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?

The standard of care for treatment of burn injury is to inject a solution of epinephrine under the skin of the injured site in order to reduce blood loss during skin grafting. This solution of epinephrine has been shown to have effects on the body outside the donor site. Some people have increases in heart rate and blood pressure. We will study the effect of a phenylephrine solution in place of an epinephrine solution to control blood loss. We think that phenylephrine will help decrease blood loss and not change blood pressure or heart rate. The injured area will be injected under the skin and a skin graft will be taken in the same way as we usually do. The only change will be the use of phenylephrine in the solution instead of epinephrine. 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.

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 phenylephrine generally safe for use in humans?

Phenylephrine is considered one of the safer nonprescription medications for people with high blood pressure, but it can cause serious bradycardia (very slow heart rate) in some cases, especially when used during spinal anesthesia for cesarean sections. ^{1 2 3 4 5}

How does the drug phenylephrine differ from other treatments for blood loss in burn surgery?

Phenylephrine is unique because it is an alpha-1 agonist that can be used to control blood loss by constricting blood vessels, which is different from other treatments like epinephrine that are more commonly used. It is also noted for its potential to cause hypertension (high blood pressure) when used in burn surgeries, which is a consideration not typically associated with other treatments. ^{2 6 7 8 9}

What data supports the effectiveness of the drug Phenylephrine for reducing blood loss in burn surgery?

The tumescent technique, which involves the use of epinephrine (a drug similar to phenylephrine), has been shown to decrease blood loss during burn surgery, suggesting that phenylephrine might also be effective in this context. ^{1 3 6 10 11}

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]

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]

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]

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 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]

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 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]

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]

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]

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 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]

Citations

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

Amphetamine Positivity Prior to Burn Surgery Does not Adversely Affect Intraoperative Outcomes. [2023]

2. England 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. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Suprathel(®) for severe burns in the elderly: Case report and review of the literature. [2017]

4. India 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. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

The tumescent technique to significantly reduce blood loss during burn surgery. [2019]

6. Thailand pubmed.ncbi.nlm.nih.gov

Safety of Phenylephrine in Antihypotensive Treatment during Spinal Anesthesia for Cesarean Section. [2018]

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

Subcutaneous adrenaline infiltration in paediatric burn surgery. [2013]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Netherlands 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. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Administration of Tumescence in Pediatric Burn Patients Causes Significant Hypertension. [2020]

11. England pubmed.ncbi.nlm.nih.gov

QA project: Hemodynamic safety of endobronchial administration of phenylephrine for control of airway bleeding by bronchoscopy. [2021]