Sepsis

Basics

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% bands

Sepsis = suspected 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):
Acute 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 tenth leading cause of death in the U.S.:
In-hospital mortality for septic shock is ∼20%

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

Diagnosis

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 vasopressors and fluids
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

Diagnostic Tests and 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/Other
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

Treatment

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
Consider central line or large bore IV access
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:
Second- or third-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 q12–24h)
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 d
 Medication
Ampicillin: 1–2 g (peds: 50–200 mg/kg/24 hr) IV q4–6h
Cefoxitin: 1–2 g (peds: 100–160 mg/kg/24 hr) IV q6–8h
Ceftazidime: 1–2 g (peds: 100–150 mg/kg/24 hr) IV q8–12h
Dopamine: 1–5 mcg/kg/min (renal dose); 5–10 mcg/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 hr div q4–6h)
Norepinephrine: 2–8 mcg/min
Piperacillin: 3–4 g IV q4–6h
Vancomycin: 500 mg (peds: 10 mg/kg) IV q6h

First Line Medication:

Normal immune function without an identifiable source:
Second- or third-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 Medication:

Immunocompromised host without an identifiable source:

Piperacillin and gentamicin
Ceftazidime and either nafcillin or vancomycin and gentamicin

Ongoing Care

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

Pearls and Pitfalls

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

Additional Reading
The ProCESS Investigators, Yealy DM, Kellum JA, et al. A randomized trial of protocol-based care for early septic shock.
N Engl J Med. 2014;370:1683–1693.
Seymour CW, Rosengart MR. Septic shock: Advances in diagnosis and treatment. JAMA. 2015;314:708–717.
Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock
(Sepsis-3). JAMA. 2016;315:801–810.
Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med.
2018;378:797–808.

Authors
Annette M. Ilg

Nathan I. Shapiro

© Wolters Kluwer Health Lippincott Williams & Wilkins