Target-controlled Infusion With Propofol in the Emergency Department : a Prospective Study on 45 Adult Patients (SIVOC)

Procedural sedation is an emergency medicine technique that provides a brief, deep sedation in order to perform very painful emergency emergent procedures such as displaced fracture or dislocated joints reduction. Propofol is recommended for this purpose, injected administered in slow IV bolus injections according to the technique known as manual titration. But despite this precaution, temporarily excessive sedation can happen, and a side effect can appear (arterial hypotension or respiratory depression). Target-controlled infusion (TCI) is an anesthesia technique that permits to obtain a precise constant and stable concentration of medication, boluses volumes of injection being calculated and delivered automatically by an electric syringe equipped with a software obedient to existing pharmacokinetic models. In the operating room, Ffor anesthetic induction, maintenance and awakening, respectively, in the operating room, the brain concentrations of propofol range respectively from 2 to 6 μg/mL, 2 to 4 μg/mL, and between 0.8 and 1.2 μg/mL, respectively. Since TCI has never been used in emergency departments (ED), the brain propofol concentrations which are necessary for sedation and awakening of the patient are not known and must be determined experimentally.

In this single-center, prospective, interventional study, safety and feasibility of TCI will be studied in one ED with the primary objective of determining the brain propofol concentrations necessary to reach the an optimal sedation in for patients with indications of sustaining very painful orthopedic emergency emergent procedures

Study Overview

• Status: Completed
• Conditions: Limb Fracture; Joint Dislocation
• Intervention / Treatment: Drug: Target control infusion with propofol

Detailed Description

Procedural sedation is an emergency medicine technique that provides a brief, deep sedation in order to perform very painful emergency emergent procedures such as displaced fracture or dislocated joints reduction. For this purpose, propofol is a remarkable sedative agent for its very short elimination half-life, antiemetic property and myorelaxant effects. It is recommended to inject administer it in slow IV boluses injections according to the technique known as manual titration, but despite this precaution, temporarily excessive sedation can happen, and a side effect appear (arterial hypotension or respiratory depression).

Target-controlled infusion (TCI) is an anesthesia technique that permits to obtain a precise constant and stable concentration of medication, boluses volumes of injection being calculated and delivered automatically by an electric syringe equipped with a software obedient to existing pharmacokinetic models.

The age, size and weight of the patient are filledentered, then the syringe delivers the volume which is necessary and sufficient to reach and maintain the target concentration chosen by the practitioner. For anesthetic induction in the operating room, the brain concentrations of propofol used range from 2 to 6 μg/mL, then the general anesthesia maintenance is obtained with 2 to 4 μg/mL, and the patient awakening usually happens between 0.8 and 1.2 μg/mL. Since TCI has never been used in emergency departments (ED), the brain propofol concentrations which are necessary for sedation and awakening of the patient are not known and must be determined experimentally.

In this single-center, prospective, interventional study, safety and feasibility of TCI will be studied in an ED with the primary objective of determining the brain propofol concentrations necessary to reach the an optimal sedation in for patients with indications ofsustaining very painful orthopedic emergency emergent procedures. As secondary objectives, we will study the characteristics of sedations obtained (level, delays, lengths); the Delays, lengths and levels of sedation obtained, overall delivered doses of propofol administered; the , nature, appearance delays and lengths of potential adverse events (AE) related to procedural sedation, particularly complications related to procedural sedation, and necessary interventions necessary to handle these AE., will be studied as secondary objectives

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Fabien LEMOEL, PhD; Phone Number: 0033 0492038535; Email: lemoel.f@chu-nice.fr
• Study Contact Backup: Name: Jocelyn RAPP; Phone Number: 0033 0492038535; Email: rapp.j@chu-nice.fr

Study Locations

• France
  • Nice, France, 06000
    • Emergency department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age of 18 or more
• Affiliated or beneficiary of a French health insurance system
• Indication of procedural sedation, by the emergency department physician in the context of the management of for a patient with an orthopedic lesion requiring a potentially painful emergentcy therapeutic actionprocedure (reduction of a joint dislocation or realignment of a limb displaced fracture)

• For women :

  • at childbearing age : effective contraception (oral, intra-uterine device or condoms)
  • postmenopausal : amenorrhea for at least 12 month before the inclusion day
  • objective infertility (diagnosis or surgically)
• Signed free informed consent or inclusion in the context of an emergency situation

Exclusion Criteria:

• Patient of more than 18 under legal protection or deprivation of liberty measures
• Ongoing pregnancy or breastfeeding women
• Patient with the incapacity to give his free informed consent, excepted if the incapacity is induced by the context of the emergency situation (inclusion in the context of an emergency situation)
• Known hypersensitivity to propofol or one of the excipients, egg, sojasoya or peanuts
• ASA comorbidity score of 4 or more
• Heart, respiratory, renal or hepatic failure
• Epilepsy
• Lipid metabolism disorder
• Mitochondrial disease
• Hemodynamic instability, multiple traumatism
• Elevated intracranial tension
• Drug or alcohol intoxication
• Simultaneous participation to another interventional study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Target-controlled infusion (TCI); Target-controlled infusion (TCI) with propofol up to 5.5µg/ml during an anticipated average maximal time of 15 minutes	Drug: Target control infusion with propofol; Target control infusion with propofol for patients with indications of sustaining very painful orthopedic emergency emergent procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Propofol brain concentration	Propofol brain concentration necessary for the patient to reach a Ramsay score of 5 (optimal sedation) (Ce_Ramsay5)	Between the beginning of sedation (T0) and the beginning of the orthopedic procedure (T_Ramsay5)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delay between the beginning of sedation (T0) and the beginning of the orthopedic procedure (T_Ramsay5)	the delay is the outcome, T_Ramsay5 (up to an anticipated average maximal time of 15 minutes after T0)]	the delay is the outcome, T_Ramsay5 (up to an anticipated average maximal time of 15 minutes after T0)]
Propofol brain concentration when the patient spontaneously reopen his eyes (Ce_OuvertureYeux)	Propofol brain concentration when the patient spontaneously reopen his eyes after the orthopedic procedure has been realized, the TCI syringe been switched off, and the immobilization been placed (Ce_OuvertureYeux)	Time after T0 when the patient spontaneously reopen his eyes (up to an anticipated average maximal time of 30 minutes after T0)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Fabien LEMOEL, PhD, Emergency Department, Universitary Hospital of Nice

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2019
• Primary Completion (Actual): October 25, 2020
• Study Completion (Actual): October 25, 2020

Study Registration Dates

• First Submitted: December 19, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 21, 2018

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 15, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: ED; emergency department; sedation; TCI; dislocation reduction; Target-controlled infusion; fracture reduction
• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Disease Attributes; Joint Diseases; Musculoskeletal Diseases; Emergencies; Joint Dislocations; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: 18-PP-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No