Effect of cardiopulmonary bypass on regional antibiotic penetration into lung tissue.

The use of cardiopulmonary bypass (CPB) during cardiac surgery causes regional ventilation-perfusion mismatch, contributing to regional disturbances in antibiotic penetration into lung tissue. Ventilation-perfusion mismatch is associated with postoperative pneumonia, a frequent and devastating complication after cardiac surgery. In this prospective clinical animal study, we performed in vivo microdialysis to determine the effect of CPB on regional penetration of levofloxacin (LVX) into lung tissue. Six pigs underwent surgery with CPB (CPB group), and another six pigs underwent surgery without CPB (off-pump coronary artery bypass grafting; OPCAB group). LVX (750 mg) was administered intravenously to all pigs immediately after surgery. For regional measurements of LVX in pulmonary concentrations, microdialysis probes were inserted in both lungs of each pig. Pigs were placed in the right lateral position. Time versus concentration profiles of unbound LVX were measured in the upper and lower lung tissue and plasma in all pigs. In all pigs, maximum concentrations (Cmax) of LVX were significantly lower in the upper lung than in the lower lung (OPCAB, P = 0.035; CPB, P < 0.001). Median Cmax of LVX showed a significant difference in the upper versus lower lung in the CPB group (P < 0.05). No significant difference was found in the median Cmax of LVX in the upper and the lower lung in the OPCAB group (P = 0.32). Our data indicate that CPB affects perioperative regional antibiotic penetration into lung tissue. Common clinical antibiotic dosing schemes should be reevaluated in patients undergoing coronary artery bypass grafting with CPB.

Monitoring C2 level predicts exposure in maintenance lung transplant patients receiving the microemulsion formulation of cyclosporine (Neoral).

BACKGROUND: Dosing of the microemulsion formulation of cyclosporine (Neoral) is conventionally based on trough levels (C(0)). However, experience in renal transplantation has shown that cyclosporine exposure during the absorption phase (AUC(0-4)) is critical for optimizing immunosuppression, and that cyclosporine (CsA) concentration at 2 hours post-dose (C(2)) shows the closest correlation with AUC(0-4). This study evaluated whether C(2) values correlate more closely with AUC(0-4) than C(0) in lung transplant patients. METHODS: Pharmacokinetic data were collected prospectively from 20 clinically stable adult lung allograft recipients receiving CsA, mycophenolate mofetil and steroids. Indications for transplantation were emphysema (n = 15), idiopathic fibrosis (n = 2), primary pulmonary hypertension (n = 1), cystic fibrosis (n = 1) and lymphangioleiomyomatosis LAM (n = 1). Blood samples were collected at 0, 1, 2, 3 and 4 hours after administration of CsA, and then AUC(0-4) was calculated. The Correlation between cyclosporine concentration at each time-point and AUC(0-4) was also calculated. RESULTS: C(2) showed the closest correlation with AUC(0-4) (r(2) = 0.85). C(0) had the poorest correlation of all time-points (r(2) = 0.64). Two patients with radiologic signs of gastroparesis had no peak cyclosporine levels at all and were excluded from the correlation analysis. Mean AUC(0-4) was 3,700 ng . h/ml during Year 1 post-transplant, 2,400 ng . h/ml during Years 1 to 3, and 1,500 ng . h/ml thereafter. Mean C(2) values were 1.2 microg/ml during Year 1, 0.8 microg/ml during Years 1 to 3, and 0.5 microg/ml thereafter. CONCLUSIONS: C(2) is the single time-point that correlates most closely with AUC(0-4) in lung transplant recipients without gastroparesis. It remains to be demonstrated whether monitoring CsA based on C(2) levels results in a lower incidence of rejection without additional toxicity.

Continuous beta-lactam antibiotic therapy in a double-lung transplanted patient with a multidrug-resistant Pseudomonas aeruginosa infection.

BACKGROUND: It is well known that the bactericidal effect of beta-lactam antibiotics is closely related to the time which the serum concentration of the antibiotic remains above the minimal inhibitory concentration of the target pathogen. Thus, the optimal administration of beta-lactam antibiotics would be the continuous infusion of the drug. METHODS: We present a case report with a critically ill double-lung transplanted patient with pneumonia due to a multidrug-resistant Pseudomonas aeruginosa who received continuously 8 g meropenem/24 hr. Based on a previous pharmacokinetic study showing that continuous infusion of meropenem is at least equivalent to intermittent administration this case report is reported to demonstrate the clinical efficacy of continuous infusion. RESULTS: C-reactive protein and pneumonia decreased rapidly when clinical conditions were improved significantly. Continuous administration of meropenem did not interfere with cyclosporine, no side effects were seen, and the patient's renal function was not impaired during the whole period of treatment. CONCLUSION: The continuous administration of beta-lactam antibiotics is a powerful application in critically ill patients to intensify antimicrobial therapy.

Low-potassium UW solution for lung preservation. Comparison with regular UW, LPD, and Euro-Collins solutions.

University of Wisconsin solution has been used successfully in clinical kidney and liver preservation. The object of this study was to determine if low-potassium UW (LPUW) solution could be applied to pulmonary preservation. Rabbit lungs were stored after hypothermic pulmonary artery (PA) flush with four different solutions (group 1: low-potassium dextran (LPD) solution, group 2: high-potassium UW (HPUW) solution, group 3: LPUW solution, group 4: modified Euro-Collins (E-C) solution). The lungs were preserved at 10 degrees C for 30 hr and evaluated in an ex vivo ventilation/perfusion apparatus using fresh pooled venous rabbit blood. Mean PA flush pressures (MFP) during harvesting were significantly lower in groups 1 and 3 (8.1 +/- 1.0 mmHg and 7.3 +/- 0.6 mmHg, respectively; mean +/- SEM) than in groups 2 and 4 (15.5 +/- 1.7 mmHg and 12.3 +/- 0.9 mmHg, respectively). Lungs in groups 1 and 3 showed significantly higher PaO2 (103.5 +/- 8.0 mmHg and 89.3 +/- 7.2 mmHg) than groups 2 and 4 (48.3 +/- 7.7 mmHg, 66.7 +/- 4.7 mmHg). Groups 1 and 3 showed significantly lower wet/dry weight (W/D) ratios after reperfusion (6.21 +/- 0.15 and 6.39 +/- 0.23) than groups 2 and 4 (7.70 +/- 0.57 and 7.13 +/- 0.21, respectively). There were no significant differences in MFP, PaO2, PaCO2, mean pulmonary artery pressure, or W/D ratio between groups 1 and 3. These results suggest that LPUW solution may be as beneficial as LPD solution for pulmonary arterial flush and lung preservation.

The pulmonary nodule after lung transplantation. Cause and outcome.

In the immunocompromised patient, the pulmonary nodule remains a diagnostic and therapeutic challenge. We studied the incidence, cause, diagnosis, and therapy of pulmonary nodules after lung transplantation (LTx). Eight out of 64 patients (12.5%) developed pulmonary nodules after a median follow-up of 5.8 months (range, 1 to 10 months). The median age was 30.5 years (range, 21 to 62 years). Solitary pulmonary nodules (n = 2) disappeared spontaneously within 3 weeks and were suspected to be of infectious origin. The cause of multiple nodules (n = 6) was posttransplant lymphoproliferative disorder (PTLD [n = 3]), aspergillosis (n = 2), and abscesses caused by Pseudomonas aeruginosa and Staphylococcus aureus (n = 1). After an initial chest radiograph, CT with fine-needle biopsy was the most valuable diagnostic tool. In six patients, nodules resolved within 10 weeks (median, 8 weeks). Two patients, however, died of sepsis (P aeruginosa and S aureus and Aspergillus, respectively). The differential diagnosis of pulmonary nodules after LTx primarily comprises PTLD and infection (bacterial or fungal). To improve the outcome, early, aggressive treatment is mandatory; therefore, serial CT scans are strongly recommended to be part of the diagnostic armamentarium in LTx recipients.

Early postoperative stress: video-assisted wedge resection/lobectomy vs conventional axillary thoracotomy.

Postoperative pain is a major cause of ineffective breathing after lung surgery, predisposing patients to hypoxemia. Because potent analgesics like opioids depress ventilation and other analgesic techniques are time-consuming, efficient postoperative pain therapy is difficult. Therefore, a less painful surgical approach could be beneficial. Forty-seven patients with diagnosis of a pulmonary nodule were prospectively studied. Patients were assigned to a video-assisted thoracic surgery (VATS) group (n=22) or a group undergoing axillary thoracotomy (n=25). Visual analogue scale (VAS) scores, plasma glucose levels, plasma epinephrine and plasma norepinephrine levels, as well as arterial oxygen (PaO2) and carbon dioxide (PaCO2) tension were determined the day before surgery, and 3, 15, 24, 48, and 72 h after surgery. Postoperative piritramide (a synthetic morphine compound) demand was recorded. VAS values were significantly lower (p<0.05) during the whole observation period in the VATS group. Significantly higher epinephrine levels were observed 3 and 15 h after surgery (267.4 +/- 28 vs 111.8 +/- 13 ng/L; p<0.01; and 176.6 +/- 46.5 vs 96 +/- 14.5 ng/L; p<0.05) in the thoracotomy group, whereas there was no significant difference in norepinephrine (correction of norephinephrine) levels. Piritramide demand was significantly (p<0.05) reduced in the VATS group throughout the whole observation period. There was no difference in PaCO2 values but PaO2 Values were higher in the VATS group over 72 h, with maximum differences occurring at 15 h after operation: 60.9 +/- 1.9 vs 49.2 +/- 2.4 mm Hg (p<0.01). In conclusion, the videoendoscopic approach is associated with less postoperative pain and better oxygenation than traditional surgical approaches.

Neural drive to the diaphragm after lung volume reduction surgery.

STUDY OBJECTIVES: The aim of this study was to investigate prospectively the changes in neural drive to the diaphragm in the first year after lung volume reduction surgery (LVRS) in patients with COPD. PATIENTS AND METHODS: In 14 patients with severe emphysema (mean +/- SD; age, 53.7 +/- 8.3 years; FEV(1), 0.64 +/- 0. 18 L; residual volume [RV], 5.33 +/- 1.25 L; PaO(2), 62.3 +/- 9.0 mm Hg; PaCO(2), 39.0 +/- 6.0 mm Hg), we assessed lung function, arterial blood gases, maximal exercise capacity (Wmax), and oxygen uptake (f1.gif" BORDER="0">O(2)max); intrinsic positive end-expiratory pressure (PEEPi); diaphragmatic strength (transdiaphragmatic pressure, Pdisniff) and endurance capacity (tlim); central diaphragmatic drive assessed by root mean square analysis of the esophageal electromyogram (rmsdia); and isotime dyspnea during loaded breathing tests (BS). RESULTS: Despite a significant increase (expressed as a percentage of baseline) in FEV(1) (40.6%) and a decrease in RV (30.0%) and PEEPi (75.7%) 1 month after LVRS, the improvements in Wmax (31.2%) and f1.gif" BORDER="0">O(2)max (13.7%); Pdisniff (25.4%) and tlim (64.9%); rmsdia (34.6%); and BS (21.7%) did not reach statistical significance (p < 0.05) until 6 months after LVRS. Arterial blood gases did not change significantly. Significant correlations were found between decrease in rmsdia and changes in PEEPi (r = 0.69), Wmax (r = -0.56), Pdisniff (r = -0.65), tlim (r = -0.59), and BS (r = 0.71) 6 months after LVRS. CONCLUSIONS: Our results show that LVRS is able to increase the efficacy of the respiratory pump and by this way reduce ventilatory drive and respiratory effort sensation.

Early experience with sequential bilateral lung transplantation.

We performed 20 sequential bilateral lung transplantation in 19 consecutive patients from April 1990 to May 1992. Perioperative mortality was low (2 patients). One-year actuarial survival was 70%. All survivors had normal blood oxygen tension (82 mm Hg, mean) while breathing room air and continuing improvement of pulmonary function. Bronchial dehiscence did not occur. Stents were implanted in 7 patients to control bronchial stenosis. Aggressive treatment of graft rejection has been effective in preventing obliterative bronchiolitis.

Pulmonary surfactant in bronchoalveolar lavage after canine lung transplantation: effect of L-carnitine application.

Pulmonary surfactant during lung transplantation was investigated in the control group of a canine single lung transplantation model by measuring dipalmitoyl-phosphatidylcholine, the main phosphocholine fraction of surfactant in bronchoalveolar lavage. In a second group of dogs, L-carnitine, an essential cofactor for transfer of long-chain fatty acids into the mitochondria, was applied. Organ function after pulmonary artery flushing with modified Euro-Collins solution and hypothermic storage for 4 hours was adequate in both groups, with significantly higher arterial oxygen pressure levels in the L-carnitine group after 12 (p less than 0.05) and 24 (p less than 0.025) hours, respectively. In the control group, a reduction of the dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholines was observed 4 and 12 hours after transplantation of the left lung (p less than 0.005 and p less than 0.01, respectively, both specified by Student's t test for dependent data, not significant by Bonferroni correction). In the simultaneously stored right lungs, a constant fall of the dipalmitoyl-phosphotidylcholine portion was demonstrated. In the L-carnitine group, significantly higher dipalmitoyl-phosphotidylcholine levels were observed in the transplanted left lungs after 4 hours (p less than 0.01) and in the continuously stored right lungs after 24 hours (p less than 0.005), when compared with the control group. These results suggest that dipalmitoyl-phosphotidylcholine portion on total phosphotidylcholine decreases parallel to the extent of the ischemic damage. Furthermore, the application of L-carnitine improved pulmonary function after transplantation, possibly by reducing the impairing effect of ischemia on alveolar type II cell metabolism and thereby on pulmonary surfactant system.

A new flush solution for extended lung preservation.

BACKGROUND: The aim of this study was to compare the effect of the most frequently used clinical preservation solution (Euro-Collins, group I) with a newly composed low potassium, glucose- and insulin-containing preservation solution (141 mmol/L sodium, 6.4 mmol/L potassium, 119 mmol/L chloride, 5 mmol/L magnesium, 10 gm/L glucose, 10 gm/L dextrane and 20 U/L insulin) (group II) on postischemic lung function. METHODS: We studied 12 isolated New Zealand White rabbit lungs in a closed circuit model during the first 4 hours of reperfusion after 24 hours of ischemic hypothermic storage. RESULTS: Oxygenation capacity, defined by the difference between the arterial and venous oxygen tension was significantly higher in group II compared with group I after 10 (58.7 +/- 5.8 versus 34.9 +/- 7.5 mm Hg), 30 (63.5 +/- 7.8 versus 27.3 +/- 10.4 mm Hg) and 180 minutes (77.7 +/- 7.2 versus 8.8 +/- 5.6 mm Hg). Ventilatory pressure was significantly lower in group II after 1 minute (11.3 +/- 1.3 mm Hg versus 13.7 +/- 0.5 mm Hg, p < 0.05), with no significant difference thereafter. No significant difference was found in pulmonary vascular resistance except after 20 minutes (30.8 +/- 1.2 dyns/cm5 [group I] versus 27.1 +/- 1.1 dyns/cm5 [group II], p < 0.05). CONCLUSION: These data suggest that this new solution provides superior lung function after 24 hours ischemic time compared with Euro-Collins solution.

Lung retransplantation: institutional report on a series of twenty patients.

BACKGROUND AND METHODS: Between 1986 and 1995, 124 isolated lung and 29 combined heart-lung transplantations were performed at our institution. Twenty of these procedures were retransplantations. Four different types of reoperations were performed: ipsilateral single lung retransplantation (n = 3), single lung retransplantation after bilateral or heart-lung transplantation (n = 7), bilateral retransplantation after bilateral lung transplantation (n = 5), and bilateral retransplantation after single lung transplantation (n = 5). Nine patients underwent retransplantation while still in the intensive care unit after the primary transplantation. Indications for retransplantation in these patients were primary graft failure in seven and bronchial complications in two patients. In 11 patients a late retransplantation (3 to 30 months after the first transplantation) was performed. The indication was obliterative bronchiolitis in nine and late bronchial complications in two patients. Overall, 13 patients were ventilator-dependent before retransplantations. RESULTS: Overall survival was 52.8% and 36.2% at 1 and 12 months, respectively. For early retransplantation the survival rate at 1 month was only 22.2% with 2 patients alive 5 and 22 months after the retransplantation. For late retransplantation survival at 1 and 12 months was 70.7% and 50.5%, respectively (p = 0.07), and the longest surviving patient was at 47 months after retransplantation at the time this article was written. Patients who were ventilator-dependent before retransplantation had a significantly worse outcome (survival at 1 and 12 months: 33.8% and 25.4% versus 85.7% and 57.1% for all others, p = 0.055). Of those surviving to date, all were in New York Heart Association class I or II. CONCLUSIONS: We conclude that late and elective lung retransplantation achieves acceptable results when offered to patients with chronic pulmonary dysfunction but with otherwise stable conditions. In view of the poor results, early acute retransplantation should be performed much more restrictively.

Diaphragmatic dysfunction after heart or lung transplantation.

BACKGROUND: The aim of this study was to evaluate the incidence and outcome of diaphragmatic dysfunction in patients after heart or lung transplantation and to assess the value of bedside sonography for the detection of diaphragmatic dysfunction. METHODS: We prospectively evaluated 33 heart transplant recipients and 27 lung transplant recipients by use of sonography of the diaphragm and fluoroscopy. RESULTS: Diaphragmatic dysfunction, diagnosed with ultrasonography and confirmed with fluoroscopy, was present in four heart transplant recipients (12.1%) and two lung transplant recipients (7.4%) and such dysfunction led to a statistically significant higher incidence of pneumonia during hospitalization and a nonstatistically significant increased length of intubation compared with patients with normal diaphragmatic function. CONCLUSION: Diaphragmatic dysfunction, which can be reliably diagnosed with bedside sonography, is common after heart and lung transplantation and seems to have a negative influence on patient recovery.

Tailoring of the lung to overcome size disparities in lung transplantation.

BACKGROUND: Between October 1989 and December 1994 in 13 (four single and nine bilateral lung transplantations) of 124 lung transplantations, pulmonary allografts were considered to be too large to fit into the recipient thoracic cavity. METHODS: In all these patients (emphysema n = 6, fibrosis n = 4, pulmonary hypertension n = 3), the transplanted lungs were trimmed by extra anatomic wedge resections with the use of mechanical stapling devices to reach an acceptable size. RESULTS: No postoperative complication attributable to the tailoring procedure was observed. CONCLUSIONS: Tailoring of the lung is a safe and efficient method to overcome moderate size disparities between donor and recipient lungs.

Influence of human leukocyte antigen matching on long-term outcome after lung transplantation.

BACKGROUND AND METHODS: The importance of human leukocyte antigen matching for long-term outcome after lung transplantation is uncertain. We therefore analyzed retrospectively 78 consecutive primary, isolated lung transplantations (37 female, 41 male; 40 single, 38 bilateral) performed between October 1989 and October 1995 for which human leukocyte antigen typing of both donor and recipient was available. The follow-up ranged from 1 day to 60.3 months. Graft failure, defined as retransplantation or patient death, served as end point. RESULTS: Graft survival was significantly better with one mismatch at the B locus than with two mismatches (p = 0.046): 67% versus 51% and 61% versus 25% graft survival at 12 and 36 months, respectively. For the B and DR loci combined, a marked matching effect was also observed (p = 0.21 for zero to two mismatches versus three to four mismatches: 81% versus 62% and 51% versus 29% graft survival at 12 and 36 months, respectively. The sum of mismatches at the A, B, C, and DR loci combined showed a similar effect (p = 0.17 for zero to four mismatches versus five to eight mismatches: 83% versus 62% and 58% versus 29% graft survival at 12 and 36 months, respectively. Although no clear effect could be shown for the isolated DR locus, the outcome for the three patients with zero mismatches was notably good: one patient is alive at 27 months, two died 37 and 48 months after transplantation. The number of acute rejection episodes showed a clear but insignificant correlation to the number of mismatches. A similar trend was observed for the incidence of bronchiolitis obliterans syndrome. CONCLUSIONS: In summary, a strong influence of human leukocyte antigen matching on the long-term outcome after lung transplantation is suggested by our results. A clear trend toward improved graft survival with better human leukocyte antigen matching was observed, with the most significant effect occurring at the B locus.

Lung transplantation following lung volume reduction surgery.

OBJECTIVE: Lung volume reduction surgery (LVRS) has been proposed as a possible alternative treatment to lung transplantation (LTX) for selected patients with end-stage emphysema. But whether LVRS is a temporary or permanent alternative to LTX is still under investigation. The aim of this study was to analyze the course of patients undergoing LVRS followed by subsequent LTX. METHODS: Fifteen patients (10 male, 5 female, mean age 53.3 +/- 1.7 years) out of 102 patients, who underwent LVRS between September 1994 and August 1998, underwent LTX 19.6 +/- 3.1 months after LVRS (range 1.7 to 37.6 months) between June 1996 and October 1998. In 9 patients bilateral LVRS was performed, in 6 patients unilateral LVRS. Subsequent LTX was performed bilaterally in 10 patients and unilaterally in 5 patients (1 of these on the contralateral side) to the previous LVRS. The course of lung function and clinical outcome were analyzed in these 15 patients. RESULTS: Mean forced expiratory volume in 1 second (FEV(1)) in the 15 patients prior to LVRS was 18.3 +/- 1.2% of predicted (%p) and increased to 27.0 +/- 2.9 %p (best value within the first 6 months postLVRS) (p = 0.043). In 8 of these patients (non-responders) (53%) LVRS failed to improve FEV(1), whereas in the other 7 patients (responders) (47%) a significant improvement was detected (FEV(1) 18.1 +/- 1.8 %p and 31.9 +/- 3.7 %p, pre- and post-LVRS, respectively, p = 0.003), but declined after 6 to 36 months. At the time of listing for LTX the mean FEV(1) was 18.0 +/- 1.9 %p (no difference between the 2 groups). LTX was performed 15.5 +/- 3.6 months (non-responders) and 25.7 +/- 4.6 months (responders) after LVRS. FEV(1) improved to 81.0 +/- 5.6 %p after LTX (p < 0.001 compared to pre-LTX). The mortality after LVRS was 0%. The 3-month mortality after LTX was 20% (1 patient with primary organ failure, 1 patient with ongoing rejection, 1 patient with sepsis). All 3 patients belonged to the group of nonresponders. Two patients died 5. 5 and 8.5 months after LTX (13.3%) due to fungal infection (Aspergillus spp.) and MRSA sepsis, respectively (1 non-responder, 1 responder). CONCLUSIONS: Successful LVRS delays the need for LTX and offers better conditions for LTX. However, patients without functional improvement after LVRS have a high perioperative risk at subsequent LTX.

Comparison between mycophenolate mofetil- and azathioprine-based immunosuppressions in clinical lung transplantation.

BACKGROUND: The aim of the study was to assess the impact of mycophenolate mofetil (MMF) on the early phase after lung transplantation. PATIENTS AND METHODS: Thirty-eight consecutive patients between November 1994 and January 1997 were treated with cyclosporine, prednisolone, antithymocyte globuline induction therapy, and either MMF (n = 21) or azathioprine (Aza) (n = 17). Four patients from the MMF group and 2 patients from the Aza group were intubated and in the ICU prior to transplantation. Demographic data and primary diagnosis were comparable. MMF was administered at a dosage of 2 gm/day whereas Aza was initiated at 2 mg/kg/day and adapted by leukocyte count. Three-month survival and incidence of rejections and infections were compared. RESULTS: Six-month survival in the MMF group was 76% compared to 65% in the Aza group (n.s.). The mean number of acute rejection episodes in the MMF and Aza group were 0.29+/-0.10 and 1.53+/-0.29 (p<0.01) respectively. Transbronchial biopsy (TBB) results > or =grade 2 ISHLT were seen in 10% of MMF and in 43% of Aza-treated patients; completely free from rejection were 17 MMF and 3 Aza patients. The mean number of infections per patient in the MMF and Aza group were 1.57+/-0.29 and 2.29+/-0.40 respectively, bacterial (1.10 vs. 1.71), viral (0.35 vs. 0.33), and fungal (0.14 vs. 0.24) infections were the same in both groups. CONCLUSIONS: These data result suggest that mycophenolate mofetil therapy is more effective in preventing rejection episodes in patients early after lung transplantation than therapy with azathioprine. We therefore conclude that MMF is a safe and effective drug to optimize immunosuppressive therapy in the early phase after lung transplantation.

Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols.

BACKGROUND: The need for better immunosuppressive protocols after lung transplantation led us to investigate tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and steroids or cyclosporine (CsA) in combination with MMF and steroids in a prospective, open, randomized trial after lung transplantation. METHODS: Between September 1997 and April 1999, 50 lung transplant recipients were randomized to receive either Tac (n = 26) or CsA (n = 24) in combination with MMF and steroids. All patients underwent induction therapy with rabbit antithymocyte globulin (ATG) for 3 days. Freedom from acute rejection (AR), patient survival, infection episodes, and side effects were monitored. RESULTS: There was no difference in patient demographics between the two groups. Six-month and 1-year survival was similar (84.6% and 73.1% in the Tac group vs 83.3% and 79.2% in the CsA group). Freedom from AR at 6 months and 1 year after lung transplantation was slightly higher in the Tac group (57.7% and 50% vs 45.8% and 33.3%, p = not significant [n.s.]), whereas the number of treated rejection episodes per 100 patient days in the Tac group was significantly lower (0.225 vs 0.426, p < .05). Four patients in the CsA group had to be switched to Tac. Two patients in the CsA group had to be retransplanted. Incidence of infections was similar in both groups with a trend toward more fungal infections in the Tac group (n = 7 vs n = 1, p = n.s.). CONCLUSIONS: The combination of Tac and MMF seems to have slightly higher immunosuppressive potential compared with CsA and MMF. The effectiveness of Tac as a rescue agent is not paralleled with undue signs of overimmunosuppression.

Management of severe bronchial ischemia after bilateral sequential lung transplantation.

A case of severe diffuse bronchial ischemia after bilateral sequential lung transplantation is presented. A combination of initial conservative treatment with silicone stenting and late bilateral retransplantation under stable conditions resulted in good clinical outcome. Factors in decision making and technical aspects of the stenting procedure are discussed.

T4 lung tumors with infiltration of the thoracic aorta: is an operation reasonable?

BACKGROUND: Only anecdotal reports about the results of combined resection of T4 lung tumors infiltrating the thoracic aorta exist. METHODS: Seven patients (mean age, 57.5 years; range, 43 to 78 years) underwent a resection of the infiltrated segment of the thoracic aorta together with a left pneumonectomy (n = 6) or left upper lobectomy (n = 1). Five tumors were primary non-small cell lung carcinomas (T4N2 in 3 patients, T4N1 in 2), one was a metastasis of breast cancer, and one was rhabdomyosarcoma. RESULTS: No patient died perioperatively. The 2 patients with rhabdomyosarcoma and metastasis of breast cancer died 2 and 7 months postoperatively. Of the 5 patients with bronchial carcinoma, 3 died after 17, 26, and 27 months as a result of distant metastasis. Two patients are alive after 14 and 50 months without evidence of disease recurrence. One-year, 2-year, and 4-year survival rates for patients with bronchial carcinoma were 100%, 75%, and 25%, respectively. CONCLUSIONS: Combined resection of the lung and thoracic aorta can be performed with low morbidity and mortality when offered to highly selected patients. Adequate local control of tumor can be achieved for N1 and single-level N2 non-small cell lung carcinomas, but not for tumors with other histologies.

Functional improvement after volume reduction: sternotomy versus videoendoscopic approach.

BACKGROUND: Volume reduction has been proved to increase ventilatory mechanics in diffuse, nonbullous lung emphysema. However, the best approach is still controversial. METHODS: We retrospectively compared the perioperative data of and functional results in 15 patients having sternotomy (group I) with those of 15 patients having a videoendoscopic approach (group II). RESULTS: The 30-day mortality was 2 patients in group I and 1 patient in group II. Mean duration of chest tube drainage was 8.7 +/- 1.8 days and 8.0 +/- 1.9 days and mean hospital stay, 12.3 +/- 1.9 and 12.5 +/- 2.1 days in groups I and II, respectively. Work of breathing decreased from 1.89 +/- 0.33 J/L and 1.76 +/- 0.22 J/L preoperatively to 0.75 +/- 0.06 J/L and 0.8 +/- 0.06 J/L (p < 0.01 and p < 0.05, respectively) after 3 months; and intrinsic positive end-expiratory pressure decreased from 7.15 +/- 1.31 cm H2O and 6.24 +/- 1.33 cm H2O to preoperatively 0.79 +/- 0.46 cm H2O and 1.13 +/- 0.44 cm H2O (p < 0.005 and p < 0.01, respectively) after 3 months in groups I and II, respectively. Forced expiratory volume in 1 second increased from preoperative values of 21.6% +/- 2.9% and 25.3% +/- 2.4% of predicted to 34.5% +/- 5.0% and 40.9% +/- 7.5% of predicted after 3 months (p < 0.05 in both groups) in groups I and II, respectively. CONCLUSIONS: Both surgical approaches resulted in similar substantial improvement in lung function and physical fitness. The incidence of air leakage, the duration of chest tube drainage, and the hospital stay were the same for both procedures.