This prospective study included 164 consecutive patients who underwent cardiac surgery with CPB from November 2008 through November 2009 at the Hospital Clinico Universitario of Santiago de Compostela (Spain). We included all patients who underwent coronary surgery (isolated coronary surgery or coronary surgery plus valvular surgery) and noncoronary surgery (isolated valvular surgery) during this time period. We excluded patients who had undergone any type of transplantation procedure; patients who were being treated with corticosteroids or immunosuppressants; patients who had infections, active tumors, autoimmune diseases, or acute renal failure; and patients who were undergoing surgery on an emergency basis.
The 164 patients included in the study were divided into 2 study groups: group A (n = 60) included patients with elevated preoperative levels of IL-6; and group B (n = 104) included patients with normal preoperative IL-6 levels. Each group was subdivided according to whether patients were (group 1) or were not (group 2) treated preoperatively with statins. Thus, the study groups were as follows: group A1 (n = 40), group A2 (n = 20), group B1 (n = 56), and group B2 (n = 48).
All group 1 patients (those in groups A1 and B1) had dyslipidemia and were treated with statins for a minimum of 3 weeks before surgery. In this group, statins were administered in accordance with routine protocols, and, as usual, were administered the night before surgery. After surgery, statin treatment continued throughout the entire hospitalization period. In both groups, antiplatelet agents were discontinued 10 days before surgery. Other medications were not administered on the morning of surgery. The study protocol was approved by the local ethics committee. Informed consent was obtained from each of the patients included in the study.
Surgical Procedure and Postoperative Care
Anesthesia induction and maintenance were similar for all patients and consisted of weight-appropriate doses of midazolam, vecuronium bromide, remifentanil, and sevoflurane. During the surgical procedure, the following values were monitored using a Datex-Ohmeda Aestiva 3000® standard anesthesia device with an AS/3 monitor® (Datex-Ohmeda Instrumentarium Corp.; Helsinki, Finland): systemic and pulmonary blood pressure, central venous pressure, esophageal and urethral temperature, and ventilation capacity. Pulse oximetry and 5-lead electrocardiography were also used throughout the procedure. All patients underwent valvular surgery or CABG with CPB, with induction of mild hypothermia (between 32 and 33 °C) and electromechanical arrest of the heart by aortic clamping and the intermittent administration (every 20 minutes) of cold-blood cardioplegic solution.
We used a Stöckert SIII® extracorporeal circulation machine (Stöckert Instrumente GmbH; Munich, Germany) that was equipped with an SCP Revolution® centrifugal pump (Stöckert) and an attached SIII® heat exchanger (Stöckert). Before connection to the extracorporeal circulation, the patients were given 3 mg/kg of sodium heparin; an activated coagulation time of above 300 seconds was maintained during the entire procedure. Additional doses of heparin were used as necessary. A Dideco D903 Avant® membrane oxygenator (Dideco S.p.A.; Modena, Italy) was used; the circuit was primed with a base of 1,000 mL of lactated Ringer's crystalloid solution, 0.5 mg/kg of mannitol, 100 mL of 1 M sodium bicarbonate, and 0.5 mg/kg of sodium heparin.
The surgical approach was always performed through a standard median sternotomy. In patients with ischemic heart disease, venous or arterial grafts (or both) were used for coronary revascularization. The ascending aorta and the right atrium were cannulated in the usual manner. Two cannulae were used in the right atrium for mitral- and tricuspid-valve disease interventions, as well as a single cavoatrial cannula for coronary and aortic procedures.
At the end of the surgical procedures, the patients were transferred to the recovery unit, where they remained sedated with propofol, morphine, and midazolam (administered as needed). The patients remained intubated and connected to a mechanical ventilator set in synchronized intermittent mandatory ventilation mode between 6 and 10 mL/kg at a respiratory rate of 12 breaths/min; the positive end-expiratory pressure set between 5 and 7 cmH2O, with a trigger between –1 and 1 cmH2O; and the fraction of inspired oxygen adjusted according to arterial blood gas analysis. The minimum mechanical ventilation time was 6 hours; after 6 hours, patients with suitably stable hemodynamic, ventilation, oxygenation, and temperature conditions were extubated. Hemodynamic monitoring was maintained for at least the first 12 hours of the postoperative period.
Blood Sample Collection, Storage, and Analysis
The following biochemical values were measured at baseline (before the surgical intervention) and after surgery once the patients were stabilized: erythrocyte sedimentation rate, iron, transferrin, ferritin, thyroid-stimulating hormone, total bilirubin, serum oxaloacetic transaminase, serum glutamic pyruvic transaminase, gamma-glutamyl transferase, alkaline phosphatase, hematocrit, creatinine, and blood urea nitrogen.
Interleukin-6 serum levels were determined in venous blood samples at the following time points: before anesthesia induction; at the end of the CPB surgery; 6 and 24 hours after surgery, and before discharge from the hospital, when the patient was in stable condition.
The samples of blood for IL-6 determination were collected via venipuncture in tubes with ethylenediaminetetraacetic acid (EDTA) and immediately centrifuged at 4 °C and stored at −20 °C until analysis. The IL-6 was measured using the IMMULITE® DCP® system (Siemens AG; Erlangen, Germany), which is an enzyme immunometric assay that uses solid-phase chemiluminescence in conjunction with the IMMULITE® DCP® automatic analyzer and is designed for the quantitative measurement of interleukins.
The qualitative data are expressed in absolute numbers (percentages). The quantitative data are presented as the average values ± SD; the median value (interquartile range) is given as well (or instead), when the distribution of the variable values is markedly outside of the normal distribution as shown by the Kolmogorov-Smirnoff and Shapiro-Wilks tests. Univariate analyses were performed to compare the variables obtained in the patient groups that had received (groups A1 and B1) or had not received (groups A2 and B2) preoperative statins. For comparison of quantitative data, Student's t test (parametric) or the Mann-Whitney U test (nonparametric) was used as appropriate. Comparison of the qualitative data was performed using the χ2 test, applying the Yates correction to obtain the most conservative results.
The data were analyzed with the SPSS statistical package for Windows, version 15.0 (IBM Corporation; Armonk, NY). P values of less than 0.05 were considered statistically significant.