# b3i. Indications {#b3i.-indications .TOC}

**Indications:**

The SensorMedics 3100B is indicated for use in the ventilatory support
and treatment of selected patients 35 kilograms and greater with acute
respiratory failure.

**Contraindications:**

The SensorMedics 3100B Oscillatory Ventilator has no specific
contraindications.

**b3ii. Device Description**

The 3100B ventilator is based on the technology of the 3100A, but
features slight changes to some of the subsystems to provide enhanced
performance, safety and reliability for its intended application. Table
1 features the comparison of these system enhancements from the 3100A to
the 3100B. Outlined below is a more in-depth discussion of each of these
features.

# Differences between 3100A and 3100B {#differences-between-3100a-and-3100b .TOC}

+---------------------------+------------------+----------------------+
| **Specification**         | **3100A**        | **3100B**            |
+---------------------------+------------------+----------------------+
| Max Mean Airway Pressure  | 49 cmH2O         | 59 cmH2O             |
| (4B)(1)(2)                |                  |                      |
+---------------------------+------------------+----------------------+
| Bias Flow (2)             | 40 LPM           | 60 LPM               |
+---------------------------+------------------+----------------------+
| Max Delta-P (1)(2)        | \~ 105 cmH2O     | \~ 140 cmH2O         |
+---------------------------+------------------+----------------------+
| Safety Dump Pressure      | 50 cmH2O         | 60 cmH2O             |
| (1)(2)                    |                  |                      |
+---------------------------+------------------+----------------------+
| Safety Dump Alarm Delay   | No Delay         | 1.5 Second Delay     |
| (1)                       |                  |                      |
+---------------------------+------------------+----------------------+
| Circuit Length (external) | 25 inches        | 51 inches            |
+---------------------------+------------------+----------------------+
| Minimum Paw (1)           | \>20% High Paw   | Fixed @ 5 cmH2O      |
|                           | Alarm Set        |                      |
+---------------------------+------------------+----------------------+
| Mean Airway Pressure      | Manual           | Automatic            |
| Limit (1)                 |                  |                      |
|                           | (Approx. 10-45   | (Linked to Max Paw   |
|                           | cmH2O)           | Alarm)               |
+---------------------------+------------------+----------------------+
| Piston Centering (4A)(5)  | Manual           | Automatic            |
+---------------------------+------------------+----------------------+
| Visual Set Max Paw Alarm  | Red LED          | Red LED (latching)   |
| (1)                       | (non-latching)   |                      |
+---------------------------+------------------+----------------------+
| Cooling Gas Flow (3)      | 10 lpm           | 25 lpm               |
+---------------------------+------------------+----------------------+
| Driver Setting, Amplitude | 42 v Pk to Pk    | 75 v Pk to Pk        |
| (5)                       |                  |                      |
+---------------------------+------------------+----------------------+

Table 1

(1) -- Minor changes to Alarm Board (schematic beginning on page 607)

(2) Minor changes to Pneumatics Assembly (drawings beginning on page
    607)

(3) Minor changes to Driver Cover Assembly (assembly diagram beginning
    on page 607)

(4) Minor changes to Front Panel (assembly diagram beginning on page
    607)

> (4A) AutoCentering, DDI Board (schematic beginning on page 607)
>
> (4B) Thumbwheel switch 49 to 59 (assembly diagram beginning on page
> 607)

\(5\) Minor changes to the Driver Controller board (schematic beginning
on page 607)

# Maximum Mean Airway Pressure

In consideration of the treatment of large patients whose body weight
and chest wall compliance may represent significant barriers to adequate
lung recruitment, the maximum mean airway pressure of the 3100B has been
expanded from the 49 centimeters of water pressure used in neonates and
pediatrics on the 3100A to 59 centimeters of water pressure. Although
this pressure is the maximum capable, during operation of the
oscillatory subsystem, typical mean airway pressures do not exceed 55
centimeters of water pressure.

Additionally, the typical use of an asymmetrical waveform (I:E ratio
1:2) causes the ventilator to contribute more towards expiratory
pressure than inspiratory pressure. This results in the distal mean
airway pressure being less than the proximal airway pressure. This
combination of higher oscillatory amplitudes and asymmetrical pressure
waves may result in reductions in actual distal mean airway pressure;
increasing the range to 59 cmH20 may compensate for this loss.

# Bias Flow

With the increased mean airway pressure capability of the 3100B, the
maximum bias flow has been increased to 60 liters per minute. This was
required to allow stable mean airway pressures to be maintained with the
significantly larger tidal volumes achievable by the instrument. During
normal operation the 3100B draws exhaled patient gases into the
inspiratory limb of the patient breathing circuit. The additional flow
enables the practitioner to increase bias flow to assure purging of
carbon dioxide from the longer, higher volume, ventilator circuit
utilized by the 3100B.

# Amplitude

The 3100B is intended for use on patients 35 kilograms and larger. As
such, the stroke volume of the linear motor has been increased to allow
for adequate ventilation of this patient population. This increase in
stroke volume results in a greater change in pressure within the patient
breathing circuit, which is displayed as the oscillatory amplitude
pressure.

# Safety Dump Pressure / Delay

Since the maximum achievable mean airway pressure of the instrument has
been increased, the safety dump pressure has been increased to 60
centimeters of water pressure to match the instrument's performance.

Unlike the 3100A, the 3100B features a delay of approximately 1.5
seconds on the safety pressure dump. This delay has been incorporated to
prevent the inadvertent triggering of the safety pressure dump system,
which can occur with large oscillatory pressure amplitudes, and low
ventilatory frequencies typically employed to treat this patient
population. The pressure limit valve normally opens instantaneously when
mean airway pressures exceed the set limit. The safety dump valve is a
secondary safety system.

# Circuit Length

The length of the patient breathing circuit of the 3100B has been
increased to facilitate patient movement and positioning without the
need to relocate the instrument. Additionally, this circuit employs a
heated wire to reduce the accumulation of condensate within the circuit.

# 

# Minimum Mean Airway Pressure

The low-pressure alarm of 20% of Set Max (user setting) in the 3100A has
been fixed to a level of 5 cmH20. This change is related to the increase
in oscillatory pressure amplitude of the 3100B. In clinical applications
which employ a high oscillatory pressure amplitude and relatively low
mean airway pressures, the sudden decrease in circuit pressure which
occurs with activation of the oscillating linear motor may cause
inadvertent activation of the low pressure dump valve, resulting in an
inability to start the instrument.

Fixing activation of the low mean airway pressure dump valve at 5
centimeters of water pressure avoids this, while providing patient
protection by not allowing the oscillating linear motor to start without
supporting distending pressure and volume in the patient's lungs.

# Mean Airway Pressure Limit / Visual Set Max Paw Alarm

The 3100A employs a operator set mean airway pressure limit which
functions to provide patient protection in the event of an occlusion of
the expiratory limb of the patient breathing circuit. This manual airway
pressure limit includes no audible or visual indicators of activation.

The 3100B has linked the functions of the limit valve and maximum mean
airway pressure alarms to provide enhanced patient safety as well as
audible and visual indicators of activation.

During normal operation, the system pressurizes the patient breathing
circuit limit valve to the dump valve seat pressure (i.e. 59 cmH2O).
Should the maximum mean airway pressure alarm threshold be met, the
ventilator will deliver an audible and visual signal and the limit valve
will be depressurized to the control valve seat pressure (i.e. set mean
airway pressure). Once the mean airway pressure has decreased to 80% of
the maximum mean pressure alarm setting, the limit valve will
re-pressurize to the dump valve pressure. Should alarm conditions
continue, the valve will depressurize again and continue to cycle,
providing audible and visual alarms until the fault is resolved.

Once the fault has been resolved, the ventilator will return to normal
operation and the maximum mean airway pressure visual alarm will latch.
The operator may clear this alarm by depressing the reset / power
failure button.

# Piston Centering

The 3100A features a manual piston centering control which requires the
operator to read a visual indicator and adjust a baseline
electromagnetic counter-force to offset the mean airway pressure load
against the oscillating linear motor front plate. To avoid potential
misapplication of this control at the higher mean airway pressures
employed with the 3100B, this function is controlled internally by the
instrument and requires no operator intervention.

# Cooling Gas Flow

The higher stroke volumes delivered by the 3100B are the result of an
increase in the drive voltage to the oscillating linear motor. This
increased voltage produces an increase in the normal operation
temperature. In order to maintain adequate cooling of the linear motor,
the cooling gas flow has been increased from 10 to 25 liters per minute.

#### b3iii. Alternate Treatment Practices {#b3iii.-alternate-treatment-practices .unnumbered}

Alternative Strategies for Managing ARDS

Mechanical ventilation has many potential sequelae, but of particular
concern in Acute Respiratory Distress Syndrome (ARDS) is its potential
to further damage the already injured lung. Early in the history of
mechanical ventilation this insult was recognized chiefly as "classical"
barotrauma in the form of, for example, pneumothorax or
pneumomediastinum.^2^ Recently it has become increasingly apparent that
in addition to "classical" barotrauma, mechanical ventilation may add to
lung injury by a number of other mechanisms. These processes have become
known collectively as Ventilator-induced Lung Injury (VILI).^3^ They
can, in turn, lead to a prolonged duration of mechanical ventilation and
can cause both pulmonary and non-pulmonary morbidity, potentially
including multiple organ failure.^4^

A number of mechanisms are thought to contribute in varying degrees to
the development of VILI, which is histopathologically identical to ARDS:
(1) oxygen toxicity; (2) overdistention injury (v*olutrauma*); (3) shear
injury (a*telectrauma*); and, (4) *biotrauma.*

The first mechanism recognized to contribute to VILI is exposure to high
fractional inspired oxygen concentrations (F~I~O~2~). This phenomenon
has been well studied and has been generally accepted for many years. In
addition to VILI, oxygen toxicity can cause absorption atelectasis,
hypoventilation, systemic vasoconstriction and a decrease in cardiac
output.^5^

Lung overdistention injury can occur when high tidal volumes and plateau
pressures are delivered. Regional lung overdistention commonly occurs in
ARDS because low lung compliance and significant hypoxemia prompt
clinicians to raise pressures and tidal volumes. Additionally, because
of the patchy nature of ARDS^6^, there are small areas of relatively
normal lung which will receive the bulk of the tidal volume, and be at
particular risk of volutrauma.^7^ This effect will be magnified if
"classical" tidal volumes (10-15 ml/kg) are used. Over the last 25 years
numerous animal studies have been performed using both small and large
animals, consistently showing that high peak inspiratory pressures can
cause a clinical and histological picture similar to ARDS without any
other noxious stimulus.^8-13^. Additional data show that a low chest
wall compliance is relatively protective against the hazards of high
peak airway pressures, suggesting that end-expiratory stretch, related
to transpulmonary pressure is the key factor for this mechanism of
injury^14^

VILI can also be caused by repeated opening and closing of alveolar
units. This has been termed *shearing injury* or more recently
*atelectrauma.*^15^ This repetitive opening and closing will occur
whenever atelectatic lung regions are forced open with high pressures on
inspiration and then allowed to close again with low expiratory
pressures. There is a substantive body of animal evidence showing that
efforts to limit lung unit closing on expiration by maintaining an
adequate end-expiratory pressure are relatively protective against this
shearing injury. This has been demonstrated using HFOV^16,17^ and with
the use of Positive End Expiratory Pressure (PEEP) in CMV.^27,32,42-44^

In addition to simple mechanical injury, both *volutrauma* and
*atelectrauma* are thought to play a role in activating an inflammatory
reaction, which can then progress autonomously, further injuring the
lung. This phenomenon has recently been termed *biotrauma*.^18^ This
process is central to the theory that VILI can contribute to a systemic
inflammatory response and multi-organ failure.^4^ Studies comparing
injurious with relatively safe ventilation strategies in CMV have found
higher levels of inflammatory cytokines in the injured lungs.^19,20^
Similarly, studies in animal models of lung injury have shown that
initiating HFOV as a lung protective ventilatory strategy can lead to a
decrease in inflammatory markers.^21,22^ Indeed, animal evidence exists
showing that HFOV produced less histological damage and lower cytokine
levels when compared to a high PEEP and low stretch CMV strategy.^23^
These studies suggest that, at the least, local inflammation can be
attenuated by employing a lung-protective ventilation strategy. Newly
available data, collected from human patients randomly assigned to a
lung-protective (high PEEP, low stretch) or a conventional ventilation
strategy, confirm these findings.^24^ Importantly, Ranieri *et al* also
found lower levels of inflammatory cytokines in the plasma of patients
treated with the lung protective strategy, demonstrating that mechanical
ventilation can cause a systemic inflammatory response which can be
attenuated by manipulating ventilator settings.^24^

**Strategies to Minimize VILI**

With an increased appreciation of the mechanisms of VILI, the next
logical step is to employ ventilatory strategies that attempt to limit
overdistention, repetitive opening and closing injury, and oxygen
toxicity.^1,25,26^ Clinicians can try and achieve the first goal by
limiting inspiratory pressures and tidal volumes. Using conventional
ventilation this frequently means accepting hypercapnea and respiratory
acidosis along with their potential consequences. ^26-29^ In order to
prevent repetitive opening and closing, the end-expiratory pressure must
be kept above a critical closing volume. This is achieved with CMV
through the use of PEEP, but again a potential problem exists because
with higher PEEP and constant tidal volume comes a higher transpulmonary
pressure and more risk for overdistention injury. The goals of
mechanical ventilation in a patient at risk of VILI should be to
ventilate and oxygenate the patient while staying within a "safe
window", avoiding both overdistention and derecruitment.^30^

**Randomized Controlled Trials of Lung-protective Ventilation
Strategies**

Four randomized controlled trials have been published examining whether
ventilation strategies which attempted to limit VILI would reduce
mortality. Three of these limited inspiratory pressures and tidal
volumes in an effort to reduce overdistention injury.^27-29^ None of
their results showed any difference in mortality between the groups, and
although they were all under-powered, the point estimates of treatment
effect actually favoured the control group in all three trials. The
fourth study, by Amato and colleagues, also used limited tidal volumes
but these were employed in the setting of a multi-dimensional lung
protective strategy.^31^ The other components of this strategy were
individual tailoring of PEEP above the lower inflection point of the
pressure-volume curve and the use of frequent recruitment maneuvers (a
sustained inflation at CPAP of 35-40 cm H~2~0 for 40 seconds), both of
which were designed to avoid atelectasis and derecruitment. These
investigators found a striking increase in 8-day survival, demonstrating
for the first time that ventilation strategies can affect mortality.

Very recently, a large multi-centre trial of tidal volume limitation in
patients with ALI or ARDS was stopped early after an analysis of the
first 800 patients showed a significant reduction in mortality for the
treatment group (http://www.hedwig.mgh.harvard.edu). This trial was
conducted under the auspices of the NIH/NHLBI ARDS Network, and its
results were reported at the 1999 American Thoracic Society
International Conference. The investigators compared tidal volumes of 6
ml/kg with 12 ml/kg and did not use a lung recruitment strategy in
either group. They found a statistically significant 9% absolute risk
reduction (ARR) in 28 day mortality rates favouring the treatment group
(40% control, 31% low-stretch).

The results of all of these trials need to be taken in context. The
negative results of the first three studies do not mean that one can use
high inspiratory pressures and tidal volumes with impunity. It seems
likely that these trials did not show any benefit either because the
control groups were also relatively pressure-volume controlled and the
incremental differences between groups were too small, or because the
beneficial effects of limiting overdistention were counterbalanced by
the adverse effects of increasing derecruitment. The preliminary results
from the ARDS Network study confirm the fact that limiting
overdistention is indeed important. These results do not, however,
address the relative importance of avoiding derecruitment and
atelectrauma. In fact, the possible creation of auto-PEEP and subsequent
avoidance of derecruitment as a result of high respiratory rates in the
treatment arm is one hypothesis explaining the difference in results
between this and the other trials that only limited lung overdistention.
Amato's results, while exciting and encouraging, should also be viewed
with a critical eye. Concerns with this study include the high mortality
rate in the control arm, the possibility of significant cointerventions,
and a lack of generalization in both patients and maneuvers. This was a
single, small randomized trial. Its results should not cause clinicians
to think that the "correct" way to ventilate patients with ARDS is now
certain, but rather should prompt further research into the use of
ventilation strategies in ARDS.^54^ Because of its size and
multi-centered nature, the ARDS Network study will likely become the
current standard against which other ventilatory strategies are
measured. Its results are exciting because they reinforce the fact that
ventilation strategies can positively influence mortality. It should be
noted that the ARDS Network treatment strategy is not necessarily the
best way to ventilate patients with acute lung injury, but simply a
successful approach that has been well studied. While it is true that
the mortality rate was quite low in the treatment group of this study,
the mortality in the control group was also lower than in other studies,
illustrating that caution must be exercised when comparing mortality
rates across study populations. Replication of Amato's results using a
similar treatment protocol and the exploration of new ventilatory
modalities with similar physiologic goals such as HFOV^32-33^, are both
needed and these should, at the current time, be compared with the
treatment arm of the ARDS Network study.

####   {#section-1 .unnumbered}

#### References:

1.  Slutsky AS. Mechanical ventilation. American College of Chest
    Physicians\' Consensus Conference. Chest 1993; 104:1833-1859.

2.  Haake R, Schlichtig R, Ulstad DR, Henschen RR. Barotrauma.
    Pathophysiology, risk factors, and prevention. Chest 1987;
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3.  Dreyfuss D, Saumon G. Ventilator-induced Lung Injury: Lessons from
    Experimental Studies. American Journal of Respiratory & Critical
    Care Medicine 1998; 157:294-323.

4.  Slutsky AS, Tremblay LN. Multiple system organ failure. Is
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5.  Bryan CL, Jenkinson SG. Oxygen toxicity. Clinics in Chest Medicine
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6.  Gattinoni L, Pelosi P, Vitale G, Pesenti A, D\'Andrea L,
    Mascheroni D. Body position changes redistribute lung
    computed-tomographic density in patients with acute respiratory
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7.  Roupie E, Dambrosio M, Servillo G, Mentec H, El Atrous S, Beydon L,
    et al. Titration of Tidal Volume and Induced Hypercapnia in Acute
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8.  Webb HH, Tierney DF. Experimental pulmonary edema due to
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    Review of Respiratory Disease 1974; 110:556-565.

9.  Dreyfuss D, Basset G, Soler P, Saumon G. Intermittent
    positive-pressure hyperventilation with high inflation pressures
    produces pulmonary microvascular injury in rats. American Review of
    Respiratory Disease 1985; 132:880-884.

10. Kolobow T, Moretti MP, Fumagalli R, Mascheroni D, Prato P, Chen V,
    et al. Severe impairment in lung function induced by high peak
    airway pressure during mechanical ventilation. An experimental
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11. Dreyfuss D, Soler P, Basset G, Saumon G. High inflation pressure
    pulmonary edema. Respective effects of high airway pressure, high
    tidal volume, and positive end-expiratory pressure. American Review
    of Respiratory Disease 1988; 137:1159-1164.

12. Parker JC, Hernandez LA, Longenecker GL, Peevy K, Johnson W. Lung
    edema caused by high peak inspiratory pressures in dogs. Role of
    increased microvascular filtration pressure and permeability.
    American Review of Respiratory Disease 1990; 142:321-328.

13. Tsuno K, Miura K, Takeya M, Kolobow T, Morioka T. Histopathologic
    pulmonary changes from mechanical ventilation at high peak airway
    pressures. American Review of Respiratory Disease 1991;
    143:1115-1120.

14. Hernandez LA, Peevy KJ, Moise AA, Parker JC. Chest wall restriction
    limits high airway pressure-induced lung injury in young rabbits.
    Journal of Applied Physiology 1989; 66:2364-2368.

15. Slutsky AS. Lung injury caused by mechanical ventilation. American
    Journal of Respiratory & Critical Care Medicine 1998; Supplement:In
    Press

16. Hamilton PP, Onayemi A, Smyth JA, Gillan JE, Cutz E, Froese AB, et
    al. Comparison of conventional and high-frequency oscillatory
    ventilation. Journal of Applied Physiology 1983; 55:131-138.

17. McCulloch PR, Forkert PG, Froese AB. Lung volume maintenance
    prevents lung injury during high frequency oscillatory ventilation
    in surfactant-deficient rabbits. American Review of Respiratory
    Disease 1988; 137:1185-1192.

18. Tremblay LN, Slutsky AS. Ventilation-induced lung injury: from
    barotrauma to biotrauma. Proceedings of the Association of American
    Physicians 1998; 110:482-488.

19. Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious
    ventilatory strategies increase cytokines and c-fos m-RNA expression
    in an isolated rat lung model. Journal of Clinical Investigation
    1997; 99:944-952.

20. Tremblay L, Govindarajan A, Veldhuizen R, Slutsky AS. TNF levels
    are both time and ventilation strategy dependent in *ex vivo* rat
    lungs. American Journal of Respiratory & Critical Care Medicine
    1998; 157:A213

21. Sugiura M, McCulloch PR, Wren S, Dawson RH, Froese AB. Ventilator
    pattern influences neutrophil influx and activation in
    atelectasis-prone rabbit lung. Journal of Applied Physiology 1994;
    77:1355-1365.

22. Takata M, Abe J, Tanaka H, Kitano Y, Doi S, Kohsaka T, et al.
    Intraalveolar expression of tumor necrosis factor-alpha gene during
    conventional and high-frequency ventilation. American Journal of
    Respiratory & Critical Care Medicine 1997; 156:272-279.

23. Imai Y, Nakagawa S, Ito Y, Kawano T, Miyasaka K. Comparison of Lung
    Protection Strategies Using Conventional and High Frequency
    Oscillatory Ventilation. Submitted 2000;

24. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza
    A, et al. Efect of Mechanical Ventilation on Inflammatory Mediators
    in Patients with Acute Respiratory Distress Syndrome. JAMA 1999;
    282:54-61.

25. Stewart TE, Slutsky AS. Mechanical Ventilation: A shifting
    philosophy. Current Science 1995; 1:49-56.

26. Stewart TE. Lung Protection During Mechanical Ventilation. Ontario
    Thoracic Reviews 1997; 9:1-4.

27. Stewart TE, Meade MO, Cook DJ, Granton JT, Hodder RV, Lapinsky SE,
    et al. Evaluation of a ventilation strategy to prevent barotrauma in
    patients at high risk for acute respiratory distress syndrome.
    Pressure- and Volume-Limited Ventilation Strategy Group. New England
    Journal of Medicine 1998; 338:355-361.

28. Brochard L, Roudot-Thoraval F, Roupie E, Delclaux C, Chastre J,
    Fernandez-Mondejar E, et al. Tidal volume reduction for prevention
    of ventilator-induced lung injury in acute respiratory distress
    syndrome. The Multicenter Trail Group on Tidal Volume reduction in
    ARDS. American Journal of Respiratory & Critical Care Medicine 1998;
    158:1831-1838.

29. Brower R, Stanholtz C, Shade D, et al. Randomized trial of small
    tidal volume ventilation (STV) in ARDS. American Journal of
    Respiratory & Critical Care Medicine 1997; 155:A93

30. Froese AB. High-frequency oscillatory ventilation for adult
    respiratory distress syndrome: let\'s get it right this time.
    Critical Care Medicine 1997; 25:906-908.

31. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP,
    Lorenzi-Filho G, et al. Effect of a protective-ventilation strategy
    on mortality in the acute respiratory distress syndrome. New England
    Journal of Medicine 1998; 338:347-354.

32. Herridge MS, Slutsky AS, Colditz GA. Has high-frequency ventilation
    been inappropriately discarded in adult acute respiratory distress
    syndrome? Critical Care Medicine 1998; 26:2073-2077.

33. MacIntyre NR. High-frequency ventilation. Critical Care Medicine
    1998; 26:1955-1956.

#### b3iv. Marketing History {#b3iv.-marketing-history .unnumbered}

On March 29, 1991 SensorMedics received Premarket Approval for the Model
3100 High Frequency Oscillatory Ventilator for treatment of neonates
with respiratory failure and barotrauma. Subsequently, SensorMedics
received approval for the Model 3100A on June 27, 1991. The indications
for use of the 3100A were expanded to include pediatric patients failing
conventional ventilation on September 15, 1995. This instrument is
currently in production and has demonstrated some success in the rescue
treatment of large patients with acute respiratory failure.

In November of 1991 SensorMedics was granted an IDE for evaluation of a
new version of ventilator, the Model 3100B Adult High Frequency
Ventilator. This pilot clinical trial involved treatment of seventeen
patients ranging from 16 to 83 years of age. The results of this trial
demonstrated that HFOV was both safe and effective in adult patients
with severe ARDS failing conventional ventilation. HFOV demonstrated
improvements in oxygenation and reduced the mean airway pressure cost of
oxygenation. Overall survival was 37% which is consistent with prior
studies in similar patients.

#### The results of this clinical trial were supportive of further research and subsequently a second IDE was received for a prospective randomized controlled trial of high frequency oscillatory ventilation in adults with ARDS in 1996. This clinical trial, known as MOAT 2, had its final patient enrolled in December 2000. {#the-results-of-this-clinical-trial-were-supportive-of-further-research-and-subsequently-a-second-ide-was-received-for-a-prospective-randomized-controlled-trial-of-high-frequency-oscillatory-ventilation-in-adults-with-ards-in-1996.-this-clinical-trial-known-as-moat-2-had-its-final-patient-enrolled-in-december-2000. .unnumbered}

#### The model 3100A has been in International Commercial distribution since 1991. More than 3,000 units have been built and shipped to date.  {#the-model-3100a-has-been-in-international-commercial-distribution-since-1991.-more-than-3000-units-have-been-built-and-shipped-to-date. .unnumbered}

The model 3100B, has been shipped to countries outside of the United
States since 1993. Approximately 100 units have been shipped
internationally. Prior to June 1998 units were shipped freely to Europe;
since June 1998, all units shipped to the European Union have been
marked with the CE-Mark of conformity. SensorMedics maintains a
certificate to export an un-approved product under section 802 of the
exporting regulations.

3100B units have been shipped to the following countries:

Austria

Belgium

France

Germany

Italy

Norway

Qatar

Saudi Arabia

South Africa

Spain

Sweden

Switzerland

Netherlands

UK

**b3v. Summary of Studies**

#### b3vA. Nonclinical Studies {#b3va.-nonclinical-studies .unnumbered}

The following nonclinical studies were performed to ensure that the
minor physical changes and the increased work load applied to the 3100B
did not adversely affect the safety and efficacy of the function of the
device.

1\) A set of tests was performed on the driver assembly to ensure that
the increased tidal volume being demanded could be provided reliably.

2\) Tests were performed to validate each of the minor physical changes
to the 3100A that allowed it to become and function as a 3100B.

3\) FMEA analysis was performed to identify and ensure adequate
mitigation of potential risks and hazards.

4\) Tests were performed to ensure that none of the minor changes
adversely affected the electrical safety or EMC of the 3100B. These
tests (IEC 601-1 and IEC 601-2-12) were performed by ETL Laboratories.

Details of each of these three tests are included beginning with page
43.

# b3vB. Summary of clinical investigations {#b3vb.-summary-of-clinical-investigations .TOC}

Pivotal Trial (MOAT2)

PROSPECTIVE RANDOMIZED MULTICENTER OSCILLATOR ARDS TRIAL (MOAT2) **(IDE
G960017)**

***STUDY DESIGN***

MOAT2 was designed as a prospective multicenter randomized trial to
compare the model 3100B High Frequency Oscillatory Ventilator (HFOV) and
conventional mechanical ventilation (CMV) for the respiratory management
of patients with acute respiratory distress syndrome (ARDS). While many
patients were likely to have exposure to both ventilators, the study
design did not include crossover treatment and all analyses were to be
based on the intention to treat. Both ventilator strategies were aimed
at establishing and maintaining a normalized lung volume and minimizing
peak lung pressures.

Patients 16 years or older, and weighing at least 35 kilograms were
eligible for enrollment if they meet the American-European Consensus
definition of ARDS (i.e., PaO2/FiO2 \< 200, bilateral pulmonary
infiltrates not resulting from left atrial hypertension), with a
positive end expiratory pressure of at least 10 cm H2O. Patients
otherwise eligible for enrollment were excluded for any of the following
reasons: 1) lack of informed consent, 2) FiO2 greater than .80 for 48
hours, 3) severe persistent air leak, 4) non pulmonary terminal
prognosis, 5) severe chronic obstructive pulmonary disease, or asthma,
6) or recent enrollment in another ARDS or septic shock investigation.

The aim of the study was to show HFOV treatment was at least comparable
to CMV treatment. Four primary end points were prospectively
identified, 1) death or continued respiratory support at 30 days, 2)
death at 30 days, 3) development of acute intractable hypotension, and
4) development of new air leak. A power analysis suggested this could be
accomplished with an enrollment of 148 patients.

The study protocol is included beginning on page105. The study was
approved for use in 1997 as IDE **\#**G960017. There were two minor
changes made to the protocol after the study began, both affected the
enrollment criteria. First, the enrollment criteria requiring a PEEP of
at least 10 was included at the first investigators meeting on February
6, 1998 shortly after the study began. Only 4 patients had previously
been enrolled with initial PEEP\'s less than 10. In January 1999, after
enrollment of 39 patients, the enrollment exclusion for extended high
FiO2's was increased from 24 to 48 hours to improve enrollment by
facilitating informed consent.

***STUDY CENTERS AND ENROLLMENT***

The first of 148 patients was enrolled on 10/26/97 and the last on
12/7/00. Enrollment for the 4 years was as follow: 1997 - 6, 1998 - 31,
1999 - 65, 2000 -46.

The patients were enrolled from 10 centers, as shown in the Table 1
below. Three centers gained IRB approval, but found it impractical to
enroll patients and were dropped from participation. One of these three
centers enrolled one patient, the other two none. Three of the 10
enrolling centers were located in Toronto Canada. Each received approval
from their respective institutional ethics and research committees and
agreed to participate in accordance with USA Investigational Device
regulations 21CRF part 812, which was not inconsistent with Canadian
patient protection requirements. Details of the IRB approvals and site
participation are included on page 153 . Two of the centers represented
multiple sites, each with corresponding institutional approval for each
site and with the same Principal Investigator. The Wilford Hall Medical
Center included Brook Army Medical Center, with one patient being
enrolled at the latter site. Mt Sinai Hospital included Wellesley
Hospital, the later having enrolled 5 patients. In this case, as
originally anticipated, the ICU at Wellesley was closed and the staff
transferred to Mt Sinai where the study continued. The study was
conducted, to the best of our knowledge, according to CFR Part 812, with
the exception that written informed consent was not received at the time
of enrollment of one patient. (4/26/99 patient 8.02). The Principal
Investigator reported this to his IRB, once discovered. This event is
identified in a Table on page 159.

Table 1

+-----------------------------+-----------+-------+---------+--------+
|                             | HFOV      | CV    | Total   | Rate   |
|                             |           |       |         |        |
|                             |           |       |         | #/m    |
+-----------------------------+-----------+-------+---------+--------+
| Wilford Hall / BAMC         | 10        | 10    | 20      | .53    |
+-----------------------------+-----------+-------+---------+--------+
| Toronto General             | 11        | 10    | 21      | .62    |
+-----------------------------+-----------+-------+---------+--------+
| Wellselley / Mt Sinai       | 9         | 10    | 19      | .79    |
+-----------------------------+-----------+-------+---------+--------+
| Maine Medical Center        | 7         | 8     | 15      | .48    |
+-----------------------------+-----------+-------+---------+--------+
| Bronson Methodist           | 1         |       | 1       |        |
+-----------------------------+-----------+-------+---------+--------+
| Loma Linda                  | 6         | 5     | 11      | .44    |
+-----------------------------+-----------+-------+---------+--------+
| University Virginia         | 7         | 10    | 17      | .85    |
+-----------------------------+-----------+-------+---------+--------+
| Allegheny General           | 4         | 3     | 7       | .30    |
+-----------------------------+-----------+-------+---------+--------+
| Barnes Jewish               | 14        | 13    | 27      | 1.50   |
+-----------------------------+-----------+-------+---------+--------+
| Sunnybrook                  | 5         | 5     | 10      | .83    |
+-----------------------------+-----------+-------+---------+--------+

***STUDY POPULATION***

Seventy-five patients were assigned to HFOV treatment and 73 to CMV
treatment. The four tables that follow describe the patients enrolled in
the CMV and HFOV treatment arms of the study. They are quite similar.
Statistical evaluation of specific differences between the treatment
groups using chi-square and t-test found none that reached significance
(p=0.05). In cases were the n does not equal the enrollment, data was
unavailable from the site.

Table 2: Demographics

+---------------------+------+---------------+---+------+--------------+
|                     | \#   | HFOV          |   | \#   | #### CMV     |
+---------------------+------+---------------+---+------+--------------+
| Age (years)         | 75   | 48 (17)       |   | 72   | 51 (18)      |
+---------------------+------+---------------+---+------+--------------+
| Weight (kg)         | 75   | 78 (25)       |   | 72   | 81 (26)      |
+---------------------+------+---------------+---+------+--------------+
| Gender (% male)     | 75   | 52%           |   | 73   | 64%          |
+---------------------+------+---------------+---+------+--------------+

Continuous data presented as mean (stdev).

Table 3: Pre Enrollment Ventilator Settings

  --------------------- ------- --------------- -- ------- ---------------
                        \#      HFOV               \#      CMV

  PIP                   75      39 (7)             73      38 (8)

  PEEP                  75      13 (3)             73      14 (3)

  mPaw                  71      22 (5)             71      24 (7)

  TV/KG                 72      8.2 (3)            69      7.8 (3)

  FiO2                  75      .71 (.19)          73      .72 (.19)
  --------------------- ------- --------------- -- ------- ---------------

> Continuous data present as mean (stdev). PIP is peak inspiratory
> pressure, PEEP is positive end expiratory pressure, mPaw is mean
> airway pressure, all presented as centimeters of water. TV/KG is the
> tidal volume (milliliters) divided by the body weight in kilograms.

Table 4: Pre-Enrollment Clinical indicators

  -------------------------- ------- -------------- -- ------- --------------
                             \#      HFOV              \#      CMV

  PaO2                       75      76 (20)           73      73 (18)

  PaCO2                      75      44 (12)           73      45 (12)

  pH                         73      7.37 (.09)        73      7.34 (.11)

  PaO2/FiO2                  75      114 (37)          73      111 (42)

  Oxygenation Index          71      24 (15)           71      27 (19)

                                                               

  Mean Blood Pressure        65      80 (14)           61      76 (12)

  Cardiac Output             36      7 (2)             37      7 (3)

                                                               

  APACHE II                  68      22 (6)            65      22 (9)
  -------------------------- ------- -------------- -- ------- --------------

> Continuous data present as mean (stdev). PaO2 is the partial pressure
> of arterial oxygen, PaCO2 is the partial pressure of arterial carbon
> dioxide, both presented in millimeters of Hg. FiO2 is the fraction of
> inspired oxygen. Oxygenation Index is the mPaw x100/PaO2/FiO2. Mean
> blood pressure is presented in millimeters of Hg, and cardiac output
> in liters per minute. APACHE II is a disease severity score.

Table 5: Pre-Enrollment Diagnoses

  -------------------------- ------- -------------- -- ------- --------------
                             \#      HFOV              \#      CMV

  Primary ARDS Trigger:      75                        73      

  Sepsis Syndrome                    47%                       47%

  Pulmonary Infection                19%                       16%

  Trauma                             21%                       18%

  other                              13%                       19%

                                                               

  Confounding Dx                                               

  Air leak                   75      16%               73      19%

  Immune compromise          61      12%               62      14%

  \>4 days mech. vent        74      22%               73      36%
  -------------------------- ------- -------------- -- ------- --------------

> Incidences rounded to nearest percent

Table 6 below details the reasons for exit from the study. A chi-squared
test suggests the patterns of exit are different for the two ventilator
treatments, (p=0.015). The data suggests that HFOV patients were less
likely to exit as a result of death, more likely to exit after being
weaned from mechanical ventilation, and more likely to still be on
mechanical ventilation at 30 days. Exit data was available for all 148
patients enrolled in the study.

Details on the 56 patients who exited the study because of death can be
found beginning on page 170. Twenty patients exited the study
prematurely, either because of Withdrawal of Informed Consent, HFO
Treatment Failure or "Other". Details of these patients can be found on
page 344. The exit for 6 patients are identified as "Other", a category
not prospectively defined. One of these patients was exited in the first
day after a decision was made that bilateral infiltrates had not been
present on the radiograph, and thus the patient had not been eligible
for enrollment. Two exited because they were transferred to other
facilities while still on mechanical ventilation. The other 3 patients
were withdrawn by the attending physician so that therapy could be
modified. These last three identified as "Other", could also have been
treated as Withdrawal of Consent.

Table 6: Study Exit

+---------------------------------+-----------------+-----------------+
|                                 | HFOV            | CMV             |
+---------------------------------+-----------------+-----------------+
| number                          | 75              | 73              |
+---------------------------------+-----------------+-----------------+
| Withdrawal of consent           | 3 %             | 11 %            |
+---------------------------------+-----------------+-----------------+
| Weaned from mechanical          | 37 %            | 27 %            |
| ventilation                     |                 |                 |
+---------------------------------+-----------------+-----------------+
| 30 days from entry              | 21%             | 11 %            |
+---------------------------------+-----------------+-----------------+
| TX failure, stop HFO            | 5 %             | 0 %             |
+---------------------------------+-----------------+-----------------+
| Died                            | 31 %            | 45 %            |
+---------------------------------+-----------------+-----------------+
| Other                           | 3%              | 6 %             |
+---------------------------------+-----------------+-----------------+
| # p= 0.015                      |                 |                 |
+---------------------------------+-----------------+-----------------+

> Incidences rounded to nearest percent

The average mortality rate varied among centers. This was expected,
considering differences in patient populations (trauma vs. medical) and
referral basin. Overall, mortality was consistent with differences in
pre enrollment length of ventilation and APACHE II scores. Importantly,
only one center experienced a higher mortality in the HFOV patients.
Therefore as planned the data from all the sites were pooled.

######### 

######### PATIENT COMPLAINTS

No patient complaints were reported through the course of the study.
Considering the general health and other vital statistics attributed to
the patient population complaints were not anticipated nor were they
reported.

***PRIMARY OUTCOMES***

Table 7 below includes the results for the four primary safety and
effectiveness outcomes. This outcome data was available for all 148
patients enrolled in the study. The results are shown as percent
incidence with a corresponding 95% confidence limit of the difference in
the incidences (corrected for continuity). None of the differences
reached statistical significance.

Table 7: Primary Outcomes

+------------------------------+--------+--------+--------------------+
|                              | HFOV   | CMV    | 95% CL Difference  |
+------------------------------+--------+--------+--------------------+
| number                       | 75     | 73     |                    |
+------------------------------+--------+--------+--------------------+
| Status @ 30 days             |        |        |                    |
+------------------------------+--------+--------+--------------------+
| ## D                         | 79%    | 74%    | -10% to +20%       |
| eath or respiratory support  |        |        |                    |
+------------------------------+--------+--------+--------------------+
| Death                        | 37%    | 52%    | -32% to +3%        |
+------------------------------+--------+--------+--------------------+
| On Study                     |        |        |                    |
+------------------------------+--------+--------+--------------------+
| ## Intractable hypotension   | 0%     | 3%     | -8% to +2%         |
+------------------------------+--------+--------+--------------------+
| Develop new air leak         | 8%     | 8%     | -12% to +11%       |
+------------------------------+--------+--------+--------------------+

Incidences rounded to nearest percent

The primary effectiveness measure in this study was death or continuing
respiratory support at 30 days. Because the goal of this study was to
determine if HFOV treatment was at least comparable to CMV treatment,
the hypothesis was that HFOV was not more than 10% worse than CMV. As
can be seen, HFOV was approximately 5% worse (59/75 and 54/73), with a
95% confidence of being between 10% better and 20% worse. Interestingly,
a post-hoc analysis looking at death or continued mechanical ventilation
at 30 days (as compared to including supplement oxygen as "respiratory
support"), identified a 7% difference (47/75 & 51/73), with a 95%
confidence that HFOV is between 34% better and 9% worse.

***SECONDARY OUTCOMES***

The status of the patients at 1 month (30 days) and 6 months is shown in
Table 8. Data is available for all 148 patients. The status for patients
discharged without respiratory support is based on discharge status.
Follow up on all patients discharged or transferred while still on
respiratory support was completed. Chi-squared analysis of the status at
1 month (30 days) and 6 months suggests the HFOV assigned patients had
different outcomes than the CMV assigned patients. (p= 0.038 @ 1 month,
0.086 @ 6 months )

Table 8: Status at 1 month and 6 months

+------------------------------+--------+--------+---+--------+--------+
|                              | HFO    | HFO    |   | CMV    | CMV    |
+------------------------------+--------+--------+---+--------+--------+
| number                       | 75     | 75     |   | 73     | 73     |
+------------------------------+--------+--------+---+--------+--------+
| End Points                   | 1 M    | 6 M    |   | 1 M    | 6 M    |
+------------------------------+--------+--------+---+--------+--------+
| Died                         | 37 %   | 47 %   |   | 52 %   | 59 %   |
+------------------------------+--------+--------+---+--------+--------+
| Survived (resp. support)     | 41 %   | 0 %    |   | 21 %   | 3 %    |
+------------------------------+--------+--------+---+--------+--------+
| Survived                     | 21%    | 53 %   |   | 26 %   | 38 %   |
+------------------------------+--------+--------+---+--------+--------+
| ##  1 month p= 0.038         |        |        |   |        |        |
|                              |        |        |   |        |        |
| 6 months p=0.086             |        |        |   |        |        |
+------------------------------+--------+--------+---+--------+--------+

Incidences rounded to nearest percent

Table 9 below describes the incidence of four prospectively defined
secondary outcome parameters. Data for these parameters was available
for all of the patients for these variables.

Table 9: Secondary Treatment Failures

  ------------------------------------ ------- ------- ------------------
                                       HFO     CMV     95% CL Diff

  number                               75      73      

  Oxygenation                          5%      8%      -12% to +7%

  Respiratory Acidosis                 5%      8%      -12% to +7%

  Develop new or worsening ALS         9%      12%     -14% to +8%

  Mucous Plugged ET Tube               3%      1%      -5% to +7%
  ------------------------------------ ------- ------- ------------------

Incidences rounded to nearest percent. ALS is air leak syndrome.

***ADVERSE EFFECTS***

As anticipated in this treatment population, and reflected in Table 6,
death was a common reason for exit from the study. Table 10 below
summaries the causes of death for the 56 patients who died on study,
tabulated with regard to whether life support was withdrawn. Details of
each case are listed on page 172. Note the causes of death were often
multifactoral.

Reported unanticipated adverse effects were infrequent. The most common
event was a mucous plug of the ET Tube that required suctioning, which
was reported twice for each ventilator group. All the reported Adverse
Effects, protocol violations and investigational device failures are
listed on page 159. Four HFOV failures were reported. There were no
reports of complaints from patients or their families.

No new Precautions or Warnings were identified, other than those
included in the Operating Instructions, in the Appendix pages 497
through 502.

Table 10: On Study Deaths

+----------------------------------+-----------------+-----------------+
| Cause of Deaths when Study Exit  | Support         | ### **Not**     |
|                                  | withdrawn       |                 |
|                                  |                 | withdrawn       |
+----------------------------------+-----------------+-----------------+
|                                  | HFO/CMV         | HFO/CMV         |
+----------------------------------+-----------------+-----------------+
| Total number                     | 16 / 22         | 9 / 14          |
+----------------------------------+-----------------+-----------------+
| Cardiac Arrhythmia               | 2 / 0           | 2 / 6           |
+----------------------------------+-----------------+-----------------+
| Multiple Organ Failure           | 10 / 14         | 4 / 4           |
+----------------------------------+-----------------+-----------------+
| Sepsis                           | 6 / 6           | 4 / 5           |
+----------------------------------+-----------------+-----------------+
| ## Profound Hypoxemia            | 2 / 2           | 2 / 6           |
+----------------------------------+-----------------+-----------------+
| other                            | 2 / 2           | 2 / 2           |
+----------------------------------+-----------------+-----------------+

***TREATMENT COURSE***

The length of mechanical ventilation in the two treatment groups was
quite similar. In the CMV control group the average was 20 days (stdev
31) for all patients and 33 days (stdev 45) for survivors. The HFOV
treatment strategy included transition to conventional ventilation
during recovery and then weaning from conventional ventilation. The
average total length of mechanical ventilation for the HFOV patients was
22 days (stdev 21), 6 of these were on HFOV (stdev 5). The average
length of mechanical ventilation for HFOV survivors was 29 days (stdev
25).

Multivariate repeated measures analysis of variance was used to identify
differences in the course of clinical indicators during the first 3 days
of treatment course of the two ventilator groups. Data was collected at
initiation of the treatment and then every 8 hours. In addition to
ventilator, the model included outcome and time trend. The clinical
indicators evaluated were: mean airway pressure, PaO2, PaCO2, pH,
Oxygenation Index, PaO2/FiO2, mean arterial blood pressure, pulmonary
capillary wedge pressure and cardiac output. Because of the likelihood
of a type 1 error with so many comparisons, differences were only
considered significant if they reached a p\< 0.01.

As anticipated as a result of the treatment strategy, the mean airway
pressure was significantly higher in the HFOV treated patients (average
28.9 vs. 22.7, p \< 0.0001). It was further expected that this higher
airway pressure would result in improved lung recruitment, which was in
fact reflected in an improved and significantly higher PaO2/FiO2 status
for the HFOV patients during this period. (average 167 vs. 147, p
\<0.001). The pulmonary capillary wedge pressure was also found to be
slightly higher in the HFOV patients (average 19.5 vs. 18.5, p\< 0.01).
The PaCO2 in the HFOV patients was also slightly higher (average 48 vs.
43, p\< 0.01). There were no ventilator-outcome interactions or
ventilator-time interactions that were identified that were
statistically significant. There was a significant association of higher
Oxygenation Index with poor outcome (p \<0.001), but this effect was
independent of ventilator group.

This study design did not include crossover. However, patients in the
investigational arm (HFOV) were permitted to be exited and treated with
conventional ventilation if the patient met specific treatment failure
criteria and the attending physician felt conventional ventilation might
be advantageous for the patient. This situation occurred 4 times. Two of
these four patients died. While not the intent of the study design, nine
patients assigned to CMV, were treated with HFOV at the direction of the
attending physician. Only two of these nine patients survived.

***LIMITS OF EFFECTIVENESS***

The therapeutic role of mechanical ventilation is to provide adequate
oxygenation and ventilation while minimizing trauma from ventilator
airway pressures. Excessive pressure usually manifests acutely as
pulmonary air leaks or compromise of the cardiovascular system
(hypotension). The study was designed with prospective criteria for
oxygenation, ventilation (respiratory acidosis) and hypotensive failures
as well as development of pulmonary air leaks. As can be seen in Table
11 these failures were infrequent in both treatment groups and do not
appear to be more frequent in the HFOV treated patients. No limits of
effectiveness were identified in this study.

Table 11: Limit of Effectiveness Treatment Failures

+-----------------------------------+-------+-------+------------------+
|                                   | HFO   | CMV   | 95% CL Diff      |
+-----------------------------------+-------+-------+------------------+
| Oxygenation                       | 5%    | 8%    | -12% to +7%      |
+-----------------------------------+-------+-------+------------------+
| Respiratory Acidosis              | 5%    | 8%    | -12% to +7%      |
+-----------------------------------+-------+-------+------------------+
| Develop new Air leak              | 8%    | 8%    | -12% to +11%     |
+-----------------------------------+-------+-------+------------------+
| ## Intractable hypotension        | 0%    | 3%    | -8% to +2%       |
+-----------------------------------+-------+-------+------------------+

######### DEVICE FAILURE AND REPLACEMENTS

The majority of the device failures were routine in nature. In each
case, the study device was able to be repaired back to original factory
specifications. The following list indicates the particular failures
that were reported during the study.

# Summary of 3100B Service History

# 

# 

# S/N 31B004

Date: 18 May 1999

C/D #: 40035

Problem: Torn driver diaphragms

Solution: Sent replacement driver diaphragms; Krytox lubricant useage

Date: 9 July 1999

C/D #: 44500

Problem: Machine not working right

Solution: Unknown ("resolved by Terry Blansfield")

# S/N 31B011

Date: 2 July 1999

C/D #: 43953

Problem: Not stated

Solution: "Steve on site, problem take care of."

# S/N 31B014

Date: 7 May 1998

C/D #: 5361

Problem: Source Gas Low LED on

Solution: Replaced leaking pressure switch

Date: 8 May 2000

C/D #: 75488

Problem: Torn diaphragm

Solution: Send new 3-ohm driver

Date: 31 Oct 2000

C/D #: 96911

Problem: MAP fluctuating by 10 cm on patient

Solution: Replaced Alarm board

# S/N 31B019

Date: 7 July 2000

C/D #: 82852

Problem: Driver over-heated after a few hours on patient

Solution: Installed 3-ohm driver and Auto-Limit pnuematics

# S/N 31B020

Date: 27 Nov 2000

C/D #: 100065/100078

Problem: Burning smell

Solution: Replaced alarm board (burnt capacitor C30).

# S/N 31B023

Date: 20 Nov 2000

C/D #: 99276

Problem: Power ON/OFF switch (circuit breaker) intermittently trips

Solution: Installed new circuit breaker

# S/N 31B024

Date: 4 Dec 1998

C/D #: 26030

Problem: Low MAP during Performance checks

Solution: Adjusted pneumatics

Date: 6 May 1999

C/D #: 38992

Problem: Low Delta-P during performance checks

> Solution: Replaced PR8 with new style, adjusted pneumatic functions
> and driver
>
> control.
>
> Date: 4 June 1999
>
> C/D #: 40899
>
> Problem: Pressure bad
>
> Solution: Replaced driver and driver power module.
>
> Date: 5 July 2000
>
> C/D #: 82745
>
> Problem: Driver began to "miss a beat"
>
> Solution: Installed 3-ohm driver, Auto-Limit pneumatics and Driver
> Power
>
> Module.
>
> Date: 30 Oct 2000
>
> C/D #: 96748
>
> Problem: Delta-P low during Performance checks
>
> Solution: Replaced Alarm board, calibrated all electrical/pneumatic
> functions

# S/N 31B025

Date: 13 Sep 2000

C/D #: 90810

Problem: Leaking/hissing pressure switch in pneumatics

Solution: Replaced pressure switch

# S/N 31B030

Date: 14 Jan 2000

C/D #: 62632

Problem: Would not pass Patient Circuit Calibration

Solution: Repaired possibly bad electrical connection at dump valve
solenoid,

replace regulator PR3, and replaced dump valve solenoid.

# S/N 31B032

Date: 20 June 2000

C/D #: 80702

Problem: Driver diaphragm ruptured

Solution: Replaced driver

Date: 30 Nov 2000

C/D #: 100360

Problem: Torn driver diaphragm

Solution: Replaced driver

# S/N 31B033

Date: 12 Sep 2000

C/D #: 90725

Problem: Torn driver diaphragm (after 362 hours useage)

Solution: Replaced driver

# S/N 31B036

Date: 16 Dec 1998

C/D #: 27070

Problem: Low MAP

Solution: Adjusted pneumatic functions

# S/N TMA03488

Date: 26 May 2000

C/D #: 81090

Problem: Torn driver diaphragm

Solution: Replaced driver with 3-ohm one; upgrade with Auto Limit

# 

***CONTRAINDICATIONS AND PRECAUTIONS***

The 3100B Oscillatory Ventilator has no specific contraindications.

# b3vi. Conclusions drawn from the study  {#b3vi.-conclusions-drawn-from-the-study .TOC}

MOAT2 was a prospective randomized multicenter comparison of the
SensorMedics 3100B HFOV and conventional mechanical ventilation for the
treatment of ARDS. Both ventilators used a strategy aimed at
normalization of lung volumes and minimization of peak ventilatory
pressures. Patients were exited from the study at 30 days, death or upon
successful weaning from mechanical ventilation. The primary endpoint was
status at 30 days, however secondary endpoints included status at 6
months and the incidence of specific adverse events while on study.

To explore the potential benefit of HFOV the data from the HFOV treated
patients must be considered both in comparison with the control patients
as well as compared with other published ventilator trials in similar
patient populations. Specific characteristics associated with higher
risk of mortality include patient age^1,3,10^ , specific ARDS triggering
etiologies^3,8-11^, severity of hypoxemia ^3,10-13^, existing air
leaks^14^, immune compromised^4^, and ventilator strategies that use
high volumes and pressures^5,6^. To evaluate any benefit from the use of
HFOV, adverse effects that might pose excessive risk to the patient with
its use must also be taken into consideration.

The two populations for the treatment and control arms in this study
were very well balanced and contained no statistically significant
differences in any of the identified characteristics of increased
mortality. At 30 days of study entry, the mortality in the
conventionally ventilated patients was 52 percent while in the HFOV
group the mortality was 37 percent, a 29 percent lower mortality. While
there were more patients on some form of respiratory support in the HFOV
group at 30 days, fewer of them required mechanical ventilation versus
supplemental oxygen than in the control group (61% vs. 73%). At six
months, although the mortality differences narrowed, there was still a
20 percent mortality benefit for patients in the HFOV group. There was
no residual need for respiratory support in the HFOV treated patients at
six months.

The identified risks associated with HFOV are similar to the risks
associated with conventional ventilation. These include developing or
worsening of air leaks, mucous plugging of the endotracheal tube or
airways, and hypotension. In this study, incidences of these events, as
well as unanticipated adverse events, were low in both arms and there
were no statistical differences in these occurrences. This suggests that
HFOV is at least as safe as conventional ventilation and poses no
significant additional risk.

The only large multicenter prospective randomized ventilator trial in
ARDS that has demonstrated a statistically significant benefit with use
of a specific management approach has been the NIH lower tidal volume as
compared with higher tidal volume study.^5^ This study compared patients
managed with 6 ml/kg tidal volume as compared with patients managed with
12 ml/kg. They reported a lower mortality of 31 percent in the patients
treated with 6 ml/kg tidal volume as compared with the 39.8 percent
mortality in the control group (reduction of 22%). A comparison of the
patients in the MOAT2 study with the NIH patients may be important when
considering the effectiveness of HFOV.

The NIH trial enrolled patients with less severe respiratory failure, as
the entrance criteria included patients who had acute lung injury as
define by a PaO2/FiO2 (P/F) ratio \<300 torr.^5^ There was also no
minimum level of end expiratory pressure (PEEP) required for entry.
Entrance in the MOAT2 trial required a P/F \<200 on a minimum PEEP of 10
cmH2O. As a result, the severity of the patients in the MOAT2 trial was
very different than in the NIH trial. The average P/F in the NIH trial
was 136 and in the MOAT2 trial it was 112. The MOAT2 patients had
significantly worse oxygenation with PEEP levels approximately 50%
higher. A prior publication evaluating the influence of a P/F \<150 with
a PEEP of 5 cmH2O on mortality reported that if the P/F was \>150, the
mortality was 23%.^3^ However, if the P/F on 5 cmH2O was \<150, the
mortality rose to 68%. Similar increases in mortality have been reported
with P/F's less than 100.^7^

Sepsis syndrome was the triggering mechanism for ARDS in 47% of both
groups in the MOAT2 trial, while it accounted for only 27% of the NIH
patients. Analysis of prior HFOV data and consistent with other
conventional ventilation data, the presence of sepsis has a negative
impact on survival and/or morbidity.^4,8-11^ This alone could account
for the outcome differences seen between these trials.

When the MOAT2 trial was designed, there was no evidence that low tidal
volumes during mechanical ventilation would be beneficial. The MOAT2
strategy for conventional ventilation was not a high stretch as was used
in the control arm of the NIH trial. The targeted tidal volume was at
6-10 ml/kg of actual body weight. However, as a result of the NIH
report, a post-hoc analysis of the mortality in the control arm was
performed with recalculation of actual tidal volume per kilogram of
ideal body weight. The mortality in the conventionally ventilated
patients in MOAT2, stratified by ideal body weight follows in table 1.

  -------------- -------------- -------------- -------------- --------------
  TV/kg (IBW)    Mortality      N              Average VT     Std Dev

  \< 8 ml/kg     0.67           6              7.13           0.62

  8 to 10 ml/kg  0.44           25             9.15           0.58

  \> 10 ml/kg    0.46           28             11.54          0.66
  -------------- -------------- -------------- -------------- --------------

Table 1. Mortality by ideal body weight (IBW)

The analysis demonstrated that while the mortality in the MOAT2 patients
treated with conventional ventilation was higher than the patients from
the NIH trial, actual tidal volume appeared to have no impact on
outcome. It is evident that there may be other differences in the
patient population that resulted in the difference in outcome (e.g.
sepsis syndrome, derangement of oxygenation, etc.).

While the large differences in mortality at 30 days (29%) did not reach
statistical significance, the status (died or alive requiring
respiratory support or alive requiring no respiratory support) does
reflect a statistically significantly difference (p\<0.05) at 30 days.
Additionally, considering the persistence of a trend toward reduced
mortality at 6 months, the 30 day status can be interpreted as
supporting HFOV effectiveness.

We conclude that use of the 3100B HFOV for treating patients with acute
respiratory failure is at least as effective as conventional ventilation
and that there are no increased risks that outweigh any potential
benefit.

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