eMedicine Specialties > Critical Care > Medical Topics

Shock, Distributive

Lalit K Kanaparthi, MD, Fellow in Pulmonary Medicine, Lenox Hill Hospital
Klaus-Dieter Lessnau, MD, FCCP, 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; Ruben Peralta, MD, FACS, Professor of Surgery, Anesthesia and Emergency Medicine, Senior Medical Advisor, Board of Directors, Program Chief of Trauma, Emergency and Critical Care, Consulting Staff, Professor Juan Bosch Trauma Hospital, Dominican Republic; Sarah Guzofski, MD, Staff Physician, Department of Psychiatry, University of Massachusetts Medical School; Scott P Neeley, MD, Medical Director, Intensive Care Unit, St Alexius Medical Center; Consulting Staff, Chest Medicine Consultants

Updated: Mar 4, 2009

Introduction

Background

Shock is a clinical syndrome characterized by inadequate tissue perfusion that results in end-organ dysfunction. Shock can be divided into the following 4 categories:

• Distributive shock (vasodilation), which is a hyperdynamic process
• Cardiogenic shock (pump failure)
• Hypovolemic shock (intravascular volume loss)
• Obstructive shock (blood vessels and heart)

This article discusses distributive shock.

Distributive shock has several causes. Septic shock is the most common form of distributive shock, with considerable mortality. In the United States, this is the leading cause of noncardiac death in intensive care units (ICUs). Other causes of distributive shock include systemic inflammatory response syndrome (SIRS) due to noninfectious inflammatory conditions like burns & pancreatitis; toxic shock syndrome (TSS); anaphylaxis; drug or toxin reactions, including insect bites, transfusion reaction, and heavy metal poisoning; Addisonian crisis; hepatic insufficiency; and neurogenic shock due to brain or spinal cord injury.

Pathophysiology

In distributive shock, the inadequate tissue perfusion is caused by decreased systemic vascular resistance (SVR) and a high cardiac output.  The early changes are primarily characterized by the evolution of changes in contractility and dilation of peripheral small vessels and the impact of resuscitation efforts. 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 a possible drug targets.

Cytokines and phospholipids-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 American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference Committee defined the following 4 clinical subcategories of systemic inflammatory response:¹

• Systemic inflammatory response with 2 or more of the following:
• A core temperature of higher than 38° C or lower than 36° C
• A heart rate of more than 90 beats per minute; respiratory rate of more than 20 breaths per minute; WBC count of more than 12,000 10³/µL, less than 4,000 10³/µL, or more than 10% bands.
• Systemic inflammatory response with sepsis - Meets criteria for SIRS, source of infection is presumed or confirmed
• Systemic inflammatory response with severe sepsis - Sepsis plus hypoperfusion and dysfunction or organs, as evidenced by hypotension (systolic blood pressure of more than 90 mm Hg or a decrease of more than 40 mm Hg from baseline), lactic acidosis, oliguria, a change in mental status
• Systemic inflammatory response with septic shock - Severe sepsis in a patient who does not respond to intravenous fluid resuscitation and vasopressors   

The coagulation cascade is also affected.  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 nervous system.

Frequency

United States

Sepsis develops in more than 750,000 patients per year. Angus and colleagues have estimated that, by 2010, 1 million people per year will be diagnosed with sepsis.⁴ From 1979-2000, the incidence of sepsis has increased by 9% per year.

International

Sepsis is a common cause of death throughout the world and kills approximately 1,400 people worldwide every day.^5,6

Mortality/Morbidity

• The mortality rate after development of septic shock is 20-80%.⁷ Recent data suggest that mortality due to septic shock has decreased slightly from new therapeutic interventions.⁸
• Higher mortality rates have been associated with advanced age, the finding of positive blood cultures, infection with antibiotic-resistant organisms such as Pseudomonas aeruginosa, elevated serum lactate levels, impaired immune function, alcohol use, and poor functional status prior to the onset of sepsis.
• Mortality rates associated with other forms of distributive shock are not well documented.

Age

Increased age correlates with increased risk of death from sepsis.

Clinical

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.
• 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 HIV-infected patients that varies with the criteria used to diagnose adrenal insufficiency.⁹
  • 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 also be a cause of distributive shock; expect symptoms of abdominal pain that radiate to the back and nausea and vomiting.
  • Burns have been described as a cause of distributive shock.

Physical

• Cardinal features of distributive shock include the following:
  • Change in mental status
  • Heart rate - Greater than 90 beats per minute (Note that heart rate elevation is not evident if the patient is on a beta-blocker.)
  • Hypotension - Systolic blood pressure less than 90 mm Hg or a reduction of 40 mm Hg from baseline
  • Respiratory rate - Greater than 20 breaths per minute
  • Extremities - Frequently warm with bounding pulses and increased pulse pressure (systolic minus diastolic blood pressure) in early shock (Late shock may present as critical organ dysfunction.)
  • Hyperthermia - Core body temperature greater than 38.3° C or 101° F
  • Hypothermia - Core body temperate less than 36° C or 96.8° F
  • Pulse oximetry - Relative hypoxemia
  • Decreased urine output
• Underlying infection
  • Pneumonia
    • Dullness to percussion
    • Rhonchi
    • Crackles
    • Bronchial breath sounds
  • Urinary tract infection
    • Costovertebral angle tenderness
    • Suprapubic tenderness
    • Dysuria & polyuria
  • Intra-abdominal infection or acute abdomen
    • Focal or diffuse tenderness to palpation
    • Diminished or absent bowel sounds
    • Rebound tenderness
  • Gangrene or soft tissue infection
    • Pain out of proportion to lesion
    • Skin discoloration & ulceration
    • Desquamating rash
    • Areas of subcutaneous necrosis
• Anaphylaxis
  • Respiratory distress
  • Wheezing
  • Urticarial rash
  • Angioedema
• Toxic shock syndrome
  • High fever
  • Diffuse rash with desquamation on the palms and soles over a subsequent 1-2 weeks
  • Hypotension (may be orthostatic) and evidence of involvement of 3 other organ systems
  • Streptococcal TSS more frequently presents with focal soft tissue inflammation and is less commonly associated with diffuse rash.
• Adrenal insufficiency
  • Hyperpigmentation of skin, oral, vaginal, and anal mucosal membranes may be present in chronic adrenal insufficiency.
  • In acute or acute-on-chronic adrenal insufficiency brought on by physiologic stress, hypotension may be the only physical sign.

Causes

The most common etiology of distributive shock is sepsis. Other causes include SIRS due to noninfectious conditions such as pancreatitis, burns and trauma, TSS, anaphylaxis, adrenal insufficiency, drug or toxin reactions, heavy metal poisoning, hepatic insufficiency, and neurogenic shock. All these conditions share the common characteristic of hypotension due to decreased systemic vascular resistance 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 the gram-negative bacteria which in the past were considered to be the predominant organisms. Multidrug-resistant organisms are increasingly common.¹⁰
• SIRS (see ACCP/SCCM definition in the Pathophysiology section)
  • Infection
  • Burns
  • Surgery
  • Trauma
  • Pancreatitis
  • Fulminant hepatic failure
• Toxic shock syndrome
  • Streptococcus pyogenes (group A Streptococcus)
  • Staphylococcus aureus
• Adrenal insufficiency
  • Destruction of adrenal glands due to autoimmune disease, infection (tuberculosis, fungal infection, AIDS), hemorrhage, cancer, or surgical removal
  • Suppression of hypothalamic-pituitary-adrenal axis by exogenous steroid
  • Hypopituitarism
  • Metabolic failure in hormone production due to congenital conditions or drug-induced inhibition of synthetic enzymes (eg, metyrapone, ketoconazole)
• Anaphylaxis
  • Drugs such as penicillins and cephalosporins
  • Heterologous proteins such as Hymenoptera venom, foods, pollen, and blood serum products

Differential Diagnoses

Other Problems to Be Considered

Burns
Carbon monoxide poisoning
Drug reaction
Heavy metal poisoning
Insect bite
Major surgery
Neurogenic shock
Thyrotoxicosis

Workup

Laboratory Studies

• All patients with evidence of distributive shock should undergo the following studies:
  • CBC count with differential
  • Urinalysis
  • Electrolytes
  • BUN
  • Creatinine
  • Glucose
  • Urine cultures
  • Blood cultures
  • Arterial blood gas
  • Serum lactate if metabolic acidosis or elevated anion gap is present
• If pneumonia is suspected, sputum Gram stain and culture should be performed.
• All patients with a suspected intraabdominal pathologic condition or hepatic insufficiency should undergo the following studies:
  • Serum bilirubin
  • Alkaline phosphatase
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT)
  • Prothrombin time (PT)/activated partial thromboplastin time (aPTT)/ INR (International Normalized Ratio)
  • Amylase, lipase 
• All patients with suspected disseminated intravascular coagulation (DIC) should undergo the following studies:
  • Obtain PT, aPTT, fibrin split products, D-dimer assay, fibrinogen level, and platelet count.
  • Examine peripheral blood smear for signs of erythrocyte microangiopathic changes, such as schistocytes.

Imaging Studies

Imaging studies may be integral to defining the source of infection and identifying areas in need of drainage. 

• All patients should undergo chest radiography.
• With the advent of CT scanning, the use of abdominal radiography has become less common in the diagnostic workup of shock. These studies may not be sensitive enough to reveal intra-abdominal pathologic conditions.
• In suspected cases of cholecystitis or pancreatitis, abdominal ultrasound is most useful to assess for cholelithiasis, biliary dilatation, and fluid collections around the gallbladder or the head of the pancreas.
• CT scanning is the diagnostic test of choice for suspected intra-abdominal cause 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.

Other Tests

• EKG should be performed to examine for evidence of underlying cardiac pathologic conditions (left ventricular hypertrophy, cor pulmonale, low voltage, bundle branch block) or acute changes of ischemia or pericarditis.
• Point-of-care ultrasonography/echocardiography may be performed at the bedside in the critically ill patients to evaluate the cardiac function, fluid status, response to hemodynamic intervention, and exclude tamponade.

Procedures

• 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; however, recent data 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 recent 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.^11,12 See Table 1
• Table 1. Pulmonary Artery Catheter Findings in Common Shock States

  Diagnosis	Pulmonary Capillary  Wedge Pressure	Cardiac Output
  Cardiogenic shock*	Increased	Decreased
  Extracardiac obstructive shock 1. Pericardial tamponade† 2. Pulmonary embolism	Increased                                  Normal or decreased	DecreasedDecreased
  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, PA end-diastolic, and pulmonary capillary wedge pressures.

• Arterial catheter placement should be considered in hemodynamically unstable patients who are receiving continuous infusions of vasoactive drugs, or those patients requiring frequent arterial blood gas measurements (eg, patients on mechanical ventilation).
• Transthoracic (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: it is time consuming, operator dependent, and limited by pre-existing 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 include the following:
• 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.
• PiCCO, LiCO, and FloTrac: Via an arterial catheter, cardiac output 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.
• Measurement of total circulating blood volume (TCBV) is measured using indocyanine green infusion and 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 the early goal-directed therapy in shock.

Treatment

Medical Care

All patients with distributive shock should be admitted to an ICU. Vital signs, fluid intake and output should be measured and charted on an hourly basis. Daily weights should be obtained. 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, as discussed in the Procedures section. 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. This avoids 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).

Resuscitation

Early efficient resuscitation is the key. The duration of hypotension before antibiotic treatment was recently 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. 

The SSC 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 a 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. 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 SAFE trial found crystalloid and colloid to be equally safe and as effective for ICU patients. in contrast to prior studies, it also found no difference or increased mortality among those patients receiving albumin.

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.¹⁴

In patients with hypotension due to sustained septic shock in whom fluid resuscitation does not reverse hypotension, the use of a 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 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).

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 systemic vascular resistance and may be considered in patients who are refractory to inotropic agents in whom cardiac output 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.

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 its use, a recent randomized trial of adding vasopressin to ongoing norepinephrine treatment did not find a benefit of vasopressin over norepinephrine, suggesting that additional investigation will be required to define its role.¹⁵

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.

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 are suspected clinically.

Patients who receive prompt effective antimicrobial therapy are more likely to survive than those patients whose antibiotic therapy is delayed; measurable increases in mortality occur for each hour 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. Choice of agent should be guided by history, suspected site of infection, co-morbid diseases, 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 anti-fungal agent should be guided by the local prevalence of Candida species. Recommended empiric antibiotic regimens based on suspected site are outlined in Table 3, below.

Antimicrobial regimens should be tailored once the causative pathogen and its susceptibility is identified because narrow-spectrum treatment decrease 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). See the Surgical Care section for more details.

Preventing microvascular thrombosis

This has become a key strategy for preventing sepsis-related organ failure. Disseminated intravascular coagulation is a critical factor to drive the progression of sepsis. Activated protein C (APC), an endogenous protein that decreases thrombosis and inflammation, has become central to the treatment of severe sepsis.

• Three large clinical trials have been completed using APC. In the patient in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study, APC was shown to decrease the mortality from severe sepsis at 28 days from 31% to 25%. However, additional follow-up in these patients shows no benefit in long-term mortality. Serious bleeding risk increased from 2% in control patients to 3.5% in study patients. The greatest benefit was demonstrated in patients with severe sepsis (acute physiology and chronic health evaluation [APACHE] II > 25).¹⁶
• The Extended Evaluation of Recombinant Human Activated Protein C (ENHANCE) nonrandomized open-label trial also demonstrated a decreased 28-day mortality similar to that of the PROWESS study and also found that activated protein C carries an increased risk of bleeding. Risk of intracranial hemorrhage was increased (1.5% in those treated with APC vs 0.2% in the control patients) and fatal hemorrhage was 0.5% in the APC group, compared with 0.2% in the non-APC group.¹⁷
• The Administration of drotrecogin alfa (activated) Early Stage Severe Sepsis (ADDRESS) trial evaluated patients with APACHE II scores higher than 25 or single organ failure. The study was discontinued at the interim analysis; no mortality benefit was observed and bleeding risk was increased. Patients with recent surgery (subgroup analysis) had an increased mortality (21% vs 14%).¹⁸
• The most recent SSC recommendations suggest treating patients with sepsis-induced multiple organ failure and high mortality risk (usually with APACHE II score >25) with APC unless contraindications (eg, bleeding risk) outweigh the potential benefits. APC is not recommended for patients at low risk of death, with single organ failure, or with APACHE II scores of less than 20.

Corticosteroids

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 both 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.

In contrast to prior studies, a recent multi-site double-blind placebo-controlled trial found that low-dose hydrocortisone did not affect mortality at 28 days, although those 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 recent findings that suggest the 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.

Prophylaxis

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

Glucose

Protocol-driven management of glucose (target <150 mg/dL) is recommended, with monitoring every 1-2 hours until glucose levels are stable, then every 4 hours thereafter. This SSC recommendation is based on studies that found decreased morality, 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.

Newer therapies

Hemoglobin-based nitric oxide scavenger, pyridoxalated hemoglobin polyoxyethylene (PHP), is a NO scavenger that has been shown to increase systemic blood pressure and reduce vasopressor and ventilation needs in patients with nitric oxide–induced shock without adversely affecting cardiac output, organ function, or survival. The results of its use in distributive shock in a phase II multicenter, randomized, placebo controlled study have been promising, but further studies are needed to provide a definitive answer.

Anaphylactic shock

If anaphylaxis is suspected, 0.2-0.5 mL SC 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 IM or IV may be administered for urticaria or angioedema. Inhaled bronchodilators or intravenous aminophylline can be administered for bronchospasm.  

Surgical Care

Effective treatment of shock includes a multidisciplinary approach. 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. 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:

• Removal of infected catheters, infected prosthesis, and foreign bodies
• Drainage (operative, endoscopic, percutaneous) of intra-abdominal abscess, postoperative collections, soft tissue abscess, and gallbladder sludge
• Debridement of devitalized (traumatic or infected) tissue, pancreatic necrosis, and soft tissue infections
• Operative resection of inflamed, infarcted, ischemic, and perforated hollow viscus
• Amputation of gangrenous extremities

Consultations

• Consultation with a critical care specialist
  • 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 an 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.
• Consultation with a 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).

Diet

• Once the initial phase of resuscitation is complete, promptly institute nutritional support, usually within 24 hours.
• 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.

Medication

Initial drug therapy in distributive shock is discussed in the Medical Care section and summarized in Table 1 and Table 2 in the Medical Care section.

Antibiotics

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

Ceftazidime (Ceptaz, Fortaz, Tazicef, Tazidime)

Third-generation cephalosporin with broad-spectrum gram-negative activity, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.

Dosing

Adult

2 g IV q8h

Pediatric

Not established

Interactions

Nephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid; probenecid may increase ceftazidime levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Adjust dose in renal impairment

Nafcillin (Nafcil, Unipen)

Initial therapy for suspected penicillin G–resistant streptococcal or staphylococcal infections. Use parenteral therapy initially in severe infections. Change to oral therapy as condition warrants. Because of thrombophlebitis, particularly in elderly patients, administer parenterally only for short term (1-2 d); change to oral route as clinically indicated.

Dosing

Adult

2 g IV q4h

Pediatric

Not established

Interactions

Associated with warfarin resistance when administered concurrently; effects may decrease with bacteriostatic action of tetracycline derivatives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

To optimize therapy, determine causative organisms and susceptibility; >10 d of treatment is needed to eliminate infection and to prevent sequelae (eg, endocarditis, rheumatic fever); obtain cultures after treatment to confirm that infection is eradicated

Levofloxacin (Levaquin)

For infections due to multidrug-resistant gram-negative organisms.

Dosing

Adult

750 mg IV q24h

Pediatric

Not established

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; levofloxacin reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Ampicillin (Marcillin, Omnipen, Polycillin)

Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.

Dosing

Adult

2 g IV q4h

Pediatric

Not established

Interactions

Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes that cause RNA-dependent protein synthesis to arrest.

Dosing

Adult

600 mg IV q8h

Pediatric

Not established

Interactions

Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin

Contraindications

Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Gentamicin (Garamycin, Gentacidin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with an agent against gram-positive organisms and one that covers anaerobes.
Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM.

Dosing

Adult

2 mg/kg IV when using multiple daily dosing
5-7 mg/kg/d IV when once daily dosing used

Pediatric

Not established

Interactions

Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)

Contraindications

Documented hypersensitivity; non–dialysis-dependent renal insufficiency

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Tobramycin (Nebcin)

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.

Dosing

Adult

2 mg/kg IV/IM bid/qid or 5-7 mg/kg IV/IM qd; subsequent dosing is individualized based on renal function

Pediatric

Not established

Interactions

Increases effects of neuromuscular blockers and potentiates effect of extended-spectrum penicillins; concurrent administration with amphotericin B, cephalosporins, and loop diuretics increases risk of nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Avoid use in renal impairment, preexisting auditory or vestibular impairment, and in patients with neuromuscular disorders; aminoglycosides are associated with nephrotoxicity and ototoxicity

Amikacin (Amikin)

Irreversibly binds to 30S subunit of bacterial ribosomes; blocks recognition step in protein synthesis; causes growth inhibition. Use the patient's IBW for dosage calculation.

Dosing

Adult

7.5 mg/kg IV bid/qid or 15 mg/kg/d IV qd; individualize subsequent dosing based on renal function

Pediatric

Not established

Interactions

Coadministration with other aminoglycosides, penicillins, cephalosporins, and amphotericin B increases nephrotoxicity; enhances effects of neuromuscular blocking agents; causes respiratory depression; irreversible hearing loss may occur with coadministration of loop diuretics

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Not intended for long-term therapy; caution in patients with renal failure (not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission

Vancomycin (Vancocin, Vancoled)

Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in the treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined with an agent active against enteric flora and anaerobes.
To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use CrCl to adjust dose in patients diagnosed with renal impairment.
Used in conjunction with gentamicin for prophylaxis in patients allergic to penicillin undergoing gastrointestinal or genitourinary procedures.

Dosing

Adult

15 mg/kg IV q12h; individualize dosing based on renal function

Pediatric

Not established

Interactions

Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; when taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in renal failure, neutropenia; red man syndrome is caused by too rapid IV infusion (dose administered over a few minutes) but rarely happens when dose is administered as a 2-hour administration or as PO or IP administration; red man syndrome is not an allergic reaction

Erythromycin (Erythrocin, Eryc, E-Mycin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes that cause RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.
In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.

Dosing

Adult

15 mg/kg IV q6h, up to 4 g/d

Pediatric

Not established

Interactions

Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis

Contraindications

Documented hypersensitivity; hepatic impairment

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Azithromycin (Zithromax)

Treats mild-to-moderate microbial infections

Dosing

Adult

500 mg IV qd

Pediatric

Not established

Interactions

May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine

Contraindications

Documented hypersensitivity; hepatic impairment; do not administer with pimozide

Precautions

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients

Corticosteroids

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

Dexamethasone (Decadron)

For various allergic and inflammatory diseases. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Dosing

Adult

0.4 mg/kg IV q12h for 48 h, first dose administered with or just before antibiotics

Pediatric

Not established

Interactions

Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; dexamethasone decreases effect of salicylates and vaccines used for immunization

Contraindications

Documented hypersensitivity; fungal infection

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Increases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use

Vasopressors

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

Dopamine (Intropin)

Stimulates both adrenergic and dopaminergic receptors. Hemodynamic effect is dependent on the dose. 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 dose by 1-4 mcg/kg/min q10-30min until optimal response is obtained. More than 50% of patients are maintained satisfactorily on doses less than 20 mcg/kg/min.

Dosing

Adult

>10 mcg/kg/min IV, effects similar to norepinephrine

Pediatric

Not established

Interactions

Phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects of dopamine

Contraindications

Documented hypersensitivity; pheochromocytoma; ventricular fibrillation

Precautions

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Tachycardia may limit use; phenytoin, alpha- and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects of dopamine

Follow-up

Further 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 they 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 capable of delivering and monitoring mechanical ventilation and invasive monitoring devices such as PA catheters and arterial lines.
• Modern surgical facilities, a radiology department equipped with ultrasound and CT scanner, 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, cardiac, or neurosurgical problems or units where organ transplantation is available.

Patient Education

For excellent patient education resources, visit eMedicine's Shock Center and Public Health Center. Also, see eMedicine's patient education articles Shock and Cardiopulmonary Resuscitation (CPR).

Miscellaneous

Medicolegal Pitfalls

• Failure to begin prompt antibiotic therapy
• Failure to electively intubate and mechanically ventilate, resulting in cardiopulmonary arrest
• Failure to localize site of infection, particularly when surgical drainage is indicated
• Failure to obtain appropriate consultation, such as infectious disease or surgical consults
• Failure to provide prophylaxis against venous thromboembolic disease, gastric bleeding, and pressure ulcers of the skin
• Failure to recognize and treat secondary infections, such as line infection, urinary catheter-associated infection, and nosocomial or ventilator-associated pneumonia
• Failure to provide nutritional support

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Keywords

distributive shock, end-organ dysfunction, hypotension, systemic vascular resistance, SVR, septic shock, systemic inflammatory response syndrome, SIRS, toxic shock syndrome, TSS, anaphylaxis, drug reactions, toxin reactions, transfusion reaction, heavy metal poisoning, addisonian crisis, hepatic insufficiency, neurogenic shock

Contributor Information and Disclosures

Author

Lalit K Kanaparthi, MD, Fellow in Pulmonary Medicine, Lenox Hill Hospital
Lalit K Kanaparthi, MD is a member of the following medical societies: American College of Chest Physicians, American Medical Association, and American Thoracic Society
Disclosure: Nothing to disclose.

Coauthor(s)

Klaus-Dieter Lessnau, MD, FCCP, 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
Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Society for Artificial Internal Organs, American Thoracic Society, Physicians for Social Responsibility, and Society of Critical Care Medicine
Disclosure: sepracor Ownership interest None

Ruben Peralta, MD, FACS, Professor of Surgery, Anesthesia and Emergency Medicine, Senior Medical Advisor, Board of Directors, Program Chief of Trauma, Emergency and Critical Care, Consulting Staff, Professor Juan Bosch Trauma Hospital, Dominican Republic
Ruben Peralta, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, Association for Academic Surgery, Eastern Association for the Surgery of Trauma, Massachusetts Medical Society, Society of Critical Care Medicine, and Society of Laparoendoscopic Surgeons
Disclosure: Nothing to disclose.

Sarah Guzofski, MD, Staff Physician, Department of Psychiatry, University of Massachusetts Medical School
Sarah Guzofski, 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; Consulting Staff, Chest Medicine Consultants
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.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

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: Boehringer Ingleheim Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, Professor of Critical Care Medicine, Bioengineering, Cardiovascular Diseases and Anesthesiology, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center
Michael R Pinsky, MD, CM is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Association of University Anesthetists, Shock Society, and Society of Critical Care Medicine
Disclosure: LiDCO Ltd Honoraria Consulting; iNTELOMED Intellectual property rights Board membership; Edwards Lifesciences Honoraria Consulting; Applied Physiology, Ltd Honoraria Consulting; Cheetah Medical Consulting fee Consulting

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