Distributive Shock

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Practice Essentials

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 (treated, around 30%; untreated, probably >80%). 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.)

Types of shock

Shock is a clinical syndrome characterized by inadequate tissue perfusion that results in end-organ dysfunction. It can be divided into the following four categories:

Systemic inflammatory response syndrome

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)[1] :

The clinical suspicion of systemic inflammatory response syndrome by an experienced clinician is of utmost importance.

Pathophysiology

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 pressure; 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) –1, 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. Activated monocytes and endothelial cells are sources of tissue factors that activate 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.

Etiology

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.

Septic shock

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.[4]

Systemic inflammatory response syndrome

Causes of SIRS include the following:

Toxic shock syndrome

TSS can result from infection with Streptococcus pyogenes (group A Streptococcus) or Staphylococcus aureus.

Adrenal insufficiency

Adrenal insufficiency can result from the following:

Anaphylaxis

Anaphylaxis can develop as a result of the following:

Epidemiology

Occurrence in the United States

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.[5] From 1979-2000, the incidence of sepsis increased by 9% per year.

International occurrence

Sepsis is a common cause of death throughout the world and kills approximately 1,400 people worldwide every day.[6, 7]

Age-related demographics

Increased age correlates with increased risk of death from sepsis.

Prognosis

The mortality rate after development of septic shock is 20-80%.[8] 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.[9]

Higher mortality rates have also been associated with the following:

Mortality rates associated with other forms of distributive shock are not well documented.

Complications

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 remain severely impaired.[10, 11, 12]

History

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

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.[13]

Physical Examination

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:

Approach Considerations

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

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

Imaging studies may be integral to defining the source of infection and identifying areas in need of drainage.  The American College of Radiology recommends chest radiography (see the images below) as the initial imaging for patients with suspected or confirmed sepsis and cough, dyspnea or chest pain. Chest computed tomography (CT) scanning with or without contrast should be performed if further imaging is required following chest radiographs that are normal, equivocal  or nonspecific.[14]

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  intravenous contrast if these sites are found to be clinically suspicious for infection.[14] Cohen et al reported contrast-enhanced thoraco-abdominal shock protocol CT to be useful in the discrimination of shock etiology.[15]

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.[16] Ramadan et al found that an echocardiography-ultrasound protocol was 100% accurate for the diagnosis of cases of obstructive and mixed obstructive distributive shock and also an extremely useful method for ruling out cardiogenic shock.[17]

Geng et al have reported on an ultrasound protocol for the diagnosis of undifferentiated shock. Called THIRD, the protocol assesses for tamponade, tension pneumothorax, numerous cardiac parameters, inferior vena cava anatomy and function, lung pathologies, aortic dissection, and deep venous thrombosis. In a study of 112 patients, there was a kappa index of 0.81 (95% confidence interval=0.73-0.89; P< 0.001) for agreement between assessment using the THIRD protocol and final diagnosis.[18]



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An 8-year-old boy developed septic shock secondary to Blastomycosis pneumonia. Fungal infections are a rare cause of septic shock.



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A 28-year-old woman who was a previous intravenous drug user (human immunodeficiency virus [HIV] status: negative) developed septic shock secondary to....

Procedures

Lumbar puncture

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.

Arterial catheters

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.[19, 20]

Table 1. Pulmonary Artery Catheter Findings in Common Shock States



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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 and transesophageal echocardiography

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.

Other minimally invasive techniques

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

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.[21, 22]

Approach Considerations

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.[23, 24, 25, 26, 27] Of note, the Surviving Sepsis Campaign (SSC), composed of international experts, assessed the available evidence and published consensus guidelines beginning in 2004.[28]   The most recent guidelines were published in 2021 and revised by the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). The 2021 guidelines have been endorsed by 24 international societies including the Infectious Diseases Society of America (IDSA).[29]  

Monitoring

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).

Prophylaxis

All patients should be treated prophylactically against thromboembolic disease, gastric stress ulceration, and pressure ulcers.

Resuscitation

Early, efficient resuscitation is the key. The duration of hypotension before antibiotic treatment has been found to be a critical factor in determining mortality.[30] Rivers et al found a significant decrease in in-hospital mortality when patients were treated with early, goal-directed therapy.[31] 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.[32, 33, 34, 35]

As soon as hypoperfusion is detected, continue fluid over the first 6 hours using protocol-defined goals for central venous pressure, mean arterial pressure, urine output, and/or mixed venous oxygen saturation.[29] However, two major studies (ARISE [Australasian Resuscitation in Sepsis Evaluation],[36] ProCESS [Protocolized Care for Early Septic Shock][37] ) have not shown improved survival with protocol-based therapy, as compared with nonprotocol "usual" therapy. Furthermore, a major study on a perioperative, cardiac output–guided hemodynamic therapy algorithm, with the use of inotropic medication for patients with major gastrointestinal surgery, also did not show increased survival.[38] The impact of these three studies on protocol-based therapy is currently controversial.

The choice of fluid for resuscitation has been a matter of ongoing debate. The SSC recommends at least 30 mL/kg of IV crystalloid fluid should be given within the first 3 hours of resuscitation.[29] 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.[39, 40, 41, 42, 43]

Owing to the findings of various trials such as ARISE,[36] ProCESS,[37] and OPTIMISE (Optimisation of Cardiovascular Management to Improve Surgical Outcome),[38] the SSC guidelines now recommend frequent clinical reassessment of patients after initial fluid resuscitation.[29] A plausible way to do so is with point-of-care ultrasound. Monitoring of fluid status via ultrasound assessment of the inferior vena cava[44, 45] and the lungs[46, 47, 48] has been studied to assess fluid responsiveness in sepsis/septic shock.

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.[49] 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.[50]

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.[51, 52]

Vasoactive drugs

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 (preferred), epinephrine or dopamine should be used as first-line treatment.[29] Several vasopressor agents are available. (See Table 2, below.)

A meta-analysis of 33 randomized controlled studies reported that norepinephrine plus dobutamine was associated with the lowest risk for 28-day mortality in septic patients.  Dopamine was associated with the highest incidence of cardiac arrhythmia and 28-day mortality.  Epinephrine and terlipressin were associated with the highest incidences of myocardial infarction and peripheral ischemia.[53]

If dopamine is tried first and fails to increase mean arterial pressure to more than 60 mm 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).

In December 2017, synthetic human angiotensin II (Giapreza) was approved by the US Food and Drug Administration for adults with septic or other distributive shock. Approval was based on the ATHOS-3 clinical trial (n = 321) in patients with vasodilatory shock and critically low blood pressure. Eligible patients had vasodilatory shock despite intravenous volume resuscitation with at least 25 mL/kg over the previous 24 hours and the administration of high-dose vasopressors. Significantly more patients responded to treatment with the angiotensin II injection added to conventional therapy compared with those on conventional therapy plus placebo. At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (P = .01).[54]

A 2024 meta-analysis of 10 studies encompassing 1555 patients with distributive shock reported that ATII did not decrease mortality compared to controls, however the administration of ATII resulted in significant reduction in norepinephrine at 3 hours after treatment initiation without increased rates of adverse events.[55]

Important to note, 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.

Vasopressin

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.[56, 57, 58, 59]

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.[59] 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.[60]

Table 2. Vasoactive Drugs in Sepsis and the Usual Hemodynamic Responses



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Antimicrobial Treatment

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, and the SSC guidelines suggest sing shorter over longer duration as well as daily assessment for de-escalation of antimicrobials over using fixed durations of therapy without daily reassessment.[29]

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



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Corticosteroids

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.[62, 63, 64, 65]

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 suggests IV corticosteroids be given to patients who remain on vasopressor therapy. The recommended dosage is 200 mg/d hydrocortisone given as 50 mg intravenously every 6 hours or as a continuous infusion. It is suggested that this is commenced at a dose of norepinephrine or epinephrine ≥ 0.25 mcg/kg/min at least 4 hours after initiation.[29]

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.[66]

Glucose

Protocol-driven management of glucose (target 144-180 mg/dL) is recommended.[29] 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.

NO Scavenger

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.[67]

Treatment of Anaphylaxis

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.

Surgical Control of Shock Sources

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.[68]

Multiple surgical modalities for source control are indicated, including the following:

Diet

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.

Inpatient Care

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).

Transfer

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.

Consultations

Intensivist

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.

Infectious disease specialist

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.

Surgeon

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).

Guidelines Summary

In 2004, the first set of formal treatment guidelines for septic shock were published.[28]  These guidelines, known as the Surviving Sepsis Campaign, 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 are reviewed and updated periodically. 

The most recent guidelines were published in 2021 and revised by the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). The 2021 guidelines have been endorsed by 24 international societies including the Infectious Diseases Society of America (IDSA) which declined to endorse the 2016 revision.[69] The 2021 guidelines are summarized below.[29]

Screening for sepsis and performance improvement

Hospitals and hospital systems should have a performance improvement program in place for sepsis, including screening practices. The use of qSOFA compared with SIRS, NEWS, or MEWS as a single screening tool for sepsis or septic shock is recommended against. Blood lactate should be measured in adults when sepsis is suspected.

Initial resuscitation

Septic shock is a medical emergency and treatment and resuscitation should begin immediately. Intravenous fluid resuscitation for sepsis-induced hypoperfusion should consist of at least 30 mL/kg of intravenous crystalloid fluid being given within the first 3 hours. Balanced crystalloid is suggested instead of normal saline for resuscitation.   

Dynamic over static variables are favored in assessing patient response to fluid resuscitation. Dynamic parameters include response to a passive leg raise or a fluid bolus, using stroke volume (SV), stroke volume variation (SVV), pulse pressure variation (PPV), or echocardiography, where available. Guide resuscitation to decrease serum lactate in patients with elevated lactate level, over not using serum lactate.  Capillary refill time may be used as an adjunct to other measures of perfusion.

The initial recommended target mean arterial pressure is 65 mm Hg in patients with septic shock requiring vasopressors.

If admission to the ICU is required, it is recommended to occur within 6 hours.

Diagnosis

In patients with unconfirmed infection, continuously re-evaluating and searching for alternative diagnoses and discontinuing empiric antimicrobials if an alternative cause of illness is demonstrated or strongly suspected is recommended.

Antimicrobial therapy

Empiric broad-spectrum intravenous antibiotics should be initiated within 1 hour if septic shock is possible or sepsis is highly likely.  For possible sepsis without shock, we suggest a time-limited course of rapid investigation and if concern for infection persists, the initiation of antimicrobials within 3 hours from the time sepsis was first recognized.

Rapid assessment including history and clinical examination, tests for both infectious and non-infectious causes of acute illness and immediate treatment for acute conditions that can mimic sepsis should be performed. 

Antibiotics should be deferred in patients without shock and the likelihood of an infectious cause of the sepsis is low.  Continued close monitoring of the patient is recommended.

Using procalcitonin plus clinical evaluation to decide when to start antimicrobials is NOT recommended, however procalcitonin plus clinical evaluation is recommended to decide when to discontinue antimicrobials

Empiric antimicrobials with methicillin-resistance Staphylococcus aureus (MRSA) coverage over using antimicrobials without MRSA coverage is recommended only for patients at high-risk of MRSA infection.

Empiric treatment with two gram-negative agents is recommended over one gram-negative agent for patients at high-risk for multidrug resistant (MDR) organisms. 

Empiric antifungal therapy is recommended for patients at high-risk for fungal infection.

Prolonged infusion of beta-lactams for maintenance (after an initial bolus) over conventional bolus infusion is suggested.

Daily assessment for de-escalation of antimicrobials is recommended over using fixed durations of antimicrobial therapy.

Source control

Rapid identification or exclusion of a specific anatomical diagnosis of infection is recommended. Any required intervention to eradicate the source of infection should be done as soon as possible. Intravascular access devices that are a possible source of sepsis or septic shock should be removed promptly after other vascular access has been established.

Fluid therapy

Crystalloids are the intravenous fluids of choice for initial resuscitation. Using albumin in patients who received large volumes of crystalloids is suggested.  Hydroxyethyl starches for intravascular volume replacement or gelatins are not recommended choices for fluid resuscitation.

Vasoactive medications

Norepinephrine is the first-line vasopressor for patients in septic shock. If norepinephrine is not available, epinephrine or dopamine can be used as an alternative. Special attention should be given to patients at risk for arrhythmias when using dopamine and epinephrine.

For patients receiving norepinephrine with inadequate MAP levels, adding vasopressin is suggested instead of escalating the dose of norepinephrine. Vasopressin is usually started when the dose of norepinephrine is in the range of 0.25−0.5 μg/kg/min.  If inadequate MAP levels persist despite norepinephrine and vasopressin, adding epinephrine is suggested.

The use of terlipressin is not recommended.

Adding dobutamine to norepinephrine or using epinephrine alone is suggested patients with cardiac dysfunction with persistent hypoperfusion despite adequate volume status and arterial blood pressure.  The use of levosimendan is not recommended.

Corticosteroids

The typical corticosteroid used in adults with septic shock is IV hydrocortisone at a dose of 200 mg/d given as 50 mg intravenously every 6 hours or as a continuous infusion. It is suggested that this is commenced at a dose of norepinephrine or epinephrine ≥ 0.25 mcg/kg/min at least 4 hours after initiation.

Blood products

A restrictive transfusion strategy is recommended and includes a hemoglobin concentration transfusion trigger of 70 g/L; however, RBC transfusion should not be guided by hemoglobin concentration alone. Assessment of a patient’s overall clinical status and consideration of extenuating circumstances such as acute myocardial ischemia, severe hypoxemia or acute hemorrhage is required.

Immunoglobulins

The use of intravenous immunoglobulins is not recommended in patients with sepsis or septic shock.

High-Flow Nasal Oxygen Therapy

High flow nasal oxygen over noninvasive ventilation is suggested for the treatment of sepsis-induced hypoxemic respiratory failure.

Acute Respiratory Distress Syndrome (ARDS)

A low tidal volume ventilation strategy (6 mL/kg) is recommended over a high tidal volume strategy (> 10 mL/kg) for the treatment of sepsis-induced acute respiratory distress syndrome (ARDS).  The upper limit goal for plateau pressures is 30 cm water.  Higher positive end-expiratory pressure (PEEP) and recruitment maneuvers in adult patients is preferred in sepsis-induced moderate-to-severe ARDS.  Prone positioning is recommended in adult patients with sepsis-induced ARDS for more than 12 hours a day.

Intermittent neuromuscular blocking agent boluses are preferred over continuous infusion.

When conventional mechanical ventilation fails, venovenous extracorporeal membrane oxygenation (VV-ECMO) may be used in experienced centers.

Glucose control

Initiation of insulin therapy at a glucose level of ≥ 180 mg/dL (10 mmol/L) is recommended.  Following initiation of an insulin therapy, a typical target blood glucose range is 144−180 mg/dL (8−10 mmol/L).

Renal replacement therapy

Continuous or intermittent forms of renal replacement therapy can be used in septic patients with acute kidney injury. 

Bicarbonate therapy

Sodium bicarbonate therapy may improve hemodynamics in patients with severe metabolic acidemia (pH ≤ 7.2) and AKI (AKIN score 2 or 3).

Venous thromboembolism prophylaxis

In the absence of contraindications, pharmacologic prophylaxis against venous thromboembolism (VTE) should be initiated. Low molecular weight heparins are preferred over unfractionated heparin for VTE.  Mechanical VTE is not recommended in addition to pharmacologic prophylaxis.

Stress ulcer prophylaxis

If a patient has risk factors for gastrointestinal bleeding, stress ulcer prophylaxis should be given.

Nutrition

Early initiation (within 72 hours) of enteral feeding is recommended in patients with sepsis or septic shock who can be fed enterally. 

Setting goals of care and palliative care

Goals of care and prognosis should be discussed with patients and their families or healthcare proxies as early as possible (within 72 hours).  

Principles of palliative care (which may include palliative care consultation based on clinician judgement) should be integrated into the treatment plan, when appropriate, to address patient and family symptoms and suffering.  

 

Medication Summary

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.[66]

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.

Nafcillin

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.

Ceftazidime (Fortaz, Tazicef)

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.

Levofloxacin (Levaquin)

Clinical Context:  Levofloxacin is used for infections caused by multidrug-resistant, gram-negative organisms.

Ampicillin

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.

Clindamycin (Cleocin)

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.

Gentamicin

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.

Tobramycin (TOBI)

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.

Amikacin

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.

Vancomycin

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.

Erythromycin (Erythrocin, E.E.S., Ery-Tab, EryPed)

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.

Azithromycin (Zithromax, Zmax)

Clinical Context:  Azithromycin is used to treat mild to moderate microbial infections.

Linezolid (Zyvox)

Clinical Context:  Linezolid provides gram-positive coverage, similar to vancomycin coverage.

Piperacillin/tazobactam (Zosyn)

Clinical Context:  This combination provides broad-spectrum coverage for gram-positive, gram-negative, and anaerobic bacteria. It does not cover MRSA.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Hydrocortisone (Solu-Cortef, Cortef)

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.

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Norepinephrine (Levarterenol, Levophed)

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.

Synthetic human angiotensin II (Giapreza)

Clinical Context:  Angiotensin II, the major bioactive component of the renin-angiotensin-aldosterone system (RAAS), serves as one of the body’s central regulators of blood pressure. It raises blood pressure by vasoconstriction and increased aldosterone release; direct action of angiotensin II on the vessel wall is mediated by binding to the G-protein–coupled angiotensin II receptor type 1 on vascular smooth muscle cells, which stimulates Ca2+/calmodulin-dependent phosphorylation of myosin and causes smooth muscle contraction. It is indicated for adults with septic or other distributive shock.

Vasopressin (ADH, Pitressin)

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.

Dopamine

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.

Class Summary

These agents augment coronary and cerebral blood flow present during a state of low blood flow.

Author

Klaus-Dieter Lessnau, MD, FCCP, Former Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory, Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Disclosure: Nothing to disclose.

Coauthor(s)

Chuan Jiang, MD, Physician, Lenox Hill Hospital, Northwell Health

Disclosure: Nothing to disclose.

Kevin Gerard G Lazo, DO, Pulmonologist, Englewood Health Physician Network

Disclosure: Nothing to disclose.

Oki Ishikawa, MD, Chief Resident Physician, Department of Internal Medicine, Lenox Hill Hospital, Northwell Health

Disclosure: Nothing to disclose.

Ruben Peralta, MD, FACS, FCCM, FCCP, Deputy Trauma Medical Director, Professor and Director of Trauma, Emergency and Critical Care Fellowship Program, Senior Consultant in Surgery, Trauma, Emergency and Critical Care Medicine, Associate Director of Trauma Intensive Care Unit, Hamad General Hospital and Hamad Medical Corporation, Weill Cornell Medical College in Qatar

Disclosure: Nothing to disclose.

Chief Editor

Ali H Al-Khafaji, MD, MPH, FACP, FCCP, FCCM, Professor of Critical Care Medicine, Professor of Surgery, University of Pittsburgh School of Medicine; Medical Director, Transplant Intensive Care Unit, Medical Director, ICU Telemedicine, Department of Critical Care Medicine, University of Pittsburgh Medical Center

Disclosure: Nothing to disclose.

Additional Contributors

Lalit K Kanaparthi, MD, Attending Physician, North Florida Lung Associates

Disclosure: Nothing to disclose.

Acknowledgements

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

Disclosure: Nothing to disclose.

Sarah C Langenfeld, MD Assistant Professor, Department of Psychiatry, University of Massachusetts Medical School; Attending Psychiatrist, Community HealthLink

Sarah Langenfeld, MD is a member of the following medical societies: American Medical Association, American Psychiatric Association, and Massachusetts Medical Society

Disclosure: Nothing to disclose.

Scott P Neeley, MD Medical Director, Intensive Care Unit, St Alexius Medical Center

Scott P Neeley, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American Thoracic Society, Phi Beta Kappa, and Sigma Xi

Disclosure: Nothing to disclose.

Daniel R Ouellette, MD, FCCP Associate Professor of Medicine, Wayne State University School of Medicine; Consulting Staff, Pulmonary Disease and Critical Care Medicine Service, Henry Ford Health System

Daniel R Ouellette, MD, FCCP is a member of the following medical societies: American College of Chest Physicians and American Thoracic Society

Disclosure: Nothing to disclose.

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

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An 8-year-old boy developed septic shock secondary to Blastomycosis pneumonia. Fungal infections are a rare cause of septic shock.

A 28-year-old woman who was a previous intravenous drug user (human immunodeficiency virus [HIV] status: negative) developed septic shock secondary to bilateral pneumococcal pneumonia.

An 8-year-old boy developed septic shock secondary to Blastomycosis pneumonia. Fungal infections are a rare cause of septic shock.

A 28-year-old woman who was a previous intravenous drug user (human immunodeficiency virus [HIV] status: negative) developed septic shock secondary to bilateral pneumococcal pneumonia.

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.

Ultrasound clip demonstrating a collapsing inferior vena cava (IVC) on inspiration. A change in IVC diameter with respiration of at least 12-18% has been associated with fluid responsiveness (defined as an increase in cardiac output of >15% after a fluid bolus).

Lung ultrasound image over one lung zone showing the A-line pattern. This represents normal aeration and absence of pulmonary edema. A patient who demonstrates this pattern in conjunction with an inferior vena cava diameter that shows respirophasic variation of at least 12-18% will likely be fluid responsive.

Diagnosis Pulmonary Capillary Wedge Pressure Cardiac Output
Cardiogenic shock*IncreasedDecreased
Extracardiac obstructive shock



1. Pericardial tamponade†



2. Pulmonary embolism



Increased



Normal or decreased



Decreased



Decreased



Hypovolemic shockDecreasedDecreased
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
Dobutamine2-20 mcg/kg/minBeta 1++++
Dopamine



(low dose)



5-10 mcg/kg/minBeta 1, dopamine++++
Epinephrine (low dose)0.06-0.20 mcg/kg/minBeta 1, beta 2 >alpha++++
Inotropic agents and vasoconstrictors
Dopamine (high dose)>10 mcg/kg/minAlpha, beta 1, dopamine+++++
Epinephrine



(high dose)



0.21-0.42 mcg/kg/minAlpha >beta 1, beta 2+++++
Norepinephrine0.02-0.25 mcg/kg/minAlpha >beta 1, beta 2+++++
Vasoconstrictors
Synthetic human angiotensin II20 ng/kg/min; up to 80 ng/kg/min during first 3 h of therapy



Maintenance: 1.25-40 ng/kg/min



Renin-angiotensin-aldosterone system (RAAS)+/-+++/-
Phenylephrine0.2-2.5 mcg/kg/minAlpha+++++
Vasopressin0.10-0.40 U/minV1 receptor++++
Vasodilators
Dopamine



(very low dose)



1-4 mcg/kg/minDopamine+/-+/--
Milrinone0.4-0.6 mcg/kg/min after loading dose; 50 mcg/kg bolus over 5 minPhosphodiesterase 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.[61]



Suspected Source Recommended Antibiotic Therapy Alternative Therapy
No source evident in a healthy hostThird-generation cephalosporin, eg, ceftriaxone 2 g IV q12h, ceftizoxime, ceftazidimeNafcillin and aminoglycoside, imipenem, piperacillin/tazobactam
No source evident in an immunocompromised hostCeftazidime 2 g IV q8h plus aminoglycosideImipenem or piperacillin/tazobactam plus aminoglycoside
No source evident in a user of intravenous drugsNafcillin 2 g IV q4h plus aminoglycosideVancomycin plus aminoglycoside, ceftazidime, imipenem, or piperacillin/tazobactam
Bacterial pneumonia, community acquiredCeftriaxone 2 g IV q12-24 h plus macrolideLevofloxacin 750mg IV q24h, cotrimoxazole or imipenem plus macrolide
Bacterial pneumonia, hospital acquiredPiperacillin/tazobactam 4.5 g IV q6h plus aminoglycoside, plus levofloxacin 750 mg IV q24hImipenem plus aminoglycoside, plus macrolide
Urinary tract infectionAmpicillin 2 g IV q4h plus aminoglycosideFluoroquinolone or third-generation cephalosporin plus aminoglycoside
Mixed aerobic and anaerobic abdominal sepsis, aspiration pneumonia, pelvic infection, and necrotizing cellulitisThird-generation cephalosporin or ampicillin 2 g IV q4h plus aminoglycoside plus clindamycin 600 mg IV q8h or metronidazole 500 mg IV q6hFluoroquinolone plus clindamycin, imipenem, piperacillin/tazobactam
MeningitisCeftriaxone 2 g IV q12h plus vancomycinMeropenem plus vancomycin, chloramphenicol plus cotrimoxazole plus vancomycin
Cellulitis/erysipelasNafcillin 2 g IV q4hCefazolin, vancomycin, clindamycin
Toxic shock syndrome (TSS) or streptococcal necrotizing fasciitisClindamycin 600 mg IV q8hCephalosporin, vancomycin, nafcillin