Sepsis

Definition
- Systemic inflammatory response syndrome (SIRS) is an inflammatory cascade that is initiated
by the host in response to infection with bacteria, rickettsiae, fungi, viruses, and protozoa.
- Sepsis is defined as SIRS resulting from a suspected or proven infection.
o Severe sepsis - the presence of sepsis combined with organ dysfunction
o Septic shock - severe sepsis plus the persistence of hypoperfusion or hypotension for >1
hr despite adequate fluid resuscitation or a requirement for inotropic agents or
vasopressors.

International Consensus Definitions for Pediatric Sepsis

Infection: Suspected or proven infection or a clinical syndrome associated with high probability
of infection

SIRS: 2 out of 4 criteria, 1 of which must be abnormal temperature or abnormal

leukocyte count
1. Core temperature >38.5°C or <36°C (rectal, bladder, oral, or central catheter)
2. Tachycardia: mean heart rate >2 SD above normal for age in absence of external
stimuli, chronic drugs or painful stimuli; OR unexplained persistent elevation over 0.5–
4 hr; OR in children <1 yr old persistent bradycardia over 0.5 hr (mean heart rate <10th
percentile for age in absence of vagal stimuli, β blocker drugs, or congenital heart
disease)
3. Respiratory rate >2 SD above normal for age or acute need for mechanical ventilation
not related to neuromuscular disease or general anesthesia
4. Leukocyte count elevated or depressed for age (not secondary to chemotherapy) or
>10% immature neutrophils

Sepsis: SIRS plus a suspected or proven infection

Severe Sepsis: Sepsis plus 1 of the following

1. Cardiovascular organ dysfunction defined as
Despite >40 mL/kg of isotonic intravenous fluid in 1 hr
Hypotension <5th percentile for age, systolic blood pressure <2 SD
below normal for age
OR
Need for vasoactive drug to maintain blood pressure
OR
2 of the following
Unexplained metabolic acidosis: base deficit >5 mEq/L
 Increased arterial lactate >2 times upper limit of normal
Oliguria: urine output <0.5 mL/kg/hr
Prolonged capillary refill 5 sec
Core to peripheral temperature gap >3°C

2. Acute respiratory distress syndrome (ARDS) as defined by the presence of a

PaO2/FiO2 ratio ≤300 mm Hg, bilateral infiltrates on chest radiograph, and no
evidence of left heart failure
OR
Sepsis plus 2 or more organ dysfunctions (respiratory, renal, neurologic,
hematologic, or hepatic)

Septic Shock: Sepsis plus cardiovascular organ dysfunction as defined above

Multiple Organ Dysfunction Syndrome (MODS): Presence of altered organ function
such that homeostasis cannot be maintained without medical intervention

Etiology
In the neonatal age group, group B streptococcus, Escherichia coli, Listeria monocytogenes,
enteroviruses, and herpes simplex virus are the pathogens most commonly associated with sepsis.

Pathogenesis
Septic shock is a combination of the three classic types of shock: hypovolemic, cardiogenic, and
distributive.
- Hypovolemia from intravascular fluid losses occurs through capillary leak.
- Cardiogenic shock results from the myocardial-depressant effects of sepsis.
- Distributive shock is the result of decreased systemic vascular resistance.
The degree to which a patient will exhibit each of these responses is variable. Warm shock occurs in
some patients with increased cardiac output and decreased systemic vascular resistance. Cold shock
occurs in other patients with decreased cardiac output and elevated systemic vascular resistance. In
both cases, perfusion to major organ systems may be compromised.
Recent data suggest that, unlike adults in septic shock who present with vasodilation and high cardiac
output, newborns and children may have fluid refractory shock and develop progressive myocardial
dysfunction.
Clinical Manifestation
The initial signs and symptoms of sepsis include
- alterations in temperature regulation (hyperthermia or hypothermia),
- tachycardia, and
- tachypnea.
In the early stages (hyperdynamic phase), the cardiac output increases in an attempt to maintain
adequate oxygen delivery to meet the increased metabolic demands of tissues. As sepsis progresses,
cardiac output falls in response to the effects of numerous mediators. Although hypotension (systolic
arterial pressure <2 standard deviations below the mean for age) is a late finding in children with sepsis,
it is not a criteria for the diagnosis of shock in infants and young children.
Other signs of poor cardiac output include
- delayed capillary refill,
- diminished peripheral and central pulses,
 - cool extremities,
- and decreased urine output.
- Alterations in mental status
Capillary leak develops from altered vascular permeability. Lactic acidosis occurs as shock progresses
and is the consequence of increased tissue production and decreased hepatic clearance.
Cutaneous lesions seen in septic patients include petechiae, diffuse erythema, ecchymoses, ecthyma
gangrenosum, and symmetric peripheral gangrene.
Jaundice can be seen either as a sign of infection or as a result of MODS.
The patient may also have evidence of focal infection such as meningitis, pneumonia, arthritis, cellulitis,
or pyelonephritis.

Diagnosis
- Culture appropriate specimens taken from body fluids (blood, urine, cerebrospinal fluid,
abscesses, peritoneal fluid, etc.).
- Physical examination findings
- Imaging - chest radiograph with evidence of pneumonia

Laboratory Findings
- Evidence of
o hematologic abnormalities
 thrombocytopenia, prolonged prothrombin and partial thromboplastin times,
reduced serum fibrinogen levels and elevated fibrin split products, and anemia.
 elevated neutrophil and increased immature forms (bands, myelocytes,
promyelocytes), vacuolation of neutrophils, toxic granulations, and Döhle bodies
can be seen with infection.
 Neutropenia is an ominous sign of overwhelming sepsis.
o electrolyte disturbances.
 hyperglycemia as a stress response or hypoglycemia if glycogen reserves are
exhausted.
 hypocalcemia, hypoalbuminemia, metabolic acidosis, and low serum
bicarbonate.
 Lactic acidosis can occur if there is significant anaerobic metabolism.
 Renal and liver function may be abnormal if the patient develops MODS.
 Patients with acute respiratory distress syndrome or pneumonia will have
impaired oxygenation (decreased Pao2) and ventilation (increased Paco2).

Treatment
Early administration of antimicrobial agents is associated with a reduction of mortality.
Neonate Ampicillin plus aminoglycoside or cefotaxime
Add vancomycin if nosocomial infection
 Add acyclovir if suspect herpes simplex virus

Toxic shock syndrome Penicillin plus clindamycin

Vancomycin if methicillin Staphylococcus aureus is
suspected

Suspected anaerobic Add clindamycin or metronidazole to above regimens

infections

- Fluid resuscitation of 60 mL/kg

o Fluid resuscitation in increments of 20 mL/kg should be titrated to normalize heart rate
(using age-based heart rates), urine output (to at least 1 mL/kg/hr), capillary refill (<2
sec), and mental status.
- Maintain the hemoglobin at 10 g/dL.
- Use of vasopressors and inotropic agents in an attempt to maintain a normal cardiac index.
o Dopamine is the initial choice for fluid-refractory shock. In dopamine-resistant shock,
epinephrine or norepinephrine should be considered.
o Dobutamine is useful in cases where cardiac output is low.
- Electrolytes should be monitored closely and corrected as needed.
o Hypoglycemia should be treated with 0.5–1.0 g/kg of glucose.
o Hypocalcemia, which can contribute to cardiac dysfunction, should be treated with 10–
20 mg/kg of calcium chloride through a central venous catheter.
- Monitoring patients with septic shock should minimally include central venous pressure, arterial
blood pressure, pulse oximetry, and hourly urine output. Other clinical parameters that should
be monitored include heart rate, capillary refill, and mental status.

Prevention
Immunization with the conjugate H. influenzae type b and S. pneumoniae vaccines is recommended for
all infants (see Chapter 170 ). High-risk patients should also receive recommended immunizations.