Evidence map›Paper›PMID 35639046›Full record

ArticleThe Journal of physiology2022

Epidural electrical stimulation of the cervical spinal cord opposes opioid-induced respiratory depression.

Ruyi Huang, Jason Worrell, Eric Garner, Stephanie Wang, Tali Homsey, Bo Xu, Erika L Galer, Yan Zhou, Sherwin Tavakol, Meelod Daneshvar and 8 more

Abstract read
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In one paragraph

Article in The Journal of physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 42% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 1 country.

Ruyi HuangDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0003-3575-3793
Jason WorrellDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0002-6631-4534
Eric GarnerDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0002-6258-6698
Stephanie WangDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0002-9244-2492
Tali HomseyDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Bo XuDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0003-4311-9864
Erika L GalerDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0002-4687-0381
Yan ZhouDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0002-7907-1148
Sherwin TavakolDepartment of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.ORCID 0000-0003-3968-0464
Meelod DaneshvarUniversity of California Fresno, Department of Surgery, Fresno, CA, USA.ORCID 0000-0003-4269-6168
Timothy LeDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0001-6159-674X
Harry V VintersDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0002-2965-1240
Noriko SalamonDepartment of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0002-3520-9467
David L McArthurDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0003-3385-1314
Marc R NuwerDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0001-6916-153X
Irene WuDepartment of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0002-4780-8600
James C LeiterDepartment of Molecular and Systems Biology, Geisel School of Medicine, Lebanon, NH, USA.ORCID 0000-0001-8572-6035
Daniel C LuDepartment of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0003-2162-3672
University of California, Los Angeles · USCalifornia State University, Fresno · USDartmouth College · USUniversity of Southern California · US

Funding

Characterization of Novel Neural Respiratory Circuit to Counter Opioid-Induced Respiratory DepressionR01DA047637 · NIDA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LU, DANIEL · 2020 to 2024
$3.5M
National Institute on Drug Abuse within the National Institutes of Health R01DA047637NIDA NIH HHS R01 DA047637
6 · The paper itself

Abstract

Opioid overdose suppresses brainstem respiratory circuits, causes apnoea and may result in death. Epidural electrical stimulation (EES) at the cervical spinal cord facilitated motor activity in rodents and humans, and we hypothesized that EES of the cervical spinal cord could antagonize opioid-induced respiratory depression in humans. Eighteen patients requiring surgical access to the dorsal surface of the spinal cord between C2 and C7 received EES or sham stimulation for up to 90 s at 5 or 30 Hz during complete (OFF-State) or partial suppression (ON-State) of respiration induced by remifentanil. During the ON-State, 30 Hz EES at C4 and 5 Hz EES at C3/4 increased tidal volume and decreased the end-tidal carbon dioxide level compared to pre-stimulation control levels. EES of 5 Hz at C5 and C7 increased respiratory frequency compared to pre-stimulation control levels. In the OFF-State, 30 Hz cervical EES at C3/4 terminated apnoea and induced rhythmic breathing. In cadaveric tissue obtained from a brain bank, more neurons expressed both the neurokinin 1 receptor (NK1R) and somatostatin (SST) in the cervical spinal levels responsive to EES (C3/4, C6 and C7) compared to a region non-responsive to EES (C2). Thus, the capacity of cervical EES to oppose opioid depression of respiration may be mediated by NK1R+/SST+ neurons in the dorsal cervical spinal cord. This study provides proof of principle that cervical EES may provide a novel therapeutic approach to augment respiratory activity when the neural function of the central respiratory circuits is compromised by opioids or other pathological conditions. KEY POINTS: Epidural electrical stimulation (EES) using an implanted spinal cord stimulator (SCS) is an FDA-approved method to manage chronic pain. We tested the hypothesis that cervical EES facilitates respiration during administration of opioids in 18 human subjects who were treated with low-dose remifentanil that suppressed respiration (ON-State) or high-dose remifentanil that completely inhibited breathing (OFF-State) during the course of cervical surgery. Dorsal cervical EES of the spinal cord augmented the respiratory tidal volume or increased the respiratory frequency, and the response to EES varied as a function of the stimulation frequency (5 or 30 Hz) and the cervical level stimulated (C2-C7). Short, continuous cervical EES restored a cyclic breathing pattern (eupnoea) in the OFF-State, suggesting that cervical EES reversed the opioid-induced respiratory depression. These findings add to our understanding of respiratory pattern modulation and suggest a novel mechanism to oppose the respiratory depression caused by opioids.

Indexed as

Cervical CordRespiratory InsufficiencySpinal Cord InjuriesAnalgesics, OpioidApneaElectric StimulationHumansRemifentanilSpinal CordAnalgesics, OpioidRemifentanilepidural electrical stimulation (EES)intraoperative neuromodulationopioid-induced respiratory depression (OIRD)respiratory pattern modulation

Identifiers

PMID35639046
OpenAlexW4281864042

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.