Arrhythmia/Electrophysiology

Transthoracic Incremental Monophasic Versus Biphasic

Defibrillation by Emergency Responders (TIMBER)
A Randomized Comparison of Monophasic With Biphasic Waveform
Ascending Energy Defibrillation for the Resuscitation of Out-of-Hospital
Cardiac Arrest due to Ventricular Fibrillation
Peter J. Kudenchuk, MD; Leonard A. Cobb, MD; Michael K. Copass, MD; Michele Olsufka, RN;
Charles Maynard, PhD; Graham Nichol, MD

Background—Although biphasic, as compared with monophasic, waveform defibrillation for cardiac arrest is increasing
in use and popularity, whether it is truly a more lifesaving waveform is unproven.
Methods and Results—Consecutive adults with nontraumatic out-of-hospital ventricular fibrillation cardiac arrest were
randomly allocated to defibrillation according to the waveform from automated external defibrillators administered by
prehospital medical providers. The primary event of interest was admission alive to the hospital. Secondary events
included return of rhythm and circulation, survival, and neurological outcome. Providers were blinded to automated
defibrillator waveform. Of 168 randomized patients, 80 (48%) and 68 (40%) consistently received only monophasic or
biphasic waveform shocks, respectively, throughout resuscitation. The prevalence of ventricular fibrillation, asystole, or
organized rhythms at 5, 10, or 20 seconds after each shock did not differ significantly between treatment groups. The
proportion of patients admitted alive to the hospital was relatively high: 73% in monophasic and 76% in biphasic
treatment groups (P⫽0.58). Several favorable trends were consistently associated with receipt of biphasic waveform
shock, none of which reached statistical significance. Notably, 27 of 80 monophasic shock recipients (34%), compared
with 28 of 68 biphasic shock recipients (41%), survived (P⫽0.35). Neurological outcome was similar in both treatment
groups (P⫽0.4). Earlier administration of shock did not significantly alter the performance of one waveform relative to
the other, nor did shock waveform predict any clinical outcome after multivariate adjustment.
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Conclusions—No statistically significant differences in outcome could be ascribed to use of one waveform over another
when out-of-hospital ventricular fibrillation was treated. (Circulation. 2006;114:2010-2018.)
Key Words: cardiopulmonary resuscitation 䡲 defibrillation 䡲 heart arrest

H undreds of thousands of transthoracic defibrillators

worldwide provide life-saving therapy for cardiac arrest
from ventricular fibrillation (VF). Monophasic waveform
defibrillators account for a substantial proportion of those in
current clinical use and are estimated to number well over one
half million in the United States alone (oral communication,
Medtronic Emergency Response Systems, Inc, April 2006).1
Recently, the safety and efficacy of biphasic waveform
shocks have been demonstrated in a variety of settings,2–5
reported to have greater success than monophasic shocks in
terminating VF,6 –10 and heralded by many as the new
standard for defibrillation. On the basis of this perceived
superiority, there is likely to be mounting pressure on
hospitals and particularly on prehospital providers to replace
all monophasic with biphasic defibrillators, despite consider-
able expense and little evidence that either waveform is more
lifesaving.
Clinical Perspective p 2018
This randomized prehospital trial (Transthoracic Incremen-
tal Monophasic Versus Biphasic Defibrillation by Emergency
Responders [TIMBER]) tested whether transthoracic biphasic
or monophasic waveform defibrillation improves clinical
outcome after out-of-hospital cardiac arrest.
Methods
Seattle, Wash, is a city of 550 000 residents served by a single fire
department– based, 2-tiered Emergency Medical Service (EMS)11
that follows treatment protocols adhering to American Heart Asso-
ciation guidelines.12 From November 1, 2002, to September 30,
2004, all adults in Seattle with nontraumatic out-of-hospital cardiac

Received April 26, 2006; revision received September 7, 2006; accepted September 12, 2006.
From the Departments of Medicine (P.J.K., L.A.C., M.K.C., M.O., G.N.) and Health Services (C.M.), University of Washington, Seattle.
Clinical trial registration information—URL: http://www.clinicaltrials.gov/ct/show/NCT00101881?order⫽6. Unique identifier: NCT00101881.
Correspondence to Peter J. Kudenchuk, MD, Division of Cardiology, Box 356422, University of Washington, 1959 NE Pacific St, Seattle, WA
98195-6422. E-mail kudenchu@u.washington.edu
© 2006 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org DOI: 10.1161/CIRCULATIONAHA.106.636506

2010
 Kudenchuk et al
arrest occurring before EMS arrival who had an initial recorded
rhythm of VF and received all defibrillator shocks by EMS personnel
were prospectively studied. Typically, emergency medical techni-
cians (EMTs) initiated chest compressions with ventilation (CPR)
and administered shocks from external defibrillators with automated
rhythm analysis (automated external defibrillators [AEDs]).13 All
patients received 90 seconds of CPR from EMS responders before
the first shock. Up to 3 shocks were administered consecutively after
the initial AED analyses, unless there was an interim no-shock
advisory. Single shocks were given thereafter with intervening
periods of CPR. On their arrival on the scene, paramedics provided
advanced life support, including manually administered defibrillator
shocks. In ⬇10% of cases, paramedics arrived on the scene before or
simultaneously with EMTs.
Defibrillators
LIFEPAK 500 (Medtronic Emergency Response Systems Inc, Red-
mond, Wash) AEDs were used by all EMTs. Paramedics used the
LIFEPAK 12 from the same manufacturer, which permitted rhythm
interpretation and manual defibrillation. The respective monophasic
and biphasic waveform defibrillators used for this study were
identical in appearance and were differentiated by an anonymous
numerical code. According to the manufacturer, monophasic defi-
brillators delivered a damped sinusoidal waveform of 3100 to 4450
V at 200- and 360-J settings, respectively. Biphasic defibrillators
provided a truncated exponential waveform of 1400 to 2000 V at
similar settings. All AEDs used an identical rhythm detection
algorithm, voice prompts, and automatically escalating energy set-
tings (20032003360 J).12 Energy settings on manual defibrillators
were selectable but were almost exclusively administered at 360 J
after they replaced AEDs. Although indistinguishable in their phys-
ical appearance, the waveform of manual defibrillators was identi-
fiable by information displayed on their screens during use.
Randomization
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Patients were assigned to defibrillation according to the waveform of
the device (typically AED) deployed for the first shock. Random-
ization occurred at the level of each EMS unit, to which a
monophasic or biphasic defibrillator was randomly allocated and
changed for its counterpart quarterly.
Insofar as possible, AEDs and manual defibrillators were matched
to achieve use of the same waveform throughout a resuscitation.
Assignment of defibrillators with matching waveform was derived
from review of prior years’ responses to cardiac arrest, identifying
EMT and paramedic units most likely to be paired. All responders
were blinded to the waveform of the AED and whether the
corresponding manual defibrillator administered a matching
waveform.
Data
Prehospital data included a narrative report and detailed sequence of
resuscitation events. AEDs with real-time clocks provided audio
records of the resuscitation and continuous tracings of cardiac
rhythm, recorded from cutaneous defibrillator patches that approxi-
mated a lead II configuration. Waveform type was unavoidably
reported by analytical software on retrieved rhythm tracings. These
were interpreted by a research nurse and characterized at 5, 10, and
20 seconds after each shock, as suggested by others,6 with the use of
the objective criteria defined below. Rhythms whose diagnosis was
uncertain underwent separate blinded review by 2 cardiologists.
Functional status before cardiac arrest and neurological condition
and disposition at hospital discharge were evaluated from the
medical record. Before cardiac arrest, patients were characterized as
independent if able to perform activities of daily living and manage
their personal affairs without assistance. Neurological condition at
discharge was assessed with the use of the Cerebral Performance
Category (CPC)14,15 and by an index of functional status (whether
discharged home rather than to a skilled-care facility). Except as
noted above for rhythm analysis, all data were collected and
analyzed without knowledge of treatment assignment.
Monophasic vs Biphasic Defibrillation 2011
Definitions
VF was defined as irregular, disorganized ventricular activity of
variable amplitude (⬎0.1 mV)16 without distinct QRS complexes.
Ventricular tachycardia (a wide QRS [⬎120 ms] rhythm without
associated P waves, at rate ⬎120 bpm) was uncommon in both
treatment groups (ranging from 3 to 6 patients [1.8% to 5.6%] after
initial shocks) and was grouped together with VF. Termination of VF
was defined as its displacement to a nonshockable rhythm (organized
or asystole). Asystole was defined as 0 to 1 QRS complex occurring
over any 5-second time interval (⬍12 bpm), and an organized
rhythm was defined as ⱖ2 QRS complexes with rate ⱕ120 bpm.
Return of spontaneous circulation (ROSC) meant confirmed palpa-
tion of an arterial pulse or recordable blood pressure for any duration
associated with an organized rhythm; sustained ROSC meant that
these persisted until hospital arrival. Dispatch time was defined as
the time when EMS providers were sent to the scene, and arrival time
was defined as the time when providers reached the appropriate
street address.
Events
The primary event of interest was admission of patients to the
hospital (formal assignment to a bed) with a spontaneously perfusing
rhythm. Secondary events included termination of VF, return of an
organized rhythm, and ROSC, regardless of their duration; the
number of shocks required for and time to sustained ROSC; survival
to hospital discharge; and neurological status at discharge.
Consent
This study was approved by the University of Washington institu-
tional review board. Because it evaluated Food and Drug Adminis-
tration–approved defibrillators during standard resuscitation proce-
dures, the study was viewed as having minimal risk and was
conducted with exception from informed consent, in compliance
with interpretation of the federal policy for the protection of human
subjects. Survivors or their families were later notified of their
participation, and consent was obtained for review of hospital
records. Records of patients who did not survive or could not be
contacted after discharge were accessed through a confidentiality
agreement.
Statistical Analysis
On the basis of reported admission rates after biphasic defibrillation
in another prehospital trial7 and those observed historically with
monophasic defibrillation in Seattle (65%), we estimated that it
would require 150 patients to detect a 30% relative improvement in
the proportion of those admitted alive to the hospital after biphasic
defibrillation, with 80% power and a 2-sided ␣ of 0.05. Differences
in continuous and dichotomous variables were analyzed with the
Student t test or the ␹2 test. Logistic regression analyses that included
demographic and resuscitation care variables were also performed,
proper selection of which was confirmed by the goodness-of-fit ␹2
(Hosmer-Lemeshow) test. Statistical significance was indicated by
2-tailed P⬍0.05.
Blinding
Even when statistically significant differences are not evident, subtle
biases may affect the manner in which data are presented and
interpreted, once treatment assignment is disclosed. So as not to
sway objectivity, in addition to our attempts to collect and analyze
data anonymously, the primary writers were unaware of treatment
assignment until after the article was formally accepted and revised
for publication.
The authors had full access to and take responsibility for the
integrity of the data. All authors have read and agree to the
manuscript as written.
Results
Patients
Of 862 consecutive patients treated for cardiac arrest from all
causes during the trial period, 168 met eligibility criteria and
 2012 Circulation November 7, 2006

Figure 1. Profile of the manner in which

patients were entered, excluded, ran-
domized, and analyzed in the trial.
Patients in the mixed-shock group each
received shocks of both waveform types
during resuscitation. Seventeen of these
patients in whom the waveform type for
the first shock was known were com-
bined with those having the correspond-
ing waveform in monophasic and bipha-
sic shock groups for the first shock
analysis. Because events that followed
the administration of ⬎1 shock could not
necessarily be ascribed to consistent use
of one or the other waveform, patients in
the mixed-shock group were excluded
from subsequent analyses. However,
their inclusion would not have altered
study findings or conclusions. BLS indi-
cates basic life support; DNAR, do not
attempt resuscitation, representing
patients with such an advance directive
in whom resuscitation was not
attempted; PEA, pulseless electric activ-
ity; and VT, ventricular tachycardia.

were allocated to either monophasic or biphasic defibrillation
(Figure 1). Of these, 80 patients (48%) and 68 patients (40%)
consistently received the same shock waveform (monophasic
or biphasic, respectively) throughout their resuscitation.
Twenty patients received shocks of both waveform types
because of a “mismatch” in defibrillators deployed by EMTs
and paramedics, including 3 for whom the identity of the first
administered waveform was not known. The characteristics
of these patients are shown in the Table. No statistically
significant differences in these parameters were observed

Baseline and Resuscitation Care Characteristics

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P P
Monophasic Biphasic (Monophasic vs Mixed (Monophasic vs
All Patients Shocks Shocks Biphasic Shocks Biphasic vs
Variable (n⫽168) (n⫽80) (n⫽68) Shocks) (n⫽20) Mixed Shocks)
Age, y 64⫾15 63⫾13 67⫾16 0.14 59⫾15 0.10
Men 77% 80% 75% 0.47 75% 0.74
Witnessed 71% 69% 74% 0.81 70% 0.87
Bystander CPR 52% 51% 48% 0.74 63% 0.045
Location of arrest 0.52 0.61
Home 48% 49% 52% 35%
Other residence 3% 4% 2% 5%
Public indoors 17% 20% 12% 25%
Public outdoors 26% 22% 29% 25%
Nursing home 5% 5% 4% 5%
Doctor’s or dentist’s office 1% 0% 2% 5%
VF amplitude, mV 0.5⫾0.3 0.51⫾0.34 0.49⫾0.28 0.67 0.5⫾0.23 0.91
Dispatch to first responder arrival, min 3.5⫾1.3 3.4⫾1.3 3.6⫾1.4 0.25 3.1⫾1.1 0.24
Dispatch to paramedic arrival, min 6.9⫾3.1 6.6⫾3.1 6.9⫾2.7 0.44 8.5⫾4.1 0.052
Paramedics first on scene or 9.5% 12.5% 9% 0.34 0 0.21
simultaneously with EMTs
Dispatch to first shock, min 7.5⫾2.1 7.7⫾2.3 7.5⫾1.9 0.49 6.9⫾1.8 (median 6.5) 0.33
(median 7.2) (median 7.4) (median 7.3)
Dispatch to IV,* min 12.6⫾3.3 12.4⫾3.3 12.5⫾2.7 0.94 14.3⫾4.8 0.14
Shock energy setting, J
First shock 200 200 200 1 200 1
Second shock 218⫾49 221⫾55 214⫾43 0.44 214⫾42 0.68
Third shock 327⫾64 320⫾69 326⫾66 0.65 352⫾21 0.24
*Intravenous access established.
 Kudenchuk et al
between monophasic and biphasic treatment groups; by-
stander CPR was more common and paramedics arrived later
in patients who received shocks of both waveform types than
in those treated exclusively with monophasic or biphasic
shocks.
Because patients in the mixed-shock group each received
shocks of both types during resuscitation, events that fol-
lowed the administration of ⬎1 shock could not necessarily
be ascribed to consistent use of one or the other waveform.
Hence we determined, a priori, to evaluate events after ⬎1
shock strictly in patients who were treated consistently with
the same waveform throughout resuscitation. Conversely,
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responses to the first shock were determined in all patients in
whom the waveform type was known by combining patients
from the mixed-shock group with those having the corre-
sponding waveform in the monophasic or biphasic shock
groups, denoted as monophasic1 and biphasic1 shock groups,
respectively, for these comparisons. Inclusion of patients with
mixed-waveform shocks in all analyses would not have
altered study findings or conclusions.
Response to the First Shock
Whether evaluated at 5, 10, or 20 seconds after the first
shock, the prevalence of VF, asystole, or organized or
Monophasic vs Biphasic Defibrillation 2013
Figure 2. The proportion of patients in
respective treatment groups with VF,
asystole, or an organized or unknown
rhythm assessed at 5, 10, and 20 sec-
onds after the first shock. Typically,
unknown rhythms represented those
whose recordings were obscured by
CPR artifact, preventing their classifica-
tion. Probability values denote the statis-
tical significance of differences in the fre-
quency of observed rhythms between
treatment groups at the specified time
periods. *Included in the treatment
groups (designated as monophasic1 and
biphasic1 in the text) were 17 patients
from the mixed-shock group in whom
the identity of the first shock waveform
was known. VF/VT indicates ventricular
fibrillation or ventricular tachycardia.
unidentifiable rhythms was similar in both treatment groups
(Figure 2). VF was terminated by the first shock in 75 patients
in the monophasic1 treatment group (82%) and 65 in the
biphasic1 group (88%) (P⫽0.33), resulting in an organized
rhythm in 24 (26%) and 24 patients (34%), respectively
(P⫽0.30) (Figure 5) and sustained ROSC in 18 patients in
each group (20% and 24%, respectively) (P⫽0.51)). VF
recurred in 18 of 75 patients in the monophasic1 group (24%)
and in 16 of 65 in the biphasic1 treatment group (25%)
(P⫽0.9).
Subsequent Shocks
A comparable proportion of patients in both treatment groups
had either unremitting or recurrent VF that required a second
shock after their first (70 of 91 patients in the monophasic1
group [77%] and 54 of 74 in the biphasic1 group [73%]
[P⫽0.5]) or a third shock after their second (54 of 80 patients
treated with monophasic shocks [68%] and 43 of 68 treated
with biphasic shocks [63%] [P⫽0.7]). The prevalence of
rhythms assessed at 5, 10, or 20 seconds after the second and
third shocks paralleled our observations after the first shock
and, when we considered the multiple comparisons of data,
did not significantly differ between treatment groups (Figures
Figure 3. The proportion of patients in
respective treatment groups with VF,
asystole, or an organized or unknown
rhythm assessed at 5, 10, and 20 sec-
onds after their second shock. Unknown
rhythms are as defined in Figure 2. Prob-
ability values denote the statistical signif-
icance of differences in the frequency of
observed rhythms between monophasic
and biphasic treatment groups at the
specified time periods. *Given the multi-
ple comparisons of data, this single
probability value is not likely to represent
a statistically significant finding. VF/VT
indicates ventricular fibrillation or ventric-
ular tachycardia.
 2014 Circulation November 7, 2006
3 and 4). There were also no statistically significant differ-
ences between groups in the proportion of patients in whom
1 to 3 shocks terminated VF or returned an organized rhythm
(Figure 5) or in whom circulation was restored during
resuscitation (Figure 6). The mean⫾SD time from first shock
to sustained ROSC was 14.4⫾12.8 minutes in recipients of
monophasic shocks and 11.6⫾6.7 minutes in those receiving
biphasic shocks (P⫽0.3). Patients treated with a monophasic
waveform tended to require more shocks before sustained
ROSC than recipients of the biphasic waveform (4.9⫾4.2
[mean⫾SD] [median 4] compared with 3.8⫾3.7 [median 2.5]
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shocks, respectively [P⫽0.18]).
Outcome
Among patients treated with monophasic waveform shocks,
58 (73%) were resuscitated and admitted alive to the hospital,
as compared with 52 recipients of biphasic shocks (76%)
(P⫽0.58). Twenty-seven patients (34%) who received
monophasic shocks and 28 recipients of biphasic shocks
(41%) were discharged alive (P⫽0.35); 18 (23%) and 16
patients (24%), respectively, went home rather than to a
Figure 4. The proportion of patients in
respective treatment groups with VF,
asystole, or an organized or unknown
rhythm assessed at 5, 10, and 20 sec-
onds after their third shock. Unknown
rhythms are as defined in Figure 2. Prob-
ability values denote the statistical signif-
icance of differences in the frequency of
observed rhythms between monophasic
and biphasic treatment groups at the
specified time periods. VF/VT indicates
ventricular fibrillation or ventricular
tachycardia.
skilled-care facility (P⫽0.48) (Figure 6). Before their cardiac
arrest, a comparable proportion of surviving patients in both
treatment groups (24 of 27 survivors treated with monophasic
shocks [89%] and 22 of 28 treated with biphasic shocks
[79%] [P⫽0.5]) were functionally independent; baseline
functional status was not known in 3 (11%) and 4 survivors
(14%), respectively. Neurological condition at hospital dis-
charge (CPC) could be determined in all but 2 surviving
patients (1 from each treatment group); 2 additional patients
from the biphasic treatment group had neurological recovery
that could not be distinguished from the medical record as being
either full or partial. No statistically significant differences were
observed between treatment groups in their neurological out-
come at hospital discharge (P⫽0.4) (Figure 7).
Early Shock
To determine whether treatment with one waveform or the
other was more effective when administered earlier in the
course of cardiac arrest,9,17 a prespecified subgroup of 91
patients was identified with witnessed cardiac arrest and no
reported delay in summoning EMS and who were shocked
Figure 5. The proportion of patients in
monophasic and biphasic treatment groups
in whom VF was terminated to a nonshock-
able rhythm (either an organized rhythm or
asystole) (solid bars) and those in whom it
resulted in a return of an organized rhythm
(shaded bars) of any duration. Results are
shown for the response to the first 3 shocks
analyzed individually and the cumulative
response to up to 2 shocks and up to 3
shocks. Probability values atop solid bars
depict the statistical significance of differ-
ences between monophasic and biphasic
treatment groups in whom defibrillation
resulted in a nonshockable rhythm (orga-
nized or asystole); those atop shaded bars
depict differences between these groups of
patients in whom defibrillation resulted in an
organized rhythm. *Included with the treat-
ment groups for the first shock analysis only
were 17 patients from the mixed-shock
group in whom the identity of the first shock
waveform was known.
 Kudenchuk et al
Figure 6. Clinical outcomes are depicted in patients who con-
sistently received either monophasic or biphasic waveform defi-
brillation throughout resuscitation.
within 10 minutes of EMS dispatch. After this first shock, an
organized rhythm returned in an identical proportion of
patients in the monophasic1 (16 of 48 [33%]) and biphasic1
treatment groups (14 of 43 [33%]). Of 81 patients who were
treated thereafter with the same waveform, circulation re-
turned in 38 of 42 recipients of monophasic shocks (90%) and
36 of 39 recipients of biphasic waveform shocks (92%)
(P⫽0.7). Among patients treated with monophasic shocks, 34
patients (81%) were admitted alive to the hospital compared
with 30 recipients of biphasic shocks (77%) (P⫽0.6); 18
(43%) and 20 patients (51%), respectively, were discharged
alive (P⫽0.5).
By comparison, among patients who received their first
shock ⬎10 minutes after EMS dispatch, clinical outcomes
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were poorer than in the former group but were not statistically
different between recipients of the 2 waveforms. Seven of 12
such patients treated with monophasic shocks (64%) com-
pared with 5 of 7 recipients of biphasic shocks (71%) were
admitted alive to the hospital (P⫽0.7); 2 (18%) and 1 patient
(14%), respectively, were discharged alive (P⫽0.9).
Figure 7. Neurological outcome at hospital discharge is
depicted for 26 surviving recipients of monophasic waveform
shock and 27 recipients of biphasic shock in whom CPC could
be determined. Full recovery refers to CPC 1, mild impairment
to CPC 2, severe impairment to CPC 3, and comatose to CPC
4. CPC could not be determined in 2 survivors (1 per treatment
group). Two additional recipients of biphasic shock had neuro-
logical recovery that could not be distinguished from the medi-
cal record as being either full or partial. The probability value
(P⫽0.4) reflects inclusion of these patients as a separate cate-
gory for statistical comparisons. If excluded, P⫽0.56.
Monophasic vs Biphasic Defibrillation 2015
Predictors of Mortality
Death was independently predicted only by older age (odds
ratio, 1.67 per 10-year increment; 95% confidence interval,
1.24 to 2.23). Multivariate adjustment did not alter the
absence of an association between defibrillation waveform
and mortality (odds ratio for biphasic versus monophasic
waveform shock, 0.57; 95% confidence interval, 0.26 to
1.23). No variable was found that independently predicted the
likelihood of admission alive to the hospital.
Discussion
We found no statistically significant differences between
waveforms in the likelihood of terminating VF, restoring an
organized rhythm or circulation, improving hospital admis-
sion, or survival after cardiac arrest. This contrasts with the
reported greater efficacy of biphasic shock for electively
terminating atrial arrhythmias or VF of brief duration under
controlled circumstances.18 –20 Such discordance could result
from the reduced performance of any shock waveform under
the conditions typically encountered in cardiac arrest. For
example, when VF is protracted or associated with acute
myocardial ischemia, the energy required for its termination
increases substantially regardless of waveform.21–26 These
and other differences between the experimental and cardiac
arrest environment23,27 underscore the importance of evaluat-
ing the efficacy and effectiveness of shock waveforms under
the same clinical conditions in which defibrillation is most
likely to be emergently needed and used.
Clinical Studies
Nearly all previous clinical evaluations of shock waveform in
cardiac arrest were potentially confounded by the use of
AEDs from different manufacturers. Different AEDs vary
widely in waveform design,28,29 in the magnitude of voltage
and current delivered even at identical energy settings,4,28 and
in the “hands off” time each requires to analyze rhythms,
charge, and shock.30 Apart from delaying shock, interruption
of CPR for these analyses has recognized adverse conse-
quences.31 The potential for unconscious bias in the manner
in which resuscitation might be conducted is also higher
when devices are easily distinguishable to care providers.
Notably, the greater apparent defibrillation efficacy of
biphasic shock reported in most studies has not been regularly
accompanied by improved clinical outcomes; in fact, these
have sometimes even trended in the opposite direction. For
example, although biphasic shocks were found, retrospec-
tively, to be better than escalating energy monophasic shocks
for terminating VF, no statistically significant differences in
ROSC (67% with biphasic versus 69% with monophasic
shocks; P⫽0.82) or survival (31% versus 41%, respectively;
P⫽0.32) were observed between treatment groups.6 A similar
study found that an organized rhythm was restored more
frequently after biphasic than monophasic shocks, but this
was not accompanied by significant differences in ROSC
(55% with biphasic versus 65% with monophasic shocks;
Pⱖ0.1) or in survival (20% versus 30%, respectively) be-
tween treatment groups.32
 2016 Circulation November 7, 2006
Randomized Trials
In a multicenter prehospital trial, biphasic shocks proved
better than escalating energy monophasic shocks for termi-
nating VF, resulting in improved hospital admission rates
(69% versus 46%, respectively; P⫽0.02) but not survival
rates (33% versus 27%; P⫽0.45) or the proportion of survi-
vors found suitable for discharge home (63% versus 50%;
P⫽0.3).7
When patients in VF were defibrillated by AEDs that
differed only in waveform, the return of an organized
rhythm was independently predicted by receipt of a bipha-
sic rather than monophasic shock. Notably, ROSC did not
significantly differ between treatment groups (61% versus
65% of patients, respectively; P⫽0.62), nor did hospital
admission rates (40% versus 48%; P⫽0.35) or survival
(14% versus 19% in biphasic versus monophasic groups,
respectively; P⫽0.46).8
Another prehospital trial observed a higher conversion rate
to an organized rhythm in recipients of biphasic compared
with monophasic waveform defibrillation. However, ROSC,
survival, and neurological recovery were virtually identical
between treatment groups.9
Favorable Trends
Our randomized trial consistently administered the same
waveform type at the same ascending energy settings
throughout resuscitation, used defibrillators that were identi-
cal apart from waveform type, and emphasized the uniform
provision of CPR before the first shock. That we did not find
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statistically significant differences in clinical outcome, under
conditions that we believe tested the unique contribution of
waveform type more rigorously than in previous studies,
should not necessarily be taken to mean that the differences
seen were unimportant. For example, several beneficial
trends were observed in this trial that consistently favored
treatment with biphasic waveform shock. These included a
higher reversion of VF and return of an organized rhythm
after the first shock; a requirement for fewer shocks and a
shorter mean time from first shock to sustained ROSC; and a
higher proportion of patients in whom circulation was re-
stored and who survived. Most intriguing of these, a 21%
relative (7% absolute) improvement in survival was observed
with biphasic compared with monophasic waveform defibril-
lation, more than has ever been ascribed to any single
intervention during cardiac arrest, except perhaps for defibril-
lation itself. That none of these differences was statistically
significant could be attributed to true absence of benefit or to
lack of statistical power, proof of which would require
performance of considerably larger trials. For example, to
establish statistical significance for the differences we ob-
served in hospital admission and survival rates, with 80%
power and a 2-sided ␣ of 0.05, would demand enrollment of
at least 3700 and 1300 patients, respectively, and would take
decades to complete.
Shock Energy
Experimental evidence suggests that biphasic defibrillation
provokes less ventricular dysfunction, with better hemody-
namic recovery from shock.33 We observed that biphasic
compared with monophasic waveform defibrillation short-
ened the time from first shock to sustained ROSC by nearly
3 minutes. That this difference was not statistically significant
could be because the study was underpowered or because a
waveform effect, if present, was attenuated by the severity of
cardiac dysfunction that accompanies protracted VF. It may
be argued that the use of ascending energy shocks in both
treatment groups may also have been a factor in our failure to
see a benefit specific to waveform type. However, the energy
settings we used all fell well below thresholds associated with
myocardial injury in animals,34 and lower energy shocks
might not have been as effective in terminating VF. Notably,
others have not confirmed a waveform-dependent reduction
in cardiac function after shock35 and suggest that most of the
dysfunction in the aftermath of VF is caused by the ischemic
period associated with the arrhythmia.36
Limitations
Although attempted, blinding was imperfect. Although wave-
form type from manual defibrillators was apparent to para-
medics during the later phases of resuscitation, this seems
unlikely to have influenced outcome, particularly because
initial (blinded) shocks had already been administered from
AEDs. Waveform type was unavoidably annotated on rhythm
tracings when later retrieved, but these were classified ac-
cording to strict objective criteria and without knowledge of
final outcome. Hospital admission rates were higher than
anticipated in both treatment groups, and differences between
them were smaller than expected. This may have stemmed
from the mandatory provision of CPR before the first shock,
which might have “leveled the playing field” and served to
make either waveform perform better. As a result, this trial
may have been underpowered to assign statistical signifi-
cance to otherwise potentially important trends in outcome.
That a survival benefit associated with biphasic waveform
defibrillation, in particular, cannot be summarily dismissed
by our findings invites further study. Alternatively, on the
basis of the absence of statistical significance and the rela-
tively large numbers of patients that would be required for its
achievement, it could be argued that attention to, and expen-
ditures for, aspects of resuscitation other than shock wave-
form may be more productive ways of improving outcome
after cardiac arrest.
This study focused on the treatment of VF arrest in the
prehospital setting. Although our results may also pertain to
in-hospital cardiac arrest, they should not be taken to apply to
elective procedures, such as cardioversion of atrial fibrilla-
tion, for which there is more established advantage in using a
specific waveform.18
Conclusions
Potentially important trends, but no statistically significant
differences in outcome, could be ascribed to use of one wave-
form over another in the treatment of out-of-hospital VF.
Acknowledgments
Special appreciation is extended to all the EMS personnel of the
Seattle Fire Department, without whose efforts and dedication this
trial would not have been possible.
 Kudenchuk et al
Sources of Funding
Drs Kudenchuk, Maynard, and Graham and Michele Olsufka are
supported by the Resuscitation Outcomes Consortium through the
National Heart, Lung, and Blood Institute (UO1-HL77867-02). This
study was supported by the Medic One Foundation (Seattle, Wash).
Defibrillators were provided by Medtronic Emergency Response
Systems Inc (Redmond, Wash). Neither had any role in design,
conduct, analysis, manuscript preparation, or approval.
Disclosures
Drs Kudenchuk and Cobb have received speaker honoraria from
Medtronic; Michele Olsufka has performed contract work for
Medtronic ERS. The remaining authors report no conflicts.
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CLINICAL PERSPECTIVE
Although biphasic shock is heralded by many as the new standard for defibrillation, proof of whether it is a more life-saving
waveform remains elusive. In previous clinical trials, evaluation of shock waveform was confounded by a failure to control
for a number of important variables. When controlled for these variables in this trial and uniformly preceded by 90 seconds
of CPR, both waveforms performed comparably, although several nonsignificant trends consistently favored treatment with
biphasic shock. How are these results reconciled with the recognized superior performance of biphasic shock during
elective cardioversion procedures, and how might they guide decisions about whether to retain or replace existing
defibrillators? It may be argued that if greater benefit is associated with use of a biphasic waveform, it may be attenuated
by the compromising conditions typically encountered in clinical cardiac arrest. From our findings, relatively large
numbers of patients would be required to establish such differences. Given that monophasic defibrillators are no longer
being manufactured, it is unlikely that such studies will ever be conducted. Alternatively, one possible conclusion from the
results of this trial is that biphasic defibrillation was statistically no less effective than monophasic defibrillation. Perhaps,
given a larger study, it might have even proved better. Thus, cost issues aside, adoption of biphasic waveform defibrillation
seems reasonable. Conversely, faced with the costs of such change, other spending priorities, and the limitations of this
trial, we do not have compelling evidence that replacement of monophasic by biphasic defibrillators is mandatory or could
not be justifiably deferred until needed for other reasons.
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