崔紅，王麗麗，周敏，賴西南，肖南

·軍事醫(yī)學·

艙室內爆炸傷復合失血致休克大鼠液體復蘇的研究

崔紅，王麗麗，周敏，賴西南，肖南

目的比較高滲鹽溶液與生理鹽水用于艙室內爆炸傷復合失血致休克大鼠液體復蘇的治療效果。方法健康成年雄性SD大鼠147只，固定于模擬艙室內，點爆源距大鼠胸腹部中心11～12cm瞬時引爆，迅速抽離艙內煙霧。炸后將大鼠靜置于實驗臺上測量炸后10min平均動脈壓(MAP)并以此為零時相點，由股動脈導管勻速放血造成中度休克。將108只大鼠隨機分為無復蘇組(對照組)、生理鹽水組(NS組)及高滲鹽溶液組(HSD組)，每組36只。對照組致傷后不予治療；NS組于傷后90min由股靜脈勻速輸入失血量3倍的NS，30min輸注完畢；HSD組以4ml/kg勻速輸入7.5%高滲氯化鈉/6%右旋醣酐高滲鹽溶液，5min輸注完畢。各組分別于150、210、270min時點在存活大鼠中隨機處死8只大鼠，測量血氣指標，并收集肺、腦組織標本檢測含水量。另39只大鼠同上分組，每組13只，致傷復蘇方法同前，記錄30、90、150、210、270min時點各組血壓變化及死亡狀況。結果對照組13只大鼠有6只死亡，NS組有3只死亡，HSD組大鼠全部存活至270min時點，組間存活率比較差異有統(tǒng)計學意義(P＜0.05)。傷后150min時點，NS組及HSD組大鼠MAP顯著增高，210、270min時點NS組MAP逐漸降低，而HSD組降低不明顯，270min時點各組間比較差異顯著(P＜0.05)。在150、210、270min時點，HSD組大鼠肺、腦含水量逐漸下降，而NS組則有上升趨勢，組間比較差異有統(tǒng)計學意義(P＜0.05或P＜0.01)。與對照組比較，HSD與NS對血氣指標均有一定的改善作用，且在210min及270min時間點，HSD組pH值、PO2高于NS組，乳酸水平低于NS組(P＜0.05或P＜0.01)。結論HSD可維持爆炸傷復合失血致休克大鼠血流動力學穩(wěn)定，且在改善血氣指標及肺、腦水腫方面的作用優(yōu)于NS。

艙室爆炸傷；休克，出血性；鹽水，高滲；液體復蘇

戰(zhàn)爭環(huán)境及日常生活中，密閉艙室爆炸傷發(fā)生率均逐年增高。休克是戰(zhàn)創(chuàng)傷死亡的重要原因之一，文獻報道，戰(zhàn)時有32.6%～59.5%的傷員死于創(chuàng)傷失血性休克[1]。若得不到早期救治，休克的死亡率可高達31%。目前關于何種液體更適用于休克的早期復蘇尚無定論，美國陸軍醫(yī)學研究和物資司令部(MRMC)及海軍研究辦公室(ONR)均推薦高滲鹽液、人工膠體液或二者的混合液作為容量復蘇的首選液體[2]，但有臨床研究表明，高滲鹽溶液與傳統(tǒng)等滲晶體液復蘇對低血容量休克患者存活率的影響無顯著差異[3]。既往對高滲鹽溶液的研究多集中在單純低血容量性休克或顱腦傷合并低血容量休克的液體復蘇方面，在艙室密閉環(huán)境中多系統(tǒng)受累的爆炸沖擊傷基礎上發(fā)生的創(chuàng)傷失血性休克有其自身特點[4-7]，是否可采用高滲鹽溶液進行復蘇尚未見報道。本研究以高滲鹽溶液及生理鹽水作為早期容量復蘇液體，比較二者對艙室內爆炸傷復合失血致休克大鼠的復蘇效果，以期為艙室爆炸傷合并失血致休克患者的早期救治提供理論依據(jù)。

1 材料與方法

1.1實驗儀器及設備 按照陸軍裝甲車輛艙室等比例縮小，模擬裝甲艙室；MFB-50型發(fā)爆器，柱狀紙質點爆源(成分包括黑素金0.35g，二硝基重氮酚300mg)，NOVA 9型血氣分析儀(美國)，Sartorius BA61型電子天平(瑞士)。

1.2實驗動物 清潔級雄性SD大鼠147只，體重200～220g，由第三軍醫(yī)大學大坪醫(yī)院野戰(zhàn)外科研究所實驗動物中心提供。實驗前12h禁食，自由飲水。

1.3方法

1.3.1動物模型制備 戊巴比妥鈉36mg/kg腹腔注射麻醉大鼠，固定于實驗平臺上，行左側股動脈插管，測量并記錄爆炸前平均動脈壓(MAP)；將大鼠固定于模擬艙室內，點爆源距大鼠胸腹部中心11～12cm瞬時引爆，迅速抽離艙內煙霧；炸后將大鼠靜置于實驗臺，測量炸后10min的MAP并以此為零時相點，由股動脈導管勻速放血(30min放總血量的30%)致中度休克。

1.3.2實驗方法 108只大鼠按隨機數(shù)字表法分為無復蘇組(對照組)、高滲鹽溶液(7.5%高滲氯化鈉/6%右旋醣酐)組(HSD組)、生理鹽水組(NS組)，每組36只。對照組不予任何治療；NS組于傷后90min由股靜脈勻速輸入生理鹽水，輸入量為失血量的3倍，30min輸注完畢；HSD組按照4ml/kg液體量勻速輸入7.5%高滲氯化鈉/6%右旋醣酐高滲鹽溶液，5min輸入完畢。各組于150、210、270min時間點在存活大鼠中隨機處死8只，處死前由股動脈抽取0.3ml血液抗凝用于血氣分析，處死后立即收集肺、腦組織標本用于含水量檢測。另39只大鼠分組同上，每組13只，觀察記錄30、90、150、210、270min時間點各組血壓變化及死亡狀況。實驗過程中大鼠體溫始終維持在37.0±0.5℃水平。

1.4統(tǒng)計學處理 采用SPSS 13.0軟件進行統(tǒng)計分析，數(shù)據(jù)結果以±s表示，多組間比較采用重復測量的方差分析，進一步兩兩比較采用t檢驗。P＜0.05為差異有統(tǒng)計學意義。

2 結 果

2.1各組死亡率比較 對照組13只大鼠有6只死亡，死亡率46.2%，其中3只大鼠死亡發(fā)生在爆炸傷后210min時。NS組在210min時有1只、270min時有2只動物死亡占23.1%。HSD組大鼠至270min時全部存活，死亡率為0%。各組間死亡率比較差異有統(tǒng)計學意義(P＜0.05)。

2.2大鼠MAP變化 爆炸后30min大鼠MAP低于40mmHg，停止放血后有所上升，于90min升至60mmHg左右。對照組大鼠MAP在90min后再次迅速下降，于270min降低至30mmHg左右。NS組及HSD組大鼠MAP均逐漸升高，其中HSD組升高更明顯，210min及270min時相點NS組大鼠MAP存在明顯下降趨勢，HSD組下降不明顯。在150、210、270min時間點，NS組及HSD組MAP顯著高于對照組，且HSD組MAP顯著高于NS組(P＜0.05或P＜0.01，表1)。

2.3各組大鼠肺、腦含水量比較 對照組大鼠肺含水量自傷后呈逐漸增高趨勢，150min時為82.06%±0.76%，270min時稍增高至82.24%±0.67%。NS組大鼠肺含水量同樣呈逐漸增高趨勢，在傷后210、270min與對照組比較差異顯著(P＜0.05或P＜0.01)。HSD組大鼠肺含水量在150min時輕度升高，升高程度低于對照組及NS組，210min及 270min時呈下降趨勢，各時相點與對照組、NS組比較均有顯著差異(P＜0.01)。各組腦含水量變化趨勢與肺含水量基本相同(表2)。

2.4各組大鼠血氣指標比較 與對照組比較，雖然治療過程中NS組及HSD組pH值、PO2整體仍呈降低趨勢，血乳酸水平逐漸增高，但變化幅度明顯低于對照組。在210、270min時相點，HSD組大鼠pH值、PO2均高于NS組，血乳酸則低于NS組，差異有統(tǒng)計學意義(P＜0.05或P＜0.01，表3)。

表1 各組大鼠MAP值比較(mmHg，n=13)Tab. 1 Comparison of MAP in different groups (mmHg, n=13)

表2 各組大鼠肺、腦含水量比較(%，±s，n=8)Tab. 2 Comparison of brain and lung tissue moisture in different groups (%,±s, n=8)

表2 各組大鼠肺、腦含水量比較(%，±s，n=8)Tab. 2 Comparison of brain and lung tissue moisture in different groups (%,±s, n=8)

(1)P＜0.05, (2)P＜0.01 compared with control group; (3)P＜0.01 compared with NS group; (4)P＜0.05, (5)P＜0.01 compared with 150min; (6)P＜0.05, (7)P＜0.01 compared with 210min

Index Time(minute) 150 210 270 Lung tissue moisture Control group 82.06±0.76 81.11±0.99(4) 82.24±0.67 NS group 83.16±1.84 82.27±0.82(1) 84.02±1.00(1)HSD group 77.85±1.51(2)(3)76.76±0.97(2)(3) 74.57±0.75(2)(3)(6)(7)Brain tissue moisture Control group 78.23±0.84 80.10±1.5 82.16±0.76 NS group 81.07±1.60(2) 82.39±1.57(2) 83.20±1.07(5)(6)HSD group 77.46±0.64(3) 76.96±1.60(2)(3)75.25±1.09(2)(3)

表3 各組大鼠血氣指標比較(±s，n=8)Tab. 3 Comparison of blood gas index in different groups (±s, n=8)

表3 各組大鼠血氣指標比較(±s，n=8)Tab. 3 Comparison of blood gas index in different groups (±s, n=8)

(1)P＜0.05, (2)P＜0.01 compared with control group; (3)P＜0.05, (4)P＜0.01 compared with NS group; (5)P＜0.05, (6)P＜0.01 compared with 150min; (7)P＜0.05, (8)P＜0.01 compared with 210min

Group pH PO2(mmHg) Blood lactic acid (mmol/L) 150min Control group7.14±0.05 118.86±7.10 2.30±0.26 NS group 7.12±0.04(2) 126.67±9.00 2.36±0.39 HSD group 7.25±0.06(2)(4)130.71±17.71 1.99±0.16(3)210min Control group7.15±0.05 109.14±13.26 3.03±0.26(6)NS group 7.06±0.05(5) 97.86±13.37(6) 2.93±0.41(5)HSD group 7.21±0.03(3) 126.86±11.73(1)(4)2.44±0.41(2)(3)270min Control group6.73±0.07(6)(8) 88.57±13.04 3.67±0.35(6)(7)NS group 6.95±0.06(2)(6)(8)87.86±7.01 2.99±0.31(2)HSD group 7.19±0.05(2)(4) 116.71±15.98(2)(4)2.49±0.33(2)(3)

3 討 論

近年來全球范圍內爆炸傷發(fā)生率不斷增加，休克是爆炸傷患者死亡的重要原因之一[8-10]。休克最終會導致多臟器功能衰竭，成功實施早期容量復蘇以盡快恢復血流動力學穩(wěn)定性，糾正代謝紊亂，恢復組織器官的正常灌注，對休克治療至關重要[11]。因艙室具有相對密閉的特點，密閉艙室爆炸時沖擊波反射增強，肺、胃腸等空腔臟器沖擊傷發(fā)生率遠高于開闊地爆炸傷，若合并大量失血則血壓下降快、幅度大，重要臟器血流灌注水平低[12]，多器官、臟器損傷發(fā)生率高[13-14]，炎癥反應明顯，肺、腦水腫程度進一步加重，死亡率明顯增高。目前有大量關于失血性休克、感染性休克、創(chuàng)傷性休克液體復蘇的研究，而對艙室內爆炸傷復合失血致休克患者如何進行早期液體復蘇鮮見報道。

NS短時間內能有效擴充血容量，糾正鈉缺失，與乳酸林格液相比，用于存在顱腦損傷的患者中可減輕腦水腫[15]。但NS單獨使用時用量大，需要失液量的3～4倍才能維持有效循環(huán)[16]，且過量輸注會加重組織損傷[17]。HSD中的高滲成分可提高晶體滲透壓，通過內源性液體轉移促進組織間液及細胞液進入血管內，右旋糖酐可維持膠體滲透壓，延長液體(細胞間液/細胞液)在血管內的存留時間，因此可快速恢復有效循環(huán)血量，改善微循環(huán)[18-20]。但對于艙室爆炸傷復合失血致休克患者，高滲鹽溶液是否能滿足治療需求仍有待研究[21]。

本研究應用3倍失血量NS，可以在一定程度上改善循環(huán)灌注，但液體需要量大，維持循環(huán)穩(wěn)定時間較短，死亡率高于HSD組，且肺、腦水腫較對照組有一定程度加重，說明NS有一定的加重肺水腫的作用，而在低海拔或平原地區(qū)，創(chuàng)傷失血性休克輸注3～4倍失血量的平衡鹽液，不會引起肺水腫和肺功能不全[22]，考慮與沖擊傷導致大鼠全身多臟器損傷，毛細血管通透性升高，機體對輸液的耐受力降低有關。

本研究采用4ml/kg的HSD進行輸注以避免大量輸注后血漿氯、鈉濃度升高影響酸堿平衡，導致代謝性酸中毒[23]。結果表明，HSD可明顯提高大鼠存活率，升高MAP，延長血流動力學穩(wěn)定時間，休克復蘇后3h仍能維持較高的MAP，與既往研究結果一致[24-25]，且可在一定程度上減輕肺、腦水腫，改善微循環(huán)，降低血乳酸水平，升高動脈氧分壓，糾正代謝性酸中毒。雖然血液是最佳的復蘇液體，但因戰(zhàn)時環(huán)境特殊，專業(yè)醫(yī)療人員及設施缺乏，不可能將血液及血液制品用于一線治療。HSD具有易攜帶、方便運輸和保存、使用方法簡單、作用效果強、作用時間長等特點，且能夠明顯減輕肺、腦水腫，即使在戰(zhàn)場或突發(fā)爆炸傷事故現(xiàn)場也能在短期內實現(xiàn)供給，并能為轉運及高級生命支持爭取時間，在一定程度上滿足實際醫(yī)療的需求。

綜上所述，HSD維持血流動力學穩(wěn)定性較持久，改善血氣指標及肺、腦水腫的程度優(yōu)于NS，更適用于艙室內爆炸傷復合失血致休克的大鼠早期液體復蘇。

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Fluid resuscitation in rats suffering from explosion injury in closed cabin combined with hemorrhagic shock

CUI Hong1,2, WANG Li-li1, ZHOU Min1, LAI Xi-nan1*, XIAO Nan1*
1Institute of Field Surgery, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Third Military Medical University, Chongqing 400042, China
2Department of Anesthesiology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China
*

. LAI Xi-nan, E-mail: laixinan@163.com; XIAO Nan, E-mail: xiao_nan_99@yahoo.com
This work was supported by the Major Project of "Twelfth Five-Year Plan" Medical Science Development Foundation of PLA (2009BAI87B00), and the Medical and Health Research Foundation of PLA (06Z034)

ObjectiveTo compare the therapeutic efficacy of fluid resuscitation with hypertonic or normal saline on the rats suffering explosion injury in closed cabin combined with hemorrhagic shock.MethodsOne hundred and forty-seven anesthetized male SD rats undergoing explosion injury in a closed cabin where detonator was detonated instantaneously, while they were fixed at the site where the explosive was 11-12cm from the center of thoraco-abdominal junction of the rats. Smog was quickly removed from the cabin. The 10min time point after explosion was set as the zero point to record mean arterial pressure (MAP), and moderate hemorrhagic shock was conducted by uniform femoral exsanguination. One hundred and eight rats were randomly divided into three groups (36 each): control group (no resuscitation), hypertonic saline solution (HSD, 75% NaCl/6% Dextran) group (4ml/kg) and normal saline (NS) group (NS:blood loss=3:1). Fluid was given via femoral vein catheter 90min after injury, and the infusion lasted for 5min in HSD group and 30min in NS group. Eight rats were randomly sacrificed in each group at the time points of 150, 210 and 270min to analyze the arterial blood gas and water content in the brain and lung tissues. The other 39 rats were alsorandomly and equally divided into 3 groups and the treatment was the same as above, but with recording of the MAP and survival rate at the time points of 30, 90, 150, 210 and 270min.ResultsSix rats died in control group, three died in NS group, and all rats of HSD group survived up to 270min. There were significant differences in survival rate among the 3 groups. The MAP rose obviously in NS and HSD groups at the time point of 150min, while it lowered gradually at 210min and 270min in NS group, but no obvious lowering was found in HSD group, and the difference was significant at 270min among the 3 groups (P＜0.05). The water contents in the lung and brain tissues decreased in HSD group but increased in NS group at 150min, 210min and 270min, and the differences were significant among the 3 groups (P＜0.05 orP＜0.01). Arterial blood gas improvement was detected in both HSD and NS groups. At 210min and 270min, pH and PO2were higher but lactate level was lower in HSD group than in NS group (P＜0.05 orP＜0.01). Conclusion HSD could maintain the hemodynamic stability of rats suffering from explosion injury combined with hemorrhagic shock, and its positive effect on arterial blood gas and edema of the lung and brain is superior to normal saline.

enclosed space blast injuries; shock, hemorrhagic; saline solution, hypertonic; fluid resuscitation

R826.56

A

0577-7402(2013)06-0512-04

2013-01-08；

2013-04-21)

(責任編輯：胡全兵)

全軍“十二五”醫(yī)學科研重大項目(2009BAI87B00)；全軍醫(yī)藥衛(wèi)生科研基金(06Z034)

崔紅，醫(yī)學碩士，住院醫(yī)師。主要從事創(chuàng)傷急救方面的基礎與臨床研究

400042 重慶 第三軍醫(yī)大學大坪醫(yī)院野戰(zhàn)外科研究所，創(chuàng)傷、燒傷與復合傷國家重點實驗室[崔紅(現(xiàn)在重慶醫(yī)科大學附屬第一醫(yī)院麻醉科)、王麗麗、周敏、賴西南、肖南]

賴西南，E-mail：laixinan@163.com；肖南，E-mail：xiao_nan_99@yahoo.com