Observation of Propofol Titration at Different Speeds
Condition: Anesthesia, General; Hemodynamics
Study type: Interventional

Summary: 
      Propofol is one of the most widely used anesthetics for its fast onset and quick elimination.
      The conventional speed of its induction dose often causes severe hemodynamics fluctuations
      with hypotension and arrhythmia. The recommended dosage on the drug insert comes from group
      pharmacokinetic studies which does not apply to the specific situation of every patient, so
      the investigators emphasize individualized medication. The investigators have observed the
      titration of propofol in general anesthesia induction, and found that the dosage was less and
      the hemodynamics was becoming more stable. At the same time, the investigators found that the
      hemodynamics still has obvious fluctuations in the titration of the administration rate
      recommended in the instructions. The investigators intend to further compare the effects of
      propofol titration administration at different rates for hemodynamics and stress during the
      induction period of general anesthesia, and find a safer and more appropriate rate of
      administration.
    

Detailed description: 
      Based on the recommended dosing speed in the propofol instructions, this research protocol
      further reduces the dosing speed (40 mg administered every 10 seconds), and sets three
      different titration dosing speeds: group I 2 mg/kg/min; group II 1 mg /kg/min; group III 0.5
      mg/kg/min. The program is calculated by statistics, and it will be planned to enroll 276
      participants undergoing elective surgery under general anesthesia with oral endotracheal
      intubation, and randomly divided into 3 groups according to a random number table, with 92
      cases in each group. When participants reach the titration endpoint (OAAS score 1 point)
      during the titration of propofol in the induction, the investigators stop the dosing and
      switch to a maintenance dose, and give rocuronium 0.15 mg/kg and remifentanil 2 ug/kg; 2
      minutes later the chief anesthetist performs tracheal intubation. The investigators will
      observe hemodynamics changes and brain electrical activity throughout the process, and adjust
      the drugs according to the blood pressure to make the hemodynamics as stable as possible.

      After confirming the successful tracheal intubation, the investigators will give participants
      machine-controlled ventilation, and the total intravenous anesthesia (TIVA) will be given
      with propofol, remifentanil, and cis-atracurium. During the operation, remifentanil will be
      injected with a constant rate of 0.2ug/kg/min, and propofol will be injected with a
      fluctuating rate of 2-8mg/kg/h (the pump injection rate will be adjusted according to blood
      pressure and BIS, and the rate of remifentanil can be adjusted if necessary) to maintain BIS
      between 40-60.Fluid therapy will be performed according to the participants' hemodynamics and
      intraoperative conditions. After extubation, participants will be sent to the postoperative
      recovery room; a follow-up visit will be performed the next day, and a telephone return visit
      will be performed on the 30th day.

      The investigators record the visual analogue scale(VAS) score for preoperative anxiety of
      each participant, bispectral index (BIS) and hemodynamics of patients when participants reach
      different stages of sedation as determined by the Observer's Assessment of Alertness/Sedation
      Scale (OAAS) score, and the lowest value and specific time of mean blood pressure(MBP) and
      BIS during induction of anesthesia；the investigators record various parameters at the
      following time points(10 minutes after entering the operating room before propofol
      administration, every minute after administration until intubation, immediately after
      tracheal intubation, and 1, 2, 4, 6, 8, 10, 20 min after intubation), and parameters include:
      systolic blood pressure(SBP) , diastolic blood pressure(DBP), MBP, heart rate(HR),
      electrocardiogram ST-T changes (V1), BIS, cardiac function parameters (heart rate
      variability(HRV), stroke volume (SV), stroke index(SVI), cardiac output (CO), cardiac
      index(CI) ), oxygen delivery parameters (oxygen delivery (DO2), oxygen delivery index
      (DO2I)), peripheral vascular resistance parameters (systemic vascular resistance (SVR),
      systemic vascular resistance index (SVRI)), volume parameters (stroke volume variation(SVV),
      pulse pressure variation (PPV), increase in stroke volume(△SV)); the investigators record the
      time for each participant reach the titration endpoint and the amount of propofol used, the
      time from the start of induction to the completion of the tracheal intubation and the amount
      of propofol, and the total amount of propofol during the operation.

      The investigators record invasive blood during the trial, and use cameras to video the entire
      process of anesthesia induction.

      The 11-30th participants in each group will be given arterial blood samples at 1, 3, 5, and 7
      minutes after the administration of propofol to measure the blood concentration of propofol;
      when rocuronium is given and 30 seconds after the completion of tracheal intubation, venous
      blood will be drawn to measure the catecholamine concentration; ten cases of propofol with
      high, medium and low sensitivity will be selected for transcriptome RNA sequencing; Single
      nucleotide polymorphism（SNP） analysis of propofol-related genes in special cases.

      During the induction period, the investigators will monitor EEG of the left and right
      frontal, temporal and occipital lobes, and analyze the power spectrum of β, α, θ, and σ brain
      waves; observe the pupil reflex and auditory evoked potential(brain stem auditory evoked
      potentials(BAEP): the incubation period and amplitude of III, V ; middle latency auditory
      evoked potentials（MLAEP）: the incubation period and amplitude of Pa, Nb) before induction ,
      when the titration endpoint reaches and after finishing intubation.

      Blind design:

      The observer performs pre-entry screening, and does not know the group of participants during
      the induction process. The anesthesia nurse receives the experiment envelope in advance,
      adjusts the infusion pump according to the group, and adjusts the pump to the position facing
      away from the observer and the chief anesthetist. The chief anesthetist communicates with
      patients and performs OAAS scores scoring. When the titration endpoint reaches, the
      anesthesia nurse will stop propofol administer and shift to the maintenance dose, following
      the observer's order to add vasoactive drugs or propofol during the induction process, and do
      not participate in the postoperative follow-up work. The chief anesthetist (working for more
      than 3 years) is responsible for assisted ventilation and tracheal intubation. The
      anesthesiologist in the resuscitation room, the patient, and the post-operative return
      visitor do not know the group of the participant.
    

Intervention name(s): 2mg/kg/min; 1mg/kg/min; 0.5mg/kg/min
Intervention type(s): Drug; Drug; Drug
Intervention description(s): titration dosing speeds of propofol at 2mg/kg/min; titration dosing speeds of propofol at 1mg/kg/min; titration dosing speeds of propofol at 0.5mg/kg/min
Other intervention name(s): Remifentanil 2ug/kg; Rocuronium 1.5mg/kg; Remifentanil 2ug/kg; Rocuronium 1.5mg/kg; Remifentanil 2ug/kg; Rocuronium 1.5mg/kg
Intervention MeSH terms: Remifentanil; Rocuronium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: titration of propofol