Eriksen Vibeke Ramsgaard
Dan Med J. 2017 Jul;64(7).
Hypotension in critically ill newborn infants is associated with higher mortality and higher risk of cerebral injuries. Yet treating hypotension has never been shown to improve outcomes. In fact, some studies have found that hypotensive newborn infants who were treated with dopamine fared worse than a comparable group of newborn infants who were not. Therefore, a concern has been raised that dopamine might cause the observed adverse outcomes. Cerebral autoregulation is a protective mechanism that maintains a fairly constant cerebral blood flow despite fluctuations in blood pressure. We hypothesized that dopamine might impair the cerebral autoregulation by inducing a rightward shift of the cerebral autoregulation curve. An increased cerebrovascular resistance due to a dopaminergic stimulation of α-adrenoceptors might cause this effect. The main focus of this thesis is to clarify whether dopamine induces a rightward shift of the cerebral autoregulatory pressure curve. The thesis is based on four papers: (I) A methodological study comparing the two most commonly used methods of estimating cerebral autoregulation: time-domain analysis and frequency-domain analysis. We found that the consistency between the two methods was poor, and that time-domain analysis appeared a more robust - and simpler - method for describing cerebral autoregulation when estimates of cerebral autoregulation are based on spontaneous changes in blood pressure. (II) A retrospective study estimating cerebral autoregulation in very preterm infants by time domain analysis. This study found an association between dopamine therapy and impaired cerebral autoregulation. (III) An experimental animal study examining whether dopamine affected cerebral autoregulation in newborn piglets with low blood pressure. We found that dopamine did not negatively affect cerebral venous saturation, cerebral blood flow, or cerebral autoregulation capacity in hypotensive newborn piglets. (IV) An in vitro experiment where middle cerebral arteries from newborn piglets were examined by wire myography and pressure myography. In the wire myograph, increasing concentrations of dopamine caused a biphasic response: starting with vasodilation at low concentrations followed by vasoconstrictions at higher concentrations. In the pressure myograph, dopamine mainly induced vasodilation and the internal arterial diameter only tended to decrease at the highest concentrations. In summary, dopamine has been associated with impaired cerebral autoregulation and our conclusions in study II accorded with this. However, other work has found that initiation of dopamine infusion does not affect cerebral autoregulation. This may indicate that dopamine itself does not lead to impaired cerebral autoregulation. In support of these counter-observations, we did not find any causal relationship between dopamine therapy and impaired cerebral autoregulation in newborn piglets in study III. Also, dopamine in therapeutic concentrations did not induce vasoconstriction in pial arteries in study IV. Based on a review of the current literature, and on the studies included in this thesis, the answer to the central question in this thesis is: "No, dopamine did not induce a rightward shift of the cerebral autoregulation curve".
危重新生儿的低血压与较高的死亡率和脑损伤风险相关。然而，治疗低血压从未被证明能改善预后。事实上，一些研究发现，接受多巴胺治疗的低血压新生儿比未接受治疗的对照组新生儿情况更糟。因此，有人担心多巴胺可能会导致观察到的不良后果。脑自动调节是一种保护机制，尽管血压波动，但能维持相当恒定的脑血流量。我们假设多巴胺可能通过诱导脑自动调节曲线向右移动来损害脑自动调节。多巴胺对α - 肾上腺素能受体的刺激导致脑血管阻力增加可能会引起这种效应。本论文的主要重点是阐明多巴胺是否会诱导脑自动调节压力曲线向右移动。该论文基于四篇论文：（I）一项方法学研究，比较了两种最常用的估计脑自动调节的方法：时域分析和频域分析。我们发现这两种方法之间的一致性较差，并且当基于血压的自发变化来估计脑自动调节时，时域分析似乎是一种更可靠且更简单的描述脑自动调节的方法。（II）一项回顾性研究，通过时域分析估计极早产儿的脑自动调节。该研究发现多巴胺治疗与脑自动调节受损之间存在关联。（III）一项实验动物研究，检查多巴胺是否会影响低血压新生仔猪的脑自动调节。我们发现多巴胺对低血压新生仔猪的脑静脉饱和度、脑血流量或脑自动调节能力没有负面影响。（IV）一项体外实验，通过线肌电图和压力肌电图检查新生仔猪的大脑中动脉。在线肌电图中，多巴胺浓度增加会引起双相反应：低浓度时开始血管舒张，随后高浓度时血管收缩。在压力肌电图中，多巴胺主要诱导血管舒张，仅在最高浓度时动脉内径才趋于减小。总之，多巴胺与脑自动调节受损有关，我们在研究II中的结论与此相符。然而，其他研究发现开始输注多巴胺并不影响脑自动调节。这可能表明多巴胺本身不会导致脑自动调节受损。为支持这些相反的观察结果，我们在研究III中未发现多巴胺治疗与新生仔猪脑自动调节受损之间存在任何因果关系。此外，在研究IV中，治疗浓度的多巴胺并未诱导软脑膜动脉血管收缩。基于对当前文献的综述以及本论文中包含的研究，本论文核心问题的答案是：“不，多巴胺不会诱导脑自动调节曲线向右移动”。
