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Objective: To describe the experience with CytoSorb treatment in patients with refractory acute respiratory distress syndrome (ARDS) following SARS-CoV-2 infection. Methods: Retrospective observational study on 15 patients treated in a University Hospital. Results: All patients were male, with a mean age of 55 ± 14 years; eight patients (53%) were on venovenous extracorporeal membrane oxygenation (VV ECMO) due to refractory ARDS and all (100%) under mechanical ventilation at the time of CytoSorb use. We observed reduction in the level of C reactive protein (−52%, p = 0.002), total bilirubin (−46%, p = 0.03), direct bilirubin (−50%, p = 0.02), and D-dimers (−39%, p = 0.04) during CytoSorb treatment and a trend toward reduction in lactate dehydrogenase (−20%, p = 0.2), creatine phosphokinase (−38%, p = 0.1), and fibrinogen (−15%, p = 0.07). Eight patients died (53%) and seven (47%) were discharged from the ICU, of which five had recovery of the native lung function and two were successfully bridged to lung transplantation on VV ECMO support. No difference between survivors and non-survivors was present at baseline. Patients received three CytoSorb cycles on average: mean duration of CytoSorb cycle was 17 h 21 min, but premature circuit clotting despite appropriate level of systemic anticoagulation was frequently observed. Conclusions: CytoSorb treatment was effective in improving several laboratory parameters and inflammation in our experience and no treatment-related adverse effects were recorded. In the light of the unique pathophysiology of SARS-CoV-2 infection, CytoSorb treatment is extremely promising, since it might both reduce inflammation and activation of coagulation.

Results from recent large randomized trials investigating the use of high PEEP in patients without ARDS all suggest that high levels may increase mortality due to hypotension and bradycardia. A careful assessment of cardiac function — with particular focus on the right ventricle — should be performed before planning our ventilation strategy in any setting, including COVID-19 and ARDS in general. Mechanical ventilation should be respectful in regards of heart function, and tolerant with moderate hypoxia and hypercapnia, noninvasive (whenever possible) and synchronized.

OBJECTIVE: The use of angiotensin II in invasively ventilated patients with coronavirus disease 2019 (COVID-19) is controversial. Its effect on organ function is unknown. DESIGN: Prospective observational study. SETTING: Intensive care unit (ICU) of a tertiary academic hospital in Milan, Italy. PARTICIPANTS: Adult patients receiving mechanical ventilation due to COVID-19. INTERVENTIONS: Use angiotensin II either as rescue vasopressor agent or as low dose vasopressor support. MAIN OUTCOME MEASURES: Patients treated before angiotensin II was available or treated in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of angiotensin II on organ function. RESULTS: We compared 46 patients receiving angiotensin II therapy with 53 controls. Compared with controls, angiotensin II increased the mean arterial pressure (median difference, 9.05 mmHg; 95% CI, 1.87–16.22; P = 0.013) and the Pao2/Fio2 ratio (median difference, 23.17; 95% CI, 3.46–42.88; P = 0.021), and decreased the odds ratio (OR) of liver dysfunction (OR, 0.32; 95% CI, 0.09–0.94). However, angiotensin II had no effect on lactate, urinary output, serum creatinine, C-reactive protein, platelet count, or thromboembolic complications. In patients with abnormal baseline serum creatinine, Bayesian modelling showed that angiotensin II carried a 95.7% probability of reducing the use of renal replacement therapy (RRT). CONCLUSIONS: In ventilated patients with COVID-19, angiotensin II therapy increased blood pressure and Pao2/Fio2 ratios, decreased the OR of liver dysfunction, and appeared to decrease the risk of RRT use in patients with abnormal baseline serum creatinine. However, all of these findings are hypothesis-generating only. TRIAL REGISTRATION: ClinicalTrials.gov NCT04318366.

Objective Patients with COVID-19 frequently develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. Data on long-term survival of these patients are lacking. We investigated 1-year survival, quality of life and functional recovery of COVID-19 ARDS patients requiring invasive mechanical ventilation Design Prospective observational study Setting Tertiary-care university hospital Participants All COVID-19 ARDS patients receiving invasive mechanical ventilation and discharged alive from hospital Interventions Patients were contacted by phone after 1-year. Functional, cognitive, and psychological outcomes were explored through a questionnaire and assessed using validated scales. Patients were offered the possibility to undergo a follow-up chest CT scan. Measurements and Main Results The study included all adult (age ≥ 18 years) patients with COVID-19-related ARDS admitted to an ICU of our institution between February 25th, 2020 - April 27th, 2020), who received at least one day of invasive mechanical ventilation (IMV). Of 116 patients who received IMV, 61 (52.6%) survived to hospital discharge. These survivors were assessed one year after discharge and 56 completed a battery of tests of cognition, activities of daily living and interaction with family members. They had overall good functional recovery, with >80% reporting good recovery and no difficulties in usual activities. A total of 52 (93%) of patients had no dyspnea at rest. Severe anxiety/depression was reported by five (8.9%) of patients. Comparing 2-months and 1-year data, we observed the most significant improvements in the areas of working status and exertional dyspnea. One-year Chest CT scans were available for 36 patients: fibrotic-like changes were present in four patients. Conclusions All patients who survived the acute phase of the COVID-19 disease and were discharged from the hospital were alive at the 1-year follow up and the vast majority of them had good overall recovery and quality of life. Study Registration ClinicalTrials.gov NCT04318366

Objective: To analyze the survival rates of patients with COVID-19 supported with extracorporeal membrane oxygenation (ECMO) and compare the survival rates of patients with COVID-19 supported with ECMO to patients with influenza supported with ECMO. Design: A systematic review and meta-analysis to assess the impact of ECMO as supportive therapy of COVID-19. Setting: The authors performed a search through the Cochrane, EMBASE, and MEDLINE/PubMed databases from inception to February 19, 2021, for studies reporting hospitalized patients with COVID-19 managed with ECMO. Participants: A total of 134 studies were selected, including 6 eligible for the comparative meta-analysis of COVID-19 versus influenza. Interventions: The authors pooled the risk ratio and random effects model. Measurements and Main Results: The primary endpoint was the overall mortality of patients with COVID-19 receiving ECMO. Of the total number of 58,472 patients with COVID-19 reported, ECMO was used in 4,044 patients. The analysis suggested an overall in-hospital mortality of 39% (95% CI 0.34-0.43). In the comparative analysis, patients with COVID-19 on ECMO had a higher risk ratio (RR) for mortality when compared to influenza patients on ECMO: 72/164 (44%) v 71/186 (38%) RR 1.34; 95% CI 1.05-1.71; p = 0.03. Conclusions: ECMO could be beneficial in patients with COVID-19, according to the authors’ meta-analysis. The reported mortality rate was 39%. This systematic analysis can provide clinical advice in the current era and ongoing pandemic.

Severe Coronavirus disease 2019 (COVID-19) is characterized by acute respiratory distress syndrome (ARDS) which may lead to long-lasting pulmonary sequelae in the survivors. COVID-19 shares common molecular signatures with interstitial lung diseases (ILDs), including pro-angiogenic and tissue-remodeling mechanisms mediated by vascular endothelial growth factor receptor (VEGF-R), fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R). Nintedanib mainly targets these factors and is approved for ILDs. Therefore, we administered nintedanib through compassionate use to three patients with COVID-19 pneumonia requiring extra-corporeal membrane-oxygenation (ECMO). Here, we describe our experience in an attempt to explore the role of nintedanib in lung recovery in COVID-19. Three obese patients aged between 42 and 52 years were started on nintedanib due to difficulty in obtaining lung function restoration and weaning from ECMO support following the removal of orotracheal intubation (OTI). Soon after the start of the treatment, systemic inflammation and respiratory function rapidly improved and ECMO support was withdrawn. Serial chest CT scans confirmed the progressive lung amelioration, also reflected by functional tests during follow-up. Nintedanib was well-tolerated by all the three patients at the dosage used for ILDs and continued for 2–3 months based on drug availability. Although caution in interpreting events is required; it is tempting to speculate that nintedanib may have contributed to modulate lung inflammation and remodeling and to sustain lung repair. Altogether, nintedanib appears as a promising agent in patients with severe COVID-19 and delayed respiratory function recovery, for whom molecularly targeted therapies are still lacking. Clinical trials are necessary to confirm our observations.

Objective: Open repair of thoraco-abdominal aortic aneurysm (TAAA) is a challenging procedure, associated with high rates of peri-operative bleeding and blood product transfusions. A large intra-operative volume transfusion has been associated with higher in hospital mortality and prolonged mechanical ventilation. A propensity score matched study was carried out to assess whether the introduction of a rotational thromboelastometry (ROTEM) based transfusion strategy reduces allogenic blood transfusion and affects morbidity in patients undergoing open TAAA repair. Methods: All patients undergoing open TAAA repair at the San Raffaele Scientific Institute between 2009 and 2017 were included. Until 2016, a protocol based on estimated blood loss and conventional coagulation tests was used. After March 2016 a ROTEM guided transfusion protocol was developed and adopted. To account for selection bias, propensity score matching was performed. Results: Five hundred and forty-seven consecutive patients were included. After propensity score matching, 77 patients in the ROTEM algorithm group were successfully matched with 77 patients in the standard algorithm group. Patients managed with ROTEM received fewer red blood cells units (3.5 [range 0–11] vs. 4 [range 0–17]; p = .026) and a lower volume of fresh frozen plasma (286 ± 496 vs. 2,050 ± 1,120; p < .001). In addition, fewer patients received fresh frozen plasma (35% vs. 97%; p < .001). Patients in the ROTEM group showed a significant decrease in the occurrence of pulmonary complications (44% vs. 83%; p = .01). Cost analysis showed a relevant reduction of per-patient expense after the introduction of ROTEM (€834 ± €577 vs. €1,285 ± €851; p < .001) Conclusion: A ROTEM guided transfusion strategy significantly limited the quantity of transfused blood products during open TAAA repair, improving clinical outcomes while reducing costs, allowing for better resource distribution in a setting where blood loss is relevant.

To identify reliable predictors of periprocedural intensive care unit (ICU) admission after transvenous lead extraction (LE) in a high-volume center.Retrospective observational study.University tertiary-care hospital.All patients undergoing LE at San Raffaele Scientific Institute, Milan, Italy, from 2005 to 2015.LE procedures were performed in the electrophysiology laboratories with a cardiac operating room on standby between the end of the morning surgical case and before the start of the afternoon surgical case. Most procedures were conducted with the patient under procedural sedation and analgesia. After LE, patients were admitted either to the ward or to the ICU. Medical history and intraprocedural data were recorded.Of the 389 procedures performed during the study period, 50 patients (13%) were admitted to the ICU owing to persistent hemodynamic instability or intraoperative complications requiring endotracheal intubation. Complete procedural success was achieved in 370 patients (95%), and the clinical success rate was 98.4%. No deaths were recorded. Five complications requiring emergency surgery (1.3%) were reported. Preprocedural right ventricular dysfunction (odds ratio (OR) 7.41; confidence interval 1.85-29.7; p0.01) and the need for general anesthesia (OR 12; confidence interval 1.49-97.06; p = 0.019) were independent predictors of ICU admission.Preoperative identification of patients who need ICU admission after LE is crucial to increase patient safety and decrease hospital costs. Severe right ventricular dysfunction and need for general anesthesia identify patients with low cardiac reserve who are at increased risk for ICU admission after the procedure.

Background Pain management after surgery is crucial to decrease perioperative morbidity and mortality. Acute pain services (APS) are multidisciplinary teams that represent a modern strategy to address pain inside hospitals. The APS defines and applies pain treatment protocols specific for each surgery. To evaluate the performance of the APS at our institute, we performed a large retrospective cohort study focusing on complications of epidural analgesia and IV opiates. Methods Data from the 10 years of activity of the APS were collected. Pain was assessed using the VAS at rest (VASr) and during movement (VASm) at each daily visit; the presence of side effects and complications was also assessed. Results A total of 17,913 adult patients were followed by APS during the study period. Epidural analgesia was used in 7,776 cases (43%), while 9,239 (52%) patients used IV patient-controlled analgesia (PCA). A combination of the 2 was used in 87 patients (0.5%). A total of 456 perineural catheters (2.6%) were placed, while 442 patients(2.5%) used other analgesic techniques. We recorded 163 dural punctures during catheter placement, with no epidural hematoma, epidural abscess, or meningitis, and no permanent modification in sensitive or motor functions. Conclusions In our large case series, APS was confirmed safe and effective in treating postoperative pain, using both epidural analgesia and IV PCA with morphine.

BACKGROUND: COVID-19 is associated with elevated levels of inflammatory cytokines. We present the characteristics and outcomes of patients treated in the Intensive Care Unit (ICU) with immunosuppressive drugs, either tocilizumab or anakinra compared with controls. METHODS: A single-center observational prospective study on ICU invasively ventilated COVID-19 patients. The primary outcome was the clinical improvement at day 28. A Bayesian framework was employed, and all analyses were adjusted for confounders. RESULTS: Sixty-one consecutive invasively ventilated patients were included, nine (14.7%) received tocilizumab and 15 (24.6%) received anakinra. Over the first seven days, tocilizumab was associated with a greater decrease in C-reactive protein (P

Context: Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin—a 1:1 ratio protamine sparing effects—but this is based more on experience and practice than literature evidence. The use of Hemostasis Management System (HMS) allows an individualized heparin and protamine titration. This usually results in a decreased protamine dose, thus limiting its side effects, including paradox anticoagulation. Aims: This study aims to assess how the use of HMS allows to reduction of protamine administration while restoring the basal activated clotting time (ACT) at the end of cardiac surgery. Settings and Design: A retrospective observational study in a tertiary care university hospital. Subjects and Methods: We analyzed data from 42 consecutive patients undergoing cardiopulmonary bypass (CPB) for cardiac surgery. For all patients HMS tests were performed before and after CPB, to determine how much heparin was needed to reach target ACT, and how much protamine was needed to reverse it. Results: At the end of cardiopulmonary bypass, 2.2 ± 0.5 mg/kg of protamine was sufficient to reverse heparin effects. The protamine-to-heparin ratio was 0.56:1 over heparin total dose (a 44% reduction) and 0.84:1 over heparin initial dose (a 16% reduction). Conclusion: A lower dose of protamine was sufficient to revert heparin effects after cardiopulmonary bypass. While larger studies are needed to confirm these findings and detect differences in clinically relevant outcomes, the administration of a lower protamine dose is endorsed by current guidelines and may help to avoid the detrimental effects of protamine overdose, including paradox bleeding.

CytoSorb is a promising tool to treat severe inflammatory status with multiple mechanisms in the acute care setting. Its effect on drugs is, however, poorly documented in vivo, although removal of small molecules might translate into decreased blood levels of life-saving medications. The aim of this study was to assess the impact of CytoSorb on vancomycin and bivalirudin clearance in a large population of critically ill patients. We performed a single-center analysis of CytoSorb treatments performed between January 2018 and March 2019 in critically ill patients admitted to our intensive care unit. A total of 109 CytoSorb treatments were performed in 89 patients. A decrease in lactate dehydrogenase (P = .007), troponin T (P = .022), and creatine phosphokinase (P = .013) was reported during treatment. Vancomycin dose required significant adjustments during treatment (P < .001), but no significant change was necessary after the first 3 days. Similarly, the requirements of bivalirudin significantly changed over days (P < .001), but no dose adjustment was needed after the first 3 days of treatment. No differences in terms of vancomycin and bivalirudin dose need was observed between patients on extracorporeal membrane oxygenation and those who were not (P = .6 and P = .6, respectively), between patients with and without continuous veno-venous hemofiltration (P = .9 and P = .9, respectively), and between CytoSorb responders or not (P = .4 and P = .7, respectively). CytoSorb is effective in mitigating the systemic inflammatory response and safe with respect to vancomycin and bivalirudin administration. These preliminary data further support the use of CytoSorb as adjunct therapy in critically ill patients.

Background: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems. Objective: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients. Methods: Observational study in a tertiary care hospital in Milan, Italy. Results: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients. Conclusions: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality.

Procalcitonin (PCT) is a blood biomarker used in clinical practice to detect bacterial etiology in patients with sepsis or acute respiratory tract infection, to assess infection severity, and to monitor the effectiveness of antibiotic therapy. In February 2017, the U.S. Food and Drug Administration (FDA) approved the use of the first PCT assay to guide antibiotic use in the context of lower respiratory tract infections (LRTI) and sepsis [1].

Background The detrimental effects of inotropes are well-known, and in many fields they are only used within a goal-directed therapy approach. Nevertheless, standard management in many centers includes administering inotropes to all patients undergoing cardiac surgery to prevent low cardiac output syndrome and its implications. Randomized evidence in favor of a patient-tailored, inotrope-sparing approach is still lacking. We designed a randomized controlled noninferiority trial in patients undergoing cardiac surgery with normal ejection fraction to assess whether an dobutamine-sparing strategy (in which the use of dobutamine was guided by hemodynamic evidence of low cardiac output associated with signs of inadequate tissue perfusion) was noninferior to an inotrope-to-all strategy (in which all patients received dobutamine). Results A total of 160 patients were randomized to the dobutamine-sparing strategy (80 patients) or to the dobutamine-to-all approach (80 patients). The primary composite endpoint of 30-day mortality or occurrence of major cardiovascular complications (arrhythmias, acute myocardial infarction, low cardiac output syndrome and stroke or transient ischemic attack) occurred in 25/80 (31%) patients of the dobutamine-sparing group (p = 0.74) and 27/80 (34%) of the dobutamine-to-all group. There were no significant differences between groups regarding the incidence of acute kidney injury, prolonged mechanical ventilation, intensive care unit or hospital length of stay. Discussion Although it is common practice in many centers to administer inotropes to all patients undergoing cardiac surgery, a dobutamine-sparing strategy did not result in an increase of mortality or occurrence of major cardiovascular events when compared to a dobutamine-to-all strategy. Further research is needed to assess if reducing the administration of inotropes can improve outcomes in cardiac surgery. Trial registration ClinicalTrials.gov, NCT02361801. Registered Feb 2nd, 2015. https://clinicaltrials.gov/ct2/show/NCT02361801

Objective To assess whether the administration of the ultra-short–acting β-blocker esmolol in cardiac surgery could have a cardioprotective effect that translates into improved postoperative outcomes. Design Single-center, double-blinded, parallel-group randomized controlled trial. Setting A tertiary care referral center. Participants Patients undergoing elective cardiac surgery with preoperative evidence of left ventricular end-diastolic diameter >60 mm and/or left ventricular ejection fraction Interventions Patients were assigned randomly to receive either esmolol (1 mg/kg as a bolus before aortic cross-clamping and 2 mg/kg mixed in the cardioplegia solution) or placebo in a 1:1 allocation ratio. Measurements and Main Results The primary composite endpoint of prolonged intensive care unit stay and/or in-hospital mortality occurred in 36/98 patients (36%) in the placebo group versus 27/102 patients (27%) in the esmolol group (p = 0.13). In the esmolol group, a reduction in the maximum inotropic score during the first 24 postoperative hours was observed (10 [interquartile range 5-15] v 7 [interquartile range 5-10.5]; p = 0.04), as well as a trend toward a reduction in postoperative low-cardiac-output syndrome (13/98 v 6/102; p = 0.08) and the rate of hospital admission at one year (26/95 v 16/96; p = 0.08). A trend toward an increase in the number of patients with ejection fraction ≥60% at hospital discharge also was observed (4/95 v 11/92; p = 0.06). Conclusions In the present trial, esmolol as a cardioplegia adjuvant enhanced postoperative cardiac performance but did not reduce a composite endpoint of prolonged intensive care unit stay and/or mortality.

Objective The objective of this study was to compare the efficacy of renal perfusion with Custodiol (Dr Franz-Kohler Chemie GmbH, Bensheim, Germany) versus enriched Ringer's solution for renal protection in patients undergoing open thoracoabdominal aortic aneurysm (TAAA) repair. Methods Ninety consecutive patients scheduled for elective open TAAA repair were enrolled between 2015 and 2017 in a single-center, phase IV, prospective, parallel, randomized, double-blind trial (the CUstodiol versus RInger: whaT Is the Best Agent [CURITIBA] trial), and randomized to renal arteries perfusion with 4°C Custodiol (Dr Franz-Kohler Chemie GmbH, Bensheim, Germany; n = 45) or 4°C lactated Ringer's solution (n = 45). The incidence of acute kidney injury (AKI) in patients undergoing TAAA open surgery using Custodiol renal perfusion versus an enriched Ringer's solution was the primary end point. Results Ninety patients completed the study (45 patients in each group). The incidence of postoperative AKI was significantly lower in the Custodiol group (48.9% vs 75.6%; P = .02). In the multivariable model, only the use of Custodiol solution resulted as protective from the occurrence of any AKI (odds ratio, 0.230; 95% confidence interval, 0.086-0.614; P = .003), whereas TAAA type II extent was associated with the development of severe AKI (odds ratio, 4.277; 95% confidence interval, 1.239-14.762; P = .02). At 1-year follow-up, serum creatinine was not significantly different from the preoperative values in both groups. Conclusions The use of Custodiol during open TAAA repair was safe and resulted in significantly lower rates of postoperative AKI compared with Ringer's solution. These findings support safety and efficacy of Custodiol in this specific setting, which is currently off-label.

Since the publication of the landmark paper by Dr. Emanuel Rivers in The New England Journal of Medicine in 2001, the world of critical care massively adopted his protocol for the resuscitation of severe sepsis and/or septic shock—which was named “early goal-directed therapy” [1]. The concept of goal-directed therapy rapidly arose from sepsis and was applied to shock in general in the intensive care unit. Goal-directed therapy is a bundle of care that embraces the use of fluids, blood transfusion, and inotropes aiming to precise hemodynamic targets [2]. In case of hypotension or lactate raise, a fluid challenge of 30 ml/kg of crystalloid solution is administered to the patient. Fluid responsiveness is assessed in terms of low central venous pressure (CVP) and decreases in heart rate. In the following hours, hemodynamic targets include: a CVP of 8–12 mmHg, a superior vena cava oxygen saturation (ScvO2) >70% or a mixed venous oxygen saturation (SvO2) >65%, a mean arterial pressure (MAP) ≥65 mmHg, and a urine output ≥0.5 mL/kg/h. Strategies to achieve these target involve additional fluids, transfusion of packed red blood cells or inotrope infusion. In the original study, the application of this protocol reduced mortality by more of one third and halved that of patients with severe sepsis [1].

In spite of advances in support of all organ functions over the last decades, cognitive aspects of intensive care unit admission rarely take the central light. It is a common belief that patients admitted to the ICU are completely asleep at all times, but that does not correspond to truth. In fact, a large and growing body of evidence has shown that sedation is harmful, increasing the risk of infection, delirium, and death, and prolonging the time on mechanical ventilation in the ICU and hospital [1–3]. Modern approach to intensive care aims to a comprehensive approach to the patient well-being, including aspects related to pain, agitation/sedation, delirium, immobility, and sleep disruption [4].

Background: The use of angiotensin II (ANGII) in invasively ventilated COVID-19 patients is controversial. Its effect on markers of organ function is unknown.Methods: We used ANGII either as rescue vasopressor agent or as low dose vasopressor support. Patients treated before ANGII availability or in an adjacent COVID-19 ICU served as controls. For data analysis, we applied Bayesian modelling as appropriate. We assessed the effects of ANG on markers of organ function.Results: We compared 46 ANGII patients with 53 controls. Compared with controls, ANGII increased MAP (median difference, 9.05 mmHg [95% confidence interval, 1.87 to 16.22]; p = 0.013) and PaO2/FiO2 ratio (median difference, 23.17 [95% confidence interval, 3.46 to 42.88]; p = 0.021). ANGII had no effect on lactate, urinary output, serum creatinine, C-Reactive protein, platelet count, or thromboembolic complications. However, it significantly decreased the odd ratio of liver dysfunction (odds ratio: 0.32; 0.09 to 0.94) and, on Bayesian modelling, in patients with abnormal baseline serum creatinine, ANGII carried a 95.7% probability of decreasing renal replacement therapy use. Conclusions: In ventilated COVID-19 patients, ANGII therapy was associated with increased blood pressure and PaO2/FiO2 ratios, decreased odds ratio of liver dysfunction, and a high probability of decreasing renal replacement therapy use in patients with abnormal baseline serum creatinine.

Study objective To assess the effect of a rotational thromboelastometry (ROTEM)-enhanced transfusion algorithm with hemostatic agents on allogenic blood transfusion in patients undergoing frozen elephant trunk (FET) surgery. Design Retrospective observational study conducted in a tertiary-care center. Setting A tertiary care referral center for cardiac surgery. Patients All patients undergoing elective FET were included in the study. Intervention Until 2016, a protocol based on estimated blood losses and conventional coagulation tests was used. After, a ROTEM-enhanced transfusion protocol was adopted. Measurements The transfusion rate of each blood component was observed and reported. Methods Retrospective, observational study. Main results Out of 40 consecutive patients, 19 underwent FET surgery with a conventional transfusion approach and 21 with a ROTEM-enhanced transfusion strategy. Considering the overall transfusion rate, the administration of fresh frozen plasma and platelets was significantly lower in the ROTEM compared to conventional group (1000 [0–2500] vs 0 [0–875] ml, p = 0.015 and 1 [1, 2] vs 0 [0–1], p = 0.016, respectively). ROTEM algorithm allowed to decrease the number of patients who required plasma and platelets transfusion of 31%. Furthermore, a 40% reduction in overall allogenic blood products was observed. Number of red blood cells administered, percentage of patients transfused with red blood cells, blood losses, reoperation for bleeding and mortality did not significantly differ between the two groups. At the multiple linear regression analysis only ROTEM algorithm was associated with a significant decrease in the number of plasma and platelets units administered intraoperatively, at 24 h, at the ICU discharge and overall. ROTEM algorithm allowed to save 1435 ml of plasma, 0.91 unit of platelets and overall transfusion cost of the 21% per patient. Conclusions A ROTEM-enhanced transfusion strategy halved intraoperative transfusion in the setting of FET. Further studies are needed to confirm the magnitude of our findings on clinically relevant endpoints.

Since the first cases of a different type of pneumonia in Wuhan, China in December 2019, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected more than 6 3 million people, with 376,294 confirmed deaths in 185 different countries as of June 1, 2020 [8] Furthermore, the cellular damage and inflammatory response could be elicited by an interaction between the virus and the cell surface receptor angiotensin-converting enzyme 2 (ACE-2), expressed on the surface of lung epithelial cells, enterocytes of the small intestine, arterial, and venous endothelial cells, and in arterial smooth muscle cells of multiple organs [ ]as an increasing number of reports confirm that severe COVID-19 implies an elevated rate of life-threatening thrombotic complications, a close monitoring of D-dimer, fibrinogen, prothrombin time, partial thromboplastin time, and platelet count should be performed

To investigate the effects of the administration of 4% albumin on lactated Ringer's, when compared with lactated Ringer's alone, in the early phase of sepsis in cancer patients.Single-center, randomized, double-blind, controlled-parallel trial.A tertiary care university cancer hospital.Cancer patients with severe sepsis or septic shock.Between October 2014 and December 2016, patients were randomly assigned to receive either bolus of albumin in a lactated Ringer's solution or lactated Ringer's solution alone during the first 6 hours of fluid resuscitation after intensive care medicine (ICU) admission. Primary outcome was defined as death from any cause at 7 days. Secondary outcomes were defined as death from any cause within 28 days, change in Sequence Organ Failure Assessment scores from baseline to day 7, days alive and free of mechanical ventilation, days alive and free of vasopressor, renal replacement therapy during ICU stay, and length of ICU and hospital stay.A total of 360 patients were enrolled in the trial. At 7 days, 46 of 180 patients (26%) died in the albumin group and 40 of 180 (22%) died in the lactated Ringer's group (p = 0.5). At 28 days, 96 of 180 patients (53%) died in the albumin group and 83 of 180 (46%) died in the lactated Ringer's group (p = 0.2). No significant differences in secondary outcomes were observed.Adding albumin to early standard resuscitation with lactated Ringer's in cancer patients with sepsis did not improve 7-day survival.

Background Bleeding and transfusions affect mortality in aortic surgery. Although tranexamic acid significantly reduced bleeding in multiple settings, its role in major vascular surgery was never studied. The aim of this study was to determine if tranexamic acid reduces blood loss in open abdominal aortic aneurysm (AAA) surgery. Methods A total of 100 patients undergoing elective open AAA repair were randomised to receive tranexamic acid (a loading dose of 500 mg and a continuous infusion of 250 mg h−1) or placebo. The primary outcome was intraoperative blood loss, and the secondary outcomes were the number of patients receiving red blood cells, occurrence of thromboembolic events, and mortality. Data were analysed using the intention-to-treat principle. Results Fifty patients were randomised into each group. Median (inter-quartile range) intraoperative blood loss was 400 (300–1050) ml in the tranexamic acid group vs 500 (360–1000) ml in the placebo group (P=0.44). Transfusion rate was seven/50 (14%) in the tranexamic group vs 12/50 (24%) in the placebo group (P=0.20). No thrombosis was recorded. In a post hoc analysis, postoperative blood loss was reduced in the tranexamic group both at 4 h (60 [40–80] ml vs 100 [60–140] ml, P Conclusions Tranexamic acid did not reduce intraoperative blood loss or blood transfusions in open AAA repair, although it may reduce postoperative blood loss without increasing adverse effects. Clinical trial registration NCT02335359.

ObjectiveFew randomized trials have evaluated the use of non-invasive ventilation (NIV) for early acute respiratory failure (ARF) in non-intensive care unit (ICU) wards. The aim of this study is to test the hypothesis that early NIV for mild-moderate ARF in non-ICU wards can prevent development of severe ARF.DesignPragmatic, parallel group, randomized, controlled, multicenter trial.SettingNon-intensive care wards of tertiary centers.PatientsNon-ICU ward patients with mild to moderate ARF without an established indication for NIV.InterventionsPatients will be randomized to receive or not receive NIV in addition to best available care.Measurements and main resultsWe will enroll 520 patients, 260 in each group. The primary endpoint of the study will be the development of severe ARF. Secondary endpoints will be 28-day mortality, length of hospital stay, safety of NIV in non-ICU environments, and a composite endpoint of all in-hospital respiratory complications.ConclusionsThis trial will help determine whether the early use of NIV in non-ICU wards can prevent progression from mild-moderate ARF to severe ARF.

Purpose CytoSorb treatment is a promising tool to treat severe inflammatory status in the acute care setting. Its effect on drugs is, however, poorly documented in vivo, although unselective and unpredictable removal of small molecules might translate into decreased blood levels of potentially life-saving medications. The aim of this study was to assess the impact of Cytosorb treatment on clereance of small drug molecules, measured as dose adjustements need, in a large population of critically ill patients. Methods Single-center analysis of Cytosorb treatments performed between 01-2018 and 03-2019 in patients with cardiogenic shock of several origins. Results 109 Cytosorb treatments were performed in 86 patients. A decrease in LDH (p=0.007), troponin T (p=0.022) and CPK (p=0.013), together with a trend toward lower need of inotropes, was reported during treatment, supporting its clinical efficacy in the study population. Vancomycin dose was significantly changed during the days of treatment (p Conclusion Cytosorb therapy was effective in improving shock parameters in a large population of cardiogenic shock patients, without affecting the dose need of vancomycin and bivalirudin after reaching target concentration. The results of this study further support the role of Cytosorb in the treatment of critically ill.

Objective To assess the beneficial effects of noninvasive ventilation in treating postoperative pulmonary complications in patients undergoing thoracoabdominal aortic aneurysm (TAAA) open repair surgery. Design Randomized controlled trial. Setting University tertiary-care hospital. Participants Forty patients who underwent elective TAAA open repair. Interventions Patients were randomized to the “noninvasive ventilation” group, receiving 2-hour cycles of noninvasive ventilation every 8 hours for at least 3 days in addition to the best available postoperative treatment currently in use at the authors’ institution versus the “standard” group, not receiving noninvasive ventilation treatment Measurements and Main Results The primary outcome of clinical worsening, described as a composite outcome of need for therapeutic noninvasive ventilation, need for mechanical ventilation owing to respiratory causes, need for intensive care unit admission owing to respiratory causes, and in-hospital mortality, occurred in 2 (11%) patients in the noninvasive ventilation group versus 12 (57%) in the standard group (p = 0.002; relative risk 0.18; 95% confidence interval 0.047-0.72). Conclusion Noninvasive ventilation is a promising, affordable, and easy-to-use tool to prevent postoperative respiratory complications after TAAA open surgical repair.

A 35-year-old female dentist laid on her chair to test an N2O machine, and after only a few minutes of inhaling the N2O, she developed acute pyramidal syndrome. The patient started walking again eight months later, but still suffers from lower limb motor deficit, in spite of intensive re-habilitation. Genetic tests later showed that the patient had Type 3 homocystinuria. This is the first case report of acute neu-rological toxicity after brief administration of N2O. We suggest starting vitamin B12 and folic acid supplements promptly in pa-tients who experience neurological symp-toms after receiving N2O.

Bispectral Index Scale (BIS)-guided closed-loop delivery of anesthetics has been extensively studied. We performed a meta-analysis of all the randomized clinical trials comparing efficacy and performance between BIS-guided closed-loop delivery and manually controlled administration of total IV anesthesia. Scopus, PubMed, EMBASE, and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and closed-loop delivery systems versus manually controlled administration of total IV anesthesia in any surgical setting. Exclusion criteria were duplicate publications and nonadult studies. Twelve studies were included, randomly allocating 1284 patients. Use of closed-loop anesthetic delivery systems was associated with a significant reduction in the dose of propofol administered for induction of anesthesia (mean difference [MD] = 0.37 [0.17-0.57], P for effect

Objectives Postoperative pulmonary complications (PPC) are among the most common complications after noncardiac surgery. Men, smokers, and elderly patients with chronic obstructive pulmonary disease or heart failure are more likely to experience PPC. The majority of patients undergoing vascular surgery belong in these categories and are at higher risk of developing PPC. Moreover, the surgical site is one of the most important risk factors associated with PPC, and aortic surgery carries the highest risk. The aim of this systematic review was to obtain an additional understanding of the real incidence of PPC after open abdominal aortic surgery and the impact of PPC on survival. Design Systematic review and meta-analysis. Setting Hospitals Participants Patients who underwent open abdominal aortic surgery. Interventions None. Measurements and Main Results A literature search was performed on BioMedCentral, PubMed, Embase, and the Cochrane Register of clinical trials. All prospective or retrospective studies reporting data on PPC after open abdominal aortic surgery were included. Co-primary endpoints were the PPC rate and the correlation between PPC and perioperative mortality. The secondary endpoint was the difference in the PPC rate and mortality between elective and urgent surgery. Data on 269,637 patients from 213 studies were analyzed. The overall median incidence of PPC was 10.3% (interquartile range 5.55%-19.1%). Pneumonia, respiratory insufficiency, prolonged mechanical ventilation, need for unplanned mechanical ventilation, atelectasis, acute respiratory distress syndrome, pulmonary edema, and pleural effusions were the most common PPC reported in the literature. Occurrence of PPC was associated with postoperative mortality (r = 0.65, p

BACKGROUND: Carotid endarterectomy remains the most effective surgical treatment for reducing the risk of stroke in patients with significant carotid stenosis. In fact, endovascular approach is associated with a higher incidence of perioperative and long-term minor stroke when compared to carotid endarterectomy although long-term functional outcome and risk of major stroke are similar. However, advanced age resulted to be associated with an increased risk of complications after carotid endarterectomy. Therefore we decided to evaluate the outcome of carotid endarterectomy in octogenarians in our high-volume centre.METHODS: Data of all patients who underwent CEA between June 2009 and December 2014 were retrospectively recorded. Patients were categorized as

Objectives Methylene blue commonly is used as a dye or an antidote, but also can be used off label as a vasopressor. Serotonin toxicity is a potentially lethal and often misdiagnosed condition that can result from drug interaction. Mild serotonin toxicity previously was reported in settings in which methylene blue was used as a dye. The authors report 3 cases of life-threatening serotonin toxicity in patients undergoing chronic selective serotonin reuptake inhibitor (SSRI) therapy who also underwent cardiac surgery and received methylene blue to treat vasoplegic syndrome. Design An observational study. Setting A cardiothoracic intensive care unit (ICU) in a teaching hospital. Participants Three patients who received methylene blue after cardiac surgery, later discovered to be undergoing chronic SSRI therapy. Interventions None. Measurements and Main Results All 3 patients received high doses of fentanyl during general anesthesia. They all developed vasoplegic syndrome and consequently were given methylene blue in the ICU. All 3 patients developed serotonin toxicity, including coma, after this administration and diagnostic tests were negative for acute intracranial pathology. Coma lasted between 1 and 5 days. Two patients were discharged from the ICU shortly after awakening, whereas the third patient experienced a complicated postoperative course for concomitant refractory low-cardiac-output syndrome. Conclusions Patients undergoing chronic SSRI therapy should not be administered methylene blue to treat vasoplegic syndrome.

The use of noninvasive ventilation (NIV) for the treatment of patients with acute respiratory failure has greatly increased. The growing knowledge of NIV efficacy and clinicians’ confidence in managing this technique have been accompanied by a wide reduction in the number of available intensive care unit (ICU) beds. Therefore, the application of NIV outside the ICU is common and increasing worldwide.

Aims: To determine if percutaneous tracheostomy is safe in critically ill patients treated with anticoagulant therapies. Settings and Design: Single-center retrospective study including all the patients who underwent percutaneous dilatational tracheostomy (PDT) placement over a 1-year period in a 14-bed, cardiothoracic and vascular Intensive Care Unit (ICU). Materials and Methods: Patients demographics and characteristics, anticoagulant and antiplatelet therapies, coagulation profile, performed technique and use of bronchoscopic guidance were retrieved. Results: Thirty-six patients (2.7% of the overall ICU population) underwent PDT over the study period. Twenty-six (72%) patients were on anticoagulation therapy, 1 patient was on antiplatelet therapy and 2 further patients received prophylactic doses of low molecular weight heparin. Only 4 patients had normal coagulation profile and were not receiving anticoagulant or antiplatelet therapies. Overall, bleeding of any severity complicated 19% of PDT. No procedure-related deaths occurred. Conclusions: PDT was proved to be safe even in critically ill-patients treated with anticoagulant therapies. Larger prospective studies are needed to confirm our findings.

Objective: Carotid endarterectomy is the most effective treatment for reducing the risk of stroke in patients with significant carotid stenosis. Few studies have focused on the failure rate of regional anesthesia. Methods: Data of all patients undergoing carotid endarterectomy (June 2009 to December 2014) in a single center were collected. Combined deep and superficial cervical plexus block or superficial plexus block alone was used according to the attending anesthesiologist's choice and the patient's characteristics (eg, dual antiplatelet or anticoagulation therapy). Intraoperative remifentanil (0.025-0.05 mu g/kg/min) was administered to maintain an adequate level of comfort, responsiveness, and cooperation. General anesthesia was planned only in the case of major contraindications or the patient's refusal of locoregional anesthesia. The primary end point of our study was the incidence of intraoperative conversion from locoregional to general anesthesia. Results: A total of 2463 carotid endarterectomies were included in the analysis. Regional anesthesia was initially chosen in 2439 patients, whereas 24 patients received planned general anesthesia. In seven cases, regional anesthesia was converted to general anesthesia because of severe agitation of the patient (before clamping in four cases, after carotid clamping in two cases, and after declamping in one case). A shunt was used in 302 patients (12.3%) because of neurologic deterioration at the carotid clamping test. Intraoperative complications were emergent repeated surgical procedures in 13 cases (0.53%) because of acute neurologic deterioration, 1 intraoperative acute myocardial infarction (0.04%), and 3 cases (0.04%) of hemodynamically relevant supraventricular tachyarrhythmia. No intraoperative death occurred. In-hospital mortality was 0.12% (three patients). Major stroke occurred in 23 patients (0.93%); minor stroke occurred in 16 patients (0.65%). The combined stroke and death rate was 1.62% (40 patients). Conclusions: In our practice, carotid endarterectomy under regional anesthesia is safe and associated with a very low rate of conversion to general anesthesia. OI tshomba, yamume/0000-0001-8316-4702; LANDONI, Giovanni/0000-0002-8594-5980

IntroductionCardioprotective properties of volatile agents and of remote ischemic preconditioning have survival effects in patients undergoing cardiac surgery. We performed a Bayesian network meta-analysis to confirm the beneficial effects of these strategies on survival in cardiac surgery, to evaluate which is the best strategy and if these strategies have additive or competitive effects.MethodsPertinent studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register (updated November 2013). A Bayesian network meta-analysis was performed. Four groups of patients were compared: total intravenous anesthesia (with or without remote ischemic preconditioning) and an anesthesia plan including volatile agents (with or without remote ischemic preconditioning). Mortality was the main investigated outcome.ResultsWe identified 55 randomized trials published between 1991 and 2013 and including 6,921 patients undergoing cardiac surgery. The use of volatile agents (posterior mean of odds ratio = 0.50, 95% CrI 0.28-0.91) and the combination of volatile agents with remote preconditioning (posterior mean of odds ratio = 0.15, 95% CrI 0.04-0.55) were associated with a reduction in mortality when compared to total intravenous anesthesia. Posterior distribution of the probability of each treatment to be the best one, showed that the association of volatile anesthetic and remote ischemic preconditioning is the best treatment to improve short- and long-term survival after cardiac surgery, suggesting an additive effect of these two strategies.ConclusionsIn patients undergoing cardiac surgery, the use of volatile anesthetics and the combination of volatile agents with remote preconditioning reduce mortality when compared to TIVA and have additive effects. It is necessary to confirm these results with large, multicenter, randomized, double-blinded trials comparing these different strategies in cardiac and non-cardiac surgery, to establish which volatile agent is more protective than the others and how to best apply remote ischemic preconditioning.

High frequency oscillatory ventilation is characterized by very low tidal volumes, often smaller than anatomic death space, and high respiratory frequencies (3–15 Hz). This strategy was thought to reduce ventilator induced lung injury, avoiding volutrauma and barotrauma. According to most recent data, high frequency oscillatory ventilation does not offer any real advantage when compared to current protective lung ventilation. Moreover it is associated with an increased need for sedative and neuromuscular blocker drugs, unstable hemodynamics and lung barotrauma. The OSCILLATE trial demonstrated an increased risk of death in patients undergoing high frequency oscillatory ventilation. Therefore, high frequency oscillatory ventilation should be avoided as a first-line treatment in patients with acute respiratory distress syndrome.

Glutamine supplementation in intensive care unit patients is supposed to improve outcome by modulating inflammatory response, preventing organ injury, modulating glucose metabolism and inducing cellular protection pathways. Trials showed conflicting results on mortality. Heyland et al showed a significant increase in mortality in critically ill patients who received glutamine supplementation. Their results were confirmed by a subsequent meta-analysis considering only high quality evidence. Therefore, glutamine supplementation should be avoided in this setting.

BACKGROUND: Use of noninvasive ventilation (NIV) for the treatment of patients with acute respiratory failure (ARF) has greatly increased in the last decades. In contrast, the increasing knowledge of its effectiveness and physician confidence in managing this technique have been accompanied by a declining number of available ICU beds. As a consequence, the application of NIV outside the ICU has been reported as a growing phenomenon. Previously published surveys highlighted a great heterogeneity in NIV use, clinical indications, settings, and efficacy. Moreover, they revealed a marked heterogeneity with regard to staff training and technical and organizational aspects. We performed the first worldwide web-based survey focused on NIV use in general wards for ARF.METHODS: A questionnaire to obtain data regarding hospital and ICU characteristics, settings and modalities of NIV application and monitoring, estimated outcomes, technical and organizational aspects, and observed complications was developed. The multiple-choice anonymous questionnaire to be filled out online was distributed worldwide by mail, LinkedIn, and Facebook professional groups.RESULTS: One-hundred fifty-seven questionnaires were filled out and analyzed. Respondents were from 51 countries from all 5 continents. NIV application in general wards was reported by 66% of respondents. Treatments were reported as increasing in 57% of cases. Limited training and human resources were the most common reasons for not using NIV in general wards. Overall, most respondents perceived that NIV avoids tracheal intubation in most cases; worsening of ARF, intolerance, and inability to manage secretions were the most commonly reported causes of NIV failure.CONCLUSIONS: Use of NIV in general wards was reported as effective, common, and gradually increasing. Improvement in staff training and introduction of protocols could help to make this technique safer and more common when applied in general wards setting.

Objectives Delirium frequently is observed in critically ill patients in the intensive care unit (ICU) and is associated strongly with a poor outcome. Dexmedetomidine seems to reduce time to extubation and ICU stay without detrimental effects on mortality. The objective of the authors’ study was to evaluate the effect of this drug on delirium, agitation, and confusion in the ICU setting. Design Meta-analysis of all the randomized clinical trials ever performed on dexmedetomidine versus any comparator in the ICU setting. Setting Intensive care units. Participants Critically ill patients. Interventions None Measurements and Main Results Pertinent studies were independently searched in BioMedCentral, PubMed, Embase, and the Cochrane Central Register of clinical trials. Primary endpoint was the rate of delirium, including the adverse events, agitation and confusion. The 13 included manuscripts (14 trials) randomized 3,029 patients. Overall analysis showed that the use of dexmedetomidine was associated with significant reductions in the incidence of delirium, agitation and confusion (298/1,565 [19%] in the dexmedetomidine group v 337/1,464 [23%] in the control group, RR = 0.68 [0.49 to 0.96], p = 0.03). Results were confirmed in subanalyses performed on patients undergoing noninvasive ventilation (1/53 [2%] in the dexmedetomidine group v 7/49 [14%] in the control group, RR=0.18 [0.03 to 1.01], p = 0.05), receiving midazolam as a comparator (268/1,164 [23%] in the dexmedetomidine group v 277/1,025 [27%] in the control group, RR = 0.68 [0.47 to 1.00], p = 0.05) and in general ICU setting patients (204/688 [30%] in the dexmedetomidine group v 204/560 [36%] in the control group, RR = 0.68 [0.45 to 0.81], p Conclusions This meta-analysis of randomized controlled studies suggests that dexmedetomidine could help to reduce delirium in critically ill patients.