Elizabeth S. Jewell

Common genetic variation in the 3β-BCL11B gene desert is associated with carotid-femoral pulse wave velocity and excess cardiovascular disease risk the aortagen consortium

Background— Carotid-femoral pulse wave velocity (CFPWV) is a heritable measure of aortic stiffness that is strongly associated with increased risk for major cardiovascular disease events. Methods and Results— We conducted a meta-analysis of genome-wide association data in 9 community-based European ancestry cohorts consisting of 20 634 participants. Results were replicated in 2 additional European ancestry cohorts involving 5306 participants. Based on a preliminary analysis of 6 cohorts, we identified a locus on chromosome 14 in the 3′-BCL11B gene desert that is associated with CFPWV (rs7152623, minor allele frequency=0.42, &bgr;=−0.075±0.012 SD/allele, P=2.8×10−10; replication &bgr;=−0.086±0.020 SD/allele, P=1.4×10−6). Combined results for rs7152623 from 11 cohorts gave &bgr;=−0.076±0.010 SD/allele, P=3.1×10−15. The association persisted when adjusted for mean arterial pressure (&bgr;=−0.060±0.009 SD/allele, P=1.0×10−11). Results were consistent in younger (<55 years, 6 cohorts, n=13 914, &bgr;=−0.081±0.014 SD/allele, P=2.3×10−9) and older (9 cohorts, n=12 026, &bgr;=−0.061±0.014 SD/allele, P=9.4×10−6) participants. In separate meta-analyses, the locus was associated with increased risk for coronary artery disease (hazard ratio=1.05; confidence interval=1.02–1.08; P=0.0013) and heart failure (hazard ratio=1.10, CI=1.03–1.16, P=0.004). Conclusions— Common genetic variation in a locus in the BCL11B gene desert that is thought to harbor 1 or more gene enhancers is associated with higher CFPWV and increased risk for cardiovascular disease. Elucidation of the role this novel locus plays in aortic stiffness may facilitate development of therapeutic interventions that limit aortic stiffening and related cardiovascular disease events.

Preoperative and intraoperative predictors of postoperative acute respiratory distress syndrome in a general surgical population.

Background:Acute respiratory distress syndrome (ARDS) is a devastating condition with an estimated mortality exceeding 30%. There are data suggesting risk factors for ARDS development in high-risk populations, but few data are available in lower incidence populations. Using risk-matched analysis and a combination of clinical and research data sets, we determined the incidence and risk factors for the development of ARDS in this general surgical population. Methods:We conducted a review of common adult surgical procedures completed between June 1, 2004 and May 31, 2009 using an anesthesia information system. This data set was merged with an ARDS registry and an institutional death registry. Preoperative variables were subjected to multivariate analysis. Matching and multivariate regression was used to determine intraoperative factors associated with ARDS development. Results:In total, 50,367 separate patient admissions were identified, and 93 (0.2%) of these patients developed ARDS. Preoperative risk factors for ARDS development included American Society of Anesthesiologist status 3–5 (odds ratio [OR] 18.96), emergent surgery (OR 9.34), renal failure (OR 2.19), chronic obstructive pulmonary disease (OR 2.16), number of anesthetics during the admission (OR 1.37), and male sex (OR 1.65). After matching, intraoperative risk factors included drive pressure (OR 1.17), fraction inspired oxygen (OR 1.02), crystalloid administration in liters (1.43), and erythrocyte transfusion (OR 5.36). Conclusions:ARDS is a rare condition postoperatively in the general surgical population and is exceptionally uncommon in low American Society of Anesthesiologists status patients undergoing scheduled surgery. Analysis after matching suggests that ARDS development is associated with median drive pressure, fraction inspired oxygen, crystalloid volume, and transfusion.

Regional versus general anesthesia in surgical patients with chronic obstructive pulmonary disease: does avoiding general anesthesia reduce the risk of postoperative complications?

BACKGROUND:Surgical patients with chronic obstructive pulmonary disease (COPD) are at increased risk of perioperative complications. In this study, we sought to quantify the benefit of avoiding general anesthesia in this patient population. METHODS:Data from the National Surgical Quality Improvement Program database (2005–2010) were used for this review. Patients who met the National Surgical Quality Improvement Program definition for COPD and underwent surgery under general, spinal, epidural, or peripheral nerve block anesthesia were included in this study. For each primary current procedural terminology code with ≥1 general and ≥1 regional (spinal, epidural, or peripheral nerve block) anesthetic, regional patients were propensity score--matched to general anesthetic patients. Propensity scoring was calculated using all available demographic and comorbidity data. This match yielded 2644 patients who received regional anesthesia and 2644 matched general anesthetic patients. These groups were compared for morbidity and mortality. RESULTS:Groups were well matched on demographics, comorbidities, and type of surgery. Compared with matched patients who received regional anesthesia, patients who received general anesthesia had a higher incidence of postoperative pneumonia (3.3% vs 2.3%, P = 0.0384, absolute difference with 95% confidence interval = 1.0% [0.09, 1.88]), prolonged ventilator dependence (2.1% vs 0.9%, P = 0.0008, difference = 1.2% [0.51, 1.84]), and unplanned postoperative intubation (2.6% vs 1.8%, P = 0.0487, difference = 0.8% [0.04, 1.62]). Composite morbidity was 15.4% in the general group versus 12.6% (P = 0.0038, difference = 2.8% [0.93, 4.67]). Composite morbidity not including pulmonary complications was 13.0% in the general group versus 11.1% (P = 0.0312, difference = 1.9% [0.21, 3.72]). Thirty-day mortality was similar (2.7% vs 3.0%, P = 0.6788, difference = 0.3% [−1.12, 0.67]). As a test for validity, we found a positive association between pulmonary end points because patients with 1 pulmonary complication were significantly more likely to have additional pulmonary complications. CONCLUSIONS:The use of regional anesthesia in patients with COPD is associated with lower incidences of composite morbidity, pneumonia, prolonged ventilator dependence, and unplanned postoperative intubation.

A Description of Intraoperative Ventilator Management in Patients with Acute Lung Injury and the Use of Lung Protective Ventilation Strategies

Background:The incidence of acute lung injury (ALI) in hypoxic patients undergoing surgery is currently unknown. Previous studies have identified lung protective ventilation strategies that are beneficial in the treatment of ALI. The authors sought to determine the incidence and examine the use of lung protective ventilation strategies in patients receiving anesthetics with a known history of ALI. Methods:The ventilation parameters that were used in all patients were reviewed, with an average preoperative Paco2/Fio2 ratio of ≤ 300 between January 1, 2005 and July 1, 2009. This dataset was then merged with a dataset of patients screened for ALI. The median tidal volume, positive end-expiratory pressure, peak inspiratory pressures, fraction inhaled oxygen, oxygen saturation, and tidal volumes were compared between groups. Results:A total of 1,286 patients met criteria for inclusion; 242 had a diagnosis of ALI preoperatively. Comparison of patients with ALI versus those without ALI found statistically yet clinically insignificant differences between the ventilation strategies between the groups in peak inspiratory pressures and positive end-expiratory pressure but no other category. The tidal volumes in cc/kg predicted body weight were approximately 8.7 in both groups. Peak inspiratory pressures were found to be 27.87 cm H2O on average in the non-ALI group and 29.2 in the ALI group. Conclusion:Similar ventilation strategies are used between patients with ALI and those without ALI. These findings suggest that anesthesiologists are not using lung protective ventilation strategies when ventilating patients with low Paco2/Fio2 ratios and ALI, and instead are treating hypoxia and ALI with higher concentrations of oxygen and peak pressures.

Impact of Adding Aspirin to Beta-Blocker and Statin in High-Risk Patients Undergoing Major Vascular Surgery

BACKGROUND Beta-blockers (BB) and statins (S) independently have been shown to reduce perioperative mortality and myocardial infarction (MI) in patients undergoing vascular surgery. In this study we evaluated the benefits of adding aspirin (A) to BB and S (ABBS), with/without angiotensin-converting enzyme inhibitor (ACE-I) on postoperative outcome in high-risk patients undergoing major vascular surgery. METHODS Analysis of consecutive patients undergoing elective vascular surgery at the University of Michigan Cardiovascular Center was performed. Univariate and multivariate analyses were done using cardiac risk index [Revised Cardiac Risk Index (RCRI), coronary artery disease (CAD), insulin-dependent diabetes mellitus (IDDM), cerebral vascular disease, renal dysfunction, congestive heart failure, and major surgery]; pulmonary disease; and A, BB, S (ABBS)±ACE-I use. Baseline clinical characteristics and medication were adjusted using propensity scores. Endpoints were bleeding, 30-day MI, stroke, and 12-month mortality. RESULTS Between 2003 and 2010, 4,149 arterial procedures were performed, 819 of which were risk stratified as RCRI≥3. The incidence of MI was 3-fold lower (2.5% vs. 7.8%, OR 0.31, 95% CI 0.15-0.61, P=0.001) in ABBS±ACE-I (n=513) as compared with non-ABBS±ACE-I (n=306). The 12-month mortality was 8-fold lower in ABBS±ACE-I as compared non-ABBS±ACE-I (5.9% vs. 37.5%, HR 0.13, 95% CI 0.08-0.20, P<0.0001). After adjustment for the propensity to use various therapies, A (HR 0.35, 95% CI 0.24-0.53, P<0.0001), BB (HR 0.65, 95% CI 0.43-1.0, P=0.05), and S (HR 0.36, 95% CI 0.25-0.53, P<0.0001) remained associated with improved 12-month survival. ACE-I use (HR 0.80, 95% CI 0.54-1.19, P=0.27) was not predictive. Aspirin did not predict severe/moderate bleeding. CONCLUSIONS In high-risk patients undergoing major vascular surgery, ABBS therapy has superior 30-day and 12-month risk reduction benefits for MI, stroke, and mortality as compared with A, BB, or S independently. ACE-I did not demonstrate additional risk-reduction benefits.

Worsening preoperative heart failure is associated with mortality and noncardiac complications, but not myocardial infarction after noncardiac surgery: a retrospective cohort study.

BACKGROUND:Heart failure (HF) is an important risk factor for perioperative morbidity and mortality. While these patients are at high risk for cardiac adverse events, there are few current data describing the types of noncardiac complications that occur in this population. METHODS:We performed a multicenter cohort study of patients undergoing noncardiac surgery from 2005 to 2010 as part of the American College of Surgeons National Surgical Quality Improvement Program. A HF cohort (HF that is new or worsening within 30 days of surgery) was compared with a control cohort that was matched regarding other surgical risk factors. RESULTS:Five thousand ninety-four patients with worsening preoperative HF were compared with an otherwise similar cohort of patients without worsening preoperative HF. Worsening preoperative HF was associated with increased risk of 30-day all-cause mortality (relative risk [RR] 2.08; 95% confidence interval [CI], 1.75–2.46; P < 0.001) and increased risk of morbidity (any recorded postoperative complication) (RR 1.54; 95% CI, 1.40–1.69; P < 0.001). HF patients had increased risk of developing renal failure (RR 1.85; 95% CI, 1.37–2.49; P < 0.001), need for mechanical ventilation longer than 48 hours (RR 1.81; 95% CI, 1.52–2.15; P < 0.001), pneumonia (RR 1.73; 95% CI, 1.44–2.08; P < 0.001), cardiac arrest (RR 1.69; 95% CI, 1.29–2.21; P < 0.001), unplanned intubation (RR 1.68; 95% CI, 1.41–1.99; P < 0.001), renal insufficiency (RR 1.64; 95% CI, 1.10–2.44; P = 0.014), sepsis (RR 1.43, 95% CI, 1.24–1.64; P < 0.001), and urinary tract infection (RR 1.29; 95% CI, 1.06–1.58; P = 0.011). The incidence of myocardial infarction in the sample was similar between the 2 groups (RR 1.07; 95% CI, 0.75–1.52; P = 0.719). CONCLUSIONS:Worsening preoperative HF is associated with a significant increase in postoperative morbidity and mortality when controlling for other comorbidities. Although these likely have a multifactorial etiology, patients are much more likely to suffer from respiratory, renal, and infectious complications than cardiac complications.

Automated Alerting and Recommendations for the Management of Patients with Preexisting Hypoxia and Potential Acute Lung Injury: A Pilot Study

Background:Acute lung injury (ALI) is associated with high mortality. Low tidal volume (Vt) ventilation has been shown to reduce mortality in ALI patients in the intensive care unit. Anesthesiologists do not routinely provide lung-protective ventilation strategies to patients with ALI in the operating room. The authors hypothesized that an alert, recommending lung-protective ventilation regarding patients with potential ALI, would result in lower Vt administration. Methods:The authors conducted a randomized controlled trial on anesthesia providers caring for patients with potential ALI. Patients with an average or last collected ratio of partial pressure of arterial oxygen to inspired fraction of oxygen less than 300 were randomized to providers being sent an alert with a recommended Vt of 6 cc/kg predicted body weight or conventional care. Primary outcomes were Vt/kg predicted body weight administered to patients. Secondary outcomes included ventilator parameters, length of postoperative ventilation, and death. Results:The primary outcome was a clinically significant reduction in mean Vt from 508–458 cc (P = 0.033), with a reduction in Vt when measured in cc/kg predicted body weight from 8 to 7.2 cc/kg predicted body weight (P = 0.040). There were no statistically significant changes in other outcomes or adverse events associated with either arm. Conclusions:Automated alerts generated for patients at risk of having ALI resulted in a statistically significant reduction in Vt administered when compared with a control group. Further research is required to determine whether a reduction in Vt results in decreased mortality and/or postoperative duration of mechanical ventilation.

Cumulative Total Effective Whole-Body Radiation Dose in Critically Ill Patients

BACKGROUND Uncertainty exists about a safe dose limit to minimize radiation-induced cancer. Maximum occupational exposure is 20 mSv/y averaged over 5 years with no more than 50 mSv in any single year. Radiation exposure to the general population is less, but the average dose in the United States has doubled in the past 30 years, largely from medical radiation exposure. We hypothesized that patients in a mixed-use surgical ICU (SICU) approach or exceed this limit and that trauma patients were more likely to exceed 50 mSv because of frequent diagnostic imaging. METHODS Patients admitted into 15 predesignated SICU beds in a level I trauma center during a 30-day consecutive period were prospectively observed. Effective dose was determined using Hudas method for all radiography, CT imaging, and fluoroscopic examinations. Univariate and multivariable linear regressions were used to analyze the relationships between observed values and outcomes. RESULTS Five of 74 patients (6.8%) exceeded exposures of 50 mSv. Univariate analysis showed trauma designation, length of stay, number of CT scans, fluoroscopy minutes, and number of general radiographs were all associated with increased doses, leading to exceeding occupational exposure limits. In a multivariable analysis, only the number of CT scans and fluoroscopy minutes remained significantly associated with increased whole-body radiation dose. CONCLUSIONS Radiation levels frequently exceeded occupational exposure standards. CT imaging contributed the most exposure. Health-care providers must practice efficient stewardship of radiologic imaging in all critically ill and injured patients. Diagnostic benefit must always be weighed against the risk of cumulative radiation dose.

Is Transfusion Associated With Graft Occlusion After Cardiac Operations

BACKGROUND Packed red blood cell (RBC) transfusions are associated with increased mortality after coronary artery bypass grafting (CABG) but not after cardiac valve operations. Transfusions are associated with increased strokes and deep venous thromboses after cardiac operations as well as increased peripheral vascular graft thrombosis. The purpose of this study was to determine if RBC transfusions were associated with a greater hazard of an occluded graft developing after CABG. METHODS Patients who underwent symptom-driven coronary artery angiography after CABG were analyzed using Cox models and propensity scoring to compare outcomes based on the RBC transfusion status during their index CABG hospitalization. RESULTS We analyzed 940 patients. We found that patients who received transfusions were more likely to have occluded grafts on angiography (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.03-1.50; p = 0.02). After adjusting for other factors, we found that RBC transfusion was associated with about a 20% increased hazard of graft occlusion (HR, 1.21; 95% CI,1.07-1.37; p = 0.003). CONCLUSIONS Perioperative RBC transfusion is associated with graft occlusion after CABG at both the patient and graft levels. These results add to the growing body of evidence that homologous RBC transfusion is not risk free but is associated with a variety of adverse effects including midterm graft failure.

Timing of Preoperative Troponin Elevations and Postoperative Mortality After Noncardiac Surgery.

BACKGROUND:Even small elevations in preoperative troponin levels have been shown to be associated with adverse outcomes. However, there are currently limited data on the relationship between troponin increase and timing of surgery. METHODS:We performed a single-institution, retrospective cohort study of 6030 individuals with a troponin measurement made during the 30 days preceding a noncardiac surgical procedure. Subjects with detectable troponin levels were separated into terciles based on both the magnitude of the value and the time elapsed between this value and the surgery. For those undergoing nonemergent procedures, these 9 cohorts were compared with the group of individuals with undetectable preoperative troponin levels using bivariable and multivariable logistic regression. RESULTS:Thirty-day mortality was 4.7% in the group with undetectable troponin levels and increased with higher concentrations, with rates of 8.9%, 12.7%, and 12.7% in the low, medium, and high tercile groups, respectively. Unadjusted risk of 30-day mortality was highest in those with the highest troponin levels and shortest duration between the measurement and surgery (odds ratio, 4.497; 95% confidence interval, 2.058–9.825). After adjusting for subject characteristics, troponin remained associated with 30-day mortality in several groups, including individuals with troponin levels in the normal range. CONCLUSIONS:Higher levels of preoperative cardiac troponin I were associated with higher postoperative mortality, and longer time to surgery appeared to reduce this risk for individuals with mild preoperative troponin elevations. Prospective studies are needed to determine whether delaying surgery in patients with elevated preoperative troponin levels improves postoperative outcomes.