The Effect-site Concentration of Remifentanil Blunting Endotracheal Intubation Responses During Anesthesia Induction With Lidocaine or Sufentanil Combined With Etomidate: A Randomized Controlled Study

Overview

The aim of this study was to compare the effect-site target concentration (including EC₅₀ and EC₉₀) of remifentanil required to suppress cardiovascular responses to tracheal intubation during anesthesia induction with etomidate combined with either lidocaine or sufentanil.

Detailed description

This study is a single-center, randomized controlled trial utilizing a modified sequential method to determine the effect site target concentration of remifentanil, including the median effective concentration (EC₅₀) and the 90% effective concentration (EC₉₀). The study population consists of ASA class I-II patients undergoing general anesthesia with endotracheal intubation. Patients will be randomly assigned to one of three groups: placebo group, lidocaine group, and sufentanil group. Patients in each group will receive anesthesia induction with a combination of either saline, lidocaine, or sufentanil along with etomidate, followed by target-controlled infusion of remifentanil. The primary outcome measure is the median effective target concentration of remifentanil in the effect site (EC₅₀) for suppressing the intubation response. Secondary outcomes include the 90% effective target concentration of remifentanil (EC₉₀), changes in mean arterial pressure (MAP), heart rate (HR), and bispectral index (BIS) before and after intubation. Each group is expected to enroll 33 patients, totaling 99 patients across all three groups.

Interventions

• Drug Intravenous normal saline (NS 0.9)
  Under target-controlled infusion (TCI) of remifentanil, anesthesia induction is performed using placebo (normal saline) combined with etomidate (0.3 mg/kg).
• Drug intravenous sufentanil
  Under target-controlled infusion (TCI) of remifentanil, anesthesia induction is performed using sufentanil (0.2μg/kg) combined with etomidate (0.3 mg/kg).
• Drug Intravenous lidocaine
  Under target-controlled infusion (TCI) of remifentanil, anesthesia induction is performed using lidocaine (1.5 mg/kg) combined with etomidate (0.3 mg/kg).

Primary outcome measures

• The 50% effective effect-site target concentration (EC₅₀) of remifentanil for suppressing patients' tracheal intubation response [Time frame: Through study completion, an average of 1 year.]

Secondary outcome measures (2)

• The 90% effective effect-site target concentration (EC₉₀) of remifentanil for suppressing patients' tracheal intubation response [Time frame: Through study completion, an average of 1 year.]
• complications [Time frame: Operative day, Postoperative day 1, Postoperative day 5.]

Eligibility criteria

Inclusion criteria

• Patients scheduled for elective surgery under general anesthesia with endotracheal intubation;
• Classified as ASA physical status I-II.

Exclusion criteria

• Age <18 years or >65 years;
• Body mass index (BMI) >30 kg/m² or <18.5 kg/m²;
• Diagnosis of hypertension or severe cardiovascular diseases (including myocardial infarction, heart failure, atrial fibrillation, atrioventricular block, moderate-to-severe valvular diseases) or respiratory diseases (including acute exacerbation of chronic obstructive pulmonary disease, acute respiratory distress syndrome, acute asthma attack, moderate-to-severe pulmonary hypertension, severe pneumonia);
• Diagnosis of obstructive sleep apnea syndrome or history of difficult intubation or preoperatively anticipated difficult airway;
• Renal, hepatic or hematologic diseases;
• High risk of aspiration or reflux;
• Current use of analgesics for chronic pain or β-blockers for cardiovascular diseases;
• Current use of psychotropic medications;
• Contraindications to remifentanil or sufentanil, including: known hypersensitivity to any component of these drugs or other fentanyl analogues, current use of monoamine oxidase inhibitors, myasthenia gravis or conditions predisposing to respiratory depression, bronchial asthma or related disorders;
• Contraindications to lidocaine, including: known allergy to local anesthetics, concurrent Adams-Stokes syndrome, Wolff-Parkinson-White syndrome, or severe cardiac conduction block.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Peking University Shenzhen Hospital — Shenzhen

Publications

• Lee IW, Schraag S. The Use of Intravenous Lidocaine in Perioperative Medicine: Anaesthetic, Analgesic and Immune-Modulatory Aspects. J Clin Med. 2022 Jun 20;11(12):3543. doi: 10.3390/jcm11123543. PMID 35743617
• Guignard B, Menigaux C, Dupont X, Fletcher D, Chauvin M. The effect of remifentanil on the bispectral index change and hemodynamic responses after orotracheal intubation. Anesth Analg. 2000 Jan;90(1):161-7. doi: 10.1097/00000539-200001000-00034. PMID 10624998
• Gelberg J, Jonmarker C, Stenqvist O, Werner O. Intravenous boluses of fentanyl, 1 mug kg(-)(1), and remifentanil, 0.5 mug kg(-)(1), give similar maximum ventilatory depression in awake volunteers. Br J Anaesth. 2012 Jun;108(6):1028-34. doi: 10.1093/bja/aes029. Epub 2012 Mar 22. PMID 22440314
• Baldo BA. Toxicities of opioid analgesics: respiratory depression, histamine release, hemodynamic changes, hypersensitivity, serotonin toxicity. Arch Toxicol. 2021 Aug;95(8):2627-2642. doi: 10.1007/s00204-021-03068-2. Epub 2021 May 11. PMID 33974096
• Trujillo C, Rudd D, Ogutcu H, Dong F, Wong D, Neeki M. Objective Characterization of Opiate-Induced Chest Wall Rigidity. Cureus. 2020 Jun 5;12(6):e8459. doi: 10.7759/cureus.8459. PMID 32566433
• Oron AP, Souter MJ, Flournoy N. Understanding Research Methods: Up-and-down Designs for Dose-finding. Anesthesiology. 2022 Aug 1;137(2):137-150. doi: 10.1097/ALN.0000000000004282. PMID 35819863
• Burlacu CL, McKeating K, McShane AJ. Remifentanil for the insertion and removal of long-term central venous access during monitored anesthesia care. J Clin Anesth. 2011 Jun;23(4):286-91. doi: 10.1016/j.jclinane.2010.12.007. PMID 21663812
• Perez JJ, Strunk JD, Preciado OM, DeFaccio RJ, Chang LC, Mallipeddi MK, Deal SB, Oryhan CL. Effect of an opioid-free anesthetic on postoperative opioid consumption after laparoscopic bariatric surgery: a prospective, single-blinded, randomized controlled trial. Reg Anesth Pain Med. 2025 Sep 4;50(9):699-705. doi: 10.1136/rapm-2024-105632. PMID 38839427

Identifiers

NCT: NCT07089173 · 2025-112

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗