1. Running head: LITERATURE REVIEW 1
What is the value of epinephrine drip when the external pacer fails to sense and capture in
treatment of second-degree type two and third degree atrioventricular (AV) block?
Vela Karakeshishyan
Miami Dade College Benjamin School of Nursing

2. LITERATURE REVIEW 2
What is the value of epinephrine drip when the external pacer fails to sense and capture in
treatment of second-degree type two and third degree atrioventricular block?
“Quality Healthcare is a degree to which health services for individuals and populations
increase the likelihood of desired health outcomes and are consistent with current professional
knowledge” (Stevens, 2013). The American Hearth Association (AHA) continues to partner with
International Liaison Committee on Resuscitation (ILCOR) in overviewing the problems in
Advance Cardiac Life Support (ACLS) guideline in order to improve quality healthcare. Before
2015, there was five-year cycle period of evidence review; however, beginning with 2015 they
decided to switch this process to continue base (Neumar et al., 2015). It is definitely a
logistically wise decision that will allow the revising, evaluating and translating clinically
significant evidence into practice right a way without delay. ILCOR prioritizes the problems that
should be reviewed according to clinical significance and availability of new evidence. Each
addressed topic is examined in terms of PICO question format, which means problem,
intervention, comparator, and outcome. In 2010, 274 PICO questions were addressed, whereas in
2015 there were only 165 (Neumar et al., 2015). Obviously, the number of clinically significant
issued have not decreased in the last few years; however, there is less evidence that can help to
make improvements. One of these problems is an ACLS guideline in terms of management of
symptomatic bradycardia in high degree atrioventricular block (HAVB), which are second-
degree type two and third degree atrioventricular block (AV). Despite the fact that there is a
knowledge gap in terms of HAVB management, this issue was not addressed in 2015.

3. LITERATURE REVIEW 3
How the phenomena impacts health care delivery?
“Quality improvement of healthcare process and outcomes is the goal of knowledge
transformation” (Stevens, 2013). AHA ACLS policy is a perfect example of how research is
translated into coherent step-by-step guidelines. However, there is a knowledge gap in different
areas of ACLS, which should be addressed and its constant renewal is crucial in the global
improvement of health care delivery. This is why AHA and ILCOR have decided to
continuously renew the ACLS guide. Any updates based on thorough systemic review of
available research studies around the world globally impacts health care delivery by decreasing
the rate of mortality and increasing patients’ outcome. Consequently, updates of management of
one of the most severe AV blocks will definitely have positive impact on health care delivery.
How the phenomena impacts the nursing care?
Quality of nursing care directly affects hospital quality because nurses represent one of
the main forces of any hospital. “Through the Magnet Recognition Program the profession of
nursing has been a leader in catalyzing adoption of evidence based practice (EBP) and using it as
a marker of excellence…The function of clinical practice guidelines is to guide practice”
(Stevens, 2013). Unfortunately, there is a knowledge gap and an absence of evidence in terms of
HAVB management, which makes the ACLS guideline for unstable bradycardia a little bit
ambiguous and not straightforward. As a result, it might affect patients’ outcome, quality of care,
hospital length of stay, rates of hospital readmission, patient satisfaction and cost of care.
Literature Review
Atrioventricular block refers to abnormality conduction between the atria and ventricles
(Kozik, 2016). AV block may be induced by medications, electrolyte imbalance, and structural
problems resulting from AMI or other myocardial diseases. Some AV blocks might be

4. LITERATURE REVIEW 4
reversible; others require a pacemaker placement for life. Atrioventricular blocks are classified
as first, second and third degree (Neumar et al., 2010). Type two-second degree and third degree
blocks are considered to be the most severe ones because they might lead to abrupt asystole
(Swift, 2013).
Second-degree type two AV block usually occurs below the atrioventricular node, either
at the bundle of His or in the bundle branch. As a result, some impulses from sinoatrial (SA)
node fail to depolarize the ventricles. There is a risk that impulses will become completely
blocked resulting in third degree AV block and eventually in an asystole. Third-Degree AV
Block can be located at the level of the AV node, bundle of His or bundle branches
(Cardiovascular 10: Bradycardia Treatment Portal, 2011). There is a complete dissociation
between the atria and ventricles. Each of these chambers contracts at its own pace and as a result
cardiac output is significantly reduced. Because the impulses originate in the AV node or below,
patients experience bradycardia with a heart rate that is usually less than 50 beats per minute.
According to AHA ACLS (2010) guidelines, the key to managing these conditions is the ability
to recognize symptoms and signs of hemodynamic presentation of symptomatic bradycardia.
Some examples of these symptoms and signs are chest discomfort or pain, shortness of breath,
decreased level of consciousness, syncope, and hypotension, due to the decreased heart rate and
inadequate perfusion (Sinz, Navarro, Soderberg, Callaway, 2011). According to ACLS guide
2010, first-line drug for acute symptomatic bradycardia is atropine. Atropine is an
anticholinergic drug and works on the levels of SA and AV nodes by blocking the action of the
vagus nerve. However, in type-two second degree and third degree AV blocks the location of the
obstacle on the way of cardiac impulses is likely to be below the AV node within His-Purkinje
system. As a result, these bradyarrhytmias are not likely to be responsive to reversal of

5. LITERATURE REVIEW 5
anticholinergic effects by atropine. Moreover, in patients with infranodal HAVB, atropine might
cause paradoxical slowing of heart rate (Cardiovascular 10: Bradycardia Treatment Portal,
2011). Consequently, ACLS guide 2010 recommends, “avoid relying on atropine in type two
second- degree or third-degree AV block...” Also, the use of atropine is not recommended if
there is an AV block with acute coronary ischemia or Myocardial Infarction (MI), which are
common causes of HAVB (Sinz et al., 2011). In these cases atropine will decrease vagal impute
on the SA node and increase heart rate and oxygen demand, which will worsen the situation.
According to ACLS (2010) guidelines recommendations, all these conditions should be treated
with equally effective methods, such as transcutaneous pacing (TCP), or epinephrine drip at a
dose of 2 to10 mcg/min, or dopamine drip at a dose of 2 to10 mcg/kg/min (both titrate to patient
response) as temporizing measures while the patient is prepared for transvenous pacing.
However, healthcare providers should consider immediate pacing in unstable patients with
HAVB if IV access is not available (Sinz et al., 2011). There is obviously some degree of
obscurity. For example, what is the most effective treatment of HAVB if the patient has IV
access? Should TCP be started immediately or is it better to instantly begin low dose of
epinephrine or dopamine drip? Or should we solely rely on TCP? Or could we activate TCP and
at the same time start epinephrine drip with low doses in order to be sure that patient will not end
up with asystole in case of TCP failure? Is there any evidence, which advocates for the one or the
other choices?
Transcutaneous or external pacing was invented by Zoll in 1952 and was achieved by
stimulation through needle electrode on the chest wall (Timothy & Rodeman, 2004).
Transcutaneous pacing is a temporary means of pacing for patients with unstable bradycardia. It
is accomplished by delivering impulses of electrical current through the patient’s chest,

6. LITERATURE REVIEW 6
stimulating the heart ventricles to contract and improve cardiac output. The evidence of
mechanical capture are palpable femoral pulse, increased blood pressure, improve level of
consciousness, and improved skin color and temperature. Also, there is evidence of electrical
capture on the ECG, and for successful TCP there should be both mechanical and electrical
capture. Unfortunately, there might be some pitfalls of this seemingly easy procedure. For
example, “most common reason for not obtaining true capture is not adequately increasing the
current which should be increased as much as necessary for electrical capture” (Tintinalli et al.,
2010). The other problem might be an inability to differentiate a true capture from a muscle
artifact when there is pacemaker oversensing. Pacemaker oversensing is an inappropriate
inhibition of the pacemaker due to detection of signals other than R waves. Also, without any
warning, there might be change of pacing threshold and as a result the capture can be readily lost
(Tintinalli et al., 2010). Capture threshold is the magnitude of current, which the pacemaker
sends to initiate ventricular contraction. Moreover, there might be factors affecting mechanical
capture, such as well-developed thoracic wall musculature, inrathoracic surgery, myocardial
ischemia, hypoxemia, prolonged resuscitation efforts, chronic obstructive pulmonary disease,
pleural or pericardial effusion, or positive pressure ventilation. Other complications might
include induction of atrial or ventricular dysrhythmias, skin erythema and irritation, failure to
recognize intrinsic activity (Timothy & Rodeman, 2004). Despite the fact that TCP is considered
a noninvasive and easily operable procedure, the ability to instantly and correctly interpret results
requires an extensive knowledge in EKG and cardiology, and a sufficient amount of experience.
Epinephrine is an alpha, beta-one, and beta-two agonist, resulting in an increase of
systemic vascular resistance, blood pressure, heart rate, myocardial contractility and vasodilation
(Jentzer, Coons, Link, Schmidhofer, 2015). The vascular effect of epinephrine depends on its

7. LITERATURE REVIEW 7
dosage and receptors type and location. The receptors that are responsible for vasodilation and
vasoconstriction are beta-two and alpha-one respectfully. The activation of high numbers of beta
two receptors in vessels of myocardium and skeletal muscle lead to vasodilation and better
perfusion of myocardium and skeletal muscles with infusion of low doses. The vasoconstirctive
properties of epinephrine on the other hand are exerted on tissues with a prevalence of alpha-
receptors located in the vessels of intestines, skin and kidneys. This vasoconstriction shunts
blood from these tissues, enhancing circulation to essential organs (Parry, 2012). Because beta-
two receptors have more affinity to epinephrine than alpha-one receptors, low doses of
epinephrine infusion lead to vasodilation whereas higher doses cause vasoconstriction.
Consequently, systemic vascular resistance, which dependent on vasoconstrictions, increases
with higher doses of epinephrine. Epinephrine also has a strong affinity for beta-1 receptors,
which are located on the cardiac tissue, and when stimulated, increase cardiac contractility by
increasing the availability of calcium for contractions. Additionally, beta-one receptor activation
by epinephrine increases heart rate by improving automaticity of the heart (Timmerman, 2016).
Consequently, at low doses, activation of beta-receptors leads to increased heart rate and force of
heart contractions, which improves cardiac output. On the other hand, at higher doses, activation
of alpha-receptors leads to increase systemic vascular resistance and blood pressure. All these
powerful properties of epinephrine are extensively used in critical and intensive patient care.
“Epinephrine is approximately 100-fold more potent as an inotrope than dobutamine or
dopamine, and low epinephrine doses of 0.01 to 0.1 mcg/kg/min (2-10mcg/min) are used to
therapeutically increase cardiac output and or heart rate via strong beta-1 and beta-2 receptor
stimulation” (Jentzer, et al., p. 254, 2015). According to ACLC (2010) guideline, these doses are
recommended as a second- line drug therapy for AV block. Epinephrine is a powerful drug and

8. LITERATURE REVIEW 8
even slight error in dosing and inability to evaluate patients hemodynamic status might lead to
serious adverse reactions such as tachycardia, dysrhythmias, myocardial ischemia, and poor
peripheral perfusion (Timmerman, 2016). Consequently, in order to better understand the value
of different doses of epinephrine and their effect on functions of the cardiovascular system and
the body in general, extensive randomized clinical trials (RCT) should be done.
There are several case series and one systemic review that demonstrate that in-hospital
transcutaneous pacing has higher success rate for rhythm capture and survival to discharge
compared to the survival-to-discharge rates when transcutaneous pacing was given for out-of-
hospital bradycardia (Deakin et al., 2010).
Limited studies have been done to compare prehospital TCP with second-line drug
therapy such as epinephrine and dopamine in patients with symptomatic bradycardia. One
feasibility study compared dopamine with transcutaneous pacing in patients with bradycardia
refractory to atropine. In this RCT 82 patients with symptomatic bradycardia refractory to
atropine and fluids were involved. The enrollment process was slow because most patients got
better with full-dose atropine in the out-of-hospital setting, making them ineligible for
randomization. The participants were randomized to receive ether TCP or dopamine “starting
with 5mcg/kg/min and increasing the dose until an improvement in sign and symptom was
observed, titrating to a maximum of 20 mcg/kg/min” (Morison et al., 2008). No differences were
observed between treatment groups with TCP (69%) and dopamine drip (70%) in outcomes of
survival to hospital discharge 30 days. According to results of this study, “it is feasible to
conduct a prehospital randomized controlled trial of TCP for unstable bradycardia and a
definitive trial would require a multi-center study” (Morison et al., 2008). Despite the fact that
this study shows that it is feasible to conduct randomized clinical trials in terms of TCP and the

9. LITERATURE REVIEW 9
second-line drug for unstable bradycardia, no further significant randomized clinical studies in
humans were done since than.
According to Deakin et al. (2010), because there is low incidence of bradycardia that is
resistant to atropine, trials comparing TCP and second-line drug of treatment such as epinephrine
and dopamine may not be pragmatic or possible (Deakin et al., 2010). Nowadays, the
development of better reperfusion strategies in patients with MI with ST-segment elevation led
to decreased occurrence of HAVB as a complication of this condition (Kim et al., 2016).
However, it is not eliminated yet, and there are other causes of HAVB such as drug induced AV
block. Despite the fact that it is still “known as reversible and curable disease and drug
withdrawal is considered to be enough”, there is a study that suggests that half of patients
presenting with AV block require a pacemaker implantation even though the culprit drug was
discontinued, meaning that drug induced AV block might be persistent. In this study, the
inclusive criterion was having AV block diagnosis while receiving beta-blockers, verapamil,
digoxin, and class I and class III antiarrhythmics (Osmonov et al., 2012). Even though this study
has some limitations and further investigations should be done, the possibility of drug induced
AV block should be taken into consideration because of numerous patients who take some of
these medications for the rest of their lives.
Conclusion
“While epinephrine infusion is widely used in critical care for inotropic support, there is
no direct method to detect the onset and measure the magnitude of this response,” meaning that
there is a knowledge gap in terms of how different doses of epinephrine affect the body (Maslov,
Pezone, Edelman & Lovich, 2015). For the last five years, extensive research has been done in
animals and humans to better understand the value of epinephrine in cardiac arrest. In 2015,

10. LITERATURE REVIEW 10
AHA and ILCOR addressed this problem and made some updates in terms of cardiac arrest
resuscitation based on the evidence obtained in the past five years. Unfortunately, this
tremendous research work cannot be applied in management of unstable bradycardia because the
doses of epinephrine and the methods of infusion in these two conditions are completely
different. Unfortunately, AHA and ILCOR did not address to management of unstable
bradycardia in 2015, maybe because of an absence of clinically significant RCT in humans in
terms of treatment HAVB with TCP and low doses of epinephrine for last five years.
Consequently, the questions remain open: what is the value of epinephrine drip when the
external pacer fails to sense and capture in treatment of second degree type two and third degree
AV block? And should we wait until this failure occurs or is it better to start epinephrine IV drip
with low doses anyway to save the patient form possible asystole?

11. LITERATURE REVIEW 11
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12. LITERATURE REVIEW 12
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