Skip to main content
SpringerLink
Log in

THAM for Control of ICP

  • Review
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Our goal was to perform a systematic review of the literature on the use of tromethamine (THAM) and its effects on intracranial pressure (ICP) in patients with neurological illness. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to February 2014), reference lists of relevant articles, and gray literature were searched. Two reviewers independently identified all manuscripts pertaining to the administration of THAM in human patients that recorded effects on ICP. Secondary outcomes of effect on cerebral perfusion pressure, mean arterial pressure, patient outcome, and adverse effects were recorded. Two reviewers independently extracted data including population characteristics and treatment characteristics. The strength of evidence was adjudicated using both the Oxford and GRADE methodology. Our search strategy produced a total 2,268 citations. Twelve articles, 9 manuscripts, and 3 meeting proceedings were considered for the review with all utilizing THAM while documenting ICP in neurosurgical patients. All studies were prospective. Across all studies, there were a total of 488 patients studied, with 263 receiving THAM and 225 serving as controls in a variety of heterogeneous studies. All but one study documented a decrease in ICP with THAM administration, with both bolus and continuous infusions. One study documented a reduction in cerebral perfusion pressure. No significant renal dysfunction, hepatocellular injury, or hypoglycemia were reported. Three prospective randomized control trials displayed trends to improved outcome in severe traumatic brain injury (TBI) patients with THAM administration. There currently exists Oxford level 2b, GRADE B evidence to support that THAM reduces ICP in the TBI and malignant ischemic infarct population, with minimal side effects. The literature suggests THAM may be useful for ICP reduction in certain cases, though the safety of the compound in these circumstances is still unclear. Further prospective study is warranted.

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

Similar content being viewed by others

References

  1. DeSalles AAF, Kontos HA, Becker DP, Yang MS, Ward JD, Moulton R, et al. Prognostic significance of ventricular CSF lactic acidosis in severe head injury. J Neurosurg. 1986;65:615–24.

    Article  PubMed  CAS  Google Scholar 

  2. Yao H, Haddad GG. Calcium and pH homeostasis in neurons during hypoxia and ischemia. Cell Calcium. 2004;36:247–55.

    Article  PubMed  CAS  Google Scholar 

  3. Staub F, Baethmann A, Peters J, Weigt H, Kempski O. Effects of lactacidosis on glial cell volume and viability. J Cereb Blood Flow Metab. 1990;10:866–76.

    Article  PubMed  CAS  Google Scholar 

  4. Staub F, Winkler A, Peters J, Kempski O, Kachel V, Baethmann A. Swelling, acidosis, and irreversible damage of glial cells from exposure to arachidonic acid in vitro. J Cereb Blood Flow Metab. 1994;14:1030–9.

    Article  PubMed  CAS  Google Scholar 

  5. Tran ND, Kim S, Vincent HK, Rodriguez A, Hinton DR, Bullock MR, et al. Aquaporin-1-mediated cerebral edema following traumatic brain injury: effects of acidosis and corticosteroid administration. J Neurosurg. 2010;112:1095–104.

    Article  PubMed  CAS  Google Scholar 

  6. Nahas GG, Sutin KM, Fermon C, Streat S, Wikland L, Wahlander S, et al. Guidelines for the treatment of acidemia with THAM. Drugs. 1998;55(2):191–224.

    Article  PubMed  CAS  Google Scholar 

  7. Bardutzky J, Schwab S. Antiedema therapy in ischemic stroke. Stroke. 2007;38:3084–94.

    Article  PubMed  CAS  Google Scholar 

  8. Jantzen JPAH. Prevention and treatment of intracranial hypertension. Best Pract Res Clin Anaesthesiol. 2007;21(4):517–38.

    Article  PubMed  Google Scholar 

  9. Juttler E, Schellinger PD, Aschoff A, Zweckberger K, Unterberg A, Hacke W. Clinical review: therapy for refractory intracranial hypertension in ischemic stroke. Crit Care. 2007;11(5):231.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Maas AIR, Roozenbeek B, Manley GT. Clinical trials in traumatic brain injury: past experience and current developments. Neurotherapeutics. 2009;7(1):115–26.

    Article  Google Scholar 

  11. Tresguerres M, Buck J, Levin LR. Physiological carbon dioxide, bicarbonate, and pH sensing. Pflugers Arch. 2010;460(6):953–64.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Marmarou A, Holdaway R, Ward JD, Yoshida K, Choi SC, Muizelaar JP, et al. Traumatic brain tissue acidosis: experimental and clinical studies. Acta Neurochir. 1993;57(Suppl):160–7.

    CAS  Google Scholar 

  13. Dos SD, Lande AJ, Lillihei CW. Hypercapneic cerebrospinal fluid hypertension: a pharmacological study. Surgery. 1968;63(5):788–99.

    PubMed  CAS  Google Scholar 

  14. Duthie SE, Goulin GD, Zornow MH, Scheller MS, Peterson BM. Effects of THAM and sodium bicarbonate on intracranial pressure and mean arterial pressure in an animal model of focal cerebral injury. J Neurosurg Anesthesiol. 1994;6(3):201–8.

    Article  PubMed  CAS  Google Scholar 

  15. Rosner MJ, Becker DP. Experimental brain injury: successful therapy with the weak base, tromethamine. J Neurosurg. 1984;60:961–71.

    Article  PubMed  CAS  Google Scholar 

  16. Chang W, Li Q, Cao H. Therapeutic effect of THAM in lactic acidosis of severe brain injury. Chung-Hua Wai Ko Tsa Chih [Chinese Journal of Surgery]. 1996;34(6):364–7.

    CAS  Google Scholar 

  17. Fox JL. Reduction of intracranial pressure by THAM during brain surgery. Med Ann Dist Columbia. 1964;33:269–73.

    PubMed  CAS  Google Scholar 

  18. Gaab MR, Seegers K, Smedema RJ, Heissler HE, Goetz C. Acta Neurochir Suppl. 1990;51:320–3.

    PubMed  CAS  Google Scholar 

  19. Keller E, Steiner T, Fandino J, Schwab S, Hacke W. Jugular venous oxygen saturation thresholds in trauma patients may not extrapolate to ischemic stroke patients. J Neurosurg Anesthesiol. 2002;14(2):130–6.

    Article  PubMed  Google Scholar 

  20. Muizelaar JP, Marmarou A, Ward JD, Kontos HA, Choi SC, Becker DP, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg. 1991;75:731–9.

    Article  PubMed  CAS  Google Scholar 

  21. Pfenninger E, Linder KH, Ahnefeld FW. Use of THAM (tris-hydroxymethylaminomethan) for rapid control of high intracranial pressure in severe head injury. Anaesthesist. 1989;38:189–92.

    PubMed  CAS  Google Scholar 

  22. Rosner MJ, Elias KG, Coley I. Prospective, randomized trial of THAM therapy in severe brain injury: preliminary results. In: Hoff JT, BetzI AL, editors. Intracranial pressure VII. Berlin: Springer-Verlag; 1989. p. 611–5.

    Chapter  Google Scholar 

  23. Schwab S, Schellinger P, Aschoff A, Albert F, Spranger M, Hacke W. Epidurale hirndruckmessung und hirndrucktherapie bei “malignem” mediainfarkt. Nervenarzt. 1996;67:659–66.

    Article  PubMed  CAS  Google Scholar 

  24. Steiner T, Pilz J, Schellinger P, Wirtz R, Friederichs V, Aschoff A, et al. Multimodal online monitoring in middle cerebral artery territory stroke. Stroke. 2001;32:2500–6.

    Article  PubMed  CAS  Google Scholar 

  25. Ward JD, Choi S, Marmarou A, Moulton R, Muizelaar JP, DeSalles A, et al. Effect of prophylactic hyperventilation on outcome in patients with severe head injury. In: Hoff JT, BetzI AL, editors. Intracranial pressure VII. Berlin: Springer-Verlag; 1989. p. 630–3.

    Chapter  Google Scholar 

  26. Wolf AL, Levi L, Marmarou A, Ward JD, Muizelaar PJ, Choi S, et al. Effect of THAM on outcome in severe head injury: a randomized prospective trial. J Neurosurg. 1993;78:54–9.

    Article  PubMed  CAS  Google Scholar 

  27. Wolf AL, Levi L, Marmarou A, Ward JD, Rigamonti D, Muizelaar JP, et al. A prospective randomized clinical trial of tromethamine (THAM) and its effects on outcome in severe head injury. In: Avezaat CJJ, et al., editors. Intracranial pressure VIII. Berlin: Springer-Verlag; 1993. p. 615–9.

    Chapter  Google Scholar 

  28. Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0. http://www.handbook.cochrane.org. Accessed 25 Oct 2013.

  29. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analysis: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.

    Article  PubMed  Google Scholar 

  30. Phillips B, Ball C, Sackett D, Straus S, Haynes B, Dawes M. Oxford Centre for evidence-based medicine levels of evidence version 2009. http://www.cebm.net/?o=1025. Accessed Oct 2013.

  31. Guyatt GH, Oxman AD, Vist G, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. Rating quality of evidence and strength of recommendations GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–6.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ, et al. Rating quality of evidence and strength of recommendations: what is “quality of evidence” and why is it important to clinicians? BMJ. 2008;336(7651):995–8.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Schünemann HJ, Oxman AD, Brozek J, Glasziou P, Jaeschke R, Vist GE, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336(7653):1106–10.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Guyatt GH, Oxman AD, Kunz R, Jaeschke R, Helfand M, Liberati A, et al. Rating quality of evidence and strength of recommendations: incorporating considerations of resources use into grading recommendations. BMJ. 2008;336(7654):1170–3.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Guyatt GH, Oxman AD, Kunz R, Falck-Ytter Y, Vist GE, Liberati A, et al. Rating quality of evidence and strength of recommendations: going from evidence to recommendations. BMJ. 2008;336(7652):1049–51.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Jaeschke R, Guyatt GH, Dellinger P, Schünemann H, Levy MM, Kunz R, et al. Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive. BMJ. 2008;337:a744.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Neurosurgery, Department of Surgery, University of Manitoba, Winnipeg, Canada

    F. A. Zeiler & M. West

  2. Section of Neurocritical Care, Montreal Neurological Institute, McGill University, Montreal, Canada

    F. A. Zeiler & J. Teitelbaum

  3. Section of Neurology, Montreal Neurological Institute, McGill University, Montreal, Canada

    J. Teitelbaum

  4. Section of Critical Care Medicine, Department of Medicine, University of Manitoba, Winnipeg, Canada

    L. M. Gillman

  5. Section of General Surgery, Department of Surgery, University of Manitoba, Winnipeg, Canada

    L. M. Gillman

Authors
  1. F. A. Zeiler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Teitelbaum
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. M. Gillman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. West
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F. A. Zeiler.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 24 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zeiler, F.A., Teitelbaum, J., Gillman, L.M. et al. THAM for Control of ICP. Neurocrit Care 21, 332–344 (2014). https://doi.org/10.1007/s12028-014-9978-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-014-9978-7

Keywords

Search

Navigation