乌司他丁联合血必净对复苏后多器官功能障碍综合征干预效果的临床观察
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摘要
心搏骤停（cardiac arrest，CA）是一种多发又极为凶险的急危重症。尽管随着心肺复苏技术(cardiopulmonary resuscitation，CPR)的不断进展与普及，CA后自主循环恢复(resumption of spontaneous circulation，ROSC)率较前有明显升高，但复苏成功后仍存在较高死亡率，这与复苏后多器官功能障碍综合征(post-resuscitation multiple organdysfunction syndrome，PR-MODS)是密切相关的。近年来大量研究显示PR-MODS的发生是导致复苏成功患者预后不佳的独立因素[1]。尽管对PR-MODS进行了大量的研究，但到目前为止，临床上仍然没有发现或研发出对复苏后多器官功能障碍综合征具有确切疗效的药物。有研究显示乌司他丁具有抑制多种水解酶的活性、增加溶酶体膜稳定性、下调氧自由基(Oxygen Free Radical，OFR)水平及拮抗炎症反应等作用；血必净注射液具有下调内源性炎症介质及内毒素水平，改善机体微循环障碍等作用。目前乌司他丁与血必净已被广泛应用于临床治疗急性胰腺炎、各种原因所致休克、脓毒症、急性肺损伤、ARDS、SIRS等，并取得了一定的疗效。但二者单独及联合应用于PR-MODS的辅助治疗目前尚未见报道。在本研究中我们将乌司他丁与血必净联合应用于PR-MODS患者，并通过对各项指标的监测和分析探讨两者联合治疗PR-MODS患者的临床疗效。
目的：探讨乌司他丁与中药制剂血必净注射液联合应用对复苏后患者多脏器保护的临床疗效及对患者预后的影响，为其在PR-MODS的治疗领域联合应用提供更科学合理的依据，为PR-MODS的治疗寻找更好的救治方案。
方法：本研究收集了我科2006年3月至2012年2月收治的发生心搏骤停经CPR成功后并发MODS的患者共计84例，根据患者是否应用乌司他丁及血必净共分为四个治疗组：常规治疗组22例，乌司他丁治疗组20例，血必净治疗组21例，乌司他丁+血必净治疗组21例。所有患者均采用积极纠正病因、高级生命支持、早期预防感染、亚低温、纠正内环境紊乱及多器官保护等常规治疗，在常规治疗基础上乌司他丁治疗组加用乌司他丁50万单位2/日静点治疗，血必净治疗组加用血必净注射液100毫升2/日静点治疗，乌司他丁+血必净治疗组加用乌司他丁和血必净注射液上述剂量联合应用。分别收集和分析四组患者以下监测指标：ROSC后24h、48h、72h的总胆红素(totalbilirubin，TBIL)、肌酐(creatinine，Cr)、血小板（platelet，Plt）计数、动脉血氧分压(partialpressure of oxygen in arterial，PaO2)水平、肌酸激酶同工酶（creatine kinase-MB，CK-MB）、乳酸(lactic acid，Lac）水平、意识状态、收缩压(systolic blood pressure，SBP)、肠鸣音和便潜血情况。比较四组患者复苏后24h、48h、72h的MODS病情严重度评分、复苏后28天时脑功能分类（cerebral performance category，CPC）、复苏后28天生存率（部分患者采用电话随访）。
结果：1、复苏后24h、48h、72h时间段乌司他丁治疗组、血必净治疗组的CK-MB水平与常规治疗组比较，均存在统计学差异（P<0.05），乌司他丁+血必净治疗组的CK-MB水平与常规治疗组比较，存在统计学差异（P<0.05），其中24h、72h时段差异显著（P<0.01）；复苏后各时间段乌司他丁治疗组、血必净治疗组的CK-MB水平均高于乌司他丁+血必净治疗组，但三者相比差异无统计学意义（P>0.05）；2、复苏后72h时段常规治疗组Lac水平较乌司他丁治疗组及血必净治疗组明显升高，差异具有统计学意义（P<0.05）；复苏后48h、72h时段乌司他丁+血必净治疗组Lac水平明显低于常规治疗组，差异有统计学意义（P<0.05），其中72h时段差异显著（P<0.01）；3、复苏后24h、48h、72h乌司他丁+血必净治疗组的MODS病情严重度评分均低于常规治疗组，其中72h时段差异具有统计学意义（P<0.05）；复苏后各时间段乌司他丁+血必净治疗组的MODS病情严重度评分均低于乌司他丁、血必净治疗组，但三者相比差异无统计学意义（P>0.05）；4、乌司他丁治疗组、血必净治疗组、乌司他丁+血必净治疗组患者复苏28天时CPC与常规治疗组比较，差异无统计学意义（P>0.05）；5、乌司他丁治疗组、血必净治疗组患者28天生存率与常规治疗组比较，差异均无统计学意义（P>0.05），乌司他丁+血必净治疗组患者28天生存率与常规治疗组比较，差异有统计学意义（P<0.05）。
结论：乌司他丁联合血必净注射液辅助治疗心搏骤停CPR后患者的多器官功能障碍综合征，可改善组织器官的微循环灌注，对心脏等多器官具有一定的保护作用，从而减轻多器官损伤的严重程度，改善患者的预后。
Cardiac arrest is a common critical illness. With the continuous development andpopularization of cardiopulmonary resuscitation(CPR), the rate of resumption ofspontaneous circulation(ROSC) after cardiac arrest has improved, but also there is a highmortality after successful resuscitation, which are closely related with PR-MODS(post-resuscitation multiple organ dysfunction syndrome). It is reported that the PR-MODShas become an independent factor which affects the survival after resuscitation.Therefore,how to prevent PR-MODS has now become the difficulty in the region of CPR. There isno western drug is confirmed to be effective until now. The UTI which can inhibit theactivity of various hydrolytic enzymes, stabilize lysosomal membrane, clear oxygen freeradicals (OFR), regulate the inflammatory mediator releasing, is widely used in thetreatment of acute pancreatitis, acute lung injury, Acute Respiratory DistressSyndrome(ARDS), systemic inflammatory response syndrome(SIRS), multiple organdysfunction syndrome MODS and used to protect perioperative organ injury. Xuebijinginjection is widely used in the therapy of systemic inflammatory response syndrome (SIRS)and multiple organ dysfunction syndrome(MODS) which is caused by various kinds ofcritical illnesses these years because it can suppress inflammatory response and protect thefunction of multiple organs. The intervention of Ulinastatin combining with Xuebijinginjection in the therapy of PR-MODS is lack and the outcome measures aren’t enough so itcan not reflect the influence of its function of protecting multiple organs and finalprognosis. So we discuss the effect of Ulinastatin combining with Xuebijing injection toPR-MODS by several outcome measures.
Objective: We discuss the function of Ulinastatin combining with Xuebijing injectionin the therapy of PR-MODS by means of use it to patient who suffer from CA and ROSCas adjuvant therapy in order to discuss the clinical evaluation of Ulinastatin combiningwith Xuebijing injection to PR-MODS patients.
Methods: We analyzed84cardiac arrest patients retrospectively who weresuccessfully resuscitated and accompanied with MODS. Both of them were givencomprehensive treatment including correct the cause, circulation support, mechanical ventilation, mild hypothermia, infection control and so on. They were divided into fourgroups, conventional therapy group, Ulinastatin therapy group, Xuebijing therapy groupand Ulinastatin combining with Xuebijing therapy group by whether they had usedUlinastatin and Xuebijing injection or not, and22patients in conventional therapygroup,20in the Xuebijing therapy group,21in the Ulinastatin therapy group,while21inthe combining therapy group. We collected total bilirubin(TBIL), creatinine (Cr), platelet(Plt), PaO2, the level of creatine kinase-MB (CK-MB), lactic acid (Lac), and Consciousstate, systolic blood pressure(SBP), melena and borborygmus of the four groups at the timeof24h,48h,72h after the restoration of spontaneous circulation (ROSC). By comparingthe score of multiple organ dysfunction syndrome of24h,48h,72h after the restoration ofspontaneous circulation (ROSC), the cerebral performance category(CPC) and the survivalrate at the time of28d after the restoration of spontaneous circulation (ROSC) to findwhether there were differences among the four groups.
Results:1.The level of CK-MB was higher in the conventional therapy group thanthat in the Ulinastatin therapy group, Xuebijing therapy group at the time of24h,48h,72htime point after ROSC（P<0.05）. The level of CK-MB was higher in the conventionaltherapy group than that in the Ulinastatin combining with Xuebijing therapy group at thetime of24h,48h,72h time point after ROSC（P<0.05）, and at the time of24h,72h timepoint after ROSC, great significant differences was observed between them（P＜0.01）；2.The level of Lac was higher in the conventional therapy group than that in the Ulinastatintherapy group, Xuebijing therapy group at the time of72h time point after ROSC（P<0.05）.The level of Lac was higher in the conventional therapy group than that in the Ulinastatincombining with Xuebijing therapy group at the time of48h,72h time point after ROSC（P<0.05）；3. The scores of the severity of MODS was higher in the conventional therapygroup than that in the Ulinastatin combining with Xuebijing therapy group at the time ofevery time point after ROSC,while at the time of72h time point after ROSC, significantdifferences was observed between them（P<0.05）. At every time point after ROSC, thescore of the severity of MODS in the Ulinastatin combining with Xuebijing therapy groupis lower than that in Ulinastatin therapy group and Xuebijing therapy group with on nosignificant differences was observed between them（P>0.05）;4. Differences of CPC at thetime of28d after ROSC were not statistically significant in the four group（sP<0.05）;5.Thesurvival rates at the time of28d after ROSC among the Ulinastatin therapy group, Xuebijing therapy group and the conventional therapy group were not statisticallysignificant（P>0.05）.while the survival rate at the time of28d after ROSC between theconventional therapy group and the combining group was statistically significan（tP<0.05）.
Conclusion: Using UTI combining with Xuebijing injection as adjuvant therapy toPR-MODS can improve the function of multiple organs, alleviate the heart injury obviouslyand improve tissue perfusion, reduce the mortality.
目的：探讨乌司他丁与中药制剂血必净注射液联合应用对复苏后患者多脏器保护的临床疗效及对患者预后的影响，为其在PR-MODS的治疗领域联合应用提供更科学合理的依据，为PR-MODS的治疗寻找更好的救治方案。
方法：本研究收集了我科2006年3月至2012年2月收治的发生心搏骤停经CPR成功后并发MODS的患者共计84例，根据患者是否应用乌司他丁及血必净共分为四个治疗组：常规治疗组22例，乌司他丁治疗组20例，血必净治疗组21例，乌司他丁+血必净治疗组21例。所有患者均采用积极纠正病因、高级生命支持、早期预防感染、亚低温、纠正内环境紊乱及多器官保护等常规治疗，在常规治疗基础上乌司他丁治疗组加用乌司他丁50万单位2/日静点治疗，血必净治疗组加用血必净注射液100毫升2/日静点治疗，乌司他丁+血必净治疗组加用乌司他丁和血必净注射液上述剂量联合应用。分别收集和分析四组患者以下监测指标：ROSC后24h、48h、72h的总胆红素(totalbilirubin，TBIL)、肌酐(creatinine，Cr)、血小板（platelet，Plt）计数、动脉血氧分压(partialpressure of oxygen in arterial，PaO2)水平、肌酸激酶同工酶（creatine kinase-MB，CK-MB）、乳酸(lactic acid，Lac）水平、意识状态、收缩压(systolic blood pressure，SBP)、肠鸣音和便潜血情况。比较四组患者复苏后24h、48h、72h的MODS病情严重度评分、复苏后28天时脑功能分类（cerebral performance category，CPC）、复苏后28天生存率（部分患者采用电话随访）。
结果：1、复苏后24h、48h、72h时间段乌司他丁治疗组、血必净治疗组的CK-MB水平与常规治疗组比较，均存在统计学差异（P<0.05），乌司他丁+血必净治疗组的CK-MB水平与常规治疗组比较，存在统计学差异（P<0.05），其中24h、72h时段差异显著（P<0.01）；复苏后各时间段乌司他丁治疗组、血必净治疗组的CK-MB水平均高于乌司他丁+血必净治疗组，但三者相比差异无统计学意义（P>0.05）；2、复苏后72h时段常规治疗组Lac水平较乌司他丁治疗组及血必净治疗组明显升高，差异具有统计学意义（P<0.05）；复苏后48h、72h时段乌司他丁+血必净治疗组Lac水平明显低于常规治疗组，差异有统计学意义（P<0.05），其中72h时段差异显著（P<0.01）；3、复苏后24h、48h、72h乌司他丁+血必净治疗组的MODS病情严重度评分均低于常规治疗组，其中72h时段差异具有统计学意义（P<0.05）；复苏后各时间段乌司他丁+血必净治疗组的MODS病情严重度评分均低于乌司他丁、血必净治疗组，但三者相比差异无统计学意义（P>0.05）；4、乌司他丁治疗组、血必净治疗组、乌司他丁+血必净治疗组患者复苏28天时CPC与常规治疗组比较，差异无统计学意义（P>0.05）；5、乌司他丁治疗组、血必净治疗组患者28天生存率与常规治疗组比较，差异均无统计学意义（P>0.05），乌司他丁+血必净治疗组患者28天生存率与常规治疗组比较，差异有统计学意义（P<0.05）。
结论：乌司他丁联合血必净注射液辅助治疗心搏骤停CPR后患者的多器官功能障碍综合征，可改善组织器官的微循环灌注，对心脏等多器官具有一定的保护作用，从而减轻多器官损伤的严重程度，改善患者的预后。
Cardiac arrest is a common critical illness. With the continuous development andpopularization of cardiopulmonary resuscitation(CPR), the rate of resumption ofspontaneous circulation(ROSC) after cardiac arrest has improved, but also there is a highmortality after successful resuscitation, which are closely related with PR-MODS(post-resuscitation multiple organ dysfunction syndrome). It is reported that the PR-MODShas become an independent factor which affects the survival after resuscitation.Therefore,how to prevent PR-MODS has now become the difficulty in the region of CPR. There isno western drug is confirmed to be effective until now. The UTI which can inhibit theactivity of various hydrolytic enzymes, stabilize lysosomal membrane, clear oxygen freeradicals (OFR), regulate the inflammatory mediator releasing, is widely used in thetreatment of acute pancreatitis, acute lung injury, Acute Respiratory DistressSyndrome(ARDS), systemic inflammatory response syndrome(SIRS), multiple organdysfunction syndrome MODS and used to protect perioperative organ injury. Xuebijinginjection is widely used in the therapy of systemic inflammatory response syndrome (SIRS)and multiple organ dysfunction syndrome(MODS) which is caused by various kinds ofcritical illnesses these years because it can suppress inflammatory response and protect thefunction of multiple organs. The intervention of Ulinastatin combining with Xuebijinginjection in the therapy of PR-MODS is lack and the outcome measures aren’t enough so itcan not reflect the influence of its function of protecting multiple organs and finalprognosis. So we discuss the effect of Ulinastatin combining with Xuebijing injection toPR-MODS by several outcome measures.
Objective: We discuss the function of Ulinastatin combining with Xuebijing injectionin the therapy of PR-MODS by means of use it to patient who suffer from CA and ROSCas adjuvant therapy in order to discuss the clinical evaluation of Ulinastatin combiningwith Xuebijing injection to PR-MODS patients.
Methods: We analyzed84cardiac arrest patients retrospectively who weresuccessfully resuscitated and accompanied with MODS. Both of them were givencomprehensive treatment including correct the cause, circulation support, mechanical ventilation, mild hypothermia, infection control and so on. They were divided into fourgroups, conventional therapy group, Ulinastatin therapy group, Xuebijing therapy groupand Ulinastatin combining with Xuebijing therapy group by whether they had usedUlinastatin and Xuebijing injection or not, and22patients in conventional therapygroup,20in the Xuebijing therapy group,21in the Ulinastatin therapy group,while21inthe combining therapy group. We collected total bilirubin(TBIL), creatinine (Cr), platelet(Plt), PaO2, the level of creatine kinase-MB (CK-MB), lactic acid (Lac), and Consciousstate, systolic blood pressure(SBP), melena and borborygmus of the four groups at the timeof24h,48h,72h after the restoration of spontaneous circulation (ROSC). By comparingthe score of multiple organ dysfunction syndrome of24h,48h,72h after the restoration ofspontaneous circulation (ROSC), the cerebral performance category(CPC) and the survivalrate at the time of28d after the restoration of spontaneous circulation (ROSC) to findwhether there were differences among the four groups.
Results:1.The level of CK-MB was higher in the conventional therapy group thanthat in the Ulinastatin therapy group, Xuebijing therapy group at the time of24h,48h,72htime point after ROSC（P<0.05）. The level of CK-MB was higher in the conventionaltherapy group than that in the Ulinastatin combining with Xuebijing therapy group at thetime of24h,48h,72h time point after ROSC（P<0.05）, and at the time of24h,72h timepoint after ROSC, great significant differences was observed between them（P＜0.01）；2.The level of Lac was higher in the conventional therapy group than that in the Ulinastatintherapy group, Xuebijing therapy group at the time of72h time point after ROSC（P<0.05）.The level of Lac was higher in the conventional therapy group than that in the Ulinastatincombining with Xuebijing therapy group at the time of48h,72h time point after ROSC（P<0.05）；3. The scores of the severity of MODS was higher in the conventional therapygroup than that in the Ulinastatin combining with Xuebijing therapy group at the time ofevery time point after ROSC,while at the time of72h time point after ROSC, significantdifferences was observed between them（P<0.05）. At every time point after ROSC, thescore of the severity of MODS in the Ulinastatin combining with Xuebijing therapy groupis lower than that in Ulinastatin therapy group and Xuebijing therapy group with on nosignificant differences was observed between them（P>0.05）;4. Differences of CPC at thetime of28d after ROSC were not statistically significant in the four group（sP<0.05）;5.Thesurvival rates at the time of28d after ROSC among the Ulinastatin therapy group, Xuebijing therapy group and the conventional therapy group were not statisticallysignificant（P>0.05）.while the survival rate at the time of28d after ROSC between theconventional therapy group and the combining group was statistically significan（tP<0.05）.
Conclusion: Using UTI combining with Xuebijing injection as adjuvant therapy toPR-MODS can improve the function of multiple organs, alleviate the heart injury obviouslyand improve tissue perfusion, reduce the mortality.
引文
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