D-Amphetamine Accelerates Recovery of Consciousness and Respiratory Drive After High-Dose Fentanyl in Rats.
D-Amphetamine Accelerates Recovery of Consciousness and Respiratory Drive After High-Dose Fentanyl in Rats.
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DOI：
10.3389/fphar.2020.585356
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发表时间：
2020
影响因子：
5.6
通讯作者：
Solt K
中科院分区：
文献类型：
--
作者：
Moody OA;Zhang ER;Arora V;Kato R;Cotten JF;Solt K
在美国，芬太尼每年导致约6万人药物过量死亡。芬太尼也经常在围手术期环境中作为镇痛剂给药，其中呼吸抑制仍然是常见的临床问题。纳洛酮是一种有效的阿片拮抗剂，但它具有短半衰期和不良副作用。本研究的目的是检验右旋苯丙胺改善呼吸抑制和加速大剂量芬太尼后意识恢复的假设。成年大鼠静脉给予芬太尼（55 µg/kg）（剂量足以诱导翻正和呼吸抑制丧失），随后静脉给予d-苯丙胺（3 mg/kg）或生理盐水（溶剂）后，进行行为终点（首次头部运动、双爪向下和翻正恢复）、动脉血气分析和前额皮质局部场电位记录。与生理盐水对照组相比，D-苯丙胺使翻正恢复时间加快了36.6%。与对照组相比，D-苯丙胺也加速了动脉pH值的恢复，以及CO2、O2和sO2的分压，5 min和15 min后pH值的统计学显著差异。前额叶皮层的局部场电位记录显示，在给予d-安非他明5分钟内，芬太尼产生的<20 Hz的升高的宽带功率恢复到清醒的基线水平，与意识的恢复一致。总的来说，d-安非他明减轻了呼吸性酸中毒，增加了动脉氧合，并加速了芬太尼中毒的意识恢复。这表明，d-苯丙胺可能是一个有用的辅助或替代阿片受体拮抗剂，如纳洛酮。
In the United States, fentanyl causes approximately 60,000 drug overdose deaths each year. Fentanyl is also frequently administered as an analgesic in the perioperative setting, where respiratory depression remains a common clinical problem. Naloxone is an efficacious opioid antagonist, but it possesses a short half-life and undesirable side effects. This study was conducted to test the hypothesis that d-amphetamine ameliorates respiratory depression and hastens the return of consciousness following high-dose fentanyl. Behavioral endpoints (first head movement, two paws down, and return of righting), arterial blood gas analysis and local field potential recordings from the prefrontal cortex were conducted in adult rats after intravenous administration of of fentanyl (55 µg/kg) at a dose sufficient to induce loss of righting and respiratory depression, followed by intravenous d-amphetamine (3 mg/kg) or saline (vehicle). D-amphetamine accelerated the time to return of righting by 36.6% compared to saline controls. D-amphetamine also hastened recovery of arterial pH, and the partial pressure of CO2, O2 and sO2 compared to controls, with statistically significant differences in pH after 5 min and 15 min. Local field potential recordings from the prefrontal cortex showed that within 5 min of d-amphetamine administration, the elevated broadband power <20 Hz produced by fentanyl had returned to awake baseline levels, consistent with the return of consciousness. Overall, d-amphetamine attenuated respiratory acidosis, increased arterial oxygenation, and accelerated the return of consciousness in the setting of fentanyl intoxication. This suggests that d-amphetamine may be a useful adjunct or alternative to opioid receptor antagonists such as naloxone.
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DOI：
10.1056/nejmra0808281
发表时间：
2010-12-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brown EN;Lydic R;Schiff ND
通讯作者：
Schiff ND
影响因子：
3.5
作者：
Guidera JA;Taylor NE;Lee JT;Vlasov KY;Pei J;Stephen EP;Mayo JP;Brown EN;Solt K
通讯作者：
Solt K
影响因子：
25
作者：
Eban-Rothschild A;Rothschild G;Giardino WJ;Jones JR;de Lecea L
通讯作者：
de Lecea L
影响因子：
4.7
作者：
MEDIAVILLA, A;FERIA, M;FLOREZ, J
通讯作者：
FLOREZ, J
影响因子：
7.3
作者：
Kilkenny, Carol;Browne, William;Altman, Douglas G.
通讯作者：
Altman, Douglas G.