Evidence map›Paper›PMID 39465453›Full record

Trial reportClinical pharmacokinetics2024

Population Pharmacokinetic Modelling of Norepinephrine in Healthy Volunteers Prior to and During General Anesthesia.

Yingxue Li, Jeroen V Koomen, Douglas J Eleveld, Johannes P van den Berg, Jaap Jan Vos, Ilonka N de Keijzer, Michel M R F Struys, Pieter J Colin

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical pharmacokinetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
–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

6 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. 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

8 authors.

Yingxue LiDepartment of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jeroen V KoomenDepartment of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Douglas J EleveldDepartment of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Johannes P van den BergDepartment of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Jaap Jan VosDepartment of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Ilonka N de KeijzerDepartment of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Michel M R F StruysDepartment of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Pieter J ColinDepartment of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands. p.j.colin@umcg.nl.ORCID 0000-0003-3616-5539

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntraoperation hypotension (IOH) is commonly observed in patients undergoing surgery under general anesthesia, and even a brief episode of IOH can lead to unfavorable outcomes. To reduce the risk, blood pressure is closely measured during general anesthesia, and norepinephrine (NE) is frequently administered if hypotension is detected. Despite its routine application, information on the dose-exposure-response relationship of NE remains limited. Additionally, quantification of the influence of general anesthesia on the pharmacokinetics (PK) of NE is lacking.

objectiveIn this study, we aimed to describe NE PK in healthy volunteers and the influence of general anesthesia on its PK.

methodsA single-center, cross-over study was conducted in healthy volunteers. The volunteers received a step-up NE dosing scheme (0.04, 0.08, 0.12, 0.16 and 0.20 mcg

resultsA total of 1219 samples were analyzed from 36 volunteers. A two-compartment model with a first-order elimination best described the data. Weight, age, and session effect (awake vs general anesthesia) were identified as relevant covariates on the clearance (CL) of NE. A 10% decrease in NE CL was observed after general anesthesia induction. This difference between sessions is better explained by the measured concentration of propofol, rather than the anticipated impact of cardiac output. The estimated post-stimulation NE concentration is 0.66 nmol/L

conclusionThe NE PK is well described with a two-compartment model with a first-order elimination. NE CL exhibiting a 10% decrease under general anesthesia, with this difference being attributed to the measured concentration of propofol. The impact of stimulation on NE PK under general anesthesia is very limited. CLINICAL TRIALS REGISTRATION NUMBER: NL9312.

Indexed as

Anesthesia, GeneralCross-Over StudiesHealthy VolunteersModels, BiologicalNorepinephrinePropofolAdultAnesthetics, IntravenousDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedPiperidinesRemifentanilYoung AdultAnesthetics, IntravenousNorepinephrinePiperidinesPropofolRemifentanil

Identifiers

PMID39465453
PMCPMC11573843

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.