DESCRIPTION

• Presence of an infection with an associated systemic inflammatory response
• The systemic inflammatory response syndrome (SIRS) is composed of 4 criteria:
  • Temperature > 38°C or < 36°C
  • Heart rate > 90 bpm
  • Respiratory rate > 20/min or PaCO₂ < 32 mm Hg
  • WBC > 12,000/mm³, < 4,000/mm³, or > 10% band forms
• Sepsis = infection with ≥2 SIRS criteria:
  • Release of chemical messengers by the inflammatory response
  • Macrocirculatory failure through decreased cardiac output or decreased perfusion pressure
  • Microcirculatory failure through impaired vascular autoregulatory mechanisms and functional shunting of oxygen
  • Cytopathic hypoxia and mitochondrial dysfunction
• Hemodynamic changes result from the inflammatory response:
  • Elevated cardiac output in response to vasodilatation
  • Later myocardial depression:
• Multiple organ dysfunction syndrome (MODS):
  • Adult respiratory distress syndrome (ARDS)
  • Acute tubular necrosis and kidney failure
  • Hepatic injury and failure
  • Disseminated intravascular coagulation
• Sepsis should be viewed as a continuum of severity from a proinflammatory response to organ dysfunction and tissue hypoperfusion:
  • Severe sepsis: Sepsis with at least 1 of the following organ dysfunctions:
    • Acidosis
    • Renal dysfunction
    • Acute change in mental status
    • Pulmonary dysfunction
    • Hypotension
    • Thrombocytopenia or coagulopathy
    • Liver dysfunction
  • Septic shock: Sepsis-induced hypotension despite fluid resuscitation:
    • Systolic BP < 90 mm Hg or reduction of > 40 mm Hg from baseline
• Sepsis is the 10th leading cause of death in US:
  • In-hospital mortality for septic shock is ~30%

ETIOLOGY

• Gram-negative bacteria most common:
  • Escherichia coli
  • Pseudomonas aeruginosa
  • Rickettsiae
  • Legionella spp.
• Gram-positive bacteria:
  • Enterococcus spp.
  • Staphylococcus aureus
  • Streptococcus pneumoniae
• Fungi (Candida species)
• Viruses

Pediatric Considerations

• Children with a minor infection may have many of the findings of SIRS.
• Major causes of pediatric bacterial sepsis:
  • Neisseria meningitidis
  • Streptococcal pneumonia
  • Haemophilus influenzae

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

History

• Question for signs of infection and a systemic inflammatory response:
  • Fever
  • Dyspnea
  • Altered mental status:
    • Change in mental status
    • Confusion
    • Delirium
  • Nausea and vomiting
• Look for a source of the infection:
  • Cough, shortness of breath
  • Abdominal pain
  • Diarrhea
  • Dysuria/frequency
• Past history should highlight risk factors and immunosuppressive states:
  • Underlying terminal illness
  • Recent chemotherapy
  • Malignancy
  • History of a splenectomy
  • HIV
  • Diabetes
  • Nursing home resident

Physical Exam

• An elevated respiratory rate is an early warning sign of sepsis and occurs without underlying pulmonary pathology or acidosis.
• BP is often normal early in sepsis.
• Hypotension when septic shock occurs
• Extremities are often warmed and flushed despite hypotension.
• Look for a source of the infection:
  • Abdominal exam
  • Rectal exam to assess for an abscess
  • Chest exam for signs of pneumonia
  • Any rash is important:
    • Localized erythema with lymphangitis (streptococcal or staphylococcal cellulitis)
    • Rash involving palms of hands and soles of feet (rickettsial infection)
    • Petechiae scattered on the torso and extremities (meningococcemia)
    • Ecthyma gangrenosum (pseudomonas septicemia)
    • Round, indurated, painless lesion with surrounding erythema and central necrotic black eschar
  • Decubitus ulcers
  • Indwelling catheter:
• CNS infections:
  • Coma
  • Neck stiffness (meningitis)

ESSENTIAL WORKUP

• Serum lactate should be done early in the course to assess severity and need for goal-directed therapy
• Blood cultures prior to antibiotics:
  • Broad spectrum of lab tests and imaging studies to locate the source of the infection and assess for MOF.
  • Placement of a central line with an ScvO₂ catheter may be used to adjust therapy.

DIAGNOSIS TESTS & INTERPRETATION

Lab

• Serum lactate:
  • > 4 mmol/L defines severe sepsis
  • Normal lactate does not rule out septic shock
• CBC with differential:
  • Leukocytosis is insensitive and nonspecific
  • Neutrophil count < 500 cells/mm³ should prompt isolation and empiric IV antibiotics in chemotherapy patients.
  • > 5% bands on a peripheral smear is an imperfect indicator of infection.
  • Hematocrit:
    • Patients should be maintained with a hematocrit > 30% and hemoglobin > 10 g/dL.
  • Platelets:
    • May be elevated in the presence of infection or sepsis-induced volume depletion
    • Low platelet count is a significant predictor of bacteremia and death.
• Electrolytes, BUN, creatinine, glucose:
• Ca, Mg, pH
• C-reactive protein
• Cortisol level
• INR/prothrombin time/partial thromboplastin time
• Liver function tests
• ABG or VBG:
  • Mixed acid–base abnormalities: Respiratory alkalosis with metabolic acidosis
  • VBG correlates very closely with ABG, except for SaO₂
• Blood cultures:
  • From 2 different sites
  • 1 may be drawn through an indwelling central line (i.e., Broviac).
• Urine analysis and culture

Imaging

• CXR:
  • Determine whether pneumonia is the infectious source.
  • Fluffy, bilateral infiltrates may indicate that ARDS is already present.
  • Free air under the diaphragm indicates the source of the infection in intraperitoneal and a surgical intervention is mandatory.
• Soft tissue plain films:
  • Indicated if extremity erythema or severe pain
  • Air in the soft tissues associated with necrotizing or gas-forming infection
• Imaging studies to locate the source of the infection based on the presentation:
  • CT scan of the abdomen and pelvis
  • Abdominal US for gallbladder disease
  • Transthoracic or transesophageal echocardiogram

Diagnostic Procedures/Surgery

• Lumbar puncture:
  • For meningeal signs or altered mental status
• Central venous access:
  • Central venous pressure (CVP) and ongoing measurement of central venous oximetry.

DIFFERENTIAL DIAGNOSIS

• Pancreatitis
• Trauma
• Hemorrhage
• Cardiogenic shock
• Toxic shock syndrome
• Anaphylaxis
• Adrenal insufficiency
• Drug or toxin reactions
• Heavy metal poisoning
• Hepatic insufficiency
• Neurogenic shock

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

PRE-HOSPITAL

Aggressive fluid resuscitation for hypotension

INITIAL STABILIZATION/THERAPY

• ABCs
• Supplemental oxygen to maintain PaO₂ > 60 mm Hg
• Intubation and mechanical ventilation if shock or hypoxia are present
• Administer 0.9% NS IV.

ED TREATMENT/PROCEDURES

• Early goal-directed therapy:
  • 500 cc boluses of 0.9% saline up to 1–2 L empirically
  • Place central line.
  • Continue 500 cc saline boluses until CVP > 8 cm H₂O.
  • If the mean arterial pressure < 65 mm Hg and CVP > 8, then initiate pressors:
    • Norepinephrine or dopamine to raise BP
    • Norepinephrine is preferred if tachycardia or dysrhythmias are present.
    • Epinephrine for cases where shock is refractory to other pressors
    • If the ScvO₂ < 70 and HCT < 30, transfuse 2 U PRBCs.
    • If ScvO₂ > 70 and HCT > 30 and MAP > 60, then add dobutamine.
• Administer antibiotics early, based on the most likely organisms or site of infection.
• If source identified, or highly suspected, treat the most likely organisms:
  • Cover for MRSA, VRE, and Pseudomonas if there are risk factors
  • Pulmonary source:
    • 2nd- or 3rd-generation cephalosporin and gentamicin
  • Intra-abdominal source:
    • Ampicillin and metronidazole and gentamicin
    • Cefoxitin and gentamicin
  • Urinary tract source:
    • Ampicillin or piperacillin and gentamicin or levofloxacin
• Consider stress-dose hydrocortisone if recent steroid use or possible adrenal insufficiency

Pediatric Considerations

• Antibiotic therapy based on age:
  • < 3 mo (2 drugs): Ampicillin and gentamicin or cefotaxime (50–180 mg/kg/d div. q4–6h)
  • ≥3 mo: Cefotaxime or ceftriaxone (50–100 mg/kg/d div. q12–24 h)
• Initiate vasopressors after no response to 60 mL/kg IV fluid.
• Avoid hyponatremia and hypoglycemia.
• Dexamethasone for children with bacterial meningitis:
  • 0.15 mg/kg q6h for 4 days

MEDICATION

• Ampicillin: 1–2 g (peds: 50–200 mg/kg/24 h) IV q4–6h
• Cefoxitin: 1–2 g (peds: 100–160 mg/kg/24 h) IV q6–8h
• Ceftazidime: 1–2 g (peds: 100–150 mg/kg/24 h) IV q8–12h
• Dopamine: 1–5 µg/kg/min (renal dose); 5–10 µg/kg/min (pressor dose)
• Gentamicin: 1–1.5 mg/kg (peds: 2–2.5 mg/kg q8h) IV q8h
• Hydrocortisone: 100 mg IV q6–8h
• Metronidazole: Load with 1 g (peds: 15 mg/kg) IV, then 500 mg (peds: 7.5 mg/kg q6h)
• Nafcillin: 1–2 g IV q4h (peds: 50 mg/kg/24 h div. q4–6h)
• Norepinephrine: 2–8 µg/min
• Piperacillin: 3–4 g IV q4–6h
• Vancomycin: 500 mg (peds: 10 mg/kg) IV q6h

First Line

• Normal immune function without an identifiable source:
  • 2nd- or 3rd-generation cephalosporin and gentamicin
  • Nafcillin and gentamicin
  • Add vancomycin if there is a history of methicillin-resistant S. aureus, or the patient resides in a nursing facility, or there is a history of recent hospitalizations.

Second Line

Immunocompromised host without an identifiable source:

• Piperacillin and gentamicin
• Ceftazidime and either nafcillin or vancomycin and gentamicin

[Outline]

• PRE-HOSPITAL
• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

DISPOSITION

Admission Criteria

Sepsis almost always requires inpatient care.

Discharge Criteria

Patients with less severe infections (e.g., streptococcal pharyngitis) meeting the criteria for sepsis with stabilized vital signs

Issues for Referral

Sepsis with toxicity, septicemia, or septic shock requires admission, generally to an ICU.

• Start antibiotics as soon as sepsis is suspected.
• Failure to recognize multiorgan failure and initiate aggressive fluid resuscitation in the initial presentation of sepsis is a pitfall.

ICD9

• 038.42 Septicemia due to escherichia coli [E. coli]
• 038.43 Septicemia due to pseudomonas
• 995.91 Sepsis

ICD10

• A41.9 Sepsis, unspecified organism
• A41.51 Sepsis due to Escherichia coli [E. coli]
• A41.52 Sepsis due to Pseudomonas

[Outline]

• ICD9
• ICD10

• Barochia AV, Cui X, Vitberg D, et al. Bundled care for septic shock: An analysis of clinical trials. Crit Care Med. 2010;38:668–678.
• Martin JB, Wheeler AP. Approach to the patient with sepsis. Clin Chest Med. 2009;30:1–16.
• Rivers E, Nguyen B, Havstad S, et al.; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368–1377.
• Schuetz P, Jones AE, Aird WC, et al. Endothelial cell activation in emergency department patients with sepsis-related and non-sepsis-related hypotension. Shock. 2011;36(2):104–108.
• Shapiro NI, Wolfe RE, Moore RB, et al. Mortality in Emergency Department Sepsis (MEDS) score: A prospectively derived and validated clinical prediction rule. Crit Care Med. 2003;31(3):670–675.

Daniel J. Henning

Nathan Shapiro