Prevalence of and Associations With Avascular Necrosis After Pediatric Sepsis: A Single-Center Retrospective Study.

OBJECTIVES: Avascular necrosis (AVN) is a rare, but serious, complication after sepsis in adults. We sought to determine if sepsis is associated with postillness diagnosis of AVN, as well as potential-associated risk factors for AVN in children with sepsis. DESIGN: Retrospective observational study. SETTING: Single academic children's hospital. PATIENTS: Patients less than 18 years treated for sepsis or suspected bacterial infection from 2011 to 2017. Patients who developed AVN within 3 years after sepsis were compared with patients who developed AVN after suspected bacterial infection and with patients with sepsis who did not develop AVN. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: AVN was determined using International Classification of Diseases, 9th Edition/10th Edition codes and confirmed by chart review. The prevalence of AVN after sepsis was 0.73% (21/2,883) and after suspected bacterial infection was 0.43% (53/12,276; risk difference, 0.30; 95% CI, 0.0-0.63; p = 0.05). Compared with 43 sepsis controls without AVN, AVN in the 21 sepsis cases was associated with being older, having sickle cell disease and malignancy, higher body mass index, unknown source of infection, and low platelet count in the first 7 days of sepsis. Half of sepsis patients were treated with corticosteroids, and higher median cumulative dose of steroids was associated with AVN (23.2 vs 5.4 mg/kg; p < 0.01). Older age at infection (odds ratio [OR], 1.3; 95% CI, 1.1-1.4), malignancy (OR, 8.8; 95% CI, 2.6-32.9), unknown site of infection (OR, 12.7; 95% CI, 3.3-48.6), and minimal platelet count less than 100,000/µL in first 7 days of sepsis (OR, 5.0; 95% CI, 1.6-15.4) were identified as potential risk factors for AVN after sepsis following adjustment for multiple comparisons. CONCLUSIONS: Although rare, sepsis was associated with a higher risk of subsequent AVN than suspected bacterial infection in children. Older age, malignancy, unknown site of infection, and minimum platelet count were potential risk factors for AVN after sepsis.

PRagMatic Pediatric Trial of Balanced vs nOrmaL Saline FlUid in Sepsis: study protocol for the PRoMPT BOLUS randomized interventional trial.

BACKGROUND/AIMS: Despite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock. METHODS: The Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to < 18 years treated for suspected septic shock with abnormal perfusion in an emergency department will be randomized to receive either balanced/buffered crystalloids (intervention) or 0.9% saline (control) for initial resuscitation and maintenance fluids for up to 48 h. Eligible patients are enrolled and randomized using serially numbered, opaque envelopes concurrent with clinical care. Given the life-threatening nature of septic shock and narrow therapeutic window to start fluid resuscitation, patients may be enrolled under "exception from informed consent" in the USA or "deferred consent" in Canada and Australia/New Zealand. Other than fluid type, all decisions about timing, volume, and rate of fluid administration remain at the discretion of the treating clinicians. For pragmatic reasons, clinicians will not be blinded to study fluid type. Anticipated enrollment is 8800 patients. The primary outcome will be major adverse kidney events within 30 days (MAKE30), a composite of death, renal replacement therapy, and persistent kidney dysfunction. Additional effectiveness, safety, and biologic outcomes will also be analyzed. DISCUSSION: PRoMPT BOLUS will provide high-quality evidence for the comparative effectiveness of buffered/balanced crystalloids versus 0.9% saline for the initial fluid management of children with suspected septic shock in emergency settings. TRIAL REGISTRATION: PRoMPT BOLUS was first registered at ClinicalTrials.gov ( NCT04102371 ) on September 25, 2019. Enrollment started on August 25, 2020.