The use of push-dose vasopressors in emergency medicine is a widely accepted clinical practice, however there is negligible data to support this utilization (1). While research has been performed by anesthesiology examining the use in sedation and intubation related hypotension, these patient populations and clinical scenarios significantly differ from those encountered in the Emergency Department (ED) (1-7). Anesthesia studies generally examined either elective surgical procedures (such as spinal surgery) or obstetrical patients, who would be expected to be younger and healthier than the average hypotensive ED patient (1-7). The hemodynamic profiles of these operative patient populations cannot be extrapolated to those in shock in the emergency room. Up to this point, the endorsement of push-dose pressors (PDPs) has been overwhelmingly based on anecdotal or observational data (8), and multiple authors have suggested the urgent need for deeper examinations of the practice (9-20). Our goal is to determine the efficacy and safety of use of push dose pressor in the ED. We present the following article in accordance with the Narrative Review reporting checklist (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-21-98/rc).
This study evaluated publications regarding the clinical use of push-dose vasopressors in the ED. Using the Cochrane Database and PubMed, literature was reviewed based on the following keywords: push dose pressor* OR push-dose pressor* OR bolus dose pressor* OR bolus-dose pressor* OR push dose vasopressor* OR push-dose vasopressor* OR bolus dose vasopressor* OR bolus-dose vasopressor*. Refer to Table 1 for full search strategy summary. These databases were last reviewed in August 2021. Inclusion criteria was determined based on a consensus of pertinent information, including pre-hospital articles and in-hospital critical care settings. A total of 529 articles met criteria, and after evaluation by three different reviewers, 24 relevant articles were identified. Several of the papers identified were single case or editorials. Control/case series trials found are summarized in Tables 2,3.
|Date of search (specified to date, month and year)||August 15th, 2021|
|Databases and other sources searched||PubMed, Cochrane|
|Search terms used (including MeSH and free text search terms and filters)||Push dose pressor* OR push-dose pressor* OR bolus dose pressor* OR bolus-dose pressor* OR push dose vasopressor* OR push-dose vasopressor* OR bolus dose vasopressor* OR bolus-dose vasopressor*|
|Inclusion and exclusion criteria (study type, language restrictions, etc.)||Limited to English language, emergency/critical/anesthesia settings, excluded pediatric (age <18 years)|
|Selection process (who conducted the selection, whether it was conducted independently, how consensus was obtained, etc.)||Three authors conducted search independently and each created list of pertinent articles. Results compiled and all authors reviewed each article for relevance. Article was included if all authors felt it met search criteria|
|Patrick 2020||Ground EMS transport||Retrospective, observational||Non-cardiac arrest, hypotensive due to presumed non-traumatic cause while transported via EMS||42 patients||Epinephrine 20 mg IV Q2m PRN||Median SBP 78 mmHg (pre) to 93 mmHg (post), MAP 58 mmHg (pre) to 69 mmHg (post)||Not reported||54.8% required >2 doses, 1 patient with severe hypertension (SBP >180 mmHg) post-PDP|
|Clifford 2021||Emergency Department||Prospective cohort||Consecutive patients with hypotension from an acute drug overdose and circulatory shock||55 patients||Phenylephrine, epinephrine||PDP used in 32 of 55 patients (12 phenylephrine, 20 epinephrine)||11/12 phenylephrine survived; 4/20 epinephrine survived||None noted|
|Nowadly 2020||Emergency Department||Case report||n/a||Single patient||Vasopressin 1-unit IVP||BP 80/51 mmHg (pre), 141/102 mmHg (immediately post), gradual decline over 92 min until vasopressor drip started||Discharged after 30 days in hospital||None noted|
|Guyette 2019||Prehospital critical care transport||Retrospective, case cohort pre- and post-protocol comparison||Patients with documented SBP <70 mmHg undergoing critical care transport||574 patients||Epinephrine 100 μg||Patients receiving PDP were more likely to have both hypotension (68.4% vs. 49.4%) and hypertension (2.63% vs. 0.99%), less likely to have a perfusing rhythm (63.9% vs. 93.0%)||PDP patients less likely to be alive at 24 h (64.6% vs. 82.2%) and 30 days (37.9% vs. 56.3%)||None noted|
|Nawrocki 2020||Prehospital critical care transport||Retrospective, observational||Patients documented as receiving at least one dose of PDP epinephrine for SBP <90 mmHg or MAP <65 mmHg||52 patients||Epinephrine 10–20 μg||Use of PDP increased mean MAP by 13 mmHg, hypotension resolved in 58.5% of recipients. Repeat PDP dose administration required in 42 instances||Data only available for 38 patients. 11/38 (28.9%) survived to discharge||Severe HTN (SBP >180 mmHg) in 1/94 (1.1%) administrations|
|Rotando 2019||Any clinical area outside of the OR||Retrospective, observational||Patients documented as receiving bolus dose pressor in EMR||146 patients (155 PDP events)||Phenylephrine, ephedrine||Mean SBP 80 mmHg (pre) to 106 mmHg (post), DBP 48 mmHg (pre) to 61 mmHg (post), HR 93 beats/min (pre) to 99 beats/min (post)||Not reported||17 (11.6%) adverse hemodynamic events, 13 patients (11.2%) with medication dose error|
|Hardwick 2018||Medical evacuation during disaster response||Case series||Hypotensive patients requiring intubation in a pre-hospital transport environment||2 patients||Epinephrine bolus and/or “ad hoc” drip||Improvement in SBP/MAP pre and post intubation||Both patients admitted to ICU||None noted|
|Gottleib 2018||Emergency Department||Case series||Refractory post arrest hypotension||3 patients||Epinephrine||Improvement in SBP/MAP until vasopressor infusion initiation||2 of 3 patients survived||Nonattributable to PDP use|
|Schwartz 2016||Emergency Department||Retrospective, observational||Documented use of bolus dose phenylephrine||73 patients||Phenylephrine||Patients receiving adequate fluid resuscitation required fewer PDP doses, 34 (46.6%) patients were initiated on a continuous vasopressor infusion within 30 minutes of initial PDP dose, patients receiving adequate fluid less likely to require vasopressor drip initiation||Not reported||6 (8.2%) reactive hypertension, 2 (2.7%) ventricular tachycardia, 7 (9.6%) bradycardia|
|Panchal 2015||Emergency Department||Retrospective, observational||Hypotensive patients receiving bolus dose phenylephrine in the peri-intubation period||20 patients||Phenylephrine||Mean SBP 73 mmHg (pre) to 93 mmHg (post), mean DBP 42 mmHg (pre) to 52 mmHg (post), 13 (65%) received multiple PDP doses, 14 (70%) required initiation of vasopressor infusion||Not reported||None noted|
EMS, emergency medical services; EMR, electronic medical record; IV, intravenous; Q2m, every 2 minutes; PRN, as needed; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; PDP, push-dose pressor; BP, blood pressure; IVP, intravenous push; HR, heart rate; ICU, intensive care unit.
|Swenson 2018||Emergency Department||Retrospective, observational||Patients receiving pre-mixed bolus dose phenylephrine||181 patients||Phenylephrine||80 patients received additional vasopressor infusion, 27 received more than 2 additional vasopressor infusions. 5 patients with adverse hemodynamic event—3 with hypertension, 2 with bradycardia||Not noted|
|Cole 2018||Emergency Department||Retrospective, observational||Patient documented as receiving bolus dose pressor in EMR||249 patients||Phenylephrine, epinephrine||Adverse hemodynamic events (HR >140 or <60 beats/min, hypertension, ventricular tachycardia) occurred in 98 (39%), 30 (27%) phenylephrine, 68 (50%) epinephrine, human/dosing error in 47 patients, 140 patients required >2 doses||120 (49%) survival to discharge, 70 (64%) phenylephrine, 50 (36%) epinephrine|
EMR, electronic medical record; HR, heart rate.
There are multiple vociferous proponents of push dose pressors in the emergency medicine world. However, articles cited by Weingart et al. do not provide a direct correlation with the use of push-dose vasopressors and patient outcomes (8). The article by Cole et al. from 2018 found only 2 studies regarding push dose pressor use in the ED (9). Panchal et al. analyzed 20 hypotensive patients receiving bolus-dose phenylephrine in the peri-intubation period. They found improvement in blood pressure by 20 mmHg systolic and 10 mmHg diastolic, but no significant outcome benefit by any other clinical parameters (10). Schwartz et al. assessed bolus-dose phenylephrine efficacy based on the need for patients to receive continuous vasopressor infusion (CVI) within 30 minutes of bolus dose administration. Out of 73 patients, 34 required CVI (46.6%). The patients who were considered to have an adequate preload of intravenous fluids received fewer doses of push dose pressors and were less likely to require a CVI. There was a 20.5% adverse event rate, including reactive hypertension in 8.2% of patients, ventricular tachycardia in 2.7% of patients, and bradycardia in 9.6% of patients. The authors suggested that the reliance on push dose pressors may mask inadequate fluid resuscitation and preload expansion thereby causing harm to the patient (11).
Tilton et al. warns of the high risk of medication errors in the high risk, high stress situations that push dose pressors are often used (12). Rotando et al. retrospectively analyzed the efficacy of phenylephrine 1,000 g/10 mL or ephedrine 50 mg/10 mL in a clinical area outside of the operating room. Vitals were monitored in 80 patients before and after administration of PDP, which showed a mean increase 26 mmHg in systolic blood pressure (SBP) and 13 mmHg in diastolic blood pressure (DBP). However, adverse events occurred in 17 out of 146 patients, including SBP increases by >100%, heart rate (HR) changes of >30%, or dysrhythmias. In addition, 13 out of 116 patients received >200 µg phenylephrine or >25 mg ephedrine, which was classified by the authors as a medication error (13).
Nowadly et al. reported that as of last year, there had not been a single case report published describing the use of push-dose vasopressin in the setting of the ED. Their case report followed a septic patient whose blood pressure improved from 80/51 to 141/102 within 1 minute of administration of 1unit push bolus vasopressin. She subsequently required CVIs 1 hour after push-dose administration (14). Other case reports have been published describing the use of bolus dose epinephrine in hypotensive patients following cardiac arrest. Gottlieb et al. in 2021 authored a case series describing blood pressure improvement in three patients after up to 12 doses of push dose epinephrine during central line placement (15).
An article by Acquisto et al. presented cases of dosing errors, as well as adverse events associated with the use of phenylephrine and epinephrine in the ED. Reports included that of hypertensive episodes to >300 mmHg, ST depressions, and QTc prolongation (16). Ross et al. retrospectively followed pediatric intensive care unit (ICU) patients who received pre-arrest bolus dose epinephrine. Their data showed that 9% of patients experienced reactive hypertension, while 14% and 4% experienced relative tachycardia and bradycardia, respectively (17). Swenson et al. performed a retrospective chart review, showing overall mean arterial pressure (MAP) improvement in 147 patients in ED with 5 out of 181 patients experiencing adverse reactions in the form of hypertensive crises (18). Clifford et al. presented a prospective cohort study of ED patients in circulatory shock following a drug overdose, for which they observed statistically significant in-hospital mortality in 8% of patients who received push-dose phenylephrine and 80% of patients who received push-dose epinephrine (19).
An examination of pre-hospital literature did not yield much additional evidence to support broad usage. A retrospective emergency medical services (EMS) chart review by Patrick et al. showed SBP improvement in 86% of patients, but errors in dosing were specifically excluded in the study analysis (20). Guyette et al. provided a retrospective case cohort, prehospital transport study that concluded the use of bolus-dose epinephrine had a lower 24-hour and 30-day survival rate in patients treated with push dose pressors versus those who were not (21). The Nawrocki et al. retrospective observational study showed 1 out of 52 push dose pressor administrations resulted in transient extreme hypertension, 3 out of 52 cardiac arrest events occurred within minutes of receiving push dose epinephrine, and one incident of dosing error (22). Finally, Hardwick et al. presented two aeromedical cases during the Puerto Rican disaster response in which field expedient vasopressors successfully hemodynamically stabilized patients (23).
Some proponents cite the safety and efficacy profile of push dose pressors in anesthesia literature, extrapolating the similarity to use in the ED. Seven anesthesiology articles met relevance, looking first at the Wang et al. review on rescue bolus phenylephrine compared to norepinephrine. This article emphasized the lack of quality data surrounding bolus norepinephrine use in obstetric anesthesia (1) and reiterated the points made by Ngan Kee et al. regarding negative side effects of even the well-researched vasopressor, phenylephrine (2).
A significant amount of the anesthesia published literature on this topic is conflicting. Wang et al. showed that the hemodynamic profile for bolus norepinephrine is safer than phenylephrine and ephedrine during cesarean deliveries of women with preeclampsia (3). Hassani et al. shared support for the efficacy of norepinephrine, but this randomized control trial differed in its population by studying hypertensive patients undergoing spinal surgery (4). Xia et al. also evaluated spinal surgery patients undergoing anesthesia, concluding that a bolus injection of ephedrine best counteracted hypotension while prone (5). The randomized double-blind dose-finding study Mohta et al. revealed that the incidence of reflex bradycardia was similar in both phenylephrine and norepinephrine when treating post-spinal hypotension during a cesarean section. They expanded upon the adverse side effect profile of bolus dose phenylephrine in their double-blind study Mohta et al., which called for more studies to evaluate its use in the higher dose range (6,7).
The majority of PDP literature has been published by anesthesiologists within the context of hypotension in the operating room. Repeatedly, these reviews suggested the acknowledgment of safety considerations when administering push-dose vasopressors in critical care settings due to the adverse event profile. The demand for randomized trials was made evident, as many of our relevant articles included isolated case reports or literature reviews. Our research indicates that there is limited data on the implementation and efficacy of push-dose vasopressors in the ED.
Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-21-98/rc
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jeccm.amegroups.com/article/view/10.21037/jeccm-21-98/coif). The authors have no conflicts of interest to declare.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
- Wang X, Shen X, Liu S, et al. The Efficacy and Safety of Norepinephrine and Its Feasibility as a Replacement for Phenylephrine to Manage Maternal Hypotension during Elective Cesarean Delivery under Spinal Anesthesia. Biomed Res Int 2018;2018:1869189. [Crossref] [PubMed]
- Ngan Kee WD. A Random-allocation Graded Dose-Response Study of Norepinephrine and Phenylephrine for Treating Hypotension during Spinal Anesthesia for Cesarean Delivery. Anesthesiology 2017;127:934-41. [Crossref] [PubMed]
- Wang X, Mao M, Liu S, et al. A Comparative Study of Bolus Norepinephrine, Phenylephrine, and Ephedrine for the Treatment of Maternal Hypotension in Parturients with Preeclampsia During Cesarean Delivery Under Spinal Anesthesia. Med Sci Monit 2019;25:1093-101. [Crossref] [PubMed]
- Hassani V, Movaseghi G, Safaeeyan R, et al. Comparison of Ephedrine vs. Norepinephrine in Treating Anesthesia-Induced Hypotension in Hypertensive Patients: Randomized Double-Blinded Study. Anesth Pain Med 2018;8:e79626. [PubMed]
- Xia J, Sun Y, Yuan J, et al. Hemodynamic effects of ephedrine and phenylephrine bolus injection in patients in the prone position under general anesthesia for lumbar spinal surgery. Exp Ther Med 2016;12:1141-6. [Crossref] [PubMed]
- Mohta M, Dubey M, Malhotra RK, et al. Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section. Int J Obstet Anesth 2019;38:25-31. [Crossref] [PubMed]
- Mohta M, Harisinghani P, Sethi AK, et al. Effect of different phenylephrine bolus doses for treatment of hypotension during spinal anaesthesia in patients undergoing elective caesarean section. Anaesth Intensive Care 2015;43:74-80. [Crossref] [PubMed]
- Weingart S. Push-dose pressors for immediate blood pressure control. Clin Exp Emerg Med 2015;2:131-2. [Crossref] [PubMed]
- 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. [Crossref] [PubMed]
- Panchal AR, Satyanarayan A, Bahadir JD, et al. Efficacy of Bolus-dose Phenylephrine for Peri-intubation Hypotension. J Emerg Med 2015;49:488-94. [Crossref] [PubMed]
- 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. [Crossref] [PubMed]
- Tilton LJ, Eginger KH. Utility of Push-Dose Vasopressors for Temporary Treatment of Hypotension in the Emergency Department. J Emerg Nurs 2016;42:279-81. [Crossref] [PubMed]
- 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. [Crossref] [PubMed]
- Nowadly CD, Catlin JR, Fontenette RW. Push-Dose Vasopressin for Hypotension in Septic Shock. J Emerg Med 2020;58:313-6. [Crossref] [PubMed]
- Gottlieb M. Bolus dose of epinephrine for refractory post-arrest hypotension. CJEM 2018;20:S9-S13. [Crossref] [PubMed]
- Acquisto NM, Bodkin RP, Johnstone C. Medication errors with push dose pressors in the emergency department and intensive care units. Am J Emerg Med 2017;35:1964-5. [Crossref] [PubMed]
- Ross CE, Asaro LA, Wypij D, et al. Physiologic response to pre-arrest bolus dilute epinephrine in the pediatric intensive care unit. Resuscitation 2018;126:137-42. [Crossref] [PubMed]
- 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. [Crossref] [PubMed]
- Clifford C, Sethi M, Cox D, et al. First-Line Vasopressor and Mortality Rates in ED Patients with Acute Drug Overdose. J Med Toxicol 2021;17:1-9. [Crossref] [PubMed]
- Patrick C, Ward B, Anderson J, et al. Prehospital Efficacy and Adverse Events Associated with Bolus Dose Epinephrine in Hypotensive Patients During Ground-Based EMS Transport. Prehosp Disaster Med 2020;35:495-500. [Crossref] [PubMed]
- Guyette FX, Martin-Gill C, Galli G, et al. Bolus Dose Epinephrine Improves Blood Pressure but is Associated with Increased Mortality in Critical Care Transport. Prehosp Emerg Care 2019;23:764-71. [Crossref] [PubMed]
- Nawrocki PS, Poremba M, Lawner BJ. Push Dose Epinephrine Use in the Management of Hypotension During Critical Care Transport. Prehosp Emerg Care 2020;24:188-95. [Crossref] [PubMed]
- Hardwick JM, Murnan SD, Morrison-Ponce DP, et al. Field Expedient Vasopressors During Aeromedical Evacuation: A Case Series from the Puerto Rico Disaster Response. Prehosp Disaster Med 2018;33:668-72. [Crossref] [PubMed]
Cite this article as: Kubena A, Weston S, Alvey H. Push-dose vasopressors in the Emergency Department: a narrative review. J Emerg Crit Care Med 2022;6:22.