Heyman Luckraz

Improved outcome with organs from carbon monoxide poisoned donors for intrathoracic transplantation

BACKGROUNDnThe success of intrathoracic organ transplantation has lead to a growing imbalance between the demand and supply of donor organs. Accordingly, there has been an expansion in the use of organs from nonconventional donors such as those who died from carbon monoxide poisoning. We describe our experience with 7 patients who were transplanted using organs after fatal carbon monoxide poisoning.nnnMETHODSnA retrospective study of the 1,312 intrathoracic organ transplants between January 1979 and February 2000 was completed. Seven of these transplants (0.5%) were fulfilled with organs retrieved from donors after fatal carbon monoxide poisoning. There were six heart transplants and one single lung transplant. The history of carbon monoxide inhalation was obtained in all of these donors.nnnRESULTSnFive of 6 patients with heart transplant are alive and well with survival ranging from 68 to 1,879 days (mean, 969 +/- 823 days). One patient (a 29-year-old male) died 12 hours posttransplant caused by donor organ failure. The patient who had a right single lung transplant did well initially after the transplant, but died after 8 months caused by Pneumocystis carinii pneumonia. All those recipients who were transplanted from carbon monoxide poisoned donors and ventilated for more than 36 hours, survived for more than 30 days. Moreover, these donors were assessed and optimized by the Papworth donor management protocol.nnnCONCLUSIONSnCarbon monoxide poisoned organs can be considered for intrathoracic transplantation. In view of the significant risk of donor organ failure, a cautious approach is still warranted. Ideally, the donor should be hemodynamically stable for at least 36 hours from the time of poisoning and on minimal support. A formal approach of invasive monitoring and active management further improves the chances of successful outcome.

Cytomegalovirus antibody status of donor/recipient does not influence the incidence of bronchiolitis obliterans syndrome in lung transplantation

BACKGROUNDnWe have previously reported that prophylaxis for cytomegalovirus (CMV) infection does not influence the incidence of bronchiolitis obliterans syndrome (BOS) at 2 years. The effect of CMV infection (without evidence of disease) on BOS is still not well understood. Moreover, the incidence and risk factors for development of BOS in CMV-antibody-negative donor/recipient matches in lung transplantation have not been described. The aim of this study is to determine the incidence of BOS in lung transplant patients with CMV-antibody-negative (-) donors (D) and recipients (R), and to evaluate the risk factors that predispose to BOS in this sub-group.nnnMETHODnA retrospective study of data from the transplant database of our center was performed. All single-lung (SL), double-lung (DL) and heart-lung block (HL) transplant patients who survived >2 years post-transplant were included in the study group. They were grouped as follows: D(-)/R(-), n = 102; D(-)/R(+), n = 70; D(+)/R(-), n = 33, and D(+)/R(+), n = 92.nnnRESULTSnThe 3-year BOS-free survival rates were 65%, 56%, 58% and 67%, respectively, and the incidence rates of BOS at 5 years post-transplant in the different groups were 57%, 62%, 78% and 55% (p > 0.05). In the D(-)/R(-) group, the significant risk factor for developing BOS was three or more episodes of acute rejection (p = 0.02). The mean numbers of acute rejection episodes per 100 patients-days within the first 6 months were 1.28, 1.06, 0.50 and 1.11 (p < 0.001 overall) for the four groups, respectively.nnnCONCLUSIONnAlthough CMV is believed to be a risk factor for BOS, its absence did not affect the occurrence or incidence of BOS in lung transplant patients. The main risk factor for BOS in the CMV-antibody-negative population remains the number of acute rejection episodes within the first 6 months after transplantation.

Short- and long-term outcomes of combined cardiac and renal transplantation with allografts from a single donor

Coexisting end-stage heart and kidney failure can be treated by combined cardiac and renal transplantation. This study reviews the short- and long-term outcomes after such a procedure over a 16-year period at a single institution. All patients who underwent single-donor simultaneous heart and kidney transplantation during the period of March 1986 to April 2002 (including heart retransplantation) were included (n = 13). They were listed for combined heart and kidney transplantation as they fulfilled our criteria for irreversible end-stage organ failure. Retrospective review of patient data from the transplant database, patient case notes and post-mortem reports were carried out. The mean (SD) recipient age was 45 (12) years and there were 2 females. The mean pre-operative creatinine level was 724 (415) micromol/liter with 9 patients (69.2%) on continuous ambulatory peritoneal dialysis and 2 patients (15.4%) on hemodialysis prior to transplantation. The 30-day mortality rate was 15.4% (2 of 13). For surviving patients the mean creatinine level at hospital discharge was 158 (93) micromol/liter. The mean number of acute cardiac rejection episodes per 100 patient-days was significantly lower (p = 0.01) than that for the heart-only transplant group (n = 760) during the same period. The median (interquartile range) post-operative survival was 1,969 (620 to 3,468) days. The actuarial survival rates (95% confidence interval) at 1 and 10 years were 77% (54% to 100%) and 67% (40% to 94%), respectively, and were not significantly different from the isolated heart transplant population (p = 0.68). Only 1 episode of acute renal rejection was diagnosed on clinical grounds, which was treated accordingly. There was no renal allograft loss in the long-term survivors. Combined cardiac and renal transplantation with allografts from the same donor has acceptable short- and long-term outcomes for patients with coexisting end-stage cardiac and renal failure. This group of patients may also experience fewer acute rejection episodes post-operatively.

Does cytomegalovirus status influence acute and chronic rejection in heart transplantation during the ganciclovir prophylaxis era

BACKGROUNDnThe effect of cytomegalovirus (CMV) status on acute rejection in heart transplantation is not well understood. Furthermore, there is some evidence to suggest that CMV antibody positivity is associated with cardiac allograft vasculopathy (CAV).nnnMETHODSnThis study compared the effect of CMV antibody status in heart transplant donors (D) and recipients (R) on acute and chronic rejection episodes during the ganciclovir prophylaxis era.nnnRESULTSnAll heart transplant recipients at Papworth Hospital during the ganciclovir prophylaxis era were included (n = 374). They were grouped according to recipients and their respective donor CMV serology: R(-)/D(-) (n = 82); R(+)/D(-) (n = 114); R(-)/D(+) (n = 73); and R(+)/D(+) (n = 105). Ganciclovir prophylaxis was administered to the R(-)/D(+) group. The mean (SD) recipient and donor ages were 46 (11), 51 (9), 47 (11) and 52 (8) years (p < 0.001), and 32 (11), 33 (14), 36 (12) and 38 (14) years (p = 0.01), respectively, for the CMV groups. The mean number of acute rejection episodes (as confirmed by cardiac biopsy) per 100 patient-days was 0.13 (0.36), 0.11 (0.34), 0.12 (0.34) and 0.12 (0.34), respectively (p > 0.05) There was no statistical difference in the development of CAV as assessed by angiography (p = 0.92). At 2 years, the freedom from CAV rates were 96%, 97%, 97% and 98%, respectively. The 5-year post-operative survival rates were 83%, 79%, 67% and 73% (p = 0.08 overall).nnnCONCLUSIONSnCMV status of heart transplant recipients and their respective donors does not influence acute or chronic rejection in terms of cardiac allograft vasculopathy.

Graft-versus-host disease in lung transplantation: 4 case reports and literature review.

Graft-versus-host disease (GVHD) is uncommon in lung transplant recipients despite the transfer of a significant amount of donor-derived lymphoid tissue and cells. It is associated with significant morbidity and a high mortality rate. We describe 4 cases of GVHD encountered over a 17-year period and review the literature about this peculiar pathology.

And hemolysis goes on: ventricular assist device in combination with veno-venous hemofiltration

BACKGROUNDnVentricular Assist Device (VAD) is an accepted treatment as a bridge to cardiac transplantation, and may be of help in patients as destination therapy for end-stage cardiac failure. The low output state associated with end-stage cardiac failure predisposes patients to renal dysfunction and the need for short-term renal support. The use of cardiopulmonary bypass for VAD insertion, VAD, and hemofiltration expose the blood to mechanical trauma and activated inflammatory cascades that can result in hemolysis. This produces free hemoglobin, a known nephrotoxin; this is a further renal insult. This study assesses the effect of VAD alone and in combination with continuous veno-venous hemofiltration (CVVHF) on hemolysis.nnnMETHODS AND RESULTSnFrom July 1999 to December 2000, Thoratec VAD was used in 11 patients. Nine (all males) were included in this study as all had laboratory profiles. Hemolysis was quantified by plasma free hemoglobin (PFHb) and hydroxybuterate dehydrogenase (HBD) levels measured daily, defined as PFHb level greater than 40 mg/L and HBD greater than 250 IU/L. Data relate to the following time intervals while the VAD was still in situ: T1 = 24 hours post-VAD insertion, T2 = 24 hours post-CVVHF start, T3 = 48 to 72 hours with the same CVVHF circuit, T4 = 24 hours post-stopping of CVVHF, and T5 = CVVHF off for over 48 hours. The mean (SD) PFHb levels were 19.6 (10.9) at T1, 31.7 (0.6) at T2, 93.7 (16.4) at T3 (p < 0.05), 32.5 (20.9) at T4, and 14.2 (3.8) at T5 (p < 0.05). These changes were paralleled by the mean (SD) HBD levels: T1 = 1,337 (616), T2 = 2,025 (509), T3 = 2,676 (1,170) (p < 0.05), T4 1,780 (618), and T5 = 1,310 (436).nnnCONCLUSIONSnThoratec VAD was associated with a mild degree of hemolysis. This was worsened by concomitant use of CVVHF. The effect was accentuated if the same CVVHF circuit was used for over 48 hours but was reversible within 24 hours of stopping the hemofilter.

Are non–brain stem-dead cardiac donors acceptable donors?

BACKGROUNDnThe deleterious effects of brainstem death (BSD) on donor cardiac function and endothelial integrity have been documented previously. Domino cardiac donation (heart of a heart-lung recipient transplanted into another recipient) is a way to avoid the effects of brainstem death and may confer both short- and long-term benefits to allograft recipients.nnnMETHODSnThis study evaluates short- and long-term outcome in heart recipients of BSD donors (cadaveric) as compared with domino hearts explanted from patients who underwent heart-lung transplantation.nnnRESULTSnPatients having undergone cardiac transplantation between April 1989 and August 2001 at Papworth Hospital were included (n = 571). Domino donor hearts were used in 81 (14%) of these cases. The pre-operative transpulmonary gradient was not significantly different between the two groups (p = 0.7). There was no significant difference in 30-day mortality (4.9% for domino vs 8.6% for BSD, p = 0.38) or in actuarial survival (p = 0.72). Ischemic time was significantly longer in the BSD group (p < 0.001). Acute rejection and infection episodes were not significantly different (p = 0.24 vs: 0.08). Relative to the BSD group, the risk (95% confidence interval) of acute rejection in the domino group was 0.89 (0.73 to 1.08). Similarly, the relative risk of infection was 0.78 (0.59 to 1.03). The 5-year actuarial survival rates (95% confidence interval) were 78% (69% to 87%) and 69% (65% to 73%) in the domino and BSD groups respectively. Angiography data at 2 years were available in 50 (62%) and 254 (52%) patients in the domino and BSD groups, respectively. The rates for 2-year freedom from cardiac allograft vasculopathy (CAV) were 96% (91% to 100%) and 93% (90% to 96%), respectively.nnnCONCLUSIONnDespite the lack of endothelial cell activation after brainstem death and a shorter ischemic time, the performance of domino donor hearts was similar to that of BSD donor hearts. This may indicate a similar pathology (i.e., endothelial cell activation) in the domino donors.

Systolic right ventricular dysfunction in 'good' donor hearts- a normal finding?

Cardiac enlargement was present in 5% of donors, 60% subsequently returned to normal size. Age, cause of death, sex and time from admission to harvest were not significantly different between transplanted and non-transplanted groups. Bivariate analysis demonstrated edema (p50.01), number of initial and final abnormal diagnoses (p50.007 and p50.006) initial and final right lung densities (p50.04 and p50.002) and final left lung densities (p50.02) were greater in the non-transplanted group. Worsening of lung infiltrates was more prominent in the nontransplanted group (p50.02), however improvement in densities was not associated with transplantation (p50.6). Multivariate analysis determined that moderate and severe lung densities (OR 3.8, p50.03 and 7.7 p50.012) were independent predictors of rejection for transplantation. With measures of lung density removed from the model, the number of final film abnormal diagnoses was an independent predictor of rejection for transplantation (OR 3.1, p50.004). Conclusions Over one third of organ donors initially have lung infiltrates and 28% to 38% of these abnormalities improve during evaluation but this improvement does not impact on successful procurement. Multiple abnormal radiographic diagnoses also contribute to rejection for transplantation.

Short and long term outcomes using marginal pulmonary allograft donors

23.9 8.4 in the “used” donors (p 0.01). Mean BNP was 70.7 14.5 in the “unused” compared with 32.8 9.6 in the “used” (p 0.05). RNA abundance (delta ct)for ANP was 17.6 1.8 and 11.81 3.9 in used and unused donors respectively. For BNP the values were 17.0 3.0 and 10.7 3.1 respectively. Conclusion: Measurement of natriuretic peptides may be a rapid, simple and objective method to assess donor heart function and can be used as a point-of-care assay at the donor hospital. Further studies are indicated to determine its role in donor assessment and the response to treatment.