RX Pad: When push comes to shove

Push dose pressor considerations in the ED.

It is common to have patients arrive hypotensive to the ED, and some of the initial thoughts by healthcare providers are, “What is the cause of their hypotension?” and “What can we do to make it stop?” We know that hypotension is associated with poor outcomes, resulting in decreased perfusion of vital organs and progressive hemodynamic instability, which can ultimately lead to cardiovascular collapse and death if not treated in a timely manner.[^{1, 2]}

Background

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There are many methods to treat hypotension, including volume repletion from IV fluids and/or blood products, vasopressors and removal of offending agents. An important aspect to consider when selecting hypotension treatment options is the underlying cause, as some options may be more appropriate than others. Hypotensive patients are a heterogeneous population, with low blood pressures resulting from disease states such as sepsis, hypovolemia and cardiac arrhythmias. It may also be transiently seen post-intubation and in those patients undergoing procedural sedation.

One method of treating low blood pressure is through the use of vasopressors in those patients who have been appropriately fluid resuscitated. More traditionally, these medications have been administered as continuous intravenous (IV) infusions and titrated to goal mean arterial pressures (MAP). However, for the better part of a decade, the use of push dose pressors (PDP) in the ED has been a hot topic.

The push for PDP

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PDPs are vasopressors compounded at low concentrations in a syringe and intermittently administered via IV push every few minutes as needed to achieve goal MAP. While there is a plethora of literature supporting PDP in the OR, with many studies focusing on spinal anesthesia, there are very limited data in the ED and inpatient settings.[^3-9] On the other hand, it has been widely supported by free open access medical education (FOAMed), thus the use of PDP has spread rapidly throughout many emergency departments.[^10-11]

Initial support for their use was very positive, with subsequent papers published in the last couple of years highlighting some of the negative consequences of using PDP in the ED environment. This has led us to ask a couple of very reasonable questions like, “What are the risks and benefits of using PDP?” and “When should we consider them in our ED patients?” (Table 1)

Some of the proposed benefits of PDP is the ability to mix and administer them faster than the time it takes to prepare or receive an infusion from pharmacy, prime tubing, find a pump and program it. One of the most frustrating things is to get ROSC on a cardiac arrest patient, only to have them code shortly thereafter while the team is trying to get a vasopressor infusion started.

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Many have proposed that PDP can be a bridge to a vasopressor infusion, allowing ample time to initiate infusions appropriately with fewer complications.[^{3, 5]} PDP may also be helpful in patients with transient hypotension, specifically during intubation or procedural sedation.[^{3, 4]}

Drawbacks

With the growing popularity of PDP in the ED setting, we have also begun to observe some negative sequelae. Several of the recent ED and inpatient articles have reported adverse events associated with inappropriate dilution, resulting in 10-100-fold overdoses. Many of these cases have led to significant cardiac arrhythmias, severe hypertension, myocardial ischemia/infarction and cardiac arrest.[^{9, 12]}

Some of the theories behind these overdoses are a lack of premixed products necessitating quick admixture during high-stress situations, a lack of closed looped communication, as well as a lack of understanding or experience by those preparing PDP products. To complicate matters further, common vasopressors used are manufactured in various concentrations that require significant dilution to achieve safe PDP concentrations.

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What do we do with this information? Should we choose to avoid PDP use in ED patients altogether? That’s not necessarily the right answer, but these data have appropriately caused some of us to ask, “What can we do differently?”

Table 1: Proposed PDP benefits and risks

One of the first steps to answering this question is to truly understand the medications used in PDP preparations. For starters, we should know how they work, some basic pharmacokinetics, how they are supplied and how to prepare concentrations that are safe for patient administration. Historically, in the OR, both phenylephrine and ephedrine have been vasopressors of choice. Phenylephrine appears to be a good option in the ED because of its short half-life and ability to be titrated.

PDP Prep

Phenylephrine is a pure alpha agonist and causes peripheral vasoconstriction of large arterioles, leading to an increased systemic vascular resistance (SVR) and afterload.[^15] It is manufactured in vials with a 10 mg/mL concentration, but should be administered in significantly smaller doses, necessitating dilution (Table 2). There are several different ways to safely do this, but many organizations have opted to use premixed syringes (100 mcg/mL) from third party compounding pharmacies to avoid compounding errors. These syringes may be stored in automated dispensing cabinets and have longer shelf lives than if compounded in inpatient hospital admixture centers.

Epinephrine, another PDP option, is an inotrope that works on alpha and beta-receptors, causing vasoconstriction, increased contractility, elevated heart rate and bronchodilation.[^16] There are two manufactured epinephrine concentrations with a ten-fold difference, which complicates dilution and can lead to medication errors if the end user is unfamiliar with them. Some compounding pharmacies have premixed syringe preparations, but with frequent epinephrine national shortages, they are often unavailable (Table 2).

Table 2: Common ED push dose pressors

SVR = Systemic vascular resistance

EF = Ejection fraction

CHF = Congestive heart failure

Another important consideration is identifying if it is appropriate to use a PDP in your patient by considering risk versus benefit and if other hypotension treatment options have been exhausted before using vasopressors. Some have questioned whether providers are jumping too quickly to using PDP in patients who would benefit from other management, such as receiving blood products in hypovolemia due to blood loss.[^{12, 18]} Others have suggested that if premixed vasopressor infusions are present in the ED that PDP is likely unnecessary and adverse events associated with inappropriate mixing and administration may be avoided altogether.[^12]

Conclusion

If you have decided your patient can benefit from a PDP, consider patient-specific factors to help you decide which one would be the better option.

Phenylephrine may be beneficial for those patients who are experiencing a tachyarrhythmia because of its lack of effect on beta-receptors and potential reflex bradycardia. You may want to avoid its use in congestive heart failure patients with low ejection fractions due to increased afterload and reduced cardiac output. Likewise, epinephrine may be helpful in specific disease states like post-cardiac arrest, anaphylaxis, or those with bradycardia, but would likely be avoided in patients presenting with tachyarrhythmias.

Lastly, it’s important to be very familiar with how to prepare these medications, especially since the majority of adverse events appear to be linked to human compounding and administration error (Table 3).^{9,12-14,18,19} The last thing that we want to do as healthcare providers is harm our patients when we are trying to help them. While education is important, it’s not always enough.

Other safety measures should be in place to aid in appropriate PDP compounding and administration. If carrying premixed vasopressor syringes is not possible, it has been proposed that making push dose vasopressor kits with explicit instructions may be a helpful safety measure.[^18] Another recommended safeguard that has been shown to reduce errors with inappropriate mixing and administration is ED pharmacist involvement, but at this time many hospitals have only partial or no ED pharmacist coverage.[^9,18]

Table 3: How to safely prepare push dose pressors

*Requires double dilution or single dilution with a 100 mL IVPB to achieve 10 mcg/mL concentration.

The bottom line is that PDP can be a helpful tool in our hypotension treatment arsenal. However, it’s important to remember that no drug is truly benign, especially vasopressors. As healthcare providers, we need to remember to do our due diligence and consider our patient-specific factors, as well as risk versus benefit on a case-by-case basis before making decisions about drug therapy. And while education is important, it must be coupled with other safety features, such as appropriate communication between healthcare providers, practice and other measures to take the guesswork out of how to appropriately mix and administer PDP without harming our patients.

References

1. Brunauer A, Kokofer A, Bataar O, et al. The arterial blood pressure associated with terminal cardiovascular collapse in critically ill patients: a retrospective cohort study. Crit Care. 2014;18:719.
2. Jones A, Yiannibas V, Johnson C, et al. Emergency department hypotension predicts sudden unexpected in-hospital mortality: a prospective cohort study. Chest. 2006;130:941-6.
3. Panchel AR, Satyanarayan A, Bahadir JD, et al. Efficacy of bolus-dose phenylephrine for peri-intubation hypotension. J Emerg Med. 2015;49;488-94.
4. Schwartz MB, Ferreira JA, Aaronson PM. The impact of push-dose phenylephrine use on subsequent preload expansion in the ED setting. Am J Emerg Med. 2016;34:2419-22.
5. Swenson K Rankin S, Daconti L, et al. Safety of bolus-dose phenylephrine for hypotensive emergency department patients. Am J Emerg Med. 2018;36:1802-6.
6. Gottlieb, et al. Bolus dose of epinephrine for refractory post-arrest hypotension. CJEM. 2018;20:S9-13.
7. Ross CE, Asaro LA, Wypij D, et al. Physiologic response to pre-arrest bolus dilute epinephrine in the pediatric intensive care unit. Resuscitation 2018;126:137-142.
8. Rotando A, Picard L, Delibert S, et al. Push dose pressors: Experience in critically ill patients outside of the operating room. Am J Emerg Med. 2019;37:494-8.
9. Cole JB, Knack SK, Karl ER, et al. Human Errors and Adverse Hemodynamic Events Related to “Push Dose Pressors” in the Emergency Department. J Med Toxicol. 2019;15:276-86.
10. Weingart S. Push-dose pressors for immediate blood pressure control. Clin Exp Emerg Med. 2015;2:131-132.
11. Weingart S. EMCrit podcast 6: push-dose pressors (2009). Available at: http://www.emcrit.org/podcasts/bolus-dose-pressors. Accessed Jan 29, 2020.
12. Acquisto NM, Bodkin RP. Medication errors with push dose presors in the emergency department and intensive care units. Am J Emerg Med. 2017;35:1964-5.
13. Awad NI, Mell HK, Swaminathan AK, et al. The authors respond: “Medication errors with push dose pressors in the emergency department and intensive care units.” Am J Emerg Med. 2018;36:519-20.
14. Acquisto NM, Bodkin RP. Response to: “Medication errors with push dose pressors in the ED and ICU.” Am J Emerg Med. 2018;36-520-1.
15. Phenylephrine [package insert]. Eatontown, NJ: West-Ward Pharmaceuticals; 2012.
16. Adrenalin (epinephrine) [package insert]. Rochester, MI: JHP Pharmaceuticals, LLC; 2012.
17. Holden D, Ramich J, Timm E, et al. Safety Considerations and Guideline-Based Safe Use Recommendations for “Bolus-Dose” Vasopressors in the Emergency Department. Ann Emerg Med. 2018;71:83-92.
18. Cole JB. Bolus-Dose Vasopressors in the Emergency Department: First, Do No Harm; Second, More Evidence is Needed. Ann Emerg Med. 2018;71:93-5.