Trial Outcomes & Findings for Closed Loop Propofol Administration in Pediatric Cardiac Surgery (NCT NCT01600287)

NCT ID: NCT01600287

Last Updated: 2013-08-09

Results Overview

The primary outcome to be measured is the ability of the system to keep the depth of anesthesia in the target range, i.e, Bispectral Index(BIS) value of 50+/- 10. This will assess the ability of the system to prevent intra-operative awareness of the patients and at the same time avoid excessive depth of anesthesia with its accompanying adverse effects.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 40 participants
• Primary outcome timeframe: Approximately 8 hours
• Results posted on: 2013-08-09

Participant Flow

51 patients assessed in surgical ward between january 2012 to september 2012, after excluding 11 patients, 40 remaining patients were randomised into two groups(IAADS & Manual) of 20 each- all patients in each group received allocated interventions- no patients needed to be excluded from final analysis.

5 patients were initially excluded because of having cyanotic heart disease, 6 patients excluded subsequently as they resisted pre-induction venous cannula placement.

Participant milestones

Measure	IAADS Group Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Overall Study STARTED	20	20
Overall Study COMPLETED	20	20
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Closed Loop Propofol Administration in Pediatric Cardiac Surgery

Baseline characteristics by cohort

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.	Total n=40 Participants Total of all reporting groups
Age, Categorical <=18 years	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	11.1 years STANDARD_DEVIATION 5.1 • n=5 Participants	12 years STANDARD_DEVIATION 4.1 • n=7 Participants	11.6 years STANDARD_DEVIATION 4.6 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment India	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: Approximately 8 hours

The primary outcome to be measured is the ability of the system to keep the depth of anesthesia in the target range, i.e, Bispectral Index(BIS) value of 50+/- 10. This will assess the ability of the system to prevent intra-operative awareness of the patients and at the same time avoid excessive depth of anesthesia with its accompanying adverse effects.

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Percentage of Time Bispectral Index(BIS) Remains+/-10 of Target	77.4 percentage of time Standard Deviation 13.07	75 percentage of time Standard Deviation 11

SECONDARY outcome

Timeframe: Approximately 8 hours

The difference between the observed and target of measure of depth of anesthesia (BIS) expressed as percentage of target BIS is calculated as performance error every 30 seconds. This value may be either '+' or '_' indicating whether the observed measure is above the target (overshoot-+) or below the target (undershoot-_). The median value of all performance errors during propofol anesthesia is median performance error and is a measure of bias of the system. This outcome is expressed as the mean of Median Performance Errors per participant.

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Median Performance Error(MDPE)	6 errors per participant Standard Deviation 8	-7 errors per participant Standard Deviation 5

SECONDARY outcome

Timeframe: Approximately 8 hours

The difference between the observed and target of measure of depth of anesthesia (BIS) expressed as percentage of target BIS is calculated as performance error every 30 seconds. This value may be either '+' or '_' indicating whether the observed measure is above the target (overshoot-+) or below the target (undershoot-_).The median of the absolute values of performance errors (without considering the direction of error) is median absolute performance error. This outcome measures the magnitude of error or inaccuracy of the system studied. A lower value indicates a more precise system.This outcome is expressed as the mean of Median Absolute Performance Errors per participant.

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Median Absolute Performance Error(MDAPE)	12 errors per participant Standard Deviation 3	13 errors per participant Standard Deviation 4

SECONDARY outcome

Timeframe: Approximately 8 hours

Wobble measures the intra-individual variability in performance error.The median of the difference between individual performance errors throughout anesthesia and the median performance error for each participant is the wobble of that participant. The mean value per participant is indicated in the outcome measure.

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Wobble	9 errors per participant Standard Deviation 3	11 errors per participant Standard Deviation 4

SECONDARY outcome

Timeframe: Approximately 8 hours

The duration of time heart rate remains within 25% of the pre-operative baseline value during the period propofol (general anesthetic) is administered to the study population. This value is expressed as a percentage. This outcome is expressed as the mean of percentage of time per participant.

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Percentage of Time Heart Rate Remains Within 25% of Pre-op Baseline	83.3 percentage of time Standard Deviation 11.7	80.5 percentage of time Standard Deviation 19.6

SECONDARY outcome

Timeframe: Approximately 8 hours

The duration of time mean arterial pressure remains within 25% of the pre-operative baseline value during the period propofol (general anesthetic) is administered to the study population. This value is expressed as percentage. This outcome is expressed as the mean of percentage of time per participant

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Percentage of Time Mean Arterial Pressure Remains Within 25% of Pre-op Baseline	83.8 percentage of time Standard Deviation 10.5	72.8 percentage of time Standard Deviation 18.4

SECONDARY outcome

Timeframe: Approximately 3 days and then 1 month later

The number of patients who will be able to recall the intra-operative events when assessed postoperatively. This will be assessed by a structured protocol

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Intra-operative Awareness	0 participants	0 participants

SECONDARY outcome

Timeframe: 8 hours (approx)

slope of the linear regression curve of performance error against time.

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Divergence	0.02 errors per second Standard Deviation 0.17	-0.097 errors per second Standard Deviation 0.219

SECONDARY outcome

Timeframe: 8 hours (approx)

overall performance assessment of the system calculated as= [(MDAPE+Wobble)/percentage of time BIS remains within target]x100 Lower score indicates better overall performance

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Global Score	30.09 percentage of time Standard Deviation 12.17	34.12 percentage of time Standard Deviation 15.28

SECONDARY outcome

Timeframe: 2 hours(approx)

total phenylephrine dose needed to be used in the pre CPB period to maintain hemodynamic stability

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Intraoperative Phenylephrine Used (Pre CPB)	5.79 microgram per Kg body weight Standard Deviation 5.98	16.92 microgram per Kg body weight Standard Deviation 10.92

OTHER_PRE_SPECIFIED outcome

Timeframe: 10 minutes

Dose of propofol needed for induction

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Induction Dose of Propofol	2.06 mg per kg body weight Standard Deviation 0.79	2.95 mg per kg body weight Standard Deviation 1.03

OTHER_PRE_SPECIFIED outcome

Timeframe: 10 minutes

Time required for the first time achievement of two subsequent BIS values below or equal to 55

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Induction Time	186.2 seconds Standard Deviation 91.2	160.6 seconds Standard Deviation 42

OTHER_PRE_SPECIFIED outcome

Timeframe: 15 minutes

Bispectral Index(BIS) is an EEG-based objective measure of anesthetic depth with values ranging from 100 to 0, lower number indicating greater depth of anesthesia. Values between 40 to 60 indicate adequate depth required for surgery. During induction of anesthesia, there is a tendency of overshooting the adequate depth of anesthesia, due to use of higher dose and rate of administration required for induction. The minimum BIS achieved during induction is a measure of this overshoot. The less the minimum value, the more is the overshoot, worse the outcome is. The minimum BIS during induction is automatically stored in the PC used for the study.

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Minimum BIS During Induction	45 Bispectral Index Standard Deviation 6	36 Bispectral Index Standard Deviation 11

OTHER_PRE_SPECIFIED outcome

Timeframe: 15 minutes

percentage fall in mean arterial pressure from baseline during induction

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Percentage Fall in MAP During Induction	18.5 percentage of fall from baseline Standard Deviation 13	24 percentage of fall from baseline Standard Deviation 8

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 hours (approx)

total propofol used based on per kg body weight per hour for the whole duration of surgery

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Total Propofol Used (mg/kg/hr)	4.81 mg per kg body weight per hour Standard Deviation 1.98	6 mg per kg body weight per hour Standard Deviation 2

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 hours(approx)

total fentanyl used in the whole duration of surgery on per kg body weight basis

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Total Fentanyl Used (µg/kg)	12.03 microgram per kg body weight Standard Deviation 4.51	12.5 microgram per kg body weight Standard Deviation 4.31

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 hours(approx)

total dosage of propofol used on per kg body weight per hour basis in the period before and after cardiopulmonary bypass period.

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Total Off CPB Propofol Used (mg/kg/hr	6.29 mg per kg body weight per hour Standard Deviation 2.48	7.82 mg per kg body weight per hour Standard Deviation 2.1

OTHER_PRE_SPECIFIED outcome

Timeframe: 8 hours(aprrox)

Number of times rate of propofol needed to be changed manually

Outcome measures

Measure	IAADS Group n=20 Participants Both induction and maintenance of anesthesia was done automatically by IAADS according to age, sex, height of the patient, target BIS(50) entered, risk status and maximum allowable rate entered.	Manual Group n=20 Participants dosage of propofol was adjusted manually by the attending anesthesiologist through the keyboard of the PC attached to the syringe pump for both induction and maintenance.
Number of Times Rate of Propofol Changed Manually	0 times per hour Interval 0.0 to 0.0	18 times per hour Interval 8.0 to 29.0

Adverse Events

IAADS Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Manual Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr G D Puri

Postgraduate Institute of Medical Education and Research

Phone: 00919914209509

Email: gdpuri007@hotmail.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place