Distributive shock results from excessive vasodilation and the impaired distribution of blood flow. Septic shock is the most common form of distributive shock and is characterized by considerable mortality. In the United States, this is the leading cause of noncardiac death in intensive care units (ICUs). (See Pathophysiology, Etiology, Epidemiology, and Prognosis.)
Other causes of distributive shock include systemic inflammatory response syndrome (SIRS) due to noninfectious inflammatory conditions such as burns and pancreatitis; toxic shock syndrome (TSS); anaphylaxis; reactions to drugs or toxins, including insect bites, transfusion reaction, and heavy metal poisoning; addisonian crisis; hepatic insufficiency; and neurogenic shock due to brain or spinal cord injury. (See Pathophysiology and Etiology.)
Shock is a clinical syndrome characterized by inadequate tissue perfusion that results in end-organ dysfunction. It can be divided into the following 4 categories:
The American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference Committee defined SIRS as the presence of at least 2 of the following 4 criteria (see Presentation) :
The clinical suspicion of systemic inflammatory response syndrome by an experienced clinician is also important.
For patient education information, see Shock and Cardiopulmonary Resuscitation (CPR).
In distributive shock, the inadequate tissue perfusion is caused by loss of the normal responses of vascular smooth muscle to vasoconstrictive agents coupled with a direct vasodilating effect. The net result in a fluid-resuscitated patient is a hyperdynamic, hypotensive state associated with increased mixed venous O2 saturation; however, evidence of tissue ischemia as manifest by an increased serum lactate, presumably due to intraorgan functional shunts.
Early septic shock (warm or hyperdynamic) causes reduced diastolic blood; widened pulse pressure; flushed, warm extremities; and brisk capillary refill from peripheral vasodilation, with a compensatory increase in cardiac output. In late septic shock (cold or hypodynamic), myocardial contractility combines with peripheral vascular paralysis to induce a pressure-dependent reduction in organ perfusion. The result is hypoperfusion of critical organs such as the heart, brain, and liver.
The hemodynamic derangements observed in septic shock and SIRS are due to a complicated cascade of inflammatory mediators. Inflammatory mediators are released in response to any of a number of factors, such as infection, inflammation, or tissue injury. For example, bacterial products such as endotoxin activate the host inflammatory response, leading to increased pro-inflammatory cytokines (eg, tumor necrosis factor (TNF), interleukin (IL)–1b, and IL-6). Toll-like receptors are thought to play a critical role in responding to pathogens as well as in the excessive inflammatory response that characterizes distributive shock; these receptors are considered possible drug targets.
Cytokines and phospholipid-derived mediators act synergistically to produce the complex alterations in vasculature (eg, increased microvascular permeability, impaired microvascular response to endogenous vasoconstrictors such as norepinephrine) and myocardial function (direct inhibition of myocyte function), which leads to maldistribution of blood flow and hypoxia. Hypoxia also induces the upregulation of enzymes that create nitric oxide, a potent vasodilator, thereby further exacerbating hypoperfusion.
The coagulation cascade is also affected in septic shock. In septic shock, activated monocytes and endothelial cells are sources of tissue factor that activates the coagulation cascade; cytokines, such as IL-6, also play a role. The coagulation response is broadly disrupted, including impairment of antithrombin and fibrinolysis. Thrombin generated as part of the inflammatory response can trigger disseminated intravascular coagulation (DIC). DIC is found in 25-50% of patients with sepsis and is a significant risk factor for mortality.[2, 3]
During distributive shock, patients are at risk for diverse organ system dysfunction that may progress to multiple organ failure (MOF). Mortality from severe sepsis increases markedly with the duration of sepsis and the number of organs failing.
In distributive shock due to anaphylaxis, decreased SVR is due primarily to massive histamine release from mast cells after activation by antigen-bound immunoglobulin E (IgE), as well as increased synthesis and release of prostaglandins.
Neurogenic shock is due to loss of sympathetic vascular tone from severe injury to the nervous system.
The most common etiology of distributive shock is sepsis. Other causes include the following:
All of these conditions share the common characteristic of hypotension due to decreased SVR and low effective circulating plasma volume.
The most common sites of infection, in decreasing order of frequency, include the chest, abdomen, and genitourinary tract.
Septic shock is commonly caused by bacteria, although viruses, fungi, and parasites are also implicated. Gram-positive bacteria are being isolated more, with their numbers almost similar to those of gram-negative bacteria, which in the past were considered to be the predominant organisms. Multidrug-resistant organisms are increasingly common.
Causes of SIRS include the following:
TSS can result from infection with Streptococcus pyogenes (group A Streptococcus) or Staphylococcus aureus.
Adrenal insufficiency can result from the following:
Anaphylaxis can develop as a result of the following:
Sepsis develops in more than 750,000 patients per year in the United States. Angus and colleagues estimated that, by 2010, 1 million people per year would be diagnosed with sepsis. From 1979-2000, the incidence of sepsis increased by 9% per year.
Sepsis is a common cause of death throughout the world and kills approximately 1,400 people worldwide every day.[6, 7]
Increased age correlates with increased risk of death from sepsis.
The mortality rate after development of septic shock is 20-80%. Data suggest that mortality due to septic shock has decreased slightly because of new therapeutic interventions. Early recognition and appropriate therapy are central to maximizing good outcomes. Identifying patients with septic shock in the emergency department, as opposed to identifying them outside of it, results in significantly improved mortality. In one study, the mortality rate for emergency department-identified patients was 27.7%, compared with 41.1% for patients identified outside of the emergency department.
Higher mortality rates have also been associated with the following:
Mortality rates associated with other forms of distributive shock are not well documented.
Duration of delirium is an independent predictor of long-term cognitive impairment. At 3-month and 12-month follow-up, as many as 79% and 71% of patients have cognitive impairment. About one third are severely impaired.[11, 12, 13]
Patients with shock frequently present with tachycardia, tachypnea, hypotension, altered mental status changes, and oliguria.
Patients with septic shock or systemic inflammatory response syndrome (SIRS) may have prior symptoms that suggest infection or inflammation of the respiratory tract, urinary tract, or abdominal cavity.
Septic shock occurs frequently in hospitalized patients with risk factors such as indwelling catheters or venous access devices, recent surgery, or immunosuppressive therapy.
Patients with anaphylaxis commonly have recent iatrogenic (drug) or accidental (bee sting) exposure to an allergen and coexisting respiratory symptoms, such as wheezing and dyspnea, pruritus, or urticaria.
Staphylococcal toxic shock syndrome (TSS) is still observed most commonly in women who are menstruating, but it is also associated with recent soft-tissue injury, cutaneous infections, postpartum and cesarean delivery, wound infections, pharyngitis, and focal staphylococcal infections, such as abscess, empyema, pneumonia, and osteomyelitis. Patients often have a history of influenzalike illness (fever, arthralgias, myalgias) and a desquamating rash.
Pancreatitis may be another cause of distributive shock; expect symptoms of abdominal pain that radiate to the back, as well as nausea and vomiting. Burns also have been described as a cause of distributive shock.
Adrenal insufficiency as a cause of shock should be considered in any patient with hypotension who lacks signs of infection, cardiovascular disease, or hypovolemia.
Long-term treatment with corticosteroids may result in inadequate response of the adrenal axis to stress, such as infection, surgery, or trauma, and subsequent onset or worsening of shock.
If the clinical picture is consistent with adrenal insufficiency in a person without this diagnosis, consider that this could be the first presentation of this disorder.
There is a high incidence of adrenal insufficiency in critically ill patients infected with the human immunodeficiency virus (HIV), although this incidence varies with the criteria used to diagnose adrenal insufficiency.
Cardinal features of distributive shock include the following:
Clinical symptoms of the underlying infections found in distributive shock include the following:
Anaphylaxis is characterized by the following clinical symptoms:
TSS is characterized by the following clinical symptoms:
Streptococcal TSS more frequently presents with focal soft-tissue inflammation and is less commonly associated with diffuse rash. Occasionally, it can progress explosively within hours.
Adrenal insufficiency is characterized by the following clinical symptoms:
All patients with evidence of distributive shock should undergo the following studies:
If pneumonia is suspected, sputum Gram stain and culture should be performed.
All patients with a suspected intra-abdominal pathologic condition or hepatic insufficiency should undergo the following studies:
All patients with suspected disseminated intravascular coagulation (DIC) should undergo the following studies:
Electrocardiography should be performed to examine the patient for evidence of underlying pathologic cardiac conditions (left ventricular hypertrophy, cor pulmonale, low voltage, bundle branch block) or acute changes of ischemia or pericarditis.
Imaging studies may be integral to defining the source of infection and identifying areas in need of drainage. All patients should undergo chest radiography. However, radiographic studies may not be sensitive enough to reveal intra-abdominal pathologic conditions. Consequently, computed tomography (CT) scanning has become the diagnostic test of choice for suspected intra-abdominal causes of sepsis. Consider abdominal and pelvic CT scans with oral contrast and intravenous contrast if these sites are found to be clinically suspicious for infection.
In suspected cases of cholecystitis or pancreatitis, abdominal ultrasonography is most useful to assess for cholelithiasis, biliary dilatation, and fluid collections around the gallbladder or the head of the pancreas.
Point-of-care ultrasonography/echocardiography may be performed at the bedside in critically ill patients to evaluate cardiac function, fluid status, and response to hemodynamic intervention and to exclude tamponade.
Lumbar puncture (LP) is indicated in patients with nuchal rigidity, headache, or unexplained neurologic findings or in patients with sepsis and altered level of consciousness without another apparent source of infection. A CT scan of the head should be performed prior to LP whenever feasible.
The use of pulmonary artery catheters (PACs) was the standard of care for decades (see Table 1, below). However, data now suggest an increase in mortality with the use of PAC monitoring, calling this practice into question. Additionally, current parameters for PAC-guided resuscitation may not be appropriate. A randomized trial of the use of PACs in elderly, high-risk surgical patients found no benefit to therapy directed by PACs compared with treatment per the standard of care.[15, 16]
Table 1. Pulmonary Artery Catheter Findings in Common Shock States
Arterial catheter placement should be considered in hemodynamically unstable patients who are receiving continuous infusions of vasoactive drugs or in patients requiring frequent arterial blood gas measurements (eg, patients on mechanical ventilation). The arterial catheter can be placed radially, femorally, axillary, but never brachially. Some patients can be managed with the pulse oximetry wave graphic only.
Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) may be used to estimate right atrial filling and right ventricular volumes in patients with undetermined fluid status. TTE is a noninvasive method for the assessment of left ventricular function. This technique has several limitations, being time consuming, operator dependent, and limited by preexisting pulmonary disease or chest wall injuries.
TEE is a somewhat more invasive test that provides excellent structural information in the critically ill patient. This technique allows the assessment of preload, ventricular wall motion abnormalities, and the pericardium.
Thoracic bioelectrical impedance (TBI)
This technique relies on formulas to estimate stroke volume and cardiac output based on the measured bioimpedance of blood velocity and volume of blood flow through the aorta.
Pulse-induced CO (PiCO), lithium dilution CO (LiCO), and FloTrac
Via an arterial catheter, cardiac output (CO) can be continuously monitored. FloTrac does not require calibration. Stroke volume and continuous systemic vascular resistance (SVR) can be measured and calculated using basic patient information.
Total circulating blood volume (TCBV)
This is measured using indocyanine green infusion and is quantified using spectrophotometry.
Microcirculatory imaging techniques, such as orthogonal polarization spectral and side-stream dark-field imaging, have allowed direct observation of the microcirculation at the bedside. They have demonstrated different types of heterogenous flow patterns of microcirculatory abnormalities in different types of distributive shock and may complement early goal-directed therapy in shock.[17, 18]
The primary goals of treatment are to reverse the underlying cause of shock (eg, treat the infection by draining abscesses and debridement) and hemodynamic stabilization of the patient.
The management of patients with shock is multifactorial and guidelines are evolving.[19, 20, 21, 22, 23] Of note, the Surviving Sepsis Campaign (SSC), composed of international experts, assessed the available evidence and published consensus guidelines.
All patients with distributive shock should be admitted to an intensive care unit (ICU). Vital signs and fluid intake and output should be measured and charted on an hourly basis. Daily weights should be obtained, and adequate intravascular access should be secured. A central venous access device should be considered if vasoactive drug support is required. Placement of pulmonary artery (PA) and arterial catheters should be considered. Most patients should have an indwelling urinary catheter.
Oxygen should be administered immediately by mask. In patients with altered mental status, respiratory distress, or severe hypotension, elective endotracheal intubation and mechanical ventilation should be considered; these avoid emergent intubation in the event of subsequent respiratory arrest. Mechanical ventilation can also aid in hemodynamic stabilization, by decreasing the demands posed by the respiratory muscles on the circulation (as much as 40% of the cardiac output during respiratory distress).
All patients should be treated prophylactically against thromboembolic disease, gastric stress ulceration, and pressure ulcers.
Early, efficient resuscitation is the key. The duration of hypotension before antibiotic treatment has been found to be a critical factor in determining mortality. Rivers et al found a significant decrease in in-hospital mortality when patients were treated with early, goal-directed therapy. This protocol-driven resuscitation strategy focused on optimizing hemodynamic parameters and reversing hypoperfusion beginning in the emergency department; these protocols have been successfully implemented not only in research centers, but also in community-based settings.[27, 28, 29, 30]
The SSC’s recommendations support protocol-driven resuscitation beginning as soon as hypoperfusion is detected and continuing over the first 6 hours using protocol-defined goals for central venous pressure, mean arterial pressure, urine output, and/or mixed venous oxygen saturation. If central venous oxygen saturation of more than 70% is not achieved in the first 6 hours, SSC recommendations suggest (based on clinical assessment) transfusing packed red blood cells targeting hematocrit at greater than or equal to 30% or treatment with dobutamine.[31, 32, 33]
The choice of fluid for resuscitation has been a matter of ongoing debate. The SSC recommends the use of either colloids or crystalloids, finding inadequate evidence to recommend one over the other. The Saline Versus Albumin Fluid Evaluation (SAFE) trial found crystalloid and colloid to be equally safe and effective for ICU patients. In contrast to prior studies, it also found no difference or increased mortality among patients receiving albumin.[34, 35, 36, 37, 38]
A meta-analysis revealed that passive leg raising-induced changes in cardiac output (PLR-cCO) can reliably predict fluid responsiveness, regardless of ventilation mode and cardiac rhythm. PLR-cCO has a significantly higher predictive value than arterial pulse pressure.
A retrospective cohort study of trauma patients who received allogeneic packed red blood cells sought to determine the association between infection or death and blood storage duration. Results showed that patients who received 7 units or more of older blood had a higher risk of complicated sepsis compared with patients who received 1 or fewer units. The effects of allogeneic blood is best reduced by avoiding unnecessary transfusions, but it may also be important to avoid transfusions of multiple units of older blood.
In the Multicenter Randomized Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis (VISEP) study, comparing hydroxyethyl starch (HES) to Ringer's lactate, the HES group had higher rates of renal failure and more days on renal replacement therapy. Additional investigation is required to fully appreciate the risks versus benefits of this intervention.[41, 42]
In patients with hypotension due to sustained septic shock in whom fluid resuscitation does not reverse hypotension, the use of systemic vasopressors is indicated to restore blood flow to pressure-dependent vascular beds (eg, the heart and brain). Either norepinephrine or dopamine should be used as first-line treatment; no evidence suggests the use of one over the other. Several vasopressor agents are available. (See Table 2, below.)
If dopamine is tried first and fails to increase mean arterial pressure to more than 60mm Hg or if excessive tachycardia or tachyarrhythmias develop, norepinephrine (Levophed) should be used. As a second-line treatment, phenylephrine (Neo-Synephrine) may be added to or substituted for dopamine. Dobutamine may be added to the therapeutic regimen when cardiac output is low, recognizing that this drug acts primarily as a positive inotropic agent and may further decrease systemic vascular resistance (SVR).
Importantly, because severe sepsis is usually associated with some degree of myocardial depression, the use of an unopposed alpha stimulant to increase vasomotor tone without a concomitant increase in inotropy decreases cardiac output. This was the universal finding when nitric oxide synthase inhibitors were used to treat the hypotension of septic shock in a large prospective, clinical trial. The doses and cardiovascular characteristics of commonly used vasoactive drugs for shock are summarized in Table 2, below.
As a second-line treatment, vasopressin may be helpful to increase mean arterial pressure and SVR and may be considered in patients who are refractory to inotropic agents and have a cardiac output that is already more than 3.5 L/min/m2. Endogenous vasopressin is released from the pituitary gland as part of the physiologic response to shock, acting on V1 receptors of vascular smooth muscle to induce vasoconstriction. As shock continues, endogenous vasopressin levels may be depressed, perhaps due to depletion of the stores or impaired hypophyseal function in the setting of infection. This contributes to refractory hypotension.[43, 44, 45, 46]
In this setting of hypotension, treatment with exogenous vasopressin has a role. Vasopressin treatment carries the risk of acidosis by causing splanchnic vasodilation and resultant ischemia. Myocardial ischemia is also possible, given increased afterload and coronary vasoconstriction. Although current treatment guidelines support vasopressin’s use, a randomized trial in which vasopressin was added to ongoing norepinephrine treatment did not find a benefit to the use of vasopressin over norepinephrine, suggesting that additional investigation will be required to define vasopressin’s role. In a 2012 meta-analysis, Serpa et al found that vasopressin treatment in patients with vasodilatory shock was safe and was associated with reduced mortality.
Table 2. Vasoactive Drugs in Sepsis and the Usual Hemodynamic Responses
In all patients with suspected sepsis, blood and urine cultures should be collected prior to empiric antibiotic therapy, provided that this does not cause a significant delay in treatment. At least 2 blood cultures should be collected and should be drawn percutaneously, as well as from any vascular access site. Cultures such as respiratory tract secretions and cerebrospinal fluid should be collected if infection at these sites is suspected clinically.
Patients who receive prompt effective antimicrobial therapy are more likely to survive than are patients whose antibiotic therapy is delayed; measurable increases in mortality occur for each hour’s delay in antibiotic treatment. Because initial therapy must be empiric, antimicrobial coverage should be broad and should have good penetration to all suspected sites of infection.
The choice of agent should be guided by history, suspected site of infection, comorbid diseases, and pathogen susceptibility patterns in the hospital and community. Avoid antibiotics recently received by the patient. Treatment of fungal infection should be considered and selection of an antifungal agent should be guided by the local prevalence of Candida species. Recommended empiric antibiotic regimens based on the suspected site are outlined in Table 3, below.
Antimicrobial regimens should be tailored once the causative pathogen and its susceptibility are identified because narrow-spectrum treatment decreases the risk of superinfection with resistant organisms. The duration of therapy varies based on clinical context, but the SSC guidelines suggest that the typical duration will be 7-10 days, with adjustments made for factors such as underlying immune status and undrainable foci of infection.
Consider the removal of any devices, such as intravenous or urinary catheters and prostheses. Surgical drainage or debridement should be performed promptly, when appropriate (eg, intra-abdominal abscess, necrotizing fasciitis).
Table 3. Empiric Antimicrobial Therapy in Septic Shock Based on Suspected Site of Infection
This has become a strategy for preventing sepsis-related organ failure. Disseminated intravascular coagulation (DIC) is a critical factor in driving the progression of sepsis. Activated protein C (APC), an endogenous protein that decreases thrombosis and inflammation, has been used for septic shock but was withdrawn by the company for lack of significant efficiency.[9, 49, 50, 51, 52, 53, 54, 55]
The role of corticosteroids as an adjunct treatment for septic shock has been an area of debate. The role of corticosteroids in sepsis is a matter of debate, with positive and negative studies in the literature. Low-dose hydrocortisone and fludrocortisone have been used for patients with severe sepsis and adrenal insufficiency who remain hypotensive after fluid resuscitation and pressors and were traditionally thought to reduce mortality in this subgroup.[56, 57, 58, 59]
In contrast to prior studies, however, a multi-site, double-blind, placebo-controlled trial found that low-dose hydrocortisone did not affect mortality at 28 days, although patients receiving hydrocortisone had an earlier reversal of shock. Also in contrast to prior work, this study did not find that a corticotropin stimulation test predicted response to hydrocortisone. Additional studies are required to address these discrepancies.
The SSC recommendations acknowledge this controversy and support giving hydrocortisone only to hypotensive patients poorly responsive to fluid resuscitation and vasopressors. Given findings that suggest the adrenocorticotropic hormone (ACTH) stimulation test does not predict response to steroids, this test is no longer recommended. Hydrocortisone, rather than dexamethasone or fludrocortisone, is the steroid of choice; it is not yet clear if adding fludrocortisone to hydrocortisone provides added benefit.
Protocol-driven management of glucose (target < 150-180 mg/dL) is recommended, with monitoring every 1-2 hours until glucose levels are stable and then every 4 hours thereafter. This SSC recommendation is based on studies that found decreased mortality, length of stay, and complications such as renal impairment. Of note, intensive glucose management has been associated with higher rates of severe hypoglycemic events and, in some studies, has not been associated with improved mortality.
Pyridoxalated hemoglobin polyoxyethylene (PHP) is a hemoglobin-based nitric oxide (NO) scavenger that has been shown to increase systemic blood pressure and reduce vasopressor and ventilation needs in patients with NO-induced shock without adversely affecting cardiac output, organ function, or survival. The results of its use in distributive shock in a multicenter, randomized, placebo-controlled, phase II study were promising, but further studies are needed to provide a definitive answer.
If anaphylaxis is suspected, 0.2-0.5 mL subcutaneous of 1:1000 epinephrine should be administered immediately, with repeated doses every 20 minutes as needed. Epinephrine can be administered by continuous infusion of 30-60 mL/h of 1:10,000 dilution in severe reactions. Diphenhydramine 50-80 mg intramuscular or intravenous may be administered for urticaria or angioedema. Inhaled bronchodilators or intravenous steroids can be administered for bronchospasm.
In addition to prompt fluid resuscitation, hemodynamic support with vasoactive drugs, and prompt establishment of broad-spectrum antibiotic coverage, source control is essential to effective treatment of shock. Early efforts should be made to define sources in need of surgical intervention, such as necrotizing fasciitis, cholangitis, abscess, intestinal ischemia, or an infected device. The least-invasive means of intervention should be used.
Multiple surgical modalities for source control are indicated, including the following:
Once the initial phase of resuscitation is complete, promptly institute nutritional support, usually within 24 hours. This is especially important in malnourished patients (with temporal muscle atrophy).
In patients who are intubated or obtunded, tube feedings should be initiated through a soft nasogastric or orogastric feeding tube at a slow rate and increased over 12-24 hours to the target rate.
If patients cannot be fed enterally, parenteral nutrition may be instituted until enteral feeding becomes possible. Enteral feeding is preferred because it is less expensive and is associated with lower rates of nosocomial infection than total parenteral nutrition.
Transfer of a patient admitted with distributive shock from the ICU to a stepdown or ward unit is highly individualized. The patient's condition and prognosis must be assessed and matched to the level of care in the receiving unit.
Generally, patients can be considered for transfer when they are hemodynamically stable without vasoactive drugs, when ventilation and oxygenation is stable on supplemental oxygen delivered by nasal cannula, when life-threatening metabolic derangements are absent, and when the patients no longer require the high nursing and respiratory therapy ratios characteristic of ICU care (ie, for frequent suctioning).
Transferring a patient with distributive shock from one hospital to another exposes the patient to risk and should be undertaken only when the receiving institution can offer the patient care that is not available at the transferring hospital.
In general, institutions that care for critically ill patients need an appropriately staffed ICU that is capable of delivering and monitoring mechanical ventilation and invasive monitoring devices such as pulmonary artery (PA) catheters and arterial lines.
Modern surgical facilities, a radiology department equipped with ultrasonographic and CT scanners, dialysis equipment, and medical specialists to deliver these specialized types of care and procedures are also a minimum requirement. Lack of any one of these resources may necessitate transfer.
Under certain circumstances, patients may also benefit from transfer to units that specialize in care for trauma, burns, or cardiac or neurosurgical problems or to units where organ transplantation is available.
Consultation with or primary management by a board-certified medical or surgical intensivist is indicated for all patients with distributive shock.
Experienced intensivists may be trained in pulmonary/critical care medicine, cardiology, surgery, or anesthesiology. The choice of consultant may depend on patient characteristics and the availability of local subspecialists.
Consultation with a subspecialist in infectious disease is appropriate whenever sepsis is suspected as a cause of distributive shock.
This is particularly true when the locus of infection is unknown or unique patient characteristics (such as travel history or occupation) raise the possibility of an unusual or rare infectious process.
Consultation with a surgeon should always be obtained when an abdominal source of sepsis is suspected. Other indications for consultation with a surgeon include, but are not limited to, necrotizing fasciitis, soft tissue abscess, empyema (thoracic surgeon), or brain abscess (neurosurgeon).
Because initial therapy must be empiric, antimicrobial coverage should be broad, with good penetration to all suspected sites of infection. Other important factors in choosing an agent include history, suspected site of infection, comorbid diseases, and pathogen susceptibility patterns in the hospital and community. Avoid antibiotics recently received by the patient.
Antimicrobial regimens should be tailored once the causative pathogen and its susceptibility are identified, because narrow-spectrum treatment decreases the risk of superinfection with resistant organisms.
The role of corticosteroids as an adjunct treatment for septic shock has been an area of debate. Recommendations from the Surviving Sepsis Campaign (SSC) support giving hydrocortisone only to hypotensive patients who are poorly responsive to fluid resuscitation and vasopressors. Hydrocortisone is the steroid of choice.
The use of systemic vasopressors is indicated in patients with hypotension due to sustained septic shock in whom fluid resuscitation does not reverse hypotension. Systemic vasopressors are used to restore blood flow to pressure-dependent vascular beds (eg, the heart and brain). Either norepinephrine or dopamine should be used as first-line treatment; no evidence suggests the use of one over the other.
Clinical Context: Ceftazidime is a third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; and higher efficacy against resistant organisms. It arrests bacterial growth by binding to 1 or more penicillin-binding proteins.
Clinical Context: Nafcillin is the initial therapy for suspected penicillin G–resistant streptococcal or staphylococcal infections. Use parenteral therapy initially in severe infections, and change to oral therapy as the condition warrants. Because of thrombophlebitis, particularly in elderly patients, administer nafcillin parenterally for only a short period (1-2 d); change to the oral route as clinically indicated.
Clinical Context: Levofloxacin is used for infections caused by multidrug-resistant, gram-negative organisms.
Clinical Context: Ampicillin has bactericidal activity against susceptible organisms. It serves as an alternative to amoxicillin when the patient is unable to take medication orally. It is rarely used in septic shock.
Clinical Context: Clindamycin is a lincosamide for the treatment of serious skin and soft-tissue staphylococcal infections. It is also effective against aerobic and anaerobic streptococci (except enterococci). Clindamycin inhibits bacterial growth, possibly by blocking the dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes that cause RNA-dependent protein synthesis to arrest. It also counteracts bacterial toxins.
Clinical Context: Gentamicin is an aminoglycoside antibiotic for gram-negative coverage. It is used in combination with an agent against gram-positive organisms and one that covers anaerobes.
Gentamicin is not the drug of choice (DOC). Consider using it if penicillins or other less-toxic drugs are contraindicated, when it is clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens for gentamicin are numerous; adjust the dose based on creatinine clearance (CrCl) and changes in the volume of distribution. It may be administered intravenously or intramuscularly.
Clinical Context: Tobramycin is indicated in the treatment of staphylococcal infections when penicillin or potentially less-toxic drugs are contraindicated and when bacterial susceptibility and clinical judgment justifies its use.
Clinical Context: Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes. It blocks the recognition step in protein synthesis, causing growth inhibition. Use the patient's ideal body weight (IBW) for the dosage calculation.
Clinical Context: Vancomycin is a potent antibiotic that is directed against gram-positive organisms and is active against Enterococcus species. It is useful in the treatment of septicemia and skin structure infections. Vancomycin is indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or who have infections with resistant staphylococci. For abdominal penetrating injuries, vancomycin is combined with an agent that is active against enteric flora and anaerobes.
To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose, drawn 0.5 hour prior to the next dosing. Use creatinine clearance to adjust the dose in patients diagnosed with renal impairment.
Vancomycin is used in conjunction with gentamicin for prophylaxis in patients allergic to penicillin who are undergoing gastrointestinal or genitourinary procedures.
Clinical Context: Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes that cause RNA-dependent protein synthesis to arrest. It is used for the treatment of staphylococcal and streptococcal infections.
In children, age, weight, and the severity of infection determine proper dosage. When twice-daily dosing is desired, the half-total daily dose may be taken every 12 hours. For more severe infections, double the dose.
Clinical Context: Azithromycin is used to treat mild to moderate microbial infections.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Clinical Context: Hydrocortisone is the corticosteroid of choice in shock because of its mineralocorticoid activity and glucocorticoid effects. It may be given to hypotensive patients who are poorly responsive to fluid resuscitation and vasopressors.
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Clinical Context: Vasopressin has vasopressor and antidiuretic hormone (ADH) activity. It increases water resorption at the distal renal tubular epithelium (ADH effect). It promotes smooth muscle contraction throughout the vascular bed of the renal tubular epithelium (vasopressor effects). Vasoconstriction is also increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels.
Clinical Context: Dopamine stimulates adrenergic and dopaminergic receptors. Its hemodynamic effect is dose dependent. Lower doses predominantly stimulate dopaminergic receptors that, in turn, produce renal and mesenteric vasodilation. Cardiac stimulation and renal vasodilation are produced by higher doses.
After initiating therapy, increase the dose by 1-4mcg/kg/min every 10-30 minutes until the optimal response is obtained. More than 50% of patients are maintained satisfactorily on doses of less than 20mcg/kg/min.
Clinical Context: Norepinephrine is used in protracted hypotension following adequate fluid replacement. It stimulates beta1- and alpha-adrenergic receptors, which, in turn, increases cardiac muscle contractility and heart rate, as well as vasoconstriction. As a result, it increases systemic blood pressure and cardiac output. Adjust and maintain infusion to stabilize blood pressure (eg, 80-100 mm Hg systolic) sufficiently to perfuse vital organs.
These agents augment coronary and cerebral blood flow present during a state of low blood flow.
Microcirculatory abnormalities in distributive shock. Each image represents a venule (large, curved tube) and 2 capillaries (smaller tubes) and demonstrates the 2 main capillary flow patterns found in each class of microcirculatory abnormality, as they occur in distributive shock. This classification system was introduced by Elbers and Ince. Elbers P, Ince C. Bench-to-bedside review: mechanisms of critical illness—classifying microcirculatory flow abnormalities in distributive shock. Crit Care. July 19 2006;10(4):221.
Diagnosis Pulmonary Capillary Wedge Pressure Cardiac Output Cardiogenic shock* Increased Decreased Extracardiac obstructive shock
1. Pericardial tamponade†
2. Pulmonary embolism
Normal or decreased
Hypovolemic shock Decreased Decreased Distributive shock
1. Septic shock
2. Anaphylactic shock
Normal or decreased
Normal or decreased
Increased or normal
Increased or normal
*In cardiogenic shock due to a mechanical defect, such as mitral regurgitation, forward cardiac output is reduced, although the measured cardiac output may be unreliable. Large V waves are commonly observed in the pulmonary capillary wedge tracing in mitral regurgitation.
†The hallmark finding is equalization of right atrial mean, right ventricular end-diastolic, pulmonary artery (PA) end-diastolic, and pulmonary capillary wedge pressures.
Drug Dose Principal Mechanism Cardiac Output Blood Pressure SVR Inotropic agents Dobutamine 2-20 mcg/kg/min Beta 1 ++ + + Dopamine
5-10 mcg/kg/min Beta 1, dopamine ++ + + Epinephrine (low dose) 0.06-0.20 mcg/kg/min Beta 1, beta 2 >alpha ++ + + Inotropic agents and vasoconstrictors Dopamine (high dose) >10 mcg/kg/min Alpha, beta 1, dopamine ++ ++ + Epinephrine
0.21-0.42 mcg/kg/min Alpha >beta 1, beta 2 ++ ++ + Norepinephrine 0.02-0.25 mcg/kg/min Alpha >beta 1, beta 2 + ++ ++ Vasoconstrictors Phenylephrine 0.2-2.5 mcg/kg/min Alpha + ++ ++ Vasopressin 0.10-0.40 U/min V1 receptor + + ++ Vasodilators Dopamine
(very low dose)
1-4 mcg/kg/min Dopamine +/- +/- - Milrinone 0.4-0.6 mcg/kg/min after loading dose; 50 mcg/kg bolus over 5 min Phosphodiesterase inhibitor + +/- - Alpha and beta refer to agonist activity at these adrenergic receptor sites.
Beta 1-adrenergic effects are inotropic and increase contractility.
Beta 2-adrenergic effects are chronotropic.
Suspected Source Recommended Antibiotic Therapy Alternative Therapy No source evident in a healthy host Third-generation cephalosporin, eg, ceftriaxone 2 g IV q12h, ceftizoxime, ceftazidime Nafcillin and aminoglycoside, imipenem, piperacillin/tazobactam No source evident in an immunocompromised host Ceftazidime 2 g IV q8h plus aminoglycoside Imipenem or piperacillin/tazobactam plus aminoglycoside No source evident in a user of intravenous drugs Nafcillin 2 g IV q4h plus aminoglycoside Vancomycin plus aminoglycoside, ceftazidime, imipenem, or piperacillin/tazobactam Bacterial pneumonia, community acquired Ceftriaxone 2 g IV q12-24 h plus macrolide Levofloxacin 750mg IV q24h, cotrimoxazole or imipenem plus macrolide Bacterial pneumonia, hospital acquired Piperacillin/tazobactam 4.5 g IV q6h plus aminoglycoside, plus levofloxacin 750 mg IV q24h Imipenem plus aminoglycoside, plus macrolide Urinary tract infection Ampicillin 2 g IV q4h plus aminoglycoside Fluoroquinolone or third-generation cephalosporin plus aminoglycoside Mixed aerobic and anaerobic abdominal sepsis, aspiration pneumonia, pelvic infection, and necrotizing cellulitis Third-generation cephalosporin or ampicillin 2 g IV q4h plus aminoglycoside plus clindamycin 600 mg IV q8h or metronidazole 500 mg IV q6h Fluoroquinolone plus clindamycin, imipenem, piperacillin/tazobactam Meningitis Ceftriaxone 2 g IV q12h plus vancomycin Meropenem plus vancomycin, chloramphenicol plus cotrimoxazole plus vancomycin Cellulitis/erysipelas Nafcillin 2 g IV q4h Cefazolin, vancomycin, clindamycin Toxic shock syndrome (TSS) or streptococcal necrotizing fasciitis Clindamycin 600 mg IV q8h Cephalosporin, vancomycin, nafcillin