Jan 10, 1995 - Transfusion-related acute lung injury (TRALI) is a rare but life-threatening complication of haemotherapy that has only recently gained ...
Eur J Pediatr (1996) 155 : 589-591 9 Springer-Verlag t996
Tzong-Jin Wu Ru-Jeng Teng Kuo-Inn Tsou Yau
Received: 10 January 1995 Accepted: 17 October 1995
T.-J. Wu 9R.-J. Teng (N~) K.-I. Tsou Yau Department of Paediatrics, National Talwan University Hospital, No.7, Chong San South Road, Talpei, Taiwan, 10016, Republic of China Tel.: 8862-397-0800, ext. 2408 Fax: 8862-341-2598
Transfusion-related acute lung injury treated with surfactant in a neonate
Abstract A term, m a l e neonate sudd e n l y d e v e l o p e d respiratory distress and severe c y a n o s i s w h i l e u n d e r g o ing e x c h a n g e transfusion for hyperbilirubinaemia. Transfusion-related acute lung injury was diagnosed. Because o f persistent h y p o x a e m i a despite a g g r e s s i v e treatment, two doses o f surfactant were administered, resulting in m a r k e d i m p r o v e m e n t .
Introduction Transfusion-related acute lung injury ( T R A L I ) is a rare but life-threatening c o m p l i c a t i o n o f haemotherapy that has only r e c e n t l y g a i n e d recognition. T h e clinical presentation o f T R A L I is indistinguishable from adult respiratory distress s y n d r o m e ( A R D S ) resulting from causes other than transfusion such as sepsis and m u l t i p l e t r a u m a [9, 14]. C o n s i d e r i n g the existence o f surfactant abnormalities in respiratory failure not related to respiratory distress synd r o m e (RDS), potential benefits o f surfactant r e p l a c e m e n t were s u g g e s t e d [2, 6, 7, 16] and h a v e b e e n reported to be successful in several clinical trials [1, 4, 5, 8, 10, 15, 17-20]. W e report here a rare occurrence o f T R A L I in a neonate and its successful treatment with surfactant.
Case report A male baby was delivered via Caesarean section by a 31-year-old woman gravida 1, para 1, blood group B, at the gestational age of 41 weeks with a birth weight of 3834 g. The mother had received regular prenatal care and the pregnancy course was uneventful. The infant cried vigorously at birth and both the 1 min and 5 min Ap-
K e y w o r d s Transfusion-related acute lung injury 9 Surfactant Neonate
Abbreviations ARDS adult respiratory distress s y n d r o m e 9 RDS respiratory distress s y n d r o m e . TRALI transfusion-related acute lung injury
gar scores were 9. The physical characteristics were normal, and feeding at 4 b of age was satisfactory. The baby's blood group was B. However, jaundice developed within a few hours of birth, and the serum bilirubin rose rapidly from 8 mg/dl to 12 mg/dl over a period of 2 h while undergoing intensive phototherapy. Complete investigations for hyperbilirnbinaemia were performed, including Rhesus (C, D, and E) blood group incompatibility, direct and indirect Coombs' tests, serology for TORCHES infections, as well as cultures of blood, urine, and CSF, but were all negative. Isovolaemic exchange transfusion with type B, fresh whole blood was then started at 12 h of age. However, irritability and respiratory distress developed after 92 ml of blood had been exchanged over about 20 rain. Tachycardia, fever, and hypotension were also noted. The patient soon became cyanotic and remained so despite oxygen inhalation and mask bagging. Endotracheal intubation was performed and mechanical ventilation was initiated. Cyanosis persisted even under high airway pressures and 100% oxygen, and the presence of a large amount of pink, frothy sputum was also observed. Results of the laboratory tests showed hypoxaemia, metabolic acidosis, platelet count 54000 rnm3, white blood cell count 5600]mm 3, aspartate aminotransferase 385 U/1 and lactate dehydrogenase 10,900 U/1. Chest Xray revealed diffuse alveolar infiltrates without cardiomegaly and echocardiography showed an estimated pulmonary artery pressure of 60 mm Hg with right-to-left shunting through the foramen ovate. The diagnosis of TRALI with persistent pulmonary hypertension of the newborn was made. Treatment included mechanical ventilation with high positive end expiratory pressure and infusion of dopamine, dobutamine, epinephrine, normal saline, and fresh frozen plasma for maintaining systemic blood pressure. The treat-
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ment included furthermore sodium bicarbonate, magnesium sulphate, as well as dexamethasone t mg/kg per day, antibiotics and anticonvulsants. Due to refractory respiratory failure with alveolar-arterial oxygen tension difference > 630 mm Hg and oxygenation index > 40, two doses of 5 ml/kg of a synthetic surfactant (Exosurf Neonatal) were administered via the endotracheal tube at 23 and 53 h of age after obtaining parental consent. Clinically, the patient responded gradually, as confirmed by the marked improvement in chest Xray, and was subsequently successfully extubated at 85 h of age. Continuous positive airway pressure via nasal prongs was required for 8 days, whereas oxygen inhalation was continued for another 6 days. Dexamethasone was continued for 1 month with gradual reduction. Development of active haemolysis along with hyperbilirubinaemia and haemoglobinuria necessitated two more courses of exchange transfusions at 36 and 43 h of age, which were carried out using type O packed red cells and type AB plasma. Phototherapy was also used for 3 more days. However, cholestasis was observed to develop later, with peak serum total and direct bilirubin levels of 13.7 mg/dl and 6.0 mg/1, respectively. No specific aetiology could be found and jaundice subsided over 3 weeks under ursodeoxycholic acid treatment. Follow up echocardiography at 15 days of age revealed an estimated pulmonary artery pressure of 40 mmHg. Nifedipine was therefore given in an attempt to control the pulmonary hypertension. Pulmonary function test at 17 days of age demonstrated decreased dynamic lung compliance (0.778 _+0.007 ml/cm - H20/kg, normal 1.3-1.5 ml/cm - H20/kg), normal airway resistance (13.68 -+ 0.58 cm - H20/1/s), and normal flow-volume curves, thus suggesting parencbymal lung disease. Although an EEG at 15 days of age showed rare epileptiform discharges in the right frontocentral areas during sleep, the anticonvulsants were discontinued given the absence of clinical seizure attacks. Auditory brainstem evoked potential at 1 month of age was normal. The patient was discharged at 39 days of age with only mild respiratory distress during oral feeding.
Discussion T R A M is a serious complication of haemotherapy. Early reports have used various designations, including transfusion-related noncardiogenic pulmonary oedema, allergic pulmonary oedema, pulmonary leucoagglutinin reaction and pulmonary hypersensitivity reaction, which in fact obscure the underlying mechanism [14]. In 1983, the term T R A L I was first used to associate the passively transfused antileucocyte antibodies with the clinical microvascular pulmonary injury, the incidence being estimated to be 0 . 0 2 % per unit and 0.16% per patient transfused [13]. Published reports on T R A L I are relatively rare, probably due to misdiagnoses, especially as circulatory overload. Several authors have identified serum leucoagglutinating antibodies to be the initiating factors, with almost 90% coming from the donors rather than the recipients. Multiparous women are known to be major sources of the antibody-positive blood components. Under complement activation, C 5 a promotes aggregation and sequestration of neutrophils in the pulmonary microvasculature, which in turn release proteases, acidic lipids, and oxygen radicals, thus causing damage to pulmonary vascular endothelium and subsequently, pulmonary oedema [14].
TRALI, like ARDS, is characterized by acute onset of respiratory distress, level, severe and bilateral pulmonary oedema and severe hypoxaemia, usually within 1-6 h after a transfusion. The normal or low pulmonary wedge pressure and normal central venous pressure exclude the possibility of cardiogenic pulmonary oedema. No specific risk factors, such as sex, age, type of blood components used, or underlying conditions that necessitated the transfusions, have so far been identified. Though ARDS usually entails a high rate of mortality and morbidity, most cases of T R A L I improve within 48-96 h of its onset with adequate treatment. The reported mortality rate is about 5%, and no long-term sequelae have been noted in patients with a rapid recovery [14]. The mainstay in the treatment of TRALI, as well as ARDS, is mechanical ventilation with positive end expiratory pressure. Several pharmacological therapies have been advocated, including corticosteroids, prostaglandin E l, anti-endotoxin antibodies, non-steroidal anti-inflammatory drugs, anti-tumour necrosis factor antibody, and pentoxiphylline, but definite benefits have not been established as yet [9]. Abnormalities of surfactant quantity and quality in respiratory failure caused by diseases other than RDS have been reported by many authors [2, 6, 7, 16]. In addition to the successful surfactant therapy for neonates with RDS a primary deficiency of surfactant, several preliminary trials have also reported encouraging results of exogenous surfactant in treatment of disorders involving secondary surfactant deficiency, such as ARDS, meconium aspiration syndrome, and persistent pulmonary hypertension of the newborn [1, 4, 5, 8, 10, 15, 17-20]. Most authors have suggested surfactant replacement in patients suffering from severe respiratory failure, although the long-term outcome of this treatment is still unknown. In the present case, the patient developed acute respiratory failure and non-cardiogenic pulmonary oedema 20 rain after initiation of an exchange transfusion with fresh whole blood and the chest X-ray showed diffused alveolar infiltrates. Though leucoagglutinating antibodies were not detected in either donor or recipient serum due to unavailability of proper facilities, the clinical presentations were typical of TRALI. Reviewing the literature, however, only one case of T R A L I in a neonate has been reported so far, wherein the antibodies from transfused plasma and antigens on the transfused granulocytes were implicated [11]. Considering the poorer prognosis of ARDS in paediatric patients [3, t2], neonates with T R A L I are likely to have a higher possibility of mortality and morbidity despite the generally good outcome in adults. Transfusion therapy is commonly employed in neonatal intensive care, especially in extremely premature infants. However, the risk of TRALI should not be overlooked, and early recognition and prompt treatment help to improve the prognosis. The response of the present patient to surfactant was satisfactory, showing a rapid improvement in clinical condition as confirmed by chest X-ray findings. This result
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thus supports the previous reports of effective surfactant therapy for respiratory failure due to diseases other than RDS. Despite persistent infiltrates observed on the chest X-ray, decreased lung c o m p l i a n c e and mild p u l m o n a r y hypertension at discharge, the patient was virtually asymptomatic. L o n g - t e r m follow up is h o w e v e r required to evaluate the n e u r o d e v e l o p m e n t a l and c a r d i o p u l m o n a r y outcomes.
In summary, T R A L I is a rare but serious complication of transfusion therapy, even in neonates, who are likely to be more v u l n e r a b l e to adverse outcomes. A d e q u a t e and prompt treatment is extremely important. Besides ventilatory support with positive and expiratory pressure, surfactant replacement therapy m a y also be a beneficial alternative.
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