Hyperoxia in pediatric severe traumatic brain injury (TBI): a comparison of patient classification by cutoff versus cumulative (area-under-the-curve) analysis

Abstract

Objective: Hyperoxia is associated with adverse outcome in severe traumatic brain injury (TBI). This study explored differences in patient classification of oxygen exposure by PaO 2 cutoff and cumulative areaunder-the-curve (AUC) analysis. Methods: Retrospective, explorative study including children (<18 years) with accidental severe TBI (2002-2015). Oxygen exposure analysis used three PaO 2 cutoff values and four PaO 2 AUC categories during the first 24 hours of Pediatric Intensive Care Unit (PICU) admission. Results: Seventy-one patients were included (median age 8.9 years [IQR 4.6-12.9]), mortality 18.3% (n = 13). Patient hyperoxia classification differed depending on PaO 2 cutoff vs AUC analysis: 52% vs. 26%, respectively, were classified in the highest hyperoxia category. Eleven patients (17%) classified as 'intermediate oxygen exposure' based on cumulative PaO 2 analysis whereby they did not exceed the 200 mmHg PaO2 cutoff threshold. Patient classification variability was reflected by Pearson correlation coefficient of 0.40 (p-value 0.001). Conclusions: Hyperoxia classification in pediatric severe TBI during the first 24 hours of PICU admission differed depending on PaO 2 cutoff or cumulative AUC analysis. We consider PaO 2 cumulative (AUC) better approximates (patho-)physiological circumstances due to its time-and dose-dependent approach. Prospective studies exploring the association between cumulative PaO 2 , physiological parameters (e.g. ICP, PbtO 2) and outcome are warranted as different patient classifications of oxygen exposure influences how its relationship to outcome is interpreted.

Association of Arterial Hyperoxia With Outcomes in Critically Ill Children

“…After the screening process, 16 studies, including 27 555 patients, remained (eFigure 1 in the Supplement ). 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 All included studies, except for 1 pilot randomized clinical trial, were observational (12 retrospective and 3 prospective). Study populations included were post–cardiac arrest (n = 6), traumatic brain injury (n = 1), ECMO (n = 2), and general critical care patients (n = 7).…”

“…Several measures were used to select Pa o 2 , but the highest value and the first value were the most common. Less common methods focused on cumulative exposure by grouping patients by the frequency of Pa o 2 values in the hyperoxic range (1 study 40 ) or by analyzing the area under the Pa o 2 to time relationship (3 studies 33 , 40 , 43 ).…”

“…29,42 Third, because hyperoxia-induced oxidative stress seems to be time-and dose-dependent, the assessment period of hyperoxia is also of importance. 33,40,46 Especially when periods exceeding initial admission day are taken into account, the cumulative exposure instead of a single maximum value may be a better representation of the degree of oxygen exposure. In this regard, one study showed that maximum PaO 2 correlated poorly to moderately with observed cumulative exposure, defined as the area under the PaO 2 to time relationship, over the first day of admission.…”

“…In this regard, one study showed that maximum PaO 2 correlated poorly to moderately with observed cumulative exposure, defined as the area under the PaO 2 to time relationship, over the first day of admission. 33 Another factor of importance is the primary outcome of the studies. Within this review, mortality (PICU and hospital) was the most frequently reported outcome among the studies.…”

“…Less common methods focused on cumulative exposure by grouping patients by the frequency of PaO 2 values in the hyperoxic range (1 study 40 ) or by analyzing the area under the PaO 2 to time relationship (3 studies 33,40,43 ).…”