Study design validation for consolidating global with focal neurological events in cardiac surgery stroke risk factor analyses.

Neuroimaging shows that both global and focal neurologic deficits after cardiac surgery share an acute, often multifocal, embolic cerebral infarction etiology; yet, analyses of stroke risk factors historically have emphasized the focal deficits. We test if consolidating encephalopathy and coma with focal deficits affects four stroke risk factors and a dummy variable. Overall focal and global events in 575 cardiopulmonary bypass operations identified by retrospective review matched indices reported in large prospective studies. Logistic regression in 189 records selected for completed non-invasive preoperative carotid stenosis screening showed all four conventional stroke risk factors to be independent predictors of overall consolidated global plus focal neurologic risk, specifically: age [odds ratio (OR) 1.90 per decade], carotid stenosis >50% (OR 1.91), pump time (OR 1.67 per hour), open chamber (OR 1.95); and successfully eliminated the dummy variable gender (P = 0.6). This analysis indicates that the design of future stroke risk factor studies in the setting of cardiac surgery can and should adopt a neuroimaging evidence-based investigative approach of consolidating global with focal deficits.

Heparin-protamine mismatch. A controllable factor in bleeding after open heart surgery.

OBJECTIVE: To test the effect of a new system designed to reduce heparin-protamine mismatch on bleeding after open heart surgery. DESIGN: Nonrandomized but consecutive retrospective review of patients undergoing open heart surgery during a 9-month period. SETTING: Multispecialty referral center. PATIENTS: A total of 150 patients comparable by age, body surface area, and coagulation status undergoing primary open heart surgery for either coronary bypass or heart valve replacement. INTERVENTION: In the first 75 patients (group 1), heparin sodium was neutralized with protamine sulfate, using a fixed ratio (1 mg of heparin sodium to 1.3 mg of protamine sulfate). An activated clotting time was used to confirm heparin neutralization. For the subsequent 75 patients (group 2), titration of heparin and protamine from defined lots was accomplished using activated clotting times adjusted and matched to drug lots to minimize biologic variability. Groups 1 and 2 had comparable operations, pump times, and cross-clamp times. MAIN OUTCOME MEASURES: Doses of heparin and protamine and their effect on blood product transfusion and postoperative bleeding were evaluated in all patients. RESULTS: The average protamine sulfate dose for group 2 patients (287.56 +/- 8.3 mg) was significantly lower than that for group 1 (346.01 +/- 12.6 mg) (P < .0005). Less protamine was associated with the transfusion of fewer red blood cells (0.92 +/- 0.15 vs 2.57 +/- 0.38 U) (P < .001), platelets (0.72 +/- 0.8 vs 2.96 +/- 0.80 U) (P < .01), and fresh-frozen plasma (0.83 +/- 2.0 vs 2.01 +/- 0.48 U) (P < .03). No patients in group 2 required reexploration for bleeding, compared with eight patients in group 1. CONCLUSIONS: A reduction in protamine dose was associated with significant decreases in blood product use and postoperative bleeding. Excess protamine warrants consideration as both an important and a controllable factor in coagulopathy after open heart surgery.

Hemodynamic evaluation of a bioprosthetic venous prosthesis.

PURPOSE: A prosthetic venous valve must be biocompatible and nonthrombogenic and function in the venous circulation. Biocompatibility and thrombogenicity of our prosthesis have been examined in prior animal experiments, and 91% of valve conduits including early prototypes are patent at 3 weeks. However, evaluation of valve function is much more difficult in animals; therefore in this study the function of excised valves was evaluated ex vivo. METHODS: Nine bovine jugular vein conduits, each with one bileaflet venous valve, were harvested and placed in a venous flow simulator. Flows and pressures were adjusted to mimic human respiratory and hydrostatic variations. Each valve and conduit was tested for variations in valve diameter and sinus expansion in response to flow. Valve opening and closing times and valve competence were measured in response to pressure changes. After testing, each specimen was glutaraldehyde fixed and assessed a second time. RESULTS: Valve orifice area increased in response to flow in both fresh and fixed tissues. Maximum valve orifice area was reduced by fixation (27.7%) at full flows (p < 0.05). Valve sinus dimensions increased in response to increased pressure until maximum expansion was achieved (33 mm Hg). This was reduced 15.3% in fixed tissue (p < 0.05). Valve opening times (at < 1 mm Hg gradient) were slightly longer in fixed compared with fresh tissue (0.43 +/- 0.09 vs 0.41 +/- 0.13 second; p < 0.05). Valve closing times were comparable in both states (0.43 +/- 0.08 vs 0.49 +/- 0.07 second). Three fresh and seven fixed specimens that were subjected to 287 mm Hg back pressure exhibited minimal reflux. CONCLUSIONS: Size and availability make the bovine jugular vein valve an ideal venous valve substitute. Glutaraldehyde fixation renders the tissue biocompatible and nonthrombogenic while preserving anatomic integrity and leaflet strength and flexibility. Mounted and stented in a sewing sleeve, this prosthesis could represent the first generally applicable clinical solution to chronic venous insufficiency and venous hypertension.

Embolic stroke as a sequela of cardiopulmonary bypass.

Tha pathophysiology of brain injury in patients undergoing cardiopulmonary bypass remains unclear despite several decades of inquiry. The advent of noninvasive high-resolution brain and cerebrovascular imaging by magnetic resonance, computed tomography, and pulsed Doppler ultrasonography now permits in vivo assessment of pathophysiological mechanisms. Neuroradiographic and carotid duplex studies were performed in patients who developed neurological deficits following cardiopulmonary bypass. Among 30 symptomatic patients undergoing magnetic resonance or computed tomography brain scans, 18 (60%) had findings of acute ischemic injury. Embolic infarction was evident in 14 (78%) of these 18 patients. Watershed injury was the predominant finding in a single patient, while findings consistent with global anoxia were present in another patient. Carotid atheroemboli were excluded as a possible source of embolism in 11 patients whose carotid duplex studies were unremarkable preoperatively as well as in 3 further patients whose neuroradiographic findings did not correspond with their moderate carotid disease. It is concluded that infarction due to noncarotid embolism is the primary pathophysiology of neurological deterioration following cardiopulmonary bypass.

In vitro performance of venous valve prostheses. An experimental model study.

The performance of fresh and glutaraldehyde fixed bovine jugular vein valves (10 mm diameter) was investigated in an experimental flow loop that provides adjustable flow rates and a downstream oscillatory pressure. Three different venous valve (VV) conduit geometries (curved [C], straight [S], and tapered [T]), were tested. The flow loop consisted of two independently adjustable components, with the mean flow generated by adjusting the elevation difference between the head tank and outflow chamber. An adjustable sinusoidal pressure pulse was superimposed on the downstream of a VV to mimic the respiratory effects. Flow visualizations were made using 100 microns mica chip tracers in the laser illuminated flow fields. To assess VV performance under various flow conditions, the closure opening (CO), partial opening (PO), and leaflet fluttering (LF) were evaluated. At a given pulse pressure, the three conduits required different flow rates to reach CO mode. At 12 cm H2O pulse pressure, the fresh valve in C-conduit exhibited stable CO operation at a flow rate of 1.01 ml/sec. That in S and T conduits required 1.67 ml/sec and 2.25 ml/sec, respectively. At higher flow rates, PO and LF performances were observed in all three conduits. Different threshold values of pulse pressure were needed to reestablish the CO operation mode for the C, S, and T conduits, individually. These observations provide some insight into the role of conduit geometry and sinus configuration in the function of VV.

Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery.

To examine the interaction of epidural anesthesia, coagulation status, and outcome after lower extremity revascularization, 80 patients with atherosclerotic vascular disease were prospectively randomized to receive general anesthesia combined with postoperative epidural analgesia (GEN-EPI) or general anesthesia with on-demand narcotic analgesia (GEN). Demographics did not differ between groups except that the GEN-EPI group had a higher incidence of diabetes mellitus and of previous myocardial infarction. Coagulation status was monitored using thromboelastography. An additional 40 randomly selected patients without atherosclerotic vascular disease undergoing noncardiovascular procedures served as controls for coagulation status. Vascular surgical patients were hypercoagulable compared with control patients before operation and on the first postoperative day. Postoperatively, this hypercoagulability was attenuated in the GEN-EPI group and was associated with a lower incidence of thrombotic events (peripheral arterial graft coronary artery or deep vein thromboses). The rates of cardiovascular, infectious, and overall postoperative complications, as well as duration of intensive care unit stay, were significantly reduced in the GEN-EPI group. Stepwise logistic regression demonstrated that the only significant predictors of postoperative cardiovascular complications were preoperative congestive heart failure and general anesthesia without epidural analgesia. We conclude that in patients with atherosclerotic vascular disease undergoing arterial reconstructive surgery (a) thromboelastographic evidence of increased platelet-fibrinogen interaction is associated with early postoperative thrombotic events, and (b) epidural anesthesia and analgesia is associated with beneficial effects on coagulation status and postoperative outcome compared with intermittent on-demand opioid analgesia.

In vitro testing of venous valves.

The need to test prosthetic venous valves led to the design of a hydraulic mock circuit that reliably mimics natural venous flow. Components of this system simulate calf muscle pump and thoracoabdominal suction pump action. Flow and pressures are serially measured along the circuit. Valve function can be observed and videotaped. Evaluation of biologic venous valves provides visual and quantitative assessment of venous valve function with respect to tissue processing, valve design, and implantation technique. Further improvement in this system in terms of more compliance and less rigidity of components is being pursued.

Deep venous thrombosis. Implications after open heart surgery.

We reviewed the cases of 10,638 cardiac surgical patients to determine the incidence of deep vein thrombosis (DVT) after open heart surgery (OHS). Seventy-seven patients (0.7 percent) had DVT. Group 1 included 36 patients who had DVT without pulmonary embolism (PE). Occurrence was equal in either leg. Anticoagulation with heparin and warfarin sodium (Coumadin) was employed as treatment. Extension of hospital stay was 10.8 days. Group 2 consisted of 41 patients who experienced PE 9.9 days after OHS. Sixteen patients had known DVT and were receiving heparin. In 25 patients, PE was the first event. Risk factors for PE included perioperative myocardial infarction (16 percent), atrial fibrillation (41 percent); blood type A (70 percent) (p less than 0.05), and coronary artery bypass graft (CABG) (98 percent). Twenty-four patients were treated with anti-coagulation alone. Six died of recurrent PE; mortality was 25 percent. Seventeen patients received anticoagulation plus inferior vena cava (IVC) interruption using a Hunter balloon. There were no recurrent PEs and there was one death from myocardial infarction (6 percent). Deep vein thrombosis and PE are rare complications of OHS. Routine prophylaxis with either heparin or warfarin is unnecessary. Patients with DVT, atrial fibrillation (AF), and perioperative myocardial infarction are at high risk of PE. Aggressive diagnosis to identify major venous thrombi along with anticoagulation and early consideration of IVC interruption are recommended for these patients. Patients who have undergone OHS and who have PE are at an unusually high risk for recurrent PE with death and are more safely treated with IVC interruption and anticoagulation than anticoagulation alone.

Acute renal failure associated with cardiac operations. A case-control study.

We performed a case-control study to identify risk factors for the development of acute renal failure after cardiac operations. Forty-two cases of acute renal failure were identified in a total of 572 patients who underwent cardiac operations. They were matched with a control population of patients having cardiac operations without acute renal failure. Discriminant analysis performed with preoperative variables revealed preoperative serum creatinine values, concurrent valve and bypass surgery, and age to be significant variables for identifying patients at risk for acute renal failure. The use of these three variables in a discriminant model correctly classified 77% of patients. The addition of intraoperative variables did not significantly improve the ability of the model to correctly classify patients. Acute renal failure was associated with a significant increase in the number of postoperative complications, mortality, and length of hospitalization and intensive care unit stay.

Inferior vena cava interruption with the Hunter-Sessions balloon: eighteen years' experience in 191 cases.

Over a period of 18 years, 191 consecutive patients had interruption of the inferior vena cava with the Hunter-Sessions balloon for complications of deep venous thrombosis and pulmonary embolism. Causes of deep venous thrombosis and pulmonary embolism included the postoperative state (33%), cancer (32%), and stroke (11%). There were 93 females and 98 males; ages ranged from 17 to 90 years (average, 57 years). Indications for placement of the Hunter-Sessions balloon were as follows: contraindication to anticoagulants (33%), anticoagulant complications (24%), pulmonary embolism despite anticoagulants (45%), and others including inferior vena cava thrombus (12%). Sixty-eight percent had clinical phlebitis and 36% had positive venography results. Pulmonary embolism had occurred in 165 patients (86%). It was diagnosed by ventilation-perfusion scanning (75%), angiography (23%), or on clinical grounds (2%) in patients with confirmed deep venous thrombosis. At the time of the procedure 52% were in significant cardiopulmonary distress, and 10% were intubated and on respirators. Transjugular placement was done in 188 patients, and transfemoral placement was performed in three. All All tolerated inferior vena cava interruption. Thirty patients (15%) died while in the hospital an average of 21 days after balloon placement, which was unrelated to the deaths. Follow-up was 45 months. Ninety-four patients are dead, 95 are alive, and the status of two patients is unknown. Twenty-nine of 64 patients (45%) who died after they left the hospital died of cancer. At last follow-up, 75% of patients had legs free of edema and 25% had need for elastic stockings. No malfunction or migration has occurred with the device. No patient had a pulmonary embolism while in the hospital after insertion of the Hunter-Sessions balloon, and no patient died of pulmonary embolism. Late minor pulmonary embolism occurred in three patients.

Coronary artery bypass surgery in patients less than 40 years of age.

Coronary bypass patients less than 40 years of age were identified and compared with a control group previously studied at our hospital. In patients less than 40 years, the average age was 35 years. Men comprised 90.1 percent of group 1, and 83.4 percent of group 2. Operative mortality was 2.89 percent for group 1 and 2.1 percent for group 2. Patients less than 40 years were more likely to have positive family history (46.3 percent vs 21.94 percent), elevated cholesterol levels (25.62 vs 11.36 percent), and be smokers (59.09 vs 39.9 percent). Group 1 patients were less likely to have diabetes (4.54 vs 13.37 percent) or hypertension (18.18 vs 31.43 percent). The percentage of late deaths was much higher for younger patients. Postoperative angina and the need for reoperation was higher in group 1.

Thromboelastography as an indicator of post-cardiopulmonary bypass coagulopathies.

Postoperative hemorrhage in patients undergoing open-heart surgery is a major cause of morbidity and mortality. Monitoring of coagulation in these patients has routinely involved the activated clotting time. Thromboelastography is currently used as a monitor of coagulation during liver transplantation. The thromboelastogram, by providing information on the interaction of all the coagulation precursors, gives more clinically useful information on coagulation than that available from the coagulation profile or the activated clotting time alone. This study was done to assess the usefulness of thromboelastography in open-heart surgery. Thirty-eight patients (29 undergoing coronary artery bypass grafting and 9 undergoing valve replacement) were studied with activated clotting time, thromboelastography, and coagulation profiles during three periods: before bypass, during bypass, and after protamine administration. Thromboelastography was a significantly better predictor (87% accuracy) of postoperative hemorrhage and need for reoperation than was the activated clotting time (30%) or coagulation profile (51%). Thromboelastography is easy to use and provides diagnostic data within 30 minutes of blood sampling.

Thromboembolism and cancer: treatment with the Hunter balloon.

Between 1970 and 1982, 126 inferior vena cava (IVC) balloon occlusions were performed for complications of venous thromboembolism (VTE). Forty, or 32%, were in patients with cancer. There were 20 men and 20 women. The average age was 60.8 +/- 2 years. Cancers of the brain, lung, and breast, along with diffuse metastatic disease with unknown primary disease, were equally common and represented 50% of our cases. Indications for IVC occlusion included pulmonary embolus despite anticoagulation (AC); 50% VTE and contraindication to AC, 38%; and complications of AC, 12%. Three patients died from ongoing complications of previous AC. Eight additional patients died of cancer, for a hospital mortality rate of 28%. Twenty-nine patients were discharged an average of 28.4 +/- 4.3 days after IVC balloon occlusion. Twenty of these patients subsequently died of cancer an average of 13 +/- 4.7 months after hospital discharge. Eight patients remain alive, four for more than 4 years. Pulmonary emboli did not occur after balloon occlusion, and there were no balloon complications. Only 4 of 29 discharged patients had mild leg edema. Hunter balloon occlusion of the IVC represents a safe and effective method for managing complications of VTE in patients with cancer. Early hospital discharge is possible, treatment is permanent, and future chemotherapy is not compromised by the need for long-term anticoagulation.

Hunter vena cava balloon: rationale and results.

The majority of patients with venous thromboembolism are successfully managed with anticoagulation therapy, but certain patients require inferior vena cava (IVC) interruption. Traditional open operations on the IVC have important disadvantages, among which are significant morbidity and mortality. Twenty years ago work began to develop a transvenous method to interrupt the IVC. As the requirements for a safe and effective method were defined, it became apparent that the best approach would be with a catheter-delivered detachable balloon secured by hyperinflation in the distensible IVC. The concept of a "filter" was discarded because of predicted problems with thrombosis, induced embolism, and device migration. We have treated 135 patients with the Hunter IVC balloon. Sick patients tolerate the procedure, and it is highly effective in preventing pulmonary embolism. Leg morbidity is acceptable, parallels the extent of the phlebitis, and is lessened by leg care and simultaneous anticoagulation therapy. Long-term results with follow-up to 13 years are excellent.

Coronary revascularization in septuagenarians.

Despite a 15 year experience with the aorta-coronary bypass operation, indications for its use remain unsettled, especially in the elderly. Between January, 1974, and June, 1980, 2,667 patients underwent coronary artery revascularization with an overall mortality of 3.8% (101/2,667). During the last 12 months the mortality has decreased to 1%. There were 2,562 patients below the age of 70, with a mortality of 3.5% (90/2,562), in contrast to 105 patients over the age of 70, with a mortality of 10.5% (11/105) (p = 0.002). In patients less than 70 years of age there was a significant difference between the mortality of men, 3.12% (67/2,146), and that of women, 5.53% (23/416) (p = 0.015). This disparity of operative risk was far more pronounced in patients over 70 years of age: men 6% (5/84) and women 28.6% (6/21) (p = 0.002). The overall operative mortality of women, 6.6% (29/437), was significantly different from the overall mortality of men, 3.2% (72/2,230) (p = 0.001). An in depth analysis of past medical history, risk factors, and catheterization data is presented in those patients over the age of 70. The average number of vessels bypassed was 2.40: men 2.47 and women 2.09 (p = NS). The ages varied from 70 to 81 years with a mean of 72.5. Smoking (p = 0.012) and diabetes (p = 0.0078) were significant risk factors for coronary disease. Smoking (p = 0.032) and abnormal pulmonary artery pressures (p = 0.0429) were significant variables affecting mortality. A 97.1% follow-up was obtained up to 78 months. Coronary artery revascularization can be performed in men below the age of 70 with acceptable mortality, but there is a twofold increase above the age of 70. Women can undergo revascularization below the age of 70 with a significantly higher risk than males. Those above the age of 70 are at severe risk and should undergo revascularization only after careful selection.

Neurological complications of coronary revascularization.

In a series of 3,206 consecutive coronary artery bypass procedures performed between 1976 and 1981, 89 patients died (2.8% mortality) and 32 patients (1%) suffered major neurological syndromes. Among the latter patients, four distinct groups were identified. Group 1 consisted of 10 patients who remained unresponsive after operation. In Group 2 were 10 patients who awakened after operation but had clinical evidence of focal cerebral infarction. Group 3 included 6 patients who were initially intact neurologically but in whom neurological deficits later developed. In Group 4 were 6 patients who had severe mental aberration but no focal neurological deficits. The incidence of coma or focal deficit occurring without a lucid interval (Groups 1 and 2) was 0.62%, and these patients had a 30% mortality. Causative factors were suspected in 70% of the patients in Groups 1 and 2, and included atheromatous embolism, perioperative hypotension, carotid artery occlusive disease and air embolism. The outcome was poor for unresponsive patients, with 70% dying or remaining comatose, but nearly all of the patients with focal deficits or severe mental aberration demonstrated notable improvement.

Leg wound complications associated with coronary revascularization.

One percent of 2,545 patients undergoing coronary revascularization with the saphenous vein over a 5 year period sustained leg wound complications which necessitated extra care. Fourteen complications were minor and required only drainage, a new antibiotic, and dressing changes. Thirteen major wound complications required wide debridement and, of these, five could be closed only with skin grafts. Eight wounds were infected, two with Staphylococcus aureus and six with mixed gram-negative flora. Ninety-three percent of these wounds were in the thigh. Average weight of patients with leg wound complications was 73.5 +/- 3.5 kg and not different from that of a randomly selected control group (73.8 +/-1.2 kg). However, 40% of the patients were women, a much higher incidence than control (p less than 0.005). Hospital stay increased significantly from 12.1 +/- 0.5 days for the control group to 24 +/- 2.6 days for the group with wound complications (p less than 0.005). Average hospital stay was 33.6 +/- 3.8 days (p less than 0.001) in those patients with major wound complications (estimated hospital cost $9,900). Leg wound complications of saphenous vein harvest are infrequent but serious. Efforts to prevent this complication should include minimal dissection, careful hemostasis, and closure in layers. Development of skin slough, infection, and necrosis necessitating débridement and drainage is a major and expensive complication. Wide excision and direct closure are necessary to minimize hospital stay and reduce the requirement for skin grafting.

Sternal wound complications. Management and results.

Of 4,124 patients undergoing median sternotomy for cardiac operations, 1.8% had sternal wound complications. These included wound drainage, skin separation, unstable sternum, and sternal dehiscence with or without infection. Septicemia and mediastinal abscess were found in all 19 patients who died. Incision and drainage of skin and subcutaneous tissue with frequent changes of dressing or irrigation (Method A) is recommended for those patients with (I) serosanguineous drainage only or (2) a stable sternum and superficial infection without systemic reaction. Surgical débridement of the sternum and mediastinum with reclosure followed by mediastinal irrigation via drainage tubes with 0.5% povidone-iodine solution (Method B) is recommended for patients with (1) a draining, unstable sternum, (2) infection involving the retrosternal space, or (3) infection causing a systemic reaction unresponsive to Method A. None of the eight patients in the latter group with more serious infections died when managed by Method B, and only one had recurrent infection. In contrast, of 28 patients of the latter group not treated with Method B, 11 died of infection-related causes and 13 returned with recurrent infection.