Similar effects of general and spinal anaesthesia on perioperative stress response in patients undergoing haemorrhoidectomy

Surgery induces release of neuroendocrine hormones (cortisol), cytokines (interleukin-6: IL-6, tumour necrosis factor-alpha: TNF-alpha), acute phase proteins (C-reactive protein: CRP, leptin). We studied the effects of general and spinal anaesthesia on stress response to haemorrhoidectomy. Patients were assigned to general and spinal anaesthesia groups (n = 7). Blood samples were drawn before induction and 24 hours after surgery. Perioperative levels of IL-6, TNF-alpha, CRP, cortisol, and leptin were comparable among the groups. Twenty four hours after surgery, TNF-alpha and cortisol did not change; IL-6 and CRP increased significantly in all patients. Significant increase in leptin levels was found in patients undergoing spinal anaesthesia. Except for the increase in leptin levels, there was no significant difference related to the effects of general and spinal anaesthesia.     

The time course of inflammatory cytokine secretion in a rat model of postoperative pain does not coincide with the onset of mechanical hyperalgesia

We characterized the time course of inflammatory cytokine release at the site of injury and in plasma after surgery on the rat tail. Anesthetized Sprague-Dawley rats had a 20 mm long incision made through the skin and fascia of their tails. Control rats were anesthetized, but no incision was made. Blood and tissue samples were taken 2 h and 1, 2, 4, and 8 days after surgery and analysed by ELISA for interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In another group of rats, daily behavioral measurements were made of the rats' responses to a blunt noxious mechanical stimulus (4 Newtons) applied to their tails. Primary hyperalgesia developed within 2 h of surgery and lasted for 6 days. The tissue concentrations of IL-1beta, IL-6, and CINC-1 increased within 24 h of surgery, and TNF-alpha concentration increased within 48 h of surgery. Thereafter, cytokine concentrations remained elevated for 4 (IL-1beta and IL-6) to 8 days (CINC-1, TNF-alpha) after surgery. Control animals did not develop hyperalgesia and no changes in cytokines concentrations were detected. Thus, in our model of postoperative pain, secretion of inflammatory cytokines IL-1beta, IL-6, TNF-alpha, and CINC-1 was not essential for the initiation of postoperative hyperalgesia.     

IL-6 enhances plasma IL-1ra,IL-10, and cortisol in humans

The purpose of the present study was to test the hypothesis that a transient increase in plasma IL-6 induces an anti-inflammatory environment in humans. Therefore, young healthy volunteers received a low dose of recombinant human (rh)IL-6 or saline for 3 h. Plasma IL-6 levels during rhIL-6 infusion were approximately 140 pg/ml, corresponding to the levels obtained during strenuous exercise. The infusion of rhIL-6 did not induce enhanced levels of the proinflammatory cytokine TNF-alpha but enhanced the plasma levels of the two anti-inflammatory cytokines IL-1 receptor agonist (IL-1ra) and IL-10 compared with saline infusion. In addition, C-reactive protein increased 3 h post-rhIL-6 infusion and was further elevated 16 h later compared with saline infusion. rhIL-6 induced increased levels of plasma cortisol and, consequently, an increase in circulating neutrophils and a decrease in the lymphocyte number without effects on plasma epinephrine, body temperature, mean arterial pressure, or heart rate. In conclusion, this study demonstrates that physiological concentrations of IL-6 induce an anti-inflammatory rather than an inflammatory response in humans and that IL-6, independently of TNF-alpha, enhances the levels not only of IL-1ra but also of IL-10. Furthermore, IL-6 induces an increase in cortisol and, consequently, in neutrocytosis and late lymphopenia to the same magnitude and with the same kinetics as during exercise, suggesting that muscle-derived IL-6 has a central role in exercise-induced leukocyte trafficking.     

Depression of plasma levels of cytokines and ex-vivo cytokine production in relation to the activity of the pituitary-adrenal axis, in patients undergoing major vascular surgery.

The relation between the immune and neuroendocrine response during surgery was studied. In 18 patients undergoing major vascular surgery, circulating interleukin (IL)-1beta and ex-vivo production of IL-1beta and tumour necrosis factor (TNF)-alpha were lower on day 1 after surgery compared to pre-operation values (-14+/-5%, P<0.05; -62+/-9%, P<0.05; and -31+/-54%, P<0.005, respectively). Circulating IL-1 receptor antagonist (IL-1ra) was higher on the 5th day post-operatively compared to pre-operation values (mean +640%+/-400, P<0.05).In a more detailed study in six patients, the ex-vivo production of IL-1beta and TNF-alpha started to decrease at induction of general anaesthesia and dropped to under 10% of initial values at the end of surgery. Circulating IL-1ra and ex-vivo production of IL-1ra started to increase at the end of surgery and remained elevated up to 6 days post-operatively. Plasma antidiuretic hormone (ADH) and adrenocorticotropic hormone (ACTH) increased during surgery, but cortisol remained unchanged.We demonstrate a depression of circulating pro-inflammatory IL-1beta and an increase of circulating anti-inflammatory IL-1ra during surgical stress. The ex-vivo production of IL-1beta and TNF-alpha was suppressed, indicating a downregulation of the production of these cytokines. This parallelled the hormonal reaction with high ADH and ACTH, but not of cortisol, suggesting that glucocorticoid is not the key-factor in downregulation of production and release of pro-inflammatory cytokines.     

Dynamic change in plasma leptin level during the perioperative period

OBJECTIVE: To examine the association of plasma leptin level with insulin, which is known as a metabolic regulator of leptin, and various stress-related factors during the perioperative period. METHODS: Thirty-one patients undergoing gastrectomy were enrolled and blood samples were obtained preoperatively, intraoperatively, immediately after operation, and on the first and second postoperative days. RESULTS: The plasma leptin level showed a triphasic response. Immediately after operation, the leptin level was the lowest, while the serum cortisol and interleukin-6 (IL-6) levels had their peak (PHASE 1). On the first postoperative day, the leptin level had its peak with the serum cortisol and IL-6 level remaining elevated (PHASE 2). On the second postoperative day, while the serum cortisol and IL-6 levels still remained elevated, the plasma leptin level fell to the preoperative value (PHASE 3). The plasma leptin level correlated well with the insulin level at all time points during the study period. CONCLUSION: Our results suggest a possible role of leptin in harmonizing neuroendocrine and immune responses with energy balance.     

Stress induced IL-10 does not seem to be essential for early monocyte deactivation following cardiac surgery

An increase in circulating levels of IL-10 is believed to contribute to immunosuppression caused by major surgery. Cortisol and catecholamines have been shown to be important costimulatory factors for IL-10 secretion in humans. As thoracic epidural block (TEB) should blunt the perioperative increases in cortisol and catecholamines we investigated whether IL-10 secretion is influenced by TEB. Twenty-six patients undergoing coronary artery bypass graft surgery using cardiopulmonary bypass were randomized to receive either general anesthesia (GA) or GA plus TEB. Sensory and pain levels were measured to demonstrate clinical effectiveness. Plasma concentrations of epinephrine, norepinephrine, cortisol, IL-6 and IL-10 as well as monocyte surface expression of HLA-DR and their ex vivo capacity to release TNF-alpha after LPS stimulation were measured perioperatively. TEB was clinically effective and patients receiving TEB showed decreased circulating levels of IL-10. However, this decrease was independent of decreased levels of cortisol or epinephrine. No influence of TEB on IL-6 levels, monocyte capacity to ex vivo release TNF-alpha upon LPS stimulation or their expression of HLA-DR was found. In conclusion, high TEB reduces antiinflammatory immune suppressing mediators including IL-10 and stress mediators. At least in cardiac surgery patients the monocyte functional depression is not related to systemic release of IL-10 and the influence of cortisol or epinephrine is less important for early monocyte deactivation than what in vitro and animal models have suggested.     

Ghrelin as an acute-phase reactant during postoperative stress response.

Ghrelin is a growth hormone-releasing peptide, discovered in 1999 by Kojima et al. Its potential role in inflammation and stress response is not yet clear. The purpose of this study was to characterize perioperative levels of circulating ghrelin in relation to different surgical procedures. The authors compared plasma ghrelin changes with cortisol, cytokines, and acute-phase proteins. The prospective study was performed on 22 patients with resection for colon cancer (group 1). Group 2, functioning as a comparative group, consisted of 22 patients with elective laparotomic cholecystectomy. Plasma concentrations of ghrelin, cortisol, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta, IL-6, IL-8, soluble IL-2 receptor, C reactive protein, and alpha1-antitrypsin were estimated repeatedly during a 72-hour postoperative period. Data revealed significant elevation of plasma ghrelin 24 hours after resection of coli (median 508.0 ng/l, interquartile range 398.2-633.7 ng/l) in relation to both preoperative levels (317.6 ng/l, 253.4-355.1 ng/l, p<0.01) and group 2 maximal postoperative levels (386.2 ng/l, 324-432 ng/l, p<0.05). Ghrelin levels returned to initial status 36-48 hours after surgery with subsequent decline to subnormal levels. The regression coefficient was the highest for ghrelin and TNF-alpha 24 hours after laparotomy (r=0.64, p<0.05) and for ghrelin and IL-6 24 hours after surgery (r=0.56, p<0.05). Maximal postoperative levels of all tested parameters except for cortisol and IL-1beta differed significantly between both patient groups at p<0.05. After large abdominal surgery, ghrelin shows itself as an acute-phase reactant. The significant correlation between ghrelin and inflammatory cytokines supposes their regulatory role in this period. Our comparison of more- and less-invasive surgical procedures with similar nutritional restrictions argues for a dominant role of inflammatory factors in postoperative ghrelin elevation.     

鼻内镜动力切削术对鼻前庭囊肿患者CRP、TNF-alpha、IL-6 及IL-8 的影响

目的：探讨鼻内镜下动力切削系统治疗对鼻前庭囊肿患者CRP、TNF-alpha、IL-6 和IL-8 的影响。方法：选取2012 年6 月至2013 年1 月我院收治的鼻前庭囊肿患者163 例,随机分为两组。实验组（80 例）行鼻内镜下动力切削系统行囊肿切除术,对照组（83 例）给予微波治疗。观察并比较两组患者手术前后血清CRP、TNF-alpha、IL-6 和IL-8 水平的变化情况,并比较两组患者手术情况、术 后并发症及远期疗效。结果：与对照组比较,实验组手术时间较长,术中出血量较多,差异具有统计学意义（P＜0.05）,实验组术后 感染率较低,术后复发率较低;术后CRP、TNF-alpha、IL-6 和IL-8水平升高,与对照组相比,实验组各项指标较高（P<0.05）。结论：鼻内 镜下动力切削系统治疗鼻前庭囊肿具有较好的临床治疗效果,且复发率低,值得临床推广。     

Tumor necrosis factor-alpha/interleukin-10 balance in normal and cystic fibrosis children

BACKGROUND: The balance between tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) is important for immune homeostasis maintenance. Exuberant production of TNF-alpha contributes to overwhelming inflammatory response and tissue damage. But, commonly, increase in TNF-alpha is counterbalanced by simultaneous synthesis of an anti-inflammatory cytokine IL-10, which suppresses production of many activating and regulatory mediators. AIMS: In the present study, the relationships between TNF-alpha and IL-10 in the plasma of healthy school-children and cystic fibrosis (CF) patients have been investigated. METHODS: Blood samples were obtained from 12 CF patients with chronic pulmonary disease and 18 healthy schoolchildren vaccinated with live attenuated rubella vaccine. IL-10 and TNF-alpha were determined in the plasma samples using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Before vaccination, most healthy children (13 of 18) demonstrated superiority of pro-inflammatory TNF-alpha over anti-inflammatory IL-10 (TNF-alpha/IL-10 > 1). In these subjects, a significant positive linear association between the cytokine values has been found. Vaccine challenge resulted in a marked reduction of TNF-alpha/IL-10 ratios. In addition, a disappearance of correlation between the cytokine values was observed. Such disturbance was related to exuberant elevation of the IL-10 levels after inoculation. On the contrary, in CF individuals, plasma cytokine values remained in strong linear association independently of TNF-alpha or IL-10 predominance. No spikes in the plasma levels of IL-10 in CF patients during a 6-month observation period have been revealed. CONCLUSIONS: There were no fundamental differences between CF and healthy children in the regulation of TNF-alpha and IL-10 secretion. Thus, immune quiescence seemed to be associated with the predominance of TNF-alpha, whereas immune disturbance was characterized by IL-10 superiority. The only abnormality that was found in CF patients consisted of their inability to produce unlimitedly IL-10 in response to antigen stimuli.     

Serum leptin levels in septic men correlate well with C-reactive protein (CRP) and TNF-alpha but not with BMI

Leptin, an adipocyte-derived signaling factor, is a member of the IL-6 cytokine family. However there is no direct evidence of leptin stimulation of the acute phase protein (APP) synthesis which is typical for all other IL-6-like factors. The purpose of this study was to characterize the dynamics of circulating leptin in relation to ten APPs. We used postoperative septic patients as a model of cytokine network hyperstimulation and intensive APP reaction. The prospective study was performed on 22 patients with proven postoperative intraabdominal sepsis after large abdominal surgery. Plasma levels of leptin, TNF-alpha, IL-1beta, soluble IL-2 receptor (sIL-2R), IL-6 (ELISA analysis) and ten APPs (nephelometric analysis) were estimated. We have demonstrated a statistically significant elevation of plasma leptin concentrations in the septic group compared with healthy subjects (p<0.001). The correlation of plasma leptin and BMI during postoperative sepsis was diminished. The regression coefficient was the highest for leptin and CRP (r=0.48, p<0.05), and for leptin and alpha-1-antitrypsin (r=0.46, p<0.05) in the septic group. There was significant correlation between TNF-alpha and leptin (r=0.47, p<0.05) and between IL-6 and leptin (r=0.45, p<0.05) in septic patients. No significant correlation was found between leptin and "negative" APP and between leptin and IL-1beta. Leptin has thus been shown as an acute phase reactant with a potential hematopoietic, immunomodulatory and hepatocyte stimulating activity during the infectious and non-infectious stress response. The significant correlation between leptin and CRP and leptin and alpha-1-antitrypsin indicates that leptin can participate in APP synthesis regulation during a systemic inflammatory response.     

Abrogation of surgery-induced IL-6 hypersecretion by presurgical immunotherapy with IL-2 and its importance in the prevention of postoperative complications

Because of its immunosuppressive effect, surgery-induced immunosuppression may depend at least in part on the postoperative hypersecretion of IL-6, which is also responsible for surgical complications. Most of the immunosuppressive events induced by surgery, including lymphocytopenia, NK and T lymphocyte decline, and dendritic cell deficiency have been proven to be abrogated by a preoperative injection of IL-2 for few days. However, the cytokine mechanisms responsible for IL-2-induced abrogation of surgery-related immunosuppression need to be better investigated and understood. This study was performed to analyze the influence of IL-2 presurgical immunotherapy on IL-6 secretion in the postoperative period. The study was performed in 12 operable colorectal cancer patients, who were preoperatively pretreated with IL-2 (12 million lU/day subcutaneously for 3 consecutive days before surgery). The control group consisted of 21 age-and disease-matched colorectal cancer patients who underwent surgery without a preoperative immunotherapy with IL-2. Serum levels of IL-6 were measured by an enzyme immunoassay before surgery, and at days 3 and 7 of the postoperative period. A significant increase in mean serum levels of IL-6 occurred in the postoperative period only in the control patients, whereas in the IL-2 pretreated group no significant difference was seen between presurgical and postoperative IL-6 mean concentrations. The difference between controls and IL-2 group was particularly evident for patients with abnormally elevated presurgical values of IL-6. This study, by showing that a presurgical injection of IL-2 may prevent surgery-induced IL-6 enhanced secretion, would suggest that the previously described neutralization of surgery-induced immunosuppression by IL-2 preoperative immunotherapy may depend at least in part on the inhibition of postoperative production of IL-6, whose immunosuppressive effects have been well demonstrated at least on anticancer immunity.     

Plasma inflammatory cytokine response to surgical trauma in chronic depressed patients

We investigated inflammatory cytokine response in chronic depressed patients during abdominal surgery. Twenty-five major depressed patients (Group D) and twenty-five patients (Group C) as the control were studied. Plasma interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured before and at 15 min after induction of anesthesia, the end of surgery, 24 h and 3 days after the operation. Plasma IL-6 concentrations in Group D at the end of the operation and 24 h after surgery were significantly lower than those of Group C. The plasma IL-6 concentration (87.1+/-55.3 pg/ml) of patients scoring more than 18 points in the Hamilton depression-rating score at the end of the operation was significantly higher than 57.5+/-76.7 pg/ml of patients scoring less than 18 points. Plasma IL-8 concentration (6.1+/-3.2 pg/ml) in Group D at the end of the operation was significantly lower than 8.7+/-4.2 pg/ml of Group C. We conclude that plasma IL-6 and IL-8 response to surgical trauma is inhibited in chronic depressed patients. The IL-6 response to surgical trauma is depending on the clinical state of depression.     

Serum IL-1beta,sIL-2R,IL-6, IL-8 and TNF-alpha in schizophrenic patients,relation with symptomatology and responsiveness to risperidone treatment.

Activation of the inflammatory response system and varied levels of cytokines in acute schizophrenia have been suggested by recent studies. Psychopharmacologic agents can differentially effect cytokine production, which suggests that therapeutic function of neuroleptics may involve immunomodulation. The present study was carried out to examine: (i) serum concentrations of interleukin (IL)-1beta, soluble interleukin-2 receptor (sIL-2R), IL-6, IL-8 and tumour necrosis factor (TNF)-alpha in schizophrenic patients; (ii) their relation with psychopathological assessment; and (iii) the relation of the initial cytokine levels with responsiveness to risperidone therapy. Thirty-four drug-free schizophrenic patients with acute exacerbation and 23 age- and gender-matched healthy controls were recruited for this study. Psychopathological assessments at admission and throughout risperidone treatment for 60 days were recorded. Serum cytokine concentrations were determined with chemilumunescence assays. According to our results, serum IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha concentrations adjusted for age, gender, body mass index and smoking were no different in patients with schizophrenia and controls and among subtypes of schizophrenia. However, the initial TNF-alpha concentrations had a significant effect on Brief Psychiatric Rating Scale and Scale Assessment of Positive Symptoms scores. The initial cytokine concentrations of the patients responsive to risperidone were not significantly different from those of non-responsive patients. The present study demonstrates that plasma levels of IL-1beta, sIL-2R, IL-6, IL-8 and TNF-alpha adjusted for confounding factors are not altered in drug-free schizophrenic patients at acute exacerbation. We suggest that, if cytokine production is altered in schizophrenia, these alterations may not be detectable in systemic circulation. According to our results, the therapeutic effect of risperidone is not related to basal levels of the aforementioned cytokines. However, serum TNF-alpha may contribute to symptomatology in schizophrenia     

Interleukin-6 and perioperative thermoregulation and HPA-axis activation

Surgery is followed by an acute-phase response, including hypothalamo-pituitary-adrenal (HPA)-axis activation and fever. Considering its physiological properties and its behaviour in plasma after stress and surgery, the pro-inflammatory cytokine interleukin (IL)-6 is a putative candidate in eliciting these stress-related symptoms. However, evidence for this hypothesis is lacking. Rats subjected to individual psychological stress for 1h were injected intraperitoneally with saline or 3.33 microg per 100g rat neutralizing antibodies against rat IL-6. Thereafter, the single-housed rats were anaesthetized for 25 min, with or without undergoing a laparotomy. Intermittently, oesophageal temperatures were measured at defined time points. A parallel group of rats undergoing the same study protocol were decapitated, at time points when body temperatures differed, to obtain blood for measurement of plasma adrenocorticotropic hormone and corticosterone. Individual housing resulted in hyperthermia. Antibodies against IL-6 accelerated normalization of body temperature after individualizing stress, limited postoperative hyperthermia after laparotomy, but accentuated hyperthermia after anaesthesia alone. Antibody administration was not able to significantly influence the plasma hormone levels during any experiment. The present study indicates that IL-6 is a thermoregulatory factor during psychological, anaesthesiological and surgical stress, but the cytokine does not participate in HPA-axis activation until 6h after anaesthesia or surgery. A dose-finding study with antibodies against IL-6 ought to further identify the degree of contribution of IL-6 to perioperative thermoregulation.     

IL-8 in septic shock, endotoxemia, and after IL-1 administration

Much effort has been directed toward elucidating the host response to sepsis and inflammation, resulting in the definition of a cascade of endogenous mediators that direct metabolic and immunological responses. Here we report that IL-8, a novel cytokine produced by a variety of cells in vitro in response to stimulation with bacterial LPS and the proinflammatory cytokines, appears in the circulation of primates in vivo during septic shock, sublethal endotoxemia, and after the administration of IL-1 alpha. The magnitude of the IL-8 response correlates with the severity of the insult, and levels of IL-8 peak relatively late, after those of TNF-alpha and IL-1 beta, and simultaneously with those of IL-6. IL-8 has been primarily defined as a selective activator and chemoattractant of neutrophils, and we demonstrate that after LPS or IL-1 alpha infusion, circulating neutrophil numbers rapidly recover from an initial neutropenia while IL-8 concentrations are maximal, supporting the hypothesis that IL-8 influences circulating leukocyte populations in vivo. We conclude that IL-8 is another participant in the cytokine cascade elicited by sepsis and inflammation and, as such, may play a significant role in host defense and disease.     

Androstenediol ameliorates alterations in immune cells cytokine production capacity in a two-hit model of trauma-hemorrhage and sepsis

Although administration of androstenediol (a metabolite of dehydroepiandrosterone) following trauma-hemorrhage (T-H) produces beneficial effects on inflammatory cytokines and organ function, it remains unknown whether this metabolite has any salutary effects in preventing alterations in immune cell cytokine production following a combined insult of T-H and sepsis. To examine this, male rats underwent laparotomy, hemorrhagic shock (mean BP 40 mmHg for 90 min) and resuscitation or sham operation. Androstenediol (1 mg/kg BW i.v.) or vehicle was administered at the end of resuscitation. Twenty hrs after T-H or sham operation, sepsis was induced by cecal ligation and puncture (CLP). Five hours thereafter, plasma cytokine levels and cytokine production of various immune cells were determined. In a separate set of experiments, survival was monitored for 10 days after the induction of sepsis. Administration of androstenediol markedly decreased plasma IL-6 and TNF-alpha levels following T-H and CLP. Furthermore, it prevented the increased production of IL-6 and TNF-alpha by Kupffer cells and alveolar macrophages and attenuated the decrease in IL-6 and TNF-alpha production by splenic macrophages; however, it had no significant effects on the depressed IL-6 and TNF-alpha production by PBMC following T-H and CLP. The depressed IL-2 and IFN-gamma production by splenocytes under those conditions was attenuated by the administration of androstenediol. Furthermore, survival rate following T-H and subsequent sepsis was improved by androstenediol treatment. Since androstenediol administration following T-H attenuated cytokine production and reduced mortality in a double-hit model of T-H and sepsis, this agent appears to be a novel and useful adjunct for maintaining the immune cell functions following T-H and for decreasing the mortality rate from subsequent susceptibility to sepsis.     

Tumour necrosis factor-alpha (TNFalpha) and interleukin-10 are crucial mediators in post-operative systemic inflammatory response and determine the occurrence of complications after major abdominal surgery

BACKGROUND: The course of serum cytokine levels in patients with postoperative systemic inflammatory response syndrome (SIRS) after major abdominal surgery remains currently unclear. METHODS: Blood was sampled pre- and post-operatively and on days 1 and 2 in 40 patients undergoing major abdominal surgery. Concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin (IL) -6, IL-8, and IL-10 were measured by the LINCOplex assay; those of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by an enzyme immunoassay. RESULTS: Compared to their pre-operative values, sTREM-1 was elevated on day 2; TNFalpha on day 1; IL-6 and IL-10 post-operatively and on days 1 and 2; and IL-8 post-operatively and on day 1. The duration of operation correlated with TNFalpha and IL-10 at all sampling times, and with IL-6 post-operatively. There were no differences in cytokine concentrations between patients who exhibited post-operative complications and those who did not. IL-10/TNFalpha below 30 was found in all patients with complications (100%) and in 20 patients without complications (64.5%, p: 0.043). CONCLUSIONS: SIRS following major surgery is characterised by complex alterations in cytokine concentrations. The balance between TNFalpha and IL-10 seems to determine the occurrence of post-operative complications.     

Pravastatin immunomodulates IL-6 and C-reactive protein, but not IL-1 and TNF-alpha, in cardio-pulmonary bypass

BACKGROUND: While statins are increasingly used in cardiopulmonary bypass (CPB), the anti-inflammatory effects of individual statins, within the context of various treatment regimes, need further examination. The present study evaluates the anti-inflammatory effectiveness of the short-term, preoperative and intensive postoperative use of pravastatin in CPB. METHOD: Forty three patients undergoing CPB were enrolled in a randomized, prospective clinical study. One group (n = 21), received pravastatin, the other (n = 22) did not. Patients in the pravastatin group received one dose of 40 mg per day for nine days, starting 48 hours before CPB, with an additional dose of 40 mg one hour after surgery. Plasma levels of selected inflammatory mediators were measured at baseline and tracked systematically. RESULTS: Pravastatin reduced postoperative interleukin-6 (IL-6) levels significantly at 24 and 48 hours, and at seven days. Mean +/- SD values, for treated versus untreated patients were: at 24 hours, 159.5 +/- 58.5 versus 251.2 +/- 53.0 pg/mL (p < 0.001); at 48 hours, 81.9 +/- 31.5 versus 194.2 +/- 56.3 pg/mL (p < 0.001); and at seven days, 16.4 +/- 7.2 versus 30.8 +/- 12.6 (p < 0.001). C-reactive protein (CRP) decreased significantly on the seventh postoperative day, when plasma levels were 3.6 +/- 1.1 in the treated patients versus 8.2 +/- 2.1 mg/dL in the controls (p < 0.001). No changes in plasma IL-1 and TNF-alpha were found during entire study. CONCLUSIONS: Pravastatin induced a precocious modulation of IL-6 expression and a later reduction of plasma CRP levels. Pravastatin;s effects on the expression of these pivotal inflammatory mediators strongly support its well-timed use in CPB.     

Epidural analgesia improves postoperative nitrogen balance.

Postoperative nitrogen balance was monitored in twelve patients undergoing hysterectomy under either epidural analgesia or general anaesthesia. The mean cumulative five-day nitrogen losses were significantly lower after epidural analgesia than after general anaesthesia. Nitrogen sparing presumably results from inhibiting the stress-induced release of catabolic hormones, since epidural analgesia abolished postoperative hyperglycaemia and increase in plasma cortisol concentrations. No adverse effects of inhibiting the stress response were observed. Neurogenic stimuli thus play a crucial part in the catabolic response to surgery. Inhibiting the endocrine metabolic response to trauma by neurogenic blockade may reduce the morbidity precipitated in high-risk patients by the catabolic response to surgery.