Fat Embolism and Fat Embolism Syndrome

Home , Crush injury, Embolus, Fat embolism syndrome, Petechia

Review Article Fat Embolism and Fat Embolism Syndrome

Abstract David L. Rothberg, MD Fat embolism (FE) occurs frequently after trauma and during Christopher A. Makarewich, MD orthopaedic procedures involving manipulation of intramedullary contents. Classically characterized as a triad of pulmonary distress, neurologic symptoms, and petechial rash, the clinical entity of FE syndrome is much less common. Both mechanical and biochemical pathophysiologic theories have been proposed with contributions of vascular obstruction and the inflammatory response to embolized fat and trauma. Recent studies have described the relationship of embolized marrow fat with deep venous thrombosis and postsurgical cognitive decline, but without clear treatment strategies. Because treatment is primarily supportive, our focus must be on prevention. In trauma, early fracture stabilization decreases the rate of FE syndrome; however, questions remain regarding the effect of reaming and management of bilateral femur fractures. In arthroplasty, computer navigation and alternative cementation techniques decrease fat embolization, although the clinical implications of these techniques are currently unclear, illustrating the need for ongoing education and research with an aim toward prevention.

at embolism (FE) is defined as the However, likely, it is a result of vas- Fpresence of fat globules in the cular obstruction, the body’s response pulmonary or peripheral circulation, to embolized fat, and the trauma- and FE syndrome (FES) refers to the induced inflammatory response. Di- clinical symptoms that follow an agnosis can be challenging, relying identifiable insult; it can result in the on a combination of clinical symp- From the Department of triad of respiratory distress, neuro- toms, laboratory results, and imaging Orthopaedics, University of Utah, Salt logic symptoms, and petechial rash. findings. Further research directions Lake City, UT. Frequently, FE occurs after trauma include improving our understanding 1,2 Neither of the following authors nor and during orthopaedic procedures. of predicting those at the risk of de- any immediate family member has Although typically considered benign, veloping FES, accurately diagnosing received anything of value from or has recent studies have identified possible the condition, and recognizing the stock or stock options held in a commercial company or institution links to neurocognitive impairment more subtle effects of FE. related directly or indirectly to the and deep venous thrombosis (DVT) subject of this article: Dr. Rothberg formation.3-5 Although FES exhibits and Dr. Makarewich. potentially life-threatening effects, it is History J Am Acad Orthop Surg 2019;27: much less common. Despite its origi- e346-e355 nal description in the 17th century, The clinical study of FES began in DOI: 10.5435/JAAOS-D-17-00571 FES remains incompletely understood. 1861 with Zenker, who reported the Both mechanical and biochemical presence of fat droplets in lung Copyright 2018 by the American Academy of Orthopaedic Surgeons. mechanisms have been proposed to capillaries of a railroad worker who explain the clinical picture of FES. died from a crush injury.6 This report

e346 Journal of the American Academy of Orthopaedic Surgeons

Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited. David L. Rothberg, MD and Christopher A. Makarewich, MD remained an isolated case until 1865 patients with blood sampling from the decrease by 10% in each decade of when Wagner described the corre- right atrium. Major emboli greater life.14 In addition, marrow fat com- lation of FE with fractures and than 1 cm were found in 43% of position in children may play a role. attributed the origin of fat in the patients. Children have a greater proportion lungs to bone marrow. Von Berg- The clinical entity of FES is much of palmitin and stearin, which are mann was the first to describe the less common. In the older literature, it less likely to cause an inflammatory symptoms of FES, and in 1873, he has been reported in up to 30% of response in comparison to olein reported a patient who fell from a orthopaedic trauma patients; how- found in adults.13 However, patients roof and sustained a comminuted ever, recent studies show a much with Duchenne muscular dystrophy distal femur fracture. Sixty hours lower incidence.6,7,12 In one of the warrant special consideration because after the injury, he developed con- largest clinical studies, a group from they develop FES at a relatively high fusion, dyspnea, and petechiae and the Harborview reviewed 10 years rate of 1% to 20% after minor trauma died after 19 hours. A massive pul- of patients from their trauma data- and fractures.15 monary FE was found at autopsy. base.6 Using Gurd criteria,10 27 ca- Although FES is most commonly Czerny further examined the neuro- ses of FES were identified from 3,000 associated with trauma, it has also logic symptoms of FES and described patients with long bone fractures been reported rarely in nontrauma them in 1875.7 Although these ob- with an incidence of 0.9%. The av- patients. Case reports document the servations were key in establishing a erage age of patients was 31 years, occurrence of FES during bone clinical pattern, it was not until the and the onset was typically 24 to 48 marrow harvest, lung transplant, 1920s that the two main patho- hours after an injury. Ninety-five cesarean section, liposuction, and physiologic theories of FES were first percent of these patients had frac- cosmetic procedures.7,12,16,17 proposed. In 1924 Gauss8 described tures of the lower extremities, and it the mechanical theory, and in 1927, was more common in closed frac- Lehman and Moore9 theorized tures. A more recent study in 2008 Clinical Presentation about a biochemical explanation. examined the International Classifi- Finally, in 1970, Gurd10 presented cation of Diseases, Ninth Revision The classic triad of symptoms of FES thefirstsetofdiagnosticcriteria codes from the National Hospital is respiratory distress, neurologic (Table 1) based on his experience Discharge Survey over a 26-year changes, and a petechial rash.10 Pul- with a series of 100 patients with period including one billion pa- monary symptoms occur first, typi- long bone fractures and coined the tients.13 Among all patients with cally 24 to 72 hours after trauma; term “fat embolism syndrome.” fractures, the incidence was 0.17%. but symptoms have been reported as Of isolated fractures, femur fractures early as 12 hours. A large embolus were the most common with a rate of can cause sudden cardiopulmonary Epidemiology 0.54%. This investigation excluded collapse; but more often, FES has fractures of the femoral neck, which an insidious onset with dyspnea, Fat in the peripheral circulation (FE) had only 0.09% incidence. Multiple tachypnea, and hypoxemia. About occurs fairly frequently. At autopsy, fractures that included the femur had half of all patients with FES develop pulmonary FE has been found in 68% the highest incidence of 1.29%. The respiratory failure that necessitates to 82% of blunt trauma patients.1,2 incidence was more common in male mechanical ventilation.18 In a patient During orthopaedic procedures, fat subjects, with a relative risk of 5.7, under anesthesia, findings include globules have been observed regularly and it was more common in those respiratory deterioration with hyp- passing through the heart and pul- aged 10 to 40 years. oxemia, pulmonary edema, and de- monary circulation on ultrasonogra- Pediatric patients have a much crease in lung compliance.7 phy (Figure 1). In 1995, Christie et al11 lower incidence of FES. Although FE Neurologic symptoms are present in performed transesophageal echocar- have been identified in 30% of pedi- up to 80% of patients, and usually, diography (TEE) in 111 orthopaedic atric cadavers at autopsy,14 Stein although not always, this symptoms surgeries, including reaming of tibia et al13 found no cases of FES among occur after pulmonary symptoms. They and femur fractures, as well as ce- 1,178,000 children in their discharge begin with confusion and agitation mented and uncemented hemiarthro- database study. This discrepancy similar to delirium, and it can progress plasty. Echogenic material was found may be the result of the lower fat to focal deficits, such as hemiplegia and traveling through the heart in 87% of content in pediatric patients, where aphasia, as well as seizures and coma. procedures, and this material was hematopoietic cells occupy nearly Commonly, upper motor neuron signs confirmed as FE in a subset of 12 100% of the volume at birth and are also present.7,12

April 15, 2019, Vol 27, No 8 e347

Table 1 festations of FES: the mechanical and biochemical theories. The mechani- Criteria for the Diagnosis of Fat Embolism Syndrome cal theory was first presented by Criteria Findings Points Gauss8 in 1924. He proposed that Gurd criteriaa Major trauma and fractures of long bones disrupts fat in the marrow and also Respiratory insufficiency — tears intraosseous blood vessels. Cerebral involvement — Typically, veins are characterized as Petechial rash — having weak, flexible walls; how- Minor — ever, in bone, they are contained Fever — within calcified tubules with rigid — Tachycardia perivascular sheaths. This allows — Retinal changes ruptured vein ends to remain open, — Jaundice and the negative venous pressure can — Renal changes draw free fat globules into the cir- Anemia — culation. In cases of arthroplasty and Thrombocytopenia — during intramedullary instrumenta- Elevated ESR — tion, intramedullary pressure in- Fat macroglobulinemia — creases forcing fat into the veins.19 Schonfeld criteriab Petechia 5 Once fat enters the circulation, it can Chest radiograph changes 4 create mechanical emboli and focal Hypoxemia (PaO2 , 9.3 kPA) 3 ischemia. Fever (.38C) 1 It was originally thought that to Tachycardia (.120 bpm) 1 pass from the venous to the arterial Tachypnea (.30 bpm) 1 circulation, the fat material (because c Lindeque criteria Sustained Pao2 , 8 kPa — of its large size) would have to pass through a foramen ovale from the Sustained PCo2 . 7.3 kPa or pH , 7.3 — Sustained respiratory rate . 35 bpm — right to the left atrium (present in 20 Increased work of breathing (dyspnea, — 20% to 25% of adults), either one accessory muscles, tachycardia, anxiety) that remained open from birth or one that reopened because of ele- ESR = erythrocyte sedimentation rate, FES = fat embolism syndrome vated pulmonary artery pressures. a At least 1 major feature and 4 minor features needed for diagnosis. b Cumulative score .5 required for diagnosis. However, neurologic symptoms and c One of the criteria indicates a diagnosis of FES. skin lesions occur in patients without these anatomic variants. Other ex- planations are that fat is able to Although part of the “classic triad” and are then distributed through the deform to travel through capillaries of symptoms, a petechial rash occurs carotid and subclavian vessels to or that it passes through arteriove- in only 20% to 50% of patients. Its nondependent areas.12 nous shunts present around the typical distribution is over the head, Although found to be nonspecific, lungs.20 Although logical, this theory neck, thorax, axillae, subcon- other frequently reported signs and does not explain the 24- to 72-hour junctival space, and oral mucous symptoms include tachycardia, delay in presentation, and just hav- membranes12 (Figure 2). A similar hypotension, right heart strain, fever, ing fat in the circulation, even a large rash can be found in sepsis and dis- retinopathy, renal changes, and coa- quantity of fat, does not in itself lead seminated intravascular coagulation; gulopathy. Overall mortality rates to the development of FES.11 however, the rash of FES is only are 5% to 20%, usually because of To explain cases of atruamatic FES, found anteriorly on the body in respiratory failure or right heart Lehman and Moore9 described a nondependent areas, and it has never failure.7,12 biochemical theory in 1927. They been reported on the back. Theo- proposed that after an insult or retically, this pattern of rash occurs trauma, fat was mobilized from body because in a supine patient, the fat Pathophysiology stores and embolized into the tissues, droplets (which float like oil on Two pathophysiologic mechanisms initiating an inflammatory response. water) accumulate in the aortic arch were proposed for the clinical mani- Since that time, we have learned that e348 Journal of the American Academy of Orthopaedic Surgeons

Figure 1 Figure 2

Transesophageal echocardiography images showing microemboli in the right atrium during total knee arthroplasty. LA = left atrium, LV = left ventricle, RA = right atrium, RV = right ventricle. (Reproduced with permission from Zhao J, Zhang J, Ji X, et al: Does intramedullary canal irrigation reduce fat emboli? A randomized clinical trial with transesophageal echocardiography. J Arthroplasty 2015;30[3]:451-455.) bone marrow fat embolized to the Clinical images of axillary petechiae (A) and subconjunctival hemorrhage (B). (Reproduced with permission from Maghrebi S, Cheikhrouhou H, Triki Z, Karoui lungs causes the local releases of A: Transthoracic Echocardiography in Fat Embolism: A Real-Time Diagnostic lipase, which breaks fat down into Tool. J Cardiothorac Vasc Anesth 2017;31[3]:e47-e48.) free fatty acids and glycerol. Free fatty acids are toxic to endothelial all based on small series, and none cells and cause vasogenic edema and Diagnosis have been prospectively validated. hemorrhage.20 These conditions re- Diagnostic Criteria lease proinflammatory cytokines, One of the challenges in the study such as tumor necrosis factor-alpha, and identification of FES is that there Laboratory Studies interleukin (IL)-1 and IL-6, which is no benchmark test. Gurd10 was There are no laboratory tests specific can cause acute respiratory distress the first to identify diagnostic cri- to FES (Table 2); however, common syndrome (ARDS). Elevated acute- teria based on a series of 100 pa- findings include anemia, thrombo- phase reactants, such as C-reactive tients. He divided his observations cytopenia, and elevated inflamma- protein, have also been observed, into major and minor criteria and tory markers.7 Elevated serum lipase and these reactants can cause lipids suggested needing at least one major can cause hypocalcemia, and albu- in the blood to agglutinate into and four minor findings to make min binds to free fatty acids leading larger molecules, which can occlude the diagnosis (Table 1). Lindeque to a decrease in free albumin. The vessels. In addition, bone marrow focused on respiratory symptoms presence of fat globules in the blood fat is prothrombotic, and in the cir- andcreatedcriteriabasedonasmall and urine has also been observed, culation, it is quickly covered in series of 55 patients with long bone but this is not specific to FES.12,20 platelets and fibrin setting off the fractures and decreased oxygen Inflammatory cytokines have also coagulation cascade, leading to saturation (Table 1).7,12 Schonfeld been investigated as a predictor of thrombocytopenia and, in extreme described another set of criteria FES. Based on the relationship of FES cases, disseminated intravascular based on his opinion of the most with systemic inflammation, Prakash coagulation.20 important features7,12 (Table 1). He et al21 examined IL-6 levels in In reality, the clinical symptoms weighted findings based on their trauma patients. They found that at of FES are likely a combination of observed specificity and chose scores 12 hours after injury, IL-6 was sig- mechanical vascular obstruction and of 5 or greater to define FES. Al- nificantly elevated in patients who the body’s inflammatory response to though these criteria have tried to went on to develop FES, diagnosed trauma and embolized fat (Figure 3). standardize the diagnosis, they are using Gurd criteria.

April 15, 2019, Vol 27, No 8 e349

Figure 3 radiographs show bilateral diffuse or patchy ill-defined opacities (Figure 4), butthiscanalsobeseeninARDS, pulmonary edema, aspiration, or infection.23 High-resolution CT has more specific findings. It shows patchy ground glass opacities and consolidation with interlobular thickening called the “crazy paving” pattern23 (Figure 5). The extent of these findings has correlated with disease severity.24 Although in some cases, brain CT may show diffuse edema with scattered hemorrhage, usually, it shows a negative result. However, MRI is more sensitive, and T2-weighted images typically demonstrate a “starfield pattern” with multiple, small, nonconfluent, hyperintense lesions.25 These lesions are also bright on diffusion-weighted imaging and appear dark on susceptibility-weighted sequences (Figure 6). Brain MRI of these lesions is also very consistent in where they appear anatomically and correlate with autopsy findings. The lesions occur in the periventricular, subcortical, and deep white matter. This finding is in contrast to diffuse axonal injury, which has a similar appearance but with lesions at the gray-white matter junction.25

Treatment and Prevention Flowchart showing proposed pathophysiologic mechanisms for the clinical Treatment is primarily supportive manifestations of fat embolism syndrome. DIC = disseminated intravascular care with goals being to maintain coagulation. (Reproduced with permission from KosovaE, Bergmark B, oxygenation and ventilation, support Piazza G: Fat embolism syndrome. Circulation 2015 January 20;131 hemodynamics, and resuscitate with [3]:317-320.) fluids and blood products. Beginning in the 1950s, some targeted therapies Although fat in the lungs is nonspe- and 2% in normal control subjects. In were attempted, including heparin, cificandcanbeseeninmultiorgan addition, there are significantly ele- hypertonic glucose, increased fluid failure and sepsis, bronchoalveolar vated total cholesterol (10.2 mg/mg intake, aspirin, and corticosteroids, lavage may also aid in diagnosis. phospholipid in FES as compared with all without conclusive benefit.7,12 Studies have attempted to determine 3.7to4.2inARDSand2.0incontrol Recently, experimental studies specific characteristics of the amount subjects) and lipid esters.22 have attempted to alter the renin- and composition of this fat in FES. In angiotensin pathway to prevent FES. FES, it has been shown that bronchial Imaging In addition to acting as a vasocon- lavages had .30% of alveolar mac- Imaging studies can be a useful adjunct strictor, angiotensin II is also proin- rophages filled with lipid inclusions as to provide additional diagnostic infor- flammatory and profibrotic. This may compared with 13% to 15% in ARDS mation (Table 2). Typically, chest contribute to the pathogenesis of FES e350 Journal of the American Academy of Orthopaedic Surgeons

Table 2 Figure 4 Laboratory and Imaging Findings of Fat Embolism Syndrome Lab/Imaging Study Potential Findings

Laboratory studies Anemia, thrombocytopenia, elevated ESR, CRP, and inflammatory cytokines, hypoalbuminemia, fat macroglobulinemia Bronchoalveolar lavage .30% alveolar macrophages with lipid inclusions Elevated total cholesterol and lipid esters Chest radiograph Bilateral diffuse or patchy opacities Chest CT Consolidation with interlobar thickening (“crazy paving” pattern) Brain CT Diffuse edema with scattered hemorrhage Brain MRI Multiple small nonconfluent hyperintense lesions Chest radiograph of a patient with fat on T2 (“starfield” pattern) embolism syndrome showing Bright on diffusion, dark on susceptibility- bilateral diffuse patchy infiltrates. weighted sequences

CRP = C-reactive protein, ESR = erythrocyte sedimentation rate They noted that while the number of fractures treated with early surgical fixation increased, the number of in that fat in the lungs is taken up by steroid group developed FES as cases of FES decreased. When grouped macrophages, leading to the local compared with 60 patients in the by treatment type, they found FES release of renin followed by increased control group (P , 0.05). It is diffi- rates of 22% in the nonsurgical levels of angiotensin I and II. Fletcher cult to interpret the results of these group versus 4.5% in the surgical et al26 attempted to alter this pathway articles because they are based on group. This was not randomized, in a rat model by treating with the small studies that used markedly and over this same period, support- renin inhibitor aliskiren. In rats with different dosing regimens and had ive measures and resuscitation have FES induced by triolein injection, different duration of treatment. also been changed; however, it was groups with aliskiren administration Because of the lack of high quality the first to give insight into the issue 1 hour after the injection showed evidence, as well as the low incidence of fracture fixation timing. This was significantly greater vessel diameter, of FES and the potential risks of followed by a prospective random- decreased fibrosis, and lower fat con- corticosteroid treatment, routine ized trial in 1989 that compared tent in vessels as compared with the prophylaxis is not recommended. patients with isolated femur frac- control rats. Although experimental, tures with those with multiple in- thismayrepresentawaytotreator juries.30 Within each group, patients provide prophylaxis against FES. Applications in Trauma were randomized to fixation either Given the lack of direct treatment before 24 hours or after 48 hours. Concerns in orthopaedic trauma options, an important goal is preven- Significantly more pulmonary com- affecting FES that have been debated tion. Based on the proposed role of the plications were found with late stabi- include timing to surgery, fracture inflammatory process in FES, many lization, both in the cases with isolated fixation method, and the manage- randomized trials have examined the femur fractures and the multiply ment of bilateral femur fractures. use of prophylactic corticosteroids. injured group. These studies were the These are outlined in a 2009 meta- basis for the principle of early total analysis that included seven random- Timing to Surgery care. ized trials. From the pooled data of 389 One of the earliest studies to examine However, FES and pulmonary patients, corticosteroids reduced the the effect of timing was in 1976 by complications are just one of a mul- risk of FES by 78%, with no difference Riska et al.29 He reported on a series titude of factors to consider in the in the rates of infection and mortal- of trauma patients seen with pelvic optimal timing of fracture stabiliza- ity.27 A 2012 systematic review of or long bone fractures or both from tion in multitrauma patients. Al- randomized clinical trials found simi- 1967 to 1974. During this time, though early definitive surgery is lar results.28 Of a total of 223 patients at their institution, a transition from advantageous for most, there is a receiving corticosteroids and 260 nonsurgical treatment to surgical subset of patients for whom damage control subjects, 9 patients in the treatment of fractures took place. control orthopaedics followed by

April 15, 2019, Vol 27, No 8 e351

Figure 5 Figure 6

Axial section of a chest CT scan showing interlobular septal thickening of the anterior bilateral lungs, described as the “crazy paving” pattern. (Reproduced with permission from Newbigin K, Souza CA, Torres C, Marchiori E, Gupta A, Inacio J: Fat embolism syndrome: State-of-the-art review Brain MRI of a patient with fat embolism syndrome showing multiple small focused on pulmonary imaging nonconfluent lesions in the periventricuar and subcortical white matter that are findings. Respir Med bright on T2 sequences (A) and dark on susceptibility-weighted sequences (B). 2016;113:93-100.)

in clinical studies. In reviewing pul- small sample sizes, studies examining definitive treatment at a later date monary complications, Bosse et al16 this topic may be underpowered. may increase the chance of survival. compared reamed intramedullary Pape et al31 recommend using find- nails with plating in 453 patients. No ings of shock, coagulopathy, tem- significant differences in pulmonary Decreasing Embolic Load: perature, and soft tissue injury to complications or mortality were Trauma risk stratify patients and guide observed. This study was conducted Several strategies for decreasing treatment with early total care versus at two different hospitals, one where embolic load involve alterations to damage control. This concept has nailing was more common and one intramedullary reaming technique. since been supported in multiple where plating was routinely per- In a sheep model, Mousavi et al36 clinical studies, showing improved formed, which likely introduced tested different reaming speeds, both outcomes following similar algo- confounding variables. Pape et al34 advancement of the reamer and rev- rithms.32 Following these recom- randomized multiply injured pa- olution of the reamer head. They mendations helps to balance the tients in the borderline stable group created a midshaft osteotomy, in- desire to prevent FES with the pa- to intramedullary nail versus exter- duced hemorrhagic shock, and then tient’s physiologic ability to undergo nal fixation. Six times greater inci- resuscitated the sheep before ream- surgical fixation. dence in acute lung injury was found ing. The amount of embolized fat on in the intramedullary nail group, but TEE and intramedullary pressure no difference was found in ARDS or was significantly lower with slower Fixation Method mortality. Reamed versus unreamed advancement and faster revolutions. The mainstay of definitive treatment nails have also been investigated. The use of a reamer irrigator aspi- of femoral shaft fractures is a reamed The suggested benefits of reamed nails rator (RIA) has also been proposed to intramedullary nail. It is known from are higher union rates (particularly in decrease embolic load. In a canine animal and human studies that in- distal fractures); the ability to place a model, Miller et al37 compared three tramedullary reaming increases canal biomechanically advantaged, larger nailing scenarios, including un- pressures and stimulates an inflam- diameter implant; and depending on reamed, standard reaming, and RIA. matory response.33 Theoretically, fracture pattern, allow for early A lower embolic load at the carotid this situation leads to an increased weightbearing.6 The potential for in- artery was found on ultrasonogra- the incidence of FES compared with creased pulmonary complications in phy in the RIA group. On brain other fixation methods; however, reamed nailing has not been bourn histologic assessment, the levels of this has not been conclusively shown out in the literature;35 however, given heat shock protein (representing brain e352 Journal of the American Academy of Orthopaedic Surgeons

Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited. David L. Rothberg, MD and Christopher A. Makarewich, MD stress) and hypoxia-inducible factor and prolonged embolic events on were randomized to standard tech- (representing ischemia) were signifi- TEE. Also, DVTs were detected in nique versus an additional irrigation cantly lower in the RIA and unreamed 18% of the patients in the standard and suction step to remove medullary groups as compared to the standard group compared with 3% of patients contents before reaming. A signifi- reamer. Although seemingly promis- in the bone vacuum group. cantly lower amount of fat emboliza- ing, these techniques have yet to show In addition, subtle cerebral findings tion was noted on TEE in the modified clinical benefit in pulmonary or neu- have been attributed to FE. Several technique group. rologic outcomes. review articles have discussed this Computer navigation may also lead finding in the setting of arthroplasty to decreased embolization of medul- Bilateral Femur Fractures and proposed that it could explain lary contents. Typically, conventional postsurgical delirium and cognitive knee arthroplasty uses intramedullary Another situation that deserves spe- decline.3,4 This was originally studied instrumentation, particularly in cial attention is the management of in cardiac surgery requiring bypass, the femur, to set component align- bilateral femur fractures. This is an where increased fat embolic load ment. This can cause an increase in uncommon injury pattern, and the correlated with a decline in post- intramedullary pressure leading to literature consists of small case series. surgical cognitive function. In the embolic showers. Computer-assisted These series have shown that bilateral orthopaedic literature, despite being surgery can potentially decrease the femur fractures treated with intra- discussed in those recent review ar- embolic load because it uses extra medullary nail have up to a 7.5% ticles, just four original research ar- medullary guides. Several prospec- incidence of FES, have higher injury ticles have studied the relationship of tive randomized trials have compared severity scores, resuscitation require- FE on presurgical and postsurgical computer-assisted procedures with ments, and rates of ARDS, as well as cognitive testing, three in the setting standard total knee arthroplasty. have longer hospital stays and higher of arthroplasty and one in trauma.3,4 Malhotra et al19 evaluated embolic mortality as compared with unilat- None of these found a significant load after tourniquet release using eral fractures with mortality rates of correlation, but interestingly, three TEE, transcranial doppler, and blood 5% to 6%, about 5 to 6· higher than out of four showed a trend that with sampling from the right atrium. isolated femoral shaft fractures.38 increasing fat embolization, there Decreased pulmonary and cranial No studies to date have compared was a decrease in postsurgical neu- emboli were found in the computer different treatment modalities and rocognitive testing. The lack of navigation group as compared with surgical timing in bilateral femur significance may indicate that no standard total knee arthroplasty fractures. relationship exists; however, the group using an intramedullary femur numbers in these studies are very guide. Applications in small, and as such, they are likely These techniques may not be nec- Arthroplasty underpowered. essary or cost-effective in all cases, The use of an intramedullary bone but they may be useful for certain Joint replacement procedures also cause vacuum during cementation was high-risk patient groups. intramedullary pressurization, particu- shown to significantly decrease embo- larly with cementing, leading to embolization of marrow contents.5 Second- lization of fat into the circulation.11 ary cementation through a specially Summary Fulminant FES with cardiopulmonary designed stem has also been described. collapse is rare after arthroplasty, and Intheory,thisisamoregentlece- Generally, FES is more common descriptions are found only in case menting technique because the stem is in male subjects, those aged 10 to reports. However, the recent literature placed first and cement injected 40 years, and those with closed long has examined other effects of FE in the around it. Schmidutz et al39 found a bone fractures, particularly of the setting of arthroplasty. significantly lower embolic load on femoral diaphysis, and multiple Pitto et al5 evaluated the role of TEE with secondary cementation than fractures. The clinical presentation marrow embolization on the incidence with standard cementation. includes respiratory distress, neuro- of postsurgical DVT. They random- In another approach, Zhao et al40 logic symptoms, and petechial rash ized 65 patients each to standard ce- attempted to alter the amount of em- 24 to 72 hours after injury. In trauma, menting technique versus cementing bolized fat during total knee arthro- strategies to limit FE include early with the use of an intramedullary bone plasty with an additional irrigation fracture stabilization in stable pa- vacuum. The standard cementing and suction step. Using implants that tients, slow advancement, and fast group had significantly more severe required tibial reaming, 30 patients revolutions of the reamer in reamed

April 15, 2019, Vol 27, No 8 e353

Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited. Fat Embolism Syndrome nails, and RIA. Techniques in ar- clinical trial. J Bone Joint Surg Am 2002; 21. Prakash S, Sen RK, Tripathy SK, Sen IM, 84-A:39-48. Sharma RR, Sharma S: Role of interleukin- throplasty include the use of a bone 6 as an early marker of fat embolism suction device, secondary cementa- 6. Bulger EM, Smith DG, Maier RV, syndrome: A clinical study. Clin Orthop Jurkovich GJ: Fat embolism syndrome: A Relat Res 2013;471:2340-2346. tion technique with specialized stems, 10-year review. Arch Surg 1997;132: and computer navigation. Routine 435-439. 22. Karagiorga G, Nakos G, Galiatsou E, prophylaxis with steroids is not rec- Lekka ME: Biochemical parameters of 7. Tzioupis CC, Giannoudis PV: Fat embolism bronchoalveolar lavage fluid in fat ommended. Possible future direc- syndrome: What have we learned over the embolism. Intensive Care Med 2006;32: tions include the use of inflammatory years? Trauma 2011;13:259-281. 116-123. 8. Gauss H: The pathology of fat embolism. markers, such as IL-6, to predict 23. Newbigin K, Souza CA, Torres C, et al: Fat Arch Surg 1924;9:592-605. patients at the risk for FES, novel embolism syndrome: State-of-the-art review treatments such as altering the renin- 9. Lehman E, Moore R: Fat embolism, focused on pulmonary imaging findings. including experimental production without Respir Med 2016;113:93-100. angiotensin pathway, and examining trauma. Arch Surg 1927;14:621-662. the effect of embolic load on cogni- 24. Newbigin K, Souza CA, Armstrong M, 10. Gurd AR: Fat embolism: An aid to et al: Fat embolism syndrome: Do the CT tive decline and delirium. diagnosis. J Bone Joint Surg Br 1970;52: findings correlate with clinical course and 732-737. severity of symptoms? A clinical- radiological study. Eur J Radiol 2016;85: 11. Christie J, Robinson CM, Pell AC, 422-427. References McBirnie J, Burnett R: Transcardiac echocardiography during invasive 25. Kuo KH, Pan YJ, Lai YJ, Cheung WK, Evidenced based medicine: Levels of intramedullary procedures. J Bone Joint Chang FC, Jarosz J: Dynamic MR imaging Surg Br 1995;77:450-455. patterns of cerebral fat embolism: A evidence are described in the table of systematic review with illustrative cases. contents. In this article, references 5, 12. Mellor A, Soni N: Fat embolism. AJNR Am J Neuroradiol 2014;35: Anaesthesia 2001;56:145-154. 19, 27, 28, 30, 35, 40 are level I 1052-1057. studies. References 1, 11, 14, 21, 22, 13. Stein PD, Yaekoub AY, Matta F, 26. Fletcher AN, Molteni A, Ponnapureddy R, Kleerekoper M: Fat embolism syndrome. Patel C, Pluym M, Poisner AM: The renin 34, 39 are level II studies. References Am J Med Sci 2008;336:472-477. inhibitor aliskiren protects rat lungs from 2, 10, 15, 16, 24, 25, 38 are level III 14. Eriksson EA, Rickey J, Leon SM, Minshall CT, the histopathologic effects of fat embolism. studies. References 6, 13, 29, 32 are Fakhry SM, Schandl CA: Fat embolism in J Trauma Acute Care Surg 2017;82: 338-344. level IV studies. References 7, 12, 18 pediatric patients: An autopsy evaluation of incidence and etiology. 2015;30: JCritCare 27. Bederman SS, Bhandari M, McKee MD, are level V expert opinion. e1–e5. Schemitsch EH: Do corticosteroids reduce References printed in bold type are 15. Feder D, Koch ME, Palmieri B, Fonseca FLA, the risk of fat embolism syndrome in Carvalho AAS: Fat embolism after fractures patients with long-bone fractures? A meta- those published within the last 5 years. in Duchenne muscular dystrophy: An analysis. Can J Surg 2009;52:386-393. underdiagnosed complication? A systematic 28. Sen RK, Tripathy SK, Krishnan V: Role of 1. Eriksson EA, Pellegrini DC, Vanderkolk WE, review. Ther Clin Risk Manag 2017;13: corticosteroid as a prophylactic measure in Minshall CT, Fakhry SM, Cohle SD: Incidence 1357-1361. of pulmonary fat embolism at autopsy: An fat embolism syndrome: A literature review. undiagnosed epidemic. JTrauma2011;71: 16. Bosse MJ, MacKenzie EJ, Riemer BL, et al: Musculoskelet Surg 2012;96:1-8. 312-315. Adult respiratory distress syndrome, 29. Riska EB, von Bonsdorff H, Hakkinen S, pneumonia, and mortality following 2. Mudd KL, Hunt A, Matherly RC, et al: thoracic injury and a femoral fracture Jaroma H, Kiviluoto O, Paavilainen T: Prevention of fat embolism by early internal Analysis of pulmonary fat embolism in treated either with intramedullary nailing fixation of fractures in patients with blunt force fatalities. J Trauma 2000;48: with reaming or with a plate: A multiple injuries. Injury 1976;8:110-116. 711-715. comparative study. J Bone Joint Surg Am 3. Allen M: Cerebral fat microembolism 1997;79:799-809. 30. Bone LB, Johnson KD, Weigelt J, and its potential role in postoperative 17. Rosique RG, Rosique MJ: Deaths caused by Scheinberg R: Early versus delayed cognitive dysfunction after major Gluteal lipoinjection: What are we doing stabilization of femoral fractures: A orthopaedic surgery: Commentary on an wrong? Plast Reconstr Surg 2016;137: prospective randomized study. J Bone Joint articlebyAnnaN.Miller,MD,etal.: 641e-642e. Surg Am 1989;71:336-340. “Use of the reamer/irrigator/aspirator decreases carotid and cranial embolic 18. King MB, Harmon KR: Unusual forms of 31. Pape HC, Tornetta P III, Tarkin I, events in a canine model”. J Bone Joint pulmonary embolism. Clin Chest Med Tzioupis C, Sabeson V, Olson SA: Timing Surg Am 2016;98:e33. 1994;15:561-580. of fracture fixation in multitrauma patients: The role of early total care and 4. Cox G, Tzioupis C, Calori GM, Green J, 19. Malhotra R, Singla A, Lekha C, et al: A damage control surgery. JAmAcad Seligson D, Giannoudis PV: Cerebral fat prospective randomized study to compare Orthop Surg 2009;17:541-549. emboli: A trigger of post-operative systemic emboli using the computer- delirium. Injury 2011;42(suppl 4):S6–S10. assisted and conventional techniques of 32. Vallier HA, Moore TA, Como JJ, et al: total knee arthroplasty. J Bone Joint Surg Complications are reduced with a protocol 5. Pitto RP, Hamer H, Fabiani R, Radespiel- Am 2015;97:889-894. to standardize timing of fixation based on Troeger M, Koessler M: Prophylaxis response to resuscitation. J Orthop Surg Res against fat and bone-marrow embolism 20. Husebye EE, Lyberg T, Roise O: Bone 2015;10:155. during total hip arthroplasty reduces the marrow fat in the circulation: Clinical entities incidence of postoperative deep-vein and pathophysiological mechanisms. Injury 33. Pape HC, Giannoudis P: The biological and thrombosis: A controlled, randomized 2006;37(suppl 4):S8-S18. physiological effects of intramedullary e354 Journal of the American Academy of Orthopaedic Surgeons

reaming. J Bone Joint Surg Br 2007;89: 36. Mousavi M, David R, Schwendenwein I, mortality rates? Injury 2009;40: 1421-1426. et al: Influence of controlled reaming on fat 1125-1128. intravasation after femoral osteotomy in 34. Pape HC, Rixen D, Morley J, et al: Impact sheep. Clin Orthop Relat Res 2002: 39. Schmidutz F, Dull T, Voges O, Grupp T, of the method of initial stabilization for 263-270. Muller P, Jansson V: Secondary cement femoral shaft fractures in patients with injection technique reduces pulmonary multiple injuries at risk for complications 37. Miller AN, Deal D, Green J, et al: Use of the embolism in total hip arthroplasty. Int (borderline patients). Ann Surg 2007;246: reamer/irrigator/aspirator decreases Orthop 2012;36:1575-1581. 491-501. carotid and cranial embolic events in a canine model. J Bone Joint Surg Am 2016; 40. Zhao J, Zhang J, Ji X, Li X, Qian Q, 35. Canadian Orthopaedic Trauma S: Reamed 98:658-664. Xu Q: Does intramedullary canal versus unreamed intramedullary nailing of irrigation reduce fat emboli? A the femur: Comparison of the rate of ARDS 38. Stavlas P, Giannoudis PV: Bilateral femoral randomized clinical trial with in multiple injured patients. J Orthop fractures: Does intramedullary nailing transesophageal echocardiography. J Trauma 2006;20:384-387. increase systemic complications and Arthroplasty 2015;30:451-455.

April 15, 2019, Vol 27, No 8 e355