Pediatric sepsis resident survival guide

Sepsis in Pediatric Patients

Diagnostic Criteria Systemic Inflammatory Response Syndrome Sepsis Severe Sepsis Septic Shock

Causes Children > 1 Month Children < 1 Month

Focused Initial Rapid Evaluation Infants and Children Newborns

Empiric Antibiotic Therapy

Dos and Don'ts

Main article: Sepsis

See also: Sepsis resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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 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.

Suspected Septic Shock (details) Suspected infection manifested by hypothermia or hyperthermia Clinical signs of inadequate tissue perfusion Altered mental status Decreased urine output 􏰁<1 ml/kg/h Diminished peripheral pulses compared with central pulses (cold shock) Prolonged capillary refill >􏰃2 seconds (cold shock) Mottled or cool extremities (cold shock) Bounding peripheral pulses (warm shock) Flash capillary refill (warm shock) Wide pulse pressure (warm shock)
The First Hour of Resuscitation Secure airway ± intubation (atropine / ketamine / benzodiazepine if indicated) Administer high-flow oxygen supplementation Administer IV boluses of 20 ml/kg saline until perfusion restores or rales/HMG develop Administer empiric antibiotics (details) ± Correct hypoglycemia and hypocalcemia For Fluid Refractory Shock Place central venous line and monitor CVP Reverse cold shock by titrating dopamine or epinephrine Reverse warm shock by titrating norepinephrine Administer hydrocortisone if at risk for adrenal insufficiency Therapeutic End Points Normal mental status Urine output 􏰃>1 mL/kg/h Warm extremities Capillary refill 􏰉≤2 seconds Normal peripheral and central pulses Normal blood pressure for age Normal glucose concentration Normal ionized calcium concentration
Beyond the First Hour of Resuscitation ± Transfuse RBC if Hb <􏰁10 g/dL ± Infuse FFP if prolonged INR ± Diuretics/dialysis if fluid overloaded Adjust D10%-containing isotonic fluid to maintain normoglycemia Therapeutic End Points Normal mental status Urine output 􏰃>1 mL/kg/h Capillary refill 􏰉≤2 seconds Warm extremities Threshold heart rates Normal peripheral and central pulses Perfusion pressure appropriate for age CI 􏰃>3.3 L/min/m2 and <􏰁6.0 L/min/m2 ScvO2 >􏰃70%
For Cold Shock with Normal Blood Pressure Titrate fluid and epinephrine Maintain ScvO2 >70% and Hb >10 g/dL Add nitroprusside / nitroglycerin / milrinone with volume loading if ScvO2 <70% Consider levosimendan / enoximone in recalcitrant low CO syndrome ± Thyroid hormone replacement ± Hydrocortisone replacement For Cold Shock with Low Blood Pressure Titrate fluid and epinephrine Maintain ScvO2 >70% and Hb >10 g/dL Add norepinephrine if hypotensive Consider dobutamine / milrinone / levosimendan / enoximone if ScvO2 <70% For Warm Shock with Normal Blood Pressure Titrate fluid and norepinephrine Maintain ScvO2 >70% Consider vasopressin / terripressin / angiotensin with volume if hypotensive Consider low-dose epinephrine if ScvO2 <70%
For Cateocholamine Resistant Shock Rule out and correct occult comorbidities Pericardial effusion Pneumothorax Hypoadrenalism Hypothyroidism Active hemorrhage Increased IAP (>12 mm Hg) Necrotic tissue Inappropriate control of infection source Immunocompromised / immunosuppressive state Consider PA / PiCCO / FATD catheter placement Target CI 􏰃>3.3 L/min/m2 and <􏰁6.0 L/min/m2 ± Doppler ultrasound to guide fluid therapy Consider ECMO

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.

Suspected Septic Shock (details) Suspected infection manifested by hypothermia or hyperthermia Inadequate tissue perfusion Poor feeding Diarrhea Poor tone Poor color Tachycardia Tachypnea Respiratory distress Maternal history of chorioamnionitis or prolonged rupture of membranes
The First Hour of Resuscitation Secure airway and maintain oxygenation / ventilation Administer IV boluses of 10 ml/kg saline until perfusion restores or HMG develops Administer prostaglandin until ductal-dependent lesion is excluded Administer empiric antibiotics (details) ± Correct hypoglycemia and hypocalcemia For Fluid Refractory Shock Titrate dopamine 5-9 mcg/kg/min Administer dobutamine up to 10 mcg/kg/min Consider epinephrine (0.05-0.3 􏰄g/kg/min) to restore blood pressure and perfusion For Persistent Pulmonary Hypertension Administer 100% oxygen Institute NaHCO3 / tromethamine until up to pH 7.50 and inhaled NO is available Hyperventilate to achieve 􏰁<5% difference in preductal and postductal SaO2 and 100% SaO2 Therapeutic End Points Normal mental status Urine output 􏰃>1 mL/kg/h Warm extremities Capillary refill 􏰉≤2 seconds Normal peripheral and central pulses Normal blood pressure for age Normal glucose concentration Normal ionized calcium concentration Difference in preductal and postductal O2 saturation 􏰁<5% SaO2 ≥95%
Beyond the First Hour of Resuscitation ± Transfuse RBC if Hb <􏰁10 g/dL ± Infuse FFP if prolonged INR ± Diuretics/dialysis if fluid overloaded Adjust D10%-containing isotonic fluid to maintain normoglycemia Therapeutic End Points Normal mental status Urine output 􏰃>1 mL/kg/h Capillary refill 􏰉≤2 seconds Warm extremities Normal peripheral and central pulses Normal blood pressure for age CI 􏰃>3.3 L/min/m2 SaO2 >95% ScvO2 >􏰃70% Difference in preductal and postductal O2 saturation 􏰁<5% Absence of right-to-left shunt, tricuspid regurgitation, or right ventricular failure Normal glucose concentration Normal ionized calcium concentration SVC flow >40 mL/kg/min Normal INR Normal anion gap Normal lactate Fluid overload <10%
For Cold Shock with LV Dysfunction Add nitroprusside / nitroglycerin / milrinone with volume loading if: ScvO2 <70% SVC flow <40 mL/kg/min CI <3.3 L/min/m2 For Cold Shock with Low Blood Pressure and RV Dysfunction Administer inhaled NO if persistent pulmonary hypertension with: ScvO2 <70% SVC flow <40 mL/kg/min CI <3.3 L/min/m2 Consider milrinone / inhaled iloprost / adenosine For Warm Shock with Low Blood Pressure Titrate fluid and norepinephrine Administer inotropes to maintain ScvO2 >70%, SVC flow >40 mL/kg/min, and CI >3.3 L/min/m2 Consider vasopressin / terripressin / angiotensin with volume if hypotensive
For Cateocholamine Resistant Shock Rule out and correct occult comorbidities Pericardial effusion Pneumothorax Hypoadrenalism Hypothyroidism Active hemorrhage Increased IAP (>12 mm Hg) Necrotic tissue Inappropriate control of infection source Immunocompromised / immunosuppressive state ± Thyroid hormone replacement ± Hydrocortisone replacement Administer pentoxifylline if VLBW newborn Consider closing PDA if hemodynamically significant Consider ECMO

Empiric Antibiotic Therapy

Children aged >1 month

• Cefotaxime 50 mg/kg IV q8h OR Ceftriaxone 100 mg/kg IV q24h AND
• Vancomycin 15 mg/kg IV q6h

• Aztreonam 7.5 mg/kg IV q6h AND
• Linezolid 10 mg/kg IV q8h

Children aged <1 month

• 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 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 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)

• 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 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

• 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 (< 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)

• 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)

References