Closed Loop Isoflurane Administration With Bispectral Index in Open Heart Surgery

2014-08-27 03:15:54 | BioPortfolio


With the advancement in microprocessor technology and better understanding of pharmacodynamics and pharmacokinetics of anaesthetic agents, computer facilitated closed loop control of anaesthesia using propofol has been shown to be accurate with better performance than manual control (3,4). Literature on computer controlled administration of inhalational anaesthetics is few (1), as it requires the computer to control the dial setting on the vapouriser. The investigators intend to compare the computer controlled closed loop administration of isoflurane by infusing it into the anaesthetic circuit with conventional vaporiser control in elective open heart surgery.

40 patients (ASA II-IV; 18- 65 years) undergoing elective cardiac surgery requiring cardiopulmonary bypass (CPB) will be randomly divided into manual or closed loop groups. Propofol will be used for induction of anaesthesia in both groups followed by isoflurane for maintenance. In the manual group, isoflurane will be administered through the Tech 7 vapouriser during pre and post CPB periods to target bispectral index (BIS) of 50. In closed loop group, isoflurane will be administered using infusion of liquid isoflurane into expiratory limb of the closed circuit. This rate of infusion though a conventional syringe pump will be controlled by algorithm termed 'Improvised Anaesthetic Agent Delivery System' (IAADS) to maintain BIS of 50. Patients in both groups will receive 500ml of 100 % oxygen as fresh gas flow. The % of time bispectral index (BIS) is within the 10% of set target BIS of 50 will be the primary outcome measure. The secondary outcome measures will be median performance error (MDPE)(2), median absolute performance error (MDAPE)(2), wobble(2), divergence(2), amount of isoflurane used and hemodynamic parameters will be secondary outcome measures.


The basic components in a closed loop anesthesia delivery system are: (1) a system under control- patient; (2) a controlled variable that measures depth of anesthesia, (3) a set point for this variable specified by the user, (4) an actuator which comprises an algorithm to translate a measured value of the controlled variable to a particular action or the actuator to steer the controlled variable closer to the target variable.

In the proposed study, the controlled variable will be BIS. The control actuator is a patented (2158/DEL/2007) pharmacodynamic- pharmacokinetic model based adaptive infusion system termed "Improved Anesthetic Agent Delivery System (IAADS"). An IBM compatible with PENTIUM 2 or higher processor PC (2 GHz) is used to implement the control algorithm, provide a user interface and control communication through serial ports (RS 232) with the infusion system (Pilot- C, Frasenius, France) and a Datex vital sign monitor. We will use Avance ventilator (Datex Ohmeda, software version 5.0) with CO2 absorber and ascending bellows to provide constant volume ventilation. The amount of acceptable leak in the circuit will be reduced to ≤ 100 ml min-1 determined during ventilation of a test lung. Low fresh gas flows will be used during the study. Isoflurane will injected into the expiratory limb of circle system via 20 ml Plastipak (polyethylene BD) syringe with a 100 cm long polyethylene tubing (Vygon, India) using a Pilot C Infusion pump (Fresenius vial SA, France). The stated volumetric accuracy of the infusion pump is ±2 %.

After obtaining written informed consent, patients will be randomly allocated (by closed envelope technique using computer generated random numbers) to one of the two groups- manual and automatic. The investigator will be present during the procedure for data collection purpose only and will not be involved in the conduct of anaesthesia. All patients will receive 5- 10mg oral diazepam as per institutional protocol the night before and on the morning of surgery as pre-medication. After shifting the patient to the operation table, patients will be started on normal saline 100 ml/hr (1-2 ml/kg/hr). Routine physiological monitoring will be commenced (pulse oximetry, electrocardiography, non-invasive blood pressure monitoring). BIS will be obtained by disposable sensors (Aspect medical system Inc. MA USA) attached to the forehead of the patient. Patients will receive 0.15 mg/kg of morphine sulphate before induction in aliquots of 3-5mg, during which indwelling arterial cannula, central venous line and pulmonary artery catheters (if deemed to be necessary) will be inserted.

Before induction, patients shall receive fentanyl 3μg/kg over three minutes. In automatic mode, IAADS automatically will calculate and titrate the initial and subsequent propofol infusion rate according to the weight of the patient, risk status and target BIS value, which will be set at 50 for all cases with a range of 40-60. In manual group, the propofol infusion rate will be determined by the attending anaesthesiologist according to the weight of the patient, and the target BIS of 50, with the aim to maintain BIS within 40- 60. After loss of consciousness (LOC), patients will receive 0.1mg/kg vecuronium bromide and will be intubated after 4 minutes.

The circle system will be closed after ascertaining the correct position of the endotracheal tube. In the control group, isoflurane infusion will be started into the expiratory limb of the circle at predetermined rates. The isoflurane concentration in the circuit will be built gradually over a period of 10 minutes to attain a specified BIS value. During isoflurane anaesthesia, patients will be ventilated with 100% oxygen. Fresh gas flows will be started at 500ml/min, and the ventilation will be set so as to maintain an end tidal CO2 concentration of 30-35 mmHg. If the fresh gas flows are inadequate as determined by incomplete filling of bellows, the flows will be increased gradually by 100 ml/min till a maximum of 1000 ml/min. If still there is a leak, the study will be abandoned and patient ventilated with higher flows. Thus, patients will be maintained on isoflurane injected into the expiratory limb of the circuit. Analgesia will be maintained with fentanyl 1μg/kg/hr infusion with further boluses of 1μg/kg before skin incision, sternotomy and commencement of cardiopulmonary bypass (CPB). Muscular relaxation will be maintained with a continuous infusion of vecuronium bromide 50μg/kg/hr. After 30 minutes of induction, an arterial sample will be drawn to have baseline values for blood gases, activated clotting time (ACT), and blood glucose. Patients will receive a bolus of 3 mg/kg heparin to raise the ACT above 480s. In cases of lower values, further boluses of heparin will be infused as per bull and colleagues dose response curve for heparin.

In the manual group, after the confirmation of the placement of endotracheal tube, the circle system will be closed and fresh gas flows will be started at 1000ml/min. Inhalational anaesthetics will be delivered by Fluotech 7 vapouriser (Datex ohmeda) for isoflurane. The initial dial setting will be started at 3% and after 5 minutes, flows will be reduced to 500 ml/min and isoflurane concentration will be titrated by the anaesthesiologist to maintain BIS of 50. The dial setting will be increased or decreased to maintain BIS of 50 and the number of times the vapouriser dial setting is changed will be noted. Rest of the protocol will be similar to the computer control group described above.

After the initiation of CPB, arterial blood gases, ACT and blood glucose will be determined every half an hour. An arterial partial pressure of O2 of 300-400 mmHg, ACT >480s and blood glucose <180mg/dl will be maintained throughout the bypass period. After successful completion of cardiopulmonary bypass, heparin will be antagonised with protamine sulphate.

During episodes when the mean arterial pressure exceeds 25% of the baseline or heart rate exceeds 100 beats/ min or 25% of the baseline, analgesia will be supplemented with fentanyl 1μg/kg. In case of persistent hypertension or tachycardia with BIS < 50, nitroglycerine infusion will be started and titrated to control blood pressure; Esmolol (upto 0.5mg/kg IV) will be administered to control the heart rate (HR). Similarly, in case of fall in mean arterial pressure to less than 25% of the baseline in the presence of normovolemia, initially phenylephrine will be used in boluses of 0.5μg/kg. For persistent hypotension after a cumulative Phenylephrine dose of 2μg/kg, dopamine infusion will be started and titrated to maintain MAP within 25% of the baseline. Likewise, in case of decrease in HR to <45beats/min., atropine sulphate (10μg/kg IV boluses) will be administered after excluding other treatable causes.

During CPB, patients will be shifted to propofol infusion, as the equipment for delivering fresh gases during CPB requires large fresh gas flows and circle system is not possible presently. MAP will be maintained between 50- 80 mmHg and any deviation from theses limits shall be treated with Phenylephrine boluses or sodium nitroprusside infusion. Propofol will be administered as per IAADS in computer control group and manually in the manual group to maintain BIS of 50.

Five minutes after the end of CPB, patients will be shifted back to isoflurane. In the computer control group, the concentration in the circuit for the set BIS will be achieved over 10 minutes. In the manual control group, the dial setting will be started at 3% and titrated according to the BIS. Fresh gas flows will be maintained at the same rate before the initiation of CPB.

At the end of skin closure, isoflurane, fentanyl and vecuronium will be stopped and the study protocol terminated. Patient will be shifted to propofol infusion for post operative sedation and will be shifted to post anaesthesia care unit without antagonizing muscle relaxants for elective mechanical ventilation. Patients will be extubated on meeting standard criteria for extubation. All patients will be continuously monitored for hemodynamic stability and maintenance of blood gases upto 24 hrs postoperatively. Patients will be subjected to a structured interview as modified from Brice and colleagues and described by Nordstrom for conscious awareness; on discharge from post anesthesia care unit, the day after surgery and approximately a week later.

Study Design

Allocation: Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject)


Open Heart Surgery


Conventional control, Closed loop control


Post Graduate Institute of Medical Education and Research




Postgraduate Institute of Medical Education and Research

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:15:54-0400

Clinical Trials [6598 Associated Clinical Trials listed on BioPortfolio]

Closed-loop Glucose Control for Automated Management of Type 1 Diabetes

We hypothesize that our integrated closed-loop glucose-control system can provide effective, tight, and safe blood glucose (BG) control in type 1 diabetes, thereby establishing the feasibi...

Closing the Loop for 36 Hours in Adolescents With Type 1 Diabetes

High variability of blood sugar levels and high incidence of night-time hypoglycaemia (low blood sugar) in young people with type 1 diabetes (T1D) make achieving the treatment goals in thi...

Adolescence and Diabetes:Can an Automated Closed Loop System Improve Control ?

This study evaluates the use of the FD2 automated closed loop insulin administration in Adolescents with a poor metabolic control . All youth will be treated in a random order by their usu...

Comparison of Two Closed-Loop Strategies for Glucose Control in Type 1 Diabetes The DREMED Trail- 2

The proposed study is two-arms, cross-over, randomized and single-center, in clinic Investigation in subjects with type 1 diabetes on insulin pump therapy. The purpose of the study is to ...

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

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 goa...

PubMed Articles [35623 Associated PubMed Articles listed on BioPortfolio]

Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care.

Background In patients with diabetes, hospitalization can complicate the achievement of recommended glycemic targets. There is increasing evidence that a closed-loop delivery system (artificial pancre...

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol.

Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studi...

Feasibility of Fully Automated Hypnosis, Analgesia, and Fluid Management Using 2 Independent Closed-Loop Systems During Major Vascular Surgery: A Pilot Study.

Automated titration of intravenous anesthesia and analgesia using processed electroencephalography monitoring is no longer a novel concept. Closed-loop control of fluid administration to provide goal-...

Gain-scheduled predictive extended state observer for time-varying delays systems with mismatched disturbances.

In this paper, a novel control scheme for systems with input and output time-varying delays is provided in discrete-time domain. The control strategy combines predictor-like techniques with a delay-de...

Randomized Outpatient Trial of Single- and Dual-Hormone Closed-Loop Systems That Adapt to Exercise Using Wearable Sensors.

Automated insulin delivery is the new standard for type 1 diabetes, but exercise-related hypoglycemia remains a challenge. Our aim was to determine whether a dual-hormone closed-loop system using wear...

Medical and Biotech [MESH] Definitions

Apparatus that provides mechanical circulatory support during open-heart surgery, by passing the heart to facilitate surgery on the organ. The basic function of the machine is to oxygenate the body's venous supply of blood and then pump it back into the arterial system. The machine also provides intracardiac suction, filtration, and temperature control. Some of the more important components of these machines include pumps, oxygenators, temperature regulators, and filters. (UMDNS, 1999)

Procedures that avoid use of open invasive surgery in favor of closed or local surgery. These generally involve use of laparoscopic devices and remote-control manipulation of instruments with indirect observation of the surgical field through an endoscope or similar device. With the reduced trauma associated with minimally invasive surgery, long hospital stays may be reduced with increased rates of short stay or day surgery.

Rhythmic compression of the heart by pressure applied manually over the sternum (closed heart massage) or directly to the heart through an opening in the chest wall (open heart massage). It is done to reinstate and maintain circulation. (Dorland, 28th ed)

Small pumps, often implantable, designed for temporarily assisting the heart, usually the left ventricle, to pump blood; they consist of a pumping chamber and a power source, which may be partially or totally external to the body and activated by electromagnetic motors; the devices are used after myocardial infarction or to wean the repaired heart from the heart-lung machine after open-heart surgery.

Portable or implantable devices for infusion of insulin. Includes open-loop systems which may be patient-operated or controlled by a pre-set program and are designed for constant delivery of small quantities of insulin, increased during food ingestion, and closed-loop systems which deliver quantities of insulin automatically based on an electronic glucose sensor.

More From BioPortfolio on "Closed Loop Isoflurane Administration With Bispectral Index in Open Heart Surgery"

Quick Search


Relevant Topics

Cardiovascular disease (CVD)
Acute Coronary Syndromes (ACS) Blood Cardiovascular Dialysis Hypertension Stent Stroke Vascular Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease (angina...

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Anesthesia is the loss of feeling or sensation in all or part of the body. It may result from damage to nerves or can be induced by an anesthetist (a medical professional) using anesthetics such as thiopental or propofol or sevoflurane during a surgical ...

Searches Linking to this Trial