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

Abstract

The purpose of this study was to provide validation of intracranial pressure (ICP) derived continuous indices of cerebrovascular reactivity against the lower limit of autoregulation (LLA). Utilizing an intracranial hypertension model within white New Zealand rabbits, ICP, transcranial Doppler (TCD), laser Doppler flowmetry (LDF), and arterial blood pressure were recorded. Data were 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 cerebral perfusion pressure [CPP]). LLA was derived via piecewise linear regression of CPP versus LDF or CPP versus systolic flow velocity (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. Receiver operating curve (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 areas under the curve (AUCs) of 0.795 (95% confidence interval [CI]: 0.731-0.857, p < 0.0001) and 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.

Personalizing the Definition of Hypotension to Protect the Brain

“…29 Few published methods have been validated in this way. [30][31][32] This technique involves processing digital regional cerebral oxygen saturation signals from a commercially available near-infrared spectroscopy monitor along with arterial blood pressure signals from a standard hemodynamic monitor. The signals are then time-integrated and filtered to focus on low frequencies (less than 0.05 Hz) associated with autoregulation mediating vasoreactivity.…”

“…The combinations of output surrogates and mathematical functions that can be made are varied, and they render results that are variable. 32 Generating low-frequency (i.e., 1/min) oscillations in blood pressure and evaluating the phase angle of the cerebral vascular response is one such approach. Blood pressure oscillations can be generated by simply increasing positive end-expiratory pressure by 5 cm H 2 O above background airway pressure once per minute.…”

Continuous cerebrovascular reactivity monitoring in moderate/severe traumatic brain injury: a narrative review of advances in neurocritical care

“…Of all the described continuous cerebrovascular reactivity measures in adult TBI, very few have received pre-clinical experimental validation as true measures of autoregulation in animal models. To date, only ICP-based PRx, 21e23 PAx (correlation between AMP and MAP), 22,23 and RAC 23 (correlation [R] between AMP [A] and CPP [C]) have data to support that they can detect the lower limit of autoregulation (LLA) during arterial hypotension and intracranial hypertension. NIRS based THx (or HVx; correlation between total haemoglobin index [THI] and CPP) and total oxygenation index (TOx or COx; correlation between total oxygen index [TOI] or regional oxygen saturation [rSO 2 ] and CPP) have only been assessed in experimental arterial hypotension, confirming that these measures provide information regarding the LLA.…”

Non-Invasive Pressure Reactivity Index Using Doppler Systolic Flow Parameters: A Pilot Analysis

“…ICP in this instance is considered a surrogate measure of pulsatile CBV. Thus, PRx is measuring changes in CBV in response to changes in MAP, with the corresponding correlation representing cerebral pressure autoregulation and having been validated to measure the lower-limit of autoregulation in various experimental models 6,14,15. Whereas, the TCD based cerebrovascular reactivity indices (ie.…”