Opioid-based Versus Opioid-free Endotracheal Intubation

The Effect of Opioid-free Anesthesia on Hemodynamic Response and Nociception Level Index During Laryngoscopy and Intubation

The aim of this study will be to investigate the effect of opioid-free induction versus opioid-based induction on hemodynamic response and nociception level index during elective operations

Study Overview

• Status: Completed
• Conditions: Anesthesia; Opioid Use; Fentanyl; Analgesic Non-narcotic; Anesthesia Intubation
• Intervention / Treatment: Drug: ketamine-lidocaine-dexmedetomidine; Drug: fentanyl

Detailed Description

Laryngoscopy and intubation stimuli can cause a sustained sympathetic response manifested as hypertension and tachycardia. Therefore, preadministration of opioid medication aiming at blunting this hemodynamic response is common in everyday anesthetic practice.

Opioid-based anesthesia is associated with side-effects, such as respiratory depression, postoperative nausea and vomiting and occasional induction of tolerance and hyperalgesia.

Research in recent years has focused on the quest for non-opioid-based regimens (opioid-sparing and opioid-free techniques). Most of the relevant studies however focus on the advantages that opioid-free techniques bear on early and late postoperative patient recovery. Literature on the effect of opioid-free techniques especially on laryngoscopy, intubation and subsequent hemodynamic response.

Therefore, the aim of this study will be the comparison of the hemodynamic response to laryngoscopy and intubation between two groups of patients: a group in which opioid medications will be administered before anesthetic induction and a group in which a combination of lidocaine, dexmedetomidine and ketamine will be administered before anesthetic induction.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 11528
    • ARETAIEION University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• adult patients
• American Society of Anesthesiologists (ASA) classification I-II
• Mallampati classification 1, 2 or 3

Exclusion Criteria:

• anticipated difficult airway (Mallampati 4 classification, thyromental distance < 6 cm, mouth opening < 3 cm, neck extension< 80
• atrioventricular block
• bradycardia (heart rate less than 55/min)
• preadministration of beta-blockers
• eligibility for rapid-sequence induction
• chronic use of opioid medications
• known allergy to induction agents
• history of psychiatric disease
• language or communication barriers or lack of informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ketamine-lidocaine-dexmedetomidine group; combination of ketamine-lidocaine-dexmedetomidine	Drug: ketamine-lidocaine-dexmedetomidine; Patients will be administered 0,8 mcg/kg Dexmedetomidine in 100 mL of normal saline within 10 minutes as premedication. Followingly, they will receive 1mL/10 kg of the solution containing ketamine, lidocaine and dexmedetomidine at predefined concentrations just before induction of anesthesia.; Other Names: KLD group
Active Comparator: fentanyl group; fentanyl	Drug: fentanyl; Patients will be administered 2 mcg/kg fentanyl in 100 mL of normal saline within 10 minutes as premedication. Followingly, they will receive 1mL/10 kg of normal saline solution 0.9% just before induction of anesthesia.; Other Names: control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change from baseline in systolic arterial pressure after premedication	baseline systolic arterial pressure will be measured as soon as the patient settles in the operating theatre	30 seconds after premedication
change from baseline in systolic arterial pressure immediately after premedication	baseline systolic arterial pressure will be measured as soon as the patient settles in the operating theatre	immediately after intubation
change from baseline in systolic arterial pressure 1 minute after intubation	baseline systolic arterial pressure will be measured as soon as the patient settles in the operating theatre	1 minute after intubation
change from baseline in systolic arterial pressure 3 minutes after intubation	baseline systolic arterial pressure will be measured as soon as the patient settles in the operating theatre	3 minutes after intubation
change from baseline in systolic arterial pressure 5 minutes after intubation	baseline systolic arterial pressure will be measured as soon as the patient settles in the operating theatre	5 minutes after intubation
change from baseline in diastolic arterial pressure after premedication	baseline diastolic arterial pressure will be measured as soon as the patient settles in the operating theatre	30 seconds after premedication
change from baseline in diastolic arterial pressure 1 minute after intubation	baseline diastolic arterial pressure will be measured as soon as the patient settles in the operating theatre	1 minute after intubation
change from baseline in diastolic arterial pressure 3 minutes after intubation	baseline diastolic arterial pressure will be measured as soon as the patient settles in the operating theatre	3 minutes after intubation
change from baseline in diastolic arterial pressure 5 minutes after intubation	baseline diastolic arterial pressure will be measured as soon as the patient settles in the operating theatre	5 minutes after intubation
change from baseline in heart rate after premedication	baseline heart rate will be measured as soon as the patient settles in the operating theatre	30 seconds after premedication
change from baseline in heart rate 1 minute after intubation	baseline heart rate will be measured as soon as the patient settles in the operating theatre	1 minute after intubation
change from baseline in heart rate 3 minutes after intubation	baseline heart rate will be measured as soon as the patient settles in the operating theatre	3 minutes after intubation
change from baseline in heart rate 5 minutes after intubation	baseline heart rate will be measured as soon as the patient settles in the operating theatre	5 minutes after intubation
ST segment change 1 minute post intubation	ST segment elevation or depression after intubation	1 minute after intubation
ST segment change 3 minutes post intubation	ST segment elevation or depression after intubation	3 minutes after intubation
ST segment change 5 minutes post intubation	ST segment elevation or depression after intubation	5 minutes after intubation
duration of nociception level<25 for a 5-minute period after intubation	nociception level (NOL) is a device that measures the status of analgesia intraoperatively. Levels<25 suggest adequate intraoperatively analgesia	5 minutes after intubation
time required to achieve a train-of four-ratio of 0	the train-of-four (TOF) ratio measures the ratio of the fourth stimulus to the first stimulus of four twitches of neuromuscular stimulation. When this ration reaches the value of 0, the patient is considered ready for intubation	within 2.5 minutes of neuromuscular blocking agent administration

Collaborators and Investigators

• Sponsor: Aretaieion University Hospital
• Investigators: Principal Investigator: KASSIANI THEODORAKI, PhD, DESA, Aretaieion University Hospital, National and Kapodistrian University of Athens, Greece

Publications and helpful links

General Publications

• Shribman AJ, Smith G, Achola KJ. Cardiovascular and catecholamine responses to laryngoscopy with and without tracheal intubation. Br J Anaesth. 1987 Mar;59(3):295-9. doi: 10.1093/bja/59.3.295.
• Theodoraki K, Fassoulaki A. Cardiovascular responses to laryngoscopy and tracheal intubation are not accompanied by ST-segment changes. Eur J Anaesthesiol. 2009 Jun;26(6):520-2. doi: 10.1097/EJA.0b013e32831a468d. No abstract available.
• Vickovic S, Zdravkovic R, Radovanovic D, Galambos IF, Pap D, Krtinic D, Stanisavljevic S, Preveden M, Videnovic N, Videnovic J. Effect of different doses of remifentanil on the cardiovascular response after endotracheal intubation: a randomized double-blind study. Eur Rev Med Pharmacol Sci. 2023 Jan;27(2):653-658. doi: 10.26355/eurrev_202301_31067.
• Feenstra ML, Jansen S, Eshuis WJ, van Berge Henegouwen MI, Hollmann MW, Hermanides J. Opioid-free anesthesia: A systematic review and meta-analysis. J Clin Anesth. 2023 Nov;90:111215. doi: 10.1016/j.jclinane.2023.111215. Epub 2023 Jul 27.
• Patel J, Snyder K, Brooks AK. Perioperative pain optimization in the age of the opioid epidemic. Curr Opin Anaesthesiol. 2024 Jun 1;37(3):279-284. doi: 10.1097/ACO.0000000000001370. Epub 2024 Mar 12.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Actual): March 20, 2025
• Study Completion (Actual): March 20, 2025

Study Registration Dates

• First Submitted: June 13, 2024
• First Submitted That Met QC Criteria: June 13, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): July 22, 2025
• Last Update Submitted That Met QC Criteria: July 20, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Analgesics, Opioid; Narcotics; Neurotransmitter Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Excitatory Amino Acid Agents; Anesthetics, Dissociative; Excitatory Amino Acid Antagonists; Lidocaine; Dexmedetomidine; Ketamine; Fentanyl
• Other Study ID Numbers: 548/02-02-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No