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CHAPTER 20: Nutrition Therapy in the Critically Ill 135

present and a normal number of commensal bacteria, the dendritic might have been a decrease in the number of nosocomial infections, the
cell releases interleukin-4 (IL-4). The production of IL-4 stimulates number of organs failing, and the overall length of stay in the ICU prior
a change in naïve T cells (Th0) into the Th2 subset. Differentiation to discharge.
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into Th2 lymphocytes causes further release of IL-4, interleukin-6
(IL-6), and interleukin-10 (IL-10). The Th2 response tends to oppose
or attenuate the Th1 inflammatory response. Feeding is also associated NUTRITIONAL SCREENING AND ASSESSMENT
with oral tolerance, which represents a Th3 subset of CD4 lympho- Nutrition screening at admission is essential to the identification of
cytes and is generated in the presence of IL-4, IL-10, and transforming patients who are at risk of adverse events due to their nutritional status
growth factor-β (TGF-β), all of which tend to have immunosuppres- and is recommended by various organizations. 37-39 Various screening tools
sive effects. 32 currently exist for use in hospitalized patients and are based on criteria
such as history of unplanned weight loss and decreased oral intake, body
https://kat.cr/user/tahir99/
THE IMPORTANCE OF MAINTAINING mass index, acute illness/severity of disease/gastrointestinal symptoms,
GASTROINTESTINAL INTEGRITY mobility, and physical assessment. 40-45 None of the screening tools have
been developed or validated specifically for the critically ill population, in
The increase in gut permeability, which in some patients occurs over a whom acute inflammatory responses have a rapid, catabolic effect on lean
very short period of time, has clinically important consequences for sick, body mass resulting in poor nutritional status at ICU admission.
critically ill patients. With loss of functional integrity, the tight junctions There is strong observational evidence to show that not all critically ill
between the intestinal epithelial cells open up, the gut becomes “leaky,” patients respond to artificial nutrition the same way. In a recently pub-
and the patient experiences systemic bacterial challenge (through release lished prospective study of 2772 mechanically ventilated adult patients
of endotoxin and other gut-derived factors) and an exaggerated stress from 167 ICUs around the world, the association of nutritional adequacy
response with increased severity of disease. In a prospective random- and clinical outcomes was examined. Data were collected for maximum
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9
ized trial, Windsor and colleagues showed that patients with pancreatitis of 12 days and regression models were developed to explore the rela-
maintained on enteral tube feeding had no change in IgM antibodies to tionship between nutrition received and 60-day mortality. The results
endotoxin over a week of enteral feeding. In contrast, controls placed suggested that an increase of 1000 calories per day was associated with
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on PN and gut disuse demonstrated a significant increase in IgM anti- an overall reduction in mortality (odds ratio for 60-day mortality 0.76;
bodies to endotoxin of 25% in response to a week of parenteral feeding 95% CIs 0.61-0.95; p = 0.014). Interestingly, in a subgroup analysis, the
(p < 0.05). In a second study, increased gut permeability (measured beneficial treatment effect of increased calories and protein on mortal-
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by enteric absorption and urinary excretion of polyethylene glycol) ity was observed mostly in patients with a BMI <25 and >35 with less
and systemic endotoxemia correlated significantly with greater disease benefit for patients in the BMI 25 to 35 group. These data support the
severity in patients with acute pancreatitis. In a prospective random- notion that artificial nutrition may exert a differential treatment effect
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ized trial, normal healthy volunteers randomized to PN and gut disuse with respect to mortality in different subgroups of ICU patients, thereby
for 7 days demonstrated an exaggerated stress response to a standard making it difficult to accurately assess nutritional needs even within the
IV challenge of E. coli endotoxin, as evidenced by higher glucagon, epi- same setting. Practitioners need to discriminate which subgroups might
nephrine, tumor necrosis factor, and C-reactive protein (CRP) levels and benefit the most (or least) from nutrition.
greater muscle catabolism compared to a study group receiving a week A novel approach to quantifying risk in the critically ill patient is
of enteral feeding. In two studies in patients with acute pancreatitis, therefore warranted, especially one that accounts for inflammation as
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significantly faster resolution of the SIRS response and “resolution of the well as acute and chronic starvation. Consistent with groundbreaking
disease process” (resolution of pain, decreasing amylase, and successful definitions of malnutrition by Jensen and colleagues, the NUTrition
46
advancement to oral diet) was seen in patients randomized to EN com- Risk in the Critically ill score (NUTRIC score) was developed, in which
pared to those placed on PN. 24,35 risks of adverse events that may be modifiable by nutrition therapy were
Consistent with the theoretical evidence presented, there are 13 stud- quantified. In a secondary analysis of a prospective observational study,
47
ies of critically ill patients with surgery, trauma, and medical illnesses data for key variables considered for inclusion in the score were collected
that evaluated the benefits of EN compared to PN. Compared to PN, in 598 critically ill patients. Variables included age, baseline APACHE II,
EN was associated with a significant reduction in infectious complica- baseline SOFA score, number of comorbidities, days from hospital admis-
tions (RR 0.62; 95% confidence intervals [CIs] 0.62, 0.84; p = 0.002). sion to ICU admission, Body Mass Index (BMI) <20, estimated percent
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No significant differences were seen in mortality between groups. Thus, of baseline oral intake in the week prior, weight loss in the last 3 months
in general, by feeding via the enteral route, we can expect to reduce the and serum IL-6, procalcitonin (PCT), and CRP levels. After multivariable
infectious complications associated with nutrition therapy in critically ill modeling, the final NUTRIC score consisted of six variables, that is, age,
patients without adversely affecting survival. baseline APACHE II, baseline SOFA score, number of comorbidities,
■ READINESS FOR ENTERAL NUTRITION days from hospital admission to ICU admission, and serum IL-6 and was
found to be highly predictive of outcomes such as mortality and dura-
At the bedside, clinicians fail to recognize the relationship between gut tion of mechanical ventilation. Patients with higher NUTRIC scores had
structure and function and adverse patient outcome, primarily because worse outcomes compared to those with lower scores. More importantly,
there is significant delay in the development of complications that arise patients with a higher NUTRIC score were found to benefit the most
from poor management decisions related to enteral therapy. If mistakes from meeting their estimated nutrition needs compared to patients with a
are made with oxygen delivery, hypoxemia ensues immediately and lower NUTRIC score who did not have any benefit from more nutrition.
the patient may deteriorate within minutes. If mistakes are made with This novel scoring tool will help practitioners identify which critically ill
volume resuscitation, there is a degree of delay, and problems arising patients are more likely to benefit from aggressive nutrition.
from decreased vascular volume, hypoperfusion, and increasing azote- Determination of caloric requirements is very important on the initial
mia may not develop for 12 to 24 hours. If no effort is made to maintain nutritional evaluation, helping set the goal (number of required calories)
gut integrity, the complications that arise as a result may not develop for of nutritional therapy. Caloric requirements are best determined using
3 to 5 days. At that point, when nosocomial infections occur or organs simple equations (25-30 kcal/kg per day) or by specific measurement via
begin to fail, the clinician does not connect the development of these indirect calorimetry. There is no strong evidence to suggest one method
complications with management decisions made 5 days before with of determining protein-energy requirements is better than the other.
regard to enteral nutrition. In fact, only in prospective randomized tri- What is more important is that once those targets are set, that efforts to
als can it be determined that had gut integrity been maintained, there achieve them as soon as possible are made.

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