Bronchoalveolar Lavage in Trauma Patients for Diagnosis of Fat Embolism Syndrome* Jean Marc Vedrinne, M.D.; Christian Guillaume, M.D.; Marie Claude Gagnieu, M.D.; Pierre Gratadour; M.D.; Carole Fleuret, M.D.; and]ean Motin, M.D. Fat embolism syndrome (FES) is a rare but serious complication occurring after long bone fractures. Presence of fat droplets in cells obtained by bronchoalveolar lavage has been proposed as a speci6c tool for FES diagnosis in trauma patients. We evaluated this technique over a IS-month period in 85 patients. Twenty-eight patients were excluded. The remaining 57 patients were divided into three groups: group 1,26 patients without trauma as control; group 2, 22 patients with trauma but without evidence of FES; and group 3, nine patients with trauma and evidence of FES. Six of 26 patients in group 1 and nine of 22 patients in group
2 exhibited fat droplets in alveolar macrophages, whereas three of nine patients of group 3 had not. This study suggests that (1) presence of fat droplets in alveolar macrophages is not a reliable method for diagnosis of FES after long bone trauma, and (2) many conditions are associated with fat droplets in alveolar macrophages. (Cheat 1992; 102:1323-27)
The fat embolism syndrome (FES) is a rare but serious complication occurring most of the time in patients with long bone fractures.':" Usually, after an interval of 12 to 72 h, a triad of symptoms characterize the FES4,5: acute respiratory failure with hypoxia and pulmonary infiltrates, cerebral dysfunction, and petechial rash. Occasionally, the diagnosis of FES can be easy if the patient has an isolated fracture." However, the diagnosis of FES is often difficult to ascertain clinically because of the associated injuries. 6 Chest trauma with pulmonary contusion, aspiration pneumonia, and massive transfusion are commonly encountered in trauma patients and are responsible for hypoxia and pulmonary infiltrates. Cerebral dysfunction with unconsciousness may be uninterpretable after cerebral trauma or in sedated patients. Petechial rash and low platelet count may occur after massive blood transfusion needed by posttraumatic bleeding. Other biologic signs are often nonspecific. Moreover, a key symptom of FES may be absent?" or FES may be subclinical;" The pathogenesis of the FES remains unclear and controversial. Embolization and deposition of fat and fatty acids from bone marrow to pulmonary capillaries appear to be the main event in the supervention of the illness.P-'! However, it is not possible to predict which patients will have the syndrome, and nearly all trauma patients exhibit pulmonary embolization of fat at autopsy. Recent articles emphasize that microscopic
examination of cells obtained by bronchoalveolar lavage (BAL) or tracheobronchial aspirate could allow rapid identification of patients with FES12 or amniotic fluid embolism. 13 The aim of this prospective study was to determine the value of fat droplets contained in alveolar macrophages recovered by BAL in traumatized patients compared with nontraumatized patients for diagnosis ofFES.
*From the Service d'Anesthesie-Reanimation (Drs. Vedrinne, Guillaume, Gratadour, and Motin) and the Laboratoire de Biochimie (Drs. Gagnieu and Fleuret), Hopital Edouard Herriot, Lyon, France. Manuscript received November 19; revision accepted February 20. Reprint requests: Dr. \edrinne, Hopital Edouard Herriot, Place d'Arsonval, Lyon Cedex 03, France 69437
CRP = C-reactive protein; FES = fat embolism syndrome; FI fracture index; SAPS simpli6ed acute physiologic score
=
=
METHODS
lbtients This prospective study was conducted in our hospital trauma center over a 15-month period (February 1990 to April 1991). The study population included all patients admitted to the hospital with pulmonary infiltrates causing acute respiratory failure that required intubation and mechanical ventilation. Ninety-six BALs were performed in 85 patients. The mean age was 45 ± 19 years. Sixty-three were male and 22 were female. Before undergoing BAL, the 85 patients were divided into three groups according to their probability of presenting the FES. Group 1
Twenty-six BALs were performed in 26 patients without previous trauma who developed pneumonia. They served as control subjects. They underwent BAL for bacterial diagnosis. The mean age was 56 ± 16 years. Simplified acute physiologic score (SAPS) was 16.7 ± 6.3. Sixteen were male and ten were female. Group
2
Twenty-eight BALs were performed in 22 patients with previous trauma but without evidence of FES. The mean age was 40±22 years. The SAPS was 15.3±4.3. Nineteen were male and three were female. They were divided between two subgroups according to the fracture index (FI)·4:group 2a, FI = 0 (n =9); group 2b, FI>O (n=13). Group 3
Thirteen BALs were performed in nine men with previous CHEST I 102 I 5 I NOVEMBER. 1992
1323
Table 1-Fat Embolism Scale Absent =0
Signs
o
Pulmonary infiltrates Neurologic
o
Skin petechiae Platelet count, 10"1L Retinal changes Lipids, mmoVL Fracture(s) oflong bone(s) or pelvis
o
x >200
o
Cholesterol>3.5 None
·Bilateral slow frontal waves. trauma and evidence of FES . The BAL was performed within the first six days after trauma. The mean age was 32:!: 10 years and SAPS was 16::!: 3.5 . Twenty-nine BALs (18 in group I, eight in group 2, and three in group 3) performed in 28 patients were excluded because the percentage of alveolar macrophages was too low « 1 percent in the total cell count) to provide a reliable result (n = 18), the percentage of ciliated cells was more than 10 percent (n = 8), or when the BAL was bloody (n = 3). Since most of the trauma patients exhibited chest trauma. cerebral injury, or abdominal injury associated with long bone fracture(s) , we built our own scale for the diagnosis of FES from our previous experience." Diagnosis of FES was evaluated from seven items (Table 1). Each item was graded as 0 , 1 or 2 depending on whether it was absent , present, or intense, respectively. A patient presenting a score 2:8 was highly suspected to present a FES and included in group 3.
Bronchoalveolar lAvage BALs were performed in unconscious or sedated patients under mechanical ventilation. without ventilatory change, except for an increase of Flo. to 1. The bronchoscope's tip (4.9 mm in diameter) was wedged into the subsegmental bronchus of the lobe with maximal infiltrates on the chest roentgenogram. Fifty to 100 milliliters of sterile buffered saline solution was infused through the working channel of the bronchoscope in 5O-ml a1iquots. The BAL sample was analyzed within the next 2 h. The cells contained in the lavage fluid were counted on uncentrifuged specimens using a hemacytometer. The fluid was then centrifuged (500 g for 10 min). The cell pellet was resuspended in few drops of serum. Slide preparations were obtained using either a centrifuge (Cytospin, Shandon Southern Products) when total cell count was less than 50 million cells per liter or by smearing when total cell count was higher. A minimum of two ai r- dried slides were prepared from each BAL sample. One was stained with a Wright-Giemsa stain; the other was stained with an oil red 0 stain . Differential cell counts were performed on the Wright-Giemsa slide and the percentages of neutrophils, eostnophils, lymphocytes. macrophages, and squamous cells were determined. The ratio of macrophages containing red or brown-red fat droplets was calculated after examination of at least 200 macrophages on the oil red 0 slide (Fig 1). A BAL was considered as positive when more than 5 percent of the alveolar macrophages contained fat droplets. Informed consent was obtained from all patients or their nearest relative and the experimental protocol was approved by our local ethical committee. Results are expressed as mean::!:SD . Comparisons between groups are based on x' test and variance analysis.
Present = 1
Present=2
Moderate or localized Disturbance of consciousness or typical EEG changes" Moderate 200> x >100 Hemorrhage or retinal emboli Cholesterol
2 exhibited fat droplets in alveolar macrophages, whereas three of nine patients of group 3 had not. This study suggests that (1) presence of fat droplets in alveolar macrophages is not a reliable method for diagnosis of FES after long bone trauma, and (2) many conditions are associated with fat droplets in alveolar macrophages. (Cheat 1992; 102:1323-27)
The fat embolism syndrome (FES) is a rare but serious complication occurring most of the time in patients with long bone fractures.':" Usually, after an interval of 12 to 72 h, a triad of symptoms characterize the FES4,5: acute respiratory failure with hypoxia and pulmonary infiltrates, cerebral dysfunction, and petechial rash. Occasionally, the diagnosis of FES can be easy if the patient has an isolated fracture." However, the diagnosis of FES is often difficult to ascertain clinically because of the associated injuries. 6 Chest trauma with pulmonary contusion, aspiration pneumonia, and massive transfusion are commonly encountered in trauma patients and are responsible for hypoxia and pulmonary infiltrates. Cerebral dysfunction with unconsciousness may be uninterpretable after cerebral trauma or in sedated patients. Petechial rash and low platelet count may occur after massive blood transfusion needed by posttraumatic bleeding. Other biologic signs are often nonspecific. Moreover, a key symptom of FES may be absent?" or FES may be subclinical;" The pathogenesis of the FES remains unclear and controversial. Embolization and deposition of fat and fatty acids from bone marrow to pulmonary capillaries appear to be the main event in the supervention of the illness.P-'! However, it is not possible to predict which patients will have the syndrome, and nearly all trauma patients exhibit pulmonary embolization of fat at autopsy. Recent articles emphasize that microscopic
examination of cells obtained by bronchoalveolar lavage (BAL) or tracheobronchial aspirate could allow rapid identification of patients with FES12 or amniotic fluid embolism. 13 The aim of this prospective study was to determine the value of fat droplets contained in alveolar macrophages recovered by BAL in traumatized patients compared with nontraumatized patients for diagnosis ofFES.
*From the Service d'Anesthesie-Reanimation (Drs. Vedrinne, Guillaume, Gratadour, and Motin) and the Laboratoire de Biochimie (Drs. Gagnieu and Fleuret), Hopital Edouard Herriot, Lyon, France. Manuscript received November 19; revision accepted February 20. Reprint requests: Dr. \edrinne, Hopital Edouard Herriot, Place d'Arsonval, Lyon Cedex 03, France 69437
CRP = C-reactive protein; FES = fat embolism syndrome; FI fracture index; SAPS simpli6ed acute physiologic score
=
=
METHODS
lbtients This prospective study was conducted in our hospital trauma center over a 15-month period (February 1990 to April 1991). The study population included all patients admitted to the hospital with pulmonary infiltrates causing acute respiratory failure that required intubation and mechanical ventilation. Ninety-six BALs were performed in 85 patients. The mean age was 45 ± 19 years. Sixty-three were male and 22 were female. Before undergoing BAL, the 85 patients were divided into three groups according to their probability of presenting the FES. Group 1
Twenty-six BALs were performed in 26 patients without previous trauma who developed pneumonia. They served as control subjects. They underwent BAL for bacterial diagnosis. The mean age was 56 ± 16 years. Simplified acute physiologic score (SAPS) was 16.7 ± 6.3. Sixteen were male and ten were female. Group
2
Twenty-eight BALs were performed in 22 patients with previous trauma but without evidence of FES. The mean age was 40±22 years. The SAPS was 15.3±4.3. Nineteen were male and three were female. They were divided between two subgroups according to the fracture index (FI)·4:group 2a, FI = 0 (n =9); group 2b, FI>O (n=13). Group 3
Thirteen BALs were performed in nine men with previous CHEST I 102 I 5 I NOVEMBER. 1992
1323
Table 1-Fat Embolism Scale Absent =0
Signs
o
Pulmonary infiltrates Neurologic
o
Skin petechiae Platelet count, 10"1L Retinal changes Lipids, mmoVL Fracture(s) oflong bone(s) or pelvis
o
x >200
o
Cholesterol>3.5 None
·Bilateral slow frontal waves. trauma and evidence of FES . The BAL was performed within the first six days after trauma. The mean age was 32:!: 10 years and SAPS was 16::!: 3.5 . Twenty-nine BALs (18 in group I, eight in group 2, and three in group 3) performed in 28 patients were excluded because the percentage of alveolar macrophages was too low « 1 percent in the total cell count) to provide a reliable result (n = 18), the percentage of ciliated cells was more than 10 percent (n = 8), or when the BAL was bloody (n = 3). Since most of the trauma patients exhibited chest trauma. cerebral injury, or abdominal injury associated with long bone fracture(s) , we built our own scale for the diagnosis of FES from our previous experience." Diagnosis of FES was evaluated from seven items (Table 1). Each item was graded as 0 , 1 or 2 depending on whether it was absent , present, or intense, respectively. A patient presenting a score 2:8 was highly suspected to present a FES and included in group 3.
Bronchoalveolar lAvage BALs were performed in unconscious or sedated patients under mechanical ventilation. without ventilatory change, except for an increase of Flo. to 1. The bronchoscope's tip (4.9 mm in diameter) was wedged into the subsegmental bronchus of the lobe with maximal infiltrates on the chest roentgenogram. Fifty to 100 milliliters of sterile buffered saline solution was infused through the working channel of the bronchoscope in 5O-ml a1iquots. The BAL sample was analyzed within the next 2 h. The cells contained in the lavage fluid were counted on uncentrifuged specimens using a hemacytometer. The fluid was then centrifuged (500 g for 10 min). The cell pellet was resuspended in few drops of serum. Slide preparations were obtained using either a centrifuge (Cytospin, Shandon Southern Products) when total cell count was less than 50 million cells per liter or by smearing when total cell count was higher. A minimum of two ai r- dried slides were prepared from each BAL sample. One was stained with a Wright-Giemsa stain; the other was stained with an oil red 0 stain . Differential cell counts were performed on the Wright-Giemsa slide and the percentages of neutrophils, eostnophils, lymphocytes. macrophages, and squamous cells were determined. The ratio of macrophages containing red or brown-red fat droplets was calculated after examination of at least 200 macrophages on the oil red 0 slide (Fig 1). A BAL was considered as positive when more than 5 percent of the alveolar macrophages contained fat droplets. Informed consent was obtained from all patients or their nearest relative and the experimental protocol was approved by our local ethical committee. Results are expressed as mean::!:SD . Comparisons between groups are based on x' test and variance analysis.
Present = 1
Present=2
Moderate or localized Disturbance of consciousness or typical EEG changes" Moderate 200> x >100 Hemorrhage or retinal emboli Cholesterol
