Pediatric sepsis resident survival guide

# Diagnostic Criteria

## Systemic Inflammatory Response Syndrome
Systemic inflammatory response syndrome (SIRS) represents the complex findings resulting from systemic activation of the innate immune response triggered by localized or generalized infection, trauma, thermal injury, or sterile inflammatory processes. However, criteria for SIRS are considered to be too nonspecific to be of utility in diagnosing a cause for the syndrome or in identifying a distinct pattern of host response.

## Sepsis
Sepsis is defined as the presence (probable or documented) of infection together with systemic manifestations of infection. Diagnostic criteria for sepsis are as follows:

## Severe Sepsis
Severe sepsis is defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion.

## Septic Shock
Septic shock is defined as sepsis-induced hypotension persisting despite adequate fluid resuscitation, in the absence of other causes for hypotension.
- Septic shock in adult patients refers to a state of acute circulatory failure characterized by persistent arterial hypotension unexplained by other causes.
- Septic shock in pediatric patients is defined as 1) a suspected infection manifested by hypothermia or hyperthermia, and 2) clinical signs of inadequate tissue perfusion including any of the following:
- Decreased or altered mental status
- Decreased urine output <1 ml/kg/h
- Bounding peripheral pulses (warm shock)
- Diminished peripheral pulses compared with central pulses (cold shock)
- Wide pulse pressure (warm shock)
- Prolonged capillary refill >2 seconds (cold shock)
- Flash capillary refill (warm shock)
- Mottled or cool extremities (cold shock)
- Septic shock in newborns manifests as tachycardia, respiratory distress, poor feeding, poor tone, poor color, tachypnea, diarrhea, or reduced perfusion, particularly in the presence of a maternal history of chorioamnionitis or prolonged rupture of membranes.

# Causes
Sepsis is a life-threatening condition and must be treated immediately irrespective of the underlying cause.

## Children > 1 Month
- Streptococcus pneumoniae
- Neisseria meningitidis
- Staphylococcus aureus
- Haemophilus influenzae

## Children < 1 Month
- Streptococcus agalactiae
- Escherichia coli
- Klebsiella
- Enterobacter
- Staphylococcus aureus
- Listeria
- Salmonella
- Haemophilus influenzae
- Staphylococcus epidermidis

# FIRE: Focused Initial Rapid Evaluation (Infants and Children)
Focused Initial Rapid Evaluation (FIRE) should be undertaken to identify patients requiring urgent intervention.
Abbreviations:
CBC, complete blood count;
CI, cardiac index;
CK-MB, creatine kinase MB isoform;
CVP, central venous pressure;
DC, differential count;
ECMO, extracorporeal membrane oxygenation;
FATD, femoral arterial thermodilution;
HMG, hepatomegaly;
IAP, intra-abdominal pressure;
ICU, intensive care unit;
INR, international normalized ratio;
IO, intraosseous;
IV, intravenous;
LFT, liver function test;
MAP, mean arterial pressure;
PA, pulmonary artery;
PCWP, pulmonary capillary wedge pressure;
PDA, patent ductus arteriosus;
PT, prothrombin time;
PTT, partial prothrombin time;
SaO2, arterial oxygen saturation;
SBP, systolic blood pressure;
ScvO2, central venous oxygen saturation;
SMA-7, sequential multiple analysis-7;
SvO2, mixed venous oxygen saturation;
VLBW, very low birth weight.

# FIRE: Focused Initial Rapid Evaluation (Newborns)
Focused Initial Rapid Evaluation (FIRE) should be undertaken to identify patients requiring urgent intervention.
Abbreviations:
CBC, complete blood count;
CI, cardiac index;
CK-MB, creatine kinase MB isoform;
CVP, central venous pressure;
DC, differential count;
ECMO, extracorporeal membrane oxygenation;
FATD, femoral arterial thermodilution;
HMG, hepatomegaly;
IAP, intra-abdominal pressure;
ICU, intensive care unit;
INR, international normalized ratio;
IO, intraosseous;
IV, intravenous;
LFT, liver function test;
MAP, mean arterial pressure;
PA, pulmonary artery;
PCWP, pulmonary capillary wedge pressure;
PDA, patent ductus arteriosus;
PT, prothrombin time;
PTT, partial prothrombin time;
SaO2, arterial oxygen saturation;
SBP, systolic blood pressure;
ScvO2, central venous oxygen saturation;
SMA-7, sequential multiple analysis-7;
SvO2, mixed venous oxygen saturation;
VLBW, very low birth weight.

# Empiric Antibiotic Therapy

## Children aged >1 month
- Preferred Regimen
Cefotaxime 50 mg/kg IV q8h OR Ceftriaxone 100 mg/kg IV q24h AND
Vancomycin 15 mg/kg IV q6h
- Cefotaxime 50 mg/kg IV q8h OR Ceftriaxone 100 mg/kg IV q24h AND
- Vancomycin 15 mg/kg IV q6h
- Alternative Regimen
Aztreonam 7.5 mg/kg IV q6h AND
Linezolid 10 mg/kg IV q8h
- Aztreonam 7.5 mg/kg IV q6h AND
- Linezolid 10 mg/kg IV q8h

## Children aged <1 month
- Preferred Regime
Ampicillin 25 mg/kg IV q8h AND
Cefotaxime 50 mg/kg q12h AND
Vancomycin 15 mg/kg IV q12h (if suspecting MRSA)
- Ampicillin 25 mg/kg IV q8h AND
- Cefotaxime 50 mg/kg q12h AND
- Vancomycin 15 mg/kg IV q12h (if suspecting MRSA)
- Alternative Regimen
Ampicillin 25 mg/kg IV q6h AND
Ceftriaxone 75 mg/kg IV q24h AND
Vancomycin 15 mg/kg IV q12h (if suspecting MRSA)
- Ampicillin 25 mg/kg IV q6h AND
- Ceftriaxone 75 mg/kg IV q24h AND
- Vancomycin 15 mg/kg IV q12h (if suspecting MRSA)

# Dos and Don'ts

### Initial Resuscitation
- For respiratory distress and hypoxemia, start with face mask oxygen or if needed and available, high flow nasal cannula oxygen or nasopharyngeal CPAP (NP CPAP). For improved circulation, peripheral intravenous access or intraosseus access can be used for fluid resuscitation and inotrope infusion when a central line is not available. If mechanical ventilation is required then cardiovascular instability during intubation is less likely after appropriate cardiovascular resuscitation. (Grade 2C)
- Initial therapeutic end points of resuscitation of septic shock: capillary refill of 2 secs, normal blood pressure for age, normal pulses with no differential between peripheral and central pulses, warm extremities, urine output >1 mLkg-1hr-1, and normal mental status. Scvo2 saturation 70% and cardiac index between 3.3 and 6.0 L/min/m2 should be targeted thereafter. (Grade 2C)
- Follow American College of Critical Care Medicine-Pediatric Life Support (ACCM-PALS) guidelines for the management of septic shock. (Grade 1C)
- Evaluate for and reverse pneumothorax, pericardial tamponade, or endocrine emergencies in patients with refractory shock. (Grade 1C)

### Antibiotics and Source Control
- Empiric antibiotics be administered within 1 hr of the identification of severe sepsis. Blood cultures should be obtained before administering antibiotics when possible but this should not delay administration of antibiotics. The empiric drug choice should be changed as epidemic and endemic ecologies dictate (eg H1N1, MRSA, chloroquine resistant malaria, penicillin-resistant pneumococci, recent ICU stay, neutropenia). (Grade 1D)
- Clindamycin and anti-toxin therapies for toxic shock syndromes with refractory hypotension. (Grade 2D)
- Early and aggressive source control. (Grade 1D)
- Clostridium difficile colitis should be treated with enteral antibiotics if tolerated. Oral vancomycin is preferred for severe disease. (Grade 1A)

### Fluid Resuscitation
- In the industrialized world with access to inotropes and mechanical ventilation, initial resuscitation of hypovolemic shock begins with infusion of isotonic crystalloids or albumin with boluses of up to 20 mL/kg crystalloids (or albumin equivalent) over 510 minutes, titrated to reversing hypotension, increasing urine output, and attaining normal capillary refill, peripheral pulses, and level of consciousness without inducing hepatomegaly or rales. If hepatomegaly or rales exist then inotropic support should be implemented, not fluid resuscitation. In non-hypotensive children with severe hemolytic anemia (severe malaria or sickle cell crises) blood transfusion is considered superior to crystalloid or albumin bolusing. (Grade 2C)

### Inotropes/Vasopressors/Vasodilators
- Begin peripheral inotropic support until central venous access can be attained in children who are not responsive to fluid resuscitation. (Grade 2C)
- Patients with low cardiac output and elevated systemic vascular resistance states with normal blood pressure be given vasodilator therapies in addition to inotropes. (Grade 2C)

### Extracorporeal Membrane Oxygenation (ECMO)
- Consider ECMO for refractory pediatric septic shock and respiratory failure. (Grade 2C)

### Corticosteroids
- Timely hydrocortisone therapy in children with fluid refractory, catecholamine resistant shock and suspected or proven absolute (classic) adrenal insufficiency. (Grade 1A)

### Blood Products and Plasma Therapies
- Similar hemoglobin targets in children as in adults. During resuscitation of low superior vena cava oxygen saturation shock ( 7.0 g/dL can be considered reasonable. (Grade 1B)
- Similar platelet transfusion targets in children as in adults. (Grade 2C)
- Use plasma therapies in children to correct sepsis-induced thrombotic purpura disorders, including progressive disseminated intravascular coagulation, secondary thrombotic microangiopathy, and thrombotic thrombocytopenic purpura. (Grade 2C)

### Mechanical Ventilation
- Lung-protective strategies during mechanical ventilation. (Grade 2C)

### Sedation/Analgesia/Drug Toxicities
- We recommend use of sedation with a sedation goal in critically ill mechanically ventilated patients with sepsis. (Grade 1D)
- Monitor drug toxicity labs because drug metabolism is reduced during severe sepsis, putting children at greater risk of adverse drug-related events. (Grade 1C)

### Glycemic Control
- Control hyperglycemia using a similar target as in adults  180 mg/dL. Glucose infusion should accompany insulin therapy in newborns and children because some hyperglycemic children make no insulin whereas others are insulin resistant. (Grade 2C)

### Diuretics and Renal Replacement Therapy
- Use diuretics to reverse fluid overload when shock has resolved, and if unsuccessful then continuous venovenous hemofiltration (CVVH) or intermittent dialysis to prevent > 10% total body weight fluid overload. (Grade 2C)

### Nutrition
- Enteral nutrition given to children who can be fed enterally, and parenteral feeding in those who cannot. (Grade 2C)