NoBlood

Magazine: Chest 08/01/05

Cardioprotective effects of acute normovolemic hemodilution in patients undergoing coronary artery bypass surgery *.(clinical investigations)


Study objectives: We hypothesized that lowering blood viscosity with acute normovolemic hemodilution (ANH) would confer additional cardioprotection in patients undergoing coronary artery bypass surgery (CABG) with aortic cross-clamping.

Design: In a prospective, randomized controlled trial, we studied the efficacy of ANH in anesthetized patients prior to cardiopulmonary bypass for the prevention of myocardial injuries.

Setting: Cardiac surgical center in a university hospital.

Patients and methods: Patients scheduled to undergo elective CABG entered the study protocol and were randomly allocated to one of two groups: ANH (n = 43 patients) or standard care management (n = 41 patients). In the ANH group, the whole-blood/colloid exchange was aimed to achieve a hematocrit value of 28%. All patients were managed with standard myocardial preservation techniques including cold-blood cardioplegia and anesthetic preconditioning. The outcome measures included the release of myocardial enzymes (plasma troponin I and creatinine phosphokinase), perioperative hemodynamic changes, need for pharmacologic cardiovascular support, and cardiac complications.

Results: In the hemodilution group, the postoperative release of troponin I (mean peak plasma concentration, 1.4 ng/mL; 95% confidence interval, 1.0 to 1.8) and myocardial fraction of creatine kinase (mean, 29 U/L; 95% confidence interval, 23 to 35) were significantly lower than in the control group (mean, 3.8 ng/mL; 95% confidence interval, 3.2 to 4.5; and 71 U/L; 95% confidence interval, 53 to 89). Requirement for inotropic support was significantly lower in the protocol patients (7 of 41 patients vs 15 of 39 patients), and fewer patients presented with either atrial fibrillation, atrioventricular conduction blockade, or combined disorders (12 of 41 patients vs 26 of 39 patients, p < 0.05).

Conclusions: In addition to conventional myocardial preservation techniques, preoperative ANH achieved further cardiac protection in patients undergoing on-pump myocardial revascularization.

Key words: cardiac surgery; cardiopulmonary bypass; coronary artery disease; hemodilution; troponin; myocardial ischemia

Abbreviations: ANH = acute normovolemic hemodilution; CABG = coronary artery bypass surgery; CPB = cardiopulmonary bypass

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In the Western world, coronary artery bypass surgery (CABG) is one of the most frequently performed major operations and is highly effective in improving life expectancy and quality of life in patients with coronary artery disease. (1) Although the number of surgical procedures will continue to decline along with the advances in interventional cardiology, the proportion of higher-risk patients requiring complex surgical procedures will likely continue to increase in the near future. (2) Moreover, in spite of improvements in surgical, anesthetic, and perfusion techniques, a wide spectrum of perioperative ischemic myocardial injuries still result in significant cardiac morbidity complications including contractile dysfunction, myocardial infarction, and low output syndrome requiring prolonged intensive care. (3,4)

Over the last 2 decades, the potential benefits of avoiding homologous blood transfusion and optimizing oxygen delivery in vital organs have led to a renewed interest for acute normovolemic hemodilution (ANH) in major surgery. (5) With this technique, the adequacy of tissue oxygenation and organ function is maintained by compensatory increases in cardiac output, improved blood flow distribution, and higher oxygen extraction ratios. (5-7) In the myocardium, hemodilution-induced lowering of blood viscosity is thought to facilitate blood flow through stenotic and collateral vessels, thereby counteracting the reduced blood oxygen-carrying capacity. (8) To date, although ischemic cardiac dysfunction has not been detected during moderate normovolemic hemodilution (reduction of hemoglobin concentrations to 90 g/L or hematocrit levels of 28%) even in anesthetized patients with coronary artery disease, (9,10) clinical outcome benefits (or adverse events) have not been thoroughly investigated in high-risk patients for myocardial ischemia.

In this study, we hypothesized that ANH afforded cardioprotective effects in patients undergoing CABG. Indeed, improved rheologic blood flow conditions might restore an optimal balance between flow and metabolic demand within the myocardium before the obligatory period of ischemia associated with aortic cross-damping. Therefore, we designed a randomized controlled trial in patients undergoing elective on-pump coronary revascularization procedures and evaluated the protective potential of moderate hemodilution vs standard management. Myocardial injuries were assessed postoperatively by determination of the release of myocardial enzymes (troponin I and creatine kinase), ECG changes, and the need for pharmacologic interventions.

MATERIALS AND METHODS

Selection of Patients and Sample Size

After approval by the local Ethics Committee, written informed consent was obtained from all patients scheduled for elective CABG and thought to meet the eligibility criteria. Inclusion criteria were as follows: a screening hemoglobin concentration > 120 g/L in men or 110 g/L in women; stable angina (classes I and II of the Canadian Cardiology Society); left ventricular ejection fraction > 30%; and absence of significant coexistent diseases, namely, valvular disease, recent myocardial infarct ( < 6 weeks), significant carotid stenosis (> 70%) or recent stroke ( < 3 weeks), renal insufficiency (estimated creatinine clearance < 20 mL/min), chronic respiratory disease (arterial oxygen pressure > 7 kPa on room air), liver insufficiency (aspartate transaminase or alanine transaminase two or more times the upper range), and uncontrolled hypertension or diabetes mellitus.

Samples sizes were calculated for a two-sided significance level of [alpha] = 0.05 and a power of 1-[beta] = 0.8 to detect a difference of 0.5 [micro]g/L in troponin I concentrations between the two groups. In a preliminary assessment including cardiac surgical patients, the SD of postoperative troponin I measurements was 0.8; thus, the number of subjects required was 38 per group.

Randomization and Masking

Eligible patients were randomized to one of the two groups: the ANH group and the standard care group. The allocations were generated from random-number tables by an independent observer and concealed in sealed envelopes. Although intraoperative masking was not possible in the ICU, the attending physicians and nurses were blinded to the treatment group.

Trial Protocol

Anesthesia and Surgical Procedure: On the morning of surgery, the patients were premedicated (morphine, 0.1 mg/kg; midazolam, 7.5 nag) and received their usual cardiac drug regimen, except aspirin, diuretics, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers, which were withdrawn at least 24 h before surgery. In the operating theater, cannulae were inserted in a peripheral vein, a radial artery, and the right jugular vein. Standard monitoring included pulse oximetry, leads II and [V.sub.5] of the ECG for heart rate and automated ST-segment trend analysis, continuous measurements of mean arterial and central venous pressures, nasopharyngeal temperature, end-tidal capnography, bispectral analysis of the EEG (BIS A-2000 XP; Aspect Medical Systems; De Meern, the Netherlands), as well as transesophageal echocardiography (Philips Sonos 5500; Philips Medical Systems; Andover, MA).

A balanced anesthetic technique included sufentanyl (bolus of 0.5 to 0.9 [micro]g/kg followed by 0.4 to (see link): http://www.highbeam.com/library/doc3...eePremium=BOTH