You are making rounds in the intensive care and the nurse reports the patient has spiked a fever, oxygen saturations are below 85%, tachycardia, a

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CHAPTER 141 Sepsis and Shock

Kevin Felner, MD

Robert L. Smith, MD

Key Clinical Questions

What is the definition of systemic inflammatory response syndrome (SIRS) and how do you differentiate SIRS from sepsis, severe sepsis, and septic shock?

Which patients presenting with sepsis need admission to the intensive care unit (ICU)?

Which septic patients require invasive monitoring (arterial catheter, central venous catheter)?

What interventions in the treatment of sepsis improve mortality? Which septic patients deserve empiric steroids as part of the therapeutic regimen?

INTRODUCTION

Sepsis is a clinical syndrome that complicates severe infection and is characterized by systemic inflammation and widespread tissue injury. The incidence and number of sepsis-

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related deaths has increased yearly from 1979 to 2009 with a combined peak of both primary and secondary sepsis in 2009 greater than 1 million patients in the United States; and sepsis is the ninth most common cause of death in the United States. Despite the rising number of cases, earlier identification of sepsis and improved intensive medical care has been shown to reduce the overall mortality rate to approximately 17.9%. Severity is correlated with mortality (Table 141-1).

TABLE 141-1 Sepsis Syndromes, Definitions, and Mortality Risk

Syndrome Definition Approximate Mortality

Systemic inflammatory response syndrome (SIRS)

At least two of the following four clinical features: 1. Temperature >38°C or <36°C 2. Heart rate >90 beats/min 3. Respiratory rate >20 breaths/min or

PaCO2 <32 mm Hg 4. White blood cell (WBC) count >12,000

cells/mm3, or <4000 cells/mm3, or >10% immature (band) forms

10%

Sepsis SIRS criteria plus a culture-proven infection or presumed presence of an infection

20%

Severe sepsis Sepsis plus presence of one or more organ dysfunctions including: • Pulmonary dysfunction (eg, acute

respiratory distress syndrome) • Cardiac dysfunction • Renal dysfunction • Hepatic dysfunction • Neurologic dysfunction (altered

sensorium) • Hematologic dysfunction (eg,

disseminated intravascular coagulation [DIC], thrombocytopenia)

• Lactic acidosis (indicating end-organ hypoperfusion)

20%-40%

Septic shock Sepsis and refractory hypotension with mean systemic blood pressure lower than 65 mm Hg unresponsive to crystalloid fluid challenge of 20-40 cc/kg

40%-60%

Initially successful shock resuscitation may still be associated with considerable morbidity and mortality. Multiple organ dysfunction syndrome (MODS) refers to severe

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acquired dysfunction of at least two organ systems lasting at least 24 to 48 hours in the setting of sepsis, trauma, burns, or severe inflammatory conditions so that homeostasis cannot be maintained without intervention. Mortality is directly correlated with the number of dysfunctional organs and the duration of dysfunction (Table 141-2). An uncontrolled hyperinflammatory response is believed to be the cause of multiple organ dysfunction.

TABLE 141-2 Correlation between Organ Failure and Mortality in Sepsis

Organ Failure Mortality

One organ lasting more than 1 d 20%

Two organs lasting more than 1 d 40%

Three organs lasting more than 3 d 80%

The American College of Chest Physicians (ACCP) and the Society of Critical Care Medicine (SCCM) defined the following terms to describe the spectrum of systemic inflammation and sepsis (the International Sepsis Definitions Conference, 2001):

Systemic inflammatory response syndrome (SIRS) is a clinical syndrome that results from activation of the immune system whether due to infection, trauma, burns, or a noninfectious inflammatory process. This syndrome includes at least two of the following: (1) Temperature >38°C or <36°C (2) Heart rate >90 beats/min (3) Respiratory rate >20 breaths/min or PaCO2 < 32 mm Hg (4) White blood cell count >12,000 cells/mm3, or <4000 cells/mm3, or >10%

immature (band) forms Sepsis is a clinical syndrome that results from activation of the immune system with a documented infection. The definition of sepsis includes the above SIRS criteria plus a culture-proven infection or presumed presence of an infection.

A recent study has brought into the question the sensitivity of the current definition, suggesting that many patients, usually older, do not actually even have two out of four SIRS criteria when they are septic. These caveats have not been adopted into any formal guidelines at this time. Clinicians should have a lower threshold for considering sepsis, especially in older patients with a suggestive presentation despite not fulfilling the above criteria.

The severity of sepsis is graded according to the associated organ dysfunction and hemodynamic compromise. Severe sepsis refers to the presence of sepsis and one or more organ dysfunctions. Organ dysfunction may be defined as hypotension, acute lung injury including acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), thrombocytopenia, altered mental status, mottled skin, capillary refill greater than 3 seconds, renal dysfunction, hepatic dysfunction, cardiac dysfunction based on echocardiography or measurement of cardiac index, or lactic acidosis indicating hypoperfusion. The phenomenon of sepsis-induced myocardial dysfunction occurs when patients have normal cardiac function prior to their infection and the sepsis induces a

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global cardiac dysfunction, seen on echocardiography as global hypokinesis, which may impair the expected high cardiac output usually associated with a vasodilated circulation.

Septic shock refers to the presence of sepsis and refractory hypotension with mean systemic blood pressure lower than 65 mm Hg that is unresponsive to crystalloid fluid challenge of 20 to 40 cc/kg. Septic shock leads to acute circulatory collapse.

PATHOPHYSIOLOGY Sepsis is as an uncontrolled inflammatory response to an infection in which a dysregulated host immune response leads to multiorgan involvement not limited to the source infected organ. Microbial antigens such as lipopolysaccharides (LPS) from Gram- negative bacteria bind to Toll-like receptors on inflammatory cells, thereby causing a complex immune reaction involving T-cells, macrophages, neutrophil, endothelial cells, and dendritic cells. Cytokines (such as IL-1, IL-6, IL-8), growth factors (such as TNFa), high- mobility group box-1 (HMGB-1), arachidonic acid metabolites, and nitric oxide and host genetics likely determine the nature of the response. The complement cascade, coagulation cascades, platelets, and leukocytes interact at the vascular endothelium level resulting in microvascular injury, thrombosis, and loss of endothelial integrity, which altogether results in tissue ischemia. This diffuse endothelial disruption is responsible for the various organ dysfunctions and global tissue hypoxia that accompany severe sepsis and septic shock. Multiple mechanisms including decreased preload, vasoregulatory dysfunction, myocardial depression, and impaired tissue extraction due to microcirculatory dysfunction or mitochondrial dysfunction (cytopathic hypoxia) cause global tissue hypoxia. Some noninfectious processes (eg, pancreatitis) may also lead to a dysregulated host immune response and multiorgan dysfunction, and these conditions are categorized using the term SIRS. These patients appear septic without a clear infectious source.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis for conditions that cause sepsis includes conditions that present with high-output nonshock states. Common disorders that meet SIRS criteria include nonmassive pulmonary embolus, alcohol withdrawal, even COPD exacerbations. Thyrotoxicosis, aortic regurgitation, arteriosclerosis, and cirrhosis may mimic sepsis with high cardiac output state and wide pulse pressure without shock.

Conditions that belong to the category of vasodilatory or high cardiac output shock include anaphylaxis, adrenal insufficiency, and neurogenic shock in addition to septic shock. The other causes of shock all fall into a category of low-output states, including cardiogenic shock, hypovolemic shock, and obstructive shock (Table 141-3).

TABLE 141-3 Differential Diagnosis of Shock

Vasodilatory shock Sepsis Anaphylaxis Adrenal insufficiency Neurogenic

Low-output shock states Cardiogenic (eg, massive myocardial infarction, myocarditis,

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valvular disease) Hypovolemic (eg, hemorrhagic, gastrointestinal losses, burns, pancreatitis) Obstructive (eg, massive PE, tension pneumothorax, auto- PEEP, tamponade, abdominal compartment syndrome)

PE, pulmonary embolus; PEEP, positive end expiratory pressure.

DIAGNOSIS

Presentation of sepsis often varies according to infection source, patient age, underlying comorbidities (including immune system function and cardiac status), and timing of presentation relative to onset of sepsis. Early manifestations of sepsis (tachycardia, oliguria, and hyperglycemia) may be subtle and easily overlooked in the hospitalized patient. In addition, a patient with underlying poor cardiac function who becomes septic may not be able to generate the high cardiac outputs expected in sepsis and may not have the typical findings on physical examination of a septic patient. Signs of established sepsis include altered mental status, metabolic acidosis and respiratory alkalosis, hypotension with decreased systemic vascular resistance (SVR) and elevated cardiac output, and coagulopathy. Late manifestations include acute lung injury (ALI), ARDS, acute renal failure, hepatic dysfunction, and refractory shock.

Sepsis may be related to a systemic inflammatory response to any infectious source. Less than 50% of septic patients will have positive blood cultures, and 20% to 30% of patients will have no microbial cause identified from any source. Aggressive clinical evaluation includes a detailed history and review of systems. A complete physical examination can assess for sometimes inconspicuous and missed infection sources, including skin and soft tissue, central nervous system, gastrointestinal tract, and indwelling devices.

It is critical to stabilize the patient and identify the cause of the ongoing immunologic response. Obtaining cultures for blood, urine, and other fluids early, prior to administration of antibiotics, should be a high priority and helps preserve the integrity of results, but the evaluation should not be at the expense of administering antibiotics expediently. Identification of the underlying source remains paramount, and lack of source identification and control may render choice of antibiotics meaningless. The most common sites of infection in sepsis are the urinary and respiratory tracts, but any organ system may be involved. Urinary sources include cystitis, pyelonephritis, and perinephric abscess. Patients with kidney stones may develop Gram-negative septicemia. Sinusitis, mastoiditis, pneumonia, lung abscess, and empyema may be associated with sepsis. Gastrointestinal sources of sepsis may include esophageal rupture or perforation following a procedure or after vomiting, cholangitis, cholecystitis, intestinal infarction or perforation, acute pancreatitis, Clostridium difficile colitis, diverticulitis, and intra- abdominal abscess. Postoperative mediastinitis and acute bacterial endocarditis may lead to sepsis. Skin and soft tissue sources of sepsis include infected decubitus ulcer, postoperative wound infection, soft tissue abscess, or necrotizing fasciitis. Vascular causes of infection include central and peripheral lines, arterial catheters, dialysis catheters, ventriculoperitoneal shunts and septic thrombophlebitis. Infected articular

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prosthetic devices have also been associated with sepsis. Meningitis and intracranial abscess, sometimes associated with neurosurgery, are also considerations.

Relevant diagnostic studies based on symptoms, signs, and clinical suspicion in patients may include chest or abdominal radiography and culture of blood, urine, sputum, or other relevant body fluids that may be infected such as cerebrospinal fluid (CSF) analysis, paracentesis in patients with ascites, or thoracentesis in patients with pleural effusions. When plain films, blood cultures, and fluid cultures do not yield a likely infectious culprit, advanced imaging with chest and abdominal computed tomography may identify pulmonary infiltrates, intra-abdominal abscesses, and obstructing renal stones. Biliary pathology may be better imaged with ultrasound. In hemodynamically stable patients, magnetic resonance imaging (MRI), or endoscopic retrograde pancreatography (ERCP) may be indicated. Many patients undergo echocardiography to assess cardiac function and to identify the presence of vegetations.

TRIAGE AND HOSPITAL ADMISSION All patients with a presentation of severe sepsis or septic shock should be admitted to or transferred to a monitored setting that is capable of continuous vital sign monitoring with the ability to measure central venous pressure (CVP) and central venous oxygen saturations (ScvO2).

PRACTICE POINT

Recent data suggest that most septic shock patients may be managed without the use of CVP or ScvO2 monitoring; however the values may still be used to assess response to therapy in selected patients with undifferentiated or mixed shock and in patients with underlying organ dysfunction such as chronic kidney disease and cognitive impairment.

Those patients with SIRS and sepsis should be monitored closely if not placed in an intensive care unit setting so that they can be treated promptly if they start to show signs of deterioration. Vital signs should be monitored frequently in addition to telemetry and continuous pulse oximetry. Intermediate care units (sometimes called step-down units or transitional care units) vary from facility to facility in their capabilities for invasive monitoring and use of vasoactive agents. The protocols and policies at individual institutions will help determine placement of these patients, based on monitoring requirements and response to initial resuscitation in the emergency department or on a medical floor.

PRACTICE POINT

Early aggressive resuscitation, early antibiotics (within 1 hour of severe sepsis or septic shock identification), and early source identification and control improve outcomes in patients with severe sepsis and septic shock. These patients require timely evaluation to determine admission location, and patients with marginally stable

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clinical parameters should be admitted to an intensive care unit setting to expeditiously meet early care goals to improve outcomes.

MANAGEMENT Management of severe sepsis and septic shock requires a structured approach that ensures proper diagnostic evaluation and implementation of evidence-based interventions in an expedient manner to improve outcomes (Figure 141-1). This approach requires (1) empiric antibiotic coverage of an infectious source while cultures are pending, (2) optimal fluid resuscitation, (3) pressor and/or inotrope therapy for selected patients, and (4) consideration of additional therapies such as drainage of abscesses, removal of lines, moderate (but not intensive) control of hyperglycemia, and (5) consideration of steroids in selected patient subsets when indicated.

Figure 141-1 Sepsis algorithm.

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ANTIBIOTIC THERAPY Initial emergency department management of patients with sepsis begins with a heightened awareness of the condition by assessing all patients for the presence of SIRS criteria. Numerous studies have shown that early and appropriate antibiotics are associated with markedly improved outcomes. Antibiotics should be directed against the likely organisms based upon the presumptive infection source. In many situations, especially when the presumptive source of infection is not obvious, multiple antibiotic agents should be initiated to offer broad antimicrobial coverage. Such broad coverage should then be re-evaluated daily to optimize dosing and minimize drug interactions and the development of resistance. Choice of antibiotic depends upon penetration into the suspected infection site, local resistance patterns, efficacy against the most likely organisms, prior exposure to specific antibiotics, and risks of side effects. Therapeutic drainage of an infected space is critical to diagnose the source of infection, guide the choice of antibiotic therapy, and facilitate recovery. In patients with devices, clinicians may need to evaluate and consider early and rapid removal of potentially or known infected invasive devices including central venous catheters (CVCs), peripherally inserted central venous catheters (PICCs), urinary catheters, and other implanted hardware.

Recent evidence suggests that mortality increases with delay of antibiotics more than 1 hour after identification and management of severe sepsis or septic shock. Patients at risk of fungal infections (ie, recent abdominal surgery, total parenteral nutrition (TPN) administration, chronic steroid use) may benefit from empiric antifungal agents in addition to the antimicrobial regimen.

More data is needed before recommending use of procalcitonin levels in septic patients. While there is reasonable evidence that procalcitonin may be useful in the management of community acquired pneumonia and COPD exacerbations, the evidence for its use in decisions to discontinue antibiotics in septic patients is less robust. Studies comparing a calcitonin-guided algorithm with standard management show no difference in the amount of time spent on antibiotics.

INTRAVENOUS FLUIDS

Volume resuscitation should begin simultaneously with empiric antibiotic therapy in patients suspected of having sepsis. In the vasodilatory state low blood pressures with decreased venous return lead to an underfilled, but hyperdynamic heart. Rivers and colleagues showed that early goal-directed therapy (EGDT), initiated in the emergency department, improved mortality in patients with severe sepsis and septic shock.

For routine use in sepsis, crystalloid fluid should be used first due to evidence of benefit, markedly lower expense, and demonstrated safety (lacking the inherent risks of blood product administration with albumin). The Saline Versus Albumin Fluid Evaluation (SAFE) study evaluated nearly 7,000 critically ill patients, 18% of whom had severe sepsis. Patients were randomly assigned to receive 4% albumin versus normal saline, and investigators reported no differences in mortality at 28 days. Additionally, there were no significant differences seen in the sepsis subgroup. Despite a theoretic benefit to using albumin in highly selected patients with significant volume overload, no studies support this approach. The Albumin Replacement in Severe Sepsis or Septic Shock (ALBIOS) study showed no mortality benefit, though there was a suggestion that patients with septic shock benefitted from albumin.

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The choice of crystalloid has recently come into question based on the results of recent data suggesting that normal saline (NS) is associated with renal insufficiency as well as hyperchloremic metabolic acidosis. Alternatives include lactated ringers (LR) and plasmalyte and Normosol. LR contains 4 mEq/L of potassium; however, this is unlikely to cause a meaningful increase in serum potassium levels due to the volume of distribution in the intracellular space, even in patients with renal failure, and any rise is offset by the alkalinizing effect of LR. Three small randomized control trials comparing NS versus LR in perirenal transplant surgery patients showed that patients receiving several liters of LR had marginally lower potassium levels. There is currently insufficient data to support the routine use of the more costly alternatives, plasmalyte and Normosol, which are balanced crystalloid solutions; they may offset acidosis with anions that are converted to bicarbonate.

Early goal-directed therapy includes early aggressive volume resuscitation in the first 6 hours of care, and other measures over the first hours and days of care (see Figure 141-1). Close monitoring of central venous pressure (CVP) is accomplished with a central venous catheter placed in the internal jugular or subclavian vein. Central venous pressure and ScvO2 monitoring allows adjustment of or addition of interventions based on the parameters measured within the individual patient to achieve the goal of ScvO2 at 70%, if the patient remains hypotensive (mean arterial pressure [MAP] < 65 mm Hg) after a reasonable fluid challenge with crystalloid (approximately 20-40 cc/kg) to optimize filling pressures.

The EGDT algorithm, whose utility has come into question with three recent trials, uses a CVP goal of 8 to 12 cm H2O, which is a reasonable estimate goal. However, that goal should not be applied blindly to all patients without knowledge of coexisting conditions including pulmonary arterial hypertension, dilated cardiomyopathy, and old right ventricular infarction. Clinicians may follow the trend of the CVP and correlate it with the ScvO2, patient hemodynamics, and evidence of organ perfusion including mental status and urine output. Ample data suggest that the CVP serves as a poor predictor of volume responsiveness, and multiple factors are necessary to determine the need for continued volume resuscitation including passive leg raising and pulse pressure variation. Passive leg raise is a technique in which a spontaneously breathing patient is placed with the legs elevated, essentially transferring approximately 300 cc of intravascular fluid into the thorax, followed by measurement of cardiac output. This technique avoids the administration of exogenous fluid. The measurement of ScvO2 carries valuable information and weight, offering the clinician an assessment of cardiac function and oxygen delivery balanced against oxygen consumption.

Despite strong evidence from the original Rivers et al. EGDT trial more than a decade ago, recent publications of the PROCESS (Protocolized Care for Early Septic Shock) trial, the ARISE (Australasian Resuscitation in Early Septic Shock) trial, and the PRoMISe (Protocolized Management in Septic Shock) trial have challenged the utility of the Rivers EGDT algorithm. The three trials showed that with early recognition of septic shock in the emergency department, management according to the Rivers’ EGDT algorithm, including placement of central lines and measurement of CVP and ScvO2, did not improve any outcome measures when compared to standard management. The results of these three large, multicenter, randomized control trials have seriously challenged what had become axiomatic since the publication of Rivers original EGDT trial. A change in management, however, may not be immediate as more than 50% of the patients in the EGDT and non-

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EGDT arms of the trials had central lines placed, and use of vasopressors without placement of a central line has not gained mainstream acceptance. That said, some patients with early positive response to IV fluids and other aggressive measures may not require a central line. Furthermore, use of lactate levels (rather than ScvO2 ± CVP measurements) should provide adequate evaluation of response to therapy, supported by recent studies.

In addition, there has been a change in the paradigm that calls for the use of large volume resuscitation in the treatment of septic patients. Due to the ample data regarding the dangers of over resucitation and its deleterious effects on organ function, fluid management has shifted to somewhat less aggressive volume resuscitation and earlier use of vasoconstrictors.

PRACTICE POINT

Central venous saturation (ScvO2) is a measure of oxygen saturation taken from the distal tip of a central venous line inserted just proximal to the right atrium. The ScvO2 measures the balance between oxygen delivery and oxygen consumption, with normal ScvO2 ranging between 65% and 75%. Lower values reflect a high oxygen extraction state, usually seen in states of shock with low cardiac output (cardiogenic, hypovolemic, obstructive). In sepsis, as in other vasodilatory or high cardiac output states, low oxygen extraction —possibly due to mitochondrial dysfunction—leads to higher values of ScvO2. Often, these higher values of ScvO2 are not apparent until the patient has been adequately resuscitated with intravascular volume expansion. The mean ScvO2 in the Rivers study was 55%, which is lower than values seen in other sepsis trials. Early goal-directed therapy (EGDT) studies initially suggested that clinicians should augment therapeutic interventions when ScvO2 is less than 70% in patients with severe sepsis or septic shock. Three recent studies have shown that outcomes are no worse when ScvO2 is not used to guide management. More recent studies suggest that lactate clearance of at least 10% at a minimum of 2 hours after beginning volume resuscitation is a valid way to assess the efficacy of intravenous fluid administration. For EGDT the order of therapy augmentation included: volume expansion (to achieve CVP 8-12 mm Hg) → pressor agents (to achieve MAP ≥ 65 mm Hg) → transfusion of packed RBCs (to achieve an ScvO2 ≥ 70%) → inotropic agents (to achieve an ScvO2 ≥ 70%). This sequence has been challenged by the same three studies comparing EGDT versus standard treatment. A less codified algorithm might include 20-30 cc/kg fluid administration, pressor administration for patients who remain hypotensive with signs of hypoperfusion, further evaluation of the need for additional fluid, along with lactate clearance after the first 2 hours of therapy. Placement of a CVL and measurement of ScvO2 should be individualized, and not routinely used in the care of many patients with sepsis. Of highest importance is early antibiotic administration and intravenous fluids via a secure peripheral or central venous line.

BLOOD TRANSFUSION

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Patients with severe sepsis or septic shock who have been resuscitated adequately will usually demonstrate the physiology of a low oxygen extraction state with high ScvO2 values, but importantly, preresuscitation values may make patients appear as high oxygen extractors, with low ScvO2 values more consistent with a low cardiac output state. Early goal-directed therapy protocol includes transfusing red blood cells if the hematocrit is less than 30% and the ScvO2 remains less than 70% after meeting CVP and blood pressure goals. While a subgroup analysis in the original EGDT trial favored transfusions to improve outcomes, potential deleterious effects from red blood cell transfusions, including questionable efficacy of older stored blood, the immunomodulating effects of red blood cell transfusions, and the risk of transfusion reactions, make this part of the EGDT protocol more difficult to recommend broadly for every patient meeting EGDT criteria. The 2013 Surviving Sepsis Guidelines were revised for red cell transfusions due to the controversy and conflicting data regarding the benefits and risks of red blood cell transfusions. Current recommendations employ a transfusion threshold of 7 gm/dL once tissue hypoperfusion has resolved, except in the setting of active cardiac ischemia, blood loss, severe hypoxemia, and ischemic heart disease. The target goal recommendation is 7 gm/dl to 9 mg/dL, and transfusion for hemoglobin threshold less than 7 g/dL has been shown to have equivalent outcomes for mortality and other relevant outcomes as transfusion for a hemoglobin threshold less than 9 g/dL in patients with septic shock based on the 2014 TRISS trial.

VASOACTIVE MEDICATIONS An important aspect of sepsis management includes vasoactive medications. Vasopressors are often required to maintain mean arterial blood pressures (MAP) above a target value and the choice of agent depends on the physiologic need (Table 141-4). The EGDT protocol recommends vasopressor agents to maintain MAP ≥ 65 mm Hg. There is no firm evidence favoring one vasopressor agent over another, but norepinephrine likely has the greatest vasoconstrictor potency along with some inotropic effect. The most recent Surviving Sepsis Guidelines recommend epinephrine as the second line vasopressor of choice after norepinephrine based on several randomized studies suggesting worse outcomes with use of dopamine (compared to norepinephrine). Epinephrine’s most concerning side effects include arrhythmias and elevated lactate levels, which are due to beta receptor agonism rather than ongoing organ ischemia. Dopamine may be used if a more inotropic and chronotropic effect is desired and should be avoided if cardiogenic shock is suspected due to demonstrated increased mortality and arrhythmias in that patient population. Low-dose dopamine does not provide renal protection, and should not be used solely for that purpose. Phenylephrine may be the preferred agent for blood pressure elevation in patients with prohibitive tachycardia or arrhythmias. Vasopressin, a pure vasoconstrictor, has been used to lessen the doses of adrenergic vasopressor agents; however, current available data does not support its routine use in severe sepsis or septic shock.

TABLE 141-4 Vasoactive Medications in Sepsis

Medication (Dose) Inotropy Chronotropy Arterial Vasoconstriction Practical Uses

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Norepinephrine 0.01- 3.00 mcg/kg/min; 8- 30 mcg/min typical dosing

Yes Yes (but less than dopamine)

Yes • First line for many patients with severe sepsis or septic shock

• Significant vasoconstriction with inotropy which is helpful for patients with poor left ventricular reserve or sepsis-related cardiomyopathy

Dopamine 1-5 mcg/kg/min, increased renal blood flow; 5-10 mcg/kg/min, increased chronotropy/inotropy; >10 mcg/kg/min, predominant vasoconstriction, increased blood pressure

Yes Yes Yes • Not a first line vasopressor for severe sepsis or septic shock. May be useful for severe bradycardia and mild hypotension

• Randomized comparison to norepinephrine showed no significant differences in mortality, but increased arrhythmias with dopamine and increased mortality in cardiogenic shock

• More tachycardia than with norepinephrine

• More potent inotrope than norepinephrine

• Differing effects at escalating doses with vasoconstriction at highest dose

• Available in premixed or preprepared bags and therefore can be initiated quickly during emergent need

Epinephrine Yes Yes Yes • Second line vasopressor after norepinephrine in severe sepsis, septic shock. Similar to

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dopamine with differing effects with escalating doses

• Increased production of lactate and significant tachycardia has kept this as a second-line medication. Lactate often related to beta receptor agonism rather than hypoperfusion

Phenylephrine 0.4-9.1 mcg/kg/min

No No Yes • Pure vasoconstrictor &#x

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