Fifty-five adults who had sustained a tibial fracture, or a femoral fracture, or both, were subjected to a double-blind randomised study to determine the efficacy of methylprednisolone in treating the fat embolism syndrome. This drug maintained arterial oxygen levels, stabilised or reduced the serum level of free fatty acids, and decreased the risk of the fat embolism syndrome in a statistically significant proportion of patients. Gurd's criteria for the diagnosis of the fat embolism syndrome were found inadequate. Other more sensitive criteria for early diagnosis and effective management were determined. There were no deaths or serious morbidity in our series

Pulmonary embolism is a serious complication after arthroscopy of the knee, about which there is limited information. We have identified the incidence and risk factors for symptomatic pulmonary embolism after arthroscopic procedures on outpatients. The New York State Department of Health Statewide Planning and Research Cooperative System database was used to review arthroscopic procedures of the knee performed on outpatients between 1997 and 2006, and identify those admitted within 90 days of surgery with an associated diagnosis of pulmonary embolism. Potential risk factors included age, gender, complexity of surgery, operating time defined as the total time that the patient was actually in the operating room, history of cancer, comorbidities, and the type of anaesthesia. We identified 374 033 patients who underwent 418 323 outpatient arthroscopies of the knee. There were 117 events of pulmonary embolism (2.8 cases for every 10 000 arthroscopies). Logistic regression analysis showed that age and operating time had significant dose-response increases in risk (p < 0.001) for a subsequent admission with a pulmonary embolism. Female gender was associated with a 1.5-fold increase in risk (p = 0.03), and a history of cancer with a threefold increase (p = 0.05). These risk factors can be used when obtaining informed consent before surgery, to elevate the level of clinical suspicion of pulmonary embolism in patients at risk, and to establish a rationale for prospective studies to test the clinical benefit of thromboprophylaxis in high-risk patients

Hip and knee replacements are common and successful surgeries in orthopaedics. One of the known complications is fat embolism. Cemented implants used in arthroplasty allow good implant fixation and excellent long term results. However this has been associated with an increased incidence of fat embolism. This experimental animal study compared the amount of fat embolism following three different surgeries in 30 Sprague Dawley rats. These surgeries simulated hip replacement procedures and included a control surgery, an un-cemented implant and a cemented implant. These animals were then sacrificed at 24 hours. All the lungs were fixed in formalin and then stained using Osmium Tetroxide. The amount of fat was then counted using a light microscope at 40x power. Both the uncemented implant group (p < 0.001) and the cemented implant groups (p < 0.003) had significantly higher fat emboli from the surgical control group. There were also a significantly higher number of emboli (p < 0.05) in the cemented implant group compared to the uncemented implant group. We conclude that fat embolism occurs in both the un-cemented and cemented hip replacement. The amount of emboli created by un-cemented hip replacement is less than the cemented hip replacement. The cement itself does not cause the complication of fat embolism. It is the high intramedullary pressure associated with the insertion of the implant, and the cementing process, that contributes to fat embolism. Devices or surgery that minimise this rise in pressure could reduce the amount of fat embolism

The Pulmonary Embolism Prevention (PEP) Trial was designed to assess the effects of a 35 day course of aspirin (160 mg daily) on the risks of thromboembolic events, other cardiovascular outcomes and bleeding among individuals undergoing surgery for hip fracture or joint replacement. From 1992 to 1998, 148 hospitals in Australia, New Zealand, South Africa, Sweden and the United Kingdom randomised 13,356 hip fracture patients, and 22 hospitals in New Zealand randomised 4,088 elective arthroplasty patients. Among hip fracture patients, aspirin produced proportional reductions in PE of 43% (95% confidence interval [CI] 18% to 60%; 2P=0.002) and symptomatic DVT of 29% (95% CI 3% to 48%; 2P=0.03). PE or DVT was confirmed in 105 (1.6%) of 6679 patients allocated aspirin versus 165 (2.5%) of 6677 allocated placebo, representing an absolute reduction of 9±2 per 1000 and a proportional reduction of 36% (95% CI 19% to 50%; 2P=0.0003). Aspirin prevented 4±1 fatal pulmonary emboli per 1000 treated (18 aspirin vs 43 placebo deaths), representing a proportional reduction of 58% (95% CI 27% to 76%; 2P=0.002), with no apparent effect on deaths from other vascular (hazard ratio 1.04; 95% CI 0.86 to 1.26) or non-vascular cause (1.01; 95% CI 0.84 to 1.23). Deaths due to bleeding were rare (13 aspirin vs 15 placebo), but there was an excess of 6±3 post-operative transfused bleeds per 1000 allocated aspirin (2P=0.04). Among elective arthroplasty patients, venous thromboembolism rates were lower but the proportional effects of aspirin appeared similar to those among hip fracture patients

Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight. Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A. 2. , nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid. This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome

Aims. The aim of this study was to assess whether it is possible to predict the mortality, and the extent and time of neurological recovery from the time of the onset of symptoms and MRI grade, in patients with the cerebral fat embolism syndrome (CFES). This has not previously been investigated. Methods. The study included 34 patients who were diagnosed with CFES following trauma between 2012 and 2018. The clinical diagnosis was confirmed and the severity graded by MRI. We investigated the rate of mortality, the time and extent of neurological recovery, the time between the injury and the onset of symptoms, the clinical severity of the condition, and the MRI grade. All patients were male with a mean age of 29.7 years (18 to 70). The mean follow-up was 4.15 years (2 to 8), with neurological recovery being assessed by the Glasgow Outcome Scale and the Mini-Mental State Examination. Results. In all, seven who had early-onset CFES (< 24 hours), and a severe Takahashi grade on MRI, died. There was a significant association between the time of onset of neurological signs and mortality (p = 0.035). Mortality was also significantly associated with a severe Takahashi grade (p < 0.001). Among the 27 surviving patients, 26 (96.3%) recovered completely. One (3.7%) had a cognitive deficit. The mean time to recovery was 4.7 weeks (2 to 13), with late recovery aftereight eight weeks being recorded in three patients. Conclusion. There was a significantly increased rate of mortality in patients with CFES who had an early onset of symptoms and a severe grade on MRI. Complete neurological recovery can be expected in most patients with CFES who survive. Cite this article: Bone Joint J 2022;104-B(1):142–149

This study was undertaken to assess the contribution of pulmonary fat embolism to systemic platelet activation in a rabbit model of fat embolism. Fifteen NZW rabbits were randomly assigned into one of two groups: fat embolism and control. Fat embolism was induced via intramedullary canal pressurization with a 1–1.5 ml bone cement injection. Only the animals that underwent fat embolism displayed consistent platelet activation, as demonstrated by platelet degranulation and procoagulatory surface expression. These findings suggest that fat embolism plays a role in platelet activation and in the overall activation of hemostasis following trauma. The objective of this study was to use a recently developed rabbit model of fat embolism to assess the systemic hemostatic response to pulmonary fat embolism. Our findings demonstrate platelet activation following forced liberation of bone marrow contents into the circulation only in the FE group, as demonstrated by CD62P elevation (a marker of platelet degranulation) and annexin V elevation (a marker of procoagulatory surface expression). Platelet activation also coincided with significantly lower platelet counts in the FE group at two and four hours post embolism, suggesting platelet aggregation. These findings suggest that fat embolism plays a role in platelet activation and in the overall activation of hemostasis following trauma. Platelet count decreased significantly at two and four hours post knee manipulation only in the FE group. Annexin V expression increased significantly in the FE group at two and four hours post knee manipulation. Lastly, CD62P expression only increased significantly in the FE group at two hours post knee manipulation. Fifteen New Zealand White male rabbits were randomly assigned into one of two groups: control and fat embolism (FE). In FE group (n=8), the intramedullary cavity was drilled, reamed and pressurized with a 1–1.5 ml bone cement injection. In the control group (n=7), a sham knee incision was made, exposing both femoral condyles, but was immediately closed without further manipulations. All animals were mechanically ventilated for an additional monitoring period of four hours post-surgical closure. For flow cytometric evaluation of platelet activation, blood samples were stained with fluorescence-conjugated antibodies against CD41 (FITC), CD62P (P-selectin) and annexin V (FITC). Platelet events were identified by their characteristic CD41 staining and size and were analyzed using a flow cytometer. All animals were mechanically ventilated for four hours post surgical closure. The implications of platelet activation following fat embolism are numerous, ranging from adherence and aggregation, to secretion of key components of both the coagulation and inflammatory cascades

We studied 4253 patients undergoing primary joint replacement between November 2002 and November 2007, of whom 4060 received aspirin only as chemical prophylaxis; 46 were mistakenly given low molecular weight heparin initially, which was stopped and changed to aspirin; 136 received no chemoprophylaxis and 11 patients received warfarin because of a previous history of pulmonary embolism. We identified the rate of clinical thromboembolism before and after discharge, and the mortality from pulmonary embolism at 90 days. The overall death rate was 0.31% (13 of 4253) and the rate of fatal pulmonary embolism was 0.07% (3 of 4253). Our data suggest that fatal pulmonary embolism is not common following elective primary joint replacement, and with modern surgical practice elective hip and knee replacement should no longer be considered high-risk procedures

This study was undertaken to assess the contribution of pulmonary fat embolism caused by intramedullary femoral canal pressurization to the development of acute lung injury in the presence of resuscitated hemorrhagic shock. Twenty-seven NZW rabbits were randomly assigned into one of four groups: resuscitated hemorrhagic shock and fat embolism, resuscitated hemorrhagic shock, fat embolism, and control. Fat embolism was induced via intramedullary cavity with a 1–1.5 ml bone cement injection. Only the animals that underwent resuscitated shock and fat embolism displayed amplified neutrophil activation and alveolar infiltration. These findings suggest that the combination of resuscitated shock with fat embolism initiates an inflammatory response, which may play a role in the development of fat embolism syndrome. The objective of this study was to assess the contribution of pulmonary fat embolism caused by intramedullary femoral canal pressurization to the development of acute lung injury in the presence of resuscitated hemorrhagic shock. Only the animals that underwent resuscitated shock and fat embolism displayed amplified neutrophil activation and alveolar infiltration. These findings suggest that the combination of resuscitated shock with fat embolism initiates an inflammatory response, which may play a role in the development of fat embolism syndrome. CD11b mean channel florescence was only significantly elevated in the HR/FE group at two and four hours post knee manipulation. Moreover, greater infiltration of alveoli by leukocytes was only significantly higher in the HR/FE group as compared to controls. Twenty-seven NZW rabbits were randomly assigned into one of four groups: resuscitated hemorrhagic shock + fat embolism (HR/FE), resuscitated hemorrhagic shock (HR), fat embolism (FE), and control. Hypovolemic shock was induced via carotid bleeding for one-hour prior to resuscitation. For fat embolism induction, the intramedullary cavity was drilled, reamed and pressurized with a 1–1.5 ml bone cement injection. For evaluation of neutrophil activation, blood was stained with antibodies against CD45 and CD11b and analyzed with a flow cytometer. Animals were mechanically ventilated for four hours post surgical closure. Postmortem thoracotomy was performed, and three stratified random blocks of each lung were processed for histological examination. Our findings suggest that FE by itself does not cause lung injury, as there were no apparent differences between the control and FE animals. Only the HR/FE animals revealed a higher number of infiltrating neutrophils into alveolar spaces and greater neutrophil activation

Introduction Cement leakage into adjacent structures is the main complication during vertebroplasty. The majority of these leaks are asymptomatic, but pulmonary cement embolism has been reported to cause cardiovascular disturbances and even death (. 1. ,. 2. ). Furthermore, the use of calcium phosphate (CaP) cements for vertebroplasty may aggravate cardiovascular deterioration in the event of cement embolism by stimulating coagulation [3]. The cardiovascular effects of pulmonary cement embolism were investigated using an animal model. Methods In 18 skeletally mature sheep, 2.0ml cement was injected into the pulmonary trunk during general anaesthesia (approved by Animal Ethics Committee). Three different cements were used: 1) PMMA (Simplex P, Stryker); 2) PMMA with 10% hydroxyapatite (PMMA & HA) (Vertecem, Synthes); 3) Experimental injectable CaP cement (Synthes). The following cardiovascular parameters were recorded continuously (endpoint: 60min post-injection): arterial, central venous, pulmonary arterial pressures and cardiac output. Blood gases and coagulation parameters (antithrombin, D-dimer, prothrombin fragments I & II) were measured pre-injection, 10, 30 and 60min post-injection. Postmortem, lungs were removed intact and submitted to computer tomography (CT) imaging. Results There were no fatalities. After 1min, mean pulmonary arterial pressure had increased by 9%, 14% and 21% from pre-injection value in the PMMA, PMMA & HA and CaP group respectively. Differences in pulmonary arterial pressure between the three material groups were not statistically significant. Pulmonary arterial pressure stayed elevated for the duration of the experiment (i.e. 60min post-injection). There were no other significant changes in cardiovascular, blood gas or coagulation parameters from pre- to post-injection values. Three dimensional reconstructions of the CT images showed a tendency of the CaP cement to break up into multiple smaller pieces whereas the two other cements did not. Discussion Cement embolism led to mild pulmonary hypertension in all material groups. Present results are in contrast to earlier reports (pig model) of fulminant cardiovascular deterioration after CaP cement embolism (. 3. ). Present changes were not as severe and there was no evidence of thromboembolism. This discrepancy may have been due to differences in the cement formulations or the animal model. Pulmonary hypertension was more severe in the CaP cement group. This may have been due to the disintegration of the CaP cement resulting in blockage of more pulmonary vessels compared to the PMMA cements

We report a case of fatal pulmonary embolism following a simple ankle fracture in a 17-year-old girl. The diagnosis was confirmed at post-mortem. The risk factors for deep venous thrombosis and pulmonary embolism and their significance in orthopaedic fracture management are discussed

Background: Cerebral emboli may be detected by transcranial Doppler (TCD) in patients undergoing hip arthroplasty. Venous – arterial circulation shunts (v-aCS), cerebral embolism and postoperative organ dysfunction were investigated in elective hip arthroplasty. Methods: TCD was used to identify v-aCS in (i) elective hip arthroplasty (n=45), (ii) abdominal aortic aneurysm surgery (AAA) (n=20) and (iii) transurethral resection of prostate (TURP) (n=10). A v-aCS was diagnosed when 1 or more microbubbles were detected in the middle cerebral artery by TCD following intravenous injection of a microbubble emulsion. TCD was also used to monitor for intraoperative cerebral emboli (ICE). Cognitive function was measured by a battery of computerised tests before and 5 days after surgery. Troponin T, AST, ALP, Bilirubin, Creatinine, Urea and Creatinine clearance were measured pre-operatively and 24 and 48 hours post-operatively. Results: Cerebral embolism occurred in 26 of 45 patients during hip arthroplasty (median 4, range 1 – 368) but not during AAA or TURP surgery. Cerebral embolism only occurred in patients with a v-aCS (p< 0.001) and was strongly associated with the size of the v-aCS (rs=0.8, p< 0.001). The number of ICE had no influence on Troponin T, renal function, liver function or cognitive function. Conclusion: Cerebral embolism is common in patients with a v-aCS during hip arthroplasty. There was no evidence of cerebral or multi-organ damage due to paradoxical embolism

This study was undertaken to assess the contribution of fat embolism (FE) to the development of acute lung injury in the presence of resuscitated hemorrhagic shock. Twenty-seven NZW rabbits were randomly assigned into four groups: resuscitated hemorrhagic shock and FE (HR/FE), resuscitated hemorrhagic shock, FE, and control. FE was induced via intramedullary femoral canal pressurization using a 1–1.5 ml bone cement injection. Only HR/FE animals displayed significant proinflammatory cytokine release as compared to controls. These findings suggest that the combination of resuscitated shock with FE initiates an inflammatory response, which may lead to the development of fat embolism syndrome. The objective of this study was to assess the contribution of fat embolism caused by intramedullary femoral canal pressurization to the development of acute lung injury in the presence of resuscitated hemorrhagic shock. Only the animals that underwent resuscitated shock and fat embolism displayed amplified BALF proinflammatory cytokine expression. These findings suggest that the combination of resuscitated shock with fat embolism initiates an inflammatory response, which may play a role in the development of fat embolism syndrome. Only HR/FE BALF IL-8 and MCP-1 levels were significantly higher than controls (0.72 ng/ml vs. 0.26ng/ ml, p=0.03; 18.3 ng/ml vs. 2.0 ng/ml, p=0.01, respectively). Twenty-seven NZW rabbits were randomly assigned into four groups: resuscitated hemorrhagic shock + fat embolism (HR/FE), resuscitated hemorrhagic shock (HR), fat embolism (FE), and control. Shock was induced via carotid bleeding for one-hour prior to resuscitation. For FE induction, the intramedullary cavity was drilled, reamed and pressurized with a 1–1.5 ml bone cement injection. Four hours later, postmortem bronchoalveolar lavage was performed through the right mainstem bronchus. Analyses of bronchoalveolar lavage fluid (BALF) of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were carried out in triplicate and blinded fashion using the ELISA technique. Our findings suggest that FE by itself does not initiate inflammatory lung injury, as there were no apparent differences between the control and FE cytokine levels. Only the HR/FE animals revealed elevated levels of pro-inflammatory cytokines in BALF. These findings are in agreement with our previous results, which displayed neutrophil activation only in the HR/FE group

1. Blood from forty-one healthy volunteers, seventy-one patients with fractures but without symptoms of fat embolism and seven patients with clinical evidence of fat embolism was examined microscopically for fat droplets and chemically for triglycerides. 2. Fat droplets, after Millipore filtration of the blood, were seen evenly distributed in all three groups. 3. There was no significant difference in triglyceride concentration between serum and filtrate in the three groups. 4. The results do not support the thesis that the Gurd test is a reliable aid in the diagnosis of fat embolism

Intraoperative pulmonary fat and bone-marrow embolism is a serious complication of bone and joint surgery. We have investigated the occurrence and incidence of intraoperative embolism in patients undergoing elective lumbar spinal surgery with or without instrumentation. Sixty adult patients with lumbar degenerative disease were examined by intraoperative transoesophageal echocardiography while undergoing posterior lumbar surgery. Of these, 40 underwent surgery with instrumentation and 20 without. Moderate to severe (grade 2 or 3 according to the grading scale of Pitto et al) embolic events were seen in 80% of the instrumented patients but in none of the non-instrumented patients (p < 0.001). The insertion of pedicle screws was particularly associated with large numbers of pulmonary emboli, while the surgical approach, laminectomy, disc removal and bone harvesting were associated with small numbers of emboli. We consider that, as in arthroplasty and intramedullary fixation of fractures, these embolic events are relevant to the development of potentially fatal fat embolism during spinal surgery

1. A distinction must be made between the fat embolism syndrome, a clinical entity, and fat embolism demonstrated pathologically, which may be found after death following fracture with no prior evidence of the syndrome. 2. One hundred cases of the syndrome encountered over a period of four years have been studied in detail and the diagnostic criteria have been defined. These include one major feature, four minor features and fat macroglobulaemia. 3. Sixteen of the patients died–eight from severe pulmonary insufficiency of the syndrome, eight from other traumatic causes. 4. The prevention of shock is the best measure for prevention of the syndrome. The role of proteases in the production of shock and the place of protease inhibition in treatment of the syndrome are briefly discussed. 5. For the established case the aim of treatment is to ensure an adequate pressure of arterial oxygen

1. Reports of the lipaemia-clearing effect of heparin suggested that this drug might be of therapeutic value in fat embolism. 2. In an experimental trial with rats, heparin was found both to accelerate death and to increase the number of deaths after fat embolism. 3. It is accordingly concluded that a clinical trial of heparin in human fat embolism would not be warranted

Purpose: Fat or marrow embolism during or after bone and joint surgery is a serious complication. We wanted to determine the incidence and circumstances of peroperative embolism in patients undergoing lumbar spine surgery with and without instrumentation. Material and methods: Sixty adult patients with degenerative lumbar spines underwent peroperative and early postoperative transoesophageal ultrasonography. The lumbar procedure involved instrumentation with insertion of pedicular screws in 40 patients. Results: Moderate to severe signs of embolism (Pitto classification grade 2 or 3) were observed in 80% of the patients who underwent instrumentation procedures but in none of those who had not been instrumented (p < 0.001). Discussion: Among the different procedures performed on the posterior lumbar spine, insertion of pedicular screws appears to be the leading cause of pulmonary embolism. The approach, laminectomy, discectomy, and bone abrasion do not appear to produce detectable embolism. Conclusion: We consider that the observed embolic manifestations, also observed in intramedullar procedures, are potentially fatal after spinal surgery

We made a prospective study of the incidence of fatal pulmonary embolism in patients after total knee replacement with no prophylactic anticoagulation. There were 499 consecutive patients having 527 knee replacements. They all wore anti-thromboembolic stockings and were mobilised 48 hours after surgery. No patient was lost to follow-up. One patient died of pulmonary embolism 22 days after operation. There were no other deaths within three months of operation. The incidence of fatal pulmonary embolism was 0.19% (95% confidence interval: 0 to 0.6%). Fatal pulmonary embolism is rare after total knee replacement without prophylactic anticoagulation and the routine anticoagulation of these patients is of doubtful value