CLINICAL CHARACTERISTICS AND OUTCOMES OF CHILDREN WITH ACUTE CATASTROPHIC BRAIN INJURY: A 13-YEAR RETROSPECTIVE COHORT STUDY and HEART RATE CHANGE AS A POTENTIAL DIGITAL BIOMARKER OF BRAIN DEATH IN CRITICALLY ILL CHILDREN WITH ACUTE CATASTROPHIC BRAIN INJURY
CLEAN MERGED_Thesis Dissertation Document_LaRovere_May 4 2022 copy.pdf (1.840Mb)
Access StatusFull text of the requested work is not available in DASH at this time ("dark deposit"). For more information on dark deposits, see our FAQ.
LaRovere, Kerri Lynn
MetadataShow full item record
CitationLaRovere, Kerri Lynn. 2022. CLINICAL CHARACTERISTICS AND OUTCOMES OF CHILDREN WITH ACUTE CATASTROPHIC BRAIN INJURY: A 13-YEAR RETROSPECTIVE COHORT STUDY and HEART RATE CHANGE AS A POTENTIAL DIGITAL BIOMARKER OF BRAIN DEATH IN CRITICALLY ILL CHILDREN WITH ACUTE CATASTROPHIC BRAIN INJURY. Master's thesis, Harvard Medical School.
AbstractABSTRACT (Manuscript 1)
Background & Purpose: To describe and analyze clinical characteristics and outcomes in children with acute catastrophic brain injury (CBI).
Methods: Single center, 13-year (2008-2020) retrospective cohort study of children in the pediatric and cardiac intensive care units (ICUs) with CBI, defined as 1) acute neurologic injury based on clinical and/or imaging findings; 2) need for life-sustaining ICU therapies; and 3) death or survival with GCS 13 at discharge. Patients were excluded if they were discharged directly to home 14 days from admission or had a chronic neurologic condition with baseline GCS 13. The association between the primary outcome of death and clinical variables was analyzed using Kaplan-Meier estimates and multivariable Cox proportional hazard models. Outcomes assessed after discharge were technology dependence, neurologic deficits and Functional Status Score (FSS). Improved functional status was defined as change in total FSS ≥ 2.
Results: Of 106 patients (58% male, median age 3.9 years) with CBI, 86 (81%) died. Withdrawal of life-sustaining therapies (WOLST) was the most common mode of death (60/86, 70%). In multivariable analysis, each unit increase in admission pediatric sequential organ failure assessment (pSOFA) score was associated with 10% greater hazard of death (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.04–1.17, p.01). Controlling for admission pSOFA score, compared with traumatic brain injury (TBI), all other etiologies of CBI were associated with greater hazard of death (p = 0.02; HR 3.76 – 10). Median survival time for the cohort was 22 days (95% CI 14 – 37 days). Of 23 survivors to hospital discharge, 20 were still alive after median 2 years (IQR 1–3 years), 6/20 (30%) did not have any technology dependence, 12/20 (60%) regained normal level of alertness and responsiveness, and 15/20 (75%) had improved functional status.
Conclusions: Most children with acute CBI died within one month of hospitalization. TBI as the etiology of CBI was associated with greater survival, whereas increased organ dysfunction score on admission was associated with higher hazard of mortality. Of survivors, some recovered consciousness and functional status and did not require permanent technology dependence. Larger, prospective studies are needed to improve prediction of CBI among critically ill children, understand factors guiding clinician and family decisions on continuation or withdrawal of life sustaining treatments, and characterize the natural history and long-term outcomes among CBI survivors.
ABSTRACT (Manuscript 2)
Objective: To determine whether heart rate (HR) change (HRC), calculated using numeric heart rate measurements sampled every 5 seconds, can identify patients with brain death (BD) among patients with catastrophic brain injury (CBI). Methods: Single-center, retrospective study (2008-2020) of children in intensive care unit with acute CBI. HRC was calculated as IQR of HR/median HR using 5-minute windows with 50% overlap for up to 5 days before death or end of recording. Patients meeting BD criteria (BD group) were compared to those with cardiopulmonary death and reactive pupils (CD group), or survived to discharge. Results: Of 96 patients with CBI (69% male, median age 4 years), 28 died (8 BD, 20 CD) and 20 survived (median GCS 9 at discharge). Within 24 hours before death, HRC was lower in BD compared to CD patients or survivors (0.01 vs. 0.03 vs. 0.04, p=0.001). In BD patients, HRC decreased at least 1 day prior to death. HRC discriminated BD from CD patients and survivors with 90% sensitivity, 70% specificity, 44% PPV, 96% NPV (AUROC 0.88, 95% confidence interval 0.80 – 0.93). Conclusion: HRC is a novel digital biomarker that, with further validation, may be useful as a screening test in pediatric BD.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37371561