The case: 

An 88-year-old man with a history of CABG and AAA was transferred from the OR to the ICU at a community hospital where he was undergoing hip replacement and fracture fixation. 

Two days prior he was at his baseline, active in his community and volunteering. He was showing off for his grandkids when he slipped on ice, landing on his right hip. The outside ED found a fractured right femur on xray and also performed a CT of his head and neck (negative). He was admitted with a plan for operative intervention the following day. He spent an uneventful day in the hospital and went to the OR in the afternoon.

Approximately 24 hours after the initial fracture, while in the operating room for right hip hemi-arthroplasty complicated by an iatrogenic fracture, he became hypotensive and hypoxemic. His pressure responded to push dose epinephrine and a central line was placed. Anesthesia utilized a portable ultrasound machine to identify right heart enlargement (echo was normal two months ago) and performed bronchoscopy (negative). CXR showed patchy multi-focal airspace disease. ECG at baseline and his blood work revealed a normal troponin. The surgeon finished the procedure [fig 1].

 The patient was left intubated and transferred to the care of the ICU team. Physical exam noted cool and dry skin with no rash. Repeat blood work revealed an elevated troponin; and aspirin was given, ECG remained unchanged. POCUS redemonstrated RV dilation and CT PE was performed which showed patchy nodular airspace disease, as well as consolidative airspace disease bilaterally without any filling defects. SCVO2 50%, BNP >1500, and lactate was normal, all findings consistent with cardiogenic shock. He continued to require pressors. Troponin levels peaked to just over 20, cardiology was consulted and elected not to perform a cardiac catheterization. Heparin therapy was not initiated. It was also noted that he was anemic (Hgb 10) and slightly thrombocytopenic. He was extubated and emerged delirious. Confirmatory echocardiography redemonstrated right ventricle dilation with severely reduced RV systolic function, with normal LV function. DVT studies were also negative. 

Diagnosis:

Presumed fat embolus syndrome. 

Discussion: 

Prevalence and Demographics:

Orthopedic trauma and surgeries are overwhelmingly the cause of fat embolism syndrome. The femur is the biggest culprit, but other large bones (e.g. tibia, pelvis) are not rare causes. In fact, when patients sustaining orthopedic trauma undergo autopsy the vast majority have fat emboli. Fat embolization is not the same as fat embolus syndrome (FES) which occurs in approximately 1% of orthopedic trauma patients (see “pathophysiology” below). The highest rates of FES are associated with multiple fractures, closed fractures, and lower extremity fractures, but it can be seen in patients sustaining upper extremity fractures. (1) Being male carries a relative risk of 5.7 and young adults are more prone to FES. However children are unlikely to have FES because of their different composition of marrow. (2) Any insult to fat or bone marrow can cause fat embolization; deaths from FES have even been linked to cosmetic procedures involving fat manipulation. These atypical presentations may be especially important for the ED physician (more below). (3)

Pathophysiology:

Fat embolism is the presence of fat globules in pulmonary or peripheral circulation, regardless of clinical significance. FES results from fat emboli but is exacerbated by an inflammatory response and therefore also has a delayed presentation. (1) FES is derived from two parallel processes: local obstruction/inflammation from emboli and systemic inflammation from degradation of fats. In the obstructive process, fat ordinarily contained within a bone is embolized after being exposed to vasculature at a fracture site. After entering the vasculature, pro-inflammatory fat cells act as a nidus for platelets and fibrin which snowball until this amalgam wedges into end organ vessels causing both obstruction and inflammation. If the final destination is the vascular bed of the lung it causes alveolar obstruction through local edema and bleeding with subsequent local pulmonary vasoconstriction. (4) However, mechanical obstruction and local inflammation alone do not fully explain the pathology seen in FES. 

The inflammatory process theory was proposed to explain the pathophysiology of FES. It postulates that further damage is caused by systemic inflammation triggered by marrow-fat-breakdown in circulation which leads to microvascular and organ dysfunction. For example, in the lung the inflammatory process can lead to acute lung injury or ARDS. Systemic inflammation also further exacerbates the obstructive pathology. The delay of hours or days between the insult and symptoms of FES is explained by systemic inflammation. Skin and brain involvement is derived from both processes: mechanical obstruction with emboli gaining access to arterial vessels through patent foramen ovale or by squeezing through pulmonary capillaries, and systemic inflammation causing end organ dysfunction. 

Symptoms:

Half of FES patients need mechanical ventilation and mortality is around 15%. Deaths occur from respiratory failure, right heart failure, or brain death. Generally, if FES is not fully resolved within a week it results in mortality.

Rarely, fat embolization can cause obstructive pulmonary hypertension immediately upon insult, but presentations of FES occur around 12 to 72 hours after the initial event. FES typically involves pulmonary and neurological symptoms, and sometimes cutaneous symptoms, in that order. Diffuse inflammation can cause hematological pathology including bleeding, clotting, DIC, anemia, and thrombocytopenia. 

Pulmonary symptoms present with either acute dramatic respiratory compromise from a large embolus or a more gradual progression of dyspnea, tachypnea, and hypoxemia. Most FES patients exhibit neurological symptoms, frequently delirium, sometimes followed by generalized symptoms like seizures or coma, or focal deficits such as extremity paralysis or difficulty speaking. The rash associated with FES is petechial and occurs in a minority of patients. It has a unique distribution: anteriorly in supine patients and predominantly on the upper body. An explanation for this particular distribution- is that as the lower-density fat is dispersed through the major vessels it rises against gravity, similar to salad dressing where the fat rises to the top.

Diagnostic tests in the ED: 

No tests or imaging reliably rule in or out FES. It is a clinical diagnosis. One might expect filling defects on CT PE, but they are rarely present, and when they are it is usually catastrophic. Other nonspecific CT findings can raise suspicion: ground glass opacities, septal wall thickening, nodular opacities, lobular consolidation, and evidence of alveolar edema and hemorrhage can be seen. Lab work proves similar: inflammatory markers like CRP and ESR may be elevated, low platelets, anemia and even markers of DIC can occur. Cardiac sequelae may manifest in labs or imaging much like in any other cause of acute pulmonary hypertension: elevated BNP, low SCV02%, and dilated RV with plethoric IVC noted by echocardiography. Brain CT is generally unhelpful, but MRI can indicate small areas of increased intensity. 

ED Management: 

In addition to supportive care, fracture stabilization is the mainstay of treatment. Even with ongoing FES this may limit clinical deterioration. In the ED, obtaining and maintaining reduction as quickly as possible is likely to reduce fat embolization. Supportive care can range from supplemental oxygen to advanced critical care like ECMO and pulmonary dilators. (5, 6) Access to these advanced measures may affect transfer or destination preference. Neurologic symptoms rarely demand anything beyond airway management. Intracranial pressure monitoring may be needed in severe cases. 

ED Presentation:

Examples of peri-insult pathology resulting from fat embolus do exist but are rare.  Patients rarely present in extremis from the field immediately after fracture or fat manipulation. FES occurs hours after insult, as in our case. With the push for patients to be discharged more expeditiously after many procedures including hip surgeries, it is important for ED clinicians to consider FES in their differential diagnosis for recent post-operative patients with respiratory distress or confusion; in addition to the more common: pneumonia, atelectasis, pulmonary embolism, delirium, and urosepsis. There are many uncommon and rare causes of FES, but they need not be memorized since they share a common feature, insult to bones or fat. A few examples include pancreatitis, sickle cell crisis, and CPR survivors. 

Cosmetic procedures have been linked to numerous FES deaths. Gluteal lipoinjection (aka fat grafting or Brazilian butt lift) and other procedures involving fat manipulation are rapidly gaining popularity. Unlike patients with femur fractures that are usually in the hospital in the 12-72 hrs after insult, these patients may present from home as these cosmetic procedures are often performed in the ambulatory setting. As medical tourism grows, FES should be kept on the differential along with pulmonary embolus in patients with a travel history to a popular medical tourism country like Brazil, Turkey, or India.

 

Case resolution:

Over the next two days in the ICU the patient remained delirious but his oxygen requirement improved and pressors were weaned off 30 hours after arriving to the unit. After two days he was transferred to the floor.

 

Take-aways: 

-Mechanism: embolization and inflammation

-Symptoms: pulmonary and neurological, sometimes cutaneous and hematologic

-Timeframe: hours to days after orthopedic trauma or other events that disrupts fat

-Tests: Clinical diagnosis bolstered by tests and imaging. This is mainly a clinical diagnosis

-Management: early fracture stabilization and supportive care

-Outcomes: Mortality 1:5 usually via respiratory failure or right heart failure 

-Prevention: early fracture stabilization and identification of at-risk patients 

AUTHOR: Barret Zimmerman, MD, Intern at Brown University/Rhode Island Hospital.

FACULY EDITOR: Shideh Shafie MD, EM Physician and Associate Professor at Warren Alpert School of Medicine- Brown University

REFERENCES

1.     Rothberg DL, Makarewich CA. Fat Embolism and Fat Embolism Syndrome. J Am Acad Orthop Surg. 2019;27(8):e346-e355. doi:10.5435/JAAOS-D-17-00571

2.     Stein PD, Yaekoub AY, Matta F, Kleerekoper M. Fat embolism syndrome. Am J Med Sci. 2008;336(6):472-477. doi:10.1097/MAJ.0b013e318172f5d2

3.     Cárdenas-Camarena L, Bayter JE, Aguirre-Serrano H, Cuenca-Pardo J. Deaths Caused by Gluteal Lipoinjection: What Are We Doing Wrong? Plast Reconstr Surg. 2015;136(1):58-66. doi:10.1097/PRS.0000000000001364

4.     Kosova E, Bergmark B, Piazza G. Fat embolism syndrome. Circulation. 2015;131(3):317-320. doi:10.1161/CIRCULATIONAHA.114.010835

5.     Wade R, Mkorombindo T, McElwee S, Wille K. RIGHT VENTRICULAR SUPPORT IN FAT EMBOLISM SYNDROME: A ROLE FOR PULMONARY VASODILATORS AND EXTRACORPOREAL MEMBRANE OXYGENATION? Chest. 2019;156(4):A124. doi:10.1016/j.chest.2019.08.208

6.     Popovich I, Singh V, Vickery B. Perioperative support of a patient with fat embolism syndrome with extracorporeal membrane oxygenation Novel treatment (new drug/intervention; established drug/procedure in new situation). BMJ Case Rep. 2019;12:227747. doi:10.1136/bcr-2018-227747