J. clin. Path., 23, Suppl. (Roy. Coll. Path.), 4, 123-131 The syndrome of fat embolism and its origin J Clin Pathol: first published as 10.1136/jcp.s3-4.1.123 on 1 January 1970. Downloaded from GYORGY SZABO From the National Institute of Traumatology, Budapest, Hungary The solution of the now century-old riddle of fat embolism where, depending on the criteria fat embolism has been much delayed by a of diagnosis, its frequency is said to range misunderstanding which is reflected even in between 5% and nearly 100% (Evarts, 1965). terminology. A study of the incidence and severity of fat In patients who die shortly after injury embolism at necropsy among injured and microscopic droplets of fat are found obstructing uninjured cases was therefore undertaken. small vessels, particularly in the lungs but also copyright. sometimes in other organs. Lung embolism is found in nearly all patients when injury includes a fracture of a long bone. On the other hand, Fat Embolism at Necropsy a well defined clinical syndrome is observed only in certain patients with bone fractures. The The grading of fat emboli proposed by Sevitt syndrome is characterized by severe pulmonary, (1962) was adopted. One hundred posttraumatic circulatory, and neurological signs and symptoms and 100 non-traumatic cases were studied. http://jcp.bmj.com/ which lead to death in a high percentage of cases. Forty-one of the injured patients with fractures A distinction must be made between the patho- died within a week of the accident: fat emboli logical entity of fat emboli in small vessels of were found in the lungs in every case, the average those who die after bone injury and the clinical number of emboli being 1,017 ± 259 per mm3 syndrome. The relationship between the two (Table I). After trauma fat droplets are reported phenomena is far from clear. As a consequence to disappear fairly quickly from the lungs many surgeons believe that fat embolism is (Vance, 1931; Whiteley, 1954; Sevitt, 1960), and on September 27, 2021 by guest. Protected infrequent, whilst most pathologists find necropsy this was confirmed in the 33 patients with evidence of fat embolism to be very common. fractures who died one week or later after injury: This confusion is mirrored in the statistics on in them the lung emboli count was only 89 ± 24 per mm3. In those without bone injury who succumbed to trauma within one week the lung Emboli per mm" Patients with Long Bone Fracture Patients without Fracture All Cases embolus count was surprisingly high, 213 ± 117 Lung Section Death within Death after Death within Death after One Week One Week One Week One Week Emboli per. mm" Chronic Diseases Acute Diseases Totals Lung Section o 0 4 1 6 11 0-60 6 16 5 5 32 0 28 16 44 60-180 3 9 5 0 17 0-60 33 1 1 44 Over 180 25 4 4 0 33 601-80 4 3 7 Over 1,800 7 7 over 180 5 0 5 Totals 41 33 15 11 100 Totals 70 30 100 Mean number Mean number of of emboli 1,017±259 89±24 213+117 10±6 emboli/mm' 37±11 5 14+4 Table I Lung embolism in 100 patients dying after Table II Pulmonary fat embolism in 100 non- injury traumatic necropsies Gyorgy Szabo 124 J Clin Pathol: first published as 10.1136/jcp.s3-4.1.123 on 1 January 1970. Downloaded from per mm3. In medical cases (Table II) the embolus in relation to the dose injected, the route of counts were uniformly low, with a mean value administration, and other factors. Pulmonary of only 37 + 11 emboli per mm3 of lung in the and systemic fat embolism was studied by the 70 patients who died after a chronic illness and same semiquantitative method as in the human less in those with acute diseases. However, fat cases. The distribution of the fat according to emboli were present in about half the medical dose was also investigated in other groups of cases and was more than slight in 13% (Tables I animals with 1311-labelled triolein. and II). The minimal lethal dose (MLD) of intra- Gross lung embolism was found in 78 % of venously injected triolein was found to be those who died within a week of fracture, and 1-50 ml/kg body weight, and the LD50 was in 17 % the embolism was only considerable, 1-02 ± 0.022 ml/kg. Similar resultswere reported with more than 1,800 emboli per mm3 of lung. by Peltier (1956). These doses produced a very Cerebral fat emboli were seen in over one-third severe histological degree of fat embolism in the of the cases and renal emboli in 50 %. The lungs. Even after 0.5 ml/kg lung emboli counts correlation between the severity of pulmonary were over 12,000 per mm3. Cerebral emboli were embolism and the presence of systemic emboli found even with the smallest dose given: they was confirmed. Those with cerebral embolism were seen in three of the six rabbits receiving had 1,607 ± 748 emboli per mm3 in the lungs 01 ml/kg, and in nine of the 12 receiving as against a count of 744 ± 191 in patients 0.25 ml/kg triolein. All animals injected with without cerebral embolism. larger doses had gross cerebral fat embolism. It was hoped that some insight could be gained A linear increase of the injected dose increased on the importance of these findings in the light the histological severity of cerebral fat embolism of the experimental observations. in an exponential manner: thus, 6 ± 2-4 emboli per mm3 were found in brain tissue after the injection of 0.1 ml/kg and 284 ± 55 after 1.0 ml/kg of triolein. A similar relationship was Experimental Embolism found for several embolisms (Figs. 1 and 2). After the injection of radioactive triolein the Fat embolism was produced in rabbits by the bulk of the injected oil was recovered fromcopyright. the injection of triolein. Mortality rates were studied lungs: after a dose of 0.1 ml/kg 75.5 ± 5% of Emb/mm3 fOOO I-f-I- http://jcp.bmj.com/ t00 on September 27, 2021 by guest. Protected 10 0.1 0.25 0.50 O*75 10 /25 f 50 Fig. 1 Number of cerebral fat emboli. Fig. 2 Number ofrenalfat emboli (key as in Continuous line: rabbits killed 2 hr after fat Fig. 1). injections. Interrupted line: animals killed after 24 hr. Abscissa: number ofemboli. Ordinate: dose of injected triolein. The syndrome offat embolism and its origin 125 J Clin Pathol: first published as 10.1136/jcp.s3-4.1.123 on 1 January 1970. Downloaded from appears after a latent period, the first symptoms developing only on the second or third day after injury: pulmonary symptoms, dyspnoea, and slight cyanosis may be present, but in the more severe cases the clinical picture is dominated by cerebral symptoms. In the light of these very impressive symptoms, the opinion has been repeatedly expressed that the syndrome is produced by systemic, especially cerebral, em- bolism, and that death occurs through involvement of the brain (Scriba, 1880; Grondahl, 1911; Armin and Grant, 1951; Sevitt, 1962). INTRAARTERIAL INJECTION OF FAT If death from fat embolism is a sequel of systemic embolism, the mortality must depend on the amount of fat passing the lungs and reaching the arterial side of the circulation. To test this hypothesis, rabbits were given 0.25-1-5 ml/kg of 010 0.25 0 50 1.00 triolein through a catheter introduced either into the left ventricle or simultaneously into both Fig. 3 Radioactive fat content of the lungs after carotid arteries. Animals surviving were killed intravenous administration of 13'I-triolein. 72 hours after the injection for histological Continuous line: percentage of injected dose. examination. The distribution of the fat was also Interrupted line: ,ul per gram fresh tissue. studied with 1311-labelled triolein. The results seem important. First, the injection of fat directly into the arterial circulation did not the fat was found in the lungs. The percentage increase the mortality significantly (Fig. 5). pulmonary recovery decreased as the dose Secondly, the distribution of the fat was not copyright. increased, and a greater part of the injected fat much affected by the site of injection and by far gained access to the systemic circulation and the heaviest embolism was always found in the ultimately produced fat embolism in other lungs. For instance, after injecting 0.50 ml/kg organs. Thus, the renal uptake of labelled oil triolein into the carotid arteries, 6,640 + 1,484 after a dose of 0.1 ml per kg was 0.37%, and it emboli per mm3 were found in the lungs and only increased to 1.23% after 1.0 ml/kg was given, 22.6 ± 8-3 emboli in the brain. These observa- rose to whilst the hepatic uptake from 0-82 tions were supported by the results of the http://jcp.bmj.com/ 10.4 % with these dosages. The same phenomenon experiments with radioactive triolein. Two hours was observed in the brain; with a ten-fold increase after the intravenous injection of 0.50 ml/kg of dose there was a hundred-fold increase in the '311-triolein, 68.2 ± 6-9 % of the dose was amount of fat recovered from brain tissue recovered from the lungs, and after injection into (Fig. 3). the left ventricle pulmonary recovery was 54.4 %. Comparing our necropsy observations in man The amounts found in other organs after the with the results of the rabbit experiments, it was ventricular introduction did not differ significantly interesting to note that the pulmonary embolus from those observed after intravenous injection.