiopulmonary bypass: 0.90 +/- 0.20 pg/ml, p < 0.001 for both peaks) then progressively declined to levels before bypass. Arterial interleukin-6 was maximally elevated immediately on termination of cardiopulmonary bypass and peaked again 12 to 18 hours after cardiopulmonary bypass (at 7520 +/- 2439 pg/ml and 6216 +/- 1928 pg/ml, respectively; before bypass: 746 +/- 187 pg/ml, p < 0.0001 for both peaks). Arterial interleukin-8 levels were more variable but followed a similar pattern, peaking in the early period after cardiopulmonary bypass and again at 16 to 18 hours after the operation (at 4110 +/- 1403 pg/ml and 1760 +/- 1145 pg/ml, respectively; before bypass: 461 +/- 158, p < 0.05 for both peaks). By multivariate analysis, the aortic crossclamp time was independently predictive of postoperative cytokine levels. Left ventricular wall motion abnormalities were associated with both interleukin-6 and interleukin-8 levels, worsening scores being associated with increasing levels (for interleukin-6, p = 0.003; for interleukin-8, p = 0.05). Postoperative myocardial ischemic episodes were associated with interleukin-6 levels, six of seven (85%) patients with episodes of myocardial ischemia after a peak in interleukin-6 concentrations (p < 0.01). We conclude that proinflammatory cytokines are elevated after uncomplicated coronary revascularization and may contribute to postoperative myocardial ischemia and segmental wall motion abnormalities.

A randomized clinical trial of 10% pentastarch (low molecular weight hydroxyethyl starch) versus 5% albumin for plasma volume expansion after cardiac operations.

Pentastarch is a hydroxyethyl starch similar to hetastarch, but with a lower average molecular weight (264,000 versus 450,000) and fewer hydroxyethyl groups (molar substitution ratio = 0.45 versus 0.70). These characteristics result in enhanced enzymatic hydrolysis, faster renal elimination (initial intravascular half-life = 2.5 versus 25.5 hours), and less effect on coagulation. We report on a randomized clinical trial comparing the clinical efficacy and safety of 10% pentastarch (group P) for plasma volume expansion after cardiac operations with that of 5% serum albumin (group A). During the first 24 hours after arrival of the patient in the intensive care unit, colloid was infused to maintain a cardiac index of 2.0 L/m2 or more and a mean arterial pressure within 10% of the preinduction value. Group P (n = 50) received 1706 +/- 393 ml of colloid (mean +/- standard deviation) during this period, and group A (n = 44), 1794 +/- 341 ml (p = no significant difference). Hemodynamic responses to infusion were similar for both groups, although in group P a greater increase in both cardiac index (0.5 +/- 0.5 versus 0.3 +/- 0.5 L/min/m2 in group A, p less than 0.01) and left ventricular stroke work index (10.8 +/- 8.0 versus 5.8 +/- 6.0 gm-m/m2, p less than 0.01) was observed during infusion of the first 500 ml. There were no significant differences in any of the measured respiratory parameters (alveolar-arterial oxygen gradient, estimated shunt fraction, and effective pulmonary compliance). Hemodilution with colloid significantly reduced serum protein levels in group P by 24 hours postoperatively (4.0 +/- 0.6 versus 5.0 +/- 0.7 gm/dl in group A, p less than 0.05), although mean serum colloid osmotic pressure was similar (15.4 +/- 2.6 [P] versus 15.5 +/- 2.7 mmHg [A], p = no significant difference). There were no significant between-group differences in prothrombin time, activated partial thromboplastin time, platelet count, bleeding time, or coagulation factors (fibrinogen, V, VII, VIII, or IX) on postoperative days 1 and 7. Perioperative fluid balance, weight change, chest tube output, red blood, platelet, or fresh frozen plasma usage, reexploration for bleeding, and clinical outcome were also similar. These findings indicate that pentastarch is as safe and effective s 5% albumin for plasma volume expansion after cardiac operations with no apparent adverse effects on coagulation. If commercially available at a lower cost than albumin, it would appear to be a reasonable first choice for colloid therapy in this setting.

Hematocrit value on intensive care unit entry influences the frequency of Q-wave myocardial infarction after coronary artery bypass grafting. The Institutions of the Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

OBJECTIVES: No data exist regarding "the best" hematocrit value after coronary artery bypass graft surgery. Transfusion practice varies, because neither an optimal hematocrit value nor a uniform transfusion trigger criterion has been determined. METHODS: To investigate the optimal hematocrit value, we studied 2202 patients undergoing coronary bypass. The hematocrit value on entry into the intensive care unit (IHCT) was categorized into three groups: high (> or = 34%), medium (25% to 33%), and low (< or = 24%). Characteristics and adverse events (outcomes) were compared, and the effect of IHCT on the risk of myocardial infarction was determined by logistic regression. RESULTS: High IHCT (> or = 34%) was associated with an increased rate of myocardial infarction (8.3% vs 5.5% vs 3.6%; p < or = 0.03, high, medium vs low) and with more severe left ventricular dysfunction (11.7% vs 7.4% and 5.7%; p=0.006, high, medium vs low). Mortality rate increased with higher IHCT when all the high-risk subgroups were combined (8.6% vs 4.5% vs 3.2%; p < 0.001, high, medium vs low). By multivariate analysis, IHCT remained the most significant predictor of adverse outcomes (relative risk high vs low 2.22, 95% confidence interval: 1.04 to 4.76). No characteristic, event, medication, or transfusion therapy confounded the relationship between IHCT and outcome. CONCLUSION: High IHCT is associated with a higher rate of myocardial infarction and is an independent predictor of infarction. On the basis of the risk of myocardial infarction, there is no rationale for transfusion to an arbitrary level after coronary artery bypass grafting.

Changes in blood coagulation during and following cardiopulmonary bypass: lack of correlation with clinical bleeding.

Although previous studies have documented a wide variety of derangements in laboratory measurements of blood coagulation and platelets during cardiopulmonary bypass, limited data are available concerning the magnitude of these changes and any association with excessive bleeding. To determine whether abnormalities in commonly available laboratory tests for the evaluation of coagulation, fibrinolysis and hemostasis correlate with postoperative blood loss and transfusion requirements as measures of clinical outcome, 47 consecutive patients undergoing coronary artery bypass grafting with hypothermic cardiopulmonary bypass (CPB) were studied prospectively at 12 time points before, during, and following CPB. Routine blood coagulation tests, coagulation factor levels (fibrinogen, V, VII, VIII, and IX) and fibrinolysis (FDP) became abnormal within 15 minutes after patients were placed on CPB, remained abnormal for the duration of CPB, and recovered at varying rates after discontinuation of CPB. Mean factor V levels declined by the greatest percentage, to 15% of normal, followed by factor VIII which decreased to 30%. Platelet counts declined to below 100 x 10(9)/L after the initiation of CPB and remained low in the postoperative period. Twenty-eight percent of patients had mediastinal output > or = 100 mL per hour during the immediate postoperative period, and were considered to be "bleeders." There were no clinically relevant differences in any of the laboratory measurements between patients with normal postoperative blood loss and those defined as bleeders. Thus, the absence of significant correlations between various laboratory measurements of hemostasis and actual postoperative bleeding indicates that these laboratory derangements are transient, are not predictive of clinically important hemostatic abnormalities, and should not be used in isolation to guide the use of blood components in these patients. Furthermore, although bleeders received more blood components, there was surprisingly little effect on the coagulation factor levels measured.

Effect of induction and reperfusion with warm substrate-enriched cardioplegia on ventricular function.

BACKGROUND: This study tested the hypothesis that induction and reperfusion with warm substrate-enriched (IRWSE) blood cardioplegia improves postoperative left ventricular (LV) function in patients undergoing elective coronary bypass surgery (CABG). METHODS: After giving informed consent, 67 patients scheduled for CABG surgery were randomized to either IRWSE + cold blood (CB) or CB alone. IRWSE cardioplegia consisted of 37 degrees C substrate-enriched (glutamate, aspartate, hyperkalemic) anterograde and retrograde blood cardioplegic solution followed by non-substrate-enriched cardioplegic solution given at 4 degrees C to 8 degrees C. LV function was measured with ventriculograms, volume conductance catheters, echocardiography, and multiple gated (image) acquisition. RESULTS: The end-systolic pressure-volume relationship was improved postbypass in the IRWSE + CB group (CB, 1.5 +/- 0.74 mm Hg/mL vs IRWSE + CB, 2.1 +/- 1.2 mm Hg/mL; p = 0.042). The postoperative ejection fraction (EF%) was better preserved in the CB group (CB, 65 +/- 11.53% vs IRWSE + CB, 58.62 +/- 11.75%; p < 0.04). CONCLUSIONS: Our results demonstrate a transient improvement in LV systolic function in the immediate postbypass period in CABG patients in the IRWSE + CB group. The intraoperative benefits of the IRWSE + CB technique did not persist in the postoperative period.

Association between early postoperative coagulation activation and peri-operative myocardial ischaemia in patients undergoing vascular surgery.

We investigated the association of peri-operative myocardial ischaemia with activation of coagulation and endogenous fibrinolysis in patients undergoing vascular surgery. In 50 patients, continuous Holter monitoring was performed to assess peri-operative myocardial ischaemia and 12-lead electrocardiography was recorded preoperatively and 72 h postoperatively to assess myocardial infarction. Serial blood samples were drawn peri-operatively to determine the concentrations of fibrin monomers (for activation of coagulation), D-dimer (for endogenous fibrinolysis) and cardiac troponin T and I. Patients with myocardial ischaemia showed higher concentrations of fibrin monomers at 48 h, and higher concentrations of d-dimer preoperatively and at 24 and 48 h postoperatively. In patients with peri-operative myocardial ischaemia, strong positive correlations were observed between fibrin monomer and D-dimer concentrations at 15 min and 4 h postoperatively, and cardiac troponins at 15 min and at 4, 24, 48 and 72 h postoperatively. Early postoperative activation of coagulation and fibrinolysis is associated with peri-operative myocardial cell damage among patients who are at risk for, or have a history of, coronary artery disease plus peri-operative myocardial ischaemia.

Myocardial stunning: an overview.

Over the past two decades, we have challenged the belief that transient ischemia is benign with little functional sequelae following resolution of ischemia. The phenomenon of prolonged postischemic contractile dysfunction, or of myocardial stunning, has been developed and is under investigation using multiple experimental and clinical models. Classifications of myocardial stunning have been suggested and include single and multiple reversible ischemic episodes, partially reversible episodes, and global ischemia. More challenging is the understanding of the mechanisms of myocardial stunning, including free radical protection, excitation-contraction uncoupling, altered calcium flux, microvascular dysfunction, and impaired energy production and use. Finally, advances have been made in the clinical arena, including development of new more sensitive technologies to detect dysfunction, and development of potentially important therapies, including free radical scavengers, adenosine-regulating agents, and calcium channel blockers. In this brief overview, we focus on myocardial stunning, including a historical perspective of coronary occlusion, and definition, classification, and clinical implications of myocardial stunning.