Closed Loop Propofol Administration in Pediatric Cardiac Surgery

NCT ID: NCT01600287

Last Updated: 2013-08-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2012-12-31

Brief Summary

The purpose of the study is to evaluate and compare the feasibility, efficacy and safety of IAADS (Improved Anaesthetic Agent Delivery System) for propofol anaesthesia against manual control using bispectral index in paediatric patients undergoing open heart surgery under cardio-pulmonary bypass.

Detailed Description

Automated drug delivery has gained considerable interest in recent times. It is carried out by specially programmed electro-mechanical devices where dose rate adjustment is made independent of human intervention. The desired target is chosen by the clinician. The closed loop system depends upon a feedback signal to modify the rate of drug delivery. These have an advantage that they are able to overcome the individual pharmacokinetic and pharmacodynamic differences as well as the differing levels of surgical stimulation. Majority of studies on closed loop delivery of hypnotics has been done using propofol. CLADS(Closed loop anesthesia delivery system) is a BIS guided closed loop anaesthesia delivery system developed at PGIMER (Post graduate institute of medical education and research), Chandigarh and has been used successfully for administration of propofol in various situations, eg, non-cardiac surgery, cardiac surgery, post-operative sedation and high altitude. The system used will be IAADS, Improved anesthetic agent delivery system - the present and updated version of CLADS), a pharmacokinetic-pharmacodynamic model based adaptive system . There are only a few studies/reports regarding closed loop delivery of muscle relaxants in children. In this study, the efficacy of IAADS will be compared with manual control for administration of propofol using BIS as a control variable during induction and maintenance of anaesthesia in children undergoing elective open heart surgery.

After approval from the Institutional ethics committee and written informed parental consent, 40 children, aged 5-18 years and ASA physical status II-III, planned for elective open heart surgery under general anaesthesia will be studied. Patients will be randomly allocated to one of two groups - the manual group and the IAADS group using computer-generated random numbers in sealed opaque envelopes. Exclusion criteria will be: patients weighing more than ±30% of ideal body weight, those with neurological/psychological disorders, on psychoactive medications, belonging to NYHA class IV, those with severe stenotic valvular lesions, with known allergy to propofol or any of its constituents, having severe pulmonary arterial hypertension, with cyanotic congenital heart disease and those who may require deep hypothermic circulatory arrest for repair. The investigator will be present during the procedure for data collection purpose only and was not involved in the conduct of anaesthesia. Patients will be premedicated with oral midazolam syrup 0.25mg/kg 30 minutes before shifting to operating room. EMLA cream will be applied to the site of venipuncture for at least one hour. Intravenous access will be obtained in the operating room. Routine physiological monitoring will be commenced (pulse oximetry, electrocardiography, non-invasive blood pressure). BIS will be obtained by disposable sensors (Aspect Medical System Inc. MA USA) attached to the forehead of the patients. The children resisting venous cannula placement will be excluded from the study and subjected to inhalational induction.

Before induction, patients will receive fentanyl 3µg/kg over three minutes. In automatic mode, IAADS will calculate and titrate the initial and subsequent propofol infusion rate according to the weight of the patient, the risk status, the target BIS value which will be set at 50 for all cases. In manual mode, infusion rate will be determined by the attending anaesthesiologist according to the weight of the patient and target BIS of 50, with the aim to maintain BIS within 40-60. After loss of consciousness, patients will receive 0.1mg/kg of vecuronium bromide and trachea will be intubated after 4 minutes. The lungs will be ventilated with 100% O2; tidal volume and respiratory rate will be adjusted to maintain an EtCO2 of 30-35 mm Hg. Central venous catheter and arterial cannula will be inserted subsequently.

Analgesia will be maintained with infusion of fentanyl at 1µg/kg/hr and additional boluses of 1µg/kg will be administered before skin incision, sternotomy and commencement of cardio-pulmonary bypass. Muscle relaxation will be maintained with vecuronium bromide. Tachycardia and hypertension will be treated with fentanyl bolus, esmolol, nitroglycerine as appropriate. Hypotension will be treated with fluid bolus, phenylephrine, inotropes as appropriate. Significant bradycardia will be treated with atropine sulphate. During CPB, infusion of fentanyl and propofol will be continued. MAP will be maintained between 30-50 mm Hg and any deviation from these limits will be treated with phenylephrine boluses or nitroglycerine infusion. Propofol will be administered as per IAADS protocol in automatic group and manually in control group. The number of times propofol infusion rate that will needed to be changed in the manual group will be noted.

After skin closure, fentanyl and propofol infusion will be stopped, study protocol will be terminated and the patients will be shifted to ICU without antagonizing the muscle relaxant for elective mechanical ventilation. Patients will be given propofol infusion for postoperative sedation and will be extubated when standard criteria for weaning and extubation will be met. The children will be subjected to a structured interview as described by Lopez et a for conscious awareness; on second day after surgery and approximately one month later.

Conditions

Pediatric Cardiac Surgery; Intraoperative Awareness; Automated Drug Delivery

Keywords

bispectral index; propofol; paediatric cardiac surgery; closed loop anaesthesia delivery system

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: SINGLE

Study Groups

IAADS group

dosage of propofol adjusted automatically by IAADS

Group Type: EXPERIMENTAL

IAADS

Intervention Type: OTHER

In automatic mode, the system requests an update of the BIS data every 5 seconds and calculates the BIS "error" (difference between the target and actual BIS value). This value along with the trends of BIS in the epoch of the last 30 seconds as well as in the last 5 minutes is passed on to a patient individualized, model based adaptive control algorithm. The algorithm uses the error to calculate an adjustment to the propofol delivery rate, but does not apply it immediately. Adjustments to the propofol delivery rate are only made every 30 seconds, taking into account the sum of previous six BIS "error" values, the trends of BIS in the epoch of last 30 seconds as well as in the last 5 minutes, time elapsed since the initiation of infusion, pharmacokinetics, the time delay factor between sensing and averaging of BIS data, the time delay factor between the change in infusion rate and the actual change in the plasma concentration of propofol as well as the peak effect of propofol.

Manual group

dosage of propofol adjusted manually

Group Type: ACTIVE_COMPARATOR

Manual propofol administration

Intervention Type: OTHER

In "manual" mode, the user can also control the propofol infusion rate manually, using the keyboard or the mouse of the PC. The PC displays a graph of the propofol delivery rate and trend of BIS value.

Interventions

IAADS

In automatic mode, the system requests an update of the BIS data every 5 seconds and calculates the BIS "error" (difference between the target and actual BIS value). This value along with the trends of BIS in the epoch of the last 30 seconds as well as in the last 5 minutes is passed on to a patient individualized, model based adaptive control algorithm. The algorithm uses the error to calculate an adjustment to the propofol delivery rate, but does not apply it immediately. Adjustments to the propofol delivery rate are only made every 30 seconds, taking into account the sum of previous six BIS "error" values, the trends of BIS in the epoch of last 30 seconds as well as in the last 5 minutes, time elapsed since the initiation of infusion, pharmacokinetics, the time delay factor between sensing and averaging of BIS data, the time delay factor between the change in infusion rate and the actual change in the plasma concentration of propofol as well as the peak effect of propofol.

Intervention Type: OTHER

Manual propofol administration

In "manual" mode, the user can also control the propofol infusion rate manually, using the keyboard or the mouse of the PC. The PC displays a graph of the propofol delivery rate and trend of BIS value.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Children, aged 5-18 years and ASA (American Society of Anesthesiology) physical status 2-3, planned for elective open heart surgery under general anaesthesia.

Exclusion Criteria

• Patients weighing more than ±30% of ideal body weight.
• Patients having neurological/psychological disorders or on psychoactive medications.
• Patients belonging to NYHA (New York Heart Association) class IV.
• Patients with severe stenotic valvular lesions, eg, mitral or aortic stenosis.
• Patients with known allergy to propofol or any of its constituents.
• Patients having severe pulmonary arterial hypertension.
• Patients with cyanotic congenital heart disease.
• Patients requiring deep hypothermic circulatory arrest during surgery.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role: lead

Responsible Party

INDRANIL BISWAS

Indranil Biswas

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Indranil Biswas, MBBS

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Goverdhan D Puri, MBBS,MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Preethy J Mathew, MBBS,MD

Role: PRINCIPAL_INVESTIGATOR

Post Graduate Institute of Medical Education and Research, Chandigarh

Locations

Advanced Cardiac Centre.Postgraduate Institute of Medical Education and Research.

Chandigarh, Chandigarh, India

Countries

India

References

Agarwal J, Puri GD, Mathew PJ. Comparison of closed loop vs. manual administration of propofol using the Bispectral index in cardiac surgery. Acta Anaesthesiol Scand. 2009 Mar;53(3):390-7. doi: 10.1111/j.1399-6576.2008.01884.x.

Reference Type: BACKGROUND

PMID: 19243324 (View on PubMed)

Solanki A, Puri GD, Mathew PJ. Bispectral index-controlled postoperative sedation in cardiac surgery patients: a comparative trial between closed loop and manual administration of propofol. Eur J Anaesthesiol. 2010 Aug;27(8):708-13. doi: 10.1097/EJA.0b013e328335b2d4.

Reference Type: BACKGROUND

PMID: 20299990 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17591128 (View on PubMed)

Other Identifiers

8450/PG-2Trg/2010/

Identifier Type: -

Identifier Source: org_study_id