supplementary materials for · 2020-06-22 · fig. s5. ventilator alarm response to occlusion. fig....
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stm.sciencemag.org/cgi/content/full/12/549/eabb9401/DC1
Supplementary Materials for
A rapidly deployable individualized system for augmenting ventilator capacity
Shriya S. Srinivasan, Khalil B. Ramadi, Francesco Vicario, Declan Gwynne, Alison Hayward, David Lagier, Robert Langer,
Joseph J. Frassica, Rebecca M. Baron, Giovanni Traverso*
*Corresponding author. Email: [email protected], [email protected]
Published 24 June 2020, Sci. Transl. Med. 12, eabb9401 (2020)
DOI: 10.1126/scitranslmed.abb9401
This PDF file includes:
Fig. S1. Photographs of the iSAVE setup. Fig. S2. Differential tidal volume and PEEP delivery on the iSAVE using an open-circuit ventilator and test lungs. Fig. S3. Accommodation to changes in compliance of one test lung using the iSAVE and an open-circuit ventilator. Fig. S4. Ventilation at high lung resistances. Fig. S5. Ventilator alarm response to occlusion. Fig. S6. Adding a test lung to the circuit. Fig. S7. Cross-contamination validation using artificial lungs on a closed-circuit ventilator. Fig. S8. Individualized management of ventilation using the iSAVE on a pig lung and a test lung. Fig. S9. Modification of sensing circuit for a Hamilton G5 ventilator. Fig. S10. Whistle ring designs for two types of common pressure release (PEEP) valves. Table S1. List of components required for the assembly of the iSAVE. Table S2. Mechanical components used in the iSAVE and their readily available medical industry equivalents. Table S3. Measurement of respiratory mechanics for iSAVE system using test lungs. Table S4. Blood electrolytes and chemistry during ventilation in pigs. Table S5. Stratification for patient matching.
Fig. S1. Photographs of the iSAVE setup. Left: Hamilton G5; middle: Puritan Bennett 840;
right: Philips VX850 ventilators.
Hamilton G5 Puritan Bennett 840 Philips VX850
Fig. S2. Differential tidal volume and PEEP delivery on the iSAVE using an open-circuit
ventilator and test lungs. Pressure, flow, and volume traces for two test lungs (capacity 1L),
one denoted in blue and the other in black. By adjusting the flow valve, various ratios of the
ventilator’s tidal volume of 400 mL were delivered to the two lungs. The range of ratios tested
(50:50, 65:35, 80:20) demonstrate that the iSAVE can split the ventilator's tidal volume to lungs
with markedly different needs without creating unreasonable pressure of flow conditions. The
waveform denoted in blue represents the lower proportion in the ratio.
Fig. S3. Accommodation to changes in compliance of one test lung using the iSAVE and an
open-circuit ventilator. Initially, both lungs (C = 60 cmH2O, R = Rp20) were supplied with VT
= 200 mL. (A) The compliance of one lung (blue) was decreased (C = 30 cmH2O) as indicated
by the red dotted line, causing a shift in volume delivery to the other lung (black). Titration of
the flow valve, indicated by the purple lines, restored flow to the baseline values. (B) The
compliance of one lung (blue) was increased (C = 120 cmH2O) as indicated by the red dotted
line, causing a decrease in volume delivery to the other lung (black). Titration of the flow valve,
indicated by the purple lines, restored flow to the baseline values.
5 10 15 20 25 30 35
20
40
Pre
ssu
re (
cmH
20
)
5 10 15 20 25 30 35
-0.2
0
0.2
Flo
w (
L/s
)
5 10 15 20 25 30 35
Time (s)
0
200
400
Vo
lum
e (m
L)
Vo
lum
e(m
L)
Flo
w(L
/m)
Pre
ssu
re(c
mH
2O
)
Time (s)Time (s)
A Decrease in compliance of blue lung B Increase in compliance of blue lung
Fig. S4. Ventilation at high lung resistances. The iSAVE was implemented using an open-
circuit ventilator to support two artificial lungs with high resistances (R = Rp50, C = 60 cmH2O).
The valves were serially adjusted (as indicated by vertical dotted lines) to titrate flow. At the
medium setting, 200 mL was able to be delivered at a pressure of 22 cmH2O. The resistances
simulated here are much higher resistance than what is expected in patients with ARDS, even
when comorbid with restrictive pathology. This test demonstrated the ability for the ventilator to
supply multiple patients with sufficient volume, even when resistances are high.
Fig. S5. Ventilator alarm response to occlusion. During the ventilation of two test lungs, (blue
and black) using a closed-circuit ventilator, tubing of one test lung (black) was occluded to
simulate the case of a sudden event causing a high resistance or complete shunt in one limb
(orange dotted line). The ventilator’s alarm immediately activated (photograph on lower right;
boxed orange region). This was resolved by removing the occlusion (green dotted line).
50 100
5
10
15
50 100
-50
0
50
50 100
Time (s)
-400-200
0200400600
Occlusion Alarm
Baseline
Vo
lum
e(m
L)
Flo
w(L
/m)
Pre
ssu
re(c
mH
2O
)
Time (s)
Tubing occluded Tubing unoccluded
Fig. S6. Adding a test lung to the circuit. During the ventilation of one test lung (denoted in
blue) using a closed-circuit ventilator, the second breathing circuit was isolated by closing its
flow control valve. 1) Prior to the addition of the second test lung (denoted in black), volume
was decreased to 75% of VT. 2) The second lung was attached to the second breathing circuit and
the valve was fully opened. 3) Both flow valves were titrated until the desired volumes and
pressures were achieved. Each step is denoted by a dotted vertical line.
Vo
lum
e(m
L)
Flo
w(L
/m)
Pre
ssu
re(c
mH
2O
)
Time (s)
5 15 25
1 2 3
Fig. S7. Cross-contamination validation using artificial lungs on a closed-circuit ventilator.
(A) Schematic of circuit used for cross-contamination testing. Trypan blue was nebulized in the
inspiratory circuit. Wipe/elution tests were performed in each segment of the circuit, indicated by
a numbered yellow hexagon. (B) Photographs of filters from the inspiratory and expiratory tract
of each channel. The expiratory filter (6) for subject A is purple, having trapped the nebulized
particles. (C) Absorption spectrum of samples from each segment of the test circuit.
Contaminants were contained by the filter at location 6. A sample of deionized water was used
for the negative control. A sample consisting of 0.1 mL Trypan blue in 1 mL water was used as
the positive control. Homoscedastic, two-tailed t-tests were performed to assess significance on
the data from the contamination testing with a threshold of P < 0.05.
Fig. S8. Individualized management of ventilation using the iSAVE on a pig lung and a test
lung. (A) Schematic of the setup for in vivo testing of iSAVE on a closed-circuit ventilator
supporting a 70 kg pig and an artificial test lung (1L capacity). (B) Pressure, flow, and volume
when differential tidal volumes were delivered to the pig and artificial lungs as indicated by the
ratio headings. Simulation of (C) decreased compliance in the artificial lung (black, orange
dotted line) and (D) increased compliance in the artificial lung (black, orange dotted line).
Simulation of (E) decreased compliance of the animal lung following 100 mL of saline infusion
(black, green dotted line) and (F) decreased resistance of the artificial lung (black, orange dotted
line). In all cases, titration of the valves restored ventilation (green dotted lines) to desired
baseline parameters.
A
B Differential Tidal Volume Delivery
Pre
ssure
(cm
H2O
)V
olu
me
(mL
)F
low
(L/m
)
25 50 75 1000
50
25 50 75 1000
0.5
25 50 75 100
Time (s)
0
500
Time (s) 2.5s
C Decreased compliance of artificial (black) lung D Increased compliance of artificial (blue) lung
250
20
40
60
Pre
ssu
re (
cmH
20
)
250
0.2
0.3
0.4
Flo
w (
L/s
)
250
Time (s)
0
200
400
Vo
lum
e (m
L)
0 10 20 30
20
40
Pre
ssu
re (
cmH
20)
0 10 20 300
0.5
Flo
w (
L/s
)
0 10 20 30
Time (s)
0
500
Vo
lum
e (m
L)
Pre
ssure
(cm
H2O
)
E Decreased compliance of animal (black) lung F Increased resistance of artificial (black) lung
Vo
lum
e
(mL
)F
low
(L/m
)
Time (s) Time (s)
Time (s) Time (s)50
Fig. S9. Modification of sensing circuit for a Hamilton G5 ventilator. For ventilators using
closed-loop flow control (such as Hamilton G5), the ventilator requires that the flow sensing
remain unaltered in order to complete calibration and self-test procedures. Here, the following
steps can be used to reconfigure the flow sensing from both breathing circuits. (A) Using a
standard stopcock, connect the blue and clear tubes from either patient's flow sensor to either
side of the stopcock. (B) Attach the stopcock housing the blue tubes to the blue connector port on
the ventilator. Attach the stopcock housing the clear tubes to the silver connector port on the
ventilator, pictured in the boxed area (C) Connect flow sensors to Y-piece in their normal
configuration to both patients.
A B C
Fig. S10. Whistle ring designs for two types of common pressure release (PEEP) valves. These enable an auditory alarm when the PEEP valve actuates. Whistle rings can be 3D printed
and assembled onto standard PEEP valves with a 22-mm inner diameter.
Table S1. List of components required for the assembly of the iSAVE.
Required components for closed-circuit (dual limb) ventilator
Per patient:
[ ] 2 one-way valves
[ ] 1 pressure release valve
[ ] 1 flow regulator
[ ] bacterial/viral filters
[ ] set of pressure/volume sensors
[ ] capnostat (CO2 sensor)
[ ] respiratory profile monitor
Required components for open-circuit (single limb) ventilator
Per patient:
[ ] 1 flow regulator
[ ] 1 bacterial/viral filter
[ ] 1 set of pressure/volume sensors (optional)
[ ] 1 capnostat (optional)
[ ] 1 monitor (optional)
Table S2. Mechanical components used in the iSAVE and their readily available medical
industry equivalents.
Mechanical
component Medical equivalent
One-way
valve
Positive expiratory pressure (PEP) threshold device
Unidirectional resistance/one-way valve
Duckbill valve
Pressure
release valve
Positive end-expiratory pressure (PEEP) valve
Ventilator pressure relief valve
Flow
regulator
Proportional flow control valve
Bacterial/viral
filters
HEPA filter
Pressure/volume
sensors
Mechanical
component Medical equivalent
CO2 sensor Capnostat for volumetric capnography (including EtCO2 monitoring) or
LoFlo for EtCO2 monitoring
Respiratory
profile monitor
Table S3. Measurement of respiratory mechanics for iSAVE system using test lungs. A
closed-circuit ventilator was used. Pplat, plateau pressure; PEEP, positive end-expiratory pressure.
Parameters Units Trial 1: Equal
Compliance
Trial 2: Mismatched Compliance
Trial 3: Mismatched Compliance
Lung A
Lung B
Lung A
Lung B
Lung A
Lung B
Tidal volume mL 347 262 418 257 433 89
Pplat - PEEP cmH2O 6.45 4.6 7.3 9 7 8
Computed compliance mL/cmH2O 53 56.9 53 28 61 11
Actual compliance mL/cmH2O 60 60 60 30 60 10
Error 11% 5% 11% 6% 2% 10%
Table S4. Blood electrolytes and chemistry during ventilation in pigs. BUN, blood urea
nitrogen; HCt, hematocrit; PCV, packed cell volume; HB, hemoglobin.
Parameter Units Pig A (70 kg) Pig A on iSAVE Pig B (88 kg) PigB on iSAVE
Na mmol/L 143 142 141 141
K mmol/L 2.9 3.8 3.4 3.6
Cl mmol/L 97 97 97 98
Anion Gap mmol/L 14 12 13 10
Glu mg/dL 138 127 118 125
BUN mg/dL 7 8 5 7
HCt % PCV 28 26 26 27
HB g/dL 9.5 8.8 8.8 9.2
Table S5. Stratification for patient matching.
FiO2
Patients requiring FiO2 > 60% should be grouped separately from patients
requiring FiO2 < 60% given common FiO2 settings and a desired threshold to
lower FiO2 < 60% to avoid theoretical O2 toxicity
Compliance (C) Patients with a C < 30 mLcmH20 should be grouped separately from patients with
C > 30 cmH2O
PEEP within the range of 5-18 cmH2O and the difference between patients should be
minimized to < 5 cmH2O
Driving
pressure
within the range of 5-15 cmH2O and the difference between patients should be
minimized to < 6 cmH2O
Difference in
height minimized to 3-6 inches to ensure relatively similar tidal volume needs
Comorbidities
Patients presenting with comorbid diseases (asthma, emphysema/chronic
obstructive pulmonary disease, bronchiectasis) should be grouped similarly to
make circuit dynamics more uniform