Treatment of Sepsis

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Treatment of Sepsis

• JoeBob Kirk D.O.
• Southcrest Hospital
• Tulsa, OK

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Sepsis

• All patients with severe sepsis require
  appropriate antimicrobial agents immediately.
• Antimicrobial therapy is often an empiric choice
  because of the time required for culture and
  sensitivity results.
• Many patients do not have a pathogen identified.
• Empiric antifungal therapy is necessary in some
  cases.

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Anti-infectives and source control

• Appropriate anti-infectives and source control
  are critical in treating severe sepsis.
• Treating and eradicating infection does not
  necessarily arrest the diseases progression.
• A large number of patients develop septic shock,
  multiple organ dysfunction(MODS), and eventually
  die.
• Standard supportive care alone may not adequately
  treat sever sepsis which rates of 28-50.
• The best chance for patient survival includes
  therapy targeted to the microvasculature, in
  addition to supportive care, because of the
  underlying progression that occurs in severe
  sepsis.

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Examples of supportive care therapy for patients
with severe sepsis are

• Cardiovascular support
• Respiratory support
• Renal replacement therapy
• Glucose control
• Other supportive care

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Cardiovascular Support

• Hypotension is a hallmark of severe sepsis.
• Patients with severe sepsis have intravascular
  volume deficits as a result of hemodynamic
  alterations.
• The first step in reversing hypotension is rapid
  fluid resuscitation with natural or artificial
  colloids or crystalloids
• Early goal-directed therapy to optimize cardiac
  preload, afterload, and contractility has proven
  beneficial in some cases.

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Cardiovascular Support

• When appropriate fluid challenge fails to improve
  blood pressure, patients usually require
  vasopressors.
• Even when fluid challenge is in progress and
  hypovolemia has not been corrected, vasopressor
  therapy may be required transiently if
  hypotension is life-threatening.
• Low-dose corticosteroids may improve outcomes in
  patients with septic shock.

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Respiratory Support

• Oxygenation and ventilation problems are common
  in patients with severe sepsis.
• The combination of hypoxemia refractory to
  supplemental oxygen and decreased compliance
  requires mechanical ventilation.
• Intubation and mechanical ventilation is required
  in almost all patients with acute respiratory
  distress syndrome (ARDS).
• Low tidal volume ventilations is commonly used.

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Renal Replacement Therapy

• Alterations in renal functioning can occur in
  patients with severe sepsis due to hypotension
  and hypoperfusion.
• Renal dysfunction is reflected by the following
• Decreased urine output and subsequent oliguria
• Increased blood urea nitrogen
• Increased creatinine
• Renal replacement therapy may be necessary.

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Glucose Control

• Hyperglycemia is common in severe sepsis.
• Blood glucose is frequently monitored.
• Continuous infusion of insulin and glucose may be
  used to maintain target blood glucose levels.

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Other Supportive Care

• Sedation
• Analgesia and neuromuscular blockade
• Deep-vein thrombosis prophylaxis
• Stress ulcer prophylaxis
• Blood product administration
• Nutritional support

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Sepsis

• All patients with severe sepsis require
  appropriate antimicrobial agents immediately.
• Antimicrobial therapy is often an empiric choice
  because of the time required for culture and
  sensitivity results.
• Many patients do not have a pathogen identified.
• Empiric antifungal therapy is necessary in some
  cases.

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Peritonitus and Abdominal Sepsis

• Peritoneal infections are classified as
• Primary (i.e., spontaneous)
• Secondary (i.e., related to a pathologic process
  in a visceral organ)
• Tertiary (i.e., persistent or recurrent infection
  after adequate initial therapy.)

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Peritonitis

• The most common etiology of primary peritonitis
  is spontaneous bacterial peritonitis due to
  chronic liver disease
• The common etiologic entities of secondary
  peritonitis include
• Perforated gastric and duodenal ulcer disease
• Perforated (sigmoid) colon caused by
  diverticulitis, volvulus, or cancer
• Strangulation of the small bowel

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Common Causes of Secondary Peritonitis
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Common Causes of Secondary Peritonitis
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• More than 90 of cases of SBP are caused by a
  monomicrobial infection.
• Most common pathogens include gram-negative
  organisms
• Escherichia coli (40)
• Klebsiella pnemoniae (7)
• Pseudomonas species
• Proteus species
• Gram-positive organisms (e.g. streptococcus
  pneumoniae (15)

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• Anaerobic microorganisms are found in less than
  5 of cases
• Multiple isolates are found in less than 10

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Microbiology of Primary, Secondary, and Tertiary
Peritonitis
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Microbiology of Primary, Secondary, and Tertiary
Peritonitis
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Microbiology of Primary, Secondary, and Tertiary
Peritonitis
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Tertiary Peritonitis

• Tertiary peritonitis represents the persistence
  or recurrence of peritoneal infection following
  apparently adequate therapy, often without the
  original visceral organ pathology.
• Tertiary peritonitis develops more frequently in
  patients with significant preexisting co morbid
  conditions
• Patients who are immunocompromised

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Tertiary peritonitis

• Resistant and unusual organisms (e.g.
  Enterococcus, Candida, Staphylococcus,
  Enterobacter, and Psuedomonas species) are found
  in a significant proportion of cases of tertiary
  peritonitis.
• Antibiotic therapy appears less effective
  compared to all other forms of peritonitis
• Enterococci may be important in enhancing the
  severity and persistence of tertiary peritoneal
  infections.
• This is important in light of the difficulties in
  eradicating Enterococcus faecalis with
  conventional antimicrobial therapy.

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Intra-abdominal abscess

• Abdominal infections, particularly with Candida
  species, are becoming increasingly common in
  critically ill patients.
• Studies suggest that the microbiology of
  intra-abdominal infections may be inherently
  different in severely ill patients.
• Candida albicans was the organism most commonly
  isolated from the peritoneum in critically ill
  patients with culture-proven intra-abdominal
  infections.
• Predisposing factors for the development of
  abdominal candidiasis

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Intra-abdominal abscess

• Prolonged use of broad-spectrum antibiotics
• Gastric acid suppressive therapy
• Central venous catheters and intravenous
  hyperalimentation
• Malnutrition, diabetes, and steroids and other
  forms of immunosuppression

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Other Supportive Care

• Sedation
• Analgesia and neuromuscular blockade
• Deep-vein thrombosis prophylaxis
• Stress ulcer prophylaxis
• Blood product administration
• Nutritional support

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Nutritional Support

• For clinicians caring for critically ill
  patients, the goal of nutrition support has been
  to deliver 100 of nutrient requirements,
  calculated for the specific metabolic condition,
  in the shortest time possible.
• Recently, clinical experts in intensive care
  medicine and nutrition and published studies in
  the medical literature have determined that for
  critically ill patients, administering nutrients
  at quantities less than a calculated metabolic
  expenditure may significantly improve outcomes.

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Nutritional Support

• This involves feeding patients suffering from
  sepsis, at or near 100 of nutrient requirements
  is associated with potentially worse, not better
  outcomes.
• In actuality, short-term moderate underfeeding,
  particularly during the initial phase of critical
  illness when there is marked inflammation, may be
  more beneficial than striving to administer 100
  of estimated nutritional needs.

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Nutritional Support

• It has always seemed that during stress, the body
  requires more nutrients to fight infection,
  combat inflammation, support protein synthesis,
  maintain cellular integrity and promote growth.

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Nutritional Support

• The premise of permissive underfeeding is based
  on research indicating that providing 100 of
  nutrient requirements bacterial growth and
  invasion.
• Autoimmune processes
• Oxidant production
• Cytokine release
• Inflammation
• Energy utilitization

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Nutritional Support

• Benefits for underfeeding rely on understanding
  the b asic biological process call hormesis
• Beneficial or stimulatory effect is obtained
  through the application of an agent at a low dose
• Whereas this same agent may be detrimental or
  toxic at higher doses.

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Nutritional Support

• Application of hormesis to nutrition support is
  related to the potential benefits of caloric
  restriction, which include
• Favors the survival of cell populations
• Attenuates the impact of exposure to toxins
• Delays deterioration of many physiologic
  functions
• Improves the response to physical stressors
• Enhances immune defense and repair systems
• Enhances expression of stress-and- response genes
  (i.e., heat, radiation)
• Minimizes cytokine and inflammatory responses

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Nutritional Support

• Fever, tachycardia, tachnypnea, cytokine and
  oxidant generation, catabolism, stress hormone
  release, decreased calcium, iron and zinc levels,
  and anorexia characterize the acute phase
  response to sepsis.

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Nutritional Support

• Some degree of anorexia may be advatageous,
  acting as a feedback mechanism to blunt
  exaggerated cytokine responses, oxidant
  production, organ injury and hypermetabolism.

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Nutritional Support

• The integrity of the gastrointestinal tract can
  be maintained with lower amounts of nutrient
  intake.

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Nutritional Support

• Studies show that even at 50 of requirements the
  GI tract is able to maintain
• Hormonal release
• Mass
• Blood flow
• Barrier function to prevent bacterial
  translocation
• Immune function
• Decreased oxidant production

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Nutritional Support

• Why does underfeeding seem to be protective?
• Potential mechanisms are
• Lower omega-6 fatty acid provides less substrate
  for proinflammatory mediator synthesis
• Limited carbohydrate intake may result in less
  hyperglycemia
• Decreased calcium, iron and zinc levels may
  decrease inflammatory response and cell injury
• Lower nutrient oxidation
• Less production of free radicals and cytokines
• Less DNA damage
• Less hypermetabolism results in less carbon
  dioxide production

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Nutritional Support

• There have been a variety of patient trials, both
  prospective and retrospective, to test the
  theoretical benefits of moderate short- term
  underfeeding.

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Nutritional Support

• In a prospective cohort study from Johns Hopkins
  Medical Center, ICU patients were divided into
  groups
• Group I received 0-32 of recommended intake
• Group II received 33-65
• Group III received 66-100 of caloric
  recommendations

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Nutritional Support

• Patients in Group II (33-65 of recommended
  intake) exhibited the highest survival rate and
  experienced more sepsis free days
• Group III (66-100 of the requirements)
  experienced the worst outcomes.

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Nutritional Support

• Another prospective cohort study from John
  Hopkins demonstrated that restricted feeding did
  not appear to increase the risk of bloodstream
  infection until the feeding was reduced to less
  than 25 of recommended intake.
• These studies suggest that feeding within the
  middle range (33-65 of recommended intake) is
  optimal.

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Nutritional Support

• A retrospective analysis at Methodist Research
  Institute, Indianapolis, Ind., divided 120 trauma
  patients into groups based on nutritional intake.
• The intakes were averaged over the first week in
  the ICU, and were followed and assessed for a
  variety of outcomes.
• Groups I, II, and III were cosnidered the middle
  range of nutritional intake
• Group IV was the upper range
• Patients in group IV (upper range) had more
  infections, more days on the ventilator and
  longer length of stay in both ICU and hospital
  compared with the other three groups.

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Nutritional Support

• Dickerson et al. reported in a retrospective
  analysis of obese critically ill patients that
  patients receiving less than 20 kcal/kg adjusted
  weight/day.
• Compared with patients receiving greater than 20
  kcal/kg adjusted weight/day.
• Experienced fewer days in the ICU
• Fewer days on mechanical ventilation
• Fewer days of antibiotic use

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Nutritional Support

• In a prospective randomized study, McCowen et al.
  reported
• Fewer infections (approximatelY 30 vs. 50)
• Lower mortality (9 vs. 16)
• In patients randomized to hypocaloric (1000
  kcal/day, 70 g/day protein) compared to standard
  feeding.

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Nutritional Support

• In a prospective randomized study, Taylor and
  colleagues reported lower mortality, length of
  stay, complications, pneumonia and total
  infections.
• Patients receiving moderate intake (approximately
  60 of calculated intake).
• Compared to patients receiving low intake (37 of
  calculated intakes).

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Nutritional Support

• Most evidence suggests that intake in the mid
  range seems to be associated with the best
  outcomes in critically ill patients.

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Nutritional Support

• Based upon available evidence, nutritional
  management of patients with sepsis, based on the
  following
• Begin feeding early (within 24 hours of
  admission)
• Calculate needs based on current practice
• Calories 25 kcal/kg/day
• Protein 1.2-1.5 g/kg/day (20-25 of total
  kcals)
• Lipid 30-40 of total kcals
• Carbohydrate 35-50 of total kcals

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Nutritional Support

• If patient is considered a candidate for
  permissive underfeeding, the following are
  reasonable guidelines
• Begin feeding early (within 245 hours of
  admission)
• Strive to provide 33-66 of calculated needs
• Maintain this level of moderate underfeeding for
  three to five days
• As the patient improves, advance feeding to the
  100 of calculated requirements over the next
  three to five days, as tolerated

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References

• Dickerson RN, Boschert KJ, Kudsk KA, et al.
  Nutrition 2002 18241
• McCowen KC, Friel C, Sternberg J, et al. Crit
  Care Med 2000 283606
• Taylor SJ, Fettes SB, Jewkes C, et al. Crit Care
  Med 1999 272525

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Thank You

• JoeBob Kirk D.O.