Waldemar Gozdzik

Unchanged Plasma Levels of the Soluble Urokinase Plasminogen Activator Receptor in Elective Coronary Artery Bypass Graft Surgery Patients and Cardiopulmonary Bypass Use

Objective and Design The soluble urokinase plasminogen activator receptor (suPAR) has been recently recognized as a potential biological marker of various disease states, but the impact of a major surgical intervention on the suPAR level has not yet been established. The aim of our study was to investigate if the induction of a systemic inflammatory reaction in response to cardiopulmonary bypass would be accompanied by an increase in the plasma suPAR level. Methods and Subjects Patients undergoing coronary artery bypass grafting under cardiopulmonary bypass (CPB) were added. Based on the baseline suPAR level, patients were divided into group 1 (suPAR within normal range) or group 2 (suPAR above range). Blood was collected before the induction of anesthesia and 6 and 24 hours after surgery. Plasma suPAR, IL-6, IL-8, TNF-α, troponin I, NT-proBNP, and NGAL were quantified to assess the impact of surgical trauma on these markers. Results The baseline suPAR level was within the normal range in 31 patients (3.3 ng/mL), and elevated in 29 (5.1 ng/mL) (p<0.001). Baseline mediators of systemic inflammatory reaction concentrations (IL-6, TNF-α, and IL-8) and organ injury indices (troponin I, NT-proBNP, and NGAL) were low and increased after surgery in all patients (p<0.05). The surgery did not cause significant changes in the suPAR level either at 6 or 24 hours after, however the difference between groups observed at baseline remained substantial during the postoperative period. Conclusions There was no change in the suPAR level observed in patients subjected to elective cardiac coronary artery bypass surgery and CPB, despite activation of a systemic inflammatory reaction.

Prolonged Cardiopulmonary Bypass is a Risk Factor for Intestinal Ischaemic Damage and Endotoxaemia

BACKGROUNDnIntestinal ischaemia-reperfusion, a frequent occurrence during cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction. We hypothesised that ischaemia-reperfusion following prolonged CPB could increase intestinal permeability and thus, lead to endotoxin translocation from the intestine to the bloodstream.nnnMATERIAL AND METHODSnPatients subjected to coronary artery bypass grafting with CPB were included: Group 1 (CPB ≥90minutes) or Group 2 (CPB <90minutes). Intestinal Fatty Acid Binding Protein (I-FABP), TNF alpha, IL6, IL8, and endotoxin levels were measured before the induction of general anaesthesia (T1), at 6 (T2), and 24hours (T3) after surgery.nnnRESULTSnThe low level of I-FABP at T1 increased for every patient in Group 1 at T2 (from 1015.5pg/mL to 2608.5pg/mL, p=0.02) and in Group 2 (from 1123.5pg/ml to 2284.0pg/ml, p<0.001). Furthermore, at T3, the I-FABP level was over three times higher in Group 1 than in Group 2 (2178pg/mL vs 615pg/mL; p<0.001). I-FABP correlated with CPB time (R=0.6, p<0.001) at T3. After surgery, endotoxins were elevated in 73% of patients in Group 1 and in 32% in Group 2 and correlated with CPB time (at T2, R=0.5, p=0.002; at T3, R=0.4, p=0.016).nnnCONCLUSIONSnThe duration of CPB is linked to the release of biomarkers that indicate ischaemic-reperfusion damage to the gastrointestinal mucosa and endotoxaemia. I-FABP assay may help to identify patients presenting with intestinal damage, who are at risk of bacterial translocation.

Beneficial effects of inhaled nitric oxide with intravenous steroid in an ischemia–reperfusion model involving aortic clamping

This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia–reperfusion injury animal model. The primary endpoint was the evaluation of circulatory, respiratory, and renal function over time. We also investigated the profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as well as renal mRNA TLR4 activation determined by quantitative real-time polymerase chain reaction analysis. Pigs (nu2009=u200919) under sevoflurane AnaConDa anesthesia/sedation were randomized and subjected to abdominal laparotomy and alternatively suprarenal aortic cross-clamping (SRACC) for 90u2009min or sham surgery: Group 1 (nu2009=u20098) iNO (80u2009ppm)u2009+u2009IV corticosteroids (25u2009mg ×3) started 30u2009min before SRACC and continued 2u2009h after SRACC release, followed with decreased iNO (30u2009ppm) until the end of observation, Group 2 (nu2009=u20098) 90u2009min SRACC, Group 3 (nu2009=u20093)—sham surgery. Renal biopsies were sampled 1u2009hr before SRACC and at 3 and 20u2009h after SRACC release. Aortic clamping increased TLR4 mRNA expression in ischemic kidneys, but significant changes were recorded only in the control group (Pu2009=u20090.016). Treatment with iNO and hydrocortisone reduced TLR4 mRNA expression to pre-ischemic conditions, and the difference observed in mRNA expression was significant between control and treatment group after 3u2009h (Pu2009=u20090.042). Moreover, animals subjected to treatment with iNO and hydrocortisone displayed an attenuated systemic inflammatory response and lowered pulmonary vascular resistance plus increased oxygen delivery. The results indicated that iNO therapy combined with IV corticosteroids improved central and systemic hemodynamics, oxygen delivery, and diminished the systemic inflammatory response and renal mRNA TLR4 expression.

Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis

PurposePre-clinical animal studies precede the majority of clinical trials. While the clinical sepsis definitions and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May, 2017. The conference goal was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the “Minimum Quality Threshold in Pre-Clinical Sepsis Studies” (MQTiPSS), to enhance translational value of these models.Methods31 experts from 13 countries participated and were divided into 6 thematic Working Groups (WG): (1) Study Design, (2) Humane modeling, (3) Infection types, (4) Organ failure/dysfunction, (5) Fluid resuscitation and (6) Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002–2013).ResultsOverall, the participants reached consensus on 29 points; 20xa0at “recommendation” (R) and 9xa0at “consideration” (C) strength. This Executive Summary provides a synopsis of the MQTiPSS consensus (Tablesxa01, 2 and 3).ConclusionsWe believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as “best practices” that should be implemented for animal sepsis models. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.

Coagulation abnormalities identified by thromboelastometry in patients with severe sepsis: the relationship to endotoxemia and mortality.

The aim of this study was to monitor the development of coagulation abnormalities in patients with severe sepsis using thromboelastometry and to assess whether increased endotoxin activity was associated with a change in coagulation. Data collected on ICU admission, day 2, 3, and 4 were analysed in 61 patients. Thromboelastometry made it possible to identify patients with a normal (group 1), hypercoagulable (group 2), or hypocoagulable (group 3) pattern. The best accuracy of thromboelastometry parameters as potential indices of coagulation abnormalities was yielded by the clot formation time and maximum clot firmness. The mortality rate was low in group 1(16%) and the presence of abnormalities, indicating either a hyper or hypocoagulation pattern, was associated with significantly higher mortality (42 and 39% respectively; Pu200a=u200a0.05). In group 1, baseline endotoxin activity was low [0.22 endotoxin activity units (EAU), 0.15–0.43] and did not change significantly during the observation period. In group 2, baseline endotoxin activity was elevated (0.52 EAU (0.39–0.62)) and remained high on day 2, 3, and 4. In group 3, baseline endotoxin activity was elevated (0.56 EAU (0.28–0.80)) and similarly to group 2, remained high on day 2, 3, and 4. The presence of coagulation disorders indicates a high-risk subpopulation of critically ill patients as reflected in significantly higher mortality rates and increased endotoxin activity.

A clinical comparison of the Laryngeal Tube™ and the Laryngeal Mask™ in spontaneously breathing anesthetized patients

Abstract: Background: The laryngeal mask airway (LMA) can be used in general anaesthesia without neuromuscular block. The laryngeal tube (LT) is a new airway device with similar airway features as LMA. LT is provided with a distal cuff to prevent regurgitation. In this study we compared the LMA and LT concerning patient and user aspects.Methods: Sixty patients with ASA (American Society of Anestesiologists) score 1–2 scheduled for minor surgery were randomized to be ventilated either through LMA or LT. After insertion, the number of insertion attempts, and “positioning” and “airway-assessment” was evaluated. The patients reported on “sore throat” after 30 and 60 minutes and the day after anaesthesia.Results: Gender and mean age were equal in both groups. The first insertion attempt was successful in 25 of 28 patients randomised to LMA and in 23 of 27 patients randomised to LT. LMA was evaluated to be easier in “positioning” whereas no difference in “sore throat” was reported.Conclusion: We found no difference between the LMA and the LT in terms user and patient friendliness and safety.