Dynamic versus fixed cerebral perfusion pressure targets in paediatric traumatic brain injury: a STARSHIP analysis

Abstract

Background: Cerebral perfusion pressure (CPP) represents a key target for intensive care management of paediatric traumatic brain injury (TBI) patients. Current guidelines recommend a CPP target within the range of 40-50 mmHg but emphasise that these may depend on patient age and the state of cerebrovascular autoregulation. In this analysis, we aimed to compare the fixed targets proposed by the Brain Trauma Foundation to autoregulation-based targets CPPopt (optimal CPP) and LLA (Lower Limit of Autoregulation).

Methods: Data were acquired from the STARSHIP study (a prospective, multicentre, observational, research study which enrolled 135 children (median age 96 months (interquartile range 26-152 months)) with TBI between July 2018 and March 2023 across 10 paediatric intensive care units in the UK). In this secondary analysis the dose or percentage time spent below a fixed CPP target of 50 mmHg or CPPopt or LLA (assessed continuously on a minute-by-minute basis and derived by fitting a curve to the relationship between CPP and pressure reactivity index values, as previously described) was compared by outcome using univariable and multivariable methods. ClinicalTrials.gov registration-NCT0688462.

Findings: When assessed within ordinal analyses (to account for differences in baseline severity), both hourly dose and percentage time spent below LLA (odds ratio 1.01 [95% CI 1.00-1.02], p = 0.017 and 1.05 [95% CI 1.01-1.08], p = 0.008 respectively) were independently associated with worse outcomes. LLA displayed a dynamic time-trend increasing over time in patients with unfavourable outcome (n = 44, p = 0.003). Overall, LLA exceeded 50 mmHg for more than 45% of the monitoring period across all patients, and for over 35% of the time in the youngest cohort (0-2 years).

Interpretation: Dynamic autoregulation monitoring based on LLA was associated with outcomes in paediatric TBI with higher LLA values observed in individuals experiencing unfavourable outcomes. Our findings indicate that the current fixed CPP threshold of 40-50 mmHg may be too low-highlighting the need for further investigation into autoregulation-guided CPP targets. Whether personalised management based on autoregulatory-informed thresholds offers advantages over guideline-based targets remains to be determined and should be investigated in future prospective interventional studies.

Funding: Action Medical Research for Childrens' Charity and Addenbrookes Charitable Trust (UK Grant number-GN2609).

Keywords: Cerebral perfusion pressure; Cerebrovascular autoregulation; Intensive care management; Multimodality neuromonitoring; Paediatric traumatic brain injury.

Fig. 1

Flowchart of participant recruitment and data inclusion. A total of 165 individuals were evaluated for inclusion, of whom 153 provided consent. Eighteen participants were excluded due to missing data (n = 11) or other reasons (n = 7), resulting in a final recruited cohort of 135. Twelve-month follow-up was incomplete for 11 individuals, yielding a final sample of 124 for the research database. The map illustrates the geographical distribution of participating centres across the United Kingdom (green circles).

Fig. 2

Example of optimal CPP (CPPopt) and lower limit of autoregulation (LLA) calculation. An example 8 h section of multimodality monitoring data is shown. On top the minute-by-minute ABP and CPP time trends are shown. Superimposed are the dynamic CPPopt (blue) and LLA (pink) time-trends which are estimated every minute considering the last 2–8 h of data. Below, the minute-by-minute ICP are shown. On the bottom, the overall relationship between CPP and PRx (considering the full data) is shown. When considering the overall data, CPPopt is around 67 mmHg, while the LLA is around 57 mmHg. The example also allows to visualise the different derived metrics. Specifically, the overall dose represents the area under the curve, calculated as the cumulative deviation from the target CPP when actual CPP falls below this threshold. The hourly dose is defined as the overall dose divided by the total duration of monitoring, whereas percentage time refers to the proportion of monitoring time during which the actual CPP remains below the predefined target.

Fig. 3

LLA over time for unfavourable and favourable outcome groups. When modelled using a linear mixed effects model including the patient as a random effect, there was a significant interaction between the level of LLA and day with a larger increase over time for patients with worse outcome (p = 0.003). Coloured ribbons represent the 95% confidence interval.

Fig. 4

The mean LLA distribution for each age group. Current guidelines recommend a CPP target between 40 and 50 mmHg, and hence a red vertical 50 mmHg reference line is shown. For each age group, the percentage of LLAs above this 50 mmHg line is reported. The cohort's median LLA was 50 mmHg (IQR 45–54), 51 mmHg (IQR 46–56), 53 mmHg (IQR 47–60) for the patients aged 0–2, 2–8, and above 8 respectively (p < 0.001).

Fig. 5

The receiver operating characteristics curves show the predictive benefit of LLA derived measures, over and above clinical metrics. The receiver operating characteristics curves for the different models is displayed, with models including only the clinical parameters (red), clinical parameters with the hourly dose of cerebral perfusion pressure below the lower limit of autoregulation (green), and clinical parameters with the percentage time of cerebral perfusion pressure below the lower limit of autoregulation (blue).