Sepsis is a major cause of death and disability for children worldwide, particularly for those hospitalized in the U.S. In a retrospective cohort study of 3.9 million U.S. pediatric sepsis cases, sepsis occurred in 1.3% of pediatric hospitalizations, was associated with 10% mortality, and was present in 17.8% of hospitalizations that resulted in death.1 Nationally, this equates to more than 18,000 pediatric sepsis hospitalizations and 1,800 sepsis-related deaths each year.
Recent guidance, including the 2026 Surviving Sepsis Campaign International Guidelines, the 2025 Children’s Hospital Association’s Improving Pediatric Sepsis Outcomes (IPSO) Change Package, and the 2024 Society of Critical Care Medicine’s Phoenix Pediatric Sepsis Criteria, all emphasize early recognition and evidence-based management.2-5 Yet, pediatric sepsis remains challenging to identify and treat. No single tool or laboratory value definitively confirms pediatric sepsis; symptoms often mimic common childhood illnesses, and clinical deterioration can occur rapidly. While early pediatric sepsis is harder to recognize, it is easier to treat, whereas delayed recognition makes treatment more difficult.
These challenges highlight the importance of physician awareness of pediatric sepsis presentation and management, particularly in general pediatric care settings, where sepsis-attributable in-house mortality is higher than in cases originating in the emergency department (ED).6
Pediatric Sepsis Bundle—Impact on Morbidity and Mortality
Current evidence, guidelines, and expert consensus identify several key processes linked to improved outcomes for pediatric sepsis. These include early sepsis recognition (via use of a sepsis screen, sepsis huddle, or sepsis order set), restoration of intravascular volume via rapid fluid delivery, and timely parenteral antibiotic administration. These interventions are most effective when implemented together as a coordinated bundle of care. Completing all elements of the bundle within 180 minutes of sepsis onset has been shown to significantly reduce sepsis-attributable mortality and improve outcomes.7
Case Report
A previously healthy 9-year-old girl with fever (up to 105° F at home) and vomiting for three days is seen in the emergency department. She appears tired but interacts and answers questions appropriately. Her vital signs include: temperature at 103° F, respiratory rate of 32 breaths per minute, heart rate of 154 beats per minute, blood pressure at 87/45, oxygen saturations at 92% on room air, and normal perfusion.
Her white blood cell count is 27,000; chest radiography is normal without focal infiltrate; urinalysis shows more than 50 white blood cells, positive nitrite and leukocyte esterase. No lactate or blood cultures are obtained.
On arrival to the ED, clinical suspicion for sepsis was high; rapid treatment was initiated, including IV fluid resuscitation. Due to the patient’s blood pressure and persistent tachycardia, she was given an extra 20 mL/kg of 0.9% saline while a transfer request was made. As there was no pediatric intensive care unit (PICU) on site, it was recommended that she transition to maintenance IV fluids and be transferred to higher-level care. Recalling the 2026 Surviving Sepsis Guideline Updates lists a preference for balanced or buffered crystalloid fluids such as lactated Ringer’s (LR) due to a lower incidence of progressive acute kidney injury in large, randomized trials, LR was initiated.5 As a healthy child with no immune compromise or significant risk factors for multidrug-resistant organisms, she received IV ceftriaxone single coverage. Based on initial laboratory results, this was targeted therapy within three hours for the most likely source of her presumed sepsis.
Sepsis Pathophysiology
Sepsis causes widespread dysregulation within the body in response to an infection. It is driven by immune dysregulation, cytokine storm, endothelial dysfunction, capillary leak, coagulopathy, immunothrombosis, impaired tissue perfusion, and cellular injury, which can progress to shock and multiorgan disease states.6 The patient’s clinical presentation and hemodynamic instability are highly suggestive of septic shock in the setting of pyelonephritis.
Evidence-Based Practice
This case highlights opportunities to align current guidelines with 2026 updates (see Table 1). Notably missing in this case: obtaining lactate and blood cultures, utilizing buffered solutions, like LR, instead of 0.9% saline for initial and subsequent fluid management.
PICU-Level Care for Sepsis
Once transferred to PICU, the emphasis shifts from initial recognition to titrated resuscitation, and several 2026 updates give PICU clinicians clearer guardrails.2 Fluid boluses should be delivered in 10 to 20 mL/kg increments, reassessing hemodynamic status after each one, and up to 60 mL/kg in the first hour where intensive care is available. Non-ICU settings are capped lower, at 40 mL/kg. A useful note for referring teams: if a child is approaching that volume and still shows signs of shock, this is the point to actively arrange PICU transfer rather than continue bedside boluses.
Throughout resuscitation, clinicians should watch for signs of volume overload, pulmonary edema, or new or worsening hepatomegaly, and stop boluses if they appear. Should overload develop, the 2026 updates newly endorse an active approach to fluid balance, including fluid restriction, diuretics, and renal replacement therapy in refractory cases, rather than waiting for it to resolve passively. Cardiac and lung point-of-care ultrasound is particularly useful at this stage to distinguish ongoing hypovolemia from evolving cardiac dysfunction or fluid overload, directly informing whether the next step should be more fluid, a vasoactive agent, or diuresis.
For children who remain in shock despite fluid resuscitation, the guideline offers a practical shift on vasoactive access: initiate vasoactive medications through peripheral IV access rather than delaying therapy for central line placement.2,6 A meta-analysis of six observational studies (709 children) showed reduced mortality with peripheral initiation (relative risk, 0.45) and a low extravasation risk (2.5%), concentrated in distal sites like the hand. This matters most in the ED or pre-PICU environment, where central venous catheter (CVC) placement can meaningfully delay time to vasoactive support; a peripheral intravenous line, ideally proximal, should not hold up therapy. Corticosteroids remain an area of restraint rather than routine use: the panel recommends against IV hydrocortisone when hemodynamic stability can be restored with fluids and vasoactive medications alone, and there is insufficient evidence to guide steroid use in children who remain unstable despite adequate fluid and vasoactive therapy.8 Stress-dose hydrocortisone is still appropriate, but specifically for suspected or confirmed adrenal insufficiency, not as an empiric adjunct to refractory shock.
For our patient, once septic shock in the setting of pyelonephritis was confirmed, empiric ceftriaxone was appropriately continued without broadening, consistent with the guideline’s position that multidrug empiric coverage should be reserved for immunocompromised children or those at high risk for multidrug-resistant organisms, neither of which applied here.5 Should a bloodstream infection have been confirmed, infectious disease consultation would be recommended, though this remains specific to documented bacteremia rather than sepsis broadly. Equally relevant for stewardship: the panel recommends against routinely using procalcitonin to guide antibiotic de-escalation in centers with effective stewardship programs already in place, since two pediatric, randomized, controlled trials showed no benefit in mortality or antibiotic duration over usual care. It is not a substitute for stewardship infrastructure, and absent that infrastructure, its value is unproven. Finally, for children progressing to respiratory failure requiring mechanical ventilation, the 2026 update supports a conservative oxygenation target of SpO2 88% to 92% over a more liberal target above 94%, based on more organ-support-free days without a signal for harm, a meaningful departure from reflexive high-oxygen strategies still common in general pediatric and even some intensive care unit settings.5
Conclusion
Pediatric sepsis remains a leading medical burden and cause of morbidity and mortality with short- and long-term risks. Early identification and effective early intervention remain key to successful management. Opportunities are identified in the 2026 updated sepsis guidelines to improve outcomes and compliance. Integration of these validated bundled recommendations reduces the morbidity and mortality of sepsis.
Dr. Thompkins
Ms. Leyland
Ms. Raynor
Dr. Sebring
Dr. Reed
Dr. Thompkins is a pediatric hospitalist with Atrium Health Levine Children’s Hospital in Charlotte, N.C., and Jeff Gordon’s Children’s Center in Concord, N.C. Ms. Leyland is a pediatric nurse practitioner in acute care at Levine Children’s Hospital in Charlotte, N.C. Ms. Raynor is a clinical nurse specialist at Atrium Health Levine Children’s Hospital in Charlotte, N.C., and served as a facility nursing representative and collaborative investigator with the Children’s Hospital Association’s Improving Pediatric Sepsis Outcomes Collaborative. Dr. Sebring is a pediatric critical care physician at Atrium Health Levine Children’s Hospital in Charlotte, N.C., the director and site clinical lead for the Improving Pediatric Sepsis Outcomes Collaborative, and co-director of the Levine Children’s Hospital Pediatric Residency Simulation Course. Dr. Reed is pediatric hospital medicine faculty, pediatric hospital medicine site director, and medical director of the nation’s first comprehensive pediatric hospital at home program at Levine Children’s Hospital in Charlotte, N.C. She is also an assistant professor of pediatrics at Wake Forest University School of Medicine in Winston-Salem, N.C.
References
- Rhee C, et al. National estimates of pediatric sepsis in US hospitals using clinical data. JAMA. 2026;335(15):1321-1331. https://doi.org/10.1001/jama.2026.3100. Erratum in: JAMA. 2026;335(24):2170. https://doi.org/10.1001/jama.2026.8941.
- Prescott HC, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2026. Crit Care Med. 2026;54(4):725-812. https://doi.org/10.1097/CCM.0000000000007075.
- Buckwalter E, et al. Improving pediatric sepsis outcomes change package. Children’s Hospital Association website. https://sepsis.childrenshospitals.org/change-package/. Published 2025. Accessed September 1, 2026.
- Sanchez-Pinto LN, et al. Development and validation of the Phoenix criteria for pediatric sepsis and septic shock. JAMA. 2024;331(8):675-686. https://doi.org/10.1001/jama.2024.0196.
- Weiss SL, et al. Surviving sepsis campaign international guidelines for the management of sepsis and septic shock in children 2026. Pediatr Crit Care Med. 2026;27(4):379-434. https://doi.org/10.1097/PCC.0000000000003927.
- Schafer M, et al. Characteristics and outcomes of sepsis presenting in inpatient pediatric settings. Hosp Pediatr. 2022;12(12):1048-1059. https://doi.org/10.1542/hpeds.2022-006592.
- Paul R, et al. Bundled care to reduce sepsis mortality: the improving pediatric sepsis outcomes (IPSO) collaborative. Pediatrics. 2023;152(2):e2022059938. https://doi.org/10.1542/peds.2022-059938.
- Jarczak D, et al. Sepsis—pathophysiology and therapeutic concepts. Front Med (Lausanne). 2021;8:628302. https://doi.org/10.3389/fmed.2021.628302.