Name: a model to simulate clinically relevant hypoxia in humans
Uploaded: 2016-12-22T14:00:00
Description: Watch this Scientific Journal Video about A Model to Simulate Clinically Relevant Hypoxia in Humans at JoVE.com

Special thanks to all volunteers who participated in the original study. The work of L. Eichhorn was supported through a scholarship of the Else-Kr&#246;ner-Fresenius Foundation. The authors would like to thank Springer, Part of Springer Science+Business Media, for copyright clearance (License Number 3894660871180) and the kind permission of reusing previously published data.

Ethics statement 
All procedures performed in studies involving human participants were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments. The design of this study was approved by the local ethics committee of the University Hospital of Bonn, Germany.
NOTE: Ensure that subjects are in good and healthy condition, free of any anti-hypertensive medicine and at least 24 hours free of catecholamine inducing agents like caffeine or equal substances.
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<ol>
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The total apnea time is mainly caused by lung size and oxygen consumption per minute and influenced by an individuals&#39; ability to withstand the breathing reflex caused by increasing pCO2 or decreasing pO2. Apnea divers are trained to maximize their breath-hold duration and are used to doing so in maximal inspiration. Therefore, the time until hypoxia is detectable differs between individuals and depends on the subject&#39;s physical condition and training status and might even vary by their dail...

Clinically relevant acute hypoxia and concomitant hypercapnia is mostly seen in patients with obstructive sleep apnea syndrome (OSAS), acute airway obstruction or during cardiopulmonary resuscitation. Major limitations in the field of OSAS and other hypoxemic conditions include the limited transferable knowledge about the pathophysiology derived from animal studies and that human models are non-existent 1. To mimic hypoxia in humans, hypoxic gas mixtures have so far been used 2-7. However, these conditions are more representative of high altitude surroundings than of clinical situations where hypoxia, in general, is accompanied by hypercapnia. To monitor tissue oxygenation during cardiac arrest and resuscitation, animal studies have been performed 8 to investigate physiological compensatory mechanisms.
Apneic divers are healthy athletes capable of depressing the breathing impulse that is evoked by low arterial oxygen saturation 9 and an increased pCO2 10,11. We investigated apneic divers in order to mimic clinical situations of acute hypoxia and concomitant hypercapnia 12. This model can be used to evaluate clinical setups, improve the pathophysiological understanding of patients with OSAS or pathological breathing disorders, and reveal new possibilities for studying a potential counter balancing mechanism in cases of apnea. Furthermore, different techniques to detect hypoxia in humans can be tested for feasibility and accuracy in the case of dynamic hypoxia that is present in emergency situations (i.e., airway obstructions, laryngospasm or cannot intubate, cannot ventilate situations) or to simulate intermittent hypoxia in patients with OSAS.
Noninvasive techniques to detect hypoxia in humans are limited. Peripheral pulse oximetry (SpO2) is an approved tool in pre-hospital and hospital settings to detect hypoxia 13. The method is based on light absorption of hemoglobin. However, SpO2 measurement is limited to peripheral arterial oxygenation and cannot be used in cases of pulseless electrical activity (PEA) or centralized minimal circulation 14. In contrast, Near-Infrared Spectroscopy can be used to evaluate cerebral tissue oxygen saturation (rSO2) in real-time during PEA, during hemorrhagic shock or following subarachnoid hemorrhage 15-19. Its use is constantly growing 20 and methodological studies have revealed a positive correlation between SpO2 and rSO2 3,4.
In this study, we provide a model to simulate clinically relevant hypoxia in humans and present a step-by-step methodology to compare peripheral pulse oximetry and NIRS in case of de- and re-saturation. By analyzing physiological data in case of apnea, our understanding of counter balancing mechanisms can be improved.

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			<td style="width:88px;">Dr&#228;ger Medical AG&#38;CO.KG</td>
			<td style="width:88px;">SHP ACC MCABLE-Masimo Set</td>
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			<td height="80" style="height:80px;width:88px;">Non Invasive Blood Pressure (NIBP)</td>
			<td style="width:88px;">Dr&#228;ger Medical AG&#38;CO.KG</td>
			<td style="width:88px;">NIBP cuff M+,&#160; MP00916&#160;</td>
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			<td height="60" style="height:60px;width:88px;">Electrocardiographic (ECG) &#160;</td>
			<td style="width:88px;">Dr&#228;ger Medical AG&#38;CO.KG</td>
			<td style="width:88px;">Infinity M540 Monitor</td>
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			<td height="60" style="height:60px;width:88px;">Docking station</td>
			<td style="width:88px;">Dr&#228;ger Medical AG&#38;CO.KG</td>
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			<td style="width:88px;">connection of M540 to laptop</td>
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			<td height="80" style="height:80px;width:88px;">NIRS</td>
			<td style="width:88px;">NONIN Medical&#8217;s EQUANOX</td>
			<td style="width:88px;">Model 7600 Regional Oximeter System</td>
			<td style="width:88px;">measuring of cerebral and&#160; tissue oxygenation</td>
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			<td height="120" style="height:120px;width:88px;">NIRS diodes</td>
			<td style="width:88px;">EQUANOX Advance Sensor</td>
			<td style="width:88px;">Model 8004CA</td>
			<td style="width:88px;">suited for measuring cerebral and somatic oxygen-saturation</td>
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			<td height="20" style="height:20px;width:88px;">Laptop&#160;</td>
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			<td height="80" style="height:80px;width:88px;">DataGrabber</td>
			<td style="width:88px;">Dr&#228;ger Medical AG&#38;CO.KG</td>
			<td style="width:88px;">DataGrabber v2005.10.16</td>
			<td style="width:88px;">software to synchronize M540 with laptop</td>
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			<td height="80" style="height:80px;width:88px;">eVision</td>
			<td style="width:88px;">Nonin Medical. Inc.</td>
			<td style="width:88px;">Version 1.3.0.0</td>
			<td style="width:88px;">software to synchronize NONIN with laptop</td>
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a model to simulate clinically relevant hypoxia in humans

In case of apnea, arterial partial pressure of oxygen (pO2) decreases, while partial pressure of carbon dioxide (pCO2) increases. To avoid damage to hypoxia sensitive organs such as the brain, compensatory circulatory mechanisms help to maintain an adequate oxygen supply. This is mainly achieved by increased cerebral blood flow. Intermittent hypoxia is a commonly seen phenomenon in patients with obstructive sleep apnea. Acute airway obstruction can also result in hypoxia and hypercapnia. Until now, no adequate model has been established to simulate these dynamics in humans. Previous investigations focusing on human hypoxia used inhaled hypoxic gas mixtures. However, the resulting hypoxia was combined with hyperventilation and is therefore more representative of high altitude environments than of apnea. Furthermore, the transferability of previously performed animal experiments to humans is limited and the pathophysiological background of apnea induced physiological changes is poorly understood. In this study, healthy human apneic divers were utilized to mimic clinically relevant hypoxia and hypercapnia during apnea. Additionally, pulse-oximetry and Near Infrared Spectroscopy (NIRS) were used to evaluate changes in cerebral and peripheral oxygen saturation before, during, and after apnea.

Figure 1 displays simultaneous recordings of SpO2 and NIRS values (NIRScerebral and NIRStissue) during apnea in one patient. Total apnea time was 363 sec. Following apnea NIRS and SpO2 values remained stable for approximately 140 sec. A decrease in SpO2 was detected after 204 sec by peripheral SpO2 whereas a decrease of NIRScerebral was detected after 238 sec. The lowest measured SpO2 ...

Watch this Scientific Journal Video about A Model to Simulate Clinically Relevant Hypoxia in Humans at JoVE.com

A Model to Simulate Clinically Relevant Hypoxia in Humans

Hypoxia simulation in humans has usually been performed by inhaling hypoxic gas mixtures. For this study, apneic divers were used to simulate dynamic hypoxia in humans. Additionally, physiological changes in desaturation and re-saturation kinetics were evaluated with non-invasive tools such as Near-Infrared-Spectroscopy (NIRS) and peripheral oxygenation saturation (SpO2).

In case of apnea, arterial partial pressure of oxygen (pO2) decreases, while partial pressure of carbon dioxide (pCO2) increases. To avoid damage to ...

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