Treatment of Sepsis

JoeBob Kirk D.O. Southcrest Hospital Tulsa, OK

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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
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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

Patients with severe sepsis have intravascular volume deficits as a result of hemodynamic alterations. afterload. and contractility has proven beneficial in some cases. 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.Cardiovascular Support     Hypotension is a hallmark of severe sepsis. .

Even when fluid challenge is in progress and hypovolemia has not been corrected.Cardiovascular Support    When appropriate fluid challenge fails to improve blood pressure. vasopressor therapy may be required transiently if hypotension is life-threatening. . patients usually require vasopressors. 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. Low tidal volume ventilations is commonly used. Intubation and mechanical ventilation is required in almost all patients with acute respiratory distress syndrome (ARDS).

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. .Renal Replacement Therapy   Alterations in renal functioning can occur in patients with severe sepsis due to hypotension and hypoperfusion.

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

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

Empiric antifungal therapy is necessary in some cases. Many patients do not have a pathogen identified.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.

persistent or recurrent infection after adequate initial therapy.) .e... spontaneous) Secondary (i.e.e.Peritonitus and Abdominal Sepsis  Peritoneal infections are classified as: – – – Primary (i.. related to a pathologic process in a visceral organ) Tertiary (i.

volvulus.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. or cancer Strangulation of the small bowel .

gastrointestinal stromal tumor) Trauma (mostly penetrating) latrogenic Peptic Ulcer perforation Trauma (blunt and penetrating) latrogenic Cholecystitus Stone perforation from gallbladder (i.g.. adenocarcinoma..Common Causes of Secondary Peritonitis Source Regions Esophagus Causes Borhaave syndrome Malignancy Trauma (mostly penetrating) latrogenic Stomach Peptic Ulcer Perforation Malignancy (e.e. gallstones ileus) or common duct Malignancy Choledochal cyst (rare) Trauma (mostly penetrating) Latrogenic Duodenum Biliary tract . lymphoma.

tuboovarian abscess.g. salpinx. Malignancy Ulcerative colitis and Crohn disease Appendicitus. salpingoophoritis. and ovaries .Common Causes of Secondary Peritonitis Source Regions Pancreas Small bowel Causes Pancreatitis Trauma (blunt and penetrating) latrogenic Ischemic bowel Incarcerated hernia (internal and external) Closed loop obstruction. ovarian cyst) Malignancy (rare) Trauma (uncommon) Large bowel and appendix Uterus.. Colonic volvulus Trauma (mostly penetrating ) latrogenic Pelvic inflammatory disease (e. Crohn disease Malignancy (rare) Meckel diverticulum Trauma (mostly penetrating) Ischemic bowel Diverticulitus.

streptococcus pneumoniae (15%) .  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.

– Anaerobic microorganisms are found in less than 5% of cases – Multiple isolates are found in less than 10% .

and Tertiary Peritonitis Peritonitis (Type) Etiologic Class Organisms Type of Organism Ecoli (40%) K pneumoniae (7%) Pseudomonas species (5%) Proteus species (15%) Streptococcus species (15%) Staphylococcus species (3%) Anaerobic species (<5%) Antibiotic Therapy (Suggested) Third – generation cephalosporin Primary Gramnegative . Secondary.Microbiology of Primary.

Secondary. and Tertiary Peritonitis Peritontis (Type) Etiologic Class Organisms Type of Organism E coli. Enterobacter species Klebsiella species Proteus species Antibiotic Therapy (Suggested) Secondgeneration cephalosporin Secondary Gramnegative Secondary Grampositive Secondary Anaerobic Streptococcus species Enterococcus species Third-generation cephalosporin Penicillin's with anaerobic activity Quinolones with anaerobic activity Quinolone and metronidazole Aminoglycoside and metronidazole Bacteroide fragilis Other Bacteroides species Eubacterium species Clostridium species Anaerobic Streptococcus species .Microbiology of Primary.

and Tertiary Peritonitis Peritonitis (Type) Etiologic Class Organisms Type of Organism Antibiotic Therapy (Suggested) Second-generation cephalosporin Third-generation Cephalosporin Penicillins with anaerobic activity Quinolones with anaerobic activity Quinolone and metronidazole Aminoglycoside and metronidazole Carbapenems Triazoles or amphotericin Tertiary Gramnegative Grampositive Fungal Enterobacter species Pseudomonas species Staphylococcus species Candida species Tertiary Tertiary . Secondary.Microbiology of Primary.

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

Candida. . 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. Staphylococcus. Enterobacter.g. and Psuedomonas species) are found in a significant proportion of cases of tertiary peritonitis.Tertiary peritonitis     Resistant and unusual organisms (e. Enterococcus. 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 intraabdominal 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 .

diabetes. and steroids and other forms of immunosuppression .Intra-abdominal abscess     Prolonged use of broad-spectrum antibiotics Gastric acid suppressive therapy Central venous catheters and intravenous hyperalimentation Malnutrition.

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

calculated for the specific metabolic condition. 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. the goal of nutrition support has been to deliver 100% of nutrient requirements. in the shortest time possible.Nutritional Support   For clinicians caring for critically ill patients. .

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

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

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.

e.Nutritional Support  Application of hormesis to nutrition support is related to the potential benefits of caloric restriction. radiation) Minimizes cytokine and inflammatory responses . heat.response genes (i.. 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.

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

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

.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 .

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   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.

both prospective and retrospective.Nutritional Support  There have been a variety of patient trials. to test the theoretical benefits of moderate shortterm 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.

. These studies suggest that feeding within the middle range (33%-65% of recommended intake) is optimal.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.

. and were followed and assessed for a variety of outcomes. divided 120 trauma patients into groups based on nutritional intake. Indianapolis..Nutritional Support      A retrospective analysis at Methodist Research Institute. more days on the ventilator and longer length of stay in both ICU and hospital compared with the other three groups. The intakes were averaged over the first week in the ICU. II. Groups I. 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. Ind.

Experienced fewer days in the ICU Fewer days on mechanical ventilation Fewer days of antibiotic use . Compared with patients receiving greater than 20 kcal/kg adjusted weight/day.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.

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

Nutritional Support    In a prospective randomized study. Patients receiving moderate intake (approximately 60% of calculated intake). Taylor and colleagues reported lower mortality. pneumonia and total infections. length of stay. complications. 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. based on the following: – – Begin feeding early (within 24 hours of admission) Calculate needs based on current practice:     Calories: 25 kcal/kg/day Protein: 1.5 g/kg/day (20%-25% of total kcals) Lipid: 30%-40% of total kcals Carbohydrate: 35%-50% of total kcals . nutritional management of patients with sepsis.2-1.

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.Nutritional Support  If patient is considered a candidate for permissive underfeeding. advance feeding to the 100% of calculated requirements over the next three to five days. as tolerated .

et al. Crit Care Med 1999. Crit Care Med 2000.References    Dickerson RN. 18:241 McCowen KC. Nutrition 2002. 27:2525 . 28:3606 Taylor SJ. et al. Sternberg J. Friel C. Kudsk KA. Boschert KJ. Jewkes C. et al. Fettes SB.

Thank You JoeBob Kirk D.O. .

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