IV Pressors In The Treatment Of Life-Threatening Hypotension: A Minicourse

Posted on May 27, 2026 by Tom Wade MD

Today I review a series of posts on IV Pressors In The Treatment Of Life-Threatening Hypotension. Here are links to the posts and brief summaries.

Because I have mostly practiced in critical access hospitals, my focus has always been how can we keep the critically ill patient alive and potentially salvageable until the helicopter arrives.

And the immediate appropriate treatment of  shock is an important topic for clinicians working in critical access hospitals.

It is critical to defend the Mean Arterial Pressure (MAP). Do something immediately (meaning vasopressors) when the MAP goes low while you figure out the cause of the problem and treat it.*

*See Resource (4) EMCrit 201 – Deeper on Vasopressors and Athos 3 with Mink Chawla
June 12, 2017 by Scott Weingart

So first I’ll review (1) PulmCrit- Epinephrine challenge in sepsis: An empiric approach to catecholamines April 25, 2016 by Dr. Josh Farkas, which has an outstanding approach to the use of vasopressors. I’ve reviewed this post before in Practical Vasopressors And More In Septic Shock – Help From Drs. Farkas, Weingart, and Others Posted on June 17, 2017 by Tom Wade MD but it fits with (2) so I’ll review it again.

Then I’ll review (2) PulmCrit- High dose vasopressors: Never surrender
June 4, 2018 by Josh Farkas

And finally I’ll link to Dr. Weingart’s podcast (3) Podcast 87 – Mind of the Resuscitationist: Stop Points November 26, 2012.

As always these extracts are my study notes to help fix Dr. Farkas’ posts in my mind.

Here are  extracts from (1) PulmCrit- Epinephrine challenge in sepsis: An empiric approach to catecholamines April 25, 2016 by Dr. Josh Farkas [but review the entire post – note to myself]:

Introductory case
A 55-year-old woman was admitted with toxic shock syndrome. Her norepinephrine requirement was labile, fluctuating between 15 mcg/min and 30 mcg/min. Bedside echocardiogram showed a dilated inferior vena cava without respiratory variability, and a normal ejection fraction. On examination her extremities were cool and her urine output was marginal.

Epinephrine 4 mcg/min was added, with an improvement in blood pressure, perfusion, and urine output. She reported feeling better, and over the next hour the norepinephrine was weaned off. Her lactate increased from 2 mM to 6 mM. The ICU team was pleased with this epinephrine-induced rise in lactate, a positive prognostic sign. Sure enough, she continued to improve and was weaned off vasopressors entirely over the next 18 hours.

Foundational concept #1: Vasopressors don’t always behave according to the textbook.

Individual patients vary considerably in how they respond to vasopressors.  Two factors in particular may contribute to this variability.

Endogenous sympathetic response

Variable end-organ sensitivity

The differences between various catecholamines results from the ratio of stimulation of alpha-receptors vs. beta-receptors (figure below). However, patients vary in the responsiveness of their heart and vasculature. For example, reduced cardiac sensitivity to beta-agonists is common in advanced sepsis, due to receptor down-regulation. Refractory vasodilation is also well described.

Relative differences in end-organ sensitivity affect the way vasopressors function. For example, norepinephrine typically has predominantly vasoconstrictive effects with a small amount of isotropy. In a patient with reduced cardiac responsiveness to beta-agonist stimulation, this could cause the vasoconstrictive effects of norepinephrine to predominate even further. In this scenario, norepinephrine would have nearly the same effect as a pure vasoconstrictor such as phenylephrine:

Foundational concept #2: Norepinephrine and epinephrine are both evidence-based vasopressors for use in sepsis.

Although norepinephrine is typically first-line in septic shock, epinephrine is also a reasonable choice.

Groups of patients respond similarly to norepinephrine vs. epinephrine, but this doesn’t mean that individual patients will have the same response to either drug (an assumption exemplifying the flaw of averages).  On the contrary, it is likely that some patients respond better to norepinephrine, while other patients respond better to epinephrine.

Groups of patients respond similarly to norepinephrine vs. epinephrine, but this doesn’t mean that individual patients will have the same response to either drug (an assumption exemplifying the flaw of averages). On the contrary, it is likely that some patients respond better to norepinephrine, while other patients respond better to epinephrine.

Foundational concept #3: The epinephrine hyper-responsive patient

Average responsiveness to norepinephrine vs. epinephrine

On average, equal doses of norepinephrine or epinephrine are required to achieve blood pressure targets.

The phenomenon of epinephrine hyper-responsiveness

Some patients seem to be especially responsive to epinephrine, with the following features: (3)

  • They don’t respond very well to norepinephrine, often requiring high doses of norepinephrine. Sometimes the norepinephrine dose will fluctuate widely, suggesting that the norepinephrine isn’t very effective. While on norepinephrine, they may have poor perfusion.
  • They are very responsive to epinephrine. For example, the image below shows a patient who was transitioned from 30 mcg/min of norepinephrine to 6 mcg/min of epinephrine. Following transition to epinephrine, these patients often have improved perfusion.
  • There is often an increase in lactate levels following the initiation of epinephrine, which is a positive prognostic sign (discussed below)(4).

Why are some patients epinephrine hyper-responsive?

The physiology of epinephrine hyper-responsiveness is likely multifactorial, perhaps with varying contributions from the following factors.

Factor #1: High endogenous alpha-adrenergic tone? A patient who is already quite vasoconstricted may respond poorly to additional exogenous alpha-adrenergic stimulation.

Factor #2: Relative bradycardia? Occasional patients in septic shock are encountered who have inappropriately normal heart rates (e.g. 50-70 b/m), even despite being on norepinephrine. This could relate to a deficiency of endogenous beta-adrenergic tone, or perhaps an over-reactive carotid baroreceptor response to alpha-adrenergic stimulation (5). Regardless, such patients might benefit from the stronger chronotropic effects of epinephrine.

Factor #3: Occult systolic failure? An occasional septic patient has a normal ejection fraction, but after starting norepinephrine the ejection fraction drops. Why? Such patients have likely had systolic dysfunction all along. Initially their untreated vasodilation reduced their afterload, increasing their ejection fraction. Norepinephrine normalizes the afterload, thereby unmasking this systolic dysfunction.

Patients with occult systolic failure may experience less improvement in blood pressure in response to norepinephrine. In extreme cases, their cardiac output could even drop as the norepinephrine is titrated up (6):

Observational studies show that when patients with septic shock are treated with norepinephrine, some experience a decreased cardiac output (Hamzaoui 2010, Meadows 1988, Martin 1999).

Evaluating epinephrine responsiveness: The epinephrine challenge

Baseline hemodynamics and echocardiography provide static hemodynamic variables which usually cannot predict epinephrine responsiveness (7).  Thus, the only way to be certain of how a patient will respond to epinephrine is to administer epinephrine.  One potential exception might be a patient with marked tachycardia and a hyperkinetic ventricle.

The best way to determine epinephrine responsiveness may be to simply start a low dose epinephrine infusion (e.g. 4 mcg/min)(8). The patient’s response to epinephrine may be judged based on clinical variables (table below). Although measuring cardiac output could also be performed, this is not my usual clinical practice (9).

Above is one possible approach to titrating vasopressors in septic shock.  Vasopressin is started earlier than in most algorithms (10).  More notable features of the algorithm are:

  • Epinephrine is trialed relatively early (before the patient is frankly “failing” norepinephrine).
  • Many algorithms involve sequential addition of different vasopressors.  However, it may also be useful to down-titrate vasopressors to which the patient responds poorly.

Here is an extract of (2) PulmCrit- High dose vasopressors: Never surrender
June 4, 2018 by Josh Farkas but you must read the whole post.

And finally after completely reviewing Resource (2)

This post is for use by only the most expert of clinicians  – in a critical access hospital I would only consider using this strategy with help and agreement from the critical care specialist at the tertiary care where the patient is being transferred to.

Caution about using high-dose vasopressors

The above studies [reviewed in Dr. Farkas post] show a strong correlation between high-dose vasopressors and mortality.  This is probably because the need for high-dose vasopressors correlates with greater disease severity, not because high-dose vasopressors cause mortality.  Nonetheless, the need for high-dose vasopressors should never be taken lightly.   This is generally a treatment of last resort.  Whenever high-dose vasopressors are needed, meticulous evaluation is needed (ideally including echocardiography) with particular attention to the following questions:

  • Is blood pressure truly that low?  Consider placement of a femoral or axillary arterial catheter to transduce central arterial pressure.
  • Is there a role for volume resuscitation or inotropic support?  Some patients who respond poorly to norepinephrine may do better with epinephrine (see: epinephrine challenge).
  • Is there occult right ventricular failure that could be treated (e.g. with pulmonary vasodilation)?
  • Is there low cardiac output and impaired perfusion (e.g. mottling)? In that case, additional vasoconstriction may simply aggravate matters.
  • Is there a failure of surgical source control or incorrect antibiotic selection?
  • Is the patient on adequate adjunctive therapy (stress-dose steroid, possibly thiamine/ascorbate)?
  • Is there a pH abnormality that merits correction (e.g. treatment of hyperchloremic metabolic acidosis with bicarbonate)?
  • Is there autoPEEP or elevated intra-abdominal pressure which is impairing venous return?
  • Is the patient on any medications which may be reducing the blood pressure (e.g. propofol, dexmedetomidine)?
  • Is there clinically significant hypocalcemia?

Having reviewed Resources (1) and (2) above it is a good idea to listen to Dr. Weingart’s podcast Resource (3) Podcast 87 – Mind of the Resuscitationist: Stop Points  [things to consider when you need to add a second vasopressor] November 26, 2012. This podcast reinforces with a clinical case, the points that Dr. Farkas made above  in his posts.

Here are some excerpts from Dr. Weingart’s Stop Points podcast:

When you’re getting ready to add a second vasopressor, these are the points to consider and things to do:

Stop Points

  • Volume – [Are you sure the patient is adequately volume loaded]
  • Calcium – [Check the ionized calcium as catecholamines won’t work in the face of low ionized calcium]
  • Bleeding – [Is there occult bleeding that you haven’t diagnosed yet]
  • Adrenal Insufficiency – [Consider stress dose of IV Solu-Cortef]
  • Hypothyroidism – [See Myxedema Coma or Crisis
    Updated: Mar 27, 2017 and Myxedema Coma or Crisis Treatment & Management Updated: Mar 27, 2017  from emedicine.medscaape.com.
  • Wacky stuff [Listen to the podcast]

Next Dr. Weingart states you should perform a RUSH exam [Link is to his show notes and podcast – definitely want to review this.

Resources:

(1) PulmCrit- Epinephrine challenge in sepsis: An empiric approach to catecholamines April 25, 2016 by Dr. Josh Farkas

(2) PulmCrit- High dose vasopressors: Never surrender
June 4, 2018 by Josh Farkas

(3) Podcast 87 – Mind of the Resuscitationist: Stop Points
November 26, 2012 by Scott Weingart

(4) EMCrit 201 – Deeper on Vasopressors and Athos 3 with Mink Chawla
June 12, 2017 by Scott Weingart

Links To EM Quick Hits 18 Conservative Management Pneumothorax, Microdosing Buprenorphine, Practical Use of CRITOE, Canadian TIA Score, Pediatric Surviving Sepsis Guidelines, Safety of Peripheral Vasopressors Posted on September 29, 2021 by Tom Wade MD

Topics in this EM Quick Hits podcast

Justin Morgenstern on watchful waiting for large spontaneous pneumothoraces (0:44)

Michelle Klaiman on mirco-dosing buprenorphine for opiate use disorder (5:17)

Arun Sayal on the practical application of CRITOE in pediatric elbow fractures (10:45)

Jeff Perry on The Canadian TIA Score (19:37)

Sarah Reid on updated pediatric surviving sepsis guidelines (25:59)

Salim Rezaie (Best of REBELEM) on safety of vasopressor administration through peripheral IVs (33:40)

This entry was posted in EM Quick Hits, Vasopressors. Bookmark the permalink.

And here is the timeline for the podcast:

Topics in this EM Quick Hits podcast

Anand Swaminathan on a simple approach to status epilepticus  (0:31)

David Juurlink on codeine and tramadol interactions: nasty drugs with nastier drug interactions (8:37)

Brit Long on DOACS in patients with malignancy: which patient’s with cancer can be safely prescribed DOACs? (13:05)

Ian Stiell on atrial fibrillation rate vs rhythm control controversy (20:55)

Justin Morgenstern on peripheral vasopressors: safe or unsafe? (26:39)

Michelle Klaiman on motivational interviewing that makes a difference to patient’s lives (33:56)

This entry was posted in EM Quick Hits, Emergency Medicine Cases. Bookmark the permalink.

Note: In addition to today’s resource, every clinician responsible for emergency care should purchase and carefully review PressorDex®: Critical Care Medications Guide, 5th Edition, 2024. It is an outstanding resource to always have immediately available.

EM Note is an outstanding podcast series. You can access the complete list (currently 683) at EM Note Podcast.

Today, I review, link to, and embed EM Note‘s Vasopressors and Inotropes for Shock Management.

All that follows is from the above resource.

 

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Vasopressors and Inotropes for Shock Management

Watch On YouTube

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Vasopressors and Inotropes for Shock Management

Dec 29, 2025 EMNote Podcast
📧 EM Note Newsletter https://forms.gle/8boToiKDXVE3V8U19 Signup to get free weekly PDF via email. PS: Please join our membership for more perks (members can request for specific PDF file by posting in the EM Note YouTube Membership section).
Homepage: EMNote.org ■
🚩Membership: https://tinyurl.com/joinemnote
🚩ACLS Lecture: https://tinyurl.com/emnoteacls
This lecture outlines the pharmacological strategies used to treat hemodynamic instability and shock by restoring adequate blood flow to vital organs. It categorizes life-saving medications into vasopressors, which constrict blood vessels to raise blood pressure, and inotropes, which enhance the heart’s pumping strength. By targeting specific cellular receptors, these drugs address different medical emergencies ranging from septic shock to heart failure. The source emphasizes that norepinephrine is the primary treatment for most cases, while other agents like vasopressin or dobutamine are selected based on the patient’s unique needs. Finally, the text highlights critical safety protocols, such as utilizing central venous access and monitoring for tissue necrosis caused by accidental drug leakage.

 

This entry was posted in EM Note, Vasopressors, Vasopressors and Inotropes for Shock Management. Bookmark the permalink.

Today I review and excerpt from “The Safety and Efficacy of Push Dose Vasopressors in Critically Ill Adults“* from RebelEM. June 8, 2023. Written by Courney Knieriem, MD
REBEL Crit, REBEL EM
Medical Category: Cardiovascular, Resuscitation

*Courney Knieriem, MD, “The Safety and Efficacy of Push Dose Vasopressors in Critically Ill Adults”, REBEL EM blog, June 8, 2023. Available at: https://rebelem.com/the-safety-and-efficacy-of-push-dose-vasopressors-in-critically-ill-adults/.

All that follows is from the above resource.

Background Information:

Acute Hypotension is associated with increased morbidity and mortality. Continuous vasopressor infusions have previously been the mainstay of treatment. However, peripherally dosed push dose pressors, (PDPs), are beginning to be administered more frequently for management of acute hypotension.1-4 The PDPs, phenylephrine and epinephrine, result in vasoconstriction and increased cardiac contractility. They can be associated with side effects such as reflex bradycardia, decreased stroke volume in phenylephrine, tachycardia and hypertension associated with epinephrine. The authors of this trial sought out to describe PDP and assess the efficacy and safety of PDP use in the management of hypotension. Prior literature primarily focused on safety and medication errors, and while this study did the same, they also assessed variables associated with PDP response.

Paper: Singer S, et al. The safety and efficacy of push dose vasopressors in critically ill adults. Am J Emerg Med. 2022 Sep 5. PMID: 36108346

Clinical Question:

What is the efficacy and safety of peripherally administered push dose pressors for the treatment of acute hypotension?

What They Did:

  • Single-center, retrospective cohort study performed at a single academic medical center
  • Cohorts were analyzed according to PDP response (responders vs non-responders)
  • Analyzed PDP administration in the setting of acute hypotension. Assessed clinical practice, outcome, length of stay, safety, and efficacy of both phenylephrine and epinephrine peripherally administered through a push dose.
    • Epinephrine – 10ug/mL, 10mL syringe*
    • Phenylephrine – 100ug/mL, 10mL syringe*
    • Phenylephrine bolus doses from 100-200ug and epinephrine 10-20ug administered every 2-5 minutes pursuant to provider order

*The study used premixed syringes which the authors strongly recommend.

Inclusion Criteria:

  • Adults age >18 years old
  • Received at least one bolus dose of phenylephrine or epinephrine pre-filled syringes

Exclusion Criteria:

  • Operating room patients
  • Patients with any of the following:
    • Priapism
    • Epistaxis
  • Missing vital signs within 1 hour of PDP dose
  • Received both Epinephrine (Epi), and Phenylephrine (PE) were excluded

Outcomes:

Primary 

  • Efficacy, defined as a systolic BP increase of 25% post PDP administration
  • Responder – Episodes that achieved a > 25% increase in SBP were classified as responders
  • Nonresponder – Episodes that achieved a < 25% increase in SBP were classified as responders

Safety

  • HTN (BP>180/110) within 1 hour PDP
  • Bradycardia within 1 hour of Phenylephrine
  • Tachycardia (>30% increase in HR from baseline within 1 hr of epi)

Additional Outcomes

  • Delta of SBP/DBP 1 hour pre/post
  • Requirement of a dose increase of continuous vasopressor support within 4 hours of PDP administration
  • Cardiac arrest within 1 hour of PDP
  • ICU/Hospital length of stay
  • In hospital mortality
  • Extravasation
  • Severe adverse events such as:
    • Administration of atropine for bradycardia within 1 hr of phenylephrine
    • Hypertension requiring an anti-hypertensive within 1 hr of epinephrine

Results:

  • 1727 patients (n=2183 PDP episodes) were included in the final analysis.
  • 3175 patients evaluated for inclusion however 1348 excluded due to PDP being given in OR as the main reason for exclusion
  • Median dose of phenylephrine = 400mcg (Range 200 to 888mcg) and Epinephrine = 50mcg (Range 20 to 100mcg)
  • Primary outcome achieved in 71.8% (102) pts in the epi group and 55.9% (1140) pts in the phenylephrine group

Critical Results:

 

  • The odds ratios in the chart above apply to phenylepinephrine responders, the following values apply to non-responders
    • Receipt of crystalloid boluses: OR 0.0639; 95% CI 0.432 to 0.946
    • Receipt of PRBCs: OR 0.303; 95% CI 0.099 to 0.935
  • Phenylepinephrine responders more frequently received pRBC, crystalloid boluses and sedation
  • No serious adverse events occurred in the epinephrine cohort
  • History of CHF associated with response to epinephrine (OR 11.889, 95% CI 1.030 – 137.257)
  • Neither cohort had any adverse extravasation requiring phentolamine or terbutaline

Discussion:

  • There is a recent “push” to utilize “Push dose pressors” as the correction of acute hypotension in a variety of clinical scenarios. This study chose a relevant topic to analyze that could influence acute management in the ED and has a fairly larger sample size of patients to do so.
  • Phenylephrine and epinephrine are two of the most common vasopressors and more studies need to be done to analyze long term effects of the two.
  • The retrospective design of this study omitted assessment of ventricular dysrhythmias related to push dose pressor administration, as they were reliant on information in the EMR. Adrenergic agonists certainly have the potential to affect sympathetic sequelae, and adverse events. Further studies are needed to assess the prevalence of cardiac dysrhythmia.
  • Overall, 56% of patients that received phenylephrine and 70% of patients that received epinephrine achieved a 25% increase in SBP. Both agents improved SBP, DBP, and MAP. The increase in metrics was expected, however, it is worth noting that epinephrine seems more effective……..
  • Not so fast…15.5% in phenylephrine group and 27.5% in the epi group received continuous vasopressor infusions within 50 min prior to PDP and 46.3% in the phenylephrine group and 74.6% in the epi group received continuous vasopressor infusions within the 60min after PDP administration….both would favor epi seeming more effective
  • Administration of crystalloid boluses and PRBCs were associated with a lack of response to phenylephrine. This could indicate that hypotension may have been adequately managed with preload expansion. Another study showed similar results, >30mL/kg of fluids prior to phenylephrine administration received fewer and lower cumulative phenylephrine dose.5, 6 These findings highlight the importance of adequate preload expansion in the treatment of acute hypotension.
  • Administration of any sedative was predictive of phenylephrine response. This could be useful in RSI, where sedatives are frequently used before intubation. The mechanism of peri intubation hypotension is multifactorial including vasoplegia, loss of adrenergic tone, worsening acidosis due to apnea, and reduced venous return after initiation of positive pressure ventilation
  • Epinephrine concentrations diluted at bedside showed less hemodynamic events. This highlights the importance of pre-made PDP syringes andproper labeling, storage, and staff education for PDPs.
  • The low adverse event rate that occurred in this study should emphasize the importance of premade PDP syringes, proper labeling, storage, and staff education when using PDPs
  • Caution should be taken when utilizing PDPs in patients with cardiac dysfunction or congestive heart failure. Lastly, bedside dilutions of epinephrine had less efficacy thus highlighting the importance of pre-made syringes, proper labeling, storage, and staff education regarding PDPs.
  • In regards to the role of PDP in patients with cardiac dysfunction and CHF, this study found no differences in response to either agent in patients with cardiac dysfunction. Interestingly, CHF history was associated with a positive response to epinephrine. Unfortunately, due to the small sample size of the epinephrine cohort, further studies are warranted to determine the effects of cardiac dysfunction on PDP response.
  • Caution should be taken when utilizing PDPs in patients with cardiac dysfunction or congestive heart failure. Lastly, bedside dilutions of epinephrine had less efficacy thus highlighting the importance of pre-made syringes, proper labeling, storage, and staff education regarding PDPs.

Author’s Conclusions:

This study demonstrates that PDP phenylephrine and epinephrine are safe and efficacious in treating the acute hypotensive period

Our Conclusion:

Although conclusions on mortality and clinical outcomes cannot be definitively made, this retrospective study demonstrates the safe and efficacious use of PDP in the acute hypotension period with no severe adverse effects.

Potential to Impact Current Practice:

Initiatives should be made at the institution level to develop in-service education sessions, policies and procedures for the safe administration of PDPs in the acute hypotensive period. If pre-made syringes are not financially feasible then the creation of these medications should be done by a dedicated emergency department pharmacist.

References:

  1. Singer S, et al. The safety and efficacy of push dose vasopressors in critically ill adults. Am J Emerg Med. 2022  2022 Sep 5. PMID: 36108346
  2. Cole JB, et al. Human Errors and Adverse Hemodynamic Events Related to “Push Dose Pressors” in the Emergency Department. J Med Toxicol. Epub 2019 Jul 3. PMID: 31270748
  3. Maheshwari K, et al. The relationship between ICU hypotension and in-hospital mortality and morbidity in septic patients. Intensive Care Med. 2018;44(6):857–67. PMID: 29872882
  4. Jones AE, et al. Emergency department hypotension predicts sudden unexpected in-hospital mortality: a prospective cohort study. Chest. 2006;130(4):941–6. PMID: 17035422
  5. Holler JG, et al. Nontraumatic hypotension and shock in the emergency department and the prehospital setting, prevalence, etiology, and mortality: a systematic review. PLoS One. 2015;10(3):e0119331. PMID: 25789927
  6. Schwartz MB, et al. The impact of push-dose phenylephrine use on subsequent preload expansion in the ED setting. Am J Emerg Med. 2016; PMID: 27720568

For More Thoughts on This Topic Checkout:

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter: @srrezaie)

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