Cerebral Blood Flow Hemispheric Asymmetry in Comatose Adults Receiving Extracorporeal Membrane Oxygenation

Abstract

Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing the brain to asymmetric perfusion. Though ECMO patients frequently experience brain injury, neurologic exams and imaging are difficult to obtain. Diffuse correlation spectroscopy (DCS) non-invasively measures relative cerebral blood flow (rBF) at the bedside using an optical probe on each side of the forehead. In this study we observed interhemispheric rBF differences in response to mean arterial pressure (MAP) changes in adult ECMO recipients. We recruited 13 subjects aged 21-78 years (7 with cardiac arrest, 4 with acute heart failure, and 2 with acute respiratory distress syndrome). They were dichotomized via Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; n = 4) and non-comatose (GCS-M > 4; n = 9) groups. Comatose patients had greater interhemispheric rBF asymmetry (ASYM_rBF) vs. non-comatose patients over a range of MAP values (29 vs. 11%, p = 0.009). ASYM_rBF in comatose patients resolved near a MAP range of 70-80 mmHg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Correlations between post-oxygenator pCO₂ or pH vs. ASYM_rBF were significantly different between comatose and non-comatose groups. Our findings indicate that comatose patients are more likely to have asymmetric cerebral perfusion.

Keywords: cerebral blood flow; cerebrovascular autoregulation; coma; diffuse correlation spectroscopy; extracorporeal membrane oxygenation.

FIGURE 1

Calculation of average relative blood flow (rBF, in %) vs. mean arterial pressure (MAP). An example time trace for (A) rBF and (B) MAP for a single day of monitoring are shown. Using these time traces, (C) rBF is plotted against MAP and an average rBF value at each MAP is calculated (red circle). (D) An averaged rBF vs. MAP curve is generated for both the right (red circle) and left hemisphere (blue circle). Using the data in (D), |ΔrBF_MAP| (in %/mmHg) is plotted against MAP in (E). ASYM_rBF, averaged |ΔrBF_MAP| of this monitoring day for a patient is shown on the upper right corner.

FIGURE 2

Glasgow Coma Scale Motor score (black), ASYM_rBF (red), and |ΔrBF_MAP| vs. MAP from the day of maximum ASYMrBF for subject 1 (A,C,E) and subject 11 (B,D,F) during their monitoring periods. (A) Subject 1, defined as non-comatose, displayed a constant GCS-Motor score of 6 while (B) subject 11, defined as comatose, varied between 1 and 4. ASYM_rBF data is shown for (C) subject 1 and (D) subject 11. The shaded region marked by the asterisk (*) denotes the maximum ASYM_rBF value that was chosen for each subject. | ΔrBF_MAP| of the gray shaded region shown in (C,D) is shown for (E) subject 1 and (F) subject 11. BFI data for day 3 of subject 11 was discarded due to low SNR thus ASYM_rBF was not calculated.

FIGURE 3

|ΔrBF_MAP| for all the patients for each specific day that corresponded to their maximum ASYM_rBF value. The number displayed in the legend of each plot was the ASYM_rBF for that day. Subjects 8, 9, 11, and 13, highlighted in red, were subjects defined to be comatose.

FIGURE 4

Boxplot of maximum ASYM_rBF values for all the subjects grouped by GCS-Motor score. Non-comatose patients had a median value of 11% [IQR 8–13%] and comatose patients 29% [IQR 23–34%] (one-tailed p = 0.009, two-tailed p = 0.018).

FIGURE 5

(A) Comparison between TCD and DCS measurements of cerebral blood flow asymmetry. |ΔrBF_MAP(MAP_i)| (red X marks) and |ΔrCBFV_MAP(MAP_i)| (black circles) data are shown for subject 1 over a range of MAP values. The shaded area denotes the MAP values where |ΔrBF_MAP(MAP_i)| and |ΔrCBFV_MAP(MAP_i)| overlap. (B) Bland–Altman analysis was performed to compare the difference between the two measurements against the average of the two measurements. Solid line indicates the mean of the y-axis and dashed lines are the 95% confidence interval.

FIGURE 6

Maximum ASYM_rBF vs. pCO₂ and pH values from post-oxygenator and arterial blood gas (ABG). Red circles indicate comatose subjects and blue triangles indicate non-comatose subjects. pCO₂ and pH values taken from the post-oxygenator are shown in (A,C), while values taken from the ABG are shown in (B,D). Comatose patients showed higher R-value between maximum ASYM_rBF and clinical markers (A,C) taken from the post-oxygenator compared to non-comatose patients.