Automatic Control of Total Intravenous Anesthesia (ACTIVA)

The depth of hypnosis adequacy is assessed by evaluating, for each patient enrolled, the percentage of maintenance duration during which the Bispectral Index Scale (BIS) is kept within the recommended range from 40 to 60 (BIS \[40,60\]). The outcome measure is defined as the median of these percentages calculated over all the patients enrolled in the study. The median of the percentages, calculated over all the patients enrolled in the study, of the anesthesia maintenance duration in which the BIS is kept below 40 (BIS\<40) is also specified. Maintenance duration is the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds. The BIS ranges from 0 (absence of brain activity) to 100 (fully awake patient).

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

The effect of drugs delivery on heart rate is assessed by evaluating, for each patient enrolled, the percentage of the anesthesia maintenance duration in which the heart rate (HR) is kept inside the range from 50 to 100 beats per minute (HR \[50,100\]). The outcome measure is defined as the median of these percentages calculated over all the patients enrolled in the study. The median of the percentages, calculated over all the patients enrolled in the study, of the anesthesia maintenance duration in which the HR is kept below 50 (HR\<50) is also specified. Maintenance duration is the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

The effect of drugs delivery on mean arterial pressure (MAP) is assessed by evaluating, for each patient enrolled, the anesthesia maintenance duration in which the non-invasively measured MAP is kept inside the range from 65 to 110 mmHg (MAP \[65,110\]). The outcome measure is defined as the median of these percentages calculated over all the patients enrolled in the study. The median of the percentages, calculated over all the patients enrolled in the study, of the anesthesia maintenance duration in which the MAP is kept below 65 (MAP\<65) is also specified. Maintenance duration is the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds. MAP is defined as diastolic pressure + 1/3(systolic pressure - diastolic pressure).

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

Levels of satisfaction of the experimenter regarding three aspects of the ACTIVA system. The first aspect is the ease of use of the ACTIVA software and its infusion system. The second aspect is the behavior of the ACTIVA system during the induction phase of anesthesia. The third aspect is the behavior of the ACTIVA system during the maintenance phase of anesthesia. For each aspect, the level of satisfaction is expressed by the experimenter by assigning a score on a scale ranging from 0 (extremely unsatisfied) to 10 (extremely satisfied). Thus, higher values represent a better outcome. Note that the scoring scale employed is the same for each of the three aspects. The results are reported in a table divided in three rows, one for each aspect evaluated. Each row is divided in eleven categories representing the scores from 0 to 10. For each category it is indicated the number of patients for which the experimenter expressed that specific score.

Time frame: During anesthesia from the time instant when the automatic control is started to the point at which the automatic control is turned off at the conclusion of surgery, an average of 2 hours.

Number of participants for which the ACTIVA system showed dysfunctions. The results are presented in a table where each row indicates the type of dysfunction and the number of participants for which that particular type of dysfunction occurred.

Time frame: During anesthesia from the time instant when the automatic control is started to the point at which the automatic control is turned off at the conclusion of surgery, an average of 2 hours.

The postoperative analgesia is assessed using a 10-point numeric rating scale (NRS). It is a 10 point scale from 0 (no pain) to 10 (maximum pain).

Time frame: End of anesthesia (operating room discharge, recovery room admission, recovery room discharge), 6 hours after surgery, 24 hours after surgery.

The postoperative heart rate is assessed by measuring the heart rate in beats per minute (bpm).

Time frame: End of anesthesia (operating room discharge, recovery room admission, recovery room discharge), 6 hours after surgery, 24 hours after surgery.

The postoperative mean arterial pressure (MAP) stability is assessed by non-invasively measuring the MAP with an electronic sphygmomanometer trough an inflatable cuff. Mean arterial pressure (MAP) is defined as diastolic pressure + 1/3(systolic pressure - diastolic pressure).

Time frame: End of anesthesia (operating room discharge, recovery room admission, recovery room discharge), 6 hours after surgery, 24 hours after surgery.

Postoperative Nausea and Vomiting is assessed by means of the Bellville PONV scale. It is a 3 point scale from 0 (no nausea & vomiting) to 3 (vomiting present)

Time frame: End of anesthesia (operating room discharge, recovery room admission, recovery room discharge), 6 hours after surgery, 24 hours after surgery.

The postoperative sedation is assessed by means of a Sedation Score scale. It is a 3 point scale from 0 (fully awake) to 3 (fully sedated)

Time frame: End of anesthesia (operating room discharge, recovery room admission, recovery room discharge), 6 hours after surgery, 24 hours after surgery.

The extubation time is the time interval that elapses from the time instant when the automatic control is stopped to when the patient is extubated. It is an indicator of the awakening time.

Time frame: During anesthesia from the time instant when the automatic control is stopped to when the patient is extubated, up to 11 minutes.

The Global Score (GS) is a performance index that characterize the overall control performance. It is calculated as (MDAPE+WOBBLE)/BIS \[40,60\]. For each patient (i) and for each Bispectral Index Scale (BIS) sample (j): PEij=((BISij BIS\_Target)/BIS\_Target)\*100, with BIS\_Target=50. MDAPEi=median{\|PEij\|}. WOBBLEi=median{\|PEij-MDPEi\|}. BIS \[40,60\] is the percentage of the anesthesia maintenance duration in which the BIS is kept between 40 and 60. The maintenance phase is defined as the period of time that goes from the end of anesthesia induction, defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds, to the point at which the automatic control is turned off at the conclusion of surgery. The GS ranges from zero to infinity. The lower the GS, the better the control performance. Specifically, a GS value of zero would correspond to the case where the BIS is always maintained at its target value.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

The induction time is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the automatic control is started to the point at which the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds, an average of 110 seconds.

The lowest Bispectral Index (BIS) is the lowest BIS value observed within the 60 seconds following the induction time. The BIS quantifies the cerebral activity and ranges from 99 (corresponding to a fully awake and aware patient) to 0 (corresponding to the absence of brain activity. For general anesthesia it is recommended to keep the BIS inside the range 40-60. Values above 60 represent a too light anesthesia while values below 40 represents a too deep anesthesia.

Time frame: During anesthesia from the time instant when the automatic control is started to 60 seconds following the induction time, an average of 170 seconds.

The lowest heart rate is the lowest heart rate value observed within the 5 minutes following the induction time.

Time frame: During anesthesia from the time instant when the automatic control is started to the 5 minutes following the induction time, an average of 410 seconds.

The lowest mean arterial pressure (MAP) is the lowest value of the MAP observed within the 5 minutes following the induction time. It is assessed by non-invasively measuring the MAP with an electronic sphygmomanometer embedded in a multiparametric patient monitor through an inflatable cuff. Mean arterial pressure (MAP) is defined as diastolic pressure + 1/3(systolic pressure - diastolic pressure).

Time frame: During anesthesia from the time instant when the automatic control is started to the 5 minutes following the induction time, an average of 410 seconds.

The MDAPE is the median absolute performance error calculated during the maintenance phase. The performance error (PE) is calculated for each patient (i) and for each BIS sample (j) according to the formula: PEij=((BISij-BIS\_Target)/BIS\_Target)\*100, where BIS\_Target is set equal to 50. The MDAPE is a measure of inaccuracy. The MDAPE is calculated according to the formula: MDAPEi=median{\|PEij\|}. The maintenance phase is defined as the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

The MDPE is the median performance error calculated during the maintenance phase. The performance error (PE) is calculated for each patient (i) and for each BIS sample (j) according to the formula: PEij=((BISij-BIS\_Target)/BIS\_Target)\*100, where BIS\_Target is set equal to 50. The MDPE is a measure of bias and describes whether the measured BIS values are systematically distributed either above or below the BIS target. The MDPE is calculated according to the formula: MDPEi=median{PEij}. The maintenance phase is defined as the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

It is the median propofol effect-site concentration achieved by the ACTIVA system during the maintenance phase of anesthesia. It is estimated according to the Schnider model. The outcome measure is defined as the median of the propofol effect-site concentrations achieved by the ACTIVA system during the maintenance phase of anesthesia calculated over all the patients enrolled in the study. The maintenance phase is defined as the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

It is the median value of the propofol infusion rate administered by the ACTIVA system during the maintenance phase of anesthesia. The outcome measure is defined as the median of the propofol infusion rates administered by the ACTIVA system during the maintenance phase of anesthesia calculated over all the patients enrolled in the study. The maintenance phase is defined as the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

It is the median remifentanil effect-site concentration achieved by the ACTIVA system during the maintenance phase of anesthesia. It is estimated according to the Minto model. The outcome measure is defined as the median of the remifentanil effect-site concentrations achieved by the ACTIVA system during the maintenance phase of anesthesia calculated over all the patients enrolled in the study. The maintenance phase is defined as the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

It is the median value of the remifentanil infusion rate administered by the ACTIVA system during the maintenance phase of anesthesia. The outcome measure is defined as the median of the remifentanil infusion rates administered by the ACTIVA system during the maintenance phase of anesthesia calculated over all the patients enrolled in the study. The maintenance phase is defined as the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

Number of Participants that showed cases of hypotension treated with ephedrine or etilefrine before and after the beginning of the surgical stimulation (incision).

Time frame: During anesthesia from the time instant when the automatic control is started to incision for the cases before incision. During anesthesia from incision to the time instant when the automatic control is stopped for the cases after incision.

Number of Participants that showed the occurrence of a burst-suppression episode during the maintenance phase. A burst-suppression episode is defined as a value of burst-suppression ratio (BSR) above 10% for at least 60 seconds. The maintenance phase here is defined as the period of time that goes from the 5 minutes after the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.

Number of Participants that showed the occurrence of a burst-suppression episode within the 5 minutes following the induction time. A burst-suppression episode is defined as a value of burst-suppression ratio (BSR) above 10% for at least 60 seconds.

Time frame: During anesthesia from the time instant when the automatic control is started to the 5 minutes following the induction time, an average of 410 seconds.

Propofol dose administered by the system throughout the induction time.

Time frame: During anesthesia from the time instant when the automatic control is started to the point at which the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds, an average of 170 seconds.

Remifentanil dose administered by the system throughout the induction time.

Time frame: During anesthesia from the time instant when the automatic control is started to the point at which the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds, an average of 170 seconds.

The WOBBLE is an index of time-related changes in the performance and measures the intra-patient variability in performance errors. It is calculated during the maintenance phase. The performance error (PE) is calculated for each patient (i) and for each BIS sample (j) according to the formula: PEij=((BISij BIS\_Target)/BIS\_Target)\*100, where BIS\_Target is set equal to 50. The WOBBLE is calculated according to the formula: WOBBLEi=median{\|PEij-MDPEi\|}. The maintenance phase is defined as the period of time that goes from the end of anesthesia induction to the point at which the automatic control is turned off at the conclusion of surgery. The end of anesthesia induction is defined as the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds.

Time frame: During anesthesia from the time instant when the BIS drops below 60 for the first time and remains there for the subsequent 30 seconds to the point at which the automatic control is turned off (maintenance duration), an average of 2 hours.