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Previous studies described impaired microvascular perfusion and tissue oxygenation as reliable predictors of Multiple Organ Failure in major trauma. However, this relationship has been incompletely investigated. The objective of this analysis is to further evaluate the association between organ dysfunction and microcirculation after trauma. This is a retrospective subgroup analysis on 28 trauma patients enrolled for the Microcirculation DAIly MONitoring in critically ill patients study (NCT 02649088). Patients were divided in two groups according with their Sequential Organ Failure Assessment (SOFA) score at day 4. At admission and every 24 hours, the sublingual microcirculation was evaluated with Sidestream Darkfield Imaging (SDF) and peripheral tissue perfusion was assessed with Near Infrared Spectroscopy (NIRS) and Vascular Occlusion Test (VOT). Simultaneously, hemodynamic, clinical/laboratory parameters and main organ supports were collected. Median SOFA score at Day 4 was 6.5. Accordingly, patients were divided in two groups: D4-SOFA ≤6.5 and D4-SOFA >6.5. The Length of Stay in Intensive Care was significantly higher in patients with D4-SOFA>6.5 compared to D4-SOFA≤6.5 (p = 0.013). Total Vessel Density of small vessels was significantly lower in patients with high D4-SOFA score at Day 1 (p = 0.002) and Day 2 (p = 0.006) after admission; the Perfused Vessel Density was lower in patients with high D4-SOFA score at Day 1 (p = 0.007) and Day 2 (p = 0.033). At Day 1, NIRS monitoring with VOT showed significantly faster tissue oxygen saturation downslope (p = 0.018) and slower upslope (p = 0.04) in patients with high D4-SOFA. In our cohort of major traumas, sublingual microcirculation and peripheral microvascular reactivity were significantly more impaired early after trauma in those patients who developed more severe organ dysfunctions. Our data would support the hypothesis that restoration of macrocirculation can be dissociated from restoration of peripheral and tissue perfusion, and that microvascular alterations can be associated with organ failure.

Microcirculatory dysfunction plays a key role in the pathogenesis of tissue dysoxia and organ failure in sepsis. Sublingual videomicroscopy techniques enable the real-time non-invasive assessment of microvascular blood flow. Alterations in sublingual microvascular perfusion were detected during sepsis and are associated with poor outcome. More importantly, sublingual videomicroscopy allowed to explore the effects of commonly applied resuscitative treatments in septic shock, such as fluids, vasopressors and inotropes, and showed that the optimization of macro-hemodynamic parameters may not be accompanied by an improvement in microvascular perfusion. This loss of “hemodynamic coherence,” i.e., the concordance between the response of the macrocirculation and the microcirculation, advocates for the integration of microvascular monitoring in the management of septic patients. Nonetheless, important barriers remain for a widespread use of sublingual videomicroscopy in the clinical practice. In this review, we discuss the actual limitations of this technique and future developments that may allow an easier and faster evaluation of the microcirculation at the bedside, and propose a role for sublingual microvascular monitoring in guiding and titrating resuscitative therapies in sepsis.

Mechanical ventilation with high tidal volume (TV) or positive end-expiratory pressure (PEEP) may induce lung overinflation and increased pulmonary vascular resistance to flow. In 8 healthy mechanically ventilated pigs, we evaluated whether incident dark field (IDF) vital microscopy, applied through a small thoracotomy, could be used to evaluate changes in alveolar and pulmonary microvessel dimensions under different ventilator settings. High TV (12 ml/kg) increased alveolar diameters (from 99 ± 13 to 114 ± 6 μm, p  < 0.05 repeated measures one way analysis of variance) and reduced septal capillary diameters (from 12.1 ± 1.7 to 10.5 ± 1.4 μm, p  < 0.001) as compared to 8 ml/kg TV. This effect was more pronounced in non-dependent lung. Alveolar and microvessel diameters did not change with high PEEP (12 cmH 2 O Vs. 5 cmH 2 O). High FiO 2 (100%) led to pulmonary vasodilation (from 12.1 ± 1.7 to 14.7 ± 1.4 μm, p  < 0.001), with no change in alveolar dimensions as compared to 50% FiO 2 . In conclusion, IDF imaging enabled to obtain high-quality images of subpleural alveoli and microvessels. High TV ventilation may induce alveolar distension with compression of septal capillaries, thus potentially increasing dead space ventilation.

Septic shock is associated with massive release of endogenous catecholamines. Adrenergic agents may exacerbate catecholamine toxicity and contribute to poor outcomes. We sought to determine whether an association existed between tachycardia and mortality in septic shock patients requiring norepinephrine for more than 6 h despite adequate volume resuscitation. Multicentre retrospective observational study on 730 adult patients in septic shock consecutively admitted to eight European ICUs between 2011 and 2013. Three timepoints were selected: T1 (first hour of infusion of norepinephrine), Tpeak (time of highest dose during the first 24 h of treatment), and T24 (24-h post-T1). Binary logistic regression models were constructed for the three time-points. Overall ICU mortality was 38.4%. Mortality was higher in those requiring high-dose (≥0.3 mcg/kg/min) versus low-dose (<0.3 mcg/kg/min) norepinephrine at T1 (53.4% vs 30.6%; p < 0.001) and T24 (61.4% vs 20.4%; p < 0.0001). Patients requiring high-dose with concurrent tachycardia had higher mortality at T1; in the low-dose group tachycardia was not associated with mortality. Resolving tachycardia (from T1 to T24) was associated with lower mortality compared to patients where tachycardia persisted (27.8% vs 46.4%; p = 0.001). Use of high-dose norepinephrine and concurrent tachycardia are associated with poor outcomes in septic shock. •Initial high-dose norepinephrine was associated with worse outcome in septic shock•Mortality was higher if tachycardia was present on commencement of norepinephrine•Resolving tachycardia showed lower mortality compared to persisting tachycardia

Background Impaired microcirculatory perfusion and tissue oxygenation during critical illness are associated with adverse outcome. The aim of this study was to detect alterations in tissue oxygenation or microvascular reactivity and their ability to predict outcome in critically ill patients using thenar near-infrared spectroscopy (NIRS) with a vascular occlusion test (VOT). Methods Prospective observational study in critically ill adults admitted to a 12-bed intensive care unit (ICU) of a University Hospital. NIRS with a VOT (using a 40 % tissue oxygen saturation (StO 2 ) target) was applied daily until discharge from the ICU or death. A group of healthy volunteers were evaluated in a single session. During occlusion, StO 2 downslope was measured separately for the first (downslope 1) and last part (downslope 2) of the desaturation curve. The difference between downslope 2 and 1 was calculated (delta-downslope). The upslope and area of the hyperaemic phase (receive operating characteristic (ROC) area under the curve (AUC) of StO 2 ) were calculated, reflecting microvascular reactivity. Outcomes were ICU and 90-day mortality. Results Patients ( n  = 89) had altered downslopes and upslopes compared to healthy volunteers ( n  = 27). Mean delta-downslope was higher in ICU non-survivors (2.8 (0.4, 3.8) %/minute versus 0.4 (−0.8, 1.8) in survivors, p  = 0.004) and discriminated 90-day mortality (ROC AUC 0.72 (95 % confidence interval 0.59, 0.84)). ICU non-survivors had lower mean upslope (141 (75, 193) %/minute versus 185 (143, 217) in survivors, p  = 0.016) and AUC StO 2 (7.9 (4.3, 12.6) versus 14.5 (11.2, 21.3), p  = 0.001). Upslope and AUC StO 2 on admission were significant although weak predictors of 90-day mortality (ROC AUC = 0.68 (0.54, 0.82) and 0.70 (0.58, 0.82), respectively). AUC StO 2  ≤ 6.65 (1st quartile) on admission was independently associated with higher 90-day mortality (hazard ratio 7.964 (95 % CI 2.211, 28.686)). The lowest upslope in the ICU was independently associated with survival after ICU discharge (odds ratio 0.970 (95 % CI 0.945, 0.996)). Conclusions In critically ill patients, NIRS with a VOT enables identification of alterations in tissue oxygen extraction capacity and microvascular reactivity that can predict mortality. Trial registration NCT02649088, www.clinicaltrials.gov , date of registration 23rd December 2015, retrospectively registered.

Background/Objectives: In surgical antibiotic prophylaxis (SAP), most studies continue to report the number of prescriptions aggregated at the hospital level, rarely integrating the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) classes with standardized volume indicators. This study aimed to evaluate the utilization of antibiotics for SAP in a large Italian teaching hospital using both the number of prescriptions and defined daily doses (DDDs) and mapped the AWaRe models across different surgical specialties to highlight differences relevant to management. Methods: We conducted a prospective hospital-wide surveillance of all consecutive patients undergoing surgical procedures between March and May 2023 at the Azienda Ospedaliero-Universitaria delle Marche. Data included demographics, surgical specialty, and all antibiotic administrations with indication. For SAP, each prescription was classified according to the 2023 WHO AWaRe framework, and consumption was quantified using the WHO ATC/DDD methodology. Results: A total of 914 patients were monitored, with complete antibiotic data for 793 (86.8%). Among 433 SAP prescriptions, the most frequently used agent was cefazolin (82%), followed by amoxicillin/β-lactamase inhibitor (5%) and metronidazole (5%). According to AWaRe, 93% of SAP prescriptions were Access agents and 7% were Watch agents; no Reserve antibiotics were used. When expressed in DDDs (total: 443.5), 87.8% were Access and 12.2% Watch. Cefazolin accounted for over 85% of Access DDDs. Conclusions: By combining AWaRe classes with DDDs and resolving results by surgical specialty, this study extends hospital-level metrics and provides a pragmatic framework for SAP benchmarking. The predominance of Access agents is consistent with management objectives, while differences across specialties identify concrete tools for local quality improvement.

BackgroundIn COVID-19 patients requiring mechanical ventilation, the administration of high oxygen (O2) doses for prolonged time periods may be necessary. Although life-saving in most cases, O2 may exert deleterious effects if administered in excessive concentrations. We aimed to describe the prevalence of hyperoxemia and excessive O2 administration in mechanically ventilated patients with SARS-CoV-2 pneumonia and determine whether hyperoxemia is associated with mortality in the Intensive Care Unit (ICU) or the onset of ventilator-associated pneumonia (VAP).Materials and methodsRetrospective single-center study on adult patients with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation for ≥48 h. Patients undergoing extracorporeal respiratory support were excluded. We calculated the excess O2 administered based on the ideal arterial O2 tension (PaO2) target of 55–80 mmHg. We defined hyperoxemia as PaO2 > 100 mmHg and hyperoxia + hyperoxemia as an inspired O2 fraction (FiO2) > 60% + PaO2 > 100 mmHg. Risk factors for ICU-mortality and VAP were assessed through multivariate analyses.ResultsOne hundred thirty-four patients were included. For each day of mechanical ventilation, each patient received a median excess O2 of 1,121 [829–1,449] L. Hyperoxemia was found in 38 [27–55]% of arterial blood gases, hyperoxia + hyperoxemia in 11 [5–18]% of cases. The FiO2 was not reduced in 69 [62–76]% of cases of hyperoxemia. Adjustments were made more frequently with higher PaO2 or initial FiO2 levels. ICU-mortality was 32%. VAP was diagnosed in 48.5% of patients. Hyperoxemia (OR 1.300 95% CI [1.097–1.542]), time of exposure to hyperoxemia (OR 2.758 [1.406–5.411]), hyperoxia + hyperoxemia (OR 1.144 [1.008–1.298]), and daily excess O2 (OR 1.003 [1.001–1.005]) were associated with higher risk for ICU-mortality, independently of age, Sequential Organ failure Assessment score at ICU-admission and mean PaO2/FiO2. Hyperoxemia (OR 1.033 [1.006–1.061]), time of exposure to hyperoxemia (OR 1.108 [1.018–1.206]), hyperoxia + hyperoxemia (OR 1.038 [1.003–1.075]), and daily excess O2 (OR 1.001 [1.000–1.001]) were identified as risk factors for VAP, independently of body mass index, blood transfusions, days of neuromuscular blocking agents (before VAP), prolonged prone positioning and mean PaO2/FiO2 before VAP.ConclusionExcess O2 administration and hyperoxemia were common in mechanically ventilated patients with SARS-CoV-2 pneumonia. The exposure to hyperoxemia may be associated with ICU-mortality and greater risk for VAP.

In COVID-19 patients on mechanical ventilation, VAP from remains a crucial risk factor for death. Antibiotic resistance represents an important problem in treating this infection. This study aims to describe the evolution of the superinfection from in patients with acute respiratory failure from SARS-CoV-2 infection admitted to ICU and compare the impact of two different antibiotic strategies on microbiological negativization. ingle-center observational retrospective study, including patients admitted to our ICU from March 2020 to May 2021 for acute respiratory failure from SARS-CoV-2 infection who developed superinfection. Clinical data at ICU admission were collected, as well as the timing of isolation of , its resistance profile, the site of infection, and the antibiotic therapy. Of the 32 patients enrolled, 10 patients (31.2%) were treated with the combination of high-dose ampicillin/sulbactam, high-dose tigecycline, intravenous and inhaled colistin , the other 22 (68.8%) were treated with the combination of two antibiotics . Of the 10 patients in the group, 8 patients (80%) received also fosfomycin. All patients (100%) in the group had microbiological negativization, while in the group microbiological negativization was observed in 8 (36.4%) patients, < 0.01. Our report shows microbiological negativization in all patients treated with the combination therapy of nebulized and intravenous colistin, high-dose tigecycline, and high-dose ampicillin/sulbactam. This combination of antibiotics seems to be a useful alternative when other treatments are not available or fail.

Background Cardiac surgery with extracorporeal circulation (ECC) can induce microvascular dysfunction and tissue hypoperfusion. We hypothesized that the alterations in near-infrared spectroscopy (NIRS)-derived parameters would be associated with post-operative complications in cardiac surgery patients. Methods Prospective observational study performed at two University Hospitals. Ninety patients undergoing cardiac surgery with ECC were enrolled. The NIRS sensor was applied on the thenar eminence. A vascular occlusion test (VOT, 3-min ischemia) was performed at baseline (t0), at Intensive Care Unit (ICU) admission (t1), 3 (t2) and 6 (t3) hours later. Baseline tissue oxygen saturation (StO 2 ), oxygen extraction rate and microvascular reactivity indices were calculated. Results In the first hours after cardiac surgery, StO 2 tended to increase (86% [80–89] at T3 versus 82% [79–86] at T0, p  = ns), while both tissue oxygen extraction and microvascular reactivity tended to decrease, as indicated by increasing occlusion slope (− 8.1%/min [− 11.2 to − 7] at T3 versus − 11.2%/min [− 13.9 to − 7.9] at T0, p  = ns) and decreasing recovery slope (1.9%/sec [1.1–2.9] at T3 versus 3.1%/sec [2.3–3.9] at T0, p  = ns). No substantial differences were found in NIRS-derived variables and their changes over time between patients with complications and those without complications. Conclusions Peripheral tissue oxygen extraction and microvascular reactivity were reduced during the first hours after cardiac surgery. NIRS-derived parameters were not able to predict complications in this population of cardiac surgery patients.

Objectives: Excessive oxygen (O 2 ) administration may have a negative impact on tissue perfusion by inducing vasoconstriction and oxidative stress. We aimed to evaluate the effects of different inhaled oxygen fractions (FiO 2 ) on macro-hemodynamics and microvascular perfusion in a rat model. Methods: Isoflurane-anesthetised spontaneously breathing male Wistar rats were equipped with arterial (carotid artery) and venous (jugular vein) catheters and tracheotomy, and randomized into three groups: normoxia (FiO 2 21%, n = 6), hyperoxia (FiO 2 100%, n = 6) and mild hypoxia (FiO 2 15%, n = 6). Euvolemia was maintained by infusing Lactate Ringer solution at 10 ml/kg/h. At hourly intervals for 4 h we collected measurements of: mean arterial pressure (MAP); stroke volume index (SVI), heart rate (HR), respiratory rate (by means of echocardiography); arterial and venous blood gases; microvascular density, and flow quality (by means of sidestream dark field videomicroscopy on the hindlimb skeletal muscle). Results: MAP and systemic vascular resistance index increased with hyperoxia and decreased with mild hypoxia ( p < 0.001 in both cases, two-way analysis of variance). Hyperoxia induced a reduction in SVI, while this was increased in mild hypoxia ( p = 0.002). The HR increased under hyperoxia ( p < 0.05 vs. normoxia at 3 h). Cardiax index, as well as systemic O 2 delivery, did not significantly vary in the three groups ( p = 0.546 and p = 0.691, respectively). At 4 h, microvascular vessel surface (i.e., the percentage of tissue surface occupied by vessels) decreased by 29 ± 4% in the hyperoxia group and increased by 19 ± 7 % in mild hypoxia group ( p < 0.001). Total vessel density and perfused vessel density showed similar tendencies ( p = 0.003 and p = 0.005, respectively). Parameters of flow quality (microvascular flow index, percentage of perfused vessels, and flow heterogeneity index) remained stable and similar in the three groups. Conclusions: Hyperoxia induces vasoconstriction and reduction in skeletal muscle microvascular density, while mild hypoxia has an opposite effect.