Management of transfusion-related acute lung injury with extracorporeal cardiopulmonary support in a four-year-old child

S. M. Nouraei*,1, J. P. Wallis2, D. Bolton1 and A. Hasan1

1 Regional Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK. 2 Department of Haematology, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK

Corresponding author: smnouraei@yahoo.co.uk

Accepted for publication: March 3, 2003


    Abstract
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
We report a case of successful management of transfusion-related acute lung injury (TRALI) with prolonged cardiopulmonary bypass support in a 4-yr-old patient undergoing elective cardiac surgery. TRALI was diagnosed clinically and immunologically by detection of reactive antibodies in a unit of fresh frozen plasma that had been administered to the patient. The aetiology and management of TRALI are briefly discussed and possible implications of this case for the management of TRALI are highlighted.

Br J Anaesth 2003; 91: 292–4

Keywords: complications, transfusion-related acute lung injury; surgery, cardiovascular


    Introduction
 Top
 Abstract
 Introduction
 Case report
 Discussion
 References
 
Transfusion-related acute lung injury (TRALI) is a serious complication of blood or blood product transfusion, being the third commonest cause of transfusion-related fatality in the USA.1 It occurs after transfusion of plasma-containing products, as a result of cross-reaction between donor antibodies and host leucocytes2 or, less commonly, between host antibodies and donor leucocytes.3 Post-mortem histology has been reported to show massive pulmonary oedema and granulocyte aggregation within the pulmonary vasculature.4 The clinical picture is of oxygen desaturation emerging within 6 h of transfusion, and mortality between 5 and 15%.5 Patients surviving the acute episode make a full recovery. Clinical management consists of oxygen therapy and mechanical ventilation with PEEP if necessary.

We present a case of TRALI in a 4-yr-old cardiac patient, which was refractory to standard therapy but was successfully managed with prolonged cardiopulmonary bypass support. To our knowledge, this is the first report of successful management of TRALI with extracorporeal oxygenation.


    Case report
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
A girl aged 4 yr and 10 months underwent elective cardiac surgery for replacement of her right ventricular conduit following a Ross procedure when aged 3 months. She was born with coarctation of the aorta, which was repaired at 11 days, and subaortic stenosis.

At 4 yr and 7 months she was noted to have a puffy face, and ankle and abdominal swelling, and to be reluctant to run, play or climb the stairs. Examination revealed bilateral pedal oedema to mid-calf, a distended abdomen and elevated jugular venous pressure, but no shortness of breath. The patient received furosemide and was referred for echocardiography and cardiac catheterization, which revealed high right ventricular conduit velocity (5 m s–1) and a high right ventricular pressure (70/6 mm Hg) respectively, caused by the narrowing of the conduit base. This was attributed to the patient outgrowing the conduit, and arrangements for elective replacement of the conduit were made.

At operation, the cardiopulmonary bypass circuit was primed with 2 units of leucocyte-depleted fresh frozen plasma (FFP), plus crystalloid, and the patient received 1 unit of packed red cells, also leucocyte-depleted, during the procedure. The operation was completed successfully and a transoesophageal echocardiogram, performed on the operating table immediately at the end of the operation before cessation of bypass, showed normal cardiac function with excellent conduit placement and function. Cardiopulmonary bypass was easily weaned after 97 min, with normal oxygen saturation and arterial oxygen tension. Five minutes later, however, ventilation became increasingly difficult, and she became severely hypoxic with massive pulmonary oedema on tracheal tube suction. Albumin concentrations of plasma and pulmonary exudates were 6 and 10 g litre–1 respectively. No haemodynamic cause was found for her frank pulmonary oedema. Left ventricular function remained normal on repeat transoesophageal echocardiography, with a right atrial pressure of 7 cm H2O, right ventricular pressure of 47/9 mm Hg (preoperative value 70/8 mm Hg) and an aortic pressure of 91/51 mm Hg obtained using direct needle measurements. Cardiopulmonary bypass was reinstituted and, because there was no evidence of early lung resolution, cardiopulmonary bypass was continued and eventually weaned after 893 min.

Post-bypass ventilation with an initial PEEP of 14 cm H2O and FIO2 of 0.8 were required to maintain the arterial oxygen tension above 10 kPa. These were weaned after 7 days. The patient made an uneventful recovery and was discharged home 8 days later.

The units of FFP were investigated for antibodies against recipient leucocytes and HLA tissue type, as such antibodies are thought to be causative in cases of TRALI. One of the FFP units, from a multiparous female donor, was found to contain antibodies against HLA class I antigens A2 and A9, and against HLA class II antigen DR4. The patient was found by HLA typing to carry antigens A2 and DR4. No neurophil-specific antibodies were found. A clinical and immunological diagnosis of TRALI was therefore made.

The patient is now very well and is able to run and participate normally in school activities. She will receive all future transfusions from untransfused male donors, as they have the lowest incidence of antigen exposure from fetuses or from allogenic transfusions, and therefore have the lowest chance of harbouring anti-leucocyte antibodies.


    Discussion
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
First described in the 1950s, TRALI was highlighted in 1985 with publication of the first large case series.6 Its fulminant presentation is similar to acute respiratory distress syndrome (ARDS), but, unlike ARDS, if not fatal it often resolves within 96 h with no permanent respiratory sequalae.5 Experimental and clinical evidence suggests that TRALI results from the reaction of donor antibodies with recipient leucocytes. HLA class II and class I antibodies, especially anti-HLA A2, are the commonest culprits.2 This case bears the classic hallmarks of TRALI in that the patient developed severe pulmonary oedema with massive pulmonary exudation and arterial oxygen desaturation soon after transfusion of a unit of leucocyte-depleted FFP, which was subsequently shown to contain HLA antibodies matching the recipient’s phenotype. This patient will receive all future transfusions from untransfused male donors, as they have the lowest incidence of antigen exposure from fetuses or allogenic transfusions, and therefore of anti-leucocyte antibodies.

The differential diagnosis includes cardiogenic pulmonary oedema and ‘high-flow’ pulmonary oedema as a result of increased pulmonary artery pressure. These were excluded on the evidence of normal cardiac function and perioperative right atrial and right ventricular chamber values obtained by direct needle measurements.

Our case is unique among reported cases of TRALI in its management with extracorporeal oxygenation. Maximal ventilatory support instituted immediately after the initial cessation of bypass was insufficient to maintain oxygen saturation. Without the timely reinstitution of bypass, the patient would not have survived. After 893 min of cardiopulmonary bypass, ventilation was reinstituted and the patient then maintained adequate arterial oxygen saturation. It appears that this period of bypass was sufficient to allow pulmonary function to recover sufficiently to allow mechanical ventilation, which nevertheless had to be continued for a further 7 days.

Other treatments that have been used for TRALI include high-dose steroids and plasmapheresis.7 There is no evidence that steroids are effective in established disease. Plasmapheresis has been reported in a single case and was associated with clinical improvement 6 days after the initial insult. As most cases show recovery at 24–48 h, it seems likely that plasmapheresis will only be valuable when the antibody titre is very high and there is evidence of continuing damage. At present, it does not form part of the routine management of TRALI.

This case has implications for the management of TRALI in general, as current interventions do not routinely go beyond mechanical ventilation. The fact that this was a cardiac case was fortuitous as it allowed the patient to continue to be supported by extracorporeal oxygenation through the acute episode. Extracorporeal membrane oxygenation has, however, been used in clinical practice for a number of years. It has been used successfully in the management of acute reversible pulmonary failure, such as post-lung transplantation acute respiratory failure.8 The use of extracorporeal oxygenation may be particularly valuable in severe cases of TRALI, as it is a transient condition and the patient is expected to make a full recovery after the acute episode. We therefore recommend that, where facilities exist, extracorporeal membrane oxygenation or cardiopulmonary bypass should be considered seriously in the management of patients with TRALI when conventional treatment is proving insufficient.


    References
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
1 Lee JH. Transfusion-related fatalities. Reports to US FDA: 1990–1998. ABC Newslett October 1, 1999

2 Popovsky MA, Haley NR. Further characterization of transfusion-related acute lung injury: demographics, clinical and laboratory features, and morbidity. Immunohematology 2000; 16: 157–9

3 Bux J, Becker F, Seeger W, et al. Transfusion-related acute lung injury due to HLA-A2 specific antibodies in recipient and NB1-specific antibodies in donor blood. Br J Haematol 1996; 93: 707–13[CrossRef][ISI][Medline]

4 Dry SM, Bechard KM, Milford EL, et al. The pathology of transfusion-related acute lung injury. Am J Clin Pathol 1999; 112: 216–21[ISI][Medline]

5 Popovsky MA, Robertson DD. Transfusion-related acute lung injury: femme fatale? Transfusion 2001; 41: 312–15[CrossRef][ISI][Medline]

6 Popovsky MA, Moore SB. Diagnostic and pathogenetic considerations in transfusion-related acute lung injury. Transfusion 1985; 25: 573–7[CrossRef][ISI][Medline]

7 Dooren MC, Ouwehand WH, Verhoven AJ, et al. Adult respiratory distress syndrome after experimental intravenous gamma-globulin concentrate and monocyte reactive IgG antibodies. Lancet 1998; 352: 1601–2[ISI][Medline]

8 Slaughter MS, Nielsen K, Bolman PM III. Extracorporeal membrane oxygenation after lung or heart–lung transplantation. ASAIO J 1993; 39: M453–6.[Medline]