Open Lung Biopsy in Pediatric Patients on Extracorporeal Membrane Oxygenation By Sheldon
David J. Lee, Dan L. Stewart, Louisville, Kentucky
0 Open lung biopsy has proven beneficial in the treatment of life-threatening pulmonary diseases. Its safety and efficacy in infants and children placed on extracorporeal membrane oxygenation (ECMO) for severe respiratory failure is not known. The authors reviewed eight cases (4 neonates, 3 infants, 1 child) who underwent open lung biopsy while on ECMO. The primary diagnoses were pneumonia (4), lymphoma (I), primary pulmonary hypertension (I), and complex congenital heart disease (2). The patients underwent biopsy after they had been on ECMO an average of 9.6 days (range, 1 to 14 days). Biopsy results confirmed the clinical diagnosis in five patients, two of whom had irreversible alveolar destruction resulting in ECMO withdrawal. Three patients had pathological diagnoses, which resulted in major therapy revisions (1 fungal infection and 2 noninfectious lesions that required steroid treatment). The overall average duration of ECMO treatment was 16.3 days (range, 10 to 24 days). Three patients were weaned successfully from ECMO, but only one infant survived to discharge. One nonlethal bleeding complication occurred after biopsy. Open lung biopsy is well tolerated during ECMO. It accurately determines pulmonary pathology and provides valuable prognostic information. Earlier biopsy for patients whose diagnoses are uncertain or who are not responding to ECMO may improve the mortality rate for this high-risk group. Copyright D 1996 by W.B. Saunders Company INDEX WORDS: genation.
there have been no reports of its safety or efficacy in patients whose refractory respiratory failure has required extracorporeal membrane oxygenation (ECMO). Therefore, we reviewed our use of open lung biopsy in both neonatal and pediatric patients on ECMO to determine its usefulness and morbidity. AND METHODS
We reviewed the charts of all neonatal and pediatric patients who had an open lung biopsy during ECMO between January 1989 and January 1995 at Kosair Children’s Hospital, Louisville, KY. Open lung biopsy was considered for patients whose diagnosis was
From the Departments of Surgery, Pediattics, and Pathology, School of Medicine, University of Louisville, and Kosair Children’s Hospital, Louisville, KY. Address reprint requests to Sheldon J. Bond, MD, Kosair Children s Hospital, PO Box 35070, Pediatric Surgery (Box 81), Louisville, KY 40232.5070. Copyright Q 1996 by W.B. Saunders Company 0022-346819613110-0010$03.00l0 1376
uncertain or who did not respond after 10 days of cardiopulmonary support with ECMO. The site of biopsy was chosen as the area of greatest suspected pathology demonstrated on routine chest x-ray. If equal in both lung fields, the left side was chosen. All biopsies were performed through standard anterior or posterolateral thoracic incisions. The lung edge was secured with running chromic sutures. All patients received heparin (dose of 20 to 40 U/kg/h) for anticoagulation. Activated clotting times (ACTS) were maintained at 180 to 200 seconds. Platelet infusions were administered to keep platelet counts above 100,000/min3. Neither Amicar (Lederle, Wayne, NJ) nor aprotinin was used. The age, gender, weight, admission diagnosis, and clinical course before biopsy were recorded. The timing of open lung biopsy relating to ECMO cannulation, clinical and pathological diagnoses, and treatment changes instituted based on biopsy results were noted. Biopsyrelated complications and the amount of blood loss after the biopsy were documented. Biopsy specimens were injected with 10% buffered formalin using a 27-gauge needle and then immersed in the formalin. Specimens for light microscopy were processed in paraffin, cut at 6pm intervals, and stained with H&E. Additional standard stains and immunocytochemistry were performed for infectious agents. Masson trichrome stain and Verhoeff’s elastic stains were used selectively. Portions of each specimen were fixed in 3% glutaraldehyde and processed for electron microscopic examination.
PEN LUNG BIOPSY is a safe and useful procedure in the management of adult and 0 pediatric lung disease. l-7 Despite its frequent use,
and John J. Buchino
Two hundred thirteen patients required ECMO during this 6-year period. Eight patients had undergone open lung biopsy while on ECMO. Four patients were less than 1 month of age, three were between 1 month and 1 year of age, and one was 11 years old. Five patients initially were believed to have infectious diseases (3 respiratory syncytial virus pneumonia, 1 herpes simplex virus pneumonia, 1 beta-hemolytic streptococcal sepsis). Two patients with underlying cardiac defects were placed on ECMO postoperatively. One infant had repair of total anomalous pulmonary venous return, and the other was a heart transplant recipient. The 11-year-old patient had non-Hodgkin’s lymphoma. All but one patient had the biopsy late in the ECMO course, because of failure to improve while on ECMO. The mean time from ECMO cannulation to open lung biopsy was 9.6 days (range, 1 to 14 days). One patient, the 11 year old with non-Hodgkin’s lymphoma, underwent the biopsy within 24 hours after being placed on ECMO, due to pneumonia of an unknown cause. Of the eight infants and children who underwent open lung biopsy on ECMO, five had pathological findings that confirmed the clinical diagnosis; the other three had pathologically discordant diagnoses Journaloffediatric
No 10 (October),
1996: pp 1376-1378
(Table 1). S’g 1 nl‘fi cant therapeutic changes were instituted in patients whose clinical and pathological diagnoses were discordant. Of the five whose clinical diagnoses were confirmed, two biopsies showed pathological processes so severe that they were felt to be irreversible. After discussion of the pathological results with the families, ECMO support was discontinued. These lungs demonstrated several concurrent processes including marked hypertensive changes, interstitial fibrosis, alveolar spaces filled with macrophages, lymphatic distension, and focal hemorrhage (Fig 1). Pulmonary hypertension was judged irreversible when there was muscular hypertrophy of the pulmonary arteries as well as muscularization of the small lobular arteries, veins, and venules. Scattered venous fibrin thrombi were present in these cases as well. In three patients whose lung biopsies correlated with their clinical diagnoses the pathology was judged to be at least potentially reversible, and ECMO support was continued. Only 1 patient had significant bleeding, which was easily supported by transfusion therapy and did not contribute to outcome. The overall mortality rate was 88%. Three of the eight patients were weaned from ECMO, and two of the eight were weaned from the ventilator. Only one survived to hospital discharge and is the sole longterm survivor. Table
1. Clinical and Pathological Diagnoses for Patients Underwent Open Lung Biopsy During ECMO Clinical Diagnosis
HSV pneumonia, irreversible
Necrotizing monitis, Reversible
fibrosis, thrombosis, RSV+ Pulmonary HTN,
irreversible Pulmonary HTN,
tation PPHN, 9roup
sepsis RSV pneumonia
Bronchiolitis obliterans Invasive Candida
pneumonia ARDS, radiation pneumonitis
N&V Treatment ECMO withdrawn
Steroids Amphotericin Steroids
petted pulmonary infection Abbreviations: HSV, herpes virus; TAPVR, total anomalous tent pulmonary hypertension
simplex virus; RSV, respiratory syncytial pulmonary venous return; PPHN, persisof the newborn; ARDS, adult respiratory
distress syndrome. *Weaned from ECMO. tsurvived to hospital discharge.
Fig 1. Histopathology and irreversible pulmonary
of a patient with diffuse alveolar fibrosis (H&E, original magnification
Open lung biopsy continues to be a valuable diagnostic modality in the treatment of adult,1-3 and pediatric’-’ respiratory disease. It has proven efficacy in establishing an accurate diagnosis with minimal morbidity. Foglia’s series6 of 26 open lung biopsies performed on immunocompromised children with interstitial pneumonia demonstrated that biopsy results prompted treatment changes in the majority of patients. Also, the change in therapy was associated with survival in 60%.6 Gurgurangan et al4 found that open lung biopsy altered the therapeutic strategy in 14 of 18 children with no procedure-related morbidity, and they recommended early use of open lung biopsy especially in immunocompromised children.4 Open lung biopsy also has been shown to be of benefit in critically ill premature neonates when the exclusion of an infectious cause allows the institution of steroids to reverse the ongoing fibrosis of bronchopulmonary dysplasia.5 There have been few reports of patients undergoing lung biopsy during ECM0.8,9 Early experience in adults demonstrated its feasibility as a means of documenting pulmonary fibrosis, after which the ECMO was discontinued.8 Ombrellaro et al reported successful use of open lung biopsy in an 11-month-old boy who required ECMO when respiratory distress complicated a burn injury.9 However, we were not able to find a published study of pediatric cases that examines the role of open lung biopsy in the management of patients on ECMO. Our experience indicates that open lung biopsy is safe and that it improves the diagnostic accuracy of pulmonary pathology in infants and children who are undergoing ECMO therapy. Of the eight children in the present series, three had histopathological findings that differed from their clinical diagnosis. Of the five with concordant pathological and clinical diag-
noses, two had irreversible fibrosis, and ECMO was discontinued. Therefore, significant therapeutic changes were made based on open lung biopsy results in five of the eight patients. Our results are similar to those noted in previous studies of neonatal and pediatric open lung biopsy.4-6 Possible complications of open lung biopsy in the critically ill patient include hemorrhage, persistent air leak, and sampling error. Patients who undergo surgical procedures while on ECMO have a high risk for postoperative bleeding because of the need for systemic heparinization. 1°J1In our series, one patient had bleeding that required transfusion, but it did not cause hemodynamic instability or affect the eventual outcome. The patient was weaned from ECMO and ventilator support, but did not survive to hospital discharge. Aminocaproic acid may prove helpful in decreasing such hemorrhagic complications.12 We have not entertained the possibility of bronchoscopy and endobronchial brushing but feel that the diagnostic potential would be limited by sample size and that bleeding complications would be more difficult to control than with open lung biopsy. Air leaks and bronchopleural fistulae did not occur in our patients. They are not likely to occur in patients on ECMO because pulmonary inflating pressures tend to be low, which allows the lungs to recover without additional
barotrauma. This is in direct contrast to lung biopsies obtained before ECMO cannulation, when air leaks are more common because of the high inflating pressures necessary to maintain oxygenation. The loss of positive end-expiratory pressure (PEEP) caused by an air leak can result in further clinical deterioration.13 Sampling error is inherent in any biopsy. It can be minimized by selecting the most seriously affected lung sample that is safely accessible. Our mortality rate is disappointing, especially in light of the therapeutic changes instituted because of the biopsy result. Most patients in our series had long courses of ECMO without improvement in pulmonary function before biopsy. Performing the open lung biopsy earlier in the course of ECMO may have improved the overall survival rate; however, the irreversible pathological changes that limited therapy in others may not have been apparent. The most appropriate timing for open lung biopsy needs further clarification. We recommend open lung biopsy on ECMO in infants and children whose diagnosis is uncertain. In our series the lung biopsy was well tolerated and provided valuable diagnostic information. The benefits of tissue diagnosis appear to outweigh the risks of biopsy.
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