Anaesthetist-controlled versus patient-maintained effect-site targeted propofol sedation during elective primary lower-limb arthroplasty performed under spinal anaesthesia (ACCEPTS): study protocol for a parallel-group randomised comparison trial

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Abstract

Background

The clinical efficacy of effect-site targeted patient-maintained propofol sedation (PMPS) compared to anaesthetist-controlled propofol sedation (ACPS) for patients undergoing awake joint replacement surgery is currently unknown. There is no commercially available medical device capable of delivering PMPS so we have designed and built such a device. We plan a clinical trial to compare PMPS to ACPS and to collect data relating to the safety of our prototype device in delivering sedation.

Methods

The trial is an open-label, randomised, controlled superiority trial recruiting adults who are undergoing elective primary lower-limb arthroplasty with sedation by propofol infusion by effect-site targeting into two equal-sized parallel arms: PMPS and ACPS. The primary research objective is to compare the body-weight-normalised rate of propofol consumption when sedation for surgery on adults undergoing elective primary lower-limb arthroplasty under spinal anaesthesia is patient-maintained versus when it is anaesthetist-controlled. The study primary null hypothesis is that there is no difference in the rate of propofol consumption when sedation is patient-maintained versus anaesthetist-controlled.

Discussion

This is the first trial to test the superiority of effect-site-targeted patient-maintained propofol sedation versus anaesthetist-controlled propofol sedation in terms of total propofol consumption during the sedation period. The results of this trial will help inform clinicians and device manufacturers of the clinical efficacy and safety of patient-maintained propofol sedation applied to a common operative setting.

Trial registration

International Standard Randomised Controlled Trial Number Registry, ISRCTN29129799. Prospectively registered on 12 June 2018.

Electronic supplementary material

The online version of this article (10.1186/s13063-019-3228-4) contains supplementary material, which is available to authorized users.

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Most cited references 13

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The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers.

Jonas Schnider, H Goodale, E C Minto … (1998)

Unresolved issues with propofol include whether the pharmacokinetics are linear with dose, are influenced by method of administration (bolus vs. infusion), or are influenced by age. Recently, a new formulation of propofol emulsion, containing disodium edetate (EDTA), was introduced in the United States. Addition of EDTA was found by the manufacturer to significantly reduce bacterial growth. This study investigated the influences of method of administration, infusion rate, patient covariates, and EDTA on the pharmacokinetics of propofol. Twenty-four healthy volunteers aged 26-81 yr were given a bolus dose of propofol, followed 1 h later by a 60-min infusion. Each volunteer was randomly assigned to an infusion rate of 25, 50, 100, or 200 microg x kg(-1) x min(-1). Each volunteer was studied twice under otherwise identical circumstances: once receiving propofol without EDTA and once receiving propofol with EDTA. The influence of the method of administration and of the volunteer covariates was explored by fitting a three-compartment mamillary model to the data. The influence of EDTA was investigated by direct comparison of the measured concentrations in both sessions. The concentrations of propofol with and without EDTA were not significantly different. The concentration measurements after the bolus dose were significantly underpredicted by the parameters obtained just from the infusion data. The kinetics of propofol were linear within the infusion range of 25-200 microg x kg(-1) x min(-1). Age was a significant covariate for Volume2 and Clearance2, as were weight, height, and lean body mass for the metabolic clearance. These results demonstrate that method of administration (bolus vs. infusion), but not EDTA, influences the pharmacokinetics of propofol. Within the clinically relevant range, the kinetics of propofol during infusions are linear regarding infusion rate.

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Pharmacokinetic models for propofol--defining and illuminating the devil in the detail.

A.R. Absalom, V. Mani, T. De Smet … (2009)

The recently introduced open-target-controlled infusion (TCI) systems can be programmed with any pharmacokinetic model, and allow either plasma- or effect-site targeting. With effect-site targeting the goal is to achieve a user-defined target effect-site concentration as rapidly as possible, by manipulating the plasma concentration around the target. Currently systems are pre-programmed with the Marsh and Schnider pharmacokinetic models for propofol. The former is an adapted version of the Gepts model, in which the rate constants are fixed, whereas compartment volumes and clearances are weight proportional. The Schnider model was developed during combined pharmacokinetic-pharmacodynamic modelling studies. It has fixed values for V1, V3, k(13), and k(31), adjusts V2, k(12), and k(21) for age, and adjusts k(10) according to total weight, lean body mass (LBM), and height. In plasma targeting mode, the small, fixed V1 results in very small initial doses on starting the system or on increasing the target concentration in comparison with the Marsh model. The Schnider model should thus always be used in effect-site targeting mode, in which larger initial doses are administered, albeit still smaller than for the Marsh model. Users of the Schnider model should be aware that in the morbidly obese the LBM equation can generate paradoxical values resulting in excessive increases in maintenance infusion rates. Finally, the two currently available open TCI systems implement different methods of effect-site targeting for the Schnider model, and in a small subset of patients the induction doses generated by the two methods can differ significantly.

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Preoperative anxiety: detection and contributing factors.

Joseph Nielson, C Kwiatkowska, N Badner … (1990)

The purpose of this study was to determine whether there is a correlation between anxiety the night before surgery and that existing immediately preoperatively, whether anaesthetists can detect preoperative anxiety and to establish the presence of any factors that might assist in the determination of preoperative anxiety. Anxiety was measured objectively using the Spielberger State-Trait Anxiety Inventory (STAI), and the Multiple Affect Adjective Check List (MAACL). Anxiety was found to be higher in females and those not having had a previous anaesthetic, and to remain constant from the afternoon before surgery to the immediate preoperative period. Anaesthetists were found to be poor assessors of anxiety unless they specifically questioned their patients about this.

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Author and article information

Contributors

David W. Hewson:

ORCID: http://orcid.org/0000-0002-5314-8522

david.hewson@nottingham.ac.uk

Frank Worcester: frank.worcester@ntu.ac.uk

James Sprinks: james.sprinks@ntu.ac.uk

Murray D. Smith: mdsmith@lincoln.ac.uk

Heather Buchanan: heather.buchanan@nottingham.ac.uk

Philip Breedon: philip.breedon@ntu.ac.uk

Jonathan G. Hardman: j.hardman@nottingham.ac.uk

Nigel M. Bedforth: nigel.bedforth@nuh.nhs.uk

Journal

Journal ID (nlm-ta): Trials

Journal ID (iso-abbrev): Trials

Title: Trials

Publisher: BioMed Central (London )

ISSN (Electronic): 1745-6215

Publication date (Electronic): 13 February 2019

Publication date PMC-release: 13 February 2019

Publication date Collection: 2019

Volume: 20

Electronic Location Identifier: 129

Affiliations

[1 ]ISNI 0000 0001 0440 1889, GRID grid.240404.6, Department of Anaesthesia and Critical Care, , Nottingham University Hospitals NHS Trust, ; Nottingham, UK

[2 ]ISNI 0000 0001 0727 0669, GRID grid.12361.37, Medical Design Research Group, , Nottingham Trent University, ; Nottingham, UK

[3 ]ISNI 0000 0004 0420 4262, GRID grid.36511.30, Community and Health Research Unit, , University of Lincoln, ; Lincoln, UK

[4 ]ISNI 0000 0004 1936 8868, GRID grid.4563.4, Division of Rehabilitation and Ageing, , University of Nottingham, ; Nottingham, UK

[5 ]ISNI 0000 0004 1936 8868, GRID grid.4563.4, Anaesthesia and Critical Care, , University of Nottingham, ; Nottingham, UK

Author information

David W. Hewson http://orcid.org/0000-0002-5314-8522

Article

Publisher ID: 3228

DOI: 10.1186/s13063-019-3228-4

PMC ID: 6374891

PubMed ID: 30760311

SO-VID: fceeb0d0-3e18-4887-903f-82b4316a06ae

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 16 October 2018

Date accepted : 29 January 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100009127, Invention for Innovation Programme;

Award ID: II-LA-0716-20002

Award Recipient : Nigel M. Bedforth

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: propofol sedation,patient-maintained propofol sedation,regional anaesthesia,joint arthroplasty,procedural sedation

Data availability:

ScienceOpen disciplines: Medicine

Keywords: propofol sedation, patient-maintained propofol sedation, regional anaesthesia, joint arthroplasty, procedural sedation

Anaesthetist-controlled versus patient-maintained effect-site targeted propofol sedation during elective primary lower-limb arthroplasty performed under spinal anaesthesia (ACCEPTS): study protocol for a parallel-group randomised comparison trial

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Abstract

Background

Methods

Discussion

Trial registration

Electronic supplementary material

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Most cited references 13

The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers.

Pharmacokinetic models for propofol--defining and illuminating the devil in the detail.

Preoperative anxiety: detection and contributing factors.

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