Ignite Creation Date:
2024-07-17 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06476600
Status:
RECRUITING
Last Update Posted:
2024-06-26
First Post:
2024-05-23
Brief Title:
Opioid-based Versus Opioid-free Anaesthesia for Laparoscopic Cholecystectomy
Sponsor:
Atif Shafqat
Organization:
Dow University of Health Sciences
Study Overview
Official Title:
Opioid-based OA Versus Opioid-free Anaesthesia OFA for General Surgical Procedures in a Developing Country
Status:
RECRUITING
Status Verified Date:
2024-06
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:
This is a prospective randomized parallel-group double-blinded clinical trial The study is approved by the DUHS institutional review board IRB and the trial will be registered at clinical trial registry The participants of the study will be invited once they receive full trial information from the surgeons or the anesthetists during their pre-assessment visits The study participants will join only for up to one day after the surgery Post-operative day-1 The intervention consists of administration of dexmedetomidine infusion in opioid free anesthesia OFA group versus Nalbuphine IV bolus in opioid-based anesthesia OA group five minutes before induction of anesthesia For maintenance in OFA group dexmedetomidine infusion is to be continued whereas in OA group Nalbuphine IV bolus doses will be administered Once the surgery is completed and after extubation and emergence from anesthesia all the participants will be transferred to PACU from where they will be in turn discharged to the ward once they will fulfil the recovery discharge criteria A multi-modal analgesia regimen along with a prophylactic antiemetic medication will be prescribed postoperatively to all the patients in the ward according to the standard protocol of the department
Detailed Description:
Opioid-based OA Versus Opioid-free Anaesthesia OFA for General Surgical procedures in a developing country
Introduction
Opioids and their synthetic derivatives were first used in anesthesia in 1962 They are now routinely dispensed via different routes of administration including oral subcutaneous intravenous intramuscular transdermal epidural or intrathecal In the last 20 years the world has witnessed a substantial increase in the consumption of opioids Opioids over prescription is one of the causative factors of opioid crisis in North America The current global opioid crisis has multifactorial reasons and this is gradually worsened due to the different waves of liberal opioid use The ongoing opioid crisis has led to the development of alternative techniques like opioid sparing and opioid-free anaesthesia strategies Owing to the well-researched and recognized opioid-based anaesthesia adverse effects it is essential to develop alternative therapies to achieve the main benefits of opioids like analgesia and haemodynamic stability while limiting the opioid related adverse effects A sensible use of opioids in the perioperative period is important since vulnerable patients undergoing common general surgical procedures become chronic opioid users postoperatively High doses of perioperative opioids can be associated with increased post-operative complications including respiratory depression paralytic ileus nausea and vomiting difficulty voiding pruritus hyperalgesia and opioid tolerance These can atypically increases the length of hospital stay LOS due to delayed patient recovery prolonged PACU stay delayed discharge and unanticipated hospitalization thus overall compromising the quality of recovery QoR and putting unnecessary burden on both the patients and hospital resources
Opioid-free anesthesiaOFA is a method that entirely eliminates the use of systemic neuraxial or intracavitary opioids A less restrictive practice is opioid-sparing anesthesia OSA where small amounts of opioids are used Patients suffering from chronic postsurgical pain complex regional pain syndrome cancer-related pain and other opioid-tolerant patients may also benefit from OFA and OSA approaches
OFA involves multimodal non-opioid analgesia which uses sympatholytic drugs and non-opioid analgesics These drugs can reduce or avoid the use of opioids in the postoperative period A non-opioid multimodal analgesic method is intended at enhancing adjunctive options that is applying anesthetic techniques aiming different neuro-anatomical circuits and several neurophysiological mechanisms Non-opioid analgesics include alpha-2agonists clonidine and dexmedetomidine beta-blockers esmolol gabapentinoids gabapentinand pregabalin lidocaine lidocaine hydrochloride magnesium magnesium sulfate ketamine and dexamethasone These drugs when used in combination acts synergistically and change the pathophysiology of nociception thus causes effective analgesia with minimal side effects
OFA is an efficacious mode of anaesthetic for general surgical procedures when compared to conventional opioid-based anaesthesia OA However the evidence on OFA is still debatable Therefore there is still a feasibility issue of OFA for common general surgical procedures which needed to be established
The quality of recovery after anaesthesia and surgery does not only include pain control but it also involves patients overall generalised health status in the postoperative period including return of self-care household and work activities and mobility compared to preoperative period Patient-reported outcome measures PROMs are considered as the benchmark tools for measuring global health state and post-surgical recovery after any procedure The QoR-15 is a validated PROM which is derived from QoR-40 and provides an effective assessment of post-operative recovery It consists of a total of 15-items grading each recovery item on a 10 - point numerical Likert scale with total QoR-15 score ranging from 0 extremely poor recoveryto 150 excellent recovery
Aim
The aim of our study is to explore and compare the effects of OFA using dexmedetomidine vs conventional OA on the quality of recovery and perioperative clinical outcomes for all the patients undergoing laparoscopic cholecystectomies which is one of the most common abdominal general surgical procedures The hypothesis is that the patients receiving OFA using dexmedetomidine will have better quality of recovery and perioperative outcomes than patients receiving standard OA
Methods
This is a prospective randomized parallel-group double-blinded clinical trial that will commence from February 2024 and the recruitment time will be for three to six months at department of Anaesthesia Dow university hospital DUH Dow International medical college DIMC Dow university of health sciences DUHS The study will be approved by the DUHS institutional review board IRB The participants of the study will be invited once they receive full trial information from the surgeons or the anaesthetists during their pre-assessment visits The study participants will join only for up to one day after the surgery Post-operative day-1
Intervention
Before the study commences the participants will be taught to measure their pain status via visual analog scale VAS where 0 cm no pain and 10 cm worst pain with sad or happy pictures at each end The participants will be advised to ask for analgesia proactively once the VAS pain score is 4 All the eligible patients will undergo general anaesthesia for their elective surgeries In the operating theatre the standard of monitoring will include body temperature ECG non-invasive blood pressure pulse oximetry neuromuscular monitoring using train-of-four TOF stimulation and bispectral index BIS for measuring the depth of anaesthesia
The induction and maintenance of anaesthesia for both OFA vs OA treatment groups will be administered Once the surgery is completed and after extubation and emergence from anaesthesia all the participants will be transferred to PACU from where they will be in turn discharged to the ward once they will fulfil the recovery discharge criteria A multi-modal analgesia regimen along with a prophylactic antiemetic medication is prescribed postoperatively in the ward according to the standard protocol of the department
For each participant the mean and total QoR-15 scores will be computed pre-operatively at baseline and at24 h - 2 hours post-operatively The mean change of QoR-15 scores will be evaluated to establish the difference between the baseline and post-operative day-1 scores In addition to that the secondary perioperative clinical outcomes will also be recorded in PACU and at 24 hrs postoperatively
Randomisation
The participants will be randomized in a 11 ratio using computer-generated random numbers to receive either a standard opioid-based OA or opioid-free anaesthesia OFA treatment protocols After obtaining consent the participants will be assigned a study identification number ID
Blinding
Just before surgery a concealed envelope containing the study ID will be opened by the anaesthetist which contains the random allocation of OA or OFA treatment protocols The participants will be blinded with the treatment groups during the whole study period The staff members including the recovery and ward nurses providing postoperative care and assessing outcomes in the PACU and the ward will also be kept blinded of the study groups The anaesthetist administering general anaesthesia could not be blinded due to pragmatic reasons but will not contribute to the care or outcomes assessments during the post-operative period
Sample size
According to a previous study the minimal clinically significant mean change of QoR-15 scores is eight A sample size of 18 participants is required to detect a mean change QoR-15 scores of six with a standard deviation of four and achieve a power of 80 with type-1error of 005 A maximum of 15 increase in the number of participants will be added to compensate the loss of the participants due to cancellations or follow-up losses Therefore the sample size will include 42 participants n21 OFA and n21 OA
Statistical Analysis
All participants randomized will be incorporated in the analyses on an intention-to-treat basis The Kolmogorov-Smirnov test will be used to assess the distribution of the quantitative variables For continuous data mean standard deviation median IQR and for categorical data frequencies or percentages will be measured Mean and total QoR-15 scores will be calculated for each participant at baseline and on postoperative day-1 To find out the difference between postoperative day-1 and baseline score a change of QoR-15 change scores will be documented Quantitative variables will be analysed using an Independent-sample t-test or Mann-Whitney U-test and Chi-square or Fishers exact test will be applied to investigate the qualitative variables
To adjust for the effect of baseline preoperative scores ANCOVA Analysis of Covariance will be used to study the relationship between QOR-15 and one or more independent variables A two tailed p value of 005 will be considered significant All statistical analysis will be performed using StataIC for Mac Version 161 StataCorp College Station TX USA
Introduction
Opioids and their synthetic derivatives were first used in anesthesia in 1962 They are now routinely dispensed via different routes of administration including oral subcutaneous intravenous intramuscular transdermal epidural or intrathecal In the last 20 years the world has witnessed a substantial increase in the consumption of opioids Opioids over prescription is one of the causative factors of opioid crisis in North America The current global opioid crisis has multifactorial reasons and this is gradually worsened due to the different waves of liberal opioid use The ongoing opioid crisis has led to the development of alternative techniques like opioid sparing and opioid-free anaesthesia strategies Owing to the well-researched and recognized opioid-based anaesthesia adverse effects it is essential to develop alternative therapies to achieve the main benefits of opioids like analgesia and haemodynamic stability while limiting the opioid related adverse effects A sensible use of opioids in the perioperative period is important since vulnerable patients undergoing common general surgical procedures become chronic opioid users postoperatively High doses of perioperative opioids can be associated with increased post-operative complications including respiratory depression paralytic ileus nausea and vomiting difficulty voiding pruritus hyperalgesia and opioid tolerance These can atypically increases the length of hospital stay LOS due to delayed patient recovery prolonged PACU stay delayed discharge and unanticipated hospitalization thus overall compromising the quality of recovery QoR and putting unnecessary burden on both the patients and hospital resources
Opioid-free anesthesiaOFA is a method that entirely eliminates the use of systemic neuraxial or intracavitary opioids A less restrictive practice is opioid-sparing anesthesia OSA where small amounts of opioids are used Patients suffering from chronic postsurgical pain complex regional pain syndrome cancer-related pain and other opioid-tolerant patients may also benefit from OFA and OSA approaches
OFA involves multimodal non-opioid analgesia which uses sympatholytic drugs and non-opioid analgesics These drugs can reduce or avoid the use of opioids in the postoperative period A non-opioid multimodal analgesic method is intended at enhancing adjunctive options that is applying anesthetic techniques aiming different neuro-anatomical circuits and several neurophysiological mechanisms Non-opioid analgesics include alpha-2agonists clonidine and dexmedetomidine beta-blockers esmolol gabapentinoids gabapentinand pregabalin lidocaine lidocaine hydrochloride magnesium magnesium sulfate ketamine and dexamethasone These drugs when used in combination acts synergistically and change the pathophysiology of nociception thus causes effective analgesia with minimal side effects
OFA is an efficacious mode of anaesthetic for general surgical procedures when compared to conventional opioid-based anaesthesia OA However the evidence on OFA is still debatable Therefore there is still a feasibility issue of OFA for common general surgical procedures which needed to be established
The quality of recovery after anaesthesia and surgery does not only include pain control but it also involves patients overall generalised health status in the postoperative period including return of self-care household and work activities and mobility compared to preoperative period Patient-reported outcome measures PROMs are considered as the benchmark tools for measuring global health state and post-surgical recovery after any procedure The QoR-15 is a validated PROM which is derived from QoR-40 and provides an effective assessment of post-operative recovery It consists of a total of 15-items grading each recovery item on a 10 - point numerical Likert scale with total QoR-15 score ranging from 0 extremely poor recoveryto 150 excellent recovery
Aim
The aim of our study is to explore and compare the effects of OFA using dexmedetomidine vs conventional OA on the quality of recovery and perioperative clinical outcomes for all the patients undergoing laparoscopic cholecystectomies which is one of the most common abdominal general surgical procedures The hypothesis is that the patients receiving OFA using dexmedetomidine will have better quality of recovery and perioperative outcomes than patients receiving standard OA
Methods
This is a prospective randomized parallel-group double-blinded clinical trial that will commence from February 2024 and the recruitment time will be for three to six months at department of Anaesthesia Dow university hospital DUH Dow International medical college DIMC Dow university of health sciences DUHS The study will be approved by the DUHS institutional review board IRB The participants of the study will be invited once they receive full trial information from the surgeons or the anaesthetists during their pre-assessment visits The study participants will join only for up to one day after the surgery Post-operative day-1
Intervention
Before the study commences the participants will be taught to measure their pain status via visual analog scale VAS where 0 cm no pain and 10 cm worst pain with sad or happy pictures at each end The participants will be advised to ask for analgesia proactively once the VAS pain score is 4 All the eligible patients will undergo general anaesthesia for their elective surgeries In the operating theatre the standard of monitoring will include body temperature ECG non-invasive blood pressure pulse oximetry neuromuscular monitoring using train-of-four TOF stimulation and bispectral index BIS for measuring the depth of anaesthesia
The induction and maintenance of anaesthesia for both OFA vs OA treatment groups will be administered Once the surgery is completed and after extubation and emergence from anaesthesia all the participants will be transferred to PACU from where they will be in turn discharged to the ward once they will fulfil the recovery discharge criteria A multi-modal analgesia regimen along with a prophylactic antiemetic medication is prescribed postoperatively in the ward according to the standard protocol of the department
For each participant the mean and total QoR-15 scores will be computed pre-operatively at baseline and at24 h - 2 hours post-operatively The mean change of QoR-15 scores will be evaluated to establish the difference between the baseline and post-operative day-1 scores In addition to that the secondary perioperative clinical outcomes will also be recorded in PACU and at 24 hrs postoperatively
Randomisation
The participants will be randomized in a 11 ratio using computer-generated random numbers to receive either a standard opioid-based OA or opioid-free anaesthesia OFA treatment protocols After obtaining consent the participants will be assigned a study identification number ID
Blinding
Just before surgery a concealed envelope containing the study ID will be opened by the anaesthetist which contains the random allocation of OA or OFA treatment protocols The participants will be blinded with the treatment groups during the whole study period The staff members including the recovery and ward nurses providing postoperative care and assessing outcomes in the PACU and the ward will also be kept blinded of the study groups The anaesthetist administering general anaesthesia could not be blinded due to pragmatic reasons but will not contribute to the care or outcomes assessments during the post-operative period
Sample size
According to a previous study the minimal clinically significant mean change of QoR-15 scores is eight A sample size of 18 participants is required to detect a mean change QoR-15 scores of six with a standard deviation of four and achieve a power of 80 with type-1error of 005 A maximum of 15 increase in the number of participants will be added to compensate the loss of the participants due to cancellations or follow-up losses Therefore the sample size will include 42 participants n21 OFA and n21 OA
Statistical Analysis
All participants randomized will be incorporated in the analyses on an intention-to-treat basis The Kolmogorov-Smirnov test will be used to assess the distribution of the quantitative variables For continuous data mean standard deviation median IQR and for categorical data frequencies or percentages will be measured Mean and total QoR-15 scores will be calculated for each participant at baseline and on postoperative day-1 To find out the difference between postoperative day-1 and baseline score a change of QoR-15 change scores will be documented Quantitative variables will be analysed using an Independent-sample t-test or Mann-Whitney U-test and Chi-square or Fishers exact test will be applied to investigate the qualitative variables
To adjust for the effect of baseline preoperative scores ANCOVA Analysis of Covariance will be used to study the relationship between QOR-15 and one or more independent variables A two tailed p value of 005 will be considered significant All statistical analysis will be performed using StataIC for Mac Version 161 StataCorp College Station TX 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