Evaluation of a Novel Closed-loop Propofol and Remifentanil System Guided by Bispectral Index Compared to a TCI Open-loop System

NCT ID: NCT02492282

Last Updated: 2016-06-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2016-04-30

Brief Summary

Closed loop system in intravenous anesthesia is more effective to maintain depth of anesthesia compared with manual system open, it is unclear what driver and variables to achieve this goal be more physiological; in the literature doesn´t exist studies showing that the closed-loop system for both hypnotic and opioid is better than the controlled pharmacokinetic models and open loop system (target controlled infusion-TCI) to maintain anesthetic depth. In addition, the infusion of the opioid lacks physiological controllers in closed loop. Thus, a system was designed for intravenous anesthesia in closed loop for propofol as hypnotic based on neuromonitoring bispectral index as anesthetic depth, and was integrated an additional closed system for remifentanil using hemodynamic variables and control algorithm associated with bispectral index.

The purpose of this study is to determine the therapeutic effectiveness of a new system of administration of intravenous anesthesia in closed loop to maintain a depth of anesthesia compared to an open loop system TCI.

Detailed Description

Total intravenous anesthesia (TIVA) is a technique in which general anesthesia is administered intravenously, exclusively, a combination of drugs in the absence of any anesthetic agent inhaled1. TIVA development is closely linked to that of perfusion systems; these make total intravenous anesthesia enjoy several advantages as high hemodynamic stability, anesthetic depth more balanced, rapid and predictable recovery, less medication administered, less pollution and lower toxicity , not only for the patient also for the surgical equipment 2,3, 4 .

Two methods for controlling drug administration can be distinguished: open-loop and closed-loop control.

Open loop control applies pharmacokinetics (PK)/pharmacodynamics (PD) models based on the estimation of concentration of the drug in certain parts of the body, without measuring these concentrations in real time. The inaccuracy resulting from the absolute concentration requires the clinician to manually titrate dosage and objective observation based on the concentration of the desired therapeutic effect. This titration requires high clinical experience and a process of intensive monitoring, which may divert the attention from critical situations which in turn leads to suboptimal therapy or even to put safety at risk patient5, 6.

The application of closed-loop systems for the administration of an anesthetic requires a perfect balance of all the basic components of a system of this type: a variable control of the specific therapeutic effect; a target value for this variable (usually called set point); an actuator control (in this case, the drug infusion pump); a system (in this case the patient); and control algorithm7. This system excludes the control anesthesiologist drug infusion which is determined by one or more clinical variables that directly reflect the relationship PK / PD which previously established the attending anesthesiologist. The controller automatically calculates the optimal rate of infusion based on the current value and the desired value of the controlling variable and previously established mathematical models.

With the appearance of electroencephalographic monitoring practice as a control variable, began to conduct studies to assess the cerebral effect of anesthetics. Linear model two compartments is used to describe the relationship of drug concentration and an adaptive controller and this system was used subsequently using EEG to study the interaction of opioid and propofol 8,9. After marketing bispectral index derived from the EEG, began to evaluate closed loop systems using the BIS technology in several studies concluding that such systems not only makes more predictable anesthetic depth, but provides greater intraoperative hemodynamic stability and early recovery of the sedative and hypnotic effects of propofol 10,11,12,13,14.

Closed loop system in intravenous anesthesia is more effective to maintain the depth of anesthesia compared with manual system open, it is unclear what the driver and the variables to achieve this goal be more physiological and accurately; in the literature doesn´t exist studies showing that the closed-loop system for both hypnotic and opioid is better than the controlled pharmacokinetic models and open loop system to maintain anesthetic depth. In addition, the infusion of the opioid lacks physiological controllers in closed loop. Thus, a system was designed for intravenous anesthesia in closed loop for propofol as hypnotic based on neuromonitoring bispectral index as anesthetic depth, and was integrated an additional closed system for remifentanil using hemodynamic variables and control algorithm associated with bispectral index.

The purpose of this study is to determine the therapeutic effectiveness of a new system of administration of intravenous anesthesia in closed loop to maintain a depth of anesthesia compared to an open loop system TCI.

Conditions

Anesthesia, General; Anesthesia, Intravenous

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Closed-Loop

This group includes patients with randomization process be assigned to closed loop intravenous anesthesia; the system evaluates, feeds and acts according to the patient's bispectral index, excluding the anesthesiologist. This system use a variable control of specific therapeutic effect; a target value for this variable (set point); an actuator control (infusion pump), a system (patient) and a control algorithm.

Group Type: EXPERIMENTAL

Closed-Loop propofol and remifentanil system by Bispectral Index

Intervention Type: DEVICE

propofol

Intervention Type: DRUG

Open-Loop

This group includes patients with the randomization process are assigned to open loop in which the application of anesthetics is exclusively with pharmacokinetic parameters using TCI and employs mathematical models drug. For propofol used Schneider model and Minto model for remifentanil based on effective site concentration. Changes will be made by the anesthesiologist according to his criteria, trying to keep the BIS range of 40 and 60.

Group Type: ACTIVE_COMPARATOR

Open-Loop propofol and remifentanil by Target Controlled Infusion

Intervention Type: DEVICE

propofol

Intervention Type: DRUG

Interventions

Closed-Loop propofol and remifentanil system by Bispectral Index

Intervention Type: DEVICE

Open-Loop propofol and remifentanil by Target Controlled Infusion

Intervention Type: DEVICE

propofol

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Older than 18 years
• Scheduled for noncardiac surgery elective low-risk or intermediate
• Expected surgery time greater than 1 hour
• Procedure requiring general anesthesia
• Classification of the American Society of Anesthesiologists (ASA) as I or II

Exclusion Criteria

• Pregnant women
• Surgery scheduled urgent or emergency
• Personal history of allergy to eggs or any other part of propofol
• Personal history of abnormalities or congenital or acquired cognitive sequels: infantile cerebral palsy, Down syndrome, cerebral ischemic disease, traumatic brain injury, brain tumor, autism.
• Chronic use of benzodiazepines or antipsychotics
• A patient who does not consent to participate in the study prior to surgery or before randomization
• Need for anesthetic or analgesic blockade before surgery peripheral nerve

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Universidad de Antioquia

OTHER

Sponsor Role: lead

Responsible Party

Fabian David Casas Arroyave

MD, Ms.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fabian Casas, MD, Ms

Role: PRINCIPAL_INVESTIGATOR

Universidad de Antioquia

Locations

Hospital Universitario San Vicente Fundación

Medellín, Antioquia, Colombia

Countries

Colombia

References

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Reference Type: BACKGROUND

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

PMID: 17591128 (View on PubMed)

Struys MM, De Smet T, Versichelen LF, Van De Velde S, Van den Broecke R, Mortier EP. Comparison of closed-loop controlled administration of propofol using Bispectral Index as the controlled variable versus "standard practice" controlled administration. Anesthesiology. 2001 Jul;95(1):6-17. doi: 10.1097/00000542-200107000-00007.

Reference Type: RESULT

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Hemmerling TM, Arbeid E, Wehbe M, Cyr S, Taddei R, Zaouter C. Evaluation of a novel closed-loop total intravenous anaesthesia drug delivery system: a randomized controlled trial. Br J Anaesth. 2013 Jun;110(6):1031-9. doi: 10.1093/bja/aet001. Epub 2013 Feb 20.

Reference Type: RESULT

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Other Identifiers

TIVA-15517889

Identifier Type: -

Identifier Source: org_study_id