Clinical trial NCT02492282: Evaluation of a Novel Closed-loop Propofol and Remifentanil System Guided by Bispectral Index Compared to a TCI Open-loop System
Official title: Evaluation of a Novel Closed-loop Propofol and Remifentanil System Guided by Bispectral Index Compared to a TCI Open-loop System: a Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anesthesia, General
Anesthesia, Intravenous
Lead sponsor: Universidad de Antioquia
Sponsor class: OTHER
First posted: 2015-07-08
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time in adequate anesthetic depth
timeFrame: intraoperative
Secondary outcomes:
measure: Proportion of patients with adequate anesthetic depth
timeFrame: intraoperative
measure: Difference in technical performance drivers intravenous infusion
timeFrame: intraoperative
measure: Difference in the proportion of patients with adequate intraoperative analgesia
timeFrame: intraoperative
measure: Difference in the proportion of patients in which they have to perform manual modification of the drug infusion.
timeFrame: intraoperative
measure: Difference in the rate of change of an intravenous anesthetic technique to a technique based on halogenated.
timeFrame: intraoperative
measure: Amount of anesthetic medications used during the anesthetic
timeFrame: intraoperative
measure: Proportion of patients with haemodynamic instability.
timeFrame: intraoperative
measure: Proportion of patients with intraoperative recall
timeFrame: 2 hours after surgery
measure: Proportion of patients with awakening during anesthetic maintenance
timeFrame: intraoperative
Other outcomes:
Locations:
city: Medellin
country: Colombia
facility: Hospital Universitario San Vicente Fundación
state: Antioquia
Study officials:
affiliation: Universidad de Antioquia
name: Fabian Casas, MD, Ms
role: PRINCIPAL_INVESTIGATOR
References:
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citation: De Smet T, Struys MM, Neckebroek MM, Van den Hauwe K, Bonte S, Mortier EP. The accuracy and clinical feasibility of a new bayesian-based closed-loop control system for propofol administration using the bispectral index as a controlled variable. Anesth Analg. 2008 Oct;107(4):1200-10. doi: 10.1213/ane.0b013e31817bd1a6.
citation: Puri GD, Kumar B, Aveek J. Closed-loop anaesthesia delivery system (CLADS) using bispectral index: a performance assessment study. Anaesth Intensive Care. 2007 Jun;35(3):357-62. doi: 10.1177/0310057X0703500306.
citation: 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.
citation: 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.