›10 to 20 mL per kg IV or intraosseous over 5 to 20 minutes, reassessing after each aliquot
›Where intensive care is available: up to 40 to 60 mL per kg in the first hour, titrated to markers of cardiac output
›Where intensive care or positive-pressure ventilation is not available: no bolus if the child is normotensive; if hypotensive, up to 40 mL per kg with reassessment (FEAST)
›Stop and switch to a vasoactive infusion if hepatomegaly, new crackles, a gallop, or worsening hypoxemia appear, or if there is no perfusion gain
›Verify against current pediatric guideline before use
›Known or suspected cardiac disease, or the neonate: 5 to 10 mL per kg per aliquot with echo or clinical reassessment between boluses
›Verify against current pediatric guideline before use
›Fluid choice details
›Avoid hydroxyethyl starches and gelatins
›5% albumin 10 to 20 mL per kg is a reasonable second-line fluid after large crystalloid volumes but is not first-line
›Large-volume 0.9% saline causes hyperchloremic acidosis that can be mistaken for worsening lactic acidosis
›Signs to stop resuscitating with fluid
›New or enlarging liver edge, new crackles, rising oxygen requirement, a new gallop
›No improvement in perfusion after 40 to 60 mL per kg
›Move to a vasoactive infusion rather than giving further boluses
Fluid-refractory shock and vasoactive selection
›Define fluid-refractory shock
›Shock persisting after 40 to 60 mL per kg of isotonic fluid given as reassessed aliquots, or earlier if signs of fluid overload appear
›Start a vasoactive infusion within 60 minutes of recognition when boluses are not restoring perfusion; do not wait for central access
›Choosing the first agent
›Epinephrine or norepinephrine first-line, not dopamine (Surviving Sepsis Campaign 2020)
›Cold shock (low output, high resistance, cool mottled peripheries, narrow pulse pressure): epinephrine
›Warm shock (high output, low resistance, bounding pulses, flash capillary refill, wide pulse pressure): norepinephrine
›Bedside cold-versus-warm assignment is unreliable and can reverse; reassess, get echo, and be prepared to switch or combine
›Route and monitoring during initiation
›Peripheral IV or intraosseous delivery at appropriate dilution is acceptable for the first hours
›Continuous ECG and, as soon as possible, invasive arterial pressure
›Reassess perfusion, heart rate, rhythm, blood pressure, and mental status every 5 to 10 minutes during titration
Epinephrine and norepinephrine infusions
›Epinephrine, first-line for fluid-refractory shock and preferred in cold shock
›Start 0.05 mcg per kg per minute by IV or intraosseous infusion
›Titrate by 0.05 mcg per kg per minute every 5 to 10 minutes to perfusion and blood pressure targets
›Decelerate to increments of 0.02 to 0.03 mcg per kg per minute as targets are approached to avoid tachyarrhythmia and hypertensive overshoot
›Usual effective range 0.05 to 0.3 mcg per kg per minute
›A sustained requirement at or above 0.5 mcg per kg per minute defines catecholamine-resistant shock and should trigger hydrocortisone and echo reassessment
›Verify against current pediatric guideline before use
›May run through a proximal well-functioning peripheral IV or intraosseous line at appropriate dilution while central access is obtained; do not delay
›Expect a rise in lactate and glucose from the beta-2 effect; interpret lactate with clinical perfusion and do not escalate fluids for this alone
›Monitoring: continuous ECG and pulse oximetry, invasive arterial pressure as soon as feasible, perfusion and mental status every 5 to 10 minutes, lactate and ionized calcium every 1 to 2 hours
›Norepinephrine, first-line for warm shock with low systemic vascular resistance
›Start 0.05 mcg per kg per minute by IV or intraosseous infusion
›Titrate by 0.05 mcg per kg per minute every 5 to 10 minutes to an age-appropriate mean arterial pressure
›Decelerate to 0.02 to 0.03 mcg per kg per minute increments near target
›Usual range 0.05 to 0.5 mcg per kg per minute; a persistent requirement above this is catecholamine-resistant shock
›Verify against current pediatric guideline before use
›Extravasation causes tissue necrosis; phentolamine 0.1 to 0.2 mg per kg subcutaneously infiltrated locally, maximum 10 mg, is the antidote
›Add low-dose epinephrine or an inodilator if cardiac output is low despite an adequate mean arterial pressure
Dopamine, dobutamine, and milrinone
›Dopamine, only when epinephrine and norepinephrine are unavailable
›Associated with more arrhythmia and higher mortality than epinephrine in pediatric randomized trials
›5 to 10 mcg per kg per minute IV or intraosseous, titratable to 20 mcg per kg per minute
›Maximum 20 mcg per kg per minute
›Switch to epinephrine or norepinephrine as soon as either is available
›Verify against current pediatric guideline before use
›Dobutamine, for sepsis-induced myocardial dysfunction with an adequate mean arterial pressure and preload
›2.5 mcg per kg per minute IV, titrate by 2.5 mcg per kg per minute every 10 to 15 minutes
›Usual range 2.5 to 10 mcg per kg per minute, maximum 20 mcg per kg per minute
›May worsen hypotension through beta-2 vasodilation; keep a vasopressor running if systemic vascular resistance is low
›Verify against current pediatric guideline before use
›Milrinone, an inodilator for low cardiac output with high systemic vascular resistance once blood pressure is restored
›0.25 mcg per kg per minute IV infusion, titrate toward 0.75 mcg per kg per minute
›Omit the loading dose in shock, because loading causes hypotension
›Long half-life of 2 to 4 hours, longer in renal impairment and in infants; accumulation causes refractory hypotension, so reduce the dose or stop if mean arterial pressure falls
›Maximum 0.75 mcg per kg per minute; reduce in renal dysfunction
›Verify against current pediatric guideline before use
Vasopressin and catecholamine-resistant strategies
›Vasopressin, an adjunct in catecholamine-resistant vasodilatory shock
›No mortality benefit demonstrated; it can reduce cardiac output and cause digital and splanchnic ischemia
›0.0002 to 0.002 units per kg per minute IV infusion (0.2 to 2 milliunits per kg per minute)
›Do not titrate rapidly; monitor for a fall in cardiac output, ischemic skin lesions, and hyponatremia
›Stop if cardiac output falls or ischemic lesions appear
›Verify against current pediatric guideline before use
›Combining agents
›Add a second agent rather than pushing a single catecholamine to extreme doses
›Norepinephrine plus vasopressin for vasoplegia; epinephrine or an inodilator added for low output
›When to reassess rather than escalate
›A sustained requirement at or above 0.5 mcg per kg per minute of epinephrine or norepinephrine should prompt hydrocortisone, echo, and the therapy-is-not-working checklist
Empiric antimicrobial therapy
›Give broad-spectrum antimicrobials within 60 minutes of recognizing septic shock
›Each hour of delay beyond the first 1 to 3 hours is associated with a stepwise increase in mortality
›Take cultures first only if it does not delay the first dose
›Neonate 0 to 28 days
›Ampicillin 50 mg per kg IV every 6 hours, or 100 mg per kg every 6 hours for meningitic dosing, PLUS gentamicin 4 to 5 mg per kg IV every 24 hours; or ampicillin PLUS cefotaxime 50 mg per kg IV every 6 to 8 hours
›Ampicillin monotherapy is inadequate at this age; a third-generation cephalosporin or an aminoglycoside must be added to cover Escherichia coli and other gram-negatives, and ampicillin is retained for Listeria and enterococcus
›Avoid ceftriaxone in the neonate: it displaces bilirubin with a kernicterus risk and precipitates with calcium-containing fluids; use cefotaxime
›Add aciclovir 20 mg per kg IV every 8 hours if neonatal herpes simplex is possible: vesicles, seizures, hepatitis, CSF pleocytosis, or a maternal history
›Add vancomycin 15 mg per kg IV every 6 to 8 hours if catheter-associated or MRSA risk
›Infant and child
›Ceftriaxone 50 mg per kg IV every 12 hours, or 100 mg per kg IV once daily for meningitic dosing, maximum 4 g per day; or cefotaxime
›Add vancomycin 15 mg per kg IV every 6 hours, dose-adjusted to local target trough or AUC, for suspected MRSA, toxic shock, purpura fulminans, or critical illness
›Add clindamycin 10 to 13 mg per kg IV every 8 hours, maximum 900 mg per dose, for toxin suppression in suspected staphylococcal or streptococcal toxic shock syndrome
›Immunocompromised, neutropenic, or central-line-associated
›Antipseudomonal beta-lactam: piperacillin-tazobactam 100 mg per kg of the piperacillin component IV every 6 to 8 hours, or cefepime 50 mg per kg IV every 8 hours, or meropenem 20 mg per kg IV every 8 hours (40 mg per kg for central nervous system infection)
›Add vancomycin for a line infection or mucositis; add an aminoglycoside for shock or resistant gram-negative risk
›Add an antifungal for prolonged neutropenia, prior azole exposure, or no response by 48 to 72 hours: micafungin 2 to 4 mg per kg IV daily, or liposomal amphotericin B 3 to 5 mg per kg IV daily
›Asplenia or functional asplenia, including sickle cell disease
›Ensure a third-generation cephalosporin covers encapsulated organisms and add vancomycin for penicillin-resistant pneumococcus risk
›Refine within 48 to 72 hours
›Narrow to culture and sensitivity results, stop redundant cover, and set a definitive duration with infectious diseases input
Source control, corticosteroids, and metabolic support
›Source control
›Identify and drain or remove the focus within 6 to 12 hours: abscess drainage, empyema drainage, debridement of necrotizing soft-tissue infection, relief of an obstructed urinary tract, laparotomy for a perforated or necrotic viscus
›Remove or exchange an infected central venous catheter or other colonized device once safe access is secured
›Involve surgery, interventional radiology, and the relevant subspecialty early; resuscitation will not hold without source control
›Hydrocortisone
›Indicated for catecholamine-resistant shock, or known or strongly suspected adrenal insufficiency: chronic steroid exposure, congenital adrenal hyperplasia, purpura fulminans, or prior etomidate
›2 mg per kg IV bolus, maximum 100 mg, then 1 mg per kg IV every 6 hours, or 50 mg per m2 per day by infusion
›Draw a random cortisol before the first dose when feasible but do not delay dosing for the result
›Not recommended when fluid and vasoactive therapy have already restored hemodynamic stability (Surviving Sepsis Campaign 2020)
›Verify against current pediatric guideline before use
›Glucose
›Treat a point-of-care glucose below 2.6 mmol/l
›Neonate: 2 mL per kg of 10% dextrose IV or intraosseous
›Infant and child: 2 to 4 mL per kg of 25% dextrose, or 5 mL per kg of 10% dextrose, maximum 25 g
›Recheck in 15 to 30 minutes and start a maintenance dextrose-containing fluid
›Send the critical hypoglycemia sample first when adrenal insufficiency or a metabolic disease is possible
›Verify against current pediatric guideline before use
›Avoid hyperglycemia but do not use insulin infusions to target a glucose at or below 7.8 mmol/l; accept up to about 10 mmol/l (Surviving Sepsis Campaign 2020)
›Calcium
›Correct an ionized calcium below 1.1 mmol/l when contractility or vascular tone is compromised
›Calcium gluconate 10%: 50 to 100 mg per kg IV or intraosseous over 30 to 60 minutes, maximum single dose 2 g
›Calcium chloride 10%: 20 mg per kg via a central line for refractory hypocalcemia with instability
›Recheck ionized calcium after replacement and after each large transfusion, because citrate chelates calcium
›Verify against current pediatric guideline before use
›Potassium and magnesium
›Catecholamine infusions, insulin, and alkalosis drive potassium and magnesium down; replace to keep potassium above 3.5 mmol/l and magnesium in the normal range while on infusions
›Potassium chloride 0.5 to 1 mmol per kg IV over 1 to 2 hours, maximum 20 mmol per dose, with continuous ECG
›Magnesium sulfate 25 to 50 mg per kg IV over 20 minutes, maximum 2 g
›Acidosis
›Do not give sodium bicarbonate (typical dose 1 mmol per kg IV) to improve hemodynamics or reduce the vasoactive requirement at pH 7.15 or above (Surviving Sepsis Campaign 2020)
›Correct the driver instead: perfusion, ventilation, and source control
Airway management and mechanical ventilation
›Resuscitate before intubation whenever possible
›The standard intervention that kills this patient: induction drugs plus positive-pressure ventilation cause cardiovascular collapse from loss of endogenous catecholamine tone and from reduced venous return
›Give a fluid bolus and start or increase a vasoactive infusion before induction
›Have push-dose epinephrine 1 mcg per kg IV boluses drawn up and ready
›Verify against current pediatric guideline before use
›Induction and paralysis
›Ketamine 1 to 2 mg per kg IV is the induction agent of choice for hemodynamic stability
›Reduce to 0.5 to 1 mg per kg IV in profound shock, because the catecholamine-depleted myocardium can still depress with ketamine
›Verify against current pediatric guideline before use
›Etomidate is not recommended for rapid sequence intubation in septic shock, because even a single dose suppresses adrenal cortisol synthesis (Surviving Sepsis Campaign 2020)
›If etomidate 0.3 mg per kg IV is nonetheless used, give stress-dose hydrocortisone afterward
›Verify against current pediatric guideline before use
›Propofol 1 to 2 mg per kg IV is contraindicated as an induction or infusion agent here: vasodilation, negative inotropy, and the risk of propofol infusion syndrome in children
›Rocuronium 1 to 1.2 mg per kg IV for paralysis, preferred over succinylcholine when hyperkalemia, rhabdomyolysis, or prolonged immobilization is possible
›Verify against current pediatric guideline before use
›Succinylcholine 1 to 2 mg per kg IV only when no contraindication exists
›Verify against current pediatric guideline before use
›Post-intubation ventilation
›Lung-protective tidal volume 5 to 8 mL per kg of predicted body weight, and 3 to 6 mL per kg with sepsis-associated pediatric ARDS
›Start PEEP at 5 cmH2O and escalate cautiously, because high PEEP further reduces preload in the underfilled patient
›Allow PaCO2 to rise (permissive hypercapnia) provided pH stays above 7.20
›Target SpO2 94 to 98% and avoid hyperoxia
›Cyanotic congenital heart disease or single-ventricle physiology: target the child's known baseline saturation, often 75 to 85%, not 94%
›Chronic lung disease with baseline hypoxemia: target the child's usual saturation
›Sudden post-intubation deterioration
›Work through Displacement, Obstruction, Pneumothorax, Equipment failure, and Stacked breaths or auto-PEEP
›Disconnect from the circuit to exclude breath stacking and hand-ventilate
Refractory shock, ECMO, blood products, and adjuncts
›Catecholamine-resistant shock: structured escalation
›Definition: shock persisting despite epinephrine or norepinephrine at or above 0.5 mcg per kg per minute
›Add hydrocortisone if not already given
›Obtain echocardiography to phenotype and direct therapy
›Under-filled hyperdynamic ventricle: cautious further volume
›Poor contractility with low ejection fraction: add an inodilator, dobutamine or milrinone, with a vasopressor running
›Dilated vasoplegic picture with adequate output: add vasopressin and favor norepinephrine
›Recheck and correct ionized calcium, glucose, magnesium, and severe acidosis
›Therapy is not working: reassess the whole picture
›Wrong diagnosis: myocarditis; ductal-dependent congenital lesion in the neonate (start prostaglandin E1 (alprostadil) infusion 0.01 to 0.05 mcg per kg per minute IV and get urgent echo); tamponade; tension pneumothorax; pulmonary embolism; anaphylaxis; adrenal crisis; inborn error of metabolism; MIS-C; poisoning
›Verify against current pediatric guideline before use
›Inadequate source control: undrained abscess or empyema, necrotizing soft-tissue infection, a retained infected line, an obstructed urinary tract, necrotic bowel
›Inadequate antimicrobials: MRSA not covered, a resistant gram-negative, invasive fungal disease, neonatal herpes simplex, sub-therapeutic doses, missing clindamycin for toxin-mediated disease
›Mechanical and iatrogenic: endotracheal tube malposition, auto-PEEP, abdominal compartment syndrome from large-volume resuscitation, ongoing hemorrhage, pneumothorax
›Under-recognized adrenal insufficiency: prior etomidate, chronic steroids, congenital adrenal hyperplasia, pituitary disease
›Venoarterial ECMO
›The pediatric rescue for refractory septic shock when conventional therapy fails (Surviving Sepsis Campaign 2020)
›Refer early and on trajectory; delayed cannulation worsens survival
›Venovenous ECMO for sepsis-associated pediatric ARDS refractory to lung-protective ventilation without severe cardiovascular failure
›Intra-aortic balloon counterpulsation is not used in infants and small children and is not a bridging option here
›Blood products
›Red cells 10 to 15 mL per kg for hemoglobin below 70 g/l in the stabilized child; use a higher threshold during active hemorrhage or unresolved shock
›Do not give fresh frozen plasma (10 to 15 mL per kg) solely to correct deranged coagulation numbers without bleeding or a planned procedure
›For bleeding with disseminated intravascular coagulation: fresh frozen plasma 10 to 15 mL per kg, cryoprecipitate 5 mL per kg or platelets 10 mL per kg as dictated by fibrinogen and platelet count, and phytomenadione (vitamin K) 1 mg IV in infants or 5 to 10 mg IV in older children
›Adjuncts with a limited or negative evidence base
›Intravenous immunoglobulin 2 g per kg IV over 12 to 24 hours: not routine; consider only in streptococcal toxic shock syndrome on specialist advice
›Polymyxin B hemadsorption and other blood purification: not recommended outside trials
›Renal replacement therapy for oliguric fluid overload above 10% of body weight unresponsive to furosemide 1 mg per kg IV, or for refractory hyperkalemia or acidosis
›High-dose IVIG and activated protein C are not supported for routine use
Iatrogenic harm and routine interventions to modify
›Intubation and induction
›Pre-load with fluid and a vasoactive, use ketamine, avoid propofol, avoid etomidate, and have push-dose epinephrine 1 mcg per kg ready
›Verify against current pediatric guideline before use
›Sedation and analgesia
›Propofol infusion is contraindicated: vasodilation, negative inotropy, and propofol infusion syndrome in children
›Benzodiazepine boluses drop preload and pressure; dexmedetomidine causes bradycardia and hypotension; titrate opioids slowly and expect hypotension with morphine from histamine release
›Acetaminophen 15 mg per kg IV can transiently lower blood pressure; give it slowly and avoid it in the actively unstable
›Ibuprofen 10 mg per kg: avoid in shock, acute kidney injury, or bleeding risk
›Fluid loading
›Bolus fluid increased mortality in a setting without ventilators or inotropes (FEAST); even with critical care, stop at 40 to 60 mL per kg without response and after signs of overload, and switch to vasoactives
›Cumulative fluid overload above 10% of body weight independently predicts death and prolonged ventilation
›Oxygen
›Avoid hyperoxia; target SpO2 94 to 98%
›Cyanotic congenital heart disease and single-ventricle physiology: target the child's baseline saturation, often 75 to 85%, because hyperoxia can precipitate pulmonary over-circulation and systemic hypoperfusion
›Vasopressors
›Peripheral or intraosseous epinephrine and norepinephrine are acceptable early, but extravasation causes necrosis; inspect hourly, keep phentolamine available, and move central within hours
›Dopamine causes more arrhythmia and higher mortality than epinephrine or norepinephrine in children and is not first-line
›Mechanical circulatory support
›Intra-aortic balloon counterpulsation is ineffective and not used in infants and small children; do not plan around it
›Venoarterial ECMO is the pediatric rescue, and the harm here is delay rather than the device
›Anticoagulation and fibrinolysis
›No routine anticoagulation; in disseminated intravascular coagulation and purpura fulminans do not give heparin unless there is macrovascular thrombosis, and replace factors only for bleeding or procedures
›Systemic fibrinolysis has no role in septic shock; reserve it for separately confirmed massive pulmonary embolism
›Other routine emergency interventions
›Sodium bicarbonate for acidemia at pH 7.15 or above is not recommended and worsens ionized hypocalcemia and intracellular acidosis
›Ondansetron and other QT-prolonging antiemetics: limit them and correct potassium and magnesium first when electrolytes are deranged
›Ceftriaxone in the neonate is contraindicated with calcium-containing fluids and in hyperbilirubinemia; use cefotaxime
›Iodinated CT contrast: do not withhold a management-changing scan for fear of contrast nephropathy, but minimize the dose and hydrate