Abstract
Purpose
Underwater divers face several potential neurological hazards when breathing compressed gas mixtures including nitrogen narcosis which can impact diver’s safety. Various human studies have clearly demonstrated brain impairment due to nitrogen narcosis in divers at 4 ATA using critical flicker fusion frequency (CFFF) as a cortical performance indicator. However, recently some authors have proposed a probable adaptive phenomenon during repetitive exposure to high nitrogen pressure in rats, where they found a reversal effect on dopamine release.
Methods
Sixty experienced divers breathing Air, Trimix or Heliox, were studied during an open water dive to a depth of 6 ATA with a square profile testing CFFF measurement before (T0), during the dive upon arriving at the bottom (6 ATA) (T1), 20 min of bottom time (T2), and at 5 m (1.5 ATA) (T3).
Results
CFFF results showed a slight increase in alertness and arousal during the deep dive regardless of the gas mixture breathed. The percent change in CFFF values at T1 and T2 differed among the three groups being lower in the air group than in the other groups. All CFFF values returned to basal values 5 min before the final ascent at 5 m (T3), but the Trimix measurements were still slightly better than those at T0.
Conclusions
Our results highlight that nitrogen and oxygen alone and in combination can produce neuronal excitability or depression in a dose-related response.
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Change history
19 April 2019
The original version of this article unfortunately contained a mistake.
Abbreviations
- ATA:
-
Atmospheres of pressure absolute 1 ATA = 1.01325 bar, 760 mmHg, 10 m H2O
- CFFF:
-
Critical flicker fusion frequency
- DCS:
-
Decompression sickness
- EAN:
-
Enriched air nitrox
- GABA receptors:
-
Gamma aminobutyric acid receptors
- HELIOX:
-
Helium and oxygen
- HPNS:
-
High pressure nervous syndrome
- TRIMIX:
-
Mixture of nitrogen, helium and oxygen
References
Abraini JH, Kriem B, Balon N, Rostain JC, Risso JJ (2003) Gamma-aminobutyric acid neuropharmacological investigations on narcosis produced by nitrogen, argon, or nitrous oxide. Anesth Analg 96:746–749, https://doi.org/10.1213/01.ane.0000050282.14291.38
Balestra C, Lafère P, Germonpré P (2012) Persistence of critical flicker fusion frequency impairment after a 33 mfw SCUBA dive: evidence of prolonged nitrogen narcosis? Eur J Appl Physiol 112:4063–4068. https://doi.org/10.1007/s00421-012-2391-z
Balestra C, Machado M, Theunissen S, Balestra A, Cialoni D, Clot C, Besnard S, Kammacher L, Delzenne J, Germonpré p, Lafère P (2018) Critical flicker fusion frequency is quick enough to assess and follow cerebral arousal changes during modified gravitational conditions (0 g/2 g) related to parabolic flights. Frontiers. (in press)
Blednov YA, Borghese CM, Ruiz CI, Cullins MA, Da Costa A, Osterndorff-Kahanek EA, Homanics GE, Harris RA (2017) Mutation of the inhibitory ethanol site in GABAA rho1 receptors promotes tolerance to ethanol-induced motor incoordination. Neuropharmacology 123:201–209. https://doi.org/10.1016/j.neuropharm.2017.06.013
Bove AA (2014) Diving medicine. Am J Respir Crit Care Med 189:1479–1486. https://doi.org/10.1164/rccm.201309-1662CI
Brebeck AK, Deussen A, Schmitz-Peiffer H, Range U, Balestra C, Cleveland S, Schipke JD (2017) Effects of oxygen-enriched air on cognitive performance during SCUBA-diving - an open-water study. Res Sports Med 25:345–356. https://doi.org/10.1080/15438627.2017.1314289
Brerro-Saby C, Delliaux S, Steinberg JG, Jammes Y (2010) The changes in neuromuscular excitability with normobaric hyperoxia in humans. Exp Physiol 95(1):153–159. https://doi.org/10.1113/expphysiol.2009.049460
Brubakk AO, Ross JA, Thom SR (2014) Saturation diving; physiology and pathophysiology. Compr Physiol 4:1229–1272. https://doi.org/10.1002/cphy.c130048
Choi MH, Lee SJ, Yang JW, Choi JS, Kim HS, Kim HJ, Min BC, Park SJ, Jun JH, Yi JH, Tack GR, Chung SC (2010) Activation of the limbic system under 30% oxygen during a visuospatial task: an fMRI study. Neurosci Lett. 471(2):70–73. https://doi.org/10.1016/j.neulet.2010.01.013
Chung SC, Sohn JH, Lee B, Tack GR, Yi JH, You JH, Jun JH, Sparacio R (2006) The effect of transient increase in oxygen level on brain activation and verbal performance. Int J Psychophysiol 62(1):103–108. https://doi.org/10.1016/j.ijpsycho.2006.02.006
Conte G, Scaradozzi D, Pelaia P, Screpanti L, Gala F, Rocco M (2016) A wearable critical flicker fusion frequency detector for SCUBA divers. In: The 26th international ocean and polar engineering conference. International Society of Offshore and Polar Engineers, Rhodes, Greece
Curran S, Wilson S, Musa S, Wattis J (2004) Critical flicker fusion threshold in patients with Alzheimer’s disease and vascular dementia. Int J Geriatr Psychiatry 19:575–581. https://doi.org/10.1002/gps.1134
David HN, Balon N, Rostain JC, Abraini JH (2001) Nitrogen at raised pressure interacts with the GABA(A) receptor to produce its narcotic pharmacological effect in the rat. Anesthesiology 95:921–927
Davranche K, Pichon A (2005) Critical flicker frequency threshold increment after an exhausting exercise. J Sport Exerc Psychol 27:515–520. https://doi.org/10.1123/jsep.27.4.515
Freiberger JJ, Derrick BJ, Natoli MJ, Akushevich I, Schinazi EA, Parker C, Stolp BW, Bennett PB, Vann RD, Dunworth SA, Moon RE (2016) Assessment of the interaction of hyperbaric N2, CO2, and O2 on psychomotor performance in divers. J Appl Physiol 121:953–964. https://doi.org/10.1152/japplphysiol.00534.2016
Germonpré P, Balestra C, Hemelryck W, Buzzacott P, Lafère P (2017) Objective vs. subjective evaluation of cognitive performance during 0.4-MPa dives breathing air or nitrox. Aerosp Med Hum Perform 88:469–475. https://doi.org/10.3357/amhp.4608.2017
Gravielle MC (2016) Activation-induced regulation of GABAA receptors: is there a link with the molecular basis of benzodiazepine tolerance? Pharmacol Res 109:92–100. https://doi.org/10.1016/j.phrs.2015.12.030
Grover CA, Grover DH (2014) Albert Behnke: nitrogen narcosis. J Emerg Med 46:225–227. https://doi.org/10.1016/j.jemermed.2013.08.080
Hemelryck W, Rozloznik M, Germonpré P, Balestra C, Lafère P (2013) Functional comparison between critical flicker fusion frequency and simple cognitive tests in subjects breathing air or oxygen in normobaria. Diving Hyperb Med 43:138–142
Hesser CM, Fagraeus L, Adolfson J (1978) Roles of nitrogen, oxygen, and carbon dioxide in compressed-air narcosis. Undersea Biomed Res 5:391–400
Huang KL, Wu JN, Lin HC, Mao SP, Kang B, Wan FJ (2000) Prolonged exposure to hyperbaric oxygen induces neuronal damage in primary rat cortical cultures. Neurosci Lett 293:159–162 https://doi.org/10.1016/S0304-3940(00)01493-2
Kahlbrock N, Butz M, May ES, Brenner M, Kircheis G, Haussinger D, Schnitzler A (2012) Lowered frequency and impaired modulation of gamma band oscillations in a bimodal attention task are associated with reduced critical flicker frequency. Neuroimage 61:216–227. https://doi.org/10.1016/j.neuroimage.2012.02.063
Kot J (2012) Extremely deep recreational dives: the risk for carbon dioxide (CO2) retention and high pressure neurological syndrome (HPNS). Int Marit Health 63:49–55
Kot J, Winklewski PJ, Sicko Z, Tkachenko Y (2015) Effect of oxygen on neuronal excitability measured by critical flicker fusion frequency is dose dependent. J Clin Exp Neuropsychol 37:276–284. https://doi.org/10.1080/13803395.2015.1007118
Kowacs PA, Piovesan EJ, Werneck LC, Fameli H, Zani AC, da Silva HP (2005) Critical flicker frequency in migraine. A controlled study in patients without prophylactic therapy. Cephalalgia 25:339–343. https://doi.org/10.1111/j.1468-2982.2004.00861.x
Lafère P, Balestra C, Hemelryck W, Donda N, Sakr A, Taher A, Marroni S, Germonpré P (2010) Evaluation of critical flicker fusion frequency and perceived fatigue in divers after air and enriched air nitrox diving. Diving Hyperb Med 40:114–118
Lafère P, Balestra C, Hemelryck W, Guerrero F, Germonpré P (2016) Do environmental conditions contribute to narcosis onset and symptom severity? Int J Sports Med 37:1124–1128. https://doi.org/10.1055/s-0042-110573
Lavoute C, Weiss M, Risso JJ, Rostain JC (2012) Mechanism of action of nitrogen pressure in controlling striatal dopamine level of freely moving rats is changed by recurrent exposures to nitrogen narcosis. Neurochem Res 37:655–664. https://doi.org/10.1007/s11064-011-0657-1
Lu S, Cai Y, Shen M, Zhou Y, Han S (2012) Alerting and orienting of attention without visual awareness. Conscious Cogn 21:928–938. https://doi.org/10.1016/j.concog.2012.03.012
Manning EP (2016) Central nervous system oxygen toxicity and hyperbaric oxygen seizures. Aerosp Med Hum Perform 87:477–486. https://doi.org/10.3357/amhp.4463.2016
Mewborn C, Renzi LM, Hammond BR, Miller LS (2015) Critical flicker fusion predicts executive function in younger and older adults. Arch Clin Neuropsychol 30:605–610. https://doi.org/10.1093/arclin/acv054
Micarelli A, Jacobsson H, Larsson SA, Jonsson C, Pagani M (2013) Neurobiological insight into hyperbaric hyperoxia. Acta Physiol (Oxf) 209:69–76. https://doi.org/10.1111/apha.12116
Miller KW, Paton WD, Smith RA, Smith EB (1973) The pressure reversal of general anesthesia and the critical volume hypothesis. Mol Pharmacol 9:131–143
Mitchell SJ, Doolette DJ (2013) Recreational technical diving part 1: an introduction to technical diving methods and activities. Diving Hyperb Med 43:86–93
Moss MC, Scholey AB (1996) Oxygen administration enhances memory formation in healthy young adults. Psychopharmacology 124(3):255–260
Moss MC, Scholey AB, Wesnes K (1998) Oxygen administration selectively enhances cognitive performance in healthy young adults: a placebo-controlled double-blind crossover study. Psychopharmacology 138(1):27–33
Rostain JC, Lavoute C (2016) Neurochemistry of pressure-induced nitrogen and metabolically inert gas narcosis in the central nervous system. Compr Physiol 6:1579–1590. https://doi.org/10.1002/cphy.c150024
Rostain JC, Lavoute C, Risso JJ, Vallee N, Weiss M (2011) A review of recent neurochemical data on inert gas narcosis. Undersea Hyperb Med 38:49–59
Sawatzky D (2012) Is diving addictive? Diving medicine. Diver 17/01/2012 by diver editorial. http://divermag.com/is-diving-addictive
Scholey AB, Moss MC, Wesnes K (1998) Oxygen and cognitive performance: the temporal relationship between hyperoxia and enhanced memory. Psychopharmacology 140(1):123–126
Scholey AB, Moss MC, Neave N, Wesnes K (1999) Cognitive performance, hyperoxia, and heart rate following oxygen administration in healthy young adults. Physiol Behav 67(5):783–789
Smith JM, Misiak H (1976) Critical flicker frequency (CFF) and psychotropic drugs in normal human subjects-a review. Psychopharmacologia 47:175–182
Smith RA, Paton WD (1976) The anesthetic effect of oxygen. Anesth Analg 55:734–736
Souday V, Koning NJ, Perez B, Grelon F, Mercat A, Boer C, Seegers V, Radermacher P, Asfar P (2016) Enriched air nitrox breathing reduces venous gas bubbles after simulated SCUBA diving: a double-blind cross-over randomized trial. PLoS One 11:e0154761. https://doi.org/10.1371/journal.pone.0154761
Torlot FJ, McPhail MJ, Taylor-Robinson SD (2013) Meta-analysis: the diagnostic accuracy of critical flicker frequency in minimal hepatic encephalopathy. Aliment Pharmacol Ther 37:527–536. https://doi.org/10.1111/apt.12199
Vallee N, Rostain J, Risso J (2009a) How can an inert gas counterbalance a NMDA induced glutamate release? J Appl Physiol 107:1951–1958. https://doi.org/10.1152/japplphysiol.00097.2009
Vallee N, Rostain JC, Boussuges A, Risso JJ (2009b) Comparison of nitrogen narcosis and helium pressure effects on striatal amino acids: a microdialysis study in rats. Neurochem Res 34:835–844. https://doi.org/10.1007/s11064-008-9827-1
Winklewski PJ, Kot J, Frydrychowski AF, Nuckowska MK, Tkachenko Y (2013) Effects of diving and oxygen on autonomic nervous system and cerebral blood flow. Diving Hyperb Med 43:148–156
Acknowledgements
ROAD Project Investigators include: Scaratozzo D, Gala F, Screpanti L, Argentario Diving, Nicolini S, Mesa S.
Funding
This study was funded by PRIN (Italian National Scientific Research Program) 2012.
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Contributions
RM, DBP, PP, MM, BC: conceived and designed research; GC, DBRA, ML, ROAD project investigators: designed and constructed the CFFF device; GC, RM, DBP, PP, ML, FS, BC, ROAD project investigators: supervised the protocol execution; ML,PP,DBP, FS, ROAD project investigators: collected and assembled the data; DBRA, ML, MM, GC: performed statistical analysis; RM, DBRA, MM, BC: drafted the manuscript. All the authors have read and approved the final manuscript.
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Conflict of interest
No conflicts of interest, financial or otherwise are declared by the authors.
Ethical approval
All experimental procedures were performed in accordance with the Declaration of Helsinki, and the Institutional Review Board (IRB) of Sapienza University of Rome approved all protocols (CE 2035/2015).
Informed consent
Written informed consent was obtained from all subjects.
Data availability
All data are available on the supplementary material.
Additional information
Communicated by Jean-René Lacour.
The members of the ROAD Project Investigators are mentioned in Acknowledgments section.
Electronic supplementary material
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421_2018_4020_MOESM2_ESM.pdf
Data are presented as box plots. The boundary of the box closest to zero indicates the 25th percentile, the line within the box marks the median, and the boundary of the box farthest from zero indicates the 75th percentile. Whiskers (error bars) above and below the box indicate the 90th and 10 percentiles. Points out of box are outlayers data. Air group: Tukey’s test, p < 0.05 vs baseline; Trimix: Bonferroni’ test, *p < 0.001 vs baseline Heliox: Tukey’s test, p < 0.05 vs baseline (PDF 46.439 KB)
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Rocco, M., Pelaia, P., Di Benedetto, P. et al. Inert gas narcosis in scuba diving, different gases different reactions. Eur J Appl Physiol 119, 247–255 (2019). https://doi.org/10.1007/s00421-018-4020-y
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DOI: https://doi.org/10.1007/s00421-018-4020-y