> Table of Contents > Sepsis
Sepsis
Patricia Martinez Quinones, MD
Jin Sol Oh, MD
Steven B. Holsten Jr., MD, FACS
image BASICS
DESCRIPTION
  • A systemic inflammatory response secondary to known or suspected infection
  • Synonym(s): septicemia
  • Systemic inflammatory response syndrome (SIRS)
    • Temperature >38°C (100.4°F) or <36°C (96.8°F)
    • Heart rate (HR) >90 beats/min
    • Respiratory rate (RR) >20 breaths/min
    • WBC > 12,000 cells/mm3, or <4,000 cells/mm3
  • Sepsis signs and symptoms (1)[C]
    • General variables
      • Temperature >38.3°C (100.9°F) or <36°C (96.8°F); HR >90 beats/min or >2 standard deviations (SD) above normal for age
      • Tachypnea (RR >20 breaths/min or PCO2 <32 mm Hg)
      • Acute altered mental status (AMS)
      • Significant edema or positive fluid balance (>20 mL/kg over 24 hours)
      • Hyperglycemia (plasma glucose >140 mg/dL or 7.7 mmol/L) in the absence of diabetes
    • Inflammatory variables
      • Leukocytosis (WBC > 12,000 cells/mm3), or leukopenia (<4,000 cells/mm3), or normal WBC with > 10% bands
      • Plasma C-reactive protein (CRP) >2 SD above normal
      • Plasma procalcitonin >2 SD above normal
    • Hemodynamic variables
      • Arterial hypotension (SBP <90 mm Hg, MAP <70, or SBP decrease of >40 mm Hg in adults or <2 SD below normal for age)
    • Organ dysfunction variables
      • Arterial hypoxemia (PaO2/FIO2 <300)
      • Acute oliguria (urine output <0.5 mL/kg/hr for at least 2 hours with or without adequate resuscitation)
      • Creatinine increase >0.5 mg/dL or 44.2 &mgr;mol/L
      • Coagulation abnormalities (INR >1.5 or aPTT >60 seconds)
      • Ileus (absent bowel sounds)
      • Thrombocytopenia (platelet <100,000)
      • Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 &mgr;mol/L)
    • Tissue perfusion variables
      • Elevated serum lactate (>1 mmol/L)
      • Decreased capillary refill or skin mottling
  • Severe sepsis: sepsis-induced hypoperfusion or acute organ dysfunction
  • Septic shock: refractory hypotension, unexplained by other causes, and despite adequate fluid resuscitation:
    • Hypotension is defined as SBP <90 mm Hg, MAP <70 mm Hg, and reduction in SBP >40 mm Hg from baseline.
Pediatric Considerations
  • Continuum from sepsis to multisystem organ failure (MSOF) is affected by age-specific physiologic variables in children.
  • SIRS in pediatric population requires that abnormality in temperature or WBC be present (2)[C].
  • Drug metabolism is reduced in children with severe sepsis. Monitor drug toxicity labs to prevent adverse effects.
Geriatric Considerations
Often more difficult to diagnose; change in mental status/behavior may be the only early manifestation.
EPIDEMIOLOGY
Incidence
  • 3/1,000 population
  • Increasing incidence; 750,000 new cases annually in the United States
  • 2% of hospitalized patients
ETIOLOGY AND PATHOPHYSIOLOGY
  • Multifactorial: Widespread endothelial dysfunction, dysregulation of nitric oxide production, and activation of coagulation cascade leads to maldistribution of blood flow, tissue hypoperfusion, and resulting to organ dysfunction.
  • An imbalance between proinflammatory and antiinflammatory mediators leads to systemic tissue damage and significant immunosuppression.
  • Causative organisms:
    • Gram-positive bacteria (most common): Staphylococcus sp., Streptococcus sp., Enterococcus sp.
    • Gram-negative: Escherichia coli, Klebsiella sp., Proteus sp., Pseudomonas sp. and anaerobic bacteria
    • Fungi: Candida sp. (incidence increased 207% from 1976 to 2000)
    • Causative organism not identified in 50-75% of cases
  • Common sites of infection: respiratory tract (most common), urinary tract, gastrointestinal tract, skin/soft tissue, CNS, bacteremia
RISK FACTORS
  • Extremes of age (very young or age >60 years)
  • Ethnicity: African American
  • Comorbidities: COPD, congestive heart failure (CHF), cancer, diabetes, and renal insufficiency/failure
  • Immunosuppression
  • Bacteremia
  • Community-acquired pneumonia
  • Complicated labor and delivery: premature labor and/or premature rupture of membranes, untreated maternal group B strep colonization
  • Nosocomial factors: surgical site infections, indwelling catheters
GENERAL PREVENTION
  • Vaccination: pneumococcal vaccine in children and also adults who are ≥65 years or with comorbidities placing them at high risk for disease. Haemophilus influenzae type B (infants, young children), influenza (H1N1 in pregnant women), meningococcal vaccine
  • &ggr;-Globulin for hypo- or agammaglobulinemia
  • Treat group B strep carriers during labor.
  • Regular hand washing, sterile technique for catheter placement, appropriate glove use
  • Antibiotic prophylaxis for recommended surgical procedures
COMMONLY ASSOCIATED CONDITIONS
  • Immunologic: neutropenia, HIV, hypo/agammaglobulinemia, complement deficiency, splenectomy, immunosuppressants (corticosteroids, chemotherapy, TNF-&agr; antagonists)
  • Diabetes, alcoholism, malignancy, cirrhosis, burns, multiple trauma, IV drug abuse, malnutrition
image DIAGNOSIS
PHYSICAL EXAM
  • Assess vital signs: hyper/hypothermia, tachycardia, tachypnea, hypotension
  • Signs of poor perfusion: central venous hypoxia, delayed capillary refill, cyanosis, mottled skin
  • Signs of target organ involvement: jaundice, skin lesions (erythema, petechiae, embolic lesions, purpura)
DIFFERENTIAL DIAGNOSIS
  • Bacteremia without sepsis
  • Viral, rickettsial, spirochetal, and protozoal diseases
  • Collagen vascular diseases, vasculitides, pancreatitis, myocardial infarction, CHF, pulmonary embolism, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), thyrotoxicosis, adrenal insufficiency, poisoning, drug reaction
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Two sets of blood cultures to document presence of bacteremia (not required for diagnosis; 50% of blood cultures are negative in severe sepsis/septic shock). Obtain cultures before antibiotic therapy. Do not delay the start of antibiotic therapy (1)[B].
  • Cultures/Gram stains from potential sites of infection (sputum, urine, pleural fluid, ascites, CSF, wound)
  • CBC with differential, CRP, coagulation profile, comprehensive metabolic profile, lactic acid level, arterial blood gas, urinalysis
  • Radiographic studies (plain films, ultrasound, CT, or MRI) to confirm source of infection
Diagnostic Procedures/Other
  • Aspiration, biopsy, and/or drainage of potentially infected body sites (pleural cavity, peritoneal cavity, biliary tree, CSF, abscess). Interventional radiology techniques to aid in specimen collection as needed
  • Echocardiogram if concern for endocarditis
Test Interpretation
  • Common findings: leukocytosis, bandemia (>10%), hyperglycemia, metabolic acidosis, mild hyperbilirubinemia, hypoxemia, respiratory alkalosis, proteinuria
  • Less common findings (more severe disease): leukopenia, anemia, thrombocytopenia, coagulopathy, azotemia, hypoglycemia, acidosis
image TREATMENT
GENERAL MEASURES
  • Assess oxygenation and supplement as needed. Intubate for respiratory failure.
  • Invasive monitoring for management of hemodynamic instability using goal-directed therapy.
  • P.961

  • Adequate volume resuscitation (30 mL/kg crystalloid for hypotension) within 3 hours of presentation and vasopressors for refractory hypotension (within 6 hours of presentation). Targets are:
    • Central venous pressure (CVP) 8 to 12 mm Hg, MAP ≥65 mm Hg, urine output ≥0.5 mL/kg/hr (1)[A]
    • Central/mixed venous O2 saturation ≥70%/65%
      • If goals not met with fluid resuscitation and/or vasopressor, transfuse PRBCs to achieve hematocrit >30%; if still <70%, add dobutamine (1)[C].
  • Identify source of infection and remove septic foci:
    • Early surgical consultation for acute abdomen, empyema, necrotizing fasciitis
    • Interventional radiology consultation for guided drainage
  • Transfuse PRBCs, platelets, and/or fresh frozen plasma for coagulopathic complications or in association with planned procedures.
    • Transfuse PRBC if Hgb <7.0 to target Hgb of 7.0 to 9.9 g/dL in absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1)[B]
  • Stress ulcer and DVT prophylaxis (1)[B]
  • Glucose control (≥180 mg/dL) (1)[A]
MEDICATION
First Line
  • Fluid management
    • Initial therapy: 30 mL/kg of crystalloids (1)[B]
    • Consider adding albumin for patients requiring large volumes of crystalloid (1)[C],(3)[B].
  • Vasopressors
    • Norepinephrine 0.01 to 3 &mgr;g/kg/min (1,4)[B].
    • Low-dose dopamine for renal protection is not recommended (1)[C].
  • Initiate broad-spectrum antibiotic within an hour of recognizing severe sepsis or septic shock (1,4)[A]:
    • Adult (Pseudomonas not suspected): vancomycin (loading dose 25 mg/kg) + Gram-negative coverage (3rd-generation cephalosporin, &bgr;-lactam/&bgr;-lactamase inhibitor, or carbapenem)
    • Adult (Pseudomonas suspected): vancomycin + two agents aimed at resistant Gram-negative bacteria ceftazidime/cefepime/carbapenem/piperacillin-tazobactam + either fluoroquinolone (ciprofloxacin) or aminoglycoside (gentamicin/amikacin) depending on local hospital sensitivities
    • Nonimmunocompromised child: 3rd-generation cephalosporin
    • Neonate (<7 days old): ampicillin and gentamicin (5)[B]
    • Consider narrowing antibiotic regimen at 48 to 72 hours based on culture results. Anticipate antibiotic course to last 7 to 10 days (1)[B].
  • Antifungals if fungal infection suspected: long-term antibiotic use, TPN, GI surgery
    • Adjuvant intravenous immunoglobulins (IVIGs) may reduce mortality in adults (6)[B].
Pregnancy Considerations
&bgr;-Lactam antibiotics, macrolides, and metronidazole generally are considered safe.
Second Line
  • Vasopressors: epinephrine, vasopressin
  • Consider IV hydrocortisone 200 mg per day if the patient is poorly responsive to both IV fluid resuscitation and vasopressors (1)[C].
  • Inotropic therapy with dobutamine may benefit patients with myocardial dysfunction or ongoing hypoperfusion despite adequate intravascular volume and MAP (1)[C].
ADDITIONAL THERAPIES
Intermittent hemodialysis or continuous veno-venous hemofiltration for renal failure
SURGERY/OTHER PROCEDURES
Debride necrotic tissues: Drain or remove abscesses or other foci of infection.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
ICU care
IV Fluids
Aggressive fluid resuscitation with normal saline can result in nongap metabolic acidosis. Not likely with lactated Ringer solution.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Place arterial line and central venous catheter in unstable patients
  • Chem-7 and CBC daily; lactate, mixed venous oxygen saturation q2-4h in initial resuscitation period, and daily INR/PTT if DIC is a concern.
  • Follow antibiotic drug levels (vancomycin, gentamicin).
  • Foley catheter placement to monitor urine output
DIET
NPO if intubation considered; otherwise, enteral feeds are preferred to preserve GI mucosal integrity (1)[C].
PATIENT EDUCATION
www.nlm.nih.gov/medlineplus/sepsis.html
PROGNOSIS
Mortality is 10-50% overall. Poor prognostic factors include the inability to mount a fever (>40°C), nonurinary source of infection, nosocomial infection, inappropriate antibiotic coverage, and certain comorbidities (AIDS, cancer, immunosuppression).
REFERENCES
1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637.
2. Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatric Critical Care Medicine. 2005;6(1):2-8.
3. Raghunathan K, Shaw A, Nathanson B, et al. Association between the choice of IV crystalloid and in-hospital mortality among critically ill adults with sepsis. Crit Care Med. 2014;42(7):1585-1591.
4. De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362(9):779-789.
5. Paul M, Lador A, Grozinsky-Glasberg S, et al. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev. 2014;(1):CD003344.
6. Stockmann C, Spigarelli MG, Campbell SC, et al. Considerations in the pharmacologic treatment and prevention of neonatal sepsis. Paediatr Drugs. 2014;16(1):67-81.
Additional Reading
&NA;
  • Alejandria MM, Lansang MA, Dans LF, et al. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev. 2013;(9):CD001090.
  • Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250-1256.
  • Venkataraman R, Kellum JA. Sepsis: update in the management. Adv Chronic Kidney Dis. 2013;20(1):6-13.
  • Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. 2008;300(8):933-944.
Codes
&NA;
ICD10
  • A41.9 Sepsis, unspecified organism
  • R65.10 SIRS of non-infectious origin w/o acute organ dysfunction
  • R65.20 Severe sepsis without septic shock
Clinical Pearls
&NA;
  • Treat sepsis aggressively with fluid support (with hemodynamic monitoring and pressor support if necessary) early use of broad-spectrum antimicrobial therapy and removal/drainage of foci of infection.
  • Despite aggressive treatment, overall mortality is high (10-50%) in patients with severe sepsis/septic shock.