Summary

En model til simulere klinisk relevant Hypoxi i mennesker

Published: December 22, 2016
doi:

Summary

Hypoxi simulering hos mennesker er normalt udført ved at inhalere hypoxiske gasblandinger. Til denne undersøgelse blev apnø dykkere bruges til at simulere dynamisk hypoxi hos mennesker. Derudover blev fysiologiske ændringer i desaturation og re-mætningskinetik evalueret med non-invasive værktøjer som Near-Infrared-spektroskopi (NIRS) og perifer iltning mætning (SpO 2).

Abstract

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.

Introduction

Klinisk relevant akut hypoxi og samtidig hypercapni er for det meste ses hos patienter med obstruktiv søvnapnø syndrom (OSAS), akut luftvejsobstruktion eller under genoplivning. Store begrænsninger inden for OSAS og andre hypoxemiske tilstande indbefatter den begrænsede overførbar viden om patofysiologien afledt af dyreforsøg og at humane modeller er ikke-eksisterende 1. At efterligne hypoxi hos mennesker, har hypoxiske gasblandinger hidtil blevet bruges 2 7. Men disse betingelser er mere repræsentative for højtliggende omgivelser end af kliniske situationer, hvor hypoxi generelt ledsages af hyperkapni. For at overvåge vævsoxygenering under hjertestop og genoplivning, har dyreforsøg udført 8 for at undersøge fysiologiske kompenserende mekanismer.

Apnø-dykkere er sunde atleter i stand til at trykke på vejrtrækning impulsder er fremkaldt af lav arteriel oxygenmætning 9 og en øget pCO2 10,11. Vi undersøgte apnø dykkere for at efterligne kliniske situationer med akut hypoksi og samtidig hypercapni 12. Denne model kan anvendes til at evaluere kliniske opsætninger, forbedre den patofysiologiske forståelse af patienter med OSAS eller patologiske vejrtrækning lidelser, og afslører nye muligheder for at studere en potentiel tæller afbalanceringsmekanisme i tilfælde af apnø. Endvidere til forskellige teknikker detektere hypoxi hos mennesker kan testes for gennemførlighed og nøjagtighed i tilfælde af dynamiske hypoksi, som findes i nødsituationer (dvs., luftvejsobstruktioner, laryngospasme eller kan ikke intubere, kan ikke ventilere situationer) eller til at simulere intermitterende hypoxi hos patienter med OSAS.

Noninvasive teknikker til påvisning af hypoxi hos mennesker er begrænsede. Perifer pulsoximetri (SpO 2) er en godkendt værktøj i pre-Hospital og hospitaler til at opdage hypoxi 13. Metoden er baseret på lysabsorption af hæmoglobin. Imidlertid er SpO 2 måling begrænset til perifer arteriel iltning og kan ikke anvendes i tilfælde af pulseless elektrisk aktivitet (PEA) eller centraliseret minimal cirkulation 14. I modsætning hertil kan Near-infrarød spektroskopi anvendes til at bedømme hjernevæv iltmætning (RSO 2) i realtid under PEA, under hæmorrhagisk shock eller efter subarachnoid blødning 15-19. Dens anvendelse er i konstant vækst 20 og metodiske undersøgelser har afsløret en positiv sammenhæng mellem SpO 2 og RSO 2 3,4.

I denne undersøgelse, giver vi en model til at simulere klinisk relevant hypoxi hos mennesker og præsentere en trin-for-trin metode til at sammenligne perifere pulsoximetri og NIRS i tilfælde af de- og re-mætning. Ved at analysere fysiologiske data i tilfælde af enpnea, kan vores forståelse af counter balancing mekanismer forbedres.

Protocol

Etik erklæring Alle procedurer udføres i undersøgelser med humane deltagerne var i overensstemmelse med de etiske standarder i 1964 Helsinki-erklæringen og senere ændringer. Udformningen af ​​denne undersøgelse blev godkendt af de lokale etiske komité af Universitetshospitalet i Bonn, Tyskland. BEMÆRK: Sørg for, at emner er i god og sund tilstand, fri for antihypertensiv medicin og mindst 24 timer fri for catecholamin inducerende midler som koffein eller lig stoffer. 1….

Representative Results

Figur 1 viser samtidige optagelser af SpO 2 og NIRS værdier (NIRS cerebral og NIRS væv) under apnø hos en patient. Samlet apnø tid var 363 sek. Efter apnø NIRS og SpO 2 værdier forblev stabil i ca. 140 sek. Et fald i SpO 2 blev opdaget efter 204 sek ved perifer SpO 2 mens et fald på NIRS cerebral blev opdaget efter 238 sek. Den laveste målte SpO 2 efter apnø var 58% og lavest…

Discussion

Den samlede apnø tid er primært forårsaget af lunge størrelse og ilt forbrug per minut og påvirket af en persons evne til at modstå vejrtrækningsrefleks forårsaget af stigende pCO2 eller faldende pO 2. Apnø dykkere er uddannet til at maksimere deres ånde-hold varighed og er vant til at gøre det i maksimal inspiration. Derfor tiden indtil hypoxi er påviselige adskiller mellem individer og afhænger af emnet fysiske tilstand og træning status og måske endda variere fra deres daglige sta…

Divulgazioni

The authors have nothing to disclose.

Acknowledgements

Special thanks to all volunteers who participated in the original study. The work of L. Eichhorn was supported through a scholarship of the Else-Kröner-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.

Materials

SpO2 Dräger Medical AG&CO.KG SHP ACC MCABLE-Masimo Set peripheral SpO2-Monitoring
Non Invasive Blood Pressure (NIBP) Dräger Medical AG&CO.KG NIBP cuff M+,  MP00916 
Electrocardiographic (ECG)   Dräger Medical AG&CO.KG Infinity M540 Monitor ECG monitoring
Docking station Dräger Medical AG&CO.KG M500 Docking Station connection of M540 to laptop
NIRS NONIN Medical’s EQUANOX Model 7600 Regional Oximeter System measuring of cerebral and  tissue oxygenation
NIRS diodes EQUANOX Advance Sensor Model 8004CA suited for measuring cerebral and somatic oxygen-saturation
Laptop 
DataGrabber Dräger Medical AG&CO.KG DataGrabber v2005.10.16 software to synchronize M540 with laptop
eVision Nonin Medical. Inc. Version 1.3.0.0 software to synchronize NONIN with laptop

Riferimenti

  1. Drager, L. F., Polotsky, V. Y., O’Donnell, C. P., Cravo, S. L., Lorenzi-Filho, G., Machado, B. H. Translational approaches to understanding metabolic dysfunction and cardiovascular consequences of obstructive sleep apnea. Am J Physiol Heart Circ Physiol. 309 (7), 1101-1111 (2015).
  2. Shah, N., Trivedi, N. K., Clack, S. L., Shah, M., Shah, P. P., Barker, S. Impact of hypoxemia on the performance of cerebral oximeter in volunteer subjects. J Neurosurg Anesthesiol. 12 (3), 201-209 (2000).
  3. Ricci, M., Lombardi, P., et al. Near-infrared spectroscopy to monitor cerebral oxygen saturation in single-ventricle physiology. J Thorac Cardiovasc Surg. 131 (2), 395-402 (2006).
  4. Kusaka, T., Isobe, K., et al. Quantification of cerebral oxygenation by full-spectrum near-infrared spectroscopy using a two-point method. Comp Biochem Physiol A Mol Integr Physiol. 132 (1), 121-132 (2002).
  5. Nishimura, N., Iwasaki, K., Ogawa, Y., Shibata, S. Oxygen administration, cerebral blood flow velocity, and dynamic cerebral autoregulation. Aviat Space Environ Med. 78 (12), 1121-1127 (2007).
  6. Wilson, M. H., Newman, S., Imray, C. H. The cerebral effects of ascent to high altitudes. Lancet Neurol. 8 (2), 175-191 (2009).
  7. Sanborn, M. R., Edsell, M. E., et al. Cerebral hemodynamics at altitude: effects of hyperventilation and acclimatization on cerebral blood flow and oxygenation. Wilderness Environ Med. 26 (2), 133-141 (2015).
  8. Reynolds, J. C., Salcido, D., et al. Tissue oximetry by near-infrared spectroscopy in a porcine model of out-of-hospital cardiac arrest and resuscitation. Resuscitation. 84 (6), 843-847 (2013).
  9. Andersson, J. P. A., Evaggelidis, L. Arterial oxygen saturation and diving response during dynamic apneas in breath-hold divers. Scand J Med Sci Sports. 19 (1), 87-91 (2009).
  10. Overgaard, K., Friis, S., Pedersen, R. B., Lykkeboe, G. Influence of lung volume, glossopharyngeal inhalation and P(ET) O2 and P(ET) CO2 on apnea performance in trained breath-hold divers. Eur J Appl Physiol. 97 (2), 158-164 (2006).
  11. Ferretti, G. Extreme human breath-hold diving. Eur J Appl Physiol. 84 (4), 254-271 (2001).
  12. Eichhorn, L., Erdfelder, F., et al. Evaluation of near-infrared spectroscopy under apnea-dependent hypoxia in humans. J Clin Monit Comput. 29 (6), 749-757 (2015).
  13. Eichhorn, J. H. Pulse oximetry as a standard of practice in anesthesia. Anesthesiology. 78 (3), 423-426 (1993).
  14. Schewe, J. -. C., Thudium, M. O., et al. Monitoring of cerebral oxygen saturation during resuscitation in out-of-hospital cardiac arrest: a feasibility study in a physician staffed emergency medical system. Scand J Trauma Resusc Emerg Med. 22, 58 (2014).
  15. Ahn, A., Nasir, A., Malik, H., D’Orazi, F., Parnia, S. A pilot study examining the role of regional cerebral oxygen saturation monitoring as a marker of return of spontaneous circulation in shockable (VF/VT) and non-shockable (PEA/Asystole) causes of cardiac arrest. Resuscitation. 84 (12), 1713-1716 (2013).
  16. Moritz, S., Kasprzak, P., Arlt, M., Taeger, K., Metz, C. Accuracy of cerebral monitoring in detecting cerebral ischemia during carotid endarterectomy: a comparison of transcranial Doppler sonography, near-infrared spectroscopy, stump pressure, and somatosensory evoked potentials. Anesthesiology. 107 (4), 563-569 (2007).
  17. Beilman, G. J., Groehler, K. E., Lazaron, V., Ortner, J. P. Near-infrared spectroscopy measurement of regional tissue oxyhemoglobin saturation during hemorrhagic shock. Shock. 12 (3), 196-200 (1999).
  18. Rhee, P., Langdale, L., Mock, C., Gentilello, L. M. Near-infrared spectroscopy: continuous measurement of cytochrome oxidation during hemorrhagic shock. Crit Care Med. 25 (1), 166-170 (1997).
  19. Zweifel, C., Castellani, G., et al. Continuous assessment of cerebral autoregulation with near-infrared spectroscopy in adults after subarachnoid hemorrhage. Stroke. 41 (9), 1963-1968 (2010).
  20. Scheeren, T. W. L., Schober, P., Schwarte, L. A. Monitoring tissue oxygenation by near infrared spectroscopy (NIRS): background and current applications. J Clin Monit Comput. 26 (4), 279-287 (2012).
  21. Boushel, R., Langberg, H., Olesen, J., Gonzales-Alonzo, J., Bülow, J., Kjaer, M. Monitoring tissue oxygen availability with near infrared spectroscopy (NIRS) in health and disease. Scand J Med Sci Sports. 11 (4), 213-222 (2001).
  22. Aaslid, R. Cerebral autoregulation and vasomotor reactivity. Front Neurol Neurosci. 21, 216-228 (2006).
  23. Palada, I., Obad, A., Bakovic, D., Valic, Z., Ivancev, V., Dujic, Z. Cerebral and peripheral hemodynamics and oxygenation during maximal dry breath-holds. Respir Physiol Neurobiol. 157 (2-3), 374-381 (2007).
  24. Heusser, K., Dzamonja, G., et al. Cardiovascular regulation during apnea in elite divers. Hypertension. 53 (4), 719-724 (2009).
  25. Joulia, F., Lemaitre, F., Fontanari, P., Mille, M. L., Barthelemy, P. Circulatory effects of apnoea in elite breath-hold divers. Acta Physiol (Oxf). 197 (1), 75-82 (2009).
  26. Costalat, G., Coquart, J., Castres, I., Tourny, C., Lemaitre, F. Hemodynamic adjustments during breath-holding in trained divers. Eur J Appl Physiol. 113 (10), 2523-2529 (2013).
  27. Busch, D. R., Lynch, J. M., et al. Cerebral Blood Flow Response to Hypercapnia in Children with Obstructive Sleep Apnea Syndrome. Sleep. 39 (1), 209-216 (2016).
  28. Alex, R., Bhave, G., et al. An investigation of simultaneous variations in cerebral blood flow velocity and arterial blood pressure during sleep apnea. Conf Proc IEEE Eng Med Biol Soc. , 5634-5637 (2012).
  29. Eichhorn, L., Erdfelder, F., et al. Influence of Apnea-induced Hypoxia on Catecholamine Release and Cardiovascular Dynamics. Int J Sports Med. , (2016).
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Citazione di questo articolo
Eichhorn, L., Kessler, F., Böhnert, V., Erdfelder, F., Reckendorf, A., Meyer, R., Ellerkmann, R. K. A Model to Simulate Clinically Relevant Hypoxia in Humans. J. Vis. Exp. (118), e54933, doi:10.3791/54933 (2016).

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