Zsolt Iványi

Antibacterial effect of microvesicles released from human neutrophilic granulocytes.

Cell-derived vesicles represent a recently discovered mechanism for intercellular communication. We investigated their potential role in interaction of microbes with host organisms. We provide evidence that different stimuli induced isolated neutrophilic granulocytes to release microvesicles with different biologic properties. Only opsonized particles initiated the formation of microvesicles that were able to impair bacterial growth. The antibacterial effect of neutrophil-derived microvesicles was independent of production of toxic oxygen metabolites and opsonization or engulfment of the microbes, but depended on β(2) integrin function, continuous actin remodeling, and on the glucose supply. Neutrophil-derived microvesicles were detected in the serum of healthy donors, and their number was significantly increased in the serum of bacteremic patients. We propose a new extracellular mechanism to restrict bacterial growth and dissemination.

Systemic, pulmonary, and hepatosplanchnic effects of N-acetylcysteine during long-term porcine endotoxemia

ObjectiveControversial data have been reported on the effects of N-acetylcysteine in patients with septic shock. We therefore investigated the systemic, pulmonary, and hepatosplanchnic hemodynamic, gas exchange, and metabolic effects of N-acetylcysteine during long-term, volume-resuscitated, hyperdynamic porcine endotoxemia, which mimics the features of hyperdynamic human sepsis. DesignProspective, randomized, controlled experimental study. SettingInvestigational animal laboratory. SubjectsEighteen pigs were randomized to receive endotoxin alone (controls, n = 9) or endotoxin plus N-acetylcysteine (n = 9). InterventionsAnesthetized, mechanically ventilated, and instrumented animals received continuous intravenous endotoxin and were resuscitated with hydroxyethylstarch to keep mean arterial pressure >60 mm Hg. After 12 hrs of endotoxemia, they were randomized to receive either placebo or N-acetylcysteine (150 mg/kg loading dose over 1 hr followed by 20 mg·kg−1·hr−1 for 11 hrs). Measurements and Main ResultsBefore as well as 12, 18, and 24 hrs after starting the endotoxin infusion, systemic, pulmonary, and hepatosplanchnic hemodynamics, oxygen exchange, and metabolism as well as nitric oxide, glutathione, and 8-isoprostane concentrations were assessed. N-acetylcysteine failed to improve any of the variables of the systemic, pulmonary, or hepatosplanchnic hemodynamics, gas exchange, and metabolism. Although N-acetylcysteine significantly elevated glutathione concentration, it did not influence the 8-isoprostane concentrations and even further reduced hepatic venous pH. ConclusionsDespite the increased glutathione concentration, N-acetylcysteine did not improve systemic, pulmonary, and hepatosplanchnic hemodynamics, oxygen exchange, and metabolism. When compared with previous reports in the literature, a different timing of N-acetylcysteine administration and/or an ongoing or even N-acetylcysteine-induced aggravation of oxidative stress may account for this result.

A Randomized Trial of the Amikacin Fosfomycin Inhalation System for the Adjunctive Therapy of Gram-Negative Ventilator-Associated Pneumonia: IASIS Trial

BACKGROUND: Clinical failures in ventilator‐associated pneumonia (VAP) caused by gram‐negative bacteria are common and associated with substantial morbidity, mortality, and resource utilization. METHODS: We assessed the safety and efficacy of the amikacin fosfomycin inhalation system (AFIS) for the treatment of gram‐negative bacterial VAP in a randomized double‐blind, placebo‐controlled, parallel group, phase 2 study between May 2013 and March 2016. We compared standard of care in each arm plus 300 mg amikacin/120 mg fosfomycin or placebo (saline), delivered by aerosol twice daily for 10 days (or to extubation if < 10 days) via the investigational eFlow Inline System (PARI GmbH). The primary efficacy end point was change from baseline in the Clinical Pulmonary Infection Score (CPIS) during the randomized course of AFIS/placebo, using the subset of patients with microbiologically proven baseline infections with gram‐negative bacteria. RESULTS: There were 143 patients randomized: 71 to the AFIS group, and 72 to the placebo group. Comparison of CPIS change from baseline between treatment groups was not different (P = .70). The secondary hierarchical end point of no mortality and clinical cure at day 14 or earlier was also not significant (P = .68) nor was the hierarchical end point of no mortality and ventilator‐free days (P = .06). The number of deaths in the AFIS group was 17 (24%) and 12 (17%) in the placebo group (P = .32). The AFIS group had significantly fewer positive tracheal cultures on days 3 and 7 than placebo. CONCLUSIONS: In this trial of adjunctive aerosol therapy compared with standard of care IV antibiotics in patients with gram‐negative VAP, the AFIS was ineffective in improving clinical outcomes despite reducing bacterial burden. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01969799; URL: www.clinicaltrials.gov

Etomidate versus propofol for electroconvulsive therapy in patients with schizophrenia

Among drugs used for the anesthesia of electroconvulsive therapy (ECT), propofol reduces seizure duration to a greater degree than etomidate. The perceived difference between the 2 anesthetics is smaller in patients with schizophrenia than in patients who suffer depression. In this study, propofol and etomidate were compared during the ECT of patients with schizophrenia, on the basis of their impact on seizure activity and on seizure-induced hemodynamic reactions. Schizophrenics (n = 34) who were treated with ECT participated in this randomized crossover study. Propofol (1 mg/kg) and etomidate (0.2 mg/kg) were used alternately. The 2 drugs were compared on the basis of EEG- and EMG-registered seizure duration, mean arterial pressure (MAP), pulse frequency, energy index, and postictal suppression. We also analyzed the number of necessary restimulations. In case of anesthesia with etomidate, both EEG- (61.29 ± 22.4 s, 47.9 ± 21.3 s P = 0.014) and EMG- (46.3 ± 23.8 s, 33.6 ± 15.9 s P = 0.006) registered seizure durations were significantly longer than in case of propofol. When using propofol, the increase in MAP was significantly lower than when etomidate was used (8.1 ± 10.2 mm Hg, 18.3 ± 11.2 mm Hg, P = 0.001). There were no significant differences found in the postseizure increase in pulse frequency, in postictal suppression, or in the energy index, nor did the numbers of necessary restimulations differ significantly. Propofolwas found to reduce seizure duration to a significantly greater extent than etomidate. At the same time, in electrophysiological parameters that show a correlation with clinical efficacy, there was no significant difference found between the 2 anesthetics. However, the seizureinduced increase in MAP was reduced by propofol to a significantly greater degree than by etomidate.

Systemic and hepatosplanchnic hemodynamic and metabolic effects of the PARP inhibitor PJ34 during hyperdynamic porcine endotoxemia

Activation of the poly(ADP-ribose)polymerase (PARP), a highly energy-consuming DNA-repairing enzyme, plays a crucial role in the pathogenesis of multiorgan failure. Most results, however, were derived from experiments with hypodynamic shock states characterized by a markedly decreased cardiac output (CO) and/or using a pretreatment approach. Therefore, we investigated the effects of the novel potent and selective PARP-1 inhibitor PJ34 in a posttreatment model of long-term, volume-resuscitated porcine endotoxemia. Anesthetized, mechanically ventilated and instrumented pigs received continuous intravenous (i.v.) lipopolysaccharide (LPS) over 24 h. Hydroxyethyl starch was administered to maintain a mean arterial pressure > 65 mmHg. After 12 h of LPS infusion, the animals were randomized to receive either vehicle (Control, n = 9) or i.v. PJ34 (n = 6; 10 mg/kg over 1 h followed by 2 mg/kg/h until the end of the experiment). Measurements were performed before as well as at 12, 18, and 24 h of LPS infusion. In all animals CO increased because of reduced systemic vascular resistance (SVR) and fluid resuscitation. PJ34 further raised CO (P < 0.05 vs. control group) as the result of a higher stroke volume indicating its positive inotropic effect. In addition, it diminished the rise in the ileal mucosal-arterial PCO2 gap, which returned to baseline levels at 24 h of LPS, and improved the gut lactate balance (P = 0.093 PJ34 vs. control) together with significantly lower portal venous lactate/pyruvate ratios. By contrast, it failed to influence the LPS-induced derangements of liver metabolism. Incomplete PARP inhibition because of dilutional effects and/or an only partial efficacy when used in post-treatment approaches may account for this finding.

Mucosal Immunity and the Intestinal Microbiome in the Development of Critical Illness

The intestinal community, including the commensal microbial flora as well as the host tissues, represents a functional whole in vivo. Under physiological circumstances, this symbiosis brings great benefit for the host; however, critical illness induces profound disturbances in the intestinal ecosystem affecting both procaryotic and eucaryotic members. Today, 25 years after the gut was first described as a motor of multiple organ dysfunction syndrome, the role of the injured splanchnic compartment in the pathomechanism and development of critical illness is still in the first line of research. Multiple mechanisms have been identified by which the stressed gut may affect host homeostasis, and how external intervention might help to rebalance physiology. This paper provides a brief overview of the present of this field.

Experiences of the Department of Anesthesiology and Intensive Therapy of Semmelweis University during the 2009 pandemic H1N1 (pH1N1) influenza outbreak

Abstract Introduction: The 2009 pandemic 2009 H1N1 (pH1N1) influenza A virus shows a markedly different disease pattern than seasonal strains, causing critical illness in relatively young, female, pregnant individuals as well as in comorbid patients. Materials and methods: The Department of Anesthesiology and Intensive Therapy of Semmelweis University served as a regional influenza center for the adult critically ill during the winter of pH1N1 outbreak. We analyzed data collected from 26 suspected pH1N1 critically ill patients treated in our unit during this period. Results: Sixteen cases were confirmed as pH1N1 infection with RT-PCR, while the other 10 patients with influenza like illness showed tendency to a different age and comorbidity, as well as outcome characteristics, suggesting a different pathogenesis. Confirmed pH1N1 patients showed a mean age of 50.5 years (median: 44; range: 20–85), with female predominancy (69%). Comorbidity was present in 69% of cases (chronic heart conditions, chronic pulm...

Ventilator-associated pneumonia and the importance of education of ICU nurses on prevention - Preliminary results

Background and aims Ventilator-associated pneumonia (VAP) increases intensive care unit (ICU) length of stay, ICU mortality, the number of ventilator days, and costs. We implemented a VAP bundle and investigated its efficacy on prevention. Materials and methods A prospective observational study was conducted between January 1, 2015 and December 31, 2015 in a 12-bed multidisciplinary ICU. The bundle was implemented on July 02, 2015. Comparative analysis was performed before and after the implementation of the bundle. The compliance of the nurses was also studied. Results The incidence of VAP was 21.5/1,000 ventilator days (95% CI: 14.17–31.10) in the first phase and 12.0/1,000 ventilator days (95% CI: 7.2–19.49) in the second phase. Relative risk reduction was 44% (95% CI: −0.5 to 0.98). Most common bacteria identified during the first phase were Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Staphylococcus aureus; and in the second phase P. aeruginosa, Acinetobacter baumannii, and S. maltophilia were identified. Significant improvement was achieved in the head-of-bed elevation (p = 0.004), oral care (p = 0.01), hand hygiene (p < 0.001), endotracheal suctioning (p = 0.004), and removal of condensate (p = 0.043). Discussion The incidence of VAP showed tendency for reduction. The prevalence of nursing-dependent bacteria decreased and compliance in following prevention methods increased. Conclusion These results underline the importance of education of prevention methods.

Prevention of tracheal cartilage injury with modified Griggs technique during percutaneous tracheostomy — Randomized controlled cadaver study

INTRODUCTION Tracheal stenosis is the most common severe late complication of percutaneous tracheostomy causing significant decrease in quality of life. Applying modified Griggs technique reduced the number of late tracheal stenoses observed in our clinical study. The aim of this study was to investigate the mechanism of this relationship. MATERIALS AND METHODS Forty-six cadavers were randomized into two groups according to the mode of intervention during 2006-2008. Traditional versus modified Griggs technique was applied in the two groups consequently. Wider incision, surgical preparation, and bidirectional forceps dilation of tracheal wall were applied in modified technique. Injured cartilages were inspected by sight and touch consequently. Age, gender, level of intervention, and number of injured tracheal cartilages were registered. RESULTS Significantly less frequent tracheal cartilage injury was observed after modified (9%) than original (91%) Griggs technique (p < 0.001). A moderate association between cartilage injury and increasing age was observed, whereas the level of intervention (p = 0.445) and to gender (p = 0.35) was not related to injury. Risk of cartilage injury decreased significantly (OR: 0.0264, 95%, CI: 0.005-0.153) with modified Griggs technique as determined in adjusted logistic regression model. DISCUSSION Modified Griggs technique decreased the risk of tracheal cartilage injury significantly in our cadaver study. This observation may explain the decreased number of late tracheal stenosis after application of the modified Griggs method.

Impact of anesthesia on patient and endoscopist satisfaction after colonoscopy — A pilot study

Introduction: Colonoscopy is a standard diagnostic tool for the investigation and surveillance of diseases affecting the colon. The pro - cedurecanbeuncomfortableandsometimesverypainful,resultinginincreasedcecalintubationtimeandlowercompletionrate.However,itseems tobeapparentthatanesthesiaforthisprocedureincreasespatientsatisfaction;dataarelackingabouttheimpactofanesthesiaonthetechnicalper - formance of colonoscopic examination. Aim: In our observational survey, we studied patients undergoing colonoscopy with or without anesthe - sia.Wecomparedpatientsatisfaction,difficultiesinendoscopy,andtheimpactofanesthesiaontheexaminationroomoccupancy. Methods: Ween - rolled 60 patients undergoing elective, outpatient colonoscopy because of various reasons. The patients were able to choose between anesthesia and sedation. Difficulties in colonoscopy were evaluated by the endoscopists rating and by the time to cecal intubation. We assessed patient sat - isfactionbyanumericratingscale. Results: Weobservedthatneitherthedurationofcolonoscopynorthetimespentintheexaminationroomwas different in the two groups ( p 0.825, 0.998). There was a significant improvement in both patient and endoscopist satisfaction scores in patients undergoing anesthesia ( p 0.0007). Conclusion: We found that during colonoscopy, compared to sedation, anesthesia increases both endoscopist and patient satisfaction without prolonged occupation of the examination room.