1578185 - McGraw-Hill Professional ©CHAPTER 141Sepsis an

1578185 - McGraw-Hill Professional ©
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-
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
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
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 dysfunctio n,
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,
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
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
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.
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.
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-

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
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
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

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
• Used primarily in
sepsis in patients with
excessive tachycardia
or arrhythmias to
avoid medications
with chronotropic
effect
• Used in severe aortic
stenosis

350 words per answer, Minimum 1 Academic Source for each
answer
1. Typical users of financial statements include internal users
such as managers and external users such as creditors, investors,
regulatory agencies. Which of these users would find more
helpful information on the balance sheet and why? And which
of these users would find more helpful information on the
income statement and why?
2. Discuss the opinion that ‘accounting is the language of
business.’

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