Ignite Creation Date:
2024-05-06 @ 3:48 PM
Last Modification Date:
2024-10-26 @ 1:57 PM
Study NCT ID:
NCT04765488
Status:
RECRUITING
Last Update Posted:
2024-02-09
First Post:
2021-02-15
Brief Title:
WashIn WashOut Procedure To Prevent Agitation During Recovery After Inhalational Anesthesia With Sevoflurane
Sponsor:
IM Sechenov First Moscow State Medical University
Organization:
IM Sechenov First Moscow State Medical University
Study Overview
Official Title:
WashIn WashOut Procedure To Prevent Agitation During Recovery After Inhalational Anesthesia With Sevoflurane A Multicentral Randomized Trial
Status:
RECRUITING
Status Verified Date:
2024-02
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:
OPERA
Brief Summary:
Inhalation anesthesia is the most frequently used technique and is performed in around 70 of surgeries worldwide Sevoflurane is the most frequently used halogenated anesthetic and is used in 23 of the cases
The anesthetic strength of inhalation agents was established in the classic work of Eger and colleagues who determined the minimum alveolar concentration MAC of an inhaled anesthetic at atmospheric pressure necessary to prevent a motor reaction in response to a pain stimulus in 50 of patients
Agitation is a frequent anesthesia complications and it not only lengthens the period of post anesthetic awakening and need for advance monitoring of the patient but may be a predisposing factor in the development of postoperative delirium POD and postoperative cognitive dysfunction POCD which are independent predictors of increased mortality prolonged treatment in the ICU and hospital and prolonged social adaptation of the operated patientsThe ability of the patient to serve themselves independently
There is a fairly popular point of view that there is no specific prophylaxis or treatment of postoperative agitation
However a variant of anesthesia induction with sevoflurane was recently proposed which reduced the frequency of agitation in children from 247 to 44 The technique consisted in interrupting anesthesia at the moment of loss of consciousness awakening the patient and subsequently performing re-induction Since this technique might be time consuming in the busiest period of a surgical theatre and not safe if performed with the airways still unsecured it is advisable to shift the Wash InWash Out procedure to the stage of awakening at the end of surgery
The anesthetic strength of inhalation agents was established in the classic work of Eger and colleagues who determined the minimum alveolar concentration MAC of an inhaled anesthetic at atmospheric pressure necessary to prevent a motor reaction in response to a pain stimulus in 50 of patients
Agitation is a frequent anesthesia complications and it not only lengthens the period of post anesthetic awakening and need for advance monitoring of the patient but may be a predisposing factor in the development of postoperative delirium POD and postoperative cognitive dysfunction POCD which are independent predictors of increased mortality prolonged treatment in the ICU and hospital and prolonged social adaptation of the operated patientsThe ability of the patient to serve themselves independently
There is a fairly popular point of view that there is no specific prophylaxis or treatment of postoperative agitation
However a variant of anesthesia induction with sevoflurane was recently proposed which reduced the frequency of agitation in children from 247 to 44 The technique consisted in interrupting anesthesia at the moment of loss of consciousness awakening the patient and subsequently performing re-induction Since this technique might be time consuming in the busiest period of a surgical theatre and not safe if performed with the airways still unsecured it is advisable to shift the Wash InWash Out procedure to the stage of awakening at the end of surgery
Detailed Description:
Inhalation anesthesia is the most frequently used technique and is performed in around 70 of surgeries worldwide Sevoflurane is the most frequently used halogenated anesthetic and is used in 23 of the cases
The anesthetic strength of inhalation agents was established in the classic work of Eger and colleagues who determined the minimum alveolar concentration MAC of an inhaled anesthetic at atmospheric pressure necessary to prevent a motor reaction in response to a pain stimulus in 50 of patients Since alveolar concentrations of inhaled anesthetics correspond to their concentrations in other organs after equilibrium which is most quickly achieved in organs with rich perfusion such as the brain and heart MAC is an analogue of the plasma EC50 concentration effective at 50 for intravenous anesthetics 1 MAC of sevoflurane is equal to an end-tidal concentration of 20 volume percent
Agitation is a frequent anesthesia complications and it not only lengthens the period of post anesthetic awakening and need for advance monitoring of the patient but may be a predisposing factor in the development of postoperative delirium POD and postoperative cognitive dysfunction POCD which are independent predictors of increased mortality prolonged treatment in the ICU and hospital and prolonged social adaptation of the operated patientsThe ability of the patient to serve themselves independently
Despite the fact that attempts to reduce the risk of postoperative neurological complications have been made repeatedly the frequency of occurrence of agitation in the early post operative period in adult patients is up to 30
Some authors drew attention to the need to comply with the basic requirements for the safety of anesthesia continuity and adequacy of anesthesia and avoidance of excessively deep or too superficial level of anesthesia Other authors consider it suitable to use midazolam propofol opioid and non-opioid analgesics in case of agitation Magnesium and calcium chloride were also tested to stop the described phenomenon but their beneficial effects were not confirmed in subsequent investigations
There is a fairly popular point of view that there is no specific prophylaxis or treatment of postoperative agitation
However a variant of anesthesia induction with sevoflurane was recently proposed which reduced the frequency of agitation in children from 247 to 44 The technique consisted in interrupting anesthesia at the moment of loss of consciousness awakening the patient and subsequently performing re-induction Since this technique might be time consuming in the busiest period of a surgical theatre and not safe if performed with the airways still unsecured it is advisable to shift the Wash InWash Out procedure to the stage of awakening at the end of surgery The authors also have occasionally experienced high quality awakenings in patients who received this technique without side effects or patients discomfort
Objective The primary objective for the multicentral OPERA Trial will be to explore the effect of the Wash In WashOut procedure at the end of the operation on the incidence of post-anesthetic agitation delirium and postoperative cognitive dysfunction
Treatment groups
All patients undergoing non-cardiac surgery under general inhalation anesthesia will be randomly assigned to one of two groups
1 Control group
A group of patients in relation to whom will be applied the traditional method of recovery from anesthesia In this group during the period of awakening the supply of sevoflurane will be stopped and the patient will be extubated after recovery of muscle tone spontaneous breathing and consciousness
2 Investigating group
A group of patients in relation to whom the Wash In WashOut procedure will be applied In this group the supply of sevoflurane will be stopped to the first signs of awakening and record the level of sevoflurane then the supply of sevoflurane will be resumed to the end-tidal concentration of 1 MAC maintain the anesthesia for 5 min and stop the supply of sevoflurane to the first signs of awakening again then the supply of sevoflurane will be resumed to the end-tidal concentration of 1 MAC maintain the anesthesia for 5 min and finally the third time stop supplying sevoflurane and extubate patient after recovery of muscle tone spontaneous breathing and consciousness
3 Perioperative and anesthetic management
Intraoperative monitoring will include continuous assessment of hemodynamic parameters NIBP ECG SpO2 analysis of expiratory gases CO2 O2 sevoflurane ABB analysis of arterial or mixed venous bloodfor patients from both groupwhose monitoring indicators during surgery saturation will go beyond the reference values less than 95 Benzodiazepines ketamine antipsychotics should not be used in premedication induction and while maintaining anesthesia
In both groups induction is achieved by intravenous administration of propofol to patients under the age of 55 at a dosage of 2 mg kg of ideal body weight until they lose consciousness to patients older than 55 years and to patients of classes III and IV according to ASA 1 mg kg ideal body weight until unconscious with fentanyl at a dose of 2-3 μg kg or mask induction with sevoflurane 2 l min 3 MAC with fentanyl at a dosage of 4 μg kg
Maintenance of anesthesia in both groups is ensured by the use of sevoflurane with a finite alveolar concentration 1 MAC and fentanyl 005-01 mg as needed according to the decision of the attending anesthesiologist Muscle relaxantsmonitoring of curarization and reversal will not be carried out vasoactive drugs infusion solutions adjuvants with the exception of those listed above if there is no strict need for them are selected at the discretion of the anesthesiologist
During the awakening period the time from the sevoflurane interruption until the occurrence of spontaneous breathing the time before opening the eyes the time before extubation the time before orientation is recorded The criterion of awakening the patient will be considered the ability to perform the simplest commands open your eyes raise your head show your tongue The patient is assessed on the RASS scale immediately after awakening 15 minutes after awakening and 30 minutes after awakening
After awakening assessing severity of the condition the need for prolonged mechanical ventilation vasopressor or inotropic support the need for monitoring in ICU the patient is transferred to the unit or to ICU The Aldrete Scale will be used to assessment of the patients condition where he will be monitored for hemodynamics NIBP ECG SpO2 a dynamic assessment of the general state monitoring of laboratory parameters and postoperative therapy according to current practice
Preoperative examination anesthesia management pre- and postoperative therapy will be carried out in accordance with current practice All data from laboratory and instrumental assessments as well as all medical documentation protocol of anesthesia course anesthesia card patient management cards in the ICU prescriptions will be available as part of the clinical study to treating doctor
Trial Mechanics Methodology Analysis
The following measures will allow us to achieve a high level of protocol adherence in this trial research teams will be created in each participating hospital which will consist of anesthesiologists and nurse anesthetists Each research team will be responsible for conducting a Wash In WashOut procedure to each randomized patient All members of the research team will be instructed on the technique of WashUp WashOut procedure before the start of the study All the data obtained in this study will be recorded in medical documentation protocol of anesthesia course anesthesia card patient management cards in the ICU prescriptions and patients case report forms
Statistical analysis
The frequency of the primary endpoint was considered and the relative reduction was associated with sequential awakening by sevoflurane Considering a type I error of 005 and a power of 80 type II error of 02 the required number was 98 patients per group Planned to enroll 100 patients in each groupsurgery study arm to account for possible dropouts 200 patients summary
All data will be analyzed according to the intention-to-treat principle No imputation will be applied for missing data Per-protocol analyses will be also performed Demographic and baseline disease characteristics will be summarized with the use of descriptive statistics Categorical variables will be reported as absolute numbers and percentages Unadjusted univariate analyses to compare the two treatment groups will be based on Chi-square or Fishers exact test Relative risks and 95 confidence intervals will be calculated by means of the two-by-two table method with the use of log-normal approximation Continuous variables will be reported as mean standard deviation SD or median and interquartile range IQR Between-group differences will be evaluated using the t-test or Wilcoxon signed rank test in accordance with normality of the distribution
A logistic regression model using a stepwise selection will be used to estimate the treatment effect and predictors of primary endpoint The pre-randomization clinical data and center will be entered into the model if their univariate p value is 01 and there is no correlation between them Collinearity and overfitting will be assessed using a stepwise regression model and Pearson correlation test The treatment group will be forced into the multivariate model
An independent safety committee will perform three interim analyses after recruitment of 25 50 and 75 of patients Data evaluation at each interim analysis will be based on the alpha spending function concept according to Lan and De Mets and will employ OBrien-Fleming Z-test boundaries which are very conservative early in the trial For the first interim analysis the efficacy stopping rule would require an extremely low p value p 0000015 For the second interim analysis p 0003 will be taken as efficacy stopping rule For the third interim analysis p 002 will be taken as efficacy stopping rule Investigators will be kept blind to the interim analysis results
The Data Safety and Monitoring Committees will also perform conditional power analyses in order to evaluate potential interruption for futility issues in the trial Conditional power will be calculated by assuming that the proportion of outcomes will follow the observed trend
The following analysis will be performed to determine the effect of sequential awakening by sevoflurane on different subgroups of patients
The anesthetic strength of inhalation agents was established in the classic work of Eger and colleagues who determined the minimum alveolar concentration MAC of an inhaled anesthetic at atmospheric pressure necessary to prevent a motor reaction in response to a pain stimulus in 50 of patients Since alveolar concentrations of inhaled anesthetics correspond to their concentrations in other organs after equilibrium which is most quickly achieved in organs with rich perfusion such as the brain and heart MAC is an analogue of the plasma EC50 concentration effective at 50 for intravenous anesthetics 1 MAC of sevoflurane is equal to an end-tidal concentration of 20 volume percent
Agitation is a frequent anesthesia complications and it not only lengthens the period of post anesthetic awakening and need for advance monitoring of the patient but may be a predisposing factor in the development of postoperative delirium POD and postoperative cognitive dysfunction POCD which are independent predictors of increased mortality prolonged treatment in the ICU and hospital and prolonged social adaptation of the operated patientsThe ability of the patient to serve themselves independently
Despite the fact that attempts to reduce the risk of postoperative neurological complications have been made repeatedly the frequency of occurrence of agitation in the early post operative period in adult patients is up to 30
Some authors drew attention to the need to comply with the basic requirements for the safety of anesthesia continuity and adequacy of anesthesia and avoidance of excessively deep or too superficial level of anesthesia Other authors consider it suitable to use midazolam propofol opioid and non-opioid analgesics in case of agitation Magnesium and calcium chloride were also tested to stop the described phenomenon but their beneficial effects were not confirmed in subsequent investigations
There is a fairly popular point of view that there is no specific prophylaxis or treatment of postoperative agitation
However a variant of anesthesia induction with sevoflurane was recently proposed which reduced the frequency of agitation in children from 247 to 44 The technique consisted in interrupting anesthesia at the moment of loss of consciousness awakening the patient and subsequently performing re-induction Since this technique might be time consuming in the busiest period of a surgical theatre and not safe if performed with the airways still unsecured it is advisable to shift the Wash InWash Out procedure to the stage of awakening at the end of surgery The authors also have occasionally experienced high quality awakenings in patients who received this technique without side effects or patients discomfort
Objective The primary objective for the multicentral OPERA Trial will be to explore the effect of the Wash In WashOut procedure at the end of the operation on the incidence of post-anesthetic agitation delirium and postoperative cognitive dysfunction
Treatment groups
All patients undergoing non-cardiac surgery under general inhalation anesthesia will be randomly assigned to one of two groups
1 Control group
A group of patients in relation to whom will be applied the traditional method of recovery from anesthesia In this group during the period of awakening the supply of sevoflurane will be stopped and the patient will be extubated after recovery of muscle tone spontaneous breathing and consciousness
2 Investigating group
A group of patients in relation to whom the Wash In WashOut procedure will be applied In this group the supply of sevoflurane will be stopped to the first signs of awakening and record the level of sevoflurane then the supply of sevoflurane will be resumed to the end-tidal concentration of 1 MAC maintain the anesthesia for 5 min and stop the supply of sevoflurane to the first signs of awakening again then the supply of sevoflurane will be resumed to the end-tidal concentration of 1 MAC maintain the anesthesia for 5 min and finally the third time stop supplying sevoflurane and extubate patient after recovery of muscle tone spontaneous breathing and consciousness
3 Perioperative and anesthetic management
Intraoperative monitoring will include continuous assessment of hemodynamic parameters NIBP ECG SpO2 analysis of expiratory gases CO2 O2 sevoflurane ABB analysis of arterial or mixed venous bloodfor patients from both groupwhose monitoring indicators during surgery saturation will go beyond the reference values less than 95 Benzodiazepines ketamine antipsychotics should not be used in premedication induction and while maintaining anesthesia
In both groups induction is achieved by intravenous administration of propofol to patients under the age of 55 at a dosage of 2 mg kg of ideal body weight until they lose consciousness to patients older than 55 years and to patients of classes III and IV according to ASA 1 mg kg ideal body weight until unconscious with fentanyl at a dose of 2-3 μg kg or mask induction with sevoflurane 2 l min 3 MAC with fentanyl at a dosage of 4 μg kg
Maintenance of anesthesia in both groups is ensured by the use of sevoflurane with a finite alveolar concentration 1 MAC and fentanyl 005-01 mg as needed according to the decision of the attending anesthesiologist Muscle relaxantsmonitoring of curarization and reversal will not be carried out vasoactive drugs infusion solutions adjuvants with the exception of those listed above if there is no strict need for them are selected at the discretion of the anesthesiologist
During the awakening period the time from the sevoflurane interruption until the occurrence of spontaneous breathing the time before opening the eyes the time before extubation the time before orientation is recorded The criterion of awakening the patient will be considered the ability to perform the simplest commands open your eyes raise your head show your tongue The patient is assessed on the RASS scale immediately after awakening 15 minutes after awakening and 30 minutes after awakening
After awakening assessing severity of the condition the need for prolonged mechanical ventilation vasopressor or inotropic support the need for monitoring in ICU the patient is transferred to the unit or to ICU The Aldrete Scale will be used to assessment of the patients condition where he will be monitored for hemodynamics NIBP ECG SpO2 a dynamic assessment of the general state monitoring of laboratory parameters and postoperative therapy according to current practice
Preoperative examination anesthesia management pre- and postoperative therapy will be carried out in accordance with current practice All data from laboratory and instrumental assessments as well as all medical documentation protocol of anesthesia course anesthesia card patient management cards in the ICU prescriptions will be available as part of the clinical study to treating doctor
Trial Mechanics Methodology Analysis
The following measures will allow us to achieve a high level of protocol adherence in this trial research teams will be created in each participating hospital which will consist of anesthesiologists and nurse anesthetists Each research team will be responsible for conducting a Wash In WashOut procedure to each randomized patient All members of the research team will be instructed on the technique of WashUp WashOut procedure before the start of the study All the data obtained in this study will be recorded in medical documentation protocol of anesthesia course anesthesia card patient management cards in the ICU prescriptions and patients case report forms
Statistical analysis
The frequency of the primary endpoint was considered and the relative reduction was associated with sequential awakening by sevoflurane Considering a type I error of 005 and a power of 80 type II error of 02 the required number was 98 patients per group Planned to enroll 100 patients in each groupsurgery study arm to account for possible dropouts 200 patients summary
All data will be analyzed according to the intention-to-treat principle No imputation will be applied for missing data Per-protocol analyses will be also performed Demographic and baseline disease characteristics will be summarized with the use of descriptive statistics Categorical variables will be reported as absolute numbers and percentages Unadjusted univariate analyses to compare the two treatment groups will be based on Chi-square or Fishers exact test Relative risks and 95 confidence intervals will be calculated by means of the two-by-two table method with the use of log-normal approximation Continuous variables will be reported as mean standard deviation SD or median and interquartile range IQR Between-group differences will be evaluated using the t-test or Wilcoxon signed rank test in accordance with normality of the distribution
A logistic regression model using a stepwise selection will be used to estimate the treatment effect and predictors of primary endpoint The pre-randomization clinical data and center will be entered into the model if their univariate p value is 01 and there is no correlation between them Collinearity and overfitting will be assessed using a stepwise regression model and Pearson correlation test The treatment group will be forced into the multivariate model
An independent safety committee will perform three interim analyses after recruitment of 25 50 and 75 of patients Data evaluation at each interim analysis will be based on the alpha spending function concept according to Lan and De Mets and will employ OBrien-Fleming Z-test boundaries which are very conservative early in the trial For the first interim analysis the efficacy stopping rule would require an extremely low p value p 0000015 For the second interim analysis p 0003 will be taken as efficacy stopping rule For the third interim analysis p 002 will be taken as efficacy stopping rule Investigators will be kept blind to the interim analysis results
The Data Safety and Monitoring Committees will also perform conditional power analyses in order to evaluate potential interruption for futility issues in the trial Conditional power will be calculated by assuming that the proportion of outcomes will follow the observed trend
The following analysis will be performed to determine the effect of sequential awakening by sevoflurane on different subgroups of patients
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