CHAPTER 6 
Shock
Alan E. Jones and Jeffrey A. Kline
PERSPECTIVE
In philosophic terms, shock can be viewed as a transition between
life and death. Whether shock results from hemorrhage, sepsis, or
cardiac failure, mortality rates exceed 20%.1,2 In scientific lexicon,
shock results from the widespread failure of the circulatory system
to oxygenate and nourish the body adequately. In the laboratory
the scientist defines the metabolic effect of shock quantitatively,
by examining the mechanisms by which shock alters mitochon-
drial energy transfer, evokes the production of toxic chemicals,
and reduces their removal. At the bedside, however, the clinician
identifies shock by linking the clinical impression, synthesized
from the patient’s history of present illness, age, underlying health
status, and general appearance, to quantitative data, including vital
signs, blood chemistry, urine output, and direct measurements of
oxygenation. When the clinical impression and the quantitative
data suggest widespread organ hypoperfusion, emergent resuscita-
tion is used to restore normal tissue oxygenation and substrate
delivery to prevent deterioration into systemic inflammation,
organ dysfunction, and death.
At the subcellular level, shock first affects the mitochondria.
Mitochondria function at the lowest oxygen tension in the body,
but paradoxically, they consume almost all the oxygen used by the
body. More than 95% of aerobic chemical energy comes from
mitochondrial combustion of fuel substrates (fats, carbohydrates,
ketones) plus oxygen into carbon dioxide (CO2) and water. Mito-
chondria therefore have been referred to as the “canaries in the
coal mine” because they are affected first in conditions of inade-
quate tissue perfusion.3,4 When mitochondria have inadequate
oxygen, the cell catabolizes fuels to lactate, which inexorably accu-
mulates and diffuses into the blood.
Classification
For years, shock has been classified into four broad categories
based on Blalock’s 1934 description: hematologic, neurologic,
vasogenic, and cardiogenic. This basic organization scheme
remains useful today. Box 6-1 outlines five categories of shock that
generally have specific mechanisms and treatments.
Epidemiology
The epidemiology of shock in the emergency department context
remains speculative because shock is rarely listed as a primary
coding diagnosis and depends on defining criteria. Arterial
hypotension, defined as a systolic blood pressure (BP) below
100 mm Hg, is measured at least one time in 19% of ED patients5;
however, diagnosed traumatic, cardiogenic, or septic shock is less
common, constituting about 1 to 3% of all ED visits.
This chapter reviews the metabolic, systemic, and inflammatory
responses that occur in all types of circulatory shock and discusses
specific pathophysiology of the major causes of shock.
Specific Causes
Hemorrhagic Shock
Hemorrhagic shock results from a rapid reduction in blood
volume, which causes baroreceptor activation and leads to vaso-
constriction, increased strength of cardiac contraction, and
increased heart rate (HR). Cardiovascular response to hemor-
rhage can vary with underlying cardiopulmonary status, age, and
presence of ingested drugs. Responses of HR and BP are notori-
ously variable in hemorrhage, so no firm conclusion can be made
at the bedside about the presence or absence of hemorrhagic
shock simply by evaluating HR and BP. In general, hemorrhage
first increases pulse and cardiac contraction, then increases vaso-
constriction. Blood loss causes an elevated pulse rate with a slight
increase in the diastolic BP, causing the pulse pressure (difference
between systolic and diastolic BP) to narrow. As blood loss
continues, ventricular filling decreases and cardiac output drops,
followed by a reduction in systolic BP. Before the total cardiac
output begins to decrease, blood flow to noncritical organs and
tissues begins to decrease, and their cells produce and release
lactic acid.
Consequently, acidemia will often precede any significant
decrease in cardiac output with hemorrhage. However, the blood
contains bicarbonate ions that buffer the blood pH, keeping it near
neutral, even as lactic acid accumulates in blood. The base deficit—
the amount of strong base that would have to be added to a liter
of blood to normalize the pH—represents an index of how far the
bloodstream has dipped into its reserve of bicarbonate buffer. A
normal base deficit is more positive than −2 mEq/L. Accordingly,
the arterial and venous blood base deficit can become more nega-
tive early in hemorrhage even while blood pH and BP remain in
the normal range. The base deficit, therefore, crudely represents
the physiologic endpoint that distinguishes trivial blood loss
from clinically significant hemorrhage. In addition to chemical
buffering, the body responds to small reductions in arterial pH by
activating brainstem chemoreceptors, which increase minute ven-
tilation, leading to reduced partial pressure of carbon dioxide in
the arterial blood (Paco2).
After approximately one third of the total blood volume has
been acutely lost, cardiovascular reflexes can no longer sustain
adequate filling of the arterial circuit and frank hypotension
supervenes. Arterial hypotension is generally and arbitrarily
defined as an arterial BP below 90  mm  Hg. Usually coincident
with the development of hypotension, bicarbonate buffers
67
68   PART I  ◆  Fundamental Clinical Concepts / Section One • Critical Management Principles
Categories of Shock According should not be attributed simply to blood loss, but instead should
BOX 6-1 to Primary Treatment prompt investigation for aspiration, airway obstruction, alveolar
consolidation, or lung injury.
Causes That Require Primarily the Infusion The second phase of organ injury from hemorrhagic shock
of Volume occurs during resuscitation. It has been said that the acute phase
Hemorrhagic shock
of hemorrhage “cocks the gun” by initiating the inflammatory
Traumatic
Gastrointestinal cascade, and resuscitation “pulls the trigger” by accentuating the
Body cavity inflammation-induced organ injury from hemorrhagic shock.
Hypovolemia During resuscitation, neutrophils become most aggressive, binding
Gastrointestinal losses to the lung endothelium and causing capillary leaks that charac-
Dehydration from insensible losses terize acute respiratory distress syndrome (ARDS). Inflammatory
Third-space sequestration from inflammation cytokines are liberated during resuscitation, and membrane injury
Causes That Require Improvement in Pump occurs in many cells. In the liver, damage from inflammation and
Function by Either Infusion of Inotropic Support reactive oxygen species from neutrophils is compounded by per-
or Reversal of the Cause of Pump Dysfunction sistent microischemia. During resuscitation from hemorrhagic
Myocardial ischemia shock, the normal balance of vasodilation by nitric oxide (NO)
Coronary artery thrombosis versus vasoconstriction by endothelins becomes distorted, pro-
Arterial hypotension with hypoxemia ducing patchy centrilobular ischemic damage in the liver, which
Cardiomyopathy may produce an immediate rise in blood transaminase levels. A
Acute myocarditis growing body of evidence suggests that resuscitation from hemor-
Chronic diseases of heart muscle (ischemic, diabetic,
rhage exerts greater injury on the heart than the actual hypoten-
infiltrative, endocrinologic, congenital)
Cardiac rhythm disturbances sive insult.6 Depending on the degree of hypotensive insult, the
Atrial fibrillation with rapid ventricular response kidney may manifest acute spasm of the preglomerular arterioles,
Ventricular tachycardia causing acute tubular necrosis. Systemic metabolic changes can
Supraventricular tachycardia impair fuel delivery to the heart and brain, secondary to depressed
Septic shock with myocardial failure (“hypodynamic shock”) hepatic glucose output, impaired hepatic ketone production, and
Overdose of negative inotropic drug inhibited peripheral lipolysis.
Beta-blocker
Calcium channel antagonist
Structural cardiac damage Septic Shock
Traumatic (e.g., flail mitral valve)
Ventriculoseptal rupture
Septic shock can be produced by infection with any microbe,
Papillary muscle rupture although in one half or more of cases of septic shock, no organism
is identified. One of the most well-studied mediators of sepsis
Causes That Require Volume Support and is lipopolysaccharide, contained in the outer cell membrane
Vasopressor Support of gram-negative bacteria. Infusion of lipopolysaccharide into
Septic shock
humans or animals will produce cardiovascular, immunologic,
Anaphylactic shock
Central neurogenic shock and inflammatory changes identical to those observed with micro-
Drug overdose bial infection. In recent years, multicenter trials of sepsis have
suggested the emergence of gram-positive organisms as the chief
Problems That Require Immediate Relief from cause of sepsis in hospitalized patients. Two lines of reasoning
Obstruction to Cardiac Output suggest that gram-positive sepsis will continue to increase in
Pulmonary embolism
Cardiac tamponade
prevalence:
Pneumothorax 1. More patients are being treated at home for chronic
Valvular dysfunction immunocompromising diseases with indwelling catheters,
Acute thrombosis of prosthetic valve which can serve as portals of entry into the vascular space
Critical aortic stenosis for Staphylococcus aureus and coagulase-negative
Congenital heart defects in newborn (e.g., closure of patent staphylococci.
ductus arteriosus with critical aortic coarctation) 2. The frequency of community-acquired infections caused
Critical idiopathic subaortic stenosis (hypertrophic obstructive by antibiotic-resistant gram-positive organisms has greatly
cardiomyopathy) increased in recent years, including infections caused by
Cellular Poisons That Require Specific Antidotes S. aureus, Streptococcus pneumoniae, and Streptococcus
Carbon monoxide pyogenes.
Methemoglobinemia Septic shock often causes three major effects that must be
Hydrogen sulfide addressed during resuscitation: relative hypovolemia, cardiovas-
Cyanide cular depression, and induction of systemic inflammation. Septic
shock produces relative hypovolemia from increased venous
capacitance, which reduces right ventricular filling. Septic shock
become overwhelmed, and increased alveolar ventilation becomes often causes absolute hypovolemia from gastrointestinal volume
ineffective, culminating in reduced arterial pH. Hemorrhagic losses, tachypnea, sweating, and decreased ability to drink during
shock causes an activation of the hypothalamic-pituitary- development of the illness. Sepsis also induces capillary leak,
adrenomedullary axis, with release of stress hormones that cause which leads to relative loss of intravascular volume into third
glycogenolysis, lipolysis, and mild hypokalemia. Therefore in the spaces. Recent evidence has shown that septic shock causes myo-
ED, patients who have sustained traumatic hemorrhage generally cardial depression simultaneously with vasodepression and capil-
have an arterial lactate concentration greater than 4.0  mmol/L, lary leak. Direct measurements of cardiac contractility have shown
a Paco2 less than 35  mm  Hg, and mild hyperglycemia (150- that cardiac mechanical function becomes impaired early in the
170  mg/dL) and hypokalemia (3.5-3.7  mEq/L). Although hem- course of septic shock, even in the hyperdynamic stages. Multiple
orrhagic hypotension reduces lung perfusion, arterial hypoxemia mechanisms may explain depressed heart function in sepsis,

including actions of specific cytokines (most notably tumor
necrosis factor alpha [TNF-α] and interleukin 1 beta [IL-1β]),
overproduction of NO by nitric oxide synthase (iNOS),7 and pos-
sibly impairment in mitochondrial oxidative phosphorylation
coincident with reduced mechanical efficiency.8,9 Evidence indi-
cates that circulating mediators, myocardial cellular injury from
inflammation, and deranged metabolism interact synergistically
to injure the heart during septic shock. Systemic inflammation
causes capillary leak in the lung, which may cause alveolar infiltra-
tion characteristic of ARDS early in the treatment of septic shock
in up to 40% of patients. With the potential for early development
of ARDS, more profound ventilation-perfusion ( V/Q)  mismatch-
ing, and pneumonia or pulmonary aspiration, hypoxemia is more
severe with septic shock than hemorrhagic shock.
Cardiogenic Shock
Chapter 6 / Shock   69
kg/hr), reduced (0.5-1.0 mL/kg/hr), or severely reduced (<0.5 mL/
kg/hr). Point measurements of the arterial or venous lactate con-
centration and the base deficit can be rapidly performed and
provide accurate assessment of global perfusion status. A lactate
concentration greater than 4.0 mM or a base deficit more negative
than −4 mEq/L predicts the presence of circulatory insufficiency
severe enough to cause subsequent multiple organ failure.11,12
Once the empirical criteria for circulatory shock have been
discovered, the next step is to consider the cause of the shock.
Figure 6-1 shows a potential sequence of decisions to help arrive
at a diagnosis in a patient with undifferentiated shock.
The history, vital signs, and physical examination documented
by prehospital providers afford valuable insight into a patient’s
physiologic status before any medical intervention and can be
useful in ED management. Studies suggest that both medical and
trauma patients with prehospital hypotension have a threefold to

Cardiogenic shock results when more than 40% of the myocar-

dium undergoes necrosis from ischemia, inflammation, toxins,
or immune destruction. Otherwise, cardiogenic shock essentially Search for:
produces the same circulatory and metabolic alterations as are 1. Hemorrhagic shock
History Yes
observed with hemorrhagic shock. Undoubtedly, impaired base- 2. Tension pneumothorax
of trauma?
line cardiac function can contribute to the development of 3. Cardiac tamponade
circulatory shock secondary to infection, hemorrhage, or vaso- 4. Cardiac injury
No
dilatory drug overdose. However, when shock results from a pure
cardiac cause, severe left ventricular dysfunction will be evident Evidence of
on echocardiography early in the course. Patients with severe gastrointestinal
dysfunction are far more likely to have a cardiogenic cause of Yes
hemorrhage, Volume resuscitate
shock than patients with normal or moderate left ventricular vomiting,
dysfunction.10 or diarrhea?

No
CLINICAL FEATURES 1. Begin treatment for
sepsis syndrome
Patients in the ED frequently are in shock with no obvious cause. Fever or Yes 2. Search for source
Rapid recognition of shock requires the integration of informa- hypothermia? of infection
3. Consider drawing
tion from immediate history and physical examination, and shock
No thyroid function tests
can be strongly supported by the presence of a worsening base
deficit or lactic acidosis. In general, patients with shock exhibit a 1. Treat for cardiogenic
stress response: they are ill appearing, asthenic, pale, often sweat- Electrocardiographic shock from myocardial
ing, and usually tachypneic or grunting, and often have a weak evidence of ischemia Yes ischemia
and rapid pulse (Box 6-2). HR can be normal or low in shock, or chest pain with major 2. Consider massive
risk factors for coronary pulmonary embolism
especially in cases complicated by prescribed drugs that depress artery disease?
HR or by profound hypoxemia. BP initially can be normal because with right ventricular
strain effect
of adrenergic reflexes. Although arterial BP as a sole measurement
remains an unreliable marker of circulatory status, the finding No
1. Evaluate or treat for
of a single systolic BP less than 100 mm Hg in the ED is associated ingestion of negative
with a threefold increase in in-hospital mortality and a tenfold inotropic drug
Unexplained Yes
increase in sudden and unexpected death.5 The HR/systolic bradycardia with 2. Draw thyroid function
BP ratio may provide a better marker of shock than either mea- hypotension? tests
surement alone; a normal ratio is less than 0.8. Urine output 3. Consider treatment for
addisonian crisis or
provides an excellent indicator of organ perfusion and is readily No steroid withdrawal
available with insertion of a Foley catheter into the bladder. Mea-
surement of urine output, however, requires 30 minutes to 1 hour Unexplained Yes Rule out pulmonary
for accurate determination of whether output is normal (>1.0 mL/ hypoxemia? embolism

No
1. Volume resuscitate
2. Emergent abdominal
Empirical Criteria for Diagnosis Abdominal Yes computed tomography
BOX 6-2 of Circulatory Shock* or low or surgical consultation
back pain? to evaluate for peritoneal
• Ill appearance or altered mental status inflammation or vascular
• Heart rate >100 beats/min No rupture
• Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg
• Arterial base deficit <−4 mEq/L or lactate >4 mM/L Wheezing Yes Treat for
• Urine output <0.5 mL/kg/hr with hives or
anaphylaxis
• Arterial hypotension >30 continuous minutes duration skin flushing?

*Regardless of cause. Four criteria should be met. Figure 6-1.  Flow diagram to classify undifferentiated shock.
70   PART I  ◆  Fundamental Clinical Concepts / Section One • Critical Management Principles
fourfold higher in-hospital mortality rate than patients without Definitions and Criteria for Septic, Hemorrhagic,
hypotension.13,14 BOX 6-3 and Cardiogenic Shock
On physical examination, dry mucous membranes suggest
dehydration, whereas distended jugular veins suggest cardiac Septic Shock
failure or obstruction from pulmonary embolism (PE) or cardiac Systemic Inflammatory Response
Syndrome (SIRS)
tamponade. Muffled heart sounds suggest cardiac tamponade,
Two or more of the following:
whereas a loud machine-like systolic murmur indicates acute 1. Temperature >38° C or <36° C
rupture of a papillary muscle or rupture of the interventricular 2. Heart rate >90 beats/min
septum. Bilateral pulmonary rales in a patient with a normal rectal 3. Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg
temperature help to define presence of primary left ventricular 4. White blood cell count >12,000/mm3, <4000/mm3, or
failure. Wheezing suggests bronchospasm from anaphylaxis or, >10% band neutrophilia
less likely, cardiac failure or PE. Abdominal tenderness may indi- Severe Sepsis
cate peritoneal inflammation or occult trauma. Rectal examina- SIRS with suspected or confirmed infection and associated
tion may disclose occult gastrointestinal hemorrhage. Rectal with organ dysfunction or hypotension; organ dysfunction
temperature is the preferred method for measuring temperature may include presence of lactic acidosis, oliguria, or altered
and in general should be performed as early as is reasonable on mental status
every patient with suspected shock.
Septic Shock
Neurologic examination documents responsiveness, cognition, SIRS with suspected or confirmed infection with hypotension
and the presence of any focal deficits. In children, documentation despite adequate fluid resuscitation; septic shock should still be
should include level of alertness, response to parents, appropriate- diagnosed if vasopressor therapy has normalized blood pressure
ness of crying, pupillary function, symmetry of grimace, symme-
try of extremity movements, and motor tone in infants. Hemorrhagic Shock
Simple Hemorrhage
Laboratory, radiographic, and other ancillary data should be Suspected bleeding with pulse <100 beats/min, normal
ordered to assess tissue and vital organ perfusion and to diagnose respiratory rate, normal blood pressure, and normal
injury from trauma, find the source of infection with sepsis, or base deficit
identify the cause of cardiac failure. A chest radiograph, electro-
cardiogram, finger-stick glucose measurement, complete blood Hemorrhage with Hypoperfusion
Suspected bleeding with base deficit <−4 mEq/L or persistent
count (CBC), urinalysis, serum electrolytes, and kidney and liver
pulse >100 beats/min
function tests are all indicated in the ED assessment. Arterial
blood gases are ordered for a base deficit calculation and to cor- Hemorrhagic Shock
relate arterial gas tensions (oxygen [Pao2] and Paco2) with those Suspected bleeding with at least four criteria listed in Box 6-2
measured by pulse oximetry and capnography. Serum lactate Cardiogenic Shock
measurement should be performed as early as possible in patients Cardiac Failure
with suspected shock. Either venous or arterial lactate concentra- Clinical evidence of impaired forward flow of the heart,
tions can be used.15,16 If peripheral venous lactate is used, the including presence of dyspnea, tachycardia, pulmonary edema,
effect of time, storage temperature, and tourniquet use have no peripheral edema, or cyanosis
significant effect on in vitro lactate production by erythrocytes Cardiogenic Shock
if the measurement is done within 15 minutes after the sample Cardiac failure plus four criteria listed in Box 6-2
has been obtained.17 Cardiac and abdominal bedside ultrasound
scanning can screen for inadequate central venous volume, occult
hemoperitoneum, abdominal aortic aneurysm, left ventricular
failure, and cardiac tamponade.18 A systematic ultrasound pro-
tocol can significantly improve the physician’s ability to accu-
rately diagnose the cause of undifferentiated shock in ED patients, BOX 6-4 Variables Indicating Tissue Hypoperfusion
and the finding of hyperdynamic left ventricular function in Hypotension
patients with undifferentiated shock strongly suggests sepsis as Tachycardia
the cause.19,20 Low cardiac output
Consensus definitions of shock show the spectrum of hypo­ Mottled skin
perfusion for the following three common causes of shock Delayed capillary refill
(Box 6-3): Altered mental state
1. Septic shock. The American College of Chest Physicians, Hyperlactemia
European Society of Intensive Care Medicine, Society for Low mixed venous oxygen saturation
Critical Care Medicine, American Thoracic Society, and Low central venous oxygen saturation
Surgical Infection Society developed international
consensus definitions to distinguish septic shock from its
precursor conditions—systemic inflammatory response
syndrome (SIRS), sepsis, and severe sepsis.21 Although this 2. Hemorrhagic shock. The American College of Surgeons has
particular consensus definition requires persistent divided hemorrhagic shock into four stages, depending on
hypotension after fluid resuscitation to strictly define the severity of blood loss and the physiologic response to
septic shock, initiation of treatment for empirically this loss, but such arbitrary divisions are of little value. A
diagnosed severe sepsis or septic shock should not await more useful approach defines hemorrhagic shock as being
the onset of hypotension. The incorporation of an present when systemic hypoperfusion manifests as lactic
indicator of tissue hypoperfusion into the clinical acidosis with organ dysfunction.
assessment may improve identification of hypoperfusion, 3. Cardiogenic shock. Cardiogenic shock should be thought to
particularly in subtle cases. Box 6-4 provides a list be present whenever cardiac failure (ischemic, toxic, or
of variables that can assist with detecting tissue obstructive) causes systemic hypoperfusion that manifests
hypoperfusion.22 as lactic acidosis with organ dysfunction.

MANAGEMENT
Monitoring Perfusion Status
In all patients with shock, HR, BP, and oxyhemoglobin
saturation are continuously monitored. Cuff sphygmomanometer
measurement of BP may be inaccurate in severe hypotensive
states, and insertion of an arterial pressure monitoring line should
considered, especially if vasoactive medications are being admin-
istered. BP and HR correlate poorly to cardiac index (CI) in shock
and often underestimate the severity of systemic hypoperfusion.
Moreover, children with hypovolemic shock frequently demon-
strate a normal BP until they rapidly deteriorate. Urine output
should be measured as an index of vital organ perfusion
(0.5-1 mL/kg/hr in persons without preexisting renal disease).
Downward trend of the serum lactate concentration or upward
trend of the base deficit, when observed with improving vital
signs and urine output, can reliably gauge the adequacy of resus-
citation and prognosis in shock from any cause. A rising lactate
concentration (or refractory hypotension with worsening base
deficit) despite ongoing resuscitation portends high mortality
and calls for more aggressive resuscitation or specific procedural
intervention.
Most patients with shock can be fully resuscitated with periph-
eral venous access established with two catheters of at least a size
18 gauge. Patients with cardiac failure or renal failure may benefit
from closer measurement of dynamic variables of fluid respon-
siveness that can be measured from an arterial line (such as stroke
volume variation or stroke volume index) or a central venous line
(central venous pressure [CVP]).23 An 8.5-French catheter (Cordis
sheath) allows for accurate measurement of the CVP and insertion
of a pulmonary artery catheter or other monitoring device if
needed. In children, a 3- or 5-French bilumen catheter can be
placed in the femoral vein with few complications. To reduce the
potential for limb damage from extravasation from a peripheral
intravenous injection, vasoactive medications are optimally
administered through a central venous catheter. If vasoactive
medications are administered, additional peripheral intravenous
catheters will be required for infusion of crystalloid and other
treatments. Many patients with renal disease or cancer have
indwelling catheters in place. In patients with empirical criteria
for shock, this catheter should be used for intravenous access,
unless satisfactory access has already been established at other
anatomic sites. In EDs where the standard practice is not to use
these ports at the request of other physicians, a specific hospital
policy and training session should be developed to make an
exception in the case of circulatory shock. In general, failure to
administer fluids rapidly and in sufficient quantity outweighs con-
siderations about preservation of the line for future therapy.
Quantitative Resuscitation
Quantitative resuscitation (also called goal-directed therapy, goal-
oriented resuscitation, or hemodynamic optimization) was first
described in 1988 and refers to the practice of resuscitating patients
to predefined physiologic endpoints indicating that systemic per-
fusion and vital organ function have been restored. Since that
time, many studies have evaluated the efficacy of such a therapeu-
tic approach to shock, and a meta-analysis of these studies con-
firms its benefit for reducing mortality.24,25 For many years in the
intensive care unit (ICU), physicians have relied on the use of the
pulmonary artery catheter to help optimize left ventricular filling
indices, but this practice is controversial. Several randomized
controlled trials investigating the management of critically ill
patients failed to demonstrate survival or length of stay benefit in
patients managed with pulmonary artery catheters.26-30 Insuffi-
cient data have been published to support the use or avoidance of
Chapter 6 / Shock   71
pulmonary artery catheters in ED populations, but their signifi-
cant complication rate, coupled with uncertain or no benefit,
argues strongly against their routine use.
The lactate clearance refers to serial measurements
of venous or arterial lactate and is calculated according to the
following formula31-33:
[(Lactateinitial − Lactatedelayed ) / Lactateinitial ] × 100
Lactate clearance has been shown to be equivalent to central
venous oxygen saturation as an endpoint of early septic shock
resuscitation.34 Given the increasing use of point-of-care testing
platforms in the ED and the fact that lactate clearance measure-
ments can be done from peripheral venous blood, in many patients
this may be a preferred endpoint of resuscitation. If the lactate
concentration has not decreased by 10 to 20% 2 hours after resus-
citation has begun, additional steps are undertaken to improve
systemic perfusion. Resuscitation should continue until the lactate
concentration drops below 2 mM/L.
Mixed venous oxygen saturation (SvO2) measurements reflect
the balance between oxygen delivery and oxygen consumption.
Previous studies have suggested that the SvO2 can be used as a
surrogate for CI in targeting normalization of endpoints (SvO2
65%, or CI 2.5-3.5 L/min/m2) for therapeutic intervention in criti-
cally ill patients. Although SvO2 requires the use of a pulmonary
artery catheter, the central venous oxygen saturation (Scvo2)
drawn from the central circulation has been shown to parallel the
SvO2 when changes or trends in the values are tracked over time.
Quantitative resuscitation, which incorporates multiple indices
of circulatory and oxygenation status, has been shown in meta-
analyses to significantly reduce mortality and morbidity in ED
patients with severe sepsis or septic shock when instituted as early
in the disease course as is practical.25 In such an approach, patients
are resuscitated within the first 6 hours of care to achieve normal-
ization of markers of preload (CVP) and perfusion (mean BP) and
adequate oxygen delivery (Scvo2 70% or lactate clearance 10%)
(Fig. 6-2). The most well-known quantitative resuscitation strat-
egy, termed early goal-directed therapy, has also been found effec-
tive in smaller prospective before-and-after studies of patients
with sepsis.35-37 Three large multicenter validation studies of this
resuscitation strategy in sepsis are underway.
Ventilation
Rapid sequence intubation is the preferred method of airway
control in most patients with refractory shock (see Chapter 1).
Intubation prevents aspiration, increases oxygenation, treats
acute respiratory failure, provides initial treatment for metabolic
or hypercarbic acidemia, and protects the patient who will be
sent to an uncontrolled environment (e.g., for tests). Intubation
also reduces the work of breathing, which, in the patient with
hypoperfusion, further exacerbates lactic acidemia. Strenuous use
of accessory respiratory muscles can increase oxygen consump-
tion by 50 to 100% and decrease cerebral blood flow by 50%.
More important, if the patient has increased airway resistance
(e.g., bronchospasm with anaphylaxis) or a decrease in lung com-
pliance (e.g., pulmonary edema, ARDS), a more negative intra-
thoracic pressure must be generated to fill the lungs with each
inspiration. The greater suction effect is also exerted on the left
ventricle, impeding its ability to eject and increasing functional
afterload. Positive-pressure ventilation removes this impedance
and can improve ventricular function and cardiac output up
to 30%.
Volume Replacement
The goal in volume replacement is slightly elevated left ventricular
end-diastolic volume, which is a difficult measurement to make in
72   PART I  ◆  Fundamental Clinical Concepts / Section One • Critical Management Principles

Suspected or confirmed infection

Does patient have >1 SIRS criteria?

Temperature > 100.4° F (38° C) or < 96.8° F (36° C)
Heart rate > 90
Respiration rate > 20 or PaCO2 < 32
WBC > 12,000 or < 4000, or > 10% bands

Yes

No Need for ICU care

MAP < 65 or SBP < 90 after
AND
20 mL/kg fluid bolus?
Lactate 4 mmol/L
Yes
Yes
Septic
shock

Cardiac monitoring, pulse oximetry

IJ or SC central line placement for CVP/ScvO2 monitoring
Initiate broad spectrum antibiotics
O2 or mechanical ventilation to keep Sat > 94%

CVP < 8 NS 500-1000 mL bolus Q 15-

CVP 30 min until CVP  8,
then continue at 150 mL/hr
CVP  8

MAP < 65 Arterial line placement

MAP Norepinephrine drip at 5-30 µg/hr

MAP 65-100

ScvO2  70% ScvO2 or ScvO2 < 70%

LC 10% lactate LC < 10% HCT < 30% Transfuse until
clearance HCT
HCT  30 %
(LC)
HCT > 30%

Early goals achieved Dobutamine 2.5-20 µg/kg/min

Reassess antibiotic coverage Consider intubation and mechanical ventilation

Figure 6-2.  Flow diagram outlining the protocol for quantitative resuscitation in treatment of patients with severe sepsis or septic shock. This
protocol outlines specific hemodynamic and physiologic parameters the clinician should seek to achieve within the first 6 hours of care. This
protocol is focused on resuscitation and should be used in conjunction with standard clinical care for patients with suspected infection, such as
appropriate diagnostic studies to determine the focus of infection and appropriate antimicrobial agents to treat the infection. CVP, central venous
pressure; HCT, hematocrit; ICU, intensive care unit; IJ, internal jugular; MAP, mean arterial pressure; NS, normal saline; PaCO2, partial pressure of
carbon dioxide, arterial; Sat, peripheral oxygen saturation; SBP, systolic blood pressure; SC, subclavian; ScvO2, central venous oxygen saturation;
SIRS, systemic inflammatory response syndrome; WBC, white blood cell count.

the ED. The CVP is most often used to estimate right ventricular
filling pressure and is used in some quantitative resuscitation
algorithms. Because both ventricles tend to stiffen during shock,
a high CVP (10-15 cm H2O) is often needed to produce adequate
filling volume. CVP measurement does not accurately reflect left
ventricular end-diastolic volume, and a recent systematic review
demonstrated the inability of CVP to predict the hemodynamic
response to a fluid challenge.38 Thus, a presumed adequate CVP
should be substantiated by increases in urine output and BP and
decreasing lactate concentrations. Emerging literature suggests
that the use of dynamic variables of fluid responsiveness that can
be measured from an arterial line (such as stroke volume variation
or stroke volume index) are superior to static variables (e.g., CVP),
but their use in the ED has not been studied.23
Treating Specific Causes
Box 6-5 presents the general treatment approach for the three
common causes of shock.
Hemorrhagic Shock
Standard treatment for hemorrhagic shock historically consisted
of rapidly infusing several liters of isotonic crystalloid in adults or
three successive 20-mL/kg boluses in children. Recent studies
have endorsed the concept of either delayed resuscitation or
hypotensive resuscitation for hemorrhagic shock. This is discussed
in Chapters 36, 45, and 46. Controlling hemorrhage remains
the cornerstone of treating hemorrhagic shock, and evidence

Clinical Management Guidelines for Three
BOX 6-5 Common Causes of Shock
Hemorrhagic Shock
• Ensure adequate ventilation and oxygenation.
• Provide immediate control of hemorrhage, when possible
(e.g., traction for long bone fractures, direct pressure).
• Initiate judicious infusion of isotonic crystalloid solution
(10-20 mL/kg).
• With evidence of poor organ perfusion and 30-minute
anticipated delay to hemorrhage control, begin packed red
blood cell (PRBC) infusion (5-10 mL/kg).
• With suspected central nervous system trauma or Glasgow
Coma Scale score <9, immediate PRBC transfusion may be
preferable as initial resuscitation fluid.
• Treat coincident dysrhythmias (e.g., atrial fibrillation with
synchronized cardioversion).
Cardiogenic Shock
• Ameliorate increased work of breathing; provide oxygen and
positive end-expiratory pressure (PEEP) for pulmonary edema.
• Begin vasopressor or inotropic support; norepinephrine
(0.5 µg/min) and dobutamine (5 µg/kg/min) are common
empirical agents.
• Seek to reverse the insult (e.g., initiate thrombolysis, arrange
percutaneous transluminal angioplasty).
• Consider intra-aortic balloon pump counterpulsation for
refractory shock.
Septic Shock
• Ensure adequate oxygenation; remove work of breathing.
• Administer 20 mL of crystalloid per kilogram or 5 mL of
colloid per kilogram, and titrate infusion to adequate central
venous pressure and urine output.
• Begin antimicrobial therapy; attempt surgical drainage or
débridement.
• Begin PRBC infusion for hemoglobin <8 g/dL.
• If volume restoration fails to improve organ perfusion, begin
vasopressor support; initial choice includes dopamine,
infused at 5-15 µg/kg/min, or norepinephrine, infused at
0.5 µg/min.
continues to support immediate surgery when direct vascular
control cannot otherwise be obtained (see Chapters 36 and 46).
Colloids, including albumin and hydroxyethyl hetastarch
(Hespan), can be used as well, but at considerable increase in cost
and without effect on morbidity or mortality.39 Colloids offer the
theoretic advantage of a high osmotic pressure, which should help
to maintain a normal intravascular volume after retransfusion
from hemorrhage. A recent large multicenter trial conducted
in the prehospital setting found that initial resuscitation
fluid treatment with hypertonic saline or hypertonic saline and
dextran, compared with normal saline, did not result in superior
28-day survival.40 If criteria for shock persist despite crystalloid
infusion (see Box 6-2), packed red blood cells (PRBCs) should be
infused (1-2 units in adults or 5-10 mL/kg in children). Type-
specific blood should be used when the clinical scenario permits,
but uncrossmatched blood should be immediately used for
patients with arterial hypotension and uncontrolled hemorrhage.
O-negative blood is used in women of childbearing age and
O-positive blood in all others (see Chapter 7). Substantial evi-
dence supports the use of leukodepleted blood, which has been
filtered to remove donor neutrophils. Leukodepleted blood is used
in countries outside the United States because it produces less
retransfusion-related organ damage.
The infusion of hemoglobin-based blood substitutes (HBBSs)
as alternatives to PRBCs for resuscitation of hemorrhagic shock
has been extensively studied. A recent meta-analysis that included
16 trials involving five different HBBSs in various populations
showed that the use of HBBS is associated with significant
Chapter 6 / Shock   73
increased risk of death and myocardial infarction.41 Other artificial
hemoglobin substitutes may be available in the future but at
present show no benefit, and possibly harm, compared with
PRBCs.
Septic Shock
Septic shock begins as an infectious nidus, which triggers a domino
effect of cellular, microvascular, hematologic, and cardiovascular
dysfunction. Treatment begins by establishing adequate ventila-
tion to correct hypoxia and acidosis and to reduce systemic oxygen
consumption and left ventricular work. This often requires endo-
tracheal intubation and sedation for mechanical ventilation. The
controversy regarding the use of etomidate in patients with septic
shock is discussed in Chapter 1.
The second goal is to achieve adequate ventricular filling. The
choice of fluids in treating septic shock is probably less important
than scrupulous monitoring for adequate tissue perfusion.
However, choices for fluid resuscitation should involve consider-
ation of availability and the cost-benefit ratio. Initial volume
replacement should include rapid infusion of 20 to 25 mL of
crystalloid per kilogram. If hypoperfusion is persistent, 5- to
10-mL/kg boluses of a natural colloid (such as albumin) should
be considered. Pending the results of current shock studies, blood
should be transfused in the ED to restore hematocrit to 30%.
The third directive is to eradicate the infection with antimicro-
bial therapy and, where necessary, surgical drainage. The choice of
antimicrobial agent can be directed by clinician experience and
institutional minimal inhibitory concentration (MIC) data. Anti-
microbials should be administered as soon as is practicable in a
patient with septic shock. Evidence is scant, but it is intuitively
appealing to administer antimicrobial medication at the earliest
reasonable time.42-44 One recent large observational study found
that about 60% of patients with septic shock received antibiotics
within 3 hours of ED triage, which might be a reasonable target,
depending on the patient’s presentation.45 When no focus can be
found in septic shock, a semisynthetic penicillin with a β-lactamase
inhibitor, in combination with an aminoglycoside plus vancomy-
cin, is a rational empirical choice. When neutropenia is suspected
in a patient with sepsis syndrome, the progression to refractory,
fatal septic shock can be cataclysmic. Neutropenia should be sus-
pected in patients who have recently undergone chemotherapy.
Chemotherapy patients with sepsis represent a special challenge
because the pathophysiology may be complicated by anemia,
thrombocytopenia, dehydration from vomiting, and the effect of
adjunctive steroid therapy. Chemotherapy patients often have
indwelling catheters, which predispose them to more unusual
causes of sepsis, including gram-positive bacteria and fungi (see
Chapter 138).46
Septic shock refractory to volume restoration (urine output or
BP remains low; lactate increases) requires vasopressor support.
The primary goal of vasopressor support is to increase cardiac
output and oxygen delivery to vital organs. Several recent random-
ized trials and a meta-analysis have suggested that norepinephrine
(0.5-30 µg/min) is associated with improved efficacy and lower
rates of adverse effects, making norepinephrine the vasopressor of
choice for correction of hypotension in septic shock.47-49 Dobuta-
mine may also be used with norepinephrine to increase cardiac
output and maintain adequate oxygen delivery. A recent multi-
center randomized controlled trial of 330 subjects reported that
in cases in which simultaneous BP and inotropic support were
necessary, there was not a difference in safety or efficacy between
epinephrine (0.2 µg/kg/min starting dose) alone and norepineph-
rine plus dobutamine.50
The use of corticosteroids in the treatment of sepsis and septic
shock has been investigated with mixed results. The results of two
large randomized controlled trials confirm that there is no role for
74   PART I  ◆  Fundamental Clinical Concepts / Section One • Critical Management Principles
high-dose, short-course corticosteroid therapy in septic shock.
Recently, two large multicenter randomized trials of low-dose
hydrocortisone treatment failed to show survival benefit among
all patients with septic shock.51,52 Use of low-dose hydrocortisone
among patients who did not adequately respond to a corticotropin
stimulation test was supported by one small study but refuted by
a larger one.51,52 A recent meta-analysis suggested a modest 28-day
mortality benefit of low-dose, short-course hydrocortisone treat-
ment in septic shock.53 Most current guidelines recommend
that low-dose hydrocortisone be administered only to patients
receiving chronic steroid replacement and in patients with refrac-
tory shock despite adequate fluid and vasopressor support. Even
this use is only marginally supported, if at all, by scientific evi-
dence. Corticotropin stimulation testing is no longer considered
of value.54
Cardiogenic Shock
The immediate treatment of cardiogenic shock focuses on improv-
ing myocardial contractility and pump function. Cardiogenic
shock is traditionally defined as the combination of systemic signs
of hypoperfusion with arterial systolic BP less than 90 mm Hg. If
work of breathing is tiring the patient, if severe pulmonary edema
is causing significant hypoxemia, or if respiratory failure is immi-
nent, intubation and mechanical ventilation should be initiated,
followed by emergent treatment of bradydysrhythmias or tachy-
dysrhythmias and inotropic support. Etomidate and ketamine
have the least risk for hemodynamic compromise and should be
used (but in reduced doses) for intubation, accompanied by a full
dose of succinylcholine. Before administration of vasoactive medi-
cations, if hypovolemia is present, it should be corrected by infu-
sion of crystalloid or blood products. Vasopressor or inotropic
agents improve myocardial contractility and arteriolar tone. The
choice of which agent to use depends on signs and symptoms and
the systolic blood pressure (SBP). If the SBP is below 100 mm Hg
and signs and symptoms of shock are present, norepinephrine is
the agent of choice. However, if the SBP is 70 to 100 mm Hg and
there are no signs or symptoms of shock, dobutamine is the agent
of choice.2,49 All of these agents should be started at the same doses
as used for septic shock.
When pharmacologic support fails to improve indices of per­
fusion, the next step is to initiate intra-aortic balloon pump coun-
terpulsation (IABPC). This requires the facilities and personnel of
a high-level ICU or critical care unit (CCU). Controlled trials
have shown IABPC to improve short-term survival, improve
post-thrombolytic patency rates, and reduce stroke morbidity.
IABPC increases cardiac output by a mean of 30% in refractory
cardiogenic shock and can prolong survival until interventional
procedures can be performed. IABPC may be contraindicated
in patients with aortic insufficiency or severe peripheral
vascular disease.
The dismal outcome of cardiogenic shock complicating acute
myocardial infarction (MI) has been improved in recent years.
Evidence suggests that emergent revascularization is not superior
to medical management in reducing short-term mortality;
however, significant improvements in mortality are seen at both
6 months and 1 year (see Chapter 81).55 At present the manage-
ment of acute MI with cardiogenic shock proceeds as follows,
and this constitutes optimal therapy: (1) ensure adequate ventila-
tion and oxygenation, (2) treat emergent dysrhythmias, (3) initiate
vasopressor or inotropic support, (4) administer aspirin if
the patient is not allergic, and (5) initiate heparin anticoagulation
and arrangement for emergent percutaneous coronary interven-
tion (PCI).
KEY CONCEPTS
■ Circulatory shock can occur with normal arterial blood
pressure, and not all patients with arterial hypotension have
circulatory shock.
■ A base deficit more negative than −4 mEq/L or a serum
lactate level greater than 4.0 mmol/L indicates the presence
of widespread circulatory insufficiency in suspected shock.
■ Urine output is a reliable index of vital organ perfusion in
patients with suspected shock.
■ Ill patients with tachycardia, a worsening base deficit, and
low urine output should be diagnosed with circulatory shock.
■ Use of defined physiologic endpoints to measure systemic
perfusion during resuscitation (quantitative resuscitation) is a
valuable approach to optimal resuscitation in ED patients
with shock.
The references for this chapter can be found online by
accessing the accompanying Expert Consult website.

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