Trial Outcomes & Findings for Can Adequacy of Anesthesia Depth and Quality of Recovery be Influenced by the Level of Neuromuscular Blockade? (NCT NCT02484651)

Last Updated: 2019-09-16

Results Overview

BIS (Bispetral Index of the EEG) sample standard deviation during the maintenance phase of anesthesia was used as a measure of signal variability, maintenance phase is defined as the time between the first time the BIS signal drops below 60 after loss of consciousness, until the time the BIS signal goes above 60 after the propofol infusion is stopped. BIS signal varies between 0 to 100. BIS values near 100 represent an "awake" clinical state while 0 denotes the maximal effect an isoelectric EEG. The aim was to maintain the BIS value within a target range of 40 to 60. The higher the BIS sample standard deviation the higher the oscillation around the sample mean.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

70 participants

Primary outcome timeframe

Maintenance of anesthesia, an average of 130 minutes

Results posted on

2019-09-16

Participant Flow

Recruitment started on the 2016/9/19 and finished on 2017/6/28 at Centro Hospitalar do Porto, Portugal.

3 patients were excluded from the study after screening (signing the informed consent) but before randomization and assignment to the groups, due to: * 2 patients had their surgery postponed less than 2 hours before the schedule time * the scheduled surgical position of 1 patient was altered by the surgeon just before the start of the procedure.

Participant milestones

Participant milestones
Measure	Standard Group Standard Clinical Practice Group - standard neuromuscular block, with a standard rocuronium dose for intubation (0.6 mg/kg). If required, the reversal of neuromuscular block is performed with neostigmine.	Deep NMB Group Deep Neuromuscular Block group - with a standard rocuronium dose for intubation (0.6 mg/kg), followed by a constant infusion of rocuronium (10-15 ug/kg/min) to guarantee a PTC less or equal to 2 on the TOF monitor (PTC is evaluated every 5 minutes). The reversal of neuromuscular block is performed with Sugammadex (4 mg/kg). Sugammadex: Reversal of deep neuromuscular block Rocuronium: Maintenance of deep neuromuscular block
Overall Study STARTED	35	35
Overall Study End of Clinical Study	35	35
Overall Study Data Analysis	32	31
Overall Study COMPLETED	32	31
Overall Study NOT COMPLETED	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard Group Standard Clinical Practice Group - standard neuromuscular block, with a standard rocuronium dose for intubation (0.6 mg/kg). If required, the reversal of neuromuscular block is performed with neostigmine.	Deep NMB Group Deep Neuromuscular Block group - with a standard rocuronium dose for intubation (0.6 mg/kg), followed by a constant infusion of rocuronium (10-15 ug/kg/min) to guarantee a PTC less or equal to 2 on the TOF monitor (PTC is evaluated every 5 minutes). The reversal of neuromuscular block is performed with Sugammadex (4 mg/kg). Sugammadex: Reversal of deep neuromuscular block Rocuronium: Maintenance of deep neuromuscular block
Overall Study Patients' data files were corrupted.	1	1
Overall Study BIS monitoring failed.	1	1
Overall Study Time of the procedure less than 90 min.	1	2

Baseline Characteristics

Can Adequacy of Anesthesia Depth and Quality of Recovery be Influenced by the Level of Neuromuscular Blockade?

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Group n=32 Participants Standard Clinical Practice Group - standard neuromuscular block, with a standard rocuronium dose for intubation (0.6 mg/kg). If required, the reversal of neuromuscular block is performed with neostigmine.	Deep NMB Group n=31 Participants Deep Neuromuscular Block group - with a standard rocuronium dose for intubation (0.6 mg/kg), followed by a constant infusion of rocuronium (10-15 ug/kg/min) to guarantee a PTC less or equal to 2 on the TOF monitor (PTC is evaluated every 5 minutes). The reversal of neuromuscular block is performed with Sugammadex (4 mg/kg). Sugammadex: Reversal of deep neuromuscular block Rocuronium: Maintenance of deep neuromuscular block	Total n=63 Participants Total of all reporting groups
Age, Continuous	52.4 years STANDARD_DEVIATION 10.7 • n=5 Participants	52.6 years STANDARD_DEVIATION 7.9 • n=7 Participants	52.5 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants	31 Participants n=7 Participants	63 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Portugal	32 Participants n=5 Participants	31 Participants n=7 Participants	63 Participants n=5 Participants
Mean Arterial Pressure	105.6 mmHg STANDARD_DEVIATION 12.8 • n=5 Participants	101.4 mmHg STANDARD_DEVIATION 12.5 • n=7 Participants	103.5 mmHg STANDARD_DEVIATION 12.7 • n=5 Participants

PRIMARY outcome

Timeframe: Maintenance of anesthesia, an average of 130 minutes

Outcome measures

Outcome measures
Measure	Standard Group n=32 Participants Standard Clinical Practice Group - standard neuromuscular block, with a standard rocuronium dose for intubation (0.6 mg/kg). If required, the reversal of neuromuscular block is performed with neostigmine.	Deep NMB Group n=31 Participants Deep Neuromuscular Block group - with a standard rocuronium dose for intubation (0.6 mg/kg), followed by a constant infusion of rocuronium (10-15 ug/kg/min) to guarantee a PTC less or equal to 2 on the TOF monitor (PTC is evaluated every 5 minutes). The reversal of neuromuscular block is performed with Sugammadex (4 mg/kg). Sugammadex: Reversal of deep neuromuscular block Rocuronium: Maintenance of deep neuromuscular block
BIS Signal Variability Using the Measured Standard Deviation During the Maintenance Phase of Anesthesia	7.6 units on a scale Standard Deviation 1.6	7.8 units on a scale Standard Deviation 1.6

PRIMARY outcome

Timeframe: Maintenance of anesthesia, an average of 130 minutes

Mean effect-site concentration of propofol required during maintenance of anesthesia (using target controlled infusion). Mean effect-site concentration of remifentanil required during maintenance of anesthesia (using target controlled infusion).

Outcome measures

Outcome measures
Measure	Standard Group n=32 Participants Standard Clinical Practice Group - standard neuromuscular block, with a standard rocuronium dose for intubation (0.6 mg/kg). If required, the reversal of neuromuscular block is performed with neostigmine.	Deep NMB Group n=31 Participants Deep Neuromuscular Block group - with a standard rocuronium dose for intubation (0.6 mg/kg), followed by a constant infusion of rocuronium (10-15 ug/kg/min) to guarantee a PTC less or equal to 2 on the TOF monitor (PTC is evaluated every 5 minutes). The reversal of neuromuscular block is performed with Sugammadex (4 mg/kg). Sugammadex: Reversal of deep neuromuscular block Rocuronium: Maintenance of deep neuromuscular block
Required Effect-site Concentrations of Propofol and Remifentanil Propofol	3000 ng/ml Standard Deviation 560	2450 ng/ml Standard Deviation 550
Required Effect-site Concentrations of Propofol and Remifentanil Remifentanil	3.26 ng/ml Standard Deviation 1.02	2.84 ng/ml Standard Deviation 1.12

SECONDARY outcome

Timeframe: 15 and 40 minutes after surgery

Population: 10 patients were not able to complete the PQRS test at 15 minutes, since they were not able to communicate or understand the questions. 1 patient was not able to complete the PQRS test at 15 and 40 minutes due to problems in the vocal cords.

PQRS(Post-operative Quality Recovery Scale) recovery rate at 15 minutes post surgery and PQRS recovery rate at 40 minutes post surgery. Recovery is defined as returning to PQRS baseline values.

Outcome measures

Outcome measures
Measure	Standard Group n=32 Participants Standard Clinical Practice Group - standard neuromuscular block, with a standard rocuronium dose for intubation (0.6 mg/kg). If required, the reversal of neuromuscular block is performed with neostigmine.	Deep NMB Group n=31 Participants Deep Neuromuscular Block group - with a standard rocuronium dose for intubation (0.6 mg/kg), followed by a constant infusion of rocuronium (10-15 ug/kg/min) to guarantee a PTC less or equal to 2 on the TOF monitor (PTC is evaluated every 5 minutes). The reversal of neuromuscular block is performed with Sugammadex (4 mg/kg). Sugammadex: Reversal of deep neuromuscular block Rocuronium: Maintenance of deep neuromuscular block
PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) 15 minutes · Overall recovery	2 Participants	5 Participants
PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) 15 minutes · Did not recovered	24 Participants	21 Participants
PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) 40 minutes · Overall recovery	0 Participants	3 Participants
PQRS Results at 15 and 40 Minutes After Surgery (Taking Into Account the Patient Baseline Values of the PQRS Test Done on the Preanesthetic Visit) 40 minutes · Did not recovered	32 Participants	27 Participants

SECONDARY outcome

Timeframe: 3rd day after surgery

Population: 4 patients did not complete the questionnaire on the 3rd day, since they did not pick up the phone.

Patient satisfaction with anesthetic care rated as: Not satisfied, A little satisfied, Moderately satisfied ,Satisfied, Totally Satisfied

Outcome measures

Outcome measures
Measure	Standard Group n=30 Participants Standard Clinical Practice Group - standard neuromuscular block, with a standard rocuronium dose for intubation (0.6 mg/kg). If required, the reversal of neuromuscular block is performed with neostigmine.	Deep NMB Group n=29 Participants Deep Neuromuscular Block group - with a standard rocuronium dose for intubation (0.6 mg/kg), followed by a constant infusion of rocuronium (10-15 ug/kg/min) to guarantee a PTC less or equal to 2 on the TOF monitor (PTC is evaluated every 5 minutes). The reversal of neuromuscular block is performed with Sugammadex (4 mg/kg). Sugammadex: Reversal of deep neuromuscular block Rocuronium: Maintenance of deep neuromuscular block
PQRS Satisfaction Results at Day 3 After Surgery Satisfied	3 Participants	2 Participants
PQRS Satisfaction Results at Day 3 After Surgery Moderately satisfied	0 Participants	0 Participants
PQRS Satisfaction Results at Day 3 After Surgery Not satisfied	0 Participants	0 Participants
PQRS Satisfaction Results at Day 3 After Surgery Totally satisfied	27 Participants	27 Participants
PQRS Satisfaction Results at Day 3 After Surgery A little satisfied	0 Participants	0 Participants

Adverse Events

Standard Group

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Deep NMB Group

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Standard Group n=35 participants at risk Standard Clinical Practice Group - standard neuromuscular block, with a standard rocuronium dose for intubation (0.6 mg/kg). If required, the reversal of neuromuscular block is performed with neostigmine.	Deep NMB Group n=35 participants at risk Deep Neuromuscular Block group - with a standard rocuronium dose for intubation (0.6 mg/kg), followed by a constant infusion of rocuronium (10-15 ug/kg/min) to guarantee a PTC less or equal to 2 on the TOF monitor (PTC is evaluated every 5 minutes). The reversal of neuromuscular block is performed with Sugammadex (4 mg/kg). Sugammadex: Reversal of deep neuromuscular block Rocuronium: Maintenance of deep neuromuscular block
Nervous system disorders Emergence delirium	0.00% 0/35 • Adverse event data were collected by the researchers up to 3 days after surgery.	5.7% 2/35 • Number of events 2 • Adverse event data were collected by the researchers up to 3 days after surgery.
Surgical and medical procedures Neck pain	2.9% 1/35 • Number of events 1 • Adverse event data were collected by the researchers up to 3 days after surgery.	0.00% 0/35 • Adverse event data were collected by the researchers up to 3 days after surgery.
General disorders Nausea and urinary retention	2.9% 1/35 • Number of events 1 • Adverse event data were collected by the researchers up to 3 days after surgery.	0.00% 0/35 • Adverse event data were collected by the researchers up to 3 days after surgery.
Cardiac disorders Tachycardia	0.00% 0/35 • Adverse event data were collected by the researchers up to 3 days after surgery.	2.9% 1/35 • Number of events 1 • Adverse event data were collected by the researchers up to 3 days after surgery.
General disorders Post-operative hypertension	0.00% 0/35 • Adverse event data were collected by the researchers up to 3 days after surgery.	2.9% 1/35 • Number of events 1 • Adverse event data were collected by the researchers up to 3 days after surgery.
Cardiac disorders Asystole of 20 seconds	0.00% 0/35 • Adverse event data were collected by the researchers up to 3 days after surgery.	2.9% 1/35 • Number of events 1 • Adverse event data were collected by the researchers up to 3 days after surgery.
Surgical and medical procedures Post-operative dyspnea and anxiety	0.00% 0/35 • Adverse event data were collected by the researchers up to 3 days after surgery.	2.9% 1/35 • Number of events 1 • Adverse event data were collected by the researchers up to 3 days after surgery.

Additional Information

Prof. Catarina S Nunes

Universidade Aberta, Mathematics Section

Phone: +351 300 001 705

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place