![]() Fentanyl is commonly administered as a potent analgesic in a variety of formulations, including intravenous, transdermal, and sublingual. This suggests that d-amphetamine may be a useful adjunct or alternative to opioid receptor antagonists such as naloxone.įentanyl is 50–100 times more potent than morphine ( Suzuki and El-Haddad, 2017), and causes respiratory depression, chest wall rigidity, and loss of consciousness which can rapidly lead to hypoxia, hypercarbia, and death if not treated promptly ( Henderson et al., 2014 Lalley et al., 2014 Torralva and Janowsky, 2019). Overall, d-amphetamine attenuated respiratory acidosis, increased arterial oxygenation, and accelerated the return of consciousness in the setting of fentanyl intoxication. 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. 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. D-amphetamine accelerated the time to return of righting by 36.6% compared to saline controls. 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). This study was conducted to test the hypothesis that d-amphetamine ameliorates respiratory depression and hastens the return of consciousness following high-dose fentanyl. Naloxone is an efficacious opioid antagonist, but it possesses a short half-life and undesirable side effects. Fentanyl is also frequently administered as an analgesic in the perioperative setting, where respiratory depression remains a common clinical problem. In the United States, fentanyl causes approximately 60,000 drug overdose deaths each year. 2Department of Anaesthesia, Harvard Medical School, Boston, MA, United States.1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States.Zhang 1, Vipin Arora 1,2, Risako Kato 1,2, Joseph F.
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