Category: Product Review, Polarity of "ActiBiphasic" waveform.
In
this record we reviewed the Acti-Biphasic defibrillation waveform employed by CardioLife defibrillators and we explain the reasons why CardioLife TEC-7700 series, CardioLife TEC-5500 series, CardioLife TEC-5600 series, CardioLife TEC-8300 series should be recalled from the market.
From
the operating and service manuals of CardioLife Acti-Biphasic
defibrillators, we know the Acti-Biphasic waveform looks like what is shown in below picture.
THE DECLARED WAVEFORM
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| Declared characteristics of the Acti-Biphasic waveform |
| The basic concept of a bi-phasic shock energy is to add a negative follow-up phase to the conventional mono-phasic shock to achieve the same defibrillation result using lesser energy |
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The characteristics of NIHON KOHDEN Acti-Biphasic defibrillation can be summarized as:
1. First (Launch) Phase
The Acti-Biphasic waveform is seen as operating in an open loop during the first phase (period).
- It is a positive truncated exponential pulse with a duration depending on the patient impedance.
- It is of a longer duration than the second period.
- It is of a longer duration than the second period.
2. Second (Follow-up) Phase
The Acti-Biphasic waveform operates in a closed loop
during the second phase. In a closed loop the duration of the width can be deliberately set to a specific duration.
- This second phase (period) is shorter in duration and of negative polarity.
- The duration in this phase is fixed to a constant 3.4ms duration regardless of patient impedance. How was the optimal duration of 3.4ms arrived at? It is also not clear how was the maximum energy of 270 Joules concluded?
- The duration in this phase is fixed to a constant 3.4ms duration regardless of patient impedance. How was the optimal duration of 3.4ms arrived at? It is also not clear how was the maximum energy of 270 Joules concluded?
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| Note the first phase (period) is positive and a wider pulse than the second phase |
The first to use the Acti-Biphasic waveform were the TEC-7700 series defibrillators |
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| The first Acti-Biphasic defibrillators |
| Output discharged by CardioLife TEC-7700K series defibrillators is consistent with the declared waveform |
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The
output waveform of the CardioLife TEC-7700K series on a recorder is as
shown below. The recording correctly shows the first phase is a positive pulse.
The recording shows the voltage first swings to the top (positive saturation), then to negative saturation after some time; this is fully consistent with the official description of the Acti-Biphasic waveform.
The reason we are not seeing the full shape of the Acti-Biphasic waveform on the recording is because the sensitivity is set to see the smaller ECG waveform, and not the defibrillation shock which are much higher in magnitude.
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| Output of CardioLife TEC-7700K series is consistent with the declared description |
How can we know if the Acti-Biphasic defibrillation shock actually works on patients? |
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| The margin of error is high for data from a small 75 investigated cases |
There is no white paper available. The Acti-Biphasic defibrillators were hurriedly launched (for export) before completion of proper clinical validation and the small sample size of seventy five investigated cases meant a high margin of error; we cannot be sure the Acti-Biphasic defibrillation shock works on patients! In addition, how can we be sure the investigated cases were done in an acceptable manner?
As the mono-phasic defibrillators are not predicate devices so the FDA 510(K) process cannot be used to clear the product for sales in the US market. Since the clinical data and methodology adopted by NIHON KOHDEN fell short of US FDA guide for safety and effectiveness,
the Acti-Biphasic defibrillation shock is not allowed for sales in the US market; Nihon Kohden could have engaged a consultant to ensure a proper and acceptable clinical validation process if they had wanted to do it right.
The persistent remarks we often heard from NIHON KOHDEN marketing staff on American Heart Association recommendations are in reality, meaningless to Acti-Biphasic defibrillators.
Outside of the US market, we need to question the point of buying such critical treatment devices and placing them on standby to save lives? It is so unfair to the patients needing immediate treatment in a life-threatening situation!
Biphasic Defibrillation Was A Nightmare, One That Caught NIHON KOHDEN Off Guard
In May 1997 Nihon Kohden released a new defibrillator with a semi-automatic AED mode for export using mono-phasic defibrillation. The details of this TEC-2200K series can be found in the 1997 Product Guide.
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| The monophasic CardioLife TEC-2200K series was launched for export in May 1997 |
This was a mono-phasic model using the non-proprietary Edmark single-phase pulse as illustrated and the use of rechargeable battery for energy made it very inconvenient for public use.
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| Edwark, Single Phase Pulse defibrillation waveform used by monophasic CardioLife TEC-2200K series in 1997 |
The monophasic output discharge waveform shape is shown below. Note its shape as we will be revisiting it in later part of our discussion.
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| CardioLife TEC-2200K monophasic output waveform shown on recorder dated April 1995 |
Just a few months after the
TEC-2200 series was released, then market leader Hewlett Packard made announcement to acquire Heartstream Inc.
in a stock-swap deal.
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| Heartstream ForeRunner |
Biphasic defibrillation waveform was becoming the new preference
as it allowed for a smaller and lighter defibrillator design; more importantly
it uses less current and this means less damage defibrillation will do to the
heart and skin. The deal with Heartstream was how the then defibrillator market leader HP acquired biphasic technology, since to develop one would take time.
On the other hand, there
was zero interest in the monophasic TEC-2200 series
defibrillators offered by Nihon Kohden for ex-Japan market and the products had to withdrawn from exporting.
Unlike
the monophasic pulse, biphasic waveform comes in various forms; each
type of shape is proprietary and
cannot be copied freely. This means the energy envelopes of manufacturers in the market are all
different. For some waveform, the manufacturers only recommend a maximum
of 200
joules while another can recommend energy as high as 360 joules. Since
there is practically no limits to the type of biphasic defibrillation
waveform shape a manufacturer could come up with, all
manufacturers must justify the use of their proprietary output
waveform in some reasonable ways, preferably in accordance with US FDA guide for safety and effectiveness, which calls for clinical research validations or published clinical papers which are subjected to peer review.
| NIHON KOHDEN was unprepared for the global shift to biphasic defibrillation technology |
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It was a market disruption that caught NIHON KOHDEN by surprise. After more than four years, NIHON KOHDEN remained unable to offer biphasic defibrillators and the company was at a loss how to make it happen.
When the demand for biphasic AEDs emerged in the Japanese domestic market, the company opted to rely on finding a suitable partner with biphasic technology for co-operation. A strategic OEM distribution agreement was announced in January 2002 that Nihon Kohden would market Cardiac Science's line of AEDs under Nihon Kohden's
trade name. This arrangement was a big success and many AED-9200 and AED-9231 were
sold in Japan as reflected in annual reports and presentations.
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| NIHON KOHDEN CardioLife AED-9200 and AED-9231 were highlighted to have very good sales in FY2006 financial results presentation |
The Cardiac Science STAR biphasic waveform (see white paper) was validated by researchers at Cleveland Clinic and
Cedars-Sinai
Medical Center in accordance with US FDA guides for Safety and Effectiveness |
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The success of the STAR biphasic shock in the domestic market however, could not be replicated for exports to foreign markets since distributors could buy the original models at much cheaper prices from Cardiac Science directly.
Instead of licensing the proprietary biphasic defibrillation design from Cardiac Science, we were surprised a few engineers in NIHON KOHDEN could just by experimenting biphasic circuitry on pigs easily concluded a workable, proprietry Acti-Biphasic shock circuitry. It was done internally, with minimal clinical supervision and collaboration, the company thus had great difficulty securing the necessary clinical support to advance the number of investigated cases for proper clinical validation. To date, there is not a single clinical paper published on Acti-Biphasic defibrillation.
| Customers were buying unproven defibrillators based on blind faith |
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Before completion of proper clinical validation, the company was bold enough to go ahead with exporting the unproven TEC-7700 series Acti-Biphasic defibrillators from November 2002, relying solely on reputation of being an existing supplier of mono-phasic defibrillators. The customers bought them based on blind faith, not facts, for there was no published clinical paper to show that it works. This November 2002 export launch was three long years ahead of the date Japan MHLW officially approved its use for the domestic market.
The Absence of Internal Safeguards
The desperate action was taken in response to the rapid changing preference for biphasic defibrillators in the market but the process totally overlooked the seriousness of mandatory successful clinical studies before marketing; the fact that Ministry of Health, Labour and Welfare (MHLW)
had not yet approved the sales of TEC-7700 series defibrillators in
Japan domestic market reflected the disturbing absence of internal safeguards in
corporate conduct.
Up to this point, the company had never exported a
new product before first
launching it in
Japan, showing the company was in complete disarray. It
is not just loss of credibility in overseas markets as a leading defibrillator
exporter from Japan but a ticking time bomb
with important
issues left unattended.
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| Before completion of proper clinical validation, Nihon Kohden began exporting unproven proprietary Acti-Biphasic defibrillators in 2002 |
| Japanese Regulatory Authority took three long years to grant approval for the TEC-7700 series to be allowed for sales in Japan |
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This
implied the application was turned down several times and serious
doubts by the Regulatory Authority to grant its use. What prompted the
decision to clear it after three years' wait is something we should
know. By the time of receiving approval to sell in Japan, many CardioLife TEC-7700 series defibrillators were already exported.
NIHON KOHDEN was only able to announce the launch of TEC-7700 series defibrillators for sales in
Japan market on December 1st, 2005.
There was an unlikely event before the above announcement. More than a year prior to the announcement, Nihon Kohden had incredibly gone on to launch another unproven Acti-Biphasic TEC-5500 series defibrillators for export sales in August 2004. Why was the need to launch the TEC-5500 series without Regulatory Authority approval for TEC-7700 series defibrillators? The urgent launch of TEC-5500 series defibrillators for export was highly suspicious and illogical.
We later found the Acti-biphasic waveform discharged by the TEC-5500 series defibrillators was flipped vertically upside down from that of the TEC-7700 series defibrillators! The change in the shape of the waveform was not disclosed at the time of launch, it was only discovered later by accident.
| This means the manufacturer decided at this point not to continue with the declared waveform that is being published on the service and operator manuals! |
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To reiterate, Cardiolife TEC-5500 defibrillators was the series later found to have
Acti-Biphasic discharged waveform flipped vertically upside down from that of the TEC-7700 series and it was
happening right before Japan MHLW granted approval for the TEC-7700 series, and without showing any clinical studies done to support its use!
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| Unproven CardioLife TEC-5500K series started to be exported from August 2004, when Japan MHLW had not approved the sales of CardioLife TEC-7700 series |
The Timeline
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| Export of unproven CardioLife TEC-5500K series started in August 2004, more than one year before Japan MHLW actually approved the TEC-7700 series |
CardioLife TEC-5500 series defibrillators were quickly approved for sales in Japan based on the principle of declared substantial equivalence with the newly-approved TEC-7700 series, so the Acti-biphasic waveform discharged by Japanese version TEC-5500 series defibrillators are unlikely to be different from that discharged by TEC-7700 series defibrillators in Japan.
The TEC-5500 series, TEC-5600 series and TEC-8300 series export models were all found by us to have their discharged waveform inverted, but submission documents to foreign regulatory authorities were all based on the TEC-7700 series. Are the regulatory approvals valid?
A top prestigious University Hospital in Taiwan was the first to find the polarity of TEC-5500K discharge waveform inverted from what was declared on the operator and service manuals
In the image below,
we were greatly puzzled to learn of an adverse report from a competent Biomedical
Engineering Team in National Taiwan University Hospital (Taipei City) that the polarity of measured
waveform discharged by two tested CardioLife TEC-5500K series defibrillators were inverted
(i.e. opposite in polarity) from what the manuals had described.
The tests were a result of investigation after a serious performance failure incident that raised doubts about its efficacy. The investigation brought up many unanswered questions and only the IEC60601-2-2:2002 electrical safety compliance was put to rest. We should be clear the issue was not about safety, but effectiveness of defibrillation.
There
was no doubt since they had tested both models TEC-5521K (S/N 09xx4) and
TEC-5531K (S/N 05xx4) to arrive at the same conclusion; the suffix K is
for export models using English language as interface (for example the suffix J is for Japan domestic models),
indicating more than 9000 units of TEC-5521K and more than 5000 units of TEC-5531K had been produced before the two tested units respectively.
Detailed
comparison was also done with defibrillators from another manufacturer
(Philips) using the same testing equipment (Fluke Impulse 7000DP with 7010 Selectable Load) and the polarity was consistent with the manual descriptions of Philips.
This was an input from professionals that the Acti-Biphasic waveform discharged by CardioLife TEC-5500K series defibrillators starts with a negative polarity and ends with a positive polarity; it is the exact opposite of what were shown on the operator and service manuals. As far as we know, there is no known manufacturer with a discharged biphasic waveform that starts with a negative polarity, NIHON KOHDEN is unique in this approach but there is no clinical research done to validate its use on patients!
The next image showed the illustration from another distributor (Thailand) sending in a Nihon Kohden defibrillator analyzer AX-103VK (OEM device) for repair.
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| The AX-103VK defibrillator analyzer has a discharge waveform output on the rear panel for oscilloscope display |
The analyzer was concluded by their technical staff to be defective because the display on the oscilloscope was inverted; the analyzer was of course working fine. Said Thailand distributor is a top distributor who had sold the highest number of CardioLife TEC-7700K series defibrillators in the world and knew too well what is the "Correct Graph", confident of the defect conclusion. The
conclusion turned out to be erroneous because the service manual wrongly informed them a TEC-5500K series
defibrillator has similar output as a TEC-7700K series defibrillator.
Guess what? someone in Tokyo has the audacity to ask the distributor staff to "just flip the APEX/ STERNUM connections" to obtain the "correct graph"!
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| Changing "Evaluation machine" from a TEC-7700K defibrillator to a TEC-5500K defibrillator |
What could be the reason for the sudden change of mind? Was it due to copyright pressure? Does the inverted waveform only apply to export models since Japan MHLW solely approved the TEC-7700 series version?
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| The
declared current flow direction of NIHON KOHDEN Acti-Biphasic shock
energy is the one on the left while we discovered actual biphasic flow
is the one shown on the right |
The clinical trial data cited to regulatory authorities is based on the
TEC-7700 series defibrillators for all Acti-Biphasic defibrillators,
including the TEC-5500 series, TEC-8300 series and latest TEC-5600 series.
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| There were only some clinical data from TEC-7700 series defibrillators |
When the discharged waveform is flipped upside down, the TEC-7700 series clinical data cited becomes irrelevant
It is serious matter if the actual output waveform is different from the
manual descriptions, as well as any inaccurate description documents
submitted together with operator/ service manuals to regulatory authorities.
It means there is no approval from regulatory authorities to use a discharge waveform that is flipped upside down, and this is a ticking time bomb.
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| Change in current direction demands fresh clinical trial and validation |
As
a responsible company, NIHON KOHDEN must act fast and should have by now long recalled all Acti-Biphasic defibrillators from the market. There is no denying customers are still buying Acti-Biphasic defibrillators based on blind faith.
The Acti-Biphasic output discharged by AED-2100 series is seen avoiding the declared waveform in a monophasic way
The
AED-2100K defibrillator was announced for export from October 2009 (Signal SE.C-19), it retained many features and appearance of the Cardiac Science OEM models except the proprietary output waveform.
CardioLife
AED-2100K is exported to many parts of the world, albeit in small
quantity; exception seems to be Taiwan and South Korea. It is not
exported to the US market where it does not have US FDA clearance for
the use of the Acti-Biphasic output waveform.
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| CardioLife AED-2100K seen distributed in Taiwan |
The
model AED-2100K did not have a screen display, which a later model was
added in January 2012 with this feature. A more compact and lower-cost AED-3100 has now replaced AED-2100 series with some small changes.
| The defibrillation success stories of AED-9200 and AED-9231 in Japan are routinely cited to sell later models but this is a misrepresentation |
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Current offer of AED-2152 and AED-3100 are not authorized to use the
STAR biphasic waveform and had nothing to do with earlier OEM models in
terms of defibrillation technology.
The
defibrillation success stories of AED-9200 and AED-9231 in Japan are
routinely cited to sell later models but this is a misrepresentation
that should be dropped immediately; the success stories cannot be linked
to the latest AED-3100 defibrillator! Unlike the STAR biphasic defibrillation output, the Acti-Biphasic defibrillation output employed by CardioLife AED-3100 and AED-2152 defibrillators do not meet US FDA approval for use in the USA market.
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| AED images from Japan |
| How can a user view the "Acti-Biphasic" output waveform from a defibrillator? |
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The QP-551VK defibrillator report viewer software can be used on a PC or laptop to review event recorded by any CardioLife defibrillator, including the AED defibrillators.
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| The defibrillator report viewer can be used to review events recorded by a NIHON KOHDEN defibrillator |
Below
shows a review screen of an AED-2100 defibrillation event using the QP-551VK software; the event was recorded using a simulator with TTR
value of 49 ohm.
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| Notice the output waveform of AED-2100 is the same as older TEC-2200K which discharges a monophasic output waveform |
| The waveform output discharged by AED-2100 series and AED-3100 AED defibrillators are the same as that discharged by monophasic TEC-2200K series AED defibrillators released in May 1997 |
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| The TEC-2200K series monophasic discharge waveform dated April 1995 |
What is the American Heart Association (AHA) recommendation for shock energy of mono-phasic defibrillators?
In the TEC-2200K series manual mode, the monophasic defibrillator energy storage has the following choices:
25J, 50J, 100J, 150J, 200J, 300J or 360J
When arrhythmia requiring defibrillation is detected in the semi-automatic mode, the defibrillator will automatically charge to the energy according to the following defibrillation sequence:
First Defibrillation: 200J
Second Defibrillation: 300J
Third Defibrillation: 360J
When arrhythmia requiring defibrillation is detected in the semi-automatic mode, the defibrillator will automatically charge to the energy according to the following defibrillation sequence:
First Defibrillation: 200J
Second Defibrillation: 300J
Third Defibrillation: 360J
This is consistent with American Heart Association recommendation for a monophasic defibrillator, which Nihon Kohden is allowed to sell in the US market.
The above implies AED-2100K, AED-2150K. AED-2151K, AED-3100 do not comply with AHA recommendations for a monophasic defibrillator.
| And why are the operator/ service manuals not reflecting the shape we had observed? |
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| Discharged waveform expected from AED-2100K shown on user manual |
We should pause and think about the seriousness of the points raised on the Acti-Biphasic defibrillation output.