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Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock

Evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock
Authors:
David F Gaieski, MD
Mark E Mikkelsen, MD, MSCE
Section Editors:
Polly E Parsons, MD
Robert S Hockberger, MD, FACEP
Deputy Editor:
Geraldine Finlay, MD
Literature review current through: Sep 2021. | This topic last updated: Feb 23, 2021.

INTRODUCTION — Shock is a life-threatening condition of circulatory failure that most commonly presents with hypotension. It can also be heralded by other vital sign changes or the presence of elevated serum lactate levels. The effects of shock are initially reversible but can rapidly become irreversible, resulting in multi-organ failure (MOF) and death. Thus, when a patient presents with undifferentiated hypotension and/or is suspected of having shock, it is important that the clinician rapidly identify the etiology so that appropriate therapy can be administered to prevent MOF and death [1,2].

This topic reviews the clinical presentation as well as the initial diagnostic and therapeutic approaches to the adult patient with hypotension and suspected shock of unknown etiology (ie, undifferentiated shock). The definition, classification, etiology, and pathophysiology of shock are discussed separately. (See "Definition, classification, etiology, and pathophysiology of shock in adults".)

DEFINITION AND CLASSIFICATION — Shock is defined as a state of cellular and tissue hypoxia due to reduced oxygen delivery and/or increased oxygen consumption or inadequate oxygen utilization. This most commonly occurs when there is circulatory failure manifest as hypotension (ie, reduced tissue perfusion). “Undifferentiated shock” refers to the situation where shock is recognized, but the cause is unclear.

While patients often have a combination of more than one form of shock (multifactorial shock), four classes of shock are recognized (table 1):

Distributive (eg, septic shock, systemic inflammatory response syndrome, neurogenic shock, anaphylactic shock, toxic shock, end-stage liver disease, endocrine shock)

Cardiogenic (eg, myocardial infarction, atrial and ventricular arrhythmias, valve or ventricle septal rupture)

Hypovolemic (eg, hemorrhagic and nonhemorrhagic fluid losses)

Obstructive (eg, pulmonary embolism, pulmonary hypertension, tension pneumothorax, constrictive pericarditis, restrictive cardiomyopathy)

Detailed discussion of the classification, etiology, and pathogenesis of shock is provided separately. (See "Definition, classification, etiology, and pathophysiology of shock in adults".)

WHEN TO SUSPECT SHOCK

Clinical manifestations — The clinical findings associated with undifferentiated shock (ie, cause unknown) vary according to the etiology and stage of presentation (pre-shock, shock, end-organ dysfunction) (see "Definition, classification, etiology, and pathophysiology of shock in adults", section on 'Stages of shock'). Features that are highly suspicious of shock include:

Hypotension

Tachycardia

Oliguria

Abnormal mental status

Tachypnea

Cool, clammy, cyanotic skin

Metabolic acidosis

Hyperlactatemia

Most clinical features are neither sensitive nor specific for the diagnosis of shock. However, many of the clinical manifestations provide clues to the underlying etiology and are primarily used to narrow the differential diagnosis so that empiric therapies can be administered in a timely fashion.

Features of shock — The typical clinical features that raise the suspicion for shock include the following:

Hypotension – Hypotension occurs in the majority of patients with shock. Hypotension may be absolute (eg, systolic blood pressure <90 mmHg; mean arterial pressure <65 mmHg), relative (eg, a drop in systolic blood pressure >40 mmHg), orthostatic (>20 mmHg fall in systolic pressure or >10 mmHg fall in diastolic pressure with standing), or profound (eg, vasopressor-dependent).

Importantly, patients in the early stages of shock can be normotensive or hypertensive, such that hypotension does not have to be present for the diagnosis. Conversely, not every patient who has hypotension has shock (eg, chronic hypotension, drug-induced hypotension, autonomic dysfunction, vasovagal syncope, peripheral vascular disease).

Tachycardia – Tachycardia is an early compensatory mechanism in patients with shock. It can be isolated or occur in association with hypotension. Importantly, compared with older patients, younger patients develop severe and persistent tachycardia before becoming hypotensive late in the course of shock, a compensatory feature that frequently deflects attention away from the possibility of the presence of shock in this population. Given the frequency of beta-blocker use, awareness of concurrent medications is important to incorporate into the clinical assessment of suspected shock.

Tachypnea – Tachypnea is an early compensatory mechanism in patients with shock and metabolic acidosis specifically. While elevations in respiratory rate are common amongst hospitalized patients [3], it is a useful tool to identify patients at risk of clinical deterioration, as evidenced by its incorporation into the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) score [4].

Oliguria – Oliguria in shock can be due to shunting of renal blood flow to other vital organs, direct injury to the kidney (eg, aminoglycoside toxicity), or due to intravascular volume depletion (eg, from vomiting, diarrhea, or hemorrhage).

Mental status changes – Altered sensorium in shock is usually due to poor perfusion or metabolic encephalopathy. It is a continuum that begins with agitation, progresses to confusion or delirium, and ends in obtundation or coma.

Cool skin – Cool, clammy skin is due to compensatory peripheral vasoconstriction that redirects blood centrally, to maintain vital organ perfusion (ie, coronary, cerebral, and splanchnic flow). A cyanotic, mottled appearance is a late and worrisome feature of shock. However, the appearance of cool, clammy or cyanotic skin may also be due to, or exacerbated by, ischemia from underlying peripheral arterial vascular disease. Importantly, warm, hyperemic skin does not ensure the absence of shock because such an appearance may be present in patients with early distributive shock (prior to the onset of compensatory vasoconstriction) or terminal shock (due to failure of compensatory vasoconstriction).

Metabolic acidosis – In general, the demonstration of a high anion gap metabolic acidosis should always raise the clinical suspicion for the presence of shock. Importantly, the presence of a metabolic acidosis in states of shock is not specific and can also be due to acute kidney injury or toxin ingestion. (See "Simple and mixed acid-base disorders".)

Hyperlactatemia – Either in conjunction with metabolic acidosis or not, the presence of an elevated serum lactate level has been associated with adverse outcomes, including the development of shock [5]. The relationship between hyperlactatemia and mortality has been reproduced across a number of clinical conditions, including trauma, sepsis, and post-cardiac arrest.

Features due to the underlying cause — Due to the wide range of etiologies for shock, the presenting features can be variable and frequently overlap. However, they facilitate the early identification of the etiology of shock as well as organ failure due to shock, details of which are provided in the sections below.

History and examination (see 'Differential diagnosis' below)

Laboratory tests (see 'Laboratory evaluation' below)

Imaging (see 'Imaging' below)

INITIAL APPROACH — The initial approach to patients with undifferentiated hypotension/shock is shown in the algorithms (algorithm 1A-B). When feasible, a multidisciplinary, team-based approach is preferred because it allows the simultaneous evaluation and administration of therapy to patients with hypotension and shock. In brief:

The airway should be stabilized and adequate intravenous access secured so that patients can be immediately treated with intravenous fluids to restore adequate tissue perfusion. Importantly, resuscitative efforts, particularly intravenous fluids, should not be delayed for a detailed clinical assessment, nor should clinicians be conservative in terms of fluid resuscitation to patients with heart failure or kidney injury as a rule. Related to the latter point, liberal fluid resuscitation appeared to be life-saving in septic patients with intermediate serum lactate levels, a benefit derived amongst these traditionally underresuscitated sepsis subgroups [6]. (See 'Assess airway, breathing, circulation' below.)

Patients should be assessed for the need for an immediate or early intervention so that lifesaving therapies can be administered promptly. (See 'Risk stratification' below.)

Critically ill patients who have been stabilized and patients with mild hypotension or early shock should undergo a more formal diagnostic approach while initial resuscitative therapies are ongoing. (See 'Initial diagnostic evaluation' below and 'Hemodynamic support' below.)

Importantly, patients may become hemodynamically unstable during the evaluation and early treatment period, which may necessitate rapid redirection of the approach to the administration of lifesaving therapies.

Assess airway, breathing, circulation — The first priorities are to stabilize the airway and breathing with oxygen and/or mechanical ventilation, when necessary. Intravenous access should be secured so that patients can be immediately treated with intravenous fluids to restore adequate tissue perfusion.

Patients with respiratory distress and/or marked hemodynamic instability are typically intubated. The exception is those with suspected tension pneumothorax, where the prompt drainage of air from the pleural space may quickly reverse shock and avoid intubation (mechanical ventilation can worsen tension and precipitate cardiac arrest). Rapid sequence intubation is the preferred approach; agents that worsen hypotension should be avoided. (See "Rapid sequence intubation for adults outside the operating room" and "Induction agents for rapid sequence intubation in adults outside the operating room".)

Peripheral venous access (14 to 18 gauge catheters) or intraosseous access is sufficient for the initial evaluation and management of many patients with undifferentiated shock and hypotension. However, central venous access should be obtained in those in whom peripheral access cannot be obtained, in those who need infusions of large volumes of fluids and/or blood products, or in those who need prolonged infusions of vasopressors. Central venous access may also be useful in patients who require frequent blood draws for laboratory studies and for hemodynamic monitoring (eg, central venous pressure, central venous oxyhemoglobin saturation). Importantly, the administration of resuscitative fluids and medications should not be delayed because central venous access is not available. Related, evidence suggests that the use of peripheral intravenous vasoactive medications can be used safely for hours to days, obviating the need for central venous catheterization in a number of patients [7].

Risk stratification — When patients present with undifferentiated hypotension or shock, the clinician should stratify the patient according to the severity of shock and the need for immediate or early intervention so that empiric lifesaving therapies can be administered promptly (algorithm 1A-B).

Clinicians should obtain a brief history and examination, together with bedside telemetry monitoring and/or electrocardiography [ECG], to assess whether an immediate or early lifesaving therapy is required. While a definitive diagnosis is preferred, many of these therapies are administered based upon a presumed diagnosis with or without preliminary test results. (See 'Common conditions needing lifesaving interventions' below.)

Patients with milder forms of shock/hypotension or critically ill patients who have been stabilized should undergo a thorough diagnostic evaluation while resuscitation continues. Sufficient time is typically available in such patients to obtain laboratory studies and definitive imaging so that a diagnosis can be made and appropriate therapy administered. However, the evaluation remains time-sensitive, as patients in this category are at risk of becoming hemodynamically unstable, such that a rapid redirection of the diagnostic and therapeutic strategy may be necessary. (See 'Initial diagnostic evaluation' below.)

Common conditions needing lifesaving interventions — The initial approach discussed below is often dependent upon a brief history obtained from prehospital providers, hospital staff, family members, and the patient.

Anaphylactic shock — Patients strongly suspected of having anaphylactic shock (eg, hypotension, inspiratory stridor, oral and facial edema, hives, history of recent exposure to common allergens [eg, bee stings]) should receive intramuscular epinephrine. Patients on mechanical ventilation may also have a sudden elevation in peak inspiratory pressures. The typical adult dose is 0.3 mg of 1:1000 epinephrine injected into the mid-outer thigh and repeated every 5 to 15 minutes as needed (table 2). Other pharmacologic agents frequently administered following epinephrine include antihistamines (eg, diphenhydramine 25 to 50 mg and famotidine 20 mg intravenously), nebulized albuterol (2.5 mg in 3 mL of normal saline), and methylprednisolone (1 to 2 mg/kg intravenously). Blood for total tryptase or histamine should be drawn prior to or shortly after treatment. (See "Anaphylaxis: Emergency treatment".)

Tension pneumothorax — Tension pneumothorax should be suspected in those with tachypnea, unilateral pleuritic chest pain and diminished breath sounds, distended neck veins, tracheal deviation away from the affected side, and risk factors for tension pneumothorax (eg, trauma, recent procedure, mechanical ventilation, underlying cystic lung disease). Patients on mechanical ventilation may also have a sudden elevation in plateau pressures. Patients strongly suspected to have a tension pneumothorax do not require a chest radiograph and should have an emergent tube thoracostomy (24 or 28 Fr, 36 Fr for trauma; fifth intercostal space, midaxillary line) or needle decompression using a 14 to 16 gauge intravenous catheter (second or third intercostal space, midclavicular line) followed by immediate tube thoracostomy; tube thoracostomy is indicated should decompression fail. (See "Thoracostomy tubes and catheters: Indications and tube selection in adults and children", section on 'Tension pneumothorax' and "Prehospital care of the adult trauma patient", section on 'Needle chest decompression' and "Thoracostomy tubes and catheters: Placement techniques and complications", section on 'Needle thoracostomy'.)

Ultrasound guidance is preferable for both diagnosis and tube placement. In addition, we prefer that drainage of a tension pneumothorax be performed before endotracheal intubation unless the patient is already intubated or is in cardiac arrest. For those on mechanical ventilation, positive pressure ventilation should be reduced. Radiographic confirmation of reexpansion should be performed after drainage (eg, ultrasonography, chest radiography). (See "Diagnosis, management, and prevention of pulmonary barotrauma during invasive mechanical ventilation in adults", section on 'Ventilator management'.)

Pericardial tamponade — Pericardial tamponade should be suspected in patients with dyspnea, tachycardia, hypotension, elevated jugular venous pressure, distant heart sounds, pulsus paradoxus, and known risk factors (eg, trauma, bleeding diathesis, known pericardial effusion, recent thoracic or pericardial procedure). The demonstration of an anechoic stripe and tamponade physiology on point-of-care (POC) ultrasonography or bedside echocardiography is preferred before pericardiocentesis. Ultrasonography also guides needle or catheter placement and examines the response to drainage of fluid from the pericardial sac. In rare cases, an emergency thoracotomy may be performed in those who are unresponsive to catheter drainage or in those who develop a cardiac arrest during resuscitation. (See "Cardiac tamponade", section on 'Treatment' and "Emergency pericardiocentesis" and "Initial evaluation and management of blunt thoracic trauma in adults", section on 'Emergency thoracotomy'.)

Importantly, pericardiocentesis should not be attempted in patients with a pericardial effusion due to aortic dissection or myocardial rupture, as relief of cardiac tamponade may worsen bleeding. Such patients require emergent surgical intervention. In instances where tamponade remains on the differential diagnosis, but additional data are required, hemodynamic measurements via pulmonary artery catheterization are frequently required. (See "Management of acute aortic dissection" and "Acute myocardial infarction: Mechanical complications", section on 'Rupture of the left ventricular free wall'.)

Hemodynamically significant hemorrhage — Patients with suspected hemorrhagic shock should be identified as having traumatic or nontraumatic shock:

Traumatic – Patients with a history of blunt or penetrating trauma benefit from rapid multiorgan bedside ultrasonography to identify blood in the abdomen (also known as focused assessment with sonography for trauma [FAST]). A positive study indicates the need for surgical exploration to identify and control the source of hemorrhage (algorithm 2 and table 3). (See "Emergency ultrasound in adults with abdominal and thoracic trauma" and "Initial evaluation and management of penetrating thoracic trauma in adults" and "Initial evaluation and management of blunt thoracic trauma in adults" and "Overview of damage control surgery and resuscitation in patients sustaining severe injury".)

Nontraumatic – Patients suspected of having a ruptured aorta (eg, hypotension, abdominal, chest or back pain, known history of aneurysm or dissection) may be too unstable to safely obtain a contrast-enhanced computed tomography (CT). Other options for diagnosis prior to management include transesophageal echocardiography (thoracic aorta) and abdominal ultrasound (abdominal aorta), to identify perioaortic hematoma or aneurysmal disease. (See "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm" and "Overview of acute aortic dissection and other acute aortic syndromes", section on 'Periaortic hematoma'.)

For patients with the manifestations of upper or lower gastrointestinal hemorrhage (eg, hematemesis, hematochezia, anemia, bleeding diathesis), endoscopic intervention, embolization, or surgery may be indicated (table 4 and algorithm 3 and algorithm 4). (See "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm" and "Overview of the treatment of bleeding peptic ulcers", section on 'Treatment of persistent and recurrent bleeding' and "Overview of the management of patients with variceal bleeding".)

This population typically requires large volumes of blood products, and vasopressors are avoided. Adequate peripheral access (two 14 to 18 gauge IVs) and/or a large-bore, single-lumen central cordis are essential. A type and crossmatch, a complete blood count, and coagulation studies should be obtained in all patients with suspected hemorrhage.

Life-threatening arrhythmias — Patients with rhythm disturbances resulting in shock can be cardioverted (tachyarrhythmias) (algorithm 5), receive atropine or infusions of vasoactive agents, or undergo temporary or permanent pacemaker placement (bradyarrhythmias) (algorithm 6) as part of the advanced cardiac life support (ACLS) protocol. Arrhythmias can be the primary cause of, or contribute to, shock, such that immediate treatment is important and potentially lifesaving. Additionally, arrhythmias can be secondary to the metabolic disturbances associated with shock (eg, hypokalemia, acidosis) or the underlying cause of shock (eg, sepsis [8], pulmonary embolism, myocardial infarction). Thus, their presence should prompt additional investigations (eg, serum chemistries, arterial blood gas analysis, toxicology screen, bedside cardiac ultrasound, and cultures in those with suspected infection). (See "Advanced cardiac life support (ACLS) in adults" and "Supportive data for advanced cardiac life support in adults with sudden cardiac arrest".)

Septic shock — Patients with suspected infection (eg, fever, hypotension, and a suspected septic source) benefit from the early administration of intravenous antibiotics, the choice of which is determined by the suspected source, and intravenous fluid resuscitation. If the source is unknown and Pseudomonas is unlikely, we favor combining vancomycin with a third- or fourth-generation cephalosporin (eg, ceftriaxone or cefotaxime, cefepime) or a beta-lactam/beta-lactamase inhibitor (eg, piperacillin-tazobactam, ticarcillin-clavulanate [limited supply]) or a carbapenem (eg, imipenem or meropenem). If Pseudomonas is likely, vancomycin should be combined with two antipseudomonal agents (eg, fluoroquinolone, aminoglycoside, piperacillin-tazobactam, cefepime, ceftazidime). A leukocytosis and, in particular, a bandemia, as well as laboratory and imaging findings suggestive of a source, all support the presence of sepsis as a cause of shock. Blood and other appropriate body fluid cultures should be obtained, preferably prior to the administration of antibiotics, in addition to imaging when necessary to facilitate timely source control. Serial vital signs, and serum lactate measures, can be used to risk-stratify the septic patient. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Choosing a regimen'.)

Cardiogenic shock from myocardial infarction — Patients who present with hypotension associated with anterior crushing chest pain, respiratory distress, and the ECG changes consistent with ST elevation myocardial infarction (STEMI) benefit from early intervention. Elevated troponin or creatine phosphokinase levels and pulmonary edema on chest radiography are supportive of the diagnosis. Interventions include the administration of pharmacologic agents (eg, antiplatelet agents, heparin), coronary revascularization procedures (eg, balloon angioplasty), and/or an intraaortic balloon pump. Those with non-STEMI may additionally benefit from the administration of glycoprotein IIb/IIIa inhibitors (table 5). (See "Prognosis and treatment of cardiogenic shock complicating acute myocardial infarction".)

Cardiogenic shock from acute aortic or mitral valve insufficiency — Patients with chest pain, hypotension, and new low-pitched early diastolic murmur consistent with aortic insufficiency should undergo POC ultrasonography or echocardiography prior to surgical intervention. Additional laboratory or imaging studies aimed at discovering the etiology of rupture (eg, CT chest for aortic dissection, blood cultures and transesophageal echocardiography for aortic root abscess) may be required in this population. Patients with acute respiratory distress and new systolic murmur following an acute myocardial infarction (MI) should preferably undergo urgent echocardiography to look for mitral valve insufficiency or ventricular septal defect, which also typically needs urgent surgical intervention. (See "Acute aortic regurgitation in adults" and "Acute mitral regurgitation in adults" and "Management and prognosis of ventricular septal defect in adults", section on 'Surgical repair'.)

Dissection of the ascending aorta — Patients with descending thoracic aortic dissection often present with hypertension and tearing chest or back pain. However, patients with ascending aortic dissection are more likely to present with hypotension and shock associated with acute aortic insufficiency, pericardial tamponade, or myocardial infarction. Hemodynamically unstable patients with suspected aortic dissection transesophageal echocardiography, if available or contrast-enhanced CT to evaluate the ascending aorta and aortic valve (table 6). Ascending aortic dissection is a cardiac surgical emergency and immediate consultation with a cardiac surgeon should be obtained. (See "Clinical features and diagnosis of acute aortic dissection".)

Hemodynamically significant pulmonary embolism — Patients with hypotension, acute dyspnea, and hypoxemia who are strongly suspected of having a pulmonary embolism (PE) may benefit from the administration of systemic thrombolytic therapy (algorithm 7). Normal chest radiography and elevated D-dimer, troponin, and natriuretic peptide levels are supportive diagnostically. Computed tomographic pulmonary angiography is the preferred diagnostic modality in this population. However, for those in whom CT is unsafe, a presumptive diagnosis may be obtained by POC cardiac ultrasonography or echocardiography (eg, right ventricle enlargement, thrombus) to justify the administration of a thrombolytic agent, provided no contraindications are present. The indications for thrombolysis, dosing, and choice of agent, as well as alternative therapies in patients with hemodynamically unstable PE, are discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Hemodynamically unstable' and "Approach to thrombolytic (fibrinolytic) therapy in acute pulmonary embolism: Patient selection and administration".)

Adrenal crisis — Patients suspected of having an adrenal crisis (eg, hypotension, volume depletion, history of glucocorticoid deficiency or withdrawal) should receive judicious fluid resuscitation and dexamethasone 4 mg intravenously. The selection of dexamethasone is based on the ability to interpret serum cortisol measurements as part of the evaluation. Blood for serum cortisol, corticotropin (ACTH), aldosterone, renin, and serum chemistries should be drawn to confirm the diagnosis (table 7). (See "Treatment of adrenal insufficiency in adults", section on 'Adrenal crisis'.)

Insect or animal bites — Some insect and animal bites require antivenom to reverse shock, the details of which are discussed separately. (See "Diagnostic approach to the patient with a suspected spider bite: An overview" and "Treatment of rabies" and "Snakebites worldwide: Management".)

Initial diagnostic evaluation

Clinical bedside evaluation — A high clinical suspicion for the presence of shock is critical for diagnosis. An initial efficient and targeted history from prehospital or hospital providers, the patient, their relatives, and/or the medical record should provide ample information on a patient’s risk for shock, as well as the potential etiology (algorithm 1A-B). Physical examination including electrocardiography should be directed towards uncovering the type, severity, and cause of shock. With diagnostic data, the cause of shock can usually be determined or narrowed to a few possibilities, and subsequent therapy can be appropriately tailored. (See 'Differential diagnosis' below and 'Reverse the etiology' below.)

Typically, we perform the following:

General assessment – The evaluation should include a thorough history and assessment of sensorium, mucous membranes, lips and tongue, neck veins, lungs, heart, and abdomen, as well as skin and joints. Hypotension, oliguria, mental status changes, and cool, clammy skin are sentinel clinical findings that should raise the suspicion of shock and prompt immediate treatment with intravenous fluids and further evaluation with laboratory studies and relevant imaging. (See 'When to suspect shock' above.)

Electrocardiogram – Bedside telemetry and/or electrocardiogram (ECG) should be performed in patients with undifferentiated hypotension and shock. ECG may reveal an arrhythmia or ST segment changes consistent with ischemia or pericarditis. A low-voltage ECG may be suggestive of a pericardial effusion. The classic signs of pulmonary embolism (S1, Q3, T3) or right ventricular strain may also be evident. (See "ECG tutorial: Basic principles of ECG analysis".)

Assessment for the etiology – A comprehensive assessment for the underlying etiology of shock should be performed after stabilization. A more detailed discussion of the clinical presentation and diagnostic evaluation of specific types of shock is provided below. (See 'Differential diagnosis' below.)

Laboratory evaluation — Laboratory tests should be performed early in the evaluation of patients with undifferentiated hypotension/shock to identify the cause of shock and/or early organ failure (algorithm 1A-B). An elevated serum lactate (>2 mmol/L, depending upon the institutional laboratory normal) is an early indicator of shock and is particularly useful in those who are normotensive or hypertensive (ie, those in whom shock is less likely to be suspected).

We suggest the following basic laboratory tests be obtained in most patients with undifferentiated hypotension or shock, recognizing that testing should be tailored according to the suspected etiology (see 'Common conditions needing lifesaving interventions' above and 'Differential diagnosis' below):

Serum lactate

Renal and liver function tests

Cardiac enzymes and natriuretic peptides

Complete blood count and differential

Coagulation studies and D-dimer level

Blood gas analysis

The rationale for obtaining these tests is described below:

Serum lactate level – Elevated lactate levels in states of shock are reflective of poor tissue perfusion (type A lactic acidosis) and are due to increased production from anaerobic metabolism, aerobic metabolism, and decreased clearance by the liver, kidneys, and skeletal muscle [5,9]. However, although elevated lactate is a sensitive tool for the diagnosis of shock, it is not specific and can also be found in conditions including metformin toxicity, diabetic ketoacidosis, and alcoholism (type B lactic acidosis). (See "Causes of lactic acidosis".)

Lactate has been best studied in patients with septic shock where elevated levels >2 mmol/L, and in particular those >4 mmol/L are associated with increased mortality independent of organ dysfunction or hypotension. However, studies performed in other populations also suggest that elevated lactate is similarly associated with increased mortality [10]. Details regarding the role of lactate in sepsis are discussed separately. (See "Evaluation and management of suspected sepsis and septic shock in adults".)

In addition, lactate levels can be serially measured to follow the response to therapies. (See 'Reverse the etiology' below.)

Renal and liver function tests – Elevated blood urea nitrogen (BUN), creatine, and transaminases are usually due to shock-induced end-organ damage (eg, acute kidney injury, shock liver) but may also explain the etiology of shock (eg, renal abscess, acute hepatitis, chronic cirrhosis). Serum and urinary electrolytes including hypo- or hypernatremia, hypo- or hyperkalemia, low urinary sodium concentration, or fractional excretion of sodium <1 percent may indicate hypovolemia. (See "Etiology, clinical manifestations, and diagnosis of volume depletion in adults", section on 'Laboratory abnormalities'.)

Cardiac enzymes and natriuretic peptides – Elevated troponin-I or -T levels, creatine phosphokinase, brain natriuretic peptide, or N-terminal pro-brain natriuretic peptide may indicate cardiogenic shock from ischemia but can also be due to demand ischemia or to pulmonary embolism (PE). (See "Troponin testing: Clinical use" and "Natriuretic peptide measurement in heart failure" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Laboratory tests'.)

Complete blood count and differential – A high hematocrit may suggest hemoconcentration from hypovolemia. Anemia in the setting of bleeding supports hemorrhagic shock, and concurrent thrombocytopenia may suggest an etiology for hemorrhage. An elevated eosinophil count may suggest an allergy to support anaphylaxis.

Although a leukocytosis may suggest septic shock, it is not specific for the diagnosis and may simply indicate a stress response. A low white blood cell count and especially a bandemia are more worrisome for sepsis in the setting of undifferentiated shock. As an example, in one observational study of 145 patients admitted to the intensive care unit with undifferentiated shock, infection was significantly more common among those with a band count greater than 10 percent than among those with a lower band count (odds ratio [OR] 8.7, 95% CI 3.4-22.4) [11].

Coagulation studies and D-dimer level – Elevations in the prothrombin time or international normalized ratio as well as activated partial thromboplastin time may suggest a cause for underlying hemorrhagic shock but are also frequently elevated in patients with sepsis, systemic inflammatory response syndrome due to nonspecific activation of the coagulation cascade, and liver disease. Evidence of disseminated intravascular coagulation (elevated fibrin split products and D-dimer level with low fibrinogen level) can also be found in patients with severe shock. Elevated D-dimer levels are not specific for the diagnosis of PE but, when normal, can significantly reduce the probability of PE. (See "Disseminated intravascular coagulation (DIC) in adults: Evaluation and management".)

Venous blood gas (VBG) and arterial blood gas analysis (ABG) – An ABG should be performed in most patients with undifferentiated shock if accurate estimates of gas exchange and acid–base disturbance are needed to help with diagnosis and treatment (eg, pulse oximetry may be unreliable due to poor tissue perfusion). Alternatively, a VBG may be obtained in any patient presenting with unstable blood pressure and concern for shock. The advantage of a VBG is that it can be obtained when the initial labs are drawn and will rapidly provide extensive data on the patient’s pH, CO2, bicarbonate, base deficit, and serum lactate, particularly when obtaining an ABG is delayed.

Hypoxemia can be due to obstructive shock from pulmonary embolism, cardiogenic shock from myocardial infarction, septic shock from pneumonia, or acute respiratory distress syndrome (ARDS) resulting from shock. Compensatory hypocapnia can be seen in those with a metabolic acidosis. Hypercapnia may occur in patients with encephalopathy, brain injury, or increased dead space ventilation in patients with severe ARDS. Metabolic acidosis may be due to hyperlactatemia, acute kidney injury, or toxin ingestion. Additionally, a respiratory acidosis may occur in those obtunded from end-stage shock. (See "Arterial blood gases", section on 'Interpretation'.)

Additional laboratory tests include those directed at specific etiologies or sequelae of shock. As examples, a toxicology screen may be useful in those suspected of having shock from drug intoxication, a type and crossmatch should be obtained in those with hemorrhage, and an amylase and lipase should be obtained in those with suspected pancreatitis. Urinalysis and gram stain of material from sites of possible infection (eg, blood, sputum, urine, wounds) or known organisms from prior cultures (eg, Pseudomonas in urine, clostridium difficile in stool) may provide a supportive clue to a possible source of sepsis. Tryptase and histamine levels are useful in those with suspected anaphylaxis. Urine electrolytes (sodium and creatine) should be obtained in those with hypovolemia. A peripheral smear may be useful in those suspected of having malaria, and fibrinogen levels and fibrin degradation products may be useful in those thought to have disseminated intravascular coagulation. A cortisol level or corticotrophin stimulation test may be helpful in those suspected to have an adrenal crisis, and thyroid function tests may identify those with suspected myxedema coma. (See 'Differential diagnosis' below.)

Imaging — We perform the following in patients with undifferentiated shock and hypotension:

Chest radiography – A portable chest radiograph is typically performed in most patients with suspected shock to detect common causes (eg, pneumonia) or complications of shock (eg, ARDS). A chest radiograph may be clear in hypovolemic shock or obstructive shock from PE. Alternatively, it may demonstrate a pneumonia, pneumothorax, pulmonary edema, or widened mediastinum to support an etiology for septic shock, obstructive shock, cardiogenic shock, or aortic dissection, respectively. Chest radiography may also reveal free air under the diaphragm to suggest viscus perforation, which should prompt emergent surgical consultation and additional testing, usually computed tomography (CT) of the abdomen and pelvis if the patient is stable, or immediate laparotomy if the patient is unstable.

Other imaging directed at the etiology of shock – Other imaging tests should be directed at the etiology of shock. These include abdominal radiography (intestinal obstruction, perforation), CT of the head (traumatic brain injury, stroke), spine (spinal injury), chest (pneumonia, pneumothorax, ruptured aneurysm, dissection), abdomen and pelvis (intestinal obstruction, perforation, abscess), and pulmonary artery (pulmonary embolism), as well as nuclear bleeding scans (gastrointestinal hemorrhage).

Point-of-care (POC) ultrasonography – The indications for and value of POC ultrasonography are discussed in the section below. (See 'Point-of-care ultrasonography' below and "Indications for bedside ultrasonography in the critically-ill adult patient".)

Point-of-care ultrasonography — POC ultrasonography algorithms, including rapid ultrasound in shock (RUSH), focused cardiac ultrasound (FOCUS), or abdominal and cardiac evaluation with sonography in shock (ACES), are more frequently used as portable, bedside diagnostic tools in patients with undifferentiated shock and hypotension [12-15]. When available, POC ultrasonography is typically used in patients in whom an empiric diagnosis has not been achieved with clinical and laboratory evaluation or in those in whom definitive imaging is unsafe (algorithm 1A-B), and as a complementary tool to examine fluid responsiveness. Although POC ultrasonography is not definitively diagnostic, we believe that, when performed by trained personnel as a time-sensitive diagnostic tool in critically ill patients with undifferentiated shock or hypotension, valuable information can be obtained that can be life-saving.

Multiorgan ultrasonography (RUSH, ACES) examines the heart first, followed by ultrasound of the chest and abdomen and major blood vessels; focused cardiac ultrasound (FOCUS) examines the heart only. The technical views employed for POC ultrasonography in patients with undifferentiated shock are similar to those used in trauma patients (focused assessment with sonography for trauma [FAST]), the details of which are discussed separately. (See "Emergency ultrasound in adults with abdominal and thoracic trauma".)

The components of POC ultrasonography examination are described in brief below:

First, limited views of the heart should be performed to examine the following:

Pericardium – Cardiac ultrasound may detect a pericardial effusion (anechoic stripe); chamber collapse and reciprocal changes in right and left ventricle volume during respiration may support tamponade as a cause of shock (movie 1 and movie 2 and movie 3). Cardiac ultrasound may also be used to guide pericardiocentesis and to examine the response to drainage. (See "Emergency ultrasound in adults with abdominal and thoracic trauma", section on 'Pericardial and limited cardiac examination' and "Cardiac tamponade", section on 'Echocardiography'.)

Left ventricle – A large left ventricle (LV) with reduced contractility may suggest primary pump failure and prompt referral for appropriate intervention (eg, cardiac catheterization) (image 1 and image 2 and image 3 and figure 1 and image 4). In contrast, small cardiac chambers and a hyperdynamic LV may indicate distributive shock from sepsis or hypovolemia, which may prompt further evaluation for a septic source or for hemorrhage, respectively. Imaging of the LV may also be used to confirm ventricular contraction or ventricle wall perforation with pacemaker placement (transcutaneous or transvenous), or aneurysm rupture [16,17]. (See "Emergency ultrasound in adults with abdominal and thoracic trauma", section on 'Pericardial and limited cardiac examination' and "Echocardiographic recognition of cardiomyopathies".)

Right ventricle – Reduced right ventricle (RV) contractility may suggest RV myocardial infarction; increased size of the RV (eg, >1:1 RV/LV ratio) may suggest a large pulmonary embolism (PE) or pulmonary hypertension (image 5 and movie 4); a floating thrombus in the right atrium/ventricle or clot in transit also support PE. (See "Right ventricular myocardial infarction", section on 'Echocardiography' and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Echocardiography'.)

Inferior vena cava – A collapsing inferior vena cava (IVC) at the end of expiration suggests hypovolemia from hemorrhagic or nonhemorrhagic causes. A dilated IVC may support cardiac tamponade or PE. (See "Emergency ultrasound in adults with abdominal and thoracic trauma", section on 'IVC evaluation and fluid status'.)

Second, brief imaging of the chest and abdomen should be performed to examine the following:

Lung and pleural space – The absence of lung sliding (movie 5) supports the presence of a pneumothorax. (See "Bedside pleural ultrasonography: Equipment, technique, and the identification of pleural effusion and pneumothorax".)

Pulmonary edema as evidenced by the presence of B lines may support primary pump failure or volume overload subsequent to fluid resuscitation (image 6). (See "Bedside pleural ultrasonography: Equipment, technique, and the identification of pleural effusion and pneumothorax".)

A pleural effusion (anechoic stripe or septations) may support empyema or hemothorax and guide thoracentesis (movie 6). (See "Bedside pleural ultrasonography: Equipment, technique, and the identification of pleural effusion and pneumothorax".)

Peritoneal cavity – Evidence of significant peritoneal fluid accumulation may suggest a source of blood loss in trauma or a potential source of infection (ie, spontaneous bacterial peritonitis in the patient with cirrhosis). (See "Emergency ultrasound in adults with abdominal and thoracic trauma", section on 'Abdominal examination'.)

Third, brief imaging of the major arteries and veins should be performed to examine the following:

Aorta – Although computed tomography (CT) of the chest or transesophageal echocardiography is preferred, POC ultrasonography may detect a thoracic or abdominal aneurysm or an intimal flap consistent with dissection of the aorta. Alternatively, visualization of free fluid or of a pericardial or pleural effusion may also provide indirect evidence of rupture or dissection. (See "Clinical manifestations and diagnosis of thoracic aortic aneurysm", section on 'Imaging symptomatic patients'.)

Proximal lower extremity veins – Lack of compressibility of thigh veins may be indicative of deep venous thrombosis, thereby raising the suspicion for PE. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Diagnostic ultrasonography suspected first DVT'.)

Should POC ultrasonography be nondiagnostic or unavailable, definitive imaging modalities should be used when feasible, of which comprehensive echocardiography is the most useful. Similarly, in the event of successful resuscitation from shock, follow-up testing with standard imaging is also prudent to confirm the diagnosis that was obtained by rapid bedside ultrasound.

Advantages and disadvantages of POC ultrasonography in patients with undifferentiated shock include the following:

Advantages – POC ultrasonography is portable, inexpensive, and does not expose the patient to ionizing radiation. Its major advantage is the rapid examination of multiple organs, particularly the heart, to narrow the differential diagnosis and identify a potential etiology for shock. This feature is particularly valuable for patients in whom routine imaging is unsafe. Observational studies report that empiric diagnoses can be obtained within minutes when compared with standard imaging modalities. As an example, several studies have shown ultrasonography is more sensitive than portable chest radiography for the detection of pneumothorax, with sensitivity and specificity ranging from 86 to 100 and 92 to 100 percent, respectively [18-21]. The same studies also show reduced time spent obtaining imaging with ultrasonography (2 to 3 versus 20 to 30 minutes). (See "Bedside pleural ultrasonography: Equipment, technique, and the identification of pleural effusion and pneumothorax".)

Additional advantages include the targeted application of lifesaving therapies (eg, pericardial drainage, chest tube insertion, thrombolytic therapy, peritoneal drainage, or lavage), and the safe performance of vascular access procedures (eg, central venous catheter insertion). Serial imaging can also follow the therapeutic response to interventions (eg, improved ventricle contractility following pericardiocentesis) and detect procedural complications (eg, ventricle perforation following pacemaker placement, pneumothorax following central venous catheter placement).

Disadvantages – When compared with definitive imaging modalities performed by fully-trained providers, the major disadvantage of POC ultrasonography is its limited sensitivity for many of the etiologies associated with shock. Limited sensitivity may be partially explained by the lack of standards regarding the training, performance, and indications for bedside ultrasonography.

As an example, while POC ultrasonography is sensitive and specific for the detection of pericardial effusions [22,23], comprehensive echocardiography with additional views may be required for definitive diagnosis of tamponade, particularly when effusions are complex, loculated, or small. Additionally, regional wall motion abnormalities, valvular dysfunction, ventricular septal wall perforation, ruptured aortic aneurysms, and aortic dissection cannot be readily detected using limited bedside views. A meta-analysis of nine studies that compared FoCUS-assisted clinical assessment with clinical assessment alone reported that while FoCUS examination of the left ventricle and mitral valve was more sensitive than clinical assessment alone (84 versus 43 percent), its specificity was similar (89 versus 81 percent) [24].

The advantages and disadvantages of FAST in adults with abdominal and thoracic trauma (eg, poor sensitivity for distinguishing blood from other body fluids) are discussed separately. (See "Emergency ultrasound in adults with abdominal and thoracic trauma", section on 'Limitations of FAST'.)

Most of the data that support the use of POC ultrasonography in patients with undifferentiated shock are extrapolated from patients with traumatic shock (see "Emergency ultrasound in adults with abdominal and thoracic trauma"). However, data from one randomized trial and several small observational studies have been published in patients with undifferentiated shock or hypotension. In general, these data demonstrate the identification of imaging abnormalities that narrow the differential diagnosis, confirm a clinically suspected diagnosis, prompt a change in management, and/or detect a complication from a therapeutic procedure rather than demonstrate a conclusive improvement in survival [14,25-34]. As examples:

In a randomized trial of 273 patients with undifferentiated hypotension, more than half of whom had occult sepsis, compared with standard of care, POC ultrasonography did not alter the 30 day survival, CT scanning rate, inotrope or intravenous fluid use, or length of stay [35]. However, this study stopped recruitment early due to slow accrual, and had a large number of exclusion criteria which may have limited the impact of POC ultrasonography.    

In a prospective observational study of 110 critically ill patients with undifferentiated shock, outcomes in patients who underwent bedside cardiac ultrasound were compared with historical controls who underwent standard clinical evaluation [26]. The use of ultrasound was associated with reduced infusion of intravenous fluids (49 versus 66 mL/kg), increased administration of vasopressors (22 versus 12 percent), and improved 28-day survival (66 versus 56 percent), as well as more days alive free of renal support (28 versus 25 days).

In a prospective observational study of 108 patients with nontraumatic, undifferentiated hypotension, multiorgan ultrasonography performed in the emergency department reported good agreement between the ultrasonography diagnosis and the final clinical diagnosis [27].

In a post-hoc analysis of a randomized study of 103 emergency department patients who presented with nontraumatic undifferentiated shock, the presence of a hyperdynamic LV was an independent predictor of sepsis (OR 5.5; 95% CI 1.1-45) [28]. The sensitivity and specificity of a hyperdynamic LV for predicting sepsis were 33 and 94 percent, respectively.

In a retrospective study of 411 patients who had chest pain, dyspnea, or hypotension, a moderate agreement was reported between POC ultrasonography and comprehensive echocardiography for the detection of right ventricle strain (RVS) [29]. The sensitivity and specificity of ultrasound for RVS were 26 and 98 percent, respectively.

Details regarding standard techniques and diagnostic findings in comprehensive cardiac, thoracic, abdominal, and vascular ultrasound are discussed separately. (See "Echocardiographic recognition of cardiomyopathies" and "Echocardiographic assessment of the right heart" and "Echocardiographic evaluation of the pericardium" and "Cardiac tamponade", section on 'Echocardiography' and "Echocardiographic evaluation of the thoracic and proximal abdominal aorta" and "Bedside pleural ultrasonography: Equipment, technique, and the identification of pleural effusion and pneumothorax" and "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity", section on 'Diagnostic ultrasonography suspected first DVT'.)

Pulmonary artery catheterization — Pulmonary arterial catheterization (PAC) has never been shown to improve patient-important outcomes, such that the routine insertion of Swan-Ganz catheters has fallen out of favor [36-38]. However, when the diagnosis or the type of shock remains undetermined or mixed, hemodynamic measurements obtained by PAC can be helpful (table 8 and table 9). Additional patients that may benefit from PAC are those with unknown volume status despite adequate fluid resuscitation, those with severe cardiogenic shock (eg, acute valvular disease), or those suspected to have severe underlying pulmonary artery hypertension or cardiac tamponade.

The major hemodynamic indices measured on PAC are cardiac output (ie, cardiac index), systemic vascular resistance, pulmonary artery occlusion pressure (ie, pulmonary capillary wedge pressure), right atrial pressure, and mixed venous oxyhemoglobin saturation (SvO2). These measurements are most useful diagnostically but can also be used to guide fluid resuscitation, titrate vasopressors, and assess the hemodynamic effects of changes in mechanical ventilator settings [39]. Normal hemodynamic values and values consistent with the various classes of shock are listed in the tables (table 8 and table 10). The insertion technique, indications for, and complications of PAC, as well as the interpretation of PAC tracings, are discussed separately. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults" and "Pulmonary artery catheters: Insertion technique in adults" and "Pulmonary artery catheterization: Interpretation of hemodynamic values and waveforms in adults".)

Hemodynamic support — Because shock can be present when patients are hypotensive, hypertensive, or normotensive, the precise threshold that warrants hemodynamic support is unknown. In general, those with suspected shock who are hypotensive and/or have clinical or laboratory evidence of hypoperfusion (eg, change in mental status, clammy skin, diminished urine output, elevated lactate) should receive hemodynamic support with intravenous fluids (IVFs), followed by vasopressors, should IVFs fail to restore adequate tissue perfusion; the exception is hypovolemic shock where more fluids is preferred. While the optimal end-organ perfusion pressure is unclear, in general, we suggest maintaining the mean arterial pressure greater than 65 to 70 mmHg, since higher targets (eg, >70 mmHg) do not appear to be associated with a mortality benefit and may be associated with increased risk of cardiac arrhythmias [40]. (See "Treatment of severe hypovolemia or hypovolemic shock in adults" and "Initial management of NON-hemorrhagic shock in adult trauma".)

Intravenous fluids — IVFs are first-line agents in the treatment of patients with undifferentiated hypotension and shock. We prefer to administer IVFs in well-defined boluses (eg, 500 to 1000 mL) that can be repeated until blood pressure and tissue perfusion are acceptable, pulmonary edema or intraabdominal hypertension ensues, or fluid fails to augment perfusion.

The total volume infused is determined by the etiology of shock. As an example, patients with obstructive shock from pulmonary embolism or cardiogenic shock from LV myocardial infarction usually require small volumes of IVF (500 to 1000 mL), while those with RV infarction or sepsis often need 2 to 5 L, and those with hemorrhagic shock frequently require volumes >3 to 5 L (often inclusive of blood products). The administration of diuretic therapy should be avoided in hypotensive patients with pulmonary edema until the need for hemodynamic support has been weaned.

The optimal choice of fluid is unknown. However, extrapolating from patients with septic shock, most patients are treated with crystalloids (eg, Ringer’s lactate or normal saline), and those with hemorrhagic shock should be preferentially treated with blood products. We recommend avoiding the administration of pentastarch or hydroxyethyl starch because randomized trials of patients with shock have identified potential harm from their use, the details of which are discussed separately. (See "Treatment of severe hypovolemia or hypovolemic shock in adults", section on 'Fluids to avoid: hyperoncotic starch (colloid)'.)

Vasopressors — Vasopressors are frequently required in the treatment of patients with suspected/undifferentiated shock to restore adequate tissue perfusion. Importantly, the use of vasopressors in patients with hemorrhagic or hypovolemic shock may be harmful, such that vasopressors should only be used as an additional form of hemodynamic support when aggressive resuscitation has failed to restore adequate tissue perfusion, or as a last resort for patients in extremis. (See "Initial management of moderate to severe hemorrhage in the adult trauma patient", section on 'Vasopressors'.)

The optimal initial vasopressor is unknown, as is the optimal target mean arterial pressure [41]. However, among available agents, we prefer the following (table 11):

Adrenergic agonistsNorepinephrine (Levophed; initial dosing 8 to 12 mcg/minute intravenously) is the most commonly used agent in this population. Phenylephrine (Neo-synephrine; initial dosing 100 to 200 mcg/minute intravenously) is used when tachyarrhythmias preclude the use of agents with excessive beta-adrenergic activity (eg, norepinephrine, dopamine).

Inotropic agentsDobutamine (initial dose 0.5 to 1 mcg/kg/minute but frequently 2.5 mcg/kg/minute when cardiac decompensation is severe) is the most commonly used inotropic agent in patients who have cardiogenic shock. Dobutamine is often administered together with norepinephrine to offset the fall in peripheral vascular resistance that occurs when low doses of dobutamine are used.

Vasopressor support should be titrated according to the response (ie, indices of tissue perfusion including blood pressure, urine output, mental status, and skin color) and limiting side effects (eg, tachycardia). In general, mean arterial pressure goals are targeted to 65 or greater, recognizing the importance of individualizing care. While targeting higher mean arterial pressures resulted in increased arrhythmia in patients with chronic hypertension, this complication was offset by reduced need for renal replacement therapy [42]. Additional details on the use and dosing of vasopressors are discussed separately. (See "Use of vasopressors and inotropes" and "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Vasopressors' and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Hemodynamically unstable' and "Initial management of trauma in adults", section on 'Circulation' and "Prognosis and treatment of cardiogenic shock complicating acute myocardial infarction", section on 'Vasopressors and inotropes'.)

DIAGNOSIS — A diagnosis of shock is based upon a constellation of clinical, biochemical, and hemodynamic features. Most patients have hypotension and/or clinical signs of tissue hypoperfusion (eg, cold, clammy, mottled skin; oliguria [<0.5 mL/kg/hour]; altered mental status) and hyperlactatemia (>1.5 mmol/L). Noninvasive imaging and/or hemodynamic indices of low cardiac output, systemic vascular resistance, and/or mixed venous oxyhemoglobin saturation are not diagnostic but help to classify shock into one or more of the four main classes (distributive, cardiogenic, hypovolemic, obstructive) (table 10).

Importantly, the diagnosis is dependent upon the clinical suspicion for shock. Shock should always be suspected in those with hypotension and hyperlactatemia, particularly in those with risk factors for specific forms of shock. Additionally, it should be suspected in those who present with normal blood pressure who have signs of compensatory tachycardia and/or peripheral vasoconstriction. (See 'When to suspect shock' above.)

DIFFERENTIAL DIAGNOSIS — Each class of shock (distributive, cardiogenic, hypovolemic, obstructive) is distinguished from the other by a collection of clinical features supported by laboratory, imaging, and hemodynamic findings, which are discussed in the sections below. The classification and etiology of shock are discussed in detail separately (table 1). (See "Definition, classification, etiology, and pathophysiology of shock in adults", section on 'Classification and etiology'.)

Distributive shock

General clinical manifestations – Patients presenting with distributive shock typically have hypotension without the clinical and hemodynamic signs of reduced preload (eg, normal skin turgor, moist mucous membranes, normal inferior vena cava [IVC] on imaging) or fluid overload (eg, no peripheral edema or distended neck veins, normal central venous pressure [CVP] [8 to 12 mmHg] and mixed venous oxyhemoglobin saturation [SvO2] >70 percent measured on central venous catheterization]). A preserved or hyperdynamic left ventricle is typically observed on echocardiography.

Etiologic manifestations – The clinical features that distinguish one cause of distributive shock from the other depend upon the etiology. As an example, patients may present with hypotension in association with the clinical manifestations of pneumonia (septic shock), brain or spinal trauma (neurogenic shock), anaphylaxis (anaphylactic shock), a history of toxin exposure (toxic shock), steroid withdrawal (adrenal crisis), or hypothyroidism (myxedema coma). Details regarding the clinical presentation and diagnosis of the causes of distributive shock are provided separately:

Sepsis and systemic inflammatory response syndrome (see "Evaluation and management of suspected sepsis and septic shock in adults" and "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis")

Spinal cord trauma (see "Acute traumatic spinal cord injury")

Anaphylaxis (see "Anaphylaxis: Emergency treatment")

Toxic shock (see "Invasive group A streptococcal infection and toxic shock syndrome: Epidemiology, clinical manifestations, and diagnosis")

Adrenal crisis (see "Clinical manifestations of adrenal insufficiency in adults" and "Diagnosis of adrenal insufficiency in adults" and "Treatment of adrenal insufficiency in adults")

Myxedema coma (see "Myxedema coma")

Pulmonary artery catheterization findings – Physiologically, on pulmonary artery catheterization (PAC), distributive shock is primarily distinguished from other forms of shock on the basis of low systemic vascular resistance (SVR) (<900 dynes per second/cm5) and normal or high cardiac output (CO) (cardiac index [CI] >4.2 L/min/m2) (table 10). The pulmonary capillary wedge pressure (pcwp) is typically normal or low (<15 mmHg). SvO2 is typically >65 percent and elevations in mixed central venous saturation (hyperoxia ≥90 percent) is associated with worse outcomes [43].

Cardiogenic shock

General clinical manifestations – Patients with cardiogenic shock generally present with hypotension in association with the clinical and radiologic manifestations of pulmonary edema (eg, diffuse lung crackles, distended neck veins), an elevated CVP (>12 mmHg) and low SvO2 (<70 percent) on hemodynamic monitoring from a triple-lumen catheter, large dilated ventricle(s) and poor left ventricle function, or valvular or septal abnormalities on echocardiography.

Etiologic manifestations – Distinguishing the etiologies of cardiogenic shock depends upon the cause. Patients with cardiogenic shock from myocardial infarction (MI) may have crushing substernal chest pain, acute dyspnea with elevated cardiac isoenzymes, and electrocardiographic (ECG) findings of MI. Cardiogenic shock from arrhythmias may be sudden in onset with palpitations or syncope and may be evident on telemetry or ECG. A ruptured valve or septal defect may present with the manifestations of acute pulmonary edema and a new murmur in the setting of a recent MI. Patients with myocarditis may present with pleuritic chest pain and a pericardial rub. Additional details regarding the clinical presentation and diagnosis of the causes of cardiogenic shock are provided separately:

Myocardial infarction (see "Clinical manifestations and diagnosis of cardiogenic shock in acute myocardial infarction" and "Prognosis and treatment of cardiogenic shock complicating acute myocardial infarction")

Severe cardiomyopathy (see "Approach to diagnosis and evaluation of acute decompensated heart failure in adults" and "Treatment of acute decompensated heart failure: Specific therapies")

Arrhythmia (see "Advanced cardiac life support (ACLS) in adults")

Acute valve rupture or ventricular septal defect (see "Acute mitral regurgitation in adults" and "Acute aortic regurgitation in adults" and "Clinical manifestations and diagnosis of ventricular septal defect in adults")

Myocarditis or blunt cardiac trauma (see "Clinical manifestations and diagnosis of myocarditis in adults" and "Treatment and prognosis of myocarditis in adults" and "Cardiac injury from blunt trauma")

Pulmonary artery catheterization findings – On PAC, typically, a high pcwp (>15 mmHg) distinguishes cardiogenic shock from other forms of shock, particularly in the setting of a low CO (CI <2.8 L/min/m2), and a high SVR (>1400 dynes per second/cm5) (table 10). PAC tracings can also be helpful in diagnosing certain valvular defects (eg, large v-waves of severe tricuspid valve insufficiency). SvO2 is typically <65 percent.

Hypovolemic shock

General clinical manifestations – Hypovolemic shock can be distinguished from other types of shock by the characteristic presence of reduced preload in the context of a suspected or known cause. Thus, patients with hypovolemia may display signs of reduced skin turgor, dry mucous membranes, a collapsible IVC on imaging, and low CVP (<8 mmHg) on hemodynamic monitoring through a triple-lumen catheter.

Etiologic manifestations – Patients with hypovolemic shock may present variably depending upon the etiology of fluid loss. As examples, patients may present with a history of heat exposure, vomiting, diarrhea, hematemesis, hematochezia, traumatic hemorrhage, or back pain from a ruptured abdominal aortic aneurysm. Additional details regarding the clinical presentation and diagnosis of the causes of hypovolemic shock are provided separately:

Hemorrhage due to:

-Trauma-related blood loss (see "Initial management of NON-hemorrhagic shock in adult trauma" and "Initial management of trauma in adults" and "Endovascular methods for aortic control in trauma", section on 'Resuscitative aortic occlusion')

-Nontraumatic blood loss (see "Management of symptomatic (non-ruptured) and ruptured abdominal aortic aneurysm" and "Management of thoracic aortic aneurysm in adults" and "Peptic ulcer disease: Clinical manifestations and diagnosis" and "Methods to achieve hemostasis in patients with acute variceal hemorrhage" and "Approach to acute lower gastrointestinal bleeding in adults" and "Approach to acute upper gastrointestinal bleeding in adults")

Nonhemorrhagic fluid loss (see "Etiology, clinical manifestations, and diagnosis of volume depletion in adults")

Pulmonary artery catheterization findings – PAC findings are variable depending upon the degree of hypovolemia (table 10). Initially, the CO is normal (CI 2.8 to 4.2 L/min/m2), the SVR is high (>1400 dynes per second/cm5), and the pcwp is preserved (6 to 15 mmHg). However, with increasing severity, both the CO and pcwp may become reduced.  

Obstructive shock

General clinical manifestations – Patients with obstructive shock usually have hypotension associated with distended neck veins but usually without the clinical signs of fluid overload or reduced preload. The exceptions are patients with subacute cardiac tamponade who often have evidence of fluid overload on examination. On bedside ultrasonography or echocardiography, an effusion with a small right and left ventricle and a dilated IVC may be seen in patients with pericardial tamponade; a dilated right ventricle and small left ventricle may be seen in patients with PE or pneumothorax.

Etiologic manifestations – Depending upon the cause of obstructive shock, patients may present with pleuritic chest pain and acute dyspnea (from pulmonary embolism [PE]), chronic dyspnea and a loud pulmonic component of the second heart sound (pulmonary hypertension), chest pain, tracheal deviation, unilateral reduced breath sounds, and elevated plateau pressures on mechanical ventilation (tension pneumothorax), or quiet heart sounds, pulsus paradoxus, and distended neck veins (cardiac tamponade). Additional details regarding the clinical presentation and diagnosis of the causes of obstructive shock are provided separately:

Pulmonary embolism (see "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism" and "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults")

Tension pneumothorax (see "Thoracostomy tubes and catheters: Indications and tube selection in adults and children", section on 'Tension pneumothorax' and "Pneumothorax in adults: Epidemiology and etiology")

Cardiac tamponade (see "Cardiac tamponade")

Constrictive pericarditis (see "Constrictive pericarditis")

Restrictive cardiomyopathy (see "Restrictive cardiomyopathies")

Pulmonary artery catheterization findings – On PAC, CO is initially normal (CI 2.8 to 4.2 L/min/m2) and reduces as severity progresses, SVR is increased (>1400 dynes per second/cm5), and pcwp is normal (6 to 15 mmHg) or reduced (table 10). Cardiac tamponade, constrictive pericardial disease, and restrictive cardiomyopathy present similarly to cardiogenic shock, but are distinguished from the latter by equalization of the right atrial, right ventricular end-diastolic, and pulmonary artery wedge pressures (waveform 1).

Combined — Importantly, many forms of shock coexist. As an example, hypovolemia may induce or coexist with cardiogenic shock and may result in discordant clinical, biochemical, imaging, and hemodynamic features (eg, low ejection fraction with dry mucous membranes and a collapsible IVC). In such cases, following the response to empiric therapies targeted at the suspected causes of shock may allow the clinician to determine which form of shock is predominant.

The combination of bradycardia, renal failure, AV nodal blockade, shock, and hyperkalemia may suggest BRASH syndrome [44].

REVERSE THE ETIOLOGY — Every attempt should be made to treat the underlying cause of shock. In some cases the etiology is clear (eg, hemorrhagic shock from a gunshot wound to the abdomen), but in other cases the etiology is less obvious (eg, obstructive shock from massive pulmonary embolism). Once the diagnosis is known, specific therapies should be refined, and the response to therapy monitored (eg, mean arterial blood pressure, urine output, mental status, serum lactate level). Further details regarding the treatment and follow-up of patients with specific forms of shock are discussed separately. (See 'Differential diagnosis' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Use of bedside echocardiography as a monitor for therapeutic intervention in critically ill adults".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

Basics topic (see "Patient education: Shock (The Basics)")

SUMMARY AND RECOMMENDATIONS

Shock is defined as a state of cellular and tissue hypoxia due to reduced oxygen delivery and/or increased oxygen consumption or inadequate oxygen utilization. There are four classes of shock; distributive, cardiogenic, hypovolemic, and obstructive. The term “undifferentiated shock” refers to that where the state of shock is recognized but the cause is unknown. (See "Definition, classification, etiology, and pathophysiology of shock in adults" and 'Definition and classification' above.)

The clinical manifestations of undifferentiated shock vary according to the etiology and stage of presentation. Features that are highly suspicious for shock include hypotension; oliguria; abnormal mental status; tachypnea; cool, clammy skin; and metabolic acidosis (usually hyperlactatemia). Most clinical features are neither sensitive nor specific for the diagnosis of shock and are primarily used to narrow the differential diagnosis so that empiric therapies can be administered in a timely fashion. (See 'When to suspect shock' above.)

In patients with undifferentiated hypotension or shock, the airway and breathing should be stabilized with oxygen and/or mechanical ventilation, when necessary. Intravenous access should be secured so that patients can be immediately treated with intravenous fluids (IVF) to restore adequate tissue perfusion. Resuscitative efforts should not be delayed for diagnostic evaluation or for central venous catheterization (algorithm 1A-B). (See 'Assess airway, breathing, circulation' above.)

In patients with undifferentiated hypotension or shock, the clinician should stratify the patient according to the severity of shock and the need for immediate or early intervention so that empiric lifesaving therapies can be administered promptly. Such therapies include intramuscular epinephrine (anaphylaxis), pericardiocentesis (pericardial tamponade), chest tube insertion (tension pneumothorax), surgical intervention (hemorrhagic shock, valve rupture, aortic dissection), cardioversion or pacemaker placement (life-threatening arrhythmias), intravenous antibiotics (sepsis), revascularization procedures (myocardial infarction), systemic thrombolysis (massive pulmonary embolism), and intravenous glucocorticoids (adrenal crisis). (See 'Risk stratification' above.)

For patients with undifferentiated hypotension and shock who have been stabilized or those who present with milder forms of shock, we suggest the following diagnostic evaluation (see 'Initial diagnostic evaluation' above):

Clinicians should take a thorough history and assess sensorium, mucous membranes, lips and tongue, neck veins, lungs, heart, and abdomen, as well as skin and joints. Bedside telemetry and/or electrocardiography should also be performed.

Basic laboratory tests should be performed, including serum lactate level, renal and liver function tests, troponin-I or -T level and/or creatine phosphokinase isoenzymes, brain natriuretic peptide or N-terminal pro-brain natriuretic peptide level, complete blood count and differential, prothrombin time, international normalized ratio, activated partial thromboplastin time, D-dimer level, and blood gas analysis. Additional laboratory tests include those directed at specific etiologies or sequelae of shock (eg, urinalysis, blood cultures).

Portable chest radiography should be performed in most patients with undifferentiated shock. Point-of-care ultrasonography is typically used in patients in whom the diagnosis remains unclear after clinical assessment, in those in whom definitive imaging is unsafe, and to guide resuscitative efforts. Additional imaging modalities are targeted at discovering the etiology of shock (eg, computed tomography of the chest).

Hemodynamic measurements obtained by pulmonary artery catheter can be helpful when the diagnosis or the type of shock remains undetermined (table 8 and table 9), as well as in patients with unknown volume status, severe cardiogenic shock, or in those suspected to have severe underlying pulmonary artery hypertension.

Patients with suspected shock should receive hemodynamic support with IVF (usually crystalloids in well-defined boluses of 500 to 1000 mL), followed by vasopressors (table 11), should IVF fail to restore adequate tissue perfusion. However, in patients with hypovolemic shock, we prefer to continue to administer fluids. While the optimal end-organ perfusion pressure is unclear, in general, we suggest maintaining the mean arterial pressure greater than 65 to 70 mmHg since higher targets may be associated with harm. (See 'Hemodynamic support' above.)

A diagnosis of shock is based upon a constellation of clinical, biochemical, and hemodynamic features. Using data derived from the diagnostic evaluation, shock can typically be classified and the etiology narrowed to a few possibilities. (See 'Diagnosis' above and 'Differential diagnosis' above.)

Empiric therapies should be administered early (eg, antibiotics). The response should be monitored and therapies refined once the diagnosis is clear. (See 'Reverse the etiology' above.)

REFERENCES

  1. Vincent JL, De Backer D. Circulatory shock. N Engl J Med 2013; 369:1726.
  2. Rodgers KG. Cardiovascular shock. Emerg Med Clin North Am 1995; 13:793.
  3. Churpek MM, Zadravecz FJ, Winslow C, et al. Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients. Am J Respir Crit Care Med 2015; 192:958.
  4. Seymour CW, Liu VX, Iwashyna TJ, et al. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315:762.
  5. Kraut JA, Madias NE. Lactic acidosis. N Engl J Med 2014; 371:2309.
  6. Liu VX, Morehouse JW, Marelich GP, et al. Multicenter Implementation of a Treatment Bundle for Patients with Sepsis and Intermediate Lactate Values. Am J Respir Crit Care Med 2016; 193:1264.
  7. Cardenas-Garcia J, Schaub KF, Belchikov YG, et al. Safety of peripheral intravenous administration of vasoactive medication. J Hosp Med 2015; 10:581.
  8. Walkey AJ, Wiener RS, Ghobrial JM, et al. Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis. JAMA 2011; 306:2248.
  9. Levraut J, Ciebiera JP, Chave S, et al. Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction. Am J Respir Crit Care Med 1998; 157:1021.
  10. del Portal DA, Shofer F, Mikkelsen ME, et al. Emergency department lactate is associated with mortality in older adults admitted with and without infections. Acad Emerg Med 2010; 17:260.
  11. Cavallazzi R, Bennin CL, Hirani A, et al. Is the band count useful in the diagnosis of infection? An accuracy study in critically ill patients. J Intensive Care Med 2010; 25:353.
  12. Perera P, Mailhot T, Riley D, Mandavia D. The RUSH exam: Rapid Ultrasound in SHock in the evaluation of the critically lll. Emerg Med Clin North Am 2010; 28:29.
  13. Labovitz AJ, Noble VE, Bierig M, et al. Focused cardiac ultrasound in the emergent setting: a consensus statement of the American Society of Echocardiography and American College of Emergency Physicians. J Am Soc Echocardiogr 2010; 23:1225.
  14. Atkinson PR, McAuley DJ, Kendall RJ, et al. Abdominal and Cardiac Evaluation with Sonography in Shock (ACES): an approach by emergency physicians for the use of ultrasound in patients with undifferentiated hypotension. Emerg Med J 2009; 26:87.
  15. Shokoohi H, Boniface KS, Pourmand A, et al. Bedside Ultrasound Reduces Diagnostic Uncertainty and Guides Resuscitation in Patients With Undifferentiated Hypotension. Crit Care Med 2015; 43:2562.
  16. Ettin D, Cook T. Using ultrasound to determine external pacer capture. J Emerg Med 1999; 17:1007.
  17. Macedo W Jr, Sturmann K, Kim JM, Kang J. Ultrasonographic guidance of transvenous pacemaker insertion in the emergency department: a report of three cases. J Emerg Med 1999; 17:491.
  18. Soldati G, Testa A, Sher S, et al. Occult traumatic pneumothorax: diagnostic accuracy of lung ultrasonography in the emergency department. Chest 2008; 133:204.
  19. Zhang M, Liu ZH, Yang JX, et al. Rapid detection of pneumothorax by ultrasonography in patients with multiple trauma. Crit Care 2006; 10:R112.
  20. Knudtson JL, Dort JM, Helmer SD, Smith RS. Surgeon-performed ultrasound for pneumothorax in the trauma suite. J Trauma 2004; 56:527.
  21. Sartori S, Tombesi P, Trevisani L, et al. Accuracy of transthoracic sonography in detection of pneumothorax after sonographically guided lung biopsy: prospective comparison with chest radiography. AJR Am J Roentgenol 2007; 188:37.
  22. Rozycki GS, Feliciano DV, Ochsner MG, et al. The role of ultrasound in patients with possible penetrating cardiac wounds: a prospective multicenter study. J Trauma 1999; 46:543.
  23. Mandavia DP, Hoffner RJ, Mahaney K, Henderson SO. Bedside echocardiography by emergency physicians. Ann Emerg Med 2001; 38:377.
  24. Marbach JA, Almufleh A, Di Santo P, et al. Comparative Accuracy of Focused Cardiac Ultrasonography and Clinical Examination for Left Ventricular Dysfunction and Valvular Heart Disease: A Systematic Review and Meta-analysis. Ann Intern Med 2019; 171:264.
  25. Tayal VS, Kline JA. Emergency echocardiography to detect pericardial effusion in patients in PEA and near-PEA states. Resuscitation 2003; 59:315.
  26. Kanji HD, McCallum J, Sirounis D, et al. Limited echocardiography-guided therapy in subacute shock is associated with change in management and improved outcomes. J Crit Care 2014; 29:700.
  27. Volpicelli G, Lamorte A, Tullio M, et al. Point-of-care multiorgan ultrasonography for the evaluation of undifferentiated hypotension in the emergency department. Intensive Care Med 2013; 39:1290.
  28. Jones AE, Craddock PA, Tayal VS, Kline JA. Diagnostic accuracy of left ventricular function for identifying sepsis among emergency department patients with nontraumatic symptomatic undifferentiated hypotension. Shock 2005; 24:513.
  29. Taylor RA, Moore CL. Accuracy of emergency physician-performed limited echocardiography for right ventricular strain. Am J Emerg Med 2014; 32:371.
  30. Jones AE, Tayal VS, Sullivan DM, Kline JA. Randomized, controlled trial of immediate versus delayed goal-directed ultrasound to identify the cause of nontraumatic hypotension in emergency department patients. Crit Care Med 2004; 32:1703.
  31. Derr C, Drake JM. Esophageal rupture diagnosed with bedside ultrasound. Am J Emerg Med 2012; 30:2093.e1.
  32. Moore CL, Rose GA, Tayal VS, et al. Determination of left ventricular function by emergency physician echocardiography of hypotensive patients. Acad Emerg Med 2002; 9:186.
  33. Sabia P, Abbott RD, Afrookteh A, et al. Importance of two-dimensional echocardiographic assessment of left ventricular systolic function in patients presenting to the emergency room with cardiac-related symptoms. Circulation 1991; 84:1615.
  34. Haydar SA, Moore ET, Higgins GL 3rd, et al. Effect of bedside ultrasonography on the certainty of physician clinical decisionmaking for septic patients in the emergency department. Ann Emerg Med 2012; 60:346.
  35. Atkinson PR, Milne J, Diegelmann L, et al. Does Point-of-Care Ultrasonography Improve Clinical Outcomes in Emergency Department Patients With Undifferentiated Hypotension? An International Randomized Controlled Trial From the SHoC-ED Investigators. Ann Emerg Med 2018; 72:478.
  36. Connors AF Jr, Speroff T, Dawson NV, et al. The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators. JAMA 1996; 276:889.
  37. Harvey S, Harrison DA, Singer M, et al. Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a randomised controlled trial. Lancet 2005; 366:472.
  38. Shah MR, Hasselblad V, Stevenson LW, et al. Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials. JAMA 2005; 294:1664.
  39. Mimoz O, Rauss A, Rekik N, et al. Pulmonary artery catheterization in critically ill patients: a prospective analysis of outcome changes associated with catheter-prompted changes in therapy. Crit Care Med 1994; 22:573.
  40. Hylands M, Moller MH, Asfar P, et al. A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension. Can J Anaesth 2017; 64:703.
  41. Gamper G, Havel C, Arrich J, et al. Vasopressors for hypotensive shock. Cochrane Database Syst Rev 2016; 2:CD003709.
  42. Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014; 370:1583.
  43. Pope JV, Jones AE, Gaieski DF, et al. Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis. Ann Emerg Med 2010; 55:40.
  44. Farkas JD, Long B, Koyfman A, Menson K. BRASH Syndrome: Bradycardia, Renal Failure, AV Blockade, Shock, and Hyperkalemia. J Emerg Med 2020; 59:216.
Topic 98976 Version 29.0

References

1 : Circulatory shock.

2 : Cardiovascular shock.

3 : Incidence and Prognostic Value of the Systemic Inflammatory Response Syndrome and Organ Dysfunctions in Ward Patients.

4 : Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

5 : Lactic acidosis.

6 : Multicenter Implementation of a Treatment Bundle for Patients with Sepsis and Intermediate Lactate Values.

7 : Safety of peripheral intravenous administration of vasoactive medication.

8 : Incident stroke and mortality associated with new-onset atrial fibrillation in patients hospitalized with severe sepsis.

9 : Mild hyperlactatemia in stable septic patients is due to impaired lactate clearance rather than overproduction.

10 : Emergency department lactate is associated with mortality in older adults admitted with and without infections.

11 : Is the band count useful in the diagnosis of infection? An accuracy study in critically ill patients.

12 : The RUSH exam: Rapid Ultrasound in SHock in the evaluation of the critically lll.

13 : Focused cardiac ultrasound in the emergent setting: a consensus statement of the American Society of Echocardiography and American College of Emergency Physicians.

14 : Abdominal and Cardiac Evaluation with Sonography in Shock (ACES): an approach by emergency physicians for the use of ultrasound in patients with undifferentiated hypotension.

15 : Bedside Ultrasound Reduces Diagnostic Uncertainty and Guides Resuscitation in Patients With Undifferentiated Hypotension.

16 : Using ultrasound to determine external pacer capture.

17 : Ultrasonographic guidance of transvenous pacemaker insertion in the emergency department: a report of three cases.

18 : Occult traumatic pneumothorax: diagnostic accuracy of lung ultrasonography in the emergency department.

19 : Rapid detection of pneumothorax by ultrasonography in patients with multiple trauma.

20 : Surgeon-performed ultrasound for pneumothorax in the trauma suite.

21 : Accuracy of transthoracic sonography in detection of pneumothorax after sonographically guided lung biopsy: prospective comparison with chest radiography.

22 : The role of ultrasound in patients with possible penetrating cardiac wounds: a prospective multicenter study.

23 : Bedside echocardiography by emergency physicians.

24 : Comparative Accuracy of Focused Cardiac Ultrasonography and Clinical Examination for Left Ventricular Dysfunction and Valvular Heart Disease: A Systematic Review and Meta-analysis.

25 : Emergency echocardiography to detect pericardial effusion in patients in PEA and near-PEA states.

26 : Limited echocardiography-guided therapy in subacute shock is associated with change in management and improved outcomes.

27 : Point-of-care multiorgan ultrasonography for the evaluation of undifferentiated hypotension in the emergency department.

28 : Diagnostic accuracy of left ventricular function for identifying sepsis among emergency department patients with nontraumatic symptomatic undifferentiated hypotension.

29 : Accuracy of emergency physician-performed limited echocardiography for right ventricular strain.

30 : Randomized, controlled trial of immediate versus delayed goal-directed ultrasound to identify the cause of nontraumatic hypotension in emergency department patients.

31 : Esophageal rupture diagnosed with bedside ultrasound.

32 : Determination of left ventricular function by emergency physician echocardiography of hypotensive patients.

33 : Importance of two-dimensional echocardiographic assessment of left ventricular systolic function in patients presenting to the emergency room with cardiac-related symptoms.

34 : Effect of bedside ultrasonography on the certainty of physician clinical decisionmaking for septic patients in the emergency department.

35 : Does Point-of-Care Ultrasonography Improve Clinical Outcomes in Emergency Department Patients With Undifferentiated Hypotension? An International Randomized Controlled Trial From the SHoC-ED Investigators.

36 : The effectiveness of right heart catheterization in the initial care of critically ill patients. SUPPORT Investigators.

37 : Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a randomised controlled trial.

38 : Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials.

39 : Pulmonary artery catheterization in critically ill patients: a prospective analysis of outcome changes associated with catheter-prompted changes in therapy.

40 : A systematic review of vasopressor blood pressure targets in critically ill adults with hypotension.

41 : Vasopressors for hypotensive shock.

42 : High versus low blood-pressure target in patients with septic shock.

43 : Multicenter study of central venous oxygen saturation (ScvO(2)) as a predictor of mortality in patients with sepsis.

44 : BRASH Syndrome: Bradycardia, Renal Failure, AV Blockade, Shock, and Hyperkalemia.