Immune perturbations in patients along the perioperative period: alterations in cell surface markers and leukocyte subtypes before and after surgery.

BACKGROUND: Surgery renders patients susceptible to life-threatening complications, including infections, multiple organ failure, and presumably cancer metastases. Surgery-induced immune perturbations were suggested to contribute to such deleterious effects, but also to facilitate post-injury healing. Preoperative psychological and physiological stress responses may contribute to these immune perturbations, and could thus jeopardize patients even before surgery. The current study assessed the effects of various operations on an array of immune indices during the perioperative period. To qualify immune changes before surgery, patients' immune status was also compared to that of healthy controls. METHODS: A total of 81 subjects (operated patients and healthy controls) provided up to five daily blood samples during the perioperative period, for assessment of leukocyte subtypes (granulocytes, monocytes, Tc, Th, NK, NKT, CD4+CD25+, CD8(bright)CD4(dim), and B cells) and their surface markers (HLA-DR and LFA-1). RESULTS: Even before surgery patients displayed immune perturbations, including reduced lymphocyte HLA-DR expression and increased monocyte LFA-1 expression. Following surgery, we recorded a reduction in lymphocyte numbers that was subtype specific, increased granulocyte numbers, and reduced expression of HLA-DR by lymphocytes and monocytes. Finally, no significant associations were found between alteration in leukocyte numbers and cell surface markers (although these indices showed high correlations with other variables), implying differential mediating mechanisms. CONCLUSION: Several immune alterations are manifested prior to surgery, and contribute to the marked postoperative changes, which are commonly interpreted as immune suppression. We discuss the possible adaptive and maladaptive nature of these perturbations in the context of natural injury, stress, and surgery.

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.

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.

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.

Effect of a BIOcocktail on the immune response at the early postoperative period in mice.

Since human subjects and laboratory animals may develop impaired immune response during surgery and the postoperative period, efforts have been made to preserve normal immune functions following surgery by the administration of nutritional supplements and probiotics. The present study was designed to examine the effect of a new nutritional supplement, BIOcocktail, on immune parameters in mice exposed to surgery. Forty mice were assigned to 4 groups containing 10 animals each. Two control groups (with and without subsequent sham laparotomy) were given tap water for 45 min every day for 2 weeks. The remaining 2 groups, with and without laparotomy, received BIOcocktail given orally for the same period of time. The proliferative response of splenic cells (splenocytes) stimulated with phytohemagglutinin (PHA), concanavalin A (Con A) and lipopolysaccharide (LPS) was determined by [3H]thymidine uptake. Cytokine levels were measured in splenocyte supernatants and sera using enzyme-linked immunosorbent assay (ELISA) kits. Natural killer cell activity of splenocytes was evaluated by 51Cr-release assay. Laparotomy, without BIOcocktail administration, was followed by a decreased proliferative response of splenocytes to PHA, Con A, and LPS and an increase in interleukin (IL)-6 serum level. In addition, a decreased secretion of IL-1beta, IL-12 and tumor necrosis factor (TNF)-alpha by the splenocytes was observed. Mice treated with BIOcocktail before laparotomy maintained a preoperative level of splenocyte proliferative response and serum concentrations of IL-12. It is concluded that BIOcocktail administered to mice for 2 weeks before operation resulted in the preservation of T- and B-cell proliferative response to mitogens and in the prevention of postoperative decrease in IL-12 serum level.

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.

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.