Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery.

Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.

Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial.

CONTEXT: Prophylactic corticosteroids are often administered during cardiac surgery to attenuate the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking. OBJECTIVE: To quantify the effect of intraoperative high-dose dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006, and November 23, 2011. INTERVENTION: Patients were randomly assigned to receive a single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n = 2255). MAIN OUTCOME MEASURES: A composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. RESULTS: Of the 4494 patients who underwent randomization, 4482 (99.7%) could be evaluated for the primary outcome. A total of 157 patients (7.0%) in the dexamethasone group and 191 patients (8.5%) in the placebo group reached the primary study end point (relative risk, 0.83; 95% CI, 0.67-1.01; absolute risk reduction, -1.5%; 95% CI, -3.0% to 0.1%; P = .07). Dexamethasone was associated with reductions in postoperative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels. CONCLUSION: In our trial of adults undergoing cardiac surgery, the use of intraoperative dexamethasone did not reduce the 30-day incidence of major adverse events compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00293592.

Thoracic epidural anesthesia for cardiac surgery: a randomized trial.

BACKGROUND: The addition of thoracic epidural anesthesia (TEA) to general anesthesia (GA) during cardiac surgery may have a beneficial effect on clinical outcomes. TEA in cardiac surgery, however, is controversial because the insertion of an epidural catheter in patients requiring full heparinization for cardiopulmonary bypass may lead to an epidural hematoma. The clinical effects of fast-track GA plus TEA were compared with those of with fast-track GA alone. METHODS: A randomized controlled trial was conducted in 654 elective cardiac surgical patients who were randomly assigned to combined GA and TEA versus GA alone. Follow-up was at 30 days and 1 yr after surgery. The primary endpoint was 30-day survival free from myocardial infarction, pulmonary complications, renal failure, and stroke. RESULTS: Thirty-day survival free from myocardial infarction, pulmonary complications, renal failure, and stroke was 85.2% in the TEA group and 89.7% in the GA group (P = 0.23). At 1 yr follow-up, survival free from myocardial infarction, pulmonary complications, renal failure, and stroke was 84.6% in the TEA group and 87.2% in the GA group (P = 0.42). Postoperative pain scores were low in both groups. CONCLUSIONS: This study was unable to demonstrate a clinically relevant benefit of TEA on the frequency of major complications after elective cardiac surgery, compared with fast-track cardiac anesthesia without epidural anesthesia. Given the potentially devastating complications of an epidural hematoma after insertion of an epidural catheter, it is questionable whether this procedure should be applied routinely in cardiac surgical patients who require full heparinization.

A comparison of on-pump and off-pump coronary bypass surgery in low-risk patients.

BACKGROUND: The performance of coronary bypass surgery without cardiopulmonary bypass ("off pump") may reduce perioperative morbidity and costs, but it is uncertain whether the outcome is similar to that involving the use of cardiopulmonary bypass ("on pump"). METHODS: In a multicenter, randomized trial, we randomly assigned 139 patients with predominantly single- or double-vessel coronary disease to on-pump surgery and 142 to off-pump surgery. Cardiac outcome and cost effectiveness were determined one year after surgery. The uncertainty surrounding the cost-effectiveness ratio (cost differences per quality-adjusted year of life gained) was addressed by bootstrapping. RESULTS: At one year, the rate of freedom from death, stroke, myocardial infarction, and coronary reintervention was 90.6 percent after on-pump surgery and 88.0 percent after off-pump surgery (absolute difference, 2.6 percent; 95 percent confidence interval, - 4.6 to 9.8). Graft patency in a randomized subgroup of patients was 93 percent after on-pump surgery and 91 percent after off-pump surgery (absolute difference, 2.0 percent; 95 percent confidence interval, - 6.5 to 10.4). On-pump surgery was associated with $1,839 in additional direct costs per patient ($14,908 vs. $13,069--a difference of 14.1 percent) and an increase in quality-adjusted years of life of 0.83 as compared with 0.82 (difference, 0.01 year; 95 percent confidence interval, - 0.03 to 0.04). Off-pump surgery was more cost effective than on-pump surgery in 95 percent of bootstrap estimates. CONCLUSIONS: In low-risk patients, there was no difference in cardiac outcome at one year between those who underwent on-pump bypass surgery and those who underwent off-pump surgery. Off-pump surgery was more cost effective.

Beating heart versus conventional cardiopulmonary bypass: the octopus experience: a randomized comparison of 281 patients undergoing coronary artery bypass surgery with or without cardiopulmonary bypass.

In the Octopus Study, 281 coronary artery bypass surgery patients were randomized to surgery with or without cardiopulmonary bypass. The primary objective was to compare cognitive outcome between off-pump and on-pump coronary artery bypass surgery. Before and after surgery, psychologists administered a battery of 10 neuropsychological tests to the patients. Cognitive decline was defined as a decrease in an individual's performance of at least 20% from baseline, in at least 20% of the main variables. According to this definition, cognitive decline was present in 21% in the off-pump group and 29% in the on-pump group, 3 months after the procedure (P = .15). At 12 months, cognitive decline was present in 31% in the off-pump group and 34% in the on-pump group (P = .69). These results indicated that patients undergoing coronary artery bypass surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure, but the effects were limited and became negligible at 12 months. The same definition of cognitive decline was also applied to 112 volunteers not undergoing surgery. The definition labeled 28% of the control subjects as suffering from cognitive decline, 3 months after their first assessment. This suggests that the natural fluctuations in performance during repeated neuropsychological testing should be included in the statistical analysis of cognitive decline. Using an alternative definition of cognitive decline that takes these natural fluctuations in performance into account, the proportions of coronary artery bypass surgery patients displaying cognitive decline were substantially lower. This indicates that the incidence of cognitive decline after coronary artery bypass surgery has been overestimated.

Role of coronary collaterals in off-pump and on-pump coronary bypass surgery.

BACKGROUND: Collaterals limit infarct size, preserve viability, and reduce mortality in patients with acute myocardial infarction. In patients with stable coronary disease, collaterals are associated with less angina and ischemia during angioplasty and fewer ischemic events during follow-up. The role of collaterals has not been studied in patients undergoing off-pump or on-pump bypass surgery. METHODS AND RESULTS: The population consisted of the 281 patients randomized to off-pump or on-pump CABG in the Octopus Study. Collaterals were defined on the baseline angiogram with the Rentrop score and were present in 49% and 51% of the patients in the off-pump and on-pump group, respectively. Perioperative myocardial infarction was defined by a creatine kinase-MB to CK ratio >10% and occurred in 18.2% in the off-pump group and 32.5% in the on-pump group. The unadjusted OR of perioperative myocardial infarction in the presence of collaterals was 0.31 (95% CI 0.17 to 0.84) in the off-pump group and 1.06 (95% CI 0.29 to 3.85) in the on-pump group After adjustment for age, gender, hypertension, hypercholesterolemia, diabetes, multivessel disease, ventricular dysfunction, incomplete revascularization, and ischemic time, the OR was 0.34 (95% CI 0.14 to 0.84) in the off-pump group and 1.28 (95% CI 0.30 to 5.40) in the on-pump group, respectively. Kaplan-Meier estimates of event-free survival at 1 year were 87% in patients with and 69% in those without collaterals after off-pump CABG. These estimates were 66% and 63%, respectively, after on-pump CABG. CONCLUSIONS: Collaterals protect against perioperative myocardial infarction during off-pump surgery but not during on-pump surgery and are associated with a better 1-year event-free survival.

Intraoperative High-Dose Dexamethasone in Cardiac Surgery and the Risk of Rethoracotomy.

BACKGROUND: Cardiac surgery with the use of cardiopulmonary bypass is associated with a systemic inflammatory response. Intraoperative corticosteroids are administered to attenuate this inflammatory response. The recent Dexamethasone for Cardiac Surgery (DECS) trial could not demonstrate a beneficial effect of dexamethasone on major adverse events in cardiac surgical patients. Previous studies suggest that corticosteroids may affect postoperative coagulation and blood loss, and therefore could influence the risk of surgical reinterventions. We investigated the effects of prophylactic intraoperative dexamethasone treatment on the rate of rethoracotomy after cardiac surgery. METHODS: We performed a post-hoc additional data collection and analysis in the DECS trial. A total of 4,494 adult patients undergoing cardiac surgery with cardiopulmonary bypass were randomly assigned to intravenous dexamethasone (1.0 mg/kg) or placebo. The primary endpoint for the present study was the incidence of any rethoracotomy within the first 30 postoperative days. Secondary endpoints included the reason for rethoracotomy and the incidence of perioperative transfusion of blood products. RESULTS: In the dexamethasone group, 217 patients (9.7%) underwent a rethoracotomy, and in the placebo group, 165 patients did (7.3%; relative risk 1.32, 95% confidence interval: 1.09 to 1.61, p = 0.005). The most common reason for rethoracotomy was tamponade in both groups: 3.9% versus 2.1%, respectively (relative risk 1.84, 95% confidence interval: 1.30 to 2.61, p < 0.001). CONCLUSIONS: Intraoperative high-dose dexamethasone administration in cardiac surgery was associated with an increased rethoracotomy risk.

Off-pump coronary artery bypass graft surgery with a pulsatile catheter pump for left ventricular dysfunction.

We describe the use of a novel device, the pulsatile catheter pump, in patients with left ventricular dysfunction undergoing off-pump coronary surgery. During a 1-year period, 14 patients (mean ejection fraction 28% +/- 8%) underwent off-pump coronary surgery using the pulsatile catheter pump. We recorded neither mortality nor major adverse cardiovascular and cerebral events. Mean support time was 55 +/- 13 minutes. The average flow generated by the pulsatile catheter pump, as calculated per patient, was 2.4 +/- 0.2 L/min (range, 2.2 to 2.8 L/min). Our results show that the pulsatile catheter pump is clinically safe and provides adequate mechanical circulatory support in patients with impaired left ventricular function undergoing off-pump coronary artery surgery.

Cerebral oxygen extraction and autoregulation during extracorporeal whole body hyperthermia in humans.

BACKGROUND: The effects of hyperthermia on the human brain are incompletely understood. This study assessed the effects of whole body hyperthermia on cerebral oxygen extraction and autoregulation in humans. METHODS: Nineteen patients with chronic hepatitis C virus infection, not responding to interferon treatment, were subjected to experimental therapy with extracorporeal whole body hyperthermia at 41.8 degrees C for 120 min under propofol anesthesia (23 sessions total). During treatment series A (13 sessions), end-tidal carbon dioxide was allowed to increase during heating. During series B (10 sessions), end-tidal carbon dioxide was maintained approximately constant. Cerebral oxygen extraction (arterial to jugular venous difference of oxygen content) and middle cerebral artery blood flow velocity were continuously measured. Cerebral pressure-flow autoregulation was assessed by static tests using phenylephrine infusion and by assessing the transient hyperemic response to carotid compression and release. RESULTS: For treatment series A, cerebral oxygen extraction decreased 2.2-fold and cerebral blood flow velocity increased 2.0-fold during heating. For series B, oxygen extraction decreased 1.6-fold and flow velocity increased 1.5-fold. Jugular venous oxygen saturation and lactate measurements did not indicate cerebral ischemia at any temperature. Static autoregulation test results indicated loss of cerebrovascular reactivity during hyperthermia for both series A and series B. The transient hyperemic response ratio did not decrease until the temperature reached approximately 40 degrees C. Per degree Celsius temperature increase, the transient hyperemic response ratio decreased 0.07 (95% confidence interval, 0.05-0.09; P = 0.000). This association remained after adjustment for variations in arterial partial pressure of carbon dioxide, mean arterial pressure, and propofol blood concentration. CONCLUSION: Profound hyperthermia during propofol anesthesia is associated with decreased cerebral oxygen extraction, increased cerebral blood flow velocity, and impaired pressure-flow autoregulation, indicating transient partial vasoparalysis.

Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial.

CONTEXT: Coronary artery bypass graft (CABG) surgery is associated with a decline in cognitive function, which has largely been attributed to the use of cardiopulmonary bypass (on-pump procedures). Cardiac stabilizers facilitate CABG surgery without use of cardiopulmonary bypass (off-pump procedures) and should reduce the cognitive decline associated with on-pump procedures. OBJECTIVE: To compare the effect of CABG surgery with (on-pump) and without (off-pump) cardiopulmonary bypass on cognitive outcome. DESIGN AND SETTING: Randomized controlled trial conducted in the Netherlands of CABG surgery patients enrolled from March 1998 through August 2000, with 3- and 12-month follow-up. PARTICIPANTS AND INTERVENTION: Patients scheduled for their first CABG surgery (mean age, 61 years; n = 281) were randomly assigned to off-pump surgery (n = 142) or on-pump surgery (n = 139). MAIN OUTCOME MEASURES: Cognitive outcome at 3 and 12 months, which was determined by psychologists (blinded for randomization) who administered 10 neuropsychological tests before and after surgery. Quality of life, stroke rate, and all-cause mortality at 3 and 12 months were secondary outcome measures. RESULTS: Cognitive outcome could be determined at 3 months in 248 patients. Cognitive decline occurred in 21% in the off-pump group and 29% in the on-pump group (relative risk [RR], 0.65; 95% confidence interval [CI], 0.36-1.16; P =.15). The overall standardized change score (ie, improvement of cognitive performance) was 0.19 in the off-pump vs 0.13 in the on-pump group (P =.03). At 12 months, cognitive decline occurred in 30.8% in the off-pump group and 33.6% in the on-pump group (RR, 0.88; 95% CI, 0.52-1.49; P =.69). The overall standardized change score was 0.19 in the off-pump vs 0.12 in the on-pump group (P =.09). No statistically significant differences were observed between the on-pump and off-pump groups in quality of life, stroke rate, or all-cause mortality at 3 and 12 months. CONCLUSION: Patients who received their first CABG surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure, but the effects were limited and became negligible at 12 months.