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Safety of bolus-dose phenylephrine for hypotensive emergency department patients
YAJEM-57303; No of Pages 5 American Journal of Emergency Medicine xxx (2018) xxx–xxx
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American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Safety of bolus-dose phenylephrine for hypotensive emergency department patients☆ Kjirsten Swenson, MD a,⁎, Shannon Rankin, PharmD, BCPS b, Leticia Daconti, MD b, Tomas Villarreal, MD, MPH b, Jens Langsjoen, MD b, Darren Braude, MD, MPH b a b
University of New Mexico Health Sciences Center, 2211 Lomas Blvd, Albuquerque, NM 87106, USA University of New Mexico Health Sciences Center, Albuquerque, NM, USA
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Article history: Received 9 January 2018 Accepted 30 January 2018 Available online xxxx Keywords: Phenylephrine Bolus-dose vasopressor Hypotension Resuscitation Safety
a b s t r a c t Introduction: Bolus-dose phenylephrine (BDPE) is routinely used to treat hypotension in the operating room. BDPE's fast onset of action and ability to be administered peripherally have prompted calls for its use in the Emergency Department (ED). There are few published data on the safety of BDPE use in the ED. Primary concerns include BDPE's potential to cause dangerous hypertension or reflex bradycardia. We hypothesize that BDPE is a safe short-term vasopressor choice for hypotensive ED patients. Methods: We conducted a structured chart review for all patients who received BDPE from preloaded syringes over 42 months. We defined an adverse event (AE) as sBP N 180, dBP N 110, or HR b 50 within 30 min of receiving BDPE. We defined a serious adverse event (SAE) as an AE with pharmacologic intervention to correct vital sign abnormality. We also compared mean arterial pressure (MAP), sBP, and dBP pre/post BDPE administration to assess effectiveness. We used a two-sample t-test to assess for differences between the mean delta MAP after low versus high-dose BDPE. Results: We identified 181 cases of ED use. 147 cases had complete pre/post vital signs. We identified 5 AEs and no SAEs. Three patients developed sBP N 180 mm Hg. The patients suffered no apparent harm. No patients had dBP N 110. Two patients developed bradycardia post-drug. In both cases, MAP improved despite bradycardia. Conclusions: BDPE does not appear to cause reflex bradycardia or hypertension requiring intervention among hypotensive ED patients. The apparent safety of BDPE should be confirmed in prospective trials. © 2018 Elsevier Inc. All rights reserved.
1. Introduction Hypotension in the Emergency Department (ED) is common, with one retrospective study estimating prevalence as high as 19% in nontrauma patients being admitted to the hospital [1]. Causes of hypotension in this setting are varied and often multifactorial; potential etiologies include septic, neurogenic, hemorrhagic, hypovolemic or cardiogenic shock. Patients may also have transient hypotension related to medications administered during procedural sedation or intubation. In one retrospective cohort study in an urban ED, approximately 23% of patients undergoing intubation developed post-intubation hypotension [2]. Large, single-center, prospective, cohort studies have shown exposure to hypotension in the ED to be an independent predictor of inhospital mortality with odds ratios from 2.0 (95% CI, 1.3 to 2.8; n = ☆ Meetings: An abstract entitled “Safety and Effectiveness of Bolus-Dose Phenylephrine for Hypotensive Emergency Department Patients” was presented at the Western Regional Society for Academic Emergency Medicine Conference in Los Angeles, California on April 2, 2016. ⁎ Corresponding author. E-mail addresses: [email protected] (K. Swenson), [email protected] (J. Langsjoen), [email protected] (D. Braude).
4790) (1) to 3.88 (95% CI, 2.62 to 5.75; n = 4388) [3]. Non-sustained hypotension in ED patients has also been associated with increased mortality in sepsis patients [4]. Moreover, the severity of hypotension and its duration in the ED has been associated with adverse hospital outcomes including acute organ failure, need for Intensive Care Unit (ICU) stay, and in-hospital mortality [5]. Post-intubation hypotension has also been shown to be a risk factor for in-hospital mortality with an OR of 2.1 (95% CI, 1.2–3.9) [2]. Several studies from the anesthesia literature support the use of peripherally administered bolus doses of diluted vasopressors, or “bolusdose vasopressors” for hypotension that is expected to be transient. Much of this literature examines the use of phenylephrine, ephedrine, and epinephrine in the setting of spinal anesthesia [6]. These drugs are used to counteract the rapid decrease in systemic vascular resistance (SVR) that occurs as a result of spinal anesthesia. Several studies have found phenylephrine to be effective at counteracting hypotension in this clinical scenario [6-10]. There has been increased interest in the Emergency Medicine community about the use of bolus-dose vasopressors for critically ill ED patients. Bolus-dose vasopressors may be given rapidly through a peripheral line and can serve as a temporizing measure while placing a central line or preparing a vasopressor infusion. They may also be
https://doi.org/10.1016/j.ajem.2018.01.095 0735-6757/© 2018 Elsevier Inc. All rights reserved.
Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095
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K. Swenson et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx
indicated for transient hypotension, such as during procedural sedation, post-intubation, or while crystalloid or blood product volume resuscitation is in progress. Bolus-dose phenylephrine (BDPE) has several characteristics that make it ideal for use in the ED setting. Phenylephrine is a selective alpha-1 adrenergic agonist that acts on smooth muscle in the vasculature to cause vasoconstriction, resulting in an increase in mean arterial pressure (MAP) [11]. In contrast to epinephrine, phenylephrine has no effect on inotropy. Potential adverse effects include hypertensive crisis, reflex bradycardia, cardiac arrhythmia, ischemia, reduced cardiac output and hypersensitivity reaction [12]. When administered intravenously, onset of vasoconstriction is almost immediate and peak effect occurs in 1–5 min. Phenylephrine may be safely administered through a peripheral line [13,14]. There are no published case reports of harm related to phenylephrine extravasation in the English literature [13,14]. These qualities make phenylephrine an ideal vasopressor for bolusdose use in the Emergency Department, particularly given that ED patients usually lack central venous access at the time of presentation. Several studies from the anesthesia literature investigated a doseresponse relationship for the drug when used for spinal anesthesia [6-10]. There is also literature describing phenylephrine infusion dosing for critically ill patients. We are not aware of any studies reporting a dose-response relationship for BDPE when used for critically ill patients. While BDPE has been used routinely in the operating room, we are aware of only two other studies describing its use in the ED. Panchal et al. conducted a retrospective chart review of 20 patients with periintubation hypotension who received BDPE [15]. This study found that phenylephrine was effective at increasing blood pressure in patients who were hypotensive after intubation [15]. Schwartz et al. reported that bolus-dose phenylephrine similarly increased blood pressure in their Emergency Department patient population with no significant effect on heart rate [16]. Our institution began stocking preloaded, pre-diluted syringes of phenylephrine in our resuscitation bays in 2009 in an effort to increase quick and convenient access to the drug for bolus-dose use while minimizing potential drug preparation errors. This study seeks to describe the use of BDPE in the ED setting, quantify rate of potentially dangerous hypertension and reflex bradycardia and examine circumstances of such cases, and examine its dose-response in the critically ill ED patient population. 2. Materials and methods The study was conducted at an urban, academic trauma center. Preloaded, pre-diluted syringes containing 1000 mcg/10 mL BDPE were stocked in the resuscitation bay automated medicationdispensing cabinets. We conducted a structured retrospective chart review for all patients who received BDPE from preloaded syringes over 42 months. After Institutional Review Board approval, patient encounters in which phenylephrine was pulled from any automated dispensing cabinet were retrospectively identified. Study subjects included all adult patients who received BDPE during the study period. No formal training curriculum or standard dose of phenylephrine was recommended. The decision to use BDPE was at the discretion of the treating physician. The primary investigator and a second author (an experienced ED pharmacist) used an internally developed, standardized data collection tool to manually extract data from the Cerner electronic records of all patients meeting inclusion criteria. For 12% of charts, each author independently extracted key variables (vital signs pre and post phenylephrine) to determine inter-rater reliability and ensure consistent data extraction. The demographic data recorded included age, gender, reason for visit, primary diagnosis and context of phenylephrine administration. Safety data recorded included pre and post BDPE systolic (SBP), diastolic blood pressures (DBP), mean arterial pressure (MAP), and heart rate
(HR). We also recorded the highest SBP and DBP and lowest HR within 30 min of BDPE administration. Other resuscitative medications and fluids administered, including induction agents, paralytics, vasopressors, blood products and intravenous fluids, were also documented. Our primary safety outcomes in this study were potentially dangerous vital sign abnormalities attributable to BDPE, including marked elevation in blood pressure or decreases in heart rate. We defined an adverse event as SBP N 180 or DBP N 110 or HR b 50 within 30 min of receiving BDPE. In cases of multiple doses of BDPE, all instances in which the drug was given were examined for the above vital sign abnormalities. The blood pressure thresholds were chosen based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [17]. This report characterizes patients whose blood pressure exceeds these thresholds as being at risk for hypertensive crisis. We defined a serious adverse event (SAE) as an adverse event with subsequent treatment to correct abnormal vital signs with an antihypertensive (in cases of hypertension) or atropine (in cases of bradycardia). All cases meeting criteria for an adverse event were reviewed to assess circumstances of abnormal vital signs and likelihood they were related to BDPE administration, detect any evidence of harm related to hypertension or bradycardia, and to identify any intervention taken to treat hypertension or bradycardia. As secondary outcomes, we compared HR, MAP, SBP, and DBP pre and post BDPE administration to assess effectiveness in cases in which complete pre and post drug vital signs were available. In cases of multiple doses of BDPE, we included only the first instance in which BDPE was given. We performed a two-sample t-test to assess for difference between the mean changes in MAP after low versus high dose BDPE. We also compared HR pre and post BDPE administration. 3. Results 181 cases were retrospectively identified and included in the study. Inter-rater reliability for key vital sign data points was 96%. Table 1 describes patient characteristics and context of BDPE use. 106 patients were male (58.6%) and 75 were female (41.4%). The mean age of patients was 53.6 years and the median age was 56 years. There were 144 medical resuscitation patients and 37 trauma resuscitation patients. Of the medical resuscitations, 81 were general medical resuscitations, 62 were cases in which BDPE was given in the peri-rapid sequence intubation period, and in one case BDPE was given during procedural sedation. Two authors extracted the data. For the key variables of vital signs pre and post-phenylephrine, inter-rater reliability was 95.6%. In most cases, disagreement was due to one author incorrectly reporting a value as missing. In two cases, disagreement was due to one author reporting an incorrect value. Table 2 describes the primary diagnoses of medical resuscitation patients who received BDPE. Among the medical resuscitation cases, we
Table 1 Patient characteristics and context of bolus dose phenylephrine use. n Age Mean age Median age Gender Male Female Context of BPE use Medical resuscitation General medical resuscitation Rapid sequence intubation Procedural sedation Trauma resuscitation General trauma resuscitation Rapid sequence intubation Total
53.6 years 56.0 years 106 75
59% 41%
144 81 62 1 37 15 22 181
79.5% 56.3% 43% 0.7% 20.5% 40.5% 59.5%
Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095
K. Swenson et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx Table 2 Primary diagnosis of medical resuscitation patients.
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Table 4 Etiology of hypotension in trauma cases.
Diagnosis
N (%)
Shock classification
Frequency (%)
Sepsis Respiratory distress or failure Cardiac arrest Overdose Altered mental status Gastrointestinal bleed Seizure Intracranial hemorrhage Hypovolemia Hypoglycemia Hyperglycemia Others Total
32 (22) 27 (19) 21 (15) 18 (13) 15 (10) 9 (6) 6 (4) 4 (3) 3 (2) 3 (2) 2 (1) 4 (3) 144
Hemorrhagic shock Neurogenic shock Total
28 (76) 9 (24) 37
observed a wide array of diagnoses leading to hypotension, with most patients having an initial diagnosis of sepsis (32 of 144), respiratory failure or distress (27 of 144), cardiac arrest (21 of 144), and overdose (18 of 144). Table 3 lists the mechanism of injury among trauma patients who received BDPE. The mechanism of injury for most trauma patients was motor vehicle collision (17 of 37 cases). Most trauma patients who received bolus phenylephrine were hypotensive due to hemorrhagic shock when they received BDPE. BDPE was given for hypotension in the peri-intubation period in 22 of 37 cases (Table 4). 80 patients received one vasopressor in addition to phenylephrine, 22 received two additional vasopressors, and 5 received three additional vasopressors. 28 patients received blood products, eight received two types of blood products and one received three types of blood products (Table 5). BDPE doses ranged from 10 to 500 mcg/dose. 81 patients received multiple doses of BDPE. Only the first dose was included in effectiveness calculations. Of the 181 cases, 149 had complete pre/post BDPE vital signs and were included in the effectiveness calculations. In most cases, the missing vital sign was either lack of documented pre-drug blood pressure or blood pressure documented as systolic/palpation. Mean change in MAP after BDPE administration is shown in Table 6. While all dose ranges resulted in a mean increase in MAP, BDPE doses N200 mcg were more effective than doses b100 mcg (p = 0.02). Of 181 cases included in the study, five met our criteria for a possible adverse event. Three cases developed SBP N180 mm Hg within 30 min of BDPE administration, and two met criteria for bradycardia. In the first hypertension case, elevated SBP occurred 15 min after BDPE. The patient had been recently intubated and was sedated with a 10 mcg/kg/min propofol infusion. The propofol infusion was discontinued due to hypotension 6 min before BDPE was given. MAP improved after these interventions. Subsequently, 15 min after BDPE (21 min after discontinuation of propofol), a hypertensive pressure that met our criteria for an adverse event occurred, with SBP 191. Under-sedation may have been a factor given recent discontinuation of propofol. No intervention was required to lower the blood pressure, and the patient suffered no apparent harm as a result of the transient Table 3 Mechanism of injury among trauma cases. Mechanism
N (%)
Motor vehicle collision Gunshot wound Motorcycle collision Fall Pedestrian vs auto Hanging Laceration Total
17 (46) 5 (14) 4 (11) 4 (11) 3 (8) 3 (8) 1 (3) 37
hypertension. In the second case, SBP 190 was recorded 26 min after BDPE administration. In the third case, an outlying episode of hypertension (SBP 221) was recorded 2 min after BDPE in context of normal BP immediately before (SBP 94) and continuously after this measurement (SBP 130, 5 min after BDPE), raising suspicion of a measurement or recording error. The patient suffered no apparent harm. No patient had DBP N110. No patient required intervention to lower the blood pressure after receiving BDPE. Two patients were noted to be bradycardic post-BDPE but both were bradycardic prior to BDPE administration. The first patient was being unsuccessfully externally paced on arrival with a HR of 38, which improved to 47 after 200 mcg BDPE given along with atropine prior to intubation. The second patient's heart rate decreased from 51 to 48 after 100 mcg BDPE but did not require intervention. In both cases, MAP improved despite ongoing bradycardia. 4. Discussion Our data show that BDPE did not cause dangerous hypertension or bradycardia in a heterogeneous critically ill ED patient population. Only five out of 181 patients who received BDPE met criteria for a potentially harmful vital sign abnormality that could possibly be attributed to BDPE, and no patient required intervention nor developed evidence of harm related to BDPE. Of the three patients with SBP N180 after BDPE, two developed blood pressure criteria for hypertensive crises more than two half-lives after receiving BDPE. This lowers our suspicion that the vital sign abnormality was related to BDPE. The other case had strong evidence of a measuring or recording error rather than true hypertension. BDPE can cause reflex bradycardia when a rapid increase in systemic vascular resistance activates the stretch baroreceptors in the aortic arch and carotid sinuses causing the heart rate to reflexively lower [6,9,18]. Anesthesia studies have reported incidence of bradycardia following phenylephrine administration ranging from 2.6% to 15% [6,8,19,20]. A study conducted in the ED reported bradycardia in 7/73 (9.6%) of
Table 5 Resuscitation medications and blood products given in addition to bolus dose phenylephrine. n cases Additional vasopressors Norepinephrine Epinephrine Dopamine Vasopressin Dobutamine Blood products Packed red blood cells Fresh frozen plasma Platelets Paralytics Rocuronium Succinylcholine Vecuronium Induction agents Etomidate Ketamine Midazolam Fentanyl Propofol
65 18 15 9 3 26 9 3 101 4 1 51 46 7 1 0
Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095
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Table 6 Effect of BDPE on mean arterial pressure and heart rate by dose. Dose
Mean change in MAP
Mean change in HR
b100 mcg (40 cases) 100–199 mcg (83 cases) 200–500 mcg (26 cases)
+4.0 (95% CI 1.7–6.2) +5.6 (95% CI 2.3–8.8) +12 (95% CI 4.5–20)
+2.2 (95% CI −2–6.3) −0.2 (95% CI −2.6–2.1) −2.4 (95% CI −6–1.1)
patients who received BDPE [16]. Only two of our patients experienced bradycardia after BDPE, both of whom had lowest recorded HR after BDPE in the high 40s. Neither of these bradycardic cases prompted intervention from the treating physician and both of these patients had improvement in MAP in spite of bradycardia. We also note that both of these patients were bradycardic prior to receiving the drug (HR 38 and 51), which should be a contraindication to BDPE. Mean HR for all patients prior to receiving BDPE was 101 and did not change significantly compared to after BDPE (CI 94–118). We suggest that providers who are concerned about possible reflex bradycardia limit use of BDPE to patients who have a normal HR. Phenylephrine is a pure alpha vasoconstrictor. Since it has no intrinsic inotropic effects, it should be considered as a favorable agent in tachycardic patients compared to epinephrine or ephedrine, which may further increase heart rate as well as inotropy. However, there is concern that phenylephrine may reduce cardiac output (CO) secondary to increased afterload or reflex bradycardia, which again was not observed in our study. Results from the anesthesia literature have been mixed, with some observing a decrease in CO and others observing no change [6]. In one article, changes in HR were found to correlate with CO in a study that examined the hemodynamic effects of phenylephrine during spinal anesthesia [21]. For patients with existing heart failure, use of BDPE may place them at risk for worsened cardiac function. More studies are needed to specifically evaluate the effects of phenylephrine on patients with heart failure. Until such data becomes available, it may be prudent to avoid phenylephrine use in this patient population. The trauma patient cohort who most commonly received BDPE were patients suffering from hemorrhagic shock secondary to motor vehicle collisions. In 22 of 37 trauma cases, BDPE was given for hypotension in the context of rapid sequence intubation. There are various pathophysiology arguments for and against vasopressor use in hemorrhagic shock, however no prospective clinical trials have been performed which compare traumatology interventions with and without vasopressor use. Given that our study did not enlist a trauma control group and patients received concurrent therapeutic interventions such as crystalloid and blood products, it is impossible to discern any meaningful therapeutic effect of BDPE in trauma patients. Interpretation of the effect of BDPE in trauma patients is further complicated by the fact that the majority of the trauma patients who received the drug in our study were given BDPE in the per-intubation period. Clinical studies that delineate the type of vasopressor therapy and timing of administration in trauma patients are needed. Nevertheless, none of the trauma patients in this study were observed to experience hypertensive crisis or bradycardia requiring intervention. Until an intervention strategy is better validated by the research literature, the routine use of BDPE in trauma patients cannot be recommended. A study examining the hemodynamic effects of BDPE for spinal anesthesia patients found doses of 80 mcg to result in SVR increases of 75% at 30 s after administration and increase in MAP by 36% after approximately 60 s [21]. Panchal et al. reported statistically significant increases in SBP and DBP after BDPE administration to hypotensive ED patients in the peri-intubation period for a series of 20 patients but did not specify a dose-response relationship [15]. Schwartz et al. also reported similar increases in blood pressure in ED patients who received BDPE [16]. Though we are not aware of any published data examining doseresponse data for BDPE, our data are consistent with the findings of a study that examined the dose-response relationship for varying rates
of phenylephrine infusions in surgical intensive care unit patients. This study also concluded that higher infusion doses resulted in greater increase in MAP [22]. Studies from the spinal anesthesia literature have also concluded that the effective doses of BDPE in that clinical setting are approximately 140–150 mcg [23,24]. A prior study regarding practice patterns of BDPE in the ED indicated there was no systematic pattern of dosing [15]. This study similarly demonstrated a wide range of dosing and administration timing. Our study did not include a matched control group of patients who did not receive BDPE, which highly limits interpretation of the dose-response relationship. In addition, many patients simultaneously received additional medications and/or fluids, so the effect of phenylephrine was not isolated. However, doses of 200 mcg appeared to be more effective than doses of 100 mcg, and doses 100 mcg or less demonstrated very modest increases blood pressure. We had 26 patients given doses over 199 mcg with mean increase in MAP of 12 (95% CI 4.5–20). We acknowledge that critically ill ED patients with hypotension are a highly heterogeneous patient population. Resuscitation efforts must be tailored to target the underlying causes of hypotension. For example, in the case of trauma patients, studies have shown higher mortality in blunt trauma patients with hemorrhagic shock who were treated with vasopressors [25]. Schwartz et al. reported that patients who received adequate early preload expansion with intravenous fluids required continuous vasopressor infusion less frequently after BDPE compared to patients who were under resuscitated [16]. The approach to managing hypotension in the ED should include crystalloid, blood products, and occasionally vasopressors depending on clinical scenario.
5. Limitations This study was performed at a single institution and our findings may not be generalizable to other institutions with different patient populations. All data was recorded retrospectively. Much of the data was collected from scanned handwritten nursing resuscitation flow sheets, which are subject to recording errors. Further, there were several cases in which the exact time of phenylephrine administration was thought by two agreeing data collectors to be highly likely to be inaccurately recorded. These cases were included in the safety data, but were excluded from the effectiveness data. Given the transient nature of phenylephrine effects as well as the potential for recording errors, it is possible that a blood pressure or heart rate that met criteria for an adverse event may have occurred but was not documented. There was no protocol for choosing which patients should receive BDPE. Clinician comfort and familiarity with phenylephrine usage likely varied widely. The decision to administer BDPE was done at the Emergency Physician's discretion and opens the study to a number of biases, including selection and information bias. We acknowledge that critically ill ED patients with hypotension are a highly heterogeneous patient population. During Emergency Department resuscitation, there are a tremendous number of variables that impact patient outcomes. Lack of a matched control group significantly limits interpretation of our effectiveness data. The effect of phenylephrine was not isolated as patients were in many cases receiving crystalloid, additional medications, and blood products that may have contributed to the change in blood pressure. Given the complexity and disease specific nature of each patient's resuscitative needs, it would be difficult to reliably tie one medication such as phenylephrine to patient outcome variables without performing a much larger study with a matched control group. Our sample size of 181 patients may not be large enough to definitely conclude that BDPE is safe and effective in ED patients. While we are encouraged by these results and will continue to stock preloaded syringes of phenylephrine at our institution for bolus dose use, larger prospective studies will be needed to confirm safety. Additionally, while our study did show that patients who received BDPE had improvement
Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095
K. Swenson et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx
in MAP, we are not able to demonstrate that improvement in MAP lead to improvement in outcome measures due to lack of a control group. 6. Conclusion Our results support that idea that BDPE is a safe agent to treat transient hypotension or as a bridge to improve MAP while additional comparatively time intensive resuscitative efforts are underway, such as the initiation of a vasopressor infusion and/or placement of a central venous catheter. While BDPE does not replace traditional resuscitative therapies, our study supports its use in the ED. Further studies are needed to confirm BDPE's apparent safety and effectiveness. Grants and financial support None. Conflicts of interest None. Author contributions KS, SR, and DB conceived of and designed the study. SR and KS collected the data. JL provided statistical advice and analyzed the data. LD and TV drafted the manuscript, and all authors substantially contributed to its revision. KS takes responsibility for the paper as a whole. References [1] Jones AE, Yiannibas V, Johnson C, Kline JA. Emergency department hypotension predicts sudden unexpected in-hospital mortality: a prospective cohort study. Chest Oct 2006;130(4):941–6. [2] Heffner AC, Swords D, Kline JA, Jones AE. The frequency and significance of postintubation hypotension during emergency airway management. J Crit Care Aug 2012;27(4):417.e9–417.e13. [3] Merz TM, Etter R, Mende L, et al. Risk assessment in the first fifteen minutes: a prospective cohort study of a simple physiological scoring system in the emergency department. Crit Care 2011;15(1):R25. [4] Marchick MR, Kline JA, Jones AE. The significance of non-sustained hypotension in emergency department patients with sepsis. Intensive Care Med Jul 2009;35(7): 1261–4. [5] Jones AE, Aborn LS, Kline JA. Severity of emergency department hypotension predicts adverse hospital outcome. Shock Augusta Ga Nov 2004;22(5):410–4. [6] Kuhn JC, Hauge TH, Rosseland LA, et al. Hemodynamics of phenylephrine infusion versus lower extremity compression during spinal anesthesia for cesarean delivery: a randomized, double-blind, placebo-controlled study. Anesth Analg Apr 2016; 122(4):1120–9.
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Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Safety of bolus-dose phenylephrine for hypotensive emergency department patients☆ Kjirsten Swenson, MD a,⁎, Shannon Rankin, PharmD, BCPS b, Leticia Daconti, MD b, Tomas Villarreal, MD, MPH b, Jens Langsjoen, MD b, Darren Braude, MD, MPH b a b
University of New Mexico Health Sciences Center, 2211 Lomas Blvd, Albuquerque, NM 87106, USA University of New Mexico Health Sciences Center, Albuquerque, NM, USA
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Article history: Received 9 January 2018 Accepted 30 January 2018 Available online xxxx Keywords: Phenylephrine Bolus-dose vasopressor Hypotension Resuscitation Safety
a b s t r a c t Introduction: Bolus-dose phenylephrine (BDPE) is routinely used to treat hypotension in the operating room. BDPE's fast onset of action and ability to be administered peripherally have prompted calls for its use in the Emergency Department (ED). There are few published data on the safety of BDPE use in the ED. Primary concerns include BDPE's potential to cause dangerous hypertension or reflex bradycardia. We hypothesize that BDPE is a safe short-term vasopressor choice for hypotensive ED patients. Methods: We conducted a structured chart review for all patients who received BDPE from preloaded syringes over 42 months. We defined an adverse event (AE) as sBP N 180, dBP N 110, or HR b 50 within 30 min of receiving BDPE. We defined a serious adverse event (SAE) as an AE with pharmacologic intervention to correct vital sign abnormality. We also compared mean arterial pressure (MAP), sBP, and dBP pre/post BDPE administration to assess effectiveness. We used a two-sample t-test to assess for differences between the mean delta MAP after low versus high-dose BDPE. Results: We identified 181 cases of ED use. 147 cases had complete pre/post vital signs. We identified 5 AEs and no SAEs. Three patients developed sBP N 180 mm Hg. The patients suffered no apparent harm. No patients had dBP N 110. Two patients developed bradycardia post-drug. In both cases, MAP improved despite bradycardia. Conclusions: BDPE does not appear to cause reflex bradycardia or hypertension requiring intervention among hypotensive ED patients. The apparent safety of BDPE should be confirmed in prospective trials. © 2018 Elsevier Inc. All rights reserved.
1. Introduction Hypotension in the Emergency Department (ED) is common, with one retrospective study estimating prevalence as high as 19% in nontrauma patients being admitted to the hospital [1]. Causes of hypotension in this setting are varied and often multifactorial; potential etiologies include septic, neurogenic, hemorrhagic, hypovolemic or cardiogenic shock. Patients may also have transient hypotension related to medications administered during procedural sedation or intubation. In one retrospective cohort study in an urban ED, approximately 23% of patients undergoing intubation developed post-intubation hypotension [2]. Large, single-center, prospective, cohort studies have shown exposure to hypotension in the ED to be an independent predictor of inhospital mortality with odds ratios from 2.0 (95% CI, 1.3 to 2.8; n = ☆ Meetings: An abstract entitled “Safety and Effectiveness of Bolus-Dose Phenylephrine for Hypotensive Emergency Department Patients” was presented at the Western Regional Society for Academic Emergency Medicine Conference in Los Angeles, California on April 2, 2016. ⁎ Corresponding author. E-mail addresses: [email protected] (K. Swenson), [email protected] (J. Langsjoen), [email protected] (D. Braude).
4790) (1) to 3.88 (95% CI, 2.62 to 5.75; n = 4388) [3]. Non-sustained hypotension in ED patients has also been associated with increased mortality in sepsis patients [4]. Moreover, the severity of hypotension and its duration in the ED has been associated with adverse hospital outcomes including acute organ failure, need for Intensive Care Unit (ICU) stay, and in-hospital mortality [5]. Post-intubation hypotension has also been shown to be a risk factor for in-hospital mortality with an OR of 2.1 (95% CI, 1.2–3.9) [2]. Several studies from the anesthesia literature support the use of peripherally administered bolus doses of diluted vasopressors, or “bolusdose vasopressors” for hypotension that is expected to be transient. Much of this literature examines the use of phenylephrine, ephedrine, and epinephrine in the setting of spinal anesthesia [6]. These drugs are used to counteract the rapid decrease in systemic vascular resistance (SVR) that occurs as a result of spinal anesthesia. Several studies have found phenylephrine to be effective at counteracting hypotension in this clinical scenario [6-10]. There has been increased interest in the Emergency Medicine community about the use of bolus-dose vasopressors for critically ill ED patients. Bolus-dose vasopressors may be given rapidly through a peripheral line and can serve as a temporizing measure while placing a central line or preparing a vasopressor infusion. They may also be
https://doi.org/10.1016/j.ajem.2018.01.095 0735-6757/© 2018 Elsevier Inc. All rights reserved.
Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095
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K. Swenson et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx
indicated for transient hypotension, such as during procedural sedation, post-intubation, or while crystalloid or blood product volume resuscitation is in progress. Bolus-dose phenylephrine (BDPE) has several characteristics that make it ideal for use in the ED setting. Phenylephrine is a selective alpha-1 adrenergic agonist that acts on smooth muscle in the vasculature to cause vasoconstriction, resulting in an increase in mean arterial pressure (MAP) [11]. In contrast to epinephrine, phenylephrine has no effect on inotropy. Potential adverse effects include hypertensive crisis, reflex bradycardia, cardiac arrhythmia, ischemia, reduced cardiac output and hypersensitivity reaction [12]. When administered intravenously, onset of vasoconstriction is almost immediate and peak effect occurs in 1–5 min. Phenylephrine may be safely administered through a peripheral line [13,14]. There are no published case reports of harm related to phenylephrine extravasation in the English literature [13,14]. These qualities make phenylephrine an ideal vasopressor for bolusdose use in the Emergency Department, particularly given that ED patients usually lack central venous access at the time of presentation. Several studies from the anesthesia literature investigated a doseresponse relationship for the drug when used for spinal anesthesia [6-10]. There is also literature describing phenylephrine infusion dosing for critically ill patients. We are not aware of any studies reporting a dose-response relationship for BDPE when used for critically ill patients. While BDPE has been used routinely in the operating room, we are aware of only two other studies describing its use in the ED. Panchal et al. conducted a retrospective chart review of 20 patients with periintubation hypotension who received BDPE [15]. This study found that phenylephrine was effective at increasing blood pressure in patients who were hypotensive after intubation [15]. Schwartz et al. reported that bolus-dose phenylephrine similarly increased blood pressure in their Emergency Department patient population with no significant effect on heart rate [16]. Our institution began stocking preloaded, pre-diluted syringes of phenylephrine in our resuscitation bays in 2009 in an effort to increase quick and convenient access to the drug for bolus-dose use while minimizing potential drug preparation errors. This study seeks to describe the use of BDPE in the ED setting, quantify rate of potentially dangerous hypertension and reflex bradycardia and examine circumstances of such cases, and examine its dose-response in the critically ill ED patient population. 2. Materials and methods The study was conducted at an urban, academic trauma center. Preloaded, pre-diluted syringes containing 1000 mcg/10 mL BDPE were stocked in the resuscitation bay automated medicationdispensing cabinets. We conducted a structured retrospective chart review for all patients who received BDPE from preloaded syringes over 42 months. After Institutional Review Board approval, patient encounters in which phenylephrine was pulled from any automated dispensing cabinet were retrospectively identified. Study subjects included all adult patients who received BDPE during the study period. No formal training curriculum or standard dose of phenylephrine was recommended. The decision to use BDPE was at the discretion of the treating physician. The primary investigator and a second author (an experienced ED pharmacist) used an internally developed, standardized data collection tool to manually extract data from the Cerner electronic records of all patients meeting inclusion criteria. For 12% of charts, each author independently extracted key variables (vital signs pre and post phenylephrine) to determine inter-rater reliability and ensure consistent data extraction. The demographic data recorded included age, gender, reason for visit, primary diagnosis and context of phenylephrine administration. Safety data recorded included pre and post BDPE systolic (SBP), diastolic blood pressures (DBP), mean arterial pressure (MAP), and heart rate
(HR). We also recorded the highest SBP and DBP and lowest HR within 30 min of BDPE administration. Other resuscitative medications and fluids administered, including induction agents, paralytics, vasopressors, blood products and intravenous fluids, were also documented. Our primary safety outcomes in this study were potentially dangerous vital sign abnormalities attributable to BDPE, including marked elevation in blood pressure or decreases in heart rate. We defined an adverse event as SBP N 180 or DBP N 110 or HR b 50 within 30 min of receiving BDPE. In cases of multiple doses of BDPE, all instances in which the drug was given were examined for the above vital sign abnormalities. The blood pressure thresholds were chosen based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [17]. This report characterizes patients whose blood pressure exceeds these thresholds as being at risk for hypertensive crisis. We defined a serious adverse event (SAE) as an adverse event with subsequent treatment to correct abnormal vital signs with an antihypertensive (in cases of hypertension) or atropine (in cases of bradycardia). All cases meeting criteria for an adverse event were reviewed to assess circumstances of abnormal vital signs and likelihood they were related to BDPE administration, detect any evidence of harm related to hypertension or bradycardia, and to identify any intervention taken to treat hypertension or bradycardia. As secondary outcomes, we compared HR, MAP, SBP, and DBP pre and post BDPE administration to assess effectiveness in cases in which complete pre and post drug vital signs were available. In cases of multiple doses of BDPE, we included only the first instance in which BDPE was given. We performed a two-sample t-test to assess for difference between the mean changes in MAP after low versus high dose BDPE. We also compared HR pre and post BDPE administration. 3. Results 181 cases were retrospectively identified and included in the study. Inter-rater reliability for key vital sign data points was 96%. Table 1 describes patient characteristics and context of BDPE use. 106 patients were male (58.6%) and 75 were female (41.4%). The mean age of patients was 53.6 years and the median age was 56 years. There were 144 medical resuscitation patients and 37 trauma resuscitation patients. Of the medical resuscitations, 81 were general medical resuscitations, 62 were cases in which BDPE was given in the peri-rapid sequence intubation period, and in one case BDPE was given during procedural sedation. Two authors extracted the data. For the key variables of vital signs pre and post-phenylephrine, inter-rater reliability was 95.6%. In most cases, disagreement was due to one author incorrectly reporting a value as missing. In two cases, disagreement was due to one author reporting an incorrect value. Table 2 describes the primary diagnoses of medical resuscitation patients who received BDPE. Among the medical resuscitation cases, we
Table 1 Patient characteristics and context of bolus dose phenylephrine use. n Age Mean age Median age Gender Male Female Context of BPE use Medical resuscitation General medical resuscitation Rapid sequence intubation Procedural sedation Trauma resuscitation General trauma resuscitation Rapid sequence intubation Total
53.6 years 56.0 years 106 75
59% 41%
144 81 62 1 37 15 22 181
79.5% 56.3% 43% 0.7% 20.5% 40.5% 59.5%
Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095
K. Swenson et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx Table 2 Primary diagnosis of medical resuscitation patients.
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Table 4 Etiology of hypotension in trauma cases.
Diagnosis
N (%)
Shock classification
Frequency (%)
Sepsis Respiratory distress or failure Cardiac arrest Overdose Altered mental status Gastrointestinal bleed Seizure Intracranial hemorrhage Hypovolemia Hypoglycemia Hyperglycemia Others Total
32 (22) 27 (19) 21 (15) 18 (13) 15 (10) 9 (6) 6 (4) 4 (3) 3 (2) 3 (2) 2 (1) 4 (3) 144
Hemorrhagic shock Neurogenic shock Total
28 (76) 9 (24) 37
observed a wide array of diagnoses leading to hypotension, with most patients having an initial diagnosis of sepsis (32 of 144), respiratory failure or distress (27 of 144), cardiac arrest (21 of 144), and overdose (18 of 144). Table 3 lists the mechanism of injury among trauma patients who received BDPE. The mechanism of injury for most trauma patients was motor vehicle collision (17 of 37 cases). Most trauma patients who received bolus phenylephrine were hypotensive due to hemorrhagic shock when they received BDPE. BDPE was given for hypotension in the peri-intubation period in 22 of 37 cases (Table 4). 80 patients received one vasopressor in addition to phenylephrine, 22 received two additional vasopressors, and 5 received three additional vasopressors. 28 patients received blood products, eight received two types of blood products and one received three types of blood products (Table 5). BDPE doses ranged from 10 to 500 mcg/dose. 81 patients received multiple doses of BDPE. Only the first dose was included in effectiveness calculations. Of the 181 cases, 149 had complete pre/post BDPE vital signs and were included in the effectiveness calculations. In most cases, the missing vital sign was either lack of documented pre-drug blood pressure or blood pressure documented as systolic/palpation. Mean change in MAP after BDPE administration is shown in Table 6. While all dose ranges resulted in a mean increase in MAP, BDPE doses N200 mcg were more effective than doses b100 mcg (p = 0.02). Of 181 cases included in the study, five met our criteria for a possible adverse event. Three cases developed SBP N180 mm Hg within 30 min of BDPE administration, and two met criteria for bradycardia. In the first hypertension case, elevated SBP occurred 15 min after BDPE. The patient had been recently intubated and was sedated with a 10 mcg/kg/min propofol infusion. The propofol infusion was discontinued due to hypotension 6 min before BDPE was given. MAP improved after these interventions. Subsequently, 15 min after BDPE (21 min after discontinuation of propofol), a hypertensive pressure that met our criteria for an adverse event occurred, with SBP 191. Under-sedation may have been a factor given recent discontinuation of propofol. No intervention was required to lower the blood pressure, and the patient suffered no apparent harm as a result of the transient Table 3 Mechanism of injury among trauma cases. Mechanism
N (%)
Motor vehicle collision Gunshot wound Motorcycle collision Fall Pedestrian vs auto Hanging Laceration Total
17 (46) 5 (14) 4 (11) 4 (11) 3 (8) 3 (8) 1 (3) 37
hypertension. In the second case, SBP 190 was recorded 26 min after BDPE administration. In the third case, an outlying episode of hypertension (SBP 221) was recorded 2 min after BDPE in context of normal BP immediately before (SBP 94) and continuously after this measurement (SBP 130, 5 min after BDPE), raising suspicion of a measurement or recording error. The patient suffered no apparent harm. No patient had DBP N110. No patient required intervention to lower the blood pressure after receiving BDPE. Two patients were noted to be bradycardic post-BDPE but both were bradycardic prior to BDPE administration. The first patient was being unsuccessfully externally paced on arrival with a HR of 38, which improved to 47 after 200 mcg BDPE given along with atropine prior to intubation. The second patient's heart rate decreased from 51 to 48 after 100 mcg BDPE but did not require intervention. In both cases, MAP improved despite ongoing bradycardia. 4. Discussion Our data show that BDPE did not cause dangerous hypertension or bradycardia in a heterogeneous critically ill ED patient population. Only five out of 181 patients who received BDPE met criteria for a potentially harmful vital sign abnormality that could possibly be attributed to BDPE, and no patient required intervention nor developed evidence of harm related to BDPE. Of the three patients with SBP N180 after BDPE, two developed blood pressure criteria for hypertensive crises more than two half-lives after receiving BDPE. This lowers our suspicion that the vital sign abnormality was related to BDPE. The other case had strong evidence of a measuring or recording error rather than true hypertension. BDPE can cause reflex bradycardia when a rapid increase in systemic vascular resistance activates the stretch baroreceptors in the aortic arch and carotid sinuses causing the heart rate to reflexively lower [6,9,18]. Anesthesia studies have reported incidence of bradycardia following phenylephrine administration ranging from 2.6% to 15% [6,8,19,20]. A study conducted in the ED reported bradycardia in 7/73 (9.6%) of
Table 5 Resuscitation medications and blood products given in addition to bolus dose phenylephrine. n cases Additional vasopressors Norepinephrine Epinephrine Dopamine Vasopressin Dobutamine Blood products Packed red blood cells Fresh frozen plasma Platelets Paralytics Rocuronium Succinylcholine Vecuronium Induction agents Etomidate Ketamine Midazolam Fentanyl Propofol
65 18 15 9 3 26 9 3 101 4 1 51 46 7 1 0
Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095
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K. Swenson et al. / American Journal of Emergency Medicine xxx (2018) xxx–xxx
Table 6 Effect of BDPE on mean arterial pressure and heart rate by dose. Dose
Mean change in MAP
Mean change in HR
b100 mcg (40 cases) 100–199 mcg (83 cases) 200–500 mcg (26 cases)
+4.0 (95% CI 1.7–6.2) +5.6 (95% CI 2.3–8.8) +12 (95% CI 4.5–20)
+2.2 (95% CI −2–6.3) −0.2 (95% CI −2.6–2.1) −2.4 (95% CI −6–1.1)
patients who received BDPE [16]. Only two of our patients experienced bradycardia after BDPE, both of whom had lowest recorded HR after BDPE in the high 40s. Neither of these bradycardic cases prompted intervention from the treating physician and both of these patients had improvement in MAP in spite of bradycardia. We also note that both of these patients were bradycardic prior to receiving the drug (HR 38 and 51), which should be a contraindication to BDPE. Mean HR for all patients prior to receiving BDPE was 101 and did not change significantly compared to after BDPE (CI 94–118). We suggest that providers who are concerned about possible reflex bradycardia limit use of BDPE to patients who have a normal HR. Phenylephrine is a pure alpha vasoconstrictor. Since it has no intrinsic inotropic effects, it should be considered as a favorable agent in tachycardic patients compared to epinephrine or ephedrine, which may further increase heart rate as well as inotropy. However, there is concern that phenylephrine may reduce cardiac output (CO) secondary to increased afterload or reflex bradycardia, which again was not observed in our study. Results from the anesthesia literature have been mixed, with some observing a decrease in CO and others observing no change [6]. In one article, changes in HR were found to correlate with CO in a study that examined the hemodynamic effects of phenylephrine during spinal anesthesia [21]. For patients with existing heart failure, use of BDPE may place them at risk for worsened cardiac function. More studies are needed to specifically evaluate the effects of phenylephrine on patients with heart failure. Until such data becomes available, it may be prudent to avoid phenylephrine use in this patient population. The trauma patient cohort who most commonly received BDPE were patients suffering from hemorrhagic shock secondary to motor vehicle collisions. In 22 of 37 trauma cases, BDPE was given for hypotension in the context of rapid sequence intubation. There are various pathophysiology arguments for and against vasopressor use in hemorrhagic shock, however no prospective clinical trials have been performed which compare traumatology interventions with and without vasopressor use. Given that our study did not enlist a trauma control group and patients received concurrent therapeutic interventions such as crystalloid and blood products, it is impossible to discern any meaningful therapeutic effect of BDPE in trauma patients. Interpretation of the effect of BDPE in trauma patients is further complicated by the fact that the majority of the trauma patients who received the drug in our study were given BDPE in the per-intubation period. Clinical studies that delineate the type of vasopressor therapy and timing of administration in trauma patients are needed. Nevertheless, none of the trauma patients in this study were observed to experience hypertensive crisis or bradycardia requiring intervention. Until an intervention strategy is better validated by the research literature, the routine use of BDPE in trauma patients cannot be recommended. A study examining the hemodynamic effects of BDPE for spinal anesthesia patients found doses of 80 mcg to result in SVR increases of 75% at 30 s after administration and increase in MAP by 36% after approximately 60 s [21]. Panchal et al. reported statistically significant increases in SBP and DBP after BDPE administration to hypotensive ED patients in the peri-intubation period for a series of 20 patients but did not specify a dose-response relationship [15]. Schwartz et al. also reported similar increases in blood pressure in ED patients who received BDPE [16]. Though we are not aware of any published data examining doseresponse data for BDPE, our data are consistent with the findings of a study that examined the dose-response relationship for varying rates
of phenylephrine infusions in surgical intensive care unit patients. This study also concluded that higher infusion doses resulted in greater increase in MAP [22]. Studies from the spinal anesthesia literature have also concluded that the effective doses of BDPE in that clinical setting are approximately 140–150 mcg [23,24]. A prior study regarding practice patterns of BDPE in the ED indicated there was no systematic pattern of dosing [15]. This study similarly demonstrated a wide range of dosing and administration timing. Our study did not include a matched control group of patients who did not receive BDPE, which highly limits interpretation of the dose-response relationship. In addition, many patients simultaneously received additional medications and/or fluids, so the effect of phenylephrine was not isolated. However, doses of 200 mcg appeared to be more effective than doses of 100 mcg, and doses 100 mcg or less demonstrated very modest increases blood pressure. We had 26 patients given doses over 199 mcg with mean increase in MAP of 12 (95% CI 4.5–20). We acknowledge that critically ill ED patients with hypotension are a highly heterogeneous patient population. Resuscitation efforts must be tailored to target the underlying causes of hypotension. For example, in the case of trauma patients, studies have shown higher mortality in blunt trauma patients with hemorrhagic shock who were treated with vasopressors [25]. Schwartz et al. reported that patients who received adequate early preload expansion with intravenous fluids required continuous vasopressor infusion less frequently after BDPE compared to patients who were under resuscitated [16]. The approach to managing hypotension in the ED should include crystalloid, blood products, and occasionally vasopressors depending on clinical scenario.
5. Limitations This study was performed at a single institution and our findings may not be generalizable to other institutions with different patient populations. All data was recorded retrospectively. Much of the data was collected from scanned handwritten nursing resuscitation flow sheets, which are subject to recording errors. Further, there were several cases in which the exact time of phenylephrine administration was thought by two agreeing data collectors to be highly likely to be inaccurately recorded. These cases were included in the safety data, but were excluded from the effectiveness data. Given the transient nature of phenylephrine effects as well as the potential for recording errors, it is possible that a blood pressure or heart rate that met criteria for an adverse event may have occurred but was not documented. There was no protocol for choosing which patients should receive BDPE. Clinician comfort and familiarity with phenylephrine usage likely varied widely. The decision to administer BDPE was done at the Emergency Physician's discretion and opens the study to a number of biases, including selection and information bias. We acknowledge that critically ill ED patients with hypotension are a highly heterogeneous patient population. During Emergency Department resuscitation, there are a tremendous number of variables that impact patient outcomes. Lack of a matched control group significantly limits interpretation of our effectiveness data. The effect of phenylephrine was not isolated as patients were in many cases receiving crystalloid, additional medications, and blood products that may have contributed to the change in blood pressure. Given the complexity and disease specific nature of each patient's resuscitative needs, it would be difficult to reliably tie one medication such as phenylephrine to patient outcome variables without performing a much larger study with a matched control group. Our sample size of 181 patients may not be large enough to definitely conclude that BDPE is safe and effective in ED patients. While we are encouraged by these results and will continue to stock preloaded syringes of phenylephrine at our institution for bolus dose use, larger prospective studies will be needed to confirm safety. Additionally, while our study did show that patients who received BDPE had improvement
Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095
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in MAP, we are not able to demonstrate that improvement in MAP lead to improvement in outcome measures due to lack of a control group. 6. Conclusion Our results support that idea that BDPE is a safe agent to treat transient hypotension or as a bridge to improve MAP while additional comparatively time intensive resuscitative efforts are underway, such as the initiation of a vasopressor infusion and/or placement of a central venous catheter. While BDPE does not replace traditional resuscitative therapies, our study supports its use in the ED. Further studies are needed to confirm BDPE's apparent safety and effectiveness. Grants and financial support None. Conflicts of interest None. Author contributions KS, SR, and DB conceived of and designed the study. SR and KS collected the data. JL provided statistical advice and analyzed the data. LD and TV drafted the manuscript, and all authors substantially contributed to its revision. KS takes responsibility for the paper as a whole. References [1] Jones AE, Yiannibas V, Johnson C, Kline JA. Emergency department hypotension predicts sudden unexpected in-hospital mortality: a prospective cohort study. Chest Oct 2006;130(4):941–6. [2] Heffner AC, Swords D, Kline JA, Jones AE. The frequency and significance of postintubation hypotension during emergency airway management. J Crit Care Aug 2012;27(4):417.e9–417.e13. [3] Merz TM, Etter R, Mende L, et al. Risk assessment in the first fifteen minutes: a prospective cohort study of a simple physiological scoring system in the emergency department. Crit Care 2011;15(1):R25. [4] Marchick MR, Kline JA, Jones AE. The significance of non-sustained hypotension in emergency department patients with sepsis. Intensive Care Med Jul 2009;35(7): 1261–4. [5] Jones AE, Aborn LS, Kline JA. Severity of emergency department hypotension predicts adverse hospital outcome. Shock Augusta Ga Nov 2004;22(5):410–4. [6] Kuhn JC, Hauge TH, Rosseland LA, et al. Hemodynamics of phenylephrine infusion versus lower extremity compression during spinal anesthesia for cesarean delivery: a randomized, double-blind, placebo-controlled study. Anesth Analg Apr 2016; 122(4):1120–9.
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Please cite this article as: Swenson K, et al, Safety of bolus-dose phenylephrine for hypotensive emergency department patients, American Journal of Emergency Medicine (2018), https://doi.org/10.1016/j.ajem.2018.01.095