Sepsis

By: Viroth Prak

Sepsis

BASICS

DESCRIPTION:

The systemic response to infection; it encompasses a broad array of clinical manifestations and overlaps with inflammatory reactions to other clinical insults (e.g., severe trauma or burn)
  •Bacteremia: Bacteria in the blood; may have no accompanying symptoms
  •Systemic inflammatory response syndrome (SIRS): inflammatory reaction to different clinical insults manifest by two of the following: (1) temperature >38°C or < 36°C, (2) heart rate > 90/min; (3) respiratory rate >20/min or PaCO2 < 32 mm Hg, and (4) WBC count > 12,000/mm3, < 4,000/mm3 or > 10% immature forms (bends)
  •Sepsis: SIRS with documented infection (typically bacterial)
  •Septic shock: Sepsis induced hypotension (systolic BP < 90 mmHg or ³ 40 mmHg drop from baseline) despite adequate fluid resuscitation plus hypoperfusion abnormalities (oliguria, lactic acidosis, acute change in mental status)
  •Multiple organ dysfunction syndrome (MODS): altered organ function in an acutely ill patient - requires intervention to maintain homeostasis.Read more....

System(s) affected: Cardiovascular, Endocrine/Metabolic, Hemic/Lymphatic/Immunologic, Renal/Urologic, Nervous, Pulmonary, Gastrointestinal
Genetics: N/A
Incidence/Prevalence in USA: 176/100,000 persons/year
Predominant age: All ages
Predominant sex: Male = Female

SIGNS AND SYMPTOMS:

  •Fever
  •Chills, rigors
  •Myalgias
  •Changes in mental status - restlessness, agitation, confusion, delirium, lethargy, stupor, coma
  •Tachycardia
  •Tachypnea
  •Hypotension
  •Skin lesions - erythema, petechiae, ecthyma gangrenosum, embolic lesions
  •Signs and symptoms related to site of primary infection:
      •Respiratory tract - cough, sputum production, dyspnea, chest pain
      •Urinary tract - dysuria, flank pain, frequency, urgency
      •Intra-abdominal source - nausea, vomiting, diarrhea, constipation, abdominal pain
      •Central nervous system - stiff neck, headache, photophobia, focal neurologic signs
  •Signs and symptoms related to end organ failure:
      •Pulmonary - cyanosis
      •Renal - oliguria, anuria
      •Hepatic - jaundice
      •Cardiac - congestive heart failure

CAUSES:

  •Specific etiologic agents include:
      •Gram positive organisms - most commonly Staphylococcus sp, Streptococcus sp, Enterococcus sp
      •Gram negative organisms - most commonly Escherichia coli, Klebsiella sp, Proteus sp, Pseudomonas sp
      •Fungi - most commonly Candida sp
      •Other agents - anaerobes. Also, see Differential diagnosis.
  •Common sources of septicemia include:
      •Lungs
      •Urinary tract
      •Intra-abdominal focus - biliary tree, abscess, peritonitis
      •Intravascular catheters
      •Skin - cellulitis, decubitus ulcer, gangrene
      •Heart valves

RISK FACTORS:

  •Age extremes (very old and very young)
  •Impaired host (see associated conditions)
  •Indwelling catheters - intravascular, urinary, biliary, etc.
  •Complicated labor and delivery - premature and/or prolonged rupture of membranes, etc.
  •Certain surgical procedures

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS:

  •Viral diseases (influenza, dengue and other hemorrhagic viruses, Coxsackie B virus)
  •Rickettsial diseases (Rocky Mountain spotted fever, endemic typhus)
  •Spirochetal diseases (leptospirosis, relapsing fever [Borrelia sp], Jarisch-Herxheimer reaction in syphilis)
  •Protozoal diseases (Toxoplasma gondii, Trypanosoma cruzi, Pneumocystis carinii, Plasmodium falciparum)
  •Collagen vascular diseases, vasculitides, myocardial infarction, pulmonary embolus, thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome, thyrotoxicosis, adrenal insufficiency (Addison's disease), dissecting aortic aneurysm, multiple trauma, third-degree burn

LABORATORY:

  •Positive blood cultures
  •Positive cultures from other sites (sputum, urine, cerebrospinal fluid [CSF], etc.)
  •Gram stain of clinical specimens (sputum, urine, CSF, etc.)
  •Common:
      •Leukocytosis
      •Proteinuria
      •Hypoxemia
      •Eosinopenia
      •Hypoferremia
      •Hyperglycemia
      •Hypocalcemia
      •Mild hyperbilirubinemia
  •Less common:
      •Lactic acidosis
      •Leukopenia
      •Azotemia
      •Thrombocytopenia
      •Prolonged prothrombin time
      •Anemia
      •Hypoglycemia

Drugs that may alter lab results: Prior antibiotic use
Disorders that may alter lab results: N/A

PATHOLOGICAL FINDINGS:

  •Inflammation at primary site of infection
  •Disseminated intravascular coagulation
  •Non-cardiogenic pulmonary edema

SPECIAL TESTS:

  •Antigen detection systems - counterimmunoelectrophoresis (CIE) and latex agglutination tests (pneumococcus, H. influenzae type B, group B streptococcus, meningococcus)
  •Gram stain of buffy coat smears occasionally useful

IMAGING:

  •X-rays (e.g., chest)
  •Ultrasound, CT scan, or MRI may be useful in delineating sites of infection

DIAGNOSTIC PROCEDURES:

  •Aspiration of potentially infected body fluids (pleural, peritoneal, CSF) when appropriate
  •Biopsy, drainage of potentially infected tissues (abscess, biliary tree, etc.) when appropriate

TREATMENT

APPROPRIATE HEALTH CARE:

  •Hospitalization
  •Intensive care treatment of patients with shock, respiratory failure

GENERAL MEASURES:

  •Removal or drainage of septic foci
  •Correction of metabolic abnormalities (hypoxemia, hyperglycemia, hypoglycemia, severe acidemia [pH < 7.10])
  •Mechanical ventilation for respiratory failure
  •Transfusion of RBC, platelets, and/or fresh frozen plasma for bleeding
  •Volume replacement followed by pressors for hypotension
  •Stress ulcer and deep venous thrombosis prophylactic measures

SURGICAL MEASURES:

Drainage of infected sites, débridement of necrotic tissues

ACTIVITY:

Bedrest

DIET:

NPO initially; intravenous hyperalimentation appropriate in some severely malnourished patients and in patients who will be unable to receive enteral alimentation within the week

PATIENT EDUCATION:

N/A

MEDICATIONS

DRUG(S) OF CHOICE:

  •Antibiotic coverage should be broad initially and directed against organisms associated with identified septic foci. After culture results are available, treatment should be more organism-specific. Knowledge of the antibiotic susceptibility patterns of local pathogens extremely important.
  •Neonatal (< 7 days old) sepsis - ampicillin 300 mg/kg/d in 3 divided doses and gentamicin (Garamycin) 5 mg/kg/d in 2 divided doses
  •Non-immunocompromised child - cefotaxime (Claforan) 200 mg/kg/d in 4 divided doses
  •Non-immunocompromised adult - cefotaxime (Claforan) 1-2 gm q8-12 or ticarcillin-clavulanate (Timentin) 3.1 g q6h plus gentamicin 5 mg/kg/day in 1-3 divided doses
  •Neutropenic host - ceftazidime (Fortaz) 1-2 gm q8-12h, and gentamicin (Garamycin) or tobramycin 3-5 mg/kg/d in 2-3 divided doses; vancomycin (Vancocin) is added when there is an obvious catheter-related infection or a known gram positive bacteremia or if there is an increased likelihood of infection with resistant gram positive organisms.

Contraindications: History of anaphylaxis or other allergic reaction to the antibiotic
Precautions: Dose adjustments required in renal failure
Significant possible interactions:
  •Aminoglycosides - increased nephrotoxicity with enflurane, cisplatin and possibly vancomycin; increased ototoxicity with loop diuretics; increased paralysis with neuromuscular blocking agents
  •Ampicillin - increased frequency of rash with allopurinol

ALTERNATIVE DRUGS:

  •Antibodies against gram negative cell wall antigens may reduce mortality
  •Many other drug combinations are possible to get adequate coverage
  •Antifungals
  •Antimicrobials for anaerobic infections
  •Antipseudomonals

FOLLOW UP

PATIENT MONITORING:

  •Depends upon source of infection, underlying disease(s)
  •Peak and trough drug levels for aminoglycosides, vancomycin
  •BUN, creatinine, electrolytes and complete blood counts at least twice weekly; more frequently if unstable

PREVENTION/AVOIDANCE:

  •Vaccination - pneumococcal (geriatric patients, patients with certain chronic diseases), Haemophilus influenzae type B (infants, young children)
  •Gamma globulin (for hypo- or agammaglobulinemic patients)
  •Hand washing by hospital personnel, appropriate catheter care, etc., for hospitalized patients

POSSIBLE COMPLICATIONS:

  •Death
  •Adult respiratory distress syndrome (ARDS)
  •Multi-organ failure (cardiac, pulmonary, renal, hepatic)
  •Disseminated intravascular coagulation (DIC)
  •Gastrointestinal hemorrhage

EXPECTED COURSE AND PROGNOSIS:

Even with optimal care, mortality will be 10-50% overall; this is increased in patients with neutropenia, diabetes, alcoholism, renal failure, respiratory failure, hypogammaglobulinemia, certain etiologic agents (e.g., Pseudomonas aeruginosa), a delay in appropriate antimicrobial therapy, and those patients at the age extremes

MISCELLANEOUS

ASSOCIATED CONDITIONS:

  •Neutropenia
  •Diabetes mellitus
  •Alcoholism
  •Leukemia, lymphoma, and solid tumors
  •Cirrhosis
  •Burns
  •Multiple trauma
  •Intravenous drug abuse
  •Malnutrition
  •Complement deficiencies
  •Hypo- or agammaglobulinemia
  •Splenectomy
  •HIV infection

AGE-RELATED FACTORS:

Pediatric: Screen newborns for infection due to prolonged rupture of membranes (> 24 h), maternal fever, prematurity
Geriatric:
  •Often more difficult to diagnose clinically in the elderly
  •Change in mental status/behavior may be only early manifestation
Others: N/A

PREGNANCY:

Beta lactam antibiotics, aminoglycosides, erythromycin are considered safe

SYNONYMS:

  •Septicemia
  •Sepsis neonatorum

SEE ALSO:

  • Pneumonia, bacterial
  • Pyelonephritis
  • Meningitis, bacterial
  • Endocarditis, infective (part 1)
  • Toxic shock syndrome
  • Rocky Mountain spotted fever
  • Candidiasis
  • Listeriosis
  • Tularemia

OTHER NOTES:

High dose steroids of no benefit

ABBREVIATIONS:

N/A

REFERENCES

  •Bone RC, Balk RA, Cerra FB, Dellinger RP, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644-55
  •Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Crit Care Med 1999;27:639-60
  •Wheeler AP, Bernard GR. Treating patients with severe sepsis. N Engl J Med 1999;340:207-14