CHAPTER 121 Septic Shock 843
121
INCIDENCE
Septic shock is a form of acute circulatory shock that occurs secondary
to severe infection. The incidence of septic shock may be rising, partly
related to medical progress that allows individuals to survive longer,
resulting in increased numbers of older, debilitated, or immunocom-
promised patients passing through the intensive care unit (ICU). Some
15% of ICU patients develop septic shock at one time or another, and
the mortality rate is close to 50%.1,2 Somewhat lower mortality rates
have been reported in some trials evaluating the effects of new thera-
peutic interventions, but such studies include a number of exclusion
criteria that are often associated with high mortality rates—cirrhosis,
immunosuppression, and “do-not-resuscitate orders,” for example—so
it is perhaps not surprising that mortality rates are lower in these
therapeutic trials than in “real life.”
ETIOLOGY OF SEPTIC SHOCK
Septic shock is most often bacterial, but it can also be caused by a
fungal or parasitic infection. In one-third of patients, no infectious
agent is identified.1,2 About half of the infections are nosocomial in
origin. Although an infection can arise anywhere, the lung is the most
common source of infection (40%), followed by the abdomen (20%),
indwelling venous and arterial catheters and primary bacteremias
(15%), and the urinary tract (10%).1,2
PATHOPHYSIOLOGY OF SEPTIC SHOCK
The pathophysiology of septic shock is complex. Essentially, the sys-
temic sepsis response starts with the recognition of an invading organ-
ism or its toxins. Among the bacterial factors, one of the best known
toxins is lipopolysaccharide, which is part of the outer gram-negative
bacterial membrane, but other bacterial-derived factors include lipo-
teichoic acid and peptidoglycan. In certain cases, essentially infections
involving Staphylococcus aureus or β-hemolytic group A Streptococcus,
the formation of superantigens results in toxic shock syndrome.
The early humoral response involves the complement and contact
(kinin-kallikrein) systems. Immune cells, principally monocytes/
macrophages and polymorphonuclear neutrophils (PMNs), are not
only able to recognize pathogenic agents and their products so they
can phagocytose and destroy them but also release a series of mediators
that can activate other cells. Among cell membrane receptors impli-
cated in the recognition of pathogenic agents are the so-called Toll-like
receptors. In response to cellular stimulation, intracellular signaling is
activated, resulting largely in the activation of transcriptional factors,
including nuclear factor kappa B, which in turn are responsible for the
initiation of proinflammatory reactions. A number of cytokines, two
of the key players being tumor necrosis factor alpha (TNF-α) and
interleukin (IL)-1 that interact synergistically, are released by macro-
phages and other cells. TNF-α and IL-1 are particularly important
proinflammatory cytokines whose administration in animals can
reproduce all features of septic shock including hypotension and
development of multiple organ failure. A host of secondary mediators
including lipid mediators, oxygen free radicals, proteases, and arachi-
donic acid metabolites are also released by macrophages, PMNs, and
other cells. Vasodilator substances such as nitric oxide (NO) and
prostaglandins are released by endothelial cells and are responsible
for the early hemodynamic changes of sepsis. NO, in particular, is a
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Septic Shock
Jean-Louis Vincent
powerful vasodilator acting on vascular smooth muscle. Increased NO
production is essentially due to the induction of inducible NO synthase
by proinflammatory cytokines. The formation of large quantities of NO
can also have secondary toxic effects on cells. NO can block mitochon-
drial respiration, directly by inhibiting cytochrome a,a3 and reacting
with superoxide radicals, resulting in the production of peroxynitrite,
which inhibits various phases of mitochondrial respiration.3 These
effects result in depletion of cellular adenosine triphosphate and
potentially have detrimental effects on cell function. It is important to
note that the inflammatory response also causes release of vasocon-
strictor substances including thromboxane and endothelins.
Other effects of the inflammatory reaction that accompanies septic
shock include expression of adhesion molecules on vascular endothe-
lium and circulating cells (platelets, PMNs, and monocytes), allowing
adhesion of activated leukocytes and their migration to subendothelial
tissues. Alterations in intercellular endothelial junctions result in
increased capillary permeability and generalized edema. Alterations
in coagulation and fibrinolysis complete the picture, with proinflam-
matory mediators creating a procoagulant state. Briefly, the activation
of tissue factor on the surface of various cells, particularly monocytes
and endothelial cells, initiates the coagulation system.4 In addition,
sepsis causes a significant reduction in plasma levels of natural
anticoagulants such as protein C, protein S, and antithrombin by
reducing their synthesis and increasing their consumption and clear-
ance. Thrombolysis is also stimulated with an increase in the levels
of plasminogen activator inhibitor-1. The net result is a balance in
favor of procoagulant processes, often leading to disseminated intra-
vascular coagulation and participating in the microcirculatory disor-
der that leads to multiple organ failure and death in many patients
with severe sepsis.
During the sepsis response, antiinflammatory mediators including
IL-4 and IL-10 are also released, which limit the effects of proinflam-
matory mediators and can lead to a state of relative immunosuppres-
sion sometimes called immunoparalysis.5 Many patients are already
immunosuppressed when sepsis is diagnosed.6
CLASSIFICATION
Patients with septic shock may be classified according to the letters
PIRO7 :
P = Predisposing Factors
Each patient has specific characteristics. For example, an individual
receiving long-term immunosuppressant therapy requires a different
approach than someone who was previously healthy. Factors associated
with lifestyle, such as alcoholism, may influence the course of septic
shock.8 Patient age and sex may also be important. Increasingly, genet-
ics is being considered, and studies are discovering the genetic factors
that can influence the development of and survival from sepsis.9-11
Improved understanding of these aspects should help better direct
therapeutic strategies.
I = Infectious Insult
This refers to the specific characteristics of the infection, that is, the
agent or pathogen involved (e.g., gram-positive vs. gram-negative,
bacteria vs. fungus), the source of sepsis (e.g., urinary tract vs.
843
844 PART 8 Infectious Diseases

respiratory tract), and the degree of extension of the infection (e.g.,
pneumonia confined to one lobe of one lung vs. generalized bilateral
lung involvement, appendicitis vs. generalized peritonitis). All these
factors can influence the severity of sepsis response and the patient’s
likely response to therapy.
R = Host Response
This refers to factors involved in the inflammatory response of the host
to the infection and is assessed largely by the presence or absence of
the signs and symptoms of sepsis (e.g., degree of elevation of white
blood cell count, C-reactive protein [CRP], or procalcitonin). Each
patient mounts a different response dependent on various factors
including those previously discussed, and a patient’s response will vary
with his or her clinical course and treatment.
O = Organ Dysfunction
This refers to the degree of organ dysfunction related to sepsis and can
be evaluated using various scoring systems, including the SOFA
(sequential organ failure assessment) score,12 which uses objective,
readily available measures to quantify the dysfunction of six organ
systems (Table 121-1). Dysfunction of each organ is rated according to
a scale (0 [normal function] to 4 [organ failure]), and individual scores
can then be summed to provide a total. Individual organ function as
well as a composite score can thus be followed during the course of the
disease and treatment.
CLINICAL PRESENTATION
It has been suggested that sepsis progresses in a continuum through to
septic shock, but in the clinical situation, such a progression is not
always so clear-cut or constant, and it is difficult to predict which
patients are going to develop septic shock and when. Septic shock can
develop very abruptly, without evidence of signs of sepsis in the pre-
ceding hours.
Septic shock is characterized by the persistence of severe arterial
hypotension requiring vasopressor support, despite adequate fluid
resuscitation, and the presence of perfusion abnormalities manifest by
oliguria, reduced peripheral perfusion, and altered mental status.
Septic shock is typically associated with hyperlactatemia (blood lactate
concentrations above 2 mEq/L).13
One may anticipate that patients with septic shock will have fever,
leukocytosis, and other typical features of sepsis, but this is not always
true. Fever may be an important clue, but moderate fever can be
found in other types of shock. More important, fever is often absent
in patients with septic shock; in fact, hypothermia may be present
in 10% to 15% of cases, and this feature is associated with higher
mortality rates.14 Tachycardia can be the result of circulatory altera-
tions associated with any type of shock. Leukocytosis is also nonspe-
cific and can be found in other types of circulatory failure; moreover,
acute leukopenia may occur in sepsis due to peripheral trapping of
activated leukocytes and is also associated with a worse prognosis.
Lactic acidosis, a hallmark of all types of circulatory failure, is usually
compensated by hyperventilation, so tachypnea is not specific for
septic shock.
A more typical characteristic of septic shock is the hyperkinetic
pattern characterized by high cardiac output. Although such a hemo-
dynamic pattern is not entirely specific—it can be found in other
inflammatory states such as polytrauma or pancreatitis or even ana-
phylactic shock—it should alert the attending physician to a likely
diagnosis of septic shock.
HEMODYNAMIC CHANGES
The inflammatory reaction causes intense vasodilation that increases
vascular capacity and results in a fall in arterial blood pressure. Hypo-
volemia due to fluid loss (e.g., diarrhea, vomiting, or sweating) and
alterations in capillary permeability contributes to hypotension, and
reduced myocardial contractility can further aggravate the hemody-
namic situation, although it is completely reversible when the septic
shock resolves. The pathophysiology of reduced myocardial contrac-
tility includes alterations in endothelial function, alterations in β-
adrenergic receptors, and alterations in myocardial calcium metabolism.
These effects are caused largely by sepsis mediators such as TNF-α and
IL-1, oxygen free radicals, platelet activating factor, and NO, which all
have negative inotropic effects.
After vascular filling as a result of volume resuscitation, the hemo-
dynamic status in septic shock is characterized by a fall in vascular tone
associated with reduced systemic vascular resistance and a raised
cardiac output. In addition, reduced myocardial contractility causes a
fall in the ventricular ejection fraction. Ejection volume and, particu-
larly, cardiac output may be maintained by an increase in diastolic
volumes. Hence, there is myocardial depression or dysfunction without

TABLE 121-1 The Sequential Organ Failure Assessment Score

SOFA SCORE 0 1 2 3 4
RESPIRATION
PaO2/FiO2, mm Hg >400 ≤400 ≤300 ≤200 with respiratory ≤100 with respiratory
support support
COAGULATION
Platelets × 103/mm3 >150 ≤150 ≤100 ≤50 ≤20
LIVER
Bilirubin, mg/dL (μmol/L) <1.2 (<20) 1.2-1.9 (20-32) 2.0-5.9 (33-101) 6.0-11.9 (102-204) >12.0 (>204)
CARDIOVASCULAR
Hypotension No hypotension MAP < 70 mm Hg Dopamine ≤5 or Dopamine >5 or Dopamine >15 or
dobutamine epinephrine ≤0.1 or epinephrine >0.1 or
(any dose)* norepinephrine ≤0.1* norepinephrine >0.1*
CENTRAL NERVOUS SYSTEM
Glasgow Coma Score 15 13-14 10-12 6-9 <6
RENAL
Creatinine, mg/dL (μmol/L) <1.2 (<110) 1.2-1.9 (110-170) 2.0-3.4 (171-299) 3.5-4.9 (300-440) or >5.0 (>440) or
or urine output <500 mL/d <200 mL/d

Data from Vincent JL, de Mendonca A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units. Results of a multicenter, prospective study.
Crit Care Med 1988;26:1793–800.
*Adrenergic agents administered for at least 1 hour (doses given are in μg/kg/min).

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 CHAPTER 121 Septic Shock 845

any true cardiac failure (which would be associated with reduced

cardiac output).

MONITORING
Any patient with septic shock requires monitoring with an arterial
catheter to enable reliable and continuous assessment of arterial pres-
sure. Changes in systolic and pulse pressures in mechanically ventilated
patients during the respiratory cycle may also indicate a greater likeli-
hood of response to a fluid challenge; however, this sign is not reliable
when the patient triggers the ventilator.15 The arterial catheter also
facilitates blood sampling, notably for blood gas analysis.

Invasive Versus Less Invasive Monitoring

The role of the pulmonary artery catheter (PAC) in critically ill patients
has been questioned. However, although no study has conclusively
demonstrated positive effects of this type of monitoring on outcome,16
information obtained from the PAC may help in guiding patient
management in complex cases.17 The PAC is useful not only for moni-
toring pulmonary artery occlusion pressure (PAOP) and cardiac output
but also for assessment of mixed venous oxygen saturation (Svo2), a
highly useful parameter because a fall in Svo2 is generally indicative of
inadequate oxygen transport.
Less invasive monitoring techniques are increasingly being used.
Echocardiography can provide useful additional information, largely
to visualize the degree of ventricular filling and ejection volume.
However, echocardiography requires an experienced operator, gives no
information on the adequacy of cardiac output for the patient’s needs,
and is difficult to perform continuously, so information is usually
intermittent. Other less invasive methods of monitoring cardiac output FIGURE 121-1 ■ Representative examples of sublingual microvas-
include PiCCO, LidCO, transesophageal Doppler techniques, and even culature in a healthy volunteer (top panel) and in a patient with
bioimpedance or bioreactance techniques.18 However, measurement of septic shock (lower panel). Note decrease in density of small vessels
cardiac output in isolation is not very helpful in most critically ill in sepsis. (From De Backer D, Creteur J, Preiser JC, et al. Microvascular
patients. blood flow is altered in patients with sepsis. Am J Respir Crit Care Med
2002;166:98–104, with permission.)
Blood Lactate Levels
The blood lactate level is an important biological variable in determin-
ing the adequacy of perfusion and oxygenation. The normal blood observed (Fig. 121-1) and quantified in patients with sepsis.20 More-
lactate level is around 1 mEq/L, and hyperlactatemia becomes clearly over, the impact of therapeutic interventions on such changes can be
pathologic above a level of 2 mEq/L. Although hyperlactatemia is due monitored,21,22 opening the possibility that monitoring the microcircu-
to cellular hypoxia in other forms of circulatory shock, in septic shock, lation could be used to guide treatment.
additional mechanisms may play an important role in raising blood Near-infrared spectroscopy is a technique that uses the differential
lactate levels. In sepsis, blood lactate levels may be raised by an increase absorption properties of oxygenated and deoxygenated hemoglobin to
in cellular metabolism, by inhibition of pyruvate dehydrogenase, and evaluate tissue oxygenation (Sto2). Analysis of changes in Sto2 during
by reduced clearance. Repeated measurements enable one to assess the a circulatory stress test, such as a brief episode of forearm ischemia
efficacy of treatment19 and have a predictive value superior to derived (venous or arterial occlusion), may be more useful to quantify sepsis-
oxygenation parameters. The evolution of blood lactate levels enables induced microvascular dysfunction than an isolated Sto2 value.23
a global evaluation of the state of shock in response to treatment, Although these techniques have demonstrated clearly the presence
although in view of the relatively slow rate of change, blood lactate of alterations in the microcirculation in patients with sepsis, which are
levels cannot be used to guide resuscitation. associated with prognosis,24 further research is needed to fully evaluate
the relevance of these values to the early resuscitation and care of criti-
cally ill patients.
Peripheral Perfusion Parameters
Measurement of the gastric intramucosal pH or its derivatives (mucosal
Pco2 or the difference between the mucosal and arterial Pco2 [the Pco2
MANAGEMENT
gap]) is considered to reflect splanchnic perfusion and hence provide Septic shock, which systematically causes dysfunction of other organs,
an idea of the adequacy of regional oxygenation. However, these is a serious condition, and patients must be stabilized as a matter of
techniques may be influenced by technical considerations, including urgency. Management of the patient with septic shock involves three
the influence of gastric acid and enteral nutrition, and are not used inseparable components: treatment of the infection, cardiovascular
clinically. resuscitation, and modulation of the host response (Fig. 121-2).25
Other techniques for monitoring peripheral perfusion have been
developed. While the sublingual region is not a region that would
immediately seem to be of most interest, it is easily accessible, and
Treatment of Infection
using techniques of orthogonal polarization spectral or sidestream Infection must be treated effectively and rapidly. Antibiotics must be
darkfield imaging, heterogeneity of microcirculatory flow and reduced started quickly and must cover all likely organisms.26 The choice of
perfused vessel density and proportion of perfused vessels can be antibiotics may depend on local microbiological flora and resistance

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846 PART 8 Infectious Diseases
Treatment of Septic Shock
Hemodynamic Infection control
stabilization
Fluids Vasoactive Antibiotics Source
agents control
Modulation of the septic response
Corticosteroids Low-dose
(in severe vasopressin?
septic shock)?
FIGURE 121-2 ■ The three aspects of the treatment of septic
shock.
patterns. Often, the microorganism(s) responsible for sepsis in an
individual patient is not known for sure, and empiric broad-spectrum
antibiotics must be given to ensure adequate coverage. Such empiric
therapy must then be modified as soon as microbiology culture results
become available.
In addition to antibiotic treatment, any focus of infection must be
removed or drained by emergency surgery if necessary. If no source is
identified, a systematic search should be made based on the “big five”:
lungs, abdomen, urine, wounds, and catheters.
Cardiovascular Resuscitation
The VIP rule proposed by Weil and Shubin27 should be followed. Each
patient is in fact a VIP, but the letters refer here to Ventilation, Infusion,
and Pump.
V = Ventilation
All patients with septic shock must be generously oxygenated with the
aim of correcting any hypoxemia, regardless of whether it is due to
inadequate cardiac output, pulmonary edema, or pulmonary disease.
Severe cases need endotracheal intubation and mechanical ventilation.
Noninvasive ventilation is not recommended in such hemodynami-
cally unstable patients. Even though it may represent a temporary
support rather than a treatment per se, mechanical ventilation allows
not only an improvement in gaseous exchange but also has beneficial
hemodynamic effects, notably by reducing the oxygen requirement of
the respiratory muscles.
I = Infusion
Septic shock is accompanied by absolute and relative hypovolemia, the
result of various mechanisms:
• External losses, which may be obvious, such as vomiting and
diarrhea, or less apparent, such as sweating
• Internal losses via an increase in capillary permeability with
development of edema and sometimes liquid effusions (perito-
neal, pleural effusion)
• Increase in plasma volume associated with arterial and venous
dilatation
Hypovolemia needs to be corrected rapidly as it causes hemodynamic
instability both at the level of cardiac output and in terms of peripheral
perfusion.
Assessment of an adequate volume state is essentially clinical:
restoration of arterial pressure, improvement of cutaneous perfu-
sion, improved urine output, and improved mental state. The central
venous pressure (CVP) can be a useful guide, but it is not possible to
define in advance the CVP that should be reached in any individual
patient. Measurements of CVP or PAOP are primarily used as a limit
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The Fluid Challenge Technique
TABLE 121-2
(with the TROL Mnemonic)
DEFINE EXAMPLE
Type of fluid Ringer’s lactate
Rate of infusion 200 mL in 10 min
Objective Mean arterial pressure >75 mm Hg
Limits Central venous pressure 16 mm Hg
to fluid administration in order to minimize the risk of pulmonary
edema. In fluid replacement, it is preferable to use a fluid challenge
technique, in which filling pressures are measured at regular intervals
during fluid administration (Table 121-2).28 If cardiac output is moni-
tored, one should ensure that it increases with fluid boluses, and
such fluid administration should be stopped when cardiac output
reaches a plateau.
There has been considerable debate as to which fluid should be used
in sepsis, but it is the quantity of fluid rather than the type of fluid per
se that is of greatest importance. Because of their propensity for leakage
into the extravascular space, greater volumes of crystalloids are needed
to achieve the same effect as colloids,29 thus potentially increasing the
risk of edema, but colloids are more expensive and carry their own
risks. In particular, there has been considerable controversy about the
use of albumin in critically ill patients, but the SAFE study suggested
a decrease in mortality associated with albumin administration in
patients with sepsis.30 Most clinicians would use some albumin in
septic patients with significant hypoalbuminemia.
P = Pump (Vasoactive Agents)
If fluid administration alone is unable to restore an adequate perfusion
pressure, vasoactive agents are required. Catecholamines are preferred
for their rapid action and efficacy and their short half-lives. Adrenergic
agents stimulate β1- (positive inotropes), β2- (essentially vasodilators
and bronchodilators), and α- (essentially vasoconstrictors) receptors
to varying degrees. Dopamine also stimulates dopaminergic receptors,
causing vasodilation primarily in the splanchnic and renal regions, but
the clinical relevance of this effect is doubtful.
A randomized controlled study showed that dopamine use is
associated with increased adverse effects, notably arrhythmias, in
patients with shock,31 and a meta-analysis indicated that dopamine
administration is associated with higher mortality rates than norepi-
nephrine in septic shock.32 Norepinephrine is, therefore, the preferred
first-line vasopressor in patients with septic shock. Epinephrine should
not be used as a first-line vasopressor in patients with septic shock; it
can have deleterious effects on splanchnic circulation and increase
cellular metabolism. Dobutamine is often added to vasopressor therapy,
particularly when using norepinephrine, to increase cardiac output by
its positive inotropic effects.
The place of vasopressin derivatives is not well defined. Patients
with septic shock usually have a degree of relative vasopressin defi-
ciency so that vasopressin supplementation may be warranted. Recent
studies have suggested that vasopressin is involved in endothelial
protection so that early administration of vasopressin derivatives may
limit edema formation.33 This hypothesis is presently being tested in
clinical trials.
Immunomodulation
Clinical trials assessing drugs that limit the effects of proinflammatory
cytokines such as TNF-α (anti-TNF antibodies, TNF receptors) and
IL-1 (IL-1 receptor antagonist inhibitors) have not given convincing
results on beneficial effects of these agents on outcome, probably
largely because such cytokines have multiple effects, beneficial as well
as harmful. Administration of activated protein C (drotrecogin alfa
[activated]) early in septic shock reduced mortality and morbidity in

initial studies,34 but the drug was withdrawn from the market after a
later negative placebo-controlled study.35
The administration of large doses of corticosteroids for patients
with septic shock was proposed many years ago. More recently, the
concept of relative adrenal insufficiency has emerged, and administra-
tion of moderate doses of corticosteroids (200 mg hydrocortisone in
24 hours) in patients with septic shock has been proposed, but this is
also debated.36 ,37
The treatment of fever is controversial. Increased body temperature
increases oxygen requirements, but the increased cellular metabolism
may form part of the body’s natural defense. Animal studies have
suggested that control of fever is detrimental38 and that the release of
heat shock proteins in fever may have important protective effects.39 A
multicenter study of acetaminophen in febrile ICU patients with sus-
pected infection showed that the drug was well tolerated but did not
reduce mortality.40
High-flow hemofiltration techniques can remove a range of bacte-
rial products and mediators but are not without risk, notably because
this process can remove beneficial products such as hormones and
medications, including antibiotics, as well as potentially harmful sub-
stances.41 Clinical studies have provided conflicting data regarding the
effects of these techniques on outcomes.42
Nutritional Support
Malnutrition can prolong the course of sepsis and increase the risk of
complications. When considering nutritional support in patients with
septic shock, several factors should be remembered:
• There is no urgency to start nutritional support, unless the patient
is malnourished.
• The enteral route is preferable to the parenteral route.
• Enteral nutrition should not be started during the initial phase of
resuscitation. Although studies are limited, increasing the oxygen
requirements of the gut is probably unwise in circulatory shock.
However, as soon as the patient has achieved a degree of hemody-
namic stability (after a maximum of 24-48 hours), enteral nutrition
should be started.
• There is no urgency to start parenteral nutrition. Waiting a few days
is acceptable.
• Careful control of blood glucose levels is recommended. Control of
blood glucose levels has been shown to be associated with improved
outcomes,43 but hypoglycemia can be a problem with very strict
blood glucose protocols. A suggested target glucose concentration
is, therefore, 110 to 150 mg/dL.25,44 Variability in glucose levels
should also be avoided.45
Organ Support
Organ dysfunction can involve any organ and can be quantified using
the SOFA score (see Table 121-1). Techniques for individual organ
support are covered in separate chapters, but an overview is given here.
Respiratory Alterations
Respiratory failure is a common complication of sepsis and is usually
characterized by hypoxemia. The diagnosis of acute respiratory distress
syndrome is made when the Pao2/Fio2 ratio is less than 300 mm Hg in
the presence of bilateral infiltrates on a chest radiograph, with no
evidence of left heart failure.46
When starting a patient on mechanical ventilation, several factors
need particular attention:
• Worsening of arterial hypotension when starting mechanical
ventilation suggests the presence of hypovolemia due to a reduc-
tion in venous return (and hence in cardiac output) when
intrathoracic pressures are increased.
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CHAPTER 121 Septic Shock 847
• Tidal volume should be limited, not only for hemodynamic
reasons but also to avoid a major inflammatory reaction.
• Sedation must be avoided whenever possible. Administration of
sedative drugs and analgesics should be titrated with respect to
the needs of the individual patient. Reduced administration of
sedative agents can shorten the duration of mechanical ventila-
tion and ICU stay.47 ,48
Renal Alterations
Sepsis is the leading cause of acute renal failure in the ICU.49 Renal
function can worsen as a result of combined circulatory changes and
inflammation. In addition, management of septic patients often
involves administration of nephrotoxic agents—for example, amino-
glycosides or contrast material for radiologic examinations.
Unfortunately, there is no prophylactic approach to renal failure
other than to try to maintain adequate renal perfusion and overall
volume state. Administration of low (renal)-dose dopamine is ineffec-
tive at preventing renal failure,50 and diuretics may be harmful.51
Renal replacement therapy is frequently necessary in septic patients.
In septic shock, continuous venovenous techniques, with or without
dialysis, are generally preferred over intermittent techniques to facili-
tate control of fluid balance.
Coagulation Alterations
Coagulopathy is common in septic shock. A low platelet count is
common and may be associated with a prolonged prothrombin time
and an activated partial thromboplastin time. Treatment of these
alterations revolves primarily around the cause, and there is no indica-
tion for heparin therapy. In severe cases associated with significant
bleeding, administration of fresh frozen plasma or platelet infusions
may be indicated.
Hepatic Alterations
Circulatory shock of any cause frequently results in the elevation of
liver-associated enzyme levels, but the contribution of various organs
(e.g., muscles) to increased enzyme levels is difficult to quantify. Often
there is a rise in bilirubin levels after several days, without evidence of
hemolysis, major hematomas, or biliary pathology. Supplementary
examinations such as ultrasound may be indicated to exclude any
associated biliary pathology.
Cerebral Function Alterations
Circulatory shock is typically accompanied by an alteration in intel-
lectual function, initially manifested as confusion without real coma.
Cerebral alterations can be prolonged, and the patient is then said to
have septic encephalopathy. The exact cause of the encephalopathy is
unclear, although various mediators of sepsis have been implicated.
Investigations are of little use except to exclude other causes. The
electroencephalogram generally shows a slow diffuse slowing,52
whereas cerebral computed tomography and cerebrospinal fluid
examination are normal. These alterations are usually fully reversible
with the resolution of shock.
CONCLUSION
Optimal treatment of a patient with septic shock requires a rapid and
effective management plan with the assistance of the full ICU team.
Infection control and achieving hemodynamic stability must be tackled
simultaneously. Other interventions are currently undergoing clinical
trials, with the hope that they will improve the microcirculatory
changes of sepsis or beneficially modulate the host response. A better
characterization of patients with septic shock—for example, by using
the PIRO system—is necessary to appropriately titrate therapeutic
interventions to individual patients.
848 PART 8 Infectious Diseases

KEY POINTS

1. Septic shock affects about 15% of ICU patients and has a mortal-
ity rate of close to 50%.
2. Septic shock is most commonly caused by a bacterial infection,
although fungi, viruses, and parasites can all be implicated. The
most common source of infection is the lung, followed by the
abdomen.
3. Patients with sepsis can be classified according to their predis-
posing factors, the nature of the infection, degree of immune
response, and associated organ dysfunction.
4. Septic shock is defined as sepsis with organ dysfunction with
persistent arterial hypotension requiring vasopressor administra-
tion despite adequate fluid resuscitation, in the presence of
perfusion abnormalities manifested by oliguria, reduced periph-
eral perfusion, and/or altered mental status.
5. Blood lactate levels are typically raised in septic shock, and
persistently raised levels are a poor prognostic sign.
6. Management of septic shock includes infection control, hemody-
namic stabilization, and modulation of the host response.

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