Treatment of Sepsis by duw14213

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									Treatment of Sepsis

         JoeBob Kirk D.O.
         Southcrest Hospital
         Tulsa, OK
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.
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 disease’s 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.
Examples of supportive care therapy
for patients with severe sepsis are :


                  Cardiovascular support
                  Respiratory support
                  Renal replacement therapy
                  Glucose control
                  Other supportive care
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.
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.
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.
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.
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.
Other Supportive Care

   Sedation
   Analgesia and neuromuscular blockade
   Deep-vein thrombosis prophylaxis
   Stress ulcer prophylaxis
   Blood product administration
   Nutritional support
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.
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.)
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
 Common Causes of Secondary Peritonitis
Source Regions                            Causes
                                      Borhaave syndrome
Esophagus                                 Malignancy
                                  Trauma (mostly penetrating)
                                          latrogenic
                                     Peptic Ulcer Perforation
Stomach          Malignancy (e.g., adenocarcinoma, lymphoma, gastrointestinal
                                         stromal tumor)
                                   Trauma (mostly penetrating)
                                            latrogenic

                                   Peptic Ulcer perforation
Duodenum                        Trauma (blunt and penetrating)
                                          latrogenic
                                        Cholecystitus
Biliary tract     Stone perforation from gallbladder (i.e., gallstones ileus) or
                                        common duct
                                         Malignancy
                                    Choledochal cyst (rare)
                                 Trauma (mostly penetrating)
                                          Latrogenic
Common Causes of Secondary Peritonitis
Source Regions                         Causes
                                      Pancreatitis
Pancreas                     Trauma (blunt and penetrating)
                                       latrogenic
                                     Ischemic bowel
Small bowel             Incarcerated hernia (internal and external)
                         Closed loop obstruction, Crohn disease
                                    Malignancy (rare)
                                   Meckel diverticulum
                               Trauma (mostly penetrating)
                                     Ischemic bowel
Large bowel and                 Diverticulitus, Malignancy
appendix                   Ulcerative colitis and Crohn disease
                             Appendicitus, Colonic volvulus
                              Trauma (mostly penetrating )
                                        latrogenic
                   Pelvic inflammatory disease (e.g., salpingoophoritis,
Uterus, salpinx,            tuboovarian abscess, ovarian cyst)
and ovaries                         Malignancy (rare)
                                  Trauma (uncommon)
   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%)
– Anaerobic  microorganisms are
  found in less than 5% of cases
– Multiple isolates are found in
  less than 10%
    Microbiology of Primary,
Secondary, and Tertiary Peritonitis
 Peritonitis     Etiologic     Organisms         Antibiotic
   (Type)         Class         Type of           Therapy
                               Organism         (Suggested)

Primary        Gram-         Ecoli (40%)       Third –
                             K pneumoniae      generation
               negative      (7%)              cephalosporin
                             Pseudomonas
                             species (5%)
                             Proteus species
                             (15%)
                             Streptococcus
                             species (15%)
                             Staphylococcus
                             species (3%)
                             Anaerobic
                             species (<5%)
    Microbiology of Primary,
Secondary, and Tertiary Peritonitis
 Peritontis   Etiologic         Organisms            Antibiotic
                             Type of Organism         Therapy
  (Type)       Class
                                                    (Suggested)
                          E coli, Enterobacter    Second-
Secondary Gram-           species                 generation
          negative        Klebsiella species      cephalosporin
                          Proteus species
                          Streptococcus species   Third-generation
Secondary Gram-           Enterococcus species    cephalosporin
          positive                                Penicillin's with
                                                  anaerobic activity
                          Bacteroide fragilis     Quinolones with
Secondary Anaerobic       Other Bacteroides       anaerobic activity
                          species                 Quinolone and
                          Eubacterium species     metronidazole
                          Clostridium species     Aminoglycoside
                          Anaerobic               and
                                                  metronidazole
                          Streptococcus species
     Microbiology of Primary,
 Secondary, and Tertiary Peritonitis
Peritonitis   Etiologic   Organisms          Antibiotic Therapy
(Type)        Class       Type of Organism   (Suggested)

              Gram-       Enterobacter       Second-generation
Tertiary                  species            cephalosporin
              negative                       Third-generation
                          Pseudomonas
                          species            Cephalosporin

              Gram-       Staphylococcus     Penicillins with
Tertiary                  species            anaerobic activity
              positive
              Fungal      Candida species    Quinolones with
Tertiary                                     anaerobic activity
                                             Quinolone and
                                             metronidazole
                                             Aminoglycoside
                                             and metronidazole
                                             Carbapenems
                                             Triazoles or
                                             amphotericin
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
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.
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
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
Other Supportive Care

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

   The integrity of the gastrointestinal tract can
    be maintained with lower amounts of nutrient
    intake.
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
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
Nutritional Support

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

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

   Dickerson RN, Boschert KJ, Kudsk KA, et al.
    Nutrition 2002; 18:241
   McCowen KC, Friel C, Sternberg J, et al. Crit
    Care Med 2000; 28:3606
   Taylor SJ, Fettes SB, Jewkes C, et al. Crit
    Care Med 1999; 27:2525
Thank You
    JoeBob Kirk
    D.O.

								
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