A comparison of aprotinin and lysine analogues in high-risk cardiac surgery.

BACKGROUND: Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences. METHODS: In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days. RESULTS: The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9.5%) in the aprotinin group had massive bleeding, as compared with 93 (12.1%) in the tranexamic acid group and 94 (12.1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0.79; 95% confidence interval [CI], 0.59 to 1.05). At 30 days, the rate of death from any cause was 6.0% in the aprotinin group, as compared with 3.9% in the tranexamic acid group (relative risk, 1.55; 95% CI, 0.99 to 2.42) and 4.0% in the aminocaproic acid group (relative risk, 1.52; 95% CI, 0.98 to 2.36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1.53 (95% CI, 1.06 to 2.22). CONCLUSIONS: Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery. (Current Controlled Trials number, ISRCTN15166455 [controlled-trials.com].).

Reduced mortality and strokes with off-pump coronary artery bypass grafting surgery in octogenarians.

BACKGROUND: Off-pump coronary artery bypass surgery (OPCAB) has been revived and has gained popularity, although the exact subsets of patients who might benefit most from this technique are unknown. The aim of this retrospective study was to compare the results of coronary artery bypass grafting surgery (CABG) in octogenarians using cardiopulmonary bypass (CPB) or OPCAB techniques. METHODS AND RESULTS: Over a 5-year period (1995-1999), 125 patients older than 80 years of age were operated for isolated myocardial revascularization (63 using CPB and 62 with OPCAB). There was no statistically significant difference in preoperative comorbidities between groups or in mean left ventricular ejection fraction (54.5+/-15.3% in the CPB group and 50.9+/-13.5% in the OPCAB group, respectively). The mean number of distal anastomosis per patient was 2.9 in CPB group and 2.6 in OPCAB group (P=ns). The majority of patients in both groups had unstable angina and were operated on an urgent basis. The operative mortality was 15.9% in the CPB group and 4.8% in the OPCAB group (P=0.04). There were 4 postoperative strokes (6.3%) in the CPB group and none (0%) in the OPCAB group (P=0.04). The percentage of patients transfused was 92.1% in the CPB group and 72.6% in the OPCAB group (P<0.01). Postoperative myocardial infarction occurred in 11.3% in the CPB group and 14.5% in the OPCAB group (P=NS). For all the parameters entered in the multivariate analysis with logistic regression model, the type of surgery (CPB or OPCAB) was an independent predictor of operative mortality and stroke (P=0.0375). The odds ratio (OR) indicates that operative mortality and stroke occur 4 times (OR=4.171) more often in CPB patients than in OPCAB patients. Follow-up showed no significant difference between the 2 groups in terms of cardiac events and mortality. CONCLUSIONS: This retrospective study suggests a benefit of OPCAB in terms of operative mortality and stroke for octogenarian patients when compared with CPB in our institution.

Inhaled epoprostenol (prostacyclin) and pulmonary hypertension before cardiac surgery.

OBJECTIVE: Pulmonary hypertension is commonly found in patients undergoing valvular surgery and can be worsened by cardiopulmonary bypass. Inhaled epoprostenol (prostacyclin) has been used for the treatment of pulmonary hypertension, but its effects compared with those of placebo on hemodynamics, oxygenation, echocardiographic examination, and platelet function have not been studied during cardiac surgery. METHODS: Twenty patients with pulmonary hypertension undergoing cardiac surgery were randomized in a double-blind study to receive inhaled epoprostenol (60 microg) or placebo. The inhalation occurred after induction of anesthesia and before surgical incision. The effects on left and right systolic and diastolic cardiac functions evaluated by means of pulmonary artery catheterization and transesophageal echocardiography, as well as oxygenation and platelet aggregation, were studied. RESULTS: Inhalation of epoprostenol significantly reduced indexed right ventricular stroke work from 10.7 +/- 4.57 g. m. m(-2) to 7.8 +/- 3.94 g. m. m(-2) (P =.003) and systolic pulmonary artery pressure from 48.4 +/- 18 mm Hg to 38.9 +/- 11.9 mm Hg (P =.002). The effect was correlated with the severity of pulmonary hypertension (r = 0.76, P =.01) and was no longer apparent after 25 minutes. There was no significant effect on systemic arterial pressures, left ventricular function, arterial oxygenation, platelet aggregation, and surgical blood loss. CONCLUSION: Inhaled epoprostenol reduces pulmonary pressure and improves right ventricular stroke work in patients with pulmonary hypertension undergoing cardiac surgery. A dose of 60 microg is hemodynamically safe, and its effect is completely reversed after 25 minutes. We did not observe any evidence of platelet dysfunction or an increase in surgical bleeding after administration of inhaled epoprostenol.

Can peripheral venous pressure be interchangeable with central venous pressure in patients undergoing cardiac surgery?

OBJECTIVE: Pressure measurements at the level of the right atrium are commonly used in clinical anesthesia and the intensive care unit (ICU). There is growing interest in the use of peripheral venous sites for estimating central venous pressure (CVP). This study compared bias, precision, and covariance in simultaneous measurements of CVP and of peripheral venous pressure (PVP) in patients with various hemodynamic conditions. DESIGN AND SETTING: Operating room and ICU of a tertiary care university-affiliated hospital. PATIENTS: Nineteen elective cardiac surgery patients requiring cardiopulmonary bypass were studied. INTERVENTIONS: A PVP catheter was placed in the antecubital vein and connected to the transducer of the pulmonary artery catheter with a T connector. Data were acquired at different times during cardiac surgery and in the ICU. MEASUREMENTS AND RESULTS: A total of 188 measurements in 19 patients were obtained under various hemodynamic conditions which included before and after the introduction of mechanical ventilation, following the induction of anesthesia, fluid infusion, application of positive end expiratory pressure and administration of nitroglycerin. PVP and CVP values were correlated and were interchangeable, with a bias of the PVP between -0.72 and 0 mmHg compared to the CVP. CONCLUSIONS: PVP monitoring can accurately estimate CVP under various conditions encountered in the operating room and in the ICU.

Increased early postoperative morbidity with off-pump coronary artery bypass grafting surgery in patients with diabetes.

BACKGROUND: Patients with diabetes constitute a high-risk population for myocardial revascularization due to extensive coronary disease. OBJECTIVE: To compare the early postoperative outcomes of patients with diabetes undergoing off-pump or on-pump coronary artery bypass surgery. METHODS AND RESULTS: Over a four-year period (1995 to 1998), 885 diabetics were operated for primary isolated coronary bypass; 156 patients had off-pump and 729 had on-pump coronary artery bypass surgery. Patients in the off-pump group were significantly older, had a higher incidence of hypertension and renal failure, and received fewer distal anastomoses (2.7 versus 2.9, P=0.004). Postoperative myocardial infarction, reintubation and postoperative use of intra-aortic balloon pump occurred significantly more frequently in the off-pump group (10.3% versus 5.5%, P=0.04; 8.3% versus 3.6%, P=0.03; 7.7% versus 1.5%, P=0.0001, respectively). Multivariate analysis revealed that type of surgery was an independent predictor of these complications, which occurred 1.9, 2.7 and 7.9 times more often, respectively, in the off-pump group. The 30-day mortality rate was not significantly different between the groups. CONCLUSIONS: Off-pump coronary artery bypass surgery is associated with an increased early postoperative morbidity in patients with diabetes and, thus, should be used with caution.

Randomized trial comparing off-pump to on-pump coronary artery bypass grafting in high-risk patients.

OBJECTIVE: The subset of patients most likely to benefit from off-pump coronary artery bypass grafting (CABG) remains a controversial issue, but the technique has been proposed to decrease postoperative mortality and morbidity. Th e objective of this study was to compare off-pump to onpump CABG in patients with known risk factors for mortality and morbidity. METHODS: Between October 2001 and September 2002, 65 high-risk patients were prospectively randomized to undergo off-pump or o n-pump CABG. Recruited patients had at least 3 of the following criteria: age greater than 65 years, high blood pressure, diabetes, serum creatinine greater than 133 mol/L, left ventricular ejection fraction lower than 45%, chronic pulmonary diseas e, unstable angina, congestive heart failure, repeat CABG, anemia, and carotid atherosclerosis. Hospital mortality and morbidity were the primary end-points of the study. RESULTS: Six patients (9%) crossed over from the original randomized group. Twenty-eight patients averaging 70 +/- 8 years of age underwent 3 +/- 1 grafts off pump, and 37 patients averaging 70 +/- 6 years of age underwent 3.4 +/- 1 grafts on pump. Revascularization was considered complete in 21 (7 5 %) of off-pump patients compared to 33 (89%) of onpump patients (P =.1). There were no hospital deaths in off-pump patients, and 2 patients (5%) undergoing onpump CABG died early following surgery (P =.2). Two offpump (7%) compared to 11 on-pump (30%) of patients presented composite end-points including death, neurological injury, renal failure, respiratory failure, and operative myocardial infarction after CABG (P =.02). CONCLUSION: The present study suggests that off-pump CABG, when technically feasible, significantly reduces morbidity following surgery in a group of high-risk patients.

Importance of relative pulmonary hypertension in cardiac surgery: the mean systemic-to-pulmonary artery pressure ratio.

OBJECTIVE: To determine the importance of the mean arterial pressure-to-mean pulmonary artery pressure ratio (MAP/MPAP) in cardiac surgical patients. DESIGN: Retrospective and prospective studies (3 groups). SETTING: Tertiary care hospital. PARTICIPANTS: Cardiac surgical patients (1,557). INTERVENTION: Retrospective analysis (group 1), induction of general anesthesia (group 2), and transesophageal Doppler echocardiography (group 3). MEASUREMENTS AND MAIN RESULTS: In group 1 (n = 1,439), demographic, hemodynamic, and other perioperative variables were collected with follow-up until hospital discharge. The primary outcome was a composite index of hemodynamic complications that included death, resuscitated cardiac arrest, use of vasopressive drugs for >24 hours postoperatively, or the use of an intra-aortic balloon pump that was not present preoperatively. In group 2 (n = 34), the effect of general anesthesia on the MAP/MPAP ratio was studied, and Doppler echocardiography was used to evaluate diastolic profiles in group 3 (n = 74). In group 1, a total of 302 patients experienced hemodynamic complications (21%). The MAP/MPAP ratio was significantly lower in the patients who developed complications (3.3 +/- 1.3 v 4.0 +/- 1.4, p < 0.0001). Multiple stepwise logistic regression analysis showed the MAP/MPAP ratio to be an independent predictor of hemodynamic complications (p < 0.0001). In group 2, the induction of anesthesia decreased both MAP and MPAP, but the ratio remain unchanged (p = 0.242). In group 3, patients with moderate-to-severe diastolic dysfunction (DD) had a lower ratio (3.5 +/- 0.9 v 4.0 +/- 1.1 compared with those with normal-to-mild DD, p = 0.07). CONCLUSION: The MAP/MPAP ratio is a useful hemodynamic variable in cardiac surgery. It can be used to predict hemodynamic complications after cardiac surgery, is not influenced by the induction of anesthesia, and tends to correlate with the severity of left ventricular diastolic profiles.

A pilot trial evaluating the clinical effects of prolonged storage of red cells.

The clinical consequences of prolonged storage of red cells have not been established. In this pilot study, we evaluated whether it would be feasible to provide a continuous supply of red cells stored <8 days. In addition, we examined the potential benefits attributed to "fresh" as compared to standard red cells in 66 critically ill and cardiac surgical patients. Nine patients were issued red cells but were not transfused. From the 57 remaining patients, the number of units transfused averaged 5.5 +/- 8.43 red cell units in the experimental group compared to 3.3 +/- 3.27 red cell units in the standard group (P = 0.25). The median storage time was 4 days in the experimental group compared to 19 days in the standard group (difference of 15 days; interquartile range of 12-16 days; P < 0.001). Overall, 73% of patients received red cells with storage times that corresponded to the treatment allocation more than 90% of the time. The group receiving red cells <8 days old tended to be older on average (68 +/- 8.54 yr versus 63 +/- 15.30 yr; P = 0.13) and have more comorbid illnesses (85% versus 65%; P = 0.09). In total, 27% of patients in the experimental group died or had a life-threatening complication as compared to 13% in the standard group (P = 0.31). There were no differences in prolonged respiratory, cardiovascular, or renal support after randomization (P > 0.05). A large clinical trial comparing red cell storage times is feasible and warranted given the limited available evidence.

Magnesium potentiates neuromuscular blockade with cisatracurium during cardiac surgery.

PURPOSE: Magnesium potentiates the effect of nondepolarizing neuromuscular blocking agents. It is used in cardiac anesthesia to prevent hypertension and arrhythmias. This study was performed to measure the interaction between magnesium and cisatracurium in cardiac surgery. METHODS: Twenty patients scheduled for elective cardiac surgery were randomly assigned to receive magnesium sulfate (70 mg x kg(-1) at induction followed by 30 mg x kg(-1) x hr(-1)) or placebo. The ulnar nerve was stimulated and the electromyographic response of the adductor pollicis was measured. Cisatracurium 0.1 mg x kg(-1) was given at induction, followed by 0.05 mg x kg(-1) when the first twitch in the train-of-four reached 25%. RESULTS: Ionized magnesium was 1.32 +/- 0.24 mmol x L(-1) in the treatment group vs 0.47 +/- 0.4 mmol x L(-1) in the control group. Duration of action of the intubating dose was longer in the magnesium group (74 +/- 20 min) than in the placebo group (42 +/- 6 min, P = 0.0001). Duration of the first maintenance dose was 69 +/- 16 min in the magnesium group vs 35 +/- 7 min in the placebo group (P = 0.0001). Total dose of cisatracurium administered throughout surgery was 0.19 +/- 0.07 mg x kg(-1) in the magnesium group compared with 0.29 +/- 0.01 mg x kg(-1) in the placebo group (P = 0.017). Hemodynamic variables and temperature were similar in both groups. CONCLUSION: In patients undergoing cardiac surgery, administration of magnesium sulfate, resulting in ionized levels of 1.3 mmol x L(-1), results in a 30-35 min prolongation of the neuromuscular blockade induced with intubating and maintenance doses of cisatracurium and does not alter hemodynamic stability.

Vasopressin for treatment of shock following aprotinin administration.

PURPOSE: To describe the utility of vasopressin in the treatment of acute distributive shock clinically compatible with the diagnosis of aprotinin anaphylaxis. CLINICAL FEATURES: A 57-yr-old female patient underwent repeat cardiac surgery to treat prosthetic valve endocarditis. She had received aprotinin during her first surgery 60 days ago. Despite a negative test dose of i.v. aprotinin 20,000 KIU, when aprotinin loading was initiated during the repeat surgery, the patient developed bronchospasm and hypotension secondary to acute distributive shock. Bronchospasm responded to inhaled salbutamol and ipatropium. The hypotension was refractory to high doses of phenylephrine. Two doses of i.v. vasopressin 5 U reversed the vasodilation and reestablished normal blood pressure. CONCLUSION: Vasopressin, in association with alpha-agonists, can reverse acute refractory distributive shock following aprotinin administration.