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Abstract 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

OBJECTIVES:. In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient’s respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN:. Retrospective observational cohort study. SETTING:. Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS:. Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION:. The transition period from CMV to PSV was evaluated. We defined it as “failure of assisted breathing” if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS:. Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99–1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42–3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS:. Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

Abstract Background Management of bleeding trauma patients is still a difficult challenge. Massive transfusion (MT) requires resources to ensure the safety and timely delivery of blood products. Early prediction of MT need may be useful to shorten the time process of blood product preparation. The primary aim of this study was to assess the accuracy of shock index to predict the need for MT in adult patients with trauma. For the same population, we also assessed the accuracy of SI to predict mortality. Methods This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. We performed a systematic search on MEDLINE, Scopus, and Web of Science from inception to March 2022. Studies were included if they reported MT or mortality with SI recorded at arrival in the field or the emergency department. The risk of bias was assessed using the QUADAS-2. Results Thirty-five studies were included in the systematic review and meta-analysis, for a total of 670,728 patients. For MT the overall sensibility was 0.68 [0.57; 0.76], the overall specificity was 0.84 [0.79; 0.88] and the AUC was 0.85 [0.81; 0.88]. Positive and Negative Likelihood Ratio (LR+; LR−) were 4.24 [3.18–5.65] and 0.39 [0.29–0.52], respectively. For mortality the overall sensibility was 0.358 [0.238; 0.498] the overall specificity 0.742 [0.656; 0.813] and the AUC 0.553 (confidence region for sensitivity given specificity: [0.4014; 0.6759]; confidence region for specificity given sensitivity: [0.4799; 0.6332]). LR+ and LR− were 1.39 [1.36–1.42] and 0.87 [0.85–0.89], respectively. Conclusions Our study demonstrated that SI may have a limited role as the sole tool to predict the need for MT in adult trauma patients. SI is not accurate to predict mortality but may have a role to identify patients with a low risk of mortality.

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.

Abstract Background It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. Methods Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. Results Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60–63] years vs 64 [62–66] years, p

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, while septic shock is a subset of sepsis with persistent hypotension requiring vasopressors to maintain a mean arterial pressure (MAP) of ≥65 mmHg and having a serum lactate level of >2 mmol/L, despite adequate volume resuscitation. Sepsis and septic shock are medical emergencies and time-dependent diseases with a high mortality rate for which early identification, early antibiotic therapy, and early source control are paramount for patient outcomes. The patient may require surgical intervention or an invasive procedure aiming to control the source of infection, and the anesthesiologist has a pivotal role in all phases of patient management. During the preoperative assessment, patients should be aware of all possible organ dysfunctions, and the severity of the disease combined with the patient's physiological reserve should be carefully assessed. All possible efforts should be made to optimize conditions before surgery, especially from a hemodynamic point of view. Anesthetic agents may worsen the hemodynamics of shock patients, and the anesthesiologist must know the properties of each anesthetic agent. All possible efforts should be made to maintain organ perfusion supporting hemodynamics with fluids, vasoactive agents, and inotropes if required.

Background: Accurate risk stratification of critically ill patients with coronavirus disease 2019 (COVID-19) is essential for optimizing resource allocation, delivering targeted interventions, and maximizing patient survival probability. Machine learning (ML) techniques are attracting increased interest for the development of prediction models as they excel in the analysis of complex signals in data-rich environments such as critical care. Methods: We retrieved data on patients with COVID-19 admitted to an intensive care unit (ICU) between March and October 2020 from the RIsk Stratification in COVID-19 patients in the Intensive Care Unit (RISC-19-ICU) registry. We applied the Extreme Gradient Boosting (XGBoost) algorithm to the data to predict as a binary outcome the increase or decrease in patients’ Sequential Organ Failure Assessment (SOFA) score on day 5 after ICU admission. The model was iteratively cross-validated in different subsets of the study cohort. Results: The final study population consisted of 675 patients. The XGBoost model correctly predicted a decrease in SOFA score in 320/385 (83%) critically ill COVID-19 patients, and an increase in the score in 210/290 (72%) patients. The area under the mean receiver operating characteristic curve for XGBoost was significantly higher than that for the logistic regression model (0.86 vs. 0.69, P

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.

IntroductionIn COVID-19 patients on mechanical ventilation, VAP from Acinetobacter baumannii 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 PDR Acinetobacter baumannii 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.MethodsSingle-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 PDR Acinetobacter baumannii superinfection. Clinical data at ICU admission were collected, as well as the timing of isolation of Acinetobacter baumannii, its resistance profile, the site of infection, and the antibiotic therapy.ResultsOf 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 (Protocol), the other 22 (68.8%) were treated with the combination of two antibiotics (Control). Of the 10 patients in the Protocol group, 8 patients (80%) received also fosfomycin. All patients (100%) in the Protocol group had microbiological negativization, while in the Control group microbiological negativization was observed in 8 (36.4%) patients, p < 0.01.ConclusionOur 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.

Abstract Background A cardiologist-only approach to procedural sedation with midazolam in the setting of elective cardioversion (DCC) for AF has already been proven as safe as sedation with propofol and anaesthesiologist assistance. No data exist regarding the safety of such a strategy during emergency procedures. The aim of this study is to compare the feasibility of sedation with midazolam, administered by a cardiologist, to an anaesthesiologist-assisted protocol with propofol in emergency DCC. Methods Single centre, prospective, open blinded, randomized study including all consecutive patients admitted to the Emergency Department requiring urgent or emergency DCC. Patients were randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the midazolam group were managed by the cardiologist only, while patients treated with propofol group underwent DCC with anaesthesiologist assistance. Results Sixty-nine patients were enrolled and split into two groups. Eighteen patients (26.1%) experienced peri-procedural adverse events (bradycardia, severe hypotension and severe hypoxia), which were similar between the two groups and all successfully managed by the cardiologist. No deaths, stroke or need for invasive ventilation were registered. Patients treated with propofol experienced a greater decrease in systolic and diastolic blood pressure when compared with those treated with midazolam. As the procedure was shorter when midazolam was used, the median cost of urgent/emergency DCC with midazolam was estimated to be 129.0 € (1st-3rd quartiles 114.6–151.6) and 195.6 € (1st-3rd quartiles 147.3–726.7) with propofol (p

Abstract Background Goal directed therapy (GDT) is able to improve mortality and reduce complications in selected high-risk patients undergoing major surgery. The aim of this study is to compare two different strategies of perioperative hemodynamic optimization: one based on optimization of preload using dynamic parameters of fluid-responsiveness and the other one based on estimated oxygen extraction rate (O2ER) as target of hemodynamic manipulation. Methods This is a multicenter randomized controlled trial. Adult patients undergoing elective major open abdominal surgery will be allocated to receive a protocol based on dynamic parameters of fluid-responsiveness or a protocol based on estimated O2ER. The hemodynamic optimization will be continued for 6 h postoperatively. The primary outcome is difference in overall postoperative complications rate between the two protocol groups. Fluids administered, fluid balance, utilization of vasoactive drugs, hospital length of stay and mortality at 28 day will also be assessed. Discussion As a predefined target of cardiac output (CO) or oxygen delivery (DO2) seems to be not adequate for every patient, a personalized therapy is likely more appropriate. Following this concept, dynamic parameters of fluid-responsiveness allow to titrate fluid administration aiming CO increase but avoiding fluid overload. This approach has the advantage of personalized fluid therapy, but it does not consider if CO is adequate or not. A protocol based on O2ER considers this second important aspect. Although positive effects of perioperative GDT have been clearly demonstrated, currently studies comparing different strategies of hemodynamic optimization are lacking. Trial registration ClinicalTrials.gov, NCT04053595 . Registered on 12/08/2019.

Healthcare-associated infections (HAIs) result in significant patient morbidity and can prolong the duration of the hospital stay, causing high supplementary costs in addition to those already sustained due to the patient’s underlying disease. Moreover, bacteria are becoming increasingly resistant to antibiotics, making HAI prevention even more important nowadays. The public health consequences of antimicrobial resistance should be constrained by prevention and control actions, which must be a priority for all health systems of the world at all levels of care. As many HAIs are preventable, they may be considered an important indicator of the quality of patient care and represent an important patient safety issue in healthcare. To share implementation strategies for preventing HAIs in the surgical setting and in all healthcare facilities, an Italian multi-society document was published online in November 2022. This article represents an evidence-based summary of the document.

Introduction: Microvascular alterations are involved in the development of organ injury in critical care patients. Mid-regional proadrenomedullin (MR-proADM) may predict organ damage and its evolution. The main objective of this study was to assess the correlation between MR-proADM and microvascular flow index (MFI) in a small cohort of 20 adult critical care patients diagnosed with infection, sepsis, or septic shock. Further objectives were to evaluate the correlation between the clearance of MR-proADM and the variables of microcirculation and between MR-proADM and the Sequential Organ Failure Assessment (SOFA) score.Materials and Methods: This is a prospective observational pilot study. Inclusion criteria: consecutive adult patients admitted to intensive care unit (ICU) for or with infection-related illness. Daily measurement of MR-proADM and calculation of the SOFA score from admission in ICU to day 5. Repeated evaluations of sublingual microcirculation, collection of clinical data, and laboratory tests.Results: Primary outcome: MR-proADM was not significantly correlated to the MFI at admission in ICU. A clearance of MR-proADM of 20% or more in the first 24 h was related to the improvement of the MFIs and MFIt [percentual variation of the MFIs + 12.35 (6.01–14.59)% vs. +2.23 (−4.45–6.01)%, p = 0.005; MFIt +9.09 (4.53–16.26)% vs. −1.43 (−4.36–3.12)%, p = 0.002].Conclusion: This study did not support a direct correlation of MR-proADM with the MFI at admission in ICU; however, it showed a good correlation between the clearance of MR-proADM, MFI, and other microvascular variables. This study also supported the prognostic value of the marker. Adequately powered studies should be performed to confirm the findings.

Abstract Background Polyclonal or IgM-enriched immunoglobulins may be beneficial during sepsis as an adjuvant immunomodulatory therapy. We aimed to test whether the infusion of IgM-enriched immunoglobulins improves microvascular perfusion during sepsis. Methods Single-centre, randomized, double-blind, placebo-controlled phase II trial including adult patients with a diagnosis of sepsis or septic shock for less than 24 h. Patients received an intravenous infusion of 250 mg/kg (5 mL/kg) per day of IgM-enriched immunoglobulins (Pentaglobin, n = 10) for 72 h or placebo (NaCl 0.9%, n = 9). At baseline and after 24 and 72 h of infusion, the sublingual microcirculation was assessed with Incident Dark Field videomicroscopy. Thenar near-infrared spectroscopy (NIRS) was applied with a vascular occlusion test to assess tissue oxygenation and microvascular reactivity. Levels of interleukin (IL) 1-beta, IL-6, IL-8, IL-10 and tumour necrosis factor alpha were measured in the serum. Results The perfused vessel density (PVD) for small vessels (diameter

Abstract Background Airway pressure release ventilation (APRV) has been considered a tempting mode of ventilation during acute respiratory failure within the concept of open lung ventilation. We performed a systematic review and meta-analysis to verify whether adult patients with hypoxemic respiratory failure have a higher number of ventilator-free days at day 28 when ventilated in APRV compared to conventional ventilation strategy. Secondary outcomes were difference in PaO2/FiO2 at day 3, ICU length of stay (LOS), ICU and hospital mortality, mean arterial pressure (MAP), risk of barotrauma and level of sedation. We searched MEDLINE, Scopus and Cochrane Central Register of Controlled Trials database until December 2018. Results We considered five RCTs for the analysis enrolling a total of 330 patients. For ventilatory-free day at day 28, the overall mean difference (MD) between APRV and conventional ventilation was 6.04 days (95%CI 2.12, 9.96, p = 0.003; I 2 = 65%, p = 0.02). Patients treated with APRV had a lower ICU LOS than patients treated with conventional ventilation (MD 3.94 days [95%CI 1.44, 6.45, p = 0.002; I 2 = 37%, p = 0.19]) and a lower hospital mortality (RD 0.16 [95%CI 0.02, 0.29, p = 0.03; I 2 = 0, p = 0.5]). PaO2/FiO2 at day 3 was not different between the two groups (MD 40.48 mmHg [95%CI − 25.78, 106.73, p = 0.23; I 2 = 92%, p

Abstract Background In vascular surgery with aortic cross-clamping, ischemia/reperfusion injury induces systemic haemodynamic and microcirculatory disturbances. Different anaesthetic regimens may have a varying impact on tissue perfusion. The aim of this study was to explore changes in microvascular perfusion in patients undergoing elective open abdominal aortic aneurysm repair under balanced or total intravenous anaesthesia. Methods Prospective observational study. Patients undergoing elective open infrarenal abdominal aortic aneurysm repair received balanced (desflurane + remifentanil, n = 20) or total intravenous anaesthesia (TIVA, propofol + remifentanil using target-controlled infusion, n = 20) according to the clinician’s decision. A goal-directed haemodynamic management was applied in all patients. Measurements were obtained before anaesthesia induction (baseline) and at end-surgery and included haemodynamics, arterial/venous blood gases, sublingual microvascular flow and density (incident dark field illumination imaging), peripheral muscle tissue oxygenation and microcirculatory reactivity (thenar near infrared spectroscopy with a vascular occlusion test). Results The two groups did not differ for baseline characteristics, mean aortic-clamping time and requirement of vasoactive agents during surgery. Changes in mean arterial pressure, systemic vascular resistance index, haemoglobin and blood lactate levels were similar between the two groups, while the cardiac index increased at end-surgery in patients undergoing balanced anaesthesia. The sublingual microcirculation was globally unaltered in the TIVA group at end-surgery, while patients undergoing balanced anaesthesia showed an increase in the total and perfused small vessel densities (from 16.6 ± 4.2 to 19.1 ± 5.4 mm/mm2, p

Objectives: Excessive oxygen (O2) 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 (FiO2) 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 (FiO2 21%, n = 6), hyperoxia (FiO2 100%, n = 6) and mild hypoxia (FiO2 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 O2 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.

Objective: To evaluate the outcome of patients with septic shock after the institution of a patient tailored therapy protocol in our Intensive Care Unit (ICU).Methods: Single-center retrospective observational study including 100 consecutive septic patients (≥ 16 years) requiring norepinephrine infusion, admitted to our ICU between 2018 and 2019 after the institution of a patient-tailored therapy protocol, compared with a historical control group of 100 patients admitted between 2010 and 2013 (historical controls). The patient-tailored therapy protocol included the use of IgM-enriched immunoglobulins for patients with low plasma IgM levels, blood purification strategies for patients with high plasma levels of cytokines or endotoxin, albumin correction and modulation of vasoactive agents. Clinical and therapeutic parameters were noted at the time of initiation of norepinephrine infusion and for the 1st 24 h. The primary outcome was ICU mortality.Results: ICU-mortality was lower in the patient-tailored therapy cohort as compared to historical controls (32 vs. 57%, p < 0.001). Patient-tailored therapy was associated with a lower risk of ICU-mortality even after adjusting for the main clinical severity indices (adjusted odds ratio 0.331 [95% confidence interval 0.166–0.658], p = 0.002). After propensity score matching, 48 patients in historical control group and 48 patients in the patient-tailored therapy cohort with similar general characteristics were selected. ICU-mortality was lower in the patient-tailored therapy matched subgroup as compared to historical controls (40 vs. 60%, p = 0.037).Conclusions: An individualized therapeutic approach in septic patients may be associated with a survival benefit. However, the use of an historical control group of patients admitted between 2010 and 2013 may introduce substantial bias. Further adequately designed studies are needed to demonstrate the impact of patient-tailored therapy on outcome.

Abstract Background Until now, the prognostic value of microcirculatory alterations in critically ill patients has been mainly evaluated in highly selected subgroups. Aim of this study is to monitor the microcirculation daily in mixed group of Intensive Care Unit (ICU)-patients and to establish the association between (the evolution of) microcirculatory alterations and outcome. Methods This is a prospective longitudinal observational single-centre study in adult patients admitted to a 12-bed ICU in an Italian teaching hospital. Sublingual microcirculation was evaluated daily, from admission to discharge/death, using Sidestream Dark Field imaging. Videos were analysed offline to assess flow and density variables. Laboratory and clinical data were recorded simultaneously. A priori, a Microvascular Flow Index (MFI) 2 mmol/L and MFI

INTRODUCTION: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. MATERIALS AND METHODS: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. RESULTS: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. DISCUSSION: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.

Free hemoglobin (fHb) may induce vasoconstriction by scavenging nitric oxide. It may increase in older blood units due to storage lesions. This study evaluated whether old red blood cell transfusion increases plasma fHb in sepsis and how the microvascular response may be affected.This is a secondary analysis of a randomized study. Twenty adult septic patients received either fresh or old (15 days storage, respectively) RBC transfusions. fHb was measured in RBC units and in the plasma before and 1 hour after transfusion. Simultaneously, the sublingual microcirculation was assessed with sidestream-dark field imaging. The perfused boundary region was calculated as an index of glycocalyx damage. Tissue oxygen saturation (StO2) and Hb index (THI) were measured with near-infrared spectroscopy and a vascular occlusion test was performed.Similar fHb levels were found in the supernatant of fresh and old RBC units. Despite this, plasma fHb increased in the old RBC group after transfusion (from 0.125 [0.098-0.219] mg/mL to 0.238 [0.163-0.369] mg/mL, p = 0.006). The sublingual microcirculation was unaltered in both groups, while THI increased. The change in plasma fHb was inversely correlated with the changes in total vessel density (r = -0.57 [95% confidence interval -0.82, -0.16], p = 0.008), De Backer score (r = -0.63 [95% confidence interval -0.84, -0.25], p = 0.003) and THI (r = -0.72 [95% confidence interval -0.88, -0.39], p = 0.0003).Old RBC transfusion was associated with an increase in plasma fHb in septic patients. Increasing plasma fHb levels were associated with decreased microvascular density.ClinicalTrials.gov NCT01584999.