The effect of perioperative intravenous lidocaine on postoperative pain and immune function.

BACKGROUND: Surgery-associated tissue injury leads to nociception and inflammatory reaction, accompanied by increased production of proinflammatory cytokines. These cytokines can induce peripheral and central sensitization, leading to pain augmentation. Recently, a frequently used local anesthetic, lidocaine, was introduced as a part of a perioperative pain management technique. In addition to its analgesic effects, lidocaine has an antiinflammatory property, decreasing the upregulation of proinflammatory cytokines. We focused on the effects of preincisional and intraoperative IV lidocaine on pain intensity and immune reactivity in the postoperative period. METHODS: Sixty-five female patients (ASA physical status I-II) scheduled for transabdominal hysterectomy were recruited to this randomized, placebo-controlled study. Thirty-two patients in the treatment group received IV lidocaine starting 20 min before surgery, whereas the control group (33 patients) received a matched saline infusion. Both groups received patient-controlled epidural analgesia during the postoperative period. Blood samples were collected before, 24, 48, and 72 h after surgery to measure ex vivo cytokine production of interleukin (IL)-1 receptor antagonist (IL-1ra) and IL-6, as well lymphocyte mitogenic response to phytohemagglutinin-M. A 10-cm visual analog scale was used to assess pain intensity at rest and after coughing. RESULTS: Patients in the lidocaine + patient-controlled epidural analgesia group experienced less severe postoperative pain in the first 4 and 8 h after surgery (visual analog scale 4/3.7 at rest and 5.3/5 during coughing versus 4.5/4.2 and 6.1/5.3, respectively, in the placebo group). There was significantly less ex vivo production of IL-1ra and IL-6, whereas the lymphocyte proliferation response to phytohemagglutinin-M was better maintained than in the control group. CONCLUSION: The present findings indicate that preoperative and intraoperative IV lidocaine improves immediate postoperative pain management and reduces surgery-induced immune alterations.

Relationship between fentanyl dosage and immune function in the postoperative period.

BACKGROUND: Anesthesia and surgery are associated with impairment of the immune system expressed as an excessive proinflammatory immune response and suppression of cell mediated immunity. Opioids, an integral part of anesthetic technique, possess an inhibitory effect on both humoral and cellular immune responses. It was the aim of the present study to examine the effect of various doses of fentanyl on cytokine production during the perioperative period. INTERVENTION: The effect of large (LDFA, 70-100 microg/kg), intermediate (IDFA, 23-30 microg/kg) and small (SDFA, 2-4 microg/kg) doses of fentanyl on the immune function in the postoperative period was investigated. PARTICIPANTS: Sixty patients, randomly assigned to one of the three groups according to the dose of fentanyl were included in the study. METHODS: The ex vivo secretion of IL-1beta, IL-2, IL-6, and IL-10 and NK cell cytotoxicity (NKCC) of peripheral blood mononuclear cells (PBMC) was tested before, and at 24, 48, and 72 hours following surgery. RESULTS: The pattern of postoperative secretion of the proinflammatory cytokines IL-1beta and IL-6 and that of the anti-inflammatory cytokine IL-10 differed significantly between patients receiving SDFA and those receiving IDFA and LDFA, but was similar between the last two groups. A similar suppression of NKCC and IL-2 secretion was observed in the three groups. CONCLUSIONS: The diminished proinflammatory cytokine response observed in patients treated by LDFA and IDFA suggests that although more stable immune function can be achieved by those methods in comparison with SDFA, it is recommendable to apply IDFA to avoid the side effects that might be observed using LDFA method.

Comparison of postoperative pain management techniques on endocrine response to surgery: a randomised controlled trial.

The present study compared three postoperative pain management techniques in patients undergoing lower abdominal surgery: intermittent opiate regimen (IOR), patient-controlled analgesia (PCA), and patient-controlled epidural analgesia (PCEA), on cortisol and prolactin levels during the first 48 h postoperatively. Ninety-two patients scheduled for a lower abdominal surgery, were randomly assigned to one of three study groups: IOR (N=31), PCA (N=31), and PCEA (N=30). Patients of the IOR group received postoperatively 50-75 mg of pethidine IM on demand. Patients of the PCA group received a loading dose of morphine (3-4 mg), followed by 1mg bolus of morphine IV per demand. Patients of the PCEA group received 3 ml of 0.1% bupivacaine plus 2 microg/ml of fentanyl per demand, with continuous background infusion of 6ml/h. Venous blood samples were collected preoperatively, and 24 and 48 h after surgery, and were later assayed for serum cortisol and prolactin levels. Patients of the PCEA group exhibited diminished postoperative elevation of serum cortisol levels at 24 and 48 h (24.4, 18.6 microg/dl, respectively) compared with both IOR (31.9, 21.9) and PCA (28.5, 22.3) groups. Similarly, patients of the PCEA group exhibited diminished postoperative elevation of serum prolactin level (20.7, 15.7 ng/mL) compared with PCA (24.9, 17.1) group. The present results indicate that the PCEA technique offers an advantageous treatment associated with reduced postoperative pain, and attenuated neuroendocrine response.

Tramadol does not impair the phagocytic capacity of human peripheral blood cells.

PURPOSE: The inhibitory effect of opioids on phagocytic cell capacity is well established. However, the effect of synthetic analgesics on this aspect of cell function is controversial. It was the aim of the study to compare the in vitro effect of tramadol with that of morphine on the engulfing ability of peripheral blood phagocytic cells from healthy volunteers. METHODS: Peripheral blood polymorphonuclear cells and monocytes from healthy volunteers were incubated with 5, 10 and 20 microg.mL(-1) tramadol, or with 20, 40 and 80 etag.mL(-1) morphine. To each tube, 0.05 mL of 5% suspension of latex beads 0.8 microm in diameter was added. After incubation for 60 min the percentage of cells engulfing latex particles and the phagocytic index (number of particles phagocytized by each individual cell) were detected. RESULTS: Tramadol affected neither the percentage of cells phagocyting latex particles, nor the phagocytic index of both polymorphonuclear cells and monocytes. On the other hand, incubation with 20, 40 and 80 etag.mL(-1) morphine caused 11%, 14% and 24% decrease in phagocytosis (P < 0.01 - P < 0.001). The percentage of monocytes phagocyting latex particles was lower by 16%, 19% and 12% at the three doses tested (P < 0.01 - P < 0.001). The three doses of morphine caused a dose dependent decrease in the monocyte phagocyting index by 20%, 29% and 35.5% respectively (P < 0.05). The polymorphonuclear phagocyting index was not significantly lower following incubation with the drug (P = 0.053). CONCLUSION: The lack of noxious effect of tramadol on the engulfing capacity of phagocytic cells suggests additional benefit to the relatively safe profile of the drug.