De novo immunosuppression with sirolimus and tacrolimus in heart transplant recipients compared with cyclosporine and mycophenolate mofetil: a one-year follow-up analysis.

BACKGROUND: Limited data exist regarding the safety and efficacy of sirolimus in combination with a calcineurin inhibitor in heart transplant recipients. METHODS: From January 2001 to June 2002, 31 de novo heart transplant recipients (treatment group) received a combination of sirolimus, tacrolimus, low-dose rabbit antithymocyte globulin, and glucocorticoids. Outcomes, such as actuarial survival, rate of rejection, incidence of infection, probability of developing diabetes mellitus, renal function, platelet and white blood cell counts, and incidence of coronary artery disease at 1 year, were compared with a cohort of 25 patients (control group) who underwent transplantation primarily in 2000 and in early 2002 treated with cyclosporine, mycophenolate mofetil, and glucocorticoids. All patients were followed up for at least 12 months. RESULTS: Kaplan-Meier actuarial 1-year survival rates were equivalent between groups (97% for the treatment group and 88% for the control group), as was freedom from allograft rejection (48% and 42% for treatment and control groups, respectively). No cases of transplant arteriopathy were noted within the first posttransplantation year. Renal function was not significantly affected in either group. There was a striking increased incidence of mediastinitis in the treatment group (19%) versus 0% in the control group (P = .02). Tacrolimus-sirolimus therapy was associated with a nearly 11-fold increased incidence of new-onset diabetes mellitus as well (P = .004). CONCLUSION: Tacrolimus, sirolimus, and steroids (following low-dose rabbit antithymocyte globulin) were associated with an increased incidence of mediastinitis and posttransplantation diabetes mellitus. No obvious long-term benefit on survival, arteriopathy, or renal function was noted.

Outbreak of Vero cytotoxin-producing Escherichia coli O157 in a child day care facility.

In December 1998, an outbreak of Vero cytotoxin-producing Escherichia coli (VTEC) O157 in a crèche affected ten out of 45 children and one out of five staff members. Eight cases were symptomatic and three were asymptomatic. There were two asymptomatic adult family contacts of child cases. All specimens were identified as VTEC O157:H7, phage type 32. None of the cases were seriously ill and none developed haemolytic uraemic syndrome (HUS). One child continued to excrete the organism for 14 weeks. The origin of the outbreak was not found but epidemiological investigation was suggestive of person-to-person spread. All children and staff were screened and excluded from the crèche until microbiological clearance was obtained. An inspection of the crèche revealed overcrowding and inadequacies in cleaning and in the food preparation facilities. These problems were remedied before children were re-admitted to the crèche. This outbreak demonstrates the ease with which VTEC O157 can be transmitted between small children. Two specific features of this outbreak were notable: (1) the mild self-limiting nature of the illness and (2) the prolonged shedding of the bacterium by one child.

Combined off-pump myocardial revascularization and carotid endarterectomy: early experience.

BACKGROUND: Controversy remains regarding the optimal surgical management of patients with coexisting significant carotid and coronary artery disease. The debate has deepened by the evolution of new approaches for the treatment of both coronary and carotid disease. We report our early experience with combined off-pump coronary artery bypass (OPCAB) and carotid endarterectomy (CEA) for the treatment of patients with coexisting coronary and carotid disease. METHODS: Our computer database was examined to obtain patients and their demographics and clinical profiles. Operative reports were reviewed. Telephone interviews were conducted to assess follow-up status. RESULTS: Thirteen patients underwent combined OPCAB and CEA. Average age was 71 years. The CEA was performed with intraluminal shunting and patch reconstruction. On average, 3.6 bypass grafts were performed. There were no gross neurologic complications or myocardial infarctions. Excluding an outlier, mean length of hospital stay was 8.2 days. All patients were well on follow-up (2 weeks to 16 months). CONCLUSIONS: A combined OPCAB and CEA strategy appears safe and effective. Further follow-up and experience is warranted before conclusions regarding potential benefits of this approach for staged or conventional OPCAB/CEA procedures can be made.

Advance care planning: pitfalls, progress, promise.

We now have a decade of experience with advance directives since the Patient Self-Determination Act was signed into law in November 1990. With few exceptions, empirical studies have yielded disappointing results. Advance directives are recorded by medical personnel more often but are not completed by patients more frequently. The process of recording them does not enhance patient-physician communication. When available, advance directives do not change care or reduce hospital resources. The most ambitious study of advance care planning, the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments, failed to show any change in outcomes after an extensive intervention. Investigators have attempted to identify the reasons why the optimism about the Patient Self-Determination Act has not been realized. Many interventions to facilitate advance care planning were focused on specific treatment decisions. Recent research suggests that preferences for care are not fixed but emerge in a clinical context from a process of discussion and feedback within the network of the patient's most important relationships. Clinical trials emphasizing this approach have been successful. The approach that emphasizes communication, building trust over time, and working within the patient's most important relationships offers a hopeful model for clinicians working in intensive care units.

Withholding or withdrawal of life-sustaining therapy.

Seventy percent of deaths in intensive care units are preceded by decisions to limit life-support, most of which are made in consultation with the patient's family or other surrogates. Even when the outcome is clear, surrogates and physicians may deny that death is imminent and delay removing ventilatory assistance and other supportive measures. To avoid prolonging suffering, end-of-life decisions should always be guided by the interests and wishes of the patient.

A national survey of end-of-life care for critically ill patients.

In some intensive care units (ICUs), fewer patients who die now undergo attempts at cardiopulmonary resuscitation (CPR), and many more have life support actively withdrawn prior to death than did a decade ago. To determine the frequency of withdrawal of life support, we contacted every American postgraduate training program with significant clinical exposure to critical care medicine, asking them prospectively to classify patients who died into one of five mutually exclusive categories. We received data from 131 ICUs at 110 institutions in 38 states. There were 6,303 deaths, of which 393 patients were brain dead. Of the remaining 5,910 patients who died, 1,544 (23%) received full ICU care including failed cardiopulmonary resuscitation (CPR); 1,430 (22%) received full ICU care without CPR; 797 (10%) had life support withheld; and 2,139 (38%) had life support withdrawn. There was wide variation in practice among ICUs, with ranges of 4 to 79%, 0 to 83%, 0 to 67%, and 0 to 79% in these four categories, respectively. Variation was not related to ICU type, hospital type, number of admissions, or ICU mortality. We conclude that limitation of life support prior to death is the predominant practice in American ICUs associated with critical care training programs. There is wide variation in end-of-life care, and efforts are needed to understand practice patterns and to establish standards of care for patients dying in ICUs.

The role of gender in heart transplantation.

BACKGROUND: The effect of donor and recipient gender on the outcome of heart transplantation (HT) remains uncertain. METHODS: One hundred seventy-four patients who underwent HT were divided into four groups according to donor and recipient gender. Group A consisted of 81 men who received male donor hearts, group B of 18 women who received female donor hearts, group C of 21 women who received male donor hearts, and group D of 54 men who received female donor hearts. All patients were treated by the same group of surgeons according to standard HT protocols. Comparisons were made between groups with regard to short- and long-term outcomes. RESULTS: Donor gender and recipient gender did not affect outcomes significantly. Overall, donor-recipient gender mismatching significantly increased the number of rejection episodes and reduced creatinine clearance, survival, and censored survival in the first year after HT (p < 0.05). More specifically, among female recipients, donor-recipient gender mismatching significantly increased the number of rejection episodes and decreased creatinine clearance in the first year after HT (p < 0.05); among male recipients, donor-recipient gender mismatching significantly reduced 1-year survival and censored survival to date after HT (p < 0.05). CONCLUSIONS: Donor-recipient gender matching plays a significant role in determining HT outcomes.

Visualization and measurement of flow velocity and flow reserve in aortocoronary saphenous vein bypass grafts by transesophageal echocardiography.

Transesophageal echocardiography was used to image bypass grafts and measure flow reserve in these conduits. Imaging and measurement of flow reserve were feasible in most patients.

Management of left ventricular assist device infection with heart transplantation.

BACKGROUND: Left ventricular assist devices (LVADs) are being used as bridges to heart transplantation (HT). Infection of the LVAD in this patient population represents a serious complication, as simple LVAD removal or delaying HT may result in death. To improve outcomes in this group of patients, we performed HT in the presence of LVAD infection. METHODS: Eighteen patients underwent LVAD implantation followed by HT. Ten underwent HT in the absence of LVAD infection (group 1); and 8, in the presence of LVAD infection (group 2). All patients were treated similarly except for modification of immunosuppression in group 2 patients. RESULTS: Infectious and noninfectious complications were equivalent between the two groups. There was no difference between groups in regard to intraoperative deaths (one versus none), long-term survival (8/10 versus 7/8), wound complications (three versus none), and mean length of hospital stay after HT (21 versus 26 days). CONCLUSIONS: Patients with LVAD infection are too seriously ill to allow LVAD removal or delay of HT. Transplantation in the face of infection is an effective treatment option.

The usefulness of diagnostic tests on pericardial fluid.

STUDY OBJECTIVES: To determine the physical, chemical, and cellular characteristics of pericardial fluid in various disease states and to assess their diagnostic accuracies. SETTING: A metropolitan university hospital. DESIGN: Consecutive case series. PATIENTS: One hundred seventy-five hospital patients, aged 1 month to 87 years, who had undergone pericardiocentesis (n = 165) or control subjects who had undergone open heart surgery (n = 10) between 1984 and 1996. MEASUREMENTS: The appearance of pericardial fluid and results of chemistry tests, cell counts, cytologic studies, Gram's stain, and microbial cultures were obtained by chart review. The etiology of each pericardial fluid sample was determined using prospective diagnostic criteria. RESULTS: Exudates differed from transudates by higher leukocyte counts and ratios of fluid to serum lactate dehydrogenase levels. Fluid glucose levels were significantly less in exudates. Sensitivity for detecting exudates was high for specific gravity > 1.015 (90%), fluid total protein > 3.0 g/dL (97%), fluid to serum protein ratio > 0.5 (96%), fluid lactate dehydrogenase ratio > 0.6 (94%), and fluid to serum glucose ratio < 1.0 (85%). None of these indicators were specific. Fluid total protein and specific gravity were moderately correlated (r = 0.56). Fluid cytologic study had a sensitivity of 92% and specificity of 100% for malignant effusion. No other test was diagnostic for a specific etiology. Among infection-associated effusions, culture-positive fluid had more neutrophils, higher lactate dehydrogenase levels, and lower ratios of fluid to serum glucose than culture-negative (parainfective) fluid. CONCLUSIONS: Evaluation of pericardial fluid might be limited to cell count, glucose, protein, and lactate dehydrogenase determinations plus bacterial culture and cytology. While not used routinely, other tests that may be highly specific for particular diseases should be ordered only to confirm a high clinical suspicion.

Resolving conflicts surrounding end-of-life care.

Critical care physicians are frequently called on to negotiate issues of medical management with patients, their families, and other physicians. These decisions frequently revolve around end-of-life care. Recent data suggest that such discussions are manageable. In one study, 57% of patients and surrogates agreed immediately to a physician's recommendation to limit intensive care and 90% agreed within 5 days, while multiple treating physicians came to consensus about such limits within 4 days in 92% of cases. If conflicts are rare, they are strongly felt. They arise when any one of the parties to a decision insists on continued care against the considered judgment of another. Since the alternative to aggressive ICU care is usually the death of the patient, it seems difficult to reconcile a physician's refusal to treat with patient autonomy. The concept of a fiduciary offers a model of the physician-patient relationship in which the physician commits himself to the patient's best interests but retains a role in defining those interests. This model offers significant benefits over medical futility in negotiating conflicts over end-of-life care.

Increasing incidence of withholding and withdrawal of life support from the critically ill.

To determine whether limits to life-sustaining care are becoming more common, we attempted to quantify the incidence of recommendations to withhold or withdraw life support from critically ill patients, to describe how patients respond to these recommendations, and to examine how conflicts over these recommendations are resolved. In 1992 and 1993 we prospectively enrolled 179 consecutive patients from two intensive care units (ICUs) for whom a recommendation was made to withhold or withdraw life support. Where possible, we compared results with data collected in the same units over a similar time period in 1987 and 1988. Recommendations to withhold or withdraw life support preceded 179 of 200 deaths (90%) in 1992 and 1993, compared with 114 of 224 deaths (51%) in 1987 and 1988 (chi2 = 73.76, p < 0.001]. Cardiopulmonary resuscitation was initiated in 10% of deaths in 1992 and 1993 as compared with 49% in 1987 and 1988. Ninety percent of patients agreed within less than 5 d, and only eight patients (4%) refused physicians' recommendations to limit life support. In cases of conflict, physicians in 1992 and 1993 deferred to patients with one exception: physicians were willing to refuse surrogate requests for resuscitation of patients they considered hopelessly ill. We conclude that 90% of patients who die in these ICUs now do so following a decision to limit therapy, that this represents a major change in practice in these institutions over a period of 5 yr, that most patients and surrogates accept an appropriate recommendation to withhold or withdraw life support, and that physicians will refuse surrogate requests in certain circumstances.

An outbreak of Salmonella enteritidis food poisoning in a psychiatric hospital in Dublin, Ireland.

On 29 August 1996 Ireland's Eastern Health Board (EHB) was informed of an outbreak of gastrointestinal illness in a psychiatric hospital in Dublin. Fifty people among 240 members of staff and 183 patients had reportedly fallen ill since 27 August and new

Standard criteria for an acceptable donor heart are restricting heart transplantation.

BACKGROUND: The lack of satisfactory donor organs limits heart transplantation. The purpose of this study was to determine whether the criteria for suitability of donors may be safely expanded. METHODS: One hundred ninety-six heart transplantations were performed on 192 patients at our institution from January 1992 to 1995 and were divided into two groups. Group A donors (n = 113) conformed to the standard criteria. Group B donors (n = 83) deviated by at least one factor and consisted of the following: 16 hearts from donors greater than 50 years of age, 33 with myocardial dysfunction (echocardiographic ejection fraction = 0.35 +/- 0.10, dopamine level exceeding 20 micrograms.kg-1.min-1, and resuscitation with triiodothyronine), 33 undersized donors with donor to recipient weight ratios of 0.45 +/- 0.04, 48 with extended ischemic times of 297.4 +/- 53.6 minutes, 25 with positive blood cultures, 16 with positive hepatitis C antibody titers, and 7 with conduction abnormalities (Wolff-Parkinson-White syndrome, prolonged QT interval, bifascicular block). RESULTS: Thirty-day mortality was 6.2% (7/113) in group A and 6.0% (5/83) in group B. Mortality in group A was attributed to 3 patients with myocardial dysfunction, 2 with infection, 1 with acute rejection, and 1 with pancreatitis; group B had 2 with myocardial dysfunction, 1 with infection, 1 with aspiration, and 1 with bowel infarction. At 12 months, survival and hemodynamic indices were similar between the groups. Of the 16 recipients with hepatitis C-positive hearts, 5 have become hepatitis C positive with mild hepatitis (follow up, 6 to 30 months). CONCLUSIONS: Expanding the criteria for suitability of donor hearts dramatically increases the number of transplantations without compromising recipient outcome.

Defining the role of aprotinin in heart transplantation.

BACKGROUND: Heart transplantation is associated with excessive bleeding due to recipient coagulopathy, frequent need for reoperative median sternotomy, and prolonged cardiopulmonary bypass. Aprotinin reduces bleeding and the inflammatory response after cardiopulmonary bypass, but there are concerns about efficacy and side effects. METHODS: To determine the role of aprotinin in primary and reoperative sternotomy heart transplantation, we studied 70 patients undergoing heart transplantation between August 1993 and October 1994. Thirty-eight undergoing primary sternotomy for heart transplantation and receiving no aprotinin were randomized to group A (n = 20); patients in group B (n = 18) received the full recommended dose. Similarly, 32 patients undergoing reoperative heart transplantation were randomized to group C (n = 16), receiving no aprotinin, and to group D (n = 16), receiving aprotinin at the full recommended dose. All patients received the same immunosuppression regimen. Similarities in the groups included recipient age, weight, preoperative hemodynamic indices, creatinine, creatinine clearance, platelet count, hemoglobin, percentage receiving warfarin, prothrombin time, partial thromboplastin time, cardiopulmonary bypass time, and creatinine level at 48 hours. RESULTS: There were no significant differences postoperatively between groups A and B. Differences (p < 0.05) 24 hours postoperatively between groups C and D, respectively, included: total blood product requirement (5.9 +/- 3.8 versus 3.6 +/- 2.0 U), total fluid balance (+752 +/- 300 versus -250 +/- 185 mL), chest tube drainage (894 +/- 120 versus 526 +/- 95 mL), alveolar-arterial O2 difference (120.4 +/- 45.9 versus 95.5 +/- 33.5), and pulmonary artery mean pressures (28.2 +/- 4.6 versus 21.1 +/- 3.5 mm Hg). CONCLUSIONS: Aprotinin decreases bleeding after reoperative heart transplantation without renal dysfunction. Decreased inflammation is manifested as reduced fluid requirement and improved pulmonary and right heart function, which benefit patients during the posttransplantation period. Aprotinin at recommended doses is effective and safe for patients undergoing reoperative heart transplantation.