Transplantation: Complications 8:00 AM – 8:50 AM

Wednesday, November 2, 1994 Sleep and Cardiopulmonary Function, continued Title:

SHOULD THE ASYMPTOMATIC SNORER BE TREATED?

Author(s): Howard M. Braver* MD, and A. Jay Block, MD, FCCP

The benefits of establishing nasal patency, sleeping on one's side, and the combination thereof were studied in twenty asymptomatic male snorers. Both the apnea-hypopnea index (AHI) and snoring were evaluated. Four consecutive nocturnal polysomnographic studies were done. Night 1 was a conitrol; the other three nights were randomly assigned to nasal patency, best sleeping position, and a combination of the two. Results were calculated based on sleep period time (SPT). The mean control AHI ± the standard error of the mean (SEM) was 17.5±6.5. AHI improved to 14.1 ± 6.3 with sleep in the best position (p=0.03). The AHI also improved to 13.2 ± 6.04 with both nasal patency and position (p=0.0012). Using nasal patency alone, the mean AHI was 18.1 ± 6.3 (p=0.765). During the control night, the mean number of snores/hr ± SEM was 356 ± 460. Using nasal patency alone, the mean number of snores was 381 ± 50.4 (p=O.50). With position alone, the mean number of snores was 356 ± 46.0 (p=0.8). Using the combination of nasal patency and position, mean snores were 352 ± 48.9 (p=0.91). In conclusion, a statistically significant improvement in the apnea-hypopnea index was produced using the general measures of altering the position of the body during sleep and by the combination of nasal patency and positional change. There was no significant change in snoring using any of these general measures.

Title;

THE EFFECTS OF DEXAMETHASONE ON SLEEP ARCHITECTURE

Author(s): Neal J. Moser MD', Gordon Guthrie MD, Barbara Phillips MD, FCCP

University of Kentucky College of Medicine Lexington, KY Many chest diseases are treated with systemic corticosteroids which may produce systemic side effects. Although many pulmonary patents have sleeping problems the effects of corticosteroids on sleep is not well studied. Methods: We conducted a randomized, prospective, double blind, placebo controlled crossover study of the effects of dexamethasone, 3mg every eight hours for 48 hours on the sleep architecture of six normal volunteers (mean age 28 years, five male and one female). The subjects were participants in a larger study measuring the effects of dexamethasone on ambulatory blood pressure. Each subject was studied with a full polysomnogram on two successive nights when receiving either placebo or dexamethasone. Only the second night was used for analysis to eliminate first night effect. Placebo and dexamethasone periods were seperated by at least two weeks. Analysis: Wilcoxon signed rank analysis. Results: There were significant increases in the REM latency, percent time spent in stage zero and percent time spent in slow wave sleep on drug which improved with palcebo. There were significant decreases in the percent time spent in REM and the number of REM periods on dexamethasone. Conclusions: Pharmocologic doses of dexamethasone produce deleterious effects on sleep architecture. #REM periods %REM 9.66±3.61 21±5.4 7.96±4.6 Dexameth 3.83±2.64 p value .01 .01

Placebo

% Slow Wave REM latency 202±79 min 19.9±8.6 364±74 min 22.6±9 .01 0.01

% stage 0 2.9 ±1.8

11.6±12.1

.05

Transplantation: Complications 8:00 AM- 8:50 AM Title:OSTEOPOROSIS IN LONG-TERM SURVIVORS OF

ISOLATED

LUNG TRANSPLANTATION Author(s):C Chaparro,* S Kesten, M Scavuzzo, J Maurer. University of Toronto, Toronto, Canada Improved immunosuppression and post-operative care has resulted in increased survival rates following organ transplantation (TX). Medication-related complications, however, have increased. One of these is osteoporosis, documented in cardiac, liver and bone marrow TX. To assess this complication in a lung transplant population, we retrospectively reviewed data from 161 patients transplanted All were on chronic between 11/83 and 12/93. immunosuppression including cyclosporin, imuran, and prednisone. Calcium and alkaline phosphatase levels were normal, both pre and post transplantation. We found 10 patients with bone complications: six females between 26-63 years old and 4 males between 53-57 years old. Complications appeared between 2 and 36 months after transplant and included: rib fractures (3), vertebral compression fractures (4), femoral neck stress fractures (2), intertrocanteric femoral fracture (1) fibula fracture (1). One patient had both rib and spine fractures. Stress fractures were not appreciated on plain radiographs and required bone scan or CT scan to diagnose. In 4/10 patients osteopenia was suspected on pre-operative CXR. Conclusion: Osteoporosis

is a common following lung transplantation. Pre-operative assessment of bone density and possibly other parameters may help identify at-risk patients.

UNANTICIPATED COMPLICATIONS

Title: REcpENTs. thors) Buthowsl ,V T. A

A.

Anzueto*,

S.

Levine,

IN LUNG TRANSPLANT

FCCP,

Peters,

FCCP,

Cronin, E. Sako, S. Jenkinson, FCCP, C. Bryan, FCCP. Departments Medicine and Surgery, University of Texas Health Science Center (UTHSC-SA) and Audie Murphy VA Med Ctr, San Antonio, TX. The most common complications affecting lung transplant recipients have been well described. The purpose of this report is to review surgical, infectious, and metabolic complications in lung transplant patients that are less well known. All patients underwent single lung transplantation with telescoping anastomosis, and immunosuppressive regimens as described previously (J Thorac Cardiovasc Surg 101:816, 1991). The unusual complications presented as follows.: A) Point tendemess at site of thoracotomy incision without eiythema or fever (n=3). Mean time after SLT 45+12 days. Final diagnoses: subeutaneous abscesses (n=2) and muscle rupture with a hematoma (n=1). All required surgical drainage or repair. B) Hyperkalemia not associated with supplemental potassium (n=3). Mean time after SLT 47+11 days. Maximum serum K+ level 6.1+0.13 MMol/L. This resolved in two patients following a decrease in cyclosporin dose. One patient required hospitalization and treatment with acetazolarnide to normalize serun potassium. C) Viscus organ perforation (n-3). Mean time after SLT 163+44 days. Two patients had a large bowel perforation, one due to infection with C. difficile and one due to CMV infection. A third patient had a perforated gastric ulcer due to CMV infection. D) Hepatic encephalopathy (n=1). The patient presented with elevated serum ammonia levels and normal liver functions. The condition spontaneously resolved without diagnosis. E) Idiopathic cardiomyopathy (n=l). The patient presented with recurrent congestive heart failure. Echocardiogram revealed diffuse hypokinesis. Cardiac catheterization showed normal coronaries. Endomyocardial biopsy showed myocarditis without evidence of CMV.

These complications were unanticipated and poorly described im the existing transplant literature. Other transplant programs are encouraged to consider these diagnoses in their ongoing surveillance of lung transplant patients.

1 50S

Abstracts, 60th Annual International Scientific Assembly

Wednesday, November 2, 1994

Title: DIFFUSE ALVEOLAR HEMORRHAGE IN AUTOLOGOUS BONE MARROW TRANSPLANT RECIPENTS

John D Gasman*, Norman W Rizk (FCCP), Bala Annadurai, Nelson A Chao, Karl G Blume. Stanford University Medical Center, Stanford, California. Authors:

Diffuse alveolar hemorrhage (DAH) is a recognized complication of autologous BMT. The mortality rate is reported to be 70% or more. High dose corticosteroid therapy has been reported to reduce this mortality rate. 50 autologous BMT patients underwent 68 diagnostic bronchoscopies for evaluation of pulmonary infiltrates or symptoms. DAH was identified in 7 patients (14%). DAH was diagnosed 19.6 days (range 6-42) after BMT. All patients were treated with high dose corticosteroids. Three patients (42.8%) died a mean of 15.3 days (range 12-21) after diagnosis. None of the three fatal cases had experienced engraftment after BMT. One patient had HSV II pneumonitis diagnosed by bronchoscopy one week prior to DAH. Pulmonary aspergillosis was present in two patients at autopsy. The third death was related to refractory neutropenia, sepsis and multiple system organ failure. Four patients have survived >460 days since DAH. Two of these cases developed DAH concurrent with initial engraftment, manifested as a rising WBC. Another had WBC engraftrnent well established at the time of DAH. The fourth survivor had only modest graft function (absolute neutrophil count = 127) at the time of DAH. The course of survivors was marked by prompt improvement, with resolution of infiltrates and symptoms 48-72 hours after high dose corticosteroid therapy. One case had a positive shell vial CMV culture 2 days after bronchoscopy. Steroid therapy was stopped and gancyclovir plus IVIG was initiated. The patient subsequently deteriorated and bronchoscopy suggested chemotherapy related interstitial pneumonitis. The patient improved after reinstitution of corticosteroids. DAH complicates the early course in autologous BMT patients. Corticosteroid therapy often results in prompt and durable improvement. Death is due to infectious complications, not respiratory failure.

Title:

Author(s):

SUCCESSFUL TREATMENT OF AIRWAY STRICTURES WITH BRONCHOSCOPIC BALLOON CATHETER DILATION

Reilly, Jr., M.D., FCCP,*

D.J. Sugarbaker, M.D., FCCP, Mentzer, M.D., W.J. O'Donnell, M.D., M.M. DeCamp, M.D. Depts. of Pulmonary/Critical Care Medicine and Thoracic Surgery, Brigham & Women's Hospital, Hervard Medical School, Boston, MA Symptomatic strictures of the large airways occur after lung transplantation, airway surgery including tracheotomy, thermal injury and idiopathically. Conventional treatment utilizes rigid bronchoscopy requiring general anesthesia. We report our experience with balloon dilation directed by fiberoptic bronchoscopy to treat large airway strictures. 10 patients (3 idiopathic, 1 post-sleeve resection, 1 thermal injury and 5 post lung transplant) with symptomatic airway strictures were treated. Conscious sedation was used for all procedures. Balloon catheters (810 mm inflated diameter) were passed through the working channel of a therapeutic fiberoptic bronchoscope (Olympus Co.) and directed through the narrowed area under direct vision. The balloon was then inflated to 80-100 PSI for 30 seconds and repeated 2 to 3 times. Efficacy was documented, in all patients by improvement in symptoms, increased airway caliber as documented by photographs and by pulmonary function testing. There were no complications. 3 patients required multiple dilations and 2 went on to resectional surgery. This approach avoids general anesthesia, provides access to lesions inaccessible to rigid bronchoscopy, and

J.J.

S.J.

allows better catheter control. It eliminates the need for intubation, use of guidewires or passing the catheter next to the bronchoscope. In addition, it has thetheoretic advantage of being less traumatic to airway mucosa by exterting only radial forces rather than the shearing forces associated with rigid endoscopes or dilators. It also provides temporary symptomatic and functional improvement

prior

to definitive

resectional surgery.

Authors: John D Gasman*, Norman W Rizk (FCCP), Bala Annadurai, Nelson A Chao, Karl G Blume. Stanford University Medical Center, Stanford, California.

Title: PERSISTENT AIR LEAKS AND PNEUMOTHORACES IN LUNG RECIPIENTS. Author(s):TRANSPLANT S. Levine, FCCP*, J Peters, FCCP, A. Anzueto, D. Bukowski, T. Cronin, E. Sako, S. Jenkinson, FCCP, C. Bryan, FCCP. Departments of Medicine and Surgery, University of Texas Health Science Center (UTHSC-SA),

Diffuse alveolar hemorrhage (DAH) is a recognized complication of autologous BMT, but only a single case report has described DAH in allogeneic BMT patients. Having recognized DAH among the allogeneic BMT population at Stanford, we reviewed the prevalence and outcome in our series. 39 allogeneic BMT recipients including 6 with an unrelated donor (URD) underwent 58 bronchoscopies (range 1-6) for evaluation of pulmonary infiltrates or symptoms. DAH was diagnosed in 7 patients (17.9%) including 4 of 6 URD (66.6%). The time to diagnosis of DAH was 40.3 days (range 19-71) following BMT. In 4 cases, DAH was the first or only pulmonary complication. In one patient DAH followed CMV pneumonitis by 24 days; in another DAH followed idiopathic pneumonia syndrome (IPS) by 10 days; in a third patient DAH followed both CMV and EPS by 34 and 5 days respectively. All 3 of these patients received gancyclovir prior to DAH and in both cases of confirmed CMV pneumonitis gancyclovir pulmonary toxicity was suspected on transbronchial biopsy specimens. All 7 patients were treated with high dose corticosteroids upon the diagnosis of DAH. 5 of patients 7 (71.4%) died. 4 of 5 patients died of Aspergil/us a mean of 29 days (range 12-52) after diagnosis of DAH. A fifth patient succumbed to a cardiac arrhythmia two days after diagnosis. Two patients have survived >300 and >1200 days since diagnosis. DAH is a complication of allogeneic BMT and is particularly common among URD. The mortality rate is high and high dose steroid therapy may contribute to the frequent development of aspergillosis. Altemative therapy or concomitant treatment with Amphotericin B should be considered in alloaeneic BMT recipients treated with high dose corticosteroids.

respectively. Two additional SLT patients developed persistent air leaks following diagnostic open lung biopsies for aspergillus (n='l) and obliterative bronchiolitis (nt=l). Two post-op SLT patients presented with spontaneous pneumothoraces (PTX) on the side of the lung graft. Patient 1: PTX secondary to staphylococcal pneumatocele 78 days post SLT. Patient 2: PTX secondary to candida pneumonia 89 days post SLT. This patient developed a recurrent tension PTX 1 month later. Fiberoptic bronchoscopy (FOB) in transplant patients has been performed at UTHSC-SA for clinical deterioration manifested as cough, dyspnea, decreased infiltrates. 5/225 (2.2%) were complicated by spirometry and/or radiographic were ultimately diagnosed with rejection (n=4) or iatrogenic PTX. These patients Three patients required thoracostomy tube placement. Two infection (n=I). patients deteriorated acutely and were treated with percutaneous needle aspiration alone. We conclude that: 1) Lung transplant recipients experience a greater increase in the duration of postthoracotomy air leaks 14/90 (15.6%) than that published for other thoracotomy cases. This increase may be the result of imnmunosuppressive therapy. 2) FOB-induced PTX occur in SLT patients at the same incidence as in non-SLT patients 5/225 (2.2%).

Title: DTFFUSE ALVEOLAR HEMORRHAGE IN ALLOGENEIC BONE MARROW TRANSPLANT RECIPIENTS

and Audie Murphy VA Medical Center, San Antonio, TX. Since 1988, the UTHSC-SA has performed 90 single and double lung transplants lung disease. All patients were (SLT, DLT) for end-stage parenchymal and vascular immunosuppressive subjected to similar surgical techniques and postoperative surgery the majority of patients had regimens including corticosteroids. Following air leaks (defined as the thoracostomy tubes removed within one week. Persistent >7 days) were observed in 14 patients with the following diagnoses: chronic obstructive pulmonary disease (n=6), sa-l-antitrypsin deficiency (n=3), sarcoidosis fibrosis (n=2), lymphangio-leiomyomatosis (n=l), scleroderma (n=l), pulmonary (n=l), for an incidence of 15.6% (14/90). Mean time to closure was 19 days (range 12 to 30 days). Two of these patients underwent surgical closure on days 25 and32

CHEST / 106 / 2/ AUGUST, 1994 / Supplement

151S

Wednesday, November 2, 1994 Transplantation: Complications, continued

BRONCHIAL COMPLICATIONS IN SINGLE LUNG (SLT) Title: TRANSPLANT RECIPIENTS. I. Susanto*, A. Anzueto, S. Levine, FCCP, J. Peters, FCCP, A thor(sl D .Thkowsli, T. Cronin, J. Palmaz, J. Calhoon, C. Bryan, FCCP. Departments Medicine, Surgery and Radiology, Univ Texas Flth Sci Ctr and Audie Murphy VA Med Ctr, San Antonio, TX.

Bronchial complications resulting in stenosis after SLT have been reported

to develop within a month after the surgical procedure, most likely due to technical complications or local ischemia (JAMA 259:2258, 1988). We now report our experience in 5 SLT recipients with bronchial anastomotic complications. All patients were male, mean age 40+6 yrs (range 19 - 52), and had an underlying diagnosis of pulmonary fibrosis (n=4), or alpha- I antitrypsin deficiency (n=l). Spirometry and oxygenation significantly improved in all patients within 2 weeks after transplantation. All patients had the same surgical

technique, telescopic anastomosis, and immunosuppression regimens as described previously (J Thorac Cardiovasc Surg 101:816, 1991). Five out of 86 anastomoses at risk (6%) developed bronchial complications means 76+25 days (range 44-99) after transplantation. Deterioration in pulmonary function was the indications for bronchoscopy in all patients. Prior Bronchial Concurrent Subject SLT Ischemic Infection side time Rejection Rejection None Y L 234 min Y HG Y L 194 min Y DM S. aureus L Y Y JV 233 min Aspergillus

Y N RC L 241 min Aspergillus N Y JD R 315 min C. albicans All patients received appropriate antibiotic/antifungal treatment. Bronchial stenoses were initially treated with balloon dilatation as previously described (Chest 102:995, 1992). All patients developed re-stenosis and required placement of a wire mesh stent (Palmaz®, Johnson & Johnson). These data suggest that the presence of infectious bronchitis, acute rejection, left sided position and pretransplant pulmonary fibrosis may be additional risk factors predisposing SLT recipients to the development of bronchial complications.

Title:

ENDOBRONCHIAL STENTING POST LUNG

Author(s): TRANSPLANTATION USING VASCULAR STENTS.

Neal J. Mcser MD*, Rolando Berger MD FCCP, John Gurley MD, Michael

Sekela MD. University of Kentucky Medical Center Lexington, KY A major cause of post-operatve morbidity following lung transplantation is airway stricture at the donor-recipient bronchial anastamosis. Anastomotic healing is hampered by inadequate blood supply of the donor bronchus and corticosteroid therapy resulting in airway compromise with acute or subacute respiratory failure. We report six patients with post-transplant strictures managed by implanting balloon expanded Palmaz-Schatz sloKted stainless steel vascular stent (Johnson and Johnson, Warren NJ). Two patients received metallic stents after recurrent failure of silastic stents. Four patients received metallic stents as primary treatment. Stents were deployed under general anesthesia and with flexible bronchoscopic guidance to place a 0.035 inch stiff shaft guidewire placed across the stricture. The stent was crimped over a 14mm diameter peripheral vascular angioplasty balloon and advanced over the guidewire. Placement of the stent was confirmed with a pediatric bronchoscope positioned parallel to the stent-loaded catheter. Balloon inflation at up to 7.5 atmospheres deployed the stent and dilated the stricture. Long term (4-12 months) airway patency and early epithelization has been documented by fiberoptic bronchoscopicy. No cases of prosthetic infection erosion, or endobronchial bleeding have occurred. No serious immediate compications have occured. In tlo patients the initial site of stent deployment was subopfimal and the stents were removed brochoscopically, and a new stent was deployed in the correct location. After stenfing all patients reported a significant reduction in dyspnea and improved secretion clearance. The mean FEVI in this group improved from 1.14L to 1.75L (±0.51 p=<.05). Tao patients required additional stent placement either distal or proximal to the first stent. One patient with extreme bronchomalacia required stent replacement due to stent migration into a proximal airway. In lung transplant patients who develope airway stenosis the Palmaz-Schatz stent is a safe, effective, and relatively simple method to immediately restore and maintain airway function.

1152S

Title: OPEN LUNG BIOPSY RESULTS IN LUNG TRANSPLANTS T Todd, T Winton, A deHoyos, D Chamberlain, Author(s):C Chaparro', J Maurer. Univ. of

S Kesten, Toronto, Toronto, Canada. The Toronto Lung Transplant Program has performed 153 transplants in 144 recipients; 53 single (S) and 100 double (D). During this time 33 (21% recipients) underwent 38 open lung biopsies (OLB); 24 S, 14 D-1 1 in the perioperative period (< 45 days) for persistent infiltrates, and 27 late. Indications for OLB were: perioperative period (11), acute or progressive pulmonary disease with clinical findings or progressive loss of pulmonary function (18), persistent poor graft function (3), presence of masses or nodules (3), persistent pulmonary infiltrates without functional loss (2), and presence of persisternt BAL lymphocytosis without other diagnosis (1). 28 transbronchial biopsies (TBB) were done pre-OLB and discrepant findings were found in 20, resulting in a change in therapy in onty 9 (32.1%). The OLB resulted in a change in treatment in 9, confirmed the diagnosis in 11, suggested a diagnosis in 2 and yielded no new data in 16. Of the 9 changes in therapy, 8 were performed late (8/27=29.6%) and 1 was performed perioperatively (1/1 1 9%). 24 patients have died, 22 of them 10 to 105 days after OLB. We reviewed 21 autopsy reports with three giving a new diagnosis (disseminated aspergillus (2) and disseminated Candida infection (1). Deaths were at 11, 20 and 105 days following OLB. OLB complications occurred in 3 (9%) patients: prolonged air leak with resulting empyema and Claggett procedure (2) and hemothorax requiring thoracotomy (1). We conclude that OLB is of little value in the perioperative period but yields useful information in approximately 30% a patients when performed late.

PREVALENCE OF THE HEPATOPULMONARY SYNDROME IN LIVER TRANSPLANT CANDIDATES: DETECTION BY PHYSIOLOGIC SHUNT STUDY AND BY CONTRAST-ENHANCED ECHOCARDIOGRAPHY. Lange PA, Rodriguez L, McCarthy K, Thomas J, Stoller JKI

The Cleveland Clinic Foundation, Cleveland, Ohio The hepatopulmonary syndrome (HPS) is characterized by the triad of inpaired arterial oxygenation, hepatic dysfunction, and the preselice of intrapulmonary vascular dilatations (IPVDs). Because available estimnates of the prevalence of the HPS among patients with chronic liver disease vary greatly (I13% to 47%), the current study was undertaken to ascertain the prevalence of lIPSin a series of 92 consecutive liver transplant (LTx) candidates referred to the Cleveland Clinic Foundation. Because detection of IPVDs has been achieved both by physiologic nieasuremnent of anatomic shunit and by visualizing right-to-left shunt with conitrast-enlhanced echocardiography (CEEl), the curTeiit study assessed the prevalenice of IPVDs using botli tecluiques. Methods: Ninety two conisectutive paticents (pts.) withi clhroiic liver disease referred for considerationi of Llx were stuidied. Sixty four pts. uniderweiit assessiiienit of anatomic shunt by breadting 100% oxygen (using an equation that assunsed an arterial-venous oxygen contenit difference of 5 volunes %) and by CEEl with injectioln of lsnd-agitated saline. rests were considered positive wheni the measiured shunt fraction exceeded 5% anid wheni CEE showed mnicrobubbles in the lell atnum aind/or ventricle 3 to 6 cardiac cycles aufer inijectioni. Results: Of the 64 patients that had shunt assessmenit by boLh teclusiques, 39% laid IPVDs based on the 100% 02 slhunt study and 30% had positive CEE. Detectioln of IPVDs by shunt study and CEEl was sometimes discrepamut, 23% bad normal CEll but positive shunt studies and 14% lad normal shunt studies btt positive CEE. Conclusions: llie prevalence of IPS depenids on the melhod tised to detect intrapulmonary vascular dilatationis anud varied froni 30% to 39% iu this series. Ino the extent that available nomiiograms overestimate the true arterial-venious oxygeni contentt difference ili patieiits with liver disease, shlunt stutdies inay iuiderestillate the despite prevaleisce of 1IVI)s. I lowever, the detectioni of lPVDs by sliult estimnates niornial contrast-enhanced eclhocurdiogranis emphasizes the disparity between 1)hysiologic anid iinaitgimig detection of IPVI)s

Abstracts, 60th Annual International Scientific Assembly