Clinical trial NCT01600287: Closed Loop Propofol Administration in Pediatric Cardiac Surgery
Official title: Evaluation of Closed Loop Anaesthesia Delivery System for Propofol Anaesthesia in Pediatric Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pediatric Cardiac Surgery
Intraoperative Awareness
Automated Drug Delivery
Keywords: bispectral index
propofol
paediatric cardiac surgery
closed loop anaesthesia delivery system
Lead sponsor: PIMERIndia
Sponsor class: UNKNOWN
First posted: 2012-05-17
Enrollment: 40
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.

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.

Primary outcomes:
measure: Percentage of Time Bispectral Index(BIS) Remains+/-10 of Target
timeFrame: Approximately 8 hours
Secondary outcomes:
measure: Median Performance Error(MDPE)
timeFrame: Approximately 8 hours
measure: Median Absolute Performance Error(MDAPE)
timeFrame: Approximately 8 hours
measure: Wobble
timeFrame: Approximately 8 hours
measure: Percentage of Time Heart Rate Remains Within 25% of Pre-op Baseline
timeFrame: Approximately 8 hours
measure: Percentage of Time Mean Arterial Pressure Remains Within 25% of Pre-op Baseline
timeFrame: Approximately 8 hours
measure: Intra-operative Awareness
timeFrame: Approximately 3 days and then 1 month later
measure: Divergence
timeFrame: 8 hours (approx)
measure: Global Score
timeFrame: 8 hours (approx)
measure: Intraoperative Phenylephrine Used (Pre CPB)
timeFrame: 2 hours(approx)
Other outcomes:
measure: Induction Dose of Propofol
timeFrame: 10 minutes
measure: Induction Time
timeFrame: 10 minutes
measure: Minimum BIS During Induction
timeFrame: 15 minutes
measure: Percentage Fall in MAP During Induction
timeFrame: 15 minutes
measure: Total Propofol Used (mg/kg/hr)
timeFrame: 8 hours (approx)
measure: Total Fentanyl Used (µg/kg)
timeFrame: 8 hours(approx)
measure: Total Off CPB Propofol Used (mg/kg/hr
timeFrame: 6 hours(approx)
measure: Number of Times Rate of Propofol Changed Manually
timeFrame: 8 hours(aprrox)
Locations:
city: Chandigarh
country: India
facility: Advanced Cardiac Centre.Postgraduate Institute of Medical Education and Research.
Study officials:
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Indranil Biswas, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Goverdhan D Puri, MBBS,MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Preethy J Mathew, MBBS,MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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.