骨折并发FES定量评估与联合药物预防的时间依赖性研究

发布时间：2018-07-23 10:38

【摘要】：目的骨折并发脂肪栓塞综合征(Fat Embolism Syndrome,FES)是创伤后病人死亡的主要原因之一,主要由脂肪栓子阻塞血管腔导致的一系列临床表现。下肢单纯长骨干骨折并发FES的发病率为0.5-2.0%,下肢多发骨折或骨盆骨折中为5%-10%,其主要症状为呼吸困难、低氧血症、无脑外伤的意识障碍及皮肤粘膜出血点。目前尚无直接溶解脂肪栓子的药物,FES救治起来十分凶险,危及生命,所以预防一直是FES研究的重点。本研究拟用损伤严重度改良评分法(Revised Injury Severity Score,RISS)来定量评估FES发生的风险,避免药物预防FES的盲目性,以探讨不同伤因的骨创伤规律及RISS值与FES发生的关系,根据临床经验为选择预防患者提供依据,保证联合药物预防的疗效。临床上发现糖皮质激素联合低分子右旋糖酐对FES有良好的预防作用,但药物的选择及疗程临床上差异较大,临床上无统一的用药标准,导致预防FES的疗效各异。为了探究最佳的糖皮质激素与低分子右旋糖酐联合应用、用药疗程,本实验采取同种异体兔的骨髓脂肪组织注射建立FES的动物模型,观察不同的糖皮质激素和低分子右旋糖酐组合、不同用药时间在兔的FES模型上的预防效果,指导临床上最佳糖皮质激素联合低分子右旋糖酐的用药选择及用药疗程。方法实验一:采取回顾性分析方法,对我院于1993年1月-2009年11月收治的47例骨折并发FES患者分为A、B两组,采用RISS对骨创伤患者进行计量评估,A组为不伴内脏损伤的多发性骨折患者,B组为同时合并胸、腹、颅脑等其他部位损伤的多发性骨折患者,对两组进行统计学分析,研究RISS与FES发生之间的相关性。实验二:选取雄性健康新西兰兔36只,体重在2.5-3.0kg之间,按随机数字表分为6组。A组为应用地塞米松组,B组为低分子右旋糖酐组,C组为甲强龙组,D组为地塞米松和低分子右旋糖酐联合应用组,E组为甲强龙与低分子右旋糖酐联合用药组,F组为生理盐水空白对照组。6组均采用注射同种异体兔的骨髓脂肪诱发脂肪栓塞综合征,6组在注射骨髓脂肪前1h均接收相应药物的预防性注射,随后观察6组在栓塞前及注射后各个时间点的肛温、动脉血氧分压(arterialpartialpressureofoxygen,Pa O2)、游离脂肪酸(free fatty acid,FFA)、血小板计数(platelet count,PLT),栓塞48h后处死取肺组织标本做HE、油红O染色观察。实验三:选取雄性健康新西兰兔30只,按随机数字表分为5组。A组为8h组,B组为24h组,C组为48h组,D组为72h组,E组为空白对照组。5组均采用注射同种异体兔的骨髓脂肪诱发脂肪栓塞综合征,5组在注射骨髓脂肪栓子前1h均接收药物的预防性注射,每组均间隔8h重复注射药物一次,随后观察5组在注射药物前及注射后各个时间点的呼吸频率、动脉血氧分压(arterialpartialpressureofoxygen,Pa O2)、游离脂肪酸(free fatty acid,FFA)、白细胞计数(white blood cell,WBC),随后处死模型兔取肺组织标本行HE、油红O染色、电镜观察。结果实验一:全部骨创伤并发FES患者的病例的RISS评分均在11分以上:单纯多发性创伤骨折6例,RISS值位于11-18之间;伴有颅脑或胸腹腔内脏器损伤的多发性骨折创伤患者中有38例,RISS分值在18-25之间,另外3例分值25分。FES的发生与RISS分值呈正相关(P0.05)。实验二:1.肛温:各组肛温在注射脂肪栓子后2h、4h均呈进行性上升,但注射后8h、24h、48h逐渐下降,注射后2h、4h、8h、24h、48h肛温均为D组或E组A组或C组。注射后2h、4h、8h、24h各组间差异有统计学意义(P0.05)。2.PaO2:各组PaO2在注射脂肪栓子后2h均呈迅速下降,但注射后4h、8h、24h、48h逐渐回升,注射后2h、4h、8h、24h、48h Pa O2均为D组或E组A组或C组,各组之间注射后2h、4h、8h、24h、48h各组之间均有统计学意义(P0.05)。3.FFA:各组FFA在注射脂肪栓子后2h、4h、8h呈进行性升高,但注射后24h、48h逐渐下降,注射后2h、4h、8h、24h FFA均为D组或E组A组或C组,注射后2h、4h、8h、48h各组之间差异均有统计学意义(P0.05)。4.血小板计数:各组PLT在注射脂肪栓子后各个时间点变化时高时低,无规律可循,各组注射前及注射后2h、4h、8h、24h、48h各组之间差异均无统计学意义(P0.05)。5.HE染色:处死取肺组织行常规HE染色,肺泡间质水肿,肺泡腔内毛细血管的通透性增加,红细胞外渗,中性粒细胞明显增多,病理变化程度F组B组A组C组D组E组。6.油红O染色:各组油红O染色肺泡、肺支气管毛细血管内可见染成桔红色的脂滴,桔红色的脂滴大小及数量F组B组A组C组D组E组。实验三:1.呼吸频率:各组呼吸频率在注射脂肪栓子后8h均呈进行性上升,但注射后24h、48h、72h逐渐下降。各组栓塞前呼吸频率之间差异无统计学意义(F=0.968,P=0.442),各组栓塞后8h、24h、48h、72h呼吸频率之间差异有统计学意义(P0.05)。2.Pa O2:各组PaO2在注射脂肪栓子后8h均呈逐渐下降,但注射后24h、48h、72h逐渐回升。各组栓塞前呼吸频率之间差异无统计学意义(F=0.543,P=0.706),各组栓塞后8h、24h、48h、72h呼吸频率之间差异有统计学意义(P0.05)。3.FFA:各组FFA在注射脂肪栓子后8h均呈逐渐上升,但注射后24h、48h、72h逐渐下降。各组栓塞前FFA之间差异无统计学意义(F=0.412,P=0.798),各组栓塞后8h、24h、48h、72h呼吸频率之间差异有统计学意义(P0.05)。4.白细胞计数:各组WBC在注射脂肪栓子后8h均呈逐渐上升,但注射后24h、48h逐渐下降。各组栓塞前呼吸频率之间差异无统计学意义(F=0.159,P=0.957),各组于栓塞后8h、24h、48h之间差异无统计学意义(P0.05),各组之间差异于栓塞后72h有统计学意义(F=2.805,P=0.047)。5.HE染色:光镜下可见广泛肺间质水肿,红细胞渗出,A组肺间质中度水肿,红细胞中度外渗;B组肺间质轻度水肿,轻度外渗;C组肺间质、肺泡腔轻度水肿;D组肺间质、肺泡腔轻度炎性浸润;E组肺间质严重水肿,肺泡腔出血严重。6.油红O染色:光镜下可见A组肺血管腔可见中度大小桔红色脂滴堵塞,B组可见轻度大小桔红色脂滴堵塞血管腔,C组可见广泛小脂滴堵塞血管腔,D组可见小脂滴散在分布在血管腔内,E组可见大脂滴差不多完全栓塞血管腔。7.电镜观察:A组肺泡腔内有巨噬细胞,内含较多溶解体,肺泡腔内现淋巴细胞,有炎症细胞浸润;B组肺泡腔内有少量巨噬细胞,二型细胞板层小体有排空,细胞器无明显肿胀;C组肺泡隔增宽,有炎症细胞轻度浸润,二型细胞板层小体轻微排空;D组毛细血管有炎症细胞浸润,肺泡腔有点轻度红细胞渗出,毛细血管腔内有少量巨噬细胞;E组肺泡腔见大量巨噬细胞,二型细胞板层小体较多,毛细血管内皮细胞重度肿胀,肺间质大量炎症细胞浸润。结论1、骨折创伤严重度与FES的发生之间具有相关性,当单纯多发性骨折创伤患者RISS值11、伴有颅脑或胸腹腔内脏器损伤的多发性骨折RISS值18时,易发生FES,应采取预防措施。2、糖皮质激素联合低分子右旋糖酐具有有效预防FES的作用,甲强龙联合低分子右旋糖酐组地塞米松联合低分子右旋糖酐组甲强龙组地塞米松组低分子右旋糖酐组生理盐水空白对照组。3、最佳剂量的甲强龙联合低分子右旋糖酐静脉注射疗程(24h,8h/次)优于(8h,8h/次),甲强龙联合低分子右旋糖酐静脉注射疗程(24h,8h/次)与(48h,8h/次)、(72h,8h/次)之间对脂肪栓塞综合征的预防效果无明显差异。
[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.
【学位授予单位】：湖北中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R683

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