Validation of Pressure Reactivity and Pulse Amplitude Indices against the Lower Limit of Autoregulation, Part I: Experimental Intracranial Hypertension.

Abstract

To provide validation of intracranial pressure (ICP) derived continuous indices of cerebrovascular reactivity against the lower limit of autoregulation (LLA). Utilizing an intra-cranial hypertension model within white New Zealand rabbits, ICP, TCD, laser Doppler flowmetry (LDF) and arterial blood pressure were recorded. Data was retrospectively analyzed in a cohort of 12 rabbits with adequate signals for interrogating the LLA. We derived continuous indices of cerebrovascular reactivity: PRx (correlation between ICP and mean arterial pressure (MAP)), PAx (correlation between pulse amplitude of ICP (AMP) and MAP), and Lx (correlation between LDF based cerebral blood flow (CBF) and CPP). LLA was derived via piecewise linear regression of CPP vs. LDF or CPP vs. FVs plots. We then produced error bar plots for PRx, PAx, and Lx against 2.5 mm Hg bins of CPP, to display the relationship between these indices and the LLA. We compared the CPP values at clinically relevant thresholds of PRx and PAx, to the CPP defined at the LLA. ROC analysis was performed for each index across the LLA using 2.5 mm Hg bins for CPP. The mean LLA was 51.5 +/- 8.2 mm Hg. PRx and PAx error bar plots demonstrate that each index correlates with the LLA, becoming progressively more positive below the LLA. Similarly, CPP values at clinically relevant thresholds of PRx and PAx, were not statistically different from the CPP derived at the LLA. Finally, ROC analysis indicated that PRx and PAx predicted the LAA, with AUC’s 0.795 (95% CI: 0.731 – 0.857, p<0.0001), 0.703 (95% CI: 0.631 – 0.775, p<0.0001), respectively. Both PRx and PAx generally agree with LLA within this experimental model of intracranial hypertension. Further analysis of clinically used indices of autoregulation across the LLA within pure arterial hypotension models is required. Keywords: Autoregulation, Continuous indices, Experimental, Validation, Lower Limit Autoregulation