Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA.
Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA.
Respir Physiol Neurobiol. 2020 Jun;277:103428. doi: 10.1016/j.resp.2020.103428. Epub 2020 Mar 6.
Breathing resumes within one to two minutes following fentanyl overdose induced apnea in spontaneously breathing rats. As this regular rhythm is produced at a time wherein fentanyl concentrations and receptor occupancy are likely to be extremely high, the mechanisms initiating and sustaining such a respiratory activity remain unclear. Forty-four un-anesthetized adult rats were studied in an open-flow plethysmograph. Regardless of the dose of fentanyl that was used, i.e. 50 μg.kg (n = 8), 100 μg.kg (n = 8) or 300 μg.kg (n = 7), all rats developed an immediate central apnea followed by a depressed regular rhythm that was produced 118, 97 and 81 s (median) later, respectively. Only one rat did not recover. This inspiratory and regular activity consisted of a low frequency and tidal volume pattern with a significant reduction in V̇E/V̇CO2 ratio, which persisted for at least 30 min and that was not different between 100 or 300 μg.kg. The time at which this respiratory rhythm emerged, following the highest dose of fentanyl, was not affected by 100 % O or 8% CO/15 % O. The absolute level of ventilation was however higher in hypercapnic and moderately hypoxic conditions than in hyperoxia. When a second injection of the highest dose of fentanyl (300 μg.kg) was performed at 10 min, ventilation was not significantly affected and no apnea was produced in major contrast to the first injection. When a similar injection was performed 30 min after the first injection, in a separate group of rats, an apnea and breathing depression was produced in 30 % of the animals, while in the other rats, ventilation was unaffected. We conclude that the depressed regular respiratory activity emerging during and following fentanyl overdose is uniquely resistant to fentanyl.
在自发性呼吸的大鼠中，芬太尼过量导致呼吸暂停后，呼吸会在 1 到 2 分钟内恢复。由于这种正常节律是在芬太尼浓度和受体占有率可能极高的情况下产生的，因此启动和维持这种呼吸活动的机制尚不清楚。44 只未麻醉的成年大鼠在开放式气流描记仪中进行了研究。无论使用的芬太尼剂量如何，即 50μg.kg（n=8）、100μg.kg（n=8）或 300μg.kg（n=7），所有大鼠都立即出现中枢性呼吸暂停，随后出现抑制性的规则节律，分别在 118、97 和 81 秒（中位数）后出现。只有一只大鼠没有恢复。这种吸气和规则活动包括低频和潮气量模式，V̇E/V̇CO2 比值显著降低，至少持续 30 分钟，在 100μg.kg 或 300μg.kg 之间没有差异。在最高剂量芬太尼给药后出现这种呼吸节律的时间不受 100% O2 或 8% CO/15% O2 的影响。然而，在高碳酸血症和中度低氧条件下，绝对通气水平高于高氧。当在 10 分钟时进行第二次最高剂量芬太尼（300μg.kg）注射时，通气没有明显受到影响，与第一次注射形成鲜明对比，没有出现呼吸暂停。当在第一次注射 30 分钟后在另一组大鼠中进行类似的注射时，30%的动物出现呼吸暂停和呼吸抑制，而在其他动物中，通气不受影响。我们得出结论，在芬太尼过量期间和之后出现的抑制性规则呼吸活动对芬太尼具有独特的抗性。
