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574 PART 5: Infectious Disorders

resting energy expenditure (kcal/d) using the Weir equation [1.44 (3.9
TABLE 64-5 Severe Sepsis Bundles
V O 2 + 1.1 V CO 2 )]. The ratio of V CO 2 to V O 2 also provides the respira-
Resuscitation Bundle (6 h) Management Bundle (24 h) tory quotient. The respiratory quotient evaluates substrate energy
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Blood cultures before antibiotics Low-dose steroids consumption. The normal physiologic range is 0.7 to 1.0; greater than
1.0 indicates excess CO , fat synthesis, or overfeeding. Various equa-
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Early antibiotics Activated protein C 2
tions have been developed to predict energy expenditure without using
goals Low-tidal-volume ventilation indirect calorimetry, which is not always available. Although there is
CVP, MAP, and Scv O 2
Serum lactate Glycemic control no consensus on which equation is the best predictor of resting energy
expenditure, age, body mass index, medication, and stress can be used
to predict energy needs.
Enteral Nutrition: When a patient’s resting energy expenditure is cal-
individual patient. For example, although the goal CVP for sepsis resus- culated, there are a variety of enteral feeding concentrations that can
citation is generally 8 to 12 mm Hg, for patients receiving mechanical be selected. They vary in the amount of protein, carbohydrates, and
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ventilation a higher CVP target (12-15 mm Hg) may be appropriate. glucose depending on the patients’ caloric requirements. The goal is
Individual aspects of the bundle have been studied as well. Most to match the patient’s caloric demands taking into account the hyper-
recently, a multicenter randomized trial of patients with severe sep- metabolic state of sepsis.
sis and septic shock demonstrated that in patients who were treated Enteral nutrition has been favored over parenteral nutrition for a
to normalized MAP and CVP, additional management to normalize number of reasons. It improves gut oxygenation and wound healing. In
did not result in significantly different in-hospital
lactate versus Scv O 2 addition, it keeps the normal gut flora intact, which is believed to be an eff-
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mortality. Several studies have shown improved mortality with bun- ective barrier to intraluminal toxins and bacteria translocation. Enteral
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dle implementation 172,173 with up to 20% reduction in hospital-related feeding also reduces gut permeability, inflammatory cytokines, and endo-
costs. 174,175 However, despite the well-documented benefit, several stud- toxins, and has been found to decrease infection rates. There is agree-
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ies have shown poor compliance and low utilization of the protocol. ment that when available, enteral is preferred to parenteral feeding. 183-186
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It is likely that institutional and professional barriers may play a role in Furthermore, early (within 48 hours) enteral feeding results in fewer infec-
the resistance to bundle implementation. tions and improved outcomes compared to late (greater than 48 hours)
■ RECOMBINANT HUMAN ACTIVATED PROTEIN C feeding. When enteral feeding is not possible, parenteral nutrition
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is an option. Some clinicians have started it in conjunction to enteral
An initial study of recombinant human activated protein C (rhAPC) feeding when enteral feeding cannot meet the caloric demands. Often
called PROtein C Worldwide Evaluation in Severe Sepsis (PROWESS) critically ill patients develop ileus and gastroparesis, limiting the
study randomized patients with severe sepsis to receive either rhAPC patient’s nutritional goals.
or placebo. Treatment reduced absolute mortality by 6.1% and relative Parenteral Nutrition: Parenteral nutrition can be administered as either
mortality by 19.4% (p = 0.005) for all patients; the benefit was greatest total parenteral nutrition (TPN) or peripheral parenteral nutrition
in the most acutely ill patients APACHE II scores >25. Subsequently, (PPN). TPN can only be administered by central vein because of the
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the ADministration of Drotrecogin Alfa [activated] in Early stage Severe caustic nature of the more concentrated solution, whereas PPN may
Sepsis (ADDRESS) trial assessed patients who had low risk of death and be administered by peripheral venous access. The primary concern
found no difference in 28-day mortality. Additional information came with using TPN is the increased risk of infections, either through
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from a subsequent mandatory trial called PROWESS-shock and failed direct modulation of the immune system, chronic elaboration of
to confirm survival benefit; therefore, the manufacturer withdrew the inflammatory mediators, or complications of the nutrition itself, such
drug from the market. 179 as hyperglycemia. 187,188 In addition to increased rates of bacteremia
from chronic vascular access, patients receiving TPN have also been
ANCILLARY SUPPORT MEASURES shown to be at increased risk for fungemia. 189
■ NUTRITION AND METABOLISM evaluated in each patient. 190,191 To date, parenteral nutrition has only
The risks and benefits of parenteral nutrition need to be carefully

Nutritional support has become an integral part of therapy for critically been shown to be advantageous in patients for whom enteral feeding is
ill patients. The American Society of Parenteral and Enteral Nutrition/ not possible. A meta-analysis demonstrated reduced mortality, despite
Society of Critical Care Medicine recommend starting enteral nutrition increased infections, with parenteral nutrition in patients whom enteral
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early within the first 24 to 48 hours following admission and that feed- nutrition could not be initiated. There is uncertainty regarding how to
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ing be advanced to goal by next 48 to 72 hours. Nutritional support balance the risks and benefits of parenteral feeding when the timing of
is critical in sepsis because it provides extra fuel for patients during this enteral feeding is uncertain or it is not meeting the nutritional needs
hypercatabolic state, known to occur in sepsis. Nutrition helps stabilize of the patient. The most recent trial investigated whether early (initia-
immune function by preventing oxidative cellular injury and keeping tion within 48 hours) versus late (initiation on day 8) parenteral nutri-
metabolic homeostasis. The goal of nutrition is to meet the energy tion in critically ill patients with inadequate enteral nutrition had any
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expenditure demands because if energy consumption is greater than impact on morbidity and mortality in the ICU. They found that late
intake, the body will use stored fat, carbohydrate, and protein for fuel. As initiation of parental nutrition is associated with faster recovery and
much as 100% of resting energy expenditure is used for cell membrane fewer complications, as compared with early initiation. 193
body mass is the strongest determinant of resting energy expenditure, ■ RENAL REPLACEMENT THERAPY
pump function, basic metabolic and muscular function. Although lean
age, gender, thyroid function, inflammation, and disease processes all Acute oliguric renal failure is a common presentation of acute organ
impact energy expenditure. To calculate resting expenditure clinically, dysfunction with sepsis. AKI occurs in 51% of septic shock patients
the patient’s body composition, protein level, muscle mass, and respira- with positive blood cultures, 23% in severe sepsis, and 19% in sepsis
tory function are taken into account. 181 patients. When present, AKI is associated with greater illness severity
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The gold standard to measure resting energy expenditure is indirect and a higher risk of death. 44,194 There are various types of renal replace-
) ment therapies: conventional hemodialysis (HD), continuous veno-
calorimetry. Indirect calorimetry measures oxygen consumption (V O 2
), which are needed to calculate the venous hemofiltration (CVVH), continuous veno-venous hemodialysis
and carbon dioxide excretion (V CO 2

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