This was a prospective, randomized, parallel-group clinical trial. This study was conducted between 27 May 2022 and 17 August 2022 in the IVF unit. The protocol was registered on the http://www.clinicaltrials.gov protocol registration system (NCT05631925 - 12/03/2022) and was approved by the Clinical Research Ethics Committee of Acıbadem University, Istanbul, Turkey (No:2022/05-32).
One hundred and thirty American Society of Anesthesiologist’s Class I or II patients, over age 18, undergoing transvaginal oocyte retrieval for in vitro fertilization under general anesthesia were included in this study. Patients were excluded if they had contraindication for general anesthesia, they had a history of mental illness, alcohol, or substance abuse. Patients were randomized into two groups (65 patients in group bolus, 65 patients in group BIS) by an anesthesiologist who was not included in the study. Randomization was performed by opening one of a series of sequentially numbered opaque envelopes that contained the group assignment. Written informed consent was obtained from all study participants. The patients, and the gynecologist were blinded to group assignment.
Each patient’s age, weight, height, body mass index (BMI), and ASA status were recorded preoperatively. All the patients fasted for at least 6 h prior the procedure and did not receive premedication. On the arrival in the operating room, heart rate, noninvasive blood pressure, and oxygen saturation on pulse oximetry were monitored, an intravenous canula was inserted and %0.9 NaCl infusion was started. Patients in group BIS were also monitored with BIS.
In both groups, anesthesia was induced with intravenous propofol (2mg/kg) and fentanyl (2μg/kg) administration. A second-generation laryngeal mask was inserted two minutes after the anesthesia induction in group bolus and when BIS value <60 in group BIS. Normocapnic mechanical ventilation was initiated. A 40% O2/air mixture was used during the procedure. Laryngeal mask placement was attempted 2 times, if unsuccessful, ventilation with face mask was continued, and the patient was excluded from the study. The number of insertion attempts was recorded.
In group bolus, 0.5mg/kg propofol was administered when necessary, using the 0-4 graded intraoperative movements scale (IOMs).
Intraoperative Movements Scale (IOMs) [10]
Grade 0 = No movement
Grade 1 = Ankles movement (feet dorso-flexion)
Non procedure interferent
It could deepen analgesia
Grade 2 = Knee movements (legs flexo-extension) (with/without movements)
Non procedure interference (aspiration could stop)
It could deepen analgesia/anesthesia.
Grade 3 = Pelvis/ hips movements (with/without legs/thighs movements)
Aspiration must be stopped
Must be deepen analgesia/anesthesia
Grade 4 = Rude movements of the pelvis, chest and/or arm
Aspiration must be stopped
Must be deepen anesthesia
In group BIS continuous propofol infusion (10mg/kg/hour) was started immediately after anesthesia induction. In these patients, the propofol infusion rate was adjusted to keep the BIS value between 40-60 during the procedure. If the BIS value was above the target level, the propofol infusion rate was increased by 20%, and if the BIS was below the target level, the infusion rate was decreased by 20%. Propofol infusion was stopped when oocyte aspiration was completed.
During the procedure, all the patients received paracetamol (1gr) intravenously, and diclofenac sodium 100mg suppository was applied at the end of the procedure for postoperative analgesia. The laryngeal mask was removed when the patients opened the eyes.
Heart rate, oxygen saturation, systolic, diastolic, and mean blood pressure were recorded before anesthesia, at the 5th, 10th, and 15th minutes of the procedure, at the end of the procedure and when the patient was awake. BIS values were also recorded in the group BIS at the same time points. Bradycardia (defined as heart rate < 25% from baseline or < 50 beats/min), hypotension (defined as systolic blood pressure < 25% from baseline or < 90 mmHg), and presence of rigidity were recorded. In the presence of bradycardia, 0.5mg atropine was administered. In the presence of hypotension, 5mg ephedrine was administered.
The duration of anesthesia and duration of procedure were recorded. The total amount of propofol was recorded. After the removal of the laryngeal mask, the time to reach 5 in the MOASs was recorded in the operating room.
Responsiveness Scores of the Modified Observer’s Assessment of Alertness/ Sedation Scale (MOASs) [13]
Response
|
Score Level
|
Responds readily to name spoken in normal tone
|
5 (Alert)
|
Lethargic response to name spoken in normal tone
|
4
|
Responds only after name is called loudly or repeatedly
|
3
|
Responds only after mild prodding or shaking
|
2
|
Does not respond to mild prodding or shaking
|
1
|
All the procedures were performed by same experienced gynecologist and after the procedure, the satisfaction with the anesthesia was questioned. Gynecologist satisfaction 1: very satisfied 2: satisfied 3: not satisfied 4: not satisfied at all.
After transfer to the recovery area, patients were assessed continuously by a nurse who was blinded to the group assignment. Each patient’s pain was evaluated using visual analogue scale (VAS) ranging from 0cm (no pain) to 10cm (worst pain imaginable) during the postoperative period. If the patient had a VAS score ³4, 75mg diclofenac sodium was administered intramuscularly and recorded as additional analgesic.
Nausea and vomiting of the patients were evaluated with a 4-grade scale 0: no nausea or vomiting 1: tolerable nausea or simple vomiting that does not require treatment 2: intolerable nausea or recurrent vomiting requiring treatment 3: recurrent nausea or vomiting resistant to drug therapy. If the score ³2 ondansetron 4mg was administered intravenously. Nausea and vomiting score and the use of antiemetics were also recorded.
The time of patients to reach PADSS ³9 was recorded.
Post Anesthetic Discharge Scoring System (PADSS) [13]
Vital signs
|
2=Blood pressure and heart rate within 20% of preoperative value
|
1=Blood pressure and heart rate within 20-40% of preoperative value
|
0=Blood pressure and heart rate more than 40% different from the preoperative value
|
Activity and mental status
|
2= Oriented, and has a steady gait
|
1=Oriented or has a steady gait
|
0=Neither
|
Nausea and or vomiting
|
2=Minimal
|
1=Moderate, having required treatment
|
0=Severe, requiring treatment
|
Pain
|
2=Minimal
|
1= Moderate, having required treatment
|
0= Severe, requiring treatment
|
Surgical bleeding
|
2=Minimal
|
1=Moderate
|
0=Severe
|
Patient’s satisfaction related to the anesthetic method was questioned before discharge. Patient satisfaction 1: very satisfied 2: satisfied 3: not satisfied 4: not satisfied at all (I had pain during the procedure, I was awake during the procedure). The score was recorded.
The primary outcome of our study was the total dose of propofol administered to the patients. The secondary outcomes were the time to reach the value of 5 on the MOASs, the time to reach the value of PADSS³9 in the postoperative period, and the satisfaction of the patient and the gynecologist.
Statistical Analysis
The primary outcome of the study was total propofol consumption. The power analysis was based on the results of the study conducted by Luginbuhl et al. [12]. The authors found that total consumption of propofol was 6.03±1.4 mg/kg and 6.64±0.9 mg/kg consecutively in groups using BIS and not using BIS (p=0.023). With a power of 80% and an alpha error of 5%, the sample size calculation determined that 60 patients were required for each group, using the G ∗ Power (v3.1.7) program. Considering the possibility of drop out and lack of data, the total number of patients required for the study was determined to be 130 (65 patients for each group). We analyzed the data with SPSS version 16 (SPSS Inc., Chicago, Illinois, USA). Convenience of parameters to the normal distribution was assessed with Shapiro Wilks test while assessing the study data. Student t-test was used in comparing quantitative data for comparing parameters that showed normal distribution between the two groups, while Mann-Whitney U test was used in comparing data that did not show a normal distribution between the two groups. Chi-square test and Fisher’s exact tests were used in comparing qualitative parameters. p ≤ 0.005 was considered statistically significant.