Phenylephrine for Blood Loss in Burn Surgery

Overseen By Justin Gawaziuk, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Manitoba

Must not be taking: Anticoagulants, Antidepressants, Beta-blockers

Disqualifiers: Vascular disease, Arrhythmias, Hypertension, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether phenylephrine, a medication used to increase blood pressure, can reduce blood loss during burn surgery without affecting heart rate or blood pressure. Traditionally, epinephrine is used, but it can alter these vital signs. Participants will receive injections of either phenylephrine or epinephrine to determine which is more effective and safer. The trial seeks individuals with burns requiring skin grafts, covering 5-30% of their body, excluding areas like the head, hands, or feet. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on anticoagulants (except NSAIDs), monoamine oxidase inhibitors, tricyclic antidepressants, or beta-blockers.

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

Research has shown that phenylephrine, the treatment tested in this study, is generally safe for people. Phenylephrine primarily targets specific areas in the body, minimizing side effects related to heart rate and blood pressure.

Previous studies have found that phenylephrine can reduce blood loss during surgeries. For example, phenylephrine nasal drops have successfully reduced bleeding in children's surgeries. In other procedures, such as cesarean deliveries, phenylephrine has been well-tolerated and has helped maintain stable blood pressure.

This trial is in an early phase, focusing on safety and dosage. However, existing evidence from other uses of phenylephrine suggests it is likely to be well-tolerated. These findings may reassure those considering participation about the safety of phenylephrine. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for blood loss during burn surgery, like epinephrine, act by constricting blood vessels, which helps to reduce bleeding. However, phenylephrine offers a unique approach. Unlike other treatments, phenylephrine specifically targets alpha-1 adrenergic receptors, which may provide a more controlled way to manage blood loss without affecting heart rate significantly. Researchers are excited about phenylephrine because it could offer a more precise and potentially safer option for patients undergoing such surgeries.

What evidence suggests that phenylephrine might be an effective treatment for reducing blood loss in burn surgery?

Research has shown that phenylephrine, which participants in this trial may receive, helps maintain steady blood pressure during certain medical procedures. It effectively prevents low blood pressure without significantly affecting heart rate. This makes it a promising option for reducing blood loss in surgeries, such as those for burn injuries, without the heart-related side effects associated with epinephrine, another treatment option in this trial. Phenylephrine primarily works by narrowing blood vessels, aiding in bleeding control. Overall, evidence supports its potential to manage blood loss while keeping heart rate and blood pressure stable. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals with burn injuries needing skin grafts covering 5-30% of their body, excluding burns on the head, neck, hands, feet, and genitals. Participants should not have heart or vascular diseases, arrhythmias, hypertension; nor be taking anticoagulants (except NSAIDs), monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers.

Inclusion Criteria

I need surgery for a burn covering 5-30% of my body.

Exclusion Criteria

I am currently taking a Beta-blocker medication.

I have a history of high blood pressure.

I have a history of heart or blood vessel disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either phenylephrine or epinephrine solution during surgery to control blood loss

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood pressure and heart rate measurements

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Phenylephrine

Trial Overview The study tests if phenylephrine can control blood loss during skin grafting without affecting heart rate and blood pressure like epinephrine does. Patients will receive a phenylephrine solution injection at the injury site before grafting to see if it's more effective and safer than the standard epinephrine solution.

How Is the Trial Designed?

Group I: Phenylephrine Experimental Treatment 1 Intervention

20 ug/cc

Group II: Epinephrine Active Control 1 Intervention

1:1000000

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

Approved in United States as Neo-Synephrine for:

• Nasal congestion
• Hypotension
• Burn injury management

Approved in European Union as Phenylephrine for:

• Nasal congestion
• Hypotension
• Burn injury management

Approved in Canada as Sudafed PE for:

• Nasal congestion
• Hypotension

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

Published Research Related to This Trial

A study involving 270 burn patients from two centers showed that the timing of burn excision surgery for patients with amphetamine positivity is safe, regardless of whether a negative toxicology result is obtained before surgery.

The need for vasoactive support during surgery was not influenced by the toxicology results, indicating that waiting for a negative test is unnecessary and that the severity of burns (specifically >20% body surface area burned) is a more critical factor in intraoperative management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amphetamine Positivity Prior to Burn Surgery Does not Adversely Affect Intraoperative Outcomes. Rizk, N., Crawford, D., Karanas, Y., et al.[2023]

In a study of 258 pediatric burn patients undergoing various surgical procedures, there was a high incidence of hypertension (62.8%) associated with the use of tumescence containing phenylephrine during surgery.

The weight-adjusted volume of tumescence was identified as a significant predictor of intraoperative hypertension, with an odds ratio of 2.0, indicating that careful consideration is needed when using this practice in pediatric burn operations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of Tumescence in Pediatric Burn Patients Causes Significant Hypertension. Weis, HB., Meinhardt, KE., Minhajuddin, A., et al.[2020]

In a study of 70 adult patients undergoing functional endoscopic sinus surgery, both dexmedetomidine and clonidine effectively achieved controlled hypotension and improved surgical field quality without significant adverse effects.

Dexmedetomidine was found to provide better haemodynamic stability and longer post-operative analgesia compared to clonidine, making it a potentially superior choice for managing blood pressure during surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of hypotensive properties of dexmedetomidine versus clonidine for induced hypotension during functional endoscopic sinus surgery: A randomised, double-blind interventional study. Bafna, U., Sharma, P., Singhal, RK., et al.[2022]

The 'HYPOTENS' study is a national, multi-center trial comparing the effectiveness of cafedrine/theodrenaline versus ephedrine in treating intra-operative hypotension in patients aged 50 and older, as well as those undergoing Cesarean sections, ensuring real-world clinical practice conditions.

The primary goal is to evaluate how well each treatment restores blood pressure and affects post-operative outcomes, such as heart rate and delirium, with results expected to provide insights into the best management strategies for hypotensive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A non-interventional comparative study of the 20:1 combination of cafedrine/theodrenaline versus ephedrine for the treatment of intra-operative arterial hypotension: the 'HYPOTENS' study design and rationale. Eberhart, L., Geldner, G., Huljic, S., et al.[2019]

In a study of 509 parturients undergoing cesarean sections, the use of phenylephrine to treat hypotension after spinal anesthesia resulted in a serious bradycardia incidence of 11%, highlighting a significant risk associated with this medication.

The risk of serious bradycardia increased with lower pre-therapeutic heart rates, with a heart rate of 60 bpm or lower increasing the risk by nearly 13 times, indicating the importance of monitoring heart rates closely when administering phenylephrine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Phenylephrine in Antihypotensive Treatment during Spinal Anesthesia for Cesarean Section. Anusorntanawat, R., Uerpairojkit, K., Thongthaweeporn, N., et al.[2018]

In a study of 30 patients receiving endobronchial phenylephrine during bronchoscopy, there was a significant increase in mean arterial pressure (MAP) by 12 mmHg, but no patients experienced acute cardiovascular events or severe hypertension (MAP > 140).

The administration of endobronchial phenylephrine did not significantly affect heart rates, suggesting it may be a safe alternative to epinephrine for managing airway bleeding during bronchoscopy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

QA project: Hemodynamic safety of endobronchial administration of phenylephrine for control of airway bleeding by bronchoscopy. Pu, CY., Ivanick, N.[2021]

In a study of 29 children undergoing burn surgery, the use of a 1:500,000 adrenaline solution with bupivicaine significantly reduced blood loss and postoperative pain, with no patients requiring blood transfusions.

The technique resulted in a high mean graft take of 95%, demonstrating that it effectively manages pain without compromising the assessment of burn depth or graft survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous adrenaline infiltration in paediatric burn surgery. Beausang, E., Orr, D., Shah, M., et al.[2013]

In a study of 42 pediatric patients undergoing burn wound excision, the use of topical and subcutaneous epinephrine did not significantly reduce blood loss compared to a control group that did not receive epinephrine.

No complications or side effects were reported from using epinephrine, suggesting it is safe; however, the findings indicate that its routine use during total wound excision may not be necessary when combined with topical thrombin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of topical and subcutaneous epinephrine in combination with topical thrombin in blood loss during immediate near-total burn wound excision in pediatric burned patients. Barret, JP., Dziewulski, P., Wolf, SE., et al.[2019]

Hypertensive patients should avoid using adrenergic agents for blood pressure control, with nasal phenylephrine hydrochloride being the safest option among them, while pseudoephedrine may also be safe.

Ibuprofen can raise blood pressure if taken at maximum over-the-counter doses for extended periods, highlighting the need for caution with nonprescription medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonprescription drugs and hypertension. Which ones affect blood pressure? Bradley, JG.[2019]

The tumescent technique, which involves subdermal injections of epinephrine, significantly reduced total blood loss during burn surgery in a study of 20 patients, compared to a control group that did not use this method.

This technique was found to be safe, with no clinically detectable arrhythmias or changes in heart rate or blood pressure, making it an effective and easy-to-use option for minimizing blood loss in surgical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tumescent technique to significantly reduce blood loss during burn surgery. Robertson, RD., Bond, P., Wallace, B., et al.[2019]

An 81-year-old patient with severe burns covering 51% of their body was successfully treated with Suprathel(®), which is known for its pain-free application and reduced need for analgesics and sedatives.

The use of Suprathel(®) likely contributed to the patient's favorable recovery, as it minimized pain and the need for additional medications that could destabilize cardiovascular health, leading to a discharge without significant handicaps after 69 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suprathel(®) for severe burns in the elderly: Case report and review of the literature. Fischer, S., Kremer, T., Horter, J., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7487484/

Effects of continuous infusion of phenylephrine vs ... In this dataset, continuous phenylephrine infusion reduced the incidence of SA-induced hypotension, ameliorated SVR, while decreasing overall maternal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04195321?tab=history&a=2

Record History | ver. 2: 2021-08-31 | NCT04195321 PE had been the preferred vasopressor for prophylaxis against post-spinal hypotension especially in obstetric population. it was reported that PE improved the ...

3. researchgate.net researchgate.net/publication/346565593_Efficacy_and_safety_of_norepinephrine_versus_phenylephrine_infusion_for_prophylaxis_against_spinal_anesthesia-induced_hypotension_in_elderly_population_undergoing_hip_fracture_surgery_a_randomized_con

(PDF) Efficacy and safety of norepinephrine versus ... Conclusions: Both NE and PE infusions effectively prevented spinal anesthesia-induced hypotension in elderly patients undergoing hip fracture surgery. However, ...

4. bjanaesthesia.org bjanaesthesia.org/article/S0007-0912(23)00062-4/fulltext

Norepinephrine versus phenylephrine for treating ... We broadly hypothesise that use of NE infusions instead of PE infusions will improve blood flow to vital organs during the perioperative period ...

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Phenylephrine - StatPearls - NCBI Bookshelf - NIH Phenylephrine primarily acts as an alpha-1 adrenergic receptor agonist and exhibits minimal to no beta-adrenergic activity.

7. withpower.com withpower.com/trial/phase-1-hemorrhage-11-2014-8d619

Phenylephrine for Blood Loss in Burn Surgery No complications or side effects were reported from using epinephrine, suggesting it is safe; however, the findings indicate that its routine use during ...

8. clinicaltrials.gov clinicaltrials.gov/ct2/keydates/NCT01731444

Phenylephrine Tumescence for Hemostasis in Surgery ... Our goal is to find whether or not phenylephrine or epinephrine solution results in a reduction of blood loss without affecting the rest of the body.

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The Effect of Phenylephrine Nasal Drops on Surgical ... It seems that the use of nasal phenylephrine drops in pediatric cleft palate surgeries can significantly reduce bleeding and increase the quality of the ...

10. mdpi.com mdpi.com/2077-0383/14/17/6016

Effect of Prophylactic Phenylephrine Infusion Versus ... Conclusions: Prophylactic phenylephrine infusion provides superior maternal hemodynamic stability and better tolerance during cesarean delivery compared to ...