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

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)

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

Cytocam-IDF (incident dark field illumination) imaging for bedside monitoring of the microcirculation

Orthogonal polarized spectral (OPS) and sidestream dark field (SDF) imaging video microscope devices were introduced for observation of the microcirculation but, due to technical limitations, have remained as research tools. Recently, a novel handheld microscope based on incident dark field illumination (IDF) has been introduced for clinical use. The Cytocam-IDF imaging device consists of a pen-like probe incorporating IDF illumination with a set of high-resolution lenses projecting images on to a computer controlled image sensor synchronized with very short pulsed illumination light. This study was performed to validate Cytocam-IDF imaging by comparison to SDF imaging in volunteers. This study is a prospective, observational study. The subjects consist of 25 volunteers. Sublingual microcirculation was evaluated using both techniques. The main result was that Cytocam-IDF imaging provided better quality images and was able to detect 30% more capillaries than SDF imaging (total vessels density Cytocam-IDF: 21.60 ± 4.30 mm/mm(2) vs SDF: 16.35 ± 2.78 mm/mm(2), p < 0.0001). Comparison of the images showed increased contrast, sharpness, and image quality of both venules and capillaries. Cytocam-IDF imaging detected more capillaries and provided better image quality than SDF imaging. It is concluded that Cytocam-IDF imaging may provide a new improved imaging modality for clinical assessment of microcirculatory alteration

Evaluation of the Microcirculation in Critically Ill Patients

Abstract: The first goal of therapies in critically ill patients is to improve tissue perfusion and oxygenation. Hemodynamic monitoring has long been limited to measure-ments of cardiac output and global oxygen delivery. The clinical introduction of hand-held vital microscopes in the late 1990s enabled the real-time, non-invasive, bedside ob-servation of blood flow in the microcirculation (vessels with diameter <100 µm), i.e. the real site of oxygen and nutrient exchange between blood and cells. Microcirculatory alter-ations have been described during sepsis and shock states and were associated with mor-tality. These can occur independently of systemic hemodynamic alterations. Sublingual videomicroscopy allowed evaluating the microvascular response to resuscitation proce-dures, including oxygen therapy, fluids, blood transfusions, vasopressors. Future re-search directions should be aimed to integrate microcirculatory monitoring with standard hemodynamic measurements and verify the utility of microcirculation as a therapeutic tar-get. Continuous technological developments are imperative to facilitate the introduction of sublingual videomicroscopy in the clinical practice