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Introduction: Bone marrow embolization may complicate orthopedic surgery, potentially causing fat embolism syndrome. The inflammatory potential of bone marrow emboli is unclear. We aimed to investigate the inflammatory response to femoral intramedullary nailing, specifically the systemic inflammatory effects in plasma, and local tissue responses. Additionally, the plasma response was compared to that following intravenous injection of autologous bone marrow., Methods: Twelve pigs underwent femoral nailing (previously shown to have fat emboli in lung and heart), four received intravenous bone marrow, and four served as sham controls. Blood samples were collected hourly and tissue samples postmortem. Additionally, we incubated bone marrow and blood, separately and in combination, from six pigs in vitro . Complement activation was detected by C3a and the terminal C5b-9 complement complex (TCC), and the cytokines TNF, IL-1β, IL-6 and IL-10 as well as the thrombin-antithrombin complexes (TAT) were all measured using enzyme-immunoassays., Results: After nailing, plasma IL-6 rose 21-fold, compared to a 4-fold rise in sham (p=0.0004). No plasma differences in the rest of the inflammatory markers were noted across groups. However, nailing yielded 2-3-times higher C3a, TCC, TNF, IL-1β and IL-10 in lung tissue compared to sham (p<0.0001-0.03). Similarly, heart tissue exhibited 2-times higher TCC and IL-1β compared to sham (p<0.0001-0.03). Intravenous bone marrow yielded 8-times higher TAT than sham at 30 minutes (p<0.0001). In vitro , incubation of bone marrow for four hours resulted in 95-times higher IL-6 compared to whole blood (p=0.03)., Discussion: A selective increase in plasma IL-6 was observed following femoral nailing, whereas lung and heart tissues revealed a broad local inflammatory response not reflected systemically. In vitro experiments may imply bone marrow to be the primary IL-6 source., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kristiansen, Storm, Emblem, Grønli, Pettersen, Hilmo, Jarmund, Leth-Olsen, Nyrnes, Nilsen, Nielsen and Mollnes.)

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.

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.

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The article deals with diagnosis and treatment of fat embolism concomitant with trauma. A new term is suggested, i.e. liqoroglobulism, which is concomitant with the cerebral form of fat embolism. The results of investigations of patients, who endured fat embolism, are presented. A new method is suggested for the treatment of fat embolism, i.e. a combination of hemosorption and liquosorption. A thesis on that the blood-brain barrier is damaged in the cerebral form of fat embolism is formulated.

Diffuse brain damage is a complex problem in cardiac surgery postoperatively. Liquid fat from recycled pericardial suction blood (PSB) is an embolic source. PSB can be discarded, but the recycling can be life saving, and methods have been developed to remove the fat. Blood washing by centrifugation is suggested to be the most effective method. In retained PSB, fat also separates without centrifugation, which is a novel and simple approach. Alternatively, inline fat filtration is easily accomplished but its effectiveness has been questioned. The present study aimed to investigate this phenomenon. Fat was heat extracted from retrieved pericardial fat tissue of coronary artery bypass graft (CABG) patients (n = 6), and was mixed, 1.25%, with postoperative mediastinal-shed blood. The mixture was filtered using a LipiGuard SB at constant flow rate. The filtration was scaled down to 3 mL and performed under temperature control, 37 degrees C, 20 degrees C and 10 degrees C. At these temperatures fat removal was 46.9 +/- 6.1%, 61.5 +/- 7.0% and 76.8 +/- 5.0%, respectively, with a statistical difference of P = 0.001. The improved fat removal at low temperature dramatically increased filtration pressures (P < 0.001) and caused haemolysis (P = 0.018). It is concluded that fat filtration is technically difficult. Cooling of blood increases fat extraction, but with negative side effects due to filter occlusion.

The authors discuss evaluation of the severity of fatty embolism. Three criteria are taken into consideration: clinical symptoms, presence of fat in the serum or liquor, and presence of fat on the surface of serum or liquor. The broth symptom is defined. The studies indicate that after detection of this symptom microscopy of the serum for detecting fatty globulemia is inefficient.

Background and Purpose: We sought to quantitatively and qualitatively evaluate the release of atheromatous plaque debris induced by carotid stenting procedures., Methods: Eight patients with severe carotid atheromatous stenoses were treated by stent implantation under distal balloon protection. Blood samplings were obtained after stent deployment in the blood pooled below the inflated protection balloon. The samples were centrifuged and evaluated for plaque debris with the use of light microscopy. The debris release was quantitatively estimated by dividing the total volume of debris obtained by the mean debris size. Five patients without endovascular procedure were used as a control group., Results: The 2 main debris types found were nonrefringent cholesterol crystals (4 to 389 microm; 115 to 8697 in number) and lipoid masses (7 to 600 microm; 341 to 34 000 in number). There was a statistically significant difference compared with the samples obtained in the control group (P:=0.017)., Conclusions: Blood samples collected during stent implantation procedures contain a large quantity of atheromatous plaque debris. This emphasizes the role of distal protection techniques in avoiding migration of this plaque material into the cerebral circulation.

The article is devoted to the problem of fat embolism. In 63 patients with combined and isolated traumas the maximum frequency of fat embolism was diagnosed in the investigation of blood serum from the femoral artery. It can be supposed that no isolated injury of the lesser circulation circuit can occur in fat embolism. An investigation of the venous-arterial difference of fat globulemia has shown the main role of the so-called theory of shunting for fat embolism to be doubtful.

This study was designed to investigate whether intramedullary pressure and embolization of bone marrow fat are different in unreamed compared with conventional reamed femoral nailing in vivo. In a baboon model, the femoral shaft was stabilized with interlocking nailing after a midshaft osteotomy. Intramedullary pressure was measured in the distal femoral shaft fragment at the supracondylar region. Extravasation of bone marrow fat was determined by the modified Gurd test (range: 0-5) with blood samples from the vena cava inferior. Data were monitored in eight unreamed and eight reamed intramedullary femoral nailing procedures. Intramedullary pressure increased in the unreamed group to 76 +/- 25 mm Hg (10.1 +/- 3.3 kPa) during insertion of 7-mm nails and in the reamed group to 879 +/- 44 mm Hg (117.2 +/- 5.9 kPa) during reaming of the medullary cavity. Insertion of 9-mm nails after the medullary cavity had been reamed to 10 mm produced an intramedullary pressure of 254 +/- 94 mm Hg (33.9 +/- 12.5 kPa) (p < 0.05). Fat extravasation in the unreamed group was recorded with a score of 2.9 +/- 0.4 for the Gurd test during nailing with 7-mm nails, whereas in the reamed group significantly more fat extravasation was noticed during the reaming procedures, with a score of 4.6 +/- 0.1. Liberation of fat during insertion of 9-mm nails after reaming was recorded with a score of 3.5 +/- 0.4. In both groups, a positive correlation of fat extravasation with the rise in intramedullary pressure was found (reamed group: r(s) = 0.868; unreamed group: r(s) = 0.698), resulting in significantly less liberation of bone marrow fat in the unreamed stabilized group than in the reamed control group (p < 0.05). The data indicate that fat embolization during nailing procedures after femoral osteotomy increases with increasing intramedullary pressure and occurs in a lesser degree in unreamed than in reamed intramedullary femoral shaft stabilization.

Objective: To investigate the catalytic activity of phospholipase A2 in serum during the early phase of experimental fat embolism., Design: Randomised controlled experimental study., Setting: Animal laboratory, Finland., Subjects: 18 domestic pigs weighing 25-31 kg., Interventions: Allogeneic bone marrow suspension at a dose of 100 mg/kg was infused intracavally in 9 anaesthetised, mechanically ventilated, and haemodynamically monitored pigs; 9 control pigs received saline., Main Outcome Measures: Central haemodynamics, blood gases, catalytic activity of phospholipase A2., Results: In the fat embolism group, there were significant increases in mean pulmonary arterial pressure (p < 0.001), pulmonary vascular resistance (p < 0.001) and pulmonary shunting (p < 0.05) and simultaneously, systemic oxygenation was significantly impaired. The animals with fat embolism developed gradual fever and leucocytosis, whereas the catalytic activity of phospholipase A2 remained relatively unchanged., Conclusion: In this experimental model the measurement of serum phospholipase A2 activity does not provide a useful tool for the early detection of experimental fat embolism.

In order to understand the role of vasoactive peptides in fat embolism, arterial plasma atrial natriuretic peptide (ANP) and endothelin-1 concentrations were investigated in an experimental study. Nine anesthetized and mechanically ventilated pigs received an intracaval infusion of allogeneic bone marrow suspension at a dose of 100 mg/kg (fat embolism group); 9 control pigs received saline. The observation period was 5 h. In the fat embolism group, cardiac index and heart rate decreased within 30 min, whereas mean arterial pressure remained stationary. Pulmonary capillary wedge pressure rose transiently and central venous pressure rose slightly in time, while mean pulmonary arterial pressure, pulmonary vascular resistance and pulmonary shunt increased immediately and persistently after the bone marrow suspension infusion. Simultaneously, arterial oxygen tension and arterial hemoglobin oxygen saturation decreased markedly. Arterial plasma ANP and endothelin-1 concentrations remained stable in the fat embolism animals, whereas in the controls ANP and endothelin-1 levels decreased at 3 and 5 h. Arterial epinephrine concentrations were stable in animals receiving bone marrow suspension, while in the controls arterial epinephrine concentrations decreased towards the end of the experiment. Arterial norepinephrine concentrations remained unchanged in both groups. To conclude, impaired pulmonary function and consequent systemic hypoxemia distinguish the present fat embolism model. Unchanged arterial ANP and endothelin-1 concentrations in the fat embolism group suggest that these circulating vasoactive hormones have a minor impact on the pathogenesis of the current experimental fat embolism.

Objective: To investigate the acute effects of experimental fat embolism on splanchnic and peripheral perfusion and oxygenation in pigs., Design: Randomized, controlled trial., Setting: Animal laboratory., Subjects: Eighteen domestic pigs, weighing 25 to 31 kg., Interventions: The 18 pigs were randomized to either the fat embolism or control groups. Nine anesthetized and mechanically ventilated pigs were intracavally infused with a 10% allogeneic bone marrow suspension at a dose of 100 mg/kg over 5 mins (the fat embolism group); nine control pigs received normal saline in the same volume and speed (control group)., Measurements and Main Results: Mean pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary shunt increased, and PaO2 decreased immediately after the bone marrow suspension infusion. In the fat embolism animals, oxygen delivery decreased, oxygen content difference widened, and total oxygen consumption remained high, indicating enhanced oxygen extraction. Further, superior mesenteric artery blood flow and mesenteric oxygen delivery decreased, while intramucosal pH in the small bowel was stable. Subcutaneous PO2 decreased in both groups, whereas transcutaneous PO2 decreased only in the animals receiving bone marrow suspension. Skin red cell flux showed no significant changes., Conclusions: The present model of fat embolism results in significant impairment in systemic oxygenation. Despite this fact, the intestinal oxygenation remains unaffected probably due to sufficient compensatory mechanisms. Transcutaneous PO2 measurements may provide a useful index for early detection of fat embolism.

Nine anesthetized and mechanically ventilated test pigs were intracavally infused with a 10% allogeneic bone marrows suspension at a dose of 100 mg/kg over 5 min; 9 control pigs received saline. The cardiac index decreased slightly in the fat embolism animals. Left ventricular stroke work remained unchanged in both groups, whereas right ventricular stroke work rose in the fat embolism animals. Mean arterial pressure remained stationary in the test group but rose in the controls. Pulmonary capillary wedge pressure and central venous pressure rose slightly in the test group. After infusion of the bone marrow suspension, mean pulmonary arterial pressure, pulmonary vascular resistance, pulmonary shunt and alveoloarterial oxygen tension difference increased immediately and remained elevated throughout the study period. Simultaneously, arterial and mixed venous oxygen tension and hemoglobin oxygen saturation decreased. Arterial carbon dioxide tension and hematocrit remained stationary. The fat embolism animals developed gradual fever. In conclusion, increased mean pulmonary arterial pressure, pulmonary vascular resistance, pulmonary shunt and alveoloarterial oxygen tension difference proved to be useful early indicators of experimental fat embolism.

To find the diagnostic methods for subclinical stage fat embolism syndrome (FES), we established an experimental animal model, using fat intravenous injection. The fat was obtained from the long bone marrow cavity of homologous dogs. Fourteen healthy mongrel dogs received 0.7 ml/kg fluid marrow fat injection and all of them developed FES within 48 hours. The blood samples collected from the pulmonary vessels by floating catheter and peripheral vein at different time intervals were subjected to blood gas analysis and were frozen sectioned rapidly. The sections were stained with oil red 'O'. Positive result was seen 2 hours after fat injection in both pulmonary and peripheral blood. Computer image analysis showed that the number and diameter of fat droplets in pulmonary vascular blood were obviously higher and larger than those in peripheral vein blood. These findings were correlated well with blood gas changes and clinical features. The demonstration of fat droplets from pulmonary or peripheral blood by oil red 'O' staining combined with blood gas changes (PaO2 < 7.99 kPa, P(A-a)O2 > 6.09 kPa) may be rapid and specific for early diagnosis of FES. In the treatment of FES, dexamethason can stabilize the cellular membranes and inhibit the neutrophil response to fatty acid and the release of phospholipase A2, arachidonic acid and platelet aggregation.

In multiple trauma patients with lung contusion, pulmonary complications have been reported that were attributed to intramedullary stabilization of the femur. The reaming procedure of the medullary canal is thought to play a major role. We investigated whether different types of reamers might exert different amounts of fat mobilization into the vascular system and different degrees of pulmonary dysfunction. Adult female Merino sheep were submitted to hemorrhagic shock (2 h, 50 mm Hg) and a unilateral lung contusion; in addition, a lung lymph fistula was created. Pulmonary capillary permeability, central venous triglyceride levels, 11-dehydro-thromboxane B2 (dh-TXB2) levels, and pulmonary artery pressure were determined. After recovery, animals were randomly assigned to intramedullary femoral nailing using several types of reamers: group A, AO reamer (n = 8); group B, Biomet reamer (n = 7); group H, Howmedica reamer (n = 6); group C, controls, no reaming (n = 4). Intramedullary reaming caused a significant (p < 0.05) increase in pulmonary artery pressure in groups A and B; dh-TXB2 levels increased in all groups. Statistically significant (p < 0.05) pulmonary capillary permeability damage was measured in group A only. Intramedullary femoral nailing can cause transient pulmonary hemodynamic and mediator effects as well as increased pulmonary capillary permeability. In the present study, this effect was evident in group A reamer systems only, which may be due to reamer construction.

Fat embolism syndrome is a potentially serious and life threatening complication of long bone trauma, blunt trauma, and intramedullary manipulation. In long bone fractures, fat embolism is encountered in 0.9% to 2.2% of cases. During intramedullary manipulations, such as prosthetic stem insertion or reaming, the incidence is typically lower (range, 0.5% to 0.8%). Diagnosis is dependent upon the clinical recognition of dyspnea, petechiae, and cognitive dysfunction in the first several days following fracture, trauma, or intramedullary surgery. Treatment consists of pulmonary support and aggressive resuscitation. Studies support early fracture fixation, but the role of systemic steroids, heparin, and other modalities remains speculative.

Available objective tests for fat embolism are neither sensitive nor specific. We performed frozen-section analysis of blood aspirated from a pulmonary artery catheter in a trauma victim with fat embolism syndrome and found marked levels of pulmonary microvascular blood fat. The amount of fat detected in this patient with long bone fractures was higher than that observed in a pilot study of this technique in cardiopulmonary bypass patients. This technique provided diagnostic support of our clinical findings. The procedure may prove useful in patients with an equivocal diagnosis of fat embolism or when the cause of posttraumatic acute pulmonary insufficiency is unknown.

Objective: To determine the effects of fat emboli on cardiopulmonary function in critically ill patients., Design: A prospective study., Setting: Tertiary referral medical/surgical shock/trauma intensive care unit (ICU)., Patients: A total of 51 critically ill medical and surgical (including acute trauma) patients who required supplemental oxygen (FIO2 of > or = 0.35) to maintain arterial blood oxyhemoglobin saturation of > or = 90% and who had 62 pulmonary artery catheters placed for patient care reasons., Interventions: Pulmonary capillary blood samples were obtained via the pulmonary artery catheters in the "wedged position" at insertion and postinsertion at 8, 24, 48, and 72 hrs. Cytospun smears of the buffy coat aspirates of these samples were made and were stained with Oil Red-O for fat., Measurements and Main Results: One investigator, without knowledge of the patients' cardiopulmonary function, examined all smears and graded them 0 to 4+ for amount of fat. Fat scores were correlated with chest radiograph appearance, hemodynamic and respiratory parameters, complete blood cell counts with differential white blood cell counts, whether the patient was receiving lipid-containing parenteral nutrition, principal organ system failure, and reason for ICU admission. Samples from 27 pulmonary artery catheter insertions had no fat, 13 samples had low-grade (1+) episodic fat, and 22 samples had repeated episodes of > or = 2+ fat or isolated episodes of 4+ fat. There was a significant association between the amount of pulmonary microvascular fat and trauma as the reason for ICU admission. Of the other parameters, only chest compliance and body temperature showed unequivocal significant associations. These associations were opposite to the expected findings, but would support a conclusion that fat emboli did not cause the observed cardiopulmonary dysfunction. The inconsistent associations for the FIO2, PCO2, and mixed venous blood oxyhemoglobin saturation may be random events., Conclusion: Cardiopulmonary dysfunction commonly attributed to fat emboli is likely due to other causes.

Pulmonary microvascular cytology consists of analysis of capillary blood sampled while a Swan-Ganz catheter is in the wedge position. This technique has proved to be useful in the diagnosis of lymphangitic spread of carcinoma in the lungs and there are case reports of their use in amniotic fluid embolism. Its usefulness in diagnosing fat embolism syndrome has been shown only rarely. We report a new case in which pulmonary microvascular cytologic study allowed a definite diagnosis of fat embolism syndrome. We suggest obtaining routinely samples of capillary blood when a pulmonary catheter is in place and fat embolism is suspected on a clinical basis.

The clinical and laboratory retrospective and prospective study orientated to the observation of total posttraumatic response of the organisms to serious injuries (fractures of long bones of lower extremities, fractures of bones of pelvis, serious multiple injuries of body cavities associated with fractures) has concentrated hyperglobulaemia and at the same time also of disorders of blood coagulation. These in all three institutes on the verification of the significance of hyperglobulaemia, disorders of blood coagulation and persistent tachycardia. The analysis of the relations between the findings of fat hyperglobulaemia, disorders of coagulation and persistent tachycardia has made it possible to present a thesis which is very important from the practical viewpoint, and namely that the persistent tachycardia in case of in-patients is in fact a clinical reflection or manifestation, an equivalent, even of the incidence of fat studies concentrated on the syndrome of traumatic fat embolism (F. E.) were carried out within a uniform concept of "post-traumatic dyslipidemic coagulopathy - PDC". A statistically significant relation has been proved between the incidence of fat hyperglobulaemia and the incidence of persistent tachycardia. When identifying the relations between individual laboratory and clinical findings the authors have proceeded from a pre-requisite we have objectified before, and namely that fat hyperglobulaemia and disorders in blood coagulation contribute significantly to the development of the syndrome of post-traumatic fat embolism. The origin of persistent tachycardia which is motivated in patients with fractures of bones neither by the increase of temperature nor by any other pathophysiological circumstances, represents a turning point or a time limit between PDC as a latent pathological condition and PDC with clinical manifestations, being associated in the subclinical form only with persistent tachycardia or in the manifest form with other evident symptoms (including persistent tachycardia). It is then possible to use the symptom of an early and persistent tachycardia in the clinical practice for the prognostication of possibilities of unfavourable pathophysiological development of the subclinical form of fat embolism into the clinically manifest form of fat embolism.

The body's response to the effects of mechanical injury, taking the form of shock during the first hours and the onset of fat embolism in the subsequent period, is substantially higher in patients with multiple or associated injuries, both as regards the severity of manifestations and prognostic risk. Also the death rate due to this sort of complication is seen rising. Two groups of injured persons with isolated (n = 33) and multiple fractures (n = 33) were used to show that dynamic follow-up of PaO2 in the blood could serve as a criterion of the risk of fat embolism development in the body and, in particular, as a prognostic criterion for the progress of fat embolism. Special point was made of findings demonstrating a time relationship between PaO2 deterioration in the early post-injury period (up to 24-36 hours) as compared with the period of 48-72 hours after the injury. PaO2 is seen dropping rapidly in injured persons showing signs of fat embolism syndrome development. The decrease can be recorded as early as the free interval phase, i.e. prior to the manifestation of the clinical signs of fat embolism. The findings of low PaO2 levels in the blood are in accordance with respiratory ventilation disturbances and impaired diffusion documented in our investigation.

The acute effects of a triolein infusion in dogs were secondary to the mechanical effects of this neutral fat which was distributed in the pulmonary and systemic vascular tree of all organs without inflammatory change. Hypoxia developed immediately and became progressively worse as the infusion was continued. Pulmonary hypertension developed during the fat infusion without pneumonia, congestive heart failure or pulmonary edema. There was a slow leak of 14C triolein into the systemic circulation rather than a rapid shower, and this radioactive fat was recirculated between the pulmonary and systemic vasculature. Seventy-six per cent of the 14C triolein was retained in the lungs. Terminally, the dogs had a respiratory arrest without cardiac decompensation, cardiac arrest or pulmonary edema; cerebral fat embolism in addition to severe hypoxia appears to be the cause.

Lipids of fat emboli released in the circulating blood of seven patients undergoing hip prostheses were compared with those of plasma, adipose tissue and bone marrow taken simultaneously. Similar in composition to bone marrow, fat emboli, as compared with plasma lipids, contain negligible amounts of free esterified cholesterol, a relative decrease of oleic acid and an increase of palmitic acid in triglycerides and a lower percentage of linoleic acid in phospholipids. The results of this study validate the theory that fat emboli originate from bone marrow in fractures of the long bone.