Evidence map›Paper›PMID 39049497›Full record

Trial reportBritish journal of clinical pharmacology2024

Epidural methadone and morphine pharmacokinetics and clinical effects in healthy volunteers: A randomized, crossover-design trial.

Alexander Hincker, Matthew Reschke, Yehuda Ginosar, Leonid Kagan, Evan D Kharasch, Anna Siemiątkowska, Celine Park, Kristopher Bakos, Arbi Ben-Abdallah, Simon Haroutounian

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Trial
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Alexander HinckerDepartment of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA.ORCID https://orcid.org/0000-0001-6973-8693
Matthew ReschkeDepartment of Anesthesiology, Banner University Medical Center, Phoenix, AZ, USA.
Yehuda GinosarDepartment of Anesthesiology, Critical Care and Pain Medicine, Hadassah Ein Karem Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Israel.
Leonid KaganDepartment of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Evan D KharaschDepartment of Anesthesiology, Duke University School of Medicine; Bermaride LLC, Durham, NC, USA.ORCID https://orcid.org/0000-0002-6613-922X
Anna SiemiątkowskaDepartment of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Celine ParkDepartment of Pharmaceutics and Center of Excellence for Pharmaceutical Translational Research and Education, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
Kristopher BakosInvestigational Drug Service, Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, MO, USA.
Arbi Ben-AbdallahDepartment of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA.
Simon HaroutounianDepartment of Anesthesiology, Washington University School of Medicine, Saint Louis, MO, USA.ORCID https://orcid.org/0000-0003-2231-5452

Funding

Mechanisms of obesity-induced changes in drug pharmacokineticsR01GM124046 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI KAGAN, LEONID · 2018 to 2022
$2.6M
OPTIMIZING OUTPATIENT ANESTHESIA: IMPROVING ANALGESIA AND REDUCING OPIOID MISADVENTURER01DA042985 · NIDA · WASHINGTON UNIVERSITY · PI KHARASCH, EVAN D. · 2017 to 2021
$2.2M
NIDA NIH HHS R01 DA042985NIGMS NIH HHS 1R01GM124046-01A1NIGMS NIH HHS R01 GM124046NIH HHS R01DA042985Society for Obstetric Anesthesia and Perinatology - Young Investigator Grant 003023-17015Washington University in St. Louis Institute of Clinical and Translational Sciences (ICTS) Just-in-time Programme JIT529Washington University School of Medicine in St. Louis - Department of Anesthesiology
6 · The paper itself

Abstract

aimsEpidural opioids can provide effective analgesia for acute postoperative pain. Due to its unique physicochemical properties and long systemic elimination half-life, epidural methadone may provide lasting analgesia with minimal adverse effects; however, human studies are lacking. The aim of the study was to test the hypothesis that epidural methadone would exhibit greater segmental analgesia (analgesia at the dermatome of injection vs. distant dermatomes) than epidural morphine.

methodsIn a prospective, randomized, double-blinded, crossover study, thirteen healthy volunteers received a 4-mg epidural bolus of methadone or morphine at L3-L4 and underwent repeated assessment of dermatomal heat pain tolerance and pressure pain threshold at lumbar (L3) and trigeminal (V2) dermatomes, pupil diameter, respiratory parameters and venous opioid concentration for 24 h. The primary outcome was selective (lumbar vs. trigeminal) segmental analgesia for heat pain, as a marker of a spinal analgesic mechanism.

resultsThe degree of segmental analgesia to heat pain tolerance was not different between morphine and methadone (P = .09), although morphine (P = .0009) but not methadone (P = .81) produced significant analgesia to heat pain at the lumbar vs. trigeminal dermatome over 0-12 h. Morphine overall provided longer lasting analgesia to heat pain vs. methadone (24 vs. 2 h, respectively). Morphine elicited greater systemic effects, including miosis (P = .009) and opioid-related adverse effects (P = .002).

conclusionsThese results suggest that, with equal epidural doses, both methadone and morphine produced analgesia and methadone did not produce greater segmental effects than morphine. Epidural methadone provided a more favourable adverse effect profile.

Indexed as

Analgesics, OpioidCross-Over StudiesHealthy VolunteersMethadoneMorphineAdultAnalgesia, EpiduralDouble-Blind MethodFemaleHot TemperatureHumansInjections, EpiduralMalePain MeasurementPain ThresholdProspective StudiesAnalgesics, OpioidMethadoneMorphineopioidspainpharmacodynamicspharmacokinetics

Identifiers

PMID39049497
PMCPMC11906210

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.