Closed Loop Propofol Administration in Pediatric Cardiac Surgery
Condition: Pediatric Cardiac Surgery; Intraoperative Awareness; Automated Drug Delivery
MeSH terms: Intraoperative Awareness
Study type: Interventional

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.
    

Intervention name(s): IAADS; Manual propofol administration
Intervention type(s): Other; Other
Intervention description(s): 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.; 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 MeSH terms: Propofol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Keywords: bispectral index; propofol; paediatric cardiac surgery; closed loop anaesthesia delivery system