Evidence map›Paper›PMID 33896589›Full record

Trial reportBritish journal of anaesthesia2021

Stereoselective ketamine effect on cardiac output: a population pharmacokinetic/pharmacodynamic modelling study in healthy volunteers.

Jasper Kamp, Monique van Velzen, Leon Aarts, Marieke Niesters, Albert Dahan, Erik Olofsen

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of anaesthesia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
5.5field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Jasper KampDepartment of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
Monique van VelzenDepartment of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
Leon AartsDepartment of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
Marieke NiestersDepartment of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
Albert DahanDepartment of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: a.dahan@lumc.nl.
Erik OlofsenDepartment of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
Leiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundKetamine has cardiac excitatory side-effects. Currently, data on the effects of ketamine and metabolite concentrations on cardiac output are scarce. We therefore developed a pharmacodynamic model derived from data from a randomised clinical trial. The current study is part of a larger clinical study evaluating the potential mitigating effect of sodium nitroprusside on the psychedelic effects of ketamine.

methodsTwenty healthy male subjects received escalating esketamine and racemic ketamine doses in combination with either placebo or sodium nitroprusside on four visits: (i) esketamine and placebo, (ii) esketamine and sodium nitroprusside, (iii) racemic ketamine and placebo, and (iv) racemic ketamine and sodium nitroprusside. During each visit, arterial blood samples were obtained and cardiac output was measured. Nonlinear mixed-effect modelling was used to analyse the cardiac output time-series data. Ketamine metabolites were added to the model in a sequential manner to evaluate the effects of metabolites.

resultsA model including an S-ketamine and S-norketamine effect best described the data. Ketamine increased cardiac output, whereas modelling revealed that S-norketamine decreased cardiac output. No significant effects were detected for R-ketamine, metabolites other than S-norketamine, or sodium nitroprusside on cardiac output.

conclusionsS-Ketamine, but not R-ketamine, increased cardiac output in a dose-dependent manner. In contrast to S-ketamine, its metabolite S-norketamine reduced cardiac excitation in a dose-dependent manner. CLINICAL

trial registrationDutch Cochrane Center 5359.

Indexed as

AdultAnesthetics, DissociativeCardiac OutputCross-Over StudiesDose-Response Relationship, DrugDouble-Blind MethodHealthy VolunteersHumansKetamineMaleStereoisomerismYoung AdultAnesthetics, DissociativeKetaminecardiac outputhydroxynorketamineketaminemetabolomicsmodelingNONMEMnorketaminestereoselectivity

Identifiers

PMID33896589
PMCPMC8258972
OpenAlexW3158333653

What OpenQuestion holds

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LicenceCC BY
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.