Skip to main content
SpringerLink
Log in

Efficacy and Safety of a Nasopharyngeal Catheter for Selective Brain Cooling in Patients with Traumatic Brain Injury: A Prospective, Non-randomized Pilot Study

Neurocritical Care Aims and scope Submit manuscript

Cite this article

Abstract

Background

The efficacy objective was to determine whether a novel nasopharyngeal catheter could be used to cool the human brain after traumatic brain injury, and the safety objective was to assess the local and systemic effects of this therapeutic strategy.

Methods

This was a prospective, non-randomized, interventional clinical trial that involved five patients with severe traumatic brain injury. The intervention consisted of inducing and maintaining selective brain cooling for 24 h by positioning a catheter in the nasopharynx and circulating cold water inside the catheter in a closed-loop arrangement. Core temperature was maintained at ≥ 35 °C using counter-warming.

Results

In all study participants, a brain temperature reduction of ≥ 2 °C was achieved. The mean brain temperature reduction from baseline was 2.5 ± 0.9 °C (P = .04, 95% confidence interval). The mean systemic temperature was 37.3 ± 1.1 °C at baseline and 36.0 ± 0.8 °C during the intervention. The mean difference between the brain temperature and the systemic temperature during intervention was − 1.2 ± 0.8 °C (P = .04). The intervention was well tolerated with no significant changes observed in the hemodynamic parameters. No relevant variations in intracranial pressure and transcranial Doppler were observed. The laboratory results underwent no major changes, aside from the K+ levels and blood counts. The K+ levels significantly varied (P = .04); however, the variation was within the normal range. Only one patient experienced an event of mild localized and superficial nasal discoloration, which was re-evaluated on the seventh day and indicated complete recovery.

Conclusion

The results suggest that our noninvasive method for selective brain cooling, using a novel nasopharyngeal catheter, was effective and safe for use in humans.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Majdan M, Plancikova D, Brazinova A, et al. Epidemiology of traumatic brain injuries in Europe: a cross-sectional analysis. Lancet Public Health. 2016;1(2):e76–83.

    PubMed  Google Scholar 

  2. Cheng P, Yin P, Ning P, et al. Trends in traumatic brain injury mortality in China, 2006–2013: a population-based longitudinal study. PLOS Med. 2017;14(7):e1002332.

    PubMed  PubMed Central  Google Scholar 

  3. Naghavi M, Abajobir AA, Abbafati C, et al. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1151–210.

    Google Scholar 

  4. Murray CJ, Ezzati M, Flaxman AD, et al. GBD 2010: a multi-investigator collaboration for global comparative descriptive epidemiology. Lancet. 2012;380(9859):2055–8.

    PubMed  Google Scholar 

  5. Feigin VL, Forouzanfar MH, Krishnamurthi R, et al. Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet. 2014;383(9913):245–55.

    PubMed  PubMed Central  Google Scholar 

  6. Stecker EC, Reinier K, Marijon E, et al. Public health burden of sudden cardiac death in the United States. Circ Arrhythm Electrophysiol. 2014;7(2):212–7.

    PubMed  PubMed Central  Google Scholar 

  7. Leo P, McCrea M. Epidemiology—translational research in traumatic brain injury. In: Laskowitz D, Grant G, editors. Translational research in traumatic brain injury. Boca Raton: CRC Press; 2016.

    Google Scholar 

  8. Crompton EM, Lubomirova I, Cotlarciuc I, et al. Meta-analysis of therapeutic hypothermia for traumatic brain injury in adult and pediatric patients. Crit Care Med. 2017;45(4):575–83.

    PubMed  Google Scholar 

  9. Rosario BL, Horvat CM, Wisniewski SR, et al. Presenting characteristics associated with outcome in children with severe traumatic brain injury: a secondary analysis from a randomized, controlled trial of therapeutic hypothermia. Pediatr Crit Care Med. 2018;19(10):957–64.

    PubMed  PubMed Central  Google Scholar 

  10. Arrich J, Holzer M, Havel C, Müllner M, Herkner H. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database Syst Rev. 2016;2:CD004128.

    PubMed  Google Scholar 

  11. Fox J, Vu E, Doyle-Waters M, et al. Prophylactic hypothermia for traumatic brain injury: a quantitative systematic review. CJEM. 2010;12:355–64.

    PubMed  Google Scholar 

  12. Callaway CW, Donnino MW, Fink EL, et al. Part 8: post-cardiac arrest care 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18):S465–82.

    PubMed  PubMed Central  Google Scholar 

  13. Bacher A, Kwon JY, Zornow MH. Effects of temperature on cerebral tissue oxygen tension, carbon dioxide tension, and pH during transient global ischemia in rabbits. Anesthesiology. 1998;88(2):403–9.

    CAS  PubMed  Google Scholar 

  14. Frati A, Cerretani D, Fiaschi A, et al. Diffuse axonal injury and oxidative stress: a comprehensive review. Int J Mol Sci. 2017;18(12):E2600.

    PubMed  Google Scholar 

  15. Krech J, Tong G, Wowro S, et al. Moderate therapeutic hypothermia induces multimodal protective effects in oxygen-glucose deprivation/reperfusion injured cardiomyocytes. Mitochondrion. 2017;35:1–10.

    CAS  PubMed  Google Scholar 

  16. Askalan R, Wang C, Shi H, et al. The effect of postischemic hypothermia on apoptotic cell death in the neonatal rat brain. Dev Neurosci. 2011;33(3–4):320–9.

    CAS  PubMed  Google Scholar 

  17. Boyko M, Kuts R, Gruenbaum BF, et al. The role of hypothermia in the regulation of blood glutamate levels in naive rats. J Neurosurg Anesthesiol. 2013;25(2):174–83.

    PubMed  Google Scholar 

  18. Globus MY, Busto R, Lin B, et al. Detection of free radical activity during transient global ischemia and recirculation: effects of intraischemic brain temperature modulation. J Neurochem. 1995;65(3):1250–6.

    CAS  PubMed  Google Scholar 

  19. Globus MY, Alonso O, Dietrich WD, et al. Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. J Neurochem. 1995;65(4):1704–11.

    CAS  PubMed  Google Scholar 

  20. Winfree CJ, Baker CJ, Connolly ES Jr, et al. Mild hypothermia reduces penumbral glutamate levels in the rat permanent focal cerebral ischemia model. Neurosurgery. 1996;38(6):1216–22.

    CAS  PubMed  Google Scholar 

  21. Lee BS, Jung E, Lee Y, et al. Hypothermia decreased the expression of heat shock proteins in neonatal rat model of hypoxic ischemic encephalopathy. Cell Stress Chaperones. 2017;22(3):409–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Ning XH, Chen SH, Xu CS, et al. Selected contribution: hypothermic protection of the ischemic heart via alterations in apoptotic pathways as assessed by gene array analysis. J Appl Physiol. 2002;92(5):2200–7.

    CAS  PubMed  Google Scholar 

  23. Kimura A, Sakurada S, Ohkuni H, et al. Moderate hypothermia delays proinflammatory cytokine production of human peripheral blood mononuclear cells. Crit Care Med. 2002;30(7):1499–502.

    CAS  PubMed  Google Scholar 

  24. Aibiki M, Maekawa S, Ogura S, et al. Effect of moderate hypothermia on systemic and internal jugular plasma IL-6 levels after traumatic brain injury in humans. J Neurotrauma. 1999;16(3):225–32.

    CAS  PubMed  Google Scholar 

  25. Schaller B, Graf R. Hypothermia and stroke: the pathophysiological background. Pathophysiology. 2003;10(1):7–35.

    CAS  PubMed  Google Scholar 

  26. Sato S, Takeda Y, Mizoue R, et al. Determination of the target temperature required to block increases in extracellular glutamate levels during intraischemic hypothermia. Ther Hypothermia Temp Manag. 2018;8(2):83–9.

    PubMed  Google Scholar 

  27. Dempsey RJ, Combs DJ, Maley ME, et al. Moderate hypothermia reduces postischemic edema development and leukotriene production. Neurosurgery. 1987;21(2):177–81.

    CAS  PubMed  Google Scholar 

  28. Neumar RW, Shuster M, Callaway CW, et al. Part 1: executive Summary: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 Suppl 2):S315–67.

    PubMed  Google Scholar 

  29. Krieger D, Yenari M. Therapeutic hypothermia for acute ischemic stroke: what do laboratory studies teach us? Stroke. 2004;35:1482–9.

    PubMed  Google Scholar 

  30. Polderman K. Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality. Part 1: indications and evidence. Intensive Care Med. 2004;30:556–75.

    PubMed  Google Scholar 

  31. Crossley S, Reid J, McLatchie R, et al. A systematic review of therapeutic hypothermia for adult patients following traumatic brain injury. Crit Care. 2014;18:R75.

    PubMed  PubMed Central  Google Scholar 

  32. Dumitrascu OM, Lamb J, Lyden PD. Still cooling after all these years: meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke. J Cereb Blood Flow Metab. 2016;36(7):1157–64.

    PubMed  PubMed Central  Google Scholar 

  33. Aiolfi A, Benjamin E, Khor D, et al. Brain trauma foundation guidelines for intracranial pressure monitoring: compliance and effect on outcome. World J Surg. 2017;41(6):1543–9.

    PubMed  Google Scholar 

  34. Peterson K, Carson S, Carney N. Hypothermia treatment for traumatic brain injury: a systematic review and meta-analysis. J Neurotrauma. 2008;25(1):62–71.

    PubMed  Google Scholar 

  35. Clifton G. Is keeping cool still hot? An update on hypothermia in brain injury. Curr Opinion Crit Care. 2004;10:116–9.

    Google Scholar 

  36. Bernard S, Jones B, Horne M. Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Annals Emerg Med. 1997;30:146–53.

    CAS  Google Scholar 

  37. Seule MA, Muroi C, Mink S, et al. Therapeutic hypothermia in patients with aneurysmal subarachnoid hemorrhage, refractory intracranial hypertension, or cerebral vasospasm. Neurosurgery. 2009;64(1):86–93.

    PubMed  Google Scholar 

  38. Cavaciu L, Allers M, Enblad P, et al. Intranasal selective brain cooling in pigs. Resuscitation. 2008;76:83–8.

    Google Scholar 

  39. Abou-Chebl A, Sung G, Barbut D, et al. Local brain temperature reduction through intranasal cooling with the RhinoChill device: preliminary safety data in brain-injured patients. Stroke. 2011;42(8):2164–9.

    PubMed  Google Scholar 

  40. Fazel Bakhsheshi M, Keenliside L, Lee TY. A novel selective cooling system for the brain: feasibility study in rabbits vs piglets. Med Exp. 2018;6(1):45.

    Google Scholar 

  41. Chava R, Zviman M, Raghavan MS, et al. Rapid induction of therapeutic hypothermia using transnasal high flow dry air. Ther Hypothermia Temp Manag. 2017;7(1):50–6.

    PubMed  PubMed Central  Google Scholar 

  42. Assis FR, Bigelow MEG, Chava R, et al. Efficacy and safety of transnasal CoolStat cooling device to induce and maintain hypothermia. Ther Hypothermia Temp Manag. 2019;9(2):108–17.

    PubMed  PubMed Central  Google Scholar 

  43. Sedlacik J, Kjørstad Å, Nagy Z, et al. Feasibility study of a novel high-flow cold air cooling protocol of the porcine brain using MRI temperature mapping. Ther Hypothermia Temp Manag. 2018;8(1):45–52.

    PubMed  Google Scholar 

  44. Westermaier T, Nickl R, Koehler S, et al. Selective brain cooling after traumatic brain injury: effects of three different cooling methods—case report. J Neurol Surg A Cent Eur Neurosurg. 2017;78(04):397–402.

    PubMed  Google Scholar 

  45. Hagioka S, Takeda Y, Takata K, Morita K. Nasopharyngeal cooling selectively and rapidly decreases brain temperature and attenuates neuronal damage, even if initiated at the onset of cardiopulmonary resuscitation in rats. Crit Care Med. 2003;31(10):2502–8.

    PubMed  Google Scholar 

  46. Trübel H, Herman P, Kampmann C, Novotny E, Hyder F. Selective pharyngeal brain cooling. Biomed Tech (Berl). 2003;48(11):298–300.

    Google Scholar 

  47. Yu T, Barbut D, Ristagno G, et al. Survival and neurological outcomes after nasopharyngeal cooling or peripheral vein cold saline infusion initiated during cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest. Crit Care Med. 2010;38(3):916–21.

    PubMed  Google Scholar 

  48. Busch H-J, Eichwede F, Födisch M, et al. Safety and feasibility of nasopharyngeal evaporative cooling in the emergency department setting in survivors of cardiac arrest. Resuscitation. 2010;81(8):943–9.

    PubMed  Google Scholar 

  49. de Paiva BLC, Bor-Seng-Shu E, Silva E, et al. Inducing brain cooling without core temperature reduction in pigs using a novel nasopharyngeal method: an effectiveness and safety study. Neurocrit Care. 2020;32(2):564–74.

    PubMed  Google Scholar 

  50. Covaciu L, Allers M, Enblad P, et al. Intranasal selective brain cooling in pigs. Resuscitation. 2008;76(1):83–8.

    CAS  PubMed  Google Scholar 

  51. Medtech Innovation Briefing [MIB4]. National Institute for Health and Care Excellence. The RhinoChill intranasal cooling system for reducing temperature after cardiac arrest | Guidance and guidelines, NICE [Internet]. 2014 [cited 2018 Nov 28]. https://www.nice.org.uk/advice/mib4.

  52. Poli S, Purrucker J, Priglinger M, et al. Safety evaluation of nasopharyngeal cooling (RhinoChill®) in stroke patients: an observational study. Neurocrit Care. 2014;20(1):98–105.

    PubMed  Google Scholar 

  53. Elliott DC. Frostbite of the mouth: a case report. Mil Med. 1991;156(1):18–9.

    CAS  PubMed  Google Scholar 

  54. Divya V, Saravanakarthikeyan B. Intraoral frostbite and Leidenfrost effect. Aus Dent J. 2018;63(3):382–4.

    Google Scholar 

  55. Vega C, Conde MM, McBride C, et al. Heat capacity of water: a signature of nuclear quantum effects. J Chem Phys. 2010;132(4):046101.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful for the assistance of Prof. Dr. Feres Chaddad, head of the of neurosurgery department at the Universidade Federal de São Paulo, and also for his guidance during this research. We are also immensely grateful to Fabio Lacreta, Murilo Barbosa, and Ronaldo Escudeiro for their assistance with equipment and with the patients’ records. It is with gratitude that we acknowledge their contributions. A contract research organization (EUROTRIALS™, Lisbon, Portugal) was responsible for monitoring, data management, statistical analysis, and preparation of all study reports. The authors would also like to thank all study participants and their families and all the multidisciplinary team of the emergency department and intensive care unit of the São Paulo Hospital.

Funding

This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001.

Author information

Authors and Affiliations

  1. Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, Av. Moema 170, Cj. 83. Moema, São Paulo, SP, 04077-020, Brazil

    Raphael Einsfeld Simões Ferreira, Gisele Sampaio Silva, Conrado Feisthauer Silveira & Ricardo Silva Centeno

  2. Serviço de Terapia Intensiva, Hospital Santa Paula, São Paulo, Brazil

    Bernardo Lembo Conde de Paiva

  3. Departamento de Anestesiologia, Dor e Terapia Intensiva, Universidade Federal de São Paulo, São Paulo, Brazil

    Flávio Geraldo Rezende de Freitas & Flávia Ribeiro Machado

  4. Serviço de Otorrinolaringologia UNIFESP e Serviço de Otorrinolaringologia, Hospital Santa Paula, São Paulo, Brazil

    Rafael Mônaco Raposo

Authors
  1. Raphael Einsfeld Simões Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bernardo Lembo Conde de Paiva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Flávio Geraldo Rezende de Freitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Flávia Ribeiro Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gisele Sampaio Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rafael Mônaco Raposo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Conrado Feisthauer Silveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ricardo Silva Centeno
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RESF, BLCP, FGRF, FRM, GSS, RMR, CFS, and RSC contributed to protocol/project development and manuscript writing/editing other; RESF, BLCP, GSS, RMR, and CFS helped in data collection or management.

Corresponding author

Correspondence to Raphael Einsfeld Simões Ferreira.

Ethics declarations

Conflict of interest

Dr. Einsfeld Simões Ferreira and Dr. Lembo Conde de Paiva received grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES) during the conduct of the study. In addition, Dr. Einsfeld Simões Ferreira and Dr. Lembo Conde de Paiva have a patented catheter system and method for target body temperature management licensed to Floe Ind Com e Importação de equipamentos. Bernardo Paiva and Raphael Einsfeld are founders of the company which developed the investigational device.

Ethical Approval

The study protocol and associated documents were submitted to the Institutional Review Board of the Federal University of São Paulo, and the study protocol was approved by the Institutional Review Board.

Informed Consent

Written informed consent was obtained from all patients.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ferreira, R.E.S., de Paiva, B.L.C., de Freitas, F.G.R. et al. Efficacy and Safety of a Nasopharyngeal Catheter for Selective Brain Cooling in Patients with Traumatic Brain Injury: A Prospective, Non-randomized Pilot Study. Neurocrit Care 34, 581–592 (2021). https://doi.org/10.1007/s12028-020-01052-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-020-01052-9

Keywords

search

Navigation