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.

Comparison of two patient-controlled analgesia techniques on neuropsychological functioning in the immediate postoperative period.

Pain may contribute to cognitive decline, which is a common complication in the early postoperative period. We compared the effects of two common pain management techniques, intravenous patient-controlled analgesia (PCA-IV) and patient-controlled epidural analgesia (PCEA), on cognitive functioning in the immediate postoperative period. Patients hospitalized for elective surgery were randomly assigned to one of the treatment groups (30 patients per group). A battery of objective, standardized neuropsychological tests was administered preoperatively and 24 hours after surgery. Pain intensity was also evaluated. Nonoperated volunteers served as controls. Patients of the PCA-IV group exhibited significantly higher pain scores than did patients of the PCEA group. PCA-IV patients exhibited significant deterioration in the postoperative period in all the neuropsychological measures, while the PCEA patients exhibited significant deterioration only in one cognitive index, compared to controls.

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.

Blood rheology in PCA and PCEA after total knee arthroplasty.

The rheological events in 2 groups of patients undergoing total knee arthroplasty were compared--15 patients were given general anesthesia and controlled their postoperative pain applying intravenous patient-controlled analgesia; 17 individuals received combined spinal-epidural anesthesia and controlled their postoperative pain by patient-controlled epidural analgesia (PCEA). Twenty-four and 48 hours after surgery, the patient-controlled analgesia group showed a significant increase in whole-blood viscosity at the 3 shear rates (P < .01), as well as in relative viscosity at both periods (P < .001 and .01, respectively). Similar findings were observed for red blood cell aggregation (P < .001) and fibrinogen level (P < .001). These values were less expressed in the PCEA group, particularly 48 hours after surgery (P < .01), and the patients showed lower scores on the visual analog pain scale. The better results observed in the PCEA group favor the application of epidural anesthesia and PCEA analgesia in patients undergoing total knee arthroplasty.

The effects of perioperative pain management techniques on food consumption and body weight after laparotomy in rats.

UNLABELLED: We examined the effects of two perioperative pain management techniques on recovery after laparotomy, as assessed by body weight (BW) and food consumption (FC). All rats received a preoperative intrathecal mixture of morphine plus bupivacaine combined with one of two treatments: (a) injection of slow-release morphine at the end of the surgery or (b) an antiinflammatory drug, interleukin-1 receptor antagonist (IL-1ra), combined with the preoperative mixture. Laparotomy significantly decreased FC and BW. Both analgesic treatments resulted in a faster recovery of FC and BW. This beneficial effect was more pronounced in the group receiving preoperative analgesics combined with IL-1ra. IMPLICATIONS: Effective perioperative pain management can improve postoperative recovery. We studied the effects of two preoperative pain management techniques on recovery after laparotomy in rats. Both analgesic treatments resulted in a faster recovery, especially preoperative analgesics combined with interleukin-1 receptor antagonist.

Effects of surgical stress on brain prostaglandin E2 production and on the pituitary-adrenal axis: attenuation by preemptive analgesia and by central amygdala lesion.

Surgical stress is the combined result of tissue injury, anesthesia, and postoperative pain. It is characterized by elevated levels of adrenocorticotropin (ACTH), corticosterone (CS), and elevated levels of prostaglandin E2 (PGE2) in the periphery and in the spinal cord. The present study examined the effects of perioperative pain management in rats undergoing laparotomy on serum levels of ACTH, CS, and on the production of PGE2 in several brain regions, including the amygdala. The amygdala is known to modulate the pituitary-adrenal axis response to stress. We, therefore, also examined the effects of bilateral lesions in the central amygdala (CeA) on laparotomy-induced activation of the pituitary-adrenal axis in rats. In the first experiment, rats either underwent laparotomy or were not operated upon. Half the rats received preemptive analgesia extended postoperatively, the other received saline. ACTH, CS serum levels, and ex vivo brain production of PGE2 were determined. In the second experiment, rats underwent bilateral lesions of the CeA. Ten days later, rats underwent laparotomy, and ACTH and CS serum levels were determined. Laparotomy significantly increased amygdala PGE2 production, and CS and ACTH serum levels. This elevation was markedly attenuated by perioperative analgesia. Bilateral CeA lesions also attenuated the pituitary-adrenal response to surgical stress. The present findings suggest that the amygdala plays a regulatory role in mediating the neuroendocrine response to surgical stress. Effective perioperative analgesia attenuated the surgery-induced activation of pituitary-adrenal axis and PGE2 elevation. The diminished elevation of PGE2 may suggest a mechanism by which pain relief mitigates pituitary-adrenal axis activation.

Rheological events following laparoscopic and conventional laparotomy.

Laparoscopic surgery has become a widely used procedure with many advantages compared to conventional laparotomy. Although rare, this technique is not entirely absent from clinical hazards and particularly thromboembolic events. This complication is due to activation of the coagulation cascade, as well as factors that may cause alterations in blood rheology. Apart from high hematocrit, presence of abnormal proteins and elevated fibrinogen level, the type of anesthesia, temperature, and increased intra-abdominal pressure following CO(2) insufflation may affect blood viscosity. Therefore, the objective of the study was to compare rheological events in 17 patients undergoing laparoscopic surgery to those in 15 patients who underwent laparotomy. Both groups of patients did not show any complications during the early and late post-operative period. The values of whole blood viscosity in patients undergoing laparoscopy did not differ from those in patients treated by laparotomy. A slight, although significant decrease in plasma viscosity and red blood cell aggregation was observed in patients who underwent laparotomy. The results suggest that the benefits of laparoscopic surgery in the present series were not affected by alterations in blood and plasma viscosity, as well as in red blood cell aggregation.

The effects of postoperative pain management on immune response to surgery.

Surgery is associated with immune alterations, which are the combined result of tissue damage, anesthesia, postoperative pain, and psychological stress. In the present study, we compared the effects of several postoperative pain management techniques on postoperative immune function. Patients hospitalized for abdominal surgery were randomly assigned to one of three postoperative pain management techniques: opiates on demand (intermittent opiate regimen [IOR]), patient-controlled analgesia (PCA), and patient-controlled epidural analgesia (PCEA). Postoperative pain was assessed. Blood samples were collected before and 24, 48, and 72 h after surgery. Production of interleukin (IL)-1beta, IL-2, and IL-6, natural killer cell cytotoxicity, and lymphocyte mitogenic responses were assessed. Patients of the PCEA group exhibited lower pain scores in the first 24 h after surgery compared with patients of the IOR and PCA groups. Mitogenic responses were suppressed in all groups in the first 24 h, returned to preoperative values by 72 h in the PCEA group, but remained suppressed in the PCA group. Production of IL-1beta and IL-6 increased in the IOR and PCA groups, whereas it remained almost unchanged in the PCEA group. Patients receiving an epidural mixture of opiate and local anesthetics (PCEA group) exhibited reduced suppression of lymphocyte proliferation and attenuated proinflammatory cytokine response in the postoperative period.

Effects of preemptive analgesia on pain and cytokine production in the postoperative period.

BACKGROUND: The postoperative period is associated with increased production of proinflammatory cytokines, which are known to augment pain sensitivity, among other effects. In a previous study, the authors found that patients treated with patient-controlled epidural analgesia (PCEA) exhibited attenuated proinflammatory cytokine response in the postoperative period. In the present study, the authors examined whether preemptive analgesia continued with PCEA may further attenuate the proinflammatory cytokine response and reduce pain sensitivity in the postoperative period. They compared cytokine production in two groups of patients, one receiving PCEA, the other receiving preemptive epidural analgesia continued by PCEA. METHODS: Female patients hospitalized for transabdominal hysterectomy were randomly assigned to one of two pain management techniques: PCEA or preemptive epidural analgesia followed by PCEA (PA + PCEA). Postoperative pain was assessed using the visual analog scale. Blood samples were collected before, 24, 48, and 72 h following surgery. Production of the following cytokines was assessed in stimulated peripheral blood mononuclear cells: interleukin (IL)-1beta, tumor necrosis factor alpha, IL-6, IL-1ra, IL-10, and IL-2. RESULTS: Patients of the PA + PCEA group exhibited lower pain scores throughout the 72 h postoperatively, compared with patients of the PCEA group. In patients of the PA + PCEA group in the postoperative period, production of IL-1beta, IL-6, IL-1ra, and IL-10 was significantly less elevated, while IL-2 production was significantly less suppressed. CONCLUSIONS: Proinflammatory cytokines are key mediators of illness symptoms, including hyperalgesia. The present results suggest that preemptive epidural analgesia is associated with reduced postoperative pain and attenuated production of proinflammatory cytokines.