ORIGINAL RESEARCH : Hypoxic guard systems do not prevent rapid hypoxic inspired mixture formation

Sofie De Cooman • Caroline Schollaert •
Jan F. A. Hendrickx • Philip J. Peyton •
Tom Van Zundert • Andre M. De Wolf
Received: 7 July 2014 / Accepted: 25 September 2014 / Published online: 1 October 2014
Springer Science+Business Media New York 2014
Abstract Because a case report and theoretical mass
balances suggested that hypoxic guard systems may not
prevent the formation of hypoxic inspired mixtures (FIO2
B 21 %) over the clinically used fresh gas flow (FGF)
range, we measured FIO2 over a wide range of hypoxic
guard limits for O2/N2O and O2/air mixtures. After IRB
approval, 16 ASA I–II patients received sevoflurane in
either O2/N2O (n = 8) or O2/air (n = 8) using a Zeus
anesthesia machine in the conventional mode. After using
an 8 L/min FGF with FDO2 = 25 % for 10 min, the following
hypoxic guard limits were tested for 4 min each,
expressed as [total FGF in L/min; FDO2 in %]: [0.3;85],
[0.4;65], [0.5;50], [0.7;36], [0.85;30], [1.0;25], [1.25;25],
[1.5;25], [2;25], [3;25], [5;25], and [8;25]. In between these
[FGF;FDO2] combinations, 8 L/min FGF with 25 % O2
was used for 4 min to return to the same baseline FIO2
(25 %) before the start of the next combination. This
sequence was studied once in each patient receiving O2/air
(n = 8), but twice in each patient who received O2/N2O
(n = 8) to examine the effect of decreasing N2O uptake
over time, resulting in three groups: early O2/N2O, late
O2/N2O, and O2/air group. The [FGF;FDO2]–FIO2 relationship
was examined. The overall [FGF;FDO2]–FIO2
relationship in the three groups was similar. In all 1, 1.25,
and 1.5 L/min FGF groups, FIO2 decreased below 21 % in
all but one patient; this occurred within 1 min in at least
one patient. In the 0.7 L/min O2/air group and the 3 L/min
late O2/N2O and O2/air groups, FIO2 decreased below 21 %
in one patient. Current hypoxic guard systems do not
reliably prevent a hypoxic FIO2 with O2/N2O and O2/air
mixtures, particularly between 0.7 and 3 L/min.
Keywords Machine standards Hypoxic guard system
Hypoxia Hypoxic mixtures Rebreathing
1 Introduction
According to standards ASTM F1850-00 (clause 51.13.1)
and EN60601-2-13 (clause 51.102.2) (see Appendix 1),
hypoxic guard systems have to ensure an FDO2 of C21 %
when O2/N2O is used. The following case report and
simple mass balances prompted us to hypothesize that
hypoxic guard systems may not prevent the formation of
inspired hypoxic mixtures.
A 76 years old female ASA II patient (167 cm, 75 kg)
presented for robot assisted cystectomy. After intravenous
induction, anesthesia was maintained with sevoflurane in
O2/N2O, supplemented with sufentanil and rocuronium.
A Zeus anesthesia machine (Dra¨ger, Lu¨beck, Germany,
software version 4.03) was used in automated closed-
Jan Hendrickx, Philip Peyton, and Andre De Wolf are members of the
NAVAt group.
Electronic supplementary material The online version of this
article (doi:10.1007/s10877-014-9626-y) contains supplementary
material, which is available to authorized users.
S. De Cooman
Department of Anaesthesia, Kliniek Sint-Jan, Brussels, Belgium
C. Schollaert J. F. A. Hendrickx (&) T. Van Zundert
Department of Anaesthesia, Intensive Care and Pain Therapy,
OLV Hospital, Moorselbaan 164, 9300 Aalst, Belgium
e-mail: jcnwahendrickx@yahoo.com
P. J. Peyton
Department of Anaesthesia, Austin Hospital, University of
Melbourne, Parkville, Australia
A. M. De Wolf
Department of Anaesthesia, Feinberg School of Medicine,
Northwestern University, Chicago, IL, USA
123
J Clin Monit Comput (2015) 29:491–497
DOI 10.1007/s10877-014-9626-y
circuit target control delivery mode. The inspired O2 concentration
(FIO2) target was set at 30 %, with balance gas
N2O; the end-expired sevoflurane target concentration (FA)
ranged from 0.6 to 1.2 %. After 6 h, the surgeon
announced wound closure was imminent. Anticipating
extubation, sevoflurane wash-out was started by changing
the delivery mode from target control to conventional, with
a fresh gas flow (FGF) of 18 L/min and a delivered O2
concentration (FDO2) of 25 %, again with N2O as balance
gas (Fig. 1a, b). Four minutes after increasing the FGF, the
anesthesia provider realized that the patient was going to be
transferred to the intensive care unit and would remain
intubated, sedated and ventilated. In conventional mode
still, the FGF was consequently lowered to an arbitrary
0.95 L/min, and the hypoxic guard system could be seen to
increase FDO2 from 25 to 27 % (Fig. 1a, b). Three minutes
later, both visual and auditive alarms warned that the FIO2
had decreased below 21 %. After another 2 min, FIO2 had
further decreased to 18 % (Fig. 1), and pulse oximeter O2
saturation (SpO2) was 90 %. After increasing FDO2 to
100 % and FGF to 8 L/min, FIO2 and SpO2 rapidly
increased without any further untoward events.
Simple (approximate) mass balances explain the
sequence of events (Table 1—see Appendix 2 for additional
details): the FO2 in this theoretical model decreases
from 25 to 22.7, 20.7, 19.0 and 17.5 % in 1, 2, 3, and
4 min, respectively—a course that resembles that of the
FIO2 in our patient.
Based on the case report and mass balances, we
hypothesize that hypoxic guard systems do not prevent the
Fig. 1 Rapid formation of inspired hypoxic mixture in a patient
undergoing a radical cystectomy. Course of the fresh gas flow (FGF,
upper panel—note log scale) of O2 and N2O and the resulting O2
concentrations (lower panel). Despite a properly functioning S-ORC that
increased FDO2 from 25 to 27 % upon lowering FGF to 950 mL/min
(arrow), FIO2 decreased below 21 % within 3 min, and continued to
decrease to 18 % after 5 min
Table 1 Approximate mass balances in the case report
Baseline Time interval
0–1 min 1–2 min 2–3 min 3–4 min
Carrier gas O2 N2O O2 N2O O2 N2O O2 N2O O2 N2O
Delivered amount per minute in fresh gas (mL/min) 4,500 13,500 257 694 257 694 257 694 257 694
Delivered fraction (%) 25.0 75.0 27.0 73.0 27.0 73.0 27.0 73.0 27.0 73.0
Fraction (%) in circuit at start of time interval 25.0 75.0 22.7 77.3 20.7 79.3 19.0 81.0
Content (mL) in circuit ? FRC (total 5,000 mL)
at start of time interval
1,250 3,750 1,136 3,864 1,037 3,963 952 4,048
Amount (mL) removed per minute by patient 200 0 200 0 200 0 200 0
Total mass balance (mL) at the end of each time interval 1,307 4,444 1,193 4,558 1,094 4,657 1,009 4,742
Amount (mL) wasted via pop-off valve 171 580 156 595 143 608 132 619
Mass balance (mL) in circuit at the end of each time interval 1,136 3,864 1,037 3,963 952 4,084 877 4,123
Fraction (%) at end of time interval 22.7 77.3 20.7 79.3 19.0 81.0 17.5 82.5
Simple mass balances illustrate how a hypoxic mixture can be rapidly formed despite a 950 mL/min FGF and a delivered O2 concentration of
27 %
FRC functional residual capacity
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formation of a hypoxic FIO2 across the entire FGF used
clinically with certain O2/N2O and O2/air mixtures. We
therefore prospectively studied the FIO2 that results from
using the lowest possible FDO2 over a wide FGF range, for
both O2/N2O and O2/air mixtures, with one of the most
stringent hypoxic guards, the S-ORC (Sensitive Oxygen
Ratio Controller; Dra¨ger, Lu¨beck, Germany). Assuming
the correct gases are flowing through the gas pipelines, the
S-ORC is designed to ensure an FDO2 of C25 % O2 and
an O2 FGF C 250 mL/min across the entire FGF range.
With FGF C 1 L/min, the lowest FDO2 allowed by the
S-ORC is 25 % (and by implication, at least 250 mL/min
O2 is administered in the total FGF mixture); with FGF\1
L/min, FDO2 increases in order to meet the 250 mL/min
requirement (and by implication, FDO2[25 %). The
resulting S-ORC limits are presented in Fig. 2. The
S-ORC applies the same limits to O2/N2O and O2/air
mixtures, and is active irrespective of the agent and carrier
gas administration mode (conventional or target control).
2 Materials and methods
After obtaining IRB approval and written patient consent,
16 ASA I–II patients undergoing a variety of peripheral or
abdominal surgery were enrolled. After preoxygenation
and intravenous induction with propofol (3 mg/kg) and
sufentanil (0.1 lg/kg), the trachea was intubated (facilitated
with 0.7 mg/kg rocuronium). Controlled mechanical
ventilation was adjusted to maintain the end-expired CO2
partial pressure between 30 and 38 mmHg. All results were
obtained with the Zeus anesthesia machine in the conventional
mode of agent and carrier gas administration.
Anesthesia was maintained with sevoflurane (C1.5 %
end-expired) in either O2/N2O (n = 8) or O2/air (n = 8).
Assignment of the patients to one of the carrier gas groups
was randomized with Excel’s random function. The initial
FGF of the selected carrier gas was 8 L/min, with
FDO2 = 25 % (corresponding carrier FGFs are regulated
by an electronic mixer). After 10 min, the following [total
FGF in L/min; FDO2 in %] combinations were used in
each patient: [0.3;85], [0.4;65], [0.5;50], [0.7;36],
[0.85;30], [1.0;25], [1.25;25], [1.5;25], [2;25], [3;25],
[5;25], and [8;25]. These FDO2s are all S-ORC limits—
the lowest FDO2 (%) that the S-ORC allows at that particular
FGF (Fig. 2). In between these [FGF;FDO2] combinations,
FGF was increased to 8 L/min with FDO2 of
25 % for at least 4 min to return to the same FIO2 baseline
(25 %) before moving to the next combination (preliminary
testing had indicated that a FIO2 plateau phase
was reached within 4 min). For the same reason, each
[FGF;FDO2] combination was used for 4 min. However, if
FIO2 decreased to 20 % and/or SpO2 to 95 % before the
end of this 4 min period, FGF was increased to 8 L/min
with FDO2 = 25 %. In the O2/N2O group, the same
sequence of combinations were used twice in the same
patient to examine the effect of decreasing N2O uptake
over time; each set took about 106 min of observation.
Thus three groups were analyzed: (1) the early O2/N2O
group, with the first [FGF;FDO2] combination tested
10 min after the start of N2O administration; (2) the late
O2/N2O group, with the first [FGF;FDO2] tested after
completion of the early N2O study limb (&120 min after
the start of N2O administration) and (3) the O2/air group.
In each of the three groups, data were analyzed as follows.
If FIO2 remained C21 % in all the patients for a
particular S-ORC limit (=[FGF;FDO2] pair), we report the
FIO2 (%) after 4 min for that combination (mean ± standard
deviation). If FIO2 dropped below 21 % before the
end of the 4 min period in even a single patient in a particular
[FGF;FDO2] group, we did not report the average
FIO2 after 4 min because per protocol the O2 FGF had to be
increased; for these groups, we report (1) the % of patients
in whom FIO2 did drop below 21 %, and (2) the time after
which these O2 concentrations were reached in this subset
of patients. Data are presented as mean ± standard deviation.
Differences in demographic data were analyzed
using an unpaired t test; p\0.05 denoted significance.
3 Results
Age, height and weight of the patients in the O2/N2O
groups were 72 ± 6 years, 169 ± 7 cm, and 69 ± 13 kg,
and in the O2/air groups 56 ± 14 years, 172 ± 7 cm, and
70 ± 13 kg; only the difference in age was statistically
significant.
Fig. 2 Limits imposed on FDO2 by the hypoxic guard system, the
S-ORC . Lowest possible FDO2 that can be delivered over a range of
fresh gas flows (FGF, X-axis) in O2/air or O2/N2O with the S-ORC .
Limits for O2/N2O and O2/air are identical
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After using a particular [FGF;FDO2] combination for
4 min, the overall [FGF;FDO2]–FIO2 relationship in the
three groups was similar (Table 2). In all 1, 1.25, and
1.5 L/min FGF groups, FIO2 decreased below 21 % in all
but one patient; this occurred within 1 min in at least one
patient. In the 0.7 L/min O2/air group and the 3 L/min late
O2/N2O and O2/air groups, FIO2 decreased below 21 % in
one patient. The S-ORC did consistently prevent
FIO2\21 % only with FGF\0.7 or[3 L/min.
4 Discussion
According to standards ASTM F1850-00 (clause 51.13.1)
and EN60601-2-13 (clause 51.102.2) (see Appendix 1),
hypoxic guard systems have to ensure an FDO2 of C21 %
when O2/N2O is used. Simple mass balances predict that
this cannot prevent the formation of a hypoxic FIO2 when
FGF\minute ventilation, because rebreathing will make
the composition of the inspired mixture different from the
delivered mixture. In addition, the standards are written in
an ambiguous way: ‘‘… a device to protect against an
operator selected delivery of a mixture of O2 and N2O
having an O2 concentration below 21 % O2 in the fresh gas
or in the inspiratory gas’’. This definition allows the
anesthesia machine manufacturer to develop a hypoxic
guard system that only prevents the formation of a hypoxic
FDO2. Further evidence that mass balances have been
overlooked is the fact that the standards require no hypoxic
guard system for O2/air mixtures although rebreathing of
N2 may result even faster in a hypoxic FIO2 than when O2/
N2O is used because N2 uptake is lower (it is 34 times less
soluble than N2O) and because most tissues are already
saturated with N2 at the start of the surgical procedure.
An example is provided in an accompanying video in
which a volunteer is breathing air from a circle breathing
system with a 8 L/min FGF: after switching the flow to
1 L/min, FIO2 decreases to 12 % within 2 min. Most
anesthesia textbooks insufficiently consider N2 kinetics
even though the development of a hypoxic FIO2 with the
use of O2/air mixtures at reduced FGF has been described
[1]. Hypoxic guard limits are not consistent among anesthesia
machines, and the rationale for these differences is
either not or poorly described in major textbooks on
anesthesia equipment [2]. The lack of good descriptions of
hypoxic guard systems and their performance is also
reflected in the limited number of references in this
manuscript.
The S-ORC hypoxic guard uses more stringent criteria
to prevent hypoxic FIO2 because it delivers a higher FDO2
than recommended by the published standards. This is
especially apparent at very low FGF: at FGF of 0.3 L/min,
the S-ORC limits the lowest possible FDO2 to 85 %. At
FGF of 0.7–1.5 L/min, the S-ORC limits the lowest
possible FDO2 to 36–25 %. However, our case report
(Fig. 1), theoretical mass balances (Fig. 3), and the results
of our prospective study (Table 2) indicate that within a
FGF range of 0.7–3 L/min the S-ORC limits are insufficient
to prevent the development of a hypoxic FIO2 in all
study subjects. Unfortunately, many anesthesiologists are
quite comfortable with exactly this FGF range when
working in the conventional mode, because the rather
limited degree of rebreathing gives the clinician the
impression of ‘‘better control’’ than with FGF\1 L/min
where the difference between delivered and inspired concentration
of carrier gasses and inhaled anesthetics
becomes larger.
To prevent the formation of a hypoxic FIO2, it would
seem logical to adjust the hypoxic guard algorithms by
increasing the lowest possible FDO2 at FGF between 0.7
and 1.5 L/min. However, this may not always work,
because mass balances are complex and not amenable to a
uniform approach: different anesthesia machines may have
different rebreathing characteristics because their circle
system configuration may differ, different patients can have
a widely different O2 consumption and N2O uptake
(pediatric vs. adult patients). For example, if N2O uptake is
0.1 L/min, hypoxic guard limits that ensure FIO2 C 21 %
range from 29 to 48 % with an O2 uptake of 150–375 mL/
min, respectively (Fig. 4).
In our opinion, in order to prevent a hypoxic FIO2 it is
much better to use a feedback loop system based on
measured FIO2 instead of applying rather artificial restrictions
to FDO2. Target controlled anesthesia machines
already include measured FIO2 data in their control loops.
This same technology (feedback loops) should be used in
the conventional administration mode to prevent the formation
of a hypoxic FIO2, either by providing strong recommendations
(smart alarms) to the user to adjust
individual carrier FGF, or by overruling the user’s individual
carrier FGF settings if appropriate action is not
taken in due time (see our case report).
In conclusion, the S-ORC , the hypoxic guard system of
the Zeus anesthesia machine did not prevent the rapid
formation of an inspired hypoxic mixture at reduced FGF,
although it is one of the most stringent hypoxic guard
systems. Simple mass balances predict this, and our prospective
study confirms this. Future hypoxic guard systems
should be inspired hypoxic guard systems that incorporate
algorithms based on measured FIO2, both for O2/N2O and
O2/air mixtures. New standards that address these issues
are urgently warranted because the use of low fresh gas
flow in either conventional or target control mode is
increasing.
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Table 2 FIO2 with O2 delivered at different S-ORC limits in O2/N2O and O2/air mixtures
Early N2O group Late N2O group N2 group
FGF
(L/min)
FDO2
(%)
FIO2 at 40
(if FIO2
[20 %
in all pts) (%)
Incidence of
FIO2\21 %
within 40
(% of pts)
Dt to
FIO2
\21 %
(min)
FIO2 at
40 (if FIO2
[20 %
in all pts) (%)
Incidence of
FIO2\21 %
within 40
(% of pts)
Dt to
FIO2
\21 %
(min)
FIO2 at 40
(if FIO2
[20 % in
all pts) (%)
Incidence
of FIO2
\21 %
within 40
(% of pts)
Dt to
FIO2
\21 %
(min)
0.3 85 40 ±5 0 31 ±2 0 37 ±4 0
0.4 65 36 ±3 0 31 ±1 0 34 ±3 0
0.5 50 31 ±2 0 27 ±1 0 30 ±2 0
0.7 36 25 ±1 0 24 ± 1 0 17 3.3
0.85 30 22 ± 1 0 38 3.4 ± 0.5 38 2.7 ± 1.2
1 25 88 2.2 ± 0.7 100 1.6 ± 0.5 100 2.1 ± 0.8
1.25 25 100 2.1 ± 0.9 100 1.4 ± 0.5 100 1.6 ± 0.3
1.5 25 100 2.2 ± 0.8 100 1.7 ± 0.8 100 2 ± 0.7
2 25 63 2.7 ± 0.5 75 2.3 ± 0.6 50 1.8 ± 0.5
3 25 22 ± 1 0 13 3.2a 13 3.9
5 25 23 ±1 0 23 ±1 0 24 ±0 0
8 25 23 ±1 0 23 ±0 0 24 ±0 0
FGF fresh gas flow (L/min), FDO2 delivered O2 concentration (%), FIO2 inspired O2 concentration (%), pts patients; Dt time interval (min)
See text for details
a One patient only
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Ethical standard The experiments comply with the current laws of
Belgium—all patients were enrolled at the OLV hospital, Aalst,
Belgium. The volunteer on the accompanying video had given consent
to both the experiment and publication of the video.
Conflict of interest Jan Hendrickx has received lecture fees, travel
support, equipment loans, and support for the NAVAT meetings from
AbbVie, Acertys, Air Liquide, Allied healthcare, Armstrong Medical,
Baxter, Draeger, GE, Hospithera, Heinen und Lowensein, Intersurgical,
Maquet, MDMS, MEDEC, Micropore. Molecular, NWS, Philips,
Quantum Medical.
Appendix 1: Anesthesia machine standards
ASTM (American Society for Testing and Materials)
standard F1850-00, clause 51.13.1 protection against
accidental delivery of hypoxic gas mixtures
The anesthesia workstation shall be provided with a device
to protect against an operator selected delivery of a mixture
of oxygen and nitrous oxide having an oxygen concentration
below 21 % oxygen in the fresh gas or in the inspiratory
gas. If an override mechanism is provided to permit
operator selection of oxygen concentration below 21 %,
the activation of this mechanism shall be continuously
indicated.
International Organization for Standardization (ISO)
and the International Electrotechnical Commission
(IEC) Standard EN60601-2-13, clause 51.102.2
Anaesthetic gas delivery system
*51.102.3 Protection against selection of an oxygen concentration
below that of ambient air the anesthetic gas
delivery system shall be provided with means to prevent
the unintentional selection of a mixture of oxygen and
nitrous oxide having an oxygen concentration below that of
ambient air. If an operator-selected override mechanism is
provided, its activation shall be clearly indicated. Compliance
is checked by visual inspection and functional
testing.
Appendix 2: Reconstruction of mass balances in case
report
By assuming instantaneous gas mixing between the lung
and anesthesia circuit, only one O2 and one N2O concentration
has to be considered in the determination of mass
balances. Let us assume that the combined volume of the
circuit and the lungs is&5 L and that gases sampled by the
gas analyzer are returned to the circuit. Analogous to what
happened in the patient presented in the case report, the 5 L
system contains 25 % O2 and 75 % N2O, or &1,250 mL
Fig. 3 Simulation of the course of the oxygen concentration in the
system (FO2) with the lowest delivered O2 concentration the S-ORC
allows with six different O2/N2O fresh gas flows. It is assumed (1)
that O2 and N2O uptake are 0.2 and 0.1 L/min, respectively, and (2)
that gases are mixed instantaneously in a 5 L system volume with an
initial FO2 = 25 %. The course of the FO2 was calculated as
described in Appendix 2. The lowest FO2 occurred with
FGF = 1.0 L/min
Fig. 4 Complexity of developing a ‘‘one size fits all’’ hypoxic guard
system. Because the minimum O2 FGF that is required to keep the
oxygen concentration in the system (FO2) C 21 % depends on total
FGF, O2 consumption and N2O uptake, the FDO2 that ensures
FO2 C 21 % ranges widely. The example presented in this figure
applies for just one particular fresh gas flow (FGF) (1 L/min) and one
particular value for N2O uptake (0.1 L/min), but it illustrates that the
O2 FGF that ensures FIO2 C 21 % is 0.29 (a), 0.39 (b), and 0.48
(c) L/min when O2 uptake (VO2) is 125, 250, and 375 mL/min,
respectively, which would correspond to a hypoxic guard limit of 29,
39, and 48 %, respectively
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O2 and &3,750 mL N2O just before lowering the FGF to
950 mL/min. The amounts added per minute with the
lower FGF of 950 mL/min and an FDO2 of 27 % are
256 mL O2 and 694 mL N2O. The amounts removed per
minute by the patient are &200 mL O2/min (approximate
oxygen consumption by a healthy patient during general
anesthesia) and almost no N2O (because N2O uptake after
6 h has almost ceased). Subtracting the amounts taken up
by the patient from those added by the FGF yields a balance
of ?56 mL O2 and ?694 mL N2O/min. Adding the
latter amounts to those present in the circuit and lungs just
before lowering the FGF yields 1,306 mL O2 (=1,250 ?
56) and 3,750 mL N2O (=4,444 ? 694), which results in
an FO2 of 22.7 %. After scavenging the amount of gas
administered in excess of patient uptake, 1,136 mL O2 and
3,864 mL N2O remain present in the circuit and lungs after
1 min, and the same mass balances as described during the
first minute can be repeated for the next minute and so on.
FO2 can be calculated to decrease from 25 to 22.7, 20.7,
19.0 and 17.5 % after 1, 2, 3, and 4 min, respectively—a
course that resembles that of the FIO2 in our patient
(Fig. 1).
Analogous mass balances can be used to calculate the
predicted time course of change in FO2 in the system for a
range of FGF, with VO2 = 0.2 L/min, VN2O = 0.1 L/min,
and system volume = 5 L (Fig. 3).
References
1. Hendrickx JF, De Cooman S, Vandeput DM, Van Alphen J,
Coddens J, Deloof T, De Wolf AM. Air–oxygen mixtures in circle
systems. J Clin Anesth. 2001;13:461–4.
2. Dorsch JA, Dorsch SE. Understanding anesthesia equipment. 5th
ed. Philadelphia: Lippincott Williams & Wilkins; 2007. p. 108–10.
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