Clemmesen J O, Gerbes A L, Gülberg V, Hansen B A, Larsen F S, Skak C, Tygstrup N, Ott P
Department of Hepatology, Rigshospitalet, University of Copenhagen, Denmark.
Hepatology. 1999 Feb;29(2):347-55. doi: 10.1002/hep.510290206.
Liver failure represents a major therapeutic challenge, and yet basic pathophysiological questions about hepatic perfusion and oxygenation in this condition have been poorly investigated. In this study, hepatic blood flow (HBF) and splanchnic oxygen delivery (DO2, sp) and oxygen consumption (VO2,sp) were assessed in patients with liver failure defined as hepatic encephalopathy grade II or more. Measurements were repeated after high-volume plasmapheresis (HVP) with exchange of 8 to 10 L of plasma. HBF was estimated by use of constant infusion of D-sorbitol and calculated according to Fick's principle from peripheral artery and hepatic vein concentrations. In 14 patients with acute liver failure (ALF), HBF (1.78 +/- 0.78 L/min) and VO2,sp (3.9 +/- 0.9 mmol/min) were higher than in 11 patients without liver disease (1.07 +/- 0.19 L/min, P <.01) and (2.3 +/- 0.7 mmol/min, P <.001). In 9 patients with acute on chronic liver disease (AOCLD), HBF (1.96 +/- 1.19 L/min) and VO2,sp (3.9 +/- 2.3 mmol/min) were higher than in 18 patients with stable cirrhosis (1.00 +/- 0.36 L/min, P <.005; and 2.0 +/- 0.6 mmol/min, P <.005). During HVP, HBF increased from 1.67 +/- 0.72 to 2.07 +/- 1.11 L/min (n=11) in ALF, and from 1.89 +/- 1.32 to 2.34 +/- 1.54 L/min (n=7) in AOCLD, P <.05 in both cases. In patients with ALF, cardiac output (thermodilution) was unchanged (6.7 +/- 2.5 vs. 6.6 +/- 2.2 L/min, NS) during HVP. Blood flow was redirected to the liver as the systemic vascular resistance index increased (1,587 +/- 650 vs. 2, 020 +/- 806 Dyne. s. cm-5. m2, P <.01) whereas splanchnic vascular resistance was unchanged. In AOCLD, neither systemic nor splanchnic vascular resistance was affected by HVP, but as cardiac output increased from 9.1 +/- 2.8 to 10.1 +/- 2.9 L/min (P <.01) more blood was directed to the splanchnic region. In all liver failure patients treated with HVP (n=18), DO2,sp increased by 15% (P <.05) whereas VO2,sp was unchanged. Endothelin-1 (ET-1) and ET-3 were determined before and after HVP. Changes of ET-1 were positively correlated with changes in HBF (P <.005) and VO2,sp (P <.05), indicating a role for ET-1 in splanchnic circulation and oxygenation. ET-3 was negatively correlated with systemic vascular resistance index before HVP (P <.05) but changes during HVP did not correlate. Our data suggest that liver failure is associated with increased HBF and VO2, sp. HVP further increased HBF and DO2,sp but VO2,sp was unchanged, indicating that splanchnic hypoxia was not present.
肝衰竭是一个重大的治疗挑战，然而，关于这种情况下肝脏灌注和氧合的基本病理生理问题却鲜有研究。在本研究中，对定义为肝性脑病二级及以上的肝衰竭患者评估了肝血流量（HBF）、内脏氧输送（DO2,sp）和氧消耗（VO2,sp）。在进行8至10升血浆置换的大容量血浆置换（HVP）后重复测量。通过持续输注D - 山梨醇来估计HBF，并根据菲克原理从外周动脉和肝静脉浓度计算得出。在14例急性肝衰竭（ALF）患者中，HBF（1.78±0.78升/分钟）和VO2,sp（3.9±0.9毫摩尔/分钟）高于11例无肝病患者（1.07±0.19升/分钟，P<.01）和（2.3±0.7毫摩尔/分钟，P<.001）。在9例慢性肝病急性发作（AOCLD）患者中，HBF（1.96±1.19升/分钟）和VO2,sp（3.9±2.3毫摩尔/分钟）高于18例稳定肝硬化患者（1.00±0.36升/分钟，P<.005；2.0±0.6毫摩尔/分钟，P<.005）。在HVP期间，ALF患者的HBF从1.67±0.72升/分钟增加到2.07±1.11升/分钟（n = 11），AOCLD患者从1.89±1.32升/分钟增加到2.34±1.54升/分钟（n = 7），两种情况P均<.05。在ALF患者中，HVP期间心输出量（热稀释法）无变化（6.7±2.5对6.6±2.2升/分钟，无显著性差异）。随着全身血管阻力指数增加（1,587±650对2,020±806达因·秒·厘米⁻⁵·米²，P<.01），血流重新导向肝脏，而内脏血管阻力不变。在AOCLD患者中，HVP对全身和内脏血管阻力均无影响，但随着心输出量从9.1±2.8升/分钟增加到10.1±2.9升/分钟（P<.01），更多血液流向内脏区域。在所有接受HVP治疗的肝衰竭患者（n = 18）中，DO2,sp增加了15%（P<.05），而VO2,sp不变。在HVP前后测定了内皮素 - 1（ET - 1）和ET - 3。ET - 1的变化与HBF变化呈正相关（P<.005）和VO2,sp变化呈正相关（P<.05），表明ET - 1在内脏循环和氧合中起作用。ET - 3在HVP前与全身血管阻力指数呈负相关（P<.05），但HVP期间的变化无相关性。我们的数据表明，肝衰竭与HBF和VO2,sp增加有关。HVP进一步增加了HBF和DO2,sp，但VO2,sp不变，表明不存在内脏缺氧。
