Distinguishing between transfusion related acute lung injury and

transfusion associated circulatory overload

Robert C. Skeatea and Ted Eastlundb

Purpose of review
The purpose of this review is to provide an overview of
concepts recently presented in the literature that impact our
understanding of transfusion related acute lung injury
(TRALI) and transfusion associated circulatory overload
(TACO), and how to distinguish between the two disorders.
Recent findings
An exceptionally clear review article by Brux and Sachs
clarified the two-hit model of TRALI pathogenesis. The
TRALI definition developed at the 2004 consensus
conference helped demonstrate that TRALI is likely
underreported. Brain natriuretic peptide can be useful in
distinguishing cardiogenic from noncardiogenic pulmonary
edema. Blood centers are implementing male predominant
plasma programs to limit TRALI, and preliminary evidence
suggests that this is a useful intervention.
Summary
TACO and TRALI have emerged as important causes of
posttransfusion morbidity and mortality. As understanding
of their pathogenesis improves, incidence, risk factors,
differences, and possible preventive interventions are
becoming clearer. There is no sentinel feature that
distinguishes TRALI from TACO. Developing a thorough
clinical profile including presenting signs and symptoms,
fluid status, cardiac status including measurement of brain
natriuretic peptide, and leukocyte antibody testing is the
best strategy currently available to distinguish the two
disorders.
Keywords
circulatory overload, diagnosis, TACO, TRALI, transfusion
Curr Opin Hematol 14:682687.
2007 Wolters Kluwer Health | Lippincott Williams & Wilkins.
a
American Red Cross, North Central Blood Services, Saint Paul and bDivision of
Transfusion Medicine, Department of Laboratory Medicine and Pathology,
University of Minnesota Medical School, Minneapolis, Minnesota, USA

Correspondence to Robert C. Skeate, MD, American Red Cross, North Central

Blood Services, 100 South Robert Street Saint Paul, MN 55107, USA
Tel: +1 651 291 3374; e-mail: skeatero@usa.redcross.org
Current Opinion in Hematology 2007, 14:682687
Abbreviations
ALI
HLA
PAC
TACO
TRALI

acute lung injury

human leukocyte antigen
pulmonary artery catheter
transfusion associated circulatory overload
transfusion-related acute lung injury

2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

1065-6251

Introduction
Transfusion reactions can be difficult to evaluate [1].
Determining the correct diagnosis is important because
there are implications for the patient, the donor, and the
other products associated with the involved donation [2].
Pulmonary transfusion reactions can be especially difficult to investigate. The differential diagnosis includes
allergic/anaphylactic reactions, transfusion related acute
lung injury (TRALI), transfusion associated circulatory
overload (TACO), bacterial contamination, and hemolytic transfusion reaction [3]. Particularly troublesome is
the scenario wherein the patient presents with acute
respiratory distress due to pulmonary edema, and the
transfusing physician suspects TRALI versus TACO
[4]. The clinical features are similar, and there are no
diagnostic tests that reliably discriminate. The fact that a
patient could have both simultaneously only adds to the
complexity [5,6,7]. Yet the therapy and management
of the patient, and the implications for the donor of the
two different reactions are completely different.
This paper will review recent articles in the scientific
literature relevant to diagnosing TRALI and TACO, and
to distinguishing between them.

Transfusion associated circulatory overload

Despite the fact that circulatory overload has been a
recognized complication of transfusion for decades, it
still receives relatively little attention in the scientific
literature [8].
There is no universally agreed-upon definition for what
constitutes TACO [9]. During or within several hours of
transfusion, patients develop respiratory distress, and
may develop orthopnea, cyanosis, tachycardia, and hypertension. Rales can be identified on auscultation, and some
patients may have jugular venous distention, an S3 on
cardiac auscultation, or lower extremity edema. A chest
radiograph can reveal cardiomegaly and interstitial infiltrates, but not all patients with heart failure will have
these abnormalities [10].
TACO incidence estimates have ranged from one in
approximately 3000 transfusions to 8% of transfusions
depending upon patient population and reporting method
[5,11]. In a recent retrospective review of 8902 transfusions in 1351 consecutive ICU patients, TACO was identified in one in 356 transfusions [12]. Patients at the

682

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Acute lung injury and circulatory overload Skeate and Eastlund 683

highest risk for TACO include those younger than 3 and

those older than 60 years of age, particularly those with
underlying cardiac dysfunction [13].

cognate antigens. Neutrophil-specific antibodies appear

to be capable of both priming and activating neutrophils,
and can cause TRALI in even healthy recipients [17].

The pathogenesis of TACO is felt to be similar to other

causes of acute congestive heart failure: an increase in
central venous pressure and pulmonary blood volume
causes an increase in hydrostatic pressure leading to fluid
extravasation into the alveolar space [8].

In April of 2004, an international consensus conference

was convened to develop a definition of TRALI [18].
Participants felt that a useful definition of ALI had
already been proposed [19], and they decided to use this
as the basis for establishing the presence of ALI in
candidate TRALI patients. ALI was defined as acute
onset hypoxemia with bilateral infiltrates on chest radiograph, and with no evidence of circulatory overload [20].
Because patients with other risk factors for ALI often
receive transfusions, they created a two-tiered definition:
TRALI and possible TRALI. TRALI is ALI that occurs
during or within 6 h of transfusion, and with no temporal
relationship to an alternative risk factor for ALI (risk
factors for ALI are summarized in [21]). Possible TRALI
is used when there is a clear temporal relationship to an
alternative risk factor for ALI. An important limitation of
this definition is that patients with circulatory overload
cannot be defined as having ALI or TRALI.

Treatment of TACO starts with discontinuing any

ongoing transfusion. Respiratory distress is treated with
the degree of respiratory support needed to maintain the
patients oxygenation. Diuretics are administered to
remove excess fluid. It is common to infuse subsequent
transfusions slowly, but no formal evidence exists that
this is an effective intervention [9].

Transfusion related acute lung injury

TRALI is acute lung injury (ALI) that occurs during or
following transfusion. It has emerged as the leading cause
of transfusion-related fatality reported to the United
States Food and Drug Administration [14].
Recently transfused patients present with respiratory
distress, hypoxemia, rales on auscultation, and diffuse
bilateral infiltrates on chest radiograph. The respiratory
distress can be severe enough to require mechanical
ventilation. Other features include hypotension, fever,
and transient leukopenia. Treatment is with increasingly
aggressive respiratory support depending on the degree
of respiratory distress. Five to 25% of cases are fatal, but
most patients fully recover within 3 days [15,16].
TRALI results from neutrophil-mediated damage to the
pulmonary microvasculature. The current proposed
model is a two-hit hypothesis wherein a primary
stimulus causes neutrophil sequestration in the pulmonary capillaries, and a secondary stimulus causes the
neutrophils to activate, damaging the endothelial layer
such that fluid and protein leaks into the alveolar space
[17]. Neutrophils can be first primed and subsequently activated by pro-inflammatory stimuli present
either in patients with certain disease states, or infused
with blood products.
Patient exposures that can lead to neutrophil priming
include surgery, tissue injury, and infection. Pro-inflammatory stimuli that can be infused with blood products
include neutrophil-specific or anti-human leukocyte antigen (HLA) antibodies, or bioactive lipids. The requirement for both priming and activation of neutrophils
explains why a product from a donor with HLA antibodies may induce TRALI in a surgical patient, and
cause no clinical reaction in a relatively healthy anemic
patient, even if both patients are positive for the relevant

Because a usable case definition was developed only

recently, earlier estimates of the incidence of TRALI
have varied widely [18]. The retrospective review
referred to earlier [12] used the consensus conference
definition of TRALI, and the investigators reported a
TRALI incidence of one in 1271 units transfused, and a
possible TRALI incidence of one in 534 units transfused.
This is a higher incidence than that seen in other studies,
but the authors point out that they investigated each
transfusion event for the possibility of TRALI rather
than depending on the typical passive reporting strategy.
They conclude that their results suggest that TRALI is
an underreported disorder.
The case definition presented above describes a clinical
syndrome. Laboratory studies are available to investigate
TRALI cases, but the participants in the conference felt
they were not specific enough to be included in the
definition [21]. The laboratory tests (testing donors for
neutrophil and HLA antibodies, antigen typing recipients to demonstrate the presence of cognate antigen,
performing donorrecipient leukocyte crossmatches,
testing residual product for bioactive lipids) can be
expensive, are not universally available, and are difficult
to arrange [22]. While results are often not available in a
clinically relevant timeframe for an individual case, they
are very important for the evaluation of the eligibility of
the implicated donor [16], and are proving useful for
efforts to identify and evaluate possible TRALI prevention interventions [23].
The United Kingdoms Serious Hazards of Transfusion
(SHOT) hemovigilance system was founded in 1996 as a

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684 Transfusion medicine and immunohematology

way of tracking transfusion-related complications [24].

Their earlier data suggested that the most frequent
products associated with TRALI were plasma-containing
products from female donors who were positive for leukocyte antibodies [25]. In 2003, SHOT recommended using
only male plasma for plasma products and platelet pools
whenever possible. By 2005, male donors provided 90%
of frozen plasma and 84% of the plasma for platelets.
TRALI cases dropped from 22 in 2003 to six in 2005,
deaths from TRALI dropped from seven to two, and
the number of cases of TRALI from plasma containing
leukocyte antibodies dropped from 10 to zero [25]. The
authors admit that this was not a controlled experiment,
but the data do suggest that use of predominantly male
plasma might decrease TRALI rates.
Investigators from the American Red Cross recently
performed a retrospective review of all TRALI cases
reported to their surveillance system from 2003 to 2005
[23]. Five hundred and fifty cases were examined
including 72 fatalities. A female, leukocyte antibodypositive donor was involved in 71% of the fatalities.
The authors conclude that converting to predominantly
male plasma could be a prudent step towards limiting
TRALI. The American Red Cross and other United
States blood centers are currently involved in efforts to
convert to predominantly male plasma, and this should be
a useful first step in limiting TRALI [26].
Antileukocyte antibodies do not always cause TRALI. A
recent report describes reactions in both recipients of a
split platelet product from a donor who was subsequently
shown to be positive for an antibody directed against one
of the neutrophil-specific antigens (HNA-2a) [27]. One
patient developed dyspnea, chills, and rigors, the other

developed chills and headache, and both developed

significant, transient leukopenia. A lookback was performed on the donors previous 26 donations that resulted
in 39 transfusions. There were 12 mild to moderate
reactions in nine patients. Seventy-five percent of the
transfusions with reactions resulted in leukopenia, and
35% of those without reactions resulted in leukopenia.
This article highlights the fact that antileukocyte antibodies can cause no reaction, or a mild reaction with or
without transient leukopenia. Transient leukopenia is
also seen in severe TRALI related to antileukocyte
antibodies [28].

TRALI versus TACO

While it is clear from the above discussion that our
knowledge of TRALI and TACO is improving, it is still
the case that distinguishing between the two can be quite
difficult. There are features, however, that can help to
discriminate (Table 1).
Clinical presentation

Both TRALI and TACO are clinical diagnoses, and

clinical features can sometimes distinguish between them.
With both, patients present with respiratory distress due to
acute onset pulmonary edema. With TRALI, patients also
often have hypotension and fever, and can have transient
leukopenia. With TACO, one would typically expect
hypertension and a lack of fever and leukopenia. Features
sometimes seen with TACO that would not be expected in
TRALI include jugular venous distention, an S3 heard on
cardiac auscultation, and peripheral edema.
Fluid balance

A careful investigation of the patients fluid balance can

sometimes provide a clue to the underlying diagnosis. In

Table 1 Comparison of the features of transfusion related acute lung injury and transfusion associated circulatory overload
Feature

TRALI

TACO

Body temperature
Blood pressure
Respiratory symptoms
Neck veins
Auscultation
Chest radiograph
Ejection fraction
PA occlusion pressure
Pulmonary edema fluid
Fluid balance
Response to diuretic
White count
BNP
Leukocyte antibodies

Fever can be present

Hypotension
Acute dyspnea
Unchanged
Rales
Diffuse, bilateral infiltrates
Normal, decreased
18 mmHg or less
Exudate
Positive, even, negative
Minimal
Transient leukopenia
<200 pg/ml
Donor leukocyte antibodies present,
crossmatch incompatibility between
donor and recipient

Unchanged
Hypertension
Acute dyspnea
Can be distended
Rales, S3 may be present
Diffuse, bilateral infiltrates
Decreased
Greater than 18 mmHg
Transudate
Positive
Significant
Unchanged
>1200 pg/ml
Donor leukocyte antibodies may or
may not be present, positive results
can suggest TRALI even with true
TACO cases

The typical patterns that would be expected for cases of transfusion related acute lung injury (TRALI) or transfusion associated circulatory overload
(TACO) are represented. Readers are reminded that a given case of TRALI or TACO may lack some of the typical features. Also, a case of TRALI may
have some features suggesting TACO or vice versa, and TRALI and TACO can be present together. The best strategy is to develop a full clinical profile
of the case using the feature list above, and determine which diagnosis is most supported. BNP, brain natriuretic peptide; PA, pulmonary artery.

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Acute lung injury and circulatory overload Skeate and Eastlund 685

a patient with excess fluid intake pretransfusion [9] or

significant diuresis postreaction [29], TACO should be
carefully considered. A normal fluid balance does not rule
out TACO or rule in TRALI.

Cardiac function

Evidence of a new myocardial infarct can suggest that

pulmonary edema may not be transfusion related.
Patients with known preceding congestive heart failure
are at risk for TACO [3]. Systolic dysfunction identified
on echocardiography is also suggestive of TACO [5],
but does not rule out TRALI.
Pulmonary artery occlusion pressure can distinguish cardiogenic (greater than 18 mmHg) from noncardiogenic
(18 mmHg or less) pulmonary edema [30]. There is much
debate in the literature, however, concerning the utility
of pulmonary artery catheters (PACs) [31,32]. A report
from the Acute Respiratory Distress Syndrome Network
(ARDSN) of a clinical trial comparing the utility of
PAC monitoring versus central venous catheter (CVC)
monitoring in patients with ALI found increased complications and no significant benefit to PAC over CVC
[33]. As has been noted before in the literature [34], the
ARDSN found that some of their ALI patients had
pulmonary artery occlusion pressures of greater than
18 mmHg, suggesting that one can not rely solely on
PAC monitoring when trying to distinguish TRALI
from TACO.
Elevated levels of brain natriuretic peptide (BNP) and
n-terminal pro-brain natriuretic peptide (NT-proBNP)
are established markers for congestive heart failure
[35,36]. Investigators recently reported evidence that
BNP levels can be used to distinguish between cardiogenic and noncardiogenic pulmonary edema in patients
presenting with acute respiratory failure [37]. BNP
levels were measure in 80 respiratory failure patients
who also underwent PAC placement. BNP levels of
200 pg/ml or less were 91% specific for ALI, and BNP
levels of 1200 pg/ml or greater were 92% specific for
cardiogenic pulmonary edema.
Analogously, case reports have been published that
suggest that elevated levels of BNP can imply TACO
[29], and normal levels of BNP can support a diagnosis of
TRALI [38]. Zhou and colleagues [13] measured pretransfusion and posttransfusion BNP levels in 21 patients
with suspected TACO and 19 transfused controls. BNP
change was considered significant if the posttransfusion
to pretransfusion ratio was 1.5 or greater, and the posttransfusion BNP was 100 pg/ml or greater. A significant
change in BNP was 81% sensitive and 89% specific for
TACO, and had a positive predictive value of 89% and a
negative predictive value of 81%. While not conclusive,

these papers suggest that BNP has a role in distinguishing

TACO from TRALI.
Pulmonary edema fluid

With TACO the pulmonary edema fluid is a low-protein

plasma filtrate, and with TRALI the pulmonary edema
fluid is relatively high in plasma proteins. The edema
fluid to serum protein ratio has been used clinically to
suggest the presence of noncardiogenic edema (ratio
0.75) and therefore more likely TRALI [28]. The
utility of this metric for distinguishing TRALI from
TACO has not been evaluated in a formal experiment,
and there are aspects to the technique (e.g., sample
timing, can be used only in intubated patients) that limit
its utility [5].
Leukocyte antibody testing

Depending upon gender and pregnancy history, between

seven and 25% of donors are positive for leukocyte
antibodies [22]. Given the low incidence of TRALI,
the majority of transfusions from leukocyte alloimmunized donors must be uneventful. Also, there are TRALI
cases reported in the literature in which leukocyte antibodies were not detected [15,22]. These findings must
be kept in mind when interpreting leukocyte antibody
results. For example, one or more donors to a multiply
transfused patient who is experiencing TACO could be
positive for leukocyte antibodies, and these results would
obscure rather than confirm the correct diagnosis.
Despite these concerns, leukocyte antibody testing
should be performed where possible for cases with a
strong clinical suspicion of TRALI, and the test results
can support the diagnosis. Demonstration of cognate
antigen in the recipient, or crossmatch incompatibility
between donor and recipient makes the case for TRALI
even more credible [22].
Overall profile

There is no one feature that discriminates TRALI and

TACO. A true case of TRALI may have some of the
features typical of TACO, and vice versa. The best
strategy is to evaluate all of the features available from
the above discussion (Table 1), and determine which
diagnosis best fits the scenario in question.

Conclusion
As our understanding of TRALI and TACO improves, it
becomes clear that both are significant risks to transfusion
recipients. Unfortunately, there is no single feature
that distinguishes TRALI from TACO. Developing a
thorough clinical profile including presenting signs and
symptoms, fluid status, cardiac status including measurement of BNP, and leukocyte antibody testing is the
best strategy currently available to distinguish the two
disorders.

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686 Transfusion medicine and immunohematology

Acknowledgements
The authors would like to thank Monika M. Wahi, MPH for her effort on
this manuscript.

References and recommended reading

Papers of particular interest, published within the annual period of review, have
been highlighted as:

of special interest
 of outstanding interest
Additional references related to this topic can also be found in the Current
World Literature section in this issue (p. 705).
1 Sanders RP, Geiger TL, Heddle N, et al. A revised classification scheme for
 acute transfusion reactions. Transfusion 2007; 47:621628.
The authors report an evaluation of a new system they developed that provides
strict criteria for the classification and diagnosis of transfusion reactions. While
128 of the 595 transfusion reactions in their study could not be conclusively
classified by the system presented in the AABB Technical Manual, only five of the
reactions could not be classified with the new system.
2 Eder AF, Chambers LA. Noninfectious complications of blood transfusion.
 Arch Pathol Lab Med 2007; 131:708718.
This is a review of the English language literature published since 1990 on
noninfectious complications of transfusions. The authors focus on the incidence
per transfusion and the prevalence in transfusion recipients, and on the cause,
management, and prevention of each complication.
3 Stroncek DF. Pulmonary transfusion reactions. Semin Hematol 2007; 44:
 214.
This excellent review article describes the incidence, pathogenesis, presenting signs
and symptoms, and treatment and prevention of each of the items on the differential
diagnosis list for a pulmonary transfusion reaction. There is a more in-depth section on
the role of leukocyte antibodies in pulmonary reactions, and a section on how to
evaluate donors when they are implicated in a pulmonary transfusion reaction.
4 Popovsky MA. Pulmonary consequences of transfusion: TRALI and TACO.
 Transfus Apher Sci 2006; 34:243244.
This recent review article gives a concise and effective description of the
phenomenology of TRALI and TACO.
Gajic O, Gropper MA, Hubmayr RD. Pulmonary edema after transfusion: how
to differentiate transfusion-associated circulatory overload from transfusionrelated acute lung injury. Crit Care Med 2006; 34:S109S113.
This review article describes the different diagnostic tools that are available to
distinguish between hydrostatic and permeability pulmonary edema including
pulmonary artery catheterization, pulmonary edema fluid protein content, chest
radiography and echocardiography, B-type natriuretic peptide, and biomarkers of
acute lung injury. They also present an algorithm for evaluating posttransfusion
acute pulmonary edema.

5


Fiebig EW, Wu AH, Krombach J, et al. Transfusion-related acute lung injury

and transfusion-associated circulatory overload: mutually exclusive or coexisting entities? Transfusion 2007; 47:171172.

Kleinman S. A perspective on transfusion-related acute lung injury two years

after the Canadian Consensus Conference. Transfusion 2006; 46:1465
1468.
This editorial describes the limitations of the current case definition for TRALI
including the fact that patients with current acute lung injury or congestive heart
failure can not be defined as having TRALI. The author stresses the concepts that
efforts at TRALI prevention should be evidence-based, and that the degree to
which these efforts threaten the adequacy of the blood supply should be carefully
considered.

7


Popovsky MA. Transfusion reactions. 2nd ed. Bethesda: American Association of Blood Banks; 2001.

Popovsky MA. Breathlessness and blood: a combustible combination. Vox

Sang 2002; 83 (Suppl 1):147150.

13 Zhou L, Giacherio D, Cooling L, et al. Use of B-natriuretic peptide as a

diagnostic marker in the differential diagnosis of transfusion-associated
circulatory overload. Transfusion 2005; 45:10561063.
14 Holness L, Knippen MA, Simmons L, et al. Fatalities caused by TRALI.
Transfus Med Rev 2004; 18:184188.
15 Silliman CC, McLaughlin NJ. Transfusion-related acute lung injury. Blood Rev

2006; 20:139159.
This is an excellent review article on TRALI including sections on historical
background, definition, clinical presentation, incidence, the two-hit model of
pathogenesis, and animal models.
16 Sheppard CA, Logdberg LE, Zimring JC, et al. Transfusion-related acute lung

injury. Hematol Oncol Clin North Am 2007; 21:163176.
This is an excellent review article on TRALI with sections addressing whether or not
TRALI is a form of ALI, and the incidence, clinical presentation and case definition,
animal models of, and donor evaluation and screening for TRALI.
17 Bux J, Sachs UJ. The pathogenesis of transfusion-related acute lung injury
 (TRALI). Br J Haematol 2007; 136:788799.
This is the most thorough review article on the pathogenesis of TRALI available.
The authors present a historical perspective on the development of the two-hit
hypothesis, and carefully detail the evidence for the list of factors that can prime
and activate neutrophils.
18 Kleinman S, Caulfield T, Chan P, et al. Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel. Transfusion
2004; 44:17741789.
19 Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes,
and clinical trial coordination. Am J Respir Crit Care Med 1994; 149:818
824.
20 Bernard GR, Artigas A, Brigham KL, et al. Report of the American-European
Consensus conference on acute respiratory distress syndrome: definitions,
mechanisms, relevant outcomes, and clinical trial coordination. Consensus
Committee. J Crit Care 1994; 9:7281.
21 Toy P, Popovsky MA, Abraham E, et al. Transfusion-related acute lung injury:
definition and review. Crit Care Med 2005; 33:721726.
22 Curtis BR, McFarland JG. Mechanisms of transfusion-related acute lung
 injury (TRALI): antileukocyte antibodies. Crit Care Med 2006; 34:S118
S123.
This is a review article on the role of leukocyte antibodies in TRALI authored by
investigators from one of the main leukocyte antibody reference laboratories in the
United States. The evidence for the role of human leukocyte antigen and human
neutrophil antigen antibodies in TRALI is reviewed, and the fact that leukocyte
antibodies do not sufficiently explain all cases of TRALI is highlighted.
23 Eder AF, Herron R, Strupp A, et al. Transfusion-related acute lung injury
 surveillance (2003005) and the potential impact of the selective use of
plasma from male donors in the American Red Cross. Transfusion 2007;
47:599607.
This is a report of a retrospective review of 550 TRALI cases reported to the
American Red Cross during the time period from 2003 to 2005 including 72
fatalities. Expert review of the fatalities generated 38 cases of probable TRALI, the
majority of which involved plasma from female donors who were positive for
leukocyte antibodies. The authors conclude that providing plasma produced
predominantly from male donors is a prudent measure to limit TRALI.
24 Stainsby D, Jones H, Asher D, et al. Serious hazards of transfusion: a decade

of hemovigilance in the UK. Transfus Med Rev 2006; 20:273282.
This article describes the history and purpose of the United Kingdoms Serious
Hazards of Transfusion (SHOT) hemovigilance system. The scope and methodology, use of data, and an analysis of the data collected from 1996 to 2004 are
presented.
25 Serious Hazards of Transfusion Steering Committee. Serious hazards of
transfusion: Annual Report 2005. London: SHOT; 2005.

11 Popovsky MA, Audet AM, Andrzejewski C Jr. Transfusion-associated circulatory overload in orthopedic surgery patients: a multiinstitutional study.
Immunohematol 1996; 12:8789.

26 Stroncek DF, Klein HG. Heavy breathing in the blood bank: is it transfusion
related acute lung injury, our anxiety, or both? Transfusion 2007; 47:559
562.
In this editorial the authors caution that interventions to limit TRALI need to be
evaluated for their effect on the adequacy of the blood supply before being
implemented, and that because there are multiple factors that can lead to TRALI,
a multimodal approach will be required to eliminate TRALI altogether.

12 Rana R, Fernandez-Perez ER, Khan SA, et al. Transfusion-related acute lung

 injury and pulmonary edema in critically ill patients: a retrospective study.
Transfusion 2006; 46:14781483.
The authors performed a retrospective review of consecutive patients newly requiring
ventilatory support posttransfusion in four intensive care units at one institution in an
effort to establish the incidence of TRALI and TACO; 8902 units were transfused to
1351 patients, 49 of whom developed acute pulmonary edema. The incidence of
TRALI was one in 1271 units transfused, possible TRALI was one in 534 units
transfused, and TACO was one in 356 units transfused. The consensus conference
definition was used to identify TRALI and possible TRALI cases.

27 Fadeyi EA, De Los Angeles Muniz M, Wayne AS, et al. The transfusion of

neutrophil-specific antibodies causes leukopenia and a broad spectrum of
pulmonary reactions. Transfusion 2007; 47:545550.
This case report describes relatively mild reactions and transient leukopenia in both
recipients of a split platelet product from a donor who was positive for a neutrophilspecific (HNA-2a) antibody. A lookback on the donors previous 26 donations
demonstrated 12 mild to moderate reactions in nine patients, and instances of
leukopenia not associated with a clinical reaction. The authors conclude that
neutrophil antibodies do not always cause severe reactions, and cause leukopenia
with or without a clinical reaction.

10 Collins SP, Lindsell CJ, Storrow AB, et al. Prevalence of negative chest
radiography results in the emergency department patient with decompensated heart failure. Ann Emerg Med 2006; 47:1318.

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Acute lung injury and circulatory overload Skeate and Eastlund 687
28 Church GD, Price C, Sanchez R, et al. Transfusion-related acute lung injury in

the paediatric patient: Two case reports and a review of the literature. Transfus
Med 2006; 16:343348.
This article presents two cases of pediatric TRALI, and a review of the literature on
pediatric TRALI. The authors highlight the fact that TRALI patients can experience
transient, profound leukopenia, and that the protein content of pulmonary edema
fluid can help distinguish cardiogenic from noncardiogenic pulmonary edema.
29 Burgher AH, Aslan D, Laudi N, et al. Use of brain natriuretic peptide to evaluate
transfusion-related acute lung injury. Transfusion 2004; 44:15331534.
30 Ware LB, Matthay MA. Clinical practice. Acute pulmonary edema. N Engl J
Med 2005; 353:27882796.
31 Ramsay J. Pro: Is the pulmonary artery catheter dead? J Cardiothorac Vasc

Anesth 2007; 21:144146.
In this editorial the author argues that use of pulmonary artery catheters (PACs) will
likely decrease if not cease. His key arguments include that multiple clinical trials
have been performed showing that management of patients using PACs does not
improve outcomes, and that a few of these studies have shown an increased risk of
complications with PACs.
32 Murphy GS, Vender JS. Con: Is the pulmonary artery catheter dead?

J Cardiothorac Vasc Anesth 2007; 21:147149.
In this editorial the authors argue that use of pulmonary artery catheters (PACs) will
likely continue. They argue that the clinical trials that have shown no benefit to
PACs are misleading because they have been performed with the wrong types of
patients, and because the physicians who were using the PACs in the studies did
not have a standardized algorithm of practice guiding how they used the PAC data.
33 Wheeler AP, Bernard GR, Thompson BT, et al. Pulmonary-artery versus
 central venous catheter to guide treatment of acute lung injury. N Engl J
Med 2006; 354:22132224.
This is a report of a prospective clinical trial performed by the Acute Respiratory
Distress Syndrome Network that compared outcomes for 1000 patients with acute
lung injury randomized to receive care guided by either a pulmonary artery catheter
or a central venous catheter. The authors showed no benefit to pulmonary artery
catheter over central venous catheter, but did identify more complications in the
pulmonary artery catheter group.

34 Ferguson ND, Meade MO, Hallett DC, et al. High values of the pulmonary
artery wedge pressure in patients with acute lung injury and acute respiratory
distress syndrome. Intensive Care Med 2002; 28:10731077.
35 Emdin M, Passino C, Prontera C, et al. Comparison of brain natriuretic peptide

(BNP) and amino-terminal proBNP for early diagnosis of heart failure. Clin
Chem 2007; 53:813822.
The authors compared the diagnostic accuracy of brain natriuretic peptide (BNP)
and amino-terminal proBNP (NT-proBNP) for the diagnosis of mild heart failure by
measuring plasma NT-proBNP and BNP in 182 healthy controls and in a prospective cohort of 820 heart failure patients. They conclude that monitoring BNP
or NT-proBNP enabled identification of asymptomatic patients at risk for the
development of heart failure, but that NT-proBNP showed better accuracy than
BNP.
36 Mueller C, Scholer A, Laule-Kilian K, et al. Use of B-type natriuretic peptide in
the evaluation and management of acute dyspnea. N Engl J Med 2004;
350:647654.
37 Karmpaliotis D, Kirtane AJ, Ruisi CP, et al. Diagnostic and prognostic utility of
 brain natriuretic Peptide in subjects admitted to the ICU with hypoxic
respiratory failure due to noncardiogenic and cardiogenic pulmonary edema.
Chest 2007; 131:964971.
This is a report of a prospective study wherein brain natriuretic peptide (BNP)
levels were measured in 80 ICU patients with acute hypoxic respiratory failure and
bilateral pulmonary infiltrates on chest radiograph in an effort to determine the utility
of BNP for discriminating cardiogenic versus noncardiogenic pulmonary edema.
BNP levels of 200 pg/mL or less were 91% specific for noncardiogenic pulmonary
edema, and BNP levels of 1200 pg/ml or greater were 92% specific for cardiogenic pulmonary edema.
38 Edelson BT, Despotis GJ, Lublin DM. B-type natriuretic peptide measured

during transfusion-related acute lung injury. Transfusion 2006; 46:1453
1454.
This is a case report of a patient who experienced acute respiratory distress due to
pulmonary edema and who was demonstrated to have had normal levels of brain
natriuretic peptide (BNP) posttransfusion. The authors felt the normal BNP levels
were supportive of a diagnosis of TRALI.

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