Indications
Both epinephrine and phenylephrine can be considered in the management of significant transient or sustained hypoperfusion. Although the definition of significant hypotension is complex, Brunauer et al6 have suggested that a mean arterial pressure (MAP) of approximately 35 mm Hg is associated with a significant risk of CV collapse. Of course, a MAP of 40 to 50 mm Hg is also very concerning clinically, with significant risk of deterioration and CV collapse.
Procedural events, such as conscious sedation or rapid sequence intubation (RSI), can produce significant hypotension; PDP can rapidly correct hypotension. In other clinical scenarios in which sustained hypotension is likely and not transient (eg, sepsis with shock), PDP can be used as a bridge to definitive care (eg, volume replacement, continuous vasopressor infusion). It is important to note, however, that PDP administration must occur in conjunction with or after the patient has received other appropriate therapies such as a normal saline bolus and continuous vasopressor infusions. Push-dose pressors are not a replacement for these proven interventions, but rather are an important augmentation to these therapies.
Emergency Medicine Literature
As previously noted, the literature base describing and supporting the clinical use of PDP in EM is extremely limited. The few articles that comprise this literature base address significant hypotension in periendotracheal intubation intervention, post-return of spontaneous circulation (ROSC) management, and shock management with preload augmentation.7-9In addition, there are several articles in the literature that address safety concerns surrounding the use of PDP in the ED.4,5
Panchal et al10 investigated the use of phenylephrine in hypotensive patients undergoing RSI-assisted endotracheal intubation. The authors performed a 1-year retrospective review of hypotensive patients managed with endotracheal intubation for a range of clinical conditions that required clinical care intervention. In this study, 20 of the 119 patients received phenylephrine in the peri-intubation period. A range of clinical conditions requiring critical care intervention were encountered; in addition, almost three-quarters of these patients were receiving at least one other vasopressor infusion. Further differences were seen in the timing of PDP administration. In those patients receiving bolus-dose phenylephrine, blood pressure (BP) improved without change in HR. Panchal et al10 concluded that while push-dose phenylephrine improved hemodynamic status, there was significant variation among clinicians regarding dosing, timing of use, and overall clinical situation The significant variation in PDP management in this study was noted to be a potential source of medical error, thus increasing the chance of adverse clinical event.
Push-dose pressor therapy can be employed for significant hypotension while more definitive therapy is being readied and applied. For instance, patients with significant hypotension requiring continuous vasopressor infusion can be managed with PDP while appropriate venous access is established, intravenous fluids are administered, and medications are prepared. The immediate period after resuscitation from cardiac arrest can be complicated by shock of many types. In fact, hypotension following ROSC in the cardiac arrest patient is not uncommon and has been identified as a risk issue associated with poor outcome. Prompt treatment of this altered perfusion may improve outcome. Gottlieb8 described three patients with ROSC after cardiac arrest. All three patients experienced significant, sustained hypotension with systolic blood pressure reading in the 50 to 60 mm Hg range; bolus-dose epinephrine was administered with significant improvement in the hemodynamic status while central venous access was established.
In a related clinical scenario, Schwartz et al9 considered the impact of PDP on central venous line (CVL) placement with continuous vasopressor infusion. In this ED study, although patients experienced an increase in BP, this impact was transient with approximately half of these individuals ultimately requiring CVL. In addition, serious adverse effect was noted more commonly in the phenylephrine-treated patients with “reactive” hypertension and ventricular tachycardia occurring in study patients.
Patient-Safety Considerations
In addition to the limited literature base supporting PDP use in the ED, another major significant issue focuses on safety concerns and adverse effects. Extremely limited data is available describing adverse events related to ED-administered PDP. Extrapolating from other EM and critical care administrations of peripheral epinephrine, both local and systemic adverse effects have been reported.11,12 The range of adverse events noted in these studies are considerable, including local skin and soft-tissue injury (necrosis), end-organ tissue ischemia (eg, digits, tip of nose), acute hypertension, cardiac ischemic events, and left ventricular (LV) dysfunction.11,12
When comparing peripheral infusion with central infusion, the risk of extravasation with resultant local tissue injury is markedly greater with peripheral vasopressor administration. In a systematic review of this issue, Loubani and Green11 noted that such local adverse events were much more commonly associated with peripheral administration.
In another report of vasopressor use in the ED, Kanwar et al12 described apparent confusion with epinephrine dosing and route of administration, resulting in very significant, systemic CV maladies, including severe elevations in BP, acute LV dysfunction, and chest pain associated with ST segment elevation.
It must be stressed that the publications by Loubani and Green11 and Kanwar et al12 described peripheral vasopressor administration: neither study included PDP therapy. Therefore, as previously noted, the aforementioned statements are extrapolated from when applied to PDP strategy.
Acquisto et al4 describe several errors in medication administration of PDP in the ED and other critical care areas of the hospital. In this report, all treating physicians were present at the patients’ bedside, either administering the medication or directly supervising its use. Agents involved included epinephrine and phenylephrine, delivered at exceedingly high doses. In their study, the authors noted several issues which they believe contributed to medication errors, including heterogeneity of pathology treated in these patients, apparent “earlier-than-appropriate” use of vasopressors (ie, prior to giving an appropriate fluid bolus), and medication preparation at the bedside by clinicians who may not possess the experience and training to mix these agents.
From a patient-safety perspective, Holden et al5 noted the potential for dosing error with significant adverse medical consequence related to PDP, as well as several contributing issues. First, they highlight the lack of a solid literature base to support administration of PDP in the ED and the development of decision-making guidelines for use in the ED. They also observed an inconsistency in approach to patient selection, medication choice, agent preparation, dosing, and other therapies. As seen in the Acquisto et al4 report, the patient-care scenarios are high risk and quite dynamic.