Cerebrovascular Pressure Reactivity According to Long-Pressure Reactivity Index During Spreading Depolarizations in Aneurysmal Subarachnoid Hemorrhage

Abstract

Background: Spreading depolarization (SD) has been linked to the impairment of neurovascular coupling. However, the association between SD occurrence and cerebrovascular pressure reactivity as a surrogate of cerebral autoregulation (CA) remains unclear. Therefore, we analyzed CA using the long-pressure reactivity index (L-PRx) during SDs in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Methods: A retrospective study of patients with aSAH who were recruited at two centers, Heidelberg (HD) and Berlin (BE), was performed. Continuous monitoring of mean arterial pressure (MAP) and intracranial pressure (ICP) was recorded. ICP was measured using an intraparenchymal probe in HD patients and was measure in BE patients through external ventricular drainage. Electrocorticographic (ECoG) activity was continuously recorded between 3 and 13 days after hemorrhage. Autoregulation according to L-PRx was calculated as a moving linear Pearson's correlation of 20-min averages of MAP and ICP. For every identified SD, 60-min intervals of L-PRx were averaged, plotted, and analyzed depending on SD occurrence. Random L-PRx recording periods without SDs served as the control.

Results: A total of 19 patients (HD n = 14, BE n = 5, mean age 50.4 years, 9 female patients) were monitored for a mean duration of 230.4 h (range 96-360, STD ± 69.6 h), during which ECoG recordings revealed a total number of 277 SDs. Of these, 184 represented a single SD, and 93 SDs presented in clusters. In HD patients, mean L-PRx values were 0.12 (95% confidence interval [CI] 0.11-0.13) during SDs and 0.07 (95% CI 0.06-0.08) during control periods (p < 0.001). Similarly, in BE patients, a higher L-PRx value of 0.11 (95% CI 0.11-0.12) was detected during SDs than that during control periods (0.08, 95% CI 0.07-0.09; p < 0.001). In a more detailed analysis, CA changes registered through an intraparenchymal probe (HD patients) revealed that clustered SD periods were characterized by signs of more severely impaired CA (L-PRx during SD in clusters: 0.23 [95% CI 0.20-0.25]; single SD: 0.09 [95% CI 0.08-0.10]; control periods: 0.07 [95% CI 0.06-0.08]; p < 0.001). This group also showed significant increases in ICP during SDs in clusters compared with single SD and control periods.

Conclusions: Neuromonitoring for simultaneous assessment of cerebrovascular pressure reactivity using 20-min averages of MAP and ICP measured by L-PRx during SD events is feasible. SD occurrence was associated with significant increases in L-PRx values indicative of CA disturbances. An impaired CA was found during SD in clusters when using an intraparenchymal probe. This preliminary study validates the use of cerebrovascular reactivity indices to evaluate CA disturbances during SDs. Our results warrant further investigation in larger prospective patient cohorts.

Keywords: Aneurysmal subarachnoid hemorrhage; Cerebrovascular autoregulation; Cerebrovascular reactivity; Long-pressure reactivity index; Spreading depolarization.

Fig. 1

Plots of long-pressure reactivity index (L-PRx) in Heidelberg (a–c) and Berlin patients (d–f) according to the different time periods are shown. Time windows of 30 min before and after spreading depolarization (SD) detection in electrocorticography (ECoG) were used. Please note the autoregulatory fluctuations of L-PRx during the monitoring time. c, Accumulative episodes of L-PRx values greater than 0.2 are exhibited during clusters measured with intracranial pressure (ICP) probes. Please consider that the true origin and time point of SD occurrence might only represent its detection in ECoG in some cases. L-PRx during time periods without SDs (a and d), during a single SD (b and e), and during clustered SDs (c and f). c, The time course of L-PRx during SD in clusters shows a peak greater than 0.2, suggesting a loss of autoregulation at the time of SD occurrence. In this group of patients, ICP values were obtained through intraparenchymal ICP probes. A peak L-PRx > 0.3 can be observed 3 min after SD detection

Fig. 2

Long-pressure reactivity index (L-PRx) values in patients with aneurysmal subarachnoid hemorrhage (aSAH). a and b, Box plots show autoregulation differences between periods with and without spreading depolarizations (SDs) in Heidelberg (HD) and Berlin (BE) patients. In both groups, HD and BE, significant increases of L-PRx values > 0.1 during SDs were detected (p < 0.001). c–e, L-PRx, intracranial pressure (ICP), and mean arterial pressure (MAP) values of HD patients are shown according to the different time periods. c, A loss of autoregulation (L-PRx > 0.2) was detected during clustered SDs (p < 0.001). d, Mean ICP values according to the different time periods are shown. ICP values were obtained through an intraparenchymal probe. Significantly higher ICP values were detected during SD in clusters (p < 0.001). e, MAP values of HD patients during the different time periods are shown. No difference was found between periods (p > 0.05). f–h, L-PRx, ICP, and MAP values of BE patients are shown according to the different periods. f, Mean L-PRx values during single and clustered SDs remained above 0.1. These values were still higher than those in SD-free periods. g and h, No differences between time periods in mean ICP and MAP values were found in BE patients (p > 0.05). Data are expressed as mean and 95% confidence interval