Fibrin Glue for Persistent Pneumothorax in Neonates Shikha Sarkar, MD Naveed Hussain, MBBS Victor Herson, MD INTRODUCTION Fibrin glue is a biologic tissue adhesive found to be an effective sealant and topical hemostatic agent. 1,2 It consists of concentrated fibrinogen and factor XIII combined with thrombin and calcium to form a coagulum. This preparation stimulates the final stage of clotting cascade, producing a fibrin clot from fibrinogen in the presence of calcium within seconds after administration of the thrombin - activating solution. 3 Some products include antifibrino- lytic agents to prevent clot lysis. Fibrin glue has been used clinically in newborns to achieve hemostasis at cannulation sites in ECMO patients and to seal postoperative thoracic duct leak. 4,5 Fibrin glue has also been used successfully to treat intractable pneumothorax (PTX) in premature infants, but the literature is limited to single case reports. 6,7 This report documents the response to therapy and associated complications in a series of eight infants treated with fibrin glue for PTX persisting despite conventional management. METHODS Using computerized databases from two tertiary neonatal intensive care units comprising a single teaching program (John Dempsey Hospital and Connecticut Children’s Medical Center), patients admitted from 1990 to 2001 with PTX were identified. From this cohort, patients with persistent PTX treated with fibrin glue therapy were identified and a detailed chart review was then performed, focusing on the PTX and its management, treatment with fibrin glue, and post-fibrin glue responses including complications. Parental verbal or written informed consent was obtained prior to the initiation of fibrin glue therapy. The protocol for the fibrin glue application in each institution was based on the method described by Berger and Gilhooly. 7 A 16 - or 18 - gauge angiocath was inserted into the pleural air pocket and the chest tube( s ) was briefly clamped. The contents of two separate syringes — the first containing thrombin (5000 U) and 10% calcium chloride (5 ml total), and the second containing the source of fibrinogen (either cryoprecipitate or commercially available protein concentrate) with or without an antifibrinolytic agent (aprotinin) (5 ml total) — were injected into the pleural air pocket in rapid succession. The chest tube( s ) was unclamped after 3 to 5 minutes. RESULTS Eight infants (five boys, three girls) with intractable PTX despite conventional management (chest tube drainage, low lung volume strategy, positioning with the affected side down, and high - frequency oscillation) receiving a total of 10 fibrin glue treatments were identified. These eight patients represent 1.25% (8/636) of all patients with PTX in either NICU during this same time period. Among infants equal to or less than 1500 g ( N =2475), 150 (6.1%) developed PTX and seven of these (4.7%) were treated with fibrin glue. The median birth weight was 635 g ( range 440 – 3455 g ) and the median gestational age was 24.5 weeks (range 24–39 weeks). Fibrin glue was used when the PTX had persisted for an average of 9.8 days (range 8–16). Seven of the eight infants had respiratory distress syndrome and one had pneumonia as the underlying diagnosis. None of the patients had clinical evidence of pulmonary hypoplasia. Details of each case are shown in Table 1. Six of the eight infants had a reduction or resolution of the air leak within 24 hours, both clinically and radiographically, with discontinuance of the chest Fibrin glue was used to treat significant pneumothoraces persisting for an average of 10 days in eight newborns. Six of the eight infants had reduction or resolution of persistent air leak within 24 hours of therapy. Two infants received a second course of therapy for recurrences. Complications encountered were bradycardia requiring manual ventilation ( N =2), significant hypercalcemia ( N = 2 ), diaphragmatic paralysis ( N =2), pneumothorax ( PTX ) on the contralateral side ( N = 1 ), and localized tissue necrosis ( N = 1 ). Fibrin glue is an effective treatment for intractable PTX but has significant risks. Journal of Perinatology (2003) 23, 82 – 84 doi:10.1038/sj.jp.7210852 Department of Pediatrics ( S.S., N.H. ), Division of Neonatal – Perinatal Medicine, University of Connecticut School of Medicine, Farmington, CT, USA; and Department of Pediatrics ( V.H. ), Division of Neonatology, Connecticut Children’s Medical Center, 282 Washington Street, Hartford, CT, USA. This paper was presented as a poster at the American Academy of Pediatrics meeting, San Francisco, 2001. The authors have no conflict of interest and have no financial obligations to disclose. No reprints requested. Address correspondence and reprint requests to Victor Herson, MD, Division of Neonatology, Department of Pediatrics, Connecticut Children’s Medical Center, 282 Washington Street, Hartford, CT 06106, USA. Perinatal/Neonatal Case Presentation & & & & & & & & & & & & & & 82 Journal of Perinatology 2003; 23:82 – 84 #2003 Nature Publishing Group All rights reserved. 0743-8346/03 $25 www.nature.com / jp