Mid-Regional Pro-Adrenomedullin in Combination With Pediatric Early Warning Scores for Risk Stratification of Febrile Children Presenting to the Emergency Department: Secondary Analysis of a Nonprespecified United Kingdom Cohort Study

Pediatr Crit Care Med. 2022 Dec 1;23(12):980-989. doi: 10.1097/PCC.0000000000003075. Epub 2022 Oct 14.

Abstract

Objectives: Current sepsis guidelines do not provide good risk stratification of subgroups in whom prompt IV antibiotics and fluid resuscitation might of benefit. We evaluated the utility of mid-regional pro-adrenomedullin (MR-proADM) in identification of patient subgroups at risk of requiring PICU or high-dependency unit (HDU) admission or fluid resuscitation.

Design: Secondary, nonprespecified analysis of prospectively collected dataset.

Setting: Pediatric Emergency Department in a United Kingdom tertiary center.

Patients: Children less than 16 years old presenting with fever and clinical indication for venous blood sampling ( n = 1,183).

Interventions: None.

Measurements and main results: Primary outcome measures were PICU/HDU admission or administration of fluid resuscitation, with a secondary outcome of definite or probable bacterial infection. Biomarkers were measured on stored plasma samples and children phenotyped into bacterial and viral groups using a previously published algorithm. Of the 1,183 cases, 146 children (12.3%) required fluids, 48 (4.1%) were admitted to the PICU/HDU, and 244 (20.6%) had definite or probable bacterial infection. Area under the receiver operating characteristic (AUC) was used to assess performance. MR-proADM better predicted fluid resuscitation (AUC, 0.73; 95% CI, 0.67-0.78), than both procalcitonin (AUC, 0.65; 95% CI, 0.59-0.71) and Pediatric Early Warning Score (PEWS: AUC, 0.62; 95% CI, 0.56-0.67). PEWS alone showed good accuracy for PICU/HDU admission 0.83 (0.78-0.89). Patient subgroups with high MR-proADM (≥ 0.7 nmol/L) and high procalcitonin (≥ 0.5 ng/mL) had increased association with PICU/HDU admission, fluid resuscitation, and bacterial infection compared with subgroups with low MR-proADM (< 0.7 nmol/L). For children with procalcitonin less than 0.5 ng/mL, high MR-proADM improved stratification for fluid resuscitation only.

Conclusions: High MR-proADM and high procalcitonin were associated with increased likelihood of subsequent disease progression. Incorporating MR-proADM into clinical risk stratification may be useful in clinician decision-making regarding initiation of IV antibiotics, fluid resuscitation, and escalation to PICU/HDU admission.

MeSH terms

  • Adolescent
  • Adrenomedullin / analysis
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Infections* / drug therapy
  • Biomarkers
  • Child
  • Cohort Studies
  • Early Warning Score*
  • Emergency Service, Hospital
  • Fever / diagnosis
  • Fever / drug therapy
  • Fever / etiology
  • Humans
  • Procalcitonin
  • Prognosis
  • Protein Precursors / analysis
  • Risk Assessment
  • United Kingdom

Substances

  • Adrenomedullin
  • Procalcitonin
  • Protein Precursors
  • Biomarkers
  • Anti-Bacterial Agents