Inhibition of complement activation by pexelizumab reduces death in patients undergoing combined aortic valve replacement and coronary artery bypass surgery.

OBJECTIVE: We sought to evaluate the effects of pexelizumab, a C5 complement inhibitor, on death and myocardial infarction in patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. METHODS: The Pexelizumab for Reduction in Myocardial Infarction and Mortality in Coronary Artery Bypass Graft surgery trial, a phase III prospective, randomized, double-blind, placebo-controlled study, enrolled 3099 patients at 205 centers. The primary end point was the composite of death, myocardial infarction, or both at postoperative day 30 in patients undergoing coronary artery bypass grafting without valve surgery. Postoperative myocardial infarction was defined as a creatine kinase MB fraction value of 100 ng/mL or greater, Q-wave myocardial infarction with a creatine kinase MB fraction value of 70 ng/mL or greater, or new Q-wave evidence of myocardial infarction by postoperative day 30. Because patients undergoing coronary artery bypass grafting with a valve procedure were not included in the primary population, separate analysis of death and myocardial infarction was conducted in 218 patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery. RESULTS: Of the 353 patients randomized to any valve procedure, 106 (61%) underwent combined aortic valve replacement and coronary artery bypass grafting in the pexelizumab treatment group compared with 112 (63%) patients in the placebo group. Coronary artery bypass grafting was performed with 1 or more internal thoracic artery grafts in 139 (64%) patients and with 1 or more saphenous vein grafts in 179 (82%) patients. There were 4 (3.8%) deaths in the pexelizumab group versus 11 (9.9%) in the placebo group by postoperative day 30 and 6 (5.7%) deaths in the active group versus 16 (14.4%) in the placebo group by postoperative day 180 (P =.107 and P =.043, respectively, Fisher exact test). The incidence of myocardial infarction 30 days after surgical intervention was identical in the 2 groups, but the study was not designed to detect differences in this cohort of patients. CONCLUSIONS: Inhibition of complement activation by pexelizumab resulted in a decreased mortality at 180 days among 218 patients who underwent combined aortic valve replacement and coronary artery bypass grafting surgery. Additional studies are warranted to confirm this decrease in mortality with pexelizumab in combined aortic valve replacement and coronary artery bypass grafting procedures.

Bedside percutaneous tracheostomy in acquired immunodeficiency syndrome.

Tracheostomy tube insertion is periodically performed when patients with acquired immunodeficiency syndrome (AIDS) require prolonged mechanical ventilation. In this population, bedside percutaneous tracheostomy may be a better technique than conventional operating room tracheostomy because it reduces procedural cost, requires no patient transport, and requires few sharp instruments, thereby potentially decreasing risk to surgical staff. A retrospective review was conducted in the Department of Medical Records at St. Vincents Hospital and Medical Center of New York City. Nine consecutive patients diagnosed with AIDS and undergoing percutaneous tracheostomy from January 1, 1992, to December 31, 1996, were identified. All patients were males (mean age 32.1 +/- 4 years, CD4 count average 145) and were ventilator-dependent for mean of 24 +/- 3 days. The procedure was successful and without complications in all patients. Follow-up was 27 months (range 1-42 months) and in-hospital mortality was 77 per cent. The average length of survival for those patients who died in the hospital was 29 days (range, 3-120). Two patients survived the hospitalization after undergoing decannulation on postoperative days 29 and 52, respectively. Despite the poor prognosis after tracheostomy in patients with AIDS this procedure allows better oral care and may improve patient comfort. Bedside percutaneous tracheostomy can be performed with less risk to surgical personnel and patient when compared to conventional surgery. This minimally invasive procedure safely and efficiently provides prolonged tracheal access in patients with AIDS.

Thoracoscopy in acquired immunodeficiency syndrome.

OBJECTIVE: The role of thoracic surgery in patients with acquired immunodeficiency syndrome (AIDS) continues to evolve. This review seeks to evaluate the outcome, morbidity, and mortality associated with video-assisted thoracoscopic surgery for empyema and pneumothorax in patients with AIDS. METHODS: A retrospective review was conducted of patients with AIDS in whom video-assisted thoracoscopic surgery was performed for empyema (group 1) or intractable pneumothorax (group 2). RESULTS: Twenty patients with AIDS (95% male, mean age 37.4 years, mean CD4 count 76 cells/ml3) underwent thoracoscopy. Surgery was performed for empyema (group 1) in 11 (55%) and intractable pneumothorax (group 2) in nine (45%). Three patients (15%) died within 30 days of the operation. At mean follow-up (29 months), overall survival was 55%. For those who survived the hospitalization and died within the follow-up period (35.3%), mean survival time was 8.2 months (range 1 month to 27 months). In group 1, surgical procedures were performed after 8 days of chest tube drainage and included pleural debridement and mechanical pleurodesis (n = 11) along with lung biopsy (n = 6). Survivals at 30 days and 29 months' follow-up were 90.9% and 45.4%, respectively. In group 2, significantly depressed CD4 counts (average 33.2 cells/ml3) were noted along with a more prolonged preoperative hospitalization (18.5 days) with 14.2 days spent with a chest tube before the operation. In this group, operative procedures included mechanical pleurodesis and talc poudrage (n = 9), bleb resection (n = 7), and lung biopsy (n = 1). Two deaths (22%) occurred within 30 days of the operation and survival at 29 months' follow-up was 66%. CONCLUSION: Video-assisted thoracoscopic surgery performed in patients with AIDS for the treatment of empyema and intractable pneumothorax is effective, can be performed with little operative morbidity and mortality, and is associated with acceptable long-term survival. Video-assisted thoracoscopic surgery is best performed soon after the diagnosis of intractable pneumothorax or empyema has been established.

Use of profound hypothermia and circulatory arrest in complex intra-cardiac repair in adults.

Profound hypothermia and circulatory arrest is a well worked out technique for total repair of congenital defects in infants. Recently, it has been popularized for the repair of aneurysms of the transverse aortic arch. We have applied this technique of profound hypothermia and circulatory arrest in three other adult patients in whom conventional techniques would not allow safe and adequate complete repair of acquired intra-cardiac defects. The first patient, a 76-year-old female, had a large chronic ascending aortic aneurysm involving the aortic valve, as well as the innominate and left common carotid arteries. Resuspension of the aortic valve, resection of the ascending aneurysm, and reconstruction of the ascending and transverse aorta were performed under profound circulatory arrest. In addition, multi-dose hypothermic blood K+ cardioplegia was utilized to protect the myocardium. The second patient underwent valve replacement during a period of circulatory arrest because of extensive calcification of the entire ascending aorta and transverse aortic arch. Arrest time was 56 minutes. The third patient was a 54-year-old female and had a large patent ductus arteriosus with a 3:1 left-to-right shunt as well as significant aortic and mitral valve disease. The ductus was closed through an incision in the pulmonary artery during a 13-minute period of profound hypothermia and circulatory arrest. Aortic valve replacement and mitral repair were also performed at the same time, utilizing conventional techniques. All three patients recovered uneventfully with no evidence of any significant neurologic defect. Long-term follow-up has shown improvement in functional classification in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Strategy for treatment of acute evolving myocardial infarction with pulsatile left heart assist device. Can this modality increase survival and enhance myocardial salvage?

This article describes the technique of left heart bypass in the treatment of both experimental and clinical acute myocardial infarction. A new technique of closed-chest percutaneous left heart bypass that can be used in patients with acute evolving myocardial infarction and cardiogenic shock is also described.

Surgical management of infected median sternotomy: closed irrigation vs. muscle flaps.

Mediastinitis remains a serious complication of median sternotomy which requires prompt and aggressive surgical management. Debridement and closed irrigation has been the conventional mode of treatment. Failure to respond results in open drainage and delayed healing with its associated increased morbidity and mortality. Secondary closure with rectus muscle flaps has been a marked advance in the treatment of these patients. In an attempt to define guidelines for the treatment of mediastinitis complicating median sternotomy, a retrospective review of 2,400 cardiac surgical cases at St. Vincent's Hospital from 1977 through 1982 was performed. There were 25 cases (1%) of mediastinitis. Debridement and closed irrigation was successful in 16 patients (64%) with an average postoperative hospital stay of 19 days. Failure resulted in open drainage in 2 patients (8%) with an average hospital stay of 66 days and debridement and secondary closure by rectus muscle flaps in 7 patients (28%) with an average hospital stay of 28 days. There were no deaths in the entire series. Failure to respond to closed irrigation was not due to delay in diagnosis. The length of time between operation and the first sign of sternal dehiscence did not vary significantly. Sternal dissolution, the presence of anaerobic organisms, large volumes of purulent and necrotic material, however, were responsible for continued mediastinitis and further sternal dehiscence. Open irrigation and delayed closure with muscle flaps should be reserved for these patients and appears to decrease significantly morbidity and length of hospital stay. Surgical debridement and closed irrigation, however, remains the primary method of treatment of the less virulent forms of mediastinitis following median sternotomy.

Variations in total and ionized calcium during cardiac surgery.

Twenty patients undergoing cardiac surgery were studied to examine variations in total and ionized serum calcium and urine calcium during cardiopulmonary bypass. Serial samples of blood and urine were analyzed during bypass using a highly specific calcium electrode to determine the effects of hemodilution, various pharmacologic agents, and transfusions of citrated blood. Calcium chloride was routinely added to the crystalloid pump prime (400 mgs/L) and also administered when additional blood or crystalloid were infused. An average of 4.8 +/- .50 grams of calcium chloride was given per procedure. After induction of general anesthesia with nitrous oxide and Halothane, total serum calcium decreased from 10.0 +/- 0.3 to 8.5 +/- 0.8 mg% (p less than 0.05). Following heparinization, ionized calcium decreased from 4.2 +/- .08 to 3.9 +/- 12 mg% (p less than 0.05). Ionized calcium was not affected by reversal of heparin with Protamine. Following institution of cardiopulmonary bypass the ratio of ionized to total calcium declined about 13.4% (0.49 vs. 0.43). This ratio did not change during bypass but returned to normal immediately post-perfusion. Urinary calcium excretion averaged 1.9 +/- 0.6 mg/min and could not be implicated as a cause of hypocalcemia during bypass. Post-perfusion, ionized serum calcium rose 1.3 +/- .01 mg% for each gram of exogenously administered calcium chloride (p less than 0.05). From these observations, we conclude: (1) ionized and total serum calcium levels decreased significantly following institution of cardiopulmonary bypass alone, presumably as a result of hemodilution from the crystalloid pump prime and addition of citrated blood products; (2) induction of general anesthesia alone with nitrous oxide and Halothane is associated with a significant decrease in total serum calcium; (3) ionized calcium declined following heparinization but is unchanged by Protamine administration; (4) changes in total and ionized serum calcium are unaffected by urinary excretion during bypass; (5) exogenously administered calcium chloride significantly increases serum ionized calcium and these changes are inversely related to the circulating pool of calcium; (6) current protocols for administration of exogenous calcium chloride during bypass may result in insufficient levels of ionized calcium and we have adopted measures to correct these deficiencies, when indicated.

Release of particulate matter from extracorporeal tubing: ineffectiveness of standard arterial line filters during bypass.

Microemboli resulting from extracorporeal circulation have been considered to be a cause of organ dysfunction after cardiopulmonary bypass. A scanning electron microscopic study was carried out to quantitate the number of nonbiological particles which escape capture by the arterial line filter in a standard extracorporeal circulation circuit. Five different lots of polyvinylchloride (PVC) tubing from the same manufacturer were used in closed circuit extracorporeal pump set-ups consisting of a typical length of PVC tubing, a cardiotomy reservoir, and an arterial line filter (Pall 40 microns (mu)). A liter of Plasmalyte was circulated through this set-up for 15 minutes at 2 liters/minute with the pump head set at almost total occlusion. The circulated Plasmalyte from each pump line was then collected and passed through a 0.22 mu Millipore filter. Numerous particles ranging from 5-40 mu in diameter were observed on the surface of the filters. A mean of 51.2 particles/mm2 of filter was found after the first recirculation period. By extrapolation the mean total number of particles contained in the Plasmalyte was calculated to be 70,943. A second similar 15 minute rinse on the same pump set-ups revealed the release of a mean of 51.0 particles/mm2, or a mean total number of 70,665 particles. Analysis of variance showed no significant difference in the number of particles produced by the first compared with the second recirculation period but there were significant differences (P less than .05) between the numbers of particles produced by the different lots of tubing. This study demonstrates that commonly employed tubing packs and standard roller pump designs for extracorporeal circulation are associated with continuous release of particulate matter (5-40 mu) which is not removed by the arterial line filters most often employed. These particles seem to be released at a constant rate which makes an initial pre-bypass filtration run ineffective. Such particles can only be removed by continuous use of lower porosity filters in the pump circuit. The clinical significance of these large numbers of small particles is unknown, but they may contribute to the multi-organ failure often seen in prolonged (greater than 2 hour) periods of cardiopulmonary bypass.

Early open radical commissurotomy: surgical treatment of choice for mitral stenosis.

Between 1967 and 1979, 411 patients underwent surgical treatment of isolated mitral stenosis at our institution. Open radical mitral commissurotomy was performed in 150 patients (1967-1978; mean follow-up, 46 months; range, 4 to 116 months). Mitral valve replacement using a porcine prosthesis was performed in 74 patients (1976-1979; mean follow-up, 23 months; range, 2 to 48 months). Mitral valve replacement with a cloth-covered Starr-Edwards prosthesis was performed in 187 patients (1967-1975; mean follow-up, 45 months; range, 2 to 106 months). Preoperative characteristics were similar in the three groups. The open commissurotomy and Starr-Edwards groups were followed up to 9 years and the porcine valve group up to 4 years, with 97% follow-up in each group. Life-table analysis (6-month intervals) of all postoperative complications revealed significantly greater complication-free survival for patients who had open radical commissurotomy compared with Starr-Edwards (p less than 0.05) valve replacement. Similar analysis of thromboembolic and warfarin-related complications revealed significantly fewer complications in commissurotomy patients. No significant differences were found (p greater than 0.05) when comparing the need for subsequent reoperation in each group. Operative mortality following open radical mitral commissurotomy (0%; 0 out of 150) was significantly less (p less than 0.05) than after mitral valve replacement in both porcine (8.1%; 6 out of 74) and Starr-Edwards (11.2%; 21 out out 187) groups. Life-table analysis of late cardiac-related mortality revealed a significantly greater cumulative survival rate for the commissurotomy versus the Starr-Edwards groups at all intervals from 12 to 108 months (100 versus 84 +/- 5%, p less than 0.05). No significant differences were noted between commissurotomy and porcine valve groups during the 4-year follow-up period (100 +/- 0% versus 96 +/- 3%, p greater than 0.05). Based on these findings, we conclude that when the anatomy is favorable, the surgical treatment of choice for isolated mitral stenosis is open radical mitral commissurotomy.

An on-line system for delivery of blood cardioplegia.

A simplified system for delivery of cold blood potassium cardioplegia was tested in 12 experimental animals subjected to 180 minutes of aortic cross-clamping. This on-line system utilized blood drawn from the pump oxygenator which was volumetrically combined with a pre-mixed electrolyte solution (9 parts blood: 1 part drug). A separate heat exchanger was employed to deliver the cardioplegic infusate at 10-15 degrees C. Use of this system permits accurate regulation of infusate potassium concentration, pH, injection pressure and flow rate. Less than one minute is required to obtain an unlimited quantity of arrest solution at steady state values for these parameters. The efficacy of this method of delivery of blood cardioplegia was verified by biochemical and functional studies which revealed no significant changes in myocardial ATP, ultrastructure, compliance, or ventricular function after 3 hours of crossclamping. It is concluded that this system offers a safe and more simplified method of delivering blood cardioplegia than heretofore available.

Long-term survival with partial left heart bypass following perioperative myocardial infarction and shock.

During the period from July 1, 1978 to Dec. 31, 1980, we employed a partial left heart bypass (left atrium to ascending aorta) in 16 patients who could not be weaned from cardiopulmonary bypass with inotropic agents and the intra-aortic balloon pump. Flow rates up to 3,500 ml/min could be obtained with this device. Eight of the 16 patients survived and left the hospital. One patient died of a cardiac arrest 4 months postoperatively and one has recurrent angina and moderate congestive heart failure 24 months postoperatively. Six patients are well 5 to 17 months after discharge. Seven of the eight deaths were characterized by progressive myocardial failure. One patient died of ventricular fibrillation 18 hours after discontinuation of the left heart bypass. All survivors had significant improvement in ventricular function 12 to 24 hours afer institution of the left heart bypass, which was continued for 16 to 68 hours. These results indicate that early institution of left heart bypass in seriously ill patients can provide satisfactory long-term results.

Myocardial protection with cold blood potassium cardioplegia during prolonged aortic cross-clamping.

The efficacy of cold blood potassium cardioplegia during periods of aortic cross-clamping (greater than 100 minutes) was assessed in 127 patients undergoing a variety of open-heart surgical procedures at New York University Medical Center from january, 1978, to April, 1979. Ischemic intervals ranged from 100 to 267 minutes (mean, 128 minutes). Cardiac-related deaths occurred in only 3 patients (2.4%), and overall operative mortality was 8.7% (11 patients). The rate of perioperative infarction was 10%. Fourteen patients (11%) required vasopressor support or balloon counterpulsation after cardiopulmonary bypass despite the lengthy cross-clamp intervals. Multivariate analysis revealed no significant relationship between the length of cross-clamp time and operative mortality (p = 0.29), incidence of perioperative infarction (p = 0.54), or the occurrence of low-output syndrome postoperatively (p = 0.68). These findings suggest that cold blood potassium cardioplegia provides adequate myocardial protection when periods of arrest as long as 3 to 4 hours are required for complex cardiac surgical procedures.

A simplified method for delivery of cold blood cardioplegia and aortic root venting during coronary artery bypass.

We present a simplified method for delivery of cold blood cardioplegia and left ventricular decompression during coronary artery bypass surgery when aortic occlusion is utilized. The system provides immediate delivery of the cardioplegic solution followed by continuous sump suction on the aortic root to decompress the left ventricle and to aspirate non-coronary collateral flow. This system has been utilized in over 200 consecutive cases of coronary revascularization without complication and is a safe, effective and inexpensive method of both delivery of the cardioplegic agent and maintenance of a dry quiet operative field.

Cardiac output determination after cardiac operation. Lack of correlation between direct measurements and indirect estimates.

Ninety-two mean thermodilution cardiac indices were determined in 25 patients following cardiac operations. Arterial and venous blood gases, hematocrit, body temperature, central venous pressure, left atrial pressures, urine output, heart rate, and mean arterial pressure were simultaneously recorded. Six variables, arterial and venous pH, arterial and venous PCO2, venous PO2, and temperature, showed significant simple correlations with cardiac index, but the degree of correlation was inadequate for use of these variables as reliable indices of cardiac function. When stepwise multiple regression analysis was performed, two variables, venous PO2 and left atrial pressure were associated with the best correlation with cardiac index, such that CI = 0.073 PO2V -- 0.060 LAP + 1.39 (r = 0.60, p less than 0.001). When measured values for venous PO2 and left atrial pressure were substituted into this equation, a "predicted" value for cardiac index could be obtained with only slightly improved reliability. The data indicate that indirect estimation of cardiac output by measurement of the various laboratory parameters described above is not sufficiently reliable for clinical use. The importance of obtaining direct measurements of cardiac output by thermodilution or other means in order to properly evaluate postoperative cardiac function is stressed.

Blood potassium cardioplegia administration. Comparison of myocardial protection offered by three techniques.

To investigate the best method of administration of blood potassium cardioplegia, 19 dogs were studied while undergoing 120 minutes each of aortic crossclamping (myocardial temperature, less than 15 degrees C). Group 1 (six dogs) underwent a single 120-minute period of aortic crossclamping with the heart protected by multiple reinjections (1,000 mL every 30 minutes) of blood potassium cardioplegia solution (potassium chloride, 30 mEq/L; pH, 8; temperature, less than 15 degrees C). Group 2 (six dogs) underwent four separate 30-minute periods of aortic crossclamping, but allowing hearts to beat in a nonworking state for 20 minutes at 35 degrees C between each arrest interval. Hearts in group 3 (seven dogs) were initially arrested as described above, following which a continuous infusion (75 mL/min; KCl, 10 mEq/L) of blood potassium cardioplegia solution was maintained throughout the arrest period. Measurements of myocardial metabolism, ventricular function, regional blood flow, and ultrastructure were carried out before arrest and 30 minutes after final unclamping. Analysis of the data revealed no significant benefit of one method over another, with the exception that adenosine triphosphate level was least preserved with intermittent unclamping and reperfusion. Because continuous perfusion techniques are more cumbersome than multidose reinjection, and intermittent aortic crossclamping lengthens total cardiopulmonary bypass time, we favor the simplest approach, multidose reinjection during a single uninterrupted period of aortic crossclamping.

Constant-pressure aortic root perfusion versus cardioplegia and hypothermia. Comparison of methods of myocardial protection.

Both coronary perfusion and hypothermic cardioplegia are widely used methods of myocardial protection during aortic valve replacement. A theoretical objection to coronary perfusion is that it is not synchronized with cardiac contractions. Accordingly, a special pump was designed to provide perfusion at a constant range of pressure. Twenty dogs were studied during 4 hours of bypass. In six dogs no manipulations were carried out and hearts were allowed to beat in a nonworking state. Seven dogs underwent 2 hours of aortic cross-clamping and constant-pressure aortic root perfusion. Seven dogs underwent 2 hours of uninterrupted aortic occlusion with myocardial protection being maintained by cold potassium-induced arrest, Contractility did not change significantly in any of the three groups. All animals demonstrated significant hyperemia after bypass but normal endocardial/epicardial flow ratios. Although compliance deteriorated in all groups, the most striking changes were seen following 4 hours of bypass alone or constant-pressure aortic root perfusion. Hypothermic potassium arrest, in contrast, provided a slightly greater degree of myocardial protection, perhaps both by limiting the degree of ischemic injury directly and by excluding the heart from the circulating blood and the pump oxygenator system.