Clinical significance of increased peripheral venous blood adipocyte-specific protein FABP4 after joint replacement.

A new method of diagnosing fat embolism (FE) at the molecular level was proposed, and the diagnostic value of adipocyte-specific protein fatty acid-binding protein 4 (Homo sapiens [human]) gene ID = 2167 (FABP4) for FE was preliminarily explored. Eight joint replacement patients, 5 internal medicine patients, and 6 healthy persons were recruited. Serum of internal medicine patients, healthy people, and patients before and 24 hours after joint replacement were taken as study samples. Subcutaneous adipose, intra-articular adipose and intramedullary yellow bone marrow of patients undergoing joint replacement were taken as study samples. The level of FABP4 in the above samples was detected by enzyme-linked immunoassay. Normal distribution was tested. Paired sample T test was used for self-control. Univariate analysis of variance was used for multigroup comparison.There was no significant difference in serum FABP4 level between healthy persons, medical patients, and preoperative patients. The FABP4 level in yellow bone marrow and subcutaneous adipose was significantly higher than that in serum of healthy people, medical patients, and preoperative patients. FABP4 level in the serum after joint replacement was significantly higher than that before joint replacement. FABP4 may be a specific indicator of FE diagnosis, but further studies are needed to confirm its clinical value.

Neurologic Complications of Fat Embolism Syndrome.

PURPOSE OF REVIEW: Fat embolism syndrome (FES) is a rare disorder with potentially devastating neurologic complications. This article reviews the history, pathophysiology, clinical features, diagnosis, and treatment of FES with a focus on its neurologic aspects. RECENT FINDINGS: The neurologic complications of FES are more commonly recognized with current diagnostic testing and increase awareness of the disorder. FES may present initially with neurologic manifestations. Prompt diagnosis of FES and of its neurologic manifestations could be lifesaving. This includes respiratory support and management of neurological complications. The classic clinical triad of pulmonary insufficiency, neurologic disturbances, and petechial skin rash typically presents 24 to 72 h following an initial insult, most commonly a traumatic long bone fracture. Early onset (< 24 h) and delayed onset (> 72 h) have been described. Neurologic manifestations may include ischemic/hemorrhagic strokes, retinal ischemia, seizures, autonomic dysfunction, and diffuse brain injury. Diagnosis remains clinical. Management consists mainly of supportive care.

Coronary fat embolism following subarachnoid hemorrhage: an experimental study.

BACKGROUND: Subarachnoid hemorrhage (SAH) can lead to neurogenic pulmonary edema (NPE), and chylomicron metabolism may be altered unfavorably in acute lung injury. This study aimed to investigate the possible effect of NPE on the development of coronary fat embolism. METHODS: This study was conducted on 27 rabbits, 5 of which were used as the control (n=5). Experimental SAH was induced in 15 of the animals by injecting homologous blood into the cisterna magna, and the remaining 7 animals were administered only isotonic saline solution (Sham, n=7) in the same manner under general anesthesia. After 21 days, all the animals were euthanized, and their hearts, lungs, and brains underwent histopathological examination. RESULTS: Six animals died of SAH during the experiment, and foamy hemorrhagic parenchymal lesions and intra-alveolar hemorrhage were observed in their lungs. The histopathologic findings revealed minimal changes in the lungs, heart, and brains of the surviving animals; however, an abundant amount of fat globules was found in the coronary arteries of the six nonsurviving animals. There was a meaningful difference between the number of occluded coronary arteries with fatty globules in the surviving and nonsurviving animals (P<.001). However, the difference between the survivors and the isotonic-saline-injected group was not meaningful (P>.05). Coronary fat embolism was an important mortality factor following SAH (P<.005). CONCLUSIONS: In SAH-induced NPE, the leakage of chylomicrons into the systemic circulation may lead to coronary fat embolism, which has not yet been reported in the literature.

Fat Intravasation from Intraosseous Flush and Infusion Procedures.

STUDY HYPOTHESIS: The primary study objective was to delineate the procedural aspects of intraosseous (IO) infusions responsible for fat intravasation by testing the hypothesis that the fat content of effluent blood increases during IO infusions. METHODS: IO cannulas were inserted into the proximal tibiae of 35 anesthetized swine (Sus scrofa, 50.1 ± 3.5 kg) and intravasated fat was assessed using a lipophilic fluoroprobe (Nile red) and by vascular ultrasound imaging. Effluent blood bone marrow fat was assessed at baseline, during flush, and with regimens of controlled infusion pressures (73-300 mmHg) and infusion flow rates (0.3-3.0 mL per second). Fat intravasation was also assessed with IO infusions at different tibial cannulation sites and in the distal femur. In 7 animals, the lipid uptake of alveolar macrophages and lung tissue assessed for fat embolic burden using oil red O stain 24 hours post infusion. Additionally, bone marrow shear-strain was assessed radiographically with IO infusions. RESULTS: Fat intravasation was observed during all IO infusion regimens, with subclinical pulmonary fat emboli persisting 24 hours post infusion. It was noted that initial flush was a significant factor in fat intravasation, low levels of intravasation occurred with infusions ≤300 mmHg, fat intravasation and bone marrow shear-strain increased with IO infusion rates, and intravasation was influenced by cannula insertion site. Ultrasound findings suggest that echogenic particles consistent with fat emboli are carried in fast and slow venous blood flow fields. Echo reflective densities were observed to rise to the nondependent endovascular margins and coalesce in accordance with Stoke's law. In addition, ultrasound findings suggested that intravasated bone marrow fat was thrombogenic. CONCLUSION: Results suggest that in swine the intravasation of bone marrow fat is a common consequence of IO infusion procedures and that its magnitude is influenced by the site of cannulation and infusion forces. Although the efficacy and benefits of IO infusions for emergent care are well established, emergency care providers also should be cognizant that infusion procedures affect bone marrow fat intravasation.

Role of interleukin-6 as an early marker of fat embolism syndrome: a clinical study.

BACKGROUND: A few animal studies have shown that IL-6 can serve as an early marker of fat embolism syndrome. The degree to which this is true in human trauma victims is unknown. QUESTIONS/PURPOSES: In this clinical study, we sought to determine (1) whether elevated serum IL-6 levels at 6, 12, and 24 hours in patients with skeletal trauma were associated with the development of fat embolism syndrome (FES) within 72 hours after injury, and (2) at what time after trauma peak IL-6 levels are observed. METHODS: Forty-eight patients between 16 and 40 years old who presented to our tertiary trauma center within 6 hours of injury with long bone and/or pelvic fractures were included in this study. Serum IL-6 levels were measured at 6, 12, and 24 hours after injury. The patients were observed clinically and monitored for 72 hours for development of FES symptoms. Gurd's criteria were used to diagnose FES. RESULTS: Elevated serum IL-6 levels 12 hours after trauma correlated with an increased likelihood of having FES develop; no significant relationship was observed between IL-6 levels at 6 or 24 hours and the development of FES. Patients with FES had a mean IL-6 level of 131 pg/mL, whereas those without FES had a mean IL-6 level of 72 pg/mL. Peak IL-6 levels were observed at 12 hours. CONCLUSIONS: An elevated serum IL-6 level may be useful as an early marker of FES in patients with isolated skeletal trauma. LEVEL OF EVIDENCE: Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Emergency oxygenator change-out after massive fat embolism.

We present a case with an unusually high transmembrane pressure gradient over the oxygenator during initiation of extracorporeal membrane oxygenation (ECMO). This necessitated an immediate emergency oxygenator exchange. A detailed inspection revealed a large lipid formation in the oxygenator. We hypothesize that this lipid was dislodged during the cannulation process.

[The laboratory diagnostics of fat embolism].

The examination was applied to 598 patients with polytrauma and patients after surgery on bones and joints on the subject of various diseases of locomotor apparatus. All patients were tested on fat embolism in blood serum and cerebrospinal fluid. The modificated Guard's technique was applied. The test data permitted to develop the method of express diagnostics of oil embolism. It is established that fat liquorglobulia is a pathognomonic symptom of cerebral form of fat embolism.

Lipid emboli distribution in cardiac surgery is dependent on the state of emulsification.

OBJECTIVE: Lipid embolizations from retransfused shed blood during cardiac surgery have been shown to enter the circulation and end up in different organs. The purpose of this investigation was to evaluate differences in the kinetics and deposition between emulsified and non-emulsified lipid emboli in a porcine model. DESIGN: Twelve animals were anesthetized and put on cardiopulmonary bypass. A shed-blood phantom (6 animals given emulsified and 6 given non-emulsified lipids) was produced from arterial blood, saline, and tritium-labeled triolein. The phantom was infused into the cardiopulmonary bypass circuit. Arterial and venous blood samples were taken at short intervals. Tissue samples were taken post-mortem from examined organs and prepared for scintillation counting. Levels of radioactivity were used to measure lipid emboli content in blood and tissue. RESULTS: Emulsified lipid emboli generated a 5-fold higher embolic load in the arterial and a 12-fold higher in the venous circulation, compared with non-emulsified lipid emboli. Emulsified lipid micro emboli resulted in a 2-15-fold higher tissue deposition in investigated organs compared with non-emulsified lipid micro emboli. CONCLUSIONS: This study shows that the state of emulsion significantly alter the kinetics and tissue deposition of lipid emboli. Emulsified lipid emboli give higher embolic load in the arterial and venous circulation, and higher tissue deposition versus non-emulsified lipid emboli. In both groups, the embolic load was higher in the arterial circulation than on the venous side.

Occurrence of fat embolism after liposuction surgery with or without lipografting: an experimental study.

BACKGROUND: Liposuction in plastic surgery consists of the removal of excess fatty tissue in healthy individuals. In recent decades, this procedure has become more common worldwide. Associated with liposuction, lipografting has also been used for improving body contours, and has become known as liposculpture. Liposuction sometimes causes complications, including fat embolism, as described in the medical literature. The present study aims at ascertaining whether there is intravascular mobilization of fat after mechanical liposuction surgery and/or fat graft when carried out using one of the most common specific procedures used for liposuction, the superwet technique. METHODS: A total of 30 Wistar rats were included in this study. Before the surgery, the animals were placed in the supine position and anesthetized with thiopental for 50 to 60 minutes, as it is generally performed in clinical practice. The animals were divided in the following 3 groups. Group A, consisting of 10 rats, served as controls, and were only anesthetized. Group B consisted of 10 rats, which underwent only liposuction. Group C also comprised 10 rats, which were liposuctioned and then lipografted in the dorsal region. Blood was collected just before and again, 48 hours after the procedure. After 48 hours, the animals were killed, and the lungs, kidneys, liver, and brain were histologically examined. RESULTS: All the collected samples were analyzed microscopically with 2 different stains, namely, hematoxylin and eosin, and Sudan black. Fat particles were found in the lungs of 3 animals in group B (those that underwent only liposuction) and in 6 animals of group C (liposuction and lipografting). No fat particles were found in any organ of the control group. CONCLUSIONS: With this experiment, the authors showed that there is a risk of systemic mobilization of fat after liposuction surgery and that this risk is even higher when fat grafts are also carried out.

Efficacy of a new oxygenator-integrated fat and leukocyte removal device.

We evaluated the effectiveness of a new oxygenator-integrated device for removing lipid particles and leukocytes from shed mediastinal blood in 20 patients undergoing elective cardiac surgery under cardiopulmonary bypass. Another 20 patients undergoing cardiac surgery without the device served as controls. After filtration with the RemoveLL device, lipid particles, leukocytes, and fats were significantly reduced compared to preoperative levels. In the control group, blood fats and lipid particles at the end of cardiopulmonary bypass were significantly increased compared to preoperative levels. Leukocyte counts at the end of bypass were significantly lower in patients who had the filtration device compared to the control group. Platelets counts and hematocrit changes were not significantly different between the 2 groups.

[Experimental study of early blood purification in the treatment of post traumatic pulmonary fat embolism].

OBJECTIVE: To study the effect of early continuous blood purification (CBP) in the treatment of post-traumatic pulmonary fat embolism in dog. METHODS: Twelve healthy male mongrel dogs were randomly divided into two groups: group A received intramedullary reaming and bone cement injection of bilateral femurs (n=6), and group B received CBP simultaneously at the beginning of the same operation and continued until 120 minutes after the end of the operation (n=6). The changes in arterial blood gas and related cytokines were monitored at various time points. The animals were sacrificed 120 minutes after the operation, and the lungs were obtained for examination, and the amount of oil red O stained fat emboli was recorded. RESULTS: In group A, the mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP) and extravascular lung water (EVLW) increased after the manipulation in single femur, and these changes persisted after the manipulation on both femurs (all P<0.05). There was a decrease in pH and arterial partial pressure of oxygen (PaO2) and an increase in arterial partial pressure of carbon dioxide (PaCO2), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-6 after the operation on both femurs, showing significant differences compared with those of pre-operation period (all P<0.05). In group B, the hemodynamics, contents of cytokines and arterial blood gases were stable. Compared with those of group A, there was a significant decrease in the number of pulmonary fat emboli in group B (4.17+/-1.99 vs. 18.13+/-6.25, P<0.05). CONCLUSION: The therapy of CBP could decrease the level of the serum TNF-alpha, IL-1 beta , IL-6 and EVLW, MPAP, PCWP, which could ameliorate gas exchange and oxygenation of the lung. And it also could reduce the number of pulmonary fat emboli and decrease the incidence of pulmonary fat embolism caused by femoral intramedullary operation.

Gravity separation of pericardial fat in cardiotomy suction blood: an in vitro model.

Fat emboli generated during cardiac surgery have been shown to cause neurologic complications in patients postoperatively. Cardiotomy suction has been known to be a large generator of emboli. This study will examine the efficacy of a separation technique in which the cardiotomy suction blood is stored in a cardiotomy reservoir for various time intervals to allow spontaneous separation of fat from blood by density. Soybean oil was added to heparinized porcine blood to simulate the blood of a patient with hypertriglyceridemia (> 150 mg/dL). Roller pump suction was used to transfer the room temperature blood into the cardiotomy reservoir. Blood was removed from the reservoir in 200-mL aliquots at 0, 15, 30 45, and 60 minutes. Samples were taken at each interval and centrifuged to facilitate further separation of liquid fat. Fat content in each sample was determined by a point-of-care triglyceride analyzer. Three trials were conducted for a total of 30 samples. The 0-minute group was considered a baseline and was compared to the other four times. Fat concentration was reduced significantly in the 45- and 60-minute groups compared to the 0-, 15-, and 30-minute groups (p < .05). Gravity separation of cardiotomy suction blood is effective; however, it may require retention of blood for more time than is clinically acceptable during a routing coronary artery bypass graft surgery.

Fat extravasation due to unreamed and experimentally reamed intramedullary nailing of the sheep femur.

AIM: To compare systemic fat extravasation in unreamed and experimentally reamed nailing. METHODS: An osteotomy was created in the proximal third of the femoral shaft in 16 sheep, and intramedullary pressure increase and fat extravasation were monitored for the two nailing techniques. RESULTS: The highest intramedullary pressures, median 2700 mm Hg, and highest percentages of fat extravasation, peaking at almost 90% of fat, were found for the unreamed nailing technique. The values for the reamed group were significantly lower. CONCLUSIONS: The extravasation of intramedullary fat can be attributed to the great increase in intramedullary pressure that occurs during unreamed nailing. Correctly performed intramedullary reaming with the new reaming system produces lower pressures and much less systemic fat extravasation, reducing the risk for fat embolism.

Circulating particles during cardiac surgery.

Shed blood is known to be a source of lipid micro-emboli in cardiac surgery. The aim of this study was to characterize the occurrence of these particles at different stages of the operation, and to study their occurrence in the circulation at multiple time-points after the retransfusion of shed blood. Forty-four patients undergoing routine surgery with cardiopulmonary bypass were included. Blood was sampled from the surgical field at different sampling locations during the operation. Shed blood was collected in a transfusion bag and retransfused. After which, blood was sampled from the arterial line of the heart-lung machine. A Coulter counter was used for particle determinion. The mean volume of shed blood collected was 340+/-215 ml. Particles in the size range 10-60 microm were found at varying concentrations, with the highest concentrations being found in blood collected after cannulation and from the pleura. After retransfusion of this blood, a biphasic response was seen in the blood drawn from the efferent line of the heart-lung machine. Particles are found in shed blood at all times during cardiac surgery, and when this blood was retransfused an increase was seen in particle concentration in the heart-lung machine.

Plasma levels of endothelin-1 after a pulmonary embolism of bone marrow fat.

BACKGROUND: During orthopedic surgery, embolization of bone marrow fat can lead to potentially fatal, intra-operative cardiovascular deterioration. Vasoactive mediators may also be released from the bone marrow and contribute to these changes. Increased plasma levels of endothelin-1 (ET-1) have been observed after pulmonary air and thrombo-embolism. The role of ET-1 in the development of acute cardiovascular deterioration as a result of bone marrow fat embolization during vertebroplasty was therefore investigated. METHODS: Bone cement was injected into three lumbar vertebrae of six sheep in order to force bone marrow fat into the circulation. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output, arterial and mixed venous blood gas parameters and plasma ET-1 concentrations were measured at selected time points. Post-mortem, lung biopsies were taken for analysis of intravascular fat. RESULTS: Cement injections resulted in a sudden (within 1 min) and severe increase in pulmonary arterial pressure (>100%). Plasma concentrations of ET-1 started to increase after the second injection, but no significant changes were observed. Intravascular fat and bone marrow cells were present in all lung lobes. CONCLUSION: Cement injections into vertebral bodies elicited fat embolism resulting in subsequent cardiovascular changes that were characterized by an increase in pulmonary arterial pressure. Cardiovascular complications as a result of bone marrow fat embolism should thus be considered in patients undergoing vertebroplasty. No significant changes in ET-1 plasma values were observed. Thus, ET-1 did not contribute to the acute cardiovascular changes after fat embolism.

Fat content in pericardial suction blood and the efficacy of spontaneous density separation and surface adsorption in a prototype system for fat reduction.

OBJECTIVE: Fat embolization to the brain is a potential problem in cardiac surgery, assumed to originate from retransfused pericardial suction blood. Our aim was to measure the fat content in pericardial suction blood and to determine how it can be reduced by simple spontaneous density separation and surface absorption. METHODS: Pericardial suction blood was collected during routine coronary bypass procedures and analyzed for blood-suspended fat and plastic surface binding. A single-chamber bag (n = 10) was compared with a fat-reducing system having a stacked 2-chamber design (n = 10). The fat-reducing system was also tested experimentally (n = 12) with heat-extracted liquid wound fat (1.25%) mixed with mediastinal drain blood. RESULTS: Pericardial suction blood contained 1.5 mL (0.63/2.19) of fat suspended in 418 mL (269/631) of blood (median and quartiles). Surface-bound fat accounted for 24% (12/35). Experimental analysis of the new system revealed an 83% (71/92) fat-reduction rate (P < .001). This rate was confirmed under clinical conditions, suggesting 80% reduction (72/86; P = .001). The fat-reducing system also gave a small but significant red blood cell concentrating effect (P = .001). CONCLUSIONS: It was confirmed that pericardial suction blood contains fat, possibly having an embolic potential. The new system allowed fat to separate by density while pericardial suction blood was temporally retained and incubated. A significant portion of fat adheres to the plastic surface, which added to the reduction. The method appeared efficient. It is proposed that pericardial suction blood should be collected during surgery to evaluate the need for retransfusion and to allow fat reduction.

Quantification of fat mobilization in patients undergoing coronary artery revascularization using off-pump and on-pump techniques.

Fat mobilization during cardiopulmonary bypass (CPB) is a recognized risk of the procedure. Intravascular mobilization of fat emboli subsequent to CPB has been implicated in some of its recognized pathophysiologies, particularly with regard to cerebral embolic injury. The aim of this study was to investigate whether fat mobilization is still a real issue in modern perfusion practice and to determine whether off pump coronary artery bypass techniques minimize this risk. Thirty patients undergoing routine elective coronary artery bypass graft (CABG) surgery were divided into two groups. Group 1 patients underwent off pump coronary artery bypass (OPCAB) procedures, and group 2 underwent CABG supported with CPB. Blood samples were taken from the CPB patients at the beginning, middle, and end of the procedure, from the suction line, from the arterial line, and from the venous line for measurement of fat emboli present. Samples were taken at corresponding time-points from the OPCAB patients for similar measurements. Fat emboli were counted manually using Oil red O staining and light microscopy. The fat emboli were sized using calibrated microspheres as a visual size contrast. No fat emboli were observed in any of the blood samples taken from the OPCAB patients. There were fat emboli present in all samples taken during CPB from all sources. The count was highest in the suction system and lowest in the venous blood and tended to increase during CPB. There was an absence of large fat emboli in the venous blood, which tends to indicate that the larger fat emboli lodge in the microvasculature. OPCAB surgery eliminates the risk of fat embolization in patients undergoing coronary revascularization. The suction system is the major source of fat emboli during CPB, and despite the multiple filtration components of the CPB system, fat emboli of various and significant sizes do reach the patient. Fat embolization remains a risk in routine elective CABG surgery. Cardiotomy suction should be eliminated where possible.

Secretory phospholipase A2 levels in patients with sickle cell disease and acute chest syndrome.

In a multicenter study (eight centers), we determined secretory phospholipase A(2) (sPLA(2)) levels in patients with sickle cell disease and acute chest syndrome (ACS). The diagnosis of ACS was made according to established criteria. The sPLA2 levels were determined in blood samples collected at baseline (time of diagnosis) and serially thereafter up to day 22-35 follow-up visits. Thirty-four of 43 (80%) patients with ACS had enzyme levels > or =1.00 AU at baseline. The enzyme levels decreased significantly on Days 2 through Days 25-35 after baseline. Nine of 43 (20%) patients had baseline sPLA2 values of <1.00 AU with six of them never exceeding 1.00 AU at any point in time during follow-up. The data indicate that the reliability of sPLA(2( for predicting the development of ACS is not perfect (100%) as was previously reported but occurs in about 80% of the patients.