Acute respiratory distress syndrome during neutropenia recovery.
ABSTRACT Acute respiratory failure is a life-threatening complication in cancer patients. During neutropenia, patients are at high risk for bacterial pneumonia or invasive fungal infections, when neutropenia is prolonged. A high proportion of patients in whom neutropenia had been complicated by pneumonia will present with substantial respiratory deterioration during neutropenia recovery. Patients with fungal pneumonia and those receiving granulocyte colony-stimulating factor to shorten neutropenia duration may be at higher risk for this acute lung injury/acute respiratory distress syndrome during neutropenia recovery. Routine screening of patient's risk factors is crucial since first symptoms of acute respiratory distress syndrome may occur before biological leukocyte recovery.
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ABSTRACT: Neutropenia recovery may be associated with deterioration in oxygenation and exacerbation of pre-existing pulmonary disease. However, risk factors for acute respiratory distress syndrome (ARDS) during neutropenia recovery in patients with hematologic malignancies have not been studied. We studied critically ill patients with hematologic malignancies with the dual objectives of describing patients with ARDS during neutropenia recovery and identifying risk factors for ARDS during neutropenia recovery. A cohort of consecutive neutropenic patients with hematologic malignancies who were admitted to the intensive care unit (ICU) was studied. During a 6-year period, 71 patients recovered from neutropenia, of whom 38 (53.5%) developed ARDS during recovery. Compared with non-ARDS patients, patients who experienced ARDS during neutropenia recovery were more likely to have pneumonia, be admitted to the ICU for respiratory failure, and receive mechanical ventilator therapy. The in-ICU mortality was significantly different between the two groups (86.8% versus 51.5%, respectively, for patients who developed ARDS during neutropenia recovery versus those who did not during neutropenia recovery). In multivariate analysis, only occurrence of pneumonia during the neutropenic episode was associated with a marked increase in the risk of ARDS (odds ratio, 4.76). Patients with hematologic malignancies complicated by pneumonia during neutropenia are at increased risk for ARDS during neutropenia recovery.Critical care (London, England) 11/2009; 13(6):R173. · 4.72 Impact Factor
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ABSTRACT: Infection remains a major complication in patients with malignant disease. There are many factors predisposing to infection in this patient population, including local factors due to the tumor, specific deficiencies in host defense mechanisms due to certain malignant processes, and deficiencies in host defense mechanisms secondary to cancer chemotherapy. Neutropenia is probably the most important factor predisposing to infection in cancer patients. These patients require prompt broad-spectrum antibiotic therapy when fever develops. The majority of infections occurring in this patient population are caused by gram-negative bacilli and cure rates usually are between 65 and 75 percent. The most important prognostic factor is whether or not the neutrophil count recovers during the course of infection. Fungal infections have increased in frequency in neutropenic patients and often present as fevers of unknown origin. Increasingly, neutropenic patients are receiving antifungal agents as empiric therapy for persistent fever that fails to respond to antibacterial antibiotics. The most critical factor in recovery from fungal infection is remission of the underlying malignant disease.The American Journal of Medicine 08/1986; 81(1A):11-26. · 4.77 Impact Factor
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ABSTRACT: Neutropenic enterocolitis (NE) is a severe complication of intensive chemotherapy and is barely identifiable by clinical signs alone. Ultrasonography (US) supports the diagnosis of NE by showing pathologic thickening of the bowel wall. The aim of this study was to evaluate the prognostic value of the degree of mural thickening evaluated by US in patients with clinically suspected NE. Neutropenic patients with fever, diarrhea, and abdominal pain after intensive chemotherapy for hematologic malignancies were studied with abdominal US. We evaluated the degree of bowel wall thickening detected by US and its correlation with the duration of the clinical syndrome as well as NE-related mortality. Eighty-eight (6%) of 1,450 consecutive patients treated for leukemia had clinical signs of NE. In 44 (50%) of 88 patients, US revealed pathologic wall thickening (mean +/- SD, 10.2 +/- 2.9 mm; range, 6 to 18). The mean duration of symptoms was significantly longer in this group (7.9 days) than among patients without mural thickening (3.8 days, P <.0001), and the NE-related mortality rate was higher (29.5% v 0%, P <.001). Patients with bowel wall thickness of more than 10 mm had a significantly higher mortality rate (60%) than did those with bowel wall thickness < or = 10 mm (4.2%, P <.001). Symptomatic patients with sonographically detected bowel wall thickening have a poor prognosis compared with patients without this finding. In addition, mural thickness of more than 10 mm is associated with poorer outcome among patients with NE.Journal of Clinical Oncology 02/2001; 19(3):756-61. · 18.04 Impact Factor
Cancer chemotherapy is administered every day to
numerous cancer patients, with neutropenia mostly a
normally expected event [1,2]. During neutropenia,
bacterial sepsis remains a major threat . Potential
sources of infection include primarily the lungs, the
digestive tract, and the bloodstream [4,5]. Some of the
patients with prolonged neutropenia are more likely to
present with nonbacterial infections, namely acute
leukemia patients and stem cell/bone marrow transplant
recipients . Although neutrophils are believed to have
a pivotal role in the pathophysiology of acute lung injury
(ALI) and acute respiratory distress syndrome (ARDS),
early evidence emerged that neutropenic patients were
not spared from ALI and ARDS . Several hypotheses
have been raised, including alveolar macrophage or
monocyte deactivation  in relation to malignancy,
cancer chemotherapy or sepsis.
Neutropenia recovery occurs silently in the vast
majority of patients. Deterioration of the respiratory
status, however, has been reported during resolution of
leukopenia [9,10] – that is, 2 to 3 days before and after
the neutrophil count reaches 500/mm3 or the leukocyte
count reaches 1,000/mm3 . An aggravating role of
granulocyte colony-stimulating factor (G-CSF) has been
suggested in both clinical and experimental fi ndings
[12,13]. Patients at risk for ALI/ARDS during neutropenia
recovery are those with pulmonary infi ltrates during
neutropenia [10,12,13]. Other risk factors that have been
suggested include delayed or pro longed neutropenia 
and invasive pulmonary aspergillosis .
In the previous issue of Critical Care, Rhee and
coworkers assessed the risk factors for ARDS in 71
critically ill patients with hematologic malignancies and
long-lasting neutropenia . All of the patients received
G-CSF. About one-half of the patients developed ARDS
during neutropenia recovery. Th e authors identifi ed that
patients presenting pneumonia during neutropenia were
at higher risk of ARDS during neutropenia recovery.
Th e present study provides additional evidence that
neutropenic patients presenting clinically or microbio-
logically documented pneumonia should be monitored
carefully at the time of neutropenia recovery. Th e study
also raises the issue of G-CSF-related pulmonary toxicity
in this context . Th ere are, however, three potential
sources of bias in the study that should be highlighted.
First, one-half of the patients had an acute leukemia, all
of them receiving G-CSF. Although the safety of G-CSF
in patients with acute leukemia has been well established
in numerous clinical trials, its potential advantages
remain inconclusive since there is no evidence of a
reduction in the overall frequency of infectious compli-
cations or the duration of hospitalization, nor any benefi t
in terms of disease-free survival or overall survival .
Th e benefi t–risk ratio of G-CSF in these patients should
therefore be carefully addressed in each individual case.
Second, the neutropenia duration was rather long in
the present study (22.5 days), which is in agreement with
the fact that 90% of the patients received chemotherapy
Acute respiratory failure is a life-threatening
complication in cancer patients. During neutropenia,
patients are at high risk for bacterial pneumonia
or invasive fungal infections, when neutropenia is
prolonged. A high proportion of patients in whom
neutropenia had been complicated by pneumonia will
present with substantial respiratory deterioration during
neutropenia recovery. Patients with fungal pneumonia
and those receiving granulocyte colony-stimulating
factor to shorten neutropenia duration may be at
higher risk for this acute lung injury/acute respiratory
distress syndrome during neutropenia recovery. Routine
screening of patient’s risk factors is crucial since fi rst
symptoms of acute respiratory distress syndrome may
occur before biological leukocyte recovery.
© 2010 BioMed Central Ltd
Acute respiratory distress syndrome during
Élie Azoulay* and Michael Darmon
See related research by Rhee et al., http://ccforum.com/content/13/6/R173
AP-HP, Hôpital Saint-Louis, Medical ICU, University Paris-7 Paris-Diderot, UFR de
Médecine, 1 avenue Claude Vellefaux, 75010 Paris, France
Azoulay and Darmon Critical Care 2010, 14:114
© 2010 BioMed Central Ltd
for acute leukemia. Prolonged neutropenia has been
identifi ed as a risk factor for respiratory deterioration
during neutropenia recovery . Th is also indicates that
the 50% incidence and the severity of respiratory
deteriora tion during neutropenia recovery reported in
Rhee and colleagues’ study may not be generalizable to all
patients with hematological malignancies such as diff use
B-cell lymphoma or myeloma, and even less to patients
with solid tumors.
Th ird, the mortality rate reported in the study is in the
higher ranges of recently published data [17,18]. Th is is
probably further proof that patients reported in the
paper by Rhee and coworkers are among the sickest
critically ill leukemic patients. Along this line, the
absence of docu mented invasive aspergillosis in the
study is a surprising fi nding.
Although no sound causal relationship can be estab-
lished from these data between neutropenia recovery and
ARDS, we would like to emphasize the fi ve convincing
arguments supporting the reality of ARDS during
neutropenia that the authors developed in their
discussion section. First, a high proportion of patients in
whom neutropenia had been complicated by pneumonia
will present with substantial respiratory deterioration
during neutropenia recovery. Also, the incidence of ALI/
ARDS in neutropenic patients with pneumonia is far
higher during than before or after neutropenia recovery.
Th ird, several groups from diff erent parts of the world
have described this clinical entity. Further, the experi-
mental models of ALI/ARDS in neutropenic rats have
been able to reproduce this condition with reasonable
pathophysiology hypotheses. Finally, this ARDS situation
is clinically plausible in these frail lung’s patients with
established predisposition to infections , cancer
chemotherapy and G-CSF-induced pulmonary toxicity, and
sometimes to pulmonary infi ltration by the malignancy.
In the future, early recognition of those patients likely
to present ALI/ARDS in this specifi c clinical setting is a
worthwhile endeavor. Th e relevance of routine screening
for each individual patient’s risk factors is made crucial
by the fact that the fi rst symptoms of ARDS may occur
before biological leukocyte recovery, and by the need to
weight the benefi t–risk ratio of G-CSF administration in
every patient with clinically or microbiologically
pneumonia compli cating neutropenia.
ALI = acute lung injury; ARDS = acute respiratory distress syndrome; G-CSF =
granulocyte colony-stimulating factor.
The present work was supported by a grant from the Assistance-Publique
Hôpitaux de Paris (AOM 04139).
The authors declare that they have received grants from Pfi zer and Gilead but
not in relation to this publication.
Published: 10 February 2010
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Cite this article as: Azoulay E, Darmon M: Acute respiratory distress syndrome
during neutropenia recovery. Critical Care 2010, 14:114.
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