ISRCTN - ISRCTN59349598: Hemodynamic stability during anesthesia induction with ketofol mixture

Plain English Summary

Background and study aims
Surgery has to be as safe as possible and patients are prepared to be in the best condition possible before elective surgery. The main role of anesthesiologist during surgery is managing and treating changes in patient's critical life functions (such as breathing, heart rate, blood pressure etc) by giving them a medication called anesthesia. Patients are required to be in their medically induced coma temporary coma before the surgeon can begin surgery, as well it is helpful to be in the coma while the breathing tube is placed in patients throats as this is painful and unpleasant. Then, patients require their breathing airway to be secured by a breathing tube placed in the throat, which is painful and unpleasant. Therefore, it is important that patients are placed into their coma for the surgery quickly and safely. Different medications are used during surgery, and one of the most common ones used is called propofol. Another commonly used medication is called esketamine. Sometimes these are mixed together for outpatient procedure situations. The mixture is known as “ketofol”. Ketofol is not used for the induction of coma for general anesthesia but could have the potential to. The aim of this study is to see if undergoing anesthesia with ketofol is able to provide stable critical life function parameters than propofol and to examine different mixtures of ketofol in order to help establish a standardized formula of what should be in the mixture.

Who can participate?
Healthy adults aged between 18 and 80 years old with no severe chronic illness undergoing elective surgery requiring general anesthesia.

What does the study involve?
Participants are randomly allocated to one of three groups. All participants undergo the surgery but receive different anaesthesia based on their allocation. Those in the first group receive ketofol with profol:esketamin ratio of 1:1. Those in the second group receive ketofol with profol:esketamin ratio 2:1. Those in the last group receive propofol. Surgeries are done to the standard level of care. Participants have their vital signs, hemodinamic status (measuring of heart function) and coma depth monitored throughout the surgery.

What are the possible benefits and risks of participating?
There are no notable benefits or risks involved with participating.

Where is the study run from?
Maribor University Medical Centre (Slovenia)

When is the study starting and how long is it expected to run for?
January 2017 to December 2018

Who is funding the study?
Maribor University Medical Centre (Slovenia)

Who is the main contact?
Dr Domen Kogler
domen.kogler@gmail.com

Study website

Contact information

Type

Public

Contact name

Mr Domen Kogler

ORCID ID

http://orcid.org/0000-0003-1022-3032

Contact details

Maribor University Medical Centre
Ljubljanska ulica 5
Maribor
2000
Slovenia

Additional identifiers

EudraCT/CTIS number

IRAS number

ClinicalTrials.gov number

Protocol/serial number

KME 39/08/16

Study information

Scientific title

Hemodynamic stability during anesthesia induction with propofol/esketamine (ketofol) mixture – identifying optimal ratio

Acronym

Study hypothesis

The aim of this study is to compare the hemodynamic stability during anesthesia induction with ketofol in different concentration mixtures.

Ethics approval(s)

Republic of Slovenia National Medical Ethics Committee - NMEC, 25/09/2016, ref: 0120-395/2016-2; KME 39/08/16

Study design

Randomised double blind controlled parallel trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Study setting(s)

Hospital

Study type

Treatment

Patient information sheet

See additional files

Condition

Elective surgery with orotracheal intubation

Intervention

Participants undergoing elective surgery are randomly allocated to one of three groups. Randomisation is done by an independent person using a draw. The following groups are:

Group K1: Participants in this group receive an anesthetic mixture of 10 ml 1% propofol and 4 ml 2,5% esketamine

Group K2: Participants in this group receive an anesthetic mixture mixture of 10 ml 1% propofl, 2 ml 2,5% esketamine and 2 ml 0,9% NaCl solution

Group P: Participants in this group receive an anesthetic mixture of 10 ml 1% propofol and 4 ml 0,9% NaCl solution (control)

All participants are premedicated with midazolam one hour before surgery. All patients follow the same protocol for first 16 minutes, the only variable is anaesthetic mixture. Anaesthesia induction starts at time 0 when patient gets 0,25 mcg/kg of sufentanyl (concentration 5 mcg/ml, rounded to nearest ml). At 120 seconds all participants receive 5 ml bolus of anaesthetic mixture following titration with 1 ml until clinical effect (lose of palpebral efect). Then 0,6 mg/kg (concentration 10mg/ml, rounded to nearest ml) is administered to patient following another 2ml of anaesthetic mixture. Between minute 4 and 5 (time 240 s to 300 s) the patient is intubated and then mechanically ventilated, maintaining anesthesia with sevoflurane 1,0-1,5 vol%.

Dosing is titrated to clinical effect (lose of palpebral effect) with blinded recording of Bispectral index.

Total duration of treatment is one hour before surgery (premedication) untill one hour after surgery (recovery from anaesthesia) for all treatment arms (sturdy groups). Duration of data collection study is first 16 minutes after application of sufentanyl (start of anaesthesia induction). Follow up is the same for all treatments arms and ends one hour after surgery (recovery from anaesthesia).

Intervention type

Drug

Pharmaceutical study type(s)

Phase

Not Applicable

Drug/device/biological/vaccine name(s)

Propofol, esketamine

Primary outcome measure

1. Cardiac output is measured noninvasively using transthoracal electric bioimpedance every minute for first 16 minutes after induction of anesthesia
2. Blood pressure is measured noninvasively using arm cuffs every 2 minutes for first 16 minutes after induction of anesthesia
3. Heart rate is measured by ECG every minute for first 16 minutes after induction of anesthesia

Secondary outcome measures

1. Bispectral index (BIS) (depth of sedation or anaesthesia) is monitored with 15 seconds sampling using forehead electrodes every minute for first 16 minutes after induction of anesthesia.
2. Dose titrated to clinical effect (loss of palpebral effect)

Overall study start date

01/01/2017

Overall study end date

31/12/2018

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged 18-80 years
2. ASA Physical Status I or II
3. Elective surgery with orotracheal intubation

Participant type(s)

Patient

Age group

Adult

Lower age limit

18 Years

Upper age limit

80 Years

Sex

Both

Target number of participants

100

Participant exclusion criteria

1. Allergy or sensitivity to any medication used in trial
2. Alcohol or drug abuse
3. Chronical use of benzodiazepins, opiats or psyhothrophic medication
4. Body mass index higher than 35 or lower than 15
5. Anticipated difficult intubation (Mallampati III or IV)
6. Untreated arterial hypertension
7. Patients with Alzheimers, epilepsy or psychosis

Recruitment start date

01/08/2017

Recruitment end date

30/06/2018

Locations

Countries of recruitment

Slovenia

Study participating centre

University Clinical Centre Maribor
Ljubljanska ulica 5
Maribor
2000
Slovenia

Sponsor information

Organisation

University Clinical Centre Maribor

Sponsor details

Ljubljanska ulica 5
Maribor
2000
Slovenia

Sponsor type

Hospital/treatment centre

Website

http://www.ukc-mb.si/en/

ROR

https://ror.org/02rjj7s91

Funders

Funder type

University/education

Funder name