Septic Shock Treatment

11/11/13
Septic Shock Treatment & Management
Today News Reference Education Log In Register

Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM more... Updated: Aug 13, 2012
Approach Considerations
The treatment of patients with septic shock consists of the following 3 major goals: Resuscitate the patient from septic shock using supportive measures to correct hypoxia, hypotension, and impaired tissue oxygenation. Identify the source of infection and treat with antimicrobial therapy, surgery, or both. Maintain adequate organ system function guided by cardiovascular monitoring and interrupt the pathogenesis of multiple organ dysfunction syndrome (MODS). The principles in the management of septic shock, based on current literature, include the following components: Early recognition Early and adequate antibiotic therapy Source control Early hemodynamic resuscitation and continued support Corticosteroids (refractory vasopressor-dependent shock) Drotrecogin alpha (severely ill if APACHE [Acute Physiology And Chronic Health Evaluation] II score >25) Tight glycemic control Proper ventilator management with low tidal volume in patients with acute respiratory distress syndrome (ARDS) Initial treatment includes support of respiratory and circulatory function, supplemental oxygen, mechanical ventilation, and volume infusion. Treatment beyond these supportive measures includes antimicrobial therapy targeting the most likely pathogen, removal or drainage of the infected foci, treatment of complications, and interventions to prevent and treat effects of harmful host responses. Identifying and obtaining source control is an essential component of sepsis management.
General Treatment Guidelines

The major focus of resuscitation from septic shock is supporting cardiac and respiratory functions. The other organ systems also may require attention and support during this critical period. Patients in septic shock generally require intubation and assisted ventilation because respiratory failure either is present at the onset or may develop during the course of the illness. Correction of shock state and abnormal tissue perfusion is the next step in the treatment of patients with septic shock. In 2004, the first set of formal treatment guidelines for septic shock were published.[37] These guidelines were formulated by an international consensus group that was composed of experts from 11 organizations, including the Society of Critical Care Medicine (SCCM), the American College of Chest Physicians (ACCP), the European Society of Intensive Care Medicine (ESICM), and the American College of Emergency Physicians (ACEP). These guidelines, known as the Surviving Sepsis Campaign, were updated in 2008 and reflect the most modern opinion on the treatment of septic shock.[38]
emedicine.medscape.com/article/168402-treatment 1/22
11/11/13
Respiratory support
An initial assessment of airway and breathing is very important in a patient with septic shock. Supplemental oxygen should be administered to all patients with suspected sepsis. Early intubation and mechanical ventilation should be strongly considered for patients with an oxygen requirement, dyspnea or increased respiratory rate, persistent hypotension, or those with evidence of poor peripheral perfusion.
Circulatory support
Patients with suspected septic shock require an initial crystalloid fluid challenge of 20-30 mL/kg (1-2 L) over 30-60 minutes, with additional fluid challenges at rates of up to 1 L over 30 minutes. (A fluid challenge is the rapid administration of volume over a particular period, followed by an assessment of the response.) (See Fluid Resuscitation.) Crystalloid administration is titrated to a central venous pressure (CVP) goal between 8 and 12 mm Hg or signs of volume overload (dyspnea, pulmonary rales, or pulmonary edema on the chest radiograph). Patients with septic shock often require a total 4-6 L or more of crystalloid resuscitation. CVP measurement should not be entirely relied upon, because there is some debate as to how accurately it correlates with intravascular volume status, especially in fluid-resuscitated patients.[39] Urine output (UOP) should also be monitored as a measure of dehydration. UOP lower than 30-50 mL/h should prompt further fluid resuscitation. Some studies have used noninvasive means of estimating CVPfor example, ultrasonography to measure inferior vena cava diameter as a surrogate for volume status. Nagdev et al used the difference between inspiratory and expiratory caval diameter (the caval index) to predict CVP and found that a 50% difference predicted a CVP lower than 8 mm Hg with both a sensitivity and a specificity greater than 90%.[40] Given that third-spacing of intravascular fluid is a hallmark of septic shock, it makes sense that administration of colloid might be beneficial. However, colloid resuscitation (with albumin or hetastarch) has not been shown in meta-analyses to have any benefit over isotonic crystalloid resuscitation (isotonic sodium chloride solution or lactated Ringer solution).[30] The SAFE trial enrolled 7000 intensive care unit (ICU) patients requiring fluid resuscitation, only about 1200 of whom had severe sepsis. Overall, no difference was seen between the 2 treatment groups; however, there was a trend toward improved outcome in patients with severe sepsis who received 4% albumin versus normal saline.[41] These data are inconclusive, especially in regard to the initial resuscitation phase for septic shock in the emergency department (ED); therefore, crystalloid resuscitation is recommended.
Antimicrobial therapy
Recommendations are that antibiotic therapy be administered within the first hour of recognition of septic shock; delays in administration are associated with increased mortality.[38, 6] Selection of antibiotic agents is empirically based on an assessment of the patients underlying host defenses, the potential source of infection, and the most likely responsible organisms. (See Empirical Antimicrobial Therapy.) Antibiotic choice must be broad spectrum, covering gram-positive, gram-negative, and anaerobic bacteria when the source is unknown. In addition, consideration must be given to pathogens with antibiotic resistance, such as methicillin-resistant S aureus (MRSA), Pseudomonas species, and gram-negative organisms with extended-spectrum beta-lactamase (ESBL) activity. Patients who are at risk for these types of infection are nursing home residents, residents of chronic care facilities, those with recent hospitalizations, dialysis-dependent patients, or those with chronic medical conditions that require multiple hospitalizations.
Temperature control
Fever generally requires no treatment, except in patients with limited cardiovascular reserve, because of the increased metabolic requirements. Antipyretic drugs and physical cooling methods, such as sponging or cooling blankets, may be used to lower the patients temperature.
Metabolic support
Patients with septic shock develop hyperglycemia and electrolyte abnormalities. Serum glucose should be maintained in the reference range with insulin infusion. (See Tight Glycemic Control.) Hypokalemia,
11/11/13
hypomagnesemia, and hypophosphatemia should be measured and corrected if deficient.
Correction of anemia and coagulopathy

Hemoglobin as low as 8 g/dL is well tolerated and does not require transfusion unless the patient has poor cardiac reserve or demonstrates evidence of myocardial ischemia. Thrombocytopenia and coagulopathy are common in patients with sepsis and do not require replacement with platelets or fresh frozen plasma, unless the patient develops active clinical bleeding.
Management of renal dysfunction

UOP and renal function must be monitored closely in all patients with sepsis. Any abnormalities should prompt attention to adequacy of circulating blood volume, cardiac output, and blood pressure; these should be corrected if inadequate.
Nutritional support
Patients with septic shock generally have high protein and energy requirements. Although a brief period (several days) without nutrition is not going to cause deleterious effects, prolonged starvation must be avoided. Early nutritional support is of critical importance in patients with septic shock. The enteral route is preferred, unless the patient has an ileus or other intestinal abnormality. Gastroparesis commonly is observed, which can be treated with motility agents or placement of a small bowel feeding tube. Diminished bowel sounds should not prevent a trial of enteral nutrition, although motility agents or the use of a small bowel feeding tube may be necessary. The benefits of enteral nutrition are protection of gut mucosa, avoiding translocation of organisms from the gastrointestinal (GI) tract, lowering the complication rate, and lowering cost. Glutamine, an essential amino acid, influences the mucosal integrity of the GI tract. Insufficient levels of glutamine may occur from starvation or lack of enteral feeding, a condition commonly observed with total parenteral nutrition. Glutamine deficiency contributes to mucosal atrophy, predisposing translocation of bacteria or endotoxin from the gut lumen. Enteral nutrition with glutamine-containing formulas can prevent this relapse of systemic inflammatory response syndrome (SIRS) in patients on adequate therapy.
Principles of Early Goal-Directed Therapy

Sepsis treatment has evolved considerably over the past 10 years as it has transitioned from a disease that is a primary concern of critical care physicians in an ICU setting to one that has a major impact in the ED as well. Early recognition and early aggressive therapy for patients with sepsis are the keys to reducing mortality in sepsis. Rivers et al brought this issue to the forefront with a landmark study in 2001, which involved the institution of a treatment protocol for patients with septic shock, termed early goal-directed therapy (EGDT).[42] EGDT emphasizes early recognition of patients with potential sepsis in the ED, early broad-spectrum antibiotics, and a rapid crystalloid fluid challenge, followed by goal-directed therapy for those patients who remain hypotensive or severely ill after this initial therapy. In the study by Rivers et al, patients who did not respond to an initial fluid challenge (20-30 mL/kg bolus) and antibiotics received a central venous catheter in the internal jugular or subclavian vein to measure CVP and an arterial catheter to measure arterial blood pressure directly. EGDT is a 3-step protocol aimed at optimizing tissue perfusion. The first step involves titrating crystalloid fluid administration to CVP by administering 500-mL boluses of fluid until the CVP measures between 8 and 12 mm Hg. CVP is a surrogate for intravascular volume, as excess circulating blood volume is contained within the venous system. Patients with septic shock will frequently require 4-6 L or more of crystalloid to achieve this goal. Clinical signs of volume overload should be monitored as well, including developing periorbital or extremity edema, crackles on pulmonary examination, increasing oxygen requirement, or increased difficulty breathing. In patients who are mechanically ventilated, the target CVP is 12-15 mm Hg due to increased intrathoracic pressure. The second step, if the patient has not improved with fluid alone, is to administer vasopressors to attain a mean
11/11/13
arterial pressure (MAP) greater than 65 mm Hg. It is important to administer an adequate crystalloid fluid challenge (at least 2 L normal saline) before administering vasopressors, unless the patient is in extremis and requires immediate vasopressor support. The third step is to evaluate the central venous oxygen saturation (ScvO2), which is measured from the central venous line in the superior vena cava. ScvO2 is the oxygen saturation of blood returning from tissue capillary beds, and it reflects the difference between overall oxygen supply and demand. Like lactate, ScvO2 is an indicator of tissue perfusion. An ScvO2 of less than 70% is considered abnormal and indicative of suboptimal oxygen delivery compared with oxygen demand. Adequate oxygen delivery is first achieved by administering supplemental oxygen by face mask, increasing intravascular circulating volume, and increasing MAPin other words, the first 2 steps of EGDT. Additional means of increasing tissue oxygen delivery include maximizing oxygen delivery to the alveoli (mechanical ventilation with a fraction of inspired oxygen [FiO2] of 1.0), maximizing the hemoglobin concentration (transfuse packed red blood cells [pRBCs] if anemic), and augmenting cardiac output (dobutamine to increase inotropy once preload has been optimized). The protocol by Rivers et al called for a blood transfusion if the hematocrit was 30%. As a last step in the protocol, dobutamine infusion was started (increasing cardiac output via pure beta-agonism) if ScvO2 is less than 70% despite all the above measures being optimized. ScvO2 greater than 70% is therefore the target for EGDT, indicating adequate oxygen delivery. Rivers et al measured ScvO2 via a fiberoptic sensor at the tip of the central venous catheter and a standalone monitor that displayed ScvO2 continuously. This concept was based on earlier work targeting treatment goals based on increasing tissue oxygen delivery.[43, 44] An alternative to continuous ScvO2 measurement is to send a venous blood gas from the central venous line for oxygen saturation, measured by a standard blood gas analyzer. Crowe et al implemented a protocol that substituted spot-check ScvO2 measurement for continuous measurement and found that compliance with this was less than 30%. Despite low compliance, there was a trend toward decreased mortality in patients with septic shock treated with a protocol that included timely antibiotics, appropriate crystalloid administration, CVP monitoring, and vasopressors titrated to an MAP goal.[45] A recent study suggests that following lactate clearance may be no less effective than monitoring continuous ScvO2 as the third goal in EGDT.[35] However, the advantage of continuous ScvO2 monitoring is that immediate interventions can be made if the ScvO2 drops below 70%. Rivers et al enrolled 263 patients who met criteria for septic shock. These patients were randomized to EGDT or to standard therapy. The latter included placement of a central venous line and an arterial catheter (both of which are relatively invasive measures and probably not standard in most EDs). Despite this, the investigators found an absolute mortality benefit of 16% with EGDT (30% mortality with EGDT vs 46% with standard therapy). When the data were examined closely, it was found that in the EGDT group, patients received, on average, more crystalloid fluid (5.0 L vs 3.5 L), and a much higher percentage of patients received blood transfusion (64% vs 18%). The resulting average ScvO2 measured after therapy was 95% for the EGDT group versus 60% in the standard group. Since the publication of this trial, several studies have shown the value of protocolized care and of so-called sepsis treatment bundles, which include early broad-spectrum antibiotic administration, EGDT focused on achieving ScvO2 above 70%, and rapid lactate clearance. Sepsis bundles also include administration of corticosteroids for refractory shock, tight glycemic control, low tidal volume ventilatory strategies, and administration of recombinant activated protein C (APC) in an ICU setting.[46, 47, 48, 49, 50, 51, 52, 53]
Venous Access
Ensure that all patients in septic shock receive adequate venous access for volume resuscitation. Two large-bore (16-gauge) intravenous (IV) lines should be placed if possible when sepsis is suspected in order to administer aggressive fluid resuscitation and broad-spectrum antibiotics. A central venous catheter should be placed in the internal jugular or subclavian vein in patients with septic shock if
11/11/13
hypotension is refractory to a crystalloid fluid bolus of 20-30 mL/kg (1-2 L) over 30-60 minutes or if fluids cannot be infused rapidly enough. A central venous catheter allows administration of medication centrally, and it provides multiple ports for rapid fluid administration, antibiotics, and vasopressors if needed. It also allows the measurement of CVP, a surrogate for volume status, if CVP measurement capability is available.
Urinary Catheterization
An indwelling urinary catheter should be placed in order to follow UOP, which is a marker for adequate renal perfusion and cardiac output. Normal UOP in an adult is greater than 0.5 mL/kg/h or about 30-50 mL/h for most adults.
Cardiac Catheterization
Patients in septic shock require right-heart catheterization with a pulmonary artery (Swan-Ganz) catheter. This catheter provides an accurate assessment of the volume status of a septic patient. The cardiac output measurement can be obtained; furthermore, determination of mixed venous oxygenation is helpful in determining the status of tissue oxygenation. The right-sided cardiac catheterization will detect those patients (25%) with sepsis and hypotension who have underlying congestive heart failure (usually due to myocardial suppressant factor).
Intubation and Mechanical Ventilation

Most patients with sepsis develop respiratory distress as a manifestation of severe sepsis or septic shock. The lung injury is characterized pathologically as diffuse alveolar damage (DAD) and ranges from acute lung injury (ALI) to ARDS. (See Pathophysiology.) These patients need intubation and mechanical ventilation for optimum respiratory support. Intubation should be considered early in the course of sepsis, even in the absence of frank hypoxia or respiratory distress. Delivering oxygen at an FiO2 of 1 directly into the trachea is far superior to delivery via a nonrebreather oxygen mask. Mechanical ventilation, with appropriate sedation and paralysis, also eliminates the work of breathing and decreases the metabolic demands of breathing, which accounts for about 30% of the total metabolic demand at baseline. Alveolar overdistention and repetitive opening and closing of alveoli during mechanical ventilation have been associated with an increased incidence of ARDS. Low tidal volume ventilatory strategies have been used to minimize this type of alveolar injury. The recommended tidal volume is 6 mL/kg with plateau pressures kept below 30 mL H2 O. Positive end-expiratory pressure (PEEP) is required to prevent alveolar collapse at end-expiration.[54]
Goals of Hemodynamic Support

Shock refers to a state of inability to maintain adequate tissue perfusion and oxygenation, ultimately causing cellular, and then organ system, dysfunction. Therefore, the goals of hemodynamic therapy are restoration and maintenance of adequate tissue perfusion to prevent multiple organ dysfunction. Careful clinical and invasive monitoring is required for assessment of global and regional perfusion. A MAP lower than 60 mm Hg or a decrease in MAP of 40 mm Hg from baseline defines shock at the bedside. Elevation of the blood lactate level on serial measurements of lactate can indicate inadequate tissue perfusion. Mixed venous oxyhemoglobin saturation serves as an indicator of the balance between oxygen delivery and consumption. A decrease in maximal venous oxygen (MVO2) can be secondary to decreased cardiac output; however, maldistribution of blood flow in patients experiencing septic shock may artificially elevate the MVO2 levels. An MVO2 of less than 65% generally indicates decreased tissue perfusion. Regional perfusion in patients with septic shock is evaluated by adequacy of organ function. The evaluation includes evidence of myocardial ischemia, renal dysfunction manifested by decreased urine output or increased creatinine, central nervous system (CNS) dysfunction indicated by a decreased level of consciousness, hepatic injury shown by increased levels of transaminases, splanchnic hypoperfusion manifested by stress ulceration, ileus, or malabsorption.
11/11/13
The hemodynamic support in septic shock is provided by restoring the adequate circulating blood volume, and, if needed, optimizing the perfusion pressure and cardiac function with vasoactive and inotropic support to improve tissue oxygenation.
Fluid Resuscitation
Hypovolemia is an important factor contributing to shock and tissue hypoxia; therefore, all patients with sepsis require supplemental fluids. The amount and rate of infusion are guided by an assessment of the patients volume and cardiovascular status. Monitor patients for signs of volume overload, such as dyspnea, elevated jugular venous pressure, crackles on auscultation, and pulmonary edema on the chest radiograph. Improvement in the patients mental status, heart rate, MAP, capillary refill, and urine output indicate adequate volume resuscitation. Large volumes of fluid are required as initial therapy in patients with septic shock. Administer fluid therapy with predetermined boluses (500 mL or 10 mL/kg) titrated to the clinical end points of heart rate, UOP, and blood pressure. Continue fluid resuscitation until the clinical end points are reached or the pulmonary capillary wedge pressure exceeds 18 mm Hg. Volume resuscitation can be achieved with either crystalloids or colloid solutions. The crystalloids are 0.9% sodium chloride and lactated Ringer solution; the colloids are albumin, dextrans, and pentastarch. Clinical trials have failed to show either type to be superior as the resuscitation fluid of choice in septic shock. However, 2-4 times more volume of crystalloids than colloids are required, and crystalloids take a longer time to achieve the same end points, whereas the colloid solutions are much more expensive. Data from several studies suggest that formation of pulmonary edema is no different with crystalloids compared to colloids when the filling pressures are maintained at a lower level. However, if the higher filling pressures are required for maintenance of optimal hemodynamics, crystalloids may increase extravascular fluid fluxes because of a decrease in plasma oncotic pressure. In some patients, clinically assessing the response to volume infusion may be difficult. By monitoring the response of the CVP or pulmonary artery occlusion pressure to fluid boluses, the physician can assess such patients. A sustained rise in filling pressure of more than 5 mm Hg after a volume is infused indicates that the compliance of the vascular system is decreasing as further fluid is being infused. Such patients are susceptible to volume overload, and further fluid should be administered with care.
Vasopressor Therapy
If the patient does not respond to several liters of volume infusion with isotonic crystalloid solution (usually 4 L or more) or evidence of volume overload is present, the depressed cardiovascular system can be stimulated by vasopressors, such as dopamine, norepinephrine, epinephrine, phenylephrine, and vasopressin. Vasopressor administration is required for persistent hypotension once adequate intravascular volume expansion has been achieved. Persistent hypotension is typically defined as systolic blood pressure lower than 90 mm Hg or MAP lower than < 65 mm Hg with altered tissue perfusion. The mean blood pressure required for adequate splanchnic and renal perfusion (MAP of 60 or 65 mm Hg) is based on clinical indices of organ function. The goal of vasopressor therapy is to reverse the pathologic vasodilation and altered blood flow distribution that occur as a result of the activation of adenosine triphosphate (ATP)-dependent potassium channels in vascular smooth muscle cells and the synthesis of the vasodilator nitric oxide (NO). In EGDT, vasopressors are recommended once a CVP of 8-12 mm Hg is achieved in the setting of persistent hypotension, and the goal is to titrate the dose to a MAP greater than 65 mm Hg. Vasopressors should be started early, regardless of fluid resuscitation, if frank shock is apparent (systolic blood pressure < 70 mm Hg or signs of profound tissue hypoperfusion). The recommended first-line agent for septic shock is either norepinephrine or dopamine.[38] Norepinephrine has predominant alpha-receptor agonist effects and results in potent peripheral arterial vasoconstriction without significantly increasing heart rate or cardiac output. The dose range for norepinephrine is 5-20 mcg/min, and it is not based on the weight of the patient. Norepinephrine, in theory, is the ideal vasopressor in the setting of warm shock, where peripheral vasodilation exists in association with normal or increased cardiac output. The typical patient with warm shock has warm extremities but with systemic hypotension and tachycardia, the result of decreased systemic vascular resistance.
11/11/13
If dopamine is used, treatment usually begins at a rate of 5-10 g/kg/min IV, and the infusion is adjusted according to the blood pressure and other hemodynamic parameters. Often, patients may require high doses of dopamine (as much as 20 g/kg/min). Presently, norepinephrine is the preferred drug because dopamine is known to cause unfavorable flow distribution. Norepinephrine has been shown to be clinically significantly safer and somewhat more effective in treating septic shock than dopamine.[55] In a systematic review of randomized controlled trials, norepinephrine was significantly superior to dopamine in improving both in-hospital and 28-day mortality in septic shock patients.[78] Second-line vasopressors for patients with persistent hypotension despite maximal doses of norepinephrine or dopamine are epinephrine, phenylephrine, and vasopressin. Epinephrine has been shown to clearly increase MAP in patients unresponsive to other vasopressors, mainly by its potent inotropic effects on the heart. Its adverse effects include tachyarrhythmias, myocardial and splanchnic ischemia, and increased systemic lactate concentrations. Phenylephrine is a pure alpha-receptor agonist, which results in potent vasoconstriction, but this is at the expense of depressed myocardial contractility and heart rate. This agent may be considered first-line in patients with extreme tachycardia; its pure alpha-receptor activity will not result in increased chronotropy.[56] Vasopressin has been proposed as a potentially attractive agent in septic shock because it is an endogenous peptide with potent vasoactive effects, and its circulating levels are depressed in septic shock. The characteristics of these agents are described in more detail below.
Norepinephrine
Norepinephrine is a potent alpha-adrenergic agonist with minimal beta-adrenergic agonist effects. It can increase blood pressure successfully in patients with sepsis who remain hypotensive after fluid resuscitation and dopamine. The dose of norepinephrine may vary from 0.2-1.5 g/kg/min, and large doses as high as 3.3 g/kg/min have been used because of the alpha-receptor down-regulation in sepsis. In patients with sepsis, indices of regional perfusion (eg, urine flow) and lactate concentration have improved following norepinephrine infusion. Two recent trials have shown that a significantly greater proportion of patients treated with norepinephrine were resuscitated successfully, as opposed to the patients treated with dopamine. Therefore, norepinephrine should be used early and should not be withheld as a last resort in patients with severe sepsis who are in shock. The concerns about compromising splanchnic tissue oxygenation have not been proven; the studies have confirmed no deleterious effects on splanchnic oxygen consumption and hepatic glucose production, provided adequate cardiac output is maintained.
Dopamine
A precursor of norepinephrine and epinephrine, dopamine has varying effects according to the doses infused. At lower doses, it has a much greater effect on beta-receptors; at higher doses, it has more alpha-receptor effects and increases peripheral vasoconstriction. Dosages range from 2 to 20 g/kg/min. A dosage lower than 5 g/kg/min results in vasodilation of renal, mesenteric, and coronary beds. At a dosage of 5-10 g/kg/min, beta1-adrenergic effects induce an increase in cardiac contractility and heart rate. At dosages of about 10 g/kg/min, alpha-adrenergic effects lead to arterial vasoconstriction and elevation in blood pressure. Dopamine is effective in optimizing MAP in patients with septic shock who remain hypotensive after volume resuscitation. The blood pressure increases primarily as a result of inotropic effect and, thus, will be useful in patients who have concomitant reduced cardiac function. It may be particularly useful in the setting of cold shock, where peripheral vasoconstriction exists (cold extremities) and cardiac output is too low to maintain tissue perfusion. The undesirable effects are tachycardia, increased pulmonary shunting, potential to decrease splanchnic perfusion, and increase in pulmonary arterial wedge pressure. Low-dose (renal-dose) dopamine has been studied; however, several well-designed clinical trials have failed to demonstrate any beneficial effects of such regimens on renal blood flow and function in the setting of circulatory shock of any etiology. Dopamine at a dosage of 2-3 g/kg/min is known to initiate diuresis by increasing renal
11/11/13
blood flow in healthy animals and volunteers. Multiple studies have not demonstrated a beneficial effect of prophylactic or therapeutic low-dose dopamine administration in patients with sepsis who are critically ill. Considering the real side effects of dopamine infusion, the use of renal-dose dopamine should be abandoned.
Epinephrine
Epinephrine can increase MAP by increasing cardiac index and stroke volume, as well as increasing systemic vascular resistance and heart rate. Epinephrine may increase oxygen delivery and oxygen consumption and decreases the splanchnic blood flow. Administration of this agent is associated with an increase in systemic and regional lactate concentrations. The use of epinephrine is recommended only in patients who are unresponsive to traditional agents. The undesirable effects are an increase in lactate concentration, a potential to produce myocardial ischemia, development of arrhythmias, and reduced splanchnic flow.
Phenylephrine
Phenylephrine is a selective alpha1-adrenergic receptor agonist that is used primarily in anesthesia to increase blood pressure. Although studies are limited, phenylephrine increased MAP in patients who were septic and hypotensive with increased oxygen consumption. However, concern remains about its potential to reduce cardiac output and lower heart rate in patients with sepsis. Phenylephrine may be a good choice when tachyarrhythmias limit therapy with other vasopressors.
Vasopressin
Vasopressin, also known as antidiuretic hormone (ADH), is synthesized in the hypothalamus and excreted by the posterior pituitary. In contrast to endogenous catecholamines (eg, norepinephrine), whose serum levels are universally high in septic shock, vasopressin stores are limited and its levels are low.[57] Furthermore, catecholamine effectiveness on vascular smooth muscle cells is inhibited by the activation of adenosine triphosphate (ATP)-dependent potassium channels and nitric oxide, as mentioned previously. Exogenous administration of vasopressin results in vasoconstriction via activation of V1 receptors on vascular smooth muscle cells that have the effect of inhibiting ATP-dependent potassium channels and, in theory, restoring the effectiveness of catecholamines. Vasopressin is also thought to inhibit NO synthase and therefore counteract the vasodilatory effect of NO. In addition, it increases renal perfusion by causing vasodilation of afferent renal arterioles, in contrast to the renal vasoconstriction caused by catecholamines. Several small clinic trials have shown that low-dose vasopressin increases MAP and decreases the requirement for catecholamines, such as norepinephrine, while maintaining mesenteric and renal perfusion.[57] However, a large, randomized trial (the VASST trial) failed to show reduced mortality in patients who received vasopressin in addition to norepinephrine as compared with those who received norepinephrine alone, even though vasopressin reduced the requirement for norepinephrine.[58] The major adverse effects attributed to vasopressin (myocardial ischemia, cardiac arrest, mesenteric and digital ischemia) were overall not significantly increased; however, patients with known coronary artery disease or congestive heart failure were excluded from the study. The incidence of digital ischemia was higher with vasopressin use. Also note that the mean time to receiving the drug in this trial was 12 hours; therefore, it does not address the use of vasopressin in early sepsis resuscitation.
Inotropic Therapy and Augmented Oxygen Delivery

Although myocardial performance is altered during sepsis and septic shock, cardiac output generally is maintained in patients with volume-resuscitated sepsis. Data from the 1980s and 1990s suggest a linear relationship between oxygen delivery and oxygen consumption (pathologic supply dependency), indicating that the oxygen delivery likely was insufficient to meet the metabolic needs of the patient. However, recent investigators have challenged the concept of pathologic supply dependency, suggesting that elevating cardiac index and oxygen delivery (hyperresuscitation) was not associated with improved patient outcome. Therefore, the role of inotropic therapy is uncertain, unless the patient has inadequate cardiac index,
11/11/13
MAP, mixed venous oxygen saturation, and UOP despite adequate volume resuscitation and vasopressor therapy. Patients with severe sepsis or septic shock have hypermetabolism, maldistribution of blood flow, and, possibly, suboptimal oxygen delivery; therefore, attempts at detecting and correcting tissue hypoxia must be made. Lactic acidosis is an indication of either global ischemia (inadequate oxygen delivery) or regional (organ-specific) ischemia. Calculation of pH in the gastric mucosa by gastric tonometry may detect tissue hypoxia in the splanchnic circulation; however, this technique has not been validated extensively and is not available widely. Dobutamine is an inotropic agent that stimulates beta-receptors and results in increased cardiac output. In theory, it can enhance tissue oxygen delivery in patients with septic shock who have received adequate fluid resuscitation and vasopressor support. In EGDT, dobutamine is recommended if there is evidence of tissue hypoperfusion (ScvO2 < 70 mm Hg) after CVP, MAP, and hematocrit goals have been met. In the Rivers et al study, fewer than 15% of patients in the EGDT arm received dobutamine. Although initial aggressive resuscitation to maximize oxygen delivery improves outcome (EGDT), manipulation of oxygen delivery to deliver supraphysiologic oxygen to the tissues with blood transfusion, fluid boluses, or use of inotropes once organ dysfunction has developed has not improved the outcome in patients who are critically ill. Hayes et al reported a higher mortality rate in patients with sepsis who were maintained on high levels of oxygen delivery.[59] In patients with septic shock, the inability to increase oxygen consumption and to decrease lactate levels most likely is a consequence of impaired oxygen extraction or inability to reverse anaerobic metabolism. Boosting oxygen delivery to supranormal levels does not reverse these pathophysiologic mechanisms after the development of organ injury. A trial of increasing oxygen delivery is recommended in patients who have evidence of tissue hypoxia. If augmentation of oxygen delivery is associated with reduction in serum lactate levels and improved target organ perfusion, these interventions may be continued. On the other hand, adequate clinical parameters, such as a MAP, normal cardiac index, and adequate UOP, should be maintained irrespective of the concerns about supply dependence.
Empiric Antimicrobial Therapy

Empirical antimicrobial therapy should be initiated early in patients experiencing septic shock (though it should be noted that they will have little effect on the clinical outcome for at least 24 hours). The following points should always be kept in mind: Early empirical antibiotic coverage is essential; the spectrum will be narrowed when culture results are available. Waiting until cultures are back is an invalid reason to withhold antibiotics. Only 30% of patients with presumed septic shock have positive blood cultures. About 25% of presumed septic shock patients remain culture negative from all sites, but mortality with culture positive counterparts is similar. The selection of appropriate agents is based on the patients underlying host defenses, the potential sources of infection, and the most likely culprit organisms. Antibiotics must be broad-spectrum agents and must cover grampositive, gram-negative, and anaerobic bacteria because the different classes of these organisms produce an identical clinical picture of distributive shock. If the patient is antibiotic experienced, strongly consider the use of an aminoglycoside rather than a quinolone or cephalosporin for gram-negative coverage. Knowing the antibiotic resistance patterns of both the hospital itself and its referral base (ie, nursing homes) is also important. Administer the antibiotics parenterally, in doses adequate to achieve bactericidal serum levels. Many studies find that the clinical improvement correlates with the achievement of serum bactericidal levels rather than the number of antibiotics administered. When choosing empirical antibiotics, consider the increasing prevalence of methicillin-resistant S aureus (MRSA) and include an agent such as vancomycin or linezolid. This is especially true in patients with a history of IV drug use, those with indwelling vascular catheters or devices, or those with recent hospitalizations or chronic care facility residents.
11/11/13
Antianaerobic coverage is indicated in patients with intra-abdominal or perineal infections. Antipseudomonal coverage (ceftazidime, cefepime, ticarcillin, piperacillin, imipenem, meropenem) should be considered in patients who are immunocompromised, especially those with neutropenia or burns. Certain organisms, chiefly Enterobacteriaceae (eg, E coli, K pneumoniae), contain a beta-lactamase enzyme that hydrolyzes the beta-lactam ring of penicillins and cephalosporins and thus inactivates these antibiotics (extendedspectrum beta-lactamase [ESBL]). This phenomenon has become an increasing concern in recent years as its prevalence has increased. Beta-lactam antibiotics that have remained effective against ESBL-producing organisms include cephalomycins (eg, cefotetan) and carbapenems (eg, imipenem, meropenem, ertapenem).[60] In immunocompetent patients, monotherapy with carbapenems (imipenem, meropenem), certain third- or fourthgeneration cephalosporins (cefotaxime, cefoperazone, ceftazidime), or extended-spectrum penicillins (ticarcillin, piperacillin), is usually adequate, without the need for a nephrotoxic aminoglycoside.[61] Patients who are immunocompromised typically require dual broad-spectrum antibiotics with overlapping coverage. Within these general guidelines, no single combination of antibiotics is clearly superior to others.
Recombinant Human Activated Protein C Therapy

Activated protein C (APC) is an endogenous protein that modulates inflammation and coagulation. Specifically, it inhibits tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6, the mediators thought to play a major role in initiating the inflammatory response seen in sepsis. In addition, it inhibits monocyte and neutrophil adhesion to endothelial cells, and it inhibits thrombin and fibrin production, and thus prevents microvascular thrombi. Sepsis reduces the level of protein C and inhibits conversion of protein C to APC. Administration of recombinant APC inhibits thrombosis and inflammation, promotes fibrinolysis, and modulates coagulation and inflammation. Recombinant human APC (drotrecogin alfa [Xigris]) was originally approved with an indication to reduce mortality in patients with severe sepsis. The efficacy and safety of drotrecogin alfa has been debated over the past decade. Drotrecogin alfa was withdrawn from the worldwide market October 25, 2011 after analysis of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS)-SHOCK clinical trial. Drotrecogin alfa failed to demonstrate a statistically significant reduction in 28-day all-cause mortality in patients with severe sepsis and septic shock. Trial results observed a 28-day all-cause mortality rate of 26.4% in patients treated with activated drotrecogin alfa compared with 24.2% in the placebo group of the study. An early publication by the PROWESS study group demonstrated that the administration of recombinant human APC (drotrecogin alpha, activated) resulted in lower mortality rates in the treatment group than in the placebo group.[62] Notably, this study excluded patients who were expected to die within 28 days (eg, those with end-stage cancer), those with end-stage renal disease or cirrhosis, and those with HIV disease and a CD4 count less than 50. Another study showed the absolute risk of death was reduced by 6.1% in the treatment group (24.7% vs 30.8%). There was a 13% benefit in the sickest patients (817 patients with an APACHE II score >25) and an 18% benefit for the sickest patients with pneumonia (317 patients with APACHE II score >25 and pneumonia).[7] The drawback to APC is an increased incidence of bleeding complications because it inhibits coagulation pathways. Overall bleeding complications were 3.5% in the APC group versus 2% in the placebo group. For this reason, APC is contraindicated in patients with a known hypercoagulable condition, recent major surgery or need for surgery, intracranial surgery or stroke within 3 months, any history of arteriovenous malformation, and cerebral aneurysm or mass. APC is an expensive therapy that is typically instituted once the patient is in the ICU under the care of a critical care physician. Nevertheless, it is good to keep this in mind in the ED and identify patients who may benefit, especially those who are in the most critical condition. Although study data await further confirmation, current recommendations are as follows: Drotrecogin alpha (activated protein C) is the only widely accepted drug specific to the therapy of sepsis. Drotrecogin alpha should be considered for patients with APACHE II scores greater than 25. The main adverse effect of drotrecogin alpha is bleeding. A Cochrane review finally lays to rest the effectiveness of APC in severe sepsis.[63] It harms without any reasonable expectation that it helps the patient with severe sepsis.
11/11/13
Corticosteroid Therapy
Corticosteroid insufficiency has been associated with severe illness.[64] Although theoretical and experimental animal evidence exists for the use of large doses of corticosteroids (eg, methylprednisolone, hydrocortisone, dexamethasone) in patients with severe sepsis and septic shock, no support exists in the medical literature for the routine use of such doses in these patients. A meta-analysis of prospective, randomized, controlled trials of glucocorticoid use did not report any benefit from corticosteroids and suggested that their use could be harmful.[65] Therefore, high-dose corticosteroids should not be used in patients with severe sepsis or septic shock. However, in a review of 3 meta-analyses, low-dose corticosteroids did not improve survival and were associated with side effects that included superinfections, bleeding, and hyperglycemia.[66] Some trials demonstrated positive results of stress-dose administration of corticosteroids in patients with severe and refractory shock.[67] Although further confirmatory studies are awaited, stress-dose steroid coverage should be provided to patients who have the possibility of adrenal suppression. Other studies show that lower-dose steroids may be beneficial for patients with relative adrenal insufficiency. Annane et al studied 299 patients with septic shock, all of whom were intubated, were persistently hypotensive despite crystalloid resuscitation and vasopressor administration, and had evidence of end-organ failure. All patients were randomized to low-dose steroids (hydrocortisone 50 mg q6h and fludrocortisone 50 g daily) versus placebo.[68] Patients were administered a cortisol stimulation test (Cort stim test), which involves measuring cortisol levels before and 30 minutes after administration of cosyntropin (adrenocorticotropic hormone [ACTH]) 0.25 mg IV. A patient whose cortisol level increased by less than 10 g/dL was considered a nonresponder and thus adrenally insufficient. Of the 299 patients with septic shock, 77% were nonresponders. For nonresponders, there was an absolute benefit in mortality of 10% (53% vs 43%) for those who received steroids. Although performing the Cort stim test in the ED may not be practical, given time and resource constraints, it is worth noting that greater than 75% of patients with vasopressor-refractory hypotension were adrenally insufficient. This suggested that the majority of patients with vasopressor-refractory shock would benefit from steroid administration regardless of the results of the Cort stim test. A common choice is hydrocortisone 100 mg IV; a good alternative is dexamethasone 10 mg IV. In 2009, Annane et al published a systematic review of corticosteroid use for severe sepsis and septic shock. Pooled results found that the subgroup of studies using prolonged, low-dose corticosteroid therapy demonstrated a beneficial effect on short-term mortality. No clear benefit was shown with use of high-dose corticosteroids for severe sepsis or septic shock.[69] In CORTICUS, the most recent large randomized trial of hydrocortisone versus placebo in patients with septic shock, no difference in mortality rate was noted, even though the patients who received steroids had a more rapid resolution of shock as measured by a shorter duration of vasopressor therapy.[70] However, the incidence of superinfection and recurrent sepsis in those who received steroids was higher. Additionally, the result of the Cort stim test had no bearing on outcome, bringing into question the value of this test in determining who will benefit from steroid treatment. However, the CORTICUS study enrolled all patients with septic shock, regardless of vasopressor response. Therefore, patients in the CORTICUS study had a lower mortality rate than those in the Annane study. The most recent Surviving Sepsis Campaign guidelines from 2008 emphasize that steroids should be administered only in patients with septic shock whose hypotension is poorly responsive to fluid resuscitation and vasopressor therapy.[38] The following key points summarize use of corticosteroids in septic shock: Older, traditional trials of corticosteroids in sepsis were unsuccessful likely because of high doses and poor patient selection. Recent trials with low-dose (physiologic) dosages in select patient populations (vasopressor dependent and possibly relative adrenal insufficiency) have resulted in improved outcome. Corticosteroids should be initiated for patients with vasopressor-dependent septic shock. A Cort stim test may be performed to identify patients with relative adrenal insufficiency, defined recently as
11/11/13
failure to increase levels more than 9 g/dL
Tight Glycemic Control

Tight glycemic control has recently become a prominent emphasis in the care of critically ill patients, and recent data has been extrapolated to potentially apply to septic populations. It has been shown to improve mortality both in postoperative surgical patients, including (and particularly) those with sepsis, and in medical ICU patients. A 2001 Belgian study of surgical intensive care unit (SICU) patients that remained in the unit for more than 5 days showed a 10% mortality benefit in those with tighter glycemic control. The glucose levels for these patients were maintained from 80-110 mg per dL through the use of intensive insulin therapy. The benefit of glycemic control appears to result more from aggressive avoidance of the detrimental effects of hyperglycemia rather than the potential therapeutic effect of insulin. On the basis of the current evidence, the Surviving Sepsis Campaign recommends maintaining a glucose level of less than 150 mg/dL, though the logic behind choosing this level is unclear.[37, 71] Van den Berghe documented benefit only once glucose levels were maintained below 110 mg/dl, with increased mortality when blood glucose levels were allowed to reach 130-150 mg/dL.[72] This same group recently finished a large prospective study in medical patients documenting similar benefits in these patients.[73] Tight glycemic control is not without risks. In elderly persons (>75 y) and in those patients with liver failure, excessive hypoglycemic reactions limits its use. Furthermore, to be effective, glycemic control needs to be protocol driven and run by the bedside caregiver, usually the bedside nurse.
Experimental and Other Medical Therapies

Experimental and other medical therapies include nonadrenergic vasopressors and inotropes. The clinical utility of several of these agents remains unproven despite several studies indicating their beneficial effect on hemodynamic instability. Dopexamine has beta 2-adrenergic and dopaminergic effects without any alpha-adrenergic activity and is known to increase splanchnic perfusion. A few small studies have shown that dopexamine increases cardiac index and heart rate and decreases systemic vascular resistance in a dose-dependent manner. The hepatic blood flow and gastric intramucosal pH improve, but results are not reproducible consistently. Dopexamine appears to be promising for patients with sepsis and septic shock, but superiority over the other drugs has not been demonstrated. It continues to be an experimental medication in the United States. Inamrinone (formerly amrinone) and milrinone are inotropic agents with vasodilating properties, and each has a long half-life. The mechanism of action occurs via phosphodiesterase inhibition. These medications are beneficial in cardiac pump failure, but their benefit in patients experiencing septic shock is not well established. Furthermore, these agents have a propensity to worsen hypotension in patients with septic shock. NO is a potent endogenous vasodilator, synthesized from endogenous L-arginine by the enzyme NO synthase. Excessive NO production induces vasodilation and hypotension in patients with sepsis. Inhibitors of NO synthase (N -monomethyl-l-arginine, L-NMMA) in sepsis augment MAP, decreased cardiac output, and increased systemic vascular resistance. Inordinate mortality was the cause of early termination of a randomized trial of NO synthase inhibition with L-NMMA. The clinical benefit of this therapeutic approach in patients with sepsis remains unproven. Despite promising results in animal studies, the use of ibuprofen has not been proven of any benefit in patients with septic shock. The insight that endotoxin, a lipid-polysaccharide compound found in the cell wall of gram-negative bacteria, plays a key role in initiating the humoral cascade observed in septic shock led to the hypothesis that neutralizing the circulating endotoxin with IV administration of an antiendotoxin antibody might be beneficial. Several products have been developed and investigated by carefully conducted human trials. To date, no proven benefit to these agents has been observed. Other methods of extracorporeal elimination of endotoxin, polyclonal antiendotoxin antibodies, or monoclonal antiendotoxin antibodies showed neither improvement in short-term survival nor amelioration of sepsis in humans with septic shock. Trials with some of these compounds are ongoing, and, despite a tendency towards benefit, efficacy data are lacking.
11/11/13
Serum levels of TNF and IL-1 are elevated in patients with septic shock. Both produce hemodynamic effects that duplicate those found in sepsis. Many studies indicate that both the mediators play key roles in sepsis and septic shock, and some think that TNF may be the central mediator in sepsis. Like antiendotoxin antibodies, antibodies to TNF or IL-1 were hypothesized to be useful in patients with septic shock. However, anti-TNF or antiIL-1 antibodies have yet to be shown to improve the outcome in sepsis or septic shock. In 1997, Zeni conducted a meta-analysis and selected 21 trials representing 6429 patients.[74] A small but insignificant beneficial effect was demonstrated. Several other experimental interventions and therapies have undergone clinical trials for sepsis. Although some may have shown benefit, no convincing evidence suggests that these therapies are efficacious. Numerous such interventions or therapies exist, including IV immunoglobulins, interferon gamma, antithrombin III infusion, naloxone, pentoxifylline, growth hormone, granulocyte colony-stimulating factor (G-CSF), and hemofiltration or extracorporeal removal of endotoxins. None has been efficacious in properly designed controlled clinical trials. In a small preliminary study, Cruz et al compared the addition of polymyxin B hemoperfusion to conventional therapy for severe sepsis or septic shock caused by intra-abdominal infection in 64 patients.[75] Polymyxin B is an antibiotic with a high affinity to endotoxin, a principal component of the outer membrane of gram-negative organisms. Thus, polymyxin B can in theory reduce the endotoxin-induced inflammatory response in gramnegative sepsis. In the conventional therapy plus polymyxin B hemoperfusion group, a significant increase in MAP and a significant decrease in vasopressor requirement at 72 hours were observed in comparison with conventional therapy alone. The 28-day mortality rate was 32% in the polymyxin B group and 53% in the conventional therapy group. Polymyxin B hemoperfusion significantly improved hemodynamics and organ dysfunction and reduced 28-day mortality rate in severe sepsis or septic shock when added to conventional therapy.[75] Polymyxin B hemoperfusion is an example of a novel therapy that, like administration of recombinant APC, targets the pathophysiology of septic shock and that may become more widespread in the future.
Surgical Treatment
Patients with infected foci should be taken to surgery after initial resuscitation and administration of antibiotics for definitive surgical treatment. Little is gained by spending hours stabilizing the patient while an infected focus persists. A soft-tissue abscess should be drained promptly in the setting of sepsis because the patients condition will not improve until the inciting bacterial load is removed. A superficial abscess can be drained in the ED; however, any deep abscess or suspected necrotizing fasciitis should be treated in the operating room (OR) for drainage. A thorough search for abscesses should be performed in cases of sepsis of unclear etiology, with particular attention paid to the rectal and perianal area.
Management of Acute Respiratory Distress Syndrome

ALI or ARDS is a major complication of sepsis and septic shock. The incidence of ARDS in septic shock is anywhere from 20-40%, occurring more frequently when a pulmonary source of infection exists. ALI and ARDS can be associated with clinical disorders causing direct lung injury, such as gastric acid aspiration, thoracic trauma, pneumonia, and near drowning, or indirect lung injury, including severe sepsis, acute pancreatitis, drug overdose, reperfusion injury, and severe nonthoracic trauma. Sepsis-associated ARDS carries an abysmal prognosis and has the highest mortality rates. Management of ARDS is primarily supportive; the pharmacologic and other innovative therapies have not proven to be very beneficial. General supportive management includes adequate treatment of underlying sepsis with appropriate antibiotics and surgical management if indicated. Appropriate fluid management to lower the intravascular volume without affecting the cardiac output and organ perfusion may be beneficial. The fluid manipulation often requires invasive hemodynamic monitoring. The goals of mechanical ventilation include improvement in gas exchange, reduction in work of breathing, avoiding oxygen toxicity, minimizing high airway pressures, avoiding further lung damage, and allowing the injured lung to heal.
11/11/13
A lung protective and pressure-limited ventilatory strategy has been shown to improve survival rates and lower rates of barotrauma. Current recommendations are to use a tidal volume of 5-8 mL/kg, to employ a longer inspiratory time, and not to exceed a transpulmonary pressure of 30 cm H2 0. Permissive hypercapnia may ensue but is tolerated, which may occur with the use of lesser tidal volumes. The use of PEEP may reduce or prevent ventilator-induced lung injury. Sufficient PEEP to recruit atelectatic alveolar units and to increase lung volumes so that respiration happens on the most compliant part of the pressure volume curve is recommended. In clinical practice, this can be achieved by measuring plateau pressures and calculation of lung compliance at different levels of PEEP. The use of prone positioning and NO may prove to be beneficial in the short term; these interventions have not been shown to improve survival rates. High-dose corticosteroids, though not useful in early management of ARDS, have been reported to improve survival in patients who have unresolving ARDS. In a study by Meduri et al, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement and reduced mortality.[76] For the treatment group versus the placebo group, the mortality rate for the treatment group was 0 (0%) of 16 versus 5 (62%) of 8 for the placebo group in the ICU. The rate of infections, including pneumonia, was similar in both groups.
Prevention of Septic Shock

Patients with impaired host defense mechanisms are at greatly increased risk for sepsis. The main causes of impaired host defense are as follows: Chemotherapeutic drugs Malignancy Severe trauma Burns Diabetes mellitus Renal or hepatitic failure Advanced age Ventilatory support and invasive catheters further worsen the risk of infection. Avoiding the use of catheters or removing them as soon as possible may prevent severe sepsis. Prophylactic antibiotics in the perioperative phase, particularly after GI surgery, may be beneficial. The use of topical antibiotics around invasive catheters and as part of dressing for patients with burns is helpful. Maintenance of adequate nutrition, administration of pneumococcal vaccine in patients who have had a splenectomy, and early enteral feeding are other preventive measures. Prevention of sepsis with topical or systemic antibiotics is suggested for high-risk patients. Use of nonabsorbable antibiotics in the stomach to prevent translocation of bacteria and occurrence of bacteremia is a controversial issue. Numerous trials have been performed over the years using either the topical antibiotics alone or a combination of topical and systemic antibiotics. A systemic review by Nathens presented no benefit in medical patients but showed a reduced mortality rate in surgical trauma patients.[77] The beneficial effect was from a combination of systemic and topical antibiotics, predominantly by reducing lower respiratory tract infections in treated patients. Progression from infection with SIRS (ie, sepsis) to severe sepsis with organ dysfunction to septic shock with refractory hypotension can often be reversed with early identification, aggressive crystalloid resuscitation, broadspectrum antibiotic administration, and removal of the infectious source if possible.
Consultations
Consultation with a critical care physician or internist with expertise is appropriate. Consultation with an appropriate surgeon should be sought if an infectious source amenable to surgery is suspected or confirmed (especially an abdominal source). Certain conditions will not respond to standard treatment for septic shock until the source of infection is surgically removed. Some of these common foci of infection include intra-abdominal sepsis (perforation, abscesses), empyema, mediastinitis, cholangitis, pancreatic abscesses, pyelonephritis or renal abscess from ureteric obstruction, infective endocarditis, septic arthritis, infected prosthetic devices, deep cutaneous or perirectal abscess, and
11/11/13
necrotizing fasciitis.
Long-Term Monitoring
Patients with sepsis, severe sepsis, and septic shock require admission to the hospital. Patients with sepsis who respond to EGDT in the ED and show no evidence of end-organ hypoperfusion can be admitted to a general hospital unit, optimally to one with close nursing observation and monitoring. Such patients do not require invasive hemodynamic monitoring and do not usually require admission to an ICU. Patients who do not respond to initial ED treatment (ie, recurrent hypotension despite adequate fluid challenges) or those who are in septic shock require admission to an ICU for continuous monitoring and continued goaldirected therapy. If an appropriate ICU bed or physician is not available, the patient should be transferred with advanced life support monitoring to another hospital with the available resources.
Contributor Information and Disclosures

Coauthor(s) Steven Mink, MD Head, Section of Pulmonary Medicine, Department of Internal Medicine, St Boniface Hospital; Professor of Medicine, University of Manitoba, Canada Steven Mink, MD is a member of the following medical societies: Alpha Omega Alpha Disclosure: Nothing to disclose. Sat Sharma, MD, FRCPC Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association Disclosure: Nothing to disclose. Chief Editor Michael R Pinsky, MD, CM, FCCP, FCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine Michael R Pinsky, MD, CM, FCCP, FCCM is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Association of University Anesthetists, European Society of Intensive Care Medicine, Shock Society, and Society of Critical Care Medicine Disclosure: LiDCO Ltd Honoraria Consulting; iNTELOMED Intellectual property rights Board membership; Edwards Lifesciences Honoraria Consulting; Applied Physiology, Ltd Honoraria Consulting; Cheetah Medical Consulting fee Consulting Additional Contributors Fatima Al Faresi, MD Dermatologist, Tawam Hospital, Al Ain, UAE Disclosure: Nothing to disclose. Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and
11/11/13
Society for Academic Emergency Medicine Disclosure: Nothing to disclose. John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America Disclosure: Nothing to disclose. Ismail Cinel, MD, PhD Visiting Associate Professor, Division of Critical Care Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey Disclosure: Nothing to disclose. Clara-Dina Cokonis, MD Staff Physician, Department of Medicine, Division of Dermatology, Cooper Hospital University Medical Center Disclosure: Nothing to disclose. R Phillip Dellinger, MD Professor of Medicine, Program Director, Critical Care Medicine Fellowship Program, Robert Wood Johnson School of Medicine, University of Medicine and Dentistry of New Jersey; Head, Division of Critical Care Medicine, Medical Director, Medical/Surgical/Cardiovascular Surgical Intensive Care Unit, Cooper University Hospital Disclosure: Wyeth Consulting fee Consulting; BRAHMS Grant/research funds Other Clinical Trial; Artisan Grant/research funds Other Clinical Trial; Agenix Grant/research funds Other Clinical Trial Daniel J Dire, MD, FACEP, FAAP, FAAEM Clinical Professor, Department of Emergency Medicine, University of Texas Medical School at Houston; Clinical Professor, Department of Pediatrics, University of Texas Health Sciences Center San Antonio Daniel J Dire, MD, FACEP, FAAP, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American Academy of Pediatrics, American College of Emergency Physicians, and Association of Military Surgeons of the US Disclosure: Nothing to disclose. Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology Disclosure: Nothing to disclose. Michael R Filbin, MD Clinical Instructor, Department of Emergency Medicine, Massachusetts General Hospital Michael R Filbin, MD is a member of the following medical societies: American College of Emergency Physicians, Massachusetts Medical Society, and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Franklin Flowers, MD Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology Disclosure: Nothing to disclose. Cory Franklin, MD Professor, Department of Medicine, Rosalind Franklin University of Medicine and Science; Director, Division of Critical Care Medicine, Cook County Hospital Cory Franklin, MD is a member of the following medical societies: New York Academy of Sciences and Society of Critical Care Medicine
11/11/13
Disclosure: Nothing to disclose. Theodore J Gaeta, DO, MPH, FACEP Clinical Associate Professor, Department of Emergency Medicine, Weill Cornell Medical College; Vice Chairman and Program Director of Emergency Medicine Residency Program, Department of Emergency Medicine, New York Methodist Hospital; Academic Chair, Adjunct Professor, Department of Emergency Medicine, St George's University School of Medicine Theodore J Gaeta, DO, MPH, FACEP is a member of the following medical societies: Alliance for Clinical Education, American College of Emergency Physicians, Clerkship Directors in Emergency Medicine, Council of Emergency Medicine Residency Directors, New York Academy of Medicine, and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Hassan I Galadari, MD Assistant Professor of Dermatology, Faculty of Medicine and Health Sciences, United Arab Emirates University Hassan I Galadari, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Medical Student Association/Foundation, and American Society for Dermatologic Surgery Disclosure: Nothing to disclose. Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology Disclosure: Nothing to disclose. Steven M Manders, MD Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania; Associate Professor, Department of Internal Medicine, Division of Dermatology, University of Medicine and Dentistry of New Jersey Disclosure: Nothing to disclose. Mark L Plaster, MD, JD Executive Editor, Emergency Physicians Monthly Mark L Plaster, MD, JD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians Disclosure: M L Plaster Publishing Co LLC Ownership interest Management position Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Salary Employment Vicken Y Totten, MD, MS, FACEP, FAAFP Assistant Professor, Case Western Reserve University School of Medicine; Director of Research, Department of Emergency Medicine, University Hospitals, Case Medical Center Vicken Y Totten, MD, MS, FACEP, FAAFP is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association Disclosure: Nothing to disclose. Eric L Weiss, MD, DTM&H Medical Director, Office of Service Continuity and Disaster Planning, Fellowship Director, Stanford University Medical Center Disaster Medicine Fellowship, Chairman, SUMC and LPCH
11/11/13
Bioterrorism and Emergency Preparedness Task Force, Clinical Associate Progressor, Department of Surgery (Emergency Medicine), Stanford University Medical Center Eric L Weiss, MD, DTM&H is a member of the following medical societies: American College of Emergency Physicians, American College of Occupational and Environmental Medicine, American Medical Association, American Society of Tropical Medicine and Hygiene, Physicians for Social Responsibility, Southeastern Surgical Congress, Southern Association for Oncology, Southern Clinical Neurological Society, and Wilderness Medical Society Disclosure: Nothing to disclose.
References
1. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. Jun 1992;101(6):1644-55. [Medline]. 2. [Best Evidence] American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. Jun 1992;20(6):864-74. [Medline]. 3. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. Apr 2003;31(4):1250-6. [Medline]. 4. Brun-Buisson C, Doyon F, Carlet J, et al. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA. Sep 27 1995;274(12):968-74. [Medline]. 5. Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, et al. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA. Jul 16 1997;278(3):234-40. [Medline]. 6. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. Jun 2006;34(6):1589-96. [Medline]. 7. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. Mar 8 2001;344(10):699-709. [Medline]. 8. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. Mar 1994;149(3 Pt 1):818-24. [Medline]. 9. Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med. Jan 21 1999;340(3):20714. [Medline]. 10. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. Jan 9 2003;348(2):138-50. [Medline]. 11. Nguyen HB, Rivers EP, Abrahamian FM, Moran GJ, Abraham E, Trzeciak S, et al. Severe sepsis and septic shock: review of the literature and emergency department management guidelines. Ann Emerg Med. Jul 2006;48(1):28-54. [Medline]. 12. Lorente JA, Landn L, De Pablo R, Renes E, Rodrguez-Daz R, Liste D. Effects of blood transfusion on oxygen transport variables in severe sepsis. Crit Care Med. Sep 1993;21(9):1312-8. [Medline]. 13. Schuetz P, Jones AE, Aird WC, Shapiro NI. Endothelial cell activation in emergency department patients with sepsis-related and non-sepsis-related hypotension. Shock . Aug 2011;36(2):104-8. [Medline]. [Full Text]. 14. Levi M, ten Cate H, van der Poll T, van Deventer SJ. Pathogenesis of disseminated intravascular coagulation in sepsis. JAMA. Aug 25 1993;270(8):975-9. [Medline].
11/11/13
15. Mammen EF. Antithrombin III and sepsis. Intensive Care Med. Jul 1998;24(7):649-50. [Medline]. 16. Trzeciak S, Rivers EP. Clinical manifestations of disordered microcirculatory perfusion in severe sepsis. Crit Care. 2005;9 Suppl 4:S20-6. [Medline]. 17. Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. Aug 23 2001;345(8):58895. [Medline]. 18. Cetinbas F, Yelken B, Gulbas Z. Role of glutamine administration on cellular immunity after total parenteral nutrition enriched with glutamine in patients with systemic inflammatory response syndrome. J Crit Care. Dec 2010;25(4):661.e1-6. [Medline]. 19. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. Jul 2001;29(7):1303-10. [Medline]. 20. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. Apr 17 2003;348(16):1546-54. [Medline]. 21. Wang HE, Shapiro NI, Angus DC, Yealy DM. National estimates of severe sepsis in United States emergency departments. Crit Care Med. Aug 2007;35(8):1928-36. [Medline]. 22. Baughman RP, Gunther KL, Rashkin MC, Keeton DA, Pattishall EN. Changes in the inflammatory response of the lung during acute respiratory distress syndrome: prognostic indicators. Am J Respir Crit Care Med. Jul 1996;154(1):76-81. [Medline]. 23. Kieft H, Hoepelman AI, Zhou W, Rozenberg-Arska M, Struyvenberg A, Verhoef J. The sepsis syndrome in a Dutch university hospital. Clinical observations. Arch Intern Med. Oct 11 1993;153(19):2241-7. 24. Shapiro N, Howell MD, Bates DW, Angus DC, Ngo L, Talmor D. The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection. Ann Emerg Med. Nov 2006;48(5):583-90, 590.e1. [Medline]. 25. Mayr FB, Yende S, Linde-Zwirble WT, Peck-Palmer OM, Barnato AE, Weissfeld LA, et al. Infection Rate and Acute Organ Dysfunction Risk as Explanations for Racial Differences in Severe Sepsis. JAMA. Jun 2010;303(24):2495-2503. 26. Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA. Jan 11 1995;273(2):11723. [Medline]. 27. Brun-Buisson C. The epidemiology of the systemic inflammatory response. Intensive Care Med. 2000;26 Suppl 1:S64-74. [Medline]. 28. Jung B, Nougaret S, Chanques G, et al. The Absence of Adrenal Gland Enlargement during Septic Shock Predicts Mortality: A Computed Tomography Study of 239 Patients. Anesthesiology. Aug 2011;115(2):334-343. [Medline]. 29. Janda S, Young A, Fitzgerald JM, Etminan M, Swiston J. The effect of statins on mortality from severe infections and sepsis: a systematic review and meta-analysis. J Crit Care. Dec 2010;25(4):656.e7-22. [Medline]. 30. Vincent JL, Gerlach H. Fluid resuscitation in severe sepsis and septic shock: an evidence-based review. Crit Care Med. Nov 2004;32(11 Suppl):S451-4. [Medline]. 31. Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. Oct 27 2010;304(16):1787-94. [Medline]. 32. Levy B, Gibot S, Franck P, Cravoisy A, Bollaert PE. Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study. Lancet. Mar 5-11 2005;365(9462):871-5. [Medline]. 33. Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. May 2005;45(5):524-8. [Medline].
11/11/13
34. Nguyen HB, Rivers EP, Knoblich BP, Jacobsen G, Muzzin A, Ressler JA, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. Aug 2004;32(8):1637-42. [Medline]. 35. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. Feb 24 2010;303(8):739-46. [Medline]. [Full Text]. 36. Griffee MJ, Merkel MJ, Wei KS. The role of echocardiography in hemodynamic assessment of septic shock. Crit Care Clin. Apr 2010;26(2):365-82, table of contents. [Medline]. 37. Dellinger RP, Carlet JM, Masur H. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. Mar 2004;32(3):858-73. [Medline]. 38. [Guideline] Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. Jan 2008;36(1):296-327. [Medline]. 39. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. Jul 2008;134(1):172-8. [Medline]. 40. Nagdev AD, Merchant RC, Tirado-Gonzalez A, Sisson CA, Murphy MC. Emergency department bedside ultrasonographic measurement of the caval index for noninvasive determination of low central venous pressure. Ann Emerg Med. Mar 2010;55(3):290-5. [Medline]. 41. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. May 27 2004;350(22):2247-56. [Medline]. 42. Rivers E, Nguyen B, Havstad S. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. Nov 8 2001;345(19):1368-77. [Medline]. 43. Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, et al. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med. Oct 19 1995;333(16):1025-32. [Medline]. 44. Rady MY, Rivers EP, Nowak RM. Resuscitation of the critically ill in the ED: responses of blood pressure, heart rate, shock index, central venous oxygen saturation, and lactate. Am J Emerg Med. Mar 1996;14(2):218-25. [Medline]. 45. Crowe CA, Mistry CD, Rzechula K, Kulstad CE. Evaluation of a modified early goal-directed therapy protocol. Am J Emerg Med. Jul 2010;28(6):689-93. [Medline]. 46. Kortgen A, Niederprm P, Bauer M. Implementation of an evidence-based "standard operating procedure" and outcome in septic shock. Crit Care Med. Apr 2006;34(4):943-9. [Medline]. 47. Shapiro NI, Howell MD, Talmor D, Lahey D, Ngo L, Buras J, et al. Implementation and outcomes of the Multiple Urgent Sepsis Therapies (MUST) protocol. Crit Care Med. Apr 2006;34(4):1025-32. [Medline]. 48. Nguyen HB, Corbett SW, Steele R, Banta J, Clark RT, Hayes SR, et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med. Apr 2007;35(4):1105-12. [Medline]. 49. Micek ST, Roubinian N, Heuring T, Bode M, Williams J, Harrison C, et al. Before-after study of a standardized hospital order set for the management of septic shock. Crit Care Med. Nov 2006;34(11):2707-13. [Medline]. 50. Trzeciak S, Dellinger RP, Abate NL, Cowan RM, Stauss M, Kilgannon JH, et al. Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. Chest. Feb 2006;129(2):225-32. [Medline]. 51. Jones AE, Focht A, Horton JM, Kline JA. Prospective external validation of the clinical effectiveness of an emergency department-based early goal-directed therapy protocol for severe sepsis and septic shock. Chest. Aug 2007;132(2):425-32. [Medline]. [Full Text]. 52. Ferrer R, Artigas A, Levy MM, Blanco J, Gonzlez-Daz G, Garnacho-Montero J, et al. Improvement in
11/11/13
process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. May 21 2008;299(19):2294-303. [Medline]. 53. [Guideline] Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. Feb 2010;38(2):367-74. [Medline]. 54. Sevransky JE, Levy MM, Marini JJ. Mechanical ventilation in sepsis-induced acute lung injury/acute respiratory distress syndrome: an evidence-based review. Crit Care Med. Nov 2004;32(11 Suppl):S548-53. [Medline]. 55. Vasu TS, Cavallazzi R, Hirani A, et al. Norephinephrine or Dopamine for Septic Shock: A Systematic Review of Randomized Clinical Trials. J Intensive Care Med. Mar 24 2011;[Medline]. 56. Beale RJ, Hollenberg SM, Vincent JL, Parrillo JE. Vasopressor and inotropic support in septic shock: an evidence-based review. Crit Care Med. Nov 2004;32(11 Suppl):S455-65. [Medline]. 57. Russell JA. Vasopressin in septic shock. Crit Care Med. Sep 2007;35(9 Suppl):S609-15. [Medline]. 58. Russell JA, Walley KR, Singer J, Gordon AC, Hbert PC, Cooper DJ, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. Feb 28 2008;358(9):877-87. [Medline]. 59. Hayes MA, Timmins AC, Yau EH, et al. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med. Jun 16 1994;330(24):1717-22. [Medline]. 60. Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis . Mar 2008;8(3):159-66. [Medline]. 61. Bochud PY, Bonten M, Marchetti O, Calandra T. Antimicrobial therapy for patients with severe sepsis and septic shock: an evidence-based review. Crit Care Med. Nov 2004;32(11 Suppl):S495-512. [Medline]. 62. McCoy C, Matthews SJ. Drotrecogin alfa (recombinant human activated protein C) for the treatment of severe sepsis. Clin Ther. Feb 2003;25(2):396-421. [Medline]. 63. Marti-Carvajal AJ, Sola I, Lathyris D, Cardona AF. Human recombinant activated protein C for severe sepsis. Cochrane Database Syst Rev. Apr 13 2011;4:CD004388. [Medline]. 64. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. Feb 20 2003;348(8):727-34. [Medline]. 65. Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, et al. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med. Aug 1995;23(8):1430-9. [Medline]. 66. Kalil AC, Sun J. Low-dose steroids for septic shock and severe sepsis: the use of Bayesian statistics to resolve clinical trial controversies. Intensive Care Med. Mar 2011;37(3):420-9. [Medline]. 67. Briegel J, Forst H, Haller M. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med. Apr 1999;27(4):723-32. [Medline]. 68. Annane D, Sbille V, Charpentier C, Bollaert PE, Franois B, Korach JM, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. Aug 21 2002;288(7):862-71. [Medline]. 69. [Best Evidence] Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R, et al. Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA. Jun 10 2009;301(22):2362-75. [Medline]. 70. Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. Jan 10 2008;358(2):111-24. [Medline]. 71. Dellinger RP, Carlet JM, Masur H. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. Apr 2004;30(4):536-55. 72. Van den Berghe G, Wouters PJ, Bouillon R. Outcome benefit of intensive insulin therapy in the critically
11/11/13
ill: Insulin dose versus glycemic control. Crit Care Med. Feb 2003;31(2):359-66. [Medline]. 73. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. Feb 2 2006;354(5):449-61. 74. Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med. Jul 1997;25(7):1095-100. [Medline]. 75. Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. Jun 17 2009;301(23):2445-52. [Medline]. 76. Meduri GU, Headley AS, Golden E, et al. Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA. Jul 8 1998;280(2):159-65. [Medline]. 77. Nathens AB, Rotstein OD. Selective decontamination of the digestive tract in acute severe pancreatitis-an indication whose time has come. Clin Infect Dis . Oct 1997;25(4):817-8. [Medline]. 78. Vasu TS, Cavallazzi R, Hirani A, Kaplan G, Leiby B, Marik PE. Norepinephrine or dopamine for septic shock: systematic review of randomized clinical trials. J Intensive Care Med. May-Jun 2012;27(3):172-8. [Medline]. Medscape Reference 2011 WebMD, LLC
emedicine.medscape.com/article/168402-treatment
22/22

Septic Shock Treatment

Transféré par

Informations du document

Description originale:

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Septic Shock Treatment

Transféré par

Droits d'auteur :

Formats disponibles

11/11/13

Septic Shock Treatment & Management

Today News Reference Education Log In Register

Septic Shock Treatment & Management

General Treatment Guidelines

Septic Shock Treatment & Management

Septic Shock Treatment & Management

hypomagnesemia, and hypophosphatemia should be measured and corrected if deficient.

Correction of anemia and coagulopathy

Management of renal dysfunction

Principles of Early Goal-Directed Therapy

Septic Shock Treatment & Management

Septic Shock Treatment & Management

Intubation and Mechanical Ventilation

Goals of Hemodynamic Support

Septic Shock Treatment & Management

Septic Shock Treatment & Management

Septic Shock Treatment & Management

Inotropic Therapy and Augmented Oxygen Delivery

Septic Shock Treatment & Management

Empiric Antimicrobial Therapy

Septic Shock Treatment & Management

Recombinant Human Activated Protein C Therapy

Septic Shock Treatment & Management

Septic Shock Treatment & Management

failure to increase levels more than 9 g/dL

Tight Glycemic Control

Experimental and Other Medical Therapies

Septic Shock Treatment & Management

Management of Acute Respiratory Distress Syndrome

Septic Shock Treatment & Management

Prevention of Septic Shock

Septic Shock Treatment & Management

Contributor Information and Disclosures

Septic Shock Treatment & Management

Septic Shock Treatment & Management

Septic Shock Treatment & Management

Septic Shock Treatment & Management

Septic Shock Treatment & Management

Septic Shock Treatment & Management

Septic Shock Treatment & Management

Vous aimerez peut-être aussi