Authors: Michael Scott, PharmD Candidate 2019: UMKC School of Pharmacy and Jeremy Hampton, PharmD, BCPS: UMKC School of Pharmacy
Bolus dose vasopressors, also referred to as push-dose pressors (PDPs), have become a popular topic of discussion within the practice of Emergency Medicine and pre-hospital care. PDPs are so named because as the name implies they are not administered as an IV infusion, but as a volume of 0.5 to 2mL pushed slowly via syringe. There is controversy regarding appropriate use of PDPs due to the lack of published literature evaluating their safety and efficacy. This article will provide an overview of which drugs may be used as PDPs in the emergency department (ED), indications for use, safety issues regarding their use and how to mitigate those issues, general instructions for preparation, and an overview of the few retrospective studies that have analyzed their use in the ED.
Medications used as PDPs include epinephrine, phenylephrine, and ephedrine. These have been administered as bolus doses for years by anesthesiologists in operating rooms, but recently this practice has gained favor in the ED due to their utility in preventing cardiac arrest. Epinephrine and phenylephrine are the drugs of choice in the ED due to their quick onset of action and short duration of action. Ephedrine, while utilized frequently in operating rooms, does not confer much utility in the ED due to its slower onset and longer duration of action. Both epinephrine and phenylephrine can be useful depending on the presentation of the patient. Epinephrine, having both alpha and beta adrenergic activity, will provide vasoconstriction as well as positive inotropic and chronotropic effects to produce a temporary increase in cardiac output and blood pressure. Phenylephrine, being an alpha agonist, will provide a pure vasopressor response with no further elevation in heart rate. Phenylephrine also has the potential to decrease heart rate due to the parasympathetic reflex following vasoconstriction.
A controversial issue in regard to PDPs is whether it is appropriate to utilize this administration method rather than conventionally administered vasopressors. Proponents argue that PDPs are more appropriate for short term use as a temporizing measure to increase blood pressure in patients with transient hypotension, such as in the setting of post-intubation hypotension, procedural sedation, traumatic brain injury, post-cardiac arrest with return of spontaneous circulation, or as a bridge to vasopressor infusion while the infusion is being prepared or a central line is being placed.1 However, the use of PDPs should not supplant continuous infusion vasopressors in patients requiring long-term blood pressure management, e.g., as in septic shock.
Care should be exercised during administration of PDPs. The Journal of Critical Care compiled published reports on local tissue injury and extravasation occurring during vasopressor administration through peripheral intravenous and central venous catheters. They identified 318 events resulting from peripheral infusion and seven resulting from central infusion, indicating a higher risk of adverse events due to peripheral administration. Two-hundred four of the peripheral events were local tissue injury events, which included skin necrosis, tissue necrosis, and gangrene. The majority of these events were caused by norepinephrine and dopamine, with six events being caused by phenylephrine and six from epinephrine. There were 114 extravasation events due to peripheral infusion, with the majority being caused by norepinephrine and dopamine. Eleven extravasation events were caused by epinephrine and none were caused by phenylephrine. When local tissue injury was attributable to peripheral administration, the catheter site was located distal to the antecubital or popliteal fossa in 85.3% of events. The average duration of infusion before tissue injury occurred was 55.9 hours with a median of 24 hours. Of the 114 extravasation events, 52 reported infusion sites and 75% of those infusion sites were distal to the antecubital or popliteal fossa.8
Based on these data, it is possible that the incidence of adverse events may be reduced if the administration site is located at or proximal to the antecubital or popliteal fossa. While there is an inherent risk of local tissue injury with the peripheral administration of vasopressors, PDPs do not carry the increased risk associated with prolonged infusion duration due to their method of administration. The data also suggests that there is less risk of local tissue injury and extravasation with phenylephrine and epinephrine as compared to alternative vasopressor options. Furthermore, phenylephrine is approved for both intramuscular and subcutaneous administration making extravasation of little concern, and the dose used for push dose epinephrine has the same epinephrine concentration as lidocaine with epinephrine (1:100,000), which does not pose a risk for extravasation.1
One of the main safety concerns regarding PDPs is the high risk of dosage administration errors. Due to the manipulations and calculations required to prepare the appropriate dilution, the process of preparing these medications is error prone. As such, it is highly recommended that prefilled syringes be used whenever available. These syringes are typically acquired via outsourced sterile compounding facilities. However, if commercially prepared dilutions are unavailable, it is imperative that the provider use caution in preparing doses and to have dilutions double-checked by other providers in order to minimize the risk of error.
Following this process of dilution, phenylephrine is typically administered in aliquots of 0.5-2mL (50-200mcg), and epinephrine in aliquots of 0.5-2mL (5-20mcg). These should be administered via slow IV-push over 30-60 seconds every 1-5 minutes based on patient response. Due to the risk of administration errors, it is recommended that individual doses be transferred to empty 3mL syringes via the use of tip-to-tip luer lock transfer adaptors (if available).2
To date, there have only been two studies published evaluating the effectiveness of PDPs in the ED, and both were retrospective studies of phenylephrine. Panchal et al5 evaluated 20 patients receiving phenylephrine during the peri-intubation period, which they defined as 30 minutes prior to and post intubation. When phenylephrine was administered during the peri-intubation period, systolic and diastolic blood pressure significantly increased with no change in heart rate. The authors noted that there was not a systematic pattern used for administering bolus dose phenylephrine, and concluded that although hemodynamics were improved, nonsystematic use may lead to inadvertent negative side effects. Schwartz et al6 reviewed the use of bolus dose phenylephrine for acute hypotension in 73 patients in the ED. Their primary objective was to report the frequency of patients initiated on a continuous vasopressor infusion within 30 minutes of phenylephrine administration. They found that 46.5% of these patients had a continuous vasopressor infusion initiated within 30 minutes of phenylephrine administration. As a secondary objective, Schwartz et al assessed the impact of early preload expansion with intravenous fluids on the initiation of continuous vasopressor infusions. They found that only 34.2% of patients were adequately fluid challenged prior to vasopressor administration, and that receiving adequate fluid challenge was associated with fewer doses of phenylephrine.6
Holden et al2 provides an in depth summary of safety recommendations for the use of PDPs in the ED based on current safe medication practice guidelines, as well as instructions for preparing and labeling the medications. Some of these recommendations include the official approval of bolus dose vasopressors by the organization prior to their use, consensus on who can order and administer PDPs, establishment of a common name for the practice to avoid confusion, and education of all members of the healthcare team involved in their use. They also recommend specifying indications for use, compounding instructions, providing easily accessible storage of the medications and all associated supplies, readily available medication information, and having a thorough documentation process for their utilization. Online videos with demonstrations on proper dilution of PDPs have been developed by the Emergency and Critical Care physician, Scott Weingart, and may be found online at www.EMCrit.org.4
While there is currently a paucity of data regarding outcomes following PDP administration, it is a reasonable assertion that they may see increased use in the ED due to their ability to mitigate hypotensive episodes. There are significant risks and safety concerns that accompany the use of PDPs, and these risks are highest when there is not a standardized plan to be followed for their use. If PDPs are to be utilized, a systems-based approach that includes adequate training pertaining to accurate dilution and administration is necessary. If the proper policies and procedures are in place and there is ample communication amongst the healthcare team, it is possible that this administration method can be used safely and effectively to save lives in the ED.