Electroencephalogram Burst-suppression during Cardiopulmonary Bypass in Elderly Patients Mediates Postoperative Delirium

Abstract

Background: Intraoperative burst-suppression is associated with postoperative delirium. Whether this association is causal remains unclear. Therefore, the authors investigated whether burst-suppression during cardiopulmonary bypass (CPB) mediates the effects of known delirium risk factors on postoperative delirium.

Methods: This was a retrospective cohort observational substudy of the Minimizing ICU [intensive care unit] Neurological Dysfunction with Dexmedetomidine-induced Sleep (MINDDS) trial. The authors analyzed data from patients more than 60 yr old undergoing cardiac surgery (n = 159). Univariate and multivariable regression analyses were performed to assess for associations and enable causal inference. Delirium risk factors were evaluated using the abbreviated Montreal Cognitive Assessment and Patient-Reported Outcomes Measurement Information System questionnaires for applied cognition, physical function, global health, sleep, and pain. The authors also analyzed electroencephalogram data (n = 141).

Results: The incidence of delirium in patients with CPB burst-suppression was 25% (15 of 60) compared with 6% (5 of 81) in patients without CPB burst-suppression. In univariate analyses, age (odds ratio, 1.08 [95% CI, 1.03 to 1.14]; P = 0.002), lowest CPB temperature (odds ratio, 0.79 [0.66 to 0.94]; P = 0.010), alpha power (odds ratio, 0.65 [0.54 to 0.80]; P < 0.001), and physical function (odds ratio, 0.95 [0.91 to 0.98]; P = 0.007) were associated with CPB burst-suppression. In separate univariate analyses, age (odds ratio, 1.09 [1.02 to 1.16]; P = 0.009), abbreviated Montreal Cognitive Assessment (odds ratio, 0.80 [0.66 to 0.97]; P = 0.024), alpha power (odds ratio, 0.75 [0.59 to 0.96]; P = 0.025), and CPB burst-suppression (odds ratio, 3.79 [1.5 to 9.6]; P = 0.005) were associated with delirium. However, only physical function (odds ratio, 0.96 [0.91 to 0.99]; P = 0.044), lowest CPB temperature (odds ratio, 0.73 [0.58 to 0.88]; P = 0.003), and electroencephalogram alpha power (odds ratio, 0.61 [0.47 to 0.76]; P < 0.001) were retained as predictors in the burst-suppression multivariable model. Burst-suppression (odds ratio, 4.1 [1.5 to 13.7]; P = 0.012) and age (odds ratio, 1.07 [0.99 to 1.15]; P = 0.090) were retained as predictors in the delirium multivariable model. Delirium was associated with decreased electroencephalogram power from 6.8 to 24.4 Hertz.

Conclusions: The inference from the present study is that CPB burst-suppression mediates the effects of physical function, lowest CPB temperature, and electroencephalogram alpha power on delirium.

Conflict of interest statement

Conflicts of Interest: OA has received speaker’s honoraria from Masimo Corporation, and is listed as an inventor on pending patents on EEG monitoring and sleep that are assigned to Massachusetts General Hospital. All other authors declare that no competing interests exist.

Figures

Figure 1.

Initial Hypothetical Causal Model. Burst-suppression during cardiopulmonary bypass was hypothesized to mediate the association between known delirium risk factors and delirium. However, the initial model also allowed for the possibility of direct effects of the risk factors on delirium, in addition to, or instead of the indirect, mediational effect of burst-suppression. PROMIS measures included applied cognition, physical function, global health, pain, and sleep. CPB measures included duration of CPB and lowest temperature during CPB. Straight arrows indicate causal effects; double-headed arrows connecting exogenous variables on the left indicate correlations not explicated in the model. ASA, American Society of Anesthesiologists Physical Status; aMOCA, abbreviated Montreal Cognitive Assessment; PROMIS, Patient-Reported Outcomes Measurement Information System; EEG, electroencephalogram; CPB, cardiopulmonary bypass measures

Figure 2.

Predicted Probability for Burst-suppression during CPB from Multivariable Backward Logistic Regression Model. A. Relationship between alpha power and probability of burst-suppression during CPB. Physical function and lowest temperature during CPB were held constant at their grand means of 46.5 and 33.2° C, respectively. B. Relationship between physical function and probability of burst-suppression during CPB. Alpha power and lowest temperature during CPB were held constant at their grand means of 3.1 dB and 33.2° C, respectively. C. Relationship between lowest temperature during CPB and probability of burst-suppression during CPB. Alpha power and physical function were held constant at their grand means of 3.1 dB and 46.5, respectively.

Figure 3.

Final Estimated Causal Model. Physical function, electroencephalogram alpha power, and lowest temperature during CPB have effects on delirium mediated through their impact on burst-suppression during CPB. None of these predictors were found to have a separate direct effect on delirium outside of indirect effects through burst-suppression during CPB. Age had a direct positive effect on delirium. This model also suggests that the significant univariate association of age with burst-suppression during CPB (see results) may partly be mediated through one or more of the exogenous predictors on the left. EEG, electroencephalogram; CPB, cardiopulmonary bypass

Figure 4.

Group level spectra. A. Power spectra of high physical function (black) versus low physical function (red) groups (top panel). Electroencephalogram power was significantly greater in the high physical function group between 7.3 to 19 Hz (bottom panel, bootstrap difference of mean). B. Power spectra of no delirium (black) versus delirium (red) groups (top panel). Electroencephalogram power was significantly greater in the no delirium group between 6.8 to 24.4 Hz (bottom panel, bootstrap difference of mean). Median bootstrapped spectra presented with 99% confidence intervals. Horizontal solid black lines represent significantly different frequencies.