Nilas Young

Perioperative Dexmedetomidine Improves Outcomes of Cardiac Surgery

Background— Cardiac surgery is associated with a high risk of cardiovascular and other complications that translate into increased mortality and healthcare costs. This retrospective study was designed to determine whether the perioperative use of dexmedetomidine could reduce the incidence of complications and mortality after cardiac surgery. Methods and Results— A total of 1134 patients who underwent coronary artery bypass surgery and coronary artery bypass surgery plus valvular or other procedures were included. Of them, 568 received intravenous dexmedetomidine infusion and 566 did not. Data were adjusted with propensity scores, and multivariate logistic regression was used. The primary outcomes measured included mortality and postoperative major adverse cardiocerebral events (stroke, coma, perioperative myocardial infarction, heart block, or cardiac arrest). Secondary outcomes included renal failure, sepsis, delirium, postoperative ventilation hours, length of hospital stay, and 30-day readmission. Dexmedetomidine use significantly reduced postoperative in-hospital (1.23% versus 4.59%; adjusted odds ratio, 0.34; 95% confidence interval, 0.192–0.614; P<0.0001), 30-day (1.76% versus 5.12%; adjusted odds ratio, 0.39; 95% confidence interval, 0.226–0.655; P<0.0001), and 1-year (3.17% versus 7.95%; adjusted odds ratio, 0.47; 95% confidence interval, 0.312–0.701; P=0.0002) mortality. Perioperative dexmedetomidine therapy also reduced the risk of overall complications (47.18% versus 54.06%; adjusted odds ratio, 0.80; 95% confidence interval, 0.68–0.96; P=0.0136) and delirium (5.46% versus 7.42%; adjusted odds ratio, 0.53; 95% confidence interval, 0.37–0.75; P=0.0030). Conclusion— Perioperative dexmedetomidine use was associated with a decrease in postoperative mortality up to 1 year and decreased incidence of postoperative complications and delirium in patients undergoing cardiac surgery. Clinical Trial Registration— URL: www.clinicaltrials.gov. Unique identifier: NCT01683448.

Preoperative Aspirin Use and Outcomes in Cardiac Surgery Patients

Background: The effects of preoperative aspirin use on outcomes of cardiac surgery patients remain uncertain. This study was aimed to evaluate the effect of preoperative aspirin use on major outcomes in cardiac surgery patients. Methods: An observational cohort study was performed on consecutive patients (n = 4256) undergoing cardiac surgery in 2 tertiary hospitals. Of all patients, 2868 patients met the inclusion criteria and were divided into 2 groups: those taking (n = 1923) or not taking (n = 945) aspirin within 5 days preceding surgery. Results: Patients in the aspirin group presented significantly more with comorbidities including hypertension, diabetes, peripheral arterial disease, previous myocardial infarction, angina, cerebrovascular disease, older age, and male gender. With propensity scores adjusted and multivariate logistic regression, however, the results of this study showed that preoperative aspirin therapy (vs nonaspirin) significantly reduced the risk of 30-day mortality (3.5% vs 6.5%, OR: 0.611, 95% CI: 0.391–0.956, P = 0.031), postoperative renal failure (3.7% vs 7.1%, OR: 0.384, 95% CI: 0.254–0.579, P < 0.001), dialysis required (1.9% vs 3.6%, OR: 0.441, 95% CI: 0.254–0.579, P < 0.001), intensive care unit stay (mean 107.2 vs 136.1 h, P < 0.001) and a composite outcome-major adverse cardiocerebral events (8.7% vs 10.8%, OR: 0.662, 95% CI:: 0.482–0.909, P = 0.011) in the patients undergoing cardiac surgery. However, readmissions did not show a significant difference between the 2 groups (14.5% vs 12.8%, P = 0.944). Conclusions: Preoperative aspirin therapy is associated with a significant decrease in the risk of major cardiocerebral complications, renal failure, intensive care unit stay and 30-day mortality but does not increase the risk of readmissions in patients undergoing cardiac surgery.

Perioperative Dexmedetomidine Improves Mortality in Patients Undergoing Coronary Artery Bypass Surgery

OBJECTIVE This study retrospectively investigated the effect of dexmedetomidine on outcomes of patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN Retrospective investigation. SETTING Patients from a single tertiary medical center. PARTICIPANTS A total of 724 patients undergoing CABG surgery met the inclusion criteria and were categorized into 2 groups: 345 in the dexmedetomidine group (DEX) and 379 in the nondexmedetomidine group (Non-DEX). INTERVENTIONS Perioperative dexmedetomidine was used as an intravenous infusion (0.24 to 0.6 µg/kg/hour) initiated after cardiopulmonary bypass and continued for less than 24 hours postoperatively in the intensive care unit. MEASUREMENTS AND MAIN RESULTS Major outcome measures of this study were in-hospital, 30-day and 1-year all-cause mortality, delirium and major adverse cardiocerebral events. Perioperative dexmedetomidine infusion was associated with significant reductions in in-hospital, 30-day, and 1-year mortalities, compared with the patients who did not received dexmedetomidine. In-hospital, 30-day, and 1-year mortalities were 1.5% and 4.0% (adjusted odds ratio [OR], 0.332; 95% CI, 0.155 to 0.708; p = 0.0044), 2.0% and 4.5% (adjusted OR, 0.487; 95% CI, 0.253 to 0.985; p = 0.0305), and 3.2% and 6.9% (adjusted OR 0.421; 95% CI, 0.247 to 0.718, p = 0.0015), respectively. Perioperative dexmedetomidine infusion was associated with a reduced risk of delirium from 7.9% to 4.6% (adjusted OR, 0.431; 95% CI, 0.265-0.701; p = 0.0007). CONCLUSION Dexmedetomidine infusion during CABG surgery was more likely to achieve improved in-hospital, 30-day, and 1-year survival rates, and a significantly lower incidence of delirium.

Evidence for preoperative aspirin improving major outcomes in patients with chronic kidney disease undergoing cardiac surgery: a cohort study.

BACKGROUND Effects of aspirin on patients with chronic kidney disease (CKD) remains unclear. This study aimed to examine the effect of preoperative aspirin use on postoperative renal function and 30-day mortality in patients with CKD undergoing cardiac surgery. METHODS A retrospective cohort study was performed on consecutive patients (n = 5175) receiving cardiac surgery in 2 tertiary hospitals. Of all patients, 3585 met the inclusion criteria and underwent the analysis to determine the association of preoperative aspirin with incidence of acute kidney injury (AKI) and death based on estimated glomerular filtration rate (eGFR). RESULTS Of 3585 patients, 31.5% had CKD (eGFR < 60 mL/min/1.73 m2) at baseline and 27.6% had AKI postoperatively. The baseline eGFR had a nonlinear relationship with the incidence and stages of AKI. As eGFR decreased to 15 to 30 from more than or equal to 90 mL/min/1.73 m2, AKI and 30-day mortality increased to 50.5% from 23.5% and to 11.9% from 2.6%, respectively (P < 0.001). However, preoperative aspirin use was associated with a significant decrease in postoperative AKI and 30-day mortality in patients with CKD undergoing cardiac surgery, in particular, the survival benefit associated with aspirin was greater in patients with CKD (vs normal kidney function): 30-day mortality was reduced by 23.3%, 58.2%, or 70.0% for patients with baseline eGFR more than or equal to 90, 30 to 59, or 15 to 30 mL/min/1.73 m2, respectively (P trend < 0.001). CONCLUSIONS For patients with CKD undergoing cardiac surgery, preoperative aspirin therapy was associated with renal protection and mortality decline. The magnitude of the survival benefit was greater in patients with CKD than normal kidney function.

The Effects of Preoperative Renin-Angiotensin System Inhibitors on Outcomes in Patients Undergoing Cardiac Surgery

OBJECTIVE The effects of preoperative (pre-op) renin-angiotensin system (RAS) inhibitors on outcomes in patients undergoing cardiac surgery remain uncertain. The aim of this study was to evaluate whether the use of pre-op RAS inhibitors affected major outcomes of cardiac surgery. DESIGN A retrospective cohort study. SETTING A university teaching hospital. PARTICIPANTS Patients undergoing cardiac surgery between January 1, 2001 and December 31, 2011. INTERVENTIONS One thousand two hundred thirty-nine patients who received pre-op RAS inhibitors were compared with those who did not (control group, n = 1,083). MEASUREMENTS AND MAIN RESULTS Acute kidney injury (AKI) was defined using Acute Kidney Injury Network classification. Patients in the RAS inhibitors group presented with higher comorbidities. Pre-op RAS inhibitors therapy was associated with the reduction in the incidence of AKI (27.2% v 34.0%, p<0.001), septicemia (1.9% v 3.5%, p = 0.019), and operative mortality (2.99% v 4.62%, p = 0.039). After adjusted propensity scores and multivariate logistic regression, the pre-op RAS inhibitors were found to have protective effects against AKI (odds ratio [OR]: 0.764, 95% confidence interval [CI]: 0.670-0.873, p<0.001), septicemia (OR: 0.515, 95% CI: 0.348-0.761, p>0.001), and operative mortality (OR: 0.539, 95% CI: 0.348-0.758, p<0.001). CONCLUSION The results suggested that pre-op RAS inhibitor therapy was associated with significant reductions in the risk of AKI, operative mortality, and septicemia.

Response to letters regarding article, perioperative dexmedetomidine improves outcomes of cardiac surgery

We thank Hyder and colleagues for their careful, insightful reviews and thoughtful comments on our study that demonstrated that perioperative dexmedetomidine use is associated with better outcomes after cardiac surgery.1 We reported on the impact of a dexmedetomidine infusion started in the operating room after patients were separated from cardiopulmonary bypass. Because this was a retrospective, single-center study, all of the patients in both groups were managed in a similar fashion throughout the perioperative period. Intraoperative anesthesia management was consistent among our cardiac anesthesiologists, with an institutional standard of a moderate dose of narcotic (fentanyl or sufentanil) supplemented by a volatile anesthetic agent. Similarly, postoperative sedation in the intensive care unit was at the discretion of the intensive care unit care team, but the institutional protocol is infusions of fentanyl or midazolam supplemented by propofol when necessary for patient comfort. This protocol was used for patients who did not receive dexmedetomidine and those who required intubation and sedation for >24 hours. We initiated the dexmedetomidine infusion at the rate of 0.24 to 0.60 g/kg per hour to minimize the potential for bradycardia or hypotension that might be associated with loading doses or higher infusion rates. Previous studies have demonstrated that, even with loading doses and higher infusion rates, bradycardia and hypotension are not significant complications in this setting. …

Response: Does perioperative dexmedetomidine improve mortality after coronary artery bypass surgery?

LETTER TO THE EDITOR Response: Does Perioperative Dexmedetomidine Improve Mortality after Coronary Artery Bypass Surgery? To the Editor: We thank Dr. Xue and colleagues for their careful and insightful review and thoughtful comments on our study that demonstrated perioperative dexmedetomidine use was asso- ciated with better outcomes of coronary artery bypass surgery. 1 Dr. Xue and colleagues are concerned about preoperative anemia and the outcomes of cardiac surgery. We all agree that preoperative anemia is associated with outcomes of patients undergoing coronary artery bypass surgery. However, anemia was not a factor here in this study since both groups had the same preoperative hemoglobin level. On the other hand, patients in both groups were prepared the same way preopera- tively and included the adjustment of blood pressure control and preoperative anemia improvement according to the institu- tional protocol. This was the same with intraoperative anesthe- sia management. We believe none of our cardiac surgeons and anesthesiologists deviated too far away from our institutional standard. We also agree with Dr. Xue and colleagues’ com- ments that perioperative transfusion has been suggested to worsen the outcomes in coronary artery bypass surgery. 2 Again, we did not include blood and blood product transfusion because we did not believe dexmedetomidine adversely affected coagulation. This was an observational cohort study in the patient population with routine cardiac surgery. Multivariate regression in combination with propensity score adjustments were applied to this study population to reduce evident biases; however, the potential confounding biases associated with a non-randomized study remain. Data only could be included for analysis that was documented specifically on medical record. Because the data for our study was extracted from our institutional STS database, which is a voluntary database, under-reporting would be very unlikely. Although this study demonstrated that the risk of post- operative cardiocerebral events include MI, heart block, cardiac arrest, stroke, and coma, there appeared to be no significant decrease during perioperative use of dexmedetomidine after CABG surgery; the OR value of these events were all in favor of perioperative use of dexmedetomidine. Studies have demon- strated the effectiveness of dexmedetomidine as a stress- suppressing, anti-inflammatory, and anti- I/R injury agent in the prevention and treatment of cardiovascular events. 3–5 Catecholamines potentially may exacerbate myocardial injury and cause perioperative myocardial ischemia, which has been shown to increase the risk of postoperative mortality. There- fore, reducing the incidence of perioperative myocardial ischemia reduces the mortality by blunting the sympathetic- adrenal-axis response through decreasing central sympathetic activity at the locus ceruleus. 6,7 Laboratory studies have demonstrated that alpha 2 adrenergic agonists have protective effects against myocardial ischemia by reducing plasma nor- epinephrine levels and preserving myocardial blood flow to the endocardium by increasing the cAMP level and enhancing adenosine-induced coronary vasodilation effect. 8–10 Dexmede- tomidine also reduces inflammation and delirium that contri- bute to mortalities. A pre-clinical study demonstrated that dexmedetomidine reduced inflammatory reaction and mortality. Therefore, we believe the reduction of mortality represents the overall effects of dexmedetomidine. We share the commentators’ concerns on how to interpret the results. We never mentioned anywhere in our article there is a causal relationship. Instead, we repeatedly have stated that perioperative dexmedetomidine use was associated with a decrease in postoperative mortality up to 1 year and decreased incidence of postoperative complications and delirium in patients undergoing coronary artery bypass surgery. We stated in our conclusion that a prospective, multicenter, randomized study focused on the use of dexmedetomidine in patients undergoing coronary artery bypass surgery is indicated to confirm these findings. 1 However, this study was conducted in the real world; we will never find the ideal experimental condition in our everyday clinical practice. Fuhai Ji, MD *† Zhongmin Li, PhD ‡ Nilas Young, MD § Peter Moore, MD, PhD † Hong Liu, MD † *Department of Anesthesiology First Affiliated Hospital of Soochow University Suzhou, Jiangsu, China Departments of †Anesthesiology and Pain Medicine ‡Internal Medicine, and §Surgery University of California Davis Health System Sacramento, CA. REFERENCES 1. Ji F, Li Z, Young N, et al: Perioperative dexmedetomidine improves mortality in patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth 28:267-273, 2014 2. LaPar DJ, Crosby IK, Ailawadi G, et al: Investigators for the Virginia cardiac surgery quality initiative. Blood product conservation is associated with improved outcomes and reduced costs after cardiac surgery. J Thorac Cardiovasc Surg 145:796-803, 2013 3. Jalonen J, Hynynen M, Kuitunen A, et al: Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology Journal of Cardiothoracic and Vascular Anesthesia, Vol ], No ] (Month), 2014: pp ]]]–]]]

Reply to letters: "Preoperative aspirin use and outcomes in cardiac surgery patients: a role of platelet function assessment" and "Preoperative aspirin use in cardiac surgery".

D r Petricevic and colleagues raise several important questions in their letter commenting on our article published in Annals of Surgery,1 especially regarding “the lack of objective quantification of the antiplatelet effect of aspirin in group of patients taking aspirin within 5 days preceding surgery.” First, our study is an observational retrospective cohort study in which we could trace only the data collected in the databases while platelet function tests were not there. Some of the data were also lacking in the database including the chest tube draining and preoperative MACE events, although we certainly would like have them for the study. Second, the mechanisms responsible for the beneficial effects of aspirin in patients undergoing cardiac surgery remain unclear. The benefits we observed in our study could well be the results of the effects of aspirin other than just antiplatelet, such as antiinflammation. Third, Petricevic et al2 quoted their study that used a point-of-care platelet function analyzer (multiple-electrode aggregometry) to determine whether the patient’s platelet aggregation was inhibited and whether the patient was resistant to aspirin. However, platelet function testing has shown significant differences in responses in patients treated with aspirin and there is no “gold standard” laboratory test for assessing platelet function.3 Besides noncompliance, multiple confounding factors could underlie incomplete platelet response to aspirin, including bioavailability (underdosing, poor absorption, interference with other drugs), platelet function (incomplete suppression of thromboxane A2 generation, enhanced platelet turnover), polymorphisms of thromboxane receptor, smoking, hypercholesterolemia, stress, and exercise.4