Epinephrine-enhanced Anesthesia for Chronic Sinusitis

(FESS Trial)

Overseen By Cameron R Smith, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Florida

Disqualifiers: Chronic pain, Bleeding diathesis, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for managing bleeding during sinus surgery by adding epinephrine (adrenaline) to anesthesia. The focus is on patients with chronic sinusitis undergoing sinus surgery to determine if this combination reduces blood loss during the operation. Participants will receive injections both with and without epinephrine to compare outcomes. Suitable candidates have chronic sinusitis and are scheduled for sinus surgery without chronic pain or bleeding issues. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both bupivacaine and ropivacaine are generally safe and effective anesthetics. Bupivacaine can improve surgical outcomes and reduce pain after sinus surgery, though rare cases of serious side effects, such as seizures, have occurred when used as a local anesthetic.

Ropivacaine is considered safer and can be administered in higher doses with fewer side effects than bupivacaine. It is less likely to cause symptoms like dizziness or confusion.

Epinephrine is often added to anesthetics to control bleeding. It is safe in low amounts during sinus surgeries and helps reduce blood loss without causing major issues.

Dexamethasone, a type of steroid, is also included in the treatment. It helps reduce swelling and is safe when used for a short duration.

Overall, these treatments have been used safely in other medical contexts, demonstrating they are well-tolerated with minimal side effects for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for chronic sinusitis, which often involve medications like steroids or surgery to relieve symptoms, this trial explores the use of epinephrine-enhanced local anesthesia. Researchers are excited because using bupivacaine or ropivacaine with epinephrine could potentially provide longer-lasting pain relief and reduce inflammation more effectively than current options. The unique delivery method, targeting the pterygopalatine fossa on each side of the head, aims to offer precise and balanced anesthesia, which could lead to improved patient outcomes and faster recovery times.

What evidence suggests that this trial's treatments could be effective for chronic sinusitis?

Research has shown that combining bupivacaine with dexamethasone can reduce pain and the need for pain medication after surgery. One study found that bupivacaine improves the surgical area and reduces bleeding during endoscopic sinus surgery. Studies also indicate that ropivacaine is effective as a local anesthetic, particularly for controlling pain during and after surgery. In this trial, participants will receive either bupivacaine or ropivacaine, with or without epinephrine, to assess their effectiveness in managing bleeding and pain during sinus surgery. Both bupivacaine and ropivacaine have demonstrated benefits in aiding recovery and providing effective pain relief in sinus procedures. ^{1 3 5 6 7}

Who Is on the Research Team?

Cameron Smith, MD, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for adults aged 18 to 90 who are having bilateral functional endoscopic sinus surgery (FESS) for chronic sinusitis and don't have a history of chronic pain or bleeding disorders. Candidates must consent to participate and not require additional surgeries beyond FESS.

Inclusion Criteria

I do not have a chronic pain condition.

Patient consents to participate

You do not have a condition that makes you prone to bleeding.

Exclusion Criteria

Presence of any other factor which, at the discretion of any member of the study team, makes the patient a poor candidate for block placement.

I have a long-term pain condition.

I need surgery beyond sinus surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bilateral ultrasound guided pterygopalatine ganglion blocks with or without epinephrine during functional endoscopic sinus surgery

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including endoscopic grading of nasal bleeding

36 hours

Continuous monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Bupivacaine
• Dexamethasone
• Epinephrine
• Ropivacaine

Trial Overview The study tests the effect of adding epinephrine to anesthetic blocks on blood loss during FESS. There are two groups, both receiving bupivacaine or ropivacaine with epinephrine plus dexamethasone, but possibly differing in concentration or volume.

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 1 Intervention

a single injection into the LEFT pterygopalatine fossa of 4 milliliters of 0.5% Bupivacaine or Ropivacaine without epinephrine with the addition of 4 milligrams of dexamethasone (1ml) and a single injection into the RIGHT pterygopalatine fossa of 4 milliliters of 0.5% Bupivacaine or Ropivacaine with epinephrine 1:200.00 with the addition of 4 milligrams of dexamethasone (1mL) after the induction of general anesthesia. (total volume 5 ml per side).

Group II: Group 1 Experimental Treatment 1 Intervention

a single injection into the LEFT pterygopalatine fossa of 4 milliliters of 0.5% Bupivacaine or Ropivacaine with epinephrine 1:200.000 with the addition of 4 milligrams of dexamethasone (1ml) and a single injection into the RIGHT pterygopalatine fossa fo 4 milliliters of 0.5% Bupivacaine or Ropivacaine without epinephrine with the addition of 4 milligrams of dexamethasone (1mL) after the induction of general anesthesia. (total volume 5 ml per side)

Bupivacaine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in European Union as Marcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Approved in Canada as Sensorcaine for:

• Local anesthesia for surgery
• Acute pain management
• Spinal anesthesia

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

In a study of 96 elderly patients undergoing lower extremity surgery, adding 0.3 mg of epinephrine to bupivacaine significantly prolonged the duration of spinal anesthesia, enhancing the regression time to the L-2 level by 29%.

The addition of epinephrine also increased the motor blockade, indicating that it can effectively enhance the anesthetic effects of bupivacaine without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of increasing amounts of epinephrine during isobaric bupivacaine spinal anesthesia in elderly patients. Racle, JP., Benkhadra, A., Poy, JY., et al.[2013]

Bupivacaine with a vasoconstrictor has a shorter onset time for local anesthesia compared to bupivacaine without a vasoconstrictor, but the duration of anesthesia is longer without the vasoconstrictor.

Using bupivacaine without a vasoconstrictor resulted in lower postoperative pain levels and better blood circulation, which is beneficial for the osseointegration of dental implants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical parameters of the local anesthetic effects of bupivacaine applied with and without a vasoconstrictor in oral implantology. Duka, M., Lazić, Z., Stamatović, N., et al.[2019]

The addition of epinephrine to ropivacaine significantly increases the concentration of the anesthetic in the palatal mucosa and adjacent maxilla, enhancing its effectiveness for maxillary infiltration anesthesia.

Ropivacaine combined with epinephrine not only improves anesthetic efficacy but also reduces local blood flow, which may help prolong the duration of anesthesia compared to using ropivacaine alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epinephrine Affects Pharmacokinetics of Ropivacaine Infiltrated Into Palate. Yamashiro, M., Hashimoto, S., Yasuda, A., et al.[2018]

Bupivacaine (Marcaine) is effective for epidural analgesia in obstetrics, providing excellent sensory block with minimal impact on motor function and few side effects for both mothers and newborns.

When used at concentrations below 0.5%, and with careful dosing during labor, the risk of side effects and toxicity is low, and significant effects on newborns are rare due to the drug's high protein binding limiting its transfer across the placenta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. Seebacher, J., Chareire, F., Galli-Douant, P., et al.[2013]

The study evaluates the effectiveness and benefits of using Marcaine 0.25% combined with Epinephrine 1:200,000 as a supplementary pain relief method during rhinoseptoplasty in children.

This analysis focuses on pediatric patients, highlighting the potential for improved pain management and reduced need for additional analgesics during and after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined anaesthesia for rhinoseptoplasty in pediatric patients]. Mayorov, VM., Akolzina, IL., Batueva, VA., et al.[2013]

Ropivacaine, a long-acting local anesthetic, is safer than bupivacaine, showing less cardiovascular and central nervous system toxicity, making it a preferable option for various types of anesthesia.

While ropivacaine provides similar sensory block effects as bupivacaine, it causes less motor block, which may be beneficial in certain surgical situations, although its higher cost could limit its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ropivacaine. Owen, MD., Dean, LS.[2022]

In a study involving 30 patients, two forms of 0.5% bupivacaine hydrochloride (Anecaine and Marcaine) were compared for epidural anesthesia, revealing differences in how quickly and effectively they provided pain relief.

Anecaine showed a shorter onset of analgesia at the catheter site but a delayed effect in peripheral areas compared to Marcaine, indicating that even the same active ingredient can behave differently based on the manufacturer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical trial of the use of 2 forms of bupivacaine hydrochloride (Anecaine and Marcaine) for epidural anesthesia]. Kozlov, SP., Vashchinskaia, TV., Svetlov, VA.[2013]

In a study of 60 patients undergoing nasal surgery, levobupivacaine 0.25% provided significantly better and longer-lasting postoperative pain relief compared to lidocaine 2% with epinephrine, as indicated by lower pain scores at multiple time points post-surgery.

Patients receiving levobupivacaine also required less rescue analgesic treatment in the first 24 hours after surgery, highlighting its efficacy in managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasoconstriction and analgesic efficacy of locally infiltrated levobupivacaine for nasal surgery. Demiraran, Y., Ozturk, O., Guclu, E., et al.[2018]

Ropivacaine and bupivacaine showed similar hemodynamic and anesthetic effects in a study involving 12 dogs, with no significant differences in the onset or duration of sensory or motor block.

The addition of epinephrine did not affect the anesthetic effects but reduced the average blood concentration of the anesthetics without causing any residual adverse effects in the animals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of epinephrine on the anesthetic and hemodynamic properties of ropivacaine and bupivacaine after epidural administration in the dog. Hurley, RJ., Feldman, HS., Latka, C., et al.[2018]

In a randomized, double-blind study comparing 1% lidocaine with epinephrine to 0.5% bupivacaine with epinephrine for facial plastic surgery, bupivacaine demonstrated effective and safe anesthesia.

Bupivacaine, being a longer-acting local anesthetic, may provide better surgical conditions compared to lidocaine, making it a suitable choice for facial procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lidocaine v bupivacaine in facial plastic surgery. A clinical trial. Maimon, WN., Schuller, DE.[2022]

In a study involving 130 children aged 2 to 12 undergoing adenotonsillectomy, the administration of 0.5% ropivacaine with epinephrine did not significantly reduce postoperative pain compared to a placebo, with pain scores favoring the placebo group.

The use of ropivacaine was associated with higher rates of retching in the recovery room (41% vs 19% for placebo), indicating potential adverse effects, and it is not recommended for postoperative analgesia in this pediatric population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of perioperative administration of ropivacaine with epinephrine on postoperative pediatric adenotonsillectomy recovery. Park, AH., Pappas, AL., Fluder, E., et al.[2018]

The addition of epinephrine to ropivacaine significantly lowers the maximum concentration of ropivacaine in the bloodstream and delays the time it takes to reach this peak concentration, indicating altered absorption rates.

Epinephrine also slows the absorption rate of ropivacaine, which could enhance the duration of its effects when used in caudal blocks for anesthesia in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In children, the addition of epinephrine modifies the pharmacokinetics of ropivacaine injected caudally. Van Obbergh, LJ., Roelants, FA., Veyckemans, F., et al.[2018]

In a study of 80 children aged 6 to 14 undergoing tonsillectomy, bupivacaine, dexamethasone, and lidocaine significantly reduced postoperative pain compared to a placebo on the first day after surgery.

Lidocaine was found to be more effective than bupivacaine in reducing pain on the third postoperative day, suggesting it may be the preferred option for managing pain in the days following tonsillectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of dexamethasone, bupivacaine and topical lidocaine spray on pain after tonsillectomy. Kaygusuz, I., Susaman, N.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3846239/

Comparison of Local Anesthetic Effect of Bupivacaine ... This study demonstrates the positive effect of a combination of a dexamethasone with a bupivacaine in reducing pain and the need for analgesic drugs after ...

2. ejo.springeropen.com ejo.springeropen.com/articles/10.1186/s43163-023-00481-5

Bupivacaine improves surgical field and postoperative pain ... The present study investigated the effect of sphenopalatine block with bupivacaine in endoscopic sinus surgery. It found statistically ...

3. jacc.org jacc.org/doi/10.1016/S0735-1097%2823%2903270-9

BUPIVACAINE CAUSING PROLONGED SINUS ARREST ... We here present a case of epidural bupivacaine drip causing prolonged sinus arrests and sinus bradycardia.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10532572/

Management of Odontogenic Sinusitis: Results with Single- ... According to most studies, the effectiveness of this treatment is reported to be between 95% and 100% after unsuccessful conservative therapy.

5. journals.sagepub.com journals.sagepub.com/doi/10.2500/ajra.2009.23.3339?icid=int.sj-full-text.similar-articles.5

Effect of Intraoperative Injection of 0.25% Bupivacaine with ... Shi et al. also showed reduced bleeding during FESS when preoperative inflammation was controlled in patients with chronic sinusitis and nasal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5013234/

Reality bites: The establishment of accountable care ... The presenting symptoms often mimic chronic sinusitis, but the clinical outcomes differ greatly. Steele et al. performed a retrospective review and ...

7. go.drugbank.com go.drugbank.com/drugs/DB00297

Bupivacaine: Uses, Interactions, Mechanism of Action Recent clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with ...