Equipment and regimes for intermittent hypoxia therapy

Abstract

The rapid advance of intermittent hypoxia therapy (IHT) has led to the development of medical protocols that use mild, non-damaging hypoxia training to deliver measurable benefits and the drug-free treatment of a number of chronic degenerative conditions. A variety of technical implementations for this treatment has been tested and used in recent decades, including hypobaric chambers, normobaric reduced oxygen rooms, and mask-system hypoxicators, which produce hypoxic air in various ways. There are advantages and disadvantages of the different methods and equipment, so caution needs to be exercised when selecting an appropriate model for medical use. Individual variability of physiological reactions to breathing the same hypoxic air is substantial, hence it is important to conduct a hypoxic test that establishes a hypoxia reaction type and to individualize the treatment regime in order to achieve greater efficacy. The three main reaction types are defined and described in this chapter. A novel approach is suggested in order to objectively quantify the dosage of the delivered treatment in the form so-called hypoxia training index (HTi). Knowledge of HTi can be used to alter the training regime for different individuals, compensating for individual variability, and can also be used in scientific studies to ensure that the hypoxic exposure was correctly controlled for each subject. The latest advance in IHT is the biofeedback-controlled hypoxicator that is capable of automatically adjusting oxygen concentration in the inhaled hypoxic air. This automatic biofeedback control provides the desired SpO2 in each individual training session, which fully compensates for individual variability. Further research must be conducted in order to discover the optimal regimes and treatment protocols that can be used to cater for individual variability.

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Series Title
Chapter Title Hypoxicators: Review of the Operating Principles and Constructions
Chapter SubTitle
Copyright Year 2012
Copyright Holder Springer-Verlag London
Family Name Lopata
Particle
Given Name Viktor A.
Corresponding Author
Suffix
Division Department of Hypoxia
Organization Bogomoletz Institute of Physiology, National Academy of Sciences of
Ukraine
Address Kiev 01024, Ukraine
Email
Family Name Serebrovskaya
Particle
Given Name Tatiana V.
Author
Suffix
Division Department of Hypoxia
Organization Bogomoletz Institute of Physiology, National Academy of Sciences of
Ukraine
Address Kiev 01024, Ukraine
Email
Abstract Traditional treatment protocols for intermittent hypoxia training/therapy (IHT) comprises repeated
exposures to low oxygen atmosphere breathing, altered with breathing ambient air. The rapid advance of
IHT has led to the development of different medical equipment – hypoxicators – for its implementation in
sport practice, military operations and also for clinical application. A variety of technical implementations
for this treatment has been tested and used in recent decades, including hypobaric chambers, normobaric
reduced oxygen rooms and mask-system hypoxicators, which produce hypoxic air in various ways. On
the basis of hypoxicators classification, the overview of their design, medical and technical requirements
is presented, and the perspectives of their development and industry trends are described as well as
advantages and disadvantages of their operation.

L. Xi, T.V. Serebrovskaya (eds.), Intermittent Hypoxia and Human Diseases,
DOI 10.1007/978-1-4471-2906-6_24, © Springer-Verlag London 2012
Abbreviations
HGM Hypoxic gas mixture
IHT Intermittent hypoxic training/treatment
24.1 Introduction
Increasing use of intermittent hypoxic training/treatment
(IHT) methods in sports, military and medical practices has
stimulated active development of special devices for IHT
implementation such as hypoxicators. The term of “hypoxi-
cator” was suggested by Soviet scientists decades ago to
describe a new class of devices for simulated altitude train-
ing of pilots, alpinists, mountain military personnel and
sportsmen, as well as for drug-free treatment of a wide range
of human disorders [11, 14, 24]. They are assigned for the
forming and supply of a patient with hypoxic gas mixture
(HGM) of the controlled composition. Variety of principles
and constructive solutions have distinguished hypoxicators
as a separate class of respiratory equipment, classified their
designs and set medical and technical requirements for main
parameters of hypoxicators.
Hypoxicators are classified based on three main criteria
[12]: (1) methods for HGM supply; (2) methods for HGM
formation; and (3) methods for regulation and maintenance
of HGM composition.
24.2 Designs of the Hypoxicators
First division is based on the criterion of methods for HGM
supply to a patient, i.e. mask or chamber (Fig. 24.1). The
mask method stipulates the presence of flow circuit contain-
ing face mask with valves for inspiration/expiration and a
buffer container for HGM in the line of inspiration. When
using the chamber method, a patient’s body or his head is
placed directly into a chamber connected to HGM formation
unit. Such chambers can be either hermetic (closed), filled
with HGM (Berezovski et al. 1983), or nonhermetic (flow)
through which HGM is blown into the chamber [5]. The
chambers can be in a form of stationary devices, working
rooms and portable tents, as well as movable devices.
[AU2]
Abstract
Traditional treatment protocols for intermittent hypoxia training/therapy (IHT) comprises
repeated exposures to low oxygen atmosphere breathing, altered with breathing ambient air.
The rapid advance of IHT has led to the development of different medical equipment –
hypoxicators – for its implementation in sport practice, military operations and also for
clinical application. A variety of technical implementations for this treatment has been
tested and used in recent decades, including hypobaric chambers, normobaric reduced oxy-
gen rooms and mask-system hypoxicators, which produce hypoxic air in various ways. On
the basis of hypoxicators classification, the overview of their design, medical and technical
requirements is presented, and the perspectives of their development and industry trends are
described as well as advantages and disadvantages of their operation.
Hypoxicators: Review of the Operating
Principles and Constructions
Viktor A. Lopata and Tatiana V. Serebrovskaya
24
V.A. Lopata ( *) • T.V. Serebrovskaya
Department of Hypoxia, Bogomoletz Institute of Physiology,
National Academy of Sciences of Ukraine,
Kiev 01024, Ukraine
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Device “Orothron” (NORT Company, Ukraine) has an
overall dimension of 1,900 × 5,780 × 2,200 mm and volume
of 19.9 m3 and allows holding hypoxic therapy sessions for
up to six patients simultaneously (Fig. 24.2).
Hypoxico Inc. (New York, USA) produces altitude sleeping
systems like working rooms or portable tents (Fig. 24.3). The
Altitude Chamber (home office or bed) offers the utmost in
spacious and air-conditioned comfort and it is adjustable to
12,500 ft/3,800 m of simulated altitude. The portable Bed-Tent
is Hypoxico’s most universal altitude training system. It fits on
the box spring of a queen size bed with the mattress inside, or
on the floor with a twin/double/queen mattress inside.
Movable device “Borei-5” (NORT Company, Ukraine)
consists of four main units: (1) control unit, (2) isolation
Chamber:
• Close chamber
• Flow chamber
Mask
Mixing of
compressed gases
Deoxygenation
Method of HGM
formation
Methods of HGM supply
Gas-analysis Aerodynamic
Method of regulation and
maintenance of HGM composition
Breathing in semi-
closed circuit
Gas separation
on membranes
and fibers
Oxygen binding with
• Zeolites
• Electrolytes
Fig. 24.1 Hypoxicators classification
scheme
Fig. 24.2 Device “Orothron”
(NORT, Ukraine, Kiev)
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24 Hypoxicators : Review of the Operating Principles and Constructions
helmet, (3) gas-separating column and (4) compressor
(Fig. 24.4). The device forms HGM no less than 40 L/min
with oxygen content in the range of 10–16%. The overall
dimensions are control unit, 1,300 × 600 × 600 mm; gas-sep-
arating column – ø 225 × 1,180 mm.
Hypoxic treatment complex “Edelweiss” (NVF METAKS
Company, Moscow, Russian Federation), which uses mem-
brane technologies, is equipped with monitoring system of
internal environment and patient’s physiological parameters
(ECG, pO2, arterial pressure, body temperature, respiratory
rate, pulse oximetry) (Fig. 24.5). The complexes are produced
in portable (for one patient) and stationary (for two, four, six
and eight patients) variants. Device for one patient has the fol-
lowing technical characteristics: (1) air pressure in gas-sepa-
rating unit is 0.5 ± 0.05 MPa; (2) percentage of oxygen in
hypoxic mixture is 11 ± 2; (3) output is 15 ± 3 L/min; (4) power
Fig. 24.3 Exterior view of working room (a) and portable tent for hypoxic therapy (b) (Hypoxico, Inc., USA, New York, USA) (http://www.
hypoxico.com/altitude-sleeping-systems.shtml#DelBT)
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Fig. 24.4 Device “Borei-5” [15]
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consumption is no more than 800 W; (5) weight of device
without spare parts and accessories is no more than 25 kg; and
(6) overall dimensions is no more than 700 × 250 × 550 mm.
Based upon the method of HGM formation, hypoxicators
are divided into the following two categories (Fig. 24.1).
24.2.1 Hypoxicators with Compressed HGM
Gas mixture is formed from compressed or liquefied gases
through the ejection of atmospheric air by the flow of com-
pressed nitrogen in 1:1 ratio or through direct feeding of
stable composition mixture from gas cylinder [14, 34]. Such
devices are also called generative devices (NTO Bio-Nova
Company, Moscow, Russian Federation, http://www.bion-
ova.ru/?page=2). Ejection method of HGM formation with
oxygen content in the range from 18% to 13.5% is used in
AltiTrainer200 device (Fig. 24.6) produced by SMTEC S.A.
(Nyon, Switzerland). Overall dimensions of the device are
650 × 400 × 580 mm; its weight (without nitrogen cylinder
under the pressure of ³0.3 MPa) is no more than 15 kg.
However, while having certain technological advantages [5,
9], direct HGM feeding method is connected with the risk to
use containers under 12–15 MPa pressure [12] and requires
regular and expensive certification of mixture composition.
For ensuring safety, a buffer reservoir is used in current con-
structions of hypoxicators. Such arrangement is used in
2-in-1 High Performance GO2Altitude Hypoxicator device
produced by Biomedtech Australia Pty. Ltd., Melbourne,
Australia (http://www.go2altitude.com) (Fig. 24.7). The
device with power consumption of 1,500 W delivers IHT
modes with HGM in oxygen range from 9% to 16%. Overall
dimensions of microprocessor control unit are
400 × 400 × 230 mm and weight is 7 kg, whereas the overall
dimensions and weight of ERA-II gas mixtures generator are
800 × 240 × 500 mm and 37 kg in weight.
24.2.2 Hypoxicators with Deoxygenation
Process
Gas mixture is formed from atmospheric air using deoxygenat-
ing method. Deoxygenation can be carried out by one of the
following approaches: (1) gas separation on membranes [32] or
fibres [15], (2) separation of oxygen and nitrogen by solid elec-
trolytes [14], (3) temporary binding of nitrogen by zeolites with
further emission of nitrogen into the mixture [14], and (4)
breathing in semi-closed flow circuit (rebreathing) ([12];
Serebrovskaya et al. 2009). Most of the currently manufactured
hypoxicators use the methods of gas separation or rebreathing.
Fig. 24.5 Portable device
“Edelweiss” (http://www.metax.
ru/index.php?option=com_conte
nt&view=category&layout=blog
&id=3&Itemid=9)
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24 Hypoxicators : Review of the Operating Principles and Constructions
The speed of oxygen molecules transition through flat
membrane or package of hollow fibres depends on the contact
area with gas and differential pressure, which can reach
0.4 MPa to ensure necessary device output (12–15 L/min)
[14]. Desired conditions require the inclusion of compressors
to hypoxicators (Fig. 24.8). These compressors must be able
to produce sufficiently high pressure and output while having
low noise level without using piston-type devices (in order to
Fig. 24.6 Hypoxicator AltiTrainer200 (http://www.smtec.net/en/documents/altitrainer200_en.pdf)
Fig. 24.7 2-in-1 High Performance GO2Altitude Hypoxicator: 1 – ERA-II gas mixtures generator; 2 – microprocessor control unit; 3 – 120 L
buffer container
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avoid the contamination of gas-separating membranes and
formed HGM by oil aerosol). The high price of such devices
caused by the necessity to include compressor, gas analyzer
and oxygen regulation system is compensated by their ability
to work with up to eight patients simultaneously. The “Bio-
Nova-204” device (Bio-Nova, Moscow, Russian Federation)
has the embodiments depending on the number of simultane-
ously served patients (from 1 to 8) and the presence of addi-
tional standard equipment (Fig. 24.9). Individual IHT regimens
are set and controlled by special computer programmes.
In addition, Climbi Company (Moscow, Russian
Federation) offers a range of “Everest” hypoxicators in the
market (Fig. 24.10). These hypoxicators allow to obtain oxy-
gen concentration in HGM in the range from 10% to 18% and
to serve up to four patients. Overall dimensions and weight of
“Everest-1” model 08 M are 400 × 460 × 700 mm and 50 kg.
Among the various hypoxicators, a group of devices
applying rebreathing principle in semi-closed flow circuit
deserve special attention. In these devices named “autohy-
poxicators” [14], the line of expiration contains carbon diox-
ide absorber, while the circuit has pneumatic connection to
the atmosphere through buffer reservoir, rigid or elastic [1].
In such devices, the process of HGM formation depends on
three factors: (1) patient’s oxygen consumption, (2) binding
of carbon dioxide and (3) atmospheric air inflow into the cir-
cuit during inspiration. During rebreathing session the oxy-
gen concentration gradually falls with time, which is very
effective for sportsmen training and use at home [29].
Fig. 24.8 Oil-free compressor as a part of hypoxicator with gas
separation
Fig. 24.9 Four-person device
for hypoxic therapy “Bio-
Nova-204”
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24 Hypoxicators : Review of the Operating Principles and Constructions
In case of rigid buffer reservoir, which is many times big-
ger than breathing volume and has an outlet to the atmo-
sphere [14], deoxygenation of gas mixture and its oxygenation
by atmospheric air take place simultaneously during the pro-
cess of breathing. Autohypoxicator with elastic buffer reser-
voir (Douglas bag or sylphon bellows) differs in certain
special features of HGM formation, which depends on the
parameters of patient’s breathing and technical features of
the device [16]. Significant advantage of such scheme is the
possibility to use sylphon bellows as a spirometer to control
the process of patient’s pulmonary ventilation. This possibil-
ity is realized by the lines of oxygen feeding and control of
oxygen content, which are included in the circuit as well as
the transmitter of sylphon volume changes [25, 26].
The evolution of autohypoxicator constructions, which is
reflected by the number of relevant patents awarded from
1987 to 2011, was aimed at simplifying the constructions and
decreasing their weight and overall dimensions, as well as
enhancing the safety for users. According to patents analysis,
the safety is achieved due to the regulation and maintenance
of HGM composition in the circuit at given level and a
decrease of its respiratory resistance. These patented methods
of regulation and maintenance of HGM composition can be
classified as either gas analytic or aerodynamic. The gas-anal-
ysis-based method functions by the use of oxygen gas ana-
lyzer with the system of circuit blow-off when critically low
level of oxygen content in HGM is reached [16]. For example,
Biomedtech Australia PTY Ltd. (Melbourne, Australia) offers
AltiPower Pro portable autohypoxicator, which was devel-
oped on the basis of a recent patent application [2] (Fig. 24.11).
This type of hypoxicator is equipped with oxygen sensor and
Fig. 24.10 Overview of “Everest-1” Hypoxicators: models 05 M (a)
and 08 M (b)
[AU3]
Fig. 24.11 AltiPower Pro
autohypoxicator
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pulse oximeter to control the training mode. When the device
is cyclically connected to gas analyzer, the arrangement of
multi-seat IHT room on the basis of one gas analyzer is pos-
sible [14]. Similar device was also developed by AltoLab
USA LLC (Phoenix, USA) (Fig. 24.12). Breathing circuit of
the autohypoxicator includes a hypoxic unit (Hypoxic Silo)
and a set of mixers (AltoMixer). The level of hypoxia gener-
ated depends on the number of mixers in the set.
There are various constructed components to regulate and
maintain the HGM composition by aerodynamic resistance
that connect buffer reservoir to the atmosphere. The ratio of
resistance values, either constant or regulated, allows main-
taining HGM composition within necessary range. Calibrated
orifices of diaphragms [19, 27] or removable cap with cali-
brated holes [28, 31], spool valve air flow [18], movable flaps
[35], change of cross-section of vent line which connects
flow circuit to the atmosphere [6] are used as resistances.
The most widely used equipment in Russia is the
“Vershyna” hypoxicator produced by METOM Company
(Moscow, Russian Federation). This device consists of
absorber with two nipples to which breathing bag and facial
mask are connected. The mask is put on nipple, which has
several open orifices with regulating numbers, thus chang-
ing the level of hypoxia (Fig. 24.13). The hypoxicator
allows holding IHT sessions with oxygen content in HGM
from 21% to 10%, CO2 content <1.5% and respiratory
resistance of up to 150 Pa. The advantages of the device
include maximal simplicity of its construction, minimal
overall dimensions and weight, and convenience of use. At
the same time, there are several disadvantages, such as the
difficulty to regulate precisely the oxygen concentration in
HGM and the burden of changing absorbent after each IHT
session.
24.3 Development of the Autohypoxicators
Autohypoxicators ([23]; Serebrovskaya et al. 2009) advance
the regulation of buffer reservoir volume (elastic sylphon
bellows or flexible membrane with spring framework)
according to the patient’s anthropometric parameters by
fixing sylphon bellows in certain position or by spiral move-
ment of the spring (Fig. 24.14). The main trend of autohy-
poxicators perfection is the inclusion of biological feedback
[9]. It presupposes the development of new basic schemes
which must include (1) Devices for monitoring of respiratory
function and cardiovascular system parameters and (2) IHT
microprocessor control system. Advanced hypoxicators are
adequately equipped with metrological channels and micro-
processor equipment [2, 7]. As to autohypoxicators, they are
at best equipped with oxygen analyzer and device for air
flow rate measuring.
One of innovative solutions which foresees the use of
comprehensive number of monitoring channels for micro-
processor IHT mode control is patent application [22], which
is implemented in the Device for Individual Hypoxic Regime
Determination “Mountain02 Complex Device” (IHT
INTERNATIONAL LTD, New Zealand). In this device, new
[AU4]
Hipoxic silo
Hipoxic mixer
Fig. 24.12 AltoLab
autohypoxicator
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24 Hypoxicators : Review of the Operating Principles and Constructions
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Fig. 24.13 Exterior view (a)
and scheme (b) of “Vershyna”
hypoxicator: 1 – mask; 2 – con-
nection branch pipe; 3 –
adsorber; 4 – breathing bag
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Fig. 24.14 Autohypoxicators with possibility of buffer container volume regulation: (a) “Hypoxydoz” with elastic sylphon [23]; (b) “Hypoxytron”
with flexible membrane [21]
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V.A. Lopata and T.V. Serebrovskaya
methods for individual hypoxic training modes are intro-
duced based upon patient’s individual sensitivity to hypoxia
(Fig. 24.15). “Mountain02 Complex” device has the follow-
ing scheme of diagnostics, prescription of IHT regimen and
providing IHT:
1. Preparatory stage: Registration of a patient; ques-
tionnaire of health, spirography, hand dynamometry,
squatting test; selection of inspired O2 concentration
for standard hypoxic test (14%, 12%, 10%, 9% or
8% O2)
2. Standard hypoxic test: Conducting of the test (with the
setting of alarm scopes for monitoring channels); estima-
tion of results
3. Hypoxic ventilatory response (HVR, eucapnic rebreath-
ing): Conducting of the test; estimation of results; selec-
tion of training regimen
4. Conducting of Training/treatment sessions (constant or
increasing hypoxia) according to prescribed regimen.
24.4 Development and Use of the Advanced
Autohypoxicators
The medical and diagnostic device “Mountain02 Complex”
can function perfectly together with the portable device
“Mountain02 Simplex” for home or field usage (Fig. 24.16).
After a subject goes through the testing using the Diagnostic
Complex in medical or sports facility and receives the rec-
ommendations concerning the most efficient individual train-
ing mode, he or she masters the procedure using the Simplex
device (which does not take long to do). Then it is possible to
continue training at home, sports field, work place or any
other environment with periodic testing at the Complex, so
the hypoxic dose and training regime can be adjusted.
When defining areas of preferable hypoxicators usage, it
should be noted that autohypoxicators are convenient virtu-
ally in all operating conditions for individual usage. Ejection
devices are most suitable for use at organizations which can
Fig. 24.15 Medical and diagnostic device “Mountain02 Complex Device” (IHT International Ltd, New Zealand)
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24 Hypoxicators : Review of the Operating Principles and Constructions
be constantly supplied with compressed nitrogen. Gas sepa-
ration devices are suitable for the in-patient facilities that are
not supplied with compressed nitrogen.
Based upon the methodical recommendations [10, 13, 17,
30, 33] and conditions of ensuring the patient’s comfort
while breathing with HGM, the main parameters and fea-
tures of the hypoxicators described above must be set on the
basis of the following norms and precautions [12]: (1)
inspired oxygen content in HGM, from 8% to 20%; (2) respi-
ratory resistance of flow circuit not more than 150 Pa•sec/l;
(3) HGM productivity per one patient, from 9 to 20 L/min;
(4) margin of error of oxygen content measurement, ± 0.5%;
(5) excessive pressure at the inlet of HGM formation unit,
0.1–0.5 mPa; (6) excessive pressure of HGM at the outlet of
mixture formation unit, 0.002–0.005 mPa; (7) excess of rela-
tive humidity of HGM over atmospheric air relative humid-
ity, no less than 5%; (8) presence of threshold levels alarm
system: content of oxygen in HGM, HGM productivity, oxy-
gen saturation of patient’s arterial blood (SpO2) and heart
rate; and (9) patient’s minute ventilation must be ensured up
to 100 L/min.
24.5 Summary
All the set of formulated medical and technical requirements
can be applied to the most complex and multifunctional
devices for conducting IHT, but in any case, the above-men-
tioned requirements 1–3 and 9 must be complied during the
development of hypoxicators. Further development of the
equipment for hypoxic therapy will be favoured by (1)
improvement of gas analysis methods to better maintain
HGM composition; (2) combination of IHT process with
diagnostics of patient’s respiratory and cardiac functions,
which require inclusion of spirometrical and electrocardio-
graphic measurement channels; (3) toughening of medical
and technical requirements to the devices on criteria of flow
circuit respiratory resistance, acceptable error of oxygen
content measurement, safety of use; and (4) standardization
of medical and technical requirements for hypoxic therapy
equipment and software.
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Fig. 24.16 Portable device “Mountain02 Simplex” for home or field
usage (IHT International Ltd, New Zealand)
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Author Queries
Chapter No.: 24
Queries Details Required Author’s Response
AU1 Please confirm the corresponding author and also provide e-mail ID.
AU2 Berezovski et al. (1983), Serebrovskaya et al. (2009) is cited in text but not provided in the reference list. Please
check.
AU3 Please specify “a” and “b” in the artwork of Fig. 24.10.
AU4 Please confirm the inserted citation for Refs. [7, 35].
AU5 Please provided citation for Refs. [3, 4, 20].
AU6 Please provide complete details for Ref. [7].
AU7 Please provide publisher name for Refs. [9, 10, 17, 30, 33].
AU8 Please provide publisher location for Ref. [15].
AU9 Please provide better quality figures.