Effects Of Sufentanil, Remifentanil And Fentanyl On Celluar Immunity In Patients Undergoing Esophagectomy

Objective: Opioid drugs are the most potent clinically used analgesics, however, In addition to neuronal effects, opioids potently modulate the immune functions. This modulation takes the form of an alternation in the biochemical and proliferative properetics of the various celluar components of the immune system. The present study is to evaluate the effects of sufentanil, remifentanil or fentanyl on immune response of the patients undergoing esophagectomy in terms of T lymphocytes, NK cell and cytokines.Methods: Forty-five ASAâ… orâ…¡patients of both sexes aged 45-64 yrs with BMI<30kg/m2 undergoing esophagectomy were randomly divided into 3 groups (n=15 each): sufentanil group(SF), remifentanil group(RF) and fentanyl group (F).Anesthesia was induced with propofol and sufentanil, remifentanil or fentanyl, all of them were given by target controlled infusion (TCI). The target plasma concentration (CT) of propofol was set at 3μg/ml and that of sufentanil at 0.5 ng/ml (SF), remifentanil at 5 ng/ml (RF) and at fentanyl 5 ng/ml (F). Endobronchial intubation was faciliated with vecuronium 0.1mg/kg. The patients were mechanically ventilated. PETCO₂ was maintained at 30-40 mmHg. Anesthesia was maintained with sevoflurane 0.7-1.5 MAC inhalation. BIS was maintained at 45-55. CT of sufentanil, remifentanil and fentanyl were unchanged during maintenance of anesthesia. TCI of sufentanil and fentanyl were stopped at 1h before termination of operation. TCI of remifentanil was stopped immediately after the end of operation. All the patients were sent to PACU and received IV patients controlled analgesia (PCA) after the end of operation.The analgesia was assessded using VAS score(0-10, 0=no pain, 10=worst pain). The complications of post anesthesia were recorded. Venous blood samples from ulnar vein were obtained 10min after prostration (T₀, baseline), 90 min after induction of anesthesia (T₁), immediately after termination of operation (T₂), 24h (T₃) and 72h (T₄) after the end of operation for determination of the expression of CD3⁺, CD4⁺, CD8⁺ and CD3- CD16⁺CD56⁺ of lymphocytes by flow cytometry and calculation of CD4⁺/CD8⁺ ratio, serum concentrations of IL-2 and IL-10 by ELISA.Results: The 3 groups were comparable with respect to sex ratio, age, body weight and height. There was no significant difference of the operation time, anesthesia time,MAC·h of sevoflurane in three groups (P>0.05). When immediately after termination of operation (at T2), the results of CD4⁺/CD8⁺ and the expression of CD4⁺ T cells were significantly decreased as compared to the baseline value (at T₀) in all three groups, the expression of CD3—CD16+CD56+ NK cells were significantly increased in contrast. The expression of CD8⁺ was significantly increased in fentanyl group and the expression of CD3⁺ were significantly decreased in the other groups (P<0.05). When 24h after the end of operation, The expression of CD3+ T cells and CD4+ T cells were significantly decreased as compared to the baseline value (at T₀) in three groups. Serum IL-2 concentration were significantly decreased as compared to the baseline value (at T₀) in fentanyl group and remifentanil group (P<0.05). When 72h after the end of operation, The expression of CD3+ T cells and serum IL-2 concentration were significantly decreased as compared to the baseline value (at T₀) in fentanyl group. Serum IL-10 concentration were significantly increased in fentanyl group and remifentanil group (P<0.05). The expression of CD3⁺ T cells immediately after termination of operation (at T₂) was significantly higher in fentanyl group than in remifentanil group. Serum IL-2 concentration after operation (at T₃) was significantly higher in sufentanil group than in remifentanil group. Serum IL-10 concentration after operation (at T₄) was significantly higher in remifentanil group than in sufentanil (P<0.05).Conclusion: Fentanyl increases the expression of CD8⁺ T cells and sufentanil has no effects on serum concentrations of IL-2 and IL-10, however, all of fentanyl, remifentanil and sufentanil suppress celluar immunity during perioperative period.