Basics
Description
- Systemic inflammatory response syndrome (SIRS): nonspecific inflammatory response, defined as at least 2 of the following 4 criteria (one of which must be either abnormal temperature OR leukocyte count):
- Temperature >38.5 or <36 °C
- Tachycardia (mean HR >2 SDs above normal for age)
- Tachypnea (mean RR >2 SDs above normal for age)
- Leukocytosis, leukopenia, or >10% bands
- Infection: suspected or proven infection or clinical syndrome associated with high probability of infection
- Sepsis: SIRS in the presence of infection
- Severe sepsis: sepsis accompanied by evidence of altered end organ perfusion (cardiovascular dysfunction OR acute respiratory distress syndrome [ARDS] OR 2 or more other organ dysfunctions)
- Septic shock: sepsis with cardiovascular dysfunction (hypotension, need for vasoactive drug to maintain normal BP, or any combination of unexplained metabolic acidosis, increased arterial lactate, oliguria, prolonged capillary refill, and core-to-peripheral temperature gap)
Epidemiology
Incidence
- Estimated overall annual incidence of 0.6 cases per 1,000 children but varies by age
- Infants <1 year of age: 2.5 per 1,000 children
- Age 1 " 4 years: 0.5 per 1,000 children
- Age 5 " 14 years: 0.2 per 1,000 children
- Age 15 " 19 years: 0.4 per 1,000 children
Prevalence
Sepsis is among the most common (10 " 25%) medical diagnoses on admission to PICUs.
Risk Factors
Sepsis may occur in previously healthy children, but it is a particular concern for children with chronic underlying conditions that render them immunosuppressed or vulnerable to invasive infections.
- Neutropenia (neutrophils <1,000/mm3, especially <500/mm3)
- Primary or acquired immunodeficiency (e.g., AIDS, severe combined immunodeficiency)
- Malignancy
- Organ transplant recipients
- Chronic use of high-dose systemic steroids
- Indwelling central venous catheters or other invasive devices (e.g., urinary catheter)
- Hyposplenism, either surgical or functional (e.g., sickle cell anemia)
- Neuromuscular disease (e.g., static encephalopathy)
- Extensive burns
- Multiple trauma injuries
- Prematurity
- Unimmunized/underimmunized children
- Severe malnutrition
General Prevention
- Routine vaccination for Haemophilus influenzae type b (Hib), Streptococcus pneumoniae, and Neisseria meningitidis particularly in high-risk patients (e.g., asplenia)
- Antibiotic prophylaxis for household or day care exposure to confirmed cases of Hib or N. meningitidis
- Prompt evaluation of fever in immunosuppressed patients
- Aseptic technique for insertion and care of vascular catheters, minimizing duration of use
Etiology
- Microbial invasion of the bloodstream or release of microbial products/toxins into the bloodstream; stimulates host defense, resulting in activation of proinflammatory mediators and systemic inflammation
- Pathogens vary with age, host immune status, and setting (community or hospital).
- Neonates
- Group B Streptococcus
- Escherichia coli
- Staphylococcus aureus
- Listeria monocytogenes
- Enterococcus spp.
- Herpes simplex virus
- Enterovirus
- In neonates with a history of hospitalization, instrumentation, or mechanical ventilation, also consider
- Coagulase-negative staphylococci
- Gram-negative bacilli
- Candida spp.
- Otherwise healthy older infants and children
- Streptococcus pneumoniae
- N. meningitidis
- Staphylococcus aureus
- Group A Streptococcus
- Salmonella spp.
- Rickettsiae
- Influenza
- Patients with underlying immune defects are also susceptible to a broad range of additional organisms.
Diagnosis
Requires high suspicion; fever and tachycardia are nonspecific and hypotension is generally a late sign.
History
- See "Risk Factors "
- Duration of illness before presentation
- Abrupt onset of symptoms more typical of invasive bacterial infection
- Change in behavior may be initial sign of systemic infection.
- Irritability, lethargy, and poor feeding are especially important in infants and young children.
- Decreased urine output
Physical Exam
All patients with suspected sepsis should have a full set of vital signs (e.g., temperature, pulse, respiratory rate, BP, pulse oximetry).
- Temperature
- Fever is the hallmark of an infection but may be absent; infants may demonstrate hypothermia.
- General
- HEENT and neck exam
- Dehydration: sunken fontanelle, dry mucous membranes, sunken eyes
- Meningismus or bulging fontanelle
- Mucocutaneous bleeding
- Cardiovascular exam
- Tachycardia or bradycardia
- Hypotension
- Cold shock: delayed capillary refill; diminished pulses; mottling; and cool, clammy extremities
- Warm shock: flash capillary refill; bounding pulses; and warm, dry extremities
- Respiratory exam
- Hypoxia and/or cyanosis
- Apnea or tachypnea
- Retractions, flaring or grunting
- Poor air flow
- Abdominal exam
- Distension
- Hepatomegaly, splenomegaly
- Skin exam
- Presence of petechiae and purpura (associated with meningococcemia and disseminated intravascular coagulation)
- Pallor
- Neurologic
- Abnormal mental status (somnolence, confusion, agitation, irritability)
- Seizures
- Abnormal reflexes or tone
Diagnostic Tests & Interpretation
Lab
Patients with suspected sepsis should have
- Blood culture
- Prior to starting antibiotics when possible
- Culture yield is related to sample volume.
- CBC with differential
- Leukocytosis with increased band count or leukopenia may be present.
- Electrolytes, glucose, ionized calcium
- Metabolic acidosis
- Hypoglycemia or hyperglycemia
- Hypocalcemia
- BUN, creatinine:
- May reflect dehydration
- Evaluate for acute kidney injury
- Liver function tests
- Evaluate for end organ injury
- Arterial blood gas (ABG) and lactate
- Metabolic acidosis and/or hypoxemia
- Elevated lactate due to inadequate tissue perfusion
- PT, PTT, fibrinogen, fibrin degradation products, platelets, peripheral smear
- Screen for DIC: elevated PT, PTT, INR; decreased fibrinogen; increased fibrin degradation products
- Urinalysis and urine culture
- Potential source of infection
- Lumbar puncture (when hemodynamically stable)
- Required for diagnosis of meningitis
- Inflammatory biomarkers (e.g., CRP, procalcitonin) may be helpful.
- Culture other potential sources of infection: abscess, wounds, indwelling devices, sputum, tracheal aspirate
- Diagnostic testing for other potential causative organisms (e.g., HSV, enterovirus, influenza)
Imaging
- Chest x-ray
- Head CT may be necessary if with altered mental status in presence of coagulopathy.
Differential Diagnosis
- Congenital heart disease
- Myocarditis, pericarditis, cardiomyopathy
- Cardiac dysrhythmia
- Myocardial infarction
- Pulmonary embolus
- Congenital adrenal hyperplasia
- Thyrotoxicosis, hypothyroidism
- Inborn errors of metabolism
- Hypoglycemia
- Diabetic ketoacidosis
- Severe anemia
- Methemoglobinemia
- Neoplasm
- Hemophagocytic lymphohistiocytosis
- Macrophage activation syndrome
- Dehydration
- Pyloric stenosis
- Necrotizing enterocolitis
- Malrotation/volvulus
- Intussusception
- Pancreatitis
- Infant botulism
- Toxic ingestion/poisoning
- Trauma (accidental or nonaccidental)
Treatment
General Measures
- Ensure a patent airway (consider endotracheal intubation).
- Provide supplemental oxygen and assist ventilation (e.g., bag-valve-mask device) as needed.
- Obtain large-bore peripheral intravenous access (consider central venous line or intraosseous line).
- Hemodynamic support
- Early fluid resuscitation is imperative.
- Volume resuscitation: bolus 20 mL/kg of normal saline, repeat as needed; consider blood after 60 " 80 mL/kg of crystalloid
- Inotropic agents: If hemodynamic instability persists despite fluid resuscitation, start dopamine (begin at 5 mcg/kg/min, titrate up to 20 mcg/kg/min as needed). If fluid refractory/dopamine-resistant shock, start epinephrine for cold shock or norepinephrine for warm shock to normalize BP and restore perfusion.
- Broad-spectrum intravenous antibiotics to cover likely causative pathogens should be initiated promptly. Consider patient age, immune status, need for penetration into certain tissues (e.g., CNS), and whether the infection was community- or nosocomially acquired in empiric choice. In general, bactericidal drugs should be used.
- Neonates ≤4 weeks: ampicillin and gentamicin or ampicillin and cefotaxime. Add acyclovir to either regimen if herpes simplex virus infection is suspected.
- Infants and children ≥4 weeks: cefotaxime or ceftriaxone (no meningitis); vancomycin and cefotaxime or ceftriaxone (with meningitis)
- Patients with immunosuppression and/or central venous catheters: vancomycin plus aminoglycoside plus advanced-generation cephalosporin (e.g., cefepime)
- Patients with an intra-abdominal focus of infection: carbapenem; ticarcillin-clavulanate or piperacillin-tazobactam; ceftriaxone, cefotaxime, or cefepime plus metronidazole; ampicillin plus gentamicin plus metronidazole or clindamycin
- Correct hypoglycemia and hypocalcemia.
- Corticosteroids: stress-dose hydrocortisone for catecholamine-resistant hypotension and in patients at risk for adrenal insufficiency
- Drainage or eradication of focus of infection
Alert
- Rapid recognition of sepsis is critical. Provide adequate initial volume resuscitation; early reversal of shock is associated with improved outcomes.
- Continuous monitoring and reassessment of the patient are essential.
Inpatient Considerations
Admission Criteria
- Patients with sepsis should be admitted for close monitoring.
- Patients with severe sepsis or septic shock should be admitted to an ICU (e.g., requiring >60 mL/kg fluid resuscitation).
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Admit all patients with suspected sepsis to the hospital; consider ICU admission.
- Continuous BP monitoring for the development of refractory shock
- Serial vital signs and physical exams to monitor response to therapy
- Monitoring for complications of sepsis and the development of multiple organ dysfunction syndrome (MODS)
- Chest radiograph and serial ABGs for evidence of acute lung injury/ARDS
- Urine output, BUN, creatinine for acute kidney injury
- Serial coagulation studies (PT/PTT) and platelets for development of DIC
- Serial blood glucose levels for hypo- or hyperglycemia
- Serial liver function tests for evidence of hepatic dysfunction
- Serial neurologic examinations for evidence of CNS dysfunction
- Upon pathogen identification, antibiotic therapy can be narrowed appropriately.
Prognosis
- Case fatality rates have improved from nearly 50% to ¢ ¼10%. With implementation of clinical practice guidelines focused on early reversal of shock, several studies have reduced in-hospital mortality rates to ¢ ¼4 " 8% for patients with severe sepsis.
- Mortality is higher in children with chronic illnesses than in previously healthy children.
- Development of ARDS or MODS is associated with increased mortality.
Complications
- Sepsis is one of the leading causes of pediatric mortality and accounts for 7% of deaths.
- The most common complications are those resulting from hypoperfusion of vital organs or from organ injury incurred by the uncontrolled systemic inflammatory response:
- Acute lung injury
- Acute kidney injury
- DIC
- Hypoglycemia
- ARDS
- MODS
Additional Reading
- Bateman SL, Seed PC. Procession to pediatric bacteremia and sepsis: covert operations and failures in diplomacy. Pediatrics. 2010;126(1):137 " 150. [View Abstract]
- Brierley J, Carcillo JA, Choong K, et al. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock. Crit Care Med. 2009;37(2):666 " 688. [View Abstract]
- Butt W. Septic shock. Pediatr Clin North Am. 2001;48(3):601 " 625, viii. [View Abstract]
- Buttery JP. Blood cultures in newborns and children: optimising an everyday test. Arch Dis Child Fetal Neonatal Ed. 2002;87(1):F25 " F28. [View Abstract]
- Carcillo JA. Pediatric septic shock and multiple organ failure. Crit Care Clin. 2003;19(3):413 " 440. [View Abstract]
- Cazaja AS, Zimmerman JJ, Nathens AB. Readmission and late mortality after pediatric sepsis. Pediatrics. 2009;123(3):849 " 957. [View Abstract]
- Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368 " 1377. [View Abstract]
Codes
ICD09
- 995.91 Sepsis
- 995.90 Systemic inflammatory response syndrome, unspecified
- 995.92 Severe sepsis
- 785.52 Septic shock
- 038.42 Septicemia due to escherichia coli [E. coli]
- 771.81 Septicemia [sepsis] of newborn
- 038.0 Streptococcal septicemia
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
- R65.21 Severe sepsis with septic shock
- A40.1 Sepsis due to streptococcus, group B
- P36.4 Sepsis of newborn due to Escherichia coli
- P36.9 Bacterial sepsis of newborn, unspecified
- P36.0 Sepsis of newborn due to streptococcus, group B
- A41.51 Sepsis due to Escherichia coli [E. coli]
SNOMED
- 238150007 Sepsis syndrome (disorder)
- 238149007 systemic inflammatory response syndrome (disorder)
- 441596002 Systemic inflammatory response syndrome associated with organ dysfunction (disorder)
- 76571007 Septic shock (disorder)
- 447899008 Sepsis due to Escherichia coli (disorder)
- 206376005 Sepsis of the newborn
- 206379003 sepsis of newborn due to Escherichia coli (disorder)
- 448418006 Sepsis due to Streptococcus (disorder)
FAQ
- Q: What are the early clinical signs of sepsis?
- A: Vital sign changes such as tachycardia, tachypnea, along with respiratory distress/hypoxia and central nervous system alterations can be early signs of sepsis.