Understanding push dose pressors

Does bolus dose epinephrine or phenylephrine have a role in the prehospital environment?


Push dose pressors (PDP), in various different forms, have been in and out of my practice a number of times over the years. At the moment, they appear to be becoming increasingly trendy in emergency medicine. But their use poses many questions: Is this an evidence-based evolution or FOAMed fuelled fad? What can PDP do? Is there are role for them in the prehospital environment?


What are push dose pressors?

“Pressors” refers to vasopressors, a group of medications primarily used to vaso-constrict blood vessels and normally used to manage hypotension in patients when fluids or blood have either failed or are inappropriate. They include drugs such as norepinephrine, dopamine and vasopressin, drugs run almost exclusively by infusion.

Push dose pressors, also called bolus dose pressors, are just what the name implies; the drug is bolused to emergently manage hypotension.
Push dose pressors, also called bolus dose pressors, are just what the name implies; the drug is bolused to emergently manage hypotension. (Jonathan Lee)

Push dose pressors, also called bolus dose pressors, are just what the name implies; the drug is bolused to emergently manage hypotension. It is a practice that has a home in anaesthesia, as it can be useful to manage the transient hypotension associated with induction agents given during intubation. Other potential uses include:

  • A bridge to starting vasopressor infusions
  • In post-arrest hypotension
  • With specific shock states, such as anaphylaxis

While any number of agents could be used as PDP, the common ones are epinephrine and phenylephrine. Both are adrenergic agents that are fast acting and relatively short acting. The major difference between the two is the beta effects of the epinephrine. Both agents increase blood pressure through vasoconstriction, the result of alpha receptor stimulation. Epinephrine also has inotropic effects, increasing cardiac output by increasing both heart rate and stroke volume (the result of beta receptor stimulation).

Epinephrine vs. Phenylephrine [8]

  Epinephrine Phenylephrine
Pharmacology Targets alpha and beta receptors
Increases BP by increasing heart rate, stroke volume and vasoconstriction
Targets alpha receptors
Increases BP by vasoconstriction
Dose (q2-5min)     5-20 mcg     40-200 mcg
 
Onset 1 minute 1 minute
Duration 5-10 minutes 10-20 minutes
Adverse events Tachycardia, rebound hypertension Bradycardia, rebound hypertension

Push dose pressor evidence: The good

Phenylephrine is effective in correcting hypotension. The increase in blood pressure is dose dependent. Doses of 100mcg or less increase the mean arterial pressure between 4 mmHg and 4.8mmHg (147 and 188 patients respectively) [1,2]. Doses between 100-199 mcg increase MAP by 5.6 mmHg. Doses above 200 mcg increase MAP by 12mmHg [1].

Push dose epinephrine also improves hypotension, but has been studied less. A small series of post arrest patient reports the use of 10 mcg boluses used to restore systolic blood pressures in the 60s mmHg to systolics in the 100s mmHg in three patients [3]. A retrospective review of push dose epinephrine during critical care transport demonstrated MAP of 13 mmHg with a 10-20 mcg dosing protocol [4].

Push dose pressor evidence: The bad

PDP are potent adrenergic drugs, so the most common adverse events are hypertension and dysrhythmia [1,2,5]. The reported rates of adverse events vary widely from as low as 2.7%, to as high as 39% [1,6].

Adverse events occur more commonly with higher doses and undiluted medications [2,6]. 

Traditional thinking is that epinephrine, because of its beta stimulation, is more likely to cause tachycardia. Phenylephrine, because of its pure alpha stimulation, may result in reflex bradycardia.

However, episodes of tachycardia and bradycardia have been reported with both [6].

Certain patients, like those with poor left ventricle function, may be a high risk of severe adverse effects [2]. All vasopressors pose an extravasation risk, but PDP appear safe even through peripheral lines [2].

Push dose pressor evidence: The ugly

Two concerning trends come from the literature.

First, the quality of the evidence is not strong. Few studies examine PDP use outside of the operating room and they are all retrospective. As well as not being specific to paramedics, there is no consistency in criteria such as timing, indications, dosing and outcomes. It is difficult to make a strong recommendation from this kind of evidence.

Second, a number of concerning human factors have been raised surrounding PDP use. Human errors are common, occurring in 19% of patients receiving PDP [6]. Significant medication errors have been reported, such as one patient receiving 50 mg of phenylephrine instead of 50 mcg, a dose 1,000 times higher than intended [7].

There are also concerns that providers may circumvent standard resuscitation practices in favour of bolus-dose vasopressors and that 34% of patients did not receive a proper fluid challenge before PDP [8]. Mistakes involving dosing and usage could be a result of inexperience. Several authors have suggested that if PDP use is adopted as a result of social media or Free Online Access Medical education (FOAM), it lacks the systematic practice, training and quality assurance of traditional medical practice, increasing errors [7, 8].

Preparing bolus dose epinephrine [8]

Watch the slideshow for a demonstration of how to prepare a bolus dose of epinephrine.


What does the push dose pressor research mean for prehospital medicine?

There are many potential advantages to PDP. Have you ever been 5 minutes from the hospital with a post arrest patient who is hypotensive, or the BP gets a little soft after you sedate someone you have intubated? Imagine being able to reach for a phenylephrine preload and give the patient one or two millilitres and instantly add 10 or 15 to their systolic. With our relatively short time frames, having a treatment for hypotension that is quick and easy to prepare, with a rapid onset and short duration is incredibly appealing!

But the fast-paced prehospital environment also makes PDP very risky. Different partners, different agencies, different levels of care are all things that can lead to medication errors, a known problem with PDP. In the final analysis, two things can be said about prehospital use: First, more research is necessary – specifically outside of hospital. Second, to be used safely, it should not be done on the spur of the moment. A common language, preparations and guidelines for use will protect the patient (and the provider!) from the known risks of these potent drugs.

Read next: Understanding prehospital vasopressors: Dopamine, epinephrine or norepinephrine?


References

  1. Swenson, K., et al., Safety of bolus-dose phenylephrine for hypotensive emergency department patients. The American journal of emergency medicine., 2018. 36(10): p. 1802-1806.
  2. Kurish, B.A., et al., Safety of push-dose phenylephrine in adult ICU patients. The American journal of emergency medicine, 2020. 38(9): p. 1778-1781.
  3. Gottlieb, M., Bolus dose of epinephrine for refractory post-arrest hypotension. Canadian journal of emergency medicine, 2018. 20(S2): p. S9-S13.
  4. Nawrocki, P.S., M. Poremba, and B.J. Lawner, Push Dose Epinephrine Use in the Management of Hypotension During Critical Care Transport. Prehospital emergency care, 2019. 24(2): p. 1-8.
  5. Rotando, A., et al., Push dose pressors: Experience in critically ill patients outside of the operating room. The American journal of emergency medicine, 2019. 37(3): p. 494-498.
  6. Cole, J.B., et al., Human Errors and Adverse Hemodynamic Events Related to “Push Dose Pressors” in the Emergency Department. Journal of medical toxicology, 2019. 15(4): p. 276-286.
  7. Acquisto, N.M., R.P. Bodkin, and C. Johnstone, Medication errors with push dose pressors in the emergency department and intensive care units. The American journal of emergency medicine, 2017. 35(12): p. 1964-1965.
  8. Holden, D.P.B., et al., Safety Considerations and Guideline-Based Safe Use Recommendations for “Bolus-Dose” Vasopressors in the Emergency Department. Annals of emergency medicine, 2017. 71(1): p. 83-92.

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