A case of refractory ventricular fibrillation successfully treated with low-dose esmolol

Abstract

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) algorithms for the management of ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT) consist of high-quality cardiopulmonary resuscitation (CPR), defibrillation and the sequential 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 redirect 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, 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 paramedic to become unresponsive with agonal respirations, and high-quality CPR was immediately initiated.

Figure 1.

The patient’s initial emergency department ECG did not demonstrate ST elevation.

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 polymorphic VT, and he received 2 g of magnesium sulfate intravenously twice.

Figure 2.

Telemetry strips demonstrate VF and the resulting defibrillation attempts. VF, ventricular fibrillation.

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.

Treatment

After four standard defibrillation attempts with no subsequent return of spontaneous circulation (ROSC), the patient was defibrillated an additional five times using double sequential 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.

Figure 3.

Telemetry strip demonstrating ROSC. ROSC, return of spontaneous circulation.

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 neurological examination was unable to be performed prior to sedation; however, the patient did not exhibit any spontaneous or purposeful movement.

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.

In the catheterisation lab, a totally occluded proximal right coronary artery (RCA) and severe 80% diffuse left posterior descending artery (PDA) lesion were found. A drug-eluting stent was successfully 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 an ejection fraction of 20%–25%. He was extubated on hospital day 3. A repeat TTE on hospital day 5 showed only mild hypokinesis 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 associated with early defibrillation and bystander CPR, prompting the impetus to increase public access of and education on automated 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 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-adrenergic 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 temporary 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 elimination half-life of approximately 9 min.¹⁷ Esmolol is a beta-1-selective (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.

Nonetheless, the basics of cardiac arrest care must not be forgotten. Early defibrillation and bystander CPR are paramount to mitigate anoxic injuries.^{18 19} For cases of refractory cardiac arrest, extracorporeal therapies, such as venous-arterial extracorporeal membrane oxygenation (ECMO), often referred to as extracorporeal CPR (ECPR), have recently emerged as a promising intervention in patients with refractory 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

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 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.

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.