Does Type of Anesthesia Influence Inflammation Change After Breast Surgery?

Variation of the Neutrophil To Lymphocyte Ratio During Opioid-Free General Anesthesia Associated With Thoracic Wall Blocks Vs General Anesthesia, in Breast Cancer Quadrantectomy: a Randomized Controlled Trial

The Neutrophil to Lymphocyte Ratio (NLR) is a frequently used biomarker of the systemic inflammatory response and is considered one of the most sensitive markers of inflammation. Many studies have documented the association between the use of opioid drugs in the acute phase -as it can be considered the use during general anesthesia- and the increase of the NLR value. Such increase could determine a temporary phase of immunodepression in the immediate post operative period with consequent increase of the inflammatory state.

This study intends to assess whether different anesthetic techniques can be associated with different variations of the intra-patient NLR value between pre- and post-surgery. Patient will be randomized to receive either local regional anesthesia protocols with thoracic wall blocks (PEC I and serratus plane block) associated with opioid-free general anesthesia (PECS + Opioid-free GA) or general anesthesia.

Study Overview

• Status: Completed
• Conditions: Breast Cancer Female
• Intervention / Treatment: Drug: Midazolam; Procedure: PECS; Procedure: Opioid-free general anesthesia; Procedure: Postoperative analgesia; Procedure: General anesthesia

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fabrizio Brescia, MD; Phone Number: +39 0434659165; Email: fabrizio.brescia@cro.it

Study Locations

• Italy
  • PN
    • Aviano, PN, Italy, 33081
      • Centro di Riferimento Oncologico di Aviano (CRO), IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• First diagnosis of histologically confirmed breast cancer
• Candidate to external quadrantectomy and axillary surgery (biopsy of the sentinel lymph node and possible axillary lymphadenectomy)
• Able to provide adequate informed consent
• With intact cognitive abilities

Exclusion Criteria:

• Ongoing pregnancy
• In therapy or in follow-up for other cancers at the time of the study
• Concurrent therapy with opioids or other drugs, for chronic pain conditions related to cancer or other diseases
• History of documented allergy or previous adverse reaction to local anesthetics
• Documented history of anesthesiology related problems during previous surgical interventions or history of problems in airway management
• Unable to comply to study protocol schedule for logistic or other reasons
• Refusal to participate to the study (absence of signed informed consent)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PECS + Opioid-free GA; Loco-regional anesthesia with PEC I and serratus plane block with an echoguided technique and opioid-free general anesthesia	Drug: Midazolam; 1-2 mg of Midazolam as premedication.; Procedure: PECS; Loco-regional anesthesia: PEC I and serratus plane block with an echoguided technique. For the PEC I: infiltration of 10 ml of local anesthetic (Levobupivacaine 0.25% or Ropivacaine 0.5%) between the bands of the pectoralis major muscle and the small pectoralis muscle at the height of the third rib on the anterior axillary line. For the serratus plane block: identification of the fifth rib on the average axillary line and infusion of about 20 ml of local anesthetic (Levobupivacaine 0.25% or Ropivacaine 0.5%) between the bands of large dorsal muscle and of the anterior serratus muscle.; Procedure: Opioid-free general anesthesia; Induction with Propofol 1.5-2 mg/kg; laryngeal mask for airway management after eventual administration of Rocuronium 0.6 mg/kg. Anesthesia will be maintained with Propofol in Target-Controlled Infusion (TCI) of 6 mcg/ml, subsequently modified to maintain a Bispectral Index (BIS) value between 40 and 60. Fentanyl 50ug in bolus IV, in case of mean arterial pressure or heart rate increase >20%. In case of hypotension: 5mg ephedrine and infusion of 250 ml Lactated Ringer.; Procedure: Postoperative analgesia; Paracetamol 1000 mg every 8 hours for the first 24 hours, Ketorolac 30 mg in case of pain control failure (Numeric Rating Scale- NRS>4) which can be administered every 8 hours at most (max 90 mg / 24 hours), Morphine 10-20 mg IV in 24 hours as rescue analgesia.
Active Comparator: GA; General anesthesia	Drug: Midazolam; 1-2 mg of Midazolam as premedication.; Procedure: Postoperative analgesia; Paracetamol 1000 mg every 8 hours for the first 24 hours, Ketorolac 30 mg in case of pain control failure (Numeric Rating Scale- NRS>4) which can be administered every 8 hours at most (max 90 mg / 24 hours), Morphine 10-20 mg IV in 24 hours as rescue analgesia.; Procedure: General anesthesia; Induction with Propofol 1.5-2 mg/kg; Fentanyl 1μg/kg; laryngeal mask for airway management after eventual administration of Rocuronium 0.6 mg/kg. Anesthesia will be maintained with Propofol in TCI of 6 mcg/ml, subsequently modified to maintain a BIS value between 40 and 60. Fentanyl 50ug in bolus IV, in case of mean arterial pressure or heart rate increase >20%. In case of hypotension: 5mg ephedrine and infusion of 250 ml Lactated Ringer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24h NLR variation	Intra-patient variation of the NLR value between the pre-operative and the first post-operative day	Pre-operative and at 24 hours after the end of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1h NLR variation	Intra-patient variation of the NLR value between pre-operative and 1 hour after the end of surgery, and between 1 hour after the end of surgery and 24 hours after the end of surgery	Pre-operative, 1 hour and 24 hours after the end of surgery
Opioid consumption	Consumption of intra-operative Fentanyl and post-operative Morphine hydrochloride during the first 24 hours after surgery	24 hours
Complication	Complications related to the loco-regional anesthesia technique or to the administration of the local anesthetic. For pain evaluation, the validated Numeric Rating Scale (NRS) will be used, the score ranges from 0 to 10 with higher values corresponding to worse pain.	until hospital discharge, an average of 48 hours
Chronic pain	Chronic pain after surgery will be assessed with Brief Pain Inventory questionnaire (composed by pain severity and pain interference scores). "Douleur Neuropathique 4" (DN4) questionnaire will be used for the identification of neuropathic pain. All the scores range from 0 to 10, with 10 indicating the worst results.	3, 6 and 12 months after surgery

Collaborators and Investigators

• Sponsor: Centro di Riferimento Oncologico - Aviano
• Investigators: Principal Investigator: Fabrizio Brescia, MD, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2019
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2022

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 21, 2019

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; Quadrantectomy; PECS; Neutrophil to Lymphocyte ratio
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anesthetics; Midazolam
• Other Study ID Numbers: CRO-2019-26

Drug and device information, study documents

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