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出境医 / 临床实验 / Peak Plasma Levels of Bupivacaine After a Pecto-Intercostal Fascial Block Post-Sternotomy for Cardiac Surgery

Peak Plasma Levels of Bupivacaine After a Pecto-Intercostal Fascial Block Post-Sternotomy for Cardiac Surgery

Study Description
Brief Summary:
The primary objective of the study is to measure plasma levels of bupivacaine following a pecto-intercostal fascial plane block (PIFB) in patients undergoing sternotomy for cardiac surgery.

Condition or disease Intervention/treatment
Pharmacokinetics Other: Collection of blood samples

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Study Design
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Study Type : Observational
Estimated Enrollment : 18 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Peak Plasma Levels of Bupivacaine After a Pecto-Intercostal Fascial Block Post-Sternotomy for Cardiac Surgery
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 2, 2021
Arms and Interventions
Group/Cohort Intervention/treatment
Bupivacaine dosage in PIFB block
The pharmacokinetics of bupivacaine 0.25% with epinephrine 5 mcg/mL for a total dose of 2mg/kg of ideal body weight following a PIFB block will be determined by the collection of blood samples at predetermined time points.
Other: Collection of blood samples
Nine blood samples will be collected to determine bupivacaine pharmacokinetics at T10min, T20min, T30min, T45min, T60min, T90min, T120min, T180min, and T240min. T0 will be defined as the end of bupivacaine injection.

Outcome Measures
Primary Outcome Measures :
  1. Maximal plasma concentration (Cmax) of bupivacaine after pecto-intercostal fascial plane block [ Time Frame: The end of injection of bupivacaine will be considered as T0. Blood samples at T10, T20, T30, T45, T60, T90, T120, T180, and T240minutes will be collected to further analyze plasmatic bupivacaine values at these timepoints. ]
    The Cmax will be estimated by interpolation based on the plasmatic bupivacaine values obtained after the analysis of the blood samples.


Secondary Outcome Measures :
  1. Time (Tmax) to maximum plasma concentration Cmax of bupivacaine [ Time Frame: The end of injection of bupivacaine will be considered as T0. Blood samples at T10, T20, T30, T45, T60, T90, T120, T180, and T240 minutes will be performed to further analyze plasmatic bupivacaine values at these timepoints. ]
    The Tmax will be estimated by interpolation based on the plasmatic bupivacaine values obtained after the analysis of the blood samples.

  2. Total opioid and co-analgesics doses needed in the Intensive Care Unit [ Time Frame: After the surgery, from the arrival in the Intensive Care Unit to 24 hours after the entry in the Intensive Care Unit. ]
    The total dose of opioids and co-analgesics used by the patients during the first 24 hours in the Intensive Care Unit will be recorded.

  3. Time between arrival in Intensive Care Unit and extubation [ Time Frame: Time from the arrival in the Intensive Care Unit to the extubation, for an average of 4 hours following surgery. ]
    Time between the arrival of the patient in the Intensive Care Unit and the extubation of the patient will be measured in minutes.

  4. Sensory block level during the last sampling [ Time Frame: At T240 minutes (4 hours) after the end of injection, after the last sampling, at the Intensive Care Unit ]
    Sensory block level will be measured with a 6.1g von Frey filaments.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients requiring a pecto-intercostal fascial block following cardiac surgery
Criteria

Inclusion Criteria:

  • ASA l-lll
  • Undergoing sternotomy for cardiac surgery under a PIFB and general anesthesia

Exclusion Criteria:

  • Patient's refusal or inability to consent
  • Allergy, hypersensibility or resistance to local anesthetic
  • Contraindication to regional anesthesia: infection in the designated area, severe congenital coagulopathy or inadequate hemostasis before PIFB
  • Severe hepatic (Child B and C) or renal insufficiency (GFR<30 mL/min)
Contacts and Locations

Contacts
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Contact: Stephan Williams, MD, PhD 514-890-8000 ext 12132 stephanrwilliams@gmail.com
Contact: Monique Ruel, RN, CCRP 514-890-8000 ext 12171 monique.m.ruel.chum@ssss.gouv.qc.ca

Locations
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Canada, Quebec
Centre Hospitalier de l'Université de Montréal (CHUM) Recruiting
Montréal, Quebec, Canada, H2X 3E4
Contact: Stephan R Williams, Md, PhD    514-890-8000 ext 12132    stephanrwilliams@gmail.com   
Contact: Monique Ruel, RN, CCRP    514-890-8000 ext 12171    monique.m.ruel.chum@ssss.gouv.qc.ca   
Sub-Investigator: Sophie Ayoub, MD         
Sub-Investigator: Pierre-Olivier Hétu, PhD, CSPQ         
Sub-Investigator: Sarah Maximos, MD         
Sub-Investigator: Alex Moore, MD, FRCPC         
Sub-Investigator: Louis-Mathieu Stevens, MD, FRCSC         
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
Investigators
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Principal Investigator: Stephan Williams, MD, PhD Centre hospitalier de l'Université de Montréal (CHUM)
Tracking Information
First Submitted Date April 16, 2019
First Posted Date April 19, 2019
Last Update Posted Date August 27, 2020
Actual Study Start Date July 29, 2019
Estimated Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 16, 2019)
Maximal plasma concentration (Cmax) of bupivacaine after pecto-intercostal fascial plane block [ Time Frame: The end of injection of bupivacaine will be considered as T0. Blood samples at T10, T20, T30, T45, T60, T90, T120, T180, and T240minutes will be collected to further analyze plasmatic bupivacaine values at these timepoints. ]
The Cmax will be estimated by interpolation based on the plasmatic bupivacaine values obtained after the analysis of the blood samples.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: April 29, 2019)
  • Time (Tmax) to maximum plasma concentration Cmax of bupivacaine [ Time Frame: The end of injection of bupivacaine will be considered as T0. Blood samples at T10, T20, T30, T45, T60, T90, T120, T180, and T240 minutes will be performed to further analyze plasmatic bupivacaine values at these timepoints. ]
    The Tmax will be estimated by interpolation based on the plasmatic bupivacaine values obtained after the analysis of the blood samples.
  • Total opioid and co-analgesics doses needed in the Intensive Care Unit [ Time Frame: After the surgery, from the arrival in the Intensive Care Unit to 24 hours after the entry in the Intensive Care Unit. ]
    The total dose of opioids and co-analgesics used by the patients during the first 24 hours in the Intensive Care Unit will be recorded.
  • Time between arrival in Intensive Care Unit and extubation [ Time Frame: Time from the arrival in the Intensive Care Unit to the extubation, for an average of 4 hours following surgery. ]
    Time between the arrival of the patient in the Intensive Care Unit and the extubation of the patient will be measured in minutes.
  • Sensory block level during the last sampling [ Time Frame: At T240 minutes (4 hours) after the end of injection, after the last sampling, at the Intensive Care Unit ]
    Sensory block level will be measured with a 6.1g von Frey filaments.
Original Secondary Outcome Measures
 (submitted: April 16, 2019)
  • Time (Tmax) to maximum plasma concentration Cmax of bupivacaine [ Time Frame: The end of injection of bupivacaine will be considered as T0. Blood samples at T10, T20, T30, T45, T60, T90, T120, T180, and T240 minutes will be performed to further analyze plasmatic bupivacaine values at these timepoints. ]
    The Tmax will be estimated by interpolation based on the plasmatic bupivacaine values obtained after the analysis of the blood samples.
  • Total opioid and co-analgesics doses needed in the Intensive Care Unit [ Time Frame: After the surgery, from the arrival in the Intensive Care Unit to 24 hours after the entry in the Intensive Care Unit. ]
    The total dose of opioids and co-analgesics used by the patients during the first 24 hours in the Intensive Care Unit will be recorded.
  • Time between arrival in Intensive Care Unit and extubation [ Time Frame: Time from the arrival in the Intensive Care Unit to the extubation ]
    Time between the arrival of the patient in the Intensive Care Unit and the extubation of the patient will be measured in minutes.
  • Sensory block level during the last sampling [ Time Frame: At T240 minutes (4 hours) after the end of injection, after the last sampling, at the Intensive Care Unit ]
    Sensory block level will be measured with a 6.1g von Frey filaments.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Peak Plasma Levels of Bupivacaine After a Pecto-Intercostal Fascial Block Post-Sternotomy for Cardiac Surgery
Official Title Peak Plasma Levels of Bupivacaine After a Pecto-Intercostal Fascial Block Post-Sternotomy for Cardiac Surgery
Brief Summary The primary objective of the study is to measure plasma levels of bupivacaine following a pecto-intercostal fascial plane block (PIFB) in patients undergoing sternotomy for cardiac surgery.
Detailed Description

Heart disease such as ischemic cardiomyopathy and heart failure are the second leading cause of death and a leading cause of hospitalization in Canada. Approximately 35,000 heart valve or coronary artery revascularization procedures involving median sternotomy, an important component in the treatment of these diseases, are performed annually. Median sternotomy is associated with acute pain that decreases patient satisfaction, increases the risk of delirium, arrhythmias and respiratory complications. It also contributes to the development of postoperative chronic pain that can affect up to 31% of patients in the first year after surgery. Multimodal analgesia, combining drug therapy and regional anesthesia, can help in preventing acute and perhaps chronic pain in patients undergoing sternotomy for cardiac surgery.

The pecto-intercostal fascial plane block (PIFB) is a new locoregional anesthesia technique that has emerged to treat pain following cardiac surgery including sternotomy, breast surgeries and sternal fractures. It consists of injecting local anesthetics in the space located between the major pectoralis muscle and the intercostal muscles using ultrasound guidance, allowing to obtain anesthesia of the territory innervated by the anterior cutaneous intercostal branches, i.e. the medial aspect of the breast and the sternum.

The dose of local anesthetic injected after a PIFB should aim to maximize analgesia while minimizing the chance of toxic systemic concentrations. Defining the rate of absorption of local anesthetics into the blood after a PIFB will therefore help anesthesiologists to determinate optimal analgesic doses, in terms of both safety and effectiveness.

This observational study will determine bupivacaine pharmacokinetics after a PIFB with bupivacaine, to further define the right dose and duration of surveillance in post-anesthesia care.

Methods: Anesthesia and cardiac surgery will be initiated as usual. The use of bupivacaine by the anesthesiologist or surgeon will be prohibited. Following closure of the sternum, while the patient remains intubated and ventilated under general anesthesia with monitoring, including invasive blood pressure, oxygen saturation, respiratory rate and ECG, the PIFB will be done before application of sternal dressing and removal of sterile fields. Using an ultrasound machine with a high frequency linear probe (Sonosite, HFL50 15-6MHz) placed in the parasagittal plane, 3cm away from the midline, the fascia between the major pectoralis muscle and the internal intercostal muscle will be visualized. Subsequently, four injection sites, defined by the space between the fascia of the pectoral and intercostal muscles at the third and sixth intercostal spaces on each side of the patient, will be reached with an insulated hyperechoic needle (50-80 mm, 22 gauge, SonoPlex STIM, Nanoline, Pajunk, Germany) inserted cephalically and positioned in-plane.

Following negative aspiration, the anesthesiologist will confirm the correct position of the needle with the fluid spread of 1 mL of 5% dextrose. Then, he will inject bupivacaine 0.25% with epinephrine 5 mcg/mL in 5 ml aliquots for a total dose of 2mg/kg of ideal body weight (maximum of 150mg or 60 mL).

The end of injection will be considered as T0. Collection of 4.5mL of blood will be performed at T10min, T20min, T30min, T45min, T60min, T90min, T120min, T180min, and T240min.

Blood tubes will be immediately placed on ice to be ultimately sent to the laboratory for centrifugation and measurement of bupivacaine level using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for each of the samples.

After the block, the patient will be transferred to the Intensive Care Unit. At T240min, if the patient is extubated, the level of the sensory block will be identified by the pinprick test.

The time between ICU arrival and extubation, as well as the total consumption of opioids and co-analgesics for the first 24 hours will be recorded for each patient.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients requiring a pecto-intercostal fascial block following cardiac surgery
Condition Pharmacokinetics
Intervention Other: Collection of blood samples
Nine blood samples will be collected to determine bupivacaine pharmacokinetics at T10min, T20min, T30min, T45min, T60min, T90min, T120min, T180min, and T240min. T0 will be defined as the end of bupivacaine injection.
Study Groups/Cohorts Bupivacaine dosage in PIFB block
The pharmacokinetics of bupivacaine 0.25% with epinephrine 5 mcg/mL for a total dose of 2mg/kg of ideal body weight following a PIFB block will be determined by the collection of blood samples at predetermined time points.
Intervention: Other: Collection of blood samples
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 16, 2019)
18
Original Estimated Enrollment Same as current
Estimated Study Completion Date June 2, 2021
Estimated Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • ASA l-lll
  • Undergoing sternotomy for cardiac surgery under a PIFB and general anesthesia

Exclusion Criteria:

  • Patient's refusal or inability to consent
  • Allergy, hypersensibility or resistance to local anesthetic
  • Contraindication to regional anesthesia: infection in the designated area, severe congenital coagulopathy or inadequate hemostasis before PIFB
  • Severe hepatic (Child B and C) or renal insufficiency (GFR<30 mL/min)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Stephan Williams, MD, PhD 514-890-8000 ext 12132 stephanrwilliams@gmail.com
Contact: Monique Ruel, RN, CCRP 514-890-8000 ext 12171 monique.m.ruel.chum@ssss.gouv.qc.ca
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT03920904
Other Study ID Numbers 19.015
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Responsible Party Centre hospitalier de l'Université de Montréal (CHUM)
Study Sponsor Centre hospitalier de l'Université de Montréal (CHUM)
Collaborators Not Provided
Investigators
Principal Investigator: Stephan Williams, MD, PhD Centre hospitalier de l'Université de Montréal (CHUM)
PRS Account Centre hospitalier de l'Université de Montréal (CHUM)
Verification Date August 2020