Innate immunity, coagulation and surgery

Koch, Alexander; Zacharowski, Paula A.; Boehm, Olaf; Zacharowski, Kai

doi:10.2741/3427

Cited by 7 publications

(5 citation statements)

References 101 publications

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“…A perioperative rise of several cytokines following major/cardiac surgery is well described [19,28,29,62]. Regarding perioperative TNF-α and IL-6 plasma concentrations and the influence of TLR4 SNP (Asp299Gly/Thr399Ile), our findings are similar to previous trials.…”

Section: Discussionsupporting

confidence: 88%

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Genetic variation of TLR4 influences immunoendocrine stress response: an observational study in cardiac surgical patients

et al. 2011

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IntroductionSystemic inflammation (for example, following surgery) involves Toll-like receptor (TLR) signaling and leads to an endocrine stress response. This study aims to investigate a possible influence of TLR2 and TLR4 single nucleotide polymorphisms (SNPs) on perioperative adrenocorticotropic hormone (ACTH) and cortisol regulation in serum of cardiac surgical patients. To investigate the link to systemic inflammation in this context, we additionally measured 10 different cytokines in the serum.MethodsA total of 338 patients admitted for elective cardiac surgery were included in this prospective observational clinical cohort study. Genomic DNA of patients was screened for TLR2 and TLR4 SNPs. Serum concentrations of ACTH, cortisol, interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α and granulocyte macrophage-colony stimulating factor (GM-CSF) were determined before surgery, immediately post surgery and on the first postoperative day.ResultsThirteen patients were identified as TLR2 SNP carriers, 51 as TLR4 SNP carriers and 274 patients as non-carriers. Basal levels of ACTH, cortisol and cytokines did not differ among groups. In all three groups a significant, transient perioperative rise of cortisol could be observed. However, only in the non-carrier group this was accompanied by a significant ACTH rise. TLR4 SNP carriers had significant lower ACTH levels compared to non-carriers (mean (95% confidence intervals)) non-carriers: 201.9 (187.7 to 216.1) pg/ml; TLR4 SNP carriers: 149.9 (118.4 to 181.5) pg/ml; TLR2 SNP carriers: 176.4 ((110.5 to 242.3) pg/ml). Compared to non-carriers, TLR4 SNP carriers showed significant lower serum IL-8, IL-10 and GM-CSF peaks (mean (95% confidence intervals)): IL-8: non-carriers: 42.6 (36.7 to 48.5) pg/ml, TLR4 SNP carriers: 23.7 (10.7 to 36.8) pg/ml; IL-10: non-carriers: 83.8 (70.3 to 97.4) pg/ml, TLR4 SNP carriers: 54.2 (24.1 to 84.2) pg/ml; GM-CSF: non-carriers: 33.0 (27.8 to 38.3) pg/ml, TLR4 SNP carriers: 20.2 (8.6 to 31.8) pg/ml). No significant changes over time or between the groups were found for the other cytokines.ConclusionsRegulation of the immunoendocrine stress response during systemic inflammation is influenced by the presence of a TLR4 SNP. Cardiac surgical patients carrying this genotype showed decreased serum concentrations of ACTH, IL-8, IL-10 and GM-CSF. This finding might have impact on interpreting previous and designing future trials on diagnosing and modulating immunoendocrine dysregulation (for example, adrenal insufficiency) during systemic inflammation and sepsis.

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Section: Discussionsupporting

confidence: 88%

“…Major surgery, for example, cardiac surgery with CPB, leads to a systemic inflammation which is accompanied by an activation of the HPA axis [28,29]. A significant rise of postoperative serum cortisol in cardiac surgery patients has been described in several studies over the last decades [30-34].…”

Section: Discussionmentioning

confidence: 99%

Genetic variation of TLR4 influences immunoendocrine stress response: an observational study in cardiac surgical patients

et al. 2011

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“…Nevertheless, there is a growing body of research on this important aspect of the field. Surgical/anesthesia trauma-induced stress response is mediated by a massive neuro-endocrine-hormonal flux, resulting in activation of intracellular signaling pathways and production of several molecules among which cytokines play a crucial role in regulating the function of activated cells and in preserving body homeostasis [1,2]. The intensity of such an inflammatory response is dependent on many factors, including the magnitude of tissue damage, the patient's pre-existing diseases, the type of surgery and surgeon's experience, as well as the anesthesia regimen [3,4].…”

Section: Introductionmentioning

confidence: 99%

Increased HMGB1 expression and release by mononuclear cells following surgical/anesthesia trauma

et al. 2010

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IntroductionHigh mobility group box 1 (HMGB1) is a key mediator of inflammation that is actively secreted by macrophages and/or passively released from damaged cells. The proinflammatory role of HMGB1 has been demonstrated in both animal models and humans, since the severity of inflammatory response is strictly related to serum HMGB1 levels in patients suffering from traumatic insult, including operative trauma. This study was undertaken to investigate HMGB1 production kinetics in patients undergoing major elective surgery and to address how circulating mononuclear cells are implicated in this setting. Moreover, we explored the possible relationship between HMGB1 and the proinflammatory cytokine interleukin-6 (IL-6).MethodsForty-seven subjects, American Society of Anesthesiologists physical status I and II, scheduled for major abdominal procedures, were enrolled. After intravenous medication with midazolam (0.025 mg/Kg), all patients received a standard general anesthesia protocol, by thiopentone sodium (5 mg/Kg) and fentanyl (1.4 μg/Kg), plus injected Vecuronium (0.08 mg/Kg). Venous peripheral blood was drawn from patients at three different times, t0: before surgery, t1: immediately after surgical procedure; t2: at 24 hours following intervention. Monocytes were purified by incubation with anti-CD14-coated microbeads, followed by sorting with a magnetic device. Cellular localization of HMGB1 was investigated by flow cytometry assay; HMGB1 release in the serum by Western blot. Serum samples were tested for IL-6 levels by ELISA. A one-way repeated-measures analysis ANOVA was performed to assess differences in HMGB1 concentration over time, in monocytes and serum.ResultsWe show that: a) cellular expression of HMGB1 in monocytes at t1 was significantly higher as compared to t0; b) at t2, a significant increase of HMGB1 levels was found in the sera of patients. Such an increase was concomitant to a significant down-regulation of cellular HMGB1, suggesting that the release of HMGB1 might partially derive from mononuclear cells; c) treatment of monocytes with HMGB1 induced in vitro the release of IL-6; d) at t2, high amounts of circulating IL-6 were detected as compared to t0.ConclusionsThis study demonstrates for the first time that surgical/anesthesia trauma is able to induce an early intracellular upregulation of HMGB1 in monocytes of surgical patients, suggesting that HMGB1 derives, at least partially, from monocytes.

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“…Assessment of postoperative complications was not the objective of this study, however the high contamination rates of the decontaminated probes and the types of pathogens cultured raise serious concern, especially when one considers the incidence of immune impairment amongst the population serviced in Africa, coupled with the immunosuppressive effects of surgery and anaesthesia on the host immune system (20)(21)(22)(23). Patients with HIV/AIDS, diabetes mellitus and various oncological and autoimmune conditions are particularly at risk of infection from the use of with these ineffective cleaning procedures (24).…”

Section: Acinetobacter Baumanni 3%mentioning

confidence: 99%

Nasopharyngeal temperature probes: is South Africa’s current decontamination process adequate?

Davids¹,

Cilliers²

2022

Af J Clin Exp Micro

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Background: The standard practice in many institutions incorporates nasopharyngeal probes for temperature monitoring in patients undergoing general anaesthesia. Current disinfection guidelines for these devices are not clear and they are poorly adhered to. In South Africa, these temperature probes are reused and subjected to unstandardized decontamination processes. This study sought to investigate nasopharyngeal temperature probes as possible source for cross-contamination, and assess the efficacy of current disinfection practices for these probes. Methodology: This was an analytical double-blind randomized study of 4 different disinfection protocols for 48 nasopharyngeal temperature probes. The probes were randomized to disinfection protocols that included water wash, dry wipe, hibitane® and cidex® wash. After decontamination by the respective protocol, the probes were aseptically placed in nutrient broths, manually agitated and removed, and the broths were then inoculated onto blood agar plates. After 48 hours of aerobic culture incubation at 37oC, plates were examined for growth and bacteria identified using automated bioMérieux Vitek-2 microbial identification system. Chi square and logistic regression analyses were used to assess bacterial contamination rates of the disinfected probes, in order to infer the efficacy of the decontamination processes. Results: Of the 48 nasopharyngeal temperature probes disinfected by the different protocols, 22 (45.8%) had bacterial contamination, with frequency of isolation for coagulase negative staphylococci (44%), Bacillus cereus (20%), Staphylococcus aureus (10%), Enterobacter cloaca (7%), Pseudomonas aeruginosa (4%), Pseudomonas fluorescens (3%), Acinetobacter baumannii (3%), amongst other bacterial species. Dry wipe, and water and soap methods, had statistically significant higher contamination rates of 83.3% and 66.7% than hibitane® and cidex®, with 25.0% and 8.3% respectively (X2=17.69, p<0.0001). The odds of contamination when water-wipe was used as a cleaning method was 6 times (OR=6.000; 95% CI=1.018-35.374, p=0.048) that of hibitane® method while the odds for dry-wipe was 15 times (OR=15.000, 95% CI=2.024-111.174, p=0.008). No statistically significant difference was observed in the contamination rates between cidex® and hibitane® disinfection methods(OR=0.273, 95% CI=0.024-3.093, p=0.294). Conclusion: These data shows that nasopharyngeal temperature probes are possible source of cross-contamination and pathogen transmission due to inadequacy of the decontamination processes for these temperature probes.

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Innate immunity, coagulation and surgery

Cited by 7 publications

References 101 publications

Genetic variation of TLR4 influences immunoendocrine stress response: an observational study in cardiac surgical patients

Genetic variation of TLR4 influences immunoendocrine stress response: an observational study in cardiac surgical patients

Increased HMGB1 expression and release by mononuclear cells following surgical/anesthesia trauma

Nasopharyngeal temperature probes: is South Africa’s current decontamination process adequate?

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