Predictors and associated clinical outcomes of low cardiac output syndrome following cardiac surgery: insights from the LEVO-CTS trial.

AIMS: High-risk cardiac surgery is commonly complicated by low cardiac output syndrome (LCOS), which is associated with high mortality. There are limited data derived from multi-centre studies with adjudicated endpoints describing factors associated with LCOS and its downstream clinical outcomes. METHODS AND RESULTS: The Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial evaluated prophylactic levosimendan vs. placebo in patients with a reduced ejection fraction undergoing coronary artery bypass grafting (CABG) and/or valve surgery. We conducted a pre-specified analysis on LCOS, which was characterized by a four-part definition. We constructed a multivariable logistical regression model to evaluate risk factors associated with LCOS and performed Cox proportional hazards modelling to determine the association of LCOS with 90-day mortality. A total of 186 (22%) of 849 patients in the LEVO-CTS trial developed LCOS. The factors most associated with a higher adjusted risk of LCOS were pre-operative ejection fraction [odds ratio (OR) 1.26; 95% confidence interval (CI): 1.08-1.46 per 5% decrease] and age (OR 1.13; 95% CI: 1.04-1.24 per 5-year increase), whereas isolated CABG surgery (OR 0.44, 95% CI: 0.31-0.64) and levosimendan use (OR 0.65; 95% CI: 0.46-0.92) were associated with a lower risk of LCOS. Patients with LCOS had worse outcomes, including renal replacement therapy at 30-day (10 vs. 1%) and 90-day mortality (16 vs. 3%, adjusted hazard ratio of 5.04, 95% CI: 2.66-9.55). CONCLUSION: Low cardiac output syndrome is associated with a high risk of post-operative mortality in high-risk cardiac surgery.

Real Age: Red Blood Cell Aging During Storage.

BACKGROUND: During cold storage, some red blood cell (RBC) units age more rapidly than others. Yet, the Food and Drug Administration has set a uniform storage limit of 42 days. Objectives of this review are to present evidence for an RBC storage lesion and suggest that functional measures of stored RBC quality-which we call real age-may be more appropriate than calendar age. METHODS: During RBC storage, biochemical substances and byproducts accumulate and RBC shape alters. Factors that influence the rate of degradation include donor characteristics, bio-preservation conditions, and vesiculation. Better understanding of markers of RBC quality may lead to standardized, quantifiable, and operationally practical measures to improve donor selection, assess quality of an RBC unit, improve storage conditions, and test efficacy of the transfused product. RESULTS: The conundrum is that clinical trials of younger versus older RBC units have not aligned with in vitro aging data; that is, the units transfused were not old enough. In vitro changes are considerable beyond 28 to 35 days, and average storage age for older transfused units was 14 to 21 days. CONCLUSIONS: RBC product real age varies by donor characteristics, storage conditions, and biological changes during storage. Metrics to measure temporal changes in quality of the stored RBC product may be more appropriate than the 42-day expiration date. Randomized trials and observational studies are focused on average effect, but, in the evolving age of precision medicine, we must acknowledge that vulnerable populations and individuals may be harmed by aging blood.

A Randomized Clinical Trial of Red Blood Cell Transfusion Triggers in Cardiac Surgery.

BACKGROUND: Class I evidence supporting a threshold for transfusion in the cardiac surgical setting is scarce. We randomly allocated patients to a transfusion hematocrit trigger of 24% versus 28% to compare morbidity, mortality, and resource use. METHODS: From March 2007 to August 2014, two centers randomly assigned 722 adults undergoing coronary artery bypass graft surgery or valve procedures to a 24% hematocrit trigger (n = 363, low group) or 28% trigger (n = 354, high group). One unit of red blood cells was transfused if the hematocrit fell below the designated threshold. The primary endpoint was a composite of postoperative morbidities and mortality. Treatment effect was primarily assessed using an average relative effect generalized estimating equation model. RESULTS: At the second planned interim analysis, the a priori futility boundary was crossed, and the study was stopped. There was no detected treatment effect on the composite outcome (average relative effect odds ratio, low versus high, 0.86, 95% confidence interval: 0.29 to 2.54, p = 0.71). However, the low group received fewer red blood cell transfusions than the high group (54% versus 75%, p < 0.001), mostly administered in the operating room (low group, 112 [31%]; high group, 208 [59%]), followed by intensive care unit (low, 105 [31%]; high, 115 [34%]) and floor (low, 41 [12%]; high, 42 [13%]). The low group was exposed to lower hematocrits: median before transfusion, 22% (Q1 = 21%, Q3 = 23%) versus 24% (Q1 = 22%, Q3 = 25%). CONCLUSIONS: Negative exposures differed between treatment groups, with lower hematocrit in the 24% trigger group and more red blood cells used in the 28% group, but adverse outcomes did not differ. Because red blood cell use was less with a 24% trigger without adverse effects, our randomized trial results support aggressive blood conservation efforts in cardiac surgery.

Recent metformin ingestion does not increase in-hospital morbidity or mortality after cardiac surgery.

BACKGROUND: Perioperative treatment of type 2 diabetes with metformin, an oral hypoglycemic drug, is thought to increase the risk of life-threatening postoperative lactic acidosis. In contrast, metformin improves serum glucose control and has beneficial cardiovascular effects, which may decrease the risk of adverse outcomes. In this investigation we sought to determine the influence of metformin treatment on mortality and morbidity compared with treatment with other oral hypoglycemic drugs in diabetic patients undergoing cardiac surgery. METHODS: In this retrospective investigation, 1284 diabetic patients, with recent oral hypoglycemic ingestion (presumed to be 8-24 h preoperatively), underwent cardiac surgery from 1994-2004. Propensity scores were calculated from a logistic model which included baseline characteristics and perioperative variables. Four-hundred-forty-three (85%) of the metformin-treated patients were matched on nearest propensity score using greedy matching techniques with 443 nonmetformin-treated patients. Postoperative outcomes were compared between matched metformin- and nonmetformin-treated patients. RESULTS: In-hospital mortality, cardiac, renal, and neurologic morbidities were similar between groups. Metformin-treated patients had less postoperative prolonged tracheal intubation [OR (95% CI), 0.3 (0.1, 0.7), P = 0.003], infection [0.2 (0.1, 0.7), P = 0.007] and overall morbidities [0.4 (0.2, 0.8), P = 0.005]. CONCLUSIONS: These data suggest that recent metformin ingestion is not associated with increased risk of adverse outcome in cardiac surgical patients. Alternatively, metformin treatment may have beneficial effects.

Red cell transfusion is associated with an increased risk for postoperative atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common complication after cardiac surgery and is associated with increased resource utilization. Recent evidence supports a role of inflammation in the development of AF. It is also known that red blood cell transfusion modulates inflammation by increasing plasma levels of inflammatory markers. Therefore, we tested the hypothesis that red blood cell transfusion increases the risk of postoperative AF for patients undergoing cardiac surgery. METHODS: Between February 2002 and January 2005, 5,841 patients underwent isolated coronary artery bypass grafting with or without valve replacement. Patient and procedural variables associated with development of new-onset AF were identified by logistic regression. Propensity score matching was used to confirm results. RESULTS: In addition to older age, prior history of AF, higher preoperative hematocrit, beta-blocker withdrawal, longer aortic clamp time, valve surgery, and intensive care unit inotropic usage, intensive care unit red blood cell transfusion increased risk for AF (odds ratio per unit transfused, 1.18; 95% confidence limits, 1.14, 1.23; p < 0.0001). For the 1,360 propensity-matched pairs, intensive care unit red blood cell transfusion was associated with a significant increase in new-onset AF (620 [46%] versus 522 [38%]; p < 0.001). CONCLUSIONS: Intensive care unit red blood cell transfusion is associated with increased occurrence of postoperative AF after cardiac surgery. This factor should be considered in identifying patients who might benefit from prophylaxis to prevent this common postoperative complication.

Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting.

OBJECTIVE: Our objective was to quantify incremental risk associated with transfusion of packed red blood cells and other blood components on morbidity after coronary artery bypass grafting. DESIGN: The study design was an observational cohort study. SETTING: This investigation took place at a large tertiary care referral center. PATIENTS: A total of 11,963 patients who underwent isolated coronary artery bypass from January 1, 1995, through July 1, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 11,963 patients who underwent isolated coronary artery bypass grafting, 5,814 (48.6%) were transfused. Risk-adjusted probability of developing in-hospital mortality and morbidity as a function of red blood cell and blood-component transfusion was modeled using logistic regression. Transfusion of red blood cells was associated with a risk-adjusted increased risk for every postoperative morbid event: mortality (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.67-1.87; p<.0001), renal failure (OR, 2.06; 95% CI, 1.87-2.27; p<.0001), prolonged ventilatory support (OR, 1.79; 95% CI, 1.72-1.86; p<.0001), serious infection (OR, 1.76; 95% CI, 1.68-1.84; p<.0001), cardiac complications (OR, 1.55; 95% CI, 1.47-1.63; p<.0001), and neurologic events (OR, 1.37; 95% CI, 1.30-1.44; p<.0001). CONCLUSIONS: Perioperative red blood cell transfusion is the single factor most reliably associated with increased risk of postoperative morbid events after isolated coronary artery bypass grafting. Each unit of red cells transfused is associated with incrementally increased risk for adverse outcome.

Transfusion in coronary artery bypass grafting is associated with reduced long-term survival.

BACKGROUND: Perioperative red blood cell (PRBC) transfusion has been associated with early risk for morbid outcomes, but risk related to long-term survival has not been thoroughly explored. Therefore, we examined the influence of PRBC transfusion and component therapy on long-term survival after isolated coronary artery bypass grafting after controlling for the effect of demographics, comorbidities, operative factors, and the early hazard for death. METHODS: The US Social Security Death Index was used to ascertain survival status for 10,289 patients who underwent isolated coronary artery bypass grafting from January 1, 1995 through June 28, 2002. The outcome measure was all-cause mortality during the follow-up period. Unadjusted survival estimates were performed using the Kaplan-Meier techniques. Survival curves for transfusion status were compared with the log-rank test. The parametric decomposition model was used for risk-adjusted survival. A balancing score was calculated for each patient and forced into the final model. RESULTS: Survival among transfused patients was significantly reduced as compared with nontransfused patients. The instantaneous risk of death displayed a biphasic pattern: a declining hazard phase from the time of the operation (early hazard) up until 6 months postoperatively and then a late hazard that continued out until about 10 years. Transfusion of red cells was associated with a risk-adjusted reduction in survival for both the early (0.34 +/- 0.02, p < 0.0001) and late phases (0.074 +/- 0.016, p < 0.0001). CONCLUSIONS: Perioperative PRBC transfusion is associated with adverse long-term sequela in isolated CABG. Attention should be directed toward blood conservation methods and a more judicious use of PRBC.