Harry L. Bush

Use of Cytomegalovirus Immune Globulin to Prevent Cytomegalovirus Disease in Renal-Transplant Recipients

We undertook a prospective randomized trial to examine whether an intravenous cytomegalovirus (CMV) immune globulin would prevent primary CMV disease in renal-transplant recipients. Fifty-nine CMV-seronegative patients who received kidneys from donors who had antibodies against CMV were assigned to receive either intravenous CMV immune globulin or no treatment. The immune globulin was administered in multiple doses over the first four months after transplantation. The incidence of virologically confirmed CMV-associated syndromes was reduced from 60 percent in controls to 21 percent in recipients of CMV immune globulin (P less than 0.01). Fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20 percent of controls (P = 0.05). Only 4 percent of globulin recipients had marked leukopenia (reflecting serious CMV disease), as compared with 37 percent of the controls (P less than 0.01). There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17 percent of controls as compared with 4 percent of globulin recipients). A significant reduction in serious CMV-associated disease was observed even when patients were stratified according to therapy for transplant rejection (P = 0.04). We observed no effect of immune globulin on rates of viral isolation or seroconversion, suggesting that treated patients often harbored the virus but that clinically evident disease was much less likely to develop in them. We conclude that CMV immune globulin provides effective prophylaxis in renal-transplant recipients at risk for primary CMV disease.

Hypothermia during elective abdominal aortic aneurysm repair: The high price of avoidable morbidity

PURPOSEnAdverse outcomes apparently associated with hypothermia led us to examine patients undergoing elective abdominal aortic aneurysm (AAA) repairs to test the hypothesis that hypothermia (temperature less than 34.5 degrees C) is associated with increased morbidity and excess mortality rates.nnnMETHODSnTwo hundred sixty-two elective AAA repairs were retrospectively reviewed for preoperative and intraoperative risk factors. Core temperature, age, Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores (raw and temperature-adjusted), fluid resuscitation, and perioperative organ dysfunction were recorded prospectively. Outcome measures included lengths of stay in the intensive care unit and in the hospital, and hospital mortality rates.nnnRESULTSnExcept for a higher risk of hypothermia in women (p < 0.05), by univariate analysis, preoperative risk factors were similar in patients in the hypothermic and normothermic groups. After operation, patients with hypothermia had significantly greater APACHE scores (p < 0.0001), and patients in the hypothermic nonsurvivor group took significantly longer to rewarm (p < 0.05), suggesting marked hypoperfusion. Patients with hypothermia had significantly greater fluid (p < 0.05), transfusion (p < 0.01), vasopressor (p < 0.05), and inotrope (p < 0.05) requirements, resulting in significantly higher incidences of organ dysfunction (53.0% vs 28.7%, p < 0.01) and death (12.1% vs 1.5%, p < 0.01) and markedly prolonged lengths of stay in the unit (9.2 +/- 2.0 vs 5.3 +/- 0.6, p < 0.05) and in the hospital (24.3 +/- 2.9 vs 15.0 +/- 0.08, p < 0.01). By multivariate analysis, female gender (p = 0.004) was the only predictor of intraoperative hypothermia, whereas initial hypothermia was significantly predictive of both prolonged hypothermia and development of organ failure (p < 0.05). Organ failure (p < 0.05) and acute myocardial infarction (p < 0.01) were independent predictors of death.nnnCONCLUSIONSnAfter AAA repair, patients with hypothermia have multiple physiologic derangements associated with adverse outcomes. Although multiple etiologic factors are interacting, body temperature is one variable that should be controlled during aortic surgery.

Kidney transplantation from unrelated living donors. Time to reclaim a discarded opportunity.

Before dialysis therapy was routinely available in the United States, both related and unrelated living donors were accepted for renal transplantation. By 1965, data from the Registry in Human Kidn...

Favorable balance of prostacyclin and thromboxane A2 improves early patency of human in situ vein grafts

Graft thrombosis soon after reconstruction remains a major obstacle to the use of reversed vein grafts in infrapopliteal reconstruction. Our clinical experience with in situ vein grafts corroborates Leathers results by demonstrating an overall graft patency of 95% below the knee at 1 year and 94% in the infrapopliteal group. It has been postulated that this improved early patency rate of in situ vein grafts is the result of more optimal preservation of the endothelium of the vein graft. To investigate this hypothesis, human saphenous veins were handled by an in situ and a reversed technique. The intact vein segments were then tested for luminal production of prostacyclin and thromboxane A2 and fixed for scanning electron microscopic analysis of the surface morphology. This study demonstrated that endothelial cell prostacyclin release is enhanced in human in situ vein segments but not in reversed vein segments. In addition, luminal production of thromboxane A2 is significantly greater in the reversed than in the in situ vein segments. These findings are associated with marked endothelial structural damage in the reversed veins and minimal endothelial disruption in the in situ veins. Therefore the ratio of the antiaggregatory vasodilator prostacyclin to the proaggregatory vasoconstrictor thromboxane A2 is significantly more favorable for the in situ vein segment than for the reversed vein segment. The observed excellent early patency of the in situ vein grafts in our poor-risk patient population may in part be the result of this favorable balance of prostacyclin and thromboxane A2 and the more optimally preserved endothelial morphology.

Volume loading and vasodilators in abdominal aortic aneurysmectomy

Preoperative infusion of volume to increase the wedge pressure will maintain stable flow and arterial pressure at the time of aortic declamping. Usually 1,500 ml of balanced salt solution given with 75 g of albumin is sufficient to accomplish this purpose. Pressor or inotropic agents are not required. In our experience 14 percent of patients will have a down-slope in the preoperative myocardial performance curves. In these persons, volume infusions should be adjusted to keep the pulmonary arterial wedge pressure on the ascending portion of the curve. The use of vasodilator agents in normotensive patients has a deleterious effect on cardiac performance.

Intermittent pneumatic compression to prevent proximal deep venous thrombosis during and after total hip replacement: Woolson ST, Watt JM. J Bone Joint Surg 1991; 73-A: 507-12

A prospective, randomized study of the effectiveness of intraoperative and postoperative use of intermittent pneumatic compression, alone or in cornbination with oral administration of either aspirin or low-dose warfarin, was done of a consecutive series of patients who had a total hip replacement and were more than thirty-nine years old. All patients began walking by the third postoperative day. One hundred and ninetysix patients who had 217 total hip arthroplasties were included. Twenty-eight per cent of the procedures were revisions of a previous total hip replacement or of an endoprosthesis, and the remainder were primary arthroplasties. Patients were randomized as to the type of prophylaxis that they received: intermittent pneumatic compression alone, seventy-six hips; intermittent pneumatic compression and aspirin, seventy-two hips; or intermittent pneumatic compression and low-dose warfarin, sixty-nine hips. Before discharge from the hospital, and at an average of seven days after the operation, all patients were evaluated for the presence of proximal deep-vein thrombosis with either venography on the side of the operation or with bilateral venous ultrasonography. The relative frequency with which thrombosis occurred in a proximal vein was not significantly different in the three groups; the over-all relative frequency was 10 per cent. Intermittent compression during and after the operation effectively reduces the rate of proximal-vein thrombosis after total hip replacement. With the number of patients in our study, the effectiveness of this technique could not be shown to be augmented by oral administration of either aspirin or low-dose warfarin. The most common cause of death after an elective total hip replacement is pulmonary embolism7. When an operation is done on the hip and measures for the prevention of * No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject ofthis article. No funds were received in support of this study. t Suite 202, 1220 University Drive, Menlo Park, California 94025. Please address requests for reprints to Dr. Woolson. t 200 15th Avenue East, Seattle, Washington 98112. deep venous thrombosis are not employed, the risk of fatal pulmonary embolism has been reported to be 2 to 3 per cent2’9 and that of asymptomatic embolism, about 25 per cent5. When prophylaxis is given, deep venous thrombosis occurs in 20 to 50 per cent of these patients4, and proximal deep-vein thrombosis is the major cause of pulmonary embolism’2. In 1986, Hull and Raskob7 stated that prophylaxis against deep venous thrombosis was an important part of the management of patients who have an arthroplasty of the hip. A prospective, randomized study was designed to determine whether intraoperative and postoperative use of intermittent pneumatic compression effectively reduces the rate of proximal venous thrombosis when compared with the rates for historical controls and whether there is a difference in the relative frequency of proximal deep venous thrombosis after total hip replacement with one of the three prophylactic measures: intermittent pneumatic compression alone, intermittent pneumatic compression and aspirin, or intermittent pneumatic compression and low-dose warfarin. Materials and Methods All patients who were more than thirty-nine years old when a primary or revision total hip replacement was done by one of us (S. T. W.) between July 1986 and September 1989 were considered for inclusion in this study. Patients were excluded if they had an allergy to aspirin or warfann, had recently had a peptic ulcer or other bleeding diathesis, had taken any drug that affects platelet function within two weeks before the operation, or were expected to remain in bed for more than four days after the operation. This left 239 patients (27 1 total hip arthroplasties) for the study. An additional fifty patients (fifty-four procedures) were excluded: thirty-four patients (thirty-six procedures) refused to participate; in eleven patients (eleven procedures), a nonelective operation had been done for an acute fracture of the hip or femur; in two patients, bilateral total hip replacement had been done during one session of anesthesia, after preoperative percutaneous insertion of a filter in the inferior vena cava; in one patient (one hip), a one-stage total hip replacement and contralateral total knee arthroplasty had 508 S. T. WOOLSON AND J. M. WATT THE JOURNAL OF BONE AND JOINT SURGERY been done; in one patient (one hip), a postoperative test for venous thrombosis had not been done because severe medical problems had developed; and one patient (one hip) had continued bed rest for a prolonged period after the operation. Seven of the fifty patients who originally had been excluded were eventually included because an arthroplasty was done on the contralateral hip later in the study. Bilateral hip replacement was done in twenty patients. In one patient, both procedures were done during the same operative session; in eighteen patients, the procedures were done at least one week apart; and in one other patient, bilateral staged primary hip replacements were done and later one hip was revised because of late hematogenous sepsis and loosening. All three procedures were included in the series. Thus, 196 patients who had 217 total hip arthroplasties participated in the study. All 196 patients consented, in writing, to participate in the study and to be assigned at random to one of three groups. The random assignment to a treatment group was carried out with the use of sealed envelopes. During the arthroplasties on the hips, the patients in Group I wore a thigh-high stocking with graduated elasticity and a thigh-high six-chambered boot for sequential intermittent compression (Kendall, Mansfield, Massachusetts) on the side of the operation. The stocking was placed only as high as the knee during the operation, because of the need for sterile preparation of the entire thigh. A thigh-high elastic stocking and a non-sterile sequential-compression boot were placed on the contralateral extremity, as well, before the patient was draped. The patients in Group II wore the elastic stockings and the intermittent pneumaticcompression boots and were given 650 milligrams of aspirin orally twice daily, beginning on the evening before the operation. The patients in Group III wore the elastic stockings and the compression boots and received 7.5 or ten milligrams of warfarin orally on the evening before the operation. The prothrombin time was determined daily to help in regulation of the dose of warfarin. The prothrombin time was maintained at 1 .2 to 1 .3 times the control value (a range of fourteen to sixteen seconds, with the control time being twelve seconds). All operations were done with the patient in the lateral decubitus position. A posterolateral approach was used for the primary arthroplasties and a transtrochanteric approach, for the revisions. After preparing the skin over the hip and the proximal part of the thigh and draping the lower extremity with stockinette, wrapped snugly with an elastic bandage, the surgeon placed a sterile, thigh-high compression sleeve around the leg and distal part of the thigh. The end of the sterile tubing from the compression sleeve was passed off the operative field to the circulating nurse, who attached it to the compression pump on the floor near the operating table. The sterile compression sleeve has an extra length (one and a half meters [five feet]) of sterile connecting tubing to allow the lower extremity to be moved without restriction during the operation. It is important to attach the sterile connecting tubing to the operative drapes so that the unsterile portion of the tubing cannot be pulled onto the operative field by manipulation of the lower limb. The compression pump was started immediately after the draping was completed. The part of the sterile compression sleeve that was over the thigh rarely interfered with the operative incision unless the surgeon found that the distal half of the femur needed to be exposed. For the four thighs for which this was necessary, the compression sleeve was rolled down and the thigh-chambers of the compression sleeve were not used, but compression from the sleeves of the calf continued. Compression was continued throughout the procedure and was interrupted only when the patient was transferred from the operating room to the recovery room, where it was resumed. The sequence of the cycle of compression began proximal to the ankle in the two distal chambers over the calf and progressed to the two chambers over the proximal part of the calf and then to the two chambers over the thigh. The pressure was between thirty-five and fifty-five millimeters of mercury (4.7 and 7.3 kilopascals) for a period of 5.5 seconds, after which there was a period of continued inflation of 5 .5 seconds, so that the total period of inflation was eleven seconds. There was then a sixty-second period of deflation before the cycle was repeated. Until the test for deep venous thrombosis was done, usually on the day before the patient was discharged from the hospital, the elastic stockings and compression boots were worn continuously except when the patient bathed or walked. After the operation, the limb on the side of the operation was elevated on a splint in balanced suspension until the patient began walking two days later. Venography or B-mode ultrasonography, or both, was done at an average of seven days (range, four to thirteen days) after the operation, just before the patient was discharged from the hospital. The patients who had the first 105 procedures were also included in a concurrent study in which the accuracy of B-mode venous ultrasound scans was evaluated by comparison of the results with those of venography. In these patients, unilateral venography of the lower limb on the side of the operation was

Early healing after carotid endarterectomy: Effect of high- and low-dose aspirin on thrombosis and early neointimal hyperplasia in a nonhuman primate model

Platelet aggregation and release phenomena are central to most postulated mechanisms of thrombosis and neointimal hyperplasia after carotid endarterectomy. Therefore high-dose aspirin (HDA) has been advocated to minimize these sources of endarterectomy failure. We have defined low-dose aspirin (LDA) that selectively blocks platelet cyclooxygenase but preserves arterial wall cyclooxygenase in the nonhuman primate, Macaca fascicularis. We compared this theoretically optimal aspirin dose with HDA and no treatment (control) in a model of carotid endarterectomy. The aspirin was started before operation and continued for 6 weeks after operation, at which time the endarterectomized vessels were excised. The patency and morphologic findings of the arteries were measured. Platelet function was monitored by bleeding time and serum thromboxane A2 determinations. LDA and HDA were associated with 100% patency, whereas the control group had 50% patency. However, HDA did not protect the vessel from developing neointimal hyperplasia, which was seen in the control group and was associated with platelet adherence to the flow surface at 6 weeks. At 6 weeks, LDA significantly decreased but did not totally prevent neointimal hyperplasia and the flow surface was healed. Therefore the genesis of neointimal hyperplasia after endarterectomy may be more complex than simply a function of platelet-vessel wall interaction.

Management of the upper extremity with absent pulses after cardiac catheterization

Thirty-one patients had a delayed loss of brachial artery and radial artery pulse after cardiac catheterization; eleven of the patients had early embolectomy or a vein patch graft and 82% of these had immediate restoration of pulse and remained asymptomatic. Early surgery failed in two patients, requiring late vein bypass grafting for claudication. Twenty patients did not have early surgery, eleven (55%) remaining asymptomatic and nine (45%) developing ischemic symptoms. Five of these nine patients (25%) required late vein bypass grafting for severe claudication. Of the fifteen patients who lost their pulse and did not undergo surgery, the average Doppler forearm pressure immediately following the occlusion was 50 mm Hg (pressure index=0.46). The average Doppler pressure measured at the time of follow-up was 80 mm Hg (pressure index = 0.61). Early local surgery is highly successful in patients who lose their radial artery pulse after cardiac catheterization. Conservative nonoperative therapy may be successful but often results in late ischemic symptoms that may require late vein bypass grafting.

Computed tomographic angiography

Computed tomographic angiography performed by the intravenous administration of contrast medium was evaluated in 86 vascular patients. This experience demonstrates a new approach to the evaluation of patients with symptomatic aortic aneurysms, in whom computed tomographic angiography will aid in evaluating the need for emergency surgery. Nonoperative patients are serially evaluated by computed tomographic angiography to detect significant changes in the geometric configuration of their aneurysms. Computed tomographic angiography was beneficial in the evaluation of the patency of vascular reconstructive procedures such as femoropopliteal bypass, aortoiliac bypass and application of a vena caval device. More clinical experience and possibly a rapid sequence technique are needed to evaluate patients with portasystemic shunts.

Volume Loading and Vasodilators in Abdominal Aortic Aneurysmectomy

Preoperative infusion of volume to increase the wedge pressure will maintain stable flow and arterial pressure at the time of aortic declamping. Usually 1,500 ml of balanced salt solution given with 75 g of albumin is sufficient to accomplish this purpose. Pressor or inotropic agents are not required. In our experience 14 percent of patients will have a down-slope in the preoperative myocardial performance curves. In these persons, volume infusions should be adjusted to keep the pulmonary arterial wedge pressure on the ascending portion of the curve. The use of vasodilator agents in normotensive patients has a deleterious effect on cardiac performance.