Effects of Minimal-Flow Sevoflurane and Multimodal Analgesia in Head and Neck Cancer Surgery

Anesthetic-sparing and Renal Protection Effects of Minimal-flow Sevoflurane Anesthesia and Multimodal Analgesia Using a Mixture of Dexmedetomidine-ketamine-lidocaine in Head and Neck Cancer Patients With Free Flap Microvascular Surgery

This study evaluates the anesthetic-sparing and renal protection effects of minimal-flow sevoflurane anesthesia combined with multimodal analgesia using dexmedetomidine, ketamine, and lidocaine in head and neck cancer patients undergoing free flap microvascular surgery. The 2x2 factorial randomized controlled trial aims to compare sevoflurane usage and renal function changes with different fresh gas flow rates and multimodal analgesia.

Study Overview

• Status: Not yet recruiting
• Conditions: Head and Neck Cancer; Acute Kidney Injury; Anesthesia; Multimodal Analgesia; Renal Protection
• Intervention / Treatment: Drug: Multimodal analgesia using dexmedetomidine-ketamine-lidocaine mixture; Device: Minimal flow sevoflurane

Detailed Description

This study investigates the anesthetic-sparing and renal protection effects of minimal-flow sevoflurane anesthesia combined with a multimodal analgesia strategy using dexmedetomidine, ketamine, and lidocaine in head and neck cancer patients undergoing free flap microvascular surgery. The trial employs a 2x2 factorial randomized controlled design to evaluate the effectiveness of different fresh gas flow rates and multimodal analgesia on sevoflurane usage and renal function.

Background and Significance:

Sevoflurane, a widely used anesthetic for prolonged surgeries, significantly contributes to healthcare-related greenhouse gas emissions. Reducing fresh gas flow during anesthesia effectively minimizes anesthetic usage, but concerns about potential renal damage hinder its clinical application. Recent studies show that sevoflurane enhances renal sympathetic nerve activity, leading to decreased renal blood flow and increased risks of acute kidney injury, particularly when coupled with factors like low blood pressure.

Multi-modal analgesia combining drugs like dexmedetomidine, ketamine, and lidocaine has emerged as a trend in anesthesiology. These drugs not only reduce sevoflurane usage but may also counteract its renal effects. This project aims to investigate the renal protective effects and anesthetic reduction potential of a multi-modal analgesia strategy in head and neck cancer surgeries.

Study Objectives:

To evaluate the anesthetic-sparing effect of minimal-flow sevoflurane anesthesia (0.5 L/min) combined with dexmedetomidine-ketamine-lidocaine multimodal analgesia.

To assess the renal protection effects of dexmedetomidine-ketamine-lidocaine multimodal analgesia during minimal-flow sevoflurane anesthesia.

To examine the safety and other potential effects (e.g., hemodynamic stability, postoperative cognitive function) of the combined anesthesia strategy.

Methods:

The study will be conducted at National Taiwan University Hospital and will involve adult patients (18-99 years) scheduled for head and neck cancer tumor resection and free flap reconstruction surgery. Patients will be randomized into four groups in a 2x2 factorial design:

Group 1 (HL + D): Fresh gas flow at 0.5 L/min with dexmedetomidine-ketamine-lidocaine mixture.

Group 2 (HL): Fresh gas flow at 0.5 L/min with normal saline. Group 3 (D): Fresh gas flow at 1.0 L/min with dexmedetomidine-ketamine-lidocaine mixture.

Group 4 (Control): Fresh gas flow at 1.0 L/min with normal saline. The dexmedetomidine-ketamine-lidocaine mixture will be continuously infused from the induction of anesthesia until the end of surgery. Fresh gas flow settings will be maintained using the EtControl function of the GE Aisys CS2 anesthesia machine. Anesthetic depth and hemodynamic parameters will be monitored throughout the procedure.

Data Collection:

Primary Outcome Measures: Sevoflurane usage (mL/h) and changes in renal function (serum renin, AVP levels, urine KIM-1, NGAL levels).

Secondary Outcome Measures: Incidence of acute kidney injury, hemodynamic stability, postoperative pain scores, length of hospital stay, and postoperative cognitive function.

Blood and urine samples will be collected at four time points: before anesthesia induction, upon arrival in the ICU, 24 hours post-surgery, and 48 hours post-surgery. Clinical data, including demographic information, surgical details, anesthetic drug usage, hemodynamic parameters, and postoperative outcomes, will also be recorded.

Statistical Analysis:

Data will be analyzed using appropriate statistical methods, including Student's t-test, Mann-Whitney U test, Chi-square test, Fisher's exact test, and multivariate analysis of variance (MANOVA). Statistical significance will be defined as p < 0.05.

Potential Challenges and Solutions:

Potential challenges include patient recruitment and adherence to protocol. To mitigate these, the study will involve experienced anesthesiologists and research staff who will ensure proper patient selection and protocol compliance.

Expected Outcomes:

The study aims to propose a feasible strategy to mitigate sevoflurane's renal effects, crucial for patients at risk of acute kidney injury. It also seeks to validate that minimal fresh gas flow (0.5 L/min) during sevoflurane anesthesia, coupled with multimodal analgesia, reduces sevoflurane usage, saving costs and contributing to carbon reduction. Additionally, the study will explore the potential protective effects of the multimodal analgesia strategy on other organs during prolonged surgeries.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ming-Hui Hung, MD; Phone Number: +886-972653392; Email: hung.minghui@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18-99 years
• Scheduled for head and neck cancer tumor resection and free flap reconstruction surgery

Exclusion Criteria:

• Preoperative tracheostomy
• History of previous head and neck cancer tumor resection
• Anemia (hematocrit <30% or recent transfusion)
• Hypertension on ACEI/ARB medications
• Significant medical conditions (e.g., NYHA class 3 or 4 heart failure, eGFR <60 ml/min/1.73 m², Child B or C liver failure, severe respiratory disorders, pre-existing cognitive impairment)
• ASA physical status 4 or 5
• Allergies to sevoflurane, dexmedetomidine, ketamine, or lidocaine

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (HL-D); Fresh gas flow at 0.5 L/min with dexmedetomidine-ketamine-lidocaine mixture	Drug: Multimodal analgesia using dexmedetomidine-ketamine-lidocaine mixture; Multimodal analgesia using dexmedetomidine-ketamine-lidocaine mixture vs placebo normal saline; Other Names: Multimodal analgesia; Device: Minimal flow sevoflurane; Minimal flow sevoflurane anesthesia (0.5 L/min) vs low flow sevoflurane (1 L/min)
Experimental: Group 2 (HL-ND); Fresh gas flow at 0.5 L/min with placebo normal saline	Device: Minimal flow sevoflurane; Minimal flow sevoflurane anesthesia (0.5 L/min) vs low flow sevoflurane (1 L/min)
Experimental: Group 3 (L-D); Fresh gas flow at 1.0 L/min with dexmedetomidine-ketamine-lidocaine mixture	Drug: Multimodal analgesia using dexmedetomidine-ketamine-lidocaine mixture; Multimodal analgesia using dexmedetomidine-ketamine-lidocaine mixture vs placebo normal saline; Other Names: Multimodal analgesia
No Intervention: Group 4 (L-ND); Fresh gas flow at 1.0 L/min with placebo normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sevoflurane usage (mL/h)	Volatile anesthetic consumption hourly	Intraoperative period
Renal function	Changes in renal function (serum renin, AVP levels, urine KIM-1, NGAL levels)	Perioperative period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute kidney injury	Incidence of acute kidney injury	Perioperative period
Hemodynamic stability_1	Hemodynamic stability, present as heart rate fluctuation	Intraoperative period
Hemodynamic stability_2	Hemodynamic stability, present as blood pressure fluctuation	Intraoperative period
Hemodynamic stability_3	Hemodynamic stability, present as vasoactive drug amount of usage	Intraoperative period
Postoperative analgesic effect_1	Postoperative pain scores (VAS)	Perioperative period
Postoperative analgesic effect_2	Postoperative analgesic consumption	Perioperative period
Length of hospital stay	Length of hospital stay after surgery	Perioperative period
Cognitive function	Incidence of postoperative cognitive dysfunction using Confusion Assessment Method-Intensive Care Unit (CAM-ICU)	Perioperative period

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Ming-Hui Hung, MD, National Taiwan University Hosital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 12, 2024
• First Submitted That Met QC Criteria: July 21, 2024
• First Posted (Actual): July 26, 2024

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 21, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Acute kidney injury; Multimodal analgesia; Greenhouse gas; Carbon emissions
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Head and Neck Neoplasms; Acute Kidney Injury; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Platelet Aggregation Inhibitors; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Membrane Transport Modulators; Hypnotics and Sedatives; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Anesthetics, Inhalation; Ketamine; Dexmedetomidine; Lidocaine; Sevoflurane
• Other Study ID Numbers: 202403100MIND

Drug and device information, study documents

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