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Intensive Care Medicine | Pediatric Critical Care Medicine
These guidelines provide evidence-based management recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with sepsis or septic shock.
A panel of 68 international experts, representing 13 international organizations, as well as six methodologists, outlined 61 total statements on the management of children with sepsis or septic shock. Overall, five were strong recommendations, 24 were conditional recommendations, and ten were good practice statements. For 22 Population, Intervention, Comparator, and Outcome (PICO) questions, no recommendations could be made, but, for seven of these, “in our practice” statements were provided.
Compared with the 2020 guidelines, 20 recommendations were new, 13 were updated for clarity and/or new evidence, six were reviewed but not changed, and 22 were carried forward based on consensus of the panel that new evidence was not available. Only three recommendations were based on high or moderate quality of evidence.
These new guidelines also apply the more recent definition of pediatric sepsis as infection with life-threatening organ dysfunction involving the respiratory, cardiovascular, coagulation, and neurologic systems.
Review the recommendations from the guidelines below. Filter recommendations based on section, strength, or identifier.
Identifier:
Strength:
In children who are acutely unwell, there was insufficient evidence to recommend implementing systematic sepsis screening, in addition to established clinical protocols, for the timely recognition of sepsis and septic shock.
For children with sepsis or septic shock, we recommend that hospitals implement a performance improvement program, including standard operating procedures for treatment.
Certainty of evidence: Low
For children with probable sepsis or suspected septic shock, we recommend measuring blood lactate as part of initial evaluation and management.
Certainty of evidence: Very low
Clinicians should obtain blood cultures before initiating antimicrobial therapy in situations where this does not substantially delay antimicrobial administration.
For children with probable sepsis or suspected/confirmed septic shock, there is insufficient evidence to issue a recommendation for or against routine molecular testing for pathogen detection or identification.
For children with suspected septic shock, we recommend starting antimicrobial therapy as soon as possible, ideally within 1 hour of recognition of sepsis.
Certainty of evidence: Very low
For children with probable sepsis without shock, we suggest a time-limited course of rapid investigation and if concern for sepsis is substantiated, starting antimicrobial therapy as soon as possible after appropriate evaluation, ideally within 3 hours of recognition.
Certainty of evidence: Very low
For children with probable bacterial sepsis, where timely evaluation is difficult and there may be a delay due to other issues in clinical care, clinicians should consider giving antibiotics as soon as possible.
Clinicians should administer empiric broad-spectrum therapy with one or more antimicrobials to cover all likely pathogens.
For children treated for sepsis or septic shock with immune compromise and/or are at high risk for multidrug-resistant pathogens, we suggest using empiric multidrug therapy.
Certainty of evidence: Very low
For children with confirmed bacterial sepsis being treated with beta-lactam antibiotics, there is insufficient evidence to recommend for or against using a continuous and/or extended infusion strategy, compared with intermittent dosing.
Once the pathogen(s) and susceptibilities are available, empiric antimicrobial therapy coverage should be narrowed.
If no pathogen is identified, clinicians should narrow or stop empiric antimicrobial therapy according to clinical presentation, site of infection, host risk factors, and adequacy of clinical improvement in discussion with infectious disease and/or microbiological expert advice.
For children with sepsis or septic shock treated with antimicrobial therapy, we suggest not using procalcitonin routinely to guide de-escalation of therapy when effective antimicrobial stewardship programs are in place.
Certainty of evidence: Moderate
For children with sepsis or septic shock with documented bloodstream infection, we suggest hospitals implement routine infectious diseases or medical microbiology consultation for management advice.
Certainty of evidence: Very low
For children with sepsis or septic shock without documented bloodstream infection, there is insufficient evidence to provide a recommendation about whether hospitals should implement routine infectious diseases consultation.
Emergent source control intervention should be implemented as soon as possible after a diagnosis of an infection amenable to a source control procedure.
For children with sepsis or septic shock, we recommend removal of intravascular access devices that are confirmed to be the source of sepsis or septic shock after other vascular access has been established and depending on the pathogen and the risks/benefits of a surgical procedure.
Certainty of evidence: Low
For children with septic shock being treated in healthcare systems with intensive care availability, we suggest administering up to 40-60 mL/kg in bolus fluid (10-20 mL/kg per bolus) over the first hour of initial resuscitation, over no fluid bolus.
Certainty of evidence: Low
For children with sepsis without hypotension being treated in healthcare systems with no intensive care availability, we recommend against using fluid bolus therapy, while starting maintenance fluids.
Certainty of evidence: High
For children with septic shock with hypotension being treated in healthcare systems with no intensive care availability, we suggest administering up to 40 mL/kg in bolus fluid (10-20 mL/kg per bolus) over the first hour of initial resuscitation over no fluid bolus therapy.
Certainty of evidence: Low
Hemodynamic status should be reassessed after every fluid bolus. Fluid bolus therapy should be titrated to clinical markers of cardiac output and discontinued if shock resolves or if signs of fluid overload develop.
For the initial resuscitation of children with sepsis or septic shock, we suggest using crystalloids, rather than albumin.
Certainty of evidence: Moderate
For children with septic shock requiring treatment with fluid boluses, we suggest resuscitation with balanced or buffered crystalloid solutions over 0.9% saline.
Certainty of evidence: Very low
Resuscitation for children with sepsis or septic shock should be guided by ongoing clinical assessment of markers of hemodynamic status, including heart rate, blood pressure, capillary refill time, extremity temperature, pulse quality, level of consciousness, and urine output.
For children with sepsis or septic shock, there was insufficient evidence to issue a recommendation about whether to target mean arterial blood pressure at the 5th or 50th percentile for age.
For children with septic shock, we suggest targeting central venous oxygen saturation (ScvO2) greater than or equal to 70% when central venous access is available, over not targeting ScvO2.
Certainty of evidence: Very low
For children with sepsis and septic shock, there was insufficient evidence to issue a recommendation on use of advanced hemodynamic monitoring along with bedside clinical signs to guide resuscitation.
For children with sepsis or septic shock, we suggest using cardiac and lung point-of-care ultrasound (POCUS) to guide resuscitation, over not using POCUS to guide resuscitation, if local training and resources allow.
Certainty of evidence: Low
For children with septic shock, there was insufficient evidence to issue a recommendation on initiating vasoactive medications either before or after 40 mL/kg of bolus fluid therapy.
For children with septic shock requiring vasoactive medications, there was insufficient evidence to issue a recommendation on the preferred use of epinephrine or norepinephrine for first-line therapy in children with septic shock.
For children with septic shock requiring vasoactive medications, we suggest initiating vasoactive medications through peripheral venous access over delaying therapy until central venous access is obtained.
Certainty of evidence: Very low
For children with septic shock who require high-dose catecholamines, we suggest either adding vasopressin or further titrating catecholamines.
Certainty of evidence: Low
For children with septic shock and cardiac dysfunction despite treatment with initial vasoactive medications, there was insufficient evidence to issue a recommendation about adding an inodilator.
For children with septic shock with persistent hypoperfusion despite treatment with other vasoactive medication, there was insufficient evidence to issue a recommendation for co-treatment with angiotensin II.
For children with septic shock with persistent hypoperfusion despite treatment with other vasoactive medications, there was insufficient evidence to issue a recommendation for co-treatment with methylene blue.
For children with fluid-refractory, catecholamine-resistant septic shock, there was insufficient evidence to issue a recommendation about whether to intubate in the absence of respiratory failure.
For children with sepsis or septic shock, we suggest against using etomidate when intubating.
Certainty of evidence: Low
For children with sepsis or septic shock following resuscitation, we suggest titrating supplemental oxygen to target a conservative range (peripheral oxygen saturation [SpO2] (88-92%) over a more liberal target (SpO2 > 94%).
Certainty of evidence: Moderate
For children with septic shock in whom hemodynamic stability can be restored with fluid resuscitation and vasoactive therapy, we suggest against the use of IV hydrocortisone.
Certainty of evidence: Low
For children with septic shock who remain hemodynamically unstable despite adequate fluid resuscitation and vasoactive therapy, there was insufficient evidence to issue a recommendation on whether to treat with IV hydrocortisone.
For children with sepsis or septic shock with fever, there was insufficient evidence to issue a recommendation on whether to target normothermia or take a permissive approach to fever.
For children with sepsis or septic shock and metabolic acidemia, there was insufficient evidence to issue a recommendation on the use of sodium bicarbonate.
For children with sepsis or septic shock, there was insufficient evidence to issue a recommendation about whether to target normal blood calcium levels or tolerate hypocalcemia.
For children with sepsis or septic shock in a sick euthyroid state, we suggest against the routine use of levothyroxine in children with septic shock and other sepsis-associated organ dysfunction.
Certainty of evidence: Low
For children with sepsis or septic shock, we suggest against the use of vitamin C (ascorbic acid).
Certainty of evidence: Very low
For children with sepsis or septic shock, we suggest against the use of thiamine (vitamin B1).
Certainty of evidence: Very low
For children with sepsis or septic shock, we suggest against the acute repletion of vitamin D in the absence of clinical vitamin D insufficiency.
Certainty of evidence: Very low
It is reasonable to consider measures to prevent excessive fluid administration, monitor total fluid intake, and consider active fluid removal in case of fluid overload after hemodynamic stability is achieved and while closely monitoring hemodynamic changes to avoid compromising end-organ perfusion.
For children with sepsis or septic shock requiring renal replacement therapy, we suggest using high-volume hemofiltration (HVHF; > 35 mL/kg/hr) over standard-volume hemofiltration.
Certainty of evidence: Low
For children with sepsis or septic shock who meet criteria for the thrombocytopenia-associated multiple organ failure (TAMOF) subphenotype, there was insufficient evidence to issue a recommendation on whether to treat with plasma exchange (PLEX).
For children with sepsis or septic shock, there was insufficient evidence to issue a recommendation on the use of extracorporeal blood purification.
For children with sepsis or septic shock, we suggest using venovenous ECMO when refractory hypoxia is present despite other therapies.
Certainty of evidence: Very low
For children with septic shock, we suggest using venoarterial ECMO as a rescue therapy only if shock is refractory to all other treatments.
Certainty of evidence: Very low
For children with sepsis or septic shock, there was insufficient evidence to issue a recommendation on whether to taper or discontinue immunosuppressive therapies.
For children with sepsis or septic shock, we suggest against the routine use of IV immunoglobulin (IVIG).
Certainty of evidence: Low
For children with sepsis or septic shock with evidence of leukopenia or immunoparalysis, there was insufficient evidence to issue a recommendation on the use of an immune stimulant.
For children with sepsis or septic shock and hyperferritinemia, there was insufficient evidence to issue a recommendation on the use of immunosuppressive therapies.
For children with sepsis or septic shock, we suggest implementing an individualized, early rehabilitation bundle during the acute illness rather than not using a rehabilitation bundle.
Certainty of evidence: Very low
For children with sepsis or septic shock, there is insufficient evidence to recommend for or against targeted post-hospital follow-up.
For children who survive sepsis or septic shock, it is reasonable to: 1) assess risk factors for post-sepsis morbidity; 2) educate the patient, family, and clinicians on the symptoms of post-sepsis morbidity; and 3) evaluate for new, long-term sequelae after hospital discharge.
ECMO = extracorporeal membrane oxygenation.
A complete list of the guidelines authors and contributors is available within the published manuscript.