Stephen Clark

Lung transplantation for patients with cystic fibrosis and Burkholderia cepacia complex infection: A single-center experience

BACKGROUND Pre-operative infection with organisms from the Burkholderia cepacia complex (BCC), particularly B cenocepacia, has been linked with a poorer prognosis after transplantation compared to patients with cystic fibrosis (CF) without this infection. Therefore, many transplant centers do not list these patients for transplantation. METHODS We report the early and long-term results of a cohort of lung transplant recipients with CF and pre-operative BCC infection. Patients with pre-transplantation BCC infection were identified by case-note review. BCC species status was assigned by polymerase chain reaction (PCR)-based techniques. Survival rates were compared to recipients with CF without BCC infection. Survival rates in BCC subgroups were also compared, and then further analyzed pre- and post-2001, when a new immunosuppressive and antibiotic regime was introduced for such patients. RESULTS Two hundred sixteen patients with CF underwent lung transplantation and 22 had confirmed pre-operative BCC infection, with 12 of these being B cenocepacia. Nine B cenocepacia-infected recipients died within the first year, and in 8 BCC sepsis was considered to be the cause of death. Despite instituting a tailored peri-operative immunosuppressive and microbiologic care approach for such patients, post-transplantation BCC septic deaths occurred frequently in those with pre-transplantation B cenocepacia infection. In contrast, recipients infected with other BCC species had significantly better outcomes, with post-transplantation survival comparable to other recipients with CF. CONCLUSIONS Mortality in patients with B cenocepacia infection was unacceptably high and has led to our center no longer accepting patients with this condition onto the lung transplant waiting list. Long-term survival in the non-B cenocepacia BCC group was excellent, without high rates of acute rejection or bronchiolitis obliterans syndrome (BOS) longer term, and these patients continue to be considered for lung transplantation.

Outcomes of lung transplantation for cystic fibrosis in a large UK cohort

Background: Lung transplantation is an important option to treat patients with advanced cystic fibrosis (CF) lung disease. The outcomes of a large UK cohort of CF lung transplantation recipients is reported. Methods: Retrospective review of case notes and transplantation databases. Results: 176 patients with CF underwent lung transplantation at our centre. The majority (168) had bilateral sequential lung transplantation. Median age at transplantation was 26 years. Diabetes was common pretransplantation (40%). Polymicrobial infection was common in individual recipients. A diverse range of pathogens were encountered, including the Burkholderia cepacia complex (BCC). The bronchial anastomotic complication rate was 2%. Pulmonary function (forced expiratory volume in 1 s % predicted) improved from a pretransplantation median of 0.8 l (21% predicted) to 2.95 l (78% predicted) at 1 year following transplantation. We noted an acute rejection rate of 41% within the first month. Our survival values were 82% survival at 1 year, 70% at 3 years, 62% at 5 years and 51% at 10 years. Patients with BCC infection had poorer outcomes and represented the majority of those who had a septic death. Data are presented on those free from these infections. Bronchiolitis obliterans syndrome (BOS) and sepsis were common causes of death. Freedom from BOS was 74% at 5 years and 38% at 10 years. Biochemical evidence of renal dysfunction was common although renal replacement was infrequently required (<5%). Conclusion: Lung transplantation is an important therapeutic option in patients with CF even in those with more complex microbiology. Good functional outcomes are noted although transplantation associated morbidities accrue with time.

Effect of WBC reduction of transfused RBCs on postoperative infection rates in cardiac surgery

BACKGROUND : WBC‐replete blood transfusion has been suggested as an independent cause of increased postoperative infection.

Vascular complications of lung transplantation

BACKGROUND The data on vascular anastomotic complications after single-lung and bilateral lung transplantation are scant. METHODS We reviewed the data on our patients having single and bilateral lung transplantation to examine our experience and management of vascular anastomotic complications. RESULTS We retrospectively identified 5 of 109 consecutive patients undergoing lung transplantation who had postoperative pulmonary arterial or venous obstruction. There were 4 women and 1 man (age range, 32 to 53 years). Three patients had left single-lung transplantation, 1 patient had right single-lung transplantation, and 1 patient underwent bilateral sequential lung transplantation. Complications comprised two right-sided and two left-sided pulmonary artery stenoses and one combined left pulmonary arterial and venous obstruction. Isotope perfusion scanning was used in 3 patients and suggested a vascular stenosis in all of them. Pulmonary angiography was used in each as a confirmatory test and to demonstrate anatomic details. Transesophageal echocardiography was used in 1 patient and did not detect a right pulmonary artery stenosis. One patient underwent revision of a pulmonary artery stenosis with a period of warm ischemia and subsequent fatal lung injury. Two revisions were undertaken on cardiopulmonary bypass with a cold blood flush to the transplanted lung. One venous anastomotic angioplasty with stent insertion was performed. Two patients died before treatment. All 5 patients died between 5 and 630 days postoperatively. CONCLUSIONS Vascular complications carry a high mortality. Reoperation, preferably using cardiopulmonary bypass and a cold blood flush technique to avoid further lung injury, is recommended. In high-risk patients, dilation or stent insertion can be considered.

UK guidelines for referral and assessment of adults for heart transplantation

Patients with advanced heart failure have a dismal prognosis and poor quality of life. Heart transplantation provides an effective treatment for a subset of these patients. This article provides cardiologists with up-to-date information about referral for transplantation, the role of left ventricular assist devices prior to transplant, patient selection, waiting-list management and donor heart availability. Timing is of central importance; patients should be referred before complications (eg, cardiorenal syndrome or secondary pulmonary hypertension) have developed that will increase the risk of, or potentially contraindicate, transplantation. Issues related to heart failure aetiology, comorbidity and adherence to medical treatment are reviewed. Finally, the positive role that cardiologists can play in promoting and facilitating organ donation is discussed.

Effect of low molecular weight heparin (Fragmin) on bleeding after cardiac surgery

BACKGROUND Fragmin (Dalteparin, Pharmacia Ltd, Milton Keynes, UK), a low molecular weight heparin, is now recommended in the treatment of unstable angina. Due to the greater bioavailability and longer half-life of Fragmin compared with conventional heparin we postulated that this may influence postoperative bleeding after cardiac surgery for unstable angina. METHODS We investigated the influence of the agent on postoperative bleeding after cardiac surgery. Patients undergoing first-time coronary artery bypass grafting were prospectively studied in four groups: group A (n = 100) were elective patients; group B (n = 60) had unstable angina and received conventional heparin intravenously until operation; group C (n = 115) received Fragmin with the last dose administered more than 12 hours before surgery; and group D (n = 115) received Fragmin within 12 hours of operation. RESULTS Patients in group D had significantly greater blood loss (p < 0.001) and increased blood transfusion than groups A, B, and C (p = 0.047). Patients receiving Fragmin more than 12 hours before surgery (group C) had similar rates of blood loss and transfusion to group B (p > 0.05) but greater than in group A (p = 0.021). There were no differences in reopening rate. CONCLUSIONS The risks of bleeding and transfusion must be weighed against the risks of acute ischemic events if Fragmin is stopped more than 12 hours before operation.

Sutureless, rapid deployment valves and stented bioprosthesis in aortic valve replacement: recommendations of an International Expert Consensus Panel.

OBJECTIVES After a panel process, recommendations on the use of sutureless and rapid deployment valves in aortic valve replacement were given with special respect as an alternative to stented valves. METHODS Thirty-one international experts in both sutureless, rapid deployment valves and stented bioprostheses constituted the panel. After a thorough literature review, evidence-based recommendations were rated in a three-step modified Delphi approach by the experts. RESULTS Literature research could identify 67 clinical trials, 4 guidelines and 10 systematic reviews for detailed text analysis to obtain a total of 28 recommendations. After rating by the experts, 12 recommendations were identified and degree of consensus for each was determined. Proctoring and education are necessary for the introduction of sutureless valves on an institutional basis as well as for the individual training of surgeons. Sutureless and rapid deployment should be considered as the valve prosthesis of first choice for isolated procedures in patients with comorbidities, old age, delicate aortic wall conditions such as calcified root, porcelain aorta or prior implantation of aortic homograft and stentless valves as well as for concomitant procedures and small aortic roots to reduce cross-clamp time. Intraoperative transoesophageal echocardiography is highly recommended, and in case of right anterior thoracotomy, preoperative computer tomography is strongly recommended. Suitable annular sizes are 19-27 mm. There is a contraindication for bicuspid valves only for Type 0 and for annular abscess or destruction due to infective endocarditis. Careful but complete decalcification of the aortic root is recommended to avoid paravalvular leakage; extensive decalcification should be avoided not to create annular defects. Proximal anastomoses of concomitant coronary artery bypass grafting should be placed during a single aortic cross-clamp period or alternatively with careful side clamping. Available evidence suggests that the use of sutureless and rapid deployment valve is associated with (can translate into) reduced early complications such as prolonged ventilation, blood transfusion, atrial fibrillation, pleural effusions and renal replacement therapy, respectively, and may result in reduced intensive care unit and hospital stay in comparison with traditional valves. CONCLUSION The international experts recommend various benefits of sutureless and rapid deployment technology, which may represent a helpful tool in aortic valve replacement for patients requiring a biological valve. However, further evidence will be needed to reaffirm the benefit of sutureless and rapid deployment valves.

The effect of ex vivo lung perfusion on microbial load in human donor lungs

BACKGROUND Ex vivo lung perfusion (EVLP) has emerged as a technique to potentially recondition unusable donor lungs for transplantation. Beneficial effects of EVLP on physiologic function have been reported, but little is known about the effect of normothermic perfusion on the infectious burden of the donor lung. In this study, we investigated the effect of EVLP on the microbial load of human donor lungs. METHODS Lungs from 18 human donors considered unusable for transplantation underwent EVLP with a perfusate containing high-dose, empirical, broad-spectrum anti-microbial agents. Quantitative cultures of bacteria and fungi were performed on bronchoalveolar lavage fluid from the donor lung before and after 3 to 6 hours of perfusion. The identification of any organisms and changes in number of colony forming units before and after EVLP were assessed and anti-microbial susceptibilities identified. RESULTS Thirteen out of 18 lungs had positive cultures, with bacterial loads significantly decreasing after EVLP. Yeast loads increased when no anti-fungal treatment was given, but were reduced when prophylactic anti-fungal treatment was added to the circuit. Six lungs were ultimately transplanted into patients, all of whom survived to hospital discharge. There was 1 death at 11 months. CONCLUSIONS Our study shows that EVLP with high-dose, empirical anti-microbial agents in the perfusate is associated with an effective reduction in the microbial burden of the donor lung, a benefit that has not previously been demonstrated.

Controlled reperfusion and pentoxifylline modulate reperfusion injury after single lung transplantation

OBJECTIVE Rodent models have suggested that initial low-pressure reperfusion of transplanted lungs reduces injury after ischemia. We investigated this phenomenon and the use of pentoxifylline in a porcine model of left single lung transplantation. METHODS Donor lungs were preserved with Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary artery pressure, and gas exchange were assessed over a 12-hour period. Partial occlusion of the contralateral pulmonary artery allowed manipulation of the pulmonary artery pressure in the transplanted lung. Group A (n = 5) was perfused at a mean pulmonary artery pressure of 20 mm Hg, group B was reperfused at a mean pulmonary artery pressure of 45 mm Hg for 10 minutes before reducing the pressure to the same as group A, and group C was reperfused at a mean pressure of 20 mm Hg for 10 minutes, then increased to a mean of 45 mm Hg for the remainder of the experiment. Group D was reperfused as in group A with the addition of intravenous pentoxifylline. RESULTS Leukocyte sequestration was observed in the first 10 minutes after reperfusion in groups A, B, and C, with maximal sequestration at 2 minutes. Significantly more sequestration was observed in the first 6 minutes in group B than in groups A and C, which were similar. Pentoxifylline significantly reduced leukocyte sequestration. Pulmonary venous oxygen tension in the allograft lung was worst in group B. Groups A and C were similar, but group D was superior to all other groups (p < 0.001). CONCLUSIONS Low-pressure reperfusion, even when limited to the first 10 minutes, modulates reperfusion injury possibly through a leukocyte-dependent mechanism. The addition of pentoxifylline in the recipient confers significant additional benefit.

Current smoking predicts increased operative mortality and morbidity after cardiac surgery in the elderly

OBJECTIVES The effect of preoperative smoking status on the outcome of cardiac surgery remains unclear. Preoperative cessation may be associated with reduced postoperative pulmonary complications and in older patients preoperative smoking status appears to have a greater impact on outcome. This study was designed to assess the relationship between age, preoperative smoking status and outcomes from cardiac surgery. METHODS We performed a single-centre, retrospective cohort study to compare in-patient cardiac surgical mortality and morbidity in current smokers and never-smokers. We analysed the cardiac surgical population in its entirety and in age-stratified subsets using univariate and logistic regression analyses. RESULTS During a five-year period ending March 2007, 10.8% of all patients (n=554) undergoing cardiac surgery were current smokers. Five hundred and fifty-four never-smokers undergoing cardiac surgery during the same period were identified. Overall, the smokers had a tendency towards higher in-patient mortality (4.3 vs. 2.3%, P=0.067) and increased rates of morbidity. Amongst over 70-year-olds, the current smokers had significantly higher rates of pulmonary complications (24.7 vs. 8.2%, P<0.0002), new renal replacement therapy (17.3 vs. 3.1%, P<0.0001) and infections (44.4 vs. 23.8%, P<0.0007). They had longer intensive care stay (6.2 vs. 2.8 days, P=0.002) with more intensive care unit readmissions (19.8 vs. 5.2%, P<0.0002) and significantly increased in-patient mortality (14.8 vs. 2.1%, P<0.0001). In the elderly smokers, mortality was significantly associated with the rate of pulmonary complications (P=0.03). Preoperative smoking status remained a predictor of pulmonary complications after logistic regression. CONCLUSIONS The current data strengthen the observation that preoperative smoking status is predictive of adverse outcomes of cardiac surgery in the elderly. Further study into the effect of preoperative smoking cessation in the elderly may inform cessation counselling and the timing of surgery.