Thiel Christian, Lauber Johannes, Klingert Wilfried, Klingert Kathrin, Morgalla Matthias H, Beschorner Rudi, Peter Andreas, Grasshoff Christian, Königsrainer Alfred, Schenk Martin, Thiel Karolin
Department of General, Visceral and Transplant Surgery, Tuebingen University Hospital, Hoppe-Seyler-Strasse 3, 72076 Tuebingen, Germany.
Department of Anaesthesiology, Tuebingen University Hospital, Hoppe-Seyler-Strasse 3, Tuebingen 72076, Germany.
Toxicol Lett. 2017 Nov 5;281:119-126. doi: 10.1016/j.toxlet.2017.09.018. Epub 2017 Sep 27.
Critical care management of patients suffering from acute liver failure (ALF) continues to be challenging. Animal models studying the pathophysiological central nervous system alterations during the course of ALF provide an opportunity to improve diagnostic and therapeutic strategies. The aim of this study was to analyse the course of cerebral oxygenation in addition to conventional neuromonitoring during the course of acetaminophen-induced ALF.
ALF was induced by intrajejunal acetaminophen administration in 20 German landrace pigs. All animals underwent invasive hemodynamic and neuromonitoring and were maintained under standardized intensive care support. Neuromonitoring consisted of continuous intraparenchymatous recording of intracranial pressure and brain partial oxygen pressure. Hemodynamic and ventilation parameters were continuously recorded; laboratory parameters were analysed every eight hours. Mean values were compared using the Wilcoxon test.
Acute liver failure occurred in all intoxicated animals after 23±2h, resulting in death due to ALF after further 15±2h. Continuous neuromonitoring was performed in all animals during the whole experiment without observing signs of intracranial haemorrhage. Two hours after manifestation of ALF an increase in brain tissue oxygen (PtiO2) was observed. Brain oxygenation stayed stable until nine hours before death. Intracranial pressure (ICP) remained basically at a plateau level until manifestation of ALF. In the following ten hours a linear and slow increase was observed until five hours before death, followed by a fast and continuous rise in ICP to a final level of 35±1mmHg. Cerebral perfusion pressure (CPP) began to decrease 25h prior to exitus, further decreasing to 18±2mmHg at the end of the experiment. A strong negative linear correlation was found between PtiO2 and ICP (R=0.97). Arterial partial pressure of oxygen (PaO2) below 100mmHg was associated with lower PtiO2 levels. Changes in arterial partial pressure of carbon dioxide (PaC02) did not influence PtiO2 values. Hemoglobin values below 7g/dl were associated with lower PtiO2 values.
The results of our experiments demonstrate that ICP and PtiO2 measurements indicate impending damage well before serious complications occur and their use should be considered in order to protect endangered brain function in the presence of acetaminophen-induced ALF.
急性肝衰竭（ALF）患者的重症监护管理仍然具有挑战性。研究ALF病程中病理生理中枢神经系统改变的动物模型为改进诊断和治疗策略提供了机会。本研究的目的是在对乙酰氨基酚诱导的ALF病程中，除了进行传统神经监测外，分析脑氧合的变化过程。
通过空肠内给予对乙酰氨基酚在20只德国长白猪中诱导ALF。所有动物均接受有创血流动力学和神经监测，并在标准化重症监护支持下维持。神经监测包括连续脑实质内记录颅内压和脑局部氧分压。连续记录血流动力学和通气参数；每8小时分析实验室参数。使用Wilcoxon检验比较平均值。
所有中毒动物在23±2小时后发生急性肝衰竭，在进一步15±2小时后因ALF死亡。在整个实验过程中，所有动物均进行了连续神经监测，未观察到颅内出血迹象。ALF出现后两小时，观察到脑组织氧（PtiO2）增加。脑氧合在死亡前9小时保持稳定。颅内压（ICP）在ALF出现前基本保持在平台期水平。在接下来的10小时内，观察到线性缓慢增加，直至死亡前5小时，随后ICP快速持续上升至最终水平35±1mmHg。脑灌注压（CPP）在死亡前25小时开始下降，在实验结束时进一步降至18±2mmHg。发现PtiO2与ICP之间存在强负线性相关性（R = 0.97）。动脉血氧分压（PaO2）低于100mmHg与较低的PtiO2水平相关。动脉血二氧化碳分压（PaC02）的变化不影响PtiO2值。血红蛋白值低于7g/dl与较低的PtiO2值相关。
我们的实验结果表明，ICP和PtiO2测量在严重并发症发生之前就能很好地指示即将发生的损伤，在对乙酰氨基酚诱导的ALF情况下，为保护濒危脑功能，应考虑使用这些测量方法。
