Kinetics of Different Blood Biomarkers during Polymyxin-B Extracorporeal Hemoperfusion in Abdominal Sepsis.

INTRODUCTION: Comparison of the marker kinetics procalcitonin, presepsin, and endotoxin during extracorporeal hemoperfusion with polymyxin-B adsorbing cartridge (PMX-HA) has never been described in abdominal sepsis. We aimed to compare the trend of three biomarkers in septic post-surgical abdominal patients in intensive care unit (ICU) treated with PMX-HA and their prognostic value. METHODS: Ninety abdominal post-surgical patients were enrolled into different groups according to the evidence of postoperative sepsis or not. Non-septic patients admitted in the surgical ward were included in C group (control group). ICU septic shock patients with endotoxin levels <0.6 EAA receiving conventional therapy were addressed in S group and those with endotoxin levels ≥0.6 EAA receiving treatment with PMX-HA, besides conventional therapy, were included in SPB group. Presepsin, procalcitonin, endotoxin and other clinical data were recorded at 24 h (T0), 72 h (T1) and 7 days (T2) after surgery. Clinical follow-up was performed on day 30. RESULTS: SPB group showed reduced levels of the three biomarkers on T2 versus T0 (p < 0.001); presepsin, procalcitonin and endotoxin levels decreased, respectively, by 25%, 11%, and 2% on T1 versus T0, and 40%, 41%, and 26% on T2 versus T0. All patients in C group, 73% of patients in SPB group versus 37% of patients in S group survived at follow-up. Moreover, procalcitonin had the highest predictive value for mortality at 30 days, followed by presepsin. CONCLUSION: The present study showed the reliability of presepsin in monitoring PMX-HA treatment in septic shock patients. Procalcitonin showed better predicting power for the mortality riSsk.

The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study.

BACKGROUND: Septic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy. METHODS: The EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes. CONCLUSIONS: The EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

Bioimpedance-assessed muscle wasting and its relation to nutritional intake during the first week of ICU: a pre-planned secondary analysis of Nutriti Study.

BACKGROUND: Muscle mass evaluation in ICU is crucial since its loss is related with long term complications, including physical impairment. However, quantifying muscle wasting with available bedside tools (ultrasound and bioimpedance analysis) must be more primarily understood. Bioimpedance analysis (BIA) provides estimates of muscle mass and phase angle (PA). The primary aim of this study was to evaluate muscle mass changes with bioimpedance analysis during the first 7 days after ICU admission. Secondary aims searched for correlations between muscular loss and caloric and protein debt. METHODS: Patients with an expected ICU-stay ≥ 72 h and the need for artificial nutritional support were evaluated for study inclusion. BIA evaluation of muscle mass and phase angle were performed at ICU admission and after 7 days. Considering the difference between ideal caloric and protein targets, with adequate nutritional macronutrients delivered, we calculated the caloric and protein debt. We analyzed the potential correlation between caloric and protein debt and changes in muscle mass and phase angle. RESULTS: 72 patients from September 1st to October 30th, 2019 and from August 1st to October 30th, 2021 were included in the final statistical analysis. Median age was 68 [59-77] years, mainly men (72%) admitted due to respiratory failure (25%), and requiring invasive mechanical ventilation for 7 [4-10] days. Median ICU stay was 8 [6-12] days. Bioimpedance data at ICU admission and after 7 days showed that MM and PA resulted significantly reduced after 7 days of critically illness, 34.3 kg vs 30.6 kg (p < 0.0001) and 4.90° vs 4.35° (p = 0.0004) respectively. Mean muscle loss was 3.84 ± 6.7 kg, accounting for 8.4% [1-14] MM reduction. Correlation between caloric debt (r = 0.14, p = 0.13) and protein debt (r = 0.18, p = 0.13) with change in MM was absent. Similarly, no correlation was found between caloric debt (r = -0.057, p = 0.631) and protein debt (r = -0.095, p = 0.424) with changes in PA. CONCLUSIONS: bioimpedance analysis demonstrated that muscle mass and phase angle were significantly lower after 7 days in ICU. The total amount of calories and proteins does not correlate with changes in muscle mass and phase angle.

Electrical Impedance Tomography during Abdominal Laparoscopic Surgery: A Physiological Pilot Study.

BACKGROUND: Both general anesthesia and pneumoperitoneum insufflation during abdominal laparoscopic surgery can lead to atelectasis and impairment in oxygenation. Setting an appropriate level of external PEEP could reduce the occurrence of atelectasis and induce an improvement in gas exchange. However, in clinical practice, it is common to use a fixed PEEP level (i.e., 5 cmH2O), irrespective of the dynamic respiratory mechanics. We hypothesized setting a PEEP level guided by EIT in order to obtain an improvement in oxygenation and respiratory system compliance in lung-healthy patients than can benefit a personalized approach. METHODS: Twelve consecutive patients scheduled for abdominal laparoscopic surgery were enrolled in this prospective study. The EIT Timpel Enlight 1800 was applied to each patient and a dedicated pneumotachograph and a spirometer flow sensor, integrated with EIT, constantly recorded respiratory mechanics. Gas exchange, respiratory mechanics and hemodynamics were recorded at five time points: T0, baseline; T1, after induction; T2, after pneumoperitoneum insufflation; T3, after a recruitment maneuver; and T4, at the end of surgery after desufflation. RESULTS: A titrated mean PEEP of 8 cmH2O applied after a recruitment maneuver was successfully associated with the "best" compliance (58.4 ± 5.43 mL/cmH2O), with a low percentage of collapse (10%), an acceptable level of hyperdistention (0.02%). Pneumoperitoneum insufflation worsened respiratory system compliance, plateau pressure, and driving pressure, which significantly improved after the application of the recruitment maneuver and appropriate PEEP. PaO2 increased from 78.1 ± 9.49 mmHg at T0 to 188 ± 66.7 mmHg at T4 (p < 0.01). Other respiratory parameters remained stable after abdominal desufflation. Hemodynamic parameters remained unchanged throughout the study. CONCLUSIONS: EIT, used as a non-invasive intra-operative monitor, enables the rapid assessment of lung volume and regional ventilation changes in patients undergoing laparoscopic surgery and helps to identify the "optimal" PEEP level in the operating theatre, improving ventilation strategies.

Nutritional support and prevention of post-intensive care syndrome: the Italian SIAARTI survey.

BACKGROUND: Malnutrition and muscle wasting are common in ICU patients and predict adverse patient-centered outcomes. The Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) conducted a nationwide survey to identify the nutritional practices in the Italian ICUs and to plan future, training interventions to improve the national clinical practice. METHODS: Nationwide online survey, involving Italian ICUs, developed by experts affiliated with SIAARTI. Invitations to participate were distributed through emails and social networks. Data were collected over a period of three months (October 1 to December 31, 2022) during 2022. RESULTS: One hundred full responses from participating ICUs were collected. The number of beds is < 10 in most ICUs and > 20 in 11 ICUs. Most ICUs (87%) are mixed, cardiac (5%), neurosurgical (4%), or pediatric ICUs (1%). Although the nutritional program is widely prescribed based on the patients' general evaluation, 52 ICUs (52%) do not perform nutritional risk evaluation at admission in case of > 24-h stay. Daily caloric intake is mainly based on the 25 kcal/kg equation; otherwise, the Harris-Benedict formula is mostly used, whereas indirect calorimetry is less used. Most clinicians apply a personalized nutritional approach to organ failure. Most ICUs have a nutritional management protocol, and enteral nutrition (EN) is frequently started within 2 days from admission, while supplemental parenteral nutrition is used when EN is insufficient by most clinicians. The EN administered seems to correspond to that prescribed, but it is stopped if the gastric residual gastric is > 300-500 ml in most ICUs. CONCLUSION: Prescription, route, and mode of administration of nutritional support seem to be in line with international recommendations, while suggestions on the tools for assessing the nutritional risk and monitoring efficacy and complications seem far less followed. Future national clinical studies are necessary to investigate the optimal nutritional and metabolic management of critically ill patients and the correspondence with the results of this survey on actual practices.

Continuous vs Intermittent Meropenem Administration in Critically Ill Patients With Sepsis: The MERCY Randomized Clinical Trial.

Importance: Meropenem is a widely prescribed ß-lactam antibiotic. Meropenem exhibits maximum pharmacodynamic efficacy when given by continuous infusion to deliver constant drug levels above the minimal inhibitory concentration. Compared with intermittent administration, continuous administration of meropenem may improve clinical outcomes. Objective: To determine whether continuous administration of meropenem reduces a composite of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria compared with intermittent administration in critically ill patients with sepsis. Design, Setting, and Participants: A double-blind, randomized clinical trial enrolling critically ill patients with sepsis or septic shock who had been prescribed meropenem by their treating clinicians at 31 intensive care units of 26 hospitals in 4 countries (Croatia, Italy, Kazakhstan, and Russia). Patients were enrolled between June 5, 2018, and August 9, 2022, and the final 90-day follow-up was completed in November 2022. Interventions: Patients were randomized to receive an equal dose of the antibiotic meropenem by either continuous administration (n = 303) or intermittent administration (n = 304). Main Outcomes and Measures: The primary outcome was a composite of all-cause mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. There were 4 secondary outcomes, including days alive and free from antibiotics at day 28, days alive and free from the intensive care unit at day 28, and all-cause mortality at day 90. Seizures, allergic reactions, and mortality were recorded as adverse events. Results: All 607 patients (mean age, 64 [SD, 15] years; 203 were women [33%]) were included in the measurement of the 28-day primary outcome and completed the 90-day mortality follow-up. The majority (369 patients, 61%) had septic shock. The median time from hospital admission to randomization was 9 days (IQR, 3-17 days) and the median duration of meropenem therapy was 11 days (IQR, 6-17 days). Only 1 crossover event was recorded. The primary outcome occurred in 142 patients (47%) in the continuous administration group and in 149 patients (49%) in the intermittent administration group (relative risk, 0.96 [95% CI, 0.81-1.13], P = .60). Of the 4 secondary outcomes, none was statistically significant. No adverse events of seizures or allergic reactions related to the study drug were reported. At 90 days, mortality was 42% both in the continuous administration group (127 of 303 patients) and in the intermittent administration group (127 of 304 patients). Conclusions and Relevance: In critically ill patients with sepsis, compared with intermittent administration, the continuous administration of meropenem did not improve the composite outcome of mortality and emergence of pandrug-resistant or extensively drug-resistant bacteria at day 28. Trial Registration: ClinicalTrials.gov Identifier: NCT03452839.

Mucopenetration study of solid lipid nanoparticles containing magneto sensitive iron oxide.

In most chronic respiratory diseases, excessive viscous airway secretions oppose a formidable permeation barrier to drug delivery systems (DDSs), with a limit to their therapeutic efficacy for the targeting epithelium. Since mucopenetration of DDSs with slippery technology (i.e. PEGylation) has encountered a reduction in the presence of sticky and complex airway secretions, our aim was to evaluate the relevance of magnetic PEGylated Solid Lipid Nanoparticles (mSLNs) for pulling them through chronic obstructive pulmonary disease (COPD) airway secretions. Thus, COPD sputum from outpatient clinic, respiratory secretions aspirated from high (HI) and low (LO) airways of COPD patients in acute respiratory insufficiency, and porcine gastric mucus (PGM) were investigated for their permeability to mSLN particles under a magnetic field. Rheological tests and mSLN adhesion to airway epithelial cells (AECs) were also investigated. The results of mucopenetration show that mSLNs are permeable both in COPD sputum and in PGM, while HI and LO secretions are always impervious. Parallel rheological results show a different elastic property, which can be associated with different mucus mesostructures. Finally, adhesion tests confirm the role of the magnetic field in improving the interaction of SLNs with AECs. Overall, our results reveal that mesostructure is of paramount importance in determining the mucopenetration of magnetic SLNs.

Immunological effects of glutamine supplementation in polytrauma patients in intensive care unit.

BACKGROUND: In polytrauma intensive care unit (ICU) patients, glutamine (GLN) becomes a "conditionally essential" amino acid; its role has been extensively studied in numerous clinical trials but their results are inconclusive. We evaluated the IgA-mediated humoral immunity after GLN supplementation in polytrauma ICU patients. METHODS: All consecutive patients with polytrauma who required mechanical ventilation and enteral nutrition (EN) provided within 24 h since the admission in ICU at the University Hospital of Foggia from September 2016 to February 2017 were included. Thereafter, two groups were identified: patients treated by conventional EN (25 kcal/kg/die) and patients who have received conventional EN enriched with 50 mg/kg/ideal body weight of alanyl-GLN 20% intravenously. We analysed the plasmatic concentration of IgA, CD3+/CD4+ T helper lymphocytes, CD3+/CD8+ T suppressor lymphocytes, CD3+/CD19+ B lymphocytes, IL-4 and IL-2 at admission and at 4 and 8 days. RESULTS: We identified 30 patients, with 15 subjects per group. IgA levels increased significantly in GLN vs the control group at T0, T4 and T8. CD3+/CD4+ T helper lymphocyte and CD3+/CD8+ T suppressor lymphocyte levels significantly increased in GLN vs the control group at T4 and T8. CD3+/CD19+ B lymphocyte levels increased significantly in GLN vs the control group only at T8. IL-2 and IL-4 levels showed no significant differences when comparing GLN with the control group. CONCLUSIONS: Our study showed that there was an improvement in humoral and cell-mediated immunity with GLN supplementation in polytrauma ICU patients using recommended doses.

Cerebral autoregulation in anoxic brain injury patients treated with targeted temperature management.

BACKGROUND: Little is known about the prevalence of altered CAR in anoxic brain injury and the association with patients' outcome. We aimed at investigating CAR in cardiac arrest survivors treated by targeted temperature management and its association to outcome. METHODS: Retrospective analysis of prospectively collected data. INCLUSION CRITERIA: adult cardiac arrest survivors treated by targeted temperature management (TTM). EXCLUSION CRITERIA: trauma; sepsis, intoxication; acute intra-cranial disease; history of supra-aortic vascular disease; severe hemodynamic instability; cardiac output mechanical support; arterial carbon dioxide partial pressure (PaCO2) > 60 mmHg; arrhythmias; lack of acoustic window. Middle cerebral artery flow velocitiy (FV) was assessed by transcranial Doppler (TCD) once during hypothermia (HT) and once during normothermia (NT). FV and blood pressure (BP) were recorded simultaneously and Mxa calculated (MATLAB). Mxa is the Pearson correlation coefficient between FV and BP. Mxa > 0.3 defined altered CAR. Survival was assessed at hospital discharge. Cerebral Performance Category (CPC) 3-5 assessed 3 months after CA defined unfavorable neurological outcome (UO). RESULTS: We included 50 patients (Jan 2015-Dec 2018). All patients had out-of-hospital cardiac arrest, 24 (48%) had initial shockable rhythm. Time to return of spontaneous circulation was 20 [10-35] min. HT (core body temperature 33.7 [33.2-34] °C) lasted for 24 [23-28] h, followed by rewarming and NT (core body temperature: 36.9 [36.6-37.4] °C). Thirty-one (62%) patients did not survive at hospital discharge and 36 (72%) had UO. Mxa was lower during HT than during NT (0.33 [0.11-0.58] vs. 0.58 [0.30-0.83]; p = 0.03). During HT, Mxa did not differ between outcome groups. During NT, Mxa was higher in patients with UO than others (0.63 [0.43-0.83] vs. 0.31 [- 0.01-0.67]; p = 0.03). Mxa differed among CPC values at NT (p = 0.03). Specifically, CPC 2 group had lower Mxa than CPC 3 and 5 groups. At multivariate analysis, initial non-shockable rhythm, high Mxa during NT and highly malignant electroencephalography pattern (HMp) were associated with in-hospital mortality; high Mxa during NT and HMp were associated with UO. CONCLUSIONS: CAR is frequently altered in cardiac arrest survivors treated by TTM. Altered CAR during normothermia was independently associated with poor outcome.

Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design.

OBJECTIVE: Meropenem is a ß-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients. DESIGN: Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio). SETTING: Tertiary and University hospitals. INTERVENTIONS: 600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h). MEASUREMENTS: The primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group. CONCLUSIONS: The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.

Posthumous sperm retrieval: a procreative revolution.

Aim Postmortem sperm retrieval with consequent artificial insemination has become a technically possible option for future use in assisted reproductive technology (ART). The authors have set out to discuss the social and ethical significance of posthumous sperm retrieval, and the laws currently in force in Italy, the United States and elsewhere. Methods International literature from 1997 to 2020 has been reviewed from Pubmed database, Google Scholar and Scopus, drawn upon American, Italian and international sources (an ethically acceptable solution can only be achieved through an overhaul of the laws currently in effect). One of the most contentious issues was about donor consent. In Italy, a donor's will to retrieve his sperm in the event of premature disappearance can be proven according to the Law 219/2017, through advance health care directives. Results A substantial increase, both in requests and protocols, was documented in the United States. In Italy, over the last two years, three rulings were issued concerning posthumous insemination. However, no official standardized protocols, guidelines or targeted legislation exist at the national level to regulate medical activity in that realm, whereas established laws often set implicit limitations. Conclusion Current legal frameworks appear to be inadequate, because in most cases they were conceived under conditions that have radically changed. The need for newly-updated regulatory frameworks to promptly bridge that gap is increasingly clear, if current social needs related to reproductive rights are to be met in the foreseeable future.

Platelet morphological indices on Intensive Care Unit admission predict mortality in septic but not in non-septic patients.

BACKGROUND: Thrombocytopenia is associated with worse outcomes in critically ill patients. The clinical relevance of other platelets indices is less studied. We investigated the ability of the platelets distribution width (PDW) and the mean platelet volume (MPV) to predict mortality in critically ill patients. We hypothesized that the prognostic values of PDW and MPV could be different in septic and non-septic patients. METHODS: We prospectively analyzed patients with an expected ICU length of stay ≥48 hours. Repeated measurements of PDW and MPV were considered (on ICU admission and up to day 5 thereafter). The primary outcome was to investigate the ability of PDW and MPV to predict 90-day mortality in septic and non-septic patients. RESULTS: We included in the study 234 patients of which 31% patients were septic. 90-day mortality was 39% in septic and 27% non-septic patients. PDW and MPV values on admission were 12.5±2.5% and 10.7±1.1 fL, respectively. The AUROC of PDW values on admission to predict 90-day mortality in septic patients was 0.813, being higher than those in non-septic patients (0.550, P<0.001). Similarly, the AUROC for MPV in septic patients was higher than non-septic patients (0.55, P<0.001). The combined analysis of platelets morphological indices and lactate improved the predictive accuracy (PDW and lactate AUROC=0.870; MPV and lactate AUROC=0.867). CONCLUSIONS: Platelet morphological indices are independent predictor of 90-day mortality in septic patients but not in non-septic patients. A combined analysis of platelets morphological indices and lactate in septic patients resulted in improved prediction of mortality.

Effectiveness of Combined Strategies for the Prevention of Hypothermia Measured by Noninvasive Zero-Heat Flux Thermometer During Cesarean Section.

Background: Perioperative hypothermia (body temperature <36°C) is a common complication of anesthesia increasing the risk for maternal cardiovascular events and coagulative disorders, and can also influence neonatal health. The aim of our work was to evaluate the impact of combined warming strategies on maternal core temperature, measured with the SpotOn. We hypothesized that combined modalities of active warming prevent hypothermia in pregnant women undergoing cesarean delivery with spinal anesthesia. Methods: Seventy-eight pregnant women were randomly allocated into three study groups receiving warmed IV fluids and forced-air warming (AW), warmed IV fluids (WF), or no warming (NW). Noninvasive core temperature device (SpotOn) measured maternal core temperature intraoperatively and for 30 min after surgery. Maternal mean arterial pressure, incidence of shivering, thermal comfort and newborn's APGAR, axillary temperature, weight, and blood gas analysis were also recorded. Results: Incidence of hypothermia was of 0% in AW, 4% in WF, and 47% in NW. Core temperature in AW was constantly higher than WF and NW groups. Incidence of shivering in perioperative time was significantly lower in AW and WF groups compared with the NW group (p < 0.04). Thermal comfort was higher in both AW and WF groups compared with NW group (p = 0.02 and p = 0.008, respectively). There were no significant differences among groups for the other evaluated parameters. Conclusion: Combined modalities of active warming are effective in preventing perioperative hypothermia. The routine uses of combined AW are suggested in the setting of cesarean delivery.

High mobilization of CD133+/CD34+ cells expressing HIF-1α and SDF-1α in septic abdominal surgical patients.

BACKGROUND: The control of endothelial progenitor cells (CD133+/CD34+ EPCs) migrating from bone marrow to peripheral blood is not completely understood. Emerging evidence suggests that stromal cell-derived factor-1α (SDF-1α) mediates egression of EPCs from bone marrow, while the hypoxia inducible factor (HIF) transcriptional system regulates SDF-1α expression. Our study aimed to investigate the time course of circulating CD133+/CD34+ EPCs and its correlation with the expression of HIF-1α protein and SDF-1α in postoperative laparoscopic abdominal septic patients. METHODS: Postoperative patients were divided in control (C group) and septic group (S group) operated immediately after the diagnosis of sepsis/septic shock. Blood samples were collected at baseline (0), 1, 3 and 7 postoperative days for CD133+/CD34+ EPCs count expressing or not the HIF-1α and SDF-1α analysis. RESULTS: Thirty-two patients in S group and 39 in C group were analyzed. In C group CD133+/CD34+ EPCs count remained stable throughout the study period, increasing on day 7 (173 [0-421] /µl vs baseline: P = 0.04; vs day 1: P = 0.002). In S group CD133+/CD34+ EPCs count levels were higher on day 3 (vs day 1: P = 0.006 and day 7: P = 0.026). HIF-1α expressing CD133+/CD34+ EPCs count decreased on day 1 as compared with the other days in C group (day 0 vs 1: P = 0.003, days 3 and 7 vs 1: P = 0.008), while it was 321 [0-1418] /µl on day 3 (vs day 1; P = 0.004), and 400 [0-587] /µl on day 7 in S group. SDF-1α levels were higher not only on baseline but also on postoperative day 1 in S vs C group (219 [124-337] pg/ml vs 35 [27-325] pg/ml, respectively; P = 0.01). CONCLUSION: Our results indicate that sepsis in abdominal laparoscopic patients might constitute an additional trigger of the EPCs mobilization as compared with non-septic surgical patients. A larger mobilization of CD133+/CD34+ EPCs, preceded by enhanced plasmatic SDF-1α, occurs in septic surgical patients regardless of HIF-1α expression therein. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT02589535 . Registered 28 October 2015.

Pathogenesis-Targeted Preventive Strategies for Multidrug Resistant Ventilator-Associated Pneumonia: A Narrative Review.

Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in the intensive care unit (ICU), accounting for relevant morbidity and mortality among critically ill patients, especially when caused by multidrug resistant (MDR) organisms. The rising problem of MDR etiologies, which has led to a reduction in treatment options, have increased clinician's attention to the employment of effective prevention strategies. In this narrative review we summarized the evidence resulting from 27 original articles that were identified through a systematic database search of the last 15 years, focusing on several pathogenesis-targeted strategies which could help preventing MDR-VAP. Oral hygiene with Chlorhexidine (CHX), CHX body washing, selective oral decontamination (SOD) and/or digestive decontamination (SDD), multiple decontamination regimens, probiotics, subglottic secretions drainage (SSD), special cuff material and shape, silver-coated endotracheal tubes (ETTs), universal use of gloves and contact isolation, alcohol-based hand gel, vaporized hydrogen peroxide, and bundles of care have been addressed. The most convincing evidence came from interventions directly addressed against the key factors of MDR-VAP pathogenesis, especially when they are jointly implemented into bundles. Further research, however, is warranted to identify the most effective combination.

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.

OBJECTIVE: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. PATIENTS AND METHODS: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. RESULTS: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). CONCLUSIONS: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.

LPS removal reduces CD80-mediated albuminuria in critically ill patients with Gram-negative sepsis.

LPS-induced sepsis is a leading cause of acute kidney injury (AKI) in critically ill patients. LPS may induce CD80 expression in podocytes with subsequent onset of proteinuria, a risk factor for progressive chronic kidney disease (CKD) frequently observed after AKI. This study aimed to investigate the therapeutic efficacy of LPS removal in decreasing albuminuria through the reduction of podocyte CD80 expression. Between January 2015 and December 2017, 70 consecutive patients with Gram-negative sepsis-induced AKI were randomized to either have coupled plasma filtration and adsorption (CPFA) added to the standard care ( n = 35) or not ( n = 35). To elucidate the possible relationship between LPS-induced renal damage, proteinuria, and CD80 expression in Gram sepsis, a swine model of LPS-induced AKI was set up. Three hours after LPS infusion, animals were treated or not with CPFA for 6 h. Treatment with CPFA significantly reduced serum cytokines, C-reactive protein, procalcitonin, and endotoxin levels in patients with Gram-negative sepsis-induced AKI. CPFA significantly lowered also proteinuria and CD80 urinary excretion. In the swine model of LPS-induced AKI, CD80 glomerular expression, which was undetectable in control pigs, was markedly increased at the podocyte level in LPS-exposed animals. CPFA significantly reduced LPS-induced proteinuria and podocyte CD80 expression in septic pigs. Our data indicate that LPS induces albuminuria via podocyte expression of CD80 and suggest a possible role of timely LPS removal in preventing the maladaptive repair of the podocytes and the consequent increased risk of CKD in sepsis-induced AKI.

Prediction of extubation failure in Intensive Care Unit: systematic review of parameters investigated.

INTRODUCTION: Extubation failure (EF) refers to the inability to maintain spontaneous breathing after removal of endotracheal tube. The aim of this review is to identify the best parameter to predict EF in adult intensive care patients. EVIDENCE ACQUISITION: We searched for publications in PubMed (2000-2016). Studies of patients intubated and mechanically ventilated for more than 24 hours were included and divided in groups basing on the extubation method. 2x2 tables were performed to evaluate the sensitivity, specificity and the predictive values only for those parameters investigated in more than three studies. Studies were divided in groups, basing on time required to define EF (<24 hours, <72 or >72 hours), and EF percentage was calculated for each group. EVIDENCE SYNTHESIS: On 443 potentially studies, 26 were included. Rapid Shallow Breathing Index (RSBI) and cough strength parameters were found in more than three studies. RSBI or cough strength parameter showed a sensitivity of 20-88.8% or 55.5-85.2%, a specificity of 68.5-94.8% or 24-49%, a positive predictive value (PPV) of 39.5-66.6% or 24-49% and a negative predictive value of 98-82% or 89.5-96.4%, respectively. EF rate was 12.5%, 15.3% and 22% in patients evaluated within 24 hours, 72 hours and over 72 hours, respectively. CONCLUSIONS: This review shows that all parameters used to predict EF have a low PPV. Therefore, the limitation of use of such predictive tests may prolong unnecessarily the intubation and increase the unfavorable outcome. A prospective study involving all variables could be useful to predict the EF in ICU.

Peep titration based on the open lung approach during one lung ventilation in thoracic surgery: a physiological study.

BACKGROUND: During thoracic surgery in lateral decubitus, one lung ventilation (OLV) may impair respiratory mechanics and gas exchange. We tested a strategy based on an open lung approach (OLA) consisting in lung recruitment immediately followed by a decremental positive-end expiratory pressure (PEEP) titration to the best respiratory system compliance (CRS) and separately quantified the elastic properties of the lung and the chest wall. Our hypothesis was that this approach would improve gas exchange. Further, we were interested in documenting the impact of the OLA on partitioned respiratory system mechanics. METHODS: In thirteen patients undergoing upper left lobectomy we studied lung and chest wall mechanics, transpulmonary pressure (PL), respiratory system and transpulmonary driving pressure (ΔPRS and ΔPL), gas exchange and hemodynamics at two time-points (a) during OLV at zero end-expiratory pressure (OLVpre-OLA) and (b) after the application of the open-lung strategy (OLVpost-OLA). RESULTS: The external PEEP selected through the OLA was 6 ± 0.8 cmH2O. As compared to OLVpre-OLA, the PaO2/FiO2 ratio went from 205 ± 73 to 313 ± 86 (p = .05) and CL increased from 56 ± 18 ml/cmH2O to 71 ± 12 ml/cmH2O (p = .0013), without changes in CCW. Both ΔPRS and ΔPL decreased from 9.2 ± 0.4 cmH2O to 6.8 ± 0.6 cmH2O and from 8.1 ± 0.5 cmH2O to 5.7 ± 0.5 cmH2O, (p = .001 and p = .015 vs OLVpre-OLA), respectively. Hemodynamic parameters remained stable throughout the study period. CONCLUSIONS: In our patients, the OLA strategy performed during OLV improved oxygenation and increased CL and had no clinically significant hemodynamic effects. Although our study was not specifically designed to study ΔPRS and ΔPL, we observed a parallel reduction of both after the OLA. TRIAL REGISTRATION: TRN: ClinicalTrials.gov , NCT03435523 , retrospectively registered, Feb 14 2018.

Platelet indices and outcome after cardiac arrest.

BACKGROUND: Platelet variables, including platelet distribution width (PDW) and mean platelet volume (MPV), have been associated with outcome in critically ill patients. We evaluated these variables in patients after cardiac arrest (CA). METHODS: All adult CA patients admitted to the intensive care unit (ICU) over an 8-year period (2006-2014) and treated with targeted temperature management were included. We retrieved all data concerning CA characteristics as well as platelet count, PDW and MPV on the first 2 days of admission. Unfavorable 3-month neurological outcome was defined as a cerebral performance category score of 3-5. RESULTS: We included 384 patients (age 62 [52-75] years; 270/384 male): 231 patients (60%) died within 30-days and 246 patients (64%) had an unfavorable 3-month neurological outcome. On admission, platelet count, PDW and MPV were 87 [126-261] *103cells/mm3, 17 [16.3-17.3]% and 8.3 [7.6-9.2] µm3, respectively. Platelet count decreased significantly over the first 2 days, whereas PDW and MPV did not change significantly. There were no significant differences between the values on admission or time-courses of platelet count, PDW or MPV between survivors and non-survivors or between patients with unfavorable and favorable neurological outcome. CONCLUSIONS: In our cohort of post-CA patients, PDW and MPV were not associated with outcome.