Trial Title:
Opioid-free Anaesthesia in Breast Cancer Surgery
NCT ID:
NCT06404983
Condition:
Breast Cancer
Anesthesia
Pain, Postoperative
Pain, Chronic
Opioid Free Anaesthesia
Cancer Recurrence
Conditions: Official terms:
Breast Neoplasms
Recurrence
Pain, Postoperative
Chronic Pain
Lidocaine
Fentanyl
Dexmedetomidine
Ketamine
Morphine
Analgesics, Opioid
Anesthetics
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Double (Participant, Care Provider)
Intervention:
Intervention type:
Other
Intervention name:
Opioid Free Anaesthesia (OFA)
Description:
Patients are allocated to receive non-opioid anaesthesia intraoperatively. Patients will
receive a mixture of dexmedetomidine, ketamine and lidocaine for intraoperative
analgesia.
Arm group label:
Opioid Free Anaesthesia (OFA group)
Other name:
N.O.A.M (non-opioid anaesthetic mixture: dexmedetomidine, ketamine and lidocaine)
Intervention type:
Other
Intervention name:
Conventional General Anaesthesia (CGA)
Description:
Patients are allocated to receive conventional general anaesthesia intraoperatively with
the use of fentanyl and morphine for intraoperative analgesia.
Arm group label:
Conventional general anaesthesia (CGA group)
Other name:
O.A.M. (Opioid Anaesthetic Mixtute: fentanyl, morphine)
Summary:
Background:
Various analgesic modalities are adopted for perioperative analgesia in breast cancer
surgeries. Opioid-free and opioid-sparing techniques are gaining popularity due to the
lack of opioid-dependent undesirable effects, including respiratory depression, urinary
retention, nausea and vomiting, constipation, itching, opioid-induced hyperalgesia,
tolerance, addiction, and immune system disorders.
The goal of this prospective randomized clinical trial is to investigate the impact of
opioid-free anaesthesia (OFA) versus conventional general anaesthesia (CGA) on
postoperative analgesic requirements after breast cancer surgery (lumpectomy/mastectomy,
with or without axillary lymph node excision).
Secondary objectives include comparative perioperative evaluation of cognitive function
and postoperative adverse events during the first 48 hours atfter surgery. Comparative
evaluation of intraoperative haemodynamics and hospital length of stay are also secondary
objectives, as well as the incidence of neuropathic pain assessed by validated
questionnaires at 3 and 6 months postoperatively.
During the preoperative screening, body measurements, age, gender, ASA (American Society
of Anesthesiologists) physical status classification, educational level (using a 6-level
scale: elementary, middle school, high school, higher education, higher education, and
postgraduate/doctoral degree), home medication, and comorbidities (using the Charlson
Comorbidity Index) are recorded.
Intraoperatively, the duration of anaesthesia, duration of surgery, associated
intraoperative data (e.g., haemodynamic instability, adverse effects associated with
protocol-administered pharmaceutical agents, etc.), and medications administered (type
and quantity) are recorded.
The investigators expect to recruit at least 100 participants per group.
Detailed description:
INTRODUCTION. Opioids are the mainstay for achieving analgesia in the perioperative
setting. Standard anaesthetic practice in breast cancer surgery involves balanced general
anaesthesia with the use of opioids intra- and postoperatively. Opioid-free anaesthesia
(OFA) is a relatively recent anaesthetic proposal whereby no opioid is administered
intraoperatively (systemically, in neuraxial or peripheral block or intra-cavity) and the
use of opioids is avoided throughout the perioperative period.
Non-opioid anaesthesia appears to provide adequate postoperative analgesia while
protecting the patient from the side effects of opioids, which include respiratory
depression, opioid-induced hyperalgesia, postoperative nausea/vomiting, cognitive
dysfunction, etc. Recently, concerns have arisen regarding delayed healing,
immunosuppression, and worsening of oncological outcomes in cancer patients due to the
systemic use of opioids.
Side effects of opioids include:
- Respiratory depression
- Muscle stiffness
- Weakness of pharyngeal muscles
- Upper airway obstruction (muscle atony)
- Negative inotropic action
- Nausea, vomiting
- Ileus, constipation
- Urinary retention
- Tolerance and addiction
- Dizziness
- Excessive drowsiness and sleep disorder
BACKGROUND. During the past decade there has been a growing interest in opioid sparing
and opioid free techniques for general anaesthesia. The international literature started
to be enriched with interesting cases and small prospective studies supporting the
benefits of this technique, especially in patients with morbid obesity. According to its
proponents, this technique is characterized by: 1) sympatholysis, analgesia, and
anaesthesia (MAC reduction) using dexmedetomidine, 2) analgesia with low-dose of
ketamine, 3) administration of lidocaine adjunctively for anaesthesia and sympatholysis,
4) deep neuromuscular blockade until the end of the procedure, 5) use of sevoflurane or
desflurane 0.7 to 1 MAC in O2/air and titration based on entropy or BIS monitoring and 6)
administration of magnesium adjunctively for analgesia. Inadequate sympatholysis is
corrected by titrated doses of clonidine, whereas excessive sympatholysis is treated by
the administration of vasoconstrictors, preferably ephedrine because of its chronotropic
action. In addition, dexamethasone, high-dose paracetamol, NSAIDs, and gabapentin can be
used adjunctively in the context of multimodal management of surgical pain.
However, the OFA method is not without its disadvantages, of which the clinician should
be aware. Ketamine can disrupt electrocerebral monitoring (e.g., BIS) for possible
intraoperative vigilance, although according to the proponents of the method,
intraoperative vigilance is only a possibility in incorrect use of the technique, and
they argue that it is unlikely to occur if BIS is maintained below 60. The need for
hemodynamic support with vasoconstrictor administration is an additional disadvantage,
and there may be a need to infringe the OFA protocol to achieve ideal intubation
conditions using small doses of short-acting opioids during induction of anesthesia.
Also, a significant degree of cutaneous vasoconstriction may be observed, an expected a2
action of concern to the clinician. Finally, training of the nursing staff and
familiarity with the method is required.
Despite the above disadvantages of the method, OFA is becoming increasingly popular
because of its excellent management of postoperative pain, protecting the patient from
surgical and opioid-induced hyperalgesia, and because of the minimization of the risk of
respiratory depression in high-risk patients (COPD, sleep apnea, morbid obesity, etc.).
The prevalence of chronic postoperative pain after breast cancer surgery (mastectomy,
lumpectomy, with or without lymph node excision) is high and according to recent reports
is 29.8%. The OFA technique has been studied in breast cancer surgery. However, these are
mostly small studies examining the efficacy of this technique in acute postoperative
pain. The effect of the OFA technique on chronic pain after breast cancer surgery has not
been studied so far.
GOAL OF STUDY. The primary objective of the study is to evaluate postoperative analgesia
for breast cancer surgery of low and intermediate severity (mastectomy, lumpectomy, with
or without lymph node excision). Specifically, this is a prospective comparative study of
pain intensity and total postoperative consumption of opioids and other analgesics in
patients who received general anesthesia under OFA protocol (OFA group) versus those who
received general anesthesia using opioids (CGA group, conventional General Anaesthesia).
Secondary objectives are the evaluation of intraoperative haemodynamic stability by
recording the total use of vasoactive substances, time of extubation, length of stay in
the Post-Anesthesia Care Unit (PACU), and total length of hospitalization per study
group. In addition, secondary objectives include the comparative recording of serious
postoperative anaesthesia-related adverse events (postoperative hypoxaemia, postoperative
ileus, nausea/vomiting, etc.) and the comparative study of cognitive function in the
perioperative period.
As part of the second part of the study, all participants will be monitored for the
development of postoperative chronic pain using specific tools. Chronic postsurgical pain
assessment will be performed at 3 and 6 months postoperatively.
METHOD. The anaesthetic technique of the OFA group is based on the protocol of Mulier et
al. The intraoperative management of the CGA group will follow standard clinical
protocols. All patients will give written informed consent to be included in the study.
During the preoperative screening, somatometrics, age, gender, ASA (American Society of
Anesthesiologists) physical status classification, educational level (using a 6-level
scale: elementary, middle school, high school, higher education, higher education, and
postgraduate/doctoral degree), home medication, and comorbidities (using the Charlson
Comorbidity Index) are recorded.
Intraoperatively, the duration of anaesthesia, duration of surgery, and associated
intraoperative data (e.g., haemodynamic instability, adverse effects associated with
protocol-administered pharmaceutical agents, etc.) and medications administered (type and
quantity) are being recorded.
The length of stay in the Post Anaesthesia Care Unit (PACU) and the length of stay in the
hospital shall also be recorded. Serious adverse events related to general anaesthesia
for 48 hours post-operatively shall be recorded.
The intensity of acute postoperative pain shall be assessed using the NRS (Numerical
Rating Scale) scale (Numerical Rating Scale, 0-10) at predefined intervals up to 48 hours
postoperatively.
Participants' cognitive status, chronic postoperative pain, depression, anxiety, stress,
and satisfaction will be assessed using validated questionnaires at 3 and 6 months after
surgery.
STATISTICAL ANALYSIS. This is a prospective single-blind randomized clinical trial.
Randomization will be carried out using sealed envelopes sorted based on
computer-generated random numbers (Random Allocation Software).
Sample size calculation is based on a pilot study of 20 consecutive participants that was
carried out in the University Hospital of Ioannina, with the primary outcome beeing the
difference in NRS between groups at 1, 6, and 12 hours postoperatively, both at rest and
at a deep breath.
Participant recruitment is expected to take up to 2 years, and the investigators expect
to enroll at least 100 patients per study group.
Data analysis will be performed using Stata™ software (Version 10.1 MP, Stata
Corporation, College Station, TX 77845, USA).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- adult patients
- breast cancer surgery (mastectomy, lumpectomy, with or without lymph node excision)
under general anaesthesia
Exclusion Criteria:
- under 18 years
- patient refusal
- opioid use (systemic or not) for any reason (e.g., chronic malignant pain)
- language barrier (difficulty in communicating in Greek language)
- allergy to the administered agents
- severe arrhythmia or other serious cardiac disease
- severe liver and kidney failure
- dementia, psychiatric diseases, and/or preoperative cognitive impairment
Gender:
Female
Minimum age:
18 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University Hospital of Ioannina
Address:
City:
Ioannina
Zip:
455 00
Country:
Greece
Status:
Recruiting
Contact:
Last name:
Agathi Karakosta
Phone:
+306948066243
Email:
akarakosta@uoi.gr
Contact backup:
Last name:
Gloria-Evdoxia Izountouemoi
Phone:
+306982799750
Email:
gloriaizou@gmail.com
Start date:
December 28, 2022
Completion date:
September 12, 2029
Lead sponsor:
Agency:
University of Ioannina
Agency class:
Other
Source:
University of Ioannina
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06404983
http://www.researchgate.net/publication/278307444
