Mycophenolate mofetil versus azathioprine immunosuppressive regimens after lung transplantation: preliminary experience.

BACKGROUND: Mycophenolate mofetil reduces episodes of biopsy-proven acute cellular rejection or treatment failure in the first year after kidney transplantation; however, limited data exist regarding the efficacy after lung transplantation. METHODS: In a 2-center, nonrandomized concurrent cohort study (level III evidence), we analyzed the incidence of biopsy-proven acute cellular rejection (International Society for Heart and Lung Transplantation grade > or=A2) and decrement in pulmonary function during the first 12 months after successful lung transplantation. All patients received induction immunosuppression with antithymocyte globulin (< or=5 days' duration), cyclosporine and prednisone, in addition to either mycophenolate mofetil (2.0 g/d) [n=11] or azathioprine (1 to 2 mg/kg per day) [n=11]. RESULTS: During the first 12 months after lung transplantation, the mycophenolate mofetil group experienced significantly fewer episodes of acute cellular rejection than the azathioprine group (0.26+/-0.34 vs 0.72+/-0.43 episodes/100 patient-days [mean+/-SD], p < 0.01; 95% CI for the difference=0.126 to 0.813). The change in forced expiratory volume -1 second [deltaFEV1] (liters) between the 3rd and 12th months after lung transplantation was analyzed for the two treatment groups. For this interval, deltaFEV1 for the mycophenolate mofetil group was +0.158+/-0.497 L vs -0.281+/-0.406 L for the azathioprine group (p < 0.05; 95% CI for difference=+0.0356 to 0.843). During the first year, there was 1 death in each group attributed to bronchiolitis obliterans syndrome with concurrent pneumonia. There were no differences in incidence of cytomegalovirus or bacterial infections between the treatment groups; however, a higher prevalence of aspergillus sp airway colonization in bronchoalveolar lavage fluid was observed for the mycophenolate mofetil group (p < .05). The prevalence of bronchiolitis obliterans syndrome at 12 months was 36% for the azathioprine group vs 18% for the mycophenolate mofetil group (p=NS). CONCLUSIONS: Our preliminary experience with mycophenolate mofetil after lung transplantation suggests a decreased incidence of biopsy-proven acute cellular rejection. Furthermore, less decline in FEV1 after 12 months may suggest a reduced incidence or delayed onset for development of bronchiolitis obliterans syndrome. Prospective randomized trials with low beta error (level I evidence) should be performed to assess the efficacy of mycophenolate mofetil vis-à-vis acute allograft rejection and bronchiolitis obliterans syndrome.

Heart assist devices: state of the art.

The various types of available mechanical assist devices are discussed in this article. Nursing care (both intraoperatively and postoperatively) and complications are also reviewed.

Bridge to heart transplantation: importance of patient selection.

Since 1986, 26 candidates were evaluated for mechanical support as a bridge to heart transplantation. Group 1 consisted of 15 patients who were accepted and who received support with a ventricular assist device (14 patients) or a total artificial heart (1 patient). Seven of the 15 patients received transplants and survived, whereas contraindications to transplant developed in seven patients while they were receiving support, and these seven died. One patient remains hospitalized after transplantation. Group 2 consisted of 11 patients rejected for circulatory support because of renal insufficiency or infection (9), pulmonary embolus (1), and cerebrovascular accident (1). Two group 2 patients underwent transplant procedures after their complications resolved, and one survived. One other group 2 patient who recovered without transplantation or mechanical support was discharged. There was no significant difference in age, gender, or cause of cardiogenic shock between the two groups. Four of five patients accepted for mechanical support on the first evaluation survived, and three of 10 accepted after the initial evaluation survived, indicating that delayed selection often results in complications that preclude transplantation and survival. Only one of the 26 patients survived without transplantation or support. These data emphasize the importance of patient selection on the outcome of bridging to transplantation.

Retrospective analysis of the psychologic effects of mechanical circulatory support.

There is an increasing need to evaluate the psychologic impact of circulatory support because of the growing use of mechanical assist devices. Twenty-seven people, 12 survivors of mechanical circulatory assistance and 15 family members, were surveyed; nonsurvivors' families were not surveyed. The 12 survivors (ages 18 to 66 years; mean, 43 years) had been supported with Pierce-Donachy ventricular assist devices (nine patients) and the Novacor left ventricular assist system (one patient). One patient received a centrifugal pump, and one was supported with extracorporeal membrane oxygenation (ECMO). Duration of support ranged from 8 hours to 90 days (mean, 23 days). Ten people surveyed were spouses of these patients, and five were parents of children who had been supported with ECMO. Three patients were supported longer than 3 weeks, and four patients were awake and ambulatory during support. Financial worries were not a concern for 80% of the parents but were a concern for 80% of the spouses. Eighteen percent of the patients believed they were treated as an experiment, whereas 40% of their spouses thought they were. None of the parents thought their child was treated as an experiment. Sixty-seven percent of the patients stated that they have returned to a normal life-style, and 75% feel they have a brighter outlook on life. Six patients have returned to work, two are retired, two are disabled, and two have physical capabilities to work but choose not to. Eighty-nine percent of all those surveyed would recommend an assist device to someone who needed one. Although these procedures are often associated with severe medical and psychologic complications, 74% of the patients would agree to a second implant.

Hemodynamic predictors for weaning patients from ventricular assist devices (VADs).

In order to find hemodynamic parameters that can accurately predict whether patients can be successfully weaned from ventricular assist devices (VADs), we studied data from 17 patients supported with Pierce-Donachy VADs [11 left VAD (LVAD); 6 right VAD (RVAD)] following cardiogenic shock for periods from 1.3 to 22 days (mean 5.4). Myocardial recovery was determined by daily measurements of "pump on pump off" parameters, and the data from the 8 LVAD patients and 3 RVAD patients whose hearts recovered were compared to the data from those whose did not. In this study, daily pump on pump off hemodynamic measurements were found to be predictive of success for weaning patients from VADs. In particular, the most significant predictors were: increases in mixed venous oxygen saturation, cardiac index, mean arterial pressure and ventricular ejection fraction, as well as decreases in atrial pressures. An index for measuring hemodynamic function with the VAD off is proposed, as are models of recovery. Seventy percent of the patients weaned from VADs survived, indicating that patients appropriately weaned from VAD support have a reasonable chance for survival.

Nursing care of the ambulatory patient with a mechanical assist device.

Since 1986, 10 men and one woman were ambulatory while supported with mechanical assist devices as a bridge to heart transplantation. Four patients received a subclavian intraaortic balloon pump, two were supported with a Novacor left ventricular assist system, three patients received Pierce-Donachy ventricular assist devices, and one patient received a Jarvik 7 total artificial heart. One patient with an intraaortic balloon pump later received a left ventricular assist system because of hemodynamic deterioration despite the intraaortic balloon pump. Before device insertion all 11 patients were in cardiogenic shock despite inotropic and vasodilator support. The time of support ranged from 8 to 440 days (median, 24 days). In-house coverage by the circulatory support team was necessary only during the first 24 to 72 hours of support. When the patient's condition was stabilized, nursing staff monitored the devices with "on-call" availability of the circulatory support team. After implant of the device, all patients were able to perform activities of daily living. Once patients were able to walk in their hospital rooms, ambulation began in the hallways; frequency and distance were gradually increased. Four of the patients walked outside the hospital while tethered to the drive console. Daily physical therapy contributed to increased exercise tolerance. Protective isolation was used before and after transplantation to minimize the risk of infection. Sterile dressing changes (gown, gloves, mask) were applied to drive lines, cannula sites, and incisions. All invasive lines and catheters were removed as soon as the patient's clinical condition warranted, and noninvasive monitoring was used to decrease the chance of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

T cells in ventricular assist device patients.

Levels of T lymphocytes were measured in 20 consecutive patients, 18 men and two women, supported with ventricular assist devices or an artificial heart. Indications for support were bridge to transplantation (n = 10), postcardiotomy cardiogenic shock (n = 8), and acute myocardial infarction shock (n = 2). Control levels were from healthy volunteers not undergoing cardiac operation. Preoperatively, numbers of total lymphocytes and subclasses CD3, CD4, and CD8, as well as the interleukin-2 receptors (IL2R), were the same as controls (cells/microliters): lymphocytes, 1,940; CD3, 1,413 +/- 410; CD4, 894 +/- 318; CD8, 490 +/- 185; IL2R, 96. From implant to postoperative day 5, levels were below control values (p less than 0.001), reaching a nadir on postoperative day 2 (lymphocytes, 896 +/- 599; CD3, 489 +/- 267; CD4, 309 +/- 207; CD8, 183 +/- 107; IL2R, 43 +/- 47). Data from 10 patients (group 1) who survived (four weaned from cardiopulmonary bypass, six transplanted) were compared with those from 10 patients (group 2) who died of multiorgan failure, sepsis, or both. From preimplant through postoperative day 6, levels did not differ between groups. However, from postoperative day 7 to the last day of ventricular support (group 1, 24-90 days; group 2, 7-29 days), group 1 levels (lymphocytes, 2,364 +/- 618; CD3, 1,825 +/- 553; CD4, 1,013 +/- 187; CD8, 796 +/- 402) were significantly above (p less than 0.01) group 2 levels (lymphocytes, 1,290 +/- 463; CD3, 746 +/- 295; CD4, 534 +/- 253; CD8, 221 +/- 106). These data indicate that lymphocytes and particularly T cells 1) decrease after ventricular assist device insertion, reaching a nadir at postoperative day 2, 2) return to control values after patients whose clinical status improves, and 3) remain low in severely ill patients. T-cell depression in ventricular assist device patients is related to the severity of the patient's condition rather than the presence of the device.

Team approach to circulatory support.

A multidisciplinary approach to circulatory support is discussed in this article. The clinical, educational, and investigational responsibilities of each team member are presented.

Thromboembolic complications with the Pierce-Donachy ventricular assist device.

Pierce-Donachy ventricular assist devices (VADs) were used to support 54 patients. None of the 27 patients supported less than 4 days had any visible thrombi in the VAD at explant. Of the 27 patients supported longer than 4 days, nine patients had visible thrombi. In this group of 27 patients, 19 received VAD support pending myocardial recovery, and anticoagulation consisted of dextran (4-15 days) and heparin during the weaning phase (1-2 days). The other eight patients had VADs implanted as bridges to cardiac transplantation. These patients also received dextran postoperatively (1-5 days), but were switched to a regimen of oral warfarin and dipyridamole. Duration of support for the nine patients in whom thrombi were found ranged from 4-27 days (mean, 12 days). The etiology of thrombus was probably related to mechanical problems in four patients, inadequate anticoagulation in two patients, sepsis in two patients, and unknown causes in one patient. Four of these patients suffered cerebral or peripheral injuries, which were probably embolic in two, and possibly embolic in two. One of these four patients survived, and two patients with thrombi but no emboli survived. One patient suffered a stroke, but no evidence of thrombi was found. Our incidence of thrombus with this VAD was 17%. Thrombi were related to inadequate anticoagulation, interrupted flow, or sepsis, but not to duration of support.

The incidence of isolated left ventricular failure in bridge-to-transplant candidates.

Twenty-one patients (pts) were supported with mechanical devices as a bridge to cardiac transplantation (Tx). Ventricular function was assessed by a combination of angiography, echocardiography, nuclear scans, hemodynamics, and visual inspection at the time of device insertion. Twelve pts had biventricular failure (BVF) and 11 received biventricular support with extracorporeal membrane oxygenation (two pts), biventricular assist devices (VAD) (eight pts), or an artificial heart (one pt). One BVF pt received a left VAD (LVAD) and drug support for severe right ventricular failure (RVF), which resolved after 48 hr. The remaining nine pts had left ventricular failure (LVF), with only mild to moderate RVF, and received LVADs with minimal drugs. Eleven pts were tx, with nine survivors. A comparison of pts with LVF vs BVF revealed no differences in age, gender, device flows, duration of support, diagnosis, number tx, or number survived. The incidence of LVF was 43% vs 57% BVF in bridge-to-transplant pts. LVAD support alone is often successful in pts with mild or moderate BVF, but is rarely successful in pts with severe BVF.

Bridging to heart transplantation with circulatory support devices.

Several devices are currently available for bridging to cardiac transplantation, but the efficacy of each has not been established. From September 1983 to March 1988 we supported 17 transplant candidates with mechanical assist devices. Extracorporeal membrane oxygenation (ECMO) was used to bridge two patients, external ventricular assist devices (VADs) were used in 11 patients, internal left ventricular assist systems (LVAS) were used in three patients, and implantable prosthetic replacement ventricles (TAH) were used in one patient. The 14 men and three women, aged 24 to 59 years (mean 46 years), suffered cardiogenic shock caused by ischemic (13 patients), postpartum (two patients), viral (one patient), and drug-induced (one patient) cardiomyopathy. Five patients with isolated left ventricular failure (LVF) received only left VADs, three patients with severe LVF and moderate right ventricular failure received LVAS, and nine patients with severe biventricular failure received ECMO (two patients), biventricular assist devices (six patients), and TAH (one patient). Patients were supported for periods of 1/2 to 90 days (mean 22) with flows of 2.15 to 3.39 L/min/m2. Ten patients underwent transplantation (eight of whom were discharged) and seven patients died without transplants. The two patients who received ECMO died 1 and 30 days after transplantation, in part as a result of ECMO complications. Seven patients were denied transplants because of renal failure (five patients), infection (five patients), bleeding (four patients), and cerebrovascular accident (two patients). The seven survivors were supported with VADs (five patients) or LVAS (two patients). Three had driveline infections, two had bleeding complications, two developed mediastinitis, and one each had hemolysis, cerebrovascular accident, and mechanical failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Nursing care of a patient requiring prolonged mechanical circulatory support.

Four cardiac transplant candidates were supported with ventricular assist devices for periods ranging from 53 to 90 days (mean, 75 days). The patients were men who ranged in age from 36 to 49 years (mean, 44.5 years). Two patients had Pierce-Donachy biventricular assist devices (BVADs) and two patients had Novacor left ventricular assist systems (LVASs). Complications included infection (3 patients), development of antibodies (2 patients), bleeding (2 patients), and pump inflow obstruction (1 patient). All patients were maintained on an anticoagulation regimen which included warfarin and dipyridamole. They were extubated and ambulatory for most of the period of mechanical support. Thromboembolic complications did not develop in any of these patients, and they did not acquire infections which involved the mediastinum. They were successfully transplanted and discharged 11 to 25 days after transplantation. Although major complications were common in this small group of patients, all four patients achieved hemodynamic stability and became excellent candidates for cardiac transplantation. With proper patient selection and meticulous nursing care, current mechanical circulatory support technology is capable of maintaining patients consistently for periods of greater than 50 days.

Bridging to cardiac transplantation with pulsatile ventricular assist devices.

As cardiac transplantation becomes more commonplace in the treatment of end-stage heart failure and as suitable donors become less available, an increasing number of patients will require mechanical circulatory assistance to bridge to transplantation. Since 1982, refractory hemodynamic instability requiring placement of pulsatile ventricular assist devices (VADs) has developed in 11 candidates for transplantation aged 24 to 54 years (mean, 39.6 years). A pneumatic Pierce-Donachy pump was used in 9 patients and an electrical Novacor pump in 2. The cause of the cardiomyopathy was ischemic in 6, postpartum in 2, idiopathic in 2, and doxorubicin hydrochloride toxicity in 1. Seven patients required left ventricular support (LVAD); 4 required biventricular mechanical support (BVAD). Duration of support ranged from 8 hours to 91 days with flows ranging from 4.1 to 8.5 L/min (mean, 5.5 L/min). Although hemodynamic stability was achieved in all 11 patients, contraindications to transplantation developed in 5 patients during VAD support (renal failure in 4, sepsis in 3, disseminated intravascular coagulopathy in 1). The remaining 6 patients (4 with an LVAD, 2 with a BVAD) remained good candidates for transplantation despite major complications in 5 (mediastinal bleeding in 3, driveline infection in 3, development of preformed antibodies in 2, small embolic stroke caused by device malfunction in 1). The 3 patients who were supported the longest (24, 75, and 91 days) were ambulatory while awaiting a donor heart. All 6 patients underwent successful transplantation after 8 hours to 91 days (mean, 24 days) of support. Other than one sternal wound infection, there were no major complications after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Follow-up of survivors of mechanical circulatory support.

Improvements in mechanical support for profound circulatory collapse have resulted in increasing survival of these critically ill patients. Since 1980, 27 patients aged 3 days to 69 years (mean 34.9 years) who required mechanical circulatory assistance have been followed up after discharge from the hospital. The refractory cardiogenic shock necessitating mechanical support occurred postoperatively in 22 patients (coronary artery bypass in nine, valve replacement in four, correction of congenital heart defects in nine) and with end-stage cardiomyopathy in five. Fourteen patients were supported with a Pierce-Donachy ventricular assist device (left ventricular assist in seven, right ventricular assist in three, both in four); nine were supported with extracorporeal membrane oxygenation, two with a Medtronic centrifugal left ventricular assist pump, one with biventricular Biomedicus pumps, and one with a Novacor left ventricular assist system. The duration of support ranged from 8 hours to 91 days with a mean of 3.5 days in patients supported for postoperative shock. Major complications occurred in 18 patients (67%), including bleeding that necessitated operative exploration in 14, serious infection in five, renal failure in two, and stroke in two. The five patients with cardiomyopathy underwent cardiac transplantation. The remaining 22 patients who had postoperative cardiogenic shock were weaned from support. There have been four late deaths: two cardiac related at 6 months and two of cancer at 46 and 53 months (one patient was in New York Heart Association class I and the other in class II before death). The remaining 23 survivors have been followed up for 3 to 79 months (mean 29 months) and at last examination 17 (74%) were in class I, two (9%) were in class II, three (13%) were in class III, and one (4%) was in class IV. Eight patients are employed full time, three are retired, four attend school, three are in preschool, one is a housewife, and one is unemployed but free of symptoms. Only four patients have significant cardiac disability, and one of these still works. In conclusion, mechanical circulatory assistance allows adequate support to permit satisfactory long-term survival in patients with refractory cardiogenic shock.

Nursing care of the patient with a pneumatic ventricular assist device.

Recent technologic advances have led to the development of safe and effective mechanical ventricular assist devices for clinical use. Pneumatic assist devices are being used at an increasing rate at a limited number of institutions throughout the country. One of the major factors in influencing survival of these critically ill patients is establishing standards of nursing care. We recently reviewed our experience of 41 patients who received a Pierce-Donachy ventricular assist device to evaluate the effectiveness of nursing care being provided to these patients. This article includes our most recent protocols of nursing care, which have evolved over the past 6 years. Nursing interventions to prevent or treat common complications such as bleeding, renal failure, and infection are discussed.

Long-term follow-up of survivors of postcardiotomy circulatory support.

Although it is now possible to obtain, with mechanical circulatory support devices, survival of postcardiotomy patients who develop profound cardiogenic shock, their long-term functional status has not been firmly established. We studied 22 patients who survived cardiac operations by the use of circulatory support devices. Their ages ranged from 3 days to 69 years at the time of device support. Operations performed were coronary artery bypass (9 pts), valve replacement (4 pts), congenital defect correction (8 pts), and cardiac transplantation (1 pt). Ten patients were supported with a Pierce-Donachy ventricular assist device (VAD) (left 4, right 3, both 3), nine with extracorporeal membrane oxygenation (ECMO), and three with centrifugal pumps (left 2, both 1). Duration of support ranged from 22 to 189 hours (mean 84.4). There were four late deaths; two of the deaths were cardiac-related within 6 months and two were due to cancer at 46 and 53 months following discharge. The remaining 18 survivors were followed for 6 to 74 months (mean 29.9). Prior to operation three of the patients were New York Heart Association (NYHA) Class I, eight were Class II, six patients were Class III, and five were Class IV. Following discharge from the hospital 13 patients were Class I, two were Class II, and three were Class III; no patients were Class IV. Five patients work full-time, three are retired without limitation, four attend school, and three are pre-school. Only three patients suffer from moderate cardiac disability. These data suggest that patients surviving mechanical circulatory assistance for postoperative cardiogenic shock have an excellent chance for functional recovery.

Predictors for weaning patients from ventricular assist devices.

In order to determine if hemodynamic parameters can accurately predict whether patients can be successfully weaned from ventricular assists devices (VADs), we studied 24 patients supported with Pierce-Donachy VADs (11 left VAD; 6 right VAD; 7 biventricular VAD) following cardiogenic shock for periods from 1.3 to 22 days (mean 5.4). Myocardial recovery was determined by daily measurements of "pump on/pump off" parameters, and the data from seven LVAD patients (64%) and three RVAD patients (50%) whose hearts recovered were compared to the data from those whose did not. Additionally, data from the five patients (71%) weaned from biventricular support were compared to those weaned from only a single LVAD or RVAD. In this study, daily pump on/pump off hemodynamic measurements were found to be predictive of success for weaning patients from VADs. The most significant predictors were increases in mixed venous oxygen saturation, cardiac index, mean arterial pressure and ventricular ejection fraction, as well as decreases in atrial pressures. Seventy percent of the patients weaned from VADs survived, indicating that patients appropriately weaned from VAD support have a reasonable chance of survival.