The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial

Vlisides, Phillip E.; Li, Duan; McKinney, Amy S; Brooks, Joseph; Leis, Aleda; Mentz, Graciela; Tsodikov, Alexander; Zierau, Mackenzie; Ragheb, Jacqueline; Clauw, Daniel J.; Avidan, Michael S.; Vanini, Giancarlo; Mashour, George A.

doi:10.1213/ane.0000000000005532

Cited by 12 publications

(25 citation statements)

References 32 publications

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“…This was a secondary analysis of a randomized controlled trial that tested the effects of caffeine on pain and neuropsychological recovery after surgery ( 1 NCT03577730, registered 7/5/2018, PI: Vlisides) ( Vlisides et al, 2021 ). The trial was approved by the University of Michigan Medical School Institutional Review Board (Ann Arbor, MI, United States; HUM00135919), and the primary aim of this substudy was to test associations between delirium and surrogate EEG measures of neural criticality.…”

Section: Methodsmentioning

confidence: 99%

“…The trial was quadruple-blinded, as patients, clinicians, research team members, and analysts were blinded to the intervention. The original trial protocol, full methodology, adverse events, and protocol deviations are available as previously reported ( Vlisides et al, 2021 ). This manuscript contains a distinct EEG analysis relating to delirium and caffeine administration.…”

Section: Methodsmentioning

confidence: 99%

“…Adult patients (≥ 18 years of age) presenting for laparoscopic colorectal or gastrointestinal surgery were eligible for the parent trial ( Vlisides et al, 2021 ) and this substudy analysis. Exclusion criteria included emergency surgery, cognitive impairment precluding capacity for informed consent, uncontrolled cardiac arrhythmias, seizure disorders, intolerance or allergy to caffeine, preoperative opioid use, history of diabetes [because dextrose 5% in water (D5W) was the placebo], acute liver failure, pregnancy, breastfeeding, severe visual or auditory impairment (which might hinder cognitive function testing), patients unable to speak English, or enrollment in a conflicting research study.…”

Section: Methodsmentioning

confidence: 99%

“…One such candidate intervention is caffeine, which optimizes neurocognitive processing ( Kuchinke and Lux, 2012 ; Haller et al, 2013 ; Chang et al, 2018 ). In a preliminary clinical trial conducted by our team, surgical participants randomized to intraoperative caffeine demonstrated reduced risk of delirium in the postanesthesia care unit (PACU) concurrent with improved connectivity between frontal and parietal cortices ( Vlisides et al, 2021 ). However, the effects of caffeine on measures of criticality were not tested.…”

Section: Introductionmentioning

confidence: 99%

“…Specifically, this study tested the primary hypothesis that deviations from criticality would be associated with delirium in the PACU. The secondary objective was to determine whether caffeine, administered during surgical closure, would affect measures of criticality in the early postoperative setting given that caffeine has previously been demonstrated to reduce early postoperative delirium ( Vlisides et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Delirium, Caffeine, and Perioperative Cortical Dynamics

Kim

McKinney

Brooks

et al. 2021

Front. Hum. Neurosci.

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Delirium is a major public health issue associated with considerable morbidity and mortality, particularly after surgery. While the neurobiology of delirium remains incompletely understood, emerging evidence suggests that cognition requires close proximity to a system state called criticality, which reflects a point of dynamic instability that allows for flexible access to a wide range of brain states. Deviations from criticality are associated with neurocognitive disorders, though the relationship between criticality and delirium has not been formally tested. This study tested the primary hypothesis that delirium in the postanesthesia care unit would be associated with deviations from criticality, based on surrogate electroencephalographic measures. As a secondary objective, the impact of caffeine was also tested on delirium incidence and criticality. To address these aims, we conducted a secondary analysis of a randomized clinical trial that tested the effects of intraoperative caffeine on postoperative recovery in adults undergoing major surgery. In this substudy, whole-scalp (16-channel) electroencephalographic data were analyzed from a subset of trial participants (n = 55) to determine whether surrogate measures of neural criticality – (1) autocorrelation function of global alpha oscillations and (2) topography of phase relationships via phase lag entropy – were associated with delirium. These measures were analyzed in participants experiencing delirium in the postanesthesia care unit (compared to those without delirium) and in participants randomized to caffeine compared to placebo. Results demonstrated that autocorrelation function in the alpha band was significantly reduced in delirious participants, which is important given that alpha rhythms are postulated to play a vital role in consciousness. Moreover, participants randomized to caffeine demonstrated increased alpha autocorrelation function concurrent with reduced delirium incidence. Lastly, the anterior-posterior topography of phase relationships appeared most preserved in non-delirious participants and in those receiving caffeine. These data suggest that early postoperative delirium may reflect deviations from neural criticality, and caffeine may reduce delirium risk by shifting cortical dynamics toward criticality.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Delirium, Caffeine, and Perioperative Cortical Dynamics

Kim

McKinney

Brooks

et al. 2021

Front. Hum. Neurosci.

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Delirium is associated with loss of feedback cortical connectivity

Gjini,

Casey,

Kunkel

et al. 2023

Alzheimer's & Dementia

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IntroductionPost‐operative delirium (POD) is associated with increased morbidity and mortality but is bereft of treatments, largely due to our limited understanding of the underlying pathophysiology. We hypothesized that delirium reflects a disturbance in cortical connectivity that leads to altered predictions of the sensory environment.MethodsHigh‐density electroencephalogram recordings during an oddball auditory roving paradigm were collected from 131 patients. Dynamic causal modeling (DCM) analysis facilitated inference about the neuronal connectivity and inhibition–excitation dynamics underlying auditory‐evoked responses.ResultsMismatch negativity amplitudes were smaller in patients with POD. DCM showed that delirium was associated with decreased left‐sided superior temporal gyrus (l‐STG) to auditory cortex feedback connectivity. Feedback connectivity also negatively correlated with delirium severity and systemic inflammation. Increased inhibition of l‐STG, with consequent decreases in feed‐forward and feed‐back connectivity, occurred for oddball tones during delirium.DiscussionDelirium is associated with decreased feedback cortical connectivity, possibly resulting from increased intrinsic inhibitory tone.HIGHLIGHTS Mismatch negativity amplitude was reduced in patients with delirium. Patients with postoperative delirium had increased feedforward connectivity before surgery. Feedback connectivity was diminished from left‐side superior temporal gyrus to left primary auditory sensory area during delirium. Feedback connectivity inversely correlated with inflammation and delirium severity.

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