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570 PART 5: Infectious Disorders

and promptly infuse broad-spectrum antibiotics. Even though it is advis- that intervention be delayed until adequate demarcation of viable and
able to obtain cultures prior to starting antimicrobial therapy (since rapid nonviable tissues has occurred. 91
sterilization of blood cultures can occur within a few hours), antibiotic
therapy should not be unduly delayed. A large retrospective study of ■ FLUID THERAPY
18,209 Medicare patients hospitalized with community-acquired pneu-
monia showed that antibiotic administration within 4 hours of arrival at Early Goal-Directed Therapy: Patients with septic shock suffer from a
the hospital was associated with decreased mortality and hospital length combination of insults that present clinically as hypotension or tissue
of stay. Additionally, in the presence of septic shock, each hour delay hypoperfusion. These patients may be significantly volume depleted,
101
in antimicrobial administration has been found to decrease survival. 102 in addition to the vasoplegia and myocardial dysfunction inherent to
Empiric antibiotic therapy should be broad enough to cover all pos- sepsis. Because tissue hypoxia is a key antecedent to multiorgan failure,
sible and likely pathogens. Physicians should be aware of their hospital resuscitation strategies that alter preload, afterload, and contractility to
antibiotic profile, in addition to virulence patterns of pathogens in restore tissue perfusion in a timely manner are the cornerstone to septic
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their community. When deciding upon antibiotics, providers must shock resuscitation. This has been termed early goal-directed therapy
take care to not only initiate therapy quickly, but to initiate appropriate based upon a clinical trial conducted in sepsis patients in an emergency
therapy. Failure to initiate adequate antimicrobial therapy correlates department setting. In a randomized controlled trial conducted in a
with increased morbidity and mortality of septic patients admitted to the single emergency department, 263 patients with septic shock were ran-
ICU. 103-106 Once the causative pathogen has been identified, the antibiotic domized to receive standard therapy or protocolized EGDT during the
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regimen should be narrowed. However, it is important to recognize that first 6 hours of care and prior to ICU admission. Patients receiving
this restriction is not an appropriate initial strategy, and the desire to EGDT had central venous catheters placed for continuous monitor-
minimize superinfections and resistance should not take precedence ing of CVP and central venous oxygen saturation (Scv O 2 ), which was
over adequately treating patients with severe sepsis and septic shock. used to drive the treatment algorithm. Patients in the standard therapy
Although combination therapy has never been shown to significantly group received intravenous fluid resuscitation and vasopressor infu-
improve outcomes, 107-109 multiple antibiotics may be useful in certain sion to achieve a CVP of 8 to 12 mm Hg, mean arterial pressure (MAP)
clinical situations. Recent guidelines suggest that combination therapy greater than or equal to 65 mm Hg, and urine output greater than
be used for neutropenic patients and for patients with known or sus- 0.5 mL/kg per hour. Patients in the EGDT group were targeted to those
pected Pseudomonas infections as a cause of severe sepsis. When used same goals, but additionally the algorithm dictated treatments for this
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empirically, however, combination therapy should not be continued group to reach a Scv O 2 of at least 70%. Supplemental oxygen was given
for longer than 3 to 5 days. An observational study of patients with if arterial hypoxemia was present, and if Scv O 2 remained less than 70%
ventilator-associated pneumonia (VAP) showed that antimicrobial and hematocrit was less than 30%, packed erythrocytes were trans-
monotherapy was associated with inappropriate therapy and increased fused to achieve a hematocrit of greater than or equal to 30%. If Sa O 2 ,
in-hospital mortality. This suggests that initial use of combination CVP, MAP, and hematocrit were optimized and Scv O 2 was still less than
103
therapy reduces the likelihood of inappropriate therapy, thereby reduc- 70%, continuous infusion of intravenous dobutamine was initiated to
ing the risk of death. Most recently, a randomized multicenter clinical increase cardiac output and oxygen delivery. Resuscitation to these
trial showed that although there was no difference in 28-day mortality goals within 6 hours reduced in-hospital mortality in patients with
between VAP patients who were treated with combination antibiotic severe sepsis from 46.5% to 30.5% (p <0.009), and reduced mortality
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therapy versus monotherapy, the subgroup of patients at high risk for at 28 days (p = 0.01) and at 60 days (p = 0.03) as well. In addition,
difficult to treat gram-negative bacteria were better treated with com- patients in the EGDT group received more intravenous fluids, more
bination antibiotic therapy. The duration of antimicrobial therapy for erythrocyte transfusions and dobutamine in the first 6 hours; after the
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sepsis is currently recommended at 7 to 10 days, although longer courses first 6 hours they were less likely to require mechanical ventilation,
may be appropriate in some patients. 91 vasopressor infusion or pulmonary artery catheterization, and their
Acute Physiology and Chronic Health Evaluation (APACHE) illness
■ SOURCE CONTROL severity scores were lower. Although previous studies had failed to
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The principles of source control date back thousands of years and find benefit to goal-directed hemodynamic therapy, particularly when
targeting a fixed supranormal level of oxygen delivery, goal-directed
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though surgical approaches have evolved through the years, not many therapy in this fashion and early in the course of septic shock confers
approaches have been evaluated through randomized controlled trials. substantial benefits in both organ dysfunction and survival and has
Source control involves rapid diagnosis of the source of infection and been incorporated into the Surviving Sepsis Campaign guidelines.
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identifying whether or not the source requires “control,” which is not More recently, a multicenter trial compared patients with septic shock
only limited to surgical therapy. It can include, for example, removal to one of three groups for 6 hours of resuscitation: protocol-based
of an infected central venous catheter or tube thoracostomy for an EGDT; protocol-based standard therapy that did not require the place-
empyema. In some cases, source control is very obvious such as diffuse ment of a central venous catheter, administration of inotropes, or
peritonitis from a perforated ulcer or necrotizing soft tissue infection. In blood transfusions; or usual care. This study was conducted to deter-
other cases, it is not. In general, source control involves three main types mine whether the findings from the 2001 EGDT study were generaliz-
of intervention: drainage of abscesses, debridement of necrotic infected able and whether all aspects of the protocol were necessary. Sixty day
tissue, and removal of infected foreign bodies. 110 mortality among the three groups ranged from 18.2 to 21.0%, and there
The potential role of source control measures should be evaluated were no differences between any of the groups. Similar mortality rates
in all patients with severe sepsis. Foci of infection that are readily were noted for the three groups out to one year duration. Importantly,
amenable to such measures (intra-abdominal abscess, necrotizing soft mortality in this trial was substantially lower than the 30.5 to 46.5%
tissue infection, removal of infected intravascular catheters) should be range noted in the EGDT study. 224
controlled as soon as possible. 91,111,112 However, the beneficial effects of
controlling the source of infection should be balanced against the risks Fluid Resuscitation and Fluid Type: Early and targeted fluid resuscita-
of doing so; therefore, recommendations exist to control the source with tion is one of the cornerstones for treatment of severe sepsis and
the least physiologic insult (eg, percutaneous vs surgical drainage of an septic shock. As we improve our measures of intravascular volume,
abscess) following successful initial resuscitation of the patient. Of note, cardiac performance, and both macrovascular and microvascular
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delayed intervention has been shown to improve outcomes in one par- perfusion, it becomes increasingly feasible to determine the strat-
ticular scenario and that is of infected pancreatic necrosis and pancreatic egy that most expediently restores tissue perfusion. One aspect of
abscesses. Delayed surgical intervention has been shown to reduce com- uncertainty is whether intravenous fluid type makes a difference in
plication rates and mortality, and current recommendations suggest both timing and efficacy of fluid resuscitation (Table 64-3). 116-122
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