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Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children

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Published: 2/10/2020

Ped Crit Care Med. 2020 Feb;21(2)e52-e106

Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children

Citation: Ped Crit Care Med. 2020 Feb;21(2)e52-e106

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Objectives:
To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction.

Design:
A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process.

Methods:
The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, “in our practice” statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate.

Results:
The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, “in our practice” statements were provided. In addition, 49 research priorities were identified.

Conclusions:
A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

Guideline Type: Clinical

Related Resources:

Translations

Visit survivingsepsis.org to find additional resources.

Category: Sepsis,

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In children who present as acutely unwell, we suggest implementing systematic screening for timely recognition of septic shock and other sepsis-associated organ dysfunction.
Quality of Evidence: Very low

Systematic screening needs to be tailored to the type of patients, resources, and procedures within each institution. Evaluation for the effectiveness and sustainability of screening should be incorporated as part of this process.

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. However, in our practice, if lactate levels can be rapidly obtained, we often measure blood lactate in children when evaluating for septic shock and other sepsis-associated organ dysfunction.

We recommend implementing a protocol/guideline for management of children with septic shock or other sepsis-associated organ dysfunction.

We recommend obtaining blood cultures before initiating antimicrobial therapy in situations where this does not substantially delay antimicrobial administration.

In children with septic shock, we recommend starting antimicrobial therapy as soon as possible, within 1 hour of recognition.
Quality of Evidence: Very low

In children with sepsis-associated organ dysfunction but without shock, we suggest starting antimicrobial therapy as soon as possible after appropriate evaluation, within 3 hours of recognition.
Quality of Evidence: Very low

We recommend empiric broad-spectrum therapy with one or more antimicrobials to cover all likely pathogens.

Once the pathogen(s) and sensitivities are available, we recommend narrowing empiric antimicrobial therapy coverage.

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.

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.
Quality of Evidence: Very low

In certain situations, such as confirmed or strongly suspected group B streptococcal sepsis, use of empiric multiple antimicrobials directed against the same pathogen for the purpose of synergy may be indicated.

In children with immune compromise and/or at high risk for multidrug-resistant pathogens, we suggest using empiric multi-drug therapy when septic shock or other sepsis-associated organ dysfunction is present/suspected.
Quality of Evidence: Very low

We recommend using antimicrobial dosing strategies that have been optimized based on published pharmacokinetic/ pharmacodynamic principles and with consideration of specific drug properties.

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.

This assessment should include a review of the ongoing indication for empiric antimicrobial therapy after the first 48 hours that is guided by microbiologic results and in response to clinical improvement and/or evidence of infection resolution. This recommendation applies to patients being treated with empiric, targeted, and combination therapy.

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.

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.

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.
Quality of Evidence: Low

In healthcare systems with availability of intensive care, we suggest administering up to 40–60mL/kg in bolus fluid (10–20mL/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.
Quality of Evidence: Low

In healthcare systems with no availability of intensive care and in the absence of hypotension, we recommend against bolus fluid administration while starting maintenance fluids.
Quality of Evidence: High

In healthcare systems with no availability of intensive care, if hypotension is present, we suggest administering up to 40mL/kg in bolus fluid (10–20mL/kg per bolus) over the first hour with titration to clinical markers of cardiac output and discontinued if signs of fluid overload develop.
Quality of Evidence: Low

Clinical markers of cardiac output may include heart rate, blood pressure, capillary refill time, level of consciousness, and urine output. In all settings, the need for fluid administration should be guided by frequent reassessment of clinical markers of cardiac output, serial blood lactate measurement and advanced monitoring, when available. Signs of fluid overload that should limit further fluid bolus therapy may include clinical signs of pulmonary edema or new or worsening hepatomegaly.

We suggest using crystalloids, rather than albumin, for the initial resuscitation of children with septic shock or other sepsis-associated organ dysfunction. 
Quality of Evidence: Moderate

Although there is no difference in outcomes, this recommendation takes into consideration cost and other barriers of administering albumin compared with crystalloids.

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.
Quality of Evidence: Very low

We recommend against using starches in the acute resuscitation of children with septic shock or other sepsisassociated organ dysfunction.
Quality of Evidence: Moderate

We suggest against using gelatin in the resuscitation of children with septic shock or other sepsis-associated organ dysfunction.
Quality of Evidence: Low

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”.
Quality of Evidence: Very low

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.
Quality of Evidence: Low

Advanced hemodynamic monitoring may include cardiac output/cardiac index, systemic vascular resistance, or central venous oxygen saturation (Scvo2).

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.
Quality of Evidence: Very low

In children with an elevated blood lactate, repeat testing that reveals a persistent elevation in blood lactate may indicate incomplete hemodynamic resuscitation and should prompt efforts, as needed, to further promote hemodynamic stability.

We suggest using epinephrine, rather than dopamine, in children with septic shock.
Quality of Evidence: Low

We suggest using norepinephrine, rather than dopamine, in children with septic shock.
Quality of Evidence: Very low

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.

It is reasonable to begin vasoactive infusions after 40–60mL/kg of fluid resuscitation if the patient continues to have evidence of abnormal perfusion, or sooner if fluid overload develops or other concerns for fluid administration are present. Either epinephrine or norepinephrine may be administered through a peripheral vein (or intraosseous, if in place) if central venous access is not readily accessible. Dopamine may be substituted as the first-line vasoactive infusion, administered either peripherally or centrally, if epinephrine or norepinephrine is not readily available.

We suggest either adding vasopressin or further titrating catecholamines in children with septic shock who require high-dose catecholamines.
Quality of Evidence: Low

No consensus was achieved on the optimal threshold for initiating vasopressin. Therefore, this decision should be made according to individual clinician preference.

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.

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.
Quality of Evidence: Low

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.
Quality of Evidence: Very low

When noninvasive mechanical ventilation is initiated, clinicians should carefully and frequently reevaluate the patient’s condition.

We suggest using high positive end-expiratory pressure (PEEP) in children with sepsis-induced PARDS. 
Quality of Evidence: Very low

The exact level of high PEEP has not been tested or determined in PARDS patients. Some RCTs and observational studies in PARDS have used and advocated for use of the ARDS-network PEEP to Fio2 grid though adverse hemodynamic effects of high PEEP may be more prominent in children with septic shock.

We cannot suggest for or against the use of recruitment maneuvers in children with sepsis-induced PARDS and refractory hypoxemia.

If a recruitment maneuver is considered, the use of a stepwise, incremental and decremental PEEP titration maneuver is preferred over sustained inflation techniques that have not been optimized through direct testing in PARDS patients. All PARDS patients must be carefully monitored for tolerance of the maneuver.

We suggest a trial of prone positioning in children with sepsis and severe PARDS.
Quality of Evidence: Low

Research trials in adults with ARDS and children with PARDS have emphasized prone positioning for at least 12 hours per day, as tolerated.

We recommend against the routine use of inhaled nitric oxide (iNO) in all children with sepsis-induced PARDS.
Quality of Evidence: Low

We suggest using iNO as a rescue therapy in children with sepsis-induced PARDS and refractory hypoxemia after other oxygenation strategies have been optimized.
Quality of Evidence: Moderate

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.
Quality of Evidence: Very low

The exact duration of neuromuscular blockade to use in severe PARDS patients has not been determined to date. Most of the adult RCT data and pediatric observational data support treatment for 24–48 hours after ARDS onset.

We suggest against using IV hydrocortisone to treat children with septic shock if fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability.
Quality of Evidence: Low

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.
Quality of Evidence: Low

We recommend against insulin therapy to maintain a blood glucose target at or below 140mg/dL (7.8 mmol/L).
Quality of Evidence: Moderate

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 180mg/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.
Quality of Evidence: Low

We suggest either antipyretic therapy or a permissive approach to fever in children with septic shock or other sepsis-associated organ dysfunction.
Quality of Evidence: Moderate

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.
Quality of Evidence: Low

Enteral feeding is not contraindicated in children with septic shock after adequate hemodynamic resuscitation who no longer require escalating doses of vasoactive agents or in whom weaning of vasoactive agents has started.

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.
Quality of Evidence: Moderate

We suggest against supplementation with specialized lipid emulsions in children with septic shock or other sepsis-associated organ dysfunction.
Quality of Evidence: Very low

We suggest against the routine measurements of gastric residual volumes (GRVs) in children with septic shock or other sepsis-associated organ dysfunction.
Quality of Evidence: Low

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.
Quality of Evidence: Low

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.
Quality of Evidence: Low

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.
Quality of Evidence: Low

We suggest against the use of arginine in the treatment of children with septic shock or other sepsis-associated organ dysfunction.
Quality of Evidence: Very low

We suggest against using zinc supplementation in children with septic shock and other sepsis-associated organ dysfunction.
Quality of Evidence: Very low

We suggest against the use of ascorbic acid (vitamin C) in the treatment of children with septic shock or other sepsis-associated organ dysfunction.
Quality of Evidence: Very low

We suggest against the use of thiamine to treat children with sepsis-associated organ dysfunction.
Quality of Evidence: Very low

We suggest against the acute repletion of vitamin D deficiency (VDD) for treatment of septic shock or other sepsis-associated organ dysfunction.
Quality of Evidence: Very low

We suggest against transfusion of RBCs if the blood hemoglobin concentration is greater than or equal to 7 g/dL in hemodynamically stabilized children with septic shock or other sepsis-associated organ dysfunction. 
Quality of Evidence: Low

According to the 2018 Transfusion and Anemia Expertise Initiative (TAXI) guidelines, for the purposes of RBC transfusion, “hemodynamically stabilized” is defined as a MAP higher than 2 sds below normal for age and no increase in vasoactive medications for at least 2 hours.

We cannot make a recommendation regarding hemoglobin transfusion thresholds for critically ill children with unstable septic shock.

We suggest against prophylactic platelet transfusion based solely on platelet levels in nonbleeding children with septic shock or other sepsis-associated organ dysfunction and thrombocytopenia.
Quality of Evidence: Very low

We suggest against prophylactic plasma transfusion in nonbleeding children with septic shock or other sepsisassociated organ dysfunction and coagulation abnormalities.
Quality of Evidence: Very low

Prophylactic plasma transfusion refers to situations in which there is an abnormality in laboratory coagulation testing but no active bleeding.

We suggest against the routine use of IV immune globulin (IVIG) in children with septic shock or other sepsisassociated organ dysfunction.
Quality of Evidence: Low

Although routine use of IVIG is not recommended, select patients may benefit from such treatment.

We suggest against using plasma exchange (PLEX) in children with septic shock or other sepsis-associated organ dysfunction without thrombocytopenia-associated multiple organ failure (TAMOF).
Quality of Evidence: Very low

We cannot suggest for or against the use of PLEX in children with septic shock or other sepsis-associated organ dysfunction with TAMOF.

We suggest using renal replacement therapy to prevent or treat fluid overload in children with septic shock or other sepsis-associated organ dysfunction who are unresponsive to fluid restriction and diuretic therapy.
Quality of Evidence: Low

We suggest against high-volume hemofiltration (HVHF) over standard hemofiltration in children with septic shock or other sepsis-associated organ dysfunction who are treated with renal replacement therapy.
Quality of Evidence: Low

We suggest using venovenous ECMO in children with sepsis-induced PARDS and refractory hypoxia.
Quality of Evidence: Very low

We suggest using venoarterial ECMO as a rescue therapy in children with septic shock only if refractory to all other treatments.
Quality of Evidence: Very low

We suggest against the routine use of stress ulcer prophylaxis in critically ill children with septic shock or other sepsis-associated organ dysfunction, except for highrisk patients.
Quality of Evidence: Very low

Although routine stress ulcer prophylaxis is not recommended, some high-risk patients may benefit from stress ulcer prophylaxis. Studies have supported benefit of stress ulcer prophylaxis when baseline rate of clinically important bleeding is approximately 13%.

We suggest against routine deep vein thrombosis (DVT) prophylaxis (mechanical or pharmacologic) in critically ill children with septic shock or other sepsis-associated organ dysfunction, but potential benefits may outweigh risks and costs in specific populations.
Quality of Evidence: Low

A complete list of the guidelines authors and contributors is available within the published manuscript.