Effects of ketanserin on microcirculatory alterations in septic shock:An open-label pilot study

INTRODUCTION: Microcirculatory alterations in sepsis are associated with increased morbidity and mortality. These alterations occur despite macrohemodynamic resuscitation. Alternative pro-microcirculatory strategies, including vasodilatory drugs, have been suggested to improve capillary blood flow. Ketanserin, a serotonin receptor antagonist, is an attractive candidate because of its vasodilatory, antithrombotic, and anti-inflammatory effects. METHODS: This is an open-label pilot study on the effect of ketanserin administration on microcirculatory alterations in septic shock, defined as microvascular flow index (MFI) ≤ 2.5 after a strict macrohemodynamic resuscitation protocol. Sidestream dark-field imaging was applied to assess the microcirculation. A stepwise incremental dose regiment was applied until an MFI > 2.9, the primary end point, was reached. RESULTS: Ten patients (Acute Physiology and Chronic Health Evaluation IV scores of 115 [100-136]) were included. Baseline MFI was 1.71 (1.31-2.32) and was significantly increasing to 2.96 (2.54-3.00; P = .021) during the ketanserin infusion. The total ketanserin dose was 0.09 (0.08-0.13) mg/kg per patient in 60 (30-60) minutes. In 3 patients (30%), the ketanserin infusion was discontinued due to refractory hypotension. CONCLUSION: An improvement in microcirculatory perfusion was observed during ketanserin administration in patients with septic shock after macrohemodynamic resuscitation. This finding needs further exploration in a placebo-controlled setting

Too much tolerance for hyperoxemia in mechanically ventilated patients with SARS-CoV-2 pneumonia? Report from an Italian intensive care unit

Background: In 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 methods: Retrospective 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. Results: One 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. Conclusion: Excess 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

Near-infrared spectroscopy for assessing tissue oxygenation and microvascular reactivity in critically ill patients: a prospective observational study

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)

Effects of short-term hyperoxia on erythropoietin levels and microcirculation in critically Ill patients: a prospective observational pilot study

BACKGROUND: The normobaric oxygen paradox states that a short exposure to normobaric hyperoxia followed by rapid return to normoxia creates a condition of 'relative hypoxia' which stimulates erythropoietin (EPO) production. Alterations in glutathione and reactive oxygen species (ROS) may be involved in this process. We tested the effects of short-term hyperoxia on EPO levels and the microcirculation in critically ill patients.METHODS: In this prospective, observational study, 20 hemodynamically stable, mechanically ventilated patients with inspired oxygen concentration (FiO2) \ue2\u89\ua40.5 and PaO2/FiO2\ue2\u80\u89\ue2\u89\ua5\ue2\u80\u89200\uc2\ua0mmHg underwent a 2-hour exposure to hyperoxia (FiO2 1.0). A further 20 patients acted as controls. Serum EPO was measured at baseline, 24\uc2\ua0h and 48\uc2\ua0h. Serum glutathione (antioxidant) and ROS levels were assessed at baseline (t0), after 2\uc2\ua0h of hyperoxia (t1) and 2\uc2\ua0h after returning to their baseline FiO2 (t2). The microvascular response to hyperoxia was assessed using sublingual sidestream dark field videomicroscopy and thenar near-infrared spectroscopy with a vascular occlusion test.RESULTS: EPO increased within 48\uc2\ua0h in patients exposed to hyperoxia from 16.1 [7.4-20.2] to 22.9 [14.1-37.2] IU/L (p\ue2\u80\u89=\ue2\u80\u890.022). Serum ROS transiently increased at t1, and glutathione increased at t2. Early reductions in microvascular density and perfusion were seen during hyperoxia (perfused small vessel density: 85% [95% confidence interval 79-90] of baseline). The response after 2\uc2\ua0h of hyperoxia exposure was heterogeneous. Microvascular perfusion/density normalized upon returning to baseline FiO2.CONCLUSIONS: A two-hour exposure to hyperoxia in critically ill patients was associated with a slight increase in EPO levels within 48\uc2\ua0h. Adequately controlled studies are needed to confirm the effect of short-term hyperoxia on erythropoiesis.TRIAL REGISTRATION: ClinicalTrials.gov ( www.clinicaltrials.gov ), NCT02481843 , registered 15th June 2015, retrospectively registered

Effect of Whey Proteins on Malnutrition and Extubating Time of Critically Ill COVID-19 Patients

none13Abstract: The novel SARS-CoV-2 virus has led to a severe pandemic, starting from early 2020. Intensive care (ICU) management of the COVID-19 disease is difficult with high morbidity and mortality. Early nutritional support, especially with whey protein, seems to be crucial in this medical case. Thus, we aimed to assess the effects of an adequate nutritional protocol rich in whey protein on nutritional and inflammatory status, extubating time, and mortality of critically ill COVID-19 patients (CICP). Methods: A prospective single-center exploratory observational study was undertaken on 32 consecutive CICP admitted to the ICU of Santa Maria Hospital, Terni, Italy, and treated with whey protein-enriched formula. Patients’ demographics, nutritional status, indexes of inflammation, daily pre-albumin serum levels, duration of mechanical ventilation, and mortality were recorded. Results: Thirty-two patients were enrolled. Ninety-five percent of them showed a gradual reduction in C-reactive protein (CRP) values and increase in pre-albumin levels after the whey protein-enriched formula. Prealbumin levels were not correlated with a better nutritional status but with a shorter extubating time and better survival. Conclusions: An adequate administration of whey protein during COVID-19 patients’ ICU stays can provide fast achievement of protein targets, reducing the duration of mechanical ventilation, and improving inflammatory status and ICU survival. Further prospective and large-scale, controlled studies are needed to confirm these results.openScarcella, Marialaura; Scarpellini, Emidio; Ascani, Alessandra; Commissari, Rita; Scorcella, Claudia; Zanetti, Michela; Parisi, Amilcare; Monti, Riccardo; Milic, Natasa; Donati, Abele; Luzza, Francesco; De Robertis, Edoardo; Abenavoli, LudovicoScarcella, Marialaura; Scarpellini, Emidio; Ascani, Alessandra; Commissari, Rita; Scorcella, Claudia; Zanetti, Michela; Parisi, Amilcare; Monti, Riccardo; Milic, Natasa; Donati, Abele; Luzza, Francesco; De Robertis, Edoardo; Abenavoli, Ludovic

Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study

Introduction: Microvascular alterations impair tissue oxygenation during sepsis. A red blood cell (RBC) transfusion increases oxygen (O2)-delivery but rarely improves tissue O2 uptake in septic patients. Possible causes include RBC alterations due to prolonged storage or residual leukocyte-derived inflammatory mediators. The aim of this study was to compare the effects of two types of transfused-RBCs on microcirculation in septic patients. Methods: In a prospective randomized trial, 20 septic patients were divided into two separate groups and received either non-leukodepleted (n = 10) or leukodepleted (n = 10) RBC transfusions. Microvascular density and perfusion were assessed with sidestream dark-field (SDF) imaging sublingually, before and 1 hour after transfusions. Thenar tissue O2-saturation (StO2) and tissue haemoglobin index (THI) were determined with near-infrared spectroscopy (NIRS), and a vascular occlusion test was performed. The microcirculatory perfused boundary region was assessed in SDF images as an index of glycocalyx damage and glycocalyx compounds (syndecan-1, hyaluronan, heparan sulfate) were measured in the serum. Results: No differences were observed in microvascular parameters at baseline and after transfusion between the groups, except for the proportion of perfused vessels (PPV) and blood flow velocity, which were higher after transfusion in the leukodepleted group. Microvascular flow index in small vessels (MFI) and blood flow velocity exhibited different responses to transfusion between the two groups (P = 0.03 and P = 0.04, respectively), with a positive effect of leukodepleted RBCs. When looking at within-group changes, microcirculatory improvement was only observed in patients that received leukodepleted RBC transfusion as suggested by the increase in De Backer score (P = 0.02), perfused vessel density (P = 0.04), PPV (P = 0.01) and MFI (P = 0.04). Blood flow velocity decreased in the non-leukodepleted group (P = 0.03). THI and StO2-upslope increased in both groups. StO2 and StO2-downslope increased in patients who received non-leukodepleted RBC transfusions. Syndecan-1 increased after the transfusion of non-leukodepleted RBCs (P = 0.03). Conclusions: This study does not show a clear superiority of leukodepleted over non-leukodepleted RBC transfusions on microvascular perfusion in septic patients, although it suggests a more favourable effect of leukodepleted RBCs on microcirculatory convective flow. Further studies are needed to confirm these findings. © 2014 Donati et al.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Too much tolerance for hyperoxemia in mechanically ventilated patients with SARS-CoV-2 pneumonia? Report from an Italian intensive care unit

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

Microcirculatory Perfusion-Based Approach to the Critically Ill Patient: Bringing a Research Tool Technology to the Bedside

Monitorare il microcircolo nel paziente critico offre un approccio più fisiologico alla loro gestione: un microcircolo alterato, quale causa primaria di ipoperfusione tissutale e disfunzione d’organo dovrebbe rappresentare il target dei trattamenti, specialmente quando il ripristino delle variabili emodinamiche standard sembra essere insufficiente a migliorare l’outcome. Nonostante questo enorme potenziale, esso resta ancora solamente uno strumento di ricerca. Questo lavoro, una raccolta di alcuni articoli di ricerca, è stato condotto nel tentativo di avvicinare la ricerca alla pratica clinica. Lo studio di validazione della tecnologia di terza generazione per l’imaging del microcircolo, l’Incident Dark Field illumination (IDF), fornisce il confronto con il gold standard. È stata poi posta l’attenzione sulle difficoltà tecniche di acquisizione di imaging adeguato del microcircolo e sull’ impatto sull’interpretazione dei dati, con particolare riguardo all’esperienza dell’operatore e alla collaborazione del paziente. Il core del progetto è rappresentato dal MicroDAIMON, uno studio prospettico osservazionale sul monitoraggio giornaliero del microcircolo nel paziente critico che fornisce uno dei più ampi database esistenti e che ha mostrato l’associazione tra alterazioni del microcircolo al baseline e outcome. Il monitoraggio è stato eseguito anche con Near InfraRed Spectroscopy su muscolo scheletrico con test di occlusione vascolare, per valutare la reattività dinamica del microcircolo ad un insulto ischemico e la sua capacità di riserva. Un’analisi di sottogruppo ha incentrato l’attenzione sul paziente politraumatizzato, mostrando che la persistenza di un microcircolo alterato in presenza di variabili macro-emodinamiche ottimizzate può predire un aumentato rischio di disfunzione d’organo. Infine, con uno studio open label, è stato valutato l’effetto della ketanserina sul microcircolo, cercando di fornire un approccio farmacologico alle alterazioni microcircolatorie.Focusing microcirculation in critically ill patients offers a physiologic approach to their management: an impaired microcirculation, as the “motor” of tissues hypoperfusion and organ dysfunction, should represent the target of interventions, especially when the restoring of the standard macrohemodynamic variables appears to be insufficient to improve the patient outcome. Despite this huge potential, microcirculatory monitoring still remains a research tool. The present work, a collection of diverse research articles, was conducted trying to build a bridge between the research setting and the clinical practice. It includes the validation study of the third-generation technology for microcirculatory imaging, the Incident Dark Field illumination (IDF), providing a comparison with the gold standard. Moreover, it gives a deep insight on the technical issues in collecting appropriate imaging and on their impact on the data interpretation, focusing the attention on the operator experience and patient’s cooperation. The core of the project is represented by the MicroDAIMON, a prospective observational study with one of the largest databases of microcirculatory data in critically ill patients to date: it shows the association between microcirculatory abnormalities at the baseline and mortality. Daily monitoring was also performed with Near InfraRed Spectroscopy of skeletal muscle associated to a vascular occlusion test in order to evaluate the dynamic response and reserve capacity of the microcirculation to an ischemic disturbance. A subgroup analysis, focuses the attention on trauma patients, showing that the persistence of microcirculatory abnormalities in presence of normalized macro-hemodynamic variables could predict a major risk of development of organ dysfunction. Finally, with an open label pilot study, the effect of ketanserin in recruiting a dysfunctional microcirculation was investigate, trying to propose a pharmacologic approach to microcirculatory abnormalities