Remarkable progress has been made during the last decade in defining the molecular mechanisms that underlie septic shock. This rapidly expanding field is leading to new therapeutic opportunities in ...the management of severe sepsis.
To provide the clinician with a timely summary of the molecular biology of sepsis and to better understand recent advances in sepsis research.
Medline search of relevant publications in basic mechanisms of sepsis/severe sepsis/septic shock, and selected literature review of other manuscripts about the signalosome, inflammasome, apoptosis, or mechanisms of shock. DATA SYNTHESIS AND FINDINGS: The identification of the toll-like receptors and the associated concept of innate immunity based upon pathogen- or damage-associated molecular pattern molecules allowed significant advances in our understanding of the pathophysiology of sepsis. The essential elements of the inflammasome and signal transduction networks responsible for activation of the host response have now been characterized. Apoptosis, mitochondrial dysfunction, sepsis-related immunosuppression, late mediators of systemic inflammation, control mechanisms for coagulation, and reprogramming of immune response genes all have critical roles in the development of sepsis.
Many of these basic discoveries have direct implications for the clinical management of sepsis. The translation of these "bench-to-bedside" findings into new therapeutic strategies is already underway. This brief review provides the clinician with a primer into the basic mechanisms responsible for the molecular biology of sepsis, severe sepsis, and septic shock.
Objective Excessive fluid administration during lung resections is a risk for pulmonary injury. We analyzed the effect of intraoperative fluids on postoperative pulmonary complications (PCs). Methods ...Patients who underwent anatomic pulmonary resections during 2012 to 2013 were included. Age, weight, pulmonary function data, smoking (pack-years), the infusion rate and the total amount of intraoperative fluids (including crystalloid, colloid, and blood products), duration of anesthesia, hospital stay, PCs, and mortality were recorded. PCs were defined as acute respiratory distress syndrome, need for intubation, bronchoscopy, atelectasis, pneumonia, prolonged air leak, and failure to expand. Univariate analyses and multivariate logistic regression were performed. A Lowess curve was drawn for intraoperative fluid threshold. Results In 139 patients, types of resections were segmentectomy-lobectomy (n = 69; extended n = 37; video-assisted thoracoscopic surgery n = 19) and pneumonectomy (n = 9; extended n = 5). One hundred sixty-one PCs were observed in 76 patients (acute respiratory distress syndrome n = 5, need for intubation n = 9, atelectasis n = 60, need for bronchoscopy n = 19, pneumonia n = 26, prolonged air leak n = 19, and failure to expand n = 23). Overall mortality was 4.3% (6 out of 139 patients). Mean hospital stay was 8.5 ± 4.8 days. Univariate analyses showed that smoking, intraoperative total amount of fluids, crystalloids, blood products, and infusion rate as well as total amount of crystalloids and infusion rate during the postoperative first 48 hours were significant for PCs ( P = .033, P < .0001, P = .001, P = .03, P < .0001, P = .002, and P < .0001, respectively). In multivariate logistic regression analysis intraoperative infusion rate ( P < .0001) and smoking were significant ( P = .023). An infusion rate of 6 mL/kg/h was found to be the threshold. Conclusions The occurrence of postoperative PCs is seen more frequently if the intraoperative infusion rate of fluids exceeds 6 mL/kg/h.
This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a ...natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered
via
jet nebulizer. Patients received 1-5x10
10
nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) 20.8% (P < 0.05), oxygen saturation (SpO
2
) 6,7% (P < 0.05) and partial pressure of oxygen to the fraction of inspired oxygen (PaO
2
/FiO
2
) 127.9% (P < 0.05) that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia.
Wastewater (WW) carry considerable amount of chemicals that could have mutagenic or cytotoxic effect from hospital discharges to aquatic environment. Our objective was to determinate the possible ...mutagenic and toxic effects of hospital originated WWs and effectiveness of the wastewater treatment plants (WTP) functions. In the study the mutagenic and cytotoxic potential of three hospitals and influent/effluent of a treatment plant WW collected in Istanbul and was examined using AMES, XTT, and lactate dehydrogenase (LDH) assays. Mutagenic effects were detected at both hospital discharges and advanced biological wastewater plant. We observed no cytotoxic effect in fibroblasts for LDH and XTT assays whereas high cytotoxicity for all samples was found in hepatocytes by XTT assay. According to the results even if advanced technology is used for treatment of WW, mutagenic and cytotoxic effects still remain, and the present technologies need to be further improved.
Objectives The aim of this study was to evaluate the relationship between transesophageal ultrasonography-derived renal resistive index values (RRITEE ) and a standard translumbar renal ...ultrasound-derived RRI (RRITLUSG ). The effectiveness of each method to predict acute kidney injury (AKI) after cardiac surgery also was compared. Design A prospective observational study. Setting A teaching university hospital. Participants Sixty patients undergoing cardiac surgery. Interventions First, RRI was measured with both methods after anesthesia induction. Second, another measurement was performed with TEE after cardiopulmonary bypass and immediately following the surgery with translumbar ultrasound. To test the correlation between the 2 methods and to plot a Bland-Altman graph, preoperative RRI values measured by both techniques were used. Receiver operating characteristic curves also were plotted to compare the diagnostic values of RRI measured intraoperatively by TEE after cardiopulmonary bypass and by RRITLUSG after surgery. Measurements and Main Results There was a statistically significant correlation between the 2 RRI measurement approaches (r = 0.86, p<0.0001). The Bland-Altman plot indicated good agreement between the methods. The area under the curve (AUC) of RRITEE in predicting AKI was 0.82 (95% confidence interval CI = 0.64-0.9, p = 0.001), and the AUC of RRITLUSG after surgery was 0.85 (95% CI = 0.7-0.98, p<0.0001). In predicting AKI, an uncertainty zone for RRITEE values between 0.68 and 0.71 was computed by the gray-zone approach. Conclusions RRITEE showed clinically acceptable agreement with RRITLUSG . Indeed, RRI measured intraoperatively with TEE was comparable to RRITLUSG in terms of detecting postoperative AKI.
We report a nosocomial outbreak caused by Burkholderia cepacia that occurred among six patients admitted in the medical and surgical intensive care unit between 04 March 2019 and 02 April 2019 in ...Istanbul, Turkey.
The outbreak investigation was launched on 11 March 2019 five days after the detection of B. cepacia in four different patients. We defined potential reservoirs and started environmental screening. We sampled the liquid solutions used in patient care activities. Pulse-field gel electrophoresis (PFGE) was performed to determine the genetic relatedness of environmental and patient samples.
Burkholderia cepacia was isolated in tracheal aspiration cultures of six patients. Three out of six patients developed healthcare-associated pneumoniae due to B. cepacia. Environmental cultures in the ICUs revealed B. cepacia growth in 2% chlorhexidine-gluconate mouthwash solution that been used in the colonized patients as well as in samples obtained from the unused products. PFGE revealed the patient and a specific batch of chlorhexidine mouthwash solution samples had a 96% similarity.
Contamination of medical solutions used in critical patient care could cause outbreaks and should be detected early by infection control teams.
Apoptotic loss of parenchymal cells may lead to organ dysfunctions in critically ill patients with septic states. As an antioxidant, the protective effects of N-acetylcysteine (NAC) are documented in ...many experimental and clinical studies. In this experimental study, we investigated the role of chronically used NAC in septic lung injury on a cecal ligation and puncture (CLP) model. To evaluate this, 30 male Wistar rats were randomly divided into four groups as sham (n = 7), CLP (n = 8), sham + NAC (n = 7) and CLP + NAC (n = 8) groups. NAC was administered 150 mg kg(-1) day through intramuscular route beginning 6 h after the operations and lasting for a period of 1 week. One week later, histopathology and epithelial apoptosis were assessed by hematoxylin-eosin and immunohistochemically by M30 and caspase 3 staining to demonstrate septic lung injury. Additionally, lung tissue myeloperoxidase (MPO) activity, malondialdehyde (MDA), and nitrite/nitrate levels were measured. The MPO activity and MDA levels in lung homogenates were found to be increased in CLP group and the administration of NAC prevented their increase significantly (P < 0.05). However, there were no significant differences among the groups regarding nitrite/nitrate levels. The number of apoptotic cells was significantly lower in CLP+NAC group than CLP group, and this finding was supported by M30 and caspase 3 expression in lung (P < 0.05). Lung histopathology was also protected by NAC in CLP-induced sepsis. In conclusion, the chronic use of NAC inhibited MPO activity and lipid peroxidation, which resulted in reduction of apoptosis in lung in this CLP model. Because lung tissue nitrite/nitrate levels did not change significantly, organs other than the lungs may be responsible for producing the increased nitric oxide during sepsis. The chronic use of NAC needs further investigation for its possible antiapoptotic potential in septic states besides its documented antioxidant and antiinflammatory effects.
Taking into consideration the multisystemic clinical and autopsy findings in “severe” coronavirus disease 2019 patients, viral sepsis would be a more accurate term to describe the whole clinical ...picture. The most significant pathophysiological components of this picture are intense cytokine release, prolonged inflammation, immunosuppression with T cell exhaustion, and the development of organ dysfunctions. Currently, the optimal treatment for severe coronavirus disease 2019 is uncertain. Supportive treatment and immunomodulators have a critical place in the treatment of severe patients until effective antivirals are developed. Interleukin-6 antagonists, one of the immunomodulating agents, appears to be effective in the treatment of cytokine storm, but some patients continue to have severe lymphopenia and immunosuppression. We believe it can be useful as immunomodulator therapy in critical coronavirus disease 2019 patients because of the benefits of immune checkpoint inhibitors in cancer and sepsis patients.
Changing Definitions of Sepsis Gul, Fethi; Arslantas, Mustafa Kemal; Cinel, Ismail ...
Turkish Journal of Anaesthesiology and Reanimation,
06/2017, Letnik:
45, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Sepsis is one of the main causes of morbidity and mortality in critically ill patients despite the use of modern antibiotics and resuscitation therapies. Outcomes in sepsis have improved overall, ...probably because of an enhanced focus on early diagnosis and other improvements in supportive care, but mortality rates still remain unacceptably high. The diagnosis and definition of sepsis is a critical problem due to the heterogeneity of this disease process. Although it is apparent that much more needs to be done to advance our understanding, sepsis and related terms remain difficult to define. A 1991 consensus conference developed initial definitions that systemic inflammatory response syndrome (SIRS) to infection would be called sepsis. Definitions of sepsis and septic shock were revised in 2001 to incorporate the threshold values for organ damage. In early 2016, the new definitions of sepsis and septic shock have changed dramatically. Sepsis is now defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The consensus document describes organ dysfunction as an acute increase in total Sequential Organ Failure Assessment (SOFA) score two points consequently to the infection. A significant change in the new definitions is the elimination of any mention of SIRS. The Sepsis-3 Task Force also introduced a new bedside index, called the qSOFA, to identify outside of critical care units patients with suspected infection who are likely to develop sepsis. Recently updated the consensus definitions improved specificity compared with the previous descriptions.
There are several ventilator modes that are used for maintenance mechanical ventilation but no conclusive evidence that one mode of ventilation is better than another. Vibration response imaging is a ...novel bedside imaging technique that displays vibration energy of lung sounds generated during the respiratory cycle as a real-time structural and functional image of the respiration process. In this study, we objectively evaluated the differences in regional lung vibration during different modes of mechanical ventilation by means of this new technology.
Vibration response imaging was performed on 38 patients on assist volume control, assist pressure control, and pressure support modes of mechanical ventilation with constant tidal volumes. Images and vibration intensities of three lung regions at maximal inspiration were analyzed.
There was a significant increase in overall geographical area (p < 0.001) and vibration intensity (p < 0.02) in pressure control and pressure support (greatest in pressure support), compared to volume control, when each patient served as his or her own control while targeting the same tidal volume in each mode. This increase in geographical area and vibration intensity occurred primarily in the lower lung regions. The relative percentage increases were 28.5% from volume control to pressure support and 18.8% from volume control to pressure control (p < 0.05). Concomitantly, the areas of the image in the middle lung regions decreased by 3.6% from volume control to pressure support and by 3.7% from volume control to pressure control (p < 0.05). In addition, analysis of regional vibration intensity showed a 35.5% relative percentage increase in the lower region with pressure support versus volume control (p < 0.05).
Pressure support and (to a lesser extent) pressure control modes cause a shift of vibration toward lower lung regions compared to volume control when tidal volumes are held constant. Better patient synchronization with the ventilator, greater downward movement of the diaphragm, and decelerating flow waveform are potential physiologic explanations for the redistribution of vibration energy to lower lung regions in pressure-targeted modes of mechanical ventilation.
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