SUMMARY OF SAFETY AND EFFECTIVENESS DATA

I.  **General Information**

# Device Generic Name: High-Frequency Ventilator

# Device Trade Name: SensorMedics Model 3100B High-Frequency Oscillatory Ventilator

# Sponsor Name and Address: SensorMedics Corporation

## 22705 Savi Ranch Parkway

## Yorba Linda, CA 92887-4645

# PMA Number: P890057/S14

# Date of Panel Recommendation: July 16, 2001

# Date of Notice of Approval: September 24, 2001 

II. **Indications for Use**

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

III. **Contraindications**

# 

# This Model 3100B has no specific contraindications.

IV. **Device Description**

# 

# The Model 3100B consists of six subsystems, and is used with an external air/oxygen blender and an external humidifier. The six subsystems are: (1) pneumatic logic and control; (2) patient circuit; (3) oscillator subsystem; (4) airway pressure monitor; (5) electronic control and alarm subsystem; and (6) electrical power supply. During use with a patient in acute respiratory failure, the Model 3100B maintains a positive mean airway pressure, upon which pressure oscillations are superimposed at a rate between approximately 3 and 15 per second. The pressure oscillations achieve ventilation of the patient.

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height="4.727777777777778in"}

> *Pneumatic Logic and Control*
>
> The pneumatic logic and control subsystem receives pressurized,
> blended gas from the external air/oxygen blender. The subsystem
> includes three controls:

1.  A bias flow control sets the continuous rate at which the blended
    gas flows from the external blender, through the bias flow tube and
    the patient circuit, and past the tracheal tube connection port. The
    bias flow can be set as high as 60 L/min.

2.  A mean pressure adjust control opens and closes a
    variable-restriction control valve to set the mean pressure on which
    the oscillatory waveform is superimposed.

3.  A patient circuit calibration set screw is used to calibrate the
    pressure limit valve control when the patient circuit is replaced or
    when the control valve diaphragm of the patient circuit is replaced.

> *Patient Circuit*
>
> The patient circuit provides the gas flow required for ventilation of
> the patient. In conjunction with the oscillator subsystem and the
> airway pressure monitor (described below), the patient circuit
> provides: (1) means to convey bias flow from the humidifier, and to
> maintain a positive mean airway pressure; (2) means to convey pressure
> oscillations from the oscillator subsystem; (3) a pressure sensing
> port; and (4) pressure limiting valves.

1.  During normal operation, blended, humidified gas flows from the
    external humidifer, through the bias flow tube and into a continuous
    flow line on the inspiratory limb of the patient circuit. The bias
    flow passes through a wye ("Y") connector including a tracheal tube
    connector, and into the expiratory limb of the patient circuit.
    Carbon dioxide is removed from the tracheal tube by the gas mixing
    that occurs at the "Y" connector. The expiratory limb includes two
    flow paths. At the end of one path is the control valve which is
    used to set the mean airway pressure. The other path terminates in a
    fixed orifice which provides an additional exit for gas regardless
    of the setting of the control valve.

2.  The inspiratory limb of the patient circuit conveys the oscillatory
    pressure from the diaphragm of the oscillator subsystem to the
    patient through the "Y" connector and the tracheal tube.

3.  An airway pressure sensing port is provided in the "Y" connector.

4.  The patient circuit includes two valves which limit the mean airway
    pressure:

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a.  The first valve is a limit valve controlled by the pressure limit
    control described below. If the mean airway pressure exceeds the set
    pressure limit, the limit valve opens to release the excess
    pressure. When the mean airway pressure falls to approximately 80%
    of the set pressure limit, the limit valve closes again.

b.  The second valve is an electrically-controlled dump valve, which
    opens if the mean airway is greater than 60 cm H~2~O or less than
    5 cm H~2~O. When the dump valve opens, it remains open until the
    over-pressure or under-pressure condition is resolved and the
    ventilator is reset.

> *Oscillator Subsystem*
>
> The oscillator subsystem comprises an air-cooled linear motor driven
> by an electronic square-wave driver. If the coil temperature reaches
> 150°C, a panel "caution" is illuminated. If the coil temperature
> reaches 175°C, the oscillator shuts down and an audible alarm sounds.
> The coil drives a diaphragm to produce pressure oscillations which are
> conveyed to the patient through the patient circuit. The electronic
> square-wave driver is controlled by the electronic control and alarms
> subsystem: the oscillatory frequency can be set between 3 and 15 Hz;
> and the inspiratory time can be set between 30 and 50%. Two mechanical
> stops limit the displacement of the diaphragm in the "full
> inspiration" and "full expiration" directions. The entire stroke
> volume from "full expiration" to "full inspiration" is approximately
> 365 mL.
>
> *Airway Pressure Monitor*
>
> The airway pressure monitor senses the pressure within the patient
> circuit through a tube that runs from the Y connector of the patient
> circuit. A dry gas flow of 500 mL/min flows through the sensing tube
> to keep it free of water vapor. The mean airway pressure is obtained
> by low-pass filtering of the instantaneous pressure signal. The
> pressure oscillation amplitude (∆P) is computed by subtracting the
> oscillatory trough pressure from the oscillatory peak pressure.
>
> *Electronic Control and Alarm Subsystem*
>
> The electronic control and alarm subsystem includes: (1) oscillator
> subsystem controls and indicators; and (2) alarm indicators and
> controls.

1.  The oscillator subsystem controls provide input to the electronic
    square-wave driver which drives the diaphragm in the oscillator
    subsystem to produce pressure oscillations in the patient circuit.

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a.  A start/stop control enables and disables the oscillator subsystem.

b.  A power control sets the pressure oscillation amplitude, ∆P, which
    is displayed on a digital indicator.

c.  A frequency control sets the frequency of the oscillations produced
    by the oscillator subsystem between 3 and 15 per second. The set
    frequency is displayed on a digital indicator.

d.  An inspiratory time control sets the percent inspiratory time
    between 30 and 50%. The percent inspiratory time is displayed on a
    digital indicator. At high oscillator frequencies, a decrease in the
    percent inspiratory time can decrease the pressure oscillation
    amplitude because the shorter inspiratory times may not give the
    diaphragm sufficient time to reach its final inspiratory position.

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2.  The ventilator is provided with the following alarms, some of which
    have adjustable levels:

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a.  The maximum mean airway pressure can be set between 0 and 59 cm
    H~2~O. If the mean airway pressure is greater than the set level,
    audible and visible alarms are annunciated and the limit valve opens
    to release the excess pressure. When the mean airway pressure falls
    to approximately 80% of the set level, the audible alarm resets and
    the limit valve closes again. The visible alarm remains annunciated
    until the alarm reset is activated.

b.  The minimum mean airway pressure can be set between 0 and 59 cm
    H~2~O. If the mean airway pressure is less than the set level,
    audible and visible alarms are annunciated. When the alarm condition
    is corrected, the audible and visible alarms automatically reset.

c.  If the mean airway pressure exceeds 60 cm H~2~O for more than 1.5
    seconds, audible and visible safety alarms are annunciated; the dump
    valve opens; and the oscillator subsystem automatically shuts down.
    The dump valve remains open and the pressure in the patient circuit
    approaches the ambient pressure. The bias flow tube continues to
    provide fresh gas to the patient through the patient circuit. The
    dump valve remains open, and the alarms continue to annunciate until
    the alarm reset is activated.

d.  If the mean airway pressure is less than 5 cm H~2~O, audible and
    visible safety alarms are annunciated; the dump valve opens; and the
    oscillator subsystem automatically shuts down. The dump valve
    remains open and the pressure in the patient circuit approaches the
    ambient pressure. The bias flow tube continues to provide fresh gas
    to the patient through the patient circuit. When the alarm condition
    is corrected, the audible alarm resets. The dump valve remains open
    and the visible alarm continues to annunciate until the alarm reset
    is activated.

e.  If the oscillator is enabled and the magnitude of pressure
    oscillations is less than approximately 7 cm H~2~O, audible and
    visible "oscillator stopped" alarms annunciate. When the alarm
    condition is corrected, the alarms reset.

f.  If the temperature of the oscillator coil reaches 150°C, a visible
    caution annunciates to indicate that the coil is overheating, but
    the device continues to operate. When the caution condition is
    corrected, the caution resets. If the temperature of the coil
    reaches 175°C, the oscillator shuts down, and the oscillator stopped
    alarm (described in item e, above) annunciates.

g.  If the electrical power to the device is lost, audible and visible
    power failure alarms annunciate. The alarms continue to annunciate
    until the alarm reset is activated.

h.  If the voltage on the battery that supplies the power failure alarms
    is low, a visible caution annunciates to indicate that the battery
    should be changed as soon as possible to ensure continued operation
    of the power failure alarm. When the caution condition is corrected,
    the caution resets.

i.  If the gas pressure at the "inlet from blender" connection or the
    "air cooling" connection is less than 30 psig, a visible caution is
    annunciated. When the caution condition is corrected, the caution
    resets.

j.  An alarm silence button can be used to silence audible alarms for a
    period of 45 seconds. During this time, a visible caution is
    annunciated, but no audible alarms will sound.

k.  An alarm reset button resets the safety alarms and the power failure
    alarm when pressed. To begin operation of the device after a safety
    alarm, the alarm condition must be corrected, the oscillator must be
    enabled and the alarm reset button must be pressed until the dump
    valve in the patient circuit closes and the mean airway pressure is
    greater than 5 cm H~2~O.

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V.  **Warnings and Precautions**

> Please refer to the device labeling.

VI. **Alternative Practices and Procedures**

> Conventional mechanical ventilation is an alternative treatment for
> acute respiratory failure.

VII. **Adverse Effects on Health**

####### *Observed Adverse Events*

> A prospective clinical study of the Model 3100B in patients with acute
> respiratory distress syndrome (ARDS) was conducted at ten sites. The
> 148 patients enrolled in the study were randomly assigned to one of
> two groups: a treatment (i.e., "high-frequency") group, in which
> patients were treated with the Model 3100B; or a control (i.e.,
> "conventional") group, in which patients were treated with a
> conventional ventilator. Treatment outcomes and adverse events were
> determined at one and six months. Table 1 summarizes the adverse
> events observed during the study.

######## Table 1: Observed adverse events

  ------------------------------------ ----------------------------------
  Adverse event                        \# (%) of patient who had this
                                       event in the treatment group, N=75

  Mucus-plugged ET tube                2 (3%)

  Inadequate Oxygenation               4 (5%)

  Respiratory acidosis                 4 (5%)

  New or worsening air leak syndrome   7 (9%)

  Intractable hypotension              0 (0%)
  ------------------------------------ ----------------------------------

*Potential adverse events*

> The adverse events associated with the use of high-frequency
> ventilation include: atelectasis, inadequate oxygenation, intractable
> hypotension, mucus-plugging of the tracheal tube, necrotizing
> tracheobronchitis, new or worsening air leak syndrome,
> over-humidification, under-humidification, over-ventilation,
> under-ventilation, pneumothorax, pneumopericardium, pneumomediastinum,
> pneumoperitoneum, pulmonary interstitial emphysema and respiratory
> acidosis.

VIII. **Marketing History**

> On March 29, 1991, a PMA application was approved for use of the
> SensorMedics Model 3100 High-Frequency Oscillatory Ventilator in
> treatment of neonates with respiratory failure and barotrauma. On
> September 15, 1995, a PMA supplement was approved expanding the
> indications for use of the Model 3100A to include selected pediatric
> patients who are failing conventional ventilation. The Model 3100A has
> been in international commercial distribution since 1991.

The Model 3100B High-Frequency Oscillatory Ventilator is a modification
of the approved high-frequency ventilator, the Model 3100A---which is,
in turn, a modification of the Model 3100. The Model 3100B has been
shipped to countries outside of the United States since 1993.
Approximately 100 units have been shipped internationally. Model 3100B
units have been marketed in: Austria, Belgium, France, Germany, Italy,
the Netherlands, Norway, Qatar, Saudi Arabia, South Africa, Spain,
Sweden, Switzerland and the United Kingdom.

The Model 3100, Model 3100A and Model 3100B have not been withdrawn from
the market in any country for any reason related to the safety and
effectiveness.

IX. **Summary of Studies**

> *Non-Clinical Testing*

#### Performance testing

> Proper operation of the Model 3100B was verified through non-clinical
> performance testing. The non-clinical performance tests, the
> acceptance criteria, and the results of the testing are summarized in
> Table 2, below.
>
> ![](media/image2.wmf){width="4.951388888888889in"
> height="5.120138888888889in"}

Table 2: Performance testing performed for two Model 3100B units.

> The performance testing included measurement of tidal volumes attained
> with tracheal tubes of various diameters (5, 7, and 9 mm) and various
> oscillator frequencies (3 and 15 Hz), I:E ratios and amplitudes. The
> greatest tidal volume, obtained with a 9 mm endotracheal tube, an
> oscillator frequency of 3 Hz and amplitude of 10 (uncalibrated) was
> 260 mL. The results of this testing are more completely summarized by
> the detailed graphs provided on pages 20-24 of the operator's manual.

####  Finally, the performance testing included estimation of the mean time between failure of the driver diaphragm in the oscillator subsystem. Four units were allowed to run continuously at an oscillatory frequency of 3 Hz, and at 50% power. The mean time between failure of the diaphragm was 2680 hours for this test. During the clinical study, the mean time between failure was 1828 hours. Therefore, the sponsor revised the maintenance schedule to recommend replacement of the diaphragm as necessary, but at least once every 1500 hours.

#### 

#### Electrical safety and electromagnetic compatibility

> The electrical safety of the Model 3100B was demonstrated by its
> conformance to *IEC 60601-1: Medical electrical equipment, Part 1:
> General requirements for safety* and *IEC 60601-2-12: Medical
> electrical equipment, Part 2: Particular requirements for the safety
> of lung ventilators for medical use*.
>
> The electromagnetic compatibility of the Model 3100B was demonstrated
> by its conformance to *EN 60601-1-2: Medical electrical equipment,
> Part 1: General requirements for safety; 2. Collateral standard:
> Electromagnetic compatibility---Requirements and tests*. In addition,
> Model 3100B was subjected to the recommended tests outlined in the
> Reviewer Guidance for Premarket Notification Submission. The results
> demonstrated that the device met all acceptance criteria.

#### Biocompatability 

> The parts of this device which contact the patient directly or
> indirectly are made of the identical materials used in the Model
> 3100A.
>
> *Clinical Study*
>
> A prospective clinical study of the Model 3100B in patients with acute
> respiratory distress syndrome (ARDS) was conducted at ten sites. The
> 148 patients enrolled in the study were randomly assigned to one of
> two groups: a treatment (i.e., "high-frequency") group, in which
> patients were treated with the Model 3100B; or a control (i.e.,
> "conventional") group, in which patients were treated with a
> conventional ventilator.

#### Inclusion and Exclusion Criteria

> Patients were eligible for inclusion in the study if they met the
> following criteria:

-   at least 16 years of age;

-   at least 35 kilograms;

-   PaO~2~/FiO~2~ \< 200;

-   bilateral pulmonary infiltrates not resulting from left atrial
    hypertension; and

-   positive end-expiratory pressure (PEEP) of at least 10 cm H~2~O.

Patients were excluded if any of the following were true:

-   informed consent could not be obtained;

-   patient had been treated with FiO~2~ greater than 80% for at least
    48 hours;

-   patient had severe persistent air leak;

-   patient had non-pulmonary terminal prognosis;

-   patient had severe chronic obstructive pulmonary disease

-   patient had asthma; or

-   patient had been recently enrolled in another ARDS or septic shock
    investigation.

#### Methods

> The general treatment goal for the high-frequency group and the
> conventional group was the same: to maintain an O~2~ saturation of at
> least 88%; and to maintain a pH of greater than 7.15, while minimizing
> peak pressures and treating metabolic acidosis. The mean airway
> pressure was maintained until FiO~2~ had been reduced to less than
> 60%, after which mean airway pressure and FiO~2~ were given equal
> priority for reduction.
>
> In the high-frequency group, the Model 3100B was initially set to
> provide pressure oscillations at a frequency of 5 Hz, with the mean
> airway pressure set 5 cm H~2~O higher than the ventilator setting used
> before the patient was enrolled in the study, and with the oscillation
> amplitude (∆P) set for adequate chest wall vibration. If ventilation
> was inadequate, ∆P was increased. If ventilation was still inadequate
> with maximum ∆P, the frequency of pressure oscillations was reduced in
> 1 Hz steps. When mean airway pressure had been decreased to less than
> 30 cm H~2~O, or when there was no progress in weaning with the Model
> 3100B, ventilator weaning continued using a conventional ventilator. A
> patient assigned to the high-frequency group was treated with the
> Model 3100B protocol until: consent was withdrawn; the patient had
> died or been weaned from mechanical ventilation; the patient had been
> ventilated for 30 days; or the patient met defined treatment failure
> criteria and would, in the opinion of their physician, benefit from
> conventional ventilation.
>
> In the conventional group, patients were treated with conventional
> pressure-controlled, volume-limited ventilation with an inspiratory to
> expiratory (I:E) ratio of approximately 1:2. Tidal volumes nominally
> between 6 and 10 mL/kg were used. (The average tidal volume delivered
> was 10.2 mL/kg of ideal body weight.) If oxygenation was inadequate,
> PEEP was increased in increments of up to 5 cm H~2~O to improve
> oxygenation. If oxygenation was still inadequate with PEEP greater
> than or equal to 18 cm H~2~O, the I:E ratio was increased
> incrementally. A patient assigned to the conventional ventilation was
> treated in the study with the conventional ventilator until: consent
> was withdrawn; the patient had died or been weaned from mechanical
> ventilation; or the patient had been ventilated for 30 days.
>
> Patient outcomes were determined after one month and six months. The
> possible outcomes were:

-   death;

-   survival with respiratory support; or

-   survival without respiratory support.

> In this trial, "respiratory support" was defined to include mechanical
> ventilation, CPAP or supplemental oxygen. Only survival without
> respiratory support was considered a successful outcome. Outcome data
> were analyzed using an "intention to treat" analysis.

#### Hypothesis 

> The primary hypothesis was that the proportions of patients in the
> high-frequency and conventional groups with unsuccessful one-month
> outcomes would be equivalent.
>
> Statistically stated, the hypothesis was that the proportion of
> patients with an unsuccessful one-month outcome---i.e., the proportion
> of patients who died or were still receiving respiratory support after
> one month---would be no more than 10% greater in the high-frequency
> group than in the conventional group, with 95% confidence.

#### Study Population

> In this trial, 75 patients were assigned to the high-frequency group,
> and 73 patients were assigned to the conventional group. The patient
> demographics, the pre-enrollment diagnoses, the pre-enrollment
> ventilator settings and the pre-enrollment clinical indicators were
> similar for the two groups (Table 3).

![](media/image3.wmf){width="4.777083333333334in"
height="4.433333333333334in"}Table 3: Patient demographics,
pre-enrollment ventilator settings and pre-enrollment clinical
indicators.

> \* Denotes that values for this parameter were not available for all
> patients.

1.  Oxygenation index = 100 × mean airway pressure / (PaO~2~/FiO~2~)

2.  APACHE II is a disease severity score.

#### Results

> The one-month outcomes in this trial are summarized in Table 4, below.
> The patients in the high-frequency group had unsuccessful one-month
> outcomes with greater frequency than did the patients in the
> conventional group. Based on the 95% confidence interval computed from
> the one-month outcomes, the treatment in the high-frequency group
> could fail as much as 20% more often. Therefore, the prospectively
> defined hypothesis was not met. However, the mortality rate in the
> high-frequency group was lower than the mortality rate in the
> conventional group. The observed six-month outcomes are summarized in
> Table 5. Both the unsuccessful treatment rate and the mortality rate
> were lower in the high-frequency group than in the conventional group.
> The lower one-month and six-month mortality rates, and the lower
> six-month unsuccessful treatment rate, in the high-frequency group
> provide reasonable assurance that the Model 3100B is safe and
> effective.
>
> Table 4: One-month outcomes
>
> ![](media/image4.wmf){width="4.5152777777777775in"
> height="0.9618055555555556in"}
>
> ![](media/image5.wmf)Table 5: Six-month outcomes

#### Observed Treatment Failures

> Likely types of treatment failure were prospectively identified. The
> frequency with which each type of failure occurred was similar for the
> two groups, as shown in Table 6, below.
>
> ![](media/image6.wmf){width="2.9930555555555554in"
> height="2.203472222222222in"}Table 6: Observed treatment failures

#### 

#### Causes of Death

> The causes of death were identified for those patients who died while
> being treated with a ventilator. Deaths due to withdrawal of
> mechanical ventilation were also identified. For many patients, more
> than one cause of death was identified. The causes of death included
> cardiac arrhythmia, multiple organ failure, sepsis and profound
> hypoxemia. The causes of death in each group occurred with similar
> frequency (Table 7).

![](media/image7.wmf){width="3.375in"
height="2.2631944444444443in"}Table 7: Causes of death observed for
patients who died while being treated with a ventilator

X.  **Conclusions Drawn from the Study**

> Patients in the two groups were similar at study entry and analysis of
> outcomes was by intention to treat . For the primary outcome variable
> (death, mechanical ventilation, CPAP, or O2 or at 30 days) HFOV is
> worse (79%) vs Conventional (74%). However, death was less frequent in
> the HFOV group. The failure, relative to the prospective hypothesis,
> does not preclude HFOV as reasonably safe and effective in adults.
>
> The death rate for patients in the HFOV group at 30 days was 37% as
> compared to 52% in the conventional ventilation group. Observed
> mortality at 6 months was also better, 47% HFOV vs 59% conventional.
> However, the observed mortality difference was not statistically
> significant. A post-hoc combined variable was constructed (death or
> mechanical ventilation at 30 days) which would have been statistically
> significant if it were a prospective hypothesis.
>
> The FDA concluded that the data provides reasonable assurance of the
> safety and effectiveness of this device when used as indicated.

XI. **Panel Recommendation**

> An open meeting of the Anesthesiology and Respiratory Therapy Devices
> Panel was held on July 16, 2001 to discuss the safety and
> effectiveness information provided for the Model 3100B, and to obtain
> a recommendation from the Panel. The Panel recommended that the PMA
> supplement be found approvable with the following conditions:

-   That the labeling clearly state that severe COPD and asthma were
    specific exclusion criteria for the trial, and that the benefits and
    risks of use of the Model 3100B to treat patients with severe COPD
    or asthma are unknown; and

-   That the labeling clearly state that there are no data to suggest
    that aerosols can be effectively delivered during high-frequency
    oscillatory ventilation.

XII. **FDA Decision**

The conditions of approval recommended by the Panel have been met by
appropriate modification of the labeling for the Model 3100B. FDA has
determined that the information provided in the PMA supplement provides
reasonable assurance of the safety and effectiveness of this device when
used as indicated in the labeling, and has issued an approval order on
[September 24, 2001]{.underline}.