The association of perioperative red blood cell transfusions and decreased long-term survival after cardiac surgery.

BACKGROUND: Exposure to red blood cell (RBC) transfusions has been associated with increased mortality after cardiac surgery. We examined long-term survival for cardiac surgical patients who received one or two RBC units during index hospitalization. METHODS: Nine thousand seventy-nine consecutive patients undergoing coronary artery bypass graft, valve, or coronary artery bypass graft/valve surgery at eight centers in northern New England during 2001-2004 were examined after exclusions. A probabilistic match between the regional registry and the Social Security Administration's Death Master File determined mortality through June 30, 2006. Cox Proportional Hazard and propensity methods were used to calculate adjusted hazard ratios. RESULTS: Thirty-six percent of patients (n = 3254) were exposed to one or two RBC units. Forty-three percent of RBCs were given intraoperatively, 56% in the postoperative period and 1% were preoperative. Patients transfused were more likely to be anemic, older, smaller, female and with more comorbid illness. Survival was significantly decreased for all patients exposed to 1 or 2 U of RBCs during hospitalization for cardiac surgery compared with those who received none (P < 0.001). After adjustment for patient and disease characteristics, patients exposed to 1 or 2 U of RBCs had a 16% higher long-term mortality risk (adjusted hazard ratios = 1.16, 95% CI: 1.01-1.34, P = 0.035). CONCLUSIONS: Exposure to 1 or 2 U of RBCs was associated with a 16% increased hazard of decreased survival after cardiac surgery.

Characterization of a prospective human model for study of the reproductive hormone responses to major illness.

With critical illness, serum testosterone levels fall markedly, whereas estrogen levels rise. Although animal studies suggest adaptive advantages, no prospective model has been available for studies in humans. We hypothesized that coronary artery bypass graft (CABG) surgery would provide such a model by eliciting the same reproductive hormone and other endocrine responses as reported with major nonsurgical illnesses. We further hypothesized that those responses would occur consistently in all CABG patients with predictable time courses, providing reliable windows for prospective studies. In 17 men undergoing CABG, serum levels of reproductive hormones, cortisol, thyroid hormones, and IGF-I were measured before and for up to 5 wk after surgery. Changes in serum levels of reproductive and other hormones were similar to those reported in nonsurgical critically ill patients. Time course for onset, duration, and recovery of reproductive hormone changes were consistent among all patients. A window for studying the testosterone and estrogen responses was established as the first 5 days following CABG. Practical use of this model was demonstrated by evaluating, in another seven men, changes in gonadotroph responsiveness to GnRH following CABG. Finally, to determine whether our findings in CABG could be extended to other surgeries, we demonstrated similar endocrine responses in 12 men following abdominal aortic aneurysm resection. We conclude that patients undergoing CABG surgery provide a useful human model for the prospective evaluation of the reproductive axis responses to acute illness. Other major surgeries are likely to also be suitable for these studies.

Increases in serum estrogen levels during major illness are caused by increased peripheral aromatization.

Although serum testosterone levels decrease acutely in critically ill patients, estrogen levels rise. We hypothesized that increased rates of aromatization of androgens to estrogens underlie the increase in serum estrogen levels. Eleven men and three women (age 42-69 yr) were prospectively studied before and again after elective coronary artery bypass graft surgery (CABG). Each patient received priming doses of [(14)C]androgen and [(3)H]estrogen that were immediately followed by peripheral infusions for 210 min. Eight men and three women received androstenedione (A(4))/estrone (E(1)) and three men received testosterone (T)/estradiol (E(2)). Adipose tissue biopsies were obtained in another six men before and after CABG to evaluate levels of P450 aromatase mRNA. Serum T levels decreased postoperatively in all 17 men (P < 0.001), whereas E(1) levels rose (P = 0.004), with a trend toward a rise in E(2) (P = 0.23). Peripheral aromatization rates of androgens to estrogens rose markedly in all 14 patients (P < 0.0001). Estrogen clearance rates rose (P < 0.002). Mean serum A(4) levels increased slightly postoperatively (P = 0.04), although no increase in A(4) production rates (PRs) was observed. T PRs decreased in two of three men, whereas clearance rates increased in all three. Adipose tissue P450 aromatase mRNA content increased postoperatively (P < 0.001). We conclude that the primary cause of increased estrogen levels in acute illness is increased aromatase P450 gene expression, resulting in enhanced aromatization of androgens to estrogens, a previously undescribed endocrine response to acute illness. Both increased T clearance and decreased T production contribute to decreased serum T levels. Animal studies suggest that these opposing changes in circulating estrogen and androgen levels may be important to reduce morbidity and mortality in critical illness.

The preoperative intraaortic balloon pump in coronary bypass surgery: a lack of evidence of effectiveness.

BACKGROUND: There is limited evidence demonstrating the effectiveness of preoperative intraaortic balloon pump (IABP) use in isolated coronary artery bypass graft (CABG) surgery. A single-center randomized trial demonstrated its benefit. We undertook a multicenter observational study to verify this finding. METHODS: In 29,950 consecutive patients undergoing isolated CABG between 1995 and 2000 at 10 centers, we compared patients with and without a preoperative IABP. We also compared the effect of preoperative IABP use within 7 high-risk clinical subgroups. To validate the previous randomized trial, patients with any 2 of the following were also analyzed: left main > 70%, ejection fraction < 40%, redo CABG, or preoperative intravenous nitroglycerin. RESULTS: Preoperative IABPs were used in 1896 patients (6.3%). These patients had more comorbid conditions and a higher crude mortality than those who did not have preoperative IABPs (9.5% vs 2.3%, P < .0001). Preoperative IABP patients were caliper matched to non-preoperative IABP patients using a propensity score. Excess mortality associated with preoperative IABP persisted (9.2% vs 5.8%, P = .0004). In 7 high-risk subgroups, mortality was significantly higher with preoperative IABP. We used propensity caliper matching to compare preoperative IABP with non-preoperative IABP patients who met trial criteria (n = 4332). Preoperative IABP was associated with higher mortality (11.0% vs 6.5%, P = .0009). Removing emergency patients did not alter results. CONCLUSIONS: Use of preoperative IABPs was consistently associated with higher mortality. Despite detailed statistical analysis, we were unable to show benefit from preoperative IABP use or confirm the results of a single-center trial that demonstrated its benefit. Assessment of preoperative IABP efficacy will require a randomized trial.

Embolic activity subsequent to injection of the internal mammary artery with papaverine hydrochloride.

BACKGROUND: Neurologic injury is a rare yet devastating outcome of coronary artery bypass grafting surgery. Mechanisms producing both focal and global neurologic injuries include embolization, cerebral hypoperfusion, and hypotension. In this present study, we report an association between variations in the treatment of the internal mammary artery with the detection of cerebral embolic signals. METHODS: An intensive intraoperative neurologic and physiologic monitoring approach was implemented to associate discrete processes of clinical care with the concurrent detection of cerebral embolic signals, cerebral hypoperfusion, and hypotension. The method of treating the left internal mammary artery was tracked among 68 patients undergoing isolated coronary artery bypass grafting. Cerebral embolic signals were counted within 3 minutes of the treatment of the left internal mammary artery. RESULTS: Among a series of 68 patients undergoing isolated coronary artery bypass grafting, 22 were not treated with papaverine. Of those treated, 12 received injection intraluminally and 28 had a topical application. Embolic signals were noted concurrently among 7 patients receiving injection of papaverine. No embolic signals were noted among patients who were treated topically. CONCLUSIONS: We report an association between the injection of papaverine hydrochloride and cerebral embolic signals. Our findings suggest that adoption of topical applications of papaverine hydrochloride may offer opportunities to reduce a portion of cerebral embolic signals in the setting of coronary artery bypass grafting.

10-year follow-up of patients with and without mediastinitis.

Mediastinitis is a dreaded complication of CABG surgery. Short-term outcomes have been described, but there have been only a few long-term studies. We examined the survival of patients undergoing isolated CABG surgery between 1992 and 2001. Mediastinitis was identified during the index admission. Proportional hazards regression was used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI 95%). Among 36,078 consecutive patients, there were 5749 deaths during 148,319 person years of follow-up. There were 418 cases of mediastinitis (1.16%). The incidence of death was 11.15 per 100 person/years with mediastinitis and 3.81 deaths/100 person years without. (P < 0.001). We also examined the mortality rates of patients who survived at least 6 months after their CABG surgery. Patients with mediastinitis had an incidence rate of 5.70 deaths per 100 person/years while those without had a rate of 2.66 deaths per 100 person/years (P < 0.001). After adjustment for baseline differences in patient and disease characteristics, the hazard ratio was 2.12 (CI95% = 1.86,2.58; P < 0.001). The adjusted hazard ratios for patients who survived 6 months postsurgery was 1.70 (CI95% = 1.36,2.13; P < 0.001). Mediastinitis is associated with a marked increase in both acute and long-term mortality rates.

A method for identifying mechanisms of neurologic injury from cardiac surgery.

BACKGROUND: A method for linking discrete surgical and perfusion-related processes of care with cerebral emboli, cerebral oxyhemoglobin desaturation, and hemodynamic changes may offer opportunities for reducing overall neurologic injury for patients undergoing cardiac surgery. METHODS: An intensive intraoperative neurologic and physiologic monitoring approach was developed and implemented. Mechanisms likely to produce embolic (cerebral emboli), hypoperfusion (oxyhemoglobin desaturation), and hypotensive (hemodynamic changes) neurologic injuries were monitored and synchronized with the occurrence of surgical and perfusion clinical events/techniques using a case video. RESULTS: The system was tested among 32 cardiac surgery patients. Emboli were measured in the cerebral arteries and outflow of the cardiopulmonary bypass circuit among nearly 75% and 85% of patients, respectively. Oxyhemoglobin desaturation was measured among nearly 70% of patients. Hemodynamic information was recorded in 100% of patients. CONCLUSIONS: We developed and successfully implemented a method for detailed real-time associations between processes of clinical care and precursors of neurologic injury. Knowledge of this linkage will result in the redesign of clinical care to reduce a patient's risk of neurologic injury.

A multicenter comparison of intraaortic balloon pump utilization in isolated coronary artery bypass graft surgery.

BACKGROUND: Single-center studies suggest substantial variation in intraaortic balloon pump (IABP) utilization. Our purpose is to examine IABP utilization over time and across medical centers. METHODS: This was a prospective cohort of 29,961 consecutive patients undergoing isolated coronary artery bypass graft surgery, between 1995 and 2000, at 10 centers (eight in northern New England and two in Canada). RESULTS: A total of 2,678 (8.9%) patients received an IABP. The rate of preoperative IABP insertion was 6.3%, and that of intra- or postoperative insertion was 2.6%. During the 6 years, IABP use increased from 7.0% to 10.3% (p(trend) <0.001). Preoperative IABP insertion increased from 5.4% to 7.8% (p(trend) < 0.001). There was no significant increase in intra-/postoperative IABP insertion 1.7% to 3.4% (p(trend) = 0.34). Adjustment for changes in patient and disease characteristics did not substantially alter these results. The rate of IABP use varied substantially by center, from 5.9% to 16.4% (p < 0.001). Adjustment for patient and disease characteristics resulted in variation from 4.8% to 12.8% across the 10 centers (p < 0.001). The adjusted rates of preoperative IABP insertion varied from 3.6% to 13.7% (p < 0.001), and the rates of intra-/postoperative IABP insertion ranged from 1.0% to 5.2% (p < 0.001). There was no significant correlation between the rates of preoperative and intra-/postoperative IABP use (r(s) = 0.085, p = 0.815). CONCLUSIONS: During the 6 years, there was a 47% increase in the rate of IABP utilization. Even after adjustment, there was almost threefold variation in IABP use across centers. This variation likely reflects lack of consensus on the appropriate use of the IABP in CABG patients.

Determination of etiologic mechanisms of strokes secondary to coronary artery bypass graft surgery.

BACKGROUND AND PURPOSE: Current research focused on stroke in the setting of coronary artery bypass graft (CABG) surgery has missed important opportunities for additional understanding by failing to consider the range of different stroke mechanisms. We developed and implemented a classification system to identify the distribution and timing of stroke subtypes. METHODS: We conducted a regional study of 388 patients with the diagnosis of stroke after isolated CABG surgery in northern New England from 1992 to 2000. Data were collected on patient and disease characteristics, intraoperative and postoperative care, and outcomes. Stroke etiology was classified into 1 of the following: hemorrhage, thromboembolic (embolic, thrombotic, lacunar), hypoperfusion, other (subtype not listed above), multiple (>or=2 competing mechanisms), or unclassified (unknown mechanism). The reliability of the classification system was determined by percent agreement and kappa statistics. RESULTS: Embolic strokes accounted for 62.1% of strokes, followed by multiple etiologies (10.1%), hypoperfusion (8.8%), lacunar (3.1%), thrombotic (1.0%), and hemorrhage (1.0%). There were 54 strokes with unknown etiology (13.9%). There were no strokes classified as "other." Nearly 45% (105/235) of the embolic and 56% (18/32) of hypoperfusion strokes occurred within the first postoperative day. CONCLUSIONS: We used a locally developed classification system to determine the etiologic mechanism of 388 strokes secondary to CABG surgery. The principal etiologic mechanism was embolic, followed by stroke having multiple mechanisms and hypoperfusion. Regardless of mechanism, strokes predominantly occurred within the first postoperative day.

Development and validation of a prediction model for strokes after coronary artery bypass grafting.

BACKGROUND: A prospective study of patients undergoing coronary artery bypass graft surgery (CABG) was conducted to identify patient and disease factors related to the development of a perioperative stroke. A preoperative risk prediction model was developed and validated based on regionally collected data. METHODS: We performed a regional observational study of 33,062 consecutive patients undergoing isolated CABG surgery in northern New England between 1992 and 2001. The regional stroke rate was 1.61% (532 strokes). We developed a preoperative stroke risk prediction model using logistic regression analysis, and validated the model using bootstrap resampling techniques. We assessed the model's fit, discrimination, and stability. RESULTS: The final regression model included the following variables: age, gender, presence of diabetes, presence of vascular disease, renal failure or creatinine greater than or equal to 2 mg/dL, ejection fraction less than 40%, and urgent or emergency. The model significantly predicted (chi(2) [14 d.f.] = 258.72, p < 0.0001) the occurrence of stroke. The correlation between the observed and expected strokes was 0.99. The risk prediction model discriminated well, with an area under the relative operating characteristic curve of 0.70 (95% CI, 0.67 to 0.72). In addition, the model had acceptable internal validity and stability as seen by bootstrap techniques. CONCLUSIONS: We developed a robust risk prediction model for stroke using seven readily obtainable preoperative variables. The risk prediction model performs well, and enables a clinician to estimate rapidly and accurately a CABG patient's preoperative risk of stroke.

The effect of comorbid illness on mortality outcomes in cardiac surgery.

HYPOTHESIS: Comorbid conditions are associated with the risk of death from coronary artery bypass graft surgery. DESIGN: Prospective cohort study data were collected on patient and disease characteristics and comorbid conditions including hypertension, diabetes, obesity, vascular disease, chronic obstructive pulmonary disease, cancer (excluding nonmelanoma skin cancer), dialysis-dependent renal failure, liver disease, and dementia. Statistical analysis used logistic regression for the calculation of adjusted odds ratios (ORs) and 95% confidence intervals (CIs). SETTING: Regional cardiac surgery database. PATIENTS: A total of 27,239 consecutive patients undergoing isolated coronary artery bypass graft surgery. MAIN OUTCOME MEASURE: In-hospital mortality rate. RESULTS: The prevalence of comorbid conditions was as follows: hypertension, 64.3%; diabetes, 30.1%; obesity, 24.6%; severe obesity, 7.2%; vascular disease, 18.3%; chronic obstructive pulmonary disease, 10.9%; peptic ulcer, 7.5%; cancer, 3.8%; renal failure, 1.5%; liver disease, 0.6%; and dementia, 0.1%. After adjustment for patient and disease characteristics, including age, sex, previous cardiac surgery, priority of surgery, degree of left main coronary stenosis, number of diseased coronary arteries, and left ventricular ejection fraction, the following comorbid conditions were significant predictors of in-hospital mortality: diabetes (OR, 1.19; 95% CI, 1.01-1.40; P =.03), vascular disease (OR, 1.67; 95% CI, 1.41-1.97; P<.001), chronic obstructive pulmonary disease (OR, 1.57; 95% CI, 1.29-1.91; P<.001), peptic ulcer (OR, 1.34; 95% CI, 1.05-1.71; P =.02), and dialysis-dependent renal failure (OR, 3.68; 95% CI, 2.65-5.13; P<.001). There was no significant association between in-hospital mortality and hypertension, obesity or severe obesity, cancer, liver disease, or dementia. CONCLUSION: Even after adjustment for other patient and disease characteristics, comorbid conditions (especially diabetes, vascular disease, chronic obstructive pulmonary disease, peptic ulcer disease, and dialysis-dependent renal failure) are associated with significantly increased risk of death after coronary artery bypass graft surgery.

Operative technique, paraplegia, and mortality after blunt traumatic aortic injury.

HYPOTHESIS: The use of mechanical circulatory support (MCS) during repair of traumatic aortic injuries is associated with a decreased incidence of postoperative paraplegia and mortality. DESIGN AND SETTING: Historical cohort study with contemporaneous but nonrandomized controls in a tertiary care hospital from July 1, 1988, through December 31, 1999. PATIENTS AND INTERVENTIONS: Consecutive cases undergoing operation for traumatic aortic injuries. Use of MCS (with or without systemic heparinization) determined by surgeon preference. MAIN OUTCOME MEASURES: Incidence of postoperative paraplegia and mortality. RESULTS: Twenty-two patients underwent repair of traumatic aortic injuries using MCS, resulting in no paraplegia but 4 deaths, 3 of them from cerebral ischemia. Thirteen patients had their traumatic aortic injuries repaired using a "clamp-and-sew" or passive shunt technique with no deaths but paraplegia in 2. Compared with an earlier report from our group from January 1, 1975, through June 30, 1988, the annual incidence of traumatic aortic injuries has decreased, whereas the age of patients and proportion of operations using MCS have increased. A review of the recent literature on traumatic aortic injuries reveals an average postoperative paraplegia incidence of 1% with MCS and 16% without MCS. Overall mortality is similar, but others have also reported cases of cerebral ischemia after aortic repair. CONCLUSIONS: The use of MCS during repair of traumatic aortic injuries is associated with a decreased incidence of postoperative paraplegia. The occasional occurrence of cerebral ischemia deserves further study.

Association of bacterial infection and red blood cell transfusion after coronary artery bypass surgery.

BACKGROUND: Previous studies have shown an association between red blood cell transfusions (RBC) and bacterial infections following coronary artery bypass graft (CABG) surgery. We sought to assess whether there is an independent effect of RBC on the incidence of bacterial infections. METHODS: This was a prospective cohort study of 533 CABG patients over a 7-month period. Subjects were followed from time of CABG until 30 days postoperatively. Data were collected on patient and treatment characteristics, surgical management, and transfusion incidence. RESULTS: Seventy-five (14.1%) of 533 patients developed a bacterial infection. After controlling for patient and disease characteristics, invasive treatments, surgical time, and the transfusion of other substances, the adjusted rates of bacterial infection were 4.8% for no RBC transfusion, 15.2% with one to two units, 22.1% with three to five units, and 29.0% with greater than or equal to six units, (p(trend) < 0.001). Diabetes was the only patient or disease factor significantly associated with bacterial infection (p < 0.001). CONCLUSIONS: RBC transfusions were independently associated with a higher incidence of post-CABG bacterial infections. The risk of infection increased in proportion to the number of units of RBC transfused.