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Original Article

Transfusion-related acute lung injury: lack of recognition because of unawareness of this complication?

Kram, R.1; Loer, S. A.1

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European Journal of Anaesthesiology: May 2005 - Volume 22 - Issue 5 - p 369-372
doi: 10.1017/S0265021505000633
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Abstract

Transfusions of blood components can trigger immunological reactions which may result in a transfusion-related acute lung injury (TRALI). The reported incidence of TRALI is low, between 0.01% and 0.3% per unit transfused [1-9]. There is, however, increasing and convincing evidence that the true incidence may be much higher [1,4,7,9]. Thus, it is likely that TRALI is underdiagnosed and underreported, mainly because the symptoms are non-specific and many cases show mild to moderate effects on pulmonary function, which are not primarily associated with TRALI. A recently published look-back evaluation revealed that many previous recipients of donations from a single plasma donor with antibodies against leukocyte antigen had shown pulmonary reactions which had been documented, although not attributed to the transfusion [10].

A further reason for underdiagnosing TRALI may be a deficit of knowledge about this complication among clinicians working on intensive care units (ICU). Although TRALI has received more attention in recent years, we hypothesized that many clinicians are unaware of this complication and have an inadequate level of knowledge concerning TRALI. Therefore, we studied the knowledge about this complication using a confidential questionnaire which asked questions addressing the definition, incidence, pathophysiology, clinical symptoms, therapy and outcome of TRALI.

Methods

A total of 65 clinicians working on ICU of an university hospital were asked to complete a confidential questionnaire designed to evaluate their knowledge concerning TRALI. This questionnaire consisted of 13 questions which could be answered as ‘yes’, ‘no’ or ‘do not know’ (Table 1). The questions addressed common knowledge about the definition, incidence, pathophysiology, clinical symptoms, therapy and outcome of TRALI. We did not assess specific aspects related to the underlying immunology. The results are presented as percentages for the individual questions and for the individual clinicians (mean ± standard deviation (SD)). The 95% confidence interval (CI) for the number of correct statements is given. The t-test was used to compare the mean number of correct questions of anaesthetists and other clinicians.

Table 1
Table 1:
Confidential questionnaire about TRALI.

Results

The questionnaire was completed by all 65 physicians (34 anaesthetists, 24 surgeons and 7 internists) which were included in this survey. The median length of time in medical practice was 4 yr (range 2-12). Only 42 ± 18% of all answers were correct, while 33 ± 17% were wrong and 25 ± 8% unanswered (‘do not know’). The 95% CI for the correct answers ranged from 30.8% to 53.8% implying that there was no significant difference compared to the probability of arbitrary guessing (33.3%). The individual proportions of correct, incorrect and do not know answers for the 13 questions are presented in Figure 1. The distribution of correct statements for the individual participants is shown in Figure 2. We observed a huge variability in the proportions of correct (range 0-11 questions) and incorrect answers (range 0-9 questions) among the participants of this survey. In addition, we observed a difference in the number of correct questions between anaesthetists (47 ± 19%) and other clinicians (35 ± 20%), P = 0.03.

Figure 1.
Figure 1.:
Proportion of ‘correct’ (black columns), ‘incorrect’ (grey columns) and ‘do not know’ (light grey columns) answers for the 13 questions of a confidential questionnaire about TRALI which was completed by 65 intensive care clinicians. Correct answers: (1) No, (2) No, (3) No, (4) No, (5) Yes, (6) No, (7) No, (8) No, (9) Yes, (10) Yes, (11) No, (12) No, (13) No.
Figure 2.
Figure 2.:
Proportion of correct (black columns) and incorrect (grey columns) answers of 65 clinicians completing a confidential questionnaire about TRALI.

Discussion

TRALI represents one of the most common causes of mortality and serious morbidity resulting from blood transfusions [1-10]. However, there is evidence that many clinicians, remain unaware of this complication because of the non-specific symptoms of TRALI and the mild clinical course of most cases [1,7,10]. In addition, effects on pulmonary function following transfusions may be attributed to other causes and may not be primarily associated with TRALI. A further factor may be unawareness for TRALI among clinicians. We tested the hypothesis that there is a deficit of knowledge about TRALI and asked 65 physicians to complete an anonymous questionnaire with 13 questions which could be answered as ‘yes’, ‘no’ or ‘do not know’. Less than half of all answers (42%) were correct which was not significantly different from arbitrary guessing (33%). Although, anaesthetists had more correct answers than other clinicians, our study uncovered a marked deficit of knowledge about TRALI in all groups. This result implies that the observed lack of awareness for this complication may contribute to the low reported incidence and thus the underestimation of this complication.

The individual questions were designed to test general knowledge about incidence, mortality, pathophysiology, clinical symptoms and therapy of TRALI. The reported incidence is low (question 2) and ranges between 0.001% and 0.1% of all transfusions [1-9]. Mortality following TRALI is estimated to be between 5% and 10% and is lower than the mortality of acute respiratory distress syndrome (ARDS) of other causes (about 50%) (questions 1 and 11) [2-5]. Experimental and clinical observations suggest that TRALI is triggered by a reaction between donor antibodies and recipient leukocytes which are activated in the peripheral blood, and subsequently sequestered within the pulmonary circulation [11-15]. Within the lungs, the activated neutrophils induce endothelial dysfunction with an increase in capillary filtration coefficients. As a result, fluid leaks into the alveoli which is seen as non-cardiogenic bilateral hilar pulmonary oedema. TRALI can be observed after transfusion of red blood cells, platelets, fresh frozen plasma, granulocytes and cryoprecipitate containing antibodies against leukocytes. However, it may be also associated with the transfusion of biologically active lipids that accumulate during storage of blood [16,17]. Products containing large volumes of plasma, for example, fresh frozen plasma, have a higher risk of triggering TRALI than packed red blood cells (questions 3 and 4), especially when the erythrocytes have been washed and most plasma has been removed. However, the immunological reaction occurs independently of the amount of transfused blood components. Even small volumes can trigger this reaction (question 6). TRALI is not related to a volume overload following transfusion, but correlates with hypovolaemia (question 13). Clinical signs and symptoms develop within a few hours (question 7). They include pulmonary oedema, hypoxia, dyspnoea, fever, hypotension and a non-productive cough (question 8). Cardiogenic and other causes of respiratory distress should be excluded. Predisposing clinical conditions, such as hypoxaemia, cardiopulmonary bypass, complement activation or the presence of cytokines and/or adhesion molecules may play an additional role (question 9) [18-20]. As there exists no specific therapy for TRALI, (question 10) treatment is symptomatic as for other causes of ARDS. In contrast to other forms of ARDS, however, clinical signs improve within 48-96 h and mortality is lower (about 5-10% vs. 40-50%) (question 12) [1-5]. There is no evidence that the incidence of TRALI is increased by repetitive transfusions of blood products (question 12).

Our survey was conducted in a large teaching hospital among residents and clinicians involved in intensive care work. There was a small number of clinicians interviewed, from several different parent specialities and all working in the same university hospital. Therefore, it is difficult to extrapolate our results to other populations of physicians, other hospitals or to the general medical community. Nevertheless, our study suggests that there is a lack of knowledge about TRALI which may contribute to underdiagnosing of this transfusion complication. TRALI should be always included in the differential diagnosis of respiratory distress when blood components have been transfused. Any respiratory distress occurring during or following transfusion of blood or blood components should alert the responsible physician that TRALI may have occurred. We are convinced that with increasing awareness of this condition the number of diagnosed cases will increase.

References

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Keywords:

RESPIRATORY DISTRESS SYNDROME; ADULT; acute lung injury; BLOOD TRANSFUSION; adverse events; CRITICAL CARE

© 2005 European Society of Anaesthesiology