Dextromethorphan for Postoperative Pain

Overseen By Pui Yan, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Nathanael Heckmann

Disqualifiers: Bmi ≥ 35, Opioid abuse, others

Compensation: Varies

Number of Visits: 6

Duration: 48 hours

160 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Dextromethorphan Hydrobromide for postoperative pain?

Research shows that dextromethorphan can reduce pain scores and the need for additional pain medication after surgeries like hysterectomy and oral surgery, suggesting it helps manage postoperative pain. ^{1 2 3 4 5}

Is dextromethorphan safe for use in humans?

Research on dextromethorphan for postoperative pain, such as after hysterectomy, shows it is generally safe with no significant differences in side effects like nausea, vomiting, or sedation compared to a placebo. ^{1 2 4 6 7}

How does the drug dextromethorphan differ from other treatments for postoperative pain?

Dextromethorphan is unique because it is an NMDA receptor antagonist, which means it works by blocking certain receptors in the brain that are involved in pain sensation. This mechanism is different from typical pain medications like opioids, which directly target pain pathways. While it has shown some potential to reduce morphine consumption immediately after surgery, its overall effectiveness in reducing postoperative pain is still uncertain. ^{2 4 6 7 8}

What is the purpose of this trial?

A Randomized, Placebo-Controlled Study to Evaluate the Efficacy of Perioperative Dextromethorphan compared to Placebo for the Treatment of Postoperative Pain

Eligibility Criteria

This trial is for adults over 18 who are about to have knee replacement surgery and are generally healthy or have mild to moderate systemic disease. It's not for those with a BMI of 35 or higher, a history of opioid abuse, or severe vomiting after past surgeries.

Inclusion Criteria

I am 18 or older and planning to have knee replacement surgery.

You are in good to moderate health according to the ASA classification.

Exclusion Criteria

I have experienced uncontrollable vomiting after surgery in the past.

You have a body mass index (BMI) of 35 or higher.

You have a history of misusing opioid drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 60 mg oral dextromethorphan (or matching placebo) preoperatively, as well as 30 mg 8- and 16-hours postoperatively

48 hours

Preoperative visit and postoperative monitoring at 6, 12, 24, and 48 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Dextromethorphan Hydrobromide
• Placebo

Trial Overview The study is testing if Dextromethorphan, commonly used in cough medicines, can help manage pain after knee surgery better than a placebo. Participants will be randomly assigned to receive either the medication or an inactive substance.

Participant Groups

Group I: Dextromethorphan Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Nathanael Heckmann

Lead Sponsor

Trials

1

Recruited

160+

Findings from Research

In a study of 30 patients undergoing surgery, taking 90 mg of dextromethorphan before the operation significantly reduced pain intensity and sedation levels compared to a placebo, leading to a better overall feeling of well-being.

Patients who received dextromethorphan also required about 55% less morphine and diclofenac for pain relief after surgery, indicating its effectiveness in reducing the need for postoperative analgesics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia. Weinbroum, AA., Gorodezky, A., Niv, D., et al.[2013]

In a double-blinded study of 50 patients undergoing abdominal hysterectomy, those who received oral dextromethorphan experienced significantly lower pain scores at rest 48 and 72 hours post-surgery compared to the placebo group.

Patients taking dextromethorphan also showed a trend towards reduced morphine consumption in the first 24 hours and significantly lower usage of codydramol over the next 48 hours, indicating its potential as an analgesia-sparing agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative dextromethorphan reduces postoperative pain after hysterectomy. Henderson, DJ., Withington, BS., Wilson, JA., et al.[2019]

In a study of 38 children undergoing tympanomastoid surgery, premedication with oral dextromethorphan significantly reduced the total doses of opioids needed during and after surgery compared to a placebo group.

Children who received dextromethorphan reported lower pain scores post-surgery, indicating that it effectively manages pain and decreases reliance on stronger opioids like morphine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral dextromethorphan reduces perioperative analgesic administration in children undergoing tympanomastoid surgery. Hasan, RA., Kartush, JM., Thomas, JD., et al.[2014]

In a study of 100 patients undergoing abdominal hysterectomy, those receiving 30 mg of dextromethorphan (DEX) reported significantly lower pain scores in the post-anesthetic care unit compared to the placebo group.

While DEX did not reduce overall morphine consumption significantly, it did prolong the time to first morphine use, suggesting a potential benefit in managing postoperative pain with a lower incidence of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of pre- and postoperative oral dextromethorphan for reduction of intra- and 24-hour postoperative morphine consumption for transabdominal hysterectomy. Chau-In, W., Sukmuan, B., Ngamsangsirisapt, K., et al.[2013]

In a study of 75 patients undergoing oral surgery, dextromethorphan (DM) did not significantly reduce pain in the first 6 hours post-surgery, indicating it may not provide immediate analgesic effects.

However, at 48 hours post-surgery, patients taking DM reported lower pain intensity and unpleasantness, suggesting that DM may help reduce postoperative hyperalgesia by antagonizing NMDA receptors involved in pain signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antihyperalgesic effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan in the oral surgery model. Gordon, SM., Dubner, R., Dionne, RA.[2019]

In a study of 60 patients undergoing total abdominal hysterectomy, dextromethorphan did not significantly reduce pain scores or morphine consumption compared to placebo, indicating it may not be effective for postoperative pain management.

Both the dextromethorphan and placebo groups showed similar levels of secondary hyperalgesia after surgery, suggesting that dextromethorphan does not prevent this condition following tissue trauma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dextromethorphan and pain after total abdominal hysterectomy. McConaghy, PM., McSorley, P., McCaughey, W., et al.[2019]

In a study of 50 patients undergoing abdominal hysterectomy, oral dextromethorphan (150 mg) significantly reduced morphine consumption by 30% in the first 4 hours post-surgery compared to placebo, indicating its potential as an effective adjunct for pain management.

Despite the initial reduction in morphine use, dextromethorphan did not lead to significant differences in overall pain scores or hyperalgesia (increased sensitivity to pain) at 24 hours post-operation, suggesting that while it may help with immediate analgesic needs, it does not have lasting effects on pain sensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia after total abdominal hysterectomy. Ilkjaer, S., Bach, LF., Nielsen, PA., et al.[2019]

In a study of 66 patients undergoing knee surgery, a high dose of dextromethorphan (200 mg every eight hours) resulted in a modest 29.3% reduction in morphine requirements, indicating some potential for opioid-sparing effects.

However, despite its NMDA antagonist properties, dextromethorphan did not significantly improve postoperative pain levels compared to lower doses used in previous studies, suggesting limited efficacy in enhancing pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery. Wadhwa, A., Clarke, D., Goodchild, CS., et al.[2019]

References

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

Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia. [2013]

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

Perioperative dextromethorphan reduces postoperative pain after hysterectomy. [2019]

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

Oral dextromethorphan reduces perioperative analgesic administration in children undergoing tympanomastoid surgery. [2014]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of pre- and postoperative oral dextromethorphan for reduction of intra- and 24-hour postoperative morphine consumption for transabdominal hysterectomy. [2013]

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

Antihyperalgesic effect of the N-methyl-D-aspartate receptor antagonist dextromethorphan in the oral surgery model. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Dextromethorphan and pain after total abdominal hysterectomy. [2019]

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

Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia after total abdominal hysterectomy. [2019]

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

Large-dose oral dextromethorphan as an adjunct to patient-controlled analgesia with morphine after knee surgery. [2019]