Intravenous Lidocaine Does Not Improve Neurologic Outcomes after Cardiac Surgery: A Randomized Controlled Trial.

Abstract

Background

Cognitive decline after cardiac surgery occurs frequently and persists in a significant proportion of patients. Preclinical studies and human trials suggest that intravenous lidocaine may confer protection in the setting of neurologic injury. It was hypothesized that lidocaine administration would reduce cognitive decline after cardiac surgery compared to placebo.

Methods

After institutional review board approval, 478 patients undergoing cardiac surgery were enrolled into this multicenter, prospective, randomized, double-blinded, placebo-controlled, parallel group trial. Subjects were randomized to lidocaine 1 mg/kg bolus after the induction of anesthesia followed by a continuous infusion (48 μg · kg · min for the first hour, 24 μg · kg · min for the second hour, and 10 μg · kg · min for the next 46 h) or saline with identical volume and rate changes to preserve blinding. Cognitive function was assessed preoperatively and at 6 weeks and 1 yr postoperatively using a standard neurocognitive test battery. The primary outcome was change in cognitive function between baseline and 6 weeks postoperatively, adjusting for age, years of education, baseline cognition, race, and procedure type.

Results

Among the 420 allocated subjects who returned for 6-week follow-up (lidocaine: N = 211; placebo: N = 209), there was no difference in the continuous cognitive score change (adjusted mean difference [95% CI], 0.02 (-0.05, 0.08); P = 0.626). Cognitive deficit (greater than 1 SD decline in at least one cognitive domain) at 6 weeks occurred in 41% (87 of 211) in the lidocaine group versus 40% (83 of 209) in the placebo group (adjusted odds ratio [95% CI], 0.94 [0.63, 1.41]; P = 0.766). There were no differences in any quality of life outcomes between treatment groups. At the 1-yr follow-up, there continued to be no difference in cognitive score change, cognitive deficit, or quality of life.

Conclusions

Intravenous lidocaine administered during and after cardiac surgery did not reduce postoperative cognitive decline at 6 weeks.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1097/aln.0000000000002668

Publication Info

Klinger, Rebecca Y, Mary Cooter, Tiffany Bisanar, Niccolò Terrando, Miles Berger, Mihai V Podgoreanu, Mark Stafford-Smith, Mark F Newman, et al. (2019). Intravenous Lidocaine Does Not Improve Neurologic Outcomes after Cardiac Surgery: A Randomized Controlled Trial. Anesthesiology, 130(6). pp. 958–970. 10.1097/aln.0000000000002668 Retrieved from https://hdl.handle.net/10161/30496.

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Scholars@Duke

Klinger

Rebecca Yasmin Klinger

Associate Professor of Anesthesiology
Terrando

Niccolò Terrando

Professor of Anesthesiology
Berger

Miles Berger

Associate Professor of Anesthesiology

My research team focuses on 3 areas:

1) We are interested in the mechanisms of postoperative neurocognitive disorders such as delirium, and the relationship between these disorders and Alzheimer's Disease and Related Dementias (ADRD). Towards these ends, we use a combination of methods including pre and postoperative CSF and blood sampling, functional neuroimaging, EEG recordings, rigorous biochemical assays, and cognitive testing and delirium screening. In the long run, this work has the potential to help us improve long term neurocognitive outcomes for the more than 20 million Americans over age 60 who undergo anesthesia and surgery each year.

2) We are interested in the idea that altered anesthetic-induced brain EEG waveforms can serve as indicators of specific types of preclinical/prodromal neurodegenerative disease pathology, specific cognitive domain deficits, and postoperative delirium risk. We are studying this topic in the ALADDIN study, a 250 patient prospective cohort study in older surgical patients at Duke. Many people have viewed anesthesia and surgery as a "stress test" for the aging brain; we hope that this work will help us learn how to develop a real-time EEG readout of this "perioperative stress test" for the aging brain, just as ECG analysis can provide a real-time readout of cardiac treadmill stress tests. 

3) We are interested in how the APOE4 allele damages brain circuitry throughout the adult lifespan, and how this contributes to increased risk of late onset Alzheimer's disease as well as worse outcomes following other acute brain disorders such as stroke and traumatic brain injury (TBI). In particular, we are investigating the hypothesis that the APOE4 allele leads to increased CNS complement activation throughout adult life, which then contributes to increased synaptic phagocytosis and long term neurocognitive decline. We are also studying whether acutely modulating APOE signaling in older surgical patients with the APOE mimetic peptide CN-105 is sufficient to block postoperative CSF neuroinflammation and complement activation. 

Our work is transdisciplinary, and thus our team includes individuals with diverse scientific and clinical backgrounds, ranging from neuropsychology and neuroimaging to proteomics, flow cytometry and behavioral neuroscience in animal models. What unites us is the desire to better understand mechanisms of age-dependent brain dysfunction, both in the perioperative setting and in APOE4 carriers. 

Podgoreanu

Mihai V. Podgoreanu

Associate Professor of Anesthesiology

Basic-Translational:
1. Systems biology approaches to modeling perioperative cardiovascular injury and adaptation.
2. Mechanisms of perioperative myocardial injury; functional genomics applied to perioperative myocardial injury.
3. Metabolic consequences of perioperative myocardial ischemia-reperfusion injury.
4. Animal models and comparative genomic approaches to study perioperative myocardial ischemia-reperfusion injury.
5. Functional genomics of vein graft disease.
6. Animal models of vein graft disease.
7. Genetic association studies in perioperative medicine.
8. Clinico-genomic risk prediction models for perioperative and long-term adverse cardiovascular outcomes following cardiac surgery.

Clinical:
9. Intraoperative quantification of tissue perfusion by contrast echocardiography.
10. Use of myocardial tissue deformation indices to characterize perioperative ventricular dysfunction/stunning
11. 3-D echocardiographic evaluation of the right ventricle

Stafford-Smith

Mark Stafford-Smith

Professor Emeritus of Anesthesiology

My research interests are in the area of Cardiothoracic Anesthesiology. The main focus of my research is towards the understanding and prevention of acute kidney injury after cardiac and other major surgeries. Secondary interests include the study of analgesic strategies after cardiothoracic surgical procedures, performance of clinical trials, and perioperative transfusion and hemostasis.

Newman

Mark Franklin Newman

Merel H. Harmel Distinguished Professor Emeritus of Anesthesiology

Best known for his work in assessing and improving clinical outcomes and quality of life following cardiac surgery, Dr. Mark Newman is President of the Duke Private Diagnostic Clinic (The Duke Faculty Practice Organization) and the Merel H. Harmel Professor of Anesthesiology at Duke University Medical Center. In addition, Dr. Newman developed the Multicenter Perioperative Outcomes Research Group of the Duke Clinical Research Institute established at Duke in 2001 to further the study of strategies to improve the outcomes of patients undergoing surgery and anesthesia. Dr. Newman has received funding from the National Institute on Aging, the American Heart Association, the National Heart, Lung and Blood Institute, the Anesthesia Patient Safety Foundation, and the International Anesthesia Research Society  to investigate the impact of perioperative outcomes (neurocognitive decline, stroke, myocardial infarction, renal injury) on quantity and quality of life following cardiac surgery and resulting in numerous seminal publications in the New England Journal of Medicine, JAMA and Lancet. Dr. Newman is a popular lecturer and speaker, having appeared on NBC Nightly News and The Today Show and having spoken at more than 200 national and international meetings.  Dr. Newman recently stepped down as the Chairman of the Duke University Department after 13 years to assume the role of PDC President.  During Dr. Newman’s tenure the department grew exponentially doubling its clinical and academic funding, and developing many outstanding individuals that have gone on to leadership roles at Duke and other key academic institutions across the country.


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