Palliative Care Outcomes for Critically ill Children After Rapid Whole Genome Sequencing

Objectives: Clinical utility of rapid whole genome sequencing (rWGS) has been reported in 30-70% of pediatric ICU patients who receive a molecular diagnosis. Rapid molecular diagnostic techniques have been increasingly integrated into critical care, yet the influence of genetic test results on palliative care related decision making is largely unknown. This study evaluates palliative care related outcomes after rWGS.

Design: Retrospective chart review.

Setting: Tertiary children's hospital.

Patients: Acutely ill children $\le$ 18 years of age who received rWGS due to suspected genetic disease between July 2016 and November 2019.

Interventions: rWGS with associated precision medicine.

Measurements and main results: 536 patients underwent rWGS, of whom 152 (28.4%) received a molecular diagnosis. Diagnostic rWGS was associated with more code status modifications, an increase in palliative care inpatient consultations, and greater enrollment in home-based palliative services. A comparison of diagnostic and nondiagnostic rWGS groups where palliative decisions were made prior to reporting of genomic testing results did not identify differences between the groups. In the subset of patients who had palliative care interventions (n = 57, 53% with diagnostic rWGS), time to palliative care consultation and time to compassionate extubation were shorter for patients with rWGS-based diagnoses (Kaplan-Meier method, P = .008; P = .015). Significantly more patients in this subgroup with diagnostic rWGS received home-based palliative care (Chi-squared, P = .025, 95% CI [-0.47, -0.05]). Univariate Poisson regression indicated that diagnostic rWGS is associated with significantly fewer emergency visits, PICU admissions, and unplanned intubations.

Conclusions: Diagnostic rWGS correlates with more rapid engagement of pediatric palliative care services, higher enrollment rates in home-based palliative care, and shorter time to compassionate extubation. Further studies are needed with larger cohort sizes and validated pediatric palliative care outcome measurement tools to accurately determine if this change in care is driven by the underlying condition or knowledge of a molecular diagnosis.