Professional Documents
Culture Documents
ONE
Principles in the Management of
Traumatic Injuries
CHAPTER
OUTLINE
Physiologic Response
Mediators of the Response
Neuroendocrine Response
Lipid-Derived Mediators
Cytokines
Polymorphonuclear Neutrophils
Clinical Implications
Modulation of the Response
Adult Respiratory Distress Syndrome
Nutrition As Therapy
Deep Vein Thrombosis Prophylaxis
Stress Gastritis
PHYSIOLOGIC RESPONSE
Tissue damage produces an inflammatory reaction that
causes local effects, such as tissue edema, vasoconstriction, and thrombosis. Other mediators released into the
systemic circulation act at sites removed from the injury.
For example, they stimulate the autonomic nervous
system, with concomitant production of hormones, cytokines, and arachidonic acid metabolites. The orchestrated response seen with severe injury has been
described as having two phases that overlap, the ebb
phase, which occurs immediately and may last as long as
24 hours after injury, and the flow phase, which may last
for weeks.
Time
Death
Acute phase
Chronic phase
Recovery
1300
1200
1100
1000
900
800
700
600
5500
5000
4500
5000
4000
4375
3500
3750
3500
3250
3000
2750
2500
3000
2800
2600
2400
2200
2000
2250
1800
2000
1600
1750
1400
1500
1250
1200
1100
1000
1125
900
1000
800
10
875
700
750
600
Normal 0
625
500
1400
6875
6250
5625
2800
2700
2600
2500
2400
2300
2200
2100
2000
1900
1800
1700
1600
1500
Burn size
115
110
105
100
95
90
85
90
75
70
65
60
55
50
45
40
500
400
50%
40%
30%
Multiple trauma with
patient on ventilator
20%
Severe infection,
multiple trauma
35
30
25
20
10%
Long bone fracture
15
Peritonitis
Postoperative
-5
-10
500
70%
60%
Mild starvation
-15
FIGURE 1-2 Changes in resting energy expenditure associated with trauma, burns, and other common clinical conditions. (Adapted From
Wilmore DW: The metabolic management of the critically ill, New York, 1977, Plenum Press.)
LIPID-DERIVED MEDIATORS
Cyclooxygenase products of arachidonic acid metabolism are present in increased amounts in human studies
of injury. Thromboxane A2 accentuates neutrophil
aggregation and, with prostacyclin, has potent and opposing vascular effects that may have a role in pulmonary
hypoxic vasoconstriction and systemic vasodilation.
Lipoxygenase products are also released in large quantities and affect the permeability of the pulmonary vascular bed.
Platelet-activating factor (PAF) is a phospholipid
metabolite released by a number of cells, including neutrophils. The response to PAF at the endothelial surface
results in enhanced superoxide production, enhanced
platelet aggregation, altered pulmonary vascular reactivity, and changes in endothelial permeability.
CYTOKINES
Protein mediators, collectively called cytokines, are produced at the site of injury and by diverse circulating
immune cells. Monocytes, lymphocytes, macrophages,
and other cells release cytokines. They can act locally as
paracrines by way of direct cell to cell communication or
systemically when produced in excess by way of endocrine mechanisms. The most important cytokines in
trauma are tumor necrosis factor (TNF), the interleukins
(IL-1, IL-2, IL-6, and IL-8), the interferons, and various
growth factors such as granulocyte-macrophage colonystimulating factor (GM-CSF), and platelet-derived growth
factors (PDGFs). They enhance immune cell function
and are responsible for the systemic effects of inflammation and sepsis, such as fever, leukocytosis, hypotension,
delayed gastric emptying, and malaise.
Thought to be the most proximal mediator of the
inflammatory response, TNF was originally described as
the catabolic factor cachectin.22 At least two forms of TNF
exist.23,24 TNF influences cellular attraction as part of the
local inflammatory response, leukocyte migration, and
systemic hypotension.25,26 It also promotes muscle
POLYMORPHONUCLEAR NEUTROPHILS
Catecholamines and glucocorticoids marginalize peripheral polymorphonuclear neutrophils (PMNs) and recruit
them from the bone marrow.39,40 Lipids and cytokines
(e.g., IL-1, TNF, PAF) then prime these cells for enhanced
superoxide anion release and sequestration in endorgans.41 Capillary endothelial integrity is disrupted,
leading to the formation of edema, defects in oxygen
delivery, hypoxic cellular injury, and other adverse consequences for cellular homeostasis. This derangement
leads to the clinical entity of multiple-organ failure.
Human studies have supported this sequence and also
suggested that additional stress results in a rerelease of
sTNFr
IL-1RA
sIL-2r
Control
1
hour
2
hour
4
hour
12
hour
1
day
3
day
7
day
Time post-injury
CLINICAL IMPLICATIONS
The successful management of the metabolic changes
that accompany severe trauma influences and may
prevent some of the major complications of trauma
namely impaired immune function, multiple organ
failure, and sepsis.44
Critical illness
Catabolism
Starvation for
medical reasons
Impaired GI motility
Risk of aspiration
Increased energy
requirements
Unsuitable
nutrition protocols
Supplemental
parenteral
nutrition
Increased morbidity
Increased mortality
Longer length of stay
Longer recovery
FIGURE 1-4 Factors whereby enteral nutrition may result in undernutrition of critically ill and injured patientsthe potential role of
supplemental parenteral nutrition. (Adapted from Thibault R, Pichard C: Parenteral nutrition in critical illness: Can it safely improve
outcomes? Crit Care Clin 26:467480, 2010.)
NUTRITION AS THERAPY
The advantages of enteral nutrition over parenteral
nutrition have been clearly demonstrated, and the gastrointestinal tract should be used whenever possible.
Recently, a role for supplemental parenteral nutrition
has been advocated (Fig. 1-4). The traditional preference is to feed patients by the enteral route for reasons
that include a reduction of the number of enteric organisms that may be responsible for bacterial translocation.
Stimulation of the enterocyte brush border and gutassociated lymphoid tissue is an important protective
mechanism against the proliferation of the offending
organisms.64 The route of feeding may also have an
impact on the production of cytokines after injury;
thus, use of the enteral route may confer an additional
advantage.65
Considerable attention has focused on nutrients that
attenuate the metabolic response to injury. Nutrients
that appear to enhance the immune system include arginine, glutamine, and nucleic acids. The immune system
may be enhanced by altering the relative amounts of
omega-6 versus omega-3 unsaturated fatty acids.66,67
Other nutrients may act as oxidants, preventing damage
by free radicals, such as the common antioxidants vitamins A, C, E, and the trace element selenium.
There has been lukewarm interest in the concept of
immunonutritionto ameliorate the end-organ damage
from critical illness and sepsis, which may later result in
acute renal failure and ARDS. A study of supplementation with an enteral diet of omega-3 fatty acid, gammalinolenic acid, and antioxidants versus an isocaloric
enteral formulation was reported in 2011. These nutrients are typically thought to modulate the systemic
inflammatory response.68 The study randomized 272
adults who had developed acute lung injury and required
mechanical ventilation. Enteral nutrition was provided to
both patient groups using a standard protocol, and the
study supplement was provided twice daily to the study
cohort of patients. The study was halted early because of
futility. The ventilator-free and intensive care unit-free
days were lower in the omega-3 group and, although not
significant, hospital and 60-day mortality were higher in
the omega-3 group.
A recent study comparing a special enteral formulation of eicosapentaenoic acid, gamma-linolenic acid, and
antioxidants versus a standard formulation to patients
during the early stages of sepsis (without organ failure)
yielded different results.69 The study, funded in part by
the product manufacturer, revealed no significant difference in mortality between the two groups. A significant
reduction in the appearance of cardiac and respiratory
failure occurred in the study population given the special
enteral formulation versus those given the standard
formula control. Subjects in the test arm also experienced
a benefit of fewer days on mechanical ventilation, fewer
days in the intensive care unit, and shorter length of hospital stay. The concept of immunonutrition continues to
evolve and, particularly within the last 5 years, the approach
to the modulation of nutrition by timing to feed, amounts,
route of administration,and composition of the nutritional product have yielded new information regarding
how to optimally feed injured and critically ill patients.
STRESS GASTRITIS
Stress gastritis is common to the multiply injured intensive care unit population, and patients left untreated may
have clinically significant gastrointestinal bleeding. The
principal risk factors for stress gastritis are head injury,
mechanical ventilation, and abnormal coagulation profiles. Prophylaxis using histamine-2 receptor antagonists
or proton pump inhibitors is very effective.73
SUMMARY
Injury produces a series of physiologic changes mediated
by local and systemic agents and systemic effects, mainly
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