PREVENTION OF FAT GLOBULEMIA IN TOTAL HIP REPLACEMENT
Irkutsk Scientific Center of Surgery and Traumatology,
Irkutsk State Medical University, Irkutsk, Russia
There are not any specific curative techniques for fat embolism syndrome (FES). It is associated with the fact that FES is still the topic of discussions, that absence of a uniform concept explaining all pathophysiological links of FES and absence of a key link. According to the foreign literature, the main direction in FES therapy is infusion therapy with orientation to hypovolemia correction, respiratory support and early fixation of fragments [1, 2], but preventive measures consist in administration of corticosteroids [1, 3]. According to the Russian authors, the most efficient and recommendable measures for prevention of treatment of fat embolism are the early administration of Essentiale and perftoran or 5 % ethanol [4-8]. In our clinic we have performed the experimental studies of the efficiency of these agents for preventive and therapeutic goals. It has been found that the significant preventive effect is provided by 5 % ethanol, and the curative effect is achieved with perftoran and 5 % ethanol. The use of Essentiale H did not provide any clinical and laboratory significance [9, 10]. As result of the in-depth study of lipid metabolism we found that the functional insufficiency of hepatocyte was a leading factor of development of fat hyperglobulemia. These circumstances were the basis for substantiation and choice of the agent, which can normalize the metabolic and synthetic processes in the hepatocyte with elimination of manifestations of functional hepatic insufficiency and providence of preventive and curative effects, if a possibility of FES is high. Hepasol-Neo corresponds to these requirements. We used it in our study.
The objective of the study was the investigation of efficiency of prevention of fat embolism syndrome in total hip replacement with use of the agents: Hepasol-Neo, 5 % ethanol and Essentiale H.
MATERIALS AND METHODS
Three groups were created for the study of the risk of development of fat embolism syndrome in the patients who received total hip replacement. The first group included 70 patients who received Hepasol-Neo for prevention of fat globulemia, the second group – 85 patients who received Essentiale H, the third group – 39 patients who received 5 % ethanol. The study was prospective. The groups were representative and did not differ according to age, gender and patterns of main and concurrent pathology.
The presence of fat globulemia was tested with blood sampling from the central vein at the following stages: the intrasurgical stage – before surgery, during preparation of the intramedullary canal and in the end of the surgery; the postsurgical stage – on the days 1-3 after the surgery. Identification and counting of fat globules were realized by means of optical microscopy for venous blood plasma smear [11]. Two groups of the patients were selected for estimation of the influence of Hepasol-Neo on lipid metabolism (intrasurgical administration for fat globulemia prevention). The first group (22 patients) received Hepasol-Neo during the surgery (the main group), the second group (26 patients) received drug prevention of fat embolia with Essentiale solution (the comparison group). The blood sampling included 3 stages: before the surgery, immediately after the surgery and the first days after the surgery.
The lipid fractions were very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL). They were estimated with the electrophoresis technique on the gel plates with use of the diagnostic tests Cormay (Poland). The measurement devices were the semiautomatic biochemical analyzer Humalyzer 2000 (Germany), the densitometer Sebia (Cormay, Poland). The level of cholesterol was estimated with the diagnostic tests Vital (Saint Petersburg) with the enzymic technique (the reference: 3.62-8.03 mmol/l). The level of triglycerides was estimated with the enzymatic colorimetric technique with use of the test system Human GmbH (Germany) (the reference: 0.6-2.2 mmol/l). Since the patients had to refuse from the food 12 hours before the surgery, we excluded alimentary chylomicronemia, and in case of identification of at least one fat globule in one visual field at any stage of the examination, we considered the result as positive. In such case a patient received the conditional code 1. If fat globules were absent in all tests, the code was 0. The results were analyzed with the mode, absolute and relative frequencies and the chance of a studied sign. The results were analyzed in Statistica.χ2 test with Yates and Bonferroni correction was used for comparison of the data. The method of confidence intervals was used for identification of significance of the differences between the examined signs. The confidence intervals for relative risk were calculated with Katz technique, the odds ratio – with Woolf technique.
RESULTS AND DISCUSSION
The study identified that the intrasurgical administration of Hepasol-Neo reduced the risk of fat globulemia by 24 % as compared to Essentiale H and by 12 % as compared to 5 % ethanol (table 1).
Table 1. Frequency of fat globulinemia in intraoperative period
|
Parameters |
Group of fat globulinemia prevention |
|||
|
5% ethanol solution |
Hepasol-Neo |
Essentiale N |
||
|
Total number of patients |
39 | 70 | 85 | |
|
Probability of fat globulinemia |
0.65 [0.4; 0.83] | 0.54 [0.22; 0.65] | 0.78 [0.47; 0.94]* | |
|
ARR, % [95% CI] |
12 [–0.31; 0.07] | 24 [0.09; 0.38]* | ||
| NNT | 8 | 4* | ||
Note: * – р < 0.05 (χ2 test with Yates correction).
The similar time course was observed in the postsurgical period (table 2).
Table 2. Frequency of fat globulinemia in postoperative period
|
Parameters |
Group of fat globulinemia prevention |
|||
|
|
5% ethanol solution |
Hepasol-Neo |
Essentiale N |
|
|
Total number of patients |
39 |
70 |
85 |
|
|
Probability of fat globulinemia |
0.37 [0.18; 0.5]* |
0.15 [0.06; 0.28] |
0.36 [0.22; 0.48]* |
|
|
ARR, % [95% CI] |
20 [0.02; 0.37] |
19 [0.06; 0.32] |
||
|
NNT |
5 |
5 |
||
Note: * – р < 0.05 (χ2 test with Yates correction).
It was found that more intense preventive (antiglobulemic) effect was observed for administration of Hepasol-Neo. Intrasurgical intravenous infusion of this agent significantly reduced the risk of fat globulemia syndrome in comparison with the group of Essentiale H.
The stable lipid profile was observed in the group of Hepasol-Neo as compared to the comparison group during the whole period of follow-up (Fig. 1).
Figure 1. Time course of cholesterol and triglycerides (Friedman test; Wilcoxon test with Bonferroni test).
* – p < 0.05, Wilcoxon test with Bonferroni test; * – p < 0.05 (Wilcoxon test with Bonferroni correction)
The levels of triglycerides, cholesterol and the ratios of lipoprotein fractions were stable within the postsurgical period (Fig. 2).
Figure 2. The relationship between fractions of lipoproteins in the perisurgical period (Friedman test; Wilcoxon test with Bonferroni test).
* – p < 0.05, Wilcoxon test with Bonferroni test; * – p < 0.05 (Wilcoxon test with Bonferroni correction)
The intrasurgical introduction of 5 % ethanol in 5 % glucose solution (1 g/kg of body mass) did not differ significantly from Hepasol-Neo according to the efficiency in prevention of fat globulemia. But during the early postsurgical period the antiglobulemic effect of 5 % ethanol and Essentiale H is lower than Hepasol-Neo effect.
The intrasurgical use of Hepasol-Neo decreased the risk of development of fat globulemia without need for recurrent introduction. It means the prolonged preventive effect.
Essentiale H, which is commonly used for prevention and treatment of fat globulemia showed the inefficiency both in clinical and experimental conditions.
The presented results of the study have been confirmed by 10-year experience in the practical use of Hepasol-Neo in the clinic of Irkutsk Scientific Center of Surgery and Traumatology, which is the leading regional facility in the field of the treatment of diseases of the locomotor system for 3-4 thousand patients annually. For this period the clinical manifestations of fat embolism syndrome have been registered only in one patient (< 0.003 %). We present this case as a clinical example of the successful treatment of FES.
The patient B., age of 78 (the case No.1475/16) was admitted in April 12, 2016. The diagnosis was: “Bilateral gonarthrosis of degree 3. Varus deformations of knee joints. The combined contracture of the right knee joint. Pain syndrome. Osteoporosis. Concurrent pathology: arterial hypertension of degree 2, risk 4. Encephalopathy of degree 2 at the background of cerebral atherosclerosis. Chronic pyelonephritis in remission stage, cysts in both kidneys. Chronic calculous cholecystitis in remission stage. Fat hepatosis of degree 1. Pancreatic lipomatosis. Obesity of degree 1”.
The presurgical laboratory findings: the biochemical analyses: alanine aminotransferase (ALT) – 15 U/l; aspartate aminotransferase (AAT) – 20.3 U/l; total protein – 77.2 g/l; creatinine – 99 mmol/l; urea – 4.7 mmol/l; glucose – 4.79 mmol/l; cholesterol – 5.48 mmol/l; total bilirubin – 18.8 mcM/l; direct bilirubin – 6.2 mcM/l; indirect bilirubin – 13 mcM/l. Coagulogram: fibrinogen – 3.3 g/l; soluble fibrin monomer complex (SFMC) – 4.5 mg %; activated partial thromboplastin time (APTT) – 33 sec.; prothrombin time (PT) – 14.4 sec.; international normalized ratio (INR) – 1.14. Clinical blood analysis: red blood cells – 5.20; Hb – 150 g/l; Ht – 47.8 %; ESR – 5 mm/hour; formula: p-1; s-61; e-2; b-0; m-6; l-30. Fluorography – pneumosclerosis. Electrocardiogram (ECG) – sinus rhythm, heart rate (HR) – 81. Horizontal position of cardiac electric axis. Echocardiography – stroke volume (SV) – 83 ml; ejection fraction (EF) – 63 %; conclusion – decreasing diastolic ventricular function. Moderate dilatation of the right atrium. Moderate diffuse changes in aortic valve leaflets. Abdominal ultrasonic examination – fat hepatosis of degree 1. Lipomatosis of the pancreas, chronic calculous cholecystitis.
At the moment of admission the patient complained of the pain in the region of the right knee joint with increase during motion, limited motions in the right knee joint, functional limitation of the right lower extremities. Arterial pressure (AP) = 120/80 mm Hg, HR = pulse (PS) = 73 per minute.
The surgical treatment was conducted on April 14, 2016: implantation of the endoprosthesis for the right knee joint under computer navigation with simultaneous reconstruction of the biological axis of the extremity. The surgery was conducted under subchondral anesthesia with preserved spontaneous breathing and consciousness. The surgery lasted for 50 minutes, narcosis – 1 hour and 15 minutes, the blood loss – 50 ml.
The consumption of the drugs: anesthetic – Marcaine Spinal 0.5 % –15 mg; before skin incisions – Tranexam 750 mg per 500 ml; 0.9 % NaCl + S. Lendacyni 1 g. During the surgery: S. HaepasoliNeo 500 ml for prevention of fat embolism syndrome; S. Voluveni 500 ml for supporting the normal values of circulating blood volume (CBV) and venous return in conditions of subarachnoid anesthesia + 90 mg S. Prednisoloni for prevention of syndrome of cement implantation. Diuresis on the table – 150 ml.
The time course of AP: 180/100-140/90 – 120/80 – 120/80 mm Hg. PS = 86 – 82-84 – 81 per min. SpO2 = 96-98 %.
At 9:25 a.m. the patient was transferred to the intensive care unit. She was in consciousness, in adequate state, with orientation in space, without complaints. AP = 120/80, PS = 64 per min., SpO2 = 98 %. The treatment in the ICU: preemptive analgesia with ketonal solution (100 mg i.v. in 8 hours). Additionally, promedol (20 mg) + sibazon (10 mg at night) were subscribed. Clexane (80 mg) was used for prevention of thrombogenic complications in 7 hours after the surgery, with control of whole blood clotting. The polarizing solution (500 ml), Omez (20 mg 2 times) for prevention of stressor injuries to the gastrointestinal tract, Dicynon (500 mg) for activation of the vascular and platelet component of the hemostasis system at the moment of admission to the ICU. The return of the drained blood was initiated in 5 hours after intrasurgical placement of the drain.
The postsurgical course was stable within 23 hours. The patient was in adequate state. The food was introduced with enteral technique. Hemodynamics was stable: 120/80 – 115/70 mm Hg; PS = 65-80 per min. SpO2 = 96-98 %. 200 ml of blood came out through the drain. The blood was returned to the patient at 2:30 p.m.
On April 14, 2016 (11:00 p.m.) the patient demonstrated the inadequacy with psycho-motor agitation and disorientation in time and space. The skin surface is pink and warm, T = 36.6°, AP = 120/80 mm Hg, PS = 80 per min. The breathing is clear, vesicular, with conduction through all departments, with respiratory rate of 16 per minute, SpO2 = 96 %, the abdomen was soft, painless, participating in the breathing act. 500 ml of the fluid was ingested through the enteral way. Diuresis was 1,000 ml. Analgesia and sedation was conducted with intravenous introduction of 10 mg of S. Sibasoni + S. Tramadoli 5% – 2.0. The patient fell asleep.
The patient woke up at 7 a.m. on April 15, 2016. She was in inadequate state. The psycho-motor agitation and disorientation persisted. Hemodynamics was stable. The external respiratory function was normal. Additional analgesia and sedation was conducted with intravenous administration of S. Tramadoli 5 % – 2.0 + S. Sibazoni 0.5 % – 2.0. The neurologist was invited for the consultation. The neurologist’s conclusion: chronic cerebral ischemia of degree 3 at the background of arterial hypertension and cerebral atherosclerosis.
At 7:45 the patient was examined by the chief of the unit. The condition was considered as the diagnosis: “The cerebral form of fat embolism syndrome”. It was recommended to examine fat globules in the blood and to initiate the infusion of S. Haepasoli-neo 500 ml. Testing the fat in the blood – the response was positive, the single globules with diameter of 0.7 µm. The evident positive dynamics was observed already after infusion of 200 ml: agitation disappeared and the patient was able to make productive communication. The space and time orientation was good. The answers to the questions were correct. Hemodynamics was stable. The expiratory breathing was normal. The ICU stay was prolonged for one more day. She received the standard treatment: analgesia with ketonal; Clexane 80 mg; Omez 40 mg/day; Lendacin 1 g; Cytoflavin 10 ml per 200 ml of Ringer solution.
The patient’s state was stable. The response to the presence of fat globules was negative. The clinical blood analysis, the clinical urine analysis and the biochemical values were within the normal range. Blood clotting time was 6 minutes and 30 seconds. On April 17, 2016 the patient was transferred to the profile department. Her state was satisfactory. She had the postsurgical rehabilitation up to April 29, 2016, when she was discharged for outpatient treatment according to her place of residence.
This clinical case demonstrates the high efficiency of the pathogenetically determined technique of the treatment for FES.
Therefore, the results of the studies have shown all foundations for development of the National Standard for diagnostics, prevention and the treatment of fat embolism syndrome.
REFERENCES
1. Kosova E, Bergmark B, Piazza G. Fat embolism syndrome. Circulation. 2015; 131 (3): 317-320
2. Lin KY, Wang KC, Chen YL et al. Favorable outcome of cerebral fat embolism syndrome with a Glasgow coma scale of 3: a case report and review of the literature. Indian J. Surg. 2015; 77 (1): 46-48
3. Bederman SS, Bhandari M, McKee MD et al. Do corticosteroids reduce the risk of fat embolism syndrome in patients with long-bone fractures? A meta-analysis. Can. J. Surg. 2009; (52): 386-393
4. Kornilov NV, Kustov VM. Fat embolism. Saint Petersburg: Morsar AV, 2001. 287 p. Russian (Корнилов Н.В., Кустов В.М. Жировая эмболия. СПб.: Морсар АВ, 2001. 287 с.)
5. Kustov VM, Perfilyeva PE. Large joints replacement and fat embolism. In: Actual Issues of Orthopedics, Traumatology and Military Surgery: proceedings. Nizhny Novgorod, 1999. P. 30-31. Russian (Кустов В.М., Перфильева П.Е. Эндопротезирование крупных суставов и жировая эмболия // Актуальные вопросы ортопедии, травматологии и военно-полевой хирургии: сб. науч. работ. Н. Новгород, 1999. С. 30-31.)
6. Liepa ME. Fat globulinemia as a condition of fat embolism. Physiopathilogy and experimental therapy. 1973; (4): 32-36. Russian (Лиепа М.Э. Жировая глобулемия как условие возникновения жировой эмболии // Патол. физиология и эксперим. терапия. 1973. № 4. С. 32-36.)
7. Pashchuk AY, Fadeev PA. Diagnostics and treatment of fat embolism. Orthopedy, traumatology. 1991; (12): 41-43. Russian (Пащук А.Ю., Фадеев П.А. Диагностика и лечение жировой эмболии // Ортопедия, травматология. 1991. № 12. С. 41-43.)
8. Reshetnikov EA, Kyurdian LA, Ayrapetyan SA et al. To the early diagnostics, prevention and treatment of traumatic fat embolism. Orthopedy, traumatology and prosthetics. 1969; (10): 44-48. Russian (Решетников Е.А., Кюрдиан Л.А., Айрапетян С.А. и др. О ранней диагностике, профилактике и лечении травматической жировой эмболии (экспериментальное исследование) // Ортопедия, травматология и протезирование. 1969. № 10. С. 44-48.)
9. Bocharov SN, Plakhotina EN, Tvorogova SS. Prevention and treatment of experimental fat globulinemia. In: Proceedings of IX Russian National Congress “Man and his Health”. Saint Petersburg, 2004. p. 18-19. Russian (Бочаров С.Н., Плахотина Е.Н., Творогова С.С. Профилактика и лечение экспериментальной жировой глобулемии // Человек и его здоровье: материалы IX Российского национального конгресса. СПб., 2004. С. 18-19.)
10. Tvorogova SS. Comparative assessment of the effectiveness of medicinal prevention and treatment of fat embolism. Cand. med. sci. Abstractdiss. Irkutsk, 2005. 22 p. Russian (Творогова С.С. Сравнительная оценка эффективности медикаментозной профилактики и лечения жировой эмболии: автореф. дис. ... канд. мед. наук: 14.00.27. Иркутск, 2005. 22 с.)
11. Kornilov NV, Voynovich AV, Kustov VM. Diagnostics of fat globulinemia at traumas and surgeries of bones: methodical guidelines. Saint Petersburg, 2000. 24 p. Russian (Корнилов Н.В., Войнович А.В., Кустов В.М. Диагностика жировой глобумемии при травмах и операциях на костях: метод. рекомендации. СПб., 2000. 24 с.)