Fluid loading increases oxygen consumption in septic patients with lactic acidosis

We prospectively evaluated 20 patients with systemic sepsis and signs of circulatory failure to determine if fluid loading was associated with increases in systemic oxygen delivery (DO2) and consumption (VO2). Fluid loading led to an increase in DO2 in 14 patients (70%). Patients who demonstrated increased DO2 with a corresponding increase in VO2 (Group A, n = 8) had significantly higher (p less than 0.05) initial blood lactate levels (4.9 +/- 2.9 mmol/L, mean +/- SD) than did patients without an increase in VO2 (Group B, n = 6, 1.9 +/- 1.0 mmol/L). A decrease in DO2 that was attributed to hemodilution was noted in the remaining 6 patients (Group C). Group C exhibited elevated lactate levels (5.1 +/- 2.4 mmol/L) and no significant changes in VO2. We conclude that lactic acidosis, a marker of anaerobic metabolism, predicts increases in VO2 in septic patients who respond to fluid loading with an increase in DO2.     

Monocyte deactivation in septic shock

Septic shock is a complicated syndrome in which pro-inflammatory and anti-inflammatory processes are dynamically interconnected and regulated. Central to these processes is the monocyte, which produces large quantities of pro-inflammatory cytokines in the presence of bacterial products. During the course of sepsis, the production of compensatory anti-inflammatory mechanisms may deactivate monocytes and lead to a state of paralysis. This situation is in fact similar but not identical to that known as tolerance, in which normal monocytes prechallenged with lipopolysaccharide do not respond to a second challenge of lipopolysaccharide. Here, we review some of the cellular mechanisms that may lead to monocyte deactivation and discuss the clinical implications they may have.     

Endotoxemia in human septic shock

To evaluate the incidence, pattern and clinical importance of endotoxemia in septic shock, frequent, serial endotoxin determinations were made prospectively in patients with shock. Detectable endotoxin occurred in 43 of 100 patients with septic shock, but in only one of ten patients with shock due to nonseptic causes. During septic shock, endotoxemia frequently occurred in the absence of Gram-negative bacteremia. Using a logistic regression model, multiple organ failure occurred 10.3 times more frequently and depression of left ventricular ejection fraction (less than or equal to 45 percent) 4.8 times more frequently in endotoxemic patients. In patients with positive blood cultures, endotoxemia was associated with a high mortality. We conclude that endotoxemia occurs frequently in septic shock and is associated with severe manifestations of this syndrome, including cardiac depression and multiple organ failure. This study suggests that endotoxin is an important mediator of septic shock and supports efforts to develop anti-endotoxin therapies for treating patients with this disease.     

Vasopressor support in septic shock

When fluid administration fails to restore an adequate arterial pressure and organ perfusion in patients with septic shock, therapy with vasopressor agents should be initiated. The ultimate goals of such therapy in patients with shock are to restore effective tissue perfusion and to normalize cellular metabolism. Although arterial pressure is the end point of vasopressor therapy, and the restoration of adequate pressure is the criterion of effectiveness, BP does not always equate to blood flow; so, the precise BP goal to target is not necessarily the same in all patients. There has been longstanding debate about whether one catecholamine vasopressor agent is superior to another, but different agents have different effects on pressure and flow. The argument about which catecholamine is best in a given situation is best transformed into a discussion about which agent is best suited to implement the therapeutic strategy chosen. Despite the complex pathophysiology of sepsis, an underlying approach to its hemodynamic support can be formulated that takes both pressure and perfusion into account when choosing therapeutic interventions. The efficacy of hemodynamic therapy in sepsis should be assessed by monitoring a combination of clinical and hemodynamic parameters. How to optimize regional blood and microcirculatory blood flow remains uncertain. Thus, specific end points for therapy are debatable and are likely to evolve. Nonetheless, the idea that clinicians should define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis remains a fundamental principle.     

Management of septic shock

Septic shock due to bacterial and other infections remains an increasing cause of hospital mortality and morbidity. Early recognition and prompt management with diagnostic evaluation, antimicrobial therapy, surgery when indicated and advanced life support undoubtedly saves many lives. Once treatment has been instituted, careful and frequent monitoring is required to optimise therapy and detect complications at an early stage. However, once shock and organ failure have become established the mortality remains high and has changed little in the last few years despite improvements in intensive management. A variety of other approaches to treatment are under investigation but as yet there are insufficient data to recommend their use.     

Fluid management in shock

Shock is a broad category of injury to the human body caused by a variety of insults. Fluid resuscitation is the cornerstone of initial therapy for nearly all forms of shock. This article reviews the basic physiology determining body fluid composition, the goals of fluid resuscitation in shock, the types of fluids available for use, and clinical evidence for use of specific fluids based on etiology of the insult.     

Endothelial barrier dysfunction in septic shock

The endothelium provides an essential and selective membrane barrier that regulates the movement of water, solutes, gases, macromolecules and the cellular elements of the blood from the tissue compartment in health and disease. Its structure and continuous function is essential for life for all vertebrate organisms. Recent evidence indicates that the endothelial surface does not have a passive role in systemic inflammatory states such as septic shock. In fact, endothelial cells are in dynamic equilibrium with a myriad of inflammatory mediators and elements of the innate immune and coagulation systems to orchestrate the host response in sepsis. The barrier function of the endothelial surface is almost uniformly impaired in septic shock, and it is likely that this contributes to adverse outcomes. In this review, we will highlight recent advances in the understanding of the signalling events that regulate endothelial function and molecular events that induce endothelial dysfunction in sepsis. Endothelial barrier repair strategies as a treatment for sepsis include modulation of C5a, high‐mobility group box 1 and VEGF receptor 2; stimulation of angiopoietin‐1, sphingosine 1 phosphate receptor 1 and Slit; and a number of other innovative approaches.     

Immunoglobulins in sepsis and septic shock

Clinical efficacy of polyspecific immunoglobulins or monoclonal antibodies to treat patients with severe sepsis or septic shock is still under debate after several clinical trials. Only a few of them have been able to demonstrate a direct benefit to reduce mortality or this effect appears after meta-analysis. Evidence sustains that polyspecific immunoglobulin G reduces mortality in these patients, being this effect higher for IgM-enriched immunoglobulins. Best indications are postsurgical sepsis or early septic shock patients with high titers of endotoxinemia. The use of intravenous immunoglobulins is also recommended for the treatment of patients with streptococcal toxic shock, as demonstrated by the evidence obtained through case-control studies and one randomized clinical trial with a clear trend toward benefit. Evidence does not sustain a favorable impact on mortality for monoclonal antibodies directed against bacterial lypopolysaccaride, other bacterial antigens or against TNF-alpha. Furthermore, infusion of recombinant IL-1 receptor antagonist or soluble receptors for TNF-alpha that could attenuate the inflammatory response have not demonstrated utility after many clinical trials. These therapeutic tools are characterized by a high acquisition cost and adequate cost-effectiveness analysis has not been yet performed.     

Vasoactive drug use in septic shock

Sepsis accounts for more than 210,000 deaths per year. Despite adequate fluid resuscitation the associated maldistribution of blood flow may cause an imbalance between oxygen delivery and demand, leading to global tissue hypoxia, shock, and, if not reversed, death. Vasoactive therapies including catecholamine and noncatecholamine vasopressors, ionotropes, and vasodilating agents aimed at restoring perfusion and normalizing oxygen consumption have improved outcomes in patients with persistent shock despite crystalloid resuscitation. In this review we discuss the mechanisms, clinical use, and commonly observed pitfalls of the most common and a few uncommon vasodilator agents used in the management of sepsis and septic shock.     

Terlipressin for norepinephrine-resistant septic shock

Norepinephrine-resistant hypotension when associated with septic shock has a high rate of mortality, which might possibly be reduced by infusion of low-dose vasopressin. However, rebound hypotension often arises after treatment is stopped, and the drug usually has to be administered for several days. We report use of terlipressin, a long-acting vasopressin analogue, in eight patients with septic shock who did not respond to corticosteroids and methylene blue. A significant rise in blood pressure that lasted for at least 5 h was seen in all patients after a single bolus, allowing reduction or cessation of norepinephrine administration in seven patients. We were able to discharge four patients from intensive care subsequently. Terlipressin seems to be an effective rescue therapy, which is able to restore blood pressure in patients with catecholamine-resistant septic shock, without obvious complication.     

ECG changes during septic shock

We have previously found that skeletal muscle becomes electrically inexcitable in septic patients. Work in an animal model suggests that a decrease in the available sodium current underlies the loss of electrical excitability. We examined ECGs from patients during periods of septic shock to determine whether there were any ECG abnormalities that might suggest a similar loss of excitability in cardiac tissue during sepsis. Fourteen out of 17 patients had low or significantly decreased QRS amplitudes during septic shock; 8 of 17 had long or increased QRS duration with or without bundle branch block. The mean decrease in QRS amplitude in septic patients was 41%, significantly higher than in controls where no consistent decrease in QRS amplitude was found (p < 0.01). In patients who recovered from septic shock, the QRS amplitude and the increased QRS duration both returned to normal. We conclude that there is a loss of QRS amplitude during septic shock that may be due to altered cardiac excitability.     

Hemodynamic management of septic shock

Septic shock is characterized by profound cardiovascular alterations, including hypovolemia, severe alterations in vascular tone, and myocardial depression. These effects can lead to tissue hypoperfusion, the persistence of which could contribute to multiple organ failure. In addition, regional blood flow alterations and microvascular blood flow alterations may coexist and persist even after whole body hemodynamic alterations are corrected. Early aggressive interventions to improve oxygen delivery have been shown to improve outcome, but ongoing hemodynamic support is often required. This review will examine the hemodynamic management of patients with septic shock.