====<span style="background: #FFFFF0;">Initial Resuscitation</span>====
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. {{GRADE2|C}}
===Initial Resuscitation===
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. {{GRADE2|C}}
* Commence protocolized, quantitative resuscitation for patients with sepsis-induced tissue hypoperfusion. Goals during the first 6 hrs of resuscitation:
:* CVP 8–12 mm Hg
:* MAP ≥65 mm Hg
:* Urine output ≥0.5 mL/kg/hr
:* ScvO2 ≥70% or MvO2 ≥65%
* In mechanically ventilated patients or those with known preexisting decreased ventricular compliance, a higher target CVP of 12–15mm Hg should be achieved to account for the impediment in filling.
===Diagnosis===
3. Follow American College of Critical Care Medicine-Pediatric Life Support (ACCM-PALS) guidelines for the management of septic shock. {{GRADE1|C}}
* Perform routine screening for severe sepsis in potentially infected seriously ill patients to allow earlier implementation of therapy.
* Cultures as clinically appropriate before antimicrobial therapy if no significant delay (>45 mins) in the start of antimicrobials.
* At least 2 sets of blood cultures (both aerobic and anaerobic bottles) should be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently (<48 hrs) inserted. The volume of blood drawn with the culture tube should be ≥ 10 mL.
* The Gram stain can be useful, in particular for respiratory tract specimens, to determine if inflammatory cells are present (>5 PMNs/HPF and <:10 squamous cells/LPF) and if culture results will be informative of lower respiratory pathogens.
* Rapid influenza antigen testing during periods of increased influenza activity in the community is also recommended.
* The use of the 1,3 β-d-glucan assay, mannan and anti-mannan antibody assays may be useful when suspecting invasive candidiasis.
* Perform imaging studies promptly to confirm a potential source of infection. Diagnostic imaging may identify a source of infection that requires removal of a foreign body or drainage.
===Antimicrobial Therapy===
4. Evaluate for and reverse pneumothorax, pericardial tamponade, or endocrine emergencies in patients with refractory shock. {{GRADE1|C}}
* Administration of intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock.
* Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens and that penetrate in adequate concentrations into presumed source of sepsis.
* If treatment of candidiasis is warranted, the selection of empirical therapy (eg, an echinocandin, triazoles such as fluconazole, or amphotericin B) should be tailored to the local pattern of the most prevalent Candida species and any recent exposure to antifungal drugs.
* Antiviral therapy should be initiated as early as possible in patients with severe sepsis or septic shock of viral origin.
* For selected patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is suggested for ''Pseudomonas aeruginosa'' bacteremia. A combination of beta-lactam and a macrolide is suggested for patients with septic shock from ''Streptococcus pneumoniae'' bacteremia.
* The duration of therapy should typically be limited to 7–10 days if clinically indicated. Longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, ''Staphylococcus aureus'' bacteremia; some fungal and viral infections, or immunologic deficiencies including neutropenia.
* Antimicrobial regimen should be reassessed daily for potential deescalation.
===Source Control===
====<span style="background: #FFFFF0;">Antibiotics and Source Control</span>====
* A specific anatomical diagnosis of infection requiring consideration for emergent source control should be sought and diagnosed or excluded as rapidly as possible.
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). {{GRADE1|D}}
* Control infection source within the first 12 hours after the diagnosis is made.
* Intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess).
* If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established.
* If infected peripancreatic necrosis is a potential infection source, definitive intervention should be delayed until adequate demarcation of viable and nonviable tissues has occurred.
===Infection Prevention===
2. Clindamycin and anti-toxin therapies for toxic shock syndromes with refractory hypotension. {{GRADE2|D}}
* Oral chlorhexidine gluconate should be used as a form of oropharyngeal decontamination to reduce the risk of VAP in ICU patients with severe sepsis.
===Fluid Therapy of Severe Sepsis===
3. Early and aggressive source control. {{GRADE1|D}}
* Use crystalloids as the initial fluid of choice in the resuscitation of severe sepsis and septic shock.
* Initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids.
===Vasopressors===
4. Clostridium difficile colitis should be treated with enteral antibiotics if tolerated. Oral vancomycin is preferred for severe disease. {{GRADE1|A}}
* Initiate vasopressor therapy (norepinephrine as the first choice) to target a mean arterial pressure of 65 mm Hg.
* Consider epinephrine when an additional agent is required to maintain adequate blood pressure. Vasopressin may be added to norepinephrine with intent of either raising MAP or decreasing norepinephrine dosage.
* Phenylephrine is not recommended in the treatment of septic shock <u>except</u>:
:* Norepinephrine is associated with serious arrhythmias
:* Cardiac output is known to be high and blood pressure persistently low
:* As salvage therapy when combined inotrope/vasopressor drugs and low dose vasopressin have failed to achieve MAP target
===Inotropic Therapy===
====<span style="background: #FFFFF0;">Fluid Resuscitation</span>====
* A trial of dobutamine infusion up to 20 micrograms/kg/min can be administered or added to vasopressor in the presence of:
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. {{GRADE2|C}}
:* Myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output
:* Ongoing signs of hypoperfusion, despite achieving adequate intravascular volume and adequate MAP
* Cardiac index should be maintained at predetermined supranormal levels.
===Corticosteroids===
====<span style="background: #FFFFF0;">Inotropes/Vasopressors/Vasodilators</span>====
* Steroids may be indicated in the presence of a history of steroid therapy or adrenal dysfunction.
1. Begin peripheral inotropic support until central venous access can be attained in children who are not responsive to fluid resuscitation. {{GRADE2|C}}
* When low-dose hydrocortisone is administered, continuous infusion rather than repetitive bolus injections should be used.
* Steroid therapy should be tapered when vasopressors are no longer required.
2. Patients with low cardiac output and elevated systemic vascular resistance states with normal blood pressure be given vasodilator therapies in addition to inotropes. {{GRADE2|C}}
===Blood Product Administration===
====<span style="background: #FFFFF0;">Extracorporeal Membrane Oxygenation (ECMO)</span>====
* Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, RBC transfusion should be considered when Hb <7.0 g/dL to target a concentration of 7.0–9.0 g/dL in adults.
1. Consider ECMO for refractory pediatric septic shock and respiratory failure. {{GRADE2|C}}
* In patients with severe sepsis, administer prophylactic platelets when:
:* PLT <10,000/mm3 (10 x 10<sup>9</sup>/L) in the absence of apparent bleeding
:* PLT <20,000/mm3 (20 x 10<sup>9</sup>/L) in the presence of bleeding risks
:* PLT ≥50,000/mm3 (50 x 10<sup>9</sup>/L) for active bleeding, surgery, or invasive procedures
===Mechanical Ventilation of Sepsis-Induced ARDS===
====<span style="background: #FFFFF0;">Corticosteroids</span>====
* Target a tidal volume of 6mL/kg predicted body weight in patients with sepsis-induced ARDS.
1. Timely hydrocortisone therapy in children with fluid refractory, catecholamine resistant shock and suspected or proven absolute (classic) adrenal insufficiency. {{GRADE1|A}}
* Measure plateau pressures in patients with ARDS. Initial upper limit for plateau pressures in a passively inflated lung should be ≤30 cm H2O.
* Positive end-expiratory pressure (PEEP) should be applied to avoid alveolar collapse at end expiration. A PEEP >5 cm H2O is usually required to avoid lung collapse.
* Higher rather than lower levels of PEEP should be used for patients with sepsis-induced moderate to severe ARDS. Strategies to titrate PEEP include:
:* Titrate PEEP and tidal volume according to bedside measurements of thoracopulmonary compliance with the objective of obtaining the best compliance.
:* Titrate PEEP based on severity of oxygenation deficit and guided by the FiO2 required to maintain adequate oxygenation.
* Mechanically ventilated sepsis patients should be maintained with the head of the bed elevated to 30–45 degrees to limit aspiration risk and to prevent the development of ventilator-associated pneumonia.
* Mechanically ventilated patients with severe sepsis should undergo spontaneous breathing trials regularly to evaluate the ability to discontinue mechanical ventilation when they satisfy the following criteria:
:* Arousable
:* Hemodynamically stable without vasopressor agents
:* No new potentially serious conditions
:* Low ventilatory and end-expiratory pressure requirements
:* Low FiO2 requirements which can be met safely delivered with a face mask or nasal cannula.
* Prone positioning may be considered in sepsis-induced ARDS patients with a PaO2/FiO2 ratio ≤100 mm Hg.
* Undertake a conservative rather than liberal fluid strategy for patients with established sepsis-induced ARDS who do not have evidence of tissue hypoperfusion.
===Sedation, Analgesia, and Neuromuscular blockade in Sepsis===
====<span style="background: #FFFFF0;">Protein C and Activated Protein Concentrate</span>====
* Continuous or intermittent sedation should be minimized in mechanically ventilated sepsis patients, targeting specific titration endpoints.
No recommendation as no longer available.
* If neuromuscular blocking agents must be maintained, either intermittent bolus as required or continuous infusion with train-of-four monitoring of the depth of blockade should be used.
* A short course of NMBA of not greater than 48 hours may be considered for patients with early sepsis-induced ARDS and a PaO2/FiO2 of <150 mm Hg.
===Glucose Control===
====<span style="background: #FFFFF0;">Blood Products and Plasma Therapies</span>====
* A protocolized approach should be undertaken for ICU patients with severe sepsis when 2 consecutive blood glucose levels are >180 mg/dL. This protocolized approach should target an upper blood glucose ≤180 mg/dL rather than an upper target blood glucose ≤ 110 mg/dL.
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. {{GRADE1|B}}
* Blood glucose values should be monitored every 1–2 hrs until glucose values and insulin infusion rates are stable and then every 4 hrs thereafter
===Renal Replacement Therapy===
2. Similar platelet transfusion targets in children as in adults. {{GRADE2|C}}
* Either continuous renal replacement therapy or intermittent hemodialysis may be used in patients with severe sepsis and acute renal failure.
* Continuous therapies may be considered to facilitate management of fluid balance in hemodynamically unstable septic patients.
===Deep Vein Thrombosis Prophylaxis===
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. {{GRADE2|C}}
* Patients with severe sepsis should receive daily prophylaxis against venous thromboembolism (VTE).
* VTE prophylaxis should be accomplished with daily subcutaneous low-molecular weight heparin (LMWH). If creatinine clearance is <30 mL/min, use dalteparin or another form of LMWH that has a low degree of renal metabolism or UFH.
* Patients with severe sepsis should be treated with a combination of pharmacologic therapy and intermittent pneumatic compression devices whenever possible.
* Septic patients who have a contraindication for heparin use (eg, thrombocytopenia, severe coagulopathy, active bleeding, recent intracerebral hemorrhage) should not receive prophylaxis, but receive mechanical prophylactic treatment, such as compression stockings or intermittent compression devices, unless contraindicated.
===Stress Ulcer Prophylaxis===
====<span style="background: #FFFFF0;">Mechanical Ventilation</span>====
* Stress ulcer prophylaxis using H2 blocker or proton pump inhibitor should be given to patients with severe sepsis/septic shock who have bleeding risk factors.
1. Lung-protective strategies during mechanical ventilation. {{GRADE2|C}}
* When stress ulcer prophylaxis is used, use proton pump inhibitors rather than H2 blockers.
===Nutrition===
====<span style="background: #FFFFF0;">Sedation/Analgesia/Drug Toxicities</span>====
* Administer oral or enteral feedings as tolerated, rather than either complete fasting or only intravenous glucose within the first 48 hours after a diagnosis of severe sepsis/septic shock.
1. We recommend use of sedation with a sedation goal in critically ill mechanically ventilated patients with sepsis. {{GRADE1|D}}
* Use intravenous glucose and enteral nutrition rather than total parenteral nutrition alone or parenteral nutrition in conjunction with enteral feeding in the first 7 days after a diagnosis of severe sepsis/septic shock.
* Use nutrition with no specific immunomodulating supplementation rather than nutrition providing specific immunomodulating supplementation in patients with severe sepsis.
===Setting Goals of Care===
2. Monitor drug toxicity labs because drug metabolism is reduced during severe sepsis, putting children at greater risk of adverse drug-related events. {{GRADE1|C}}
* Discuss goals of care and prognosis with patients and families.
* Incorporate goals of care into treatment and end-of-life care planning, utilizing palliative care principles where appropriate.
* Address goals of care as early as feasible, but no later than within 72 hours of ICU admission.
==Don'ts==
====<span style="background: #FFFFF0;">Glycemic Control</span>====
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. {{GRADE2|C}}
===Antimicrobial Therapy===
====<span style="background: #FFFFF0;">Diuretics and Renal Replacement Therapy</span>====
* Empiric combination therapy should not be used for more than 3–5 days. De-escalation to the most appropriate monotherapy should be performed as soon as the susceptibility profile is ascertained.
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. {{GRADE2|C}}
* Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause.
===Fluid Therapy of Severe Sepsis===
====<span style="background: #FFFFF0;">Deep Vein Thrombosis (DVT) Prophylaxis</span>====
* Do not use hydroxyethyl starches for fluid therapy resuscitation of severe sepsis and septic shock.
No recommendation on the use of DVT prophylaxis in prepubertal children with severe sepsis.
===Vasopressors===
====<span style="background: #FFFFF0;">Stress Ulcer (SU) Prophylaxis</span>====
* Do not use low dose vasopressin as the single vasopressor.
No recommendation on the use of SU prophylaxis in prepubertal children with severe sepsis.
* Do not use low-dose dopamine for renal protection.
===Corticosteroids===
====<span style="background: #FFFFF0;">Nutrition</span>====
* Do not administer corticosteroids for the treatment of sepsis in the absence of shock.
1. Enteral nutrition given to children who can be fed enterally, and parenteral feeding in those who cannot. {{GRADE2|C}}
* Do not use intravenous hydrocortisone to treat adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability.
* ACTH stimulation test is not recommended for identifying adults with septic shock who should receive hydrocortisone.
===Blood Product Administration===
* Do not use erythropoietin as a specific treatment of anemia associated with severe sepsis.
* Do not use fresh frozen plasma to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedure.
===Immunoglobulins and Selenium===
* Do not use intravenous immunoglobulins in adult patients with severe sepsis or septic shock.
* Do not use intravenous selenium for the treatment of severe sepsis.
===Mechanical Ventilation of Sepsis-Induced ARDS===
* Do not routinely place the pulmonary artery catheter for patients with sepsis-induced ARDS.
* Do not use beta 2-agonists for treatment of sepsis-induced ARDS in the absence of specific indications such as bronchospasm.
===Sedation, Analgesia, and Neuromuscular blockade in Sepsis===
* Neuromuscular blocking agents (NMBAs) should be avoided if possible in the septic patient without ARDS due to the risk of prolonged neuromuscular blockade following discontinuation.
===Bicarbonate Therapy===
* Sodium bicarbonate should not be used for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥7.15.
===Stress Ulcer Prophylaxis===
* Patients without risk factors should not receive stress ulcer prophylaxis.
===Nutrition===
* Avoid mandatory full caloric feeding in the first week but rather suggest low dose feeding (eg, up to 500 calories per day), advancing only as tolerated.
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.[1]
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.
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
↑Dellinger, R. Phillip; Levy, Mitchell M.; Rhodes, Andrew; Annane, Djillali; Gerlach, Herwig; Opal, Steven M.; Sevransky, Jonathan E.; Sprung, Charles L.; Douglas, Ivor S.; Jaeschke, Roman; Osborn, Tiffany M.; Nunnally, Mark E.; Townsend, Sean R.; Reinhart, Konrad; Kleinpell, Ruth M.; Angus, Derek C.; Deutschman, Clifford S.; Machado, Flavia R.; Rubenfeld, Gordon D.; Webb, Steven A.; Beale, Richard J.; Vincent, Jean-Louis; Moreno, Rui; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup (2013-02). "Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012". Critical Care Medicine. 41 (2): 580–637. doi:10.1097/CCM.0b013e31827e83af. ISSN1530-0293. PMID23353941. Check date values in: |date= (help)
↑Rivers, E.; Nguyen, B.; Havstad, S.; Ressler, J.; Muzzin, A.; Knoblich, B.; Peterson, E.; Tomlanovich, M.; Early Goal-Directed Therapy Collaborative Group (2001-11-08). "Early goal-directed therapy in the treatment of severe sepsis and septic shock". The New England Journal of Medicine. 345 (19): 1368–1377. doi:10.1056/NEJMoa010307. ISSN0028-4793. PMID11794169.