Nancy A. Healey

Determinants of Long-Term Survival After Major Surgery and the Adverse Effect of Postoperative Complications

Objective:The objective of this study was to identify the determinants of 30-day postoperative mortality and long-term survival after major surgery as exemplified by 8 common operations. Summary Background Data:The National Surgical Quality Improvement Program (NSQIP) database contains pre-, intra-, and 30-day postoperative data, prospectively collected in a standardized fashion by a dedicated nurse reviewer, on major surgery in the Veterans Administration (VA). The Beneficiary Identification and Records Locator Subsystem (BIRLS) is a VA file that depicts the vital status of U.S. veterans with 87% to 95% accuracy. Methods:NSQIP data were merged with BIRLS to determine the vital status of 105,951 patients who underwent 8 types of operations performed between 1991 and 1999, providing an average follow up of 8 years. Logistic and Cox regression analyses were performed to identify the predictors of 30-day mortality and long-term survival, respectively. Results:The most important determinant of decreased postoperative survival was the occurrence, within 30 days postoperatively, of any one of 22 types of complications collected in the NSQIP. Independent of preoperative patient risk, the occurrence of a 30-day complication in the total patient group reduced median patient survival by 69%. The adverse effect of a complication on patient survival was also influenced by the operation type and was sustained even when patients who did not survive for 30 days were excluded from the analyses. Conclusions:The occurrence of a 30-day postoperative complication is more important than preoperative patient risk and intraoperative factors in determining the survival after major surgery in the VA. Quality and process improvement in surgery should be directed toward the prevention of postoperative complications.

Successful implementation of the department of veterans affairs' national surgical quality improvement program in the private sector: The patient safety in surgery study

Background:The Veterans Affairs ’ (VA) National Surgical Quality Improvement Program (NSQIP) has been associated with significant reductions in postoperative morbidity and mortality. We sought to determine if NSQIP methods and risk models were applicable to private sector (PS) hospitals and if implementation of the NSQIP in the PS would be associated with reductions in adverse postoperative outcomes. Methods:Data from patients (n = 184,843) undergoing major general or vascular surgery between October 1, 2001, and September 30, 2004, in 128 VA hospitals and 14 academic PS hospitals were used to develop prediction models based on VA patients only, PS patients only, and VA plus PS patients using logistic regression modeling, with measures of patient-related risk as the independent variables and 30-day postoperative morbidity or mortality as the dependent variable. Results:Nine of the top 10 predictors of postoperative mortality and 7 of the top 10 for postoperative morbidity were the same in the VA and PS models. The ratios of observed to expected mortality and morbidity in the PS hospitals based on a model using PS data only versus VA + PS data were nearly identical (correlation coefficient = 0.98). Outlier status of PS hospitals was concordant in 26 of 28 comparisons. Implementation of the NSQIP in PS hospitals was associated with statistically significant reductions in overall postoperative morbidity (8.7%, P = 0.002), surgical site infections (9.1%, P = 0.02), and renal complications (23.7%, P = 0.004). Conclusions:The VA NSQIP methods and risk models in general and vascular surgery were fully applicable to PS hospitals. Thirty-day postoperative morbidity in PS hospitals was reduced with the implementation of the NSQIP.

Heparin causes platelet dysfunction and induces fibrinolysis before cardiopulmonary bypass

BACKGROUND Platelet dysfunction and increased fibrinolysis are the most important etiologic factors in the hemostatic defect observed following the institution of cardiopulmonary bypass. This study examined the effects of heparin per se, administered before the institution of cardiopulmonary bypass, on platelet function and fibrinolysis. METHODS Sampling was performed in 55 patients undergoing cardiac operations before and 5 minutes after the routine administration of heparin, before the institution of cardiopulmonary bypass. RESULTS Heparin administration resulted in a significant prolongation of the bleeding time (from 6.3 +/- 2.1 to 12.6 +/- 4.9 minutes; p < 0.00001), a significant reduction in the level of shed blood thromboxane B2 (from 1,152 +/- 669 to 538 +/- 187 pg/0.1 mL; p = 0.00002), and an increase in the plasma levels of plasmin (from 11.8 +/- 9.7 to 125.4 +/- 34.8 U/L; p < 0.0001) and D-dimer (from 571.3 +/- 297.1 to 698.5 +/- 358.6 micrograms/mL; p = 0.05). There were no significant differences before and after heparin administration in the plasma levels of fibrinogen, plasminogen, tissue plasminogen activator, antiplasmin, antithrombin III, and von Willebrand factor. CONCLUSIONS Heparin, independent of cardiopulmonary bypass, causes both platelet dysfunction and increased fibrinolysis. The use of an alternative anticoagulant or a lower dose of heparin in conjunction with heparin-coated surfaces might improve the hemostatic balance during open heart operations.

Comparison of the effects of transfusions of cryopreserved and liquid-preserved platelets on hemostasis and blood loss after cardiopulmonary bypass

OBJECTIVE The aim of the study was to compare the clinical effects and hemostatic efficiency of transfusions of platelets preserved in the frozen state for as long as 2 years with transfusions of platelets preserved in the conventional manner for as long as 5 days in patients undergoing cardiopulmonary bypass. METHODS Seventy-three patients were prospectively randomly assigned to receive transfusions of cryopreserved or liquid-preserved platelets. Nonsurgical blood loss was measured during and after the operation. Bleeding time, hematologic variables, and the bleeding time site shed blood were assayed before cardiopulmonary bypass and at 30 minutes and 2, 4, and 24 hours after transfusion. In vitro platelet function tests were conducted on platelets obtained from healthy volunteers. RESULTS No adverse sequelae of the transfusions were observed. Blood loss and the need for postoperative blood product transfusions were lower in the group receiving cryopreserved platelets. Lower posttransfusion platelet increments and a tendency toward decreased platelet survival were observed in patients receiving cryopreserved platelets. Hematocrit and plasma fibrinogen were significantly higher in this group, and the duration of intubation was shorter. In vitro, cryopreserved platelets demonstrated less aggregation, lower pH, and decreased response to hypotonic stress but generated more procoagulant activity and thromboxane. CONCLUSIONS (1) Cryopreserved platelet transfusions are superior to liquid-preserved platelets in reducing blood loss and the need for blood product transfusions after cardiopulmonary bypass. (2) The reduction in blood loss in the patients receiving cryopreserved platelet transfusions after cardiopulmonary bypass probably reflects improved in vivo hemostatic function of cryopreserved platelets. (3) Some in vitro measures of platelet quality (aggregation, pH, hypotonic stress) may not reflect in vivo quality of platelet transfusions after cardiopulmonary bypass, whereas other in vitro measures (platelet procoagulant activity and thromboxane) do.

Continuous perfusion of donor hearts in the beating state extends preservation time and improves recovery of function

OBJECTIVES Improving methods of donor heart preservation may permit prolonged storage and remote procurement of cardiac allografts. We hypothesized that continuous, sanguineous perfusion of the donor heart in the beating, working state may prolong myocardial preservation. METHODS We developed a portable perfusion apparatus for use in donor heart preservation. Contractile, metabolic, and vasomotor functions were monitored simultaneously in an isolated swine heart. The metabolic state was monitored by myocardial tissue pH. Vasomotor function was assessed in isolated coronary ring chambers. Hearts were randomized into 3 groups: group I (n = 5), cardioplegic arrest, 12-hour storage at 4 degrees C with modified Belzer solution, and 2-hour sanguineous reperfusion in the working state; group II (n = 6), 12-hour continuous perfusion in the beating working state, 30 minutes of arrest (to simulate re-implantation time), and 2 hours of reperfusion, as above; group III (n = 7), coronary ring control hearts. RESULTS At 2 hours of reperfusion, left ventricular developed pressure in group II was higher than in group I (mean +/- standard deviation: 90 +/- 6 mm Hg, 53 +/- 15 mm Hg, P = .005). Significantly less myocardial edema was observed in group II than in group I (73% +/- 4%, 80% +/- 1% water content, P = .01). Significantly less myocardial acidosis was noted in group II than in group I during preservation (pH 7.3 +/- 0.01, 6.1 +/- 0.03, P < .001) and reperfusion (pH 7.3 +/- 0.008, 6.8 +/- 0.05, P < .001). Coronary endothelial vasomotor function was better preserved in group II than in group I as evidenced by dose-response relaxation of coronary rings to 10(-8) mol/L bradykinin (37%, 55% delta baseline, P = .01). CONCLUSION This new method extends the current preservation limit and avoids time-dependent ischemic injury, thereby allowing for distant procurement of donor organs.

Saphenous Vein Conduits Harvested by Endoscopic Technique Exhibit Structural and Functional Damage

BACKGROUND Injury to the saphenous vein endothelium during harvest impacts patency after coronary artery bypass graft surgery. Many centers are adopting endoscopic saphenous vein harvest (ESVH) instead of using the traditional open saphenous vein harvest (OSVH) technique. Our objective was to compare the effects of ESVH and OSVH on the structural and functional viability of saphenous vein endothelium using multiphoton imaging, immunofluorescence, and biochemical techniques. METHODS Ten patients scheduled for coronary artery bypass graft surgery were prospectively identified. Each underwent ESVH for one portion and OSVH for another portion of the saphenous vein. A 1-cm segment from each portion was immediately transported to the laboratory for processing. The vessel segments were labeled with fluorescent markers to quantify cell viability (esterase activity), calcium mobilization, and generation of nitric oxide. Samples were also labeled with immunofluorescent antibodies to visualize caveolin, endothelial nitric oxide synthase, von Willebrand factor, and cadherin, and extracted to identify these proteins using Western blot techniques. All labeling, imaging, and image analysis was done in a blinded fashion. RESULTS Esterase activity was significantly higher in the OSVH group (p < 0.0001). Similarly, calcium mobilization and nitric oxide production were significantly greater in the OSVH group (p = 0.0209, p < 0.0001, respectively). Immunofluoresence and Western blot techniques demonstrated an abnormal alteration in distribution of caveolin and endothelial nitric oxide synthase in the ESVH group. CONCLUSIONS Our study indicates that ESVH has a detrimental effect on the saphenous vein endothelium, which may lead to decreased graft patency and worse patient outcomes.

Evaluation of blood components exposed to coated arterial filters in extracorporeal circuits

Background: Biocompatible surfaces play an important role in the inflammatory response during cardiopulmonary bypass (CBP), with the arterial filter contributing a large surface area of the circuit. Different filter-coating materials designed to improve blood-filter biocompatibility are currently used in CPB circuits. This study evaluates eight biocompatible coatings used for arterial filters and their effects on blood components during circulation. Methods: Arterial filters were randomly assigned in eight independent heparin-bonded tubing loops and perfused by a single swine (n=8). Arterial blood was routed simultaneously, but separately, into each circuit and circulated for 30 minutes at 37°C. Blood samples were drawn for CBC, ACT, and TAT III measurements at baseline, post-heparinization and post-circulation. At study completion, filters were imaged using multiphoton microscopy. Results: RBC, platelet, and WBC counts, and TAT III complex were all decreased after 30 minutes of circulation; however, WBC count was the only parameter that showed statistically significant differences between the filters. Circulating WBC reduction ranged from 6% (Carmeda and Trillium) to 41% (Terumo-X-coating) with corresponding microscopic confirmation of increased WBC entrapment. Conclusion: All eight filter coatings altered the blood components to varying degrees. Selection of the most effective filter, in conjunction with a heparin-bonded circuit for CPB, may decrease the intraoperative foreign-surface activation of blood cells.

Role of myocardial temperature measurement in monitoring the adequacy of myocardial protection during cardiac surgery

Inadequate myocardial protection continues to be encountered despite improved methods of cardioplegia delivery. Although myocardial temperature is commonly monitored to assess the adequacy of cardioplegia delivery, its relationship to the metabolic status of the myocardium has not been investigated. We prospectively reviewed patients who underwent valvular heart surgery with blood (n = 47) or crystalloid (n = 48) cardioplegia and continuous measurement of intraoperative myocardial tissue pH and temperature. We previously demonstrated a high correlation (r = 0.99) between extracellular myocardial pH, levels of intracellular hydrogen ion concentration, and a lowering of tissue ATP during coronary occlusion. Clinically, optimal metabolic protection was defined as the absence of myocardial tissue acidosis during the period of aortic occlusion as quantified by a temperature-corrected integrated mean pH of 6.8 or greater, which has been shown to be predictive of a favorable postoperative outcome. Age, bypass time, myocardial temperature, myocardial tissue pH at the onset of aortic occlusion, cross-clamp time, and volume of cardioplegia were not significantly different between blood and crystalloid groups. Linear regression analysis demonstrated no significant correlation between mean myocardial tissue pH and the corresponding mean myocardial temperature in either group during aortic occlusion. There was also no correlation between the mean myocardial tissue pH and volume of cardioplegia delivered in both groups. These data demonstrate wide intercardiac and intracardiac variability in the degree of regional tissue acidosis encountered during of hypothermic cardioplegia. Cardioplegia delivery guided by measurement of myocardial temperature or by standardized protocol did not prevent the occurrence of tissue acidosis and thus, did not ensure optimal metabolic protection of the heart. In 95 patients undergoing valvular heart surgery with cold blood or crystalloid cardioplegia, there was no correlation between myocardial tissue pH and mycardial temperature or between myocardial tissue pH and volume of cardioplegia administered. Temperature is a poor indicator of the metabolic state of the myocardium.

Impact of intraoperative myocardial tissue acidosis on postoperative adverse outcomes and cost of care for patients undergoing prolonged aortic clamping during cardiopulmonary bypass

BACKGROUND This study examined the impact of intraoperative myocardial acidosis and adverse postoperative outcomes on the cost of cardiac surgical care. METHODS Myocardial tissue pH corrected to 37 degrees C (pH(37C)) was measured in 162 patients with cross-clamp (XC) duration of 119 minutes or longer. Perioperative data and outcomes were collected prospectively. The Veterans Affairs cost accounting system was used to determine the cost of care in a subset of 57 patients. RESULTS Long XC duration was associated with significantly increased acidosis and adverse postoperative outcomes. The cost of care for patients with adverse outcomes was increased by 110% (P < .0001). Patients with acidosis at the end of reperfusion had significantly (P = .0470) increased costs of care. End reperfusion of myocardial tissue pH(37C) of less than 7.0, diabetes mellitus, and body surface area were significant determinants of postoperative adverse outcomes. CONCLUSIONS Intraoperative myocardial acidosis is a determinant of postoperative adverse outcomes and cost in cardiac surgery. Reducing XC duration and improving intraoperative myocardial protection should improve outcomes and reduce cost.

Metabolic Correlates of Myocardial Stunning and the Effect of Cardiopulmonary Bypass

Abstract In order to study the metabolic consequences of myocardial stunning, repeated coronary occlusions were performed in dogs. The production of CO2, adenosine triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi) by myocardial cells was assessed, along with extracellular and intracellular pH. Our results indicate that regional coronary artery occlusion reduces the ability of the myocardium to produce H+ and CO2 and to replenish ATP post ischemia. These alterations, then, represent the hallmark of metabolic viability during periods of ischemic insult. Decreases in PCr and Pi were completely eliminated during reperfusion and, therefore, are not reflective of myocardial stunning. When normothermic cardiopulmonary bypass (CPB) is instituted and the coronary artery is occluded three times with reperfusion between each occlusion, alterations in myocardial H+ and high energy phosphates are identical to those observed using only repetitive coronary occlusion. Systemic hypothermia during CPB does not protect against myocardial stunning; however, it is anticipated that interventions that prevent the reduction in H+ and ATP levels may overcome the effects of myocardial stunning that occur during cardiac surgery.