Ignite Creation Date:
2024-05-11 @ 8:30 AM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06404983
Status:
RECRUITING
Last Update Posted:
2024-05-08
First Post:
2024-03-27
Brief Title:
Opioid-free Anaesthesia in Breast Cancer Surgery
Sponsor:
University of Ioannina
Organization:
University of Ioannina
Study Overview
Official Title:
A Comparative Evaluation of Opioid Free Anaesthesia Technique Versus the Conventional Technique in Oncological Breast Surgery
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 lumpectomymastectomy 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 postgraduatedoctoral degree home medication and comorbidities using the Charlson Comorbidity Index are recorded
Intraoperatively the duration of anaesthesia duration of surgery associated intraoperative data eg 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
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 lumpectomymastectomy 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 postgraduatedoctoral degree home medication and comorbidities using the Charlson Comorbidity Index are recorded
Intraoperatively the duration of anaesthesia duration of surgery associated intraoperative data eg 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 nauseavomiting 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 07 to 1 MAC in O2air 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 eg 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 298 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 nauseavomiting 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 postgraduatedoctoral degree home medication and comorbidities using the Charlson Comorbidity Index are recorded
Intraoperatively the duration of anaesthesia duration of surgery and associated intraoperative data eg 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 101 MP Stata Corporation College Station TX 77845 USA
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 nauseavomiting 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 07 to 1 MAC in O2air 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 eg 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 298 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 nauseavomiting 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 postgraduatedoctoral degree home medication and comorbidities using the Charlson Comorbidity Index are recorded
Intraoperatively the duration of anaesthesia duration of surgery and associated intraoperative data eg 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 101 MP Stata Corporation College Station TX 77845 USA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None