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140 PART 2: General Management of the Patient

aggregated results demonstrated a trend toward an increased mortal- carbohydrates and lipids in morbidly obese critically ill patients, while
ity associated with the use of combination EN and PN (RR 1.27; 95% McCowen and colleagues withheld lipids in a heterogeneous group
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CIs 0.82-1.94; p = 0.3). In one study, there was a significant increase in of patients, including critically ill patients. Only one study reported
mortality associated with supplemental PN. Supplemental PN was not infectious complications, and in that study hypocaloric feeding was
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associated with a difference in the incidence of infections (RR 1.14; 95% associated with a trend toward a reduction in infectious complications
CIs 0.66-1.96; p = 0.6), had no effect on hospital stay (standardized mean (p = 0.2). There were no significant differences in mortality or length
difference 0.12; 95% CIs 0.45, 0.2; p = 0.5), and had no effect on ventila- of stay between groups in either study. Given the lack of positive
tor days. Thus there appears to be no clinical evidence to support the treatment effect from standard PN, minimizing the dose of PN seems
practice of supplementing EN with PN when EN is initiated. However, reasonable until further data emerge to prove the contrary.
these data are old and studies were poorly designed. Given the concerns Parenteral Lipids: There are several reports that demonstrate that intrave-
about the accumulation of the protein-calorie debt that occurs within the nous soy bean emulsion lipids may adversely affect immune status and
first week of critical illness, supplemental PN is recommended by some clinical outcomes. 133,134 The results of previously described meta-analysis
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to minimize that debt. Indeed, supplemental PN can reduce this deficit, of PN suggest that the adverse effects of lipids may negate any beneficial
19
but whether this strategy benefits outcome is not clear. Observational effect of nonlipid parenteral nutritional supplementation. There are two
studies have been conflicting, with some showing benefit 126,127 while studies reviewed that compared the use of soy bean emulsion lipids to no
others have shown worse outcome with introduction of PN. 128,129 In one lipids in parenteral nutrition. 131,135 A significant reduction in pneumonia
small PRCT, hypocaloric EN supplemented with PN was associated (48% vs 73%; p = 0.05), catheter-related sepsis (19% vs 43%; p = 0.04),
with a trend toward reduced mortality compared to EN alone but was and a significantly shorter stay in both ICU (18 vs 29 days; p = 0.02) and
associated with increased infectious complications, greater duration of hospital (27 vs 39 days; p = 0.03) was observed in trauma patients not
mechanical ventilation, and longer length of ICU stay. 126 receiving lipids compared to those receiving lipids. In the McCowen
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What about the patient who has been started on EN, and after several study mentioned previously, the group that received no lipids (hypocalo-
days is only tolerating inadequate amounts of EN? Does PN have a role ric group) showed a trend toward a reduction in infections (29% vs 53%;
in this patient population? There are really insufficient data to guide p = 0.2). No difference in length of stay was seen in this study, and it did
practitioners on this point. At some point, depending on the ICU nutri- not report on ventilator days. Combining these two studies, the meta-
tional risk assessment, the risk from further deterioration of nutritional analysis done showed a significant reduction in infections in the group
status outweighs the risk of providing PN, due to the cumulative effect that received no lipids (RR 0.63; CIs 0.42-0.93; p = 0.02) and no difference
on immune function, continued losses to the lean body mass, and devel- in mortality (RR 1.29; CIs 0.16-10.7; p = 0.8).
opment of specific key nutrient deficiencies in the critically ill patient It is unknown what the effects of long-term fat-free parenteral nutri-
receiving inadequate nutritional support by EN. This time frame may tion would be, and there is a paucity of data in malnourished patients.
be considerably shortened in patients at tremendously increased risk Given these caveats, withholding soybean emulsion lipids is probably
for deterioration of nutritional status due to the presence of large open best indicated for those patients requiring PN for a short time (<10 days),
wounds, enteric fistula, or short bowel syndrome. Unfortunately, there where the risk of fatty acid deficiency would be minimal. This recom-
are no randomized trials to guide practitioners as to when PN should mendation cannot be extrapolated to those who have an absolute contra-
be initiated in patients tolerating inadequate amounts of EN. While indication to EN and need PN for a longer duration. The development
the results of our previous reviews suggest that PN is associated with of new lipid formulations that have less adverse effect on immunity and
no clinical benefit or increased harm, prolonged starvation (more than inflammation may lead to revising this recommendation in the future. 136
14 days) is equally associated with poor outcomes. 130
In summary, PN has a very limited role in the critical care setting. Tight Glycemic Control: Hyperglycemia, which occurs more often
PN should not be started in critically ill patients until all strategies to with PN than EN, is associated with increased infectious complica-
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maximize EN delivery (such as the use of small bowel feeding tubes and tions. In a pivotal trial, Van den Berghe and associates compared
motility agents) have been attempted. Waiting 10 to 14 days in someone intensive insulin therapy (target range 4.4-6.1 mmol/L) versus con-
tolerating inadequate amounts of EN is probably too long, but practitio- ventional treatment (10.0-11.1 mmol/L) in critically ill patients
ners will have to weigh the safety and benefits of initiating PN in patients receiving nutrition support. This was a large study (n = 1548)
not tolerating EN on an individual case-by-case basis. of surgical ICU patients (predominantly elective cardiovascular
■ MAXIMIZING THE BENEFITS AND MINIMIZING THE RISKS patients were started on a glucose load (200-300 g/d) and then
surgery) with a relatively low APACHE II score (median 9). Study
OF PARENTERAL NUTRITION were advanced to PN, combined PN/EN, or EN after 24 hours of
admission. Intensive insulin therapy was associated with a lower
If PN is associated with harm in critically ill patients, it may be due to a incidence of sepsis (p = 0.003), a trend toward a reduction in ven-
variety of potentially avoidable pathophysiologic mechanisms, including tilator days, and a reduced ICU (p <0.04) and hospital mortality
overfeeding, the immunosuppressant effects of soybean emulsion lipids, (p = 0.01), compared to conventional insulin therapy. However,
hyperglycemia, absence of key nutrients like glutamine, and the asso- multicenter randomized trials that followed failed to confirm this
ciation of gut disuse and systemic inflammation. Understanding these clinical benefit to tight glycemic control. In fact, the largest trial, the
potential mechanisms can guide practitioners when they utilize PN in NICE-SUGAR trial randomized over 6000 patients to receive insulin
such a way that its benefits are maximized and its risks are minimized. to achieve a target range of 81 to 108 mg/dL (4.5-6.0 mmol/L) com-
pared to keeping the blood sugar less than 180 mg/dL (10 mmol/L)
Role of Hypocaloric Parenteral Nutrition: Because of the degree of
insulin resistance so commonly observed in stressed critically ill and demonstrated an increase in mortality associated with the lower
range group (OR for death 1.14, 95%, CI 1.02-1.28, p = 0.02). The
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patients, providing large amounts of dextrose intravenously results
in hyperglycemia and predisposes critically ill patients to risk of most recent meta-analysis of intensive insulin therapy does not show
any treatment benefit overall and tight glycemic control is not recom-
infection. Other attendant complications associated with overfeed- 139
ing carbohydrates include hepatic steatosis, hypertriglyceridemia, mended. However, hyperglycemia is still harmful and efforts to
reduce glucose intake or use insulin to keep blood sugars less than
and hypercapnia. This has given rise to the notion of hypocaloric or
hypoenergetic PN as a strategy to minimize complications associ- 180 mg/dL (10 mmol/L) are still warranted.
ated with PN. There are only two small studies that have evaluated Supplementation With Glutamine: Perhaps the lack of treatment effect
the effect of hypocaloric feeding in critically ill patients. To achieve of PN relates to the lack of key nutrients necessary for repair and
a hypocaloric dose of PN, Choban and associates reduced both recovery following critical illness. As noted previously, there are
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