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 Table of Contents  
Year : 2022  |  Volume : 42  |  Issue : 5  |  Page : 253-254

Ketamine treats nalbuphine sebacate-induced hyperalgesia

1 Department of Anesthesiology, Chi Mei Medical Center, Liouying, Taiwan
2 Department of Anesthesiology, Chi Mei Medical Center, Tainan, Taiwan
3 Department of Anesthesiology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung; Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Date of Submission15-Dec-2020
Date of Decision09-Jan-2021
Date of Acceptance13-Jan-2021
Date of Web Publication04-May-2021

Correspondence Address:
Zhi-Fu Wu
No. 100, Tzyou 1st Road, Sanmin District, Kaohsiung City 80756
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmedsci.jmedsci_418_20

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How to cite this article:
Wu SZ, Chen JY, Wu ZF. Ketamine treats nalbuphine sebacate-induced hyperalgesia. J Med Sci 2022;42:253-4

How to cite this URL:
Wu SZ, Chen JY, Wu ZF. Ketamine treats nalbuphine sebacate-induced hyperalgesia. J Med Sci [serial online] 2022 [cited 2023 Jun 9];42:253-4. Available from: https://www.jmedscindmc.com/text.asp?2022/42/5/253/315478

Dear Editor,

We read the article, Nalbuphine sebacate interferes with the analgesic effect of fentanyl, there is a case suffered from nalbuphine sebacate (Naldebain®)-induced hyperalgesia after surgery and rescue fentanyl 100 μg, tenoxicam 20 mg, and tramadol 100 mg were in vain.[1] Here, we present a case who experienced postoperative severe pain after Naldebain® administration and relieved after ketamine treatment.

A 36-year-old female, with a height of 165.3 cm and a weight of 71.5 kg, had a right-side ovarian tumor. She underwent right salpingo-oophocystectomy with exploratory laparotomy. Thirteen hours before anesthesia, intramuscular Naldebain® 150 mg was administered. Anesthesia was induced with fentanyl 100 μg, rocuronium 10 mg, and propofol 120 mg and maintained with desflurane under entropy. During 3 h of the operation, fentanyl 100 mcg, morphine 10 mg, ketorolac 30 mg, and exhaled 8%–10% desflurane concentration were administered to manage her hyperdynamics (blood pressure: 160/85 mmHg, heart rate: around 80–100 bpm, and response entropy/state entropy: 56/53). In the postanesthetic care unit, the patient complained severe sharp wound pain with a Numerical Rating Scale (NRS) score of 8/10. After rescue morphine 5 mg, NRS is still 5/10. Ketamine 15 mg was given 20 min after rescue morphine, and pain relieved to 3/10, without any side effects. In the general ward, the numeric rating scale (NRS) was around 3/10 without received any pain killer.

A previous report that nalbuphine did not attenuate the antinociceptive effect of morphine at a dose of 5 mg/kg in rats.[2] However, Wu et al.[1] reported that Naldebain® may induced hyperalgesia perioperatively. Moreover, acute opioid tolerance and opioid-induced hyperalgesia have been reported in the clinical use of opioids for anesthesia and postoperative pain management.[3] Possible action mechanisms include increased presynaptic glutamate release and postsynaptic N-methyl-D-aspartate (NMDA) receptor activation.[3],[4] Huang et al.[5] reported that NMDA receptor antagonist, ketamine and dextromethorphan, can reduce neuroplasticity through inhibition of NMDA receptors. It is consistent with our present case.

In conclusion, anesthesiologists must notice the administration of Naldebain® before surgery; it may interfere with the analgesic effect of fentanyl[1] and then the management of hemodynamics and postoperative pain. We prefer multimodal analgesia, including local anesthetic infiltration and ketamine, to only opioid administration.


The consent for publication was gained.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Wu TS, Wu HC, Wu ZF, Huang YH. Nalbuphine sebacate interferes with the analgesic effect of fentanyl. J Med Sci 2020;40:101.  Back to cited text no. 1
  [Full text]  
Lee SC, Wang JJ, Ho ST, Tao PL. Nalbuphine coadministered with morphine prevents tolerance and dependence. Anesth Analg 1997;84:810-5.  Back to cited text no. 2
Chu LF, Angst MS, Clark D. Opioid-induced hyperalgesia in humans: Molecular mechanisms and clinical considerations. Clin J Pain 2008;24:479-96.  Back to cited text no. 3
Gu X, Wu X, Liu Y, Cui S, Ma Z. Tyrosine phosphorylation of the N-Methyl-D-Aspartate receptor 2B subunit in spinal cord contributes to remifentanil-induced postoperative hyperalgesia: The preventive effect of ketamine. Mol Pain 2009;5:76.  Back to cited text no. 4
Huang NC, Sun WZ, Wong CS. Prevention of chronic postsurgical pain: The effect of preventive and multimodal analgesia. Asian J Anesthesiol 2018;56:74-82.  Back to cited text no. 5


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