Determining Thresholds for Three Indices of Autoregulation to Identify the Lower Limit of Autoregulation During Cardiac Surgery

Abstract

Objectives: Monitoring cerebral autoregulation may help identify the lower limit of autoregulation in individual patients. Mean arterial blood pressure below lower limit of autoregulation appears to be a risk factor for postoperative acute kidney injury. Cerebral autoregulation can be monitored in real time using correlation approaches. However, the precise thresholds for different cerebral autoregulation indexes that identify the lower limit of autoregulation are unknown. We identified thresholds for intact autoregulation in patients during cardiopulmonary bypass surgery and examined the relevance of these thresholds to postoperative acute kidney injury.

Design: A single-center retrospective analysis.

Setting: Tertiary academic medical center.

Patients: Data from 59 patients was used to determine precise cerebral autoregulation thresholds for identification of the lower limit of autoregulation. These thresholds were validated in a larger cohort of 226 patients.

Methods and main results: Invasive mean arterial blood pressure, cerebral blood flow velocities, regional cortical oxygen saturation, and total hemoglobin were recorded simultaneously. Three cerebral autoregulation indices were calculated, including mean flow index, cerebral oximetry index, and hemoglobin volume index. Cerebral autoregulation curves for the three indices were plotted, and thresholds for each index were used to generate threshold- and index-specific lower limit of autoregulations. A reference lower limit of autoregulation could be identified in 59 patients by plotting cerebral blood flow velocity against mean arterial blood pressure to generate gold-standard Lassen curves. The lower limit of autoregulations defined at each threshold were compared with the gold-standard lower limit of autoregulation determined from Lassen curves. The results identified the following thresholds: mean flow index (0.45), cerebral oximetry index (0.35), and hemoglobin volume index (0.3). We then calculated the product of magnitude and duration of mean arterial blood pressure less than lower limit of autoregulation in a larger cohort of 226 patients. When using the lower limit of autoregulations identified by the optimal thresholds above, mean arterial blood pressure less than lower limit of autoregulation was greater in patients with acute kidney injury than in those without acute kidney injury.

Conclusions: This study identified thresholds of intact and impaired cerebral autoregulation for three indices and showed that mean arterial blood pressure below lower limit of autoregulation is a risk factor for acute kidney injury after cardiac surgery.

Conflict of interest statement

Drs. Lee, Hogue, and Brown received support for article research from the National Institutes of Health (NIH). Dr. Lee has received support from and been a paid consultant for Medtronic, and she received research support from Edwards Life Sciences. Dr. Lee’s arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Some methods used to measure and monitor autoregulation as described in this article were patented by The Johns Hopkins University, listing Dr. Brady as a coinventor. These patents are exclusively licensed to Medtronic. Dr. Brown reported receiving grants from the NIH during the conduct of the study, and consulting for and participating in a data share with Medtronic. Dr. Brady is listed as inventor on patents awarded and assigned to the Johns Hopkins University. These patents are related to the monitoring technology described in this article and are exclusively licensed to Medtronic, and Dr. Brady received a portion of the licensing fee. Dr. Venkataraman received funding from Vixiar Medical (consulting) and from universities for speaker honorariums, and she was supported by the National Science Foundation CAREER award 1845430. Dr. Hogue reported receiving grants and personal fees for being a consultant and providing lectures for Medtronic/Covidien, being a consultant to Merck, and receiving grants from the NIH outside of the submitted work, and he disclosed off-label product use of autoregulation monitoring is investigational. Drs. Czosnyka and Smielewski received funding from licensing ICM+ through Cambridge Enterprise Ltd, United Kingdom. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Figures

Figure 1.

(A) Example cerebral autoregulation Lassen curve created by plotting transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) vs. mean arterial blood pressure (MAP). The point in the regression line at which the first ascending line met the plateau was identified as the lower limit of autoregulation (LLA). This patient’s LLA was 61 mmHg. (B) LLA defined using mean flow index (Mx) at different Mx thresholds of the same patient. A U-shaped curve was created by plotting Mx against MAP, and a straight horizontal line at the cutoff value was drawn to locate the x coordinate of the cross point where the straight line met the curve. In this example, an Mx threshold of 0.45 would identify an LLA of 61 mmHg.

Figure 2.

Bland-Altman plot between the lower limit of autoregulation (LLA) defined by the Lassen curve and by the mean flow index (Mx) at a threshold of 0.45 (A), by the cerebral oximetry index (Cox) at a threshold of 0.35 (B), and by the hemoglobin volume index (HVx) at a threshold of 0.3 (C).

Figure 3.

The extent of mean arterial blood pressure (MAP) below the lower limit of autoregulation (LLA; defined by Mx, Cox, and HVx) in patients with and without acute kidney injury (AKI) using Mann-Whitney tests. The bar is expressed as mean ± SEM; n=176 for (A), n=200 for (B) and n=192 for (C). More details can be found in Supplementary Table 2. *p<0.05. Mx = mean flow index; COx = cerebral oximetry index; HVx = hemoglobin volume index.