Pediatric sepsis resident survival guide

Neonatal Sepsis Resident Survival Guide
Diagnostic Criteria
Causes
Focused Initial Rapid Evaluation
Empiric Therapy
Dos
Don'ts

Main article: Sepsis

Template:Seealso Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]; Vidit Bhargava, M.B.B.S [3]

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.

SIRS is considered to be present when patients have two or more of the following clinical findings:

Body temperature >38 °C (100.4 °F) or <36 °C (96.8 °F) Heart rate >90 beats per minute Hyperventilation evidenced by a respiratory rate of >20 breaths per minute or a PaCO2 <32 mm Hg White blood cell count of >12000 cells/mm³ or <4000 cells/mm³ (>12 x 109 cells/L or <4 x 109 cells/L) or bandemia (>10% band forms)

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:

Sepsis = infection (documented or suspected) and some of the following:

General variables Fever (>38.3°C) Hypothermia (core temperature <36°C) Heart rate >90/min–1 or more than two SD above the normal value for age Tachypnea Altered mental status Significant edema or positive fluid balance (>20 mL/kg over 24 hr) Hyperglycemia (plasma glucose >140mg/dL or 7.7 mmol/L) in the absence of diabetes

Inflammatory variables Leukocytosis (WBC count >12,000 μL–1) Leukopenia (WBC count <4000 μL–1) Normal WBC count with greater than 10% immature forms Plasma C-reactive protein more than two SD above the normal value Plasma procalcitonin more than two SD above the normal value

Hemodynamic variables Arterial hypotension (SBP <90mm Hg, MAP <70mm Hg, or an SBP decrease >40mm Hg in adults or less than two SD below normal for age)

Organ dysfunction variables Arterial hypoxemia (Pao2/Fio2 <300) Acute oliguria (urine output <0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation) Creatinine increase >0.5mg/dL or 44.2 μmol/L Coagulation abnormalities (INR >1.5 or aPTT >60 s) Ileus (absent bowel sounds) Thrombocytopenia (platelet count <100,000 μL–1) Hyperbilirubinemia (plasma total bilirubin >4mg/dL or 70 μmol/L)

Tissue perfusion variables Hyperlactatemia (>1 mmol/L) Decreased capillary refill or mottling

Severe Sepsis

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

Severe sepsis = sepsis-induced tissue hypoperfusion or organ dysfunction (any of the following thought to be due to the infection)

Sepsis-induced hypotension (SBP of <90 mm Hg or MAP <70 mm Hg or a SBP decrease >40 mm Hg or <2 SD below normal for age in the absence of other causes of hypotension) Lactate above upper limits laboratory normal Urine output <0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation Acute lung injury with PaO2/FIO2 <250 in the absence of pneumonia as infection source Acute lung injury with PaO2/FIO2 <200 in the presence of pneumonia as infection source Creatinine >2.0 mg/dL (176.8 μmol/L) Bilirubin >2 mg/dL (34.2 μmol/L) Platelet count <100,000 μL Coagulopathy (international normalized ratio >1.5)

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 a tachycardia (may be absent in the hypothermic patient) with signs of decreased perfusion including decreased peripheral pulses compared with central pulses, altered alertness, flash capillary refill or capillary refill 􏰀2 seconds, mottled or cool extremities, or decreased urine output.

Causes

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

• If associated with community-acquired pneumonia

• Streptococcus pneumoniae
• Staphylococcus aureus and MRSA
• Legionella
• Gram-negative bacilli

• If associated with urinary tract infection

• Aerobic gram-negative bacilli
• Enterococcus

• If associated with intra-abdominal infection

• Aerobic gram-negative bacilli
• Anaerobic gram-negative bacilli

• If associated with intravenous drug use

• Staphylococcus
• Nocardia

• If associated with petechiae

• Neisseria meningitidis
• Rocky Mountain spotted fever

FIRE: Focused Initial Rapid Evaluation

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; ICU, intensive care unit; INR, international normalized ratio; LFT, liver function test; MAP, mean arterial pressure; PCWP, pulmonary capillary wedge pressure; PT, prothrombin time; PTT, partial prothrombin time; SaO2, arterial oxygen saturation; SBP, systolic blood pressure; ScvO2, central venous oxygen saturation; SvO2, mixed venous oxygen saturation; SMA-7, sequential multiple analysis-7.

Suspected sepsis (details) Signs and Symptoms Fever (>38.3°C) Hypothermia (core temperature <36°C) Heart rate >90/min–1 or more than two SD above the normal value for age Tachypnea Altered mental status Significant edema or positive fluid balance (>20 mL/kg over 24 hr) Hypotension (SBP <90 mm Hg, MAP <70 mm Hg, or an SBP decrease >40 mm Hg) Hypoxemia (PaO2/FiO2 <300) Acute oliguria (urine output <0.5 mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation) Ileus (absent bowel sounds) Diminished capillary refill or mottling Laboratory Findings Hyperglycemia (plasma glucose >140mg/dL or 7.7 mmol/L) in the absence of diabetes Leukocytosis (WBC count >12,000 μL–1) Leukopenia (WBC count <4000 μL–1) Bandemia >10% immature forms C-reactive protein more than two SD above the normal value Procalcitonin greater than two SD above the normal value Creatinine increase >0.5mg/dL or 44.2 μmol/L Coagulation abnormalities (INR >1.5 or aPTT >60 s) Thrombocytopenia (platelet count <100,000 μL–1) Hyperbilirubinemia (plasma total bilirubin >4 mg/dL or 70 μmol/L) Hyperlactatemia (>1 mmol/L)

Early Goal-Directed Therapy Supplemental oxygen ± intubation / ventilatory support ± sedation to maintain SaO2 ≥93% Arterial and central venous line placement Rivers Protocol Infuse a 500 ml bolus of crystalloid q 30 minutes to maintain CVP at 8–12 mm Hg. If MAP <65 mm Hg, administer vasopressors to maintain MAP at ≥65 mm Hg. If MAP >90 mm Hg, administer vasodilators until MAP ≤90 mm Hg. If ScvO2 <70%, transfuse RBC to maintain Hct at ≥30%. Once CVP/MAP/Hct are optimized, if ScvO2 is still <70%, load dobutamine 2.5 μg/kg/min. Titrate dobutamine by 2.5 μg/kg/min q 30 minutes until 20 μg/kg/min or ScvO2 ≥70%. Taper or discontinue dobutamine if MAP <65 mm Hg or HR >120 bpm. Surviving Sepsis Campaign Care Bundles To Be Completed Within 3 Hours: Measure lactate level Obtain ≥2 sets of blood cultures prior to administration of antibiotics Administer 30 mL/kg crystalloid for hypotension or lactate ≥4 mmol/L Administer empiric antibiotics (details) To Be Completed Within 6 Hours: Administer vasopressors for persistent hypotension to maintain MAP ≥65 mm Hg For septic shock or initial lactate ≥4 mmol/L (36 mg/dL): — Measure CVP — Measure ScvO2 Remeasure lactate if initial lactate was elevated Goals of Initial Resuscitation CVP 8–12 mm Hg MAP ≥65 mm Hg Urine output ≥0.5 mL/kg/hr ScvO2 ≥70% or MvO2 ≥65% Normalization of lactate

Antimicrobial Therapy (details) Reassess antimicrobial regimen daily for potential deescalation Source Control (details) Remove potentially infected intravascular devices after establishing another accesss Infection Prevention (details) Use oral chlorhexidine gluconate in ICU patients with severe sepsis Corticosteroids (details) Continuous infusion of low-dose hydrocortisone if indicated Taper steroid therapy once vasopressors are no longer required Blood Product Administration (details) RBC transfusion if Hb <7.0 g/dL (target: 7.0–9.0 g/dL) Prophylactic platelets if indicated Mechanical Ventilation of Sepsis-Induced ARDS (details) Tidal volume at 6 mL/kg predicted body weight Plateau pressures ≤30 cm H2O PEEP >5 cm H2O Head of the bed elevated to 30–45 degrees Prone positioning if indicated Sedation, Analgesia, and Neuromuscular blockade (details) Avoid undue sedation in mechanically ventilated sepsis patients Glucose Control (details) Target an upper blood glucose ≤180 mg/dL Monitor q 1–2 hrs until glucose levels / insulin infusion rates are stable, then q 4 hrs thereafter Deep Vein Thrombosis Prophylaxis (details) LMWH / dalteparin / UFH if indicated Compression stockings or intermittent pneumatic compression devices Stress Ulcer Prophylaxis (details) H2 blocker or PPI in patients with bleeding risks Nutrition (details) Administer oral or enteral feedings as tolerated within the first 48 hours Administer intravenous glucose and enteral nutrition within the first 7 days Setting Goals of Care (details) Discuss goals of care and prognosis with patients and families within 72 hours of ICU admission

Empiric Antibiotic Therapy

History of intravenous drug use with high prevalence of MRSA

Vancomycin 1 gm IV q12h

Sepsis associated with petechiae

Ceftriaxone 2 gm IV q12h

Biliary source

Ampicillin-Sulbactam 3 gm IV q6h OR Piperacillin-Tazobactam 3.375 gm IV q4h OR Ticarcillin-Clavulanate 3.1 gm IV q4h

Community-acquired pneumonia

Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h

AND

Piperacillin-Tazobactam 3.375 gm IV q4h

AND

Vancomycin 1 gm IV q12h

Unclear infection source

Doripenem 500 mg IV q8h OR Ertapenem 1 gm IV q24h OR Imipenem 0.5 gm IV q6h OR Meropenem 1 gm IV q8h

AND

Vancomycin 1 gm IV q12h

Low prevalence of ESBL and/or carbapenemase-producing aerobic GNB

Piperacillin-Tazobactam 3.375 gm IV q4h

AND

Vancomycin 1 gm IV q12h

High prevalence of ESBL and/or carbapenemase-producing aerobic GNB

Colistin 2.5 mg/kg then 1.5 mg/kg IV q12h

AND

Meropenem 1 gm IV q8h

AND

Vancomycin 1 gm IV q12h

Dos

Initial Resuscitation

1. 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)

2. 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 mL·kg-1·hr-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)

3. Follow American College of Critical Care Medicine-Pediatric Life Support (ACCM-PALS) guidelines for the management of septic shock. (Grade 1C)

4. Evaluate for and reverse pneumothorax, pericardial tamponade, or endocrine emergencies in patients with refractory shock. (Grade 1C)

Antibiotics and Source Control

1. 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)

2. Clindamycin and anti-toxin therapies for toxic shock syndromes with refractory hypotension. (Grade 2D)

3. Early and aggressive source control. (Grade 1D)

4. Clostridium difficile colitis should be treated with enteral antibiotics if tolerated. Oral vancomycin is preferred for severe disease. (Grade 1A)

Fluid Resuscitation

1. 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 5–10 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

1. Begin peripheral inotropic support until central venous access can be attained in children who are not responsive to fluid resuscitation. (Grade 2C)

2. 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)

1. Consider ECMO for refractory pediatric septic shock and respiratory failure. (Grade 2C)

Corticosteroids

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

Protein C and Activated Protein Concentrate

No recommendation as no longer available.

Blood Products and Plasma Therapies

1. Similar hemoglobin targets in children as in adults. During resuscitation of low superior vena cava oxygen saturation shock (< 70%), hemoglobin levels of 10 g/dL are targeted. After stabilization and recovery from shock and hypoxemia then a lower target > 7.0 g/dL can be considered reasonable. (Grade 1B)

2. Similar platelet transfusion targets in children as in adults. (Grade 2C)

3. 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

1. Lung-protective strategies during mechanical ventilation. (Grade 2C)

Sedation/Analgesia/Drug Toxicities

1. We recommend use of sedation with a sedation goal in critically ill mechanically ventilated patients with sepsis. (Grade 1D)

2. 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

1. 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

1. 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)

Deep Vein Thrombosis (DVT) Prophylaxis

No recommendation on the use of DVT prophylaxis in prepubertal children with severe sepsis.

Stress Ulcer (SU) Prophylaxis

No recommendation on the use of SU prophylaxis in prepubertal children with severe sepsis.

Nutrition

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

References