Continuous measurement of autoregulation by spontaneous fluctuations in cerebral perfusion pressure: comparison of 3 methods

Abstract

Background and purpose: Clinical application of continuous autoregulation monitoring would benefit from a comparison of curves generated by online monitoring with standard autoregulation curves in animal models. We characterized the accuracy of 3 continuous monitors of autoregulation in a piglet model of hypotension.

Methods: Piglets 5 to10 days old with intracranial pressure (ICP) at naïve or elevated (20 mm Hg) levels had gradual arterial hypotension induced by a balloon catheter in the inferior vena cava. Elevated ICP was maintained by a continuous infusion of artificial cerebrospinal fluid. Three indices of autoregulation were simultaneously and continuously calculated. A moving, linear Pearson's coefficient between spontaneous slow waves of cerebral perfusion pressure and slow waves of laser-Doppler flux or cortical oxygenation rendered the laser-Doppler index and cerebral-oximetry index, respectively. Similar correlation between slow waves of arterial blood pressure and ICP rendered the pressure-reactivity index. The lower limit of autoregulation was determined directly for each animal by plotting laser-Doppler cortical red blood cell flux as a function of cerebral perfusion pressure. Receiver-operator characteristics were determined for the 3 indices.

Results: The areas under the receiver-operator characteristics curves for discriminating the individual lower limit of autoregulation at low and high ICP were 0.89 and 0.85 for the laser-Doppler index, 0.89 and 0.84 for the cerebral-oximetry index, and 0.79 and 0.79 for the pressure-reactivity index. The pressure-reactivity index performed equally well at low and high ICPs.

Conclusions: Continuous monitoring of autoregulation by spontaneous slow waves of cerebral perfusion pressure can accurately detect loss of autoregulation due to hypotension in piglets by all 3 modalities.

Figure 1

Determining the LLA for each subject. A, Construction of an autoregulation curve for a piglet with naïve ICP. ABP (mm Hg), ICP (mm Hg), LD flux (LDOPPLER, AU), and cerebral oximetry (CEREBROX, % saturation) were recorded while a balloon catheter in the inferior vena cava was gradually inflated over 2 to 4 hours. LD measurements of flux were then plotted as a function of CPP. This plot is demarcated into 2 sets of data having best-fit lines with the lowest combined residual squared error. Solving for the intersection of the 2 lines yields the LLA. Notice the spontaneous slow increase in ICP with decreasing ABP and the increase in frequency and amplitude of spontaneous B waves, also with decreasing ABP. B, Example for a piglet with an ICP of 20 mm Hg. Before a reduction in ABP, the ICP was increased to 20 mm Hg by a steady-state infusion of artificial cerebrospinal fluid, which was maintained throughout the experiment.

Figure 2

Comparison of static autoregulation curves for 8 naïve and 6 elevated ICP piglets. LD flux values are presented as a percentage of baseline values and combined in 5-mm Hg CPP bins (mean±SEM). Dashed lines show the average LLAs determined for each piglet individually (30 mm Hg in the naïve ICP group and 38 mm Hg in the elevated ICP group).

Figure 3

Continuous autoregulatory measurements. The results of continuous autoregulation monitoring during induction of hypotension are averaged separately for 2 groups of piglets: naïve (n=8) and elevated (n=6) ICP. Three monitors of autoregulation are shown: the PRx, the COx, and the LDx. Values are mean±SEM. Data for each animal are normalized to an abscissa with the origin at the LLA before averaging (LLA shown with highlighted error bars) to show the relation between the measurements and the standard autoregulation curve, derived from LDF measurements.

Figure 4

ROCs of the 3 indices of autoregulation. The ROCs of the PRx, COx, and LDx are shown for 2 conditions in piglets: naïve (n=8) and elevated (n=6) ICP. The area under the curve is where a value of 1 indicates maximum sensitivity and specificity.