Page 235 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 20: Nutrition Therapy in the Critically Ill 139

diet as in the previous three studies). This study failed to show a statis- PN. For patients with major burns or trauma, enteral diets supplemented
tically significant difference in oxygenation, infections, or mortality. 97 with glutamine could be considered. Recommendations about glutamine
More recently, Rice and colleagues reported the results from the supplementation (enteral or parenteral) in other critically ill patient popu-
OMEGA clinical trial involving patients with ALI, who were random- lations fed enterally are premature and warrant further study.
ized to omega-3 (n-3) fatty acids, docosohexanoic acid (DHA), eicosa-
pentaenoic acid (EPA), γ-linolenic acid (GLA), and antioxidants, or ■ ANTIOXIDANT VITAMINS AND TRACE MINERALS
placebo. What is unique about this study is that the active treatments While there is a putative beneficial role of reactive oxygen species (ROS)
98
were administered as a bolus twice a day separate and distinct from in modulating cell signaling (redox signaling), and thus regulating pro-
the enteral feeding strategy rather than administered continuously liferation, apoptosis, and cell protection, oxygen-derived radicals may
alongside the enteral feeding solution (as had been done in the previous cause cellular injury by numerous mechanisms, including destruction
studies). The trial was stopped prematurely because of futility. Analysis of cell membranes through the peroxidation of fatty acids, disruption of
https://kat.cr/user/tahir99/
of 272 randomized patients showed that those receiving the pharmaco- organelle membranes such as those covering lysosomes and mitochon-
nutrients compared to the control group had fewer ventilator-free days dria, degradation of hyaluronic acid and collagen, and disruption of
(14.0 vs 17.2; p = 0.02), fewer ICU-free days (14.0 vs 16.7; p = 0.035), enzymes like Na , K -ATPase, or α -proteinase inhibitor.
+
+
fewer nonpulmonary organ-failure free days (12.3 vs 15.5; p = 0.025) To protect tissues from oxygen free radical (OFR)–induced injury, the
1
and a trend to higher 60-day hospital mortality (26.6% vs 16.3%; p = body maintains a complex endogenous defense system that consists of a
0.054). There are several methodological concerns noted in this study. variety of extra- and intracellular antioxidant defense mechanisms. The
99
The most significant issue is the use of a control solution that resulted first line of intracellular defense comprises a group of antioxidant enzymes
in the control group receiving 20 g of protein/day more than the experi- such as superoxide dismutase, catalase, glutathione peroxidase, and glu-
mental group. tathione reductase, including their metal cofactors selenium, copper,
Another recent study of pure fish oils (no GLA nor antioxidants) and zinc. When these enzymatic antioxidants are overwhelmed, OFRs
administered as a bolus dose dissociated from nutrition did not have any are free to react with susceptible target molecules within the cell
effect on pulmonary or systemic markers of inflammation. Whether this (eg, unsaturated fatty acids of the cell membrane). Thus there is a need
is a failure of the fish oils to mediate a treatment effect or a failure of the for a second line of defense scavenging OFRs by means of nonenzy-
bolus administration in patients generally undernourished is unclear. matic antioxidants that are either water soluble, such as glutathione and
100
When provided continuously as a part of a complete enteral solution vitamin C, or lipid soluble, such as vitamin E and β-carotene. 116
(not bolus), these key nutrients may still have a positive treatment effect In critical illness, oxidative stress arises when the balance between pro-
(see www.criticalcarenutrition.com for most current meta-analysis). tective antioxidant mechanisms and the generation of ROS is disturbed.
■ GLUTAMINE This imbalance may be caused by excess generation of ROS by means of
ischemia/reperfusion injury, inflammation, infection, and toxic agents
The amino acid glutamine plays a central role in nitrogen transport (chemotherapy or drugs), or by low antioxidant capacity (secondary to
within the body, is a fuel for rapidly dividing cells (particularly lympho- comorbid illnesses, malnutrition, and excessive losses such as in the case
cytes and gut epithelial cells), is a precursor to glutathione, and has many of burns). Many studies have demonstrated low plasma and intracellular
other essential metabolic functions. As noted previously, plasma gluta- concentrations of the various antioxidants in critically ill patients, and
mine levels drop during critical illness, and lower levels of glutamine have the clinical consequence of these low endogenous stores of antioxidant
been associated with immune dysfunction and increased mortality. levels is increased morbidity and mortality. 117-119
102
101
Human studies suggest that glutamine supplementation maintains Most of the immune formulas are fortified with vitamins and miner-
gastrointestinal structure and is associated with decreased intestinal als that have increased antioxidant capabilities. Vitamins A, E, and C,
103
permeability compared to standard PN. 104,105 In humans, glutamine- and the trace mineral selenium have antioxidant capabilities and are
supplemented formulas have resulted in improved nitrogen balance, added in different amounts to the various formulas. The exact doses of
106
and higher intramuscular glutamine levels. Glutamine plays a crucial these components have not been standardized.
107
role in enhancing immune cell function and inducing heat shock pro-
108
teins, with no elevation in proinflammatory cytokine production. 109,110 Clinical Review of Studies of Antioxidant Nutrients: Many random-
There have been several randomized trials of perioperative or criti- ized controlled trials have chosen to administer a combination of
cally ill adults reporting on clinically important outcomes. When the antioxidants via various routes of administration, thereby making
111
results of the 27 trials in critically ill, nonelective surgery patients were it impossible to attribute the outcomes to a specific nutrient. When
aggregated, glutamine led to a trend toward a significant reduction in 18 trials of single and combined antioxidants were aggregated, overall
mortality (RR 0.86; 95% CIs 0.74-1.00; p = 0.05), a significant reduc- antioxidants were associated with a significant reduction in mortal-
tion in infectious complications (RR 0.85; 95% CIs 0.74-0.97; p = 0.02), ity (RR = 0.81; 95% CIs 0.70, 0.94; p = 0.004) and a trend toward a
and a significant reduction in overall length of stay (by 1.91 days; 95% reduction in infectious complications (RR = 0.91; 95% CIs 0.80, 1.04;
120
CIs −3.27, −0.54; p = 0.006). Subgroup analysis suggested that with p = 0.16). Thus, for critically ill patients, supplemental combined
112
respect to mortality and infectious complications, the majority of the vitamins and trace elements (selenium, vitamin E/α-tocopherol,
treatment effect observed was associated with parenteral glutamine in vitamin C, N-acetylcysteine, and zinc) may be beneficial.
The majority of glutamine provided enterally will be metabolized in the ■ ROLE OF PARENTERAL NUTRITION
patients receiving PN compared to enteral glutamine supplementation.
gut and liver, and therefore may not have a systemic effect. The only Several trials, meta-analyses, and observational studies have evaluated
study that demonstrated a mortality effect with enteral glutamine was the treatment effect of parenteral nutrition in the last few years, and none
a small study in burn patients. In a study of trauma patients, enteral has shown a positive result, while some have suggested increased harm
113
feeds supplemented with glutamine were associated with a trend toward associated with PN in the critically ill patient. 121,122 We have already stated
a reduced rate of infection compared to control feeds (20/35 [57%] vs that EN is used preferentially to PN. However, to optimize the delivery
26/37 [70%], p = 0.24). In a small PRCT, use of enteral glutamine of nutrients and minimize the calorie-protein debt that accumulates in
114
alone in the first 24 hours following trauma aided in resuscitating the many EN-fed ICU patients during the early phase of critical illness, some
gut and enhancing tolerance to subsequent delivery of EN (compared to prescribe PN at the same time EN is initiated. Then, as EN becomes
controls receiving no glutamine ). successfully established, PN is reduced and eliminated. There are five
115
Therefore, for critically ill patients requiring PN, we recommend randomized trials that address the clinical benefits of such a strategy
parenteral glutamine supplementation as long as the patient remains on in critically ill patients. All five studies reported on mortality and the
123

section02.indd 139 1/13/2015 2:04:57 PM