Does analgesia and condition influence immunity after surgery? Effects of fentanyl, ketamine and clonidine on natural killer activity at different ages

Eur J Anaesthesiol. 2010 Mar;27(3):233-40. doi: 10.1097/EJA.0b013e32832d540e.


Background and objective: Cellular immunity varies in the perioperative period. We evaluated the effects of fentanyl, clonidine and ketamine at different time points after surgery and in animals in different conditions (young vs. old).

Materials and methods: Rats undergoing laparotomy under sevoflurane anaesthesia were assigned to receive saline, fentanyl (40 microg kg(-1)), clonidine (10 microg kg(-1)) or ketamine (10 mg kg(-1)) 1 h before surgery. Natural killer (NK) activity was quantified at different time points (immediately or after 18, 24, 48, 72 h and 8 days) in vitro by the lysis of YAC-1 cells. In-vivo assessment included counting the number of lung metastases induced by the MADB-106 cells.

Results: During the first 24 h after surgery, a rapid increase in NK activity was noted, followed by a significant depression returning to baseline at 8 days. Analgesics show specific effects: fentanyl depressed NK activity with or without surgery. Clonidine depressed NK activity in nonoperated animals and during the first 24 h after surgery. Ketamine depressed NK activity in nonoperated animals but, after surgery, this activity varied with the same time course as saline. Ketamine and clonidine significantly reduced the number of lung metastases in operated animals. Ketamine significantly reduced the number of metastases in old nonoperated animals. Finally, ageing has a significant negative influence.

Conclusion: Surgery, analgesics and co-existing conditions significantly influence cellular immunity. The importance of these changes varies with time. Fentanyl had a worse influence than clonidine and ketamine, but seemed equally protective against the development of metastases.

Publication types

  • Comparative Study

MeSH terms

  • Age Factors
  • Analgesia / adverse effects*
  • Analgesia / trends
  • Animals
  • Clonidine* / toxicity
  • Fentanyl* / toxicity
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Ketamine* / toxicity
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / immunology*
  • Male
  • Rats
  • Rats, Wistar
  • Risk Factors


  • Ketamine
  • Clonidine
  • Fentanyl