Microcirculatory dysfunction in sepsis bentham science. The microcirculation is the motor of sepsis critical. Intravenous fluid resuscitation is associated with septic. The microcirculation is a vast system responsible for the transport and delivery of oxygen to tissues throughout the body. Renal haemodynamic, microcirculatory, metabolic and. It is also a common factor in the final cause of death in hospital. Especially in septic shock, alterations in metabolic pathways called cytopathic hypoxia can lead to additional tissue damage 4. Mechanisms and treatment of organ failure in sepsis. The underlying immune response is highly complex and involves activation of the complement system as a crucial entity of innate immunity. Dysfunction of one or more organs is a common occurrence in patients with sepsis owing to microcirculatory alterations and cellular dysfunction. We sought to determine the effects of alternative resuscitation. Cardiovascular dysfunction associated with fluid bolus therapy. Multiorgan failure mof represents the leading cause of death in patients with sepsis and systemic inflammatory response syndrome sirs following severe trauma. Microcirculatory dysfunction and deadspace ventilation in.
Microcirculatory dysfunction plays a pivotal role in the pathophysiology of sepsis and organ dysfunction. Sepsis is the result of a complex and dysregulated homeostatic response to infection. Endothelial and microcirculatory function and dysfunction in sepsis. Microcirculatory changes during open label magnesium. Recent studies have revealed liver dysfunction as an early event in sepsis. Microcirculatory dysfunction is a critical element of the pathogenesis of severe sepsis and septic shock.
Microcirculatory and mitochondrial hypoxia in sepsis. Microcirculatory dysfunction in sepsis has been demonstrated in stomach, small intestine, colon, liver, and kidney. Evidence of microvascular dysfunction during sepsis. Microcirculation, sepsis, shock, hypoxia, norepinephrine, fluids, nitroglycerin. Skeletal muscle and lymphocyte mitochondrial dysfunctions in. Microvascular dysfunction with reduced perfusion and oxygenation results in tissue hypoxia and, ultimately, in organ failure. Sepsis is characterized by arterio and venodilation together with microcirculatory and myocardial dysfunction, with septic patients being poorly responsive to. In sepsis, microcirculatory alterations are more complex and. Microcirculatory dysfunction is present early in the pathophysiology of sepsis, with the extent of microcirculatory derangement relating to disease severity and prognosis in icu patients. Sepsis is a condition characterized by progressive systemic haemodynamic deterioration and a massive increase in inflammatory mediators and activated leucocytes, which together cause severe microcirculatory dysfunction and disrupt oxygen homeostasis, leading to oxidative stress and hypoxaemia. Sepsis is the dominant cause of aki in the icu, accounting for nearly 50% of episodes 1, 2. Microcirculatory alterations are colocalized with low po2, production of hif or redox potential o2 sat at the capillary end of wellperfused capillaries is low, not elevated pco2 gap, is increased in sepsis perfusion abnormalities precede alterations in organ function improvement in the sublingual microcirculation in response. Its treatment is initially based on correction of systemic variables.
Because many clinical studies have shown that microcirculatory alterations during sepsis may play a role in the development of organ dysfunction and are more severe in nonsurvivors than survivors,3 we periodically assessed the sublingual microcirculation using handheld video microscopy. For decades, it has been thought that the brain dysfunction in sae is a consequence of the inflammatory response to a systemic infection. Microcirculation in acute and chronic kidney diseases. Although microcirculatory dysfunction is linked to multiple cardiac and noncardiac conditions, a conclusive diagnosis of microcirculatory dysfunction is rarely made in everyday clinical practice. These processes result in tissue dysoxia, either from impaired microcirculatory oxygen delivery andor from mitochondrial dysfunction 4. Interestingly, the pathogenetic mechanisms that underlie mods in sepsis are complex and not entirely elucidated. To test this hypothesis, we conducted a randomized controlled trial of ino for the treatment of microcirculatory dysfunction in patients with sepsis.
Microcirculatory dysfunction and tissue oxygenation in critical illness. Sepsis is characterized by a complex systemic response to an overwhelming infection that may lead to multiorgan dysfunction, including acute kidney injury aki. Microcirculatory oxygen uptake in sepsis full text view. The microcirculation describes the smallest elements of the cardiovascular conducting system and is pivotal in the maintenance of homeostasis. Microcirculatory and mitochondrial hypoxia in sepsis, shock, and resuscitation.
Experimental sepsis was induced in swiss webster mice by intraperitoneal injection of cecal material 5 mgkg, 500. The cascade initiation resulting in endothelial injury, complement activation, coagulopathy, and microcirculatory dysfunction. In the last few years, an important body of knowledge has been developed showing the pathophysiological relevance of the sublingual microcirculation in the development of multiorgan failure associated with sepsis. Abnormal microvascular perfusion, including decreased functional capillary density and increased blood flow heterogeneity, is observed in. Uncontrolled activation of the complement system during sepsis. Increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in vdvt, while respiratory mechanics and oxygenation parameters do not. Summary microcirculatory dysfunction plays a key role in the development of organ dysfunction in septic patients and after solid organ transplantation. Recent findings interlinked by a mutual cascade effect and driven by the. Sepsis and its progression to severe sepsis, septic shock and multiple organ dysfunction syndrome is a major cause of icu admissions and mortality 1. This is a pdf file of an unedited manuscript that has been. Although neuroinflammation and bloodbrain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. The development of new imaging techniques has enabled direct visualization of the human microcirculation with small handheld microscopes. Microvascular dysfunction as a cause of organ dysfunction.
Pdf a prominent feature of sepsis is dysfunction of the microcirculation, with impaired perfusion and regional tissue oxygenation causing a deficit in. Sepsis is a frequent complication of multiple organ dysfunction syndrome and remains a major problem of intensive care medicine. Severe sepsis and septic shock however, are not associated with volume loss. Recent research has shown that maintaining systemic blood pressure is associated with inadequate perfusion of the microcirculation in sepsis. Increased number of interrupted capillaries results with microcirculatory dysfunction which appears to have prognostic significance in sepsis, as the severity of. The microcirculation and its measurement in sepsis.
In severe sepsis, dysfunction of at least one organ system is present. Although microcirculatory dysfunction may occur to varying degrees in most clinical conditions that result in shock, autoregulatory mechanisms of microvascular function are most severely impaired during sepsis, indicating that microcirculatory dysfunction is a pathophysiological sign of sepsis syndrome 83, 104. Microcirculatory perfusion is regulated by an intricate interplay of many neuroendocrine and paracrine pathways, which makes blood flow though this. We demonstrated that microcirculatory perfusion is altered in patients with severe sepsis and septic shock. Dysfunction of oxygen transport pathways during intensive care underlies the sequelae that lead to organ failure, and the limitations of techniques used to. Microcirculatory disorders in sepsis and transplantation. Sepsis associated mortality is highly related to the development of the multiorgan dysfunction syndrome mods. Although dead space assessment could provide significant clinical value in ards 6, 7, to date it has remained a hypothesised impairment in lung alveoli that. The main causal mechanisms are vasoactive substances such as nitric oxide and endothelin, destroyed endothelial surfaces and microvascular occlusion by activated coagulation and leucocytes. Request pdf microcirculatory dysfunction in sepsis in the last few years, an important body of knowledge has been developed showing the pathophysiological.
Whether there is a causeeffect relationship between microcirculatory dysfunction and deadspace ventilation in ards should be addressed in future research. The exogenous application of coagulatory inhibitors may provide a new important strategy for prevention and treatment of microcirculatory. Randomized controlled trial of inhaled nitric oxide for. As mentioned earlier, fluid resuscitation using fluid bolus therapy is regarded as the initial intervention of choice in patients with sepsis induced hypotension and in. These alterations in microvascular perfusion are very similar to those occurring in experimental conditions, and are characterized by a decrease in vascular density. Microcirculatory dysfunction has been recently recognized as a key pathophysiologic process in the evolution of sepsis. Alerted microcirculation resulting in tissue metabolism remains the ultimate outcome of this interplay. Pdf pathophysiology of microcirculatory dysfunction and. Neutrophils disturb pulmonary microcirculation in sepsisinduced.
The microcirculation plays a dominant role in sepsis, and is a major contributing factor to mod, which is itself predictive of mortality in sepsis 10,11 fig. Untreated, sepsis progresses to hypoperfusion, hypoxia, and dysfunction at the level of cells, tissues, and organ systems, leading to death in at least 30% of cases the clinical syndrome of sepsis is a manifestation of pro and antiinflammatory. Microcirculatory dysfunction in sepsis request pdf. Preclinical models suggest that fluid resuscitation degrades the endothelial glycocalyx, a heparan sulfateenriched structure necessary for vascular homeostasis. In addition, the vast amount of experimental studies report on haemodynamic changes only, without providing their relationship to microcirculatory, metabolic and histopathological responses.
Intravenous fluids, an essential component of sepsis resuscitation, may paradoxically worsen outcomes by exacerbating endothelial injury. In sepsis, the microcirculation is profoundly disturbed, and the blood. We hypothesized that endothelial glycocalyx degradation. Microcirculatory dysfunction in sepsis is crucial in the pathogenesis of organ dysfunction and consists of a cascade of mechanisms, which involves many cells, such as endothelial cells, smooth muscle cells, red blood cells and leukocytes. Thus, all these elements of the microcirculation are involved in the sepsis induced inflammation.
Severe sepsis and septic shock may be characterized by a derangement in global cardiac indices typically leading to low peripheral resistance, which the body tries to compensate for by increasing the cardiac output. Circulatory failure as a result of sepsis can be initiated by various insults such as trauma, infection, and shock. If macrocirculatory and microcirculatory dysfunctions undoubtedly participate in organ dysfunction at the early stage of septic shock, an intrinsic bioenergetic failure. Mods represents a virulent and often incremental assault on virtually all organ systems. Pathophysiology of microcirculatory dysfunction and the. Prompted by these facts, we dynamically assessed the pattern of renal haemodynamics in a longterm porcine model of progressive hyperdynamic sepsis. Request pdf microcirculatory dysfunction in sepsis septic shock is a common and deadly disease that traditionally has been diagnosed and treated by evaluation and optimization of global. Microcirculation and hyperbaric oxygen treatment intechopen. Sepsis associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin lipopolysaccharide, lps, and subsequent activation of inflammatory cytokines as well as mediators. Each compartment of the microcirculatory unit plays a role, that is, the endothelium. New microcirculatory imaging techniques, such as orthogonal polarization spectral ops imaging and its technical. Advances in sepsisassociated liver dysfunction burns.