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  Table of Contents  
COMMENTARY
Year : 2019  |  Volume : 56  |  Issue : 2  |  Page : 187-188
 

Ketamine for post-thoracotomy pain: An old drug with new horizons


Department of Onco-Anesthesiology and Palliative Medicine, Dr. B.R.A Institute Rotary Cancer Hospital, AIIMS, Delhi, India

Date of Web Publication2-May-2019

Correspondence Address:
Nishkarsh Gupta
Department of Onco-Anesthesiology and Palliative Medicine, Dr. B.R.A Institute Rotary Cancer Hospital, AIIMS, Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_18_19

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How to cite this article:
Dattatri R, Gupta N. Ketamine for post-thoracotomy pain: An old drug with new horizons. Indian J Cancer 2019;56:187-8

How to cite this URL:
Dattatri R, Gupta N. Ketamine for post-thoracotomy pain: An old drug with new horizons. Indian J Cancer [serial online] 2019 [cited 2019 May 23];56:187-8. Available from: http://www.indianjcancer.com/text.asp?2019/56/2/187/257545




Thoracotomy is considered as the most painful of all surgical procedures with complex multifactorial pathophysiology. Both nociceptive and neuropathic mechanisms have been implicated. Following skin incision, rib retraction, muscle splitting, parietal pleura injury, intercostal nerves convey nociceptive somatic afferents to the ipsilateral dorsal horn of spinal cord which are then transmitted to limbic system and somatosensory cortex. Injury to visceral pleura, bronchi and pericardium activates nociceptive visceral afferents which are carried by phrenic and vagus nerves.[1] The inflammatory mediators released cause “primary sensitization” (increase the nociceptor activity and the pain response) and “central sensitization” (hyperexcitability of dorsal horn neurons and higher pain centers through calcium influx triggered NMDA receptor activation).[2] In addition, intercostal nerve injury during thoracic surgeries causes neuropathic pain via different mechanisms that leads to hyperalgesia, allodynia, hyperpathia and dysesthesia. The poorly controlled post-thoracotomy pain can lead to pulmonary dysfunction, disturbed sleep, prolonged recovery, increased hospital stay, financial burden and chronic pain. The involvement of multiple pathways, receptors, mediators in pain processing and transmission adds to the difficulty in treating this pain necessitating multimodal analgesia. The involvement of NMDA receptors in pain transmission raises the hope of possible role of ketamine (NMDA receptor antagonist) in preventing thoracotomy pain. Multimodal analgesia also helps to reduce the opioid consumption peri-operatively as it is associated with adverse effects like nausea, vomiting, paralytic ileus, constipation, pruritus, respiratory depression, urinary retention. Another concern regarding opioids in oncosugical patients is suppression of both cell mediated and humoral immunity by these drugs which might contribute to cancer recurrence and metastases.[3] Also, with increasing evidence that a significant proportion of opioid naive patients are at a risk of becoming chronic opioid users post-surgery, the onus of responsibility of minimizing opioid use peri-operatively lies on the anesthesiologist.[4]

Ketamine is a phencyclidine derivative and binds to NMDA receptor in a non-competitive manner to modulate the central sensory pain processing. It is a versatile drug with both anesthetic and analgesic actions. It also has a potent antihyperalgesic action, counteracts opioid induced hyperalgesia and prevents development of opioid tolerance.[1] The exact mechanism of ketamine is unclear. Despite these beneficial effects, the popularity of ketamine was limited mainly due to dose dependent side effects (due to D2 receptor blockade) in particular CNS and psychomimetic effects which include but not limited to dizziness, diplopia, dysphoria, hallucinations, nystagmus, confusion, sleep disturbances.[5] Ketamine at high doses may cause hepatotoxicity although single bolus dose does not affect liver function tests.[6]

Ketamine with its ability to interrupt peripheral and central transmission of pain signaling may be a promising alternative to opioids for post thoracotomy pain. Randomized controlled studies evaluating the role of intravenous ketamine for post-thoracotomy pain control and prevention of post-thoracotomy pain syndrome have demonstrated its effectiveness in reducing acute post-surgical pain thereby reducing the opioid consumption although it was not found to be effective in preventing persistent post-surgical pain.[6],[7],[8] The authors a letter in this issue have also reported the beneficial role of intravenous ketamine in successful management of persistent post-thoracotomy pain in 3 patients with high opioid requirement using a dose of 0.2-0.3 mg/kg as a slow iv infusion over 1 hour.[9]

A systematic review of perioperative ketamine use for post-thoracotomy by Moyse et al. reported its beneficial analgesic role in the immediate perioperative period due to its ability in preventing central and peripheral pain processing as well as pain transmission along with favorable side effect profile.[1] Mathew et al. established that low dose ketamine with morphine PCA is safe, provided better post-operative pain control, reduced morphine consumption and improved pulmonary function compared with morphine PCA alone.[10]

The role of NMDA receptors in pain transmission, the need for alternative analgesics to opioids especially in the light of public health crises and its possible role in immunosuppression particularly in cancer patients have led to renewed interest in ketamine. The published evidence demonstrates the opioid sparing effect of ketamine in sub anesthetic doses and its utility as a perioperative adjunct albeit in limited studies. Ketamine can have wider use in perioperative period although larger RCT's are needed to compare different dose ranges, safety profile in patients with other comorbidities (cardiovascular disease, chronic kidney disease, hepatic dysfunction, neurological disease, cancer patients). But, the dose relationship between subanesthetic dose of ketamine and psychomimetic effects is still not understood well.



 
  References Top

1.
Moyse DW, Kaye AD, Diaz JH, Qadri MY, Lindsay D, Pyati S. Perioperative ketamine administration for thoracotomy pain. Pain Physician 2017;20:173-84.  Back to cited text no. 1
    
2.
Mesbah A, Yeung J, Gao F. Pain after thoracotomy. BJA Educ 2016;16:1-7.  Back to cited text no. 2
    
3.
Colvin LA, Fallon MT, Buggy DJ. Cancer biology, analgesics, and anaesthetics: Is there a link? Br J Anaesth 2012;109:140-3.  Back to cited text no. 3
    
4.
Brummett CM, Waljee JF, Goesling J, Moser S, Lin P, Englesbe MJ, et al. New persistent opioid use after a major and minor surgical procedures in US adults. JAMA Surg 2017;152:e170504.  Back to cited text no. 4
    
5.
Seeman P, Ko F, Tallerico T. Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics. Mol Psychiatry 2005;10:877-83.  Back to cited text no. 5
    
6.
Mendola C, Cammarota G, Netto R, Cecci G, Pisterna A, Ferrante D, et al. S(+)-ketamine for control of perioperative pain and prevention of post thoracotomy pain syndrome: A randomized, double-blind study. Minerva Anestesiol 2012;78:757-66.  Back to cited text no. 6
    
7.
Chumbley GM, Thompson L, Swatman JE, Urch C. Ketamine infusion for 96 hr after thoracotomy: Effects on acute and persistent pain. Eur J Pain 2019;23:985-93.  Back to cited text no. 7
    
8.
Argiriadou H, Papagiannopoulou P, Foroulis CN, Anastasiadis K, Thomaidou E, Papakonstantinou C, et al. Intraoperative infusion of S(+)-ketamine enhances post-thoracotomy pain control compared with perioperative parecoxib when used in conjunction with thoracic paravertebral ropivacaine infusion. J Cardiothorac Vasc Anesth 2011;25:455-61.  Back to cited text no. 8
    
9.
Kumbhare PP, Bakshi SG, Purohit R. Ketamine-an essential component of post operative pain management following oncosurgeries: TMH experience. Indian J Cancer 2019;56:186.  Back to cited text no. 9
  [Full text]  
10.
Mathews TJ, Housden T, Dunning J. Does adding ketamine to morphine patient-controlled analgesia safely improve post-thoracotomy pain? Interact Cardiovasc Thorac Surg 2012;14:194-9  Back to cited text no. 10
    




 

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