The purpose of this randomised, single-centre study was to prospectively investigate the impact of anaesthetic techniques for craniotomy on the release of cytokines IL-6, IL-8, IL-10, and to determine whether intravenous anaesthesia compared to inhalational anaesthesia attenuates the inflammatory response. The study enroled 40 patients undergoing craniotomy, allocated into two equal groups to receive either sevoflurane (n = 20) or propofol (n = 20) in conjunction with remifentanil and rocuronium. The lungs were ventilated mechanically to maintain normocapnia. Remifentanil infusion was adjusted according to the degree of surgical manipulation and increased when mean arterial pressure and the heart rate increased by more than 30 % from baseline. The depth of anaesthesia was adjusted to maintain a bispectral index (BIS) of 40–60. Invasive haemodynamic monitoring was used. Serum levels of IL-6, IL-8 and IL-10 were measured before surgery and anaesthesia, during tumour removal, at the end of surgery, and at 24 and 48 h after surgery. Postoperative complications (pain, vomiting, changes in blood pressure, infection and pulmonary, cardiovascular and neurological events) were monitored during the first 15 days after surgery. Compared with patients anaesthetised with sevoflurane, patients who received propofol had higher levels of IL-10 (p = 0.0001) and lower IL-6/IL-10 concentration ratio during and at the end of surgery (p = 0.0001). Both groups showed only a minor response of IL- 8 during and at the end of the surgery (p = 0.57). Patients who received propofol had higher levels of IL-10 during surgery. Neither sevoflurane nor propofol had any significant impact on the occurrence of postoperative complications. Our findings should incite future studies to prove a potential medically important anti-inflammatory role of propofol in neuroanaesthesia. Identified as NCT02229201 at www.clinicaltrials.gov

Extracorporeal hemadsorption may reduce inflammatory reaction in cardiopulmonary bypass (CPB) surgery. Glucocorticoids have been used during open-heart surgery for alleviation of systemic inflammation after CPB. We compared intraoperative hemadsorption and methylprednisolone, with usual care, during complex cardiac surgery on CPB, for inflammatory responses, hemodynamics, and perioperative course. Seventy-six patients with prolonged CPB were recruited and randomized, with 60 included in final analysis. Allocation was into three groups: Methylprednisolone (n = 20), Cytosorb (n = 20), and Control group (usual care, n = 20). Proinflammatory (TNF-α, IL-1β, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines which complement C5a, CD64, and CD163 expression by immune cells were analyzed within the first five postoperative days, in addition to hemodynamic and clinical outcome parameters. Methylprednisolone group, compared to Cytosorb and Control had significantly lower levels of TNF-α (until the end of surgery, p<0.001), IL-6 (until 48 h after surgery, p<0.001), and IL-8 (until 24 h after surgery, p<0.016). CD64 expression on monocytes was the highest in the Cytosorb group and lasted until the 5^th postoperative day (p<0.016). IL-10 concentration (until the end of surgery) and CD163 expression on monocytes (until 48 h after surgery) were the highest in the Methylprednisolone group (p<0.016, for all measurements between three groups). No differences between groups in the cardiac index or clinical outcome parameters were found. Methylprednisolone more effectively ameliorates inflammatory responses after CPB surgery compared to hemadsorption and usual care. Hemadsorption compared with usual care causes higher prolonged expression of CD64 on monocytes but short lasting expression of CD163 on granulocytes. Hemadsorption with CytoSorb® was safe and well tolerated. This trial is registered with clinicaltrials.gov (NCT02666703).

Inflammatory response in surgery is associated with the release of cytokines. Many cytokines are produced by macrophages; therefore surgical injuries to the liver may have great influence on the release of cytokines. Ischemia creates tissue injury and may contribute to the cytokine release. A balanced ratio of pro- and anti-inflammatory cytokines is important for appropriate immune response; excessive inflammation or hypo-responsiveness can lead to post-operative complications. To determine the magnitude of the cytokine response caused by liver surgery and to evaluate the balance of pro- and anti-inflammatory cytokines released during the operation, we measured levels of tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-1beta, IL-6 and IL-10 in 19 patients undergoing liver resection. The results showed a continuous rise of IL-6 and a transient elevation of IL-10. Levels of TNFalpha remained low; IL-1beta was not detected at any sampling time. We conclude that liver surgery induces cytokine response characterized predominantly by an early appearance of IL-6 and IL-10, the elevation of IL-6 may be mainly caused by splanchnic ischemia. The IL-6/IL-10 ratio could possibly reflect the balance of pro- and anti-inflammatory cytokines in liver surgery better than the TNFalpha/IL-10 ratio, which can well represent inflammatory status in sepsis.

Measurement of cardiac troponin in serum is an essential part of diagnosing myocardial infarction in the emergency department. The guidelines suggest that high-sensitivity techniques should be used for measuring cardiac troponin I (cTnI) or cardiac troponin T (cTnT). The aim of our study was to correlate the values of both troponins, and to ascertain which type of troponin is more in agreement with the diagnosis. The patients were classified into four groups: 43 patients in non-ST-elevation myocardial infarction (NSTEMI), 7 in ST-elevation myocardial infarction (STEMI), 48 in Type 2 myocardial infarction, and 21 in the control group. A significant correlation between cTnI and cTnT was found in the NSTEMI (r = 0.70) and Type 2 (r = 0.75) groups while in the control group there was no association (r = −0.06). The ratios of cTnI and cTnT relative to their cut-off values were lower in Type 2 myocardial infarction compared to NSTEMI. This difference can be attributed to the pathophysiology of these two types of heart conditions. The ratio in the NSTEMI group was higher in female than in male patients (53.3 vs. 24.6 ng/L); the same difference was found for the ratio of cTnT (20.8 vs. 13.1 ng/L). In the same manner, the ratios in the Type 2 group were higher in female than in male patients for cTnI (25.6 vs. 12.7 ng/L) as well as for cTnT (19.0 vs. 6.73 ng/L). These differences could be due to biological differences, but they could also be influenced by other factors contributing to different damage responses.

Background and Aim. Our previous study showed that the empagliflozin-metformin combination significantly improved arterial function; i.e., it improved endothelial function (measured by flow-mediated dilation and reactive hyperaemia index) and reduced arterial stiffness (measured as pulse wave velocity and local carotid artery stiffness) in adults with type 1 diabetes. In the present study, we explored the underlying mechanism by investigating the antioxidative and anti-inflammatory properties of the empagliflozin-metformin combination (compared to the individual drugs or placebo) and its association with improving arterial function. Methods. 40 individuals with type 1 diabetes (average age of years) were randomized into four groups: (1) control (placebo), (2) empagliflozin 25 mg daily, (3) metformin 2000 mg daily, and (4) empagliflozin-metformin combination (25 mg and 2000 mg daily, respectively). At inclusion and after 12 weeks of treatment, the blood samples were collected, and the oxidative stress (total antioxidative status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx), uric acid, advanced oxidation protein products (AOPP), advanced glycosylation end products ((AGE) and isoprostane), and inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) parameters were determined. Results. The empagliflozin-metformin combination increased levels of the antioxidants (TAS, SOD, and GPx up to 1.1-fold; ), decreased the levels of prooxidants (AOPP and isoprostanes up to 1.2-fold, ; AGE up to 1.5-fold, ), and decreased inflammatory parameters (up to 1.5-fold, CRP ; IL-6 ). Antioxidative action was associated with the improvement in arterial function (obtained in the previous study) in the empagliflozin-metformin combination group. Conclusion. Empagliflozin-metformin combination has strong antioxidative and anti-inflammatory capacity, in adults with type 1 diabetes that is greater than that for the individual drugs. Its antioxidative activity at least partially explains the improvement in arterial function. Therefore, it appears that the combination provides the most powerful vascular protection.

Sugammadex reverses neuromuscular block (NMB) through binding aminosteroid neuromuscular blocking agents. Although sugammadex appears to be highly selective, it can interact with other drugs, like corticosteroids. A prospective single-blinded randomized clinical trial was designed to explore the significance of interactions between dexamethasone and sugammadex. Sixty-five patients who were anesthetized for elective abdominal or urological surgery were included. NMB was assessed using train-of-four stimulation (TOF), with rocuronium used to maintain the desired NMB depth. NMB reversal at the end of anaesthesia was achieved using sugammadex. According to their received antiemetics, the patients were randomized to either the granisetron or dexamethasone group. Blood samples were taken before and after NMB reversal, for plasma dexamethasone and rocuronium determination. Primary endpoint was time from sugammadex administration to NMB reversal. Secondary endpoints included the ratios of the dexamethasone and rocuronium concentrations after NMB reversal versus before sugammadex administration. There were no differences for time to NMB reversal between the control (mean 121 ± 61 s) and the dexamethasone group (mean 125 ± 57 s; P = 0.760). Time to NMB reversal to a TOF ratio ≥0.9 was significantly longer in patients with lower TOF prior to sugammadex administration (Beta = −0.268; P = 0.038). The ratio between the rocuronium concentrations after NMB reversal versus before sugammadex administration was significantly affected by sugammadex dose (Beta = −0.375; P = 0.004), as was rocuronium dose per hour of operation (Beta = −0.366; p = 0.007), while it was not affected by NMB depth before administration of sugammadex (Beta = −0.089; p = 0.483) and dexamethasone (Beta = −0.186; p = 0.131). There was significant drop in plasma dexamethasone after sugammadex administration and NMB reversal (p < 0.001). Administration of dexamethasone to anesthetized patients did not delay NMB reversal by sugammadex. The trial was retrospectively registered with The Australian New Zealand Clinical Trials Registry (ANZCTR) on February 28th 2012 (enrollment of the first patient on February 2nd 2012) and was given a trial ID number ACTRN12612000245897 and universal trial number U1111-1128-5104.