Dexmedetomidine + Ketamine for Postoperative Pain

Overseen By Nadia Godin, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ciusss de L'Est de l'Île de Montréal

Must not be taking: Beta-blockers, Pregabalin, Gabapentin, others

Disqualifiers: Chronic pain, Allergy, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Intraoperative

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as beta-blockers, pregabalin, gabapentin, amitryptillin, nortryptillin, and duloxetin, before participating.

What data supports the effectiveness of the drug combination of Dexmedetomidine and Ketamine for postoperative pain?

Research shows that using dexmedetomidine and ketamine together can help reduce pain after surgery. For example, studies have found that this combination can lower the need for opioids (strong painkillers) and improve pain relief in surgeries like thoracic and femur fracture surgeries. ^{1 2 3 4 5}

Is the combination of dexmedetomidine and ketamine generally safe for humans?

Research shows that dexmedetomidine and ketamine are often used together in medical settings, such as for pain relief after surgery, and are generally considered safe. However, they can have side effects, so their use is carefully monitored by healthcare professionals. ^{1 2 3 6 7}

How does the drug combination of Dexmedetomidine and Ketamine differ from other pain management options?

The combination of Dexmedetomidine and Ketamine for postoperative pain is unique because it leverages the calming effects of Dexmedetomidine and the pain-relieving properties of Ketamine, potentially reducing the need for opioids and their associated side effects. This combination can enhance pain relief and extend the duration of analgesia compared to using either drug alone or standard pain management options. ^{1 4 8 9 10}

What is the purpose of this trial?

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.

Research Team

Veronique Brulotte, MD

Principal Investigator

Ciusss de L'Est de l'Île de Montréal

Eligibility Criteria

This trial is for adults aged 18-80 undergoing elective lung surgery (VATS) who are generally healthy or have mild to moderate systemic disease. It's not for those planning to use regional anesthesia post-surgery, on certain pain medications like beta-blockers or chronic pain treatments, with allergies to the study drugs, pregnant, unable to consent, or facing language barriers.

Inclusion Criteria

My health is good to moderately impaired according to anesthesia standards.

I am scheduled for a lung surgery using a camera-assisted method.

Exclusion Criteria

You are allergic to ketamine or dexmedetomidine.

I take more than 60 mg of morphine daily for chronic pain.

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Intraoperative infusion of ketamine and dexmedetomidine to reduce postoperative morphine requirements

Intraoperative

1 visit (in-person)

Postoperative Monitoring

Monitoring of postoperative morphine requirements and pain scores at rest and after coughing

48 hours

Continuous monitoring

Follow-up

Participants are monitored for persistent postoperative pain and other outcomes

3 months

Treatment Details

Interventions

• Dexmedetomidine and Ketamine

Trial Overview The study tests if combining two non-opioid drugs—dexmedetomidine and ketamine—during surgery can better reduce the need for morphine afterward compared to using each drug alone. The goal is a further 30% reduction in morphine use after VATS when both drugs are infused together.

Participant Groups

Group I: Ketamine hydrochloride Active Control 1 Intervention

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;

Group II: dexmedetomidine hydrochloride Active Control 1 Intervention

Intraoperative bolus (1µg/kg over 20 min) and infusion (0.5µg/kg/h) of dexmedetomidine plus an intraoperative bolus and infusion of normal saline

Group III: dexmedetomidine hydrochloride and ketamine hydrochloride Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

Ciusss de L'Est de l'Île de Montréal

Lead Sponsor

Trials

81

Recruited

6,400+

Findings from Research

A mini-dose combination of esketamine and dexmedetomidine significantly reduced the incidence of moderate-to-severe pain after scoliosis correction surgery, with 65.7% of patients experiencing pain compared to 86.0% in the placebo group.

Patients receiving the combination treatment also reported better sleep quality and lower pain intensity both at rest and during movement, without an increase in adverse events, indicating a safe and effective analgesic strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. Zhang, Y., Cui, F., Ma, JH., et al.[2023]

In a study of 1,630 patients undergoing thoracic pulmonary oncologic surgery, those receiving intraoperative dexmedetomidine and ketamine were more likely to be opioid-free post-surgery (76.6% vs 60.9%, P<0.01).

Despite initial lower pain scores and opioid consumption in the recovery room for the dexmedetomidine + ketamine group, these differences were not significant after adjusting for multiple comparisons, indicating no overall impact on postoperative pain management or opioid use during the hospital stay.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Dexmedetomidine and Ketamine Infusions in an Enhanced Recovery After Thoracic Surgery Program: A Propensity Score Matched Analysis. Mena, GE., Zorrilla-Vaca, A., Vaporciyan, A., et al.[2022]

In a study of 90 patients undergoing total abdominal hysterectomy, local wound infiltration with ketamine or dexmedetomidine significantly reduced postoperative morphine consumption compared to a control group, indicating an opioid-sparing effect.

Both ketamine and dexmedetomidine delayed the first request for analgesia and lowered pain scores, with ketamine showing superior results in reducing stress markers post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of local wound infiltration with ketamine versus dexmedetomidine on postoperative pain and stress after abdominal hysterectomy, a randomized trial. Mohamed, SA., Sayed, DM., El Sherif, FA., et al.[2019]

In a study of 105 patients undergoing elective femoral surgery, adding dexmedetomidine to epidural bupivacaine significantly reduced postoperative pain scores on the first day compared to ketamine and control groups.

Patients receiving dexmedetomidine required less opioid medication post-surgery and experienced a longer duration of analgesia compared to those receiving ketamine or no adjuvant, highlighting dexmedetomidine's effectiveness as an adjuvant in epidural anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of dexmedetomidine and ketamine addition to bupivacaine 0.25% by epidural method in reducing postoperative pain in patients undergoing femur fracture surgery. Radbin, T., Kamali, A., Yazdi, B., et al.[2022]

A systematic review of 37 trials found that peri-operative ketamine significantly reduces the need for rescue analgesics and lowers pain intensity in adults after surgery, particularly decreasing morphine consumption in the first 24 hours.

Ketamine also effectively reduces post-operative nausea and vomiting (PONV) with mild or absent adverse effects, suggesting it is a safe and effective adjuvant for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review). Bell, RF., Dahl, JB., Moore, RA., et al.[2022]

In a study of 93 children aged 3 to 17 undergoing short procedures, co-administering dexmedetomidine (Dex) with ketamine significantly reduced recovery agitation compared to using ketamine alone or with propofol, with agitation rates of 3.2% in the ketadex group versus 22.6% in the other groups.

The ketadex group also experienced fewer unpleasant recovery reactions, such as hallucinations and nightmares, indicating that Dex enhances the safety and comfort of ketamine sedation without increasing the risk of oxygen desaturation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the effects of dexmedetomidine and propofol in reducing recovery agitation in pediatric patients after ketamine procedural sedation in emergency department. Azizkhani, R., Kouhestani, S., Heydari, F., et al.[2022]

In a study involving neonatal rats, ketamine was found to cause significant neuronal apoptosis and impair learning and memory, as evidenced by increased TUNEL-positive cells and poorer performance in the Morris water maze test.

Dexmedetomidine effectively reduced ketamine-induced neurotoxicity, showing a significant decrease in neuronal apoptosis and improved cognitive function, while dexmedetomidine alone did not exhibit neurotoxic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain. Duan, X., Li, Y., Zhou, C., et al.[2022]

In a study involving 126 women undergoing abdominal hysterectomy, both dexmedetomidine and ketamine significantly reduced postoperative pain compared to a placebo, with pain scores of 2.6 and 4.2 respectively, versus 1.3 for the placebo group.

While both medications were effective in managing pain, dexmedetomidine was found to be more effective than ketamine in reducing pain severity during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intradermal Dexmedmotidine and subcutaneous Ketamine for post-surgical pain management in patients with abdominal hysterectomy. Kamali, A., Zarepour, Z., Shokrpour, M., et al.[2020]

In a study of 56 patients undergoing chemoport insertion, both dexmedetomidine-ketamine (DK) and dexmedetomidine-midazolam-fentanyl (DMF) combinations provided similar recovery times and cardiorespiratory stability, indicating both are safe options for monitored anesthesia care.

However, the DMF group reported better sedation quality and higher satisfaction scores among patients and medical staff, despite a lower infusion rate of dexmedetomidine, suggesting it may be the more effective combination for procedural sedation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine-ketamine versus Dexmedetomidine-midazolam-fentanyl for monitored anesthesia care during chemoport insertion: a Prospective Randomized Study. Chun, EH., Han, MJ., Baik, HJ., et al.[2022]

In a study of 90 adults undergoing laparoscopic cholecystectomy, adding either ketamine or dexmedetomidine to total intravenous anesthesia (TIVA) significantly improved postoperative pain relief compared to a control group, with longer times before the first analgesic was needed.

Both ketamine and dexmedetomidine reduced the need for morphine after surgery, indicating they can effectively decrease opioid consumption while enhancing analgesia in the postoperative period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Effect of Ketamine and Dexmedetomidine Combined with Total Intravenous Anesthesia in Laparoscopic Cholecystectomy Procedures: A Prospective Randomized Controlled Study. Efe Mercanoglu, E., Girgin Kelebek, N., Turker, G., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Intraoperative Dexmedetomidine and Ketamine Infusions in an Enhanced Recovery After Thoracic Surgery Program: A Propensity Score Matched Analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Effect of local wound infiltration with ketamine versus dexmedetomidine on postoperative pain and stress after abdominal hysterectomy, a randomized trial. [2019]

4. India pubmed.ncbi.nlm.nih.gov

Efficacy of dexmedetomidine and ketamine addition to bupivacaine 0.25% by epidural method in reducing postoperative pain in patients undergoing femur fracture surgery. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review). [2022]

6. India pubmed.ncbi.nlm.nih.gov

Comparison of the effects of dexmedetomidine and propofol in reducing recovery agitation in pediatric patients after ketamine procedural sedation in emergency department. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Dexmedetomidine provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Comparison of intradermal Dexmedmotidine and subcutaneous Ketamine for post-surgical pain management in patients with abdominal hysterectomy. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Dexmedetomidine-ketamine versus Dexmedetomidine-midazolam-fentanyl for monitored anesthesia care during chemoport insertion: a Prospective Randomized Study. [2022]

10. India pubmed.ncbi.nlm.nih.gov

Comparison of the Effect of Ketamine and Dexmedetomidine Combined with Total Intravenous Anesthesia in Laparoscopic Cholecystectomy Procedures: A Prospective Randomized Controlled Study. [2022]