阿片类镇痛药芬太尼镇静和呼吸抑制相关的皮层电变化。,Scientific Reports

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阿片类镇痛药芬太尼镇静和呼吸抑制相关的皮层电变化。
Scientific Reports ( IF 3.8 ) Pub Date : 2019-10-01 , DOI: 10.1038/s41598-019-50613-2
Gaspard Montandon _{1,

2} , Richard L Horner _{1,

3}

Affiliation

阿片类药物是治疗疼痛的主要药物，但会产生呼吸抑制的副作用，过量服用可能致命。除了呼吸作用外，阿片类药物还会引起深度镇静状态，并产生大脑唤醒减少状态的电皮层特征，类似于麻醉或睡眠。在这种状态下，呼吸活动比清醒时更依赖于脑干呼吸网络的完整性。因此，我们提出芬太尼镇静会引起与大脑唤醒减少一致的特定皮层电变化，并且呼吸抑制的程度与明显的皮层电变化相关。为了实现这些目标，我们确定了芬太尼全身注射（剂量 100 µg·kg）与对照组相比对自由行为大鼠的皮层电和呼吸活动的影响。我们发现芬太尼引起的皮层电变化与睡眠或清醒时观察到的变化不同。芬太尼增加了 δ (1-3 Hz) 频率功率 (P < 0.001)，但降低了 α (7.5-13.5 Hz) 和 β2 (20-30 Hz) 功率（分别为 P = 0.012 和 P < 0.001）。觉醒。有趣的是，芬太尼对呼吸频率的抑制与 θ 功率的增加显着相关（R = 0.61，P < 0.001），因此显示皮层电活动与呼吸频率抑制程度之间存在明确的关联。总的来说，我们提供了新的证据，将特定的皮层电变化与阿片类药物引起的呼吸抑制的严重程度联系起来，这凸显了在评估阿片类药物引起的呼吸抑制时，除了考虑阿片类药物对呼吸的影响外，还必须考虑阿片类药物的皮质和皮质下效应。

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Electrocortical changes associating sedation and respiratory depression by the opioid analgesic fentanyl.

Opioid drugs are the mainstay of pain management but present the side-effect of respiratory depression that can be lethal with overdose. In addition to their respiratory effect, opioids also induce a profound sedative state and produce electrocortical features characteristic of a state of reduced brain arousal, similar to anaesthesia or sleep. In such states, respiratory activity depends more on the integrity of the brainstem respiratory network than it does during wakefulness. Accordingly, we propose that sedation by fentanyl induces specific electrocortical changes consistent with reduced brain arousal, and that the magnitude of respiratory depression is associated with distinct electrocortical changes. To these aims, we determined the effects of systemic injections of fentanyl (dosage 100 µg ·kg) versus control on electrocortical and respiratory activities of freely-behaving rats. We found that fentanyl induced electrocortical changes that differed from those observed in sleep or wakefulness. Fentanyl increased δ (1-3 Hz) frequency power (P < 0.001), but reduced α (7.5-13.5 Hz) and β2 (20-30 Hz) powers (P = 0.012 and P < 0.001, respectively), when compared to wakefulness. Interestingly, respiratory rate depression by fentanyl was significantly correlated with increased θ power (R = 0.61, P < 0.001), therefore showing a clear association between electrocortical activity and the magnitude of respiratory rate depression. Overall, we provide new evidence linking specific electrocortical changes to the severity of respiratory depression by opioids, which highlights the importance of considering the cortical and subcortical effects of opioids in addition to their impacts on breathing when evaluating opioid-induced respiratory depression.

更新日期：2019-10-01

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