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特利加压素对实验性高动力脓毒症局部血液动力学和肾功能的影响。

The effects of terlipressin on regional hemodynamics and kidney function in experimental hyperdynamic sepsis.

机构信息

Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia.

出版信息

PLoS One. 2012;7(2):e29693. doi: 10.1371/journal.pone.0029693. Epub 2012 Feb 15.

Abstract

BACKGROUND AND AIMS

Although terlipressin (TP) may improve renal function in cirrhotic patients, its use in sepsis remains controversial due to concerns about regional ischemia. We investigated the effects of TP on regional hemodynamics and kidney function in experimental hyperdynamic sepsis.

METHODS

We studied thirteen merino ewes in a university physiology laboratory using a randomized controlled cross over design. We implanted flow probes around the pulmonary, circumflex coronary, superior mesenteric, renal and iliac arteries. We injected live Escherichia coli and induced hyperdynamic sepsis. We treated animals with either bolus vehicle or a single dose of TP (sTP = 1 mg). In a second group, after 1 mg of TP, two additional bolus injections (mTP) of 0.5 mg were given at 2 hourly intervals.

MAIN RESULTS

sTP (1 mg) significantly increased mean arterial pressure (MAP) (74 to 89 mmHg; P<0.0001) creatinine clearance (31 to 85 mL/min; P<0.0001) and urine output (24 to 307 mL/hr) (P<0.0001). However, it decreased CO (5.7 to 3.9 L/min; p<0.0001), coronary blood flow (CBF) (43 to 32 mL/min; p<0.0001) and mesenteric blood flow (MBF) (944 to 625 mL/min; p = 0.004) and increased blood lactate (2.1 to 4.0 mmol/L; p<0.0001). Extra doses of TP caused little additional effect.

CONCLUSIONS

In hyperdynamic sepsis, bolus TP transiently improves MAP and renal function, but reduces CO, CBF and MBF, and increases blood lactate. Caution should be applied when prescribing bolus TP in septic patients at risk of coronary or mesenteric ischemia.

摘要

背景与目的

虽然特利加压素(TP)可能改善肝硬化患者的肾功能,但由于担心局部缺血,其在脓毒症中的应用仍存在争议。我们研究了 TP 对实验性高动力性脓毒症局部血液动力学和肾功能的影响。

方法

我们在大学生理学实验室使用随机对照交叉设计研究了 13 只美利奴羊。我们在肺、回旋冠状动脉、肠系膜上、肾和髂动脉周围植入了流量探头。我们注射了活大肠杆菌并诱导了高动力性脓毒症。我们用推注载体或单次剂量 TP(sTP=1mg)治疗动物。在第二组中,给予 1mgTP 后,每 2 小时给予 0.5mg 的两次推注(mTP)。

主要结果

sTP(1mg)显著增加平均动脉压(MAP)(74 至 89mmHg;P<0.0001)、肌酐清除率(31 至 85mL/min;P<0.0001)和尿量(24 至 307mL/hr)(P<0.0001)。然而,它降低了 CO(5.7 至 3.9L/min;p<0.0001)、冠状动脉血流量(CBF)(43 至 32mL/min;p<0.0001)和肠系膜血流量(MBF)(944 至 625mL/min;p=0.004)并增加了血乳酸(2.1 至 4.0mmol/L;p<0.0001)。额外剂量的 TP 几乎没有额外的效果。

结论

在高动力性脓毒症中,推注 TP 可短暂改善 MAP 和肾功能,但降低 CO、CBF 和 MBF,并增加血乳酸。在有冠状动脉或肠系膜缺血风险的脓毒症患者中,应谨慎使用推注 TP。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81c/3280248/5ce25747a988/pone.0029693.g001.jpg

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