Download Adenosine for wide-complex tachycardia: Efficacy and safety*

Adenosine for wide-complex tachycardia: Efficacy and safety*
Keith A. Marill, MD; Sigrid Wolfram, MD; Ian S. deSouza, MD; Daniel K. Nishijima, MD; Darren Kay, MD;
Gary S. Setnik, MD; Thomas O. Stair, MD; Patrick T. Ellinor, MD, PhD
Objectives: To determine whether adenosine is useful and safe
as a diagnostic and therapeutic agent for patients with undifferentiated wide QRS complex tachycardia. The etiology of sustained
monomorphic wide QRS complex tachycardia is often uncertain
acutely.
Design: A retrospective observational study.
Setting: Treatment associated with emergency visits at nine
urban hospitals.
Patients: Consecutive patients treated with adenosine for regular wide QRS complex tachycardia between 1991 and 2006.
Interventions: Treatment with adenosine infusion.
Measurements and Main Results: Measured outcomes included rhythm response to adenosine, if any, and all adverse
effects. A positive response was defined as an observed change
in rhythm including temporary atrioventricular conduction block
or tachycardia termination. A primary adverse event was defined
as emergent electrical or medical therapy instituted in response
to an adverse adenosine effect. A rhythm diagnosis was made in
each case. The characteristics of adenosine administration as a
test for a supraventricular as opposed to ventricular tachycardia
P
atients presenting with electrocardiographic (ECG) evidence of regular wide QRS
complex tachycardia (WCT)
pose both diagnostic and therapeutic
challenges. Clinicians focus on distinguishing tachycardias with a supraven-
*See also p. 2651.
From the Department of Emergency Medicine
(KAM), Massachusetts General Hospital, Boston, MA;
Department of Emergency Medicine (SW, ISdS), SUNY
Downstate Med. Center, Brooklyn, NY; Department of
Emergency Medicine (DKN), University of California,
Davis Medical Center, Sacramento, CA; Emergency
Department (DK), Northwest Medical Center, Tucson,
AZ; Department of Emergency Medicine (GSS), Mt.
Auburn Hospital, Cambridge, MA; Department of Emergency Medicine (TOS), Brigham and Women’s Hospital,
Boston, MA; Cardiovascular Research Center (PTE),
Massachusetts General Hospital, Boston, MA.
This work was supported, in part, by the Eleanor
and Miles Shore Scholars in Medicine Fellowship, Harvard Medical School.
The authors have not disclosed any potential conflicts of interest.
For information regarding this article, E-mail:
[email protected]
Copyright © 2009 by the Society of Critical Care
Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0b013e3181a93661
2512
were determined, and the adverse event rates were calculated. A
total of 197 patients were included: 104 (90%) of 116 (95%
confidence interval, 83%–95%) and two (2%) of 81 (95% confidence interval, 0.3%–9%) supraventricular tachycardia and ventricular tachycardia patients demonstrated a response to adenosine, respectively. The odds of supraventricular tachycardia
increased by a factor of 36 (95% confidence interval, 9 –143) after
a positive response to adenosine. The odds of ventricular tachycardia increased by a factor of 9 (95% confidence interval, 6 –16)
when there was no response to adenosine. The rate of primary
adverse events for patients with supraventricular tachycardia and
ventricular tachycardia was 0 (0%) of 116 (95% confidence interval, 0%–3%) and 0 (0%) of 81 (95% confidence interval, 0%– 4%),
respectively.
Conclusions: Adenosine is useful and safe as a diagnostic and
therapeutic agent for patients with regular wide QRS complex
tachycardia. (Crit Care Med 2009; 37:2512–2518)
KEY WORDS: tachycardia, ventricular; tachycardia, supraventricular; adenosine; anti-arrhythmia agents; diagnostic techniques;
cardiovascular; adverse effects
tricular vs. a ventricular origin. A number of historical factors, such as a history
of myocardial infarction (MI), physical
examination findings, and ECG indicators like atrioventricular (AV) dissociation, can be helpful to distinguish the
tachycardia origin, but none of these individual characteristics is both highly
sensitive and specific, and combined algorithms have not proven reproducible
(1– 6). Medicines, such as procainamide
and amiodarone, can be used to treat
either type of underlying rhythm, but
these agents may be poorly effective in
some cases or have potential adverse
effects, such as hypotension. Electrical
cardioversion is both safe and effective
but it can be painful without adequate
sedation, does not prevent recurrence,
and provides limited diagnostic information.
Adenosine, an endogenous nucleotide,
causes rapid AV nodal blockade when administered intravenously with an ultrashort 9-sec half-life. Investigators have
studied its utility to diagnose and treat
regular WCT in small series of up to 30
patients primarily with tachycardias in-
duced in the electrophysiology laboratory
(7–10). It is expected that adenosine will
1) terminate the majority of supraventricular tachycardias (SVTs) that rely on
the AV node to form a reentrant circuit;
2) cause transient AV block to permit the
accurate diagnosis of atrial flutter; and 3)
be unlikely to terminate most ventricular
tachycardias (VTs). Nevertheless, use of
adenosine has been tempered by a number of safety concerns including paradoxic enhancement of accessory tract
conduction and acceleration of the ventricular response in the setting of atrial
flutter or fibrillation with a bypass tract,
persistent bradycardia or asystole, change
in rhythm to atrial fibrillation, degeneration to ventricular fibrillation, myocardial ischemia due to coronary artery
vasodilation and a secondary steal syndrome, or bronchospasm (11–16). It was
hypothesized that the presence or absence of a change in heart rhythm in
response to intravenous adenosine infusion would be a useful and safe way of
distinguishing a supraventricular from
ventricular origin in patients with stable,
sustained regular WCT.
Crit Care Med 2009 Vol. 37, No. 9
Table 1. Enrollment information
Hospital
Location
Beginning Search
Date
Ending Search
Date
University of New Mexico
Hospital
Veterans Affairs Medical
Center
Albuquerque, NM
Jan-91
Feb-95
A
0
3
Albuquerque, NM
Jul-93
Nov-95
0
3
R.E. Thomason Hospital
Columbia West Medical
Center
New York University
Hospital
SUNY Downstate Medical
Center
Massachusetts General
Hospital
Brigham and Women’s
Hospital
Mount Auburn Hospital
El Paso, TX
El Paso, TX
Jul-90
Jan-93
Jan-96
Mar-96
All ECGs with WCT stored in the
hospital ECG database, and
patient diagnosed with VT
A
A
0
0
3
4
New York, NY
Dec-97
Jan-03
11
4
New York, NY
Jul-99
Feb-05
All ED patients with a pharmacy
charge for intravenous adenosine
A
0
4
Boston, MA
Oct-93
Jan-08
A and B
59
27
Boston, MA
Jan-94
Oct-06
A and B
17
18
Cambridge, MA
Sep-96
Dec-06
Digital text search of all ED
physician charts for the
consecutive letters “VT,” “vent
tach,” “aden,” “amio,” or “procain”
Total
29
15
116
81
Search Criteria
SVT Patients
Enrolled
VT Patients
Enrolled
SVT, supraventricular tachycardia; VT, ventricular tachycardia; ECGs, electrocardiograms; WCT, wide QRS complex tachycardia; A, primary discharge
diagnosis “paroxysmal ventricular tachycardia”; ED, emergency department; ICD-9 427.1; B, all ED patients with a pharmacy charge for intravenous
adenosine, amiodarone, or procainamide.
MATERIALS AND METHODS
Study Design
This report describes a retrospective observational study of consecutive patients with sustained WCT treated with intravenous adenosine
(adenocard, Astellas Pharma US, Deerfield, IL).
Setting and Selection of
Participants
This was a multicenter study performed at
nine hospitals in five cities (Table 1). Patients
were primarily identified at their emergency department (ED) presentation, but the first administration of adenosine (ranging from treatment
by emergency medical services [EMS]) to administration in another hospital unit) was analyzed. A variety of search criteria were used to
identify cases depending primarily on the medical record documentation, storage, and search
capabilities available at each facility (Table 1).
This study was performed concurrently
with a retrospective comparison of amiodarone and procainamide for the treatment of
VT. It is conceivable that a patient could have
been treated with one of these agents in the
ED, and could have received adenosine before
ED arrival by EMS providers. Thus, these patients were also included in the enrollment
criteria. Patients included in New Mexico and
Texas were previously described (17). Institutional Review Board approval with waiver of
Crit Care Med 2009 Vol. 37, No. 9
informed consent was obtained from all participating institutions.
All patients ⬎16 yrs old who presented
with sustained regular WCT and were treated
with intravenous adenosine were eligible for
inclusion. A sustained rhythm was defined as
continuous for at least 2 mins to minimize the
risk of mislabeling spontaneous termination
of a transient WCT as a response to adenosine.
A regular rhythm was defined as having ⱕ5%
beat-to-beat variability in R-to-R interval for
contiguous beats. Wide QRS tachycardia was
defined as a QRS width ⱖ120 msecs and a
heart rate (HR) of at least 120 beats/min. All
patients who received a 12-mg bolus of adenosine were eligible for inclusion. Patients who
exhibited any response to a 6-mg bolus were
also included. Patients who only received a
6-mg bolus and exhibited no response were
excluded, as it is unknown if they would have
responded to a full therapeutic dose of 12 mg.
If a patient received multiple boluses with
different doses for a single WCT episode, then
the response to the highest dose was included.
If a patient received multiple boluses of the
same dose of adenosine, then the response to
the first bolus was included in the primary
study analysis. If a patient was treated on multiple occasions, only the first event for which
there was complete data was included.
Data Collection
Five unblinded investigators collected data,
using standardized abstraction forms following a
prospectively written protocol. The principal investigator trained the other abstractors and reviewed all of the forms in periodic meetings. For
variables noted multiple times on the chart, the
first documented value was recorded. Unavailable information was documented as missing
and the decreased total number was noted in the
appropriate category in the results in Table 2.
Study data were collected from each record by a
single abstractor, and there was no measure of
interrater reliability.
Methods of Measurement
Patients’ demographics, including age and
gender, the date of the WCT presentation, the
hospital, and hospital unit were recorded. History of cardiac disease including dysrhythmias, implantable cardioverter defibrillator
(ICD) implantation, congestive heart failure,
and measured left ventricular ejection fraction, MI, or coronary artery bypass grafting,
was obtained from the medical record. Medications at presentation including antidysrhythmics and medications known to alter
adenosine effect, such as aminophylline, theophylline, and dipyridamole, were recorded.
The duration of the WCT before treatment,
if known, the initial HR and blood pressure,
and any medications administered before
adenosine were recorded. Symptoms of chest
pain, shortness of breath, or lightheadedness,
and physical signs of pulmonary rales or lower
extremity edema before treatment were noted.
The HR, QRS duration, frontal QRS axis, and
2513
Table 2. Patient characteristics
SVT
Rhythm
Adenosine Response
Demographics
Age, years
Gender, male
Past medical history
History of MI
History of CABG
EF ⱕ35%
Dysrhythmia history
Supraventricular
Spontaneous sustained VT
Other ventricular
Uncertain
None
Theophylline or aminophylline
therapy
Dipyridamole therapy
History of ICD implant
History of present illness
Chest pain
Shortness of breath
Physical examination
Heart rate, beats/min
Systolic blood
pressure (mm Hg)
Patient weight, kg
Pulmonary rales
Lower extremity edema
Automated ECG
characteristics
QRS duration (msec)
QRS axis between
180° and 270°
Corrected QT
interval (msec)
Serum electrolytes
Potassium, mmol/L
Magnesium, mEq/L
Calcium, mg/dL
No
Response
(n ⫽ 12)
VT
Positive
Response
(n ⫽ 104)
No
Response
(n ⫽ 79)
66.7 (12)
75% (9)
70.5 (16)
55% (57)
60.9 (18)
72% (57)
33% (4)
8% (1)
46% (5/11)
23% (24)
17% (18)
24% (22/93)
52% (41)
19% (15)
49% (35/72)
33% (4)
8% (1)
17% (2)
0% (0)
58% (7)
0% (0)
44% (46)
1% (1)
8% (8)
6% (6)
44% (46)
1% (1)
8% (1)
17% (2)
0% (0)
4% (4)
25% (3)
50% (6)
50% (1)
0% (0)
50% (1)
24% (28)
16% (19)
26% (27/104)
52% (42)
19% (15)
49% (36/74)
28% (22)
27% (21)
9% (7)
6% (5)
44% (35)
1% (1)
50% (1)
0% (0)
50% (1)
0% (0)
0% (0)
0% (0)
43% (50)
2% (2)
9% (10)
5% (6)
46% (53)
1% (1)
28% (23)
26% (21)
10% (8)
6% (5)
43% (35)
1% (1)
3% (2)
13% (10)
0% (0)
0% (0)
1% (1)
5% (6)
2% (2)
12% (10)
151 (21)
124 (26) (n ⫽ 102)
176 (32)
115 (24) (n ⫽ 74)
77.7 (20) (n ⫽ 95)
28% (28/102)
18% (18/101)
140 (21)
0% (0)
502 (59) (n ⫽ 12)
81.4 (22)
33% (4)
33% (4)
4.3 (.5)
1.7 (.1) (n ⫽ 7 )
9.4 (.7) (n ⫽ 7)
All VT
(n ⫽ 81)
60.4 (18)
73% (59)
33% (26/78)
44% (34/77)
43.5 (6)
100% (2)
All SVT
(n ⫽ 116)
69.9 (15)
57% (66)
24% (24/101)
37% (37/99)
144 (23)
135 (36) (n ⫽ 11)
Positive
Response
(n ⫽ 2)
24% (27/113)
39% (43/111)
34% (27/80)
43% (34/79)
188 (40)
120 (0)
150 (21)
125 (27) (n ⫽ 113)
176 (32)
115 (23) (n ⫽ 76)
77.8 (16) (n ⫽ 75)
13% (10/78)
12% (9/78)
82.4 (3)
0% (0)
0% (0)
78.1 (20) (n ⫽ 107)
28% (32/114)
19% (22/113)
77.9 (16) (n ⫽ 77)
13% (10/80)
11% (9/80)
136 (16) (n ⫽ 103)
9% (9/100)
163 (33) (n ⫽ 69)
23% (15/65)
144 (n ⫽ 1)
0% (0/1)
136 (17) (n ⫽ 115)
8% (9/112)
163 (33) (n ⫽ 70)
23% (15/66)
489 (43) (n ⫽ 97)
525 (62) (n ⫽ 52)
506 (n ⫽ 1)
491 (45) (n ⫽ 109)
524 (61) (n ⫽ 53)
4.2 (.6) (n ⫽ 72)
1.8 (.3) (n ⫽ 49)
9.1 (.9) (n ⫽ 37)
3.9 (.6)
1.9 (.1)
9.4 (.1)
4.2 (.5) (n ⫽ 115)
1.8 (.3) (n ⫽ 101)
9.1 (.6) (n ⫽ 65)
4.2 (.6) (n ⫽ 74)
1.8 (.3) (n ⫽ 51)
9.1 (.9) (n ⫽ 39)
4.2 (.5) (n ⫽ 103)
1.8 (.3) (n ⫽ 94)
9.1 (.6) (n ⫽ 58)
50% (1)
0% (0)
SVT, supraventricular tachycardia; VT, ventricular tachycardia; MI, myocardial infarction; CABG, coronary artery bypass graft; EF, ejection fraction; ICD,
implantable cardioverter defibrillator; ECG, electrocardiogram.
Count data are provided as a percentage along with the absolute count. If the history of present illness, physical examination, EF, or ECG QRS axis was
not specifically stated as positive or negative, or was unavailable, it was treated as unknown. In this case, the number of patients with the characteristic
divided by the total number known is provided. Interval data are provided as an average along with the standard deviation in parentheses. If the data were
unavailable for some patients, then the number of patients, n, upon which the data are based is provided.
QT interval corrected for HR were recorded
from automated measurements from the WCT
ECG, with manual correction for obvious errors. Measured patient weight was noted as
well as the serum potassium and magnesium.
Serum calcium was added to the data collection form for the Massachusetts hospitals.
The number and dose of adenosine infusions,
whether a post bolus flush was specified, and the
response to each infusion were recorded. Adenosine response was classified as: none, tachycardia termination with return to native rhythm,
transient change in AV nodal conduction, new
atrial or ventricular dysrhythmia, or other. Any
documented adverse effects of adenosine infu-
2514
sion and the subsequent and ultimate tachydysrhythmia treatments were recorded.
Acute MI was diagnosed in association with
the WCT event if the patient demonstrated
characteristic elevation of cardiac markers and
acute MI was diagnosed by the cardiologic
team caring for the patient. Any patient death
and the reason for death during the hospitalization were recorded.
The underlying mechanism of the WCT
rhythm was determined by the investigators using the following methods and criteria in descending order, as available: ECG evidence of AV
dissociation demonstrating VT, review of the
tachydysrhythmia from ICD recordings, repro-
duction of the dysrhythmia during an electrophysiologic study, diagnostic response to carotid
massage or adenosine, such as transient AV
block revealing atrial flutter waves, ECG analysis
by the treating cardiology team with clear evidence of the diagnosed rhythm confirmed by the
investigators, or if necessary, ECG analysis using
standard criteria by an electrophysiologist investigator blinded to all clinical data.
Outcome Measures
The primary outcome was the response to
adenosine as observed by the medical care
team based on the following predetermined
Crit Care Med 2009 Vol. 37, No. 9
criteria. A positive response to adenosine suggestive of SVT included: temporary AV block,
termination of the WCT, or any other change
in rhythm except for retrograde ventricularTable 3. Adenosine dose and response
Adenosine Dose and Response
SVT
VT
6 mg, no responsea
6 mg, positive response
Up to 12 mg, no responseb
Second 12 mg, no response
Second 12 mg, positive response
Up to 12 mg, positive response
Up to 18 mg, no response
Up to 18 mg, positive response
11
58
11
3
3
46
1
0
10
1
73
21
0
1
6
0
SVT, supraventricular tachycardia; VT, ventricular tachycardia.
a
Cases excluded from the study. One patient
also received a 9 mg dose without response, and one
patient had an uncertain response to 6 mg; bfor
those patients who did not respond to an initial
12-mg bolus and received a second 12-mg bolus,
the response to the second bolus is listed separately.
atrial block. A negative response suggestive of
VT was defined as no apparent change in
rhythm. A response of transient retrograde
ventricular-atrial conduction block would also
suggest VT. The timeframe of response was
not strictly defined, but it was generally accepted that should it occur, a response would
occur within seconds and no more than 1 min
of the adenosine infusion.
The primary safety outcome was the need
to make an emergent electrical or medical
intervention, such as direct current cardioversion, defibrillation, or epinephrine or atropine
infusion in response to adenosine administration as determined by the medical care team.
Secondary safety outcomes included any documented adverse response to adenosine including conversion to a more unstable tachy
or bradydysrhythmia, hypotension, or any new
symptoms.
Primary Data Analysis
Tabulated dichotomous and average interval data with standard deviations describing a
patient’s past medical history, physical examination, and ECG characteristics were calculated for all patients using SPSS 15 (SPSS,
Chicago, IL), and stratified by SVT or VT diagnostic group and positive or negative response to adenosine. Univariate statistics for
response to adenosine as a test for SVT vs. VT
were determined. Likelihood ratio 95% Confidence Intervals (CIs) were calculated, using
the log method (18).
Before initiation of the study, the approximate sample size needed to obtain a 95% CI
range of 5% for the primary safety outcome
was estimated to be 70 patients in each group.
All adverse effects of adenosine administration
were tabulated and the rate and 95% CI of
emergent interventions were calculated. The
rates were calculated separately for the SVT
and VT diagnostic groups because, given the
different tachycardia mechanisms and underlying cardiologic diseases, the adverse effect
rates may differ. The 95% CIs were computed,
using Statxact 3 (Cytel Software, Cambridge,
MA) for all dichotomous data.
RESULTS
Table 4. How was the diagnosis proven?
ECG with AV dissociation
ECG with VT with variable retrograde VA conduction
ICD interrogation
EP study with tachydysrhythmia reproduced
EP study with tachydysrhythmia reproduced and AV dissociation
Carotid massage response diagnostic
Adenosine response diagnostic
ECG criteria per cardiology team
ECG criteria per electrophysiologist
SVT
VT
0% (0)
0% (0)
1% (1)
15% (17)
0% (0)
1% (1)
48% (56)
20% (23)
16% (18)
15% (12)
4% (3)
5% (4)
54% (44)
6% (5)
0% (0)
0% (0)
0% (0)
16% (13)
SVT, supraventricular tachycardia; VT, ventricular tachycardia; ECG, electrocardiogram; AV, atrioventricular; VA, ventriculoatrial; ICD, implantable cardioverter defibrillator; EP, electrophysiology.
Table 5. Rhythm and response to adenosine
Any Response
to Adenosine
Rhythm
Supraventricular
Sinus tachycardia
Atrial fibrillationa
Atrial flutter
Atrial tachycardia
Atrioventricular tachycardia
AVNRT
Nodo-fascicular tachycardia
SVT, unspecified
Ventricular
VT with RV dysplasia
RVOT VT
Fascicular VT
Persistent recurrent VT
VT, unspecified
Totals
All SVT
All VT
Tachycardia Termination
Post Adenosine
Yes
No
0
0
1
2
1
6
1
17
5
4
54
6
1
6
1
27
2
0
4
1
0
1
0
4
0
0
0
0
1
0
0
0
0
2
1
3
2
1
72
104
2
12
79
AVNRT, atrioventricular nodal tachycardia; SVT, supraventricular tachycardia; VT, ventricular
tachycardia; RV, right ventricular; RVOT, right ventricular outflow tract.
a
Atrial fibrillation with maximal R to R interval variability ⬍5%.
Crit Care Med 2009 Vol. 37, No. 9
Characteristics of Study
Subjects
A total of 197 patients who presented
during the 16-yr span from January 1991
to December 2006 were included (Table
1). Twenty-one patients who demonstrated no response to the administration
of 6 mg of adenosine and received no
further adenosine were excluded (Table
3). There was no evidence of a serious
complication from adenosine in any of
these excluded patients. The distribution
of tachydysrhythmic treatment locations
included: 13 (7%) in the field treated by
EMS, 155 (79%) in the ED, seven (4%) in
clinic, one (1%) in the treadmill laboratory, 16 (8%) on an in-patient unit, and
five (3%) in the intensive care unit. Techniques used to determine the tachydysrhythmia mechanisms are listed in Table
4. Patient characteristics are listed in Table 2. Exact duration of the tachycardia
and infusion of a flush post adenosine
bolus were rarely explicitly documented
and thus are not listed.
Main Results
Response to adenosine infusion by
rhythm is listed in Table 5. One patient
each with SVT and VT had a history of
Wolff Parkinson White Syndrome. The
primary end point, any response to adenosine administration including termination or transient alteration, is listed along
2515
Table 6. Adverse effects associated with adenosine administration
Rhythm
Adverse Effect
SVT
Vertigo and diaphoresis
Nausea and dry mouth
Flushed sensation
Flushed sensation with headache and nausea
Transient increased chest pain
Transient increased chest pain with 6 mg adenosine and
transient PVCs with 12 mg
Asymptomatic PVCs
Asymptomatic NSVT
Decreased blood pressure and shortness of breath associated
with simultaneous nitropaste administration
Decreased blood pressure not requiring therapy
None
VT
1
1
1
1
1
1
1
1
1
111
1
76
SVT, supraventricular tachycardia; VT, ventricular tachycardia; PVCs, premature ventricular contrations; NSVT, nonsustained ventricular tachycardia.
with termination alone. When all variants
were combined, 104 (90%) of 116 (95%
CI ⫽ 83%–95%) and two (2%) of 81 (95%
CI ⫽ 0.3%–9%) SVT and VT patients
demonstrated a response to adenosine,
respectively. In terms of likelihood ratios,
a positive response to adenosine increased the odds of SVT by a factor of 36.3
(95% CI ⫽ 9.2–142.9) whereas a negative
response to adenosine increased the odds
of VT by a factor of 9.4 (95% CI ⫽ 5.5–
16.1). Response to adenosine infusion as
a function of dose is listed in Table 3.
Details of the two patients with VT,
who responded to adenosine, are as follows: the first patient was a 39-yr-old
man with a history of Wolff Parkinson
White Syndrome and an idiopathic dilated cardiomyopathy. His HR decreased
from 216 to 90 beats/min after 6 mg of
adenosine infusion. Electrophysiologic
study revealed inducible sustained VT
identical to the patient’s clinical WCT and
a posteroseptal accessory pathway with a
long effective refractory period that did
not participate in the tachydysrhythmia.
The second patient was a 48-yr-old
man with a history of an inferior MI, who
was noted by EMS to have a transient
decrease in HR from 160 to 120 beats/
min after 12 mg of adenosine in the field.
No rhythm strips of the event were available. The patient arrived at the ED with
an HR of 167 beats/min and was treated
successfully with intravenous amiodarone. His WCT ECG demonstrated AV dissociation. Because there was no definitive
documentation by EMS of this reported
transient response of VT to adenosine, a
sensitivity analysis was performed of the
primary outcome after removal of this
2516
case. One (1%) of 80 (95% CI ⫽ 0.03%–
7%) VT patients demonstrated a response
to adenosine. A positive response to adenosine increased the odds of SVT by a
factor of 71.7 (95% CI ⫽ 10.2–503.3)
whereas a negative response to adenosine
increased the odds of VT by a factor of 9.5
(95% CI ⫽ 5.6 –16.3).
All documented adverse effects are
listed in Table 6. No patient suffered a
sustained ventricular dysrhythmia or bradycardia, or required an emergent intervention, such as cardioversion, defibrillation, or pressor medication infusion in
response to adenosine administration.
The rate of the primary adverse events for
SVT and VT patients was 0 (0%) of 116
(95% CI ⫽ 0%–3%) and 0 (0%) of 81
(95% CI ⫽ 0%– 4%), respectively.
No patients suffered an ST elevation
MI in association with their tachycardic
event. One patient with SVT and one with
VT died in association with their tachycardic event.
DISCUSSION
The optimal treatment and prognosis
for patients with SVT and VT differ considerably. Thus, determining the tachydysrhythmia mechanism is useful to optimize emergent care. A number of
historical factors may be predictive. Sustained VT occurs most commonly in the
setting of a myocardial scar with localized
altered conduction properties that develop over time after an MI. In this sample, male gender, history of MI, low ejection fraction, and ICD implantation were
more commonly present in patients with
VT; however, as demonstrated in Table 2,
individually, these factors would have
poor test characteristics in distinguishing
VT from SVT. Not surprisingly, a history
of prior sustained VT, which was present
in 26% of patients with VT and 2% with
SVT, was most strongly associated with
current VT.
Patients with VT tended to have a
faster HR and lower blood pressure. Exceptions to this include patients with VT
who have an ICD or are taking an antidysrhythmic in whom the mean HRs
were 147 beats/min and 158 beats/min,
respectively. In our facilities, electrophysiologists most commonly program
ICDs empirically to pace terminate or
cardiovert faster VT only.
This study was not designed to assess
the utility of ECG findings to distinguish
SVT from VT; however, automated ECG
values were recorded. Although VT
tended to have a wider QRS interval as
expected, an extreme right axis deviation between 180° and 270° was a less
specific finding for VT than previously
reported (19).
A response to a single bolus of 12 mg
of adenosine, including transient AV
nodal block or tachycardia termination,
was highly associated with SVT as opposed to VT. Of 116 patients, 104 (90%)
patients with SVT exhibited a response to
adenosine, and eight (89%) of nine patients with SVT proven to involve the AV
node experienced termination. This is
comparable to the rate of adenosine termination of narrow complex SVT involving the AV node (8, 20). Similar to prior
studies, 98% (79 of 81) of patients with
VT demonstrated no observable response
to adenosine (7–9).
In contrast to all of the historical factors, physical examination, and ECG findings, nonresponse to adenosine is the
only finding that is both highly sensitive
and specific for VT. This is because adenosine acts rapidly and briefly to slow conduction in the AV node, and VT generally
does not involve or require AV nodal conduction. In contrast, SVT most commonly either involves the AV node in a
reentrant circuit or requires AV nodal
conduction to excite the ventricles.
A notable exception to the lack of response of VT to adenosine is the relatively
rare right ventricular outflow tract type
(21, 22). Right ventricular outflow tract
VT was diagnosed in 4% (three of 81) of
patients in this study and was, surprisingly, unresponsive to adenosine in all
cases. Adenosine may also cause transient retrograde ventricular-atrial conCrit Care Med 2009 Vol. 37, No. 9
duction block in the setting of VT, but
this was not observed in our patient
sample (8, 9, 13).
Using likelihood ratios, the odds of
SVT increase by a factor of 36 (95% CI ⫽
9 –143) after a positive response to adenosine. In many cases, transient AV block
is diagnostic of underlying atrial flutter
or tachycardia. The odds of VT increase
by a factor of 9 (95% CI ⫽ 6 –16) when
there is no response to adenosine infusion. The additional information gained
by a nonresponse to adenosine may not
be fully appreciated by clinicians. For example, based on the likelihood ratio of 9,
if the pretest probability of VT is 50%
with 1:1 odds, then the odds of VT would
be approximately 9:1 with a 90% probability after a nonresponse to 12 mg of
adenosine infusion. This information
could be used to guide further therapy
primarily aimed at the treatment of VT as
opposed to SVT, thus avoiding the poor
therapeutic response and adverse effects
that may occur due to misguided treatment.
Twenty-seven patients who did not respond to a single 12-mg bolus of adenosine received a second 12-mg bolus (Table 3). Three of six patients with SVT and
none of 21 patients with VT responded to
the second bolus. In this sample, the sensitivity for SVT would be increased by a
second bolus with no cost in specificity.
There may be some benefit to this common procedure. There was no apparent
benefit from a higher 18-mg adenosine
dose.
Cases of destabilization due to hypotension or an adverse change in rhythm
have been reported after the administration of essentially every agent used to
treat VT (17, 23–25). Remarkably, there is
only a single case report of destabilization
of VT to ventricular fibrillation after
treatment with adenosine (26). The absence of destabilization of VT in our study
sample is consistent with the observations in prior series (7–9, 21, 22). The
greatest concern in the treatment of patients with regular wide complex SVT
with adenosine is accelerated conduction
over an accessory pathway with possible
decompensation to ventricular fibrillation (11–14). Neither this nor other reported dysrhythmic complications of
adenosine, such as torsades de pointes or
sustained bradycardia, were observed in
this patient sample.
Dipyridamole competitively inhibits
adenosine metabolism, and the risk of
adverse adenosine effect may be increased
Crit Care Med 2009 Vol. 37, No. 9
in the presence of dipyridamole (27).
Three patients were taking dipyridamole
in this study and they received adenosine
without event. Other potential risks of
adenosine include cardiac ischemia induced by coronary vasodilation and steal
syndrome, and dyspnea possibly due to
bronchospasm (15, 16, 28). These adverse
effects were not observed. Flushing and
chest discomfort were occasionally described in this sample. These side effects
likely occurred commonly but were not
documented because they are well
known, expected, and transient without
lasting repercussions. Nevertheless, it is
likely that clinically important adverse
effects would be documented and treated.
The low rate and narrow confidence interval of such adverse effects in this sample is reassuring and should encourage
adenosine’s appropriate use.
Sustained monomorphic VT is most
commonly due to scar from a prior MI,
but as observed in this sample, it is rarely
associated with an acute STEMI. As has
been observed in other series of spontaneous wide complex and ventricular
tachycardia, mortality associated with
this condition was low, but not zero (17).
Because of the retrospective nature of
this study, there were multiple potential
limitations, including the risk of bias in
enrollment and assessment of adenosine
response by the primary physicians and
the investigators, incomplete or inaccurate data collection, and nonstandardized
treatment regimens. The utility and
safety of adenosine administration could
differ when applied to a different sample
of SVT and VT patients with WCT.
Patients who only received 6 mg adenosine and had no response were excluded.
This was decided before initiation of the
study because the primary interest was in
the response to 12 mg of adenosine, and
this outcome would remain unknown
in this subgroup. It was felt likely that
patients who responded to 6 mg of adenosine would also have responded to 12
mg. Nevertheless, if the patients with no
response to 6 mg of adenosine were included, then the sensitivity for VT would
have increased from 79 of 81 to 89 of 91;
however, the sensitivity for SVT would
have decreased from 104 of 116 to 104
of 127.
Normal saline flush post adenosine
bolus was rarely explicitly documented in
the chart. However, it is the experience of
the investigators that nurses and doctors
in all of the facilities were well trained
regarding the importance of this, and
that it was routinely administered.
CONCLUSIONS
The primary evaluation of patients
with regular WCT should be based on an
educated history, physical examination,
and ECG analysis. If, based on this analysis, the mechanism is likely to be VT,
then adenosine is unlikely to be helpful.
If there is a history of Wolff Parkinson
White Syndrome or the WCT is actually
irregularly irregular and thus consistent
with atrial fibrillation, then adenosine
should not be used. If the mechanism is
likely SVT or uncertain, then adenosine is
safe and may be useful to terminate or to
diagnose the rhythm. As for all antidysrhythmics administered to patients with
WCT, before adenosine administration,
defibrillation pads should be attached to
the patient and the defibrillator should be
prepared for immediate use in the event
of cardiovascular decompensation. Response or nonresponse to 12 mg of adenosine infusion significantly alters the
likelihood of SVT vs. VT.
ACKNOWLEDGMENT
The authors are grateful for the kind
assistance and manuscript review provided by Yuchaio Chang, PhD.
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