© 2013 Neurocritical Care Society Practice Update
Nutrition and Metabolism
Neeraj Badjatia, MD MSc
R. Adams Cowley Shock Trauma Center
University of Maryland School of Medicine
Baltimore, Maryland
CLINICAL CASE
A 65 year old female was a restrained passenger in a MVC with a GCS of 8 at the scene. She was
transported to the Emergency Department where on initial imaging she was found to have a
right sided subdural hematoma with 12 mm midline shift as well as rib fractures with associated
lung contusion (no hemothorax). There are no abdominal signs and a computed tomography
(CT) scan could not demonstrate any major intra-abdominal injury. After emergent
decompressive craniectomy, she is brought up to the ICU. She has type-2 diabetes mellitus, is
known with coronary artery disease and has a body mass index (BMI) of 32. She is sedated to a
RASS of zero with propofol and fentanyl. She has a large bore nasogastric tube (NGT) on free
drainage. A triple-lumen central venous catheter is inserted. She is noted to be stable from a
hemodynamic, respiratory, and ICP perspective.
Given hemodynamic stability, early enteral nutrition (EN) is recommended. A global fluid
allowance of 30–35 ml/kg is suggested, divided between maintenance fluids and enteral feeds.
Supplemental enteral glutamine of 0.5 g/kg is recommended for a total energy target of 20–25
kcal/kg actual bodyweight with 1.2–1.5 g protein/kg ideal bodyweight, adjusting for the caloric
intake due to propofol(1.1 calories/mL) .
Explanation: The provision of enteral nutrition to critically ill patients early upon admission to
the intensive care unit (within 24–48 hours of resuscitation) exerts beneficial physiological
effects such as down regulated systemic immune responses, reduced oxidative stress and
improved patient outcomes in terms of mortality and infectious complications. The use of a
whole-protein feeding solution (polymeric) was recommended over elemental solution given
the absence of significant abdominal injury. Glutamine, considered a conditionally essential
amino acid, exerts various beneficial effects on antioxidant mechanisms, immune function,
production of heat shock proteins, and nitrogen retention. Supplementation with enteral
glutamine (0.3–0.5 g/kg/d) to an enteral nutrition regimen (not already containing
supplemental glutamine) may be considered in trauma patient populations. Note that propofol
infusions deliver a significant amount of calories (1.1 calories/mL) that is almost entirely
consistent of omega 6 fatty acids. This should be accounted for in all calculations of nutritional
requirements and serum triglyceride levels followed every 3 days throughout the infusion
period.
© 2013 Neurocritical Care Society Practice Update
OVERVIEW
Over the past several years, there has developed an increasing awareness of the mechanisms
by which neurological injuries induce a disturbance of the normal homeostatic mechanisms,
resulting from a cascade of sympathetic nervous system activation and inflammatory response.
One of the sequelae of this interaction is hypermetabolism and subsequent malnutrition. In
contrast to simple malnutrition evoked by starvation, which is reversible by re-feeding, the
sequelae of malnourishment accompanying critical illness are the result of a catabolic response
driven by the underlying disease process and not reversed by nutritional supplementation
alone.
Malnutrition occurs in up to 40% of the critically ill patients. The metabolic changes that occur
in response to stress lead to an increase in protein catabolism, resulting in a significant loss of
lean body mass, which in turn results in a higher incidence of complications, especially
infectious ones, and unfavorable outcomes. Specifically malnutrition during critical illness has
been associated with impaired immunological function, impaired ventilatory drive, and
weakened respiratory muscles, leading to prolonged ventilator dependence and increased rate
of infection [1]. Studies in non - neurologic critical illnesses (eg sepsis) have not only
demonstrated the importance of the metabolic response and sequelae of malnutrition, but also
the possible benefit of targeted nutritional support. Beyond studies in traumatic brain injury
(TBI), there is sparse data describing the nutritional requirements in the neurocritical care
setting.
The main purpose of nutritional therapy is to prevent malnutrition and its associated
complications, by modulating the stress response of the patients. This is achieved by: (1)
providing the appropriate doses of macro- and micronutrients to meet the calculated or
measured needs; (3) reducing protein catabolism; and (4) administering substrates that can
modulate the immune response associated with injury.
PATHOPHYSIOLOGY
Metabolic Response to Injury
The metabolic response to injury results from interacting changes in the concentration of
several hormones relative to each other [2]. Numerous afferent stimuli initiate from injury and
are integrated in the hypothalamus which triggers the hormonal response. After activation, the
hypothalamus releases corticotropin-releasing factor, which stimulates the anterior pituitary
and sympathetic pathways. This leads to an increased secretion of catecholamines from the
adrenal medulla and from sympathetic nerve endings throughout the body, and increased
secretion of adrenocorticotropic hormone from the pituitary. These sympathetic and
adrenocortical responses to injury are correlated with the severity of the injury and the
magnitude of the hypermetabolic and hypercatabolic responses [2].
© 2013 Neurocritical Care Society Practice Update
Activation of the sympathetic nervous system (SNS) during acute illness is in most cases a
beneficial reaction that aims to preserve tissue oxygen supply and organ integrity. However, in
critical illness, stimulation of the SNS may exceed in time and scope the beneficial short-term
effects of the normal physiologic reaction. Comparable to the overwhelming immune response
during systemic inflammation or sepsis, in some critically ill patients, endogenous adrenergic
stress may cause adverse effects [3] [4-6]. Also commonly described in other critical illnesses is
the impact of sympathetic activation on metabolic processes. Catecholamines are known to
increase oxygen consumption (VO2) through calorigenic effects mediated primarily by beta 1
and beta 2 receptors[7], which in turn promote protein turnover and lipolysis [8,9]. Protein
catabolism and increased levels of free fatty acids result in more severe organ dysfunction,
infectious complications, and increased mortality rates. The systemic immune response is also
influenced by the sympathetic response after injury and is frequently manifested by elevated
levels of circulating inflammatory cytokines [10]. At the bedside, the net result of these
mechanisms is a well described biphasic response by which hypo and hypermetabolic responses
are observed (Figure 1).
Protein Metabolism
There is a wide acceptance that the increase in nitrogen excretion reflects the mobilization and
breakdown of amino acids to meet the increased demands for tissue fuel. However, catabolism
is not the only abnormality of protein metabolism after injury. It seems clear that the severity
of the stress governs alterations in whole-body protein turnover rates, with acute injury
producing an increase in both the protein synthesis and degradation rates.
A net negative energy balance has been shown to result in protein catabolism and depletion of
amino acids necessary for cellular repair and host defenses. Some are used for protein
synthesis while some are used as three-carbon precursors for glucose synthesis. The major
gluconeogenic amino acid, alanine, is released from muscle and carried to the liver where it
provides a three-carbon skeleton that is utilized as a substrate for glucose. The nitrogen residue
is converted to urea, and urea is excreted in the urine. Biochemical studies suggest that the
three-carbon skeleton of alanine arises in the muscle from pyruvate, which accepts nitrogen by
transamination from the branched chain amino acids, leucine, isoleucine, and valine. This
glucose-alanine cycle provides a continuous supply of glucose for glucose-dependent organs.
In critical illness vital organs are maintained at the expense of less active areas, leading to
muscle breakdown to provide amino acids for synthesis of protein and glucose. The glucose is
then utilized as fuel by the whole body in which the need for fuel is increased. If no nutrition is
provided and if no metabolic adaptation occurs, this leads to a loss of body mass and depletion
of circulating proteins. Clinically this has been manifest by low levels of amino acids such as
glutamine (Gln) [11]. Glutamine serve as a vital cell-signaling molecule in states of illness and
injury [12] and has been shown to regulate the expression of many genes related to
metabolism, signal transduction, cell defense, and repair and to activate intra- cellular signaling
pathways [13]. The release of Gln from muscle and other sources after stress, illness, and injury
serves as a “stress signal” which in results in activation of genes vital to cellular protection and
© 2013 Neurocritical Care Society Practice Update
immune regulation [14]. These new data are beginning to provide explanations for the
mechanisms by which clinical trials have revealed that Gln supplementation could improve
infectious morbidity and mortality in critically ill patients, though optimal timing, route of
administration, and dosing have yet to be determined. None of the previous studies have
investigated the relationship between serum glutamine levels, metabolic state and outcome
after non traumatic brain injuries, where the stress responses are similar to that observed
medical illnesses such as ARDS and sepsis.
Recent clinical studies in TBI patient populations have dispelled concerns over Gln crossing the
blood brain barrier and leading to increases in intracerebral glutamate levels, where after
infusion of Gln, serum levels were elevated but no changes were observed in microdialysis fluid
levels of glutamate in any of the patients[15,16]. Glutamine-supplemented formulas have
resulted in greater preservation of skeletal muscle, improved nitrogen balance, enhanced
immune cell function, and no elevation in proinflammatory cytokine production [11,17,18].
Finally, since glutamine is a precursor to glutathione, it has been demonstrated that glutamine
supplementation results in higher levels of glutathione and antioxidant capacity [19].
In summary, enteral glutamine supplementation appears to be safe to administer in the setting
of head injury, though more evidence is needed to demonstrate its clinical benefit before it
should be widely adopted.
Lipid peroxidation
Clinical and experimental data have documented that cellular damage after injury is partly
caused by oxidative damage secondary to free radical formation and lipid peroxidation. Lipid
peroxidation is self-propagating and irreversibly damages both plasma membranes and
mitochondrial membranes. Moreover, breakdown products irreversibly damage enzymes,
receptors, and membrane transport systems [20]. Because products of brain lipid peroxidation
are transported in the serum, lipid peroxide levels in the serum reflect those present in the
brain. Thus, brain damage from free radical overproduction has been documented by
measuring plasma concentrations of lipid peroxidation products [21] (Figure 2).
The administration of omega 3 fatty acids may mitigate the detrimental impact of lipid
peroxidation given their competition for lipoxygenase and cyclooxygenase and resultant
reduction and opposing effect on the inflammatory modulators which are the metabolic
products of arachidonic acid (omega 6 fatty acid) when acted on by these enzymes.
Formulations with omega 3 fatty acids have already been shown to modulate the inflammatory
response and improve physiologic profiles in ARDS and septic patients [1,22]. In addition to
modulating the immune response thru nutritional supplementation, the impact of delivering
the target level of nutrition in a timely fashion, the route of nutrition delivery, and the role of
pre morbid nutrition status on outcomes have yet to be studied in a prospective, controlled
fashion in neurocritical care patient populations, and cannot be widely recommended.
© 2013 Neurocritical Care Society Practice Update
Glucose Metabolism
Altered glucose metabolism is one of the most common clinically noted metabolic
abnormalities in the critically ill patient. Serum glucose is frequently elevated and the response
to a glucose load is similar to that observed in diabetes mellitus. Hyperglycemia appears to
result primarily from sympathetic activation, inflammation and resultant increased hepatic
glucose production rather than decreased glucose utilization. The rate of glucose oxidation in
the periphery increases after injury when a stable circulation is maintained; however, the
hepatic glucose output increases dramatically. Under the influence of increased concentration
of catecholamines, glucagon and cortisol, glucose is synthetized in the liver using lactic acid,
pyruvic acid, and amino acid as substrates [2].
The adverse effects of excessive hyperglycemia in neurocritical care patients are well described.
Data indicate that blood glucose should be carefully controlled in these populations; however,
to what level and how need further clarification [23] (Figure 3). As indicated in a recent metaanalysis, there is significant risk of hypoglycemia without a mortality benefit of tight glycemic
control in brain injured patients [24]. An NIH sponsored study is currently underway, and will
hopefully provide further data as to an optimal glycemic level in ischemic stroke patients [25].
Regardless of the results of studies investigating the optimal glycemic level, the optimal
carbohydrate intake has still to be established according to the type, severity of pathology, and
delay from onset of injury.
Micronutrients
There have been a number of studies examining the effects of micronutrients and dietary
supplements on outcomes in critical illness but so far these have been inconclusive, which may
have related to the heterogeneity in dosage and various combinations of vitamins and trace
elements amongst the studies. Previous studies have shown mortality benefits with
combination of antioxidants, vitamins and trace elements (zinc, selenium and copper) without
any effect on infectious complications or ICU length of stay. Some studies have documented
that nutrition supplementation with B-group vitamins may mitigate oxidative damage after
acute ischemic stroke, independent of their homocysteine-lowering effect. Brain damage from
oxidative stress is also inferred from reduced plasma levels of antioxidants, suggesting their
increased consumption [26].
CLINICAL FEATURES
Nutritional Assessment
Measurement of caloric requirements
Predictive equations, such as the Harris-Benedict equation, have been used to determine a
patient’s predicted energy expenditure in order to set a caloric target. So-called activity and
stress factors are used to improve the equation’s accuracy for specific clinical situations;
© 2013 Neurocritical Care Society Practice Update
however, it is important to realize that these corrections have not been validated in
neurocritical patient population. Moreover, these estimations are based on static variables and
do not reflect the reality in which critically ill patients have wide fluctuations in energy
expenditure from one day to the next. In order to accurately assess nutritional status, serial
indirect calorimetry should be performed during the ICU stay. Failing to repeat indirect
calorimetry measurements and relying instead on the extrapolation of the first indirect
calorimetry test shortly after admission to the ICU may result in more pronounced error than
continued use of predictive equations to identify energy requirements [27].
Measurement of nutritional response
Currently, there is no validated way to measure nutrition response on a day-to-day basis. A
short-term biochemical parameter that could reliably monitor response to nutrition in the
critically ill, within the same timeframe as the nutrition therapy, would be very valuable in
clinical practice. Based on the evidence in the literature for available methods, a recent review
ranked the parameters with the most support (in descending order): serum transthyretin,
nitrogen balance, retinol binding protein, total serum protein, body weight, transferrin,
lymphocyte count, and serum albumin level [27].
Serum transthyretin level is one of the more widely used biochemical parameters clinically.
Though it may have the most support as a marker of nutritional therapy, recent studies have
indicated that levels may be more closely correlated with marker of inflammation rather than
nutritional delivery. Body weight is the most commonly used indicator in assessing nutrition
status in non-critical care population, but in the ICU setting is more likely a marker of fluid
balance than of nutritional status.
Protein metabolism is commonly assessed by measurement of nitrogen balance derived from
the difference between daily nitrogen intake and daily nitrogen output. Nitrogen intake is easily
calculated from the volume and the composition of all the fluids administered to the patient.
Nitrogen loss is measured by collecting urine, feces, and drainage fluids and by determining
their nitrogen. The rise of nitrogen levels in the urine is primarily due to an increase in urea
which comprises nearly all of the total urinary nitrogen.
Specific patient populations
Traumatic Brain Injury
Traumatic brain injury (TBI), like surgery and general trauma, induces a significant
hypermetabolic response. The hypermetabolism and protein catabolism seen in TBI-related
coma is associated with an increase in resting metabolic expenditure similar to that of a burn
patient with 20-40% of body surface affected [28]. The severity of head injury correlates with
increase in REE, oxygen utilization, and temperature [29]. Protein catabolism is also greatly
increased and positive nitrogen balance is difficult to maintain [28]. Given increased REE, lack
© 2013 Neurocritical Care Society Practice Update
of appropriate feeding can lead to malnutrition and subsequent secondary complications
[30,31].
The most compelling data for early nutrition after traumatic brain injury comes from an analysis
of a large database of 22 Trauma centers in New York State [32]. The main findings from this
study clearly demonstrated that any nutrition within the first 5 days after TBI is associated with
a reduced mortality rate. An additional benefit was seen in the maximal level of nutrition
delivered in the first week of injury with a 30-40% increase in mortality observed for every 10
calorie/kilogram decrease in caloric intake. In multivariate analysis, early nutrition within 5
days was found to be an independent predictor of mortality.
A recent meta-analysis of 13 randomized controlled studies and 3 prospective observational
studies found an overall benefit of early nutrition on reducing mortality, improving functional
outcome, and decreasing infectious complications [33]. Although a trend was indicated for early
nutrition in lowering the risk of stratified specific infections, no statistical significance was
noted. Data comparing enteral versus parenteral nutritional support were also reviewed with
inconclusive results due to the probable beneficial impact early initiation of nutritional support
in patients receiving parenteral nutrition as compared to enteral nutrition.
There is little data to support a specific formulation of nutritional support and best practices
have been adopted from the general critical care literature. One small randomized-controlled
trial of a carbohydrate free diet found less hyperglycemia, lower lactate levels, higher ketone
levels, and better nitrogen balance in the carbohydrate free diet group [34]. Another small
study found zinc supplementation to improve GCS scores at 15 and 21 days [35]. However,
there is lack of confirmatory data and larger trials are needed to determine the proper
formulation and supplementation for patients with TBI.
Cerebrovascular disease
The majority of data for nutritional status and therapy for cerebrovascular diseases is found in
ischemic stroke populations. There is a paucity of data for subarachnoid hemorrhage or
intracerebral hemorrhage. The hypermetabolic response after SAH similar to that seen in
severe TBI, especially when the aneurysm is secured surgically [36,37].
The degree of
hypermetabolism is dependent on the clinical severity at presentation. Patients with worse
Hunt-Hess Grades (Grades 4-5) have RME of almost 200% on post-bleed day ten [36]. Despite
early nutritional support, these patients are often in a state of negative energy balance,
receiving on average 50% of their estimated energy expenditure based on Harris-Benedict
equations or indirect calorimetry. This negative energy balance has been associated with
increased infectious complications, especially pneumonia, despite controlling for clinical
severity at presentation [38].
In ischemic stroke, baseline rates of malnutrition recorded within 24 hours of admission range
from 8-16%, and increase to 26% after a week of hospitalization [39]. For those who remain
hospitalized after two weeks, rates rise to 35% and one study showed 49% of stroke patients
© 2013 Neurocritical Care Society Practice Update
entering a rehabilitation facility to be malnourished [40]. Dysphagia is the most important post
stroke factor related to malnutrition after stroke [39]. The incidence of dysphagia after stroke
is high and the rate depends on the screening test utilized. Rates using bedside screening
report the lowest incidences while higher rates are found using clinical testing and instrumental
testing [41].
By contrast to all other neurocritical care populations, there is robust clinical research
supporting basic approaches toward nutrition in ischemic stroke. This comes as the result of
the Feed Or Ordinary Diet (FOOD) trial that was conducted in the UK [42,43]. This multi-center
study consisted of three linked trials, with the first two enrolling only patients with dysphagia
with specific goals to study a) early versus delayed nutritional support; b) nasogastric versus
PEG route of nutritional support; c) routine oral nutrition supplementation versus standard
practice. The early versus delayed feeding trial enrolled demonstrated a minimal, nonsignificant reduction in risk of death with early tube feeding. The reduction in death or poor
outcome with early feeding was non-significant.
The nasogastric versus PEG showed PEG feeding to be associated with an increased risk of
death or poor outcome of 7.8% (0.0 to 15.5, p=0.05). These results were surprising given the
favorable results seen for early PEG in a prior single-center randomized-controlled trial, and led
the authors to suggest avoidance of early PEG placement in stroke patients with dysphagia
[42,44].
The third portion of the FOOD Trial addressed clinical outcomes for patients receiving routine
oral nutrition supplementation versus standard nutritional care[43]. Over 4,000 patients who
were able to swallow were randomized, on average 5 days post-stroke, and followed for sixmonth outcomes. Supplementation consisted of oral protein energy supplements daily until
hospital discharge. Neither death nor poor outcome was impacted by protein supplementation
on long term follow up.
Spinal Cord Injury
Unlike other neurologic injuries, spinal cord injury (SCI) can result in a reduction rather than
increase in REE when compared to that prediction equations [45,46]. The decrease in REE in
patients with complete spinal cord inury, is approximately 10% and is accompanied by a 10%
decrease in body weight and parallel nitrogen excretion [45]. There appears to be an obligate
increase in nitrogen excretion and a negative nitrogen balance remains despite adequate
intake. Immobilization and bone resorption lead to an increase in calcium excretion that peaks
at three weeks after injury. The degree of this change is dependent on the spinal cord level of
injury, with larger changes seen for higher levels of injury. Failure to account for lower REE can
lead to overfeeding, impair ventilator weaning, without improving negative nitrogen balance
[46]. Dysphagia is a common issue following SCI, particularly with higher-level injuries. Poor
appetite, disturbances in taste and olfaction can also hinder appropriate oral caloric intake.
Percutaneous endoscopic gastrostomy (PEG) insertion may provide a safe alternative with low
© 2013 Neurocritical Care Society Practice Update
complication rates in patients unable to tolerate an oral diet.
controlled trials to inform optimal timing for PEG insertion.
There are no data from
Guillain-Barre Syndrome
Approximately one-third of GBS patients require intensive care for mechanical ventilation or
management of other medical complications related to infection or dysautonomia [47]. These
patients have numerous risk factors for nutritional deficiencies: antecedent gastrointestinal
disease, prehospital weight loss, bulbar weakness leading to dysphagia, ventilator dependency
and ileus secondary to dysautonomia. Despite clinically profound neuromuscular weakness or
even paralysis, patients with GBM may experience a significant hypermetabolic and
hypercatabolic state similar to TBI patients [48]. However, given the overall lack of adequate
clinical evidence to guide specific recommendations, nutritional therapy in this population is
best guided by principles outlined for general critical care patients.
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© 2013 Neurocritical Care Society Practice Update
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48. Roubenoff RA, Borel CO, Hanley DF. Hypermetabolism and hypercatabolism in GuillainBarre syndrome. JPEN Journal of parenteral and enteral nutrition. 1992;16:464-72.
© 2013 Neurocritical Care Society Practice Update
Figure 1. Biphasic Metabolic Response to Critical Illness
© 2013 Neurocritical Care Society Practice Update
Figure 3. Impact of glycemic targets after brain injury. A-Basal state; B – Injured state
(Adapted from Reference 23.)
© 2013 Neurocritical Care Society Practice Update
NUTRITION AND METABOLISM QUESTIONS
1. Indirect calorimetry provides a measure of:
a) nitrogen balance.
b) past 24-hour dietary intake.
c) energy expenditure.
d) calorie needs for weight gain
2. Which of the following is a metabolic adaptation to simple starvation?
a) Decrease in urinary nitrogen losses
b) Increase in hepatic glucose production
c) Decrease in utilization of body fat stores
d) Increase in cerebral glucose utilization
3. Which of the following is the most accurate serum measure of nutritional status in a
critically ill patient?
a) Albumin
b) Iron
c) Transthyretin
d) Retinol binding protein
4. Physiologic changes in the body in response to injury include:
a) Decreased serum glucagon
b) Increased serum insulin
c) Decreased lipolysis
d) Increased protein catabolism
5. The best time to initiate enteral nutrition in a traumatic brain injury patient who is unable
to take adequate calories on their own is:
a) before the patient is hemodynamically stable
b) within 48 hours of injury.
c) after 7 days of supportive management.
d) prior to decompressive craniectomy.
6. Protein requirements are increased in
a) Acute Kidney Injury
b) Aneurysmal Subarachnoid Hemorrhage
c) Acute Respiratory Distress Syndrome
d) Hepatic encephalopathy
© 2013 Neurocritical Care Society Practice Update
7. Risks associated with over-feeding:
a) Hyperglycemia
b) Immunosuppression
c) Decreased respiratory muscle function
d) Increased infection
8. Refeeding syndrome is most commonly associated with the following:
a) Hypoinsulinemia
b) Hypophosphatemia
c) Hypocarbia
d) Hyponatremia
9. A 68 year old man is brought to the Emergency Department with a right hemiparesis and
dysarthria and is administered intravenous t-PA. On hospital day 2 speech therapy
evaluation states he is unsafe to take food orally. Which is the best course of action for this
patient?
a) place a nasogastric tube for enteral nutrition.
b) place a intravenous line for parenteral nutrition.
c) maintain NPO status for 48 hours and reassess swallow function.
d) consultation for gastrostomy tube placement.
10. Which of the following is not an omega 3 fatty acid?
a) arachodonic acid
b) eicosapentaenoic acid
c) docosahexaenoic acid
d) steridonic acid
© 2013 Neurocritical Care Society Practice Update
NUTRITION AND METABOLISM ANSWERS
1. The correct answer is A. Indirect calorimetry is the method by which the type and rate of
substrate utilization, and energy expenditure are estimated in vivo starting from gas
exchange measurements. In mechanically ventilated patients, the device is attached to the
ventilator and directly measures the fraction of inspired oxygen, expired oxygen, and
carbon dioxide production. With these gas measurements, the resting energy expenditure
can be calculated using the Weir equation:
REE = 3.9 x (VO2) + 1.1 x (VCO2)
The addition of nitrogen balance data, substrate utilization for carbohydrates, fats, and
protein can be estimated.
2. The correct answer is B. Increase in hepatic glucose production is the normal response to
simple starvation and can be reversed by re-feeding. However, underfeeding in critical
illness are driven by both a sympathetic and hormonal response to injury that results in
utilization of protein and fats, and many times is not reversed by simply providing caloric
support. Additional modulation of the downward inflammatory responses by delivering
specific substrates may be the key to reversing the effects of malnutrition in critical illness.
3. The correct answer is C. In a recent metaanalysis, the accuracy of serum measures of
response to nutritional therapy were assessed, and ranked parameters as follows (in
descending order): serum transthyretin, nitrogen balance, retinol binding protein, total
serum protein, body weight, transferrin, lymphocyte count, and serum albumin level[27].
Serum transthyretin (commonly known as prealbumin), is a carrier of thyroxine and retinol
binding protein bound to retinol. It is secreted into the blood by the liver and has a half-life,
2 days. Transthyretin is a negative acute phase reactant, and so its values may reflect both
a state of malnutrition or be the consequence of the severity of the underlying condition,
especially in patients demonstrating the systemic inflammatory response syndrome (SIRS).
4. The correct answer is D. The physiologic response to injury is to increase serum glucagon,
relative decrease in serum insulin, increased lipolysis and increased protein catabolism. The
net result of these pathways is hyperglycemia, increase in arachidonic acid production, and
depletion of amino acids.
5. The correct answer is B. Current evidence supports the initiation of nutrition within 48
hours of injury of any form of critical illness. A recent study by Hartl et al. clearly indicated
the benefit of starting nutrition early, with a significant relationship between the maximum
level of nutrition reached in the first week and death.
6. The correct answer is C. The FOOD collaborative study demonstarted no benefit in
outcome for routine protein supplementation in ischemic stroke patients.
© 2013 Neurocritical Care Society Practice Update
7. The correct answer is A. Overfeeding is associated with hyperglycemia and difficulty in
ventilator weaning due to excessive CO2 production; whereas underfeeding as been
associated with immunosuppression, difficulty in ventilator weaning due decreased
respiratory muscle function, and increased infection risk.
8. The correct answer is B. Refeeding syndrome can be seen in patients who present with
chronic malnutrition or those who are not fed for at least 7 days. The sudden carbohydrate
load results in increased insulin production and intracellular shift of electrolytes, especially
phoshate, magnesium, and potassium.
9. The correct answer is A. The FOOD collaborative trial demonstrated the overall safety of an
appraoch towards early enteral nutrition and avoidance of early gastrostomy tube
placement.
10. The correct answer is A. As noted in Figure 2. Arachodonic acid is in the class of omega 6
fatty acids. Metabolites from arachodonic acid are believed to contribute to the pro
inflammatory response observed after injury.