Reminder of important clinical lesson
BMJ Case Rep: first published as 10.1136/bcr-2018-228208 on 8 March 2019. Downloaded from http://casereports.bmj.com/ on 19 March 2019 by guest. Protected by copyright.
Department of Emergency
Medicine, University of Florida,
Gainesville, Florida, USA
Correspondence to
Dr Charles W Hwang,
​c7places@​ufl.​edu
Accepted 19 February 2019
© BMJ Publishing Group
Limited 2019. No commercial
re-use. See rights and
permissions. Published by BMJ.
To cite: Hwang CW,
Gamble G, Marchick M,
et al. BMJ Case Rep
2019;12:e228208.
doi:10.1136/bcr-2018-
228208
Case report
A case of refractory ventricular fibrillation successfully
treated with low-dose esmolol
Charles W Hwang, Ginger Gamble, Michael Marchick, Torben K Becker
Summary
Current advanced cardiac life support (ACLS)
guidelines for the management of ventricular
fibrillation (VF) and pulseless ventricular tachycardia
is defibrillation. However, refractory VF, which
is defined as VF that persists despite three
defibrillation attempts, is challenging for all ACLS
providers; the best resuscitation strategy for patients
that persist in refractory VF remains unclear. We
report on a 51-year-old man who presented to
the emergency department with chest pain and
subsequently went into witnessed VF cardiac arrest.
Despite standard ACLS management consisting of
high-quality cardiopulmonary resuscitation, serial
epinephrine and serial defibrillation, the return of
spontaneous circulation (ROSC) was unable to be
achieved. Double sequential defibrillation (DSD)
was attempted multiple times unsuccessfully. After
administration of low-dose esmolol, he immediately
achieved ROSC. DSD and β-blockade are increasingly
recognised in the literature and practice for
refractory VF. However, to the best of our knowledge,
this is the first case of refractory VF that responded
to low-dose esmolol β-blockade.
Background
Current advanced cardiac life support (ACLS) algo-
rithms for the management of ventricular fibril-
lation (VF) and pulseless ventricular tachycardia
(VT) consist of high-quality cardiopulmonary
resuscitation (CPR), defibrillation and the sequen-
tial administration of epinephrine/vasopressin and
antiarrhythmic agents.1–3 Epinephrine’s mechanism
of action in cardiac arrest has been attributed to
its α-adrenergic effects, which preferentially redi-
rect systemic blood flow towards the heart, thereby
increasing myocardial blood flow and achieving
the minimum coronary perfusion pressure (CPP)
necessary for successful defibrillation.2–8 Despite its
apparent benefit in cardiac arrest, epinephrine has
several significant deleterious effects thought to be
related to its β-adrenergic properties, which lower
the threshold for lethal dysrhythmias.2 4–8
Refractory VF, traditionally defined as VF that
persists despite three defibrillation attempts, is
thought to be the result of excessive endogenous
catecholamines released during severe stress and
is further augmented by exogenous epinephrine
administration.2 5 6 8 It has been suggested that
blocking β activity in the catecholamine-rich milieu
of cardiac arrest may be beneficial for resuscitation,
Hwang CW, et al. BMJ Case Rep 2019;12:e228208. doi:10.1136/bcr-2018-228208
although this is limited to animal studies and case
reports/series.2 4–6 8–13 To the best of our knowledge,
this is the first case of refractory VF that responded
to low-dose esmolol β-blockade.
Case presentation
A 51-year-old obese Caucasian man presented to the
emergency department (ED) by emergency medical
services (EMS) with chest pain and shortness of
breath. Per EMS report, the patient developed chest
pain radiating into his left shoulder approximately
90 min prior to calling EMS. He reported a history
of type 2 diabetes mellitus and hypertension but
denied any history of coronary artery disease. He
reported that he had been non-compliant with his
prescription medications for 4 years. Prehospital
vital signs and 12 lead ECG were unremarkable. He
received 324 mg oral aspirin prior to arrival at the
ED.
During the ED triage process, an ECG was
performed which did not demonstrate ST-segment
elevation (figure 1). While waiting to be roomed
in the ED, he was witnessed by the ED triage para-
medic to become unresponsive with agonal respi-
rations, and high-quality CPR was immediately
initiated.
The first rhythm check revealed coarse VF. The
standard ACLS algorithm was followed, consisting
of high-quality CPR, serial epinephrine 1:10 000
1 mg intravenous boluses, biphasic defibrillation
at the appropriate intervals and advanced airway
placement. Despite defibrillating four times at
escalating doses of energy, his rhythm remained
in VF (figure 2). He was also given ACLS-directed
amiodarone intravenously at the appropriate
doses and intervals (300 mg intravenous push
followed by 150 mg intravenous push) and started
on amiodarone intravenous infusion. During
two rhythm assessments, the monitor displayed
Figure 1 The patient’s initial emergency department
ECG did not demonstrate ST elevation.
1
 Reminder of important clinical lesson
Figure 2 Telemetry strips demonstrate VF and the resulting defibrillation attempts. VF, ventricular fibrillation.
Figure 3 Telemetry strip demonstrating ROSC. ROSC, return of spontaneous circulation.
polymorphic VT, and he received 2 g of magnesium sulfate intra-
venously twice.
Differential diagnosis
Given the patient’s initial clinical presentation of chest pain
and shortness of breath and rapid decompensation into sudden
cardiac death, the leading diagnosis was a life-threatening
arrhythmia, which included, but was not limited to VF, VT,
torsades de pointes, pulseless electrical activity and asystole. The
primary goal during the initial resuscitation was maintaining
coronary perfusion with high-quality CPR while attempting to
identify the cardiac rhythm.
The patient’s cardiac rhythm was identified as VF and VT,
both shockable rhythms. The causes of VF and VT are vast;
they include, but are not limited to, ischaemic heart disease,
cardiomyopathy, myocarditis and channelopathies. Given the
patient’s presentation of chest pain and shortness of breath in
the setting of several cardiac risk factors, ischaemic heart disease
was suspected to be the likely culprit.
Figure 4 The patient’s post-ROSC ECG demonstrates ST elevation
in lead aVR and V1 with reciprocal changes in limb and precordial
leads. aVR, augmented vector right; ROSC, return of spontaneous
circulation.
2 Hwang CW, et al. BMJ Case Rep 2019;12:e228208. doi:10.1136/bcr-2018-228208
BMJ Case Rep: first published as 10.1136/bcr-2018-228208 on 8 March 2019. Downloaded from http://casereports.bmj.com/ on 19 March 2019 by guest. Protected by copyright.
Treatment
After four standard defibrillation attempts with no subse-
quent return of spontaneous circulation (ROSC), the patient
was defibrillated an additional five times using double sequen-
tial defibrillation (DSD) for refractory VF. Despite the above
measures, including high-quality CPR, standard and double
sequential defibrillation for a total of nine times, epinephrine
boluses, antiarrhythmic boluses and infusions, and magnesium
sulfate boluses, the patient remained in refractory VF.
Based off previously reported β-blockade success in refractory
VF, we elected a trial of 500 mcg esmolol intravenous bolus.
ROSC and sinus rhythm were observed during the next pulse
check (figure 3). The patient had been in cardiac arrest for
approximately 20 min prior to achieving ROSC.
Outcome and follow-up
After the ROSC, postresuscitation care was initiated immediately. An
ECG demonstrated ST-segment elevation in leads augmented vector
right (aVR) and V1 with reciprocal changes in limb and precordial
leads (figure 4). An ST-elevation myocardial infarction alert was
issued and interventional cardiology was emergently consulted
for percutaneous coronary intervention. Targeted temperature
management, haemodynamic optimisation, antiplatelet and fluid
administration, and sedation were implemented. A full neurolog-
ical examination was unable to be performed prior to sedation;
however, the patient did not exhibit any spontaneous or purposeful
movement.
In the catheterisation lab, a totally occluded proximal right coro-
nary artery (RCA) and severe 80% diffuse left posterior descending
artery (PDA) lesion were found. A drug-eluting stent was success-
fully deployed in the proximal RCA and left PDA with resulting
Thrombolysis In Myocardial Infarction (TIMI) flow 3. On day 2
of hospitalisation, targeted temperature management protocol was
discontinued and the patient was noted to follow commands. A
transthoracic echocardiogram (TTE) showed global hypokinesis
with akinesis of the mid-distal inferoseptal and inferior walls with

Patient’s perspective
No one starts their day setting out to be a patient in a cardiac
intensive care unit (ICU), but some people just end up there.
This is the story of the heroic efforts of the staff in the
emergency department (ED) and the continued attention of the
staff in the cardiac ICU. Without their exemplary care, it would be
impossible for me to write this. Literally.
For me, my journey to the ED and cardiac ICU started several
days before I had the heart attack that put me there. Earlier in
the month, my grandson was born at the hospital and had to
be put in the neonatal intensive care unit (NICU). He had been
diagnosed with Hirschsprung’s disease and would require some
surgery before he could go home. Because of this, my wife and I
chose to stay in the town where we would be closer to the baby
and the hospital.
From the beginning, we were impressed with the care that
our grandson received. Doctors took the time to explain what
was happening to our baby. Nurses made sure that he received
special care just as they did for all the babies in the NICU. We
became very comfortable with our visits to the hospital.
The morning of January 18th started very much as the
previous days had. Wake up, breakfast at the hotel buffet and
then off to the hospital to visit my grandson. Quietly, I sat in
the chair and held him and watched as the NICU doctor and
his team went around discussing each baby’s situation and the
continuing care that was needed. These for me were peaceful
moments. The care we were receiving as visitors and family was
comforting. I was about to experience that care from a whole
different angle.
My wife and I tried to spend our hospital visits in shifts so
that we could also spend time with our older grandchild. That
morning, it was decided that I would take the older child back
to our hotel room and let her nap while my wife stayed in the
hospital with the baby. After arriving at our hotel room, I tried
to lay down and take a nap as well. I was having trouble getting
comfortable and having symptoms that were similar to a cervical
issue I had experienced 5 years earlier. I was not sure if this was
the same problem I had had before, but I could tell something
was wrong. I texted my wife to ask her to come back to the
hotel. I did not want my granddaughter to be alone if I was
going to have a medical issue. Her response was ‘Call 911’. My
response was ‘No. I do not want to’. I had been at the hospital
earlier and had turned my cellphone to vibrate and was not
aware that she was trying to call to let me know she was on the
way. The hotel staff was called. The hotel staff arrived. They had
been trained for medical emergencies and offered care. I refused.
Again, I was advised to call 911 but refused that as well. My
wife arrived. Emergency services were called and an ambulance
arrived. My granddaughter slept.
When the firefighter/paramedics arrived, they did all the
things that I would suppose are required when they make an
emergency medical service run. I was poked, stuck and had
various things attaching me to noisy equipment. I sat on the
couch in our hotel room and we discussed the issues leading
up to the moment when I began to feel uncomfortable. We
discussed my previous medical history and the current situation
regarding my grandson. At some point in the discussion, I was
asked if I wanted to transport to the hospital and it was decided
that I should go and get checked out.
The drive to the hospital was calm and uneventful. I had made
the same drive several times that week, so I knew it well. No
Continued
Hwang CW, et al. BMJ Case Rep 2019;12:e228208. doi:10.1136/bcr-2018-228208
Reminder of important clinical lesson
BMJ Case Rep: first published as 10.1136/bcr-2018-228208 on 8 March 2019. Downloaded from http://casereports.bmj.com/ on 19 March 2019 by guest. Protected by copyright.
Patient’s perspective Continued
lights. No sirens. We even stopped for a couple of stoplights.
Just a nice quiet ride in an ambulance to the hospital. I was not
concerned. I did not think there was any big problem because we
were not rushing.
When we arrived at the ED, I was moved into an area in
front of the emergency room (ER) desk. The nurse at the desk
explained that the ER was busy and I would be put into a staging
area while a room was made available. I was not concerned. At
some point, a nurse came by and attached all the leads from the
ambulance to their noisy equipment and said that everything
looked as if I was doing okay, but they wanted to do some more
tests. I was not worried.
At some point, time became fuzzy. I remember sitting up on
the gurney and looking to my left then nothing. My next clear
conscious memory is of the intubation tube being removed. In
between, I have vague memories. I remember seeing my son
at the foot of my bed. I remember seeing my son-in-law and
grandson in my room. My wife tells me that everyone was
there, but I did not see them. I remember the ‘hood’ and leads
attaching my head to more noisy equipment checking my brain.
I remember being really cold. I do not think at this point I was
aware of what had happened or how serious things were.
The rest of my stay, with the exception of my last day, was
in the cardiac ICU. The care that I got from ‘my’ nurses was top
notch. While there, I got to meet a lot of the doctors and nurses
who were involved in getting me to the ICU from the ED. I met
my team and began the journey to recovery. I learnt how to
control my diabetes. I learnt how to give myself an injection of
insulin. I learnt that my trouble swallowing water might be from
scar tissue from earlier cervical spine surgery. I learnt that it is
difficult to sleep on your side (the way I have always slept) after
having cardiopulmonary resuscitation performed on you. I learnt
that I was going to have to make a lifestyle change if I wanted to
be around for that little baby grandson that started his life in the
same place that mine almost ended.
My wife and I have joked many times since then that with
the exception of having a heart attack, my time at this hospital
was one of the best experiences of my life. To all the doctors and
nurses whom I encountered along my 7-day stay there, I want to
say ‘Thank you’ from the total of my healing heart.
an ejection fraction of 20%–25%. He was extubated on hospital
day 3. A repeat TTE on hospital day 5 showed only mild hypoki-
nesis in the inferolateral wall with an improved ejection fraction
of 40%–45%. He had no neurological deficits and was discharged
from the hospital on hospital day 6.
Discussion
Sudden cardiac mortality for all ages is approximately 350 000
deaths annually in the USA. Survival rates after cardiac arrest
are about 8%.14 Although the incidence of VF is declining, it
is estimated to be the most common initial rhythm in cardiac
arrest, accounting for approximately 30% of sudden cardiac
death cases.2 4 8 15 Higher survival rates of 37.4% are associ-
ated with early defibrillation and bystander CPR, prompting
the impetus to increase public access of and education on auto-
mated external defibrillators.14
Current ACLS guidelines for the management of VF and
pulseless VT recommend immediate initiation of high-
quality CPR, early defibrillation, and the administration of
3
 Reminder of important clinical lesson
epinephrine and antiarrhythmic agents. Epinephrine, through
its α activity, is hypothesised to preferentially redirect
systemic blood flow towards the heart, thereby increasing
the CPP necessary for successful defibrillation. Nonetheless,
α-adrenergic stimulation also causes platelet activation with
subsequent impairment of microcirculation.2–8
Epinephrine’s β activity may stimulate inotropy, but
generally, its deleterious effects predominate in patients
with cardiac arrest. It lowers the threshold for VF, further
sustaining ventricular arrhythmias, increases right-to-left
shunting with worsening of systemic oxygen supply and
increases myocardial oxygen consumption, further worsening
the imbalance between oxygen supply and demand.2 5 6 8 This
is particularly important during VF, as myocardial oxygen
demand is increased significantly when compared with
non-VF rhythms.16
Previous animal studies, case reports and case series have
hypothesised and demonstrated that by blocking β-adren-
ergic activity in the catecholamine-rich milieu of cardiac
arrest treated with multiple doses of epinephrine, ROSC was
achieved. Indeed, case reports describe higher rates of tempo-
rary ROSC, sustained ROSC and survival with β-blockade.
The successful use of low-dose propranolol and standard
dose esmolol has been reported. Due to the ethical aspects
involving research of CPR in humans, most of the evidence is
limited to animal studies, case reports, cases series or limited
retrospective reviews.2 4–6 8–13
Esmolol has multiple benefits for use in this clinical scenario.
It has a rapid onset and short duration of action with an elimina-
tion half-life of approximately 9 min.17 Esmolol is a beta-1-selec-
tive (cardioselective) adrenergic receptor blocker; however, its
selectivity is decreased at higher doses, where it could potentially
have deleterious effects on specific airway resistance.
During this case of refractory VF, the patient had already
received maximum doses of amiodarone for the cessation
of VF as recommended per the ACLS algorithm, with no
resolution.
Therefore, discussion occurred regarding consideration of
the use of esmolol given recent data. A dose of 500 mcg was
requested. Although noted that 500 mcg/kg was the dosage
utilised previously, there was concern expressed over the
usage of >30 mg of esmolol as a single push dose. Therefore,
the requested 500 mcg was administered.
Learning points
►► Sudden cardiac death portends high associated mortality.
►► Early initiation of high-quality cardiopulmonary resuscitation
and early defibrillation for shockable rhythms (ventricular
fibrillation [VF] and pulseless ventricular tachycardia) are
basic life support skills and the only interventions that have
been shown to improve return of spontaneous circulation
(ROSC), survival rates and good neurological outcomes. It is
imperative that the layperson be educated on how to deliver
these life-saving interventions.
►► The catecholamine rich milieu of cardiac arrest has
deleterious effects on ROSC and survival. Beta-blockers can
be effective in treating refractory VF.
►► In a case of refractory VF, refractory to standard advanced
cardiac life support interventions and double sequential
defibrillation, low-dose esmolol was successfully used to
achieve ROSC.
4 Hwang CW, et al. BMJ Case Rep 2019;12:e228208. doi:10.1136/bcr-2018-228208
BMJ Case Rep: first published as 10.1136/bcr-2018-228208 on 8 March 2019. Downloaded from http://casereports.bmj.com/ on 19 March 2019 by guest. Protected by copyright.
Nonetheless, the basics of cardiac arrest care must not be
forgotten. Early defibrillation and bystander CPR are para-
mount to mitigate anoxic injuries.18 19 For cases of refractory
cardiac arrest, extracorporeal therapies, such as venous-arte-
rial extracorporeal membrane oxygenation (ECMO), often
referred to as extracorporeal CPR (ECPR), have recently
emerged as a promising intervention in patients with refrac-
tory VF arrest.20 Our case challenges the notion that rapid
or even prehospital initiation of ECPR is the only option for
these patients.21 22 Treatment with esmolol may be a reasonable
option prior to or during preparation for ECMO cannulation,
which is associated with a number of potential complications.23
Contributors CWH: developed the concept. CWH, GG, TKB: drafted the
manuscript. CWH, GG, TKB, MRM: edited, proofread and approved the final version
of the manuscript.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
References
1 Neumar RW, Shuster M, Callaway CW, et al. Part 1: Executive Summary: 2015
American Heart Association Guidelines Update for Cardiopulmonary Resuscitation
and Emergency Cardiovascular Care. Circulation 2015;132:S315–67.
2 Bourque D, Daoust R, Huard V, et al. beta-Blockers for the treatment of cardiac arrest
from ventricular fibrillation? Resuscitation 2007;75:434–44.
3 Otto CW, Yakaitis RW. The role of epinephrine in CPR: a reappraisal. Ann Emerg Med
1984;13:840–3.
4 Bassiakou E, Xanthos T, Papadimitriou L. The potential beneficial effects of beta
adrenergic blockade in the treatment of ventricular fibrillation. Eur J Pharmacol
2009;616:1–6.
5 Driver BE, Debaty G, Plummer DW, et al. Use of esmolol after failure of standard
cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation.
Resuscitation 2014;85:1337–41.
6 Lee YH, Lee KJ, Min YH, et al. Refractory ventricular fibrillation treated with esmolol.
Resuscitation 2016;107:150–5.
7 Gough CJR, Nolan JP. The role of adrenaline in cardiopulmonary resuscitation. Crit
Care 2018;22:139.
8 de Oliveira FC, Feitosa-Filho GS, Ritt LE. Use of beta-blockers for the treatment
of cardiac arrest due to ventricular fibrillation/pulseless ventricular tachycardia: a
systematic review. Resuscitation 2012;83:674–83.
9 Killingsworth CR, Wei CC, Dell’Italia LJ, et al. Short-acting beta-adrenergic antagonist
esmolol given at reperfusion improves survival after prolonged ventricular fibrillation.
Circulation 2004;109:2469–74.
10 Cammarata G, Weil MH, Sun S, et al. Beta1-adrenergic blockade during
cardiopulmonary resuscitation improves survival. Crit Care Med 2004;32:S440–3.
11 Tang W, Weil MH, Sun S, et al. Epinephrine increases the severity of postresuscitation
myocardial dysfunction. Circulation 1995;92:3089–93.
12 Theochari E, Xanthos T, Papadimitriou D, et al. Selective beta blockade improves the
outcome of cardiopulmonary resuscitation in a swine model of cardiac arrest. Ann Ital
Chir 2008;79:409–14.
13 Jingjun L, Yan Z, Weijie,­ et al. Effect and mechanism of esmolol given during
cardiopulmonary resuscitation in a porcine ventricular fibrillation model. Resuscitation
2009;80:1052–9.
14 Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart Disease and Stroke Statistics-2017
Update: a Report From the American Heart Association. Circulation 2017;135:e14
6–e603.
15 Herlitz J, Engdahl J, Svensson L, et al. Decrease in the occurrence of ventricular
fibrillation as the initially observed arrhythmia after out-of-hospital cardiac arrest
during 11 years in Sweden. Resuscitation 2004;60:283–90.
16 Berglund E, Monroe RG, Schreiner GL. Myocardial oxygen consumption and coronary
blood flow during potassium-induced cardiac arrest and during ventricular fibrillation.
Acta Physiol Scand 1957;41:261–8.
17 Breviblock (Esmolol Hydrochloride) Injection [package insert]. Deerfield, IL: Baxter
Healthcare Corporation, 2014.
18 Hasselqvist-Ax I, Riva G, Herlitz J, et al. Early cardiopulmonary resuscitation in out-of-
hospital cardiac arrest. N Engl J Med 2015;372:2307–15.
19 Valenzuela TD, Roe DJ, Nichol G, et al. Outcomes of rapid defibrillation by security
officers after cardiac arrest in casinos. N Engl J Med 2000;343:1206–9.
 Reminder of important clinical lesson

20 Yannopoulos D, Bartos JA, Martin C, et al. Minnesota Resuscitation Consortium’s
Advanced Perfusion and Reperfusion Cardiac Life Support Strategy for Out-of-Hospital
Refractory Ventricular Fibrillation. J Am Heart Assoc 2016;5:1–10.
21 Lamhaut L, Hutin A, Deutsch J, et al. Extracorporeal Cardiopulmonary Resuscitation
(ECPR) in the Prehospital Setting: An Illustrative Case of ECPR Performed in the
Louvre Museum. Prehosp Emerg Care 2017;21:386–9.
BMJ Case Rep: first published as 10.1136/bcr-2018-228208 on 8 March 2019. Downloaded from http://casereports.bmj.com/ on 19 March 2019 by guest. Protected by copyright.
22 Tonna JE, Selzman CH, Mallin MP, et al. Development and Implementation
of a Comprehensive, Multidisciplinary Emergency Department
Extracorporeal Membrane Oxygenation Program. Ann Emerg Med
2017;70:32–40.
23 Rupprecht L, Lunz D, Philipp A, et al. Pitfalls in percutaneous ECMO cannulation.
Heart Lung Vessel 2015;7:320–6.

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Hwang CW, et al. BMJ Case Rep 2019;12:e228208. doi:10.1136/bcr-2018-228208 5