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骨折并發(fā)FES定量評估與聯(lián)合藥物預(yù)防的時間依賴性研究

發(fā)布時間:2018-07-23 10:38
【摘要】:目的骨折并發(fā)脂肪栓塞綜合征(Fat Embolism Syndrome,FES)是創(chuàng)傷后病人死亡的主要原因之一,主要由脂肪栓子阻塞血管腔導(dǎo)致的一系列臨床表現(xiàn)。下肢單純長骨干骨折并發(fā)FES的發(fā)病率為0.5-2.0%,下肢多發(fā)骨折或骨盆骨折中為5%-10%,其主要癥狀為呼吸困難、低氧血癥、無腦外傷的意識障礙及皮膚粘膜出血點。目前尚無直接溶解脂肪栓子的藥物,FES救治起來十分兇險,危及生命,所以預(yù)防一直是FES研究的重點。本研究擬用損傷嚴(yán)重度改良評分法(Revised Injury Severity Score,RISS)來定量評估FES發(fā)生的風(fēng)險,避免藥物預(yù)防FES的盲目性,以探討不同傷因的骨創(chuàng)傷規(guī)律及RISS值與FES發(fā)生的關(guān)系,根據(jù)臨床經(jīng)驗為選擇預(yù)防患者提供依據(jù),保證聯(lián)合藥物預(yù)防的療效。臨床上發(fā)現(xiàn)糖皮質(zhì)激素聯(lián)合低分子右旋糖酐對FES有良好的預(yù)防作用,但藥物的選擇及療程臨床上差異較大,臨床上無統(tǒng)一的用藥標(biāo)準(zhǔn),導(dǎo)致預(yù)防FES的療效各異。為了探究最佳的糖皮質(zhì)激素與低分子右旋糖酐聯(lián)合應(yīng)用、用藥療程,本實驗采取同種異體兔的骨髓脂肪組織注射建立FES的動物模型,觀察不同的糖皮質(zhì)激素和低分子右旋糖酐組合、不同用藥時間在兔的FES模型上的預(yù)防效果,指導(dǎo)臨床上最佳糖皮質(zhì)激素聯(lián)合低分子右旋糖酐的用藥選擇及用藥療程。方法實驗一:采取回顧性分析方法,對我院于1993年1月-2009年11月收治的47例骨折并發(fā)FES患者分為A、B兩組,采用RISS對骨創(chuàng)傷患者進行計量評估,A組為不伴內(nèi)臟損傷的多發(fā)性骨折患者,B組為同時合并胸、腹、顱腦等其他部位損傷的多發(fā)性骨折患者,對兩組進行統(tǒng)計學(xué)分析,研究RISS與FES發(fā)生之間的相關(guān)性。實驗二:選取雄性健康新西蘭兔36只,體重在2.5-3.0kg之間,按隨機數(shù)字表分為6組。A組為應(yīng)用地塞米松組,B組為低分子右旋糖酐組,C組為甲強龍組,D組為地塞米松和低分子右旋糖酐聯(lián)合應(yīng)用組,E組為甲強龍與低分子右旋糖酐聯(lián)合用藥組,F組為生理鹽水空白對照組。6組均采用注射同種異體兔的骨髓脂肪誘發(fā)脂肪栓塞綜合征,6組在注射骨髓脂肪前1h均接收相應(yīng)藥物的預(yù)防性注射,隨后觀察6組在栓塞前及注射后各個時間點的肛溫、動脈血氧分壓(arterialpartialpressureofoxygen,Pa O2)、游離脂肪酸(free fatty acid,FFA)、血小板計數(shù)(platelet count,PLT),栓塞48h后處死取肺組織標(biāo)本做HE、油紅O染色觀察。實驗三:選取雄性健康新西蘭兔30只,按隨機數(shù)字表分為5組。A組為8h組,B組為24h組,C組為48h組,D組為72h組,E組為空白對照組。5組均采用注射同種異體兔的骨髓脂肪誘發(fā)脂肪栓塞綜合征,5組在注射骨髓脂肪栓子前1h均接收藥物的預(yù)防性注射,每組均間隔8h重復(fù)注射藥物一次,隨后觀察5組在注射藥物前及注射后各個時間點的呼吸頻率、動脈血氧分壓(arterialpartialpressureofoxygen,Pa O2)、游離脂肪酸(free fatty acid,FFA)、白細(xì)胞計數(shù)(white blood cell,WBC),隨后處死模型兔取肺組織標(biāo)本行HE、油紅O染色、電鏡觀察。結(jié)果實驗一:全部骨創(chuàng)傷并發(fā)FES患者的病例的RISS評分均在11分以上:單純多發(fā)性創(chuàng)傷骨折6例,RISS值位于11-18之間;伴有顱腦或胸腹腔內(nèi)臟器損傷的多發(fā)性骨折創(chuàng)傷患者中有38例,RISS分值在18-25之間,另外3例分值25分。FES的發(fā)生與RISS分值呈正相關(guān)(P0.05)。實驗二:1.肛溫:各組肛溫在注射脂肪栓子后2h、4h均呈進行性上升,但注射后8h、24h、48h逐漸下降,注射后2h、4h、8h、24h、48h肛溫均為D組或E組A組或C組。注射后2h、4h、8h、24h各組間差異有統(tǒng)計學(xué)意義(P0.05)。2.PaO2:各組PaO2在注射脂肪栓子后2h均呈迅速下降,但注射后4h、8h、24h、48h逐漸回升,注射后2h、4h、8h、24h、48h Pa O2均為D組或E組A組或C組,各組之間注射后2h、4h、8h、24h、48h各組之間均有統(tǒng)計學(xué)意義(P0.05)。3.FFA:各組FFA在注射脂肪栓子后2h、4h、8h呈進行性升高,但注射后24h、48h逐漸下降,注射后2h、4h、8h、24h FFA均為D組或E組A組或C組,注射后2h、4h、8h、48h各組之間差異均有統(tǒng)計學(xué)意義(P0.05)。4.血小板計數(shù):各組PLT在注射脂肪栓子后各個時間點變化時高時低,無規(guī)律可循,各組注射前及注射后2h、4h、8h、24h、48h各組之間差異均無統(tǒng)計學(xué)意義(P0.05)。5.HE染色:處死取肺組織行常規(guī)HE染色,肺泡間質(zhì)水腫,肺泡腔內(nèi)毛細(xì)血管的通透性增加,紅細(xì)胞外滲,中性粒細(xì)胞明顯增多,病理變化程度F組B組A組C組D組E組。6.油紅O染色:各組油紅O染色肺泡、肺支氣管毛細(xì)血管內(nèi)可見染成桔紅色的脂滴,桔紅色的脂滴大小及數(shù)量F組B組A組C組D組E組。實驗三:1.呼吸頻率:各組呼吸頻率在注射脂肪栓子后8h均呈進行性上升,但注射后24h、48h、72h逐漸下降。各組栓塞前呼吸頻率之間差異無統(tǒng)計學(xué)意義(F=0.968,P=0.442),各組栓塞后8h、24h、48h、72h呼吸頻率之間差異有統(tǒng)計學(xué)意義(P0.05)。2.Pa O2:各組PaO2在注射脂肪栓子后8h均呈逐漸下降,但注射后24h、48h、72h逐漸回升。各組栓塞前呼吸頻率之間差異無統(tǒng)計學(xué)意義(F=0.543,P=0.706),各組栓塞后8h、24h、48h、72h呼吸頻率之間差異有統(tǒng)計學(xué)意義(P0.05)。3.FFA:各組FFA在注射脂肪栓子后8h均呈逐漸上升,但注射后24h、48h、72h逐漸下降。各組栓塞前FFA之間差異無統(tǒng)計學(xué)意義(F=0.412,P=0.798),各組栓塞后8h、24h、48h、72h呼吸頻率之間差異有統(tǒng)計學(xué)意義(P0.05)。4.白細(xì)胞計數(shù):各組WBC在注射脂肪栓子后8h均呈逐漸上升,但注射后24h、48h逐漸下降。各組栓塞前呼吸頻率之間差異無統(tǒng)計學(xué)意義(F=0.159,P=0.957),各組于栓塞后8h、24h、48h之間差異無統(tǒng)計學(xué)意義(P0.05),各組之間差異于栓塞后72h有統(tǒng)計學(xué)意義(F=2.805,P=0.047)。5.HE染色:光鏡下可見廣泛肺間質(zhì)水腫,紅細(xì)胞滲出,A組肺間質(zhì)中度水腫,紅細(xì)胞中度外滲;B組肺間質(zhì)輕度水腫,輕度外滲;C組肺間質(zhì)、肺泡腔輕度水腫;D組肺間質(zhì)、肺泡腔輕度炎性浸潤;E組肺間質(zhì)嚴(yán)重水腫,肺泡腔出血嚴(yán)重。6.油紅O染色:光鏡下可見A組肺血管腔可見中度大小桔紅色脂滴堵塞,B組可見輕度大小桔紅色脂滴堵塞血管腔,C組可見廣泛小脂滴堵塞血管腔,D組可見小脂滴散在分布在血管腔內(nèi),E組可見大脂滴差不多完全栓塞血管腔。7.電鏡觀察:A組肺泡腔內(nèi)有巨噬細(xì)胞,內(nèi)含較多溶解體,肺泡腔內(nèi)現(xiàn)淋巴細(xì)胞,有炎癥細(xì)胞浸潤;B組肺泡腔內(nèi)有少量巨噬細(xì)胞,二型細(xì)胞板層小體有排空,細(xì)胞器無明顯腫脹;C組肺泡隔增寬,有炎癥細(xì)胞輕度浸潤,二型細(xì)胞板層小體輕微排空;D組毛細(xì)血管有炎癥細(xì)胞浸潤,肺泡腔有點輕度紅細(xì)胞滲出,毛細(xì)血管腔內(nèi)有少量巨噬細(xì)胞;E組肺泡腔見大量巨噬細(xì)胞,二型細(xì)胞板層小體較多,毛細(xì)血管內(nèi)皮細(xì)胞重度腫脹,肺間質(zhì)大量炎癥細(xì)胞浸潤。結(jié)論1、骨折創(chuàng)傷嚴(yán)重度與FES的發(fā)生之間具有相關(guān)性,當(dāng)單純多發(fā)性骨折創(chuàng)傷患者RISS值11、伴有顱腦或胸腹腔內(nèi)臟器損傷的多發(fā)性骨折RISS值18時,易發(fā)生FES,應(yīng)采取預(yù)防措施。2、糖皮質(zhì)激素聯(lián)合低分子右旋糖酐具有有效預(yù)防FES的作用,甲強龍聯(lián)合低分子右旋糖酐組地塞米松聯(lián)合低分子右旋糖酐組甲強龍組地塞米松組低分子右旋糖酐組生理鹽水空白對照組。3、最佳劑量的甲強龍聯(lián)合低分子右旋糖酐靜脈注射療程(24h,8h/次)優(yōu)于(8h,8h/次),甲強龍聯(lián)合低分子右旋糖酐靜脈注射療程(24h,8h/次)與(48h,8h/次)、(72h,8h/次)之間對脂肪栓塞綜合征的預(yù)防效果無明顯差異。
[Abstract]:Objective Fat Embolism Syndrome (FES) is one of the main causes of posttraumatic death, mainly due to a series of clinical manifestations caused by the blocking of the vascular cavity by the fat embolus. The incidence of FES is 0.5-2.0%, the multiple fractures of the lower extremities or pelvic fractures are 5%-10%, and the main symptoms are the main symptoms. The form is dyspnea, hypoxemia, consciousness disorder of brain injury and bleeding point of skin and mucous membrane. There is no drug directly dissolving fat embolus. FES is very dangerous and life-threatening, so prevention has always been the focus of FES research. This study is to be determined by Revised Injury Severity Score (RISS). To assess the risk of FES, to avoid the blindness of drugs to prevent FES, to explore the relationship between the rules of bone trauma and the relationship between the value of RISS and the incidence of FES in different causes of injury, and to provide the basis for the prevention of the patients according to the clinical experience, and to ensure the curative effect of the combined drug prevention. In order to explore the best combination of glucocorticoid and low molecular dextran, the treatment course of FES was used to establish an animal model of FES by injection of allogenic rabbit bone marrow adipose tissue. The combination of different glucocorticoids and low molecular dextran, the effect of different medication time on the FES model of rabbit, to guide the best clinical use of glucocorticoid combined with low molecular dextran and the course of treatment. Method one: a retrospective analysis of 47 cases admitted to our hospital in November January 1993. The patients with fracture complicated with FES were divided into A and B two groups. RISS was used to evaluate the patients with bone trauma. Group A was a multiple fracture without visceral injury. Group B was a multiple fracture patient with other parts of the chest, abdomen and craniocerebral injury. The correlation between the two groups was statistically analyzed and the correlation between RISS and FES was studied. Experiment two: Two: selected experiment: selection 36 male healthy New Zealand rabbits, with a weight of 2.5-3.0kg, were divided into 6 groups of.A groups, the group B was the low molecular dextran group, the C group was a group of methylprednisolone, the D group was the combination of dexamethasone and low molecular dextran, and the group E was a combination of methylprednisolone and low molecular dextran, and the F group was the physiological salt. The.6 group of the control group of the water blank control group used the bone marrow fat injection of the allogenic rabbit to induce fat embolism syndrome. The 6 groups received the preventive injection of the corresponding drugs before the injection of bone marrow fat. Then the anal temperature, arterial oxygen partial pressure (arterialpartialpressureofoxygen, Pa O2) and free fat were observed in the 6 groups before and after the injection. Free fatty acid (FFA), platelet count (platelet count, PLT), and after embolization of 48h, the lung tissue specimens were sacrificed to do HE and oil red O staining. Experiment three: 30 male healthy New Zealand rabbits were selected and divided into 5 groups of.A group as 8h group. The bone marrow fat induced fat embolism syndrome in the allograft rabbits, the 5 groups received the prophylactic injection of the 1H before injection of the bone marrow fat embolus. Each group had a repeated 8h injection at intervals. Then the respiratory frequency of the 5 groups before and after the injection of the drugs, arterial oxygen pressure (arterialpartialpressureofoxygen, P) were observed. A O2), free fatty acid (free fatty acid, FFA), white cell count (white blood cell, WBC), then executed the model rabbit's lung tissue mark HE, oil red O staining, electron microscope observation. There were 38 cases of multiple fracture trauma patients with craniocerebral or thoracic and abdominal visceral organ injuries. The RISS score was 18-25, the other 3 cases 25.FES was positively correlated with the RISS score (P0.05). Experiment two: 1. Anal temperature: 2h, 4h after injection of fat embolus in each group was progressive, but 8h, 24h, 48h decreased gradually after injection, and 2h after injection. 4h, 8h, 24h, 48h Anal temperature were all D or E group A group or C group. After injection 2h, 4h, 8h, there were significant differences between each group. There were statistical significance between each group of 24h and 48h (P0.05).3.FFA: each group FFA after injection of the fat embolus 2h, 4h, 8h showed progressive increase, but after the injection 24h, 48h gradually decreased. After injection of fat embolus, the changes of time points were high and low and irregular to follow. There was no statistically significant difference between each group before and after injection of 2h, 4h, 8h, 24h, 48h. The lung tissue was performed routine HE staining, alveolar interstitial edema, pulmonary alveolar capillary permeability increased, erythrocyte exotic and neutrophils were fine. In group F, group B, group A, E,.6. oil and red O, group A, group C, group D, group of oil red O stained alveolus, pulmonary bronchoalveolar capillaries, orange red lipid droplets, orange red lipid droplets and B group A group F group. Experiment three: respiratory frequency: each group of respiratory frequencies was carried out after injection of fat embolus There was no significant difference between 24h, 48h and 72h after injection (F=0.968, P=0.442). There was a significant difference between 8h, 24h, 48h, and 72h respiratory frequency in each group after embolization (P0.05).2.Pa O2: each group decreased gradually after the injection of fat embolus. There was no significant difference in respiratory frequency before embolization (F=0.543, P=0.706). There was a significant difference between 8h, 24h, 48h and 72h after embolization (P0.05) in each group (P0.05) FFA in each group was gradually increased after injection of fat embolus, but 24h after injection, 48h, and gradually decreased. F=0.412, P=0.798), there was a significant difference between the respiratory frequencies of 8h, 24h, 48h and 72h after the embolization of each group (P0.05).4. leucocyte count: WBC in each group was gradually increased after the injection of the fat embolus, but the 48h gradually declined after the injection. There was no statistically significant difference between 48h (P0.05). The difference between each group was statistically significant after embolization (F=2.805, P=0.047).5.HE staining: extensive interstitial edema of the lungs, exudation of red blood cells, moderate edema of pulmonary interstitial in group A, moderate exootion of erythrocytes in group A, mild oedema of interstitial lung mass in B group, mild ooze in group B, mild edema of pulmonary alveolus in group C, D, and D. Group pulmonary interstitial and alveolar cavity mild inflammatory infiltration, E group pulmonary interstitial edema, pulmonary alveolar hemorrhage serious.6. oil red O staining: under the light microscope, the pulmonary vascular cavity of A group can be seen to be medium size orange red fat drop clogging, B group can see light size orange red lipid droplets clog the blood tube, C group can see wide fat droplets clog the blood tube cavity, D group can see small fat drops scattered in the division. .7. electron microscopic observation of large fat droplets in group E showed that there were macrophages in the alveolar cavity in group A, containing more dissolved bodies, lymphocytic lymphocytes in the alveoli, infiltration of inflammatory cells, small amount of macrophages in the alveolar cavity in B group, emptying in the two type cell lamellar bodies, no obvious swelling of organelles, and C group alveolar septum. There were slight infiltration of inflammatory cells and slight emptying of lamellar body of type two cells, inflammatory cells in the capillaries of group D, slight red cell exudation in the alveolar cavity, small amount of macrophages in the capillary cavity, large number of macrophages in the alveolar cavity in E group, more lamellar bodies of type two cells, severe swelling of capillary endothelial cells and interstitial lung. A large number of inflammatory cells infiltrated. Conclusion 1, the severity of fracture trauma is associated with the occurrence of FES. When the RISS value of the patients with simple multiple fracture trauma is 11, and the RISS value of multiple fractures with craniocerebral or abdominal visceral organ injury is 18, FES is easy to occur, and the preventive measures should be taken, and the glucocorticoid combined with low molecular dextran is effective. The effect of FES was prevented by the combination of dexamethasone combined with low molecular dextran group and low molecular dextran group with low molecular weight dextran group, low molecular weight dextran group, low molecular dextran group, low molecular dextran group, normal saline control group,.3, the best dose of methylprednisolone combined with low molecular dextran intravenous therapy (24h, 8h/ times) superior to (8h, 8h/ times), and methylprednisolone combined with low There was no significant difference in the preventive effect of dextran intravenous injection (24h, 8h/ times) and (48h, 8h/ times), (72h, 8h/ times) on fat embolism syndrome.
【學(xué)位授予單位】:湖北中醫(yī)藥大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R683

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1 李亞華;甲強龍、低分子肝素對肺脂肪栓塞致急性呼吸窘迫綜合征的防治作用的研究[D];河北醫(yī)科大學(xué);2015年

2 唐辰虹;剪接因子SR蛋白和hnRNPA1對糖皮質(zhì)激素受體外顯子9選擇性剪接調(diào)控的影響[D];安徽醫(yī)科大學(xué);2006年

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