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Multimodal Versus Opioid aNalgesia in carDiAc Surgery (MONDAY)

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ClinicalTrials.gov Identifier: NCT04987372
Recruitment Status : Recruiting
First Posted : August 3, 2021
Last Update Posted : August 3, 2021
Sponsor:
Information provided by (Responsible Party):
University Hospital, Ghent

Tracking Information
First Submitted Date  ICMJE August 14, 2019
First Posted Date  ICMJE August 3, 2021
Last Update Posted Date August 3, 2021
Actual Study Start Date  ICMJE September 1, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 2, 2021)
Postoperative pain after cardiac surgery [ Time Frame: During the first 48 hours after cardiac surgery ]
By using a NRS scale postoperative pain (at rest, when coughing and at movement) at 8hours, 16hours, 24hours, 32hours, 40hours and 48hours after cardiac surgery In a Numerical Rating Scale (NRS), patients are asked to circle the number between 0 and 10, 0 and 20 or 0 and 100 that fits best to their pain intensity . Zero usually represents 'no pain at all' whereas the upper limit represents 'the worst pain ever possible'.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2021)
(ICDSC)Delirium after stop sedation by udsing Intensive Care Delirium Screening Checklist [ Time Frame: immediately after stop sedation after the surgery until 48hours ]
delirium in the direct postoperative phase, by using the ICDSC (Intensive Care Delirium Screening Checklist) score. The ICDSC is score-based (range 0-8) where the ICDSC is positive when any four (or more) symptoms of delirium are present (i.e., altered level of consciousness, inattention, disorientation, hallucinations or delusions, psychomotor activity, inappropriate speech or mood, sleep disturbance or fluctuation of symptoms)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multimodal Versus Opioid aNalgesia in carDiAc Surgery
Official Title  ICMJE Comparison of Pain and Comfort in Patients Following Cardiac Surgery: Opioid- Morphine Managed Versus Multimodal Pain-management
Brief Summary To compare standard "Fentanyl - Tramadol - Paracetamol - Oxycodone" regimen to a multimodal painmanagement "pregabalin- minimal fentanyl-ketamine-lidocain-dexmedetomidine- paracetamol" to determine which therapy provides the most comfort, the fastest extubation time, the least pain and the least delirium.
Detailed Description

Cardiac surgery for the adult, performed by sternotomy is associated with moderate to severe acute postoperative pain. Postoperative pain is the primary reason for prolonged convalescence and one of the main concerns of the surgical patient in the Intensive Care Unit (ICU). This pain is multifactorial and multifocal; and can be caused by incision, intraoperative tissue retraction and dissection, surgical manipulation of the parietal pleura, posterior rib dislocation or fracture, possible brachial plexus injury, chest tube insertion and harvesting of the saphenous vein and internal mammarian artery.

The most common analgesic schemes for postoperative pain in cardiac surgery are based on intravenous opioids by bolus, with patient- or nurse-controlled delivery systems. Although there is no doubt they have a beneficial effect on pain, opioids are associated with dose-related side effects including "over"sedation, ileus, urinary retention, nausea, vomiting, pruritus, mental confusion and respiratory depression leading to a prolonged extubation time.

In the last decades many has been written about the value of multimodal pain protocols to treat acute postoperative pain in non-cardiac surgery. This is not only to reduce the dose and side effects of opioids. By blocking both the central and peripheral pain mechanisms the aim is to find a holy grale, by which the patient suffers the least, by which central neural hyper-excitability that increases postoperative pain is minimized and by which the transformation of acute into chronic pain is reduced to a minimum.

Pregabalin has his role in treating various neuropathic pain syndromes. It inhibits central neuronal sensitization and prevents hyperalgesia by decreasing excitatory amino acid neurotransmission in the spinal cord through a direct postsynaptic or presynaptic inhibition of Ca²+ influx. It has been shown that gabapentin reduced pain scores and opioid requirements in different surgical settings. Literature is not conclusive and because of conflicting results the routine use of gabapentin and pregabalin to reduce opioid consumption in the cardiac surgical patients is not yet recommended.

Dexmedetomidine is an alpha-2 adrenergic receptor agonist that can be directly applied to the peripheral nervous system, causing a dose-dependent inhibition of C-fibers and Aα-fibers. It is widely used for sedation and anxiolysis in ICU settings. The clinical efficacy has been proven in non-cardiac surgery by augmenting anesthesia and analgesia, and allowing a reduction in opioid requirements. Additionally, there was a significantly lower incidence of postoperative delirium.

Ketamine isn't only an anesthetic agent but also has an analgesic effect. The exact mechanism is not yet known but some of the pathways are already identified. It binds to the opioid receptors κ(kappa) δ(delta) μ(mu) and it was proven that ketamine induces phosphorylation of mitogen-activated protein kinases by 2-3 times that of traditional opioid drugs. Another way of producing its analgesic effect is by the muscarinic acetylcholine receptors in the central nervous system. Ketamine also effects other ion channels including sodium channels and voltage sensitive calcium channels leading to local anesthetic and gabapentin like effects. Because of the unique effect of keeping hemodynamic stability during induction, ketamine can be useful in cardiac surgery. The analgesic effect, the absence of respiratory depression and hemodynamic stability make it an excellent drug to use in the ICU.

Intravenous lidocain during the perioperative period has many beneficial effects in open procedures, such as an earlier return of gastrointestinal tract function, less postoperative opioid consumption, improvement of postoperative cognitive dysfunction and reduced stay in the hospital. The exact working mechanism isn't 100% identified but the anti-inflammatory effects of LA mediated through interactions with polymorphonuclear cells and the inhibition of G protein-coupled receptors may play a crucial role for the observed effects in the perioperative setting.

Magnesiumsulphate's analgesic mechanisms are also not fully identified, but it is thought that the NMDA (N-methyl-d-aspartate) receptor is blocked by calcium regulation mechanisms. Because the NMDA receptor plays a role in the transmission of pain, magnesium has become a subject of interest as potential use in postoperative painschemes. It was proven that peri-operative intravenous magnesium can reduce opioid consumption especially in the first 24h.

The investigator's goal is to compare standard "Fentanyl - Tramadol - Paracetamol - Oxycodon" regimen to a multimodal painmanagement "pregabalin- magnesiumsulphate - minimal fentanyl-ketamine-lidocain-dexmedetomidine- paracetamol" to determine which therapy provides the most comfort, the fastest extubation time, the least pain and the least delirium.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Postoperative Pain
  • Postoperative Delirium
Intervention  ICMJE Drug: Dexmedetomidine
The use of multimodal painkillers pre, per and postoperative
Other Names:
  • pregabaline
  • ketamine
  • lidocaine
  • magnesium sulfate
Study Arms  ICMJE
  • No Intervention: Classical protocol

    Fentanyl Max. 15µg/kg IV Per-operative

    Ultiva (Remifentanyl) 0.02-0.1µg/kg/h IV Post-operative

    Paracetamol 4x1g /24h IV Post-operative

    Tradonal (Tramadol) 100mg IV 4/d IV Post-operative in cas of break through pain

    Oxynorm (Oxycodon) 5-10mg 4-6/d PO Post-operative in case of Break through pain

  • Active Comparator: Multimodal protocol

    Lyrica (Pregabalin) 75mg PO 2 hours before the operation

    Dexdor (Dexmedetomidine) 0.8µg/kg/h IV Per-operative / Post-operative

    Ketalar (Ketamine) Bolus (0.5mg/kg) + 0.3mg/kg/h IV Per-operative until stop propofol

    Linisol (Lidocain) Bolus (1.5mg/kg) + 1.3mg/kg/h IV Per-operatiive until 12h post-op

    Magnesium Sulphate Induction (25mg/kg) + 25mg/kg weaning ECC IV Per-operative

    Fentanyl 2.5µg/kg IV Per-operative

    Paracetamol 4x1g /24u IV Post-operative

    Tradonal (Tramadol) 100mg IV 4/d IV Post-operative in case of Break through pain

    Oxynorm (Oxycodon) 5-10mg 4-6/d PO Post-operative in case of Break through pain

    Intervention: Drug: Dexmedetomidine
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  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 2, 2021)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients undergoing first time cardiac surgery by median sternotomy
  • Elective surgery or semi-urgent: there needs to be time to provide 1 hour before surgery the intake of pregabalin
  • ≥ 18 years for men
  • Women who are in menopause
  • Possibility to communicate with the patient to score pain and comfort
  • Signed Informed Consent, signed by subject able and willing to provide written informed consent for study participation

Exclusion Criteria:

  • Urgent surgery
  • Women who are in premenopause
  • Hypersensitivity to any of the study medication
  • In case of direct postoperative revision the patient is NOT excluded.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Harlinde Peperstraete +3293325185 harlinde.peperstraete@uzgent.com
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04987372
Other Study ID Numbers  ICMJE 2019-000515-84
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Ghent
Study Sponsor  ICMJE University Hospital, Ghent
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Harlinde Peperstraete, MD UZ Gent
PRS Account University Hospital, Ghent
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP