Regional tissue distress caused by microcirculatory dysfunction and mitochondrial depression underlies the condition in sepsis and shock where, despite correction of systemic oxygen delivery variables, regional hypoxia and oxygen extraction deficit persist. We have termed this condition microcirculatory and mitochondrial distress syndrome (MMDS). Orthogonal polarization spectral imaging allowed the first clinical observation of the microcirculation in human internal organs, and has identified the pivotal role of microcirculatory abnormalities in defining the severity of sepsis, a condition not revealed by systemic hemodynamic or oxygen-derived variables. Recently, sublingual sidestream dark-field (SDF) imaging has been introduced, allowing observation of the microcirculation in even greater detail. Microcirculatory recruitment is needed to ensure adequate microcirculatory perfusion and the oxygenation of tissue cells that follows. In sepsis, where inflammation-induced autoregulatory dysfunction persists and oxygen need is not matched by supply, the microcirculation can be recruited by reducing pathological shunting, promoting microcirculatory perfusion, supporting pump function, and controlling hemorheology and coagulation. Resuscitation following MMDS must include focused recruitment of hypoxic-shunted microcirculatory units and/or resuscitation of the mitochondria. A combination of agents is required for successful rescue of the microcirculation. Single compounds such as activated protein C, which acts on multiple pathways, can be expected to be beneficial in rescuing the microcirculation in sepsis.

/pdf/the-microcirculation-is-the-motor-of-sepsis-4v3w96qiay.pdf

The microcirculation is the motor of sepsis

Objective:To evaluate the effects of dobutamine on microcirculatory blood flow alterations in patients with septic shock.Design:Prospective, open-label study.Setting:A 31-bed, medico-surgical intensive care unit of a university hospital.Patients:Twenty-two patients with septic shock.Interventions:In

The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects

Microcirculatory perfusion is disturbed in sepsis. Recent research has shown that maintaining systemic blood pressure is associated with inadequate perfusion of the microcirculation in sepsis. Microcirculatory perfusion is regulated by an intricate interplay of many neuroendocrine and paracrine pathways, which makes blood flow though this microvascular network a heterogeneous process. Owing to an increased microcirculatory resistance, a maldistribution of blood flow occurs with a decreased systemic vascular resistance due to shunting phenomena. Therapy in shock is aimed at the optimization of cardiac function, arterial hemoglobin saturation and tissue perfusion. This will mean the correction of hypovolemia and the restoration of an evenly distributed microcirculatory flow and adequate oxygen transport. A practical clinical score for the definition of shock is proposed and a novel technique for bedside visualization of the capillary network is discussed, including its possible implications for the treatment of septic shock patients with vasodilators to open the microcirculation.

/pdf/bench-to-bedside-review-sepsis-is-a-disease-of-the-5gklp57mlz.pdf

Bench-to-bedside review: Sepsis is a disease of the microcirculation

Over 30 years ago Weil and Shubin proposed a re-classification of shock states and identified hypovolemic, cardiogenic, obstructive and distributive shock. The first three categories have in common that they are associated with a fall in cardiac output. Distributive shock, such as occurs during sepsis and septic shock, however, is associated with an abnormal distribution of microvascular blood flow and metabolic distress in the presence of normal or even supranormal levels of cardiac output. This Bench-to-bedside review looks at the recent insights that have been gained into the nature of distributive shock. Its pathophysiology can best be described as a microcirculatory and mitochondrial distress syndrome, where time and therapy form an integral part of the definition. The clinical introduction of new microcirculatory imaging techniques, such as orthogonal polarization spectral and side-stream dark-field imaging, have allowed direct observation of the microcirculation at the bedside. Images of the sublingual microcirculation during septic shock and resuscitation have revealed that the distributive defect of blood flow occurs at the capillary level. In this paper, we classify the different types of heterogeneous flow patterns of microcirculatory abnormalities found during different types of distributive shock. Analysis of these patterns gave a five class classification system to define the types of microcirculatory abnormalities found in different types of distributive shock and indicated that distributive shock occurs in many other clinical conditions than just sepsis and septic shock. It is likely that different mechanisms defined by pathology and treatment underlie these abnormalities observed in the different classes. Functionally, however, they all cause a distributive defect resulting in microcirculatory shunting and regional dysoxia. It is hoped that this classification system will help in the identification of mechanisms underlying these abnormalities and indicate optimal therapies for resuscitating septic and other types of distributive shock.

/pdf/bench-to-bedside-review-mechanisms-of-critical-illness-4bxd9wk9jx.pdf

Bench-to-bedside review: Mechanisms of critical illness – classifying microcirculatory flow abnormalities in distributive shock

For many decades arterial blood pressure regulation has been an important issue in the treatment of septic shock. The pathogenesis of this persistent hypotension is complex and multifactorial, but inability of vascular smooth muscle to contract in the presence of vasoconstrictive agents seems to be a key factor. Many mechanisms have been proposed to account for this failure, including nitric oxide (NO) overproduction and vasopressin deficiency (1). However, improvement of outcome due to intervention in these mechanisms fails to be reported despite the restoration of blood pressure. Recent studies of the microcirculation in humans by means of orthogonal polarization spectral (OPS) imaging have opened challenging new perspectives to study the microcirculation (2, 3). We report a case in which sublingual OPS imaging was performed upon administration of terlipressin in a patient with catecholamine-resistant septic shock. It indicates that much caution should be taken when considering such potent vasoconstrictor when correcting blood pressure during shock.

/pdf/sublingual-microcirculatory-flow-is-impaired-by-the-36xgrjjv68.pdf

Sublingual microcirculatory flow is impaired by the vasopressin-analogue terlipressin in a patient with catecholamine-resistant septic shock.

To assess the sublingual microcirculation in a patient during vasopressin administration for a distributive shock after cardiopulmonary bypass. Case-report in the Department of Intensive Care of a university hospital. A 53 year-old man developed severe distributive shock after cardiac transplant, requiring massive doses of vasopressor agents. Vasopressin administered twice at a dose of 0.02 U/min increased mean blood pressure and allowed partial weaning of other vasopressor drugs. Microcirculatory alterations were assessed by orthogonal polarization spectral technique: 50% and 60% of capillaries were perfused at baseline, and these proportions did not worsen when vasopressin was administered. Despite its strong vasopressor effects vasopressin infusion did not worsen microcirculatory alterations in this patient with distributive shock following cardiac surgery.

Effect of vasopressin on sublingual microcirculation in a patient with distributive shock.

Letter to the editor: "Undifferentiated non-hepatic hyperammonemia in the ICU: Diagnosis and management".

Potential Confounders in Study Concluding Higher Lactate at Vasopressin Initiation Is Associated With Higher Mortality in Septic Shock.

High-Dose Vitamin C: How an Orange Can Be a Lemon.

/pdf/membrane-adsorption-in-vancomycin-treatment-is-membrane-type-1nmsm9wi.pdf

Membrane adsorption in vancomycin treatment is membrane type dependent in CVVHDF: dose correction is crucial

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