skip to main content

Combination of Low Dose Ketamine, Paracetamol, and Tramadol for Opioid Induces Hyperalgesia in Lung Cancer with Intra Abdominal Metastases

*Boyke Marthin Simbolon  -  Department of Anaesthesiology; Intensive Care and Pain Management/ Siloam Dhirga Surya Hospital; Medan, Indonesia
Mual Kristian Sinaga  -  Department of Anaesthesiology; Intensive Care and Pain Management/ Siloam Dhirga Surya Hospital; Medan, Indonesia

Citation Format:

Background: Opioid induced hyperalgesia or OIH is one of exaggerated response to pain secondary to using of the opioid itself. High dosage of opioid in long term (days to weeks) relate to increased OIH occurrence.

Case: Female, 58 yrs, BMI 17.77, complained severe abdominal pain with NRS 8/10. Patient suffered from lung cancer stage 3 with intra abdominal metastases. Previously patient had received analgesic paracetamol 1gr TID, dexketoprofen 25mg TID, parecoxib 40mg OD, morphine 10mg BD and fentanyl patch 50 µg. Then fentanyl was given 25 µg IV twice with interval of 15 minutes. Patient still complained for pain and eventually pain severity increased to NRS 10/10. Afterwards patient was given low dose ketamin 0.1mg/kg slow IV push, paracetamol 1gr IV, and tramadol 50mg IV. After 15 minutes observation, pain decreased to NRS 5/10.

Discussion: Decreasing total dose of opioid consumed may decresed OIH. It may be performed by improving analgesia by using combination of analgesic and intervention strategy.

Conclusion: combination of low dose ketamine (0.1mg/kg), paracetamol, and tramadol may be benefit for patient with opioid induces hyperalgesia in lung cancer stage 3 with intra abdominal metastases.

Note: This article has supplementary file(s).

Fulltext View|Download |  common.other
Kombinasi Ketamin dosis rendah, Paracetamol, dan Tramadol untuk mengatasi Hiperalgesia akibat Opioid pada Tumor Intra Abdomen akibat Metastase Paru
Subject low dose ketamine, opioid-induced hyperalgesia, and NMDA receptor antagonist
Type Other
  Download (24KB)    Indexing metadata
Keywords: abdominal metastases; abdominal pain; low dose ketamine; numeric rating scale; opioid induced hyperalgesia
Funding: a person

Article Metrics:

  1. Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neural. 2014; 13:924-935
  2. DuPen A, Shen D, Ersek M. Mechanisms of opioid-induced tolerance and hyperalgesia. Pain Manag Nurs. 2007;8: 113-121
  3. Angst MS, Clarck JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006; 104: 570-587
  4. Chu LF, Angst MS, Clark D. Opioid–induced hypergesia in humans: molecular mechanisms and clinical considerations. Clin J Pain. 2008; 24: 479-496
  5. Elliot K, Minami N, Kolesnikov YA, Pastemak GW, Inturrisi CE. The NMDA receptor antagonists, LY274614 and MK-801, and the nitric oxide synthase inhibitor, NG-nitro-L-arginine, attenuate analgesic tolerance to the µ-opiod morphine but not to kappa opioids. Pain. 1994; 56, 69-75
  6. Kolesnikov YA, Pick CG, Ciszewska G, Pasternak GW. Blockade of tolerance to morphinee but not to kappa opioids by a nitric oxide synthase inhibitor. Proc Nalt Acad Sci U S A. 1993; 90: 5162-5166
  7. Majeed NH, Przewlocka B, Machelska H, Przewlocki R. Inhibition of nitric oxide synthase attenuates the development of morphinee tolerance and dependence in mice. Neuropharmacology. 1994; 33: 189-192
  8. Przewlocki R, Machelska H, Przewlocka B. inhibition of nitric oxide synthase enhances morphinee antinocicepption in the rat spinal sord. Life Sci. 1993; 53:PL1-5
  9. Mao J, Price DD, Zhu J, Lu J, Mayer DJ. The inhibition of nitric oxide-activated poly(ADP-ribose) synthetase attenuates trans synaptic alteration of spinal cord dorsal horn neurons and neuropathic pain in the rat. Pain. 1997; 72: 355-366
  10. Vanderrah TW, Gardell LR, Burgess SE, Ibrahim M, Dogrul A. Dynorphin promotes abnormal pain and spinal opioid anti nociceptive tolerance,. J Neurosci. 2000; 20: 7074-7079
  11. Gardell LR. Sustained morphinee exposure induces a spinal dynorphin-dependent enhancement of excitatory transmitter release from primary afferent fibers. J. Neurosci. 2002; 22:6747-6755
  12. Mao J, Price DD, Mayer DJ. Mechanisms of hyperalgesia and morphinee tolerance: a current view of their possible interactions. Pain. 1995; 62: 259-274
  13. Morgan MM, Heinricher MM, Fields HL. Circuitry linking opioid-sensitive nociceptive modulatory systems in periaqueductal gray and spinal cord with rostral ventromedial medulla. Neuroscience. 1992; 47, 863-867
  14. Heinricher MM, Morgan MM, Tortorici V, Fields HL. Disinhibition off-cells and antinociception produced by an opioid action within the rostral ventromedial medulla. Neuroscience. 1994; 63: 279-288
  15. Meng ID, Harasawa I. Chronic morphinee exposure increase the proportion of on-cells in the rostral ventromedial medulla in rats. Life Sci. 2007; 80: 1915-1920
  16. Vanderah,TW. tonic descending from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociception tolerance. J Neurosci. 2001; 21, 279-286
  17. Li X, Clarck JD. Hyperalgesia during opioid abstinence: mediation by glutamate and substance p. Anesth Analg. 2002; 95: 979-984, table of contents
  18. Lee M, Silverman SM, Hansen H, Patel VB, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician. 2011; 14:145-161
  19. Hemstapat K, Monteith GR, Smith D, Smith MT. Morphinee-3-glucuronide’s neuro-excitatory effect are mediated via indirect activation of N-methyl-Daspartic acid receptors: mechanistic studies in embryonic cultured hippocampal neurons. Anesth. Analg. 2003; 97: 494-505
  20. Smith MT. Neuroexitatory effects of morphinee: evidence implicating the 3-glucuronide metabolites. Clin Exp Pharmachol Physiol. 2000; 27: 524-528
  21. Wright AW, Mather LE, Smith MT. Hydromorphone-3-glucoronide: a more potent neuro-excitant than its structural analogue, morphinee-3-glucoronide. Life Sci. 2001; 69: 409-420
  22. Raffa RB, Pergolizzi Jr JV. Opioid-induced hyperalgesia: is it clinically relevant for the treatment of pain patients? Pain Manag Nurs. 2013; 14: e67-83
  23. Velayudhan A, Bellingham G, Forster MP. Opioid - induced hyperalgesia. Continiung Education in Anaesthesia, Critical Care & Pain. 2014; 14 : 125-129
  24. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg. 2003; 97:1730-9

Last update:

No citation recorded.

Last update:

No citation recorded.