Phenylephrine vs Norepinephrine for Blood Pressure Management During Surgery

Enrolling by invitation at 11 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: The University of Texas Health Science Center, Houston

Must be taking: Antihypertensives

Disqualifiers: Dementia, Carotid surgery, Intracranial surgery, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: During surgery

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines two medicines, phenylephrine and norepinephrine, to determine their effectiveness in managing blood pressure during major surgeries. The goal is to identify which medicine maintains optimal blood pressure levels more effectively. Suitable participants have a history of conditions such as diabetes or heart disease, plan to stay in the hospital overnight after surgery, and are undergoing major surgery lasting at least two hours. Participants will receive one of the two medicines at random to manage their blood pressure during the operation. As a Phase 4 trial, this research involves FDA-approved treatments and aims to understand how they benefit a broader patient population.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since participants must be chronically taking at least one anti-hypertensive medication, it seems you may continue those medications.

What is the safety track record for these treatments?

A previous study found phenylephrine effective in maintaining steady blood pressure during surgeries, with patients generally tolerating it well. Most patients did not experience serious side effects, and common side effects, such as headache or nausea, were mild.

Research has shown that norepinephrine might better maintain stable blood pressure with less impact on heart rate. It has reduced some post-surgery complications, like urinary tract infections. However, as with any treatment, some patients might experience mild side effects.

Both treatments control blood pressure during surgeries and have been studied for safety. Since this trial is in phase 4, both drugs are already approved for other uses, indicating they are generally considered safe. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using phenylephrine and norepinephrine for blood pressure management during surgery because these treatments allow for precise control of blood pressure through infusion rates, which is crucial during operations. Unlike some existing medications that might not offer the same level of targeted blood pressure control, these drugs can be adjusted to maintain specific intraoperative mean arterial pressures (MAP), ensuring better patient stability. Additionally, the comparison between routine and tight blood pressure management with both drugs could provide insights into optimizing surgical outcomes and minimizing potential risks associated with blood pressure fluctuations during surgery.

What evidence suggests that this trial's treatments could be effective for blood pressure management during surgery?

This trial will compare the effectiveness of phenylephrine and norepinephrine for managing blood pressure during surgery. Research has shown that phenylephrine, administered to some participants, can lower the risk of low blood pressure during spinal anesthesia and improve blood flow. Norepinephrine, given to others, is known to stabilize blood pressure and enhance blood flow to vital organs. Both medications effectively prevent blood pressure drops after procedures like spinal blocks during surgeries. Overall, these treatments reliably maintain steady blood pressure when needed most. ^{1 5 6 7 8}

Who Is on the Research Team?

Daniel I Sessler, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for adults over 45 facing major noncardiac surgery lasting at least 2 hours, with certain health risks like heart disease or diabetes. They must be on blood pressure medication and able to have their blood pressure closely monitored during surgery.

Inclusion Criteria

I am over 65, have had vascular surgery, or have certain health conditions.

I am scheduled for a major surgery that is not heart-related and will last at least 2 hours.

I have a serious health condition that affects my daily life.

Exclusion Criteria

Have language, vision, or hearing impairments that may compromise cognitive assessments

I am scheduled for brain surgery.

I am scheduled for surgery on my carotid artery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to norepinephrine or phenylephrine infusion to maintain intraoperative MAP

During surgery

Follow-up

Participants are monitored for major perfusion-related complications and postoperative delirium

30 days

What Are the Treatments Tested in This Trial?

Interventions

• Norepinephrine
• Phenylephrine

Trial Overview The study tests whether Phenylephrine or Norepinephrine is better at maintaining target blood pressure during major surgeries in patients who are already part of the GUARDIAN trial.

How Is the Trial Designed?

Group I: Routine Blood Pressure Management with Phenylephrine Active Control 2 Interventions

Routine blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Group II: Routine Blood Pressure Management with Norepinephrine Active Control 2 Interventions

Routine blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Group III: Tight Blood Pressure Management with Phenylephrine Active Control 2 Interventions

TIiht blood pressure control with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial

Group IV: Tight Blood Pressure Management with Norepinephrine Active Control 2 Interventions

Tight blood pressure control with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

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]

Norepinephrine significantly reduces the incidence of bradycardia and reactive hypertension compared to phenylephrine in pregnant women undergoing elective cesarean delivery under spinal anesthesia, based on a systematic review of 12 studies.

Both norepinephrine and phenylephrine show similar rates of hypotension, nausea, and vomiting, indicating that norepinephrine is a safe and effective alternative for maintaining blood pressure without adverse effects on maternal or fetal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of prophylactic norepinephrine and phenylephrine in spinal anesthesia for cesarean section: A systematic review and meta-analysis with trial sequential analysis. Liu, P., He, H., Zhang, SS., et al.[2022]

In a study of 86 pre-eclamptic women undergoing cesarean sections, both phenylephrine and norepinephrine were found to be equally effective in treating postspinal hypotension, with no significant differences in neonatal outcomes as measured by umbilical artery pH.

However, the phenylephrine group experienced fewer hypotensive episodes and lower heart rates compared to the norepinephrine group, suggesting it may be a safer option in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised double-blind comparison of phenylephrine and norepinephrine for the management of postspinal hypotension in pre-eclamptic patients undergoing caesarean section. Mohta, M., R, L., Chilkoti, GT., et al.[2022]

Topical phenylephrine can cause severe hypertension due to its action on alpha-adrenergic receptors, which is a significant safety concern, especially in pediatric patients.

In this case, a pediatric patient experienced acute pulmonary edema after receiving a large dose of phenylephrine followed by beta-blockers, highlighting the potential risks of combining these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary edema following phenylephrine intranasal spray administration during the induction of general anesthesia in a child. Son, JS., Lee, SK.[2022]

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]

A review of 12 clinical studies found that intranasal phenylephrine appears to be safe for patients with controlled hypertension, based on one double-blind randomized trial.

The evidence regarding the safety of other sympathomimetic decongestants like phenylpropanolamine and pseudoephedrine in hypertensive patients is limited and unclear, suggesting that the belief they are unsafe is not strongly supported by research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are oral decongestants safe in hypertension? An evaluation of the evidence and a framework for assessing clinical trials. Radack, K., Deck, CC.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11086183/

Evaluation of the early use of norepinephrine in major ... ... blood pressure management is highly beneficial in terms of postoperative outcomes and mortality. This study led to the implementation of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0007091225001953

Continuous versus bolus norepinephrine administration to ... This RCT tested the hypothesis that giving norepinephrine via infusion vs repeated manual boluses reduces hypotension within 15 min of inducing general ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05335954

NCT05335954 | Therapeutic Study Evaluating the Efficacy ... The hypothesis of the study is that noradrenaline initiated during preoxygenation can reduce the incidence of hypotension during induction of general ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34872102/

A Safety and Feasibility Pilot Randomized Controlled Trial The study drug infusion was titrated to achieve a minimum systolic blood pressure target, preselected within 10% of baseline value and within ...

5. nature.com nature.com/articles/s41598-023-48178-2

Norepinephrine prevents hypotension in older patients ... We hypothesized that continuous infusion of norepinephrine could effectively prevent hypotension in older patients undergoing hip surgery under spinal ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10863471/

Association Between Intraoperative Noradrenaline Infusion ... Intraoperative noradrenaline administration reduces postoperative urinary tract infection, and does not increase other postoperative complications and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01536470

Intraoperative Noradrenaline to Control Arterial Pressure ... The primary objective of the study is to compare two strategies of intraoperative blood pressure management in high-risk surgical patients: 1- Continuous ...

8. bjanaesthesia.org bjanaesthesia.org/article/S0007-0912(24)00671-8/fulltext

Association of intraoperative hypotension and cumulative ... Intraoperative hypotension is associated with acute kidney injury (AKI). Clinicians thus frequently use vasopressors, such as norepinephrine ...