We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dexmedetomidine and Ketamine in VATS Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03596424
Recruitment Status : Recruiting
First Posted : July 23, 2018
Last Update Posted : May 23, 2022
Sponsor:
Information provided by (Responsible Party):
Veronique Brulotte, Ciusss de L'Est de l'Île de Montréal

Tracking Information
First Submitted Date  ICMJE May 27, 2018
First Posted Date  ICMJE July 23, 2018
Last Update Posted Date May 23, 2022
Actual Study Start Date  ICMJE February 1, 2018
Estimated Primary Completion Date December 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
Day 1 Postoperative morphine requirement [ Time Frame: Day 1 ]
Cumulative dose of morphine used by the patient
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
  • day 2 Postoperativve morphine requirement [ Time Frame: day 2 ]
    cumulative dose of morphine used by the patient
  • Pain score at rest 24h [ Time Frame: day 1 ]
    Pain score (Verbal Numeric Scale (0-10) at rest
  • Pain score at rest 48h [ Time Frame: day 2 ]
    Pain score (Verbal Numeric Scale (0-10) at rest
  • Pain score at cough 24h [ Time Frame: day 1 ]
    Pain score (Verbal Numeric Scale (0-10) at cough
  • Pain score at cough 48h [ Time Frame: day 2 ]
    Pain score (Verbal Numeric Scale (0-10) at cough
  • intraoperative fentanyl requirement [ Time Frame: for incision to wound closure ]
    intraoperative dose of fentanyl used to treat intraoperative pain
  • chest tube removal [ Time Frame: 1 week ]
    time (days) for chest tube removal after surgery
  • chronic postoperative pain [ Time Frame: 3 months ]
    patients reporting persistent post operative pain
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 Dexmedetomidine and Ketamine in VATS Surgery
Official Title  ICMJE Impact of Dexmedetomidine and Ketamine and Their Combination for the Reduction of Postoperative Morphine Requirements After VATS Surgery
Brief Summary

Postoperative pain after VATS surgery is significant and associated with moderate to high post operative morphine requirements, which can cause opioid related side effects and delay postoperative recovery. To reduce this requirement, multimodal analgesia with non opioid medication such as dexmedetomidine and ketamine can be used. These drugs have demonstrated significant opioid-sparing properties after various types of surgeries. However, very little is known about their ability to do so in VATS surgery. Also, their relative opioid-sparing properties have not been compared, and it is not known whether their combined use can lead to an additional opioid-sparing effect. The primary goal of this study will be to determine the impact of a combined intra operative infusion of ketamine and dexmedetomidine on postoperative morphine requirements in patients undergoing elective VATS, compared to both these drugs infused separately.

The hypothesis is that this combined infusion will lead to a 30% further reduction in morphine requirements, 24h after surgery, compared to both these drugs infused separately.

Detailed Description

Video-assisted thoracic surgery (VATS) for pulmonary resection is associated with less tissue trauma, less impairment in lung function, and reduced postoperative pain compared with thoracotomy, although many patients continue to report significant acute postoperative pain. If not well-controlled, postoperative thoracic pain can lead to splinting and inadequate recovery of pulmonary function.

Enhancing the quality of postoperative analgesia while reducing intra and postoperative opioid requirements is an important issue that has been one of the main focus of Enhanced Recovery After Surgery (ERAS) protocols. Indeed, the key factors that delay postoperative recovery include parenteral opioids and bed rest and immobility secondary to postoperative pain. While opioids are effective at treating even severe pain, their use is associated with dose-related adverse effects such as respiratory depression, sedation, postoperative nausea and vomiting, urinary retention, ileus, opioid-induced hyperalgesia and chronic postoperative pain. More importantly, opioids depress host immunity and neuroendocrine function and may negatively affect cancer recurrence and survival after lung cancer surgery.

Hence, given the importance of good postoperative analgesia and the significance of opioid-related adverse effects, the reduction of opioid requirements and postoperative pain through multimodal analgesia is an important matter. Focusing on this goal, the ERAS protocols have shown great efficacy in improving patient's care after colorectal surgery and they are now being applied to pancreatic, ENT, bariatric, urologic and many more major surgeries.

It is probably only a matter of time before ERAS protocols are applied to VATS surgery; however, the optimal way of providing postoperative analgesia after VATS has not yet been determined, unlike colorectal surgery. Indeed, thoracic epidural analgesia, single-shot and continuous paravertebral and intercostal nerve blocks and patient-controlled intravenous analgesia have all been evaluated, and none of these has consistently emerged as being superior to the others or to intravenous analgesia. Thoracic epidural analgesia provides effective pain control for thoracotomy but its benefits following thoracoscopy are not uniform. Furthermore, the risks of sympathectomy-induced hypotension and neurologic injury from epidural hematoma may not be justified considering the lesser postoperative pain and impairment in pulmonary function compared to thoracotomy. Continuous paravertebral blocks are an effective alternative to epidural analgesia although their performance may be challenging and time consuming, and catheters may be difficult to thread or get accidentally removed, leading to block failure. Furthermore, as for epidural analgesia, paravertebral catheter placement is contra-indicated in patients with impaired coagulation and/or infection. Single-shot intercostal and paravertebral blocks are less invasive although their benefit is restricted to the first twelve postoperative hours.

Moreover, none of these regional anesthesia techniques can treat the ipsilateral shoulder pain that is often associated with VATS, and opioid analgesia might still be required.

An intravenous opioid patient-controlled analgesia combined to multimodal analgesia with acetaminophen and non-steroidal anti-inflammatoy drug (NSAID) is commonly used in many institutions and has shown to provide adequate and effective postoperative analgesia. However, significant acute postoperative pain and moderate to high opioid consumption are still reported after VATS. There is definitely some place for improvement, which could come from other non-opioid analgesic adjuncts such as ketamine and/or dexmedetomidine.

Ketamine is an anesthetic drug that has well-known analgesic properties due to its ability to block NMDA receptors. An intraoperative bolus followed with a low-dose infusion reduces postoperative opioid requirements by 30-40%, without causing significant side effects. Similarly, dexmedetomidine is a centrally acting α2-agonist with sedating and analgesic properties. When used intra-operatively, it significantly reduces hypnotics and opioids requirements, decreases median pain scores and reduces postoperative morphine consumption by approximately 30%. These systematic reviews seem to indicate a greater morphine-sparing effect from ketamine compared to dexmedetomidine although this has not been evaluated thoroughly. Indeed, only one study compared ketamine's morphine-sparing effects to that of dexmedetomidine, in patients undergoing spine surgery. Both infusions were started postoperatively and provided significant morphine sparing effects compared to placebo. Ketamine's morphine-sparing effect appeared greater than that of dexmedetomidine, although this was not statistically significant, as this study was not powered for that outcome. Hence, their morphine-sparing effect might be different but this difference is likely small. Their impact on postoperative opioid requirement after VATS surgery has not been studied, even though it could be highly beneficial, not only for the reduction of postoperative opioid requirements but for the reduction of chronic postoperative pain.

Another interesting reason for using these analgesic adjuvants for intra operative analgesia is their ability to prevent chronic post operative pain.

More interesting would be to investigate whether their combined use leads to greater morphine-sparing effect. Indeed, although their combination for paediatric procedural sedation is well described, the impact of a combined dexmedetomidine-ketamine intraoperative infusion on postoperative analgesia and opioid requirements has not been evaluated.

Study outcome and hypothesis

The primary goal of this study will be to determine the impact of a combined intra operative infusion of ketamine and dexmedetomidine on postoperative morphine requirements in patients undergoing elective VATS, compared to both these drugs infused separately.

The hypothesis is that this combined infusion will lead to a 30% further reduction in morphine requirements, 24h after surgery, compared to both these drugs infused separately.

Secondary outcomes will be to evaluate the impact of a combined dexmedetomidine-ketamine infusion on:

  • Postoperative pain scores at rest and after coughing at 24 and 48 h postoperatively;
  • Cumulative morphine consumption 48 h after surgery;
  • Intraoperative fentanyl requirements, determined using the NoL index (see methodology section, page);
  • Time to chest tube removal and time to hospital discharge;
  • Proportion of patients with persistent pain three months after surgery;
  • Incidence of ketamine-induced psychomimetic side effects in the postoperative period
  • Incidence of intraoperative bradycardia <50 beats/min compared to intraoperative infusions of ketamine only and dexmedetomidine only.

METHODOLOGY

Study design

This will be a prospective, randomized, double blind study.

Population

Patients undergoing elective VATS and receiving an opioid intravenous patient-controlled analgesia (PCA) combined with acetaminophen and NSAID for postoperative analgesia.

Duration of study

1 year

Sample size Postoperative cumulative morphine consumption 24h after surgery in our institution has been determined by reviewing the files of 50 patients who underwent VATS surgery and received a PCA combined to acetaminophen and NSAID for postoperative analgesia. These patients used an average (standard deviation (SD)) of 39.5 (17.3) mg of morphine.

Considering an opioid-sparing effect of 30% from dexmedetomidine and ketamine alone, a mean morphine consumption of 27.7(11) mg can be expected in the ketamine and dexmedetomidine groups.

A 30% further reduction in opioid requirement from combining ketamine to dexmedetomidine will be considered significant.

Thus, a sample size of 37 patients per group would give us 80% power to detect such a difference, alpha 0.05.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Postoperative Pain
  • Opioid Use
Intervention  ICMJE
  • Drug: Ketamine Hydrochloride
    Intraoperative bolus and infusion (see arm description)
    Other Name: ketamine
  • Drug: Dexmedetomidine Hydrochloride
    Intraoperative bolus and infusion (see arm description)
    Other Name: dexmedetomidine
  • Combination Product: dexmedetomidine Hydrochloride and Ketamine Hydrochloride
    Intraoperative bolus and infusion (see arm description)
    Other Name: dexmedetomidine and ketamine
Study Arms  ICMJE
  • Active Comparator: Ketamine hydrochloride
    Intraoperative bolus (0.25 mg/kg) and infusion (0.25mg/kg/h) of ketamine plus an intraoperative bolus (over 20 min) and infusion of normal saline;
    Intervention: Drug: Ketamine Hydrochloride
  • Active Comparator: dexmedetomidine hydrochloride
    Intraoperative bolus (1µg/kg over 20 min) and infusion (0.5µg/kg/h) of dexmedetomidine plus an intraoperative bolus and infusion of normal saline
    Intervention: Drug: Dexmedetomidine Hydrochloride
  • Active Comparator: dexmedetomidine hydrochloride and ketamine hydrochloride
    Intraoperative bolus (1µg/kg over 20 min) and infusion (0.5 µg/g/h) of dexmedetomidine plus an intraoperative bolus (0.25mg/kg) and infusion (0.25mg/kg/h) of ketamine
    Intervention: Combination Product: dexmedetomidine Hydrochloride and Ketamine Hydrochloride
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: July 20, 2018)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 1, 2024
Estimated Primary Completion Date December 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients aged 18-80 years old
  • American Society of Anesthesiology physical status I-III
  • Elective Video-Assisted Thoracic Surgery for pulmonary resection

Exclusion Criteria:

  • Patients for which a regional anesthesia technique is planned for postoperative analgesia.
  • Patients taking beta-blockers preoperatively.
  • Patients with chronic pain taking >60 mg morphine PO daily (or its equivalent).
  • Patients taking pregabalin, gabapentin, amitryptillin, nortryptillin and/or duloxetin.
  • Documented allergy to ketamine and/or dexmedetomidine.
  • Pregnancy
  • Inability to give informed consent
  • Linguistic barrier.
  • Patient refusal
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Veronique Brulotte, MD 5142523400 ext 3808 veronique.brulotte@umontreal.ca
Contact: Nadia Godin, RN 5142523400 ext 3192
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03596424
Other Study ID Numbers  ICMJE DexketVATS
Has Data Monitoring Committee Yes
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  ICMJE
Plan to Share IPD: No
Current Responsible Party Veronique Brulotte, Ciusss de L'Est de l'Île de Montréal
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Ciusss de L'Est de l'Île de Montréal
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Veronique Brulotte, MD Ciusss de L'Est de l'Île de Montréal
PRS Account Ciusss de L'Est de l'Île de Montréal
Verification Date May 2022

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