Methylprednisolone prevents inflammatory reaction occurring during cardiopulmonary bypass: effects on TNF-alpha, IL-6, IL-8, IL-10. Synergistic immunosuppression caused by high-dose methylprednisolone and cardiopulmonary bypass. Effect of dexamethasone on atrial fibrillation after cardiac surgery: prospective, randomized, double-blind, placebo-controlled trial. Stress doses of hydrocortisone in high-risk patients undergoing cardiac surgery: effects on interleukin-6 to interleukin-10 ratio and early outcome. Stress doses of hydrocortisone reduce chronic stress symptoms and improve health-related quality of life in high-risk patients after cardiac surgery: a randomized study. Hemofiltration but not steroids results in earlier tracheal extubation following cardiopulmonary bypass: a prospective, randomized double-blind trial. Complement activation during cardiopulmonary bypass: quantitative study of effects of methylprednisolone and pulsatile flow. Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass. Does steroid pretreatment increase endotoxin release during clinical cardiopulmonary bypass? Effect of methylprednisolone on myocardial preservation during coronary artery surgery. Reducing the effects of the systemic inflammatory response to cardiopulmonary bypass: can single dose steroids blunt systemic inflammatory response syndrome? The effects of glucocorticoid therapy on inflammatory responses to coronary artery bypass graft surgery. Pulmonary effects of methylprednisolone in patients undergoing coronary artery bypass grafting and early tracheal extubation. The effect of dexamethasone on side effects after coronary revascularization procedures. Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery. Corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial. Effects of different steroid treatment on reperfusion-associated production of reactive oxygen species and arrhythmias during coronary surgery. Complement activation during cardiopulmonary bypass. Comparison of bubble and membrane oxygenators. Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery. Steroids and myocardial preservation. Pulse low dose steroids attenuate post-cardiopulmonary bypass SIRS; SIRS I. Effect of low-dose methyl prednisolone on serum cytokine levels following extracorporeal circulation. Effects of methylprednisolone and a biocompatible copolymer circuit on blood activation during cardiopulmonary bypass. Effects of dexamethasone on intravascular and extravascular fluid balance in patients undergoing coronary bypass surgery with cardiopulmonary bypass. The effects of aprotinin and steroids on generation of cytokines during coronary artery surgery. Effects of dexamethasone on pulmonary and renal functions in patients undergoing CABG with cardiopulmonary bypass. Influence of steroids on complement and cytokine generation after cardiopulmonary bypass. Influence of methylprednisolone on levels of neuron-specific enolase in cardiac surgery: a corticosteroid derivative to decrease possible neuronal damage. Cardiopulmonary and systemic effects of methylprednisolone in patients undergoing cardiac surgery. Glucocorticoid effects on the inflammatory and clinical responses to cardiac surgery. Does high-dose methylprednisolone in aprotinin-treated patients attenuate the systemic inflammatory response during coronary artery bypass grafting procedures? Minor infection encouraged by steroid administration during cardiac surgery. The effect of methylprednisolone treatment on the cardiopulmonary bypass-induced systemic inflammatory response. Cardiopulmonary bypass, steroid administration, and surgical injury synergistically impair memory T cell function and antigen presentation. Dexamethasone decreases the pro- to anti-inflammatory cytokine ratio during cardiac surgery. Myocardial and lung injury after cardiopulmonary bypass: role of interleukin (IL)-10. Effect of methylprednisolone on endotoxemia and complement activation during cardiac surgery. Dexamethasone decreases the incidence of shivering after cardiac surgery: a randomized, double-blind, placebo-controlled study. The effects of steroids on the occurrence of postoperative atrial fibrillation after coronary artery bypass grafting surgery: a prospective randomized trial. The effect of oral prednisolone with chronic obstructive pulmonary disease undergoing coronary artery bypass surgery. Morbidity associated with systemic corticosteroid preparation for coronary artery bypass grafting in patients with chronic obstructive pulmonary disease: a case control study. Methylprednisolone does not benefit patients undergoing coronary artery bypass grafting and early tracheal extubation. Reducing the post-pump syndrome by using heparin-coated circuits, steroids, or aprotinin. Inhibition by dexamethasone of the reperfusion phenomena in cardiopulmonary bypass. The effects of methylprednisolone on the complications of coronary artery surgery. Preoperative administration of steroids: influence on adhesion molecules and cytokines after cardiopulmonary bypass. Effect of methylprednisolone on the oxidative burst activity, adhesion molecules and clinical outcome following open heart surgery. Influence of aminosteroid and glucocorticoid treatment on inflammation and immune function during cardiopulmonary bypass. The acute cardioprotective effect of glucocorticoid in myocardial ischemia-reperfusion injury occurring during cardiopulmonary bypass.
This study examined the correlation between tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-8, IL-10 and methylprednisolone pretreatment.
                This is a prospective, randomized and double-blinded study. Sixty patients undergoing coronary artery bypass grafting (CABG) were randomized to receive either intravenous methylprednisolone (n = 30, Group M) or intravenous placebo (n = 30, Group S). The patients received intravenously either 30 mg/kg methylprednisolone (Group M) or placebo (Group S) 10 min before and after cardiopulmonary bypass (CPB). In an intensive care unit (ICU), four additional doses were given at 6-hourly intervals. Blood samples for the measurements of TNF-alpha, IL-6, IL-8 and IL-10 were obtained before induction of anaesthesia (T0 = control value), after induction (T1), before starting CPB (T2), after aortic declamping (T3), at the end of CPB (T4) and 6 hours (T5), 12 hours (T6) and 24 hours (T7) after skin closure. Creatine kinase (CK) and creatine kinase isoenzyme MB (CK-MB) were evaluated at the following intervals: T0, T5, T6 and T7.
                When compared with the control value, TNF-alpha, IL-6 and IL-8 significantly increased in Group S and Group M (p < 0.05), but these values were significantly greater in Group S than in Group M (p < 0.05). In comparison with the control value, IL-10 increased in both groups (p < 0.05), but was significantly greater in Group M than in Group S (p < 0.05). CK and CK-MB were increased in both groups in postoperative values compared to control values. In Group S, CK and CK-MB levels were significantly lower than in Group M (p < 0.05).
                In this study, we have found that preoperative administration of methylprednisolone has decreased TNF-alpha, IL-6 and IL-8 release, and increased the perfusing IL-10 levels after CPB. Thus, methylprednisolone may decrease the inflammatory response during the CPB procedure. Steroid use during cardiac operations may reduce the risk of postperfusion lung syndrome, but both cardiopulmonary bypass and steroids are immunosuppressive. The synergistic effects of the bypass and steroids on patients' immunologic activities, hemodynamics, and metabolisms during and after heart operations have not been clarified systematically.
                Twenty-four patients undergoing valve replacement were studied in a randomized, double-blind trial. Twelve of these patients (S group) received bolus methylprednisolone, 20 mg/kg body weight, and the remaining 12 patients (C group) received a placebo intravenously before and after bypass. Blood cell count, C-reactive protein, lymphocyte surface markers (CD3, CD4, CD8, CD16, and CD20), phytohemagglutinin response, interleukin-2 production, and natural killer cell activity were examined on admission through day 7. Cardiac output, blood gas, electrolyte, lactate, and serum glucose levels were examined perioperatively.
                The peak white blood cell count in the S group was higher than that in the C group (analysis of variance: p [group] = 0.0436). The peak C-reactive protein level was higher in the C group than in the S group (p [group] < 0.0001). From the analysis of the surface markers, the steroid increased the natural killer cells before and soon after bypass (p [group] = 0.0117), and later tended to increase the CD4+ T and B cells during the postoperative recovery period. The phytohemagglutinin response in both groups decreased after bypass (p [time] < 0.0001), but the steroid caused exaggerated decreases before (p < 0.01 by Student's t test) and soon after (p < 0.001) bypass in the S group (analysis of variance: p [group] = 0.0127). The interleukin-2 production was suppressed by bypass alone after the bypass in the C group, but was further suppressed by the steroid before and after bypass in the S group (p [group] = 0.0446). The cardiac index, water balance, electrolytes, arterial oxygen tension, and timing of extubation were not different between the groups. In contrast, the glucose (p [group] = 0.0486) and lactate (p [group] = 0.0525) levels were higher in the S group than those in the C group.
                T-cell functions are synergistically suppressed by cardiopulmonary bypass and high-dose methylprednisolone in heart operations. The hemodynamic benefits of the steroid are negligible, whereas glucose tolerance is worsened by the steroid during bypass. The purpose of this study was to assess the effect of preoperative dexamethasone (DEX) on the occurrence of postoperative atrial fibrillation (AF).
                Prospective, randomized, double-blind, placebo-controlled clinical trial.
                Tertiary referral center.
                Seventy-eight adult patients undergoing combined valve and coronary artery bypass graft (CABG) surgery were randomized to receive either DEX or placebo.
                The DEX group received dexamethasone, 0.6 mg/kg, after induction of anesthesia, and the placebo group received an equal volume of normal saline. Interleukin (IL)-6, -8, and -10; tumor necrosis factor alpha; and endothelin (ET)-1 were measured preoperatively and on postoperative days (POD) 1, 2, and 3. Complement (C-4) and C-reactive protein (CRP) were measured preoperatively and on POD 2. Exhaled nitric oxide (NO) was measured preoperatively, 15 minutes after aortic unclamping, and 1 hour after intensive care unit admission.
                No significant difference in the incidence of AF was found between the placebo (41%) and DEX groups (30%) (95% confidence interval [-11%, 34%); p = 0.31). DEX significantly reduced at least 1 postoperative level of IL-6, IL-8, IL-10, CRP, and exhaled NO. DEX did not affect ET-1 or C-4 levels. IL-10 on POD 3 was positively correlated with postoperative hospital length of stay (r = 0.30, p = 0.01). Increased levels of IL-8 and IL-10 on POD 1 were positively correlated with the intubation time (r = 0.31, p = 0.01; r = 0.30, p = 0.01, respectively). Conversely, C-4 on POD 2 was negatively correlated with the intubation time and intensive care unit length of stay (r = -0.32, p = 0.006; r = -0.30, p = 0.01, respectively).
                DEX did not affect the incidence of AF in patients undergoing combined CABG and valve surgery. However, it did modulate the release of several inflammatory and acute-phase response mediators that are associated with adverse outcomes. Severe systemic inflammation (systemic inflammatory response syndrome) associated with cardiac surgery often leads to a worse short-term and long-term outcome. Stress doses of hydrocortisone have been successfully used to improve outcome of CS. The interleukin (IL)-6 to IL-10 ratio is associated with outcome after trauma and major surgery.
                To evaluate immunologic effects (especially IL-6 to IL-10 ratio) of stress doses of hydrocortisone in a high-risk group of patients after cardiac surgery with cardiopulmonary bypass.
                Prospective, randomized, double-blinded, placebo-controlled trial.
                Cardiovascular intensive care unit of a university hospital.
                High-risk patients (n = 36) undergoing CS.
                Stress doses of hydrocortisone or placebo.
                IL-6 to IL-10 ratio and other markers of systemic inflammation at predefined time points; short-term clinical outcome.
                The two study groups did not differ with regard to demographic data. The patients from the hydrocortisone group (n = 19) had significantly lower levels of IL-6 and higher levels of IL-10, resulting in an attenuated change in IL-6/IL-10 ratio (28.7 [6.4/128.7] vs. 292.8 [6.5/534.6] 4 hours after cardiopulmonary bypass; p < 0.001). Patients in the hydrocortisone group had a shorter duration of catecholamine support (1 [1/2] vs. 4 [2/4.5] days; p = 0.02), a shorter length of stay in the intensive care unit (2 [2/3] vs. 6 [4/8] days; p = 0.001), and a lower incidence of postoperative atrial fibrillation (26% vs. 59%; p = 0.04).
                Stress doses of hydrocortisone attenuate the evolution of IL-6/IL-10 ratio in patients with systemic inflammatory response syndrome after CS, which seems to be associated with an improved outcome. The immunologic effects of hydrocortisone may thus be both, inhibitory (IL-6) and permissive (IL-10), regarding the immune response. Improvement in health-related quality of life is a major object of cardiac surgery. However, high stress exposure during the perioperative period of cardiac surgery can result in the formation of traumatic memories and symptoms of chronic stress or even posttraumatic stress disorder, which can have negative effects on health-related quality-of-life outcome. In this controlled study we examined whether exogenously administered stress doses of hydrocortisone during cardiac surgery reduce perioperative stress exposure and the long-term incidence of chronic stress symptoms and improve health-related quality of life after cardiac surgery.
                Thirty-six high-risk patients undergoing cardiac surgery were prospectively randomized to receive either stress doses of hydrocortisone or placebo. Of 28 available patients at 6 months after cardiac surgery, 14 had received hydrocortisone, and 14 had received placebo. Traumatic memories, chronic stress symptoms (posttraumatic stress disorder scores), and health-related quality of life were measured by using validated questionnaires.
                Compared with patients from the placebo group, patients from the hydrocortisone group had a significantly shorter duration of intensive care unit treatment, required lower doses of the stress hormone norepinephrine during cardiac surgery, and had significantly fewer stress symptoms and a better health-related quality of life regarding physical function, chronic pain, general health, vitality, and mental health during follow-up. The groups did not differ with regard to the number or type of intensive care unit-related traumatic memories.
                The use of stress doses of hydrocortisone in high-risk cardiac surgical patients reduces perioperative stress exposure, decreases chronic stress symptoms, and improves health-related quality of life at 6 months after cardiac surgery. Activation of the inflammatory cascade is thought to account for some of the respiratory dysfunction and prolonged mechanical ventilation associated with cardiopulmonary bypass. The objective of this investigation was to identify whether perioperative steroids or hemofiltration during cardiopulmonary bypass, by their attenuation of inflammation, would reduce duration of mechanical ventilation after cardiac surgery.
                After Institutional Review Board approval and informed consent, 192 patients scheduled to undergo elective primary coronary artery bypass grafting or valvular replacement or repair were randomized in a double-blind prospective study into three groups. One group (Control) received saline at induction and at 6-h intervals for four doses. Another group (Hemofil) received saline and hemofiltration to obtain 27 ml/kg of hemofiltrate. The final group (Steroid) received 1 g methylprednisolone before anesthesia induction and then 4 mg of dexamethasone at 6-h intervals for four doses. All patients underwent normothermic cardiopulmonary bypass and received propofol for postoperative sedation. Separate two-sample comparisons were performed to compare each experimental group versus the control group using the Wilcoxon rank sum test for continuous variables and Fisher exact test for categorical variables. In all cases, two-tailed P values </= 0.05 were considered statistically significant.
                The median time until the patient reached an intermittent mandatory ventilation of 4/min (258.5 versus 385.0 min, respectively; P = 0.02) and tracheal extubation (352.0 versus 518.0 min; P = 0.03) was significantly reduced for group Hemofil but no different for Steroid compared to Control.
                Hemofiltration and steroids are both previously reported to attenuate the inflammatory response but only hemofiltration reduced time to tracheal extubation for adults after cardiopulmonary bypass in this study. Forty four patients undergoing open heart surgery were divided into three groups. Group 1 (17 patients) underwent routine anaesthesia and surgery; group 2 (17 patients) received two doses of methylprednisolone (30 mg/kg), one during induction of anaesthesia and the other immediately before induction of cardiopulmonary bypass; and group 3 (10 patients) received pulsatile flow while undergoing pulsatile perfusion by the heart-lung machine. A modification of the previously described technique was used to detect and measure complement activation in plasma before and during the bypass period using crossed immunoelectrophoresis. About 45% of all patients showed measurable complement activation (greater than 4.5%) during cardiopulmonary bypass and the mean activation in this group was 6.4%. There was no significant difference between the three groups in complement activation. In group 2, however, women showed significantly more complement activation than men (p less than 0.05). It is suggested that neither corticosteroids nor pulsatile flow affect complement activation, but caution should be exercised in women receiving methylprednisolone. In cardiac surgery with cardiopulmonary bypass (CPB), corticosteroids are administered to attenuate the physiological changes caused by the systemic inflammatory response. The effects of corticosteroids on CPB-associated renal damage have not been documented. The purpose of this study was to evaluate the effects of dexamethasone on perioperative renal dysfunction in patients undergoing cardiac surgery with CPB.
                Renal damage was prospectively studied in 20 patients without concomitant morbidity undergoing coronary artery surgery with CPB. Patients were randomized in a double-blind fashion to receive dexamethasone or placebo. Markers of glomerular function (creatinine clearance) and damage (microalbuminuria), and markers of tubular function (fractional excretion of sodium and free water clearance) and damage (N-acetyl-beta-D glucosaminidase (NAG)) were evaluated in addition to plasma and urinary glucose levels. Plasma and urinary specimens were obtained at the following time periods: (1) baseline, during the 12 h before surgery; (2) skin incision before heparinization; (3) from heparinization until the end of CPB; (4) during the 2 h following weaning from CPB; (5) in the intensive care unit from 2 to 6 h after weaning of CBP; (6) and from 36 to 60 h after weaning of CPB.
                CPB was associated with an increase in markers in the placebo group, which returned to baseline during the second postoperative day, demonstrating a transient impairment of glomerular and tubular renal function. Similar patterns were observed in patients treated with dexamethasone. While postoperative glycosuria was significantly higher in the dexamethasone-treated group, no other differences between groups were observed.
                Dexamethasone administration before CPB has no protective effect on perioperative renal dysfunction in low-risk cardiac surgical patients. The mechanism involved in the endotoxemia frequently recognized during cardiopulmonary bypass remains unclear. It has also been suggested that endotoxin levels were higher in steroid-pretreated patients undergoing cardiopulmonary bypass.
                Twenty patients undergoing cardiopulmonary bypass were randomly pretreated with steroids (methylprednisolone, 30 mg/kg) or placebo. Blood samples for endotoxin measurement were drawn simultaneously from the superior and inferior venae cavae before heparin administration, 5 and 50 minutes after the onset of bypass, 5 minutes after aortic declamping, at the end of bypass, and 1, 2, and 20 hours after the end of cardiopulmonary bypass.
                The perioperative variables in the two groups were similar. Blood endotoxin levels were higher in the inferior vena cava than in the superior vena cava immediately after the onset of bypass. Endotoxin levels in inferior vena cava blood were significantly lower in steroid-pretreated patients than those in patients not receiving steroids.
                Endotoxin is released during cardiopulmonary bypass from the region drained by the inferior vena cava. Steroid pretreatment may actually reduce endotoxin release during bypass. It has been proposed that a single preoperative dose of a corticosteroid may protect the myocardium from ischemic injury during open heart surgery. To test this hypothesis, a prospective, randomized, double blind study was carried out in ninety-five patients undergoing coronary bypass surgery using intermittent ischemic arrest with systemic and local hypothermia. Half the patients received 2 gm (approximately 30 mg/kg) of methylprednisolone 2 hours prior to the initiation of cardiopulmonary bypass and the other half received a placebo. Postoperative electrocardiograms and blood levels of serum creatine phosphokinase (CPK), lactic dehydrogenase (LDH), and serum glutamic oxalacetic transaminase (SGOT) were compared in the two groups. No apparent difference was noted in the number of patients with significantly elevated levels of CPK, LDH, or SGOT or in the number with positive isoenzyme patterns of CPK and LDH. Moreover, there was no significant difference in the mean values of CPK, LDH, or SGOT between the two groups. The number of patients with electrocardiographic evidence of myocardial injury (10 per cent) was the same in both groups and no difference was noted in (1) the ease with which patients could be weaned from cardiopulmonary bypass, (2) postoperative arrhythmias, (3) postoperative bleeding, (4) postoperative respiratory insufficiency, and (5) length of hospital stay. It is concluded that a single preoperative dose of 2 gm of methylprednisolone offers no demonstrable protection to the myocardium from the effects of ischemia during coronary artery bypass surgery. The use of cardiopulmonary bypass (CPB) is associated with the development of a significant systemic inflammatory response syndrome (SIRS) which can affect patient outcomes. Multiple pathways are involved in initiating and maintaining SIRS. We studied whether a single dose of steroids (dexamethasone) after the induction of anesthesia could blunt the SIRS from CPB. A prospective, randomized, double-blinded, placebo control trial of 28 patients (13 study vs. 15 control). The study group received 100 mg of dexamethasone whereas the control group received sterile saline. Inclusion criteria were the following: elective coronary artery bypass grafting, less than 80 years old, normal ejection fraction, no acute myocardial infarction. Serum levels of C3a, interleukin (IL)-6, and plasma norepinephrine (PNE) were measured after intubation, 30 minutes after initiation of CPB, 24 and 72 hours after termination of bypass. The study group demonstrated significantly lower levels of IL-6 (p = 0.0005) at 24 hours and PNE (p = 0.05) at 72 hours post-CPB. There were no differences in the C3a levels between the groups. No infections occurred in either group. A single dose of dexamethasone reduces IL-6 and PNE levels associated with CPB. Despite the significant reductions in IL-6 and PNE, there was no effect on clinical outcomes. Additional studies are needed to demonstrate a clinically significant effect on patient outcomes. Delayed or reduced polymorphonuclear leukocyte (PMN) apoptosis may contribute to prolongation of systemic inflammation after cardiopulmonary bypass.
                Preoperative administration of glucocorticoids has been used ostensibly to attenuate the systemic inflammation associated with cardiopulmonary bypass. Therefore, this study evaluated, in patients undergoing cardiopulmonary bypass, the efficacy of glucocorticoids in restoring peripheral blood PMN apoptosis and modulating PMN surface receptors (CD95, tumor necrosis factor receptor [TNFR]) known to be involved in proapoptotic or antiapoptotic signal transduction.
                Randomized control study.
                Medical school and affiliated tertiary care hospital.
                Thirteen patients undergoing coronary artery bypass grafting.
                Patients were randomly assigned to the control group (n = 7) or to receive 1 g of methylprednisolone sodium succinate on anesthetic induction (n = 6).
                Blood samples were drawn before induction, 20 minutes after sternotomy and bypass, immediately postoperatively, and on postoperative day 1. Isolated PMNs were incubated for 6 hours with or without the CD95 agonist CH 11. Polymorphonuclear leukocyte apoptosis was measured using propidium iodide-RNAase staining and flow cytometry. Levels of PMN cell-associated receptors (TNFR and CD95), cytokines (TNF-alpha, interleukin 6 [IL-6], IL-8, and IL-10), and soluble receptors (sTNFR1 and sTNFR2) were measured.
                In all 13 patients, spontaneous and Fas-mediated PMN apoptosis decreased more than 80% from baseline (P<.001) by postoperative day 1. Polymorphonuclear leukocyte CD95 increased (P<.003) by postoperative day 1 compared with baseline, whereas PMN TNFR was unchanged. Methylprednisolone administration did not modulate PMN apoptosis or immunocyte receptor expression; however, such treatment did decrease postoperative IL-6 secretion (P<.001) and increase postoperative IL-10 secretion (P<.001).
                The complications of major surgery include persistent inflammation, which can lead to multisystem organ failure. Polymorphonuclear leukocyte resistance to apoptosis may contribute to this process. A single preoperative dose of glucocorticoids did not effect PMN apoptosis or receptor phenotype. Numerous clinical studies suggest that methylprednisolone may facilitate early tracheal extubation after cardiac surgery, yet no investigation has rigorously examined the use of the drug in this setting. In this prospective, randomized, double-blind, placebo-controlled study, we examined the pulmonary effects of methylprednisolone in patients undergoing coronary artery bypass grafting (CABG) and early tracheal extubation. Sixty patients undergoing elective CABG and early tracheal extubation were randomized into two groups. Group MP patients received i.v. methylprednisolone (30 mg/kg during sternotomy and 30 mg/kg during initiation of cardiopulmonary bypass) and Group NS patients received i.v. placebo at the same two times. Perioperative management was standardized. Alveolar-arterial (A-a) oxygen gradient, lung compliance, shunt, and dead space were determined four times perioperatively. Postoperative tracheal extubation was accomplished at the earliest appropriate time. Both groups exhibited significant postoperative increases in A-a oxygen gradient and shunt (P < 0.000001 for each group) and significant postoperative decreases in dynamic lung compliance (P < 0.000001 for each group). Patients in Group MP exhibited significantly larger increases in postoperative A-a oxygen gradient (P = 0.001) and shunt (P = 0.001) compared with patients in Group NS. Postoperative alterations in dynamic lung compliance, static lung compliance, and dead space were not statistically significant between the groups. The time to postoperative tracheal extubation was prolonged in Group MP patients compared with Group NS patients (769 +/- 294 vs 604 +/- 315 min, respectively; P = 0.05). Methylprednisolone was associated with larger increases in postoperative A-a oxygen gradient and shunt, was unable to prevent postoperative decreases in lung compliance, and prolonged extubation time, which indicate that use of the drug may hinder early tracheal extubation in patients after cardiac surgery. Implications: Traditionally, methylprednisolone has been administered to patients undergoing cardiac surgery to decrease postoperative pulmonary dysfunction. This study revealed that the drug is associated with larger increases in postoperative alveolar-arterial oxygen gradient and shunt and prolonged tracheal extubation time in patients undergoing coronary artery bypass grafting, which indicate that use of the drug may hinder early tracheal extubation. Corticosteroids decrease side effects after noncardiac elective surgery. We designed this randomized, double-blinded, placebo-controlled study to test the hypothesis that standard doses of dexamethasone (4 mg x2) would reduce postoperative nausea, vomiting, and pain, decrease the incidence of atrial fibrillation (AF), and improve appetite after cardiac surgery, thereby facilitating the recovery process. A total of 300 patients undergoing coronary revascularization surgery were enrolled in this clinical study. The anesthetic management was standardized in all patients. Dexamethasone (4 mg/mL) or saline (1 mL) was administered after the induction of anesthesia and a second dose of the same study drug was given on the morning after surgery. The incidence of AF was determined by analyzing the first 72 h of continuously recorded electrocardiogram records after cardiac surgery. The patients were assessed at 24- and 48-h intervals after surgery, as well as at the time of hospital discharge, to determine the incidence and severity of postoperative side effects (e.g., nausea, vomiting, pain) and patient satisfaction scores. Dexamethasone significantly reduced the need for antiemetic rescue medication on the first postoperative day (30% versus 42%), and the incidences of nausea (15% versus 26%) and vomiting (5% versus 16%) on the second postoperative day (P < 0.05). In addition, dexamethasone significantly reduced the percentage of patients with a depressed appetite on the second postoperative day. However, the corticosteroid failed to decrease the incidence of AF (27% versus 32%) or the total dosage of opioid analgesic medication administered in the postoperative period. We conclude that dexamethasone (8 mg in divided doses) was beneficial in reducing emetic symptoms and improving appetite after cardiac surgery. However, this dose of the corticosteroid does not seem to have antiarrhythmic or analgesic-sparing properties.
                Dexamethasone (8 mg IV) was beneficial in reducing emetic symptoms and increasing appetite after cardiac surgery. However, this dose of the corticosteroid failed to decrease postoperative pain or the incidence of new-onset atrial fibrillation. Whilst elevated urinary transforming growth factor beta-1 (TGFbeta) is associated with chronic renal dysfunction its role in acute peri-operative renal dysfunction is unknown. In contrast, peri-operative increases in urinary IL-1 receptor antagonist (IL-1ra) and TNF soluble receptor-2 (TNFsr-2) mirror pro-inflammatory activity in the nephron and correlate with renal complications. Steroids modulate some plasma cytokines (decreasing TNFalpha, IL-8, IL-6 and increasing IL-10), whereas ability to reduce plasma and urinary TNFsr-2 and IL-1ra and peri-operative renal injury is unknown. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were randomised to receive methylprednisolone (n = 18) or placebo (n = 17) before induction of anaesthesia. Plasma and urinary pro- and anti-inflammatory cytokine balance was determined along with subclinical proximal tubular injury and dysfunction, measured by urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha-1-microglobulin/creatinine ratios, respectively. In the control group compared with baseline, plasma IL-8, TNFalpha, IL-10, IL-1ra and TNFsr-2 were significantly elevated along with urinary IL-1ra, TNFsr-2 and TGFbeta1. Urinary NAG/creatinine and alpha-1-microglobulin/creatinine ratios rose from completion of revascularisation until 6 h with recovery at 24 h with a further rise in NAG/creatinine ratio at 48 h. Compared to placebo, the methylprednisolone group showed significantly reduced plasma IL-8, TNFalpha, IL-1ra and TNFsr-2 whereas plasma IL-10 increased. Compared to placebo, the methylprednisolone group demonstrated significantly reduced urinary NAG/creatinine ratio, TNFsr-2 and TGFbeta1 at 24 h whereas urinary alpha-1-microglobulin/creatinine ratios increased.
                Methylprednisolone administration during cardiac surgery significantly reduces plasma and urinary TNFsr-2 and IL-1ra, urinary TGFbeta1 and subclinical renal injury but not dysfunction.
                Copyright 2004 Elsevier Ltd. Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery. An exaggerated inflammatory response has been proposed to be one etiological factor.
                To test whether intravenous corticosteroid administration after cardiac surgery prevents AF after cardiac surgery.
                A double-blind, randomized multicenter trial (study enrollment August 2005-June 2006) in 3 university hospitals in Finland of 241 consecutive patients without prior AF or flutter and scheduled to undergo first on-pump coronary artery bypass graft (CABG) surgery, aortic valve replacement, or combined CABG surgery and aortic valve replacement.
                Patients were randomized to receive either 100-mg hydrocortisone or matching placebo as follows: the first dose in the evening of the operative day, then 1 dose every 8 hours during the next 3 days. In addition, all patients received oral metoprolol (50-150 mg/d) titrated to heart rate.
                Occurrence of AF during the first 84 hours after cardiac surgery.
                The incidence of postoperative AF was significantly lower in the hydrocortisone group (36/120 [30%]) than in the placebo group (58/121 [48%]; adjusted hazard ratio, 0.54; 95% confidence interval, 0.35-0.83; P = .004; number needed to treat, 5.6). Compared with placebo, patients receiving hydrocortisone did not have higher rates of superficial or deep wound infections, or other major complications.
                Intravenous hydrocortisone reduced the incidence of AF after cardiac surgery.
                clinicaltrials.gov Identifier: NCT00442494. During conventional cardiac surgery ischemia and reperfusion may cause excessive production of reactive oxygen species leading to tissue damage including early arrhythmias. We therefore assessed the kinetics of markers of radical stress including oxidized and reduced glutathione (GSSG/GSH), oxidized proteins (PCG) and malondialdehyde (MDA), and tested the hypothesis that different steroid treatments inhibit these markers and early reperfusion-associated supraventricular and ventricular extrasystolic beats.
                In a randomized, controlled, blinded, prospective trial 36 patients received a preoperative infusion of methylprednisolone (MP, 15 mg kg-1, n = 12), tirilazad mesylate (TM, 10 mg kg-1, n = 12) or placebo (PL, NaCl, n = 12). Coronary sinus and arterial blood was drawn at baseline and 2, 5, 15, 30, 60 and 240 min after aortic declamping. Holter-ECG analysis was used to identify arrhythmias.
                Cardiac GSSG release occurred very early (< 15 min) and was not significantly attenuated by either drug treatment. Cardiac PCG production showed biphasic increases, lasted > 4 h and was significantly reduced only by TM. Cardiac MDA release was short (< 30 min) and significantly reduced by MP and TM. Neither treatment had a significant influence on the early occurrence of ventricular or supraventricular arrhythmias. The number of patients needing cardioversions or defibrillations also were not different.
                The results indicate that cardiac production of reactive oxygen species occurs after reperfusion in humans and is not inhibited by steroid treatment. Steroid treatment effectively reduces lipid peroxidation during cardiac surgery but has no influence on arrhythmias. A prospective randomized trial involving 91 patients undergoing cardiopulmonary bypass compared the effects of bubble oxygenators (with and without methylprednisolone sodium succinate) and membrane oxygenators on complement activation and transpulmonary sequestration of leukocytes. Patients were divided as follows: Group I, 30 patients, bubble oxygenator; Group II, 31 patients, bubble oxygenator and methylprednisolone sodium succinate (30 mg/kg); Group III, 30 patients, membrane oxygenator. In Group I, C3a increased from 323 +/- 171 ng/ml during cardiopulmonary bypass to 1,564 +/- 785 ng/ml at 25 minutes after bypass (p less than 0.0001). A significant decrease in C3a was found in Groups II and III compared to Group I (p less than 0.0001). C5a did not change significantly during cardiopulmonary bypass in any group. Reestablishment of pulmonary circulation at the end of bypass produced significant transpulmonary leukocyte sequestration in Group I; the median cell difference was 1,700/microliter. Transpulmonary sequestration was significantly (p less than 0.0001) less in Group II (median cell difference = 200/microliter) and in Group III (median cell difference = 400/microliter) than in Group I. We conclude that cardiopulmonary bypass with a bubble oxygenator alone initiates significantly (p less than 0.0001) more C3a activation and leukocyte sequestration than when methylprednisolone sodium succinate (30 mg/kg) is given 20 minutes before the start of cardiopulmonary bypass with a bubble oxygenator or when a silicone membrane oxygenator is used. Severe systemic inflammation with a vasodilatory syndrome occurs in about one third of all patients after cardiac surgery with cardiopulmonary bypass. Hydrocortisone has been used successfully to reverse vasodilation in septic patients. We evaluated if stress doses of hydrocortisone attenuate severe systemic inflammatory response syndrome in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass.
                Randomized, nonblinded, controlled trial.
                Anesthesiologic intensive care unit for cardiac surgical patients of an university hospital.
                After a risk analysis, we enrolled 91 patients into a prospective randomized trial. Patients were included according to the evaluated criteria (preoperative ejection fraction, duration of cardiopulmonary bypass, type of surgery).
                The treatment group received stress doses of hydrocortisone perioperatively: 100 mg before induction of anesthesia, then 10 mg/hr for 24 hrs, 5 mg/hr for 24 hrs, 3 x 20 mg/day, and 3 x 10 mg/day.
                We measured various laboratory (e.g., lactate) and clinical variables (e.g., duration of ventilation and length of stay in the intensive care unit), characterizing the patients' outcome. The two study groups did not differ regarding age, preoperative medication, duration of the cardiopulmonary bypass, and type of surgery. The patients in the treatment group had significantly lower concentrations of IL-6 and lactate, higher antithrombin III concentration, lower need for circulatory and ventilatory support and for transfusions, lower Therapeutic Intervention Scoring System values, and shorter length of stay in the intensive care unit and in the hospital. The mortality rate did not differ significantly between the groups.
                Although we acknowledge the limitations of a nonblinded interventional trial, stress doses of hydrocortisone seem to attenuate systemic inflammation in a predefined risk group of patients after cardiac surgery with cardiopulmonary bypass and improve early outcome. nan Cardiopulmonary bypass (CPB) initiates inflammation that contributes to multiorgan dysfunction (SIRS). Steroids have been demonstrated to attenuate this response; however, resistance to use steroids remains because of potential adverse effects of the high doses used. This study examines a lower dose steroid protocol for safety and attenuation of SIRS.
                Sixty patients undergoing CPB were randomized to pulse low doses of methylprednisolone (250 mg given twice IV) or placebo in this RCT. Outcomes pertaining to hemodynamics, ventilator requirement, arrhythmia, and metabolic derangements were recorded. Post-operative glucose control and gastrointestinal prohylaxis was instituted in all patients.
                IL-6 concentrations were lower in the steroid group at 4 and 8 h post-operatively (P < 0.0001). The steroid group demonstrated more normothermia (37.2 degrees C versus 37.6 degrees C, P = 0.002), better hemodynamic stability with less requirement for inotropes or vasopressors (0% versus 27.6%, P = 0.005), higher SVRIs (1840 versus 1340 DSm2/cm5, P = 0.002), and higher mean arterial pressures (79 versus 74 mmHg, P = 0.03). The steroid group had a shorter duration of intubation (7.7 versus 10.7 h, P = 0.02), a shorter length of ICU stay (1.0 versus 2.0 days, P = 0.03), and less blood loss (505 versus 690 ml, P = 0.04) with no difference in post-operative blood glucose levels or complications.
                Patients undergoing cardiopulmonary bypass receiving low pulse dose steroids had better hemodynamics, shorter mechanical ventilation times, less blood loss, and required less time in the ICU compared to those receiving placebo. Therefore, this study demonstrates that prophylactic low dose steroids attenuate the SIRS response to CPB without resulting in any untoward side-effects. The systemic inflammatory response to cardiopulmonary bypass (CPB) is associated with increased production of cytokines. This systemic inflammatory response characterized by the activation of interleukin-6 (IL-6) and interleukin-8 (IL-8) during and after CPB is well documented. A prospective, randomized, double-blind study was performed so as to understand the effects of low-dose methyl prednisolone sodium succinate (MPSS) on the circulating levels of serum cytokines and clinical outcome. Twenty patients were randomly divided into two groups on the basis of the administration of low-dose (1 mg/kg) MPSS (n = 10) and placebo (n = 10) into the pump prime solution. All patients were scheduled to undergo a primary elective coronary artery bypass grafting operation. Patients receiving concurrent corticosteroids, salicylates, dipyridamol or anticoagulants were excluded from the study. Other exclusion criteria were concurrent chronic obstructive pulmonary disease, chronic renal failure, insulin-dependent diabetes, congestive cardiac failure, peptic ulcer history, prior cardiac operations, recent (in a one-month period) myocardial infarction and steroid dependency. Mild systemic hypothermia (30-32 degrees C, rectal) was assured during the CPB. Four blood samples were drawn from the radial artery catheter immediately before starting CPB (T1), following protamine administration (T2) and at 24 (T3) and 48 h (T4) after completion of CPB. In each sample, creatine kinase-myocardial band (CK-MB), white blood cell (WBC), IL-6 and IL-8 levels were measured. IL-6 and IL-8 concentrations were measured by enzyme immunoassay and enzyme-linked immunoabsorbant assay methods. Serum IL-6 T2 and serum IL-6 T3 levels were significantly higher than IL-6 T1 levels in both groups (p < 0.001) and (p < 0.01), and there was no significant elevation in serum IL-8 levels in either group. Serum IL-6 levels were significantly higher in the placebo group than in the MPSS group at T3 (p < 0.009). There was no significant difference in CK-MB T1 levels between the groups. Although there was no significant difference between CK-MB T1 and T2 levels in the MPSS group, the CK-MB T2 and CK-MB T3 levels were significantly higher than T1 levels in the placebo group (p < 0.001) and (p < 0.05). There was significant elevation of WBC levels at T2 and T3 in both groups without notable difference between the groups (p < 0.05). This study has shown that low-dose MPSS suppresses CPB-induced inflammatory response. Further clinical studies (on larger and higher risk groups) may reveal more information on relations between morbidity and cytokine levels which may have some predictive value on clinical outcome following CPB. Cardiopulmonary bypass (CPB) induces derangements in physiology characterized by activation of blood pathways that may contribute to multiorgan dysfunction. This trial addresses the efficacy of a biocompatible surface alone and in combination with steroids in inhibiting these changes.
                In a factorial design, patients undergoing coronary artery bypass grafting were randomized (four groups; n = 17 per group) to CPB utilizing control circuits or a circuit prepared with a surface modifying active copolymer (SMA-CPB), with or without methylprednisolone (MPSS, 1 g intravenous). Leukocyte and complement activation, cytokine release, and bradykinin generation were measured. Clinical outcomes (blood loss, transfusion, arterial pressure response, and postoperative cardiac and pulmonary functions) were also examined.
                The SMA-CPB was associated with a significant inhibition of elastase release (p = 0.026) and bradykinin generation (p = 0.027) during CPB. Terminal complement complex (TCC) generation was inhibited as an effect of SMA-CPB (p = 0.047). There was an interaction of SMA-CPB and MPSS to decrease both TCC (p = 0.042) and bradykinin generation (p = 0.028). There were strong effects of MPSS in inhibiting release of interleukin 6 (IL-6) (p = 0.007) and IL-8 (p < 0.001) and tissue plasminogen activator over time (p = 0.009) as well as decreasing peak day 1 creatine kinase (CK, p = 0.015) levels. Clinical effects of MPSS included decreased atrial fibrillation (p = 0.02), improved cardiac index over time, increased pulmonary compliance, and increased insulin need.
                This trial suggests a potential beneficial effect for combined strategies to minimize inflammation after CPB. The specific effect of MPSS in decreasing postoperative atrial fibrillation and CK warrants further investigation of its role as a potential myocardial protective agent. Cardiac surgery with cardiopulmonary bypass is often associated with postoperative hemodynamic instability. In this regard beneficial effects of corticosteroids are known. The purpose of this study was to investigate whether these effects are due mainly to a modification of the intravascular and extravascular volume status or whether a more direct improvement of cardiovascular performance by corticosteroids is the underlying mechanism.
                Twenty patients undergoing elective coronary bypass grafting were included in this randomized double-blind study. Patients of the treatment group received 1 mg/kg-1 dexamethasone after induction of anesthesia. In addition to the use of standard monitors and detailed fluid balance assessments, the transpulmonary double-indicator technique was used to measure extravascular lung water, total blood volume, and intrathoracic blood volume. Measurements were done after induction of anesthesia and 1 h, 6 h, and 20 h after the end of surgery.
                After cardiopulmonary bypass, no relevant increase in extravascular lung water was observed, despite highly positive fluid balances in all patients. A significantly smaller increase in extravascular fluid content was observed in the dexamethasone group. Total blood volume and intrathoracic blood volume did not differ in the two groups. Patients pretreated with dexamethasone had a decreased requirement for vasoactive substances and, in contrast with the control group, no increase in pulmonary artery pressure.
                Extravascular fluid but not extravascular lung water is increased in patients after surgery with cardiopulmonary bypass. Pretreatment of adult patients with 1 mg/kg-1 dexamethasone before coronary bypass grafting decreases extravascular fluid gain and seems to improve postoperative cardiovascular performance. This effect is not caused by a better intravascular volume status. To compare the efficacy of aprotinin and methylprednisolone in reducing cardiopulmonary bypass (CPB)-induced cytokine release, to evaluate the effect of myocardial cytokine release on systemic cytokine levels, and to determine the influence of cytokine release on perioperative and postoperative hemodynamics.
                Prospective, randomized clinical trial.
                University teaching hospital and clinics.
                Thirty patients undergoing elective coronary artery bypass graft surgery.
                Patients were randomly allocated into groups treated with aprotinin (n = 10) or methylprednisolone (n = 10) or into an untreated control group (n = 10). Aprotinin-treated patients received aprotinin as a high-dose regimen (6 x 10(6) KIU), and methylprednisolone-treated patients received methylprednisolone (30 mg/kg intravenously) before CPB.
                Patients were analyzed for hemodynamic changes and alveolar-arterial PO2 difference (AaDO2) until the first postoperative day. Plasma levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, and IL-8) were measured in peripheral arterial blood immediately before the induction of anesthesia, 5 minutes before CPB, 3 minutes after the start of CPB, 2 minutes after the release of the aortic cross-clamp, 1 hour after CPB, 6 hours after CPB, and 24 hours after CPB; and in coronary sinus blood immediately before CPB and 2 minutes after the release of the aortic cross-clamp. The hemodynamic parameters did not differ among the groups throughout the study. After CPB, AaDO2 significantly increased (p < 0.05) in all groups. A significant decrease in AaDO2 was observed in aprotinin-treated patients at 24 hours after CPB compared with the other groups (p < 0.05). TNF-alpha level from peripheral arterial blood significantly increased in control patients 1 hour after CPB (p < 0.01) and did not significantly increase in methylprednisolone-treated patients throughout the study. In all groups, IL-6 levels increased after the release of the aortic cross-clamp and reached peak values 6 hours after CPB. At 6 hours after CPB, the increase in IL-6 levels in methylprednisolone-treated patients was significantly less compared with levels measured in control patients and aprotinin-treated patients (p < 0.001). In control patients, IL-8 levels significantly increased 2 minutes after the release of the aortic cross-clamp (p < 0.05), and peak values were observed 1 hour after CPB (p < 0.01). IL-8 levels in control patients were significantly higher compared with patients treated with aprotinin and patients treated with methylprednisolone 1 hour after CPB (p < 0.05).
                This study showed that methylprednisolone suppresses TNF-alpha, IL-6, and IL-8 release; however, aprotinin attenuates IL-8 release alone. Methylprednisolone does not produce any additional positive hemodynamic and pulmonary effects. An improved postoperative AaDO2 was observed with the use of aprotinin.
                Copyright 2001 by W.B. Saunders Company This study evaluates whether dexamesathone in patients undergoing CABG using CPB results in better renal and pulmonary outcome. Methods: 100 patients were randomized to receive either placebo or dexamethasone (1 mg/ kg, at induction of anesthesia and 0.5 mg/kg 8 h later). Results: The differences regarding pulmonary parameters over times were significant in relation to measurements taken 10 minutes after intubation within groups; nevertheless, differences were significant between groups only at 12, 24 hours for A-a O(2) gradient, respiratory index, PaO(2)/FiO(2) ratio. Dexamethasone had no effect on extubation time. Creatinine clearance, urinary micro albumin excretion and (NAG) levels were comparable in both the groups. The dexamethasone treated patients were more likely to have hyperglycemia. Conclusions: Dexamethasone offers no renal protective effect and the drug is associated with significant improvement in A-a O(2) gradient, respiratory index, PaO(2)/FiO( 2) at 12, 24 hours postoperatively and had no effect on extubation time and lung compliance. It is recognized that the inflammatory mediators complement and cytokines are generated during cardiopulmonary bypass as an endogenous response to extracorporeal circulation.
                Nineteen randomized patients (10 steroid/9 nonsteroid) entered an institutional review board-approved protocol to measure complement and interleukin level generation before and after elective coronary revascularization. The steroid regimen involved 1 g of methylprednisolone sodium succinate intravenously before bypass and 4 mg of dexamethasone every 6 hours for four doses during the first 24 hours of recovery. Complement and interleukin levels were measured before bypass, immediately after bypass, and at 24, 48 and 72 hours of recovery.
                In the nonsteroid group, there was a significant elevation in all inflammatory mediators relative to the steroid group. The predominant changes occurred at 24 hours after operation.
                Steroids produced a dramatic reduction in complement and interleukin levels. The number of patients was clearly too small to document a clinical consequence of steroid administration. Cerebral injury is a well-known complication after cardiac surgery with cardiopulmonary bypass (CPB), especially in adult patients. Specific biochemical markers like neuron-specific enolase (NSE) and S-100beta protein were developed previously for early detecting neuronal damage after CPB. Corticosteroids are shown to reduce multisystemic deleterious effects of cardiopulmonary bypass due to their anti-inflammatory characteristics. The aim of this study is to demonstrate the decrease of serum neuron-specific enolase levels in patients who received corticosteroids before CPB.
                Thirty patients scheduled for elective coronary bypass surgery were included in the study. Patients were divided randomly into two groups as the control group (n = 15) who underwent a standard coronary bypass surgery without any additional medication and the study group (n = 15) who received 1 gm of methylprednisolone before CPB. Blood samples for analysis of serum NSE, interleukin-6 (IL-6), and IL-10 were drawn before CPB, 4 and 24 hours after the end of extracorporeal circulation.
                Serum cytokine and NSE levels were significantly increased after CPB above their normal range in both groups. In the study group, IL-6 and NSE levels were significantly reduced while IL-10 levels were much higher after CPB. High NSE levels significantly correlated with IL-6 levels in the control group.
                The lower levels of NSE in patients who received methylprednisolone may suggest that corticosteroids might be useful in decreasing possible neuronal damage during heart surgery. However, we were not able to demonstrate an adverse neurological outcome. Cardiopulmonary bypass (CPB)-related inflammatory response can be attenuated by glucocorticoid treatment, but its impact on postoperative cardiopulmonary function remains controversial. It was investigated whether the systemic and myocardial antiinflammatory effects of glucocorticoids are associated with improved cardiopulmonary function in cardiac surgery patients.
                Eighty patients undergoing elective coronary artery bypass grafting were randomly assigned to receive a single shot of methylprednisolone (15 mg/kg) or placebo before CPB. Variables of myocardial and pulmonary function and systemic hemodynamics were measured before and 1, 4, 10, and 24 hours after CPB. Blood was sampled for measurement of proinflammatory (tumor necrosis factor-alpha, interleukin 6, interleukin 8) and antiinflammatory (interleukin 10) cytokines (by enzyme-linked immunoassay), troponin T, and C-reactive protein. Phosphorylation of inhibitory kappa-B alpha and p38 mitogen-activated protein kinase was determined in right atrial biopsies before and after CPB (phosphoprotein assay).
                Preoperative and intraoperative characteristics of patients were not different between groups. Methylprednisolone attenuated postoperative tumor necrosis factor-alpha, interleukin 6, interleukin 8, and C-reactive protein levels while increasing interleukin 10 release. Myocardial inhibitory kappa-B alpha was preserved with methylprednisolone (p < 0.05 versus placebo), but p38 mitogen-activated protein kinase activation occurred in both groups after CPB (p < 0.05 versus before CPB). Methylprednisolone improved postoperative cardiac index and was associated with decreased troponin T when compared with placebo (p < 0.05). Postoperative blood glucose, oxygen delivery index, and pulmonary shunt flow were increased in the methylprednisolone group (p < 0.05). There was no difference in postoperative oxygenation index, ventilation time, and clinical outcome between treatment groups.
                Glucocorticoid treatment before CPB attenuates perioperative release of systemic and myocardial inflammatory mediators and improves myocardial function, suggesting potential cardioprotective effects in patients undergoing cardiac surgery. To measure the effects of glucocorticoids on the systemic inflammatory response and clinical recovery after cardiac surgery.
                Randomized, prospective, double-blind, placebo-controlled clinical trial with concurrent comparison groups.
                University medical center.
                Patients scheduled for elective coronary artery bypass graft surgery using normothermic cardiopulmonary bypass (CPB) and a standardized anesthetic.
                Participants randomly received either methylprednisolone, 15 mg/kg intravenously 1 hour before surgery and 0.3 mg/kg intravenously every 6 hours x 4 doses, or placebo. Comparison groups included cardiac surgical patients who received etomidate to lower endogenous cortisol during surgery and healthy volunteers who received methylprednisolone only.
                Patients who received methylprednisolone had a significant reduction in circulating interleukin (IL)-6 at 60 minutes after CPB (p < 0.05) and on the morning of the 1st (p < 0.01) and 3rd (p < 0.05) postoperative days and a significant increase in circulating IL-10 at 60 minutes after CPB (p < 0.01) compared with the placebo group. Etomidate, given to lower cortisol during surgery, was associated with significantly decreased IL-6 and IL-10 responses to surgery compared with the placebo group, whereas methylprednisolone alone, given to healthy nonsurgical volunteers, had no effect on these cytokines. After adjusting for age, there were no significant differences in postoperative length of hospital stay between the methylprednisolone-treated (4.6 days) and placebo (6.1 days) groups or in the duration of mechanical ventilation (9.9 hours and 15.6 hours). No patient treated with methylprednisolone had nausea and vomiting on the 1st postoperative day compared with 33% of placebo-treated patients (p = 0.02). Glucose was significantly higher after methylprednisolone treatment at 1 hour after CPB (276 mg/dL v 210 mg/dL; p = 0.001) and at 2 hours (289 mg/dL v 213 mg/dL; p = 0.009) and 8 hours (247 mg/dL v 196 mg/dL; p = 0.02) after surgery. There were no differences in pain scores and no significant intergroup differences in lung peak expiratory flow rate or alveolar-arterial oxygen gradients after surgery.
                This study shows significant effects of glucocorticoids on the production of IL-6 and IL-10 in response to cardiac surgery but only minor effects on clinical recovery.
                Copyright 2002, Elsevier Science (USA). All rights reserved. To discover the possible effects of methylprednisolone on the systemic inflammatory response during aprotinin treatment.
                Randomized, double-blinded study.
                University-affiliated heart center.
                Fifty-two patients scheduled for elective coronary artery bypass grafting.
                In the methylprednisolone group (n = 26), 1 g of methylprednisolone was administered 30 minutes before cardiopulmonary bypass (CPB). The 26 control patients received a placebo instead. High-dose aprotinin was administered to all participants.
                After CPB, the concentration of the proinflammatory cytokines, interleukin-6 and interleukin-8, was significantly less in the methylprednisolone group. The anti-inflammatory interleukin-10 concentration was, in contrast, greater. After CPB, PaO2 was greater in the methylprednisolone group (245+/-17 v 195+/-16 mmHg). Dynamic pulmonary compliance was also greater, whereas the alveolar-arterial oxygen difference was less (376+/-17 v 428+/-16 mmHg). On arrival in the intensive care unit, the oxygen delivery index was greater in the methylprednisolone group (62+/-2.7 v 54+/-2.3 mL/min/m2) and the oxygen extraction rate was less (25%+/-0.02% v 30%+/-0.02%). After CPB, the cardiac index was significantly greater in the methylprednisolone group (4.1+/-0.2 v 3.6+/-0.2 L/min/m2). These patients had less blood loss postoperatively (616+/-52 v 833+/-71 mL; p = 0.017) and a greater urine output (8,015+/-542 v 6,417+/-423 mL/24 h; p = 0.024).
                The use of methylprednisolone attenuates the systemic inflammatory response during aprotinin treatment and improves clinical outcome parameters. The aim of this study was to investigate whether steroid administration would increase the risk of postoperative infection. Sixty adults who underwent elective cardiac surgery under cardiopulmonary bypass were prospectively randomized into two groups. Thirty-one patients received hydrocortisone (50 mg x kg(-1)) before and after cardiopulmonary bypass, the other 29 served as controls. Various hemodynamic and pulmonary measurements were obtained perioperatively, and the white blood cell counts and levels of C-reactive protein were checked up to the 14(th) postoperative day. Steroid administration did not have any favorable effects during the perioperative period. Re-administration of antibiotics was needed in 7 patients (22.6%) after the 7(th) postoperative day in the steroid group, and in 3 (10.3%) in the control group. The peak white cell counts and C-reactive protein levels after the 7(th) postoperative day were significantly higher in the steroid group. Steroid administration offered no clinical benefit to patients undergoing cardiac surgery with cardiopulmonary bypass, and it may encourage minor infections in the late postoperative period. Cardiac surgery with cardiopulmonary bypass (CPB) is associated with an inflammatory response caused by contact of blood with artificial surfaces of the extracorporeal circuit, ischemia-reperfusion injury, and release of endotoxin. The inflammatory reaction involves activation of complement leucocytes, and endothelial cells with secretion of cytokines, proteases, arachidonic acid metabolites, and generation of oxygen derived free radicals (OFR) by polymorphonuclear neutrophils (PMN). Although this inflammatory response to CPB often remains at subclinical levels, it can also lead to major organ dysfunction. A number of studies have demonstrated that treatment of patients with a high-dose (30 mg/kg) of corticosteroids (methylprednisolone) attenuates the CPB-induced SIR and improves the outcome of patients undergoing cardiac surgery. However, large doses of steroids can cause abnormal metabolic responses such as metabolic acidosis and hyperglycemia. In the present study, we examined the efficacy of low doses of methylprednisolone (5 and 10 mg/kg) to attenuate the CPB-induced inflammatory response, during and after heart operations.
                Thirty-six adult patients undergoing cardiac surgery, were randomized into three groups: (1) control group: group A; (2) methylprednisolone, 5 mg/kg body weight: group B; and (3) methylprednisolone, 10 mg/kg body weight: group C. Plasma levels of the cytokines interleukin-6 (IL-6) and TNF-alpha were analyzed by enzyme-linked immunosorbent assay, before, during, and after CPB. OFR production was determined by cytofluorometry (FACS) at the same end points.
                No significant differences in age, body weight, CPB time, and cross-clamp time were observed among the three groups. CPB induced a marked increased in cytokine release and OFR generation. Low-dose of methylprednisolone (5 mg/kg) effectively reduced the increase in TNF-alpha and IL-6 secretion (P<0.05 compared to control group) after release of the cross-clamp. However, OFR generation was significantly reduced with a greater dose of methylprednisolone (10 mg/kg).
                The results indicate that a single low-dose of methylprednisolone (10 mg/kg) reduces the inflammatory reaction during and after CPB, by inhibition of proinflammatory cytokine release and OFR generation after release of the aortic cross-clamp. Previous reports showed that cardiac surgery with cardiopulmonary bypass (CPB) impair cell-mediated immunity by using antigen-non-specific responses. This study elucidated the effects of cardiac surgery with CPB on antigen-specific immunity. Twenty patients who underwent elective cardiac surgery using CPB were randomly divided into two groups: group A (n=10) and group B (n=10) with and without steroid administration, respectively. Group C patients underwent off-pump CABG (n=8). Peripheral blood mononuclear cells (PBMCs) were taken before and after surgery. Proliferation responses to pure protein derivative antigen were measured. The effects of CPB and steroid on T cell response and antigen-presentation were assessed by cross-stimulation between the preoperative and the postoperative PBMCs. Antigen-specific T cell responses decreased to about 5% of the preoperative values immediately after surgery with CPB, regardless of steroid administration. The T cell response in group B on POD 7 was significantly higher than that in group A. CPB impaired mainly T cell responses, and steroid administration enhanced impairment of T cell response and antigen-presentation. Open-heart surgery with CPB severely impaired antigen-specific immunity. Steroid administration enhanced the impairment of antigen-presentation as well as T cell function, and retarded the recovery of antigen-specific immunity. Cytokines regulate inflammation associated with cardiopulmonary bypass (CPB). Pro-inflammatory cytokines may cause myocardial dysfunction and haemodynamic instability after CPB, but the release of anti-inflammatory cytokines is potentially protective. We studied the effects of dexamethasone on pro- and anti-inflammatory cytokine responses during coronary artery bypass grafting surgery.
                Seventeen patients were studied: nine patients received dexamethasone 100 mg before induction of anaesthesia (group 1) and eight patients acted as controls (group 2). Plasma levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, IL-10 and IL-4 were measured perioperatively.
                TNF-alpha and IL-8 did not increase significantly in group 1 whereas they increased in group 2 to greater than preoperative values (P<0.05). IL-6 increased in both groups, with lower values in group 1 than in group 2 (P<0.05). IL-10 increased in both groups, with higher values in group 1 (P<0.05). IL-4 did not change in group 1 but decreased in group 2 compared with pre-induction values (P<0.05). After surgery, patients in group 2 had tachycardia, hyperthermia, a greater respiratory rate and higher pulmonary artery pressure, and a longer stay in the intensive care unit.
                Dexamethasone given before cardiac surgery changes circulating cytokines in an anti-inflammatory direction. Postoperative outcome may be improved by inhibition of the systemic inflammatory response. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 play a key role in the inflammatory cascade after cardiopulmonary bypass (CPB) and may induce cardiac and lung dysfunction. Antiinflammatory cytokines such as IL-10 may also significantly limit these complications. Corticosteroid administration before CPB increases blood IL-10 levels and prevents proinflammatory cytokine release. This study examined the association of increased release of IL-10, stimulated by steroid pretreatment, with reduced myocardial and lung injury after CPB.
                Twenty patients undergoing coronary artery bypass grafting (CABG) received either preoperative steroid (n = 10, protocol group) or no steroid (n = 10, control group). Perioperative care was standardized, and all caregivers were blinded to treatment group. Seven intervals of blood samples were obtained and assayed for TNF-alpha, IL-6, IL-8, and IL-10. Various hemodynamic and pulmonary measurements were obtained perioperatively. Levels of MB isoenzyme creatine kinase (CK-MB) were also measured.
                In the protocol group, proinflammatory cytokines were significantly reduced while IL-10 levels were much higher after CPB. The protocol group had a lower alveolar-arterial oxygen gradient and higher ratio of arterial oxygen pressure to fraction of inspired oxygen after CPB. Creatine kinase (CK) and CK-MB were reduced in the patients treated with steroid. Correlations were found between plasma cytokines levels and cardiac index, and CK-MB.
                This study confirms that corticosteroids abolish proinflammatory cytokines release and increase blood IL-10 levels after CPB. Our findings demonstrate a greater release of IL-10 induced by steroid pretreatment, and better heart and lung protection after CPB. The influence of high doses of methylprednisolone on complement activation and endotoxin concentration was investigated in two groups of eight patients undergoing coronary artery bypass grafting. Group 1 received methylprednisolone, 30 mg/kg, at the induction of anesthesia; group 2 served as the control group. The endotoxin concentrations increased significantly in both groups at the start of cardiopulmonary bypass. During cardiopulmonary bypass, the endotoxin concentrations were significantly higher in the steroid group compared with the control group (p less than 0.01). After completion of surgery, the endotoxin concentrations declined to almost zero within seven days in both groups. Complement activation was significantly reduced in the steroid-treated group during cardiopulmonary bypass compared with the control group (P less than 0.01). The clinical outcome after the first postoperative week was the same in the two groups. It appears that high-dose steroids can reduce complement activation during cardiopulmonary bypass, although the clearance of endotoxins may also be reduced. Shivering after cardiac surgery is common, and may be a result of intraoperative hypothermia. Another possible etiology is fever and chills secondary to activation of the inflammatory response and release of cytokines by cardiopulmonary bypass. Dexamethasone decreases the gradient between core and skin temperature and modifies the inflammatory response. The goal of this study was to determine whether dexamethasone can reduce the incidence of shivering. Two hundred thirty-six patients scheduled for elective coronary and/or valvular surgery were randomly assigned to receive either dexamethasone 0.6 mg/kg or placebo after the induction of anesthesia. All patients received standard monitoring and anesthetic management. After arrival in the intensive care unit (ICU), nurses unaware of the treatment groups recorded visible shivering, as well as skin and pulmonary artery temperatures. Analysis of shivering rates was performed by using chi2 tests and logistic regression analysis. Compared with placebo, dexamethasone decreased the incidence of shivering (33.0% vs 13.1%; P = 0.001). It was an independent predictor of reduced incidence of shivering and was also associated with a higher skin temperature on ICU admission and a lower central temperature in the early postoperative period.
                Dexamethasone is effective in decreasing the incidence of shivering. The effectiveness of dexamethasone is independent of temperature and duration of cardiopulmonary bypass. Shivering after cardiac surgery may be part of the febrile response that occurs after release of cytokines during cardiopulmonary bypass. Atrial fibrillation remains one of the most common postoperative complications of coronary artery bypass grafting. Despite many clinical studies, there is still no consensus regarding the best prevention strategy for atrial arrhythmia. A randomized, double-blind, placebo-controlled trial was conducted to determine the effect of steroids on the occurrence of atrial fibrillation after elective coronary artery bypass grafting.
                Eighty-eight consecutive patients were prospectively entered in this study. No patient had documented or suspected arrhythmias before surgery. Forty-three patients received 1 g of methylprednisolone before surgery and 4 mg of dexamethasone every 6 hours for 1 day after surgery, and 43 patients received only placebo. The primary end point was the overall occurrence of postoperative atrial fibrillation.
                Postoperative atrial fibrillation occurred in 9 (21%) of the 43 patients in the steroid group, as compared with 22 (51%) of the 43 patients in the placebo group ( P = .003). Minor postoperative complications occurred in 15 steroid patients (35%) and in 6 patients (14%) receiving placebo ( P = .01). Major complications occurred in 4 patients who received steroids (9%) and in 2 patients (5%) who received placebo ( P = .68; for all complications, P = .05).
                Prophylactic short-term steroid administration in patients undergoing coronary artery bypass grafting significantly reduced postoperative atrial fibrillation. In this study, there was no significant difference between the steroid group and the placebo group with regard to the length of hospital stay; however, the steroid group had more complications, which may contribute to prolonged hospitalization. Chronic obstructive pulmonary disease is still one of the most important problems in patients undergoing cardiopulmonary bypass. The purpose of this prospective study was to assess the beneficial effects of oral prednisolone on pulmonary functions in patients undergoing cardiopulmonary bypass.
                Forty patients with chronic obstructive pulmonary disease were divided into two groups randomly and were given 20 mg oral prednisolone once daily perioperatively (Group I, n = 20) or identical placebo (Group II, n = 20). FEV(1) values, dates of intensive care unit and hospital stays of the two groups were compared.
                FEV1 values during the admission to our hospital were similar in each group mean predicted FEV1: 56.7 +/- 5.35% in Group I and 57.2 +/- 4.88% in Group II (p = 0.759). After 10 days of oral prednisolone treatment in Group I, predicted FEV1 values were significantly different between two groups (63.2%+/- 4.24 and 57.9%+/- 4.38) (p = 0.0001). While predicted FEV1 values revealed difference between two groups at the date of discharge (p = 0.0001) the values became similar at the third month (55.6%+/- 4.09 in Group I and 55.45%+/- 3.87 in Group II) (p = 0.897).
                Various types of complications may occur after cardiopulmonary bypass. Oral prednisolone not only decreases the rates of complications (reintubation, intubation times, and rhythm disturbances) but also decreases the cost of cardiac operations according to shorter hospital stays. Coronary artery bypass grafting (CABG) is associated with high morbidity in patients with chronic obstructive pulmonary disease (COPD).We examine the effect of preoperative systemic corticosteroids on morbidity in this setting.
                Ninety candidates for elective CABG participated in a prospective, open randomized trial, including 30 patients with COPD who received a single injection of a long-acting corticosteroid, 30 with COPD who received placebo, and 30 without COPD who served as controls. Primary end-points were postoperative pulmonary and nonpulmonary complications. Secondary end-points were length of hospital stay (LOS), ICU stay of less than 24 hours and more than 48 hours, duration of mechanical ventilation, and time to walking and sitting.
                The rate of pulmonary complications was similar in the two COPD groups and in the COPD patients and controls. The placebo group had more major nonpulmonary complications than the treatment group, but the difference was not statistically significant (26% vs. 17%, P = NS). The non-COPD control group had significantly fewer nonpulmonary complications than the COPD patients (treatment+placebo) (33% vs 70%, P = 0.014) and a similar rate of pulmonary complications. There was a statistically significant difference between the treated and placebo COPD groups in ICU stay less than 24 hours (P < or = 0.001) and more than 48 hours (P = 0.03) and hospital stay (P = 0.013). On stepwise analysis, only age and number of coronary grafts were predictors of pulmonary complications.
                The use of preoperative systemic corticosteroids in patients with COPD undergoing CABG may shorten ICU and hospital stay. We sought to determine whether methylprednisolone, when administered to patients undergoing cardiac surgery, is able to ward off the detrimental hemodynamic and pulmonary alterations associated with cardiopulmonary bypass.
                After institutional review board approval and informed consent was obtained, 90 patients scheduled for elective cardiac surgery were randomized to 1 of 3 groups. Group 30MP patients received 30 mg/kg intravenous methylprednisolone during sternotomy and 30 mg/kg during initiation of cardiopulmonary bypass, group 15MP patients received 15 mg/kg methylprednisolone at the same 2 times, and group NS patients received similar volumes of isotonic sodium chloride solution at the same 2 times. Perioperative care was standardized, and all caregivers were blinded to treatment group. Various hemodynamic and pulmonary measurements were obtained perioperatively, as well as fluid balance, weight, peak postoperative blood glucose level, and tracheal extubation time.
                Demographic and clinical characteristics of patients and intraoperative data were similar among the 3 groups. Patients receiving methylprednisolone (either dose) exhibited significantly increased cardiac index (P =.0006), significantly decreased systemic vascular resistance (P =.0005), and significantly increased shunt flow (P =.0020) during the immediate postoperative period. All 3 groups exhibited significant increases in alveolar-arterial oxygen gradient (P <.0001), significant decreases in dynamic lung compliance (P <.0001), and significant decreases in static lung compliance (P <.0001) during the immediate postoperative period, with no differences between groups. Perioperative fluid balance and weights were similar between groups. A statistically significant difference in peak postoperative blood glucose level existed (P =.016) among group NS (234 +/- 96 mg/dL), group 15MP (292 +/- 93 mg/dL), and group 30MP (311 +/- 90 mg/dL). In patients extubated within 12 hours of intensive care unit arrival, a statistically significant difference in extubation times existed (P =.025) between group NS (5.7 +/- 2.3 hours), group 15MP (5.9 +/- 2.2 hours), and group 30MP (7.5 +/- 2.7 hours).
                Methylprednisolone, as used in this investigation, offers no clinical benefits to patients undergoing elective coronary artery bypass grafting with cardiopulmonary bypass and may in fact be detrimental by initiating postoperative hyperglycemia and possibly hindering early postoperative tracheal extubation for undetermined reasons. Cardiopulmonary bypass (CPB) induces a systemic inflammatory response called 'post-pump syndrome'. As a part of a complex interaction between white cells and vascular endothelium, proinflammatory cytokines IL-6 and IL-8 are part of a phased immune response that is also balanced by anti-inflammatory cytokines such as IL-10. We compared the influence of heparin-coated circuits, steroids, and aprotinin on these cytokines, looking for ways to reduce the syndrome.
                40 patients with coronary artery disease (CAD) undergoing elective CABG were prospectively studied in four randomized groups of 10. Group A received prednisolone pre- and postoperatively (2 x 250 mg), group B received aprotinin perioperatively (6 Mio. KIU). In group C, heparin-coated circuits ('Bioline' by Jostra) were used and in group D no special measures were taken (controls). Plasma levels of cytokines were measured before and during CPB and until 12 h after surgery using an ELISA technique.
                In group A IL-6 was significantly (p<0.05) suppressed in contrast to the control group (A: peak at 4 h, 155 pg/ml vs. control: peak at 8 h, 565 pg/ml). IL-8 was also suppressed (A: peak at 30', 22 pg/ml vs. control: peak at 30', 55 pg/ml). IL-10 level changed first and was markedly upregulated in contrast to the control (A: peak at 30', 1600 pg/ml vs. control: peak at 30', 130 pg/ml; p<0.05). In group B (aprotinin) the cytokine release was similar to group A. Using heparin-coated circuits (group C) also led to a significant (p<0.05) IL-10 upregulation (C: peak at 2 h, 1380 pg/ml) and IL-6 suppression (C: peak at 4 h, 290 pg/ml). IL-8 was not influenced significantly.
                The results show a similar reduction of the inflammatory cytokine release (IL-6 and IL-8 as markers) using early steroid application and aprotinin in high dosage. Heparin coating reduces IL-6 and increases IL-10 release, whereas IL-8 is not affected. Further studies should investigate the effects of a combined application for reducing inflammatory cytokine release and the post-pump syndrome. A placebo-controlled double-blind study of patients undergoing cardiopulmonary bypass was conducted, comparing the effects of dexamethasone and a placebo on the activation of the plasmatic systems and blood cells and on the postoperative course after cardiopulmonary bypass. In the placebo group two patterns of blood activation could be distinguished. From the start of bypass, blood-material interaction caused an increase in complement C3a and elastase concentration. After release of the aortic cross-clamp, a statistically significant increase was observed in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity (p less than 0.01, p less than 0.05, p less than 0.05, respectively). Dexamethasone treatment was not able to inhibit complement activation and elastase release during cardiopulmonary bypass. However, dexamethasone treatment effectively inhibited the increase in tumor necrosis factor, leukotriene B4, and tissue plasminogen activator activity after release of the crossclamp (p less than 0.01 compared with the placebo group). In the postoperative period the patients in the placebo group had hyperthermia and hypotension and required considerable intravenous fluid administration and cardiotonic treatment. The dexamethasone-treated patients, however, showed normothermia (p less than 0.01), had significantly higher blood pressures (p less than 0.01) without supportive treatment, and consequently were in the intensive care unit for a shorter period of time. We conclude that dexamethasone prevents the hemodynamic instability after cardiopulmonary bypass and thus improves the postoperative course by inhibition of the leukocyte and tissue plasminogen activator activity generated after release of the aortic crossclamp. Complications of coronary artery surgery were analyzed in a prospective controlled study of 150 patients, one group receiving methylprednisolone before temporary cardiopulmonary bypass. The patient population was comparable in both the groups. The number of deaths were the same in both the groups, myocardial infarction and cardiac arrhythmias were definitely lower in the Solu-Medrol group. Cerebral vascular accidents were higher in the control group and there were none in the drug treated group. Incidences of pulmonary embolism was reduced by the drug. Oxygen consumption by the tissues was higher in the Solu-Medrol treated group. There were no known complications of the drug, such as stress ulcer and infection. One patient did receive prophylactic antibiotics. Solu-Medrol was deliberately given in patients who were known to have uncomplicated duodenal ulcer. Post-operative bleeding in patients with duodenal ulcer was not noted. This could be explained due to the short acting nature of Solu-Medrol. We feel that Solu-Medrol does minimize serious sequelae of heart-lung machine in coronary artery surgery. Cardiopulmonary bypass (CPB) is associated with tissue damage mediated by adhesion molecules and cytokines. Prebypass steroid administration may modulate the inflammatory response, resulting in improved postoperative recovery.
                Fifty patients undergoing elective coronary operations under normothermic CPB were randomized into two groups: group A (n = 24) received intravenous methylprednisolone (10 mg/kg) 4 hours preoperatively, and group B (n = 26) served as controls. Cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-2R [IL-2R], IL-6, IL-8), soluble adhesion molecules (sE-selectin, sICAM-1), C-reactive protein, and leukocytes were measured before steroid application, then 24 and 48 hours, and 6 days postoperatively. Adhesion molecules were measured by enzyme-linked immunosorbent assay, cytokines by chemiluminescent immunoassay. Postoperatively, hemodynamic measurements, inotropic agent requirements, blood loss, duration of mechanical ventilation, and intensive care unit stay were compared.
                Aortic cross-clamp and CPB time was similar in both groups. Prednisolone administration reduced postoperative levels of IL-6 (611 versus 92.7 pg/mL; p = 0.003), TNF-alpha (24.4 versus 11.0 pg/L, p = 0.02), and E-selectin (327 versus 107 ng/mL, p = 0.02). Postoperative recovery did not differ between groups.
                Preoperative administration of methylprednisolone blunted the increase of IL-6, TNF-alpha, and E-selectin levels after CPB but had no measurable effect on postoperative recovery. Following cardiac surgery with cardiopulmonary bypass (CPB), activated granulocytes may be involved with ischaemia/ reperfusion injury. The purpose of this study was to investigate whether steroids could reduce the oxidative burst activity of granulocytes, the expression of adhesion molecules on granulocytes and improve clinical outcome. Sixteen patients undergoing open heart surgery participated in the study. Eight were randomized to receive methylprednisolone (30 mg/kg intravenously) at the start of anaesthesia while eight patients served as a control group. The oxidative burst was measured flow cytometrically using 123-dihydrorhodamine. A panel of adhesion molecules was measured using monoclonal antibodies. Following CPB the oxidative burst activity and the expression of the adhesion molecule L-selectin more than doubled compared to initial values. There was no difference between the steroid group and the control group regarding the expression of adhesion molecules or the oxidative burst activity. In the steroid group the fluid gain during extracorporeal circulation (ECC) was 683 ml (median) compared to 1488 ml in the control group. Steroids prevented hyperthermia in the postoperative period but did not improve the weaning from the ventilator or reduce the stay in the intensive-care unit. In conclusion, treatment with steroids prevented hyperthermia following open heart surgery with CPB and reduced capillary leak during ECC. Methylprednisolone, however, did not reduce the oxidative burst activity or the expression of adhesion molecules on granulocytes following CPB. During cardiopulmonary bypass, inflammation and immunosuppression is present. We measured circulating mediators and monocyte-based functions and tested the hypothesis that these variables are influenced by methylprednisolone (MP) or tirilazad mesylate (TM) treatment.
                Randomized, controlled, double-blind prospective trial.
                A university hospital.
                Thirty-nine patients scheduled for conventional coronary surgery with three-vessel disease.
                Preoperative application of MP (15 mg/kg) or TM (10 mg/kg) compared with placebo (PL).
                Circulating proinflammatory markers including interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and C-reactive protein were all decreased by MP treatment but not by TM treatment. Whereas rapid increases in circulating anti-inflammatory IL-10 were superinduced by MP but not TM, plasma levels of IL-1RA and transforming growth factor beta were not altered by either treatment. Decreased ex vivo lipopolysaccharide-stimulated secretion of tumor necrosis factor alpha was prolonged after MP treatment but not after TM treatment. Perioperative stimulated secretion of IL-12 and interferon gamma was diminished in all groups, whereas ex vivo IL-1RA secretion tended to increase in all groups. Depression of monocyte surface expression of HLA-DR was significantly greater in patients treated with MP, whereas CD14 expression did not change.
                These data confirm that, during cardiopulmonary bypass, pro- and anti-inflammatory systems are activated at the same time, whereas monocyte-based immune functions are depressed. Treatment with MP abrogates proinflammatory mediators and induces a shift toward anti-inflammation at the cost of further functional monocyte deficits, whereas treatment with TM apparently has neither anti-inflammatory nor immunosuppressive actions in this setting. The purpose of this study was to evaluate the acute cardioprotective effect of high-dose methylprednisolone (25 mg/kg) in the controlled in vivo model of myocardial ischemia-reperfusion injury occurring during cardiopulmonary bypass. Forty nondiabetic male patients with three-vessel disease undergoing first-time bypass surgery were enrolled for this double-blind prospective study. Patients were randomized to be given 25 mg/kg methylprednisolone (Group I) and saline (Group II) 1 h before cardiopulmonary bypass. The levels of cardiac troponin-I (cTnI) were used as a marker of myocardial tissue damage in myocardial ischemia-reperfusion injury. The cTnI levels were measured before surgery, at the second hour after cardiopulmonary bypass, at the 6th and 24th hours, and 5th day postoperatively. There was no significant difference between the two groups in respect to the duration of ischemia and reperfusion. The preoperative cTnI levels were 0.22+/-0.29 ng/ml in Group I and 0.23+/-0.28 ng/ml in Group II. cTnI levels increased to 2.40+/-1.0 ng/ml in Group I and 3.19+/-0.88 ng/ml in Group II at the 2nd hour after cardiopulmonary bypass. When the differences between T1 and T0 level that showed the amount of troponin release occurring due to ischemia-repefusion injury was calculated and then compared, there was a significant difference between Groups I and II (P=0.024). The cTnI levels measured at 6 h after CPB were 1.98+/-0.63 ng/ml in Group I and 2.75+/-1.15 ng/ml in Group II (P=0.049). cTnI levels decreased to 0.22+/-0.10 ng/ml in Group I and 0.49+/-0.25 ng/ml in Group II on the postoperative day 5 (P=0.0001). Univalent regression analysis showed that preoperative high-dose corticosteroid usage decreased the troponin release in about 12% and this effect was statistically significant (R2=0.12, P<0.05). A single dose of intravenous methylpredisolone (25 mg/kg) given 1 h before ischemia reduced myocardial ischemia-reperfusion injury. These results demonstrated that the acute cardioprotective effect of corticosteroids has much potential in the future for reducing ischemia-reperfusion injury occurring during cardiopulmonary bypass when it is inevitable.
This meta-analysis showed no beneficial effect of corticosteroid use on mortality, cardiac and pulmonary complications in cardiac surgery patients.