Arch. orthop. Unfall-Chir. 82, 217--223 (1975) © by J. F. Bergmann Verlag Mfinchen 1975
Fat Embolism: Physiopathology, Diagnosis and Management George M. Weisz a n d A m i Barzilai Department of Surgery, A. Rambam Hospital, Abba Khoushy School of Medicine, Haifa, Israel l%eceived January 19, 1975 Fettembolien: Physiopathologie, Diagnose und Management
Zusammen/assung. Die Arbeit befal~t sich mit der Beschreibung der Komponenten des Xomplexes des posttraumatischen Syndromes. Das pathologische Geschehen der Fettmakroglobulinimie wird eine klinische Einheit, dnrch Verstopfung der arteriolaren Endungen der vitalen Organe, was die Form des fettembolischen Syndromes erzeugt. Das Hanptproblem in der Physiopathologie, die Lungeninsuffizienz, die sich zu einer akuten oder subakuten Form entwickelt, ist beschrieben. Ebenfalls ist die eerebrale Embolie beschrieben. Die Symptomatologic ist verschieden und nicht charakteristisch, nach der Wiehtigkeit der Sympteme und Anzeiehen als Minder- oder Hauptsymptome wurde sic in der Diagnose der Fettembolie anfgeteilt. Nur in der letzten Zeit ist die Behandlung der Patienten mit fettembolischem Syndrom bekannt, und sic besteht aus einer allgemeinen suportiven Therapie, Atmungstherapie nnd antiinflammatorisehen Therapie, hauptsichlich einer Corticoidversorgung. Summary. This paper describes the components of the post-traumatic syndrome. The pathological state of fat macroglobulinemia by occlusion of arteriolar terminal branches of vital organs causes the far5 embolie syndrome. The main physiopathological problem is pulmonary insufficiency in an acute or subacute form. The cerebral embolus is second. The symptomatology varies and is not characteristic. According to their importance they were described as minor or major in the diagnosis of fat emboli. Only recently, treatment for the fat emboli syndrome has been initiated, consisting mainly in supportive measures, respiratory care and anti-inflammatory drugs, mainly cortisone. Introduction The clinical course o f e v e r y i n j u r e d p a t i e n t d e p e n d s u p o n t h e s e v e r i t y of t h e i n j u r y itself a n d on t h e s u b s e q u e n t m a n a g e m e n t o f t h e p o s t - t r a u m a t i c complications. This a x i o m has been well k n o w n for decades. E m p h a s i s u p o n t h e l a t t e r f a c t o r has led to t h e d e v e l o p m e n t of a n e w b r a n c h o f s u r g e r y - - t h e t r a u m a m a n agement. 50 y e a r s ago, t h e i n j u r e d u s u a l l y d i e d o f shock or sepsis; 30 y e a r s ago t h e y w o u l d die f r o m shock or r e n a l failure. T o d a y i n j u r e d often recover from t h e initial shock s t a t e because o f e a r l y r e s u s c i t a t i o n a n d in t h e s e p a t i e n t s a complex, postt r a u m a t i c s y n d r o m e m a y a p p e a r [23]. Coalescence o f small l i p i d chylomicrons in t h e s e r u m a n d a b s o r p t i o n of disr u p t e d f a t globuli from t h e c o n t u s e d f a t tissue, is o n l y one f a c t o r in t h e p a t h o l o g i c r e a c t i o n s to t r a u m a . W h e n t h e s e f a t globuli a p p e a r in large aggregate form, f a t e m b o l i s m is p r e s e n t as a pathologic event. 15.
218
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The clinical entity o] the ]at embolism syndrome (F.E.S.) will be characterized by varying symptoms depending upon which organ is affected, the speed of embolisation, tissue reactions to fat and the general condition of the patient. F. E. S. will mainly affect vulnerable lung tissue and the brain, which is sensitive to low oxygen tension, l~ecent understanding of the complex clinical entity of F . E . S . has led to a change in the therapeutic approach. Treatment, at first the responsibility of the internist, later of the neurologist and then of the surgeon, should now be the responsibility of the critical care therapist [23, 29].
Physiopathology of F.E.S. Fat macroglobuli, originating in the blood stream either from the influx of disrupted traumatized fat droplets or from the coalescence of small serum lipid particles (chylomicrons), will function as emboli, in nearly every organ of the body. Most symptoms, however, result from pulmonary and cerebral fat embolism.
Pulmonary Fat Embolism Fat emboli are brought by the blood stream (and eventually also by lymphatics) to the pulmonary arterioli. They may obstruct arterioles inducing an anemic, unper]used unit of lung tissue. The alveoli will continue to be ventilated resulting in a ventilation-per]usion disturbance. The intensity of this disturbance will depend on the suddenness and the quantity of the embolie shower. These emboli may have no observable effect - - i.e. the subclinical ]orm. However, in massive fat embolism, an acute rise in pulmonary arterial pressure will produce signs of acute cor-pulmonale with right ventrieular strain, venous stasis, and hepatic congestion. The compensatory response of the heart and lungs will be evident by tachycardia, tachypnoea, dyspnoea, cyanosis, myocardial ischemia and right ventrieular strain. Additional aggravating factors include the tendency to adhesiveness of the platelets, red blood cells and fibrin around the fat macroglobuli, which will increase the size of the embolus itself. This phenomenon is enhanced by sludging of the blood. The platelets also release kinins and serotonin which induce vasoconstriction of the pulmonary vessels and the bronchiolar tree [13]. The total effect of acute hypoxia will be life threatening. The classical mechanical phase o/ the pulmonary disease in _~.E.S. is the first phase of hypoperfusion. This phase may be fulminating with immediate death. Between the two extremes of fulminating and subclinical form exists the non-]ulminant, subaeute form, progressively developing within the days immediately following the trauma. This form may present itself as a relatively mild, self-limited disease or eventually progress to a mono-organ or complex, multisystem failure. Three possibilities have been documented as to the fate of the embolized fat in the lung : (a) I f the embolus is smaller than 20 ~, it may pass through the pulmonary vascular system and enter the systemic circulation. The embolic fat will then be either trapped in body organs or eliminated through renal excretion. (b) The embolic fat particle m a y be engulfed by alveolar cells desquamated into the alveolar space and eventually be eliminated through the sputum. (c) Local lipolysis may occur in the lung parenchyma, producing a chemical, hemorrhagic
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pneumonitis, comprising the following two phases: (1) The "intermediate phase": The time interval between the trauma and the appearance of the first symptoms of F. E. S. was called by m a n y authors: "the free interval". We consider the name "intermediate phase" to be more appropriate [23, 24, 29] actually being an active biochemical, physiopathological and pathological process, taking place in the lung parenchyme, I t can be detected by proper laboratory tests, and is characterized as a silent period only from symptomatic point of view. The pathologic processes precede the development of [2] progressive pulmonary insufficiency [11]. The above mentioned pathological effect is the chemical phase of the pulmonary disease in ~. E. S. I t is theorized that a biochemical decomposition of the embolie triglycerides, under the effect of local lipase, into inert glycerol and toxic free f a t t y acids (F. F.A.) occurs. The toxicity of the F. F.A. to the alveolar cells was discovered by Peltier, who described the development of a hemorrhagic pneumonitis, as a delayed result of fat embolism [13--15, 26]. Alveolar exudates and hemorrhages, interfere with ventilation. This is the second type o] ventilation-per]usion dizturbances in F . E . S . [6, 21, 23, 24]. During this phase hypoxia is predominant and progressive. As a result of the accumulated anoxic tissue metabolites, the initial respiratory alkalosis becomes a dangerous combined respiratory and metabolic acidosis. The effect of hypoxemia will be felt by the organs most sensitive to low oxygen supply - - namely - - brain and myocardium. The myocardial damage caused by acidosis and hypoxemia, as well as the compromized cerebral oxygenation are usually terminal events, but m a y be reversible to a certain degree, as is the entire pulmonary process [13].
Systemic Fat Embolism The filter action of the lung permits only small fat globules to enter the systemic circulation. The emboli will be dispersed to practically every organ. The most important of all the organs affected is the brain and secondarily the eyes, kidneys, myocardium and skin,. Cerebral Embolism Although cerebral fat embolism is a real entity, it seldom appears as a "pure" cerebral form. I t can precede, parallel or follow the appearance of the pulmonary involvement. The symptoms and signs m a y reflect either the direct effect of the fat emboli or hypoxia. In the combined forms, the hypoxia can aggravate the deleterious effect of the cerebral arteriolar occlusion. Differentiation of hypoxemic anoxia and anemic anoxia as to their causal effect on the neuropathology in fat embolism is essential [18, 23]. Several "pure" cases of fat embolism to the brain have been described as a mild and transient form, provided that no other aggravating factors coexist. Even in severe forms, recoveries have been noted [10, 19], generally with full rehabilitation and with very few sequelae. In our experience the respiratory form predominates over the cerebral form. Signs of local pathology were evident in one of our series, where an osteogenetic stimulus, well known in cerebral pathology, was also found in eases of fat embolism to brain [28].
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Diagnosis F a t e m b o l i s m has no p a t h o g n o m o n i c sign or test. T h e diagnosis is suggested in a p a t i e n t a t r i s k i f suggestive signs c a n n o t be e x p l a i n e d on a n o t h e r basis. Because each sign h a s a m u l t i t u d e of possible causes i t is o n l y when a constellation o f signs is p r e s e n t t h a t t h e diagnosis of f a t e m b o l i s m can be m a d e . Our classificat i o n is according t o t h e d i a g n o s t i c v a l u e of each s y m p t o m or sign [25]. Minor signs
Major signs
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
1. retinal embolism 2. abnormalities at biopsy (skin, lung, kidney) 3. histological findings at autopsy
pyrexia taehycardia anemia thrombocytopenia (coagulopathy, or both) petechiae fat excretion in urine and sputum (and fat macroglobulaemia) serum lipase elevation (and lipid electrophoretie changes) hypoxia roentgenographie abnormalities in the lung neurological abnormalities (paresis, coma, E.E.G. changes)
T h e s u s p e c t e d diagnosis is confirmed b y t h e presence of one of t h r e e m a j o r signs. O n l y a few of t h e s e signs n e e d m o r e d e t a i l e d e x p l a n a t i o n . Thrombocytopenia: is explained by the trapping of the platelets in the pulmonary circulation, by the clot formation around the fat droplets or by the disseminated intravascular clotting. I)etechiae: are found over the neck, shoulders and upper chest areas and the eonjunetivas. This distribution is quite characteristic, although it is present only in a quarter of the patients. A provoked peteehiae test has been described using a negative pressure petechiometer applied on the chest wall. F a t excretion: F a t in the urine is a common finding after trauma. I t is evidence of fat macroglobulemia clearing through the kidneys, identifying a pathologic phenomena, not F.E.S. Of ~oweat importance is the method of urine examination. One method is a microscopic test using a Sudan I I I stain. Another test is a macroscopic qualitative identification with Nile blue, staining the triglycerides in red, the fatty acids in blue while other lipids (like lubricating oils used for urinary catheters) remain colourless [2]. As the sputum might be contaminated by saliva and external fat, it seems to us that staining of the tracheal aspirate is more accurate. Technics have been described for the identification of circulating fat macroglobulemia, but the significance of this finding was denied [9, 16, 20]. Serum lipase: Activity is elevated following trauma (3--:5 days) and declines to normal levels within 5--7 days. A persistently high level in F.E.S. implies a better prognosis. I t is an easily performed technic in any hospital [18, 19]. In contrast to this is the lipid electrophoresis, a relatively complicated technic with doubtful diagnostic value. ttypoxia: found in a patient with trauma or fractures has an enormous value in the diagnosis of pulmonary damage. If not explained by other direct or indirect insult of the lung physiology, fat embolism should be suspected in a patient at risk [5--7, 21--23, 25--27, 29]. Lung radiologic opacification (patchy, multiple or localized) has the same significance and generally parallels the hypoxia.
The Management of a Patient with Established Fat Embolism T h e t r e a t m e n t of t h e p u r e cerebral form o f F . E . S . is g e n e r a l l y s u p p o r t i v e w i t h t r e a t m e n t o f c o m p l i c a t i o n s a n d t h e neurological sequelae. R e c e n t l y some
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evidence has been published detailing the favorable effect of a high dose regimen of Trasylol (Bayer), i.e., 1 million units in the first 2 days, reduced to a maintenance dose of 500000 U/day [12]. The most important aspect of the management of fat embolism is the treatment of the pulmonary disease and its complications. In cases of non-fulminant fat embolism, the following treatment should be applied, with daily monitoring of all the hematologic and respiratory parameters. Central venous and arterial lines are necessary. If the patient is unconscious, a urinary catheter, intravenous infusion and nasogastrie aspiration are imperatives. Exact electrolyte, fluid and acid-base balance data are registered, and this energy demand calculated. A daily flow sheet with all the chemical data and a record of this therapy is essential for proper evaluation. Frequent electroencephalograms, electrocardiograms, and lung roentgenograms, are performed. The treatment consists of: 1. Treatment of pneumonitis and oxygenation. 2. Blood rheology stabilization and clotting mechanism normalization. 3. General supportive therapy. 1. The hemorrhagic pneumonitis, can be efficiently inhibited with administration protection of high dosages of corticosteroids. Their effect is in decreasing alveolitis, stabilization of the surfactant producing pneumocy~es, decreased permeability of membranes, and decrease of interstitial oedema [4]. The pharmacologic dose of 1.0--1.5 g hydrocortisone, or its equivalents (dexamethosone, methyl prednisolone) should be administered parenterally in divided doses in the first 2 days, followed by a slow gradual decrease. The second important task in the treatment of F. E. S. is adequate oxygenation i.e., proper respiratory care. Although it is inappropriate to standardize respiratory therapy, certain principles should be followed, with individual adjustments to the specific needs of the patient [23]. Hypoxia should be avoided even in the mild cases of pulmonary insufficiency. The breathing work and rate should be kept within normal limits by oxygen administration if necessary even at high concentration. Should oxygen mask or intranasal tube not be sufficient, mechanical ventilation will be needed. Positive-pressure breathing should continue to be provided until the patient is able to maintain adequate blood oxygenation. However, with the toxicity of prolonged high-oxygen concentration, in mind, one should decrease the concentration as soon as possible. Serial determinations of Poe, Peon, pH, oxygen saturation and base excess should be made as guides for continuing treatment, and these parameters should be correlated with measurements of the minute volume, inspiratory force and breathing rate to indicate a necessary decrease or increase in the tidal volume and/or rate of the respirator. In desperate cases, positive end-expiratory pressure breathing can be of great help in resisting alveolar collapse. Certain pharmaceutical agents such as amynophylin improve the respiratory function by its pulmonary vasodilator effect. Lower oxygen consumption can be achieved by reducing the body temperature to normal or even to hypothermic levels, using antipyretics or surface cooling with lyric cocktail [3]. 2. The blood rheology changes are influenced by the infusion of 2--3 units of Rheomacrodex (L.M.W.D.) over 4--6 hrs. I t will improve the pulmonary
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and systemic capillary flow b y its de-sludging effect. I t is administered in the first 2 days and should any sign of bleeding appear, cessation is indicated. Heparin is frequently used in F.E.S. I t is a double acting agent. I t s lypolytic activity consists of lipase activation, inducing clearing of the f a t t y serum, but it also releases f a t t y acids. I n this respect heparin is an undesired drug [2]. I t s important action is prevention of platelets aggregation and coagulation. I t m a y be possible t h a t a proper dose administration would eventually separate the desired (anticoagulant) action from the undesired one (liberation of f a t t y acid). No exact differential dosage has been determined [1]. tIeparin is administered over the 3 4 days of the disease and should be stopped at any sign of bleeding. The dosage is of 5000 units over 4 - - 6 hrs, given intravenously [8]. A complete anticoagulant state of the blood is not desired. Calcium ions and fresh blood transfusion should be administered. I n case of established disseminated intravascular coagulation, often accompanying F.E.S., heparin and/or E-aminocaproic acid should be administered, in accordance with the results of tests of clotting factors. 3. The general supportive t r e a t m e n t includes caloric, mineral and water balance correction. Calories should be supplied in this form of concentrated glucose solution and amigen preparates, decreasing in this way the necessity for lipid mobilization from storage areas. Electrolyte and water balance and acid-base equilibrium m u s t be maintained. Diuretics are necessary in cases of water retention. I n patients with serious heart disease or signs of congestive failure, full digitalization is rapidly instituted. A broad spectrum antibiothcrapy will become necessary in patients with traeheostomy as well as with long term intravenous or urinary catheters. References 1. Adar, 1~.: Pathogenesis and treatment of fat embolism, ttarefuah, Israel med. Ass. J. 83 491 (1972) 2. Adler, F., Peltier, L. F., Lai, S. P. : Fat embolism, the determination of fat in urine by macroscopic and microscopic method. Surgery 47, 959 (1960) 3. Aladyemoff, L., Weinberg, It., Alkalai, I. : Fat embolism treatment with lyric cocktail and surface cooling. Lancet 1968 II, 13 4. Ashbaugh, ]:). G., Petty, T. L. : The use of corticosteroids in the treatment of respiratory failure associated with massive fat embolism. Surg. Gynee. Obstet. 128, 493 (1966) 5. Benoit, 1). R., ttampson, L. G., Burgess, J. H.: Value of arterial hypoxemia in the diagnosis of fat embolism. Ann. Surg. 175, 128 (1972) 6. Benoit, P. t~., Hampson, L. G., Burgess, J. H. : Respiratory gas exchange following fractures. Surg. Forum 208, 214 (1969) 7. Collins, J. A., Gordon, W. C., Hudson, T. L., Irvin, R. W.: Inapparent hypoxemia in casualties with wounded limbs: pulmonary fat embolism ? Ann. Surg. 167, 511 (1968) 8. Dines, K. I~., Lindscheid, It. L., Didier, E. F. : Fat embolism syndrome. Mayo Clin. Froc. 47, 237 (1972) 9. Gurd, A. 1%.:Fat embolism: an aid to diagnosis. J. Bone Jt Surg. 52-B, 732 (1970) 10. McTaggart, D. M., Neubuerger, K. T.: Cerebral fat embolism. Acta neuropath. (Berl.) 1~, 183 (1970) 11. Moore, F. D., Lyons, L. I=L, Fierce, L. C.: Post-traumatic pulmonary insufficiency. Philadelphia: W. B. Saunders 1969 12. New aspects of trasylol therapy, Vol. 4. Stuttgart-New York: F. K. Schattauer 1971 13. Feltier, L. F. : Fat embolism: A current concept. Clin. Orthop. 66, 241 (1969) 14. Feltier, L. F. : Fat embolism a pulmonary disease. Surgery 62, 756 (1967)
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15. Peltier, L. F. : Fat embolism III. The toxic properties of neutral fat and free fatty acids. Surgery 40, 665 (1956) 16. Peltier, L. F. : Fat embolism. The detection of fat emboli in the circulating blood. Surgery a6, 198 (1954) 17. Peltier, L. F., Adler, F., Lai, S. P. : The significance of an elevated serum lipase after trauma to bone. Amer. J. Surg. 99, 821 (1960) 18. Sevitt, S.: Fat embolism. London: Butterworth's & Co. 1962 19. Silverstein, A.: The significance of cerebral fat embolism. Neurology 2, 292 (1952) 20. Tedeschi, C. G., Castelli, V., Kropp, G., Tedeschi, L. G.: Fat macroglobulemia and fat embolism. Surg. Gynec. Obstet. 126, 83 (1968) 21. Wertzberger, J. J., Peltier, L. F.: :Fat embolism: the importance of arterial hypoxia. Surgery 63, 626 (1968) 22. Wright, B. D. : :Fat embolism: Silent respiratory disease. Anaesth. Analg. 49, 279 (1970) 23. Weisz, G. M., Barzilai, A. : Non-fulminant fat embolism. Anaesth. Analg. 58, 303 (1973) 24. Weisz, G. ~[., Steiner, E.: The cause of death in fat embolism. Chest. Dis. Index 59, 511 (1971) 25. Weisz, G. M., Rang, M., Salter, R. S. : Post-traumatic fat embolism in children. J. Trauma 13, 529 (1973) 26. Weisz, G. M., Barzilai, A. : New concepts in the fat embolism syndrome. Harefuah, Israel reed. Ass. J. 81, 87 (1971) 27. Weisz, G. 5[., Schramek, A., Abrahamson, J., BarzilM, A.: Fat embolism in children: Study of its early detection. J. pedlar. Surg. 9, 163 (1974) 28. Weisz, G. ~., Fishman, J., Steiner, E. : Callus function in cases of cerebral fat embolism. Confln. neurol. (Basel) 81, 362 (1969) 29. Weisz, G. M.: Fat embolism. Current problems in surgery. Chicago (Ill.): Year Book Publisher Nov. 1974 George M. Weisz, M.D. Ami Barzilai, M.D. Department of Surgery A. Rambam Hospital Haifa, Israel
Fat Embolism: Physiopathology, Diagnosis and Management George M. Weisz a n d A m i Barzilai Department of Surgery, A. Rambam Hospital, Abba Khoushy School of Medicine, Haifa, Israel l%eceived January 19, 1975 Fettembolien: Physiopathologie, Diagnose und Management
Zusammen/assung. Die Arbeit befal~t sich mit der Beschreibung der Komponenten des Xomplexes des posttraumatischen Syndromes. Das pathologische Geschehen der Fettmakroglobulinimie wird eine klinische Einheit, dnrch Verstopfung der arteriolaren Endungen der vitalen Organe, was die Form des fettembolischen Syndromes erzeugt. Das Hanptproblem in der Physiopathologie, die Lungeninsuffizienz, die sich zu einer akuten oder subakuten Form entwickelt, ist beschrieben. Ebenfalls ist die eerebrale Embolie beschrieben. Die Symptomatologic ist verschieden und nicht charakteristisch, nach der Wiehtigkeit der Sympteme und Anzeiehen als Minder- oder Hauptsymptome wurde sic in der Diagnose der Fettembolie anfgeteilt. Nur in der letzten Zeit ist die Behandlung der Patienten mit fettembolischem Syndrom bekannt, und sic besteht aus einer allgemeinen suportiven Therapie, Atmungstherapie nnd antiinflammatorisehen Therapie, hauptsichlich einer Corticoidversorgung. Summary. This paper describes the components of the post-traumatic syndrome. The pathological state of fat macroglobulinemia by occlusion of arteriolar terminal branches of vital organs causes the far5 embolie syndrome. The main physiopathological problem is pulmonary insufficiency in an acute or subacute form. The cerebral embolus is second. The symptomatology varies and is not characteristic. According to their importance they were described as minor or major in the diagnosis of fat emboli. Only recently, treatment for the fat emboli syndrome has been initiated, consisting mainly in supportive measures, respiratory care and anti-inflammatory drugs, mainly cortisone. Introduction The clinical course o f e v e r y i n j u r e d p a t i e n t d e p e n d s u p o n t h e s e v e r i t y of t h e i n j u r y itself a n d on t h e s u b s e q u e n t m a n a g e m e n t o f t h e p o s t - t r a u m a t i c complications. This a x i o m has been well k n o w n for decades. E m p h a s i s u p o n t h e l a t t e r f a c t o r has led to t h e d e v e l o p m e n t of a n e w b r a n c h o f s u r g e r y - - t h e t r a u m a m a n agement. 50 y e a r s ago, t h e i n j u r e d u s u a l l y d i e d o f shock or sepsis; 30 y e a r s ago t h e y w o u l d die f r o m shock or r e n a l failure. T o d a y i n j u r e d often recover from t h e initial shock s t a t e because o f e a r l y r e s u s c i t a t i o n a n d in t h e s e p a t i e n t s a complex, postt r a u m a t i c s y n d r o m e m a y a p p e a r [23]. Coalescence o f small l i p i d chylomicrons in t h e s e r u m a n d a b s o r p t i o n of disr u p t e d f a t globuli from t h e c o n t u s e d f a t tissue, is o n l y one f a c t o r in t h e p a t h o l o g i c r e a c t i o n s to t r a u m a . W h e n t h e s e f a t globuli a p p e a r in large aggregate form, f a t e m b o l i s m is p r e s e n t as a pathologic event. 15.
218
G.M. Weisz and A. Barzilai
The clinical entity o] the ]at embolism syndrome (F.E.S.) will be characterized by varying symptoms depending upon which organ is affected, the speed of embolisation, tissue reactions to fat and the general condition of the patient. F. E. S. will mainly affect vulnerable lung tissue and the brain, which is sensitive to low oxygen tension, l~ecent understanding of the complex clinical entity of F . E . S . has led to a change in the therapeutic approach. Treatment, at first the responsibility of the internist, later of the neurologist and then of the surgeon, should now be the responsibility of the critical care therapist [23, 29].
Physiopathology of F.E.S. Fat macroglobuli, originating in the blood stream either from the influx of disrupted traumatized fat droplets or from the coalescence of small serum lipid particles (chylomicrons), will function as emboli, in nearly every organ of the body. Most symptoms, however, result from pulmonary and cerebral fat embolism.
Pulmonary Fat Embolism Fat emboli are brought by the blood stream (and eventually also by lymphatics) to the pulmonary arterioli. They may obstruct arterioles inducing an anemic, unper]used unit of lung tissue. The alveoli will continue to be ventilated resulting in a ventilation-per]usion disturbance. The intensity of this disturbance will depend on the suddenness and the quantity of the embolie shower. These emboli may have no observable effect - - i.e. the subclinical ]orm. However, in massive fat embolism, an acute rise in pulmonary arterial pressure will produce signs of acute cor-pulmonale with right ventrieular strain, venous stasis, and hepatic congestion. The compensatory response of the heart and lungs will be evident by tachycardia, tachypnoea, dyspnoea, cyanosis, myocardial ischemia and right ventrieular strain. Additional aggravating factors include the tendency to adhesiveness of the platelets, red blood cells and fibrin around the fat macroglobuli, which will increase the size of the embolus itself. This phenomenon is enhanced by sludging of the blood. The platelets also release kinins and serotonin which induce vasoconstriction of the pulmonary vessels and the bronchiolar tree [13]. The total effect of acute hypoxia will be life threatening. The classical mechanical phase o/ the pulmonary disease in _~.E.S. is the first phase of hypoperfusion. This phase may be fulminating with immediate death. Between the two extremes of fulminating and subclinical form exists the non-]ulminant, subaeute form, progressively developing within the days immediately following the trauma. This form may present itself as a relatively mild, self-limited disease or eventually progress to a mono-organ or complex, multisystem failure. Three possibilities have been documented as to the fate of the embolized fat in the lung : (a) I f the embolus is smaller than 20 ~, it may pass through the pulmonary vascular system and enter the systemic circulation. The embolic fat will then be either trapped in body organs or eliminated through renal excretion. (b) The embolic fat particle m a y be engulfed by alveolar cells desquamated into the alveolar space and eventually be eliminated through the sputum. (c) Local lipolysis may occur in the lung parenchyma, producing a chemical, hemorrhagic
Fat Embolism: PhysiopathoIogy, Diagnosis and Management
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pneumonitis, comprising the following two phases: (1) The "intermediate phase": The time interval between the trauma and the appearance of the first symptoms of F. E. S. was called by m a n y authors: "the free interval". We consider the name "intermediate phase" to be more appropriate [23, 24, 29] actually being an active biochemical, physiopathological and pathological process, taking place in the lung parenchyme, I t can be detected by proper laboratory tests, and is characterized as a silent period only from symptomatic point of view. The pathologic processes precede the development of [2] progressive pulmonary insufficiency [11]. The above mentioned pathological effect is the chemical phase of the pulmonary disease in ~. E. S. I t is theorized that a biochemical decomposition of the embolie triglycerides, under the effect of local lipase, into inert glycerol and toxic free f a t t y acids (F. F.A.) occurs. The toxicity of the F. F.A. to the alveolar cells was discovered by Peltier, who described the development of a hemorrhagic pneumonitis, as a delayed result of fat embolism [13--15, 26]. Alveolar exudates and hemorrhages, interfere with ventilation. This is the second type o] ventilation-per]usion dizturbances in F . E . S . [6, 21, 23, 24]. During this phase hypoxia is predominant and progressive. As a result of the accumulated anoxic tissue metabolites, the initial respiratory alkalosis becomes a dangerous combined respiratory and metabolic acidosis. The effect of hypoxemia will be felt by the organs most sensitive to low oxygen supply - - namely - - brain and myocardium. The myocardial damage caused by acidosis and hypoxemia, as well as the compromized cerebral oxygenation are usually terminal events, but m a y be reversible to a certain degree, as is the entire pulmonary process [13].
Systemic Fat Embolism The filter action of the lung permits only small fat globules to enter the systemic circulation. The emboli will be dispersed to practically every organ. The most important of all the organs affected is the brain and secondarily the eyes, kidneys, myocardium and skin,. Cerebral Embolism Although cerebral fat embolism is a real entity, it seldom appears as a "pure" cerebral form. I t can precede, parallel or follow the appearance of the pulmonary involvement. The symptoms and signs m a y reflect either the direct effect of the fat emboli or hypoxia. In the combined forms, the hypoxia can aggravate the deleterious effect of the cerebral arteriolar occlusion. Differentiation of hypoxemic anoxia and anemic anoxia as to their causal effect on the neuropathology in fat embolism is essential [18, 23]. Several "pure" cases of fat embolism to the brain have been described as a mild and transient form, provided that no other aggravating factors coexist. Even in severe forms, recoveries have been noted [10, 19], generally with full rehabilitation and with very few sequelae. In our experience the respiratory form predominates over the cerebral form. Signs of local pathology were evident in one of our series, where an osteogenetic stimulus, well known in cerebral pathology, was also found in eases of fat embolism to brain [28].
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Diagnosis F a t e m b o l i s m has no p a t h o g n o m o n i c sign or test. T h e diagnosis is suggested in a p a t i e n t a t r i s k i f suggestive signs c a n n o t be e x p l a i n e d on a n o t h e r basis. Because each sign h a s a m u l t i t u d e of possible causes i t is o n l y when a constellation o f signs is p r e s e n t t h a t t h e diagnosis of f a t e m b o l i s m can be m a d e . Our classificat i o n is according t o t h e d i a g n o s t i c v a l u e of each s y m p t o m or sign [25]. Minor signs
Major signs
1. 2. 3. 4. 5. 6. 7. 8. 9. 10.
1. retinal embolism 2. abnormalities at biopsy (skin, lung, kidney) 3. histological findings at autopsy
pyrexia taehycardia anemia thrombocytopenia (coagulopathy, or both) petechiae fat excretion in urine and sputum (and fat macroglobulaemia) serum lipase elevation (and lipid electrophoretie changes) hypoxia roentgenographie abnormalities in the lung neurological abnormalities (paresis, coma, E.E.G. changes)
T h e s u s p e c t e d diagnosis is confirmed b y t h e presence of one of t h r e e m a j o r signs. O n l y a few of t h e s e signs n e e d m o r e d e t a i l e d e x p l a n a t i o n . Thrombocytopenia: is explained by the trapping of the platelets in the pulmonary circulation, by the clot formation around the fat droplets or by the disseminated intravascular clotting. I)etechiae: are found over the neck, shoulders and upper chest areas and the eonjunetivas. This distribution is quite characteristic, although it is present only in a quarter of the patients. A provoked peteehiae test has been described using a negative pressure petechiometer applied on the chest wall. F a t excretion: F a t in the urine is a common finding after trauma. I t is evidence of fat macroglobulemia clearing through the kidneys, identifying a pathologic phenomena, not F.E.S. Of ~oweat importance is the method of urine examination. One method is a microscopic test using a Sudan I I I stain. Another test is a macroscopic qualitative identification with Nile blue, staining the triglycerides in red, the fatty acids in blue while other lipids (like lubricating oils used for urinary catheters) remain colourless [2]. As the sputum might be contaminated by saliva and external fat, it seems to us that staining of the tracheal aspirate is more accurate. Technics have been described for the identification of circulating fat macroglobulemia, but the significance of this finding was denied [9, 16, 20]. Serum lipase: Activity is elevated following trauma (3--:5 days) and declines to normal levels within 5--7 days. A persistently high level in F.E.S. implies a better prognosis. I t is an easily performed technic in any hospital [18, 19]. In contrast to this is the lipid electrophoresis, a relatively complicated technic with doubtful diagnostic value. ttypoxia: found in a patient with trauma or fractures has an enormous value in the diagnosis of pulmonary damage. If not explained by other direct or indirect insult of the lung physiology, fat embolism should be suspected in a patient at risk [5--7, 21--23, 25--27, 29]. Lung radiologic opacification (patchy, multiple or localized) has the same significance and generally parallels the hypoxia.
The Management of a Patient with Established Fat Embolism T h e t r e a t m e n t of t h e p u r e cerebral form o f F . E . S . is g e n e r a l l y s u p p o r t i v e w i t h t r e a t m e n t o f c o m p l i c a t i o n s a n d t h e neurological sequelae. R e c e n t l y some
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evidence has been published detailing the favorable effect of a high dose regimen of Trasylol (Bayer), i.e., 1 million units in the first 2 days, reduced to a maintenance dose of 500000 U/day [12]. The most important aspect of the management of fat embolism is the treatment of the pulmonary disease and its complications. In cases of non-fulminant fat embolism, the following treatment should be applied, with daily monitoring of all the hematologic and respiratory parameters. Central venous and arterial lines are necessary. If the patient is unconscious, a urinary catheter, intravenous infusion and nasogastrie aspiration are imperatives. Exact electrolyte, fluid and acid-base balance data are registered, and this energy demand calculated. A daily flow sheet with all the chemical data and a record of this therapy is essential for proper evaluation. Frequent electroencephalograms, electrocardiograms, and lung roentgenograms, are performed. The treatment consists of: 1. Treatment of pneumonitis and oxygenation. 2. Blood rheology stabilization and clotting mechanism normalization. 3. General supportive therapy. 1. The hemorrhagic pneumonitis, can be efficiently inhibited with administration protection of high dosages of corticosteroids. Their effect is in decreasing alveolitis, stabilization of the surfactant producing pneumocy~es, decreased permeability of membranes, and decrease of interstitial oedema [4]. The pharmacologic dose of 1.0--1.5 g hydrocortisone, or its equivalents (dexamethosone, methyl prednisolone) should be administered parenterally in divided doses in the first 2 days, followed by a slow gradual decrease. The second important task in the treatment of F. E. S. is adequate oxygenation i.e., proper respiratory care. Although it is inappropriate to standardize respiratory therapy, certain principles should be followed, with individual adjustments to the specific needs of the patient [23]. Hypoxia should be avoided even in the mild cases of pulmonary insufficiency. The breathing work and rate should be kept within normal limits by oxygen administration if necessary even at high concentration. Should oxygen mask or intranasal tube not be sufficient, mechanical ventilation will be needed. Positive-pressure breathing should continue to be provided until the patient is able to maintain adequate blood oxygenation. However, with the toxicity of prolonged high-oxygen concentration, in mind, one should decrease the concentration as soon as possible. Serial determinations of Poe, Peon, pH, oxygen saturation and base excess should be made as guides for continuing treatment, and these parameters should be correlated with measurements of the minute volume, inspiratory force and breathing rate to indicate a necessary decrease or increase in the tidal volume and/or rate of the respirator. In desperate cases, positive end-expiratory pressure breathing can be of great help in resisting alveolar collapse. Certain pharmaceutical agents such as amynophylin improve the respiratory function by its pulmonary vasodilator effect. Lower oxygen consumption can be achieved by reducing the body temperature to normal or even to hypothermic levels, using antipyretics or surface cooling with lyric cocktail [3]. 2. The blood rheology changes are influenced by the infusion of 2--3 units of Rheomacrodex (L.M.W.D.) over 4--6 hrs. I t will improve the pulmonary
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and systemic capillary flow b y its de-sludging effect. I t is administered in the first 2 days and should any sign of bleeding appear, cessation is indicated. Heparin is frequently used in F.E.S. I t is a double acting agent. I t s lypolytic activity consists of lipase activation, inducing clearing of the f a t t y serum, but it also releases f a t t y acids. I n this respect heparin is an undesired drug [2]. I t s important action is prevention of platelets aggregation and coagulation. I t m a y be possible t h a t a proper dose administration would eventually separate the desired (anticoagulant) action from the undesired one (liberation of f a t t y acid). No exact differential dosage has been determined [1]. tIeparin is administered over the 3 4 days of the disease and should be stopped at any sign of bleeding. The dosage is of 5000 units over 4 - - 6 hrs, given intravenously [8]. A complete anticoagulant state of the blood is not desired. Calcium ions and fresh blood transfusion should be administered. I n case of established disseminated intravascular coagulation, often accompanying F.E.S., heparin and/or E-aminocaproic acid should be administered, in accordance with the results of tests of clotting factors. 3. The general supportive t r e a t m e n t includes caloric, mineral and water balance correction. Calories should be supplied in this form of concentrated glucose solution and amigen preparates, decreasing in this way the necessity for lipid mobilization from storage areas. Electrolyte and water balance and acid-base equilibrium m u s t be maintained. Diuretics are necessary in cases of water retention. I n patients with serious heart disease or signs of congestive failure, full digitalization is rapidly instituted. A broad spectrum antibiothcrapy will become necessary in patients with traeheostomy as well as with long term intravenous or urinary catheters. References 1. Adar, 1~.: Pathogenesis and treatment of fat embolism, ttarefuah, Israel med. Ass. J. 83 491 (1972) 2. Adler, F., Peltier, L. F., Lai, S. P. : Fat embolism, the determination of fat in urine by macroscopic and microscopic method. Surgery 47, 959 (1960) 3. Aladyemoff, L., Weinberg, It., Alkalai, I. : Fat embolism treatment with lyric cocktail and surface cooling. Lancet 1968 II, 13 4. Ashbaugh, ]:). G., Petty, T. L. : The use of corticosteroids in the treatment of respiratory failure associated with massive fat embolism. Surg. Gynee. Obstet. 128, 493 (1966) 5. Benoit, 1). R., ttampson, L. G., Burgess, J. H.: Value of arterial hypoxemia in the diagnosis of fat embolism. Ann. Surg. 175, 128 (1972) 6. Benoit, P. t~., Hampson, L. G., Burgess, J. H. : Respiratory gas exchange following fractures. Surg. Forum 208, 214 (1969) 7. Collins, J. A., Gordon, W. C., Hudson, T. L., Irvin, R. W.: Inapparent hypoxemia in casualties with wounded limbs: pulmonary fat embolism ? Ann. Surg. 167, 511 (1968) 8. Dines, K. I~., Lindscheid, It. L., Didier, E. F. : Fat embolism syndrome. Mayo Clin. Froc. 47, 237 (1972) 9. Gurd, A. 1%.:Fat embolism: an aid to diagnosis. J. Bone Jt Surg. 52-B, 732 (1970) 10. McTaggart, D. M., Neubuerger, K. T.: Cerebral fat embolism. Acta neuropath. (Berl.) 1~, 183 (1970) 11. Moore, F. D., Lyons, L. I=L, Fierce, L. C.: Post-traumatic pulmonary insufficiency. Philadelphia: W. B. Saunders 1969 12. New aspects of trasylol therapy, Vol. 4. Stuttgart-New York: F. K. Schattauer 1971 13. Feltier, L. F. : Fat embolism: A current concept. Clin. Orthop. 66, 241 (1969) 14. Feltier, L. F. : Fat embolism a pulmonary disease. Surgery 62, 756 (1967)
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15. Peltier, L. F. : Fat embolism III. The toxic properties of neutral fat and free fatty acids. Surgery 40, 665 (1956) 16. Peltier, L. F. : Fat embolism. The detection of fat emboli in the circulating blood. Surgery a6, 198 (1954) 17. Peltier, L. F., Adler, F., Lai, S. P. : The significance of an elevated serum lipase after trauma to bone. Amer. J. Surg. 99, 821 (1960) 18. Sevitt, S.: Fat embolism. London: Butterworth's & Co. 1962 19. Silverstein, A.: The significance of cerebral fat embolism. Neurology 2, 292 (1952) 20. Tedeschi, C. G., Castelli, V., Kropp, G., Tedeschi, L. G.: Fat macroglobulemia and fat embolism. Surg. Gynec. Obstet. 126, 83 (1968) 21. Wertzberger, J. J., Peltier, L. F.: :Fat embolism: the importance of arterial hypoxia. Surgery 63, 626 (1968) 22. Wright, B. D. : :Fat embolism: Silent respiratory disease. Anaesth. Analg. 49, 279 (1970) 23. Weisz, G. M., Barzilai, A. : Non-fulminant fat embolism. Anaesth. Analg. 58, 303 (1973) 24. Weisz, G. ~[., Steiner, E.: The cause of death in fat embolism. Chest. Dis. Index 59, 511 (1971) 25. Weisz, G. M., Rang, M., Salter, R. S. : Post-traumatic fat embolism in children. J. Trauma 13, 529 (1973) 26. Weisz, G. M., Barzilai, A. : New concepts in the fat embolism syndrome. Harefuah, Israel reed. Ass. J. 81, 87 (1971) 27. Weisz, G. 5[., Schramek, A., Abrahamson, J., BarzilM, A.: Fat embolism in children: Study of its early detection. J. pedlar. Surg. 9, 163 (1974) 28. Weisz, G. ~., Fishman, J., Steiner, E. : Callus function in cases of cerebral fat embolism. Confln. neurol. (Basel) 81, 362 (1969) 29. Weisz, G. M.: Fat embolism. Current problems in surgery. Chicago (Ill.): Year Book Publisher Nov. 1974 George M. Weisz, M.D. Ami Barzilai, M.D. Department of Surgery A. Rambam Hospital Haifa, Israel
