Comparison of two methods of administering a short-acting sedative drug during hip and knee replacement surgery under spinal anesthesia

ISRCTN	ISRCTN11676212
DOI	https://doi.org/10.1186/ISRCTN11676212
Sponsor	Riga Stradiņš University
Funder	Investigator initiated and funded

Submission date: 18/03/2026
Registration date: 19/03/2026
Last edited: 19/03/2026

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Surgery

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Rihards Serzans
Public, Scientific, Principal investigator

Dzirciema iela 16
Riga
LV-1007
Latvia

ORCID ID	0000-0002-5805-8825
Phone	+371 (0)67061579
Email	rihards.serzans+research@rsu.lv

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Parallel
Purpose	Treatment
Scientific title	A randomized controlled trial comparing intermittent bolus administration versus target-controlled infusion of remimazolam for moderate sedation in adult patients undergoing hip or knee arthroplasty under spinal anesthesia
Study objectives
Ethics approval(s)	1. Approved 02/08/2023, Ethics Committee of the Hospital of Traumatology and Orthopaedics (Duntes iela 22, Riga, LV - 1005, Latvia; +371 (0)67 399 266; izg@tos.lv), ref: 41/2023/1 2. Approved 26/04/2024, Ethics Committee of the Hospital of Traumatology and Orthopaedics (Duntes iela 22, Riga, LV - 1005, Latvia; +371 (0)67 399 266; izg@tos.lv), ref: 29/2024/1
Health condition(s) or problem(s) studied	Sedation management in adult patients undergoing hip or knee arthroplasty under spinal anesthesia
Intervention	Participants are randomly assigned in a 1:1:1 ratio using computer-generated block randomisation to one of three intervention arms: intermittent bolus administration of remimazolam, target-controlled infusion using the Masui pharmacokinetic model, or target-controlled infusion using the Zhou pharmacokinetic model. All participants receive standard intraoperative monitoring, including electrocardiography, non-invasive blood pressure, and pulse oximetry. Supplemental oxygen is administered via nasal cannula. Moderate sedation is targeted, defined as a Modified Observer’s Assessment of Alertness/Sedation score of 2 to 3, with sedation level assessed at 5-minute intervals. In the bolus group, remimazolam is administered as an initial intravenous bolus of 0.04 mg per kilogram over 2 minutes. Additional boluses of 0.04 mg per kilogram are administered as needed to maintain the target sedation level. In the target-controlled infusion groups, remimazolam is administered using an infusion pump guided by pharmacokinetic models implemented in a clinical decision-support application. Initial effect-site concentration targets are set between 0.2 and 0.4 micrograms per millilitre, with adjustments made in increments of 0.05 to 0.10 micrograms per millilitre based on the sedation level. If oversedation occurs, the infusion is reduced or temporarily discontinued. All interventions are continued throughout the surgical procedure under spinal anesthesia.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Remimazolam
Primary outcome measure(s)	Sedation quality (time in target sedation range) measured using Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale assessed at 5-minute intervals; proportion of measurements with score 2–3 expressed as percentage at initiation of sedation to end of the surgical procedure Sedation variability (time outside target range) measured using MOAA/S scale assessed at 5-minute intervals; proportion of measurements with score <2 (oversedation) and >3 (undersedation), expressed as percentages at initiation of sedation to end of the surgical procedure
Key secondary outcome measure(s)	Sedative drug utilisation measured using total remimazolam dose normalised to body weight and duration (milligrams per kilogram per hour) at initiation of sedation to end of the surgical procedure Haemodynamic stability – hypotension measured using incidence of systolic blood pressure <90 mmHg or mean arterial pressure <60 mmHg (binary per patient) at during intraoperative period Haemodynamic stability – bradycardia measured using Incidence of heart rate < 50 beats per minute (binary per patient) at During intraoperative period Respiratory safety – hypoxia measured using incidence of peripheral oxygen saturation < 94% (binary per patient) at during intraoperative period Pharmacodynamic response (effect-site concentration–response relationship) measured using logistic regression modelling of probability of achieving MOAA/S 2–3 as a function of effect-site concentration (micrograms per millilitre) at during intraoperative period
Completion date	05/12/2024

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	90 Years
Sex	All
Target sample size at registration	45
Total final enrolment	42
Key inclusion criteria	1. Adult patients aged 18 years or older 2. Scheduled for elective hip or knee arthroplasty 3. Planned to undergo surgery under spinal anesthesia 4. American Society of Anesthesiologists physical status class I–III 5. Able to provide written informed consent
Key exclusion criteria	1. Hepatic impairment (alanine aminotransferase or aspartate aminotransferase >100 IU L⁻¹ or aspartate aminotransferase to alanine aminotransferase ratio ≥2:1) 2. Known hypersensitivity or allergy to benzodiazepines 3. Chronic or daily use of benzodiazepines 4. Cognitive impairment precluding reliable assessment of sedation level or informed consent 5. Contraindications to spinal anesthesia 6. Contraindications to procedural sedation
Date of first enrolment	01/09/2023
Date of final enrolment	05/12/2024

Locations

Countries of recruitment

Latvia

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan

Editorial Notes

18/03/2026: Study's existence confirmed by the Ethics Committee of the Hospital of Traumatology and Orthopaedics.