Tony N. Hodges

Following Universal Prophylaxis with Intravenous Ganciclovir and Cytomegalovirus Immune Globulin, Valganciclovir is Safe and Effective for Prevention of CMV Infection Following Lung Transplantation

We prospectively determined the safety and efficacy of valganciclovir for prevention of cytomegalovirus (CMV) in at‐risk (donor positive/recipient negative [D+/R−] or R+) lung transplant recipients. We also determined the length of prophylaxis required to significantly decrease both CMV infection and disease. Consecutive lung transplant recipients surviving >30 days (n = 90) received combination prophylaxis with intravenous (i.v.) ganciclovir (GCV) 5 mg/kg/day and cytomegalovirus immune globulin (CMV‐IVIG) followed by valganciclovir (450 mg twice‐daily) to complete 180, 270 or 365 days of prophylaxis. This group was compared to a historical group (n = 140) who received high‐dose oral acyclovir following i.v. GCV and CMV‐IVIG. CMV disease was significantly lower in patients receiving valganciclovir compared to acyclovir (2.2% vs. 20%; p < 0.0001). Freedom from CMV infection and disease was significantly greater (p < 0.02) in patients receiving 180, 270 or 365 days of prophylaxis (90%, 95% and 90%, respectively) compared to those receiving 100–179 days (64%) or <100 days (59%). No patient receiving valganciclovir died during the study. Following prophylaxis with i.v. GCV and CMV‐IVIG, valganciclovir is safe and effective for prevention of CMV infection and disease in at‐risk lung transplant recipients. The required length of prophylaxis was at least 180 days.

The value of polymerase chain reaction for the diagnosis of viral respiratory tract infections in lung transplant recipients.

BACKGROUND Respiratory viruses cause severe infections in lung transplant recipients, which require rapid and accurate diagnosis for appropriate management. OBJECTIVES To evaluate the added benefit of a multiplex PCR for respiratory viruses (influenza [FLU] A and B, respiratory syncytial virus [RSV] A and B and parainfluenza virus [PIV] 1, 2, and 3) complementing rapid respiratory viral culture (RRV) and FLU-A antigen detection (EIA) in this transplant population. RESULTS Over 6 months, 116 nasal washes and bronchoalveolar lavages, obtained from 72 lung transplant recipients with symptoms of upper or lower respiratory tract infections, were tested in real time by RRV and FLU-A EIA, and batched frozen by PCR. One or more methods recognized a respiratory virus in 31 (27%) specimens, including 15 FLU-A, nine RSV and seven PIV. PCR identified 26 of 31 positive samples demonstrating a sensitivity of 84%, higher than RRV (67%) or EIA (54%). PCR, RRV and EIA detected 60, 80 and 54%, respectively, FLU-A samples. PCR and RRV were equivalent for RSV-A, PIV-2 and 3, but PCR found a significantly higher number of RSV-B and PIV-1. CONCLUSIONS These data indicate that routine use of PCR will enhance the number and speed with which viral respiratory tract infections are diagnosed in lung transplant recipients.

Acute native lung hyperinflation is not associated with poor outcomes after single lung transplant for emphysema

BACKGROUND Single-lung transplantation for emphysema may be complicated by acute native lung hyperinflation (ANLH) with hemodynamic and ventilatory compromise. Some groups advocate the routine use of independent lung ventilation, double-lung transplant, or right-lung transplant with or without contralateral lung volume reduction surgery in high-risk patients. The goal of this study was to determine the incidence of ANLH and identify its potential predictors. METHODS We reviewed 51 consecutive single-lung transplants for emphysema. Symptomatic ANLH was defined as mediastinal shift and diaphragmatic flattening on chest x-ray with hemodynamic or respiratory failure requiring cardiopressor agents or independent lung ventilation. Preoperative and postoperative physiologic and hemodynamic data were analyzed from both recipients and donors. RESULTS Sixteen patients developed radiographic ANLH; 8 were symptomatic, 2 severely so. We could not identify high-risk patients before transplant by pulmonary function tests, predicted donor total lung capacity (TLC)/actual recipient TLC ratio, pulmonary artery pressures, or the side transplanted. There was a trend toward an increased incidence of symptomatic ANLH in patients with bullous emphysema on chest computed tomography, but this was accounted for primarily by patients with alpha1-antitrypsin deficiency (4/13 vs 4/38 with chronic obstructive pulmonary disease, P = 0.10). No patient required cardiopulmonary bypass or inhaled nitric oxide intraoperatively. Patients with acute native lung hyperinflation did not have increased reperfusion edema as measured by chest x-ray score or PaO2/F(I)O2 ratio. Compared to patients without ANLH, symptomatic patients had longer ventilator times (64.9+/-14.6 hours vs 40.4+/-3.9, P = 0.02, ANOVA) and longer lengths of stay (19.3+/-2.1 days vs 13.7+/-1.3, P = 0.07), but 30-day survival was 100%. Two symptomatic patients required independent lung ventilation or inhaled nitric oxide; the others were managed with decreased minute ventilation, early extubation, and cardiopressor agents. No patient required early lung volume reduction surgery or retransplantation. Acute native lung hyperinflation had no effect on FEV1 or 6-minute walk results at 1 year; survival at 1, 2, or 3 years; or the rate of acute rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. CONCLUSION Acute native lung hyperinflation is common radiographically but is rarely clinically severe. Although there was a trend toward an increase in symptomatic ANLH in patients with bullous emphysema, a high-risk group could not be identified preoperatively. Our results do not support the routine use of bilateral lung transplant, the exclusive use of right single-lung transplant, simultaneous lung volume reduction surgery, or independent lung ventilation for patients with emphysema. Management strategies should be employed that limit overdistension of the native lung and lead to early extubation.

Secondary pulmonary hypertension does not adversely affect outcome after single lung transplantation.

OBJECTIVE Primary and secondary pulmonary hypertension have been associated with poor outcomes after single lung transplantation. Some groups advocate double lung transplantation and the routine use of cardiopulmonary bypass during transplantation in this population. However, the optimal procedure for these patients remains controversial. The goal of our study was to determine the safety of single lung transplantation without cardiopulmonary bypass in patients with secondary pulmonary hypertension. METHODS We retrospectively reviewed 76 consecutive patients with pulmonary parenchymal disease who underwent single lung transplantation from 1992 to 1998. Recipients were stratified according to preoperative mean pulmonary artery pressure. Secondary pulmonary hypertension was defined as parenchymal lung disease with a preoperative mean pulmonary artery pressure of 30 mm Hg or more. Patients with primary pulmonary hypertension or Eisenmengers syndrome were excluded from analysis. RESULTS Eighteen of 76 patients had secondary pulmonary hypertension. No patient with secondary pulmonary hypertension required cardiopulmonary bypass, whereas 1 patient without pulmonary hypertension required bypass. After the operation, no significant differences were seen in lung injury as measured by chest radiograph score and PaO(2)/FIO(2) ratio, the requirement for inhaled nitric oxide, the length of mechanical ventilation, the intensive care unit or hospital length of stay, and 30-day survival. There were no differences in the forced expiratory volume in 1 second or 6-minute walk at 1 year, or the incidence of rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. Survival at 1, 2, and 4 years after transplantation was 86%, 79%, and 65%, respectively, in the low pulmonary artery pressure group and 81%, 81%, and 61%, respectively, in the group with secondary pulmonary hypertension (P >.2). CONCLUSION We found that patients with pulmonary parenchymal disease and concomitant secondary pulmonary hypertension had successful outcomes as measured by early and late allograft function and appear to have acceptable long-term survival after single lung transplantation. Our results do not support the routine use of cardiopulmonary bypass or double lung transplantation for patients with this disorder.

Lobar torsion complicating bilateral lung transplantation

We report a case of left lower lobe torsion in a patient who had undergone bilateral lung transplantation for alpha(1)-antitrypsin deficiency. The patient experienced acute pulmonary hypertension and hypoxemia on post-operative Day 3 and the chest X-ray showed bilateral alveolar infiltrates and a new focal consolidation of the left lower lobe. Fiberoptic bronchoscopy showed complete obstruction of the left lower lobe bronchus and abnormal rotation of the left upper lobe bronchus suggesting torsion, which was confirmed by pulmonary angiography and ultimately at thoracotomy. The possibility of acute lobar torsion should be considered in lung transplant recipients who demonstrate evidence of acute respiratory insufficiency in the early post-operative period.

Mycobacterium marinum infection in a lung transplant recipient.

We report a case of Mycobacterium marinum infection in a lung transplant recipient who presented with nodules on the hand and forearm following exposure to fish-tank water of a superficial hand burn. Skin biopsy revealed granulomatous inflammation and fibrosis. Tissue culture grew Mycobacterium marinum. The patient underwent surgical excision of the lesions and treatment with ethambutol and azithromycin for 12 months and experienced complete resolution of the infection. Transplant recipients who receive immunosuppressive therapy are at increased risk for opportunistic infections. For a patient with nodular lesions on the extremities, exposure to fish, fish-tank water, or swimming should suggest infection with Mycobacterium marinum.

Acute and chronic effects of bilateral lung transplantation without cardiopulmonary bypass on the first transplanted lung

BACKGROUND Bilateral lung transplantation (BLT) without cardiopulmonary bypass (CPB) may exacerbate reperfusion injury to the initially engrafted lung because of increases in pulmonary flow during implantation of the second graft. METHODS In a retrospective review of 23 BLT patients, we hypothesized that BLT without CPB injures the first transplanted lung measured by acute and late graft dysfunction compared to the second transplanted lung. Of the 23 BLT, 19 underwent transplantation without CPB while 4 patients were placed on CPB secondary to hemodynamic instability. RESULTS Acute graft function was assessed by radiographic scoring of lung quadrants (blinded radiologist; 0 = no infiltrate; 1 = infiltrate; maximum = 2 per lung) and by arterial/alveolar oxygen tension ratios (PaO2/ FiO2) ratios. Late graft function was evaluated by quantitative perfusion scan. Lung perfusion was graded as abnormal if less than 50% on the right or less than 45% on the left (Fishers exact). Radiographic scores were not different between first and second implanted lungs at 1 and 24 hours, PaO2/FiO2 ratios at 1 and 24 hours were 273+/-26 and 312+/-23, respectively, and perfusion scans at 3 and 12 months revealed normal differential blood flow. CONCLUSIONS These findings suggest no acute or chronic differences occur between the first or second transplanted lung completed without CPB.