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U N I T 5
Circulatory Function
Persons with severe sepsis and hyperglycemia (two
consecutive blood glucose readings > 180 mg/dL) should
receive insulin therapy following a protocol to maintain
their blood glucose levels at a target level of
≤
180 mg/dL.
67
Ongoing assessment of CVP, mixed venous or arterial
oxygen saturation, mean arterial pressure, urinary out-
put, and laboratory measurements of blood chemistries,
serum lactate, base deficit, and pH are used to evalu-
ate the progression of sepsis and adequacy of treatment
as well as the need for other supportive therapies. This
group of interventions lists the sepsis “bundle” that
when implemented together produce better outcomes
than when implemented individually.
67,68
Complications of Shock
As the late Carl Wiggers, a noted circulatory physiolo-
gist, once stated, “shock not only stops the machine,
but it wrecks the machinery.”
72
Many body systems are
wrecked by severe shock. Five major complications of
severe shock are lung injury, acute kidney failure, gas-
trointestinal complications, disseminated intravascular
coagulation, and multiple organ dysfunction syndrome.
These complications of shock are serious and often fatal.
Acute Lung Injury/Acute Respiratory
Distress Syndrome
Acute lung injury/acute respiratory distress syndrome
(ALI/ARDS) is a potentially lethal form of pulmonary
injury that may be either the cause or result of shock
(see Chapter 23). Acute lung injury/acute respiratory
distress syndrome represents a spectrum of acute respi-
ratory failure with ARDS being the more severe form,
associated with greater hypoxemia and mortality.
Acute lung injury/acute respiratory distress syndrome
is marked by the rapid onset of profound dyspnea that
usually occurs after an initiating event, such as trauma,
aspiration, or pancreatitis. The respiratory rate and
effort of breathing increase. Arterial blood gas analysis
establishes the presence of profound hypoxemia that
is refractory to supplemental oxygen. The hypoxemia
results from impaired matching of ventilation and per-
fusion and from the greatly reduced diffusion of blood
gases across the thickened alveolar membranes.
6
The exact cause of ALI/ARDS is unknown. Neutrophils
are thought to play a key role in its pathogenesis. A
cytokine-mediated activation and accumulation of neu-
trophils in the pulmonary vasculature and subsequent
endothelial and epithelial injury are thought to cause
leaking of fluid and plasma proteins into the interstitium
and alveolar spaces.
73
The fluid leakage causes atelectasis,
impairs gas exchange, and makes the lung stiff (poor com-
pliance) and more difficult to inflate. Abnormalities in the
production, composition, and function of surfactant may
contribute to alveolar collapse and gas exchange abnor-
malities. Inappropriate vasodilation and vasoconstriction
worsen the ventilation and perfusion mismatch.
Interventions for ALI/ARDS focus on increasing the
oxygen concentration in the inspired air and support-
ing ventilation mechanically to optimize gas exchange
while avoiding oxygen toxicity and preventing further
lung injury. Despite the delivery of high levels of oxy-
gen using high-pressure mechanical ventilatory support
and positive end-expiratory pressure, many persons with
ALI/ARDS remain hypoxic, often with a fatal outcome.
74
Acute Kidney Injury
Acute kidney injury (AKI), formerly known as acute
renal failure, often occurs in the context of sepsis and
multiple organ failure.
75
The renal tubules are particu-
larly vulnerable to ischemia, and AKI is an important
factor in mortality due to severe shock. Most cases of
AKI are due to impaired renal perfusion in response to
decreased intravascular volume.
75
The degree of renal
damage is related to the severity (or stage) and duration
of shock. The renal dysfunction most frequently seen
with progressive to severe shock states is acute tubu-
lar necrosis. Acute tubular necrosis usually is revers-
ible, although return to normal renal function may
require weeks or months (see Chapter 25). Continuous
monitoring of urinary output during shock provides a
means of assessing renal blood flow. Frequent monitor-
ing of serum creatinine and blood urea nitrogen lev-
els also provides valuable information regarding renal
status.
Gastrointestinal Complications
The gastrointestinal tract is particularly vulnerable to
ischemia because of the changes in distribution of blood
flow to its mucosal surface. In shock, there is widespread
constriction of blood vessels that supply the gastrointes-
tinal tract, causing a redistribution of blood flow and
a severe decrease in mucosal perfusion. Proton pump
inhibitors or histamine 2–receptor antagonists may be
given prophylactically to prevent gastrointestinal ulcer-
ations and bleeding in persons with shock who have risk
factors for bleeding.
67
Disseminated Intravascular Coagulation
Disseminated intravascular coagulation (DIC) is char-
acterized by widespread activation of the coagulation
system with resultant formation of fibrin clots and
thrombotic occlusion of small and mid-sized vessels (see
Chapter 12). The systemic formation of fibrin results
from increased generation of thrombin, the simultaneous
suppression of physiologic anticoagulation mechanisms,
and the delayed removal of fibrin as a consequence of
impaired fibrinolysis. Clinically overt DIC is reported
to occur in as many as 30% to 50% of persons with
Gram negative sepsis.
76
As with other systemic inflam-
matory responses, the derangement of coagulation and
fibrinolysis is thought to be mediated by inflammatory
mediators and cytokines.
The contribution of DIC to morbidity and mortality
in sepsis depends on the underlying clinical condition
and the intensity of the coagulation disorder. Depletion
of the platelets and coagulation factors increases the risk
of bleeding. Deposition of fibrin in the vasculature of
organs contributes to ischemic damage and organ failure.
