Skip to main content

Advertisement

SpringerLink
Log in

The Physiologic Effects of Indomethacin Test on CPP and ICP in Severe Traumatic Brain Injury (sTBI)

  • Original Article
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background

Refractory intracranial hypertension (RICH) is associated with high mortality in severe traumatic brain injury (sTBI). Indomethacin (INDO) can decrease intracranial cerebral pressure (ICP) improving cerebral pressure perfusion (CPP). Our aim was to determine modifications in ICP and CPP following INDO in RICH secondary to sTBI.

Methods

INDO was administered in a loading dose (0.8 mg/kg/15 min), followed by continuous 2-h infusion period (0.5 mg/kg/h). Clinical outcome was assessed at 30 days according to Glasgow Outcome Scale (GOS). Differences in ICP and CPP values were assessed using repeated-measures ANOVA. Receiver operating characteristic curve (AUC) was used for discrimination in predicting 30-day survival and good functional outcome (GOS 4 or 5). Analysis of INDO safety profile was also conducted.

Results

Thirty-two patients were included. Median GCS score was 6 (interquartile range: 4–7). The most frequent CT finding was the evacuated mass lesion (EML) according to Marshall classification (28.1 %). Mortality rate was 34.4 %. Within 15 min of INDO infusion, ICP decreased (Δ%: −54.6 %; P < 0.0001), CPP increased (Δ%: +44.0 %; P < 0.0001), and the remaining was stable during the entire infusion period. Patients with good outcome (n = 12) showed a greater increase of CPP during INDO test (P = 0.028). CPP response to INDO test discriminated moderately well surviving patients (AUC = 0.751; P = 0.0098) and those with good functional recovery (AUC = 0.763; P = 0.0035) from those who died and from those with worse functional outcome, respectively. No adverse events were observed.

Conclusions

INDO appears effective in reducing ICP and improving CPP in RICH. INDO test could be a useful tool in identifying RICH patients with favorable outcome. Future studies are needed.

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
Fig. 4

Similar content being viewed by others

References

  1. Zammit C, Knight WA. Severe traumatic brain injury in adults. Emerg Med Pract. 2013;15:1–28.

    PubMed  Google Scholar 

  2. Mauritz W, Wilbacher I, Majdan M, et al. Epidemiology, treatment and outcome of patients after severe traumatic brain injury in European regions with different economic status. Eur J Public Health. 2008;18:575–80.

    Article  PubMed  Google Scholar 

  3. Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol. 2008;7:728–41.

    Article  PubMed  Google Scholar 

  4. Rutland-Brown W, Langlois JA, Thomas KE, Xi YL. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil. 2006;21:544–8.

    Article  PubMed  Google Scholar 

  5. Miller JD, Becker DP, Ward JD, Sullivan HG, Adams WE, Rosner MJ. Significance of intracranial hypertension in severe head injury. J Neurosurg. 1977;47:503–16.

    Article  CAS  PubMed  Google Scholar 

  6. Rangel-Castilla L, Gopinath S, Robertson CS. Management of intracranial hypertension. Neurol Clin. 2008;26:521–41.

    Article  PubMed  Google Scholar 

  7. Meyer MJ, Megyesi J, Meythaler J, et al. Acute management of acquired brain injury part I: an evidence-based review of non-pharmacological interventions. Brain Inj. 2010;24:694–705.

    Article  PubMed  Google Scholar 

  8. Meyer MJ, Megyesi J, Meythaler J, et al. Acute management of acquired brain injury part II: an evidence-based review of pharmacological interventions. Brain Inj. 2010;24:706–21.

    Article  PubMed  Google Scholar 

  9. Biestro AA, Alberti RA, Soca AE, Cancela M, Puppo CB, Borovich B. Use of indomethacin in brain-injured patients with cerebral perfusion pressure impairment: preliminary report. J Neurosurg. 1995;83:627–30.

    Article  CAS  PubMed  Google Scholar 

  10. Clemmesen JO, Hansen BA, Larsen FS. Indomethacin normalizes intracranial pressure in acute liver failure: a twenty-three-year-old woman treated with indomethacin. Hepatology. 1997;26:1423–5.

    Article  CAS  PubMed  Google Scholar 

  11. Imberti R, Fuardo M, Bellinzona G, Pagani M, Langer M. The use of indomethacin in the treatment of plateau waves: effects on cerebral perfusion and oxygenation. J Neurosurg. 2005;102:455–9.

    Article  CAS  PubMed  Google Scholar 

  12. Jensen K, Ohrstrom J, Cold GE, Astrup J. The effects of indomethacin on intracranial pressure, cerebral blood flow and cerebral metabolism in patients with severe head injury and intracranial hypertension. Acta Neurochir (Wien). 1991;108:116–21.

    Article  CAS  Google Scholar 

  13. Godoy DA, Rabinstein AA, Biestro A, Ainslie PN, Di Napoli M. Effects of indomethacin test on intracranial pressure and cerebral hemodynamics in patients with refractory intracranial hypertension: a feasibility study. Neurosurgery. 2012;71:245–57 discussion 57-8.

    Article  PubMed  Google Scholar 

  14. Rasmussen M. Treatment of elevated intracranial pressure with indomethacin: friend or foe? Acta Anaesthesiol Scand. 2005;49:341–50.

    Article  CAS  PubMed  Google Scholar 

  15. Roberts RG, Redman JW. Indomethacin: a review of its role in the management of traumatic brain injury. Crit Care Resusc. 2002;4:271–80.

    CAS  PubMed  Google Scholar 

  16. Slavik RS, Rhoney DH. Indomethacin: a review of its cerebral blood flow effects and potential use for controlling intracranial pressure in traumatic brain injury patients. Neurol Res. 1999;21:491–9.

    CAS  PubMed  Google Scholar 

  17. Dahl B, Bergholt B, Cold GE, et al. CO(2) and indomethacin vasoreactivity in patients with head injury. Acta Neurochir (Wien). 1996;138:265–73.

    Article  CAS  Google Scholar 

  18. Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet. 1974;2:81–4.

    Article  CAS  PubMed  Google Scholar 

  19. Marshall LF, Marshall SB, Klauber MR, et al. A new classification of head injury based on computerized tomography. Special Supplements. 1991;75:S14–20.

    Google Scholar 

  20. Foundation BT. Guidelines for the management of severe traumatic brain injury. J Neurotrauma. 2007;24:S1–106.

    Article  Google Scholar 

  21. TBT Foundation. The American Association of Neurological Surgeons. The Joint Section on Neurotrauma and Critical Care. Guidelines for cerebral perfusion pressure. J Neurotrauma. 2000;17:507–11.

    Article  Google Scholar 

  22. Puppo C, Lopez L, Farina G, et al. Indomethacin and cerebral autoregulation in severe head injured patients: a transcranial Doppler study. Acta Neurochir (Wien). 2007;149:139–49 discussion 49.

    Article  CAS  Google Scholar 

  23. Wilson JT, Pettigrew LE, Teasdale GM. Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: guidelines for their use. J Neurotrauma. 1998;15:573–85.

    Article  CAS  PubMed  Google Scholar 

  24. Jensen K, Kjaergaard S, Malte E, Bunemann L, Therkelsen K, Knudsen F. Effect of graduated intravenous and standard rectal doses of indomethacin on cerebral blood flow in healthy volunteers. J Neurosurg Anesthesiol. 1996;8:111–6.

    Article  CAS  PubMed  Google Scholar 

  25. Rasmussen M, Tankisi A, Cold GE. The effects of indomethacin on intracranial pressure and cerebral haemodynamics in patients undergoing craniotomy: a randomised prospective study. Anaesthesia. 2004;59:229–36.

    Article  CAS  PubMed  Google Scholar 

  26. Harrigan MR, Tuteja S, Neudeck BL. Indomethacin in the management of elevated intracranial pressure: a review. J Neurotrauma. 1997;14:637–50.

    Article  CAS  PubMed  Google Scholar 

  27. Upton RN, Rasmussen M, Grant C, Martinez AM, Cold GE, Ludbrook GL. Pharmacokinetics and pharmacodynamics of indomethacin: effects on cerebral blood flow in anaesthetized sheep. Clin Exp Pharmacol Physiol. 2008;35:317–23.

    Article  CAS  PubMed  Google Scholar 

  28. Eriksson S, Hagenfeldt L, Law D, Patrono C, Pinca E, Wennmalm A. Effect of prostaglandin synthesis inhibitors on basal and carbon dioxide stimulated cerebral blood flow in man. Acta Physiol Scand. 1983;117:203–11.

    Article  CAS  PubMed  Google Scholar 

  29. Pickard J, Tamura A, Stewart M, McGeorge A, Fitch W. Prostacyclin, indomethacin and the cerebral circulation. Brain Res. 1980;197:425–31.

    Article  CAS  PubMed  Google Scholar 

  30. Pickard JD, MacDonell LA, Mackenzie ET, Harper AM. Prostaglandin-induced effects in the primate cerebral circulation. Eur J Pharmacol. 1977;43:343–51.

    Article  CAS  PubMed  Google Scholar 

  31. Quintana A, Raczka E, Quintana MA. Effects of indomethacin and diclofenac on cerebral blood flow in hypercapnic conscious rats. Eur J Pharmacol. 1988;149:385–8.

    Article  CAS  PubMed  Google Scholar 

  32. Markus HS, Vallance P, Brown MM. Differential effect of three cyclooxygenase inhibitors on human cerebral blood flow velocity and carbon dioxide reactivity. Stroke. 1994;25:1760–4.

    Article  CAS  PubMed  Google Scholar 

  33. Weigert G, Berisha F, Resch H, Karl K, Schmetterer L, Garhofer G. Effect of unspecific inhibition of cyclooxygenase by indomethacin on retinal and choroidal blood flow. Invest Ophthalmol Vis Sci. 2008;49:1065–70.

    Article  PubMed  Google Scholar 

  34. Jensen K, Freundlich M, Bunemann L, Therkelsen K, Hansen H, Cold GE. The effect of indomethacin upon cerebral blood flow in healthy volunteers. The influence of moderate hypoxia and hypercapnia. Acta Neurochir (Wien). 1993;124:114–9.

    Article  CAS  Google Scholar 

  35. Bruhn H, Fransson P, Frahm J. Modulation of cerebral blood oxygenation by indomethacin: MRI at rest and functional brain activation. J Magn Reson Imaging. 2001;13:325–34.

    Article  CAS  PubMed  Google Scholar 

  36. Gjedde A, Johannsen P, Cold GE, Ostergaard L. Cerebral metabolic response to low blood flow: possible role of cytochrome oxidase inhibition. J Cereb Blood Flow Metab. 2005;25:1183–96.

    Article  CAS  PubMed  Google Scholar 

  37. Godoy DA, Biestro A, Puppo C. Does indomethacin cause cerebral ischemia? Acta Anaesthesiol Scand. 2005;49:1577–8.

    Article  CAS  PubMed  Google Scholar 

  38. Schumann P, Touzani O, Young AR, Verard L, Morello R, MacKenzie ET. Effects of indomethacin on cerebral blood flow and oxygen metabolism: a positron emission tomographic investigation in the anaesthetized baboon. Neurosci Lett. 1996;220:137–41.

    Article  PubMed  Google Scholar 

  39. St Lawrence KS, Ye FQ, Lewis BK, Frank JA, McLaughlin AC. Measuring the effects of indomethacin on changes in cerebral oxidative metabolism and cerebral blood flow during sensorimotor activation. Magn Reson Med. 2003;50:99–106.

    Article  CAS  PubMed  Google Scholar 

  40. Ling GS, Neal CJ. Maintaining cerebral perfusion pressure is a worthy clinical goal. Neurocrit Care. 2005;2:75–81.

    Article  PubMed  Google Scholar 

  41. Stocchetti N, Chieregato A, De Marchi M, Croci M, Benti R, Grimoldi N. High cerebral perfusion pressure improves low values of local brain tissue O2 tension (PtiO2) in focal lesions. Acta Neurochirurgica Supplement. 1998;71:162–5.

    CAS  PubMed  Google Scholar 

  42. Marin-Caballos AJ, Murillo-Cabezas F, Cayuela-Dominguez A, et al. Cerebral perfusion pressure and risk of brain hypoxia in severe head injury: a prospective observational study. Crit Care. 2005;9:R670–6.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Johnston AJ, Steiner LA, Coles JP, et al. Effect of cerebral perfusion pressure augmentation on regional oxygenation and metabolism after head injury. Crit Care Med. 2005;33:189–95 discussion 255-7.

    Article  PubMed  Google Scholar 

  44. Rosner MJ, Rosner SD, Johnson AH. Cerebral perfusion pressure: management protocol and clinical results. J Neurosurg. 1995;83:949–62.

    Article  CAS  PubMed  Google Scholar 

  45. Nelson DW, Thornquist B, MacCallum RM, et al. Analyses of cerebral microdialysis in patients with traumatic brain injury: relations to intracranial pressure, cerebral perfusion pressure and catheter placement. BMC Med. 2011;9:21.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Tofteng F, Larsen FS. The effect of indomethacin on intracranial pressure, cerebral perfusion and extracellular lactate and glutamate concentrations in patients with fulminant hepatic failure. J Cereb Blood Flow Metab. 2004;24:798–804.

    Article  CAS  PubMed  Google Scholar 

  47. Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011;364:1493–502.

    Article  CAS  PubMed  Google Scholar 

  48. Kamel H, Navi BB, Nakagawa K, Hemphill JC 3rd, Ko NU. Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: a meta-analysis of randomized clinical trials. Crit Care Med. 2011;39:554–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None for all authors

Author information

Authors and Affiliations

  1. Neurocritical Care Unit, Sanatorio Pasteur, San Fernando del Valle de Catamarca, Argentina

    Daniel Agustín Godoy, Erica Alvarez & Ruben Manzi

  2. Intensive Care Unit, Hospital San Juan Bautista, Chacabuco 675, K 4700, San Fernando del Valle de Catamarca, Argentina

    Daniel Agustín Godoy

  3. Intensive Care Unit, Hospital Municipal Leonidas Lucero, Bahia Blanca, Argentina

    Gustavo Piñero

  4. Neurological Service, San Camillo de’ Lellis General Hospital, Rieti, Italy

    Mario Di Napoli

  5. Neurological Section, SMDN-Center for Cardiovascular Medicine and Cerebrovascular Disease Prevention, Via Trento, 41, 67039, Sulmona, AQ, Italy

    Mario Di Napoli

Authors
  1. Daniel Agustín Godoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erica Alvarez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ruben Manzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gustavo Piñero
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mario Di Napoli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Daniel Agustín Godoy or Mario Di Napoli.

Additional information

This paper was present in part (poster format) and was distinguished in the 10th Annual Meeting of Neurocritical Care Society, Denver, Colorado, USA. October 4–7, 2012. Neurocrit Care 2012; 17: S32.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 19 kb)

Supplementary material 2 (DOCX 55 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Godoy, D.A., Alvarez, E., Manzi, R. et al. The Physiologic Effects of Indomethacin Test on CPP and ICP in Severe Traumatic Brain Injury (sTBI). Neurocrit Care 20, 230–239 (2014). https://doi.org/10.1007/s12028-013-9924-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-013-9924-0

Keywords

Search

Navigation