Nancy A. Nussmeier

Adverse Cerebral Outcomes after Coronary Bypass Surgery

Background Acute changes in cerebral function after elective coronary bypass surgery are a difficult clinical problem. We carried out a multicenter study to determine the incidence and predictors of — and the use of resources associated with — perioperative adverse neurologic events, including cerebral injury. Methods In a prospective study, we evaluated 2108 patients from 24 U.S. institutions for two general categories of neurologic outcome: type I (focal injury, or stupor or coma at discharge) and type II (deterioration in intellectual function, memory deficit, or seizures). Results Adverse cerebral outcomes occurred in 129 patients (6.1 percent). A total of 3.1 percent had type I neurologic outcomes (8 died of cerebral injury, 55 had nonfatal strokes, 2 had transient ischemic attacks, and 1 had stupor), and 3.0 percent had type II outcomes (55 had deterioration of intellectual function and 8 had seizures). Patients with adverse cerebral outcomes had higher in-hospital mortality (21 percent of patients ...

Effectiveness-Based Guidelines for the Prevention of Cardiovascular Disease in Women—2011 Update: A Guideline From the American Heart Association

Substantial progress has been made in the awareness, treatment, and prevention of cardiovascular disease (CVD) in women since the first women-specific clinical recommendations for the prevention of CVD were published by the American Heart Association (AHA) in 1999.1 The myth that heart disease is a “mans disease” has been debunked; the rate of public awareness of CVD as the leading cause of death among US women has increased from 30% in 1997 to 54% in 2009.2 The age-adjusted death rate resulting from coronary heart disease (CHD) in females, which accounts for about half of all CVD deaths in women, was 95.7 per 100 000 females in 2007, a third of what it was in 1980.3,4 Approximately 50% of this decline in CHD deaths has been attributed to reducing major risk factors and the other half to treatment of CHD including secondary preventive therapies.4 Major randomized controlled clinical trials such as the Womens Health Initiative have changed the practice of CVD prevention in women over the past decade.5 The investment in combating this major public health issue for women has been significant, as have the scientific and medical achievements. Despite the gains that have been made, considerable challenges remain. In 2007, CVD still caused ≈1 death per minute among women in the United States.6 These represent 421 918 deaths, more womens lives than were claimed by cancer, chronic lower respiratory disease, Alzheimer disease, and accidents combined.6 Reversing a trend of the past 4 decades, CHD death rates in US women 35 to 54 years of age now actually appear to be increasing, likely because of the effects of the obesity epidemic.4 CVD rates in the United States are significantly higher for black females compared with their white counterparts (286.1/100 000 versus …

Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery

OBJECTIVE Inhibition of cyclooxygenase 2 provides analgesia in ambulatory patients. We prospectively evaluated the safety and efficacy of a newly introduced cyclooxygenase 2 inhibitor in patients undergoing coronary artery bypass grafting surgery through a median sternotomy in a randomized clinical trial. METHODS A total of 462 patients with New York Heart Association classes I to III who were less than 77 years of age and were from 58 institutions in the United States, Canada, Germany, and the United Kingdom participated in this multicenter, phase III, placebo-controlled, double-blind, randomized, parallel-group trial. Patients were allocated at a ratio of 2:1 to parecoxib/valdecoxib or standard care (control) groups, respectively. Intravenous study drug (40 mg) was administered within 30 minutes after extubation and every 12 hours for a minimum of 3 days. Subsequently, oral treatment at a dose of 40 mg every 12 hours was initiated and administered for a combined total of 14 days. Patient-controlled analgesia with morphine, oral opioids, or acetaminophen was available as required. Assessment of the analgesic efficacy of the study drug was primarily based on morphine and morphine equivalent use. Additional efficacy evaluations included daily pain intensity, patient and physician global evaluation of study medication, and pain effect on quality of life. Clinical adverse events were assessed by the principal investigator at each site from the time of the first dose through the 30-day postdosing period. RESULTS Patients in the parecoxib/valdecoxib group received significantly less morphine or morphine equivalents than patients in the control group during the 0- to 24-hour (P =.009), 24- to 48-hour (P =.017), 72- to 96-hour (P =.002), 96- to 120-hour (P =.004), and 120- to 144-hour (P =.037) periods. Both patients (P <.001) and physicians (P <.001) evaluated the study medication as significantly better than control therapy. The modified Brief Pain Inventory questionnaire used in the oral dosing period detected significant improvements in the parecoxib/valdecoxib treatment group in 6 of 8 domains tested (eg, current pain, worst pain, and mood) beginning on day 4 and continuing for at least 4 days. Although there were no differences between the groups in overall adverse events, serious adverse events occurred twice as frequently in parecoxib/valdecoxib-treated patients (19.0%, 59/311 patients) than in control patients (9.9%, 15/151 patients; P =.015). Regarding individual serious adverse events, a greater incidence in sternal wound infection was found in the parecoxib/valdecoxib patients (10 [3.2%]) versus control patients (0 [0%]) (P =.035). The incidences of other individual serious adverse events, including cerebrovascular complications, myocardial infarction, and renal dysfunction, were proportionally greater but not significantly different between the groups. CONCLUSIONS In patients undergoing coronary artery bypass grafting surgery, the cyclooxygenase 2 inhibitor combination, parecoxib/valdecoxib, was effective for postoperative analgesia. However, the 14-day treatment regimen also was associated with an increased incidence of serious adverse events overall and sternal wound infections in particular. Therefore our study raises important concerns requiring their comprehensive evaluation in a large-scale trial before these cyclooxygenase 2 inhibitors are used in patients undergoing coronary artery bypass grafting surgery.

Neuropsychiatric complications after cardiopulmonary bypass: cerebral protection by a barbiturate.

The authors prospectively investigated the ability of thiopental to decrease neuropsychiatric complications as a consequence of openventricle operations requiring cardiopulmonary bypass. Eighty-nine randomly assigned patients received sufficient thiopental to maintain electroencephalographic silence throughout the period from before atrial cannulation to termination of bypass. These patients received an average of 39.5 mg/kg of thiopental, while 93 control patients received only fentanyl. On the first postoperative day, five thiopental (5.6%) and eight control (8.6%) patients exhibited clinical neuro-psychiatric abnormalities. By the tenth postoperative day, all neuropsychiatric dysfunction had resolved in the thiopental group but persisted in seven (7.5%) control patients (P < 0.025). The incidence of complications was significantly related to calcification of replaced valves, aortic valve replacement, advanced age, and prolonged bypass, but not to low blood pressure during perfusion. The authors believe their data are consistent with embolism as the most important cause of sensory-motor neurologic dysfunction following cardiopulmonary bypass. The data also provide evidence that thiopental in sufficient dosage can reduce the clinical consequences of these events. This is the first demonstration of cerebral protection by a barbiturate in humans.

Cerebral Injury After Cardiac Surgery Identification of a Group at Extraordinary Risk

BACKGROUND AND PURPOSE Cerebral injury after cardiac surgery is now recognized as a serious and costly healthcare problem mandating immediate attention. To effect solution, those subgroups of patients at greatest risk must be identified, thereby allowing efficient implementation of new clinical strategies. No such subgroup has been identified; however, patients undergoing intracardiac surgery are thought to be at high risk, but comprehensive data regarding specific risk, impact on cost, and discharge disposition are not available. METHODS We prospectively studied 273 patients enrolled from 24 diverse US medical centers, who were undergoing intracardiac and coronary artery surgery. Patient data were collected using standardized methods and included clinical, historical, specialized testing, neurological outcome and autopsy data, and measures of resource utilization. Adverse outcomes were defined a priori and determined after database closure by a blinded independent panel. Stepwise logistic regression models were developed to estimate the relative risks associated with clinical history and intraoperative and postoperative events. RESULTS Adverse cerebral outcomes occurred in 16% of patients (43/273), being nearly equally divided between type I outcomes (8.4%; 5 cerebral deaths, 16 nonfatal strokes, and 2 new TIAs) and type II outcomes (7.3%; 17 new intellectual deterioration persisting at hospital discharge and 3 newly diagnosed seizures). Associated resource utilization was significantly increased--prolonging median intensive care unit stay from 3 days (no adverse cerebral outcome) to 8 days (type I; P<0.001) and from 3 to 6 days (type II; P<0.001), and increasing hospitalization by 50% (type II, P=0.04) to 100% (type I, P<0.001). Furthermore, specialized care after hospital discharge was frequently necessary in those with type I outcomes, in that only 31% returned home compared with 85% of patients without cerebral complications (P<0.001). Significant risk factors for type I outcomes related primarily to embolic phenomena, including proximal aortic atherosclerosis, intracardiac thrombus, and intermittent clamping of the aorta during surgery. For type II outcomes, risk factors again included proximal aortic atherosclerosis, as well as a preoperative history of endocarditis, alcohol abuse, perioperative dysrhythmia or poorly controlled hypertension, and the development of a low-output state after cardiopulmonary bypass. CONCLUSIONS These prospective multicenter findings demonstrate that patients undergoing intracardiac surgery combined with coronary revascularization are at formidable risk, in that 1 in 6 will develop cerebral complications that are frequently costly and devastating. Thus, new strategies for perioperative management--including technical and pharmacological interventions--are now mandated for this subgroup of cardiac surgery patients.

Gender and outcomes after coronary artery bypass grafting: A propensity-matched comparison

OBJECTIVE Our objective is to determine whether gender is a marker or a causal influence for poor outcomes after coronary revascularization. METHODS Propensity-modeling techniques were used to investigate whether gender adversely impacts outcomes after coronary revascularization. A parsimonious explanatory model was developed by bootstrap bagging with variable selection from 64 baseline and 37 operative variables. Propensity scores were calculated from a logistic model that included the parsimonious model and additional baseline variables. Greedy matching techniques were applied to match female and male patients to the nearest propensity scores. Comparisons were made among the propensity-matched women and men. RESULTS Of the 15,597 patients undergoing isolated coronary artery bypass graft surgery, only 26% of the 3596 women were matched on propensity scores with men. Distribution of covariates among the matched pairs was, on average, equal. Postoperative mortality (P =.76), neurologic morbidity (global deficit P =.07, focal deficit P =.51), infection (sepsis P =.88), mediastinitis (P =.18), renal failure (P =.84), intra-aortic balloon pump usage (P =.61), and reoperation for bleeding (P =.10) were similar among women and men. Occurrence of Q-wave myocardial infarction (P = <.01), postoperative inotropic usage (P = <.01), and prolonged ventilatory support (P =.02) were more common in women compared with propensity-matched men. CONCLUSIONS The preoperative profiles of women and men are markedly different. Propensity matching women and men was difficult, because only 26% of women were able to be matched with men. However, in well-matched patients, female gender was not associated with increased mortality and had minimal impact on morbidity after coronary artery bypass grafting.

Patient Safety in the Cardiac Operating Room: Human Factors and Teamwork A Scientific Statement From the American Heart Association

The cardiac surgical operating room (OR) is a complex environment in which highly trained subspecialists interact with each other using sophisticated equipment to care for patients with severe cardiac disease and significant comorbidities. Thousands of patient lives have been saved or significantly improved with the advent of modern cardiac surgery. Indeed, both mortality and morbidity for coronary artery bypass surgery have decreased during the past decade (Figure 1).1 Nonetheless, the highly skilled and dedicated personnel in cardiac ORs are human and will make errors. In 1991, Leape and colleagues2,3 estimated that among the 2 million patients hospitalized in New York in 1984, there were 27 179 adverse events that involved negligence; other evidence suggests that up to 16% of hospital inpatients are harmed.4 Gawande and associates5 found that the incidence of surgical adverse events was 12% among cardiac surgery patients versus 3% in other surgical patients; 54% of the adverse events were considered preventable. Of the roughly 350 000 to 500 000 patients who undergo cardiac surgery each year, 28 000 will have an adverse event, and one third of deaths associated with coronary artery bypass graft (CABG) operations may be preventable.6 Figure 1. Change in mortality and stroke rates in patients undergoing isolated coronary artery bypass graft (CABG) surgery, 2000 to 2009. There was a 24.4% and 26.4% reduction in the unadjusted observed operative mortality (2.4% vs 1.9%) and stroke rates (1.6% vs 1.2%), respectively, during the course of the study period. Reprinted from ElBardissi et al1 with permission from Elsevier. Copyright

Both Bias and Lack of Knowledge Influence Organizational Focus on First Case of the Day Starts

BACKGROUND: The economic costs of reducing first case delays are often high, because efforts need to be applied to multiple operating rooms (ORs) simultaneously. Nevertheless, delays in starting first cases of the day are a common topic in OR committee meetings. METHODS: We added three scientific questions to a 24 question online, anonymous survey performed before the implementation of a new OR information system. The 57 respondents cared sufficiently about OR management at the United States teaching hospital to complete all questions. RESULTS: The survey revealed reasons why personnel may focus on the small reductions in nonoperative time achievable by reducing tardiness in first cases of the day. (A) Respondents lacked knowledge about principles in reducing over-utilized OR time to increase OR efficiency, based on their answering the relevant question correctly at a rate no different from guessing at random. Those results differed from prior findings of responses at a rate worse than random, resulting from a bias on the day of surgery of making decisions that increase clinical work per unit time. (B) Most respondents falsely believed that a 10 min delay at the start of the day causes subsequent cases to start at least 10 min late (P < 0.0001 versus random chance)

Washin and washout of isoflurane administered via bubble oxygenators during hypothermic cardiopulmonary bypass.

Washin and washout of a volatile anesthetic given through the oxygenator during hypothermic (23.4 +/- 2.1 degrees C) cardiopulmonary bypass were studied in nine patients. The authors administered isoflurane and measured its partial pressure in arterial (Pa) and venous (Pv) blood and the gas exhausted from the oxygenator (PE) at 1, 2, 4, 8, 16, 32, and 48 min during washin. These measurements were repeated during washout, which coincided with rewarming. During washin, PE, Pa, and Pv progressively rose toward inlet gas partial pressure (PI). Equilibration of Pa with PI was 41% after 16 min, 51% after 32 min, and 57% after 48 min of washin. During washout, Pa declined to 24% of its peak after 16 min and to 13% after 32 min. Washin and washout were considerably slower in mixed venous blood. Washin of isoflurane appeared to occur more slowly during cardiopulmonary bypass than during administration via the lungs in normothermic patients, presumably because hypothermia increases tissue capacity, compensating for the effect of hemodilution that otherwise would decrease the blood/gas partition coefficient. During rewarming, washout appeared to occur as rapidly as from the lungs of normothermic patients. This may have resulted from the declining blood/gas partition coefficient (due to rewarming) and relatively limited tissue stores of isoflurane. The relationship between exhaust and arterial partial pressures was reasonably consistent; for clinical purposes, measurement of PE can be used to estimate Pa.

Systematic review of general thoracic surgery articles to identify predictors of operating room case durations.

BACKGROUND: Previous studies of operating room (OR) information systems data over the past two decades have shown how to predict case durations using the combination of scheduled procedure(s), individual surgeon and assistant(s), and type of anesthetic(s). We hypothesized that the accuracy of case duration prediction could be improved by the use of other electronic medical record data (e.g., patient weight or surgeon notes using standardized vocabularies). METHODS: General thoracic surgery was used as a model specialty because much of its workload is elective (scheduled) and many of its cases are long. PubMed was searched for thoracic surgery papers reporting operative time, surgical time, etc. The systematic literature review identified 48 papers reporting statistically significant differences in perioperative times. RESULTS: There were multiple reports of differences in OR times based on the procedure(s), perioperative team including primary surgeon, and type of anesthetic, in that sequence of importance. All such detail may not be known when the case is originally scheduled and thus may require an updated duration the day before surgery. Although the use of these categorical data from OR systems can result in few historical data for estimating each case’s duration, bias and imprecision of case duration estimates are unlikely to be affected. There was a report of a difference in case duration based on additional information. However, the incidence of the procedure for the diagnosis was so uncommon as to be unlikely to affect OR management. CONCLUSIONS: Matching findings of prior studies using OR information system data, multiple case series show that it is important to rely on the precise procedure(s), surgical team, and type of anesthetic when estimating case durations. OR information systems need to incorporate the statistical methods designed for small numbers of prior surgical cases. Future research should focus on the most effective methods to update the prediction of each case’s duration as these data become available. The case series did not reveal additional data which could be cost-effectively integrated with OR information systems data to improve the accuracy of predicted durations for general thoracic surgery cases.