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Current Opinion in Anaesthesiology Apr 2022Advances in the treatment of septic shock have historically focused on resuscitation endpoints, mainly mean arterial pressure and cardiac output. As the definitions of... (Review)
Review
PURPOSE OF REVIEW
Advances in the treatment of septic shock have historically focused on resuscitation endpoints, mainly mean arterial pressure and cardiac output. As the definitions of sepsis and septic shock have shifted to focus on the diversity of causes of dysregulated host-response we have seen an emerging phenotype where tissue hypoxia persists despite adequate macrocirculatory parameters. Interest in the topic of microcirculation is re-emerging as validated bedside techniques for hemodynamic monitoring, such as video microscopes, are becoming available. We review the current understanding of how sepsis induced hypoperfusion with a focus on recent advances in monitoring the microcirculation, and how a proliferation of biomarkers and emerging therapeutic targets may impact future research.
RECENT FINDINGS
Conventional hemodynamic monitoring systems fail to assess the microcirculation, and it's response to treatment. Lactate and venous oxygen saturations often drive biomarker-guided sepsis management. Visual assessments such as mottling and capillary refill time are often associated with predicting outcomes, but sometimes can have issues with inter-provider reliability. Microcirculatory damage can be observed sublingually and appears to have prognostic value.
SUMMARY
Sepsis is associated with changes in the microcirculation that can lead to tissue hypoxia and organ dysfunction. Further studies are needed to validate the usefulness of microcirculatory bedside tools in guiding resuscitative efforts.
Topics: Hemodynamics; Humans; Microcirculation; Reproducibility of Results; Resuscitation; Sepsis; Shock, Septic
PubMed: 35081058
DOI: 10.1097/ACO.0000000000001098 -
Current Opinion in Anaesthesiology Apr 2021The aim of this study was to discuss the implication of microvascular dysfunction in septic shock. (Review)
Review
PURPOSE OF REVIEW
The aim of this study was to discuss the implication of microvascular dysfunction in septic shock.
RECENT FINDINGS
Resuscitation of sepsis has focused on systemic haemodynamics and, more recently, on peripheral perfusion indices. However, central microvascular perfusion is altered in sepsis and these alterations often persist despite normalization of various macro haemodynamic resuscitative goals. Endothelial dysfunction is a key element in sepsis pathophysiology. It is responsible for the sepsis-induced hypotension. In addition, endothelial dysfunction is also implicated involved in the activation of inflammation and coagulation processes leading to amplification of the septic response and development of organ dysfunction. It also promotes an increase in permeability, mostly at venular side, and impairs microvascular perfusion and hence tissue oxygenation.Microvascular alterations are characterized by heterogeneity in blood flow distribution, with adequately perfused areas in close vicinity to not perfused areas, thus characterizing the distributive nature of septic shock. Such microvascular alterations have profound implications, as these are associated with organ dysfunction and unfavourable outcomes. Also, the response to therapy is highly variable and cannot be predicted by systemic hemodynamic assessment and hence cannot be detected by classical haemodynamic tools.
SUMMARY
Microcirculation is a key element in the pathophysiology of sepsis. Even if microcirculation-targeted therapy is not yet ready for the prime time, understanding the processes implicated in microvascular dysfunction is important to prevent chasing systemic hemodynamic variables when this does not contribute to improve tissue perfusion.
Topics: Hemodynamics; Humans; Microcirculation; Resuscitation; Shock, Septic
PubMed: 33577205
DOI: 10.1097/ACO.0000000000000957 -
Anaesthesia, Critical Care & Pain... Aug 2022Oxygen is needed to generate aerobic adenosine triphosphate and energy that is required to support vital cellular functions. Oxygen delivery (DO) to the tissues is... (Review)
Review
Oxygen is needed to generate aerobic adenosine triphosphate and energy that is required to support vital cellular functions. Oxygen delivery (DO) to the tissues is determined by convective and diffusive processes. The ability of the body to adjust oxygen extraction (ERO) in response to changes in DO is crucial to maintain constant tissue oxygen consumption (VO). The capability to increase ERO is the result of the regulation of the circulation and the effects of the simultaneous activation of both central and local factors. The endothelium plays a crucial role in matching tissue oxygen supply to demand in situations of acute drop in tissue oxygenation. Tissue oxygenation is adequate when tissue oxygen demand is met. When DO is severely compromised, a critical DO value is reached below which VO falls and becomes dependent on DO, resulting in tissue hypoxia. The different mechanisms of tissue hypoxia are circulatory, anaemic, and hypoxic, characterised by a diminished DO but preserved capacity of increasing ERO. Cytopathic hypoxia is another mechanism of tissue hypoxia that is due to impairment in mitochondrial respiration that can be observed in septic conditions with normal overall DO. Sepsis induces microcirculatory alterations with decreased functional capillary density, increased number of stopped-flow capillaries, and marked heterogeneity between the areas with large intercapillary distance, resulting in impairment of the tissue to extract oxygen and to satisfy the increased tissue oxygen demand, leading to the development of tissue hypoxia. Different therapeutic approaches exist to increase DO and improve microcirculation, such as fluid therapy, transfusion, vasopressors, inotropes, and vasodilators. However, the effects of these agents on microcirculation are quite variable.
Topics: Humans; Hypoxia; Microcirculation; Oxygen; Oxygen Consumption; Sepsis
PubMed: 35462083
DOI: 10.1016/j.accpm.2022.101087 -
Critical Care (London, England) May 2023The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is... (Review)
Review
The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients.
Topics: Critical Care; Microcirculation; Resuscitation; Hemodynamics; Artificial Intelligence
PubMed: 37193993
DOI: 10.1186/s13054-023-04474-x -
Microcirculation (New York, N.Y. : 1994) Oct 2022
Topics: Microcirculation
PubMed: 36125801
DOI: 10.1111/micc.12785 -
Comprehensive Physiology Jul 2020The anatomy and physiology of the microcirculation in human skin are complex. Normal cutaneous microcirculation is organized in two parallel plexuses with capillary... (Review)
Review
The anatomy and physiology of the microcirculation in human skin are complex. Normal cutaneous microcirculation is organized in two parallel plexuses with capillary loops extending perpendicularly from the superficial plexus. The physiological regulation of cutaneous microcirculation includes specific sympathetic activation, which causes vasoconstriction through the release of norepinephrine, neuropeptide Y, and ATP. A sympathetic cholinergic system is mainly involved in vasodilation through the co-transmission of acetylcholine, vasoactive intestinal peptide, and pituitary adenylate cyclase-activating peptide. Sensory nerves play a major role through the release of calcitonin gene-related peptide and substance P. Endothelium-dependent vasomotion implicates nitric oxide, prostacyclin, endothelium-dependent hyperpolarizing factors, and endothelin. Myogenic response also plays a role and explains why autoregulation is weak but exists in glabrous human skin. Variations in skin blood flow result from highly complex interactions between these mechanisms. In this article, we will detail the anatomy, physiology, and current methods of exploring the human microcirculation. We will further discuss the part played by cutaneous microvascular impairment in the pathophysiology of cardiovascular and metabolic diseases, or diseases more specifically affecting the skin. © 2020 American Physiological Society. Compr Physiol 10:1105-1154, 2020.
Topics: Animals; Humans; Microcirculation; Skin; Skin Diseases
PubMed: 32941681
DOI: 10.1002/cphy.c190008 -
European Heart Journal Jul 2020
Topics: Heart; Heart Failure; Humans; Hypertension; Microcirculation
PubMed: 32608497
DOI: 10.1093/eurheartj/ehaa437 -
Microcirculation (New York, N.Y. : 1994) Oct 2022Microcirculation facilitates the blood-tissue exchange of nutrients and regulates blood perfusion. It is, therefore, essential in maintaining tissue health. Aberrations... (Review)
Review
Microcirculation facilitates the blood-tissue exchange of nutrients and regulates blood perfusion. It is, therefore, essential in maintaining tissue health. Aberrations in microcirculation are potentially indicative of underlying cardiovascular and metabolic pathologies. Thus, quantitative information about it is of great clinical relevance. Photoacoustic imaging (PAI) is a capable technique that relies on the generation of imaging contrast via the absorption of light and can image at micron-scale resolution. PAI is especially desirable to map microvasculature as hemoglobin strongly absorbs light and can generate a photoacoustic signal. This paper reviews the current state of the art for imaging microvascular networks using photoacoustic imaging. We further describe how quantitative information about blood dynamics such as the total hemoglobin concentration, oxygen saturation, and blood flow rate is obtained using PAI. We also discuss its importance in understanding key pathophysiological processes in neurovascular, cardiovascular, ophthalmic, and cancer research fields. We then discuss the current challenges and limitations of PAI and the approaches that can help overcome these limitations. Finally, we provide the reader with an overview of future trends in the field of PAI for imaging microcirculation.
Topics: Microcirculation; Photoacoustic Techniques; Diagnostic Imaging; Microvessels; Hemoglobins
PubMed: 35793421
DOI: 10.1111/micc.12776 -
Hypertension (Dallas, Tex. : 1979) Apr 2023Hypertension is associated with important alterations in the morphology of small arteries and arterioles. Vascular-specific manifestations are changes in the structure... (Review)
Review
Hypertension is associated with important alterations in the morphology of small arteries and arterioles. Vascular-specific manifestations are changes in the structure and function of vascular smooth muscle cells, extracellular matrix, perivascular tissues, and endothelial cells. Arteriole and capillary remodeling and capillary rarefaction have been observed in hypertensive animals and human beings which contribute to increased vascular resistance. An impairment of different angiogenetic factors, such as VEGF (vascular endothelial growth factor), VEGFR-2 (vascular endothelial growth factor receptor-2), TIMP-1 (tissue inhibitor matrix metalloproteinases-1), and TSP-1 (thrombospondin-1), seems to be responsible for the reduction of the microvascular network. Exercise training has been shown to improve vascular structure and function in hypertension not only in the large arteries but also in the peripheral circulation. Exercise training may regress microvascular remodeling and normalize capillary density, leading to capillary growth possibly by increasing proangiogenic stimuli such as VEGF. Exercise enhances endothelium-dependent vascular relaxation through nitric oxide release increase and oxidative stress reduction. Other mechanisms include improved balance between prostacyclin and thromboxane levels, lower circulating levels of endothelin-1, attenuation of infiltration of immune cells into perivascular adipose tissue, and increase of local adiponectin secretion. In addition, exercise training favorably modulates the expression of several microRNAs leading to a positive modification in muscle fiber composition. Identifying the bioactive molecules and biological mechanisms that mediate exercise benefits through pathways that differ from those used by antihypertensive drugs may help to improve our knowledge of hypertension pathophysiology and facilitate the development of new therapeutic strategies.
Topics: Animals; Humans; Endothelial Cells; Endothelium, Vascular; Exercise; Hypertension; Microcirculation; Vascular Endothelial Growth Factor A
PubMed: 36601920
DOI: 10.1161/HYPERTENSIONAHA.122.19465 -
Vascular Pharmacology Dec 2023The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenetic mechanisms resulting in functional and/or structural changes in the coronary...
The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenetic mechanisms resulting in functional and/or structural changes in the coronary microcirculation. CMD often determines angina and myocardial ischemia in a broad spectrum of cardiovascular diseases, including patients with ischemia with non-obstructive coronary arteries or ischemia with obstructive coronary artery disease, infarction with non-obstructive coronary arteries, cardiomyopathies, the Takotsubo syndrome and heart failure, especially heart failure with preserved ejection fraction. In this article, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.
Topics: Humans; Cardiovascular Diseases; Coronary Circulation; Myocardial Ischemia; Coronary Artery Disease; Coronary Vessels; Heart Failure; Ischemia; Microcirculation
PubMed: 37898380
DOI: 10.1016/j.vph.2023.107239