Guidelines on management of sepsis and associated organ dysfunction in children
Ventilation
· We were unable to issue a recommendation about whether to intubate children with fluid-refractory, catecholamine-resistant septic shock. However, in our practice, we commonly intubate children with fluid-refractory, catecholamine-resistant septic shock without respiratory failure.
· We suggest not to use etomidate when intubating children with septic shock or other sepsis-associated organ dysfunction.
· We suggest a trial of noninvasive mechanical ventilation (over invasive mechanical ventilation) in children with sepsis-induced pediatric ARDS (PARDS) without a clear indication for intubation and who are responding to initial resuscitation.
· We suggest using high positive end-expiratory pressure (PEEP) in children with sepsis-induced PARDS.
· We cannot suggest for or against the use of recruitment maneuvers in children with sepsis-induced PARDS and refractory hypoxemia.
· We suggest a trial of prone positioning in children with sepsis and severe PARDS.
· We recommend against the routine use of inhaled nitric oxide (iNO) in all children with sepsis-induced PARDS.
· We suggest using iNO as a rescue therapy in children with sepsis-induced PARDS and refractory hypoxemia after other oxygenation strategies have been optimized.
· We were unable to issue a recommendation to use high-frequency oscillatory ventilation (HFOV) versus conventional ventilation in children with sepsis-induced PARDS. However, in our practice, there is no preference to use or not use HFOV in patients with severe PARDS and refractory hypoxia.
· We suggest using neuromuscular blockade in children with sepsis and severe PARDS.
Corticosteroids
· We suggest against using IV hydrocortisone to treat children with septic shock if fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability.
· We suggest that either IV hydrocortisone or no hydrocortisone may be used if adequate fluid resuscitation and vasopressor therapy are not able to restore hemodynamic stability.
Endocrine and Metabolic
· We recommend against insulin therapy to maintain a blood glucose target at or below 140 mg/dL (7.8 mmol/L).
· We were unable to issue a recommendation regarding what blood glucose range to target for children with septic shock or other sepsis-associated organ dysfunction. However, in our practice, there was consensus to target blood glucose levels below 180 mg/dL (10 mmol/L) but there was not consensus about the lower limit of the target range.
· We were unable to issue a recommendation as to whether to target normal blood calcium levels in children with septic shock or sepsis-associated organ dysfunction. However, in our practice, we often target normal calcium levels for children with septic shock requiring vasoactive infusion support.
· We suggest against the routine use of levothyroxine in children with septic shock and other sepsis-associated organ dysfunction in a sick euthyroid state.
· We suggest either antipyretic therapy or a permissive approach to fever in children with septic shock or other sepsis-associated organ dysfunction.
Nutrition
· We were unable to issue a recommendation regarding early hypocaloric/trophic enteral feeding followed by slow increase to full enteral feeding versus early full enteral feeding in children with septic shock or sepsis-associated organ dysfunction without contraindications to enteral feeding. However, in our practice, there is a preference to commence early enteral nutrition within 48 hours of admission in children with septic shock or sepsis-associated organ dysfunction who have no contraindications to enteral nutrition and to increase enteral nutrition in a stepwise fashion until nutritional goals are met.
· We suggest not withholding enteral feeding solely on the basis of vasoactive-inotropic medication administration.
· We suggest enteral nutrition as the preferred method of feeding and that parenteral nutrition may be withheld in the first 7 days of PICU admission in children with septic shock or other sepsis-associated organ dysfunction.
· We suggest against supplementation with specialized lipid emulsions in children with septic shock or other sepsis-associated organ dysfunction.
· We suggest against the routine measurements of gastric residual volumes (GRVs) in children with septic shock or other sepsis-associated organ dysfunction.
· We suggest administering enteral feeds through a gastric tube, rather than a postpyloric feeding tube, to children with septic shock or other sepsis-associated organ dysfunction who have no contraindications to enteral feeding
· We suggest against the routine use of prokinetic agents for the treatment of feeding intolerance in children with septic shock or other sepsis-associated organ dysfunction.
· We suggest against the use of selenium in children with septic shock or other sepsis-associated organ dysfunction.
· We suggest against the use of glutamine supplementation in children with septic shock or other sepsis-associated organ dysfunction.
· We suggest against the use of arginine in the treatment of children with septic shock or other sepsis-associated organ dysfunction.
· We suggest against using zinc supplementation in children with septic shock and other sepsis-associated organ dysfunction.
· We suggest against the use of ascorbic acid (vitamin C) in the treatment of children with septic shock or other sepsis-associated organ dysfunction.
· We suggest against the use of thiamine to treat children with sepsis-associated organ dysfunction.
Delhi: A panel of 49 international experts, representing 12 international organizations provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. These recommendations provide a foundation for consistent care to improve outcomes and inform future research.
Sepsis is a leading cause of morbidity, mortality, and healthcare utilization for children worldwide. Globally, an estimated 22 cases of childhood sepsis per 100,000 person-years and 2,202 cases of neonatal sepsis per 100,000 live births occur, translating into 1.2 million cases of childhood sepsis per year. More than 4% of all hospitalized patients less than 18 years and ~8% of patients admitted to PICUs in high-income countries have sepsis (2–6).
Mortality for children with sepsis ranges from 4% to as high as 50%, depending on illness severity, risk factors, and geographic location (2,3,7–9). The majority of children who die of sepsis suffer from refractory shock and/or multiple organ dysfunction syndrome, with many deaths occurring within the initial 48 to 72 hours of treatment (10–13). Early identification and appropriate resuscitation and management are therefore critical to optimizing outcomes for children with sepsis.
Screening, Diagnosis, and Systematic Management of Sepsis
· In children who present as acutely unwell, we suggest implementing systematic screening for timely recognition of septic shock and other sepsis-associated organ dysfunction.
· We were unable to issue a recommendation about using blood lactate values to stratify children with suspected septic shock or other sepsis-associated organ dysfunction into low- versus high-risk of having septic shock or sepsis.
· We recommend implementing a protocol/guideline for management of children with septic shock or other sepsis-associated organ dysfunction (BPS).
· We recommend obtaining blood cultures before initiating antimicrobial therapy in situations where this does not substantially delay antimicrobial administration (BPS).
· In children with septic shock, we recommend starting antimicrobial therapy, within 1 hour of recognition.
· In children with sepsis-associated organ dysfunction but without shock, we suggest starting antimicrobial therapy after appropriate evaluation, within 3 hours of recognition.
· We recommend empiric broad-spectrum therapy with one or more antimicrobials to cover all likely pathogens (BPS).
· Once the pathogen(s) and sensitivities are available, we recommend narrowing empiric antimicrobial therapy coverage (BPS).
· If no pathogen is identified, we recommend narrowing or stopping 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 (BPS).
· In children without immune compromise and without high risk for multidrug-resistant pathogens, we suggest against the routine use of empiric multiple antimicrobials directed against the same pathogen for the purpose of synergy.
· In children with immune compromise and/or at high risk for multidrug-resistant pathogens, we suggest using empirically multi-drug therapy when septic shock or other sepsis-associated organ dysfunction is present/suspected.
· We recommend using antimicrobial dosing strategies that have been optimized based on published pharmacokinetic/pharmacodynamic principles and with consideration of specific drug properties (BPS).
· In children with septic shock or sepsis-associated organ dysfunction who are receiving antimicrobials, we recommend daily assessment (e.g., clinical, laboratory assessment) for de-escalation of antimicrobial therapy (BPS).
· We recommend determining the duration of antimicrobial therapy according to the site of infection, microbial etiology, response to treatment, and ability to achieve source control (BPS).
· We recommend that emergent source control intervention be implemented as soon possible after a diagnosis of an infection amenable to a source control procedure is made (BPS).
Source Control
· We recommend that emergent source control intervention be implemented as soon possible after a diagnosis of an infection amenable to a source control procedure is made (BPS).
· 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.
Fluid Therapy
· In healthcare systems with availability of intensive care, we suggest administering up to 40–60 mL/kg in bolus fluid (10–20 mL/kg per bolus) over the first hour, titrated to clinical markers of cardiac output and discontinued if signs of fluid overload develop, for the initial resuscitation of children with septic shock or other sepsis-associated organ dysfunction.
· In healthcare systems with no availability of intensive care and , we recommend against bolus fluid administration while starting maintenance fluids
· In healthcare systems with no availability of intensive care, we suggest administering up to 40 mL/kg in bolus fluid (10–20 mL/kg per bolus) over the first hour with titration to clinical markers of cardiac output and discontinued if signs of fluid overload develop.
· We suggest using crystalloids, rather than albumin, for the initial resuscitation of children with septic shock or other sepsis-associated organ dysfunction.
· We suggest using balanced/buffered crystalloids, rather than 0.9% saline, for the initial resuscitation of children with septic shock or other sepsis-associated organ dysfunction.
· We recommend against using starches in the acute resuscitation of children with septic shock or other sepsis-associated organ dysfunction.
· We suggest against using gelatin in the resuscitation of children with septic shock or other sepsis-associated organ dysfunction.
Hemodynamic Monitoring
· We were unable to issue a recommendation about whether to target mean arterial blood pressure (MAP) at the 5th or 50th percentile for age in children with septic shock and other sepsis-associated organ dysfunction. However, in our practice, we target MAP to between the 5th and 50th percentile or greater than 50th percentile for age.
· We suggest not using bedside clinical signs in isolation to categorize septic shock in children as "warm" or "cold."
· We suggest using advanced hemodynamic variables, when available, in addition to bedside clinical variables to guide the resuscitation of children with septic shock or other sepsis-associated organ dysfunction.
· We suggest using trends in blood lactate levels, in addition to clinical assessment, to guide resuscitation of children with septic shock and other sepsis-associated organ dysfunction.
Vasoactive Medications
· We suggest using epinephrine, rather than dopamine, in children with septic shock.
· We suggest using norepinephrine, rather than dopamine, in children with septic shock.
· We were unable to issue a recommendation for a specific first-line vasoactive infusion for children with septic shock. However, in our practice, we select either epinephrine or norepinephrine as the first-line vasoactive infusion guided by clinician preference, individual patient physiology, and local system factors.
· We were unable to issue a recommendation about initiating vasoactive agents through peripheral access in children with septic shock. However, in our practice, we often or sometimes administer a dilute concentration of the initial vasoactive medication through a peripheral vein if central venous access is not readily accessible.
· We suggest either adding vasopressin or further titrating catecholamines in children with septic shock who require high-dose catecholamines.
· We were unable to issue a recommendation about adding an inodilator in children with septic shock and cardiac dysfunction despite other vasoactive agents. However, in our practice, we sometimes use inodilators in children with septic shock and evidence of persistent hypoperfusion and cardiac dysfunction despite other vasoactive agents.
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