A Phase 4 interventional study of Midazolam and Lidocaine Hydrochloride 2% in Propofol Injection Pain, Postoperative Recall of Pain and Preoperative Anxiety, sponsored by Atlas University. Not yet recruiting at 1 site in Turkey (Türkiye). Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-11-03.
Sponsored by Atlas University · Phase 4, Interventional, and Supportive care
Propofol is the most commonly used intravenous drug to start general anesthesia (induction). However, it often causes pain in the arm during injection, and remembering this pain after surgery can negatively affect the patient's experience and comfort. Adding lidocaine (a local anesthetic) to propofol reduces this pain but does not prevent it in every patient. Midazolam is a medicine commonly given to reduce anxiety, and it can also reduce the memory of events that occur after it is given (anterograde amnesia). It is not known whether midazolam reduces the memory of propofol injection pain after surgery.
In this study, adult volunteers aged 18 to 65 who are scheduled for elective surgery will be randomly assigned to one of three groups: (1) a low sedative dose of midazolam before propofol, (2) propofol mixed with lidocaine, or (3) propofol alone. Neither the participants nor the investigator giving the medication will know which group a participant is in. After surgery, once participants have recovered sufficiently, they will be asked whether they remember pain at the injection site during propofol injection. The study will also assess the severity of injection pain and the relationship between anxiety before surgery and injection pain.
All drugs used in this study are approved medicines given at doses used in routine anesthesia practice.
Rationale: Propofol injection pain is common, and recalling it after surgery negatively affects patient experience and comfort. Adding lidocaine to propofol reduces injection pain but is not effective in all patients. Midazolam produces marked anterograde amnesia, but its effect on the postoperative recall of propofol injection pain is not well established. This study aims to separate the independent amnestic effect of midazolam on recall of injection pain from the indirect effect of lidocaine on pain intensity.
Procedures: Eligible participants are screened before surgery, written informed consent is obtained, and preoperative anxiety is measured with a 0-10 Visual Analog Scale (VAS). Participants are randomized 1:1:1 using computer-generated block randomization (variable block sizes of 6 and 9). Allocation concealment is ensured with opaque, sequentially numbered envelopes. An anesthesia technician who is not involved in the assessments opens the envelope and prepares and labels freshly prepared, coded syringes for each participant. The investigator administering the study medication and the participant remain blinded to group allocation until the evaluation is complete. All participants are monitored with ECG, pulse oximetry, and non-invasive blood pressure.Sedation level before induction is assessed with the Ramsay Sedation Scale. Propofol injection pain during induction is graded by the investigator on a 4-point scale (1: no pain; 2: mild arm withdrawal; 3: marked arm withdrawal; 4: verbal expression of pain). In the recovery unit, adequate recovery is determined using the Modified Aldrete Score. After adequate recovery, participants are asked whether they remember pain at the injection site during propofol injection.
Safety: Emergency intubation and resuscitation equipment, flumazenil (midazolam antidote), atropine, epinephrine, and corticosteroids/antihistamines are kept immediately available. The technician who prepared the study solution remains next to the blinded investigator during administration to disclose the contents and dose if an emergency occurs. There is no independent data monitoring committee.
Statistical analysis: Analyses are performed with IBM SPSS Statistics version 24. Recall rates and pain incidence are compared between groups with the chi-square test (Fisher's exact test when required); pain severity is compared with the Kruskal-Wallis test; continuous variables are compared with one-way ANOVA or Kruskal-Wallis depending on distribution. The relationship between preoperative anxiety and injection pain is assessed with Spearman correlation. Sample size was calculated with G*Power 3.1.9.7 (80% power, two-sided alpha 0.05); 45 participants per group were required, and 50 per group (150 total) were planned to allow for dropouts.
Atlas University is the lead sponsor of 96 studies on the registry; 25 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ASA physical status
The anaesthetists’ scale of health before surgery: I is healthy, II has a mild illness that is under control, III a severe one, IV a severe illness that is a constant threat to life. V and VI are used for the critically ill and for organ donors.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive midazolam at an age-adjusted sedative dose, diluted with 0.9% sodium chloride to 5 mL, before induction, followed by propofol 1% 2-3 mg/kg over 30 seconds.
Drug: Midazolam · Drug: Propofol 1%
Participants receive 5 mL of 0.9% sodium chloride before induction, followed by a mixture of propofol 1% and lidocaine 2% (200 mg propofol with 40 mg lidocaine) at 2-3 mg/kg propofol over 30 seconds.
Drug: Lidocaine Hydrochloride 2% · Drug: Propofol 1%
Participants receive 5 mL of 0.9% sodium chloride before induction, followed by propofol 1% 2-3 mg/kg over 30 seconds without additives.
Drug: Propofol 1% · Drug: Sodium Chloride 0.9%
Single intravenous dose of midazolam at an age-adjusted sedative dose (0.06 mg/kg for ages 18-30, 0.05 mg/kg for ages 31-50, 0.04 mg/kg for ages 51-65), diluted with 0.9% sodium chloride to a total volume of 5 mL and given before induction of anesthesia with propofol.
Also known as: Zolamid
Lidocaine 2% (total 40 mg) mixed in the same syringe with propofol 1% (200 mg propofol : 40 mg lidocaine) and given intravenously as a single dose during induction.
Also known as: Lidon
Propofol 1% (10 mg/mL), 2-3 mg/kg administered intravenously over 30 seconds through a 20 G dorsal hand vein catheter as the standard induction agent in all groups.
Also known as: Propofol-PF
5 mL of 0.9% sodium chloride given intravenously before propofol induction as a carrier/placebo solution to maintain blinding.
Also known as: Normal saline
Postoperative recall of propofol injection pain
Proportion of participants who report remembering pain at the injection site during propofol injection, assessed by asking each participant once after adequate postoperative recovery. Compared between Group M (midazolam + propofol), Group L (lidocaine-propofol mixture), and Group P (propofol alone).
Time frame: Postoperative period on the day of surgery, after recovery from anesthesia 30 minutes after arrival in the post-anesthesia care unit (PACU)
Severity of propofol injection pain
Severity of pain during propofol injection graded by the investigator on a 4-point scale (1: no pain; 2: mild arm withdrawal; 3: marked arm withdrawal; 4: verbal expression of pain). Higher scores indicate more pain. Compared between the three groups.
Time frame: At the Baseline, During propofol administration (at the time of injection, )
Relationship between preoperative anxiety and propofol injection pain
Preoperative anxiety is measured with a 0-10 Visual Analog Scale (higher scores indicate more anxiety). The relationship between the anxiety score and propofol injection pain score is assessed with Spearman correlation.
Time frame: During propofol injection and 30 minutes after arrival in the post-anesthesia care unit (PACU)
Sedation level before propofol induction
Sedation level assessed with the Ramsay Sedation Scale (1-6; higher scores indicate deeper sedation) and compared between groups. The association between preoperative anxiety levels and the severity of propofol injection pain will be evaluated. Preoperative anxiety will be assessed before anesthesia induction, and propofol injection pain severity will be assessed based on patients' reports 30 minutes after arrival in the post-anesthesia care unit (PACU).
Time frame: Before anesthesia induction and 30 minutes after arrival in the post-anesthesia care unit (PACU)
Plan to share: No — Individual participant data will not be shared. Participant data are coded and stored securely, and only de-identified aggregate results will be reported in publications.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Midazolam
Amnesia, Anterograde
Atlas University