Table 1.

Flow chart of the study

Items	Screen		Study drug administration				Follow-up
	Day-1 to day 1 before drug administration	30 min before drug administration on day 1	From administration initiation to 1 h after administration	From 1 h after administration to the end of administration	Within 2 h after administration ended	Before using rescue drug/other analgesics	0–24 h after drug administration ended
Informed consent	×
Medical history and medication history and surgery history	×
Inclusion/exclusion criteria	×	×
Demographics	×
Vital sign		×	× (Evaluate once every 30 min ± 5 min)	× (Evaluate once every 1 h ± 10 min)	×	×	×
Physical examination	×						×
Blood test	×					×	×
Urine test	×					×	×
Blood biochemistry	×				× (Add measurement of blood lipid once)	×	×
Blood coagulation	×						×
Blood gas analysis	×				×
Pregnancy test	×
ECG	×		×	×		×	×
RASS		×	× (Evaluate once every 30 min ± 5 min)	× (Evaluate once every 2 h ± 10 min)	×
CAM-ICU	×
CPOT pain score		×	× (Evaluate once every 30 min ± 5 min)	× (Evaluate once every 2 h ± 10 min)
GCS score	×
SOFA score	×
Nursing score							×
Extubation time					×		×
Randomization		×
Start giving study drug (0 min)			×	×
Calculate drug use [study drug (loading dose, maintenance dose, top-up dose), rescue medication, amount of analgesic used and number of adjusted times]			×	×	×	×	× (If applicable)
Blood sampling for PK		×	×	×	×	×	×
Adverse events	×	×	×	×	×	×	×
Previous/concomitant medication	×	×	×	×	×	×	×

CAM-ICU Confusion Assessment Method for the Intensive Care Unit, CPOT Critical Care Pain Observation Tool, ECG electrocardiogram, GCS Glasgow Coma Scale, PK pharmacokinetic, RASS Richmond Agitation and Sedation Scale, SOFA Sequential Organ Failure Assessment