Sepsis

Description of Medical Condition

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 PaC02 <32 mm Hg, and (4) WBC count >12,000/mm3, <4,000/mm3 or >10% immature forms (bands)
• Sepsis: SIRS with documented infection (typically bacterial)
• Septic shock: Sepsis induced hypotension (systolic BP <90 mmHg or >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

System(s) affected: Cardiovascular, Endocrine/ Metabolic, Hemic/Lymphatic/lmmunologic, Renal/Urologic, Nervous, Pulmonary, Gastrointestinal Genetics: Single nucleotide polymorphisms i.e., cytokine and cytokine receptor genes influence risk for development of sepsis and risk of mortality from sepsis Incidence/Prevalence in USA: 300/100,000 persons/year Predominant age: All ages Predominant sex: Male> Female (1.28:1)

Medical Symptoms and Signs of Disease

• 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

What Causes Disease?

Specific etiologic agents include:

• Gram positive organisms — most commonly Staphylococcus spp, Streptococcus spp. Enterococcus spp
• Gram negative organisms — most commonly Escherichia coli, Klebsiella spp, Proteus spp.,Pseudomonas spp
• Fungi — most commonly Candida spp
• 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 of Disease

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, thromboticthrombocyto-penic purpura/hemolytic-uremic syndrome, thyrotoxico-sis, adrenal insufficiency (Addison 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 (Medical Therapy)

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
• Insulin therapy to keep serum glucose < 150 mg/dl

Surgical Measures

Drainage of infected sites, debridement 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 (Drugs, Medicines)

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 orticarcillin-clavulanate (Timentin) 3.1 g q6h plus gentamicin 5 mg/kg/day in 1 -3 divided doses
• Neutropenic host — cefepime (Maxipime) 1 -2 gm q12h, and gentamicin (Garamycin) ortobramycin 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 nephrotoxicitywith enflurane, cisplatin and possibly vancomycin; increased ototoxidty with loop diuretics; increased paralysis with neuromuscular blocking agents
• Ampicillin — increased frequency of rash with allopurinol

Alternative Drugs

• Intravenous hydrocortisone, 200-300 mg/day in 3-4 divided doses may benefit patients who require vasopressor therapy to maintain an adequate blood pressure. Higher doses of corticosteroids should not be used.
• Many other drug combinations are possible to get adequate coverage
• Antifungals
• Antimicrobials for anaerobic infections
• Antipseudomonals
• Drotrecogin alfa (Xigris) — 24 mcg/kg/hr for 96 hrs in patients with severe sepsis (APACHE score >24). Do not use in patients with increased risk of bleeding, thrombocytopenia with platelets < 30,000, sepsis-induced organ dysfunction for >24 hours, hypercoagu-lable states, chronic renal or hepatic failure, children or pregnancy. Very expensive.

Patient Monitoring

• Depends upon source of infection, underlying disease(s)
• Peak and trough drug levels for aminoglycosides
• 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 influ-enzae 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 / 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-oragammaglobulinemia
• Spienectomy
• 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

Pregnancy

Beta lactam antibiotics, aminoglycosides, erythromycin are considered safe

Synonyms

• Septicemia
• Sepsis neonatorum

International Classification of Diseases

038.9 Unspecified septicemia

See Also

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

Other Notes

High dose steroids of no benefit