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1.
J Surg Res ; 281: 1-12, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36095893

RESUMO

INTRODUCTION: Although the improving effect of nitric oxide (NO) donors has experimentally been demonstrated in shock, there are still no NO donor medications clinically available. Thiol-nitrosothiol-hydroxyethyl starch (S-NO-HES) is a novel molecule consisting of NO coupled to a thiolated derivative of hydroxyethyl starch (HES). It was aimed to assess the ability of S-NO-HES to serve as an NO donor under a variety of in vitro simulated physiologic conditions, which might be the first step to qualify this molecule as a novel type of NO donor-fluid. METHODS: We studied the effect of temperature on NO-releasing properties of S-NO-HES in blood, at 34°C, 37°C, and 41°C. Ascorbic acid (Asc) and amylase were also tested in a medium environment. In addition, we evaluated the activity of S-NO-HES in the isolated aortic ring and Langendorff-perfused heart setup. RESULTS: The NO release property of S-NO-HES was found at any temperature. Asc led to a significant increase in the production of NO compared to S-NO-HES incubation (P < 0.05). The addition of amylase together with Asc to the medium further increased the release of NO (P < 0.05). S-NO-HES exerted significant vasodilatory effects on phenylephrine precontracted aortic rings that were dose-dependent (P < 0.01). Furthermore, S-NO-HES significantly increased the heart rate and additionally reduced the duration of the cardiac action potential, as indicated by a reduction of QTc-B values (P < 0.01). CONCLUSIONS: We demonstrated for the first time that the S-NO-HES molecule exhibited its NO-releasing effects. The effectiveness of this new NO donor to substitute NO deficiency under septic conditions or in other indications needs to be studied.


Assuntos
Derivados de Hidroxietil Amido , Hipotensão , Humanos , Derivados de Hidroxietil Amido/farmacologia , Derivados de Hidroxietil Amido/uso terapêutico , Óxido Nítrico , Frequência Cardíaca , Amilases , Amido/farmacologia , Substitutos do Plasma
2.
J Clin Monit Comput ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36355276

RESUMO

The sublingual mucosa is a commonly used intraoral location for identifying microcirculatory alterations using handheld vital microscopes (HVMs). The anatomic description of the sublingual cave and its related training have not been adequately introduced. The aim of this study was to introduce anatomy guided sublingual microcirculatory assessment. Measurements were acquired from the floor of the mouth using incident dark-field (IDF) imaging before (T0) and after (T1) sublingual cave anatomy instructed training. Instructions consists of examining a specific region of interested identified through observable anatomical structures adjacent and bilaterally to the lingual frenulum which is next to the sublingual papilla. The anatomical location called the sublingual triangle, was identified as stationed between the lingual frenulum, the sublingual fold and ventrally to the tongue. Small, large, and total vessel density datasets (SVD, LVD and TVD respectively) obtained by non-instructed and instructed measurements (NIN (T0) and IM (T1) respectively) were compared. Microvascular structures were analyzed, and the presence of salivary duct-related microcirculation was identified. A total of 72 video clips were used for analysis in which TVD, but not LVD and SVD, was higher in IM compared to NIM (NIM vs. IM, 25 ± 2 vs. 27 ± 3 mm/mm2 (p = 0.044), LVD NIM vs. IM: 7 ± 1 vs. 8 ± 1mm/mm2 (p = 0.092), SVD NIM vs. IM: 18 ± 2 vs. 20 ± 3 mm/mm2 (p = 0.103)). IM resulted in microcirculatory assessments which included morphological properties such as capillaries, venules and arterioles, without salivary duct-associated microcirculation. The sublingual triangle identified in this study showed consistent network-based microcirculation, without interference from microcirculation associated with specialized anatomic structures. These findings suggest that the sublingual triangle, an anatomy guided location, yielded sublingual based measurements that conforms with international guidelines. IM showed higher TVD values, and future studies are needed with larger sample sizes to prove differences in microcirculatory parameters.

3.
Minerva Anestesiol ; 88(12): 1066-1072, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36287392

RESUMO

The high complexity of care in the Intensive Care Unit environment has led, in the last decades, to a big effort in term of the improvement of patient's monitoring devices, increase of diagnostic and therapeutic opportunities, and development of electronic health records. Such advancements have enabled an increasing availability of large amounts of data that were supposed to provide more insight and understanding regarding pathophysiological processes and patient's prognosis providing useful tools able to support physicians in the clinical decision-making process. On the contrary, the interpolation, analysis, and interpretation of a such big amount of data has soon proven to be much more complicated than expected, opening the way for the development of tools based on machine learning (ML) algorithms. However, at the present, most of the AI-based algorithms developed in intensive care do not reach beyond the prototyping and development environment and are still far from being able to assist physicians at the bedside in the clinical decisions to improve quality and efficiency of care. The present review aimed to provide an overview of the status of ML-based algorithms in intensive care, to explore the concept of digital transformation, and to highlight possible next steps necessary to move towards a routine use of ML-based clinical decision support systems at the bedside. Finally, we described our attempt to apply the pillars of digital transformation in the field of microcirculation monitoring with the creation of the Microcirculation Network Research Group (MNRG).

4.
Crit Care ; 26(1): 311, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-36242010

RESUMO

BACKGROUND: The sublingual microcirculation presumably exhibits disease-specific changes in function and morphology. Algorithm-based quantification of functional microcirculatory hemodynamic variables in handheld vital microscopy (HVM) has recently allowed identification of hemodynamic alterations in the microcirculation associated with COVID-19. In the present study we hypothesized that supervised deep machine learning could be used to identify previously unknown microcirculatory alterations, and combination with algorithmically quantified functional variables increases the model's performance to differentiate critically ill COVID-19 patients from healthy volunteers. METHODS: Four international, multi-central cohorts of critically ill COVID-19 patients and healthy volunteers (n = 59/n = 40) were used for neuronal network training and internal validation, alongside quantification of functional microcirculatory hemodynamic variables. Independent verification of the models was performed in a second cohort (n = 25/n = 33). RESULTS: Six thousand ninety-two image sequences in 157 individuals were included. Bootstrapped internal validation yielded AUROC(CI) for detection of COVID-19 status of 0.75 (0.69-0.79), 0.74 (0.69-0.79) and 0.84 (0.80-0.89) for the algorithm-based, deep learning-based and combined models. Individual model performance in external validation was 0.73 (0.71-0.76) and 0.61 (0.58-0.63). Combined neuronal network and algorithm-based identification yielded the highest externally validated AUROC of 0.75 (0.73-0.78) (P < 0.0001 versus internal validation and individual models). CONCLUSIONS: We successfully trained a deep learning-based model to differentiate critically ill COVID-19 patients from heathy volunteers in sublingual HVM image sequences. Internally validated, deep learning was superior to the algorithmic approach. However, combining the deep learning method with an algorithm-based approach to quantify the functional state of the microcirculation markedly increased the sensitivity and specificity as compared to either approach alone, and enabled successful external validation of the identification of the presence of microcirculatory alterations associated with COVID-19 status.


Assuntos
COVID-19 , Estado Terminal , Inteligência Artificial , Humanos , Microcirculação/fisiologia , Sensibilidade e Especificidade
5.
BMJ Open ; 12(9): e061337, 2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123067

RESUMO

INTRODUCTION: Vasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac output. The pathophysiology is complex and includes the systemic inflammatory response caused by cardiopulmonary bypass (CPB) and surgical trauma. Patients with end-stage heart failure (HF) are at increased risk for developing vasoplegia. The CytoSorb adsorber is a relatively new haemoadsorption device which can remove circulating inflammatory mediators in a concentration based manner. The CytoSorb-HF trial aims to evaluate the efficacy of CytoSorb haemoadsorption in limiting the systemic inflammatory response and preventing postoperative vasoplegia in HF patients undergoing cardiac surgery with CPB. METHODS AND ANALYSIS: This is an investigator-initiated, single-centre, randomised, controlled clinical trial. In total 36 HF patients undergoing elective cardiac surgery with an expected CPB duration of more than 120 min will be randomised to receive CytoSorb haemoadsorption along with standard surgical treatment or standard surgical treatment alone. The primary endpoint is the change in systemic vascular resistance index with phenylephrine challenge after CPB. Secondary endpoints include inflammatory markers, sublingual microcirculation parameters and 30-day clinical indices. In addition, we will assess the cost-effectiveness of using the CytoSorb adsorber. Vascular reactivity in response to phenylephrine challenge will be assessed after induction, after CPB and on postoperative day 1. At the same time points, and before induction and on postoperative day 4 (5 time points in total), blood samples will be collected and the sublingual microcirculation will be recorded. Study participants will be followed up until day 30. ETHICS AND DISSEMINATION: The trial protocol was approved by the Medical Ethical Committee of Leiden The Hague Delft (METC LDD, registration number P20.039). The results of the trial will be published in peer-reviewed medical journals and through scientific conferences. TRIAL REGISTRATION NUMBER: NCT04812717.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Insuficiência Cardíaca , Vasoplegia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/prevenção & controle , Humanos , Mediadores da Inflamação , Fenilefrina , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome de Resposta Inflamatória Sistêmica
6.
Front Pediatr ; 10: 978381, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160802

RESUMO

Background: SARS-CoV-2 can lead to excessive coagulation and thrombo-inflammation with deposition of microthrombi and microvascular dysfunction. Several studies in human and animal models have already evidenced biomarkers of endothelial injury during SARS-CoV-2 infection. Real-time observation of sublingual microcirculation using an handheld vital microscopy with an Incident Dark Field (IDF) technique could represent a non-invasive way to assess early signs of microvascular dysfunction and endothelial inflammation in patients with severe COVID-19 infection. Clinical case: We report for the first time in a pediatric patient with severe SARS-CoV-2 pneumonia findings about microcirculatory leukocytes in the sublingual microcirculation of a 7 month-old patient admitted to our PICU using handheld vital microscopy with IDF technique. Results: Sublingual microcirculation analysis revealed the presence of microcirculatory alterations and an extensive presence of leukocytes in the patient's sublingual microcirculation. It's significant to underline how the patient didn't show a contextual significant increase in inflammatory biomarkers or other clinical signs related to an inflammatory response, beyond the presence of severe hypoxic respiratory failure. Conclusion: Leukocyte activation in multiple organs can occur at the endothelial lining of the microvasculature where a surge of pro-inflammatory mediators can result in accumulation of activated leukocytes and degradation of the endothelium. The introduction of a method to assess in a non-invasive, real-time manner the extent of inflammation in a patient with COVID19 could lead to potential clinical and therapeutic implications. However, more studies are required to prove that studying leukocytes microcirculation using sublingual microcirculation analysis could be useful as a bedside point of care monitor to predict the presence of systemic inflammation associated with the impact of COVID-19, leading in a late phase of severe SARS-CoV-2 infection to a microvascular dysfunction and micro-thrombosis.

7.
Perfusion ; : 2676591221119002, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35961654

RESUMO

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.

8.
J Clin Monit Comput ; 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35838871

RESUMO

Green light with a wavelength of 520 nm is commonly used in sidestream dark field (SDF) video microscopes for sublingual microcirculation assessment in clinical practice. However, blue light could obtain a clearer microcirculatory image due to a higher light absorption coefficient of hemoglobin. The aim of this study was to compare the sublingual microcirculatory image quality acquisition and related microcirculatory parameters between 520 nm green light and 415 nm blue light probes in the SDF device named MicroSee V100. Sublingual microcirculation films from twenty-one healthy volunteers were prospectively collected by blue light and green light probes, and only one video of each wavelength was recorded and analyzed in each volunteer. Moreover, 200 sublingual microcirculation films (100 by blue light probe and 100 by green light probe) of ICU patients were retrospectively scored for microcirculation image quality. Compared to green light, an increase in the perfused vessel density (paired t test, increased by 4.6 ± 4.7 mm/mm2, P < 0.0001) and total vessel density (paired t test, increased by 5.1 ± 4.6 mm/mm2, P < 0.0001) was observed by blue light in the healthy volunteers. The blue light probe had a significantly lower rate of unacceptable films than the green light probe in the 200 films of ICU patients (10/100 vs. 39/100, P < 0.0001). Blue light provides a higher microcirculatory vessel density and image quality than the existing SDF probe using green light.

9.
Eur J Anaesthesiol ; 39(7): 582-590, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35759291

RESUMO

BACKGROUND: Handheld vital microscopy allows direct observation of red blood cells within the sublingual microcirculation. Automated analysis allows quantifying microcirculatory tissue perfusion variables - including tissue red blood cell perfusion (tRBCp), a functional variable integrating microcirculatory convection and diffusion capacities. OBJECTIVE: We aimed to describe baseline microcirculatory tissue perfusion in patients presenting for elective noncardiac surgery and test that microcirculatory tissue perfusion is preserved during elective general anaesthesia for noncardiac surgery. DESIGN: Prospective observational study. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PATIENTS: 120 elective noncardiac surgery patients (major abdominal, orthopaedic or trauma and minor urologic surgery) and 40 young healthy volunteers. MAIN OUTCOME MEASURES: We measured sublingual microcirculation using incident dark field imaging with automated analysis at baseline before induction of general anaesthesia, under general anaesthesia before surgical incision and every 30 min during surgery. We used incident the dark field imaging technology with a validated automated analysis software. RESULTS: A total of 3687 microcirculation video sequences were analysed. Microcirculatory tissue perfusion variables varied substantially between individuals - but ranges were similar between patients and volunteers. Under general anaesthesia before surgical incision, there were no important changes in tRBCp, functional capillary density and capillary haematocrit compared with preinduction baseline. However, total vessel density was higher and red blood cell velocity and the proportion of perfused vessels were lower under general anaesthesia. There were no important changes in any microcirculatory tissue perfusion variables during surgery. CONCLUSION: In patients presenting for elective noncardiac surgery, baseline microcirculatory tissue perfusion variables vary substantially between individuals - but ranges are similar to those in young healthy volunteers. Microcirculatory tissue perfusion is preserved during general anaesthesia and noncardiac surgery - when macrocirculatory haemodynamics are maintained.


Assuntos
Ferida Cirúrgica , Anestesia Geral , Hemodinâmica/fisiologia , Humanos , Microcirculação/fisiologia , Perfusão
10.
Front Cardiovasc Med ; 9: 818063, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402532

RESUMO

Clinical diagnosis of cardiac tamponade can be difficult in patients with continuous flow left ventricle assist devices (cf-LVADs). This is even more so because of the lack of adequate bedside echocardiographic windows. Previous studies on monitoring sublingual microcirculation showed deterioration of end-organ perfusion in patient with cardiogenic shock. In this paper we report alterations in the sublingual microcirculation in a cf-LVAD patient prior to clinical manifestation of tamponade. Our case report suggests that such real-time monitoring of the microcirculation may provide a new diagnostic modality for early recognition of cardiac tamponade.

11.
J Vasc Res ; 59(4): 199-208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35313312

RESUMO

PURPOSE: Monitoring the sublingual and oral microcirculation (SM-OM) using hand-held vital microscopes (HVMs) has provided valuable insight into the (patho)physiology of diseases. However, the microvascular anatomy in a healthy population has not been adequately described yet. METHODS: Incident dark field-based HVM imaging was used to visualize the SM-OM. First, the SM was divided into four different fields; Field-a (between incisors-lingua), Field-b (between the canine-first premolar-lingua), Field-c (between the first-second premolar-lingua), Field-d (between the second molar-wisdom teeth-lingua). Second, we investigated the buccal area, lower and upper lip. Total/functional vessel density (TVD/FCD), focus depth (FD), small vessel mean diameters (SVMDs), and capillary tortuosity score (CTS) were compared between the areas. RESULTS: Fifteen volunteers with a mean age of 29 ± 6 years were enrolled. No statistical difference was found between the sublingual fields in terms of TVD (p = 0.30), FCD (p = 0.38), and FD (p = 0.09). SVMD was similar in Field-a, Field-b, and Field-c (p = 0.20-0.30), and larger in Field-d (p < 0.01, p = 0.015). The CTS of the buccal area was higher than in the lips. CONCLUSION: The sublingual area has a homogenous distribution in TVD, FCD, FD, and SVMD. This study can be a description of the normal microvascular anatomy for future researches regarding microcirculatory assessment.


Assuntos
Capilares , Soalho Bucal , Voluntários Saudáveis , Humanos , Microcirculação/fisiologia , Soalho Bucal/irrigação sanguínea , Pele
13.
Eur Surg Res ; 63(1): 9-18, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34265760

RESUMO

INTRODUCTION: The microvascular events following portal vein embolization (PVE) are poorly understood despite the pivotal role of the microcirculation in liver regeneration and tumor progression. We aimed to assess the changes in hepatic microvascular perfusion and neo-angiogenesis after experimental PVE. METHODS: PVE of the cranial liver lobes was performed in 12 New Zealand White rabbits divided into 2 groups of permanent (P-PVE) and reversible PVE (R-PVE), respectively. Hepatobiliary scintigraphy and CT were used to evaluate hepatic function and volume. Hepatic microcirculation was assessed using a handheld vital microscope (Cytocam) to measure microvascular density (total vessel density; TVD) before PVE, right after PVE, and 20 min after PVE, as well as at 14 days (D14 post-PVE) and 35 days (D35 post-PVE). Additionally, on D35, microvascular PO2 and liver parenchymal VEGF were assessed. RESULTS: Eleven rabbits were included after PVE (R-PVE, n = 5; P-PVE, n = 6). TVD in the nonembo-lized (hypertrophic) lobes was higher than in the embolized (atrophic) lobes of the P-PVE group at D35 post-PVE (36.7 ± 7.2 vs. 23.4 ± 4.9 mm/mm2; p < 0.05). In the R-PVE group, TVD in the nonembolized lobes was not increased at D35. Function and volume were increased in the nonembolized lobes of the P-PVE group compared to the embolized lobes, but not in the R-PVE group. Likewise, the mmicrovascular PO2 and VEGF staining rate were higher in the nonembolized lobes of the P-PVE group at D35 post-PVE. DISCUSSION/CONCLUSION: Successful volumetric and functional hypertrophy of the nonembolized lobe was accompanied by microvascular alterations featuring increased neo-angiogenesis, microvascular density, and microvascular oxygen pressure following P-PVE.


Assuntos
Embolização Terapêutica , Neoplasias Hepáticas , Animais , Hepatectomia , Hipertrofia/patologia , Fígado/patologia , Neoplasias Hepáticas/patologia , Densidade Microvascular , Veia Porta/diagnóstico por imagem , Coelhos , Fator A de Crescimento do Endotélio Vascular
14.
Blood Purif ; 51(7): 634-638, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34535603

RESUMO

Cytokemia is associated with microcirculatory alterations often with persistent loss of coherence between the micro- and macrocirculation, linked to organ failure and poor outcome of septic patients. Addition of a hemoadsorbant filter to an extracorporeal circuit next to conventional treatment of septic shock results in the hematological clearance of cytokines, hypothetically leading to normalization of the microcirculation and thus organ perfusion. Bedside sublingual microcirculatory assessment using handheld vital microscopy allows real-time direct visualization of the microcirculation and its response to therapy. This is demonstrated in the present case report of an 83-year-old man admitted to our intensive care unit after surgical repair of a colonic perforation for fecal soiling after a low anterior resection for a rectum carcinoma, with leakage of bowel content at the resection site. The clinical course of this patient can be described as having undergone adequate surgical treatment taking away the source of the disease, followed by optimal support including antibiotic treatment in the ICU. However, during the course of his stay in the ICU, his condition deteriorated with symptoms consistent with septic shock. Our report shows that the addition of a hemoadsorbent (CytoSorb) to the continuous renal replacement therapy circuit was associated with an improvement in the condition of our severely ill patient with abdominal sepsis. Parallel to the clinical improvement of our patient, the functional parameters of the microcirculation also showed improvement suggesting that such a noninvasive real-time evaluation of the status of the microcirculation may be a sensitive diagnostic tool to monitor the effectiveness of hemoadsorbent therapy.


Assuntos
Doenças Transmissíveis , Terapia de Substituição Renal Contínua , Choque Séptico , Idoso de 80 Anos ou mais , Citocinas , Humanos , Unidades de Terapia Intensiva , Masculino , Microcirculação/fisiologia , Choque Séptico/terapia
15.
J Craniofac Surg ; 33(1): 264-269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34406155

RESUMO

ABSTRACT: Perioperative management of bleeding in children can be challenging. Microvascular imaging techniques have allowed evaluating the effect of blood transfusion on the microcirculation, but little is known about these effects in children. We aimed to investigate the effects of blood management using macro- and micro-hemodynamic parameters measurement in children undergoing craniofacial surgery. This is a prospective observational repeated measurement study including fourteen children. The indications for blood transfusion were changes of hemoglobin/hematocrit (Hct) levels, the presence of signs of altered tissue perfusion and impaired microcirculation images. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, and systemic parameters (hemoglobin, Hct, lactate, mixed venous oxygen saturation, K+, heart rate, mean arterial blood pressure) were evaluated baseline (T1), at the end of the surgical bleeding (T2) and end of the operation (T3). Four patients did not need a blood transfusion. In the other 10 patients who received a blood transfusion, capillary perfusion was higher at T3 (13[9-16]) when compared with the values of at T2 (11[8-12]) (P < 0.05) but only 6 patients reached their baseline values. Although blood transfusions increased Hct values (17 ±â€Š2.4 [T2]-19 ±â€Š2.8 [T3]) (P < 0.05), there was no correlation between microvascular changes and systemic hemodynamic parameters (P > 0.05). The sublingual microcirculation could change by blood transfusion but there was not any correlation between microcirculation changes, hemodynamic, and tissue perfusion parameters even with Hct values. The indication, guidance, and timing of fluid and blood therapy may be assessed by bedside microvascular analysis in combination with standard hemodynamic and biochemical monitoring for intraoperative bleeding in children.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Hemodinâmica , Microcirculação , Soalho Bucal , Criança , Humanos , Cuidados Intraoperatórios , Soalho Bucal/cirurgia , Oximetria
16.
Shock ; 57(3): 457-466, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34559745

RESUMO

ABSTRACT: Acute normovolemic hemodilution (ANH) is associated with low oxygen carrying capacity of blood and purposed to cause renal injury in perioperative setting. It is best accomplished in a perioperative setting by a colloid such as hydroxyl ethyl starch (HES) due its capacity to fill the vascular compartment and maintain colloidal pressure. However, alterations of intra renal microvascular perfusion, flow and its effects on renal function and damage during ANH has not been sufficiently clarified. Based on the extensive use of HES in the perioperative setting we tested the hypothesis that the use of HES during ANH is able to perfuse the kidney microcirculation adequately without causing renal dysfunction and injury in pigs. Hemodilution (n = 8) was performed by stepwise replacing blood with HES to hematocrit (Hct) levels of 20% (T1), 15% (T2), and 10% (T3). Seven control animals were investigated. Systemic and renal hemodynamics were monitored. Renal microcirculatory perfusion was visualized and quantified using contrast-enhanced ultrasound (CEUS) and laser speckle imaging (LSI). In addition, sublingual microcirculation was measured by handheld vital microscopy (HVM). Intrarenal mean transit time of ultrasound contrast agent (IRMTT-CEUS) was reduced in the renal cortex at Hct 10% in comparison to control at T3 (1.4 ±â€Š0.6 vs. 2.2 ±â€Š0.7 seconds, respectively, P < 0.05). Although renal function was preserved, the serum neutrophil gelatinase-associated lipocalin (NGAL) levels was higher at Hct 10% (0.033 ±â€Š0.004 pg/µg protein) in comparison to control at T3 (0.021 ±â€Š0.002 pg/µg protein. A mild correlation between CO and IRMTT (renal RBC velocity) (r -0.53; P = 0.001) and CO and NGAL levels (r 0.66; P = 0.001) was also found. Our results show that HES induced ANH is associated with a preserved intra renal blood volume, perfusion, and function in the clinical range of Hct (<15%). However, at severely low Hct (10%) ANH was associated with renal injury as indicated by increased NGAL levels. Changes in renal microcirculatory flow (CEUS and LSI) followed those seen in the sublingual microcirculation measured with HVM.


Assuntos
Injúria Renal Aguda/prevenção & controle , Hemodiluição/efeitos adversos , Derivados de Hidroxietil Amido/uso terapêutico , Rim/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Substitutos do Plasma/uso terapêutico , Injúria Renal Aguda/etiologia , Animais , Meios de Contraste , Modelos Animais de Doenças , Feminino , Hematócrito , Rim/diagnóstico por imagem , Imagem de Contraste de Manchas a Laser , Lipocalina-2/sangue , Suínos , Ultrassonografia
17.
Intensive Care Med ; 48(2): 148-163, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34910228

RESUMO

Clinical and pathophysiological understanding of septic shock has progressed exponentially in the previous decades, translating into a steady decrease in septic shock-related morbidity and mortality. Even though large randomized, controlled trials have addressed fundamental aspects of septic shock resuscitation, many questions still exist. In this review, we will describe the current standards of septic shock resuscitation, but the emphasis will be placed on evolving concepts in different domains such as clinical resuscitation targets, adequate use of fluids and vasoactive drugs, refractory shock, and the use of extracorporeal therapies. Multiple research opportunities remain open, and collaborative endeavors should be performed to fill in these gaps.


Assuntos
Choque Séptico , Hidratação , Humanos , Ressuscitação
18.
Expert Opin Ther Targets ; 25(9): 733-748, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34602020

RESUMO

INTRODUCTION: Endothelial cells maintain vascular integrity, tone, and patency and have important roles in hemostasis and inflammatory responses. Although some degree of endothelial dysfunction with increased vascular permeability may be necessary to control local infection, excessive dysfunction plays a central role in the pathogenesis of sepsis-related organ dysfunction and failure as it results in dysregulated inflammation, vascular leakage, and abnormal coagulation. The vascular endothelium has thus been proposed as a potential target for therapeutic intervention in patients with sepsis. AREAS COVERED: Different mechanisms underlying sepsis-related dysfunction of the vascular endothelium are discussed, including glycocalyx shedding, nitrosative stress, and coagulation factors. Potential therapeutic implications of each mechanism are mentioned. EXPERT OPINION: Multiple targets to protect or restore endothelial function have been suggested, but endothelium-driven treatments remain a future potential at present. As some endothelial dysfunction and permeability may be necessary to remove infection and repair damaged tissue, targeting the endothelium may be a particular challenge. Ideally, therapies should be guided by biomarkers related to that specific pathway to ensure they are given only to patients most likely to respond. This enrichment based on biological plausibility and theragnostics will increase the likelihood of a beneficial response in individual patients and enable more personalized treatment.


Assuntos
Sepse , Doenças Vasculares , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Glicocálix/metabolismo , Glicocálix/patologia , Humanos , Sepse/tratamento farmacológico
19.
J Clin Med ; 10(18)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34575154

RESUMO

Acute kidney injury (AKI) is a serious multifactorial conditions accompanied by the loss of function and damage. The renal microcirculation plays a crucial role in maintaining the kidney's functional and structural integrity for oxygen and nutrient supply and waste product removal. However, alterations in microcirculation and oxygenation due to renal perfusion defects, hypoxia, renal tubular, and endothelial damage can result in AKI and the loss of renal function regardless of systemic hemodynamic changes. The unique structural organization of the renal microvasculature and the presence of autoregulation make it difficult to understand the mechanisms and the occurrence of AKI following disorders such as septic, hemorrhagic, or cardiogenic shock; ischemia/reperfusion; chronic heart failure; cardiorenal syndrome; and hemodilution. In this review, we describe the organization of microcirculation, autoregulation, and pathophysiological alterations leading to AKI. We then suggest innovative therapies focused on the protection of the renal microcirculation and oxygenation to prevent AKI.

20.
Cardiorenal Med ; 11(3): 133-139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34082420

RESUMO

Severe acute respiratory syndrome coronavirus 2 has rapidly spread worldwide and resulted in the coronavirus disease 2019 (COVID-19) pandemic. The disease raised an unprecedented demand for intensive care support due to severe pulmonary dysfunction and multiorgan failure. Although the pulmonary system is the potential target of the COVID-19, recent reports have demonstrated that COVID-19 profoundly influences the cardiovascular system and the kidneys. Research studies on cadavers have shown that direct heart and kidney injury can be frequently seen in patients deceased due to COVID-19 infection. On the other hand, functional or structural dysfunction of the heart may deteriorate the renal function and vice versa. This concept is already known as the cardiorenal syndrome and may play a role in COVID-19. Proactive monitoring of micro- and macrohemodynamics could allow prompt correction of circulatory dysfunction and can be of pivotal importance in the prevention of acute kidney injury. Moreover, type and amount of fluid therapy and vasoactive drug support could help manage these patients either with or without mechanical ventilator support. This brief review outlines the current evidence regarding the COVID-19-related renal and cardiorenal complications and discusses potential hemodynamic management strategies.


Assuntos
COVID-19 , Síndrome Cardiorrenal , COVID-19/complicações , Síndrome Cardiorrenal/etiologia , Síndrome Cardiorrenal/terapia , Humanos , Rim/patologia , Pandemias
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