Neurocritical Care

, Volume 22, Issue 3, pp 437–449 | Cite as

Indomethacin for Control of ICP

  • Nick Sader
  • Frederick A. Zeiler
  • Lawrence M. Gillman
  • Michael West
  • Colin J. Kazina
Review Article


Our goal was to perform a systematic review of the literature on the use of indomethacin and its effects on intracranial pressure (ICP) in patients with neurological illness. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to July 2014), reference lists of relevant articles, and gray literature were searched. Two reviewers independently identified all manuscripts utilizing the following inclusion and exclusion criteria. Inclusion criteria: Humans, prospective studies (five or more patients), documented ICP response to indomethacin, and English. Exclusion criteria: non-English, retrospective studies, no documentation of ICP response to indomethacin, and animal studies. A two-tier filter of references was conducted. First, we screened manuscripts by title and abstract. Second, those references passing the first filter were pulled, and the full manuscript was checked to see if it matched the criteria for inclusion. 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 of 208 citations. Twelve original articles, 10 manuscripts, and 2 meeting proceeding, were considered for the review with all utilizing indomethacin, while documenting ICP in neurological patients. All studies were prospective. Across all studies, there were a total of 177 patients studied, with 152 receiving indomethacin and 25 serving as controls in a variety of heterogeneous studies. All but one study documented a decrease in ICP with indomethacin administration, with both bolus and continuous infusions. No significant complications were described. There currently exists Oxford level 2b, GRADE C evidence to support that indomethacin reduces ICP in the severe TBI population. Similar conclusions in other populations cannot be made at this time. Comments on its impact, on patient outcome, and side effects cannot be made given the available data. At this time, indomethacin for ICP control remains experimental and further prospective study is warranted.


Indomethacin ICP Intracranial pressure 

Supplementary material

12028_2014_88_MOESM1_ESM.doc (296 kb)
Supplementary material 1 (DOC 295 kb)


  1. 1.
    Stocchetti N, Maas AIR. Traumatic intracranial hypertension. N Engl J Med. 2014;370:2121–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Wilson JA, Branch CL Jr. Neuromuscular blockade in head-injured patients with increased intra-cranial pressure continuous versus intermittent use. J Neurosurg Anesthesiol. 1994;6(2):139–41.CrossRefPubMedGoogle Scholar
  3. 3.
    Georgiou AP, Manara AR. Role of therapeutic hypothermia in improving outcome after traumatic brain injury: a systematic review. Br J Anaesth. 2013;110(3):357–67.CrossRefPubMedGoogle Scholar
  4. 4.
    Sandestig A, Romner B, Grände PO. Therapeutic hypothermia in children and adults with severe traumatic brain injury. Therapeutic Hypothermia and Temperature Management. 2014;4(1):10–20.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Zeiler FA, Teitelbaum J, Gillman LM, et al. THAM for control of ICP. Neurocrit Care. 2014;21(2):332–44.CrossRefPubMedGoogle Scholar
  6. 6.
    Roberts I, Sydenham E. Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev. 2012;12:CD000033.PubMedGoogle Scholar
  7. 7.
    Bullock MR, Chesnut R, Ghajar J, et al. Surgical management of acute epidural hematomas. Neurosurgery. 2006;58(Suppl 3):S7–15.PubMedGoogle Scholar
  8. 8.
    Bullock MR, Chesnut R, Ghajar J, et al. Surgical management of acute subdural hematomas. Neurosurgery. 2006;58(Suppl 3):S16–24.PubMedGoogle Scholar
  9. 9.
    Bullock MR, Chesnut R, Ghajar J, et al. Surgical management of traumatic parenchymal lesions. Neurosurgery. 2006;58(Suppl 3):S25–46.PubMedGoogle Scholar
  10. 10.
    Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med. 2011;364(16):1493–502.CrossRefPubMedGoogle Scholar
  11. 11.
    Appelboom G, Piazza M, Zoller SD, et al. Clinical trials in decompressive craniectomy after severe diffuse traumatic brain injury. World Neurosurg. 2013;80(5):e153–5.CrossRefPubMedGoogle Scholar
  12. 12.
    El Ahmadieh TY, Adel JG, El Tecle NE, et al. Surgical treatment of elevated intracranial pressure: decompressive craniectomy and intracranial pressure monitoring. Neurosurg Clin N Am. 2013;24(3):375–91.CrossRefPubMedGoogle Scholar
  13. 13.
    Biestro AA, Alberti RA, Soca AE, et al. Use of indomethacin in brain-injured patients with cerebral perfusion pressure impairment: preliminary report. J Neurosurg. 1995;83(4):627–30.CrossRefPubMedGoogle Scholar
  14. 14.
    Bundgaard H, Jensen K, Cold GE, et al. Effects of perioperative indomethacin on intracranial pressure, cerebral blood flow, and cerebral metabolism in patients subjected to craniotomy for cerebral tumors. J Neurosurg Anesthesiol. 1996;8(4):273–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Dahl B, Bergholt B, Cold GE, et al. CO(2) and indomethacin vasoreactivity in patients with head injury. Acta Neurochir (Wien). 1996;138(3):265–73.CrossRefGoogle Scholar
  16. 16.
    De Dayne C, Vandekerckhove T, Decruyenaere J, et al. Use of indomethacin for the treatment of intracranial hypertension in severe head injury. Intensiv Care Med. 1995;21(Suppl 1):S153.Google Scholar
  17. 17.
    Förderreuther S, Straube A. Indomethacin reduces CSF pressure in intracranial hypertension. Neurology. 2000;55:1043–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Godoy DA, Pinero GR, Di Napoli M, et al. Indomethacin infusion improves cerebral perfusion pressure and reduces intracranial hypertension in refractory cases of severe traumatic brain injury. Neurocrit Care. 2012;17:S1–337.Google Scholar
  19. 19.
    Godoy DA, Rabinstein AA, Biestro A, et al. Effects of indomethacin test on intracranial pressure and cerebral hemodynamics in patients with refractory intracranial hypertension: a feasibility study. Neurosurgery. 2012;71(2):245–57.CrossRefPubMedGoogle Scholar
  20. 20.
    Godoy DA, Alvarez E, Manzi R, et al. The physiologic effects of indomethacin test on CPP and ICP in severe traumatic brain injury (sTBI). Neurocrit Care. 2014;20(2):230–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Imberti R, Fuardo M, Bellinzona G, et al. The use of indomethacin in the treatment of plateau waves: effects on cerebral perfusion and oxygenation. J Neurosurg. 2005;102(3):455–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Imberti R, Bellinzona G, Bardi M, et al. Effects of hyperventilation and indomethacin on CPP, SjvO2 and brain tissue pO2 in patients with severe traumatic brain injury. Acta Neurochir Suppl. 1998;71:408.Google Scholar
  23. 23.
    Jensen K, Ohrström J, Cold GE, et al. 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(3–4):116–21.CrossRefGoogle Scholar
  24. 24.
    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(2):139–49.CrossRefGoogle Scholar
  25. 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(3):229–36.CrossRefPubMedGoogle Scholar
  26. 26.
    Jensen K, Ohrstrøm J, Cold GE, et al. Indomethacin (Confortid) in severe head injury and elevated intracranial pressure (ICP). Acta Neurochir Suppl (Wien). 1992;55:47–8.Google Scholar
  27. 27.
    Harrigan MR, Tuteja S, Neudeck BL. Indomethacin in the management of elevated intracranial pressure: a review. J Neurotrauma. 1997;14(9):637–50.CrossRefPubMedGoogle Scholar
  28. 28.
    Rasmussen M. Treatment of elevated intracranial pressure with indomethacin: friend of foe? Acta Anaesthesiol Scand. 2005;49:341–50.CrossRefPubMedGoogle Scholar
  29. 29.
    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.PubMedGoogle Scholar
  30. 30.
    Higgins JPT, Green S (eds): Cochrane handbook for systematic reviews of interventions version 5.1.0. Accessed 25 Oct 2013.
  31. 31.
    Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analysis: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Phillips B, Ball C, Sackett D, et al. Oxford Centre for Evidence-Based Medicine Levels of Evidence. Version 2009. Accessed June 2014.
  33. 33.
    Guyatt GH, Oxman AD, Vist G, 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.CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Guyatt GH, Oxman AD, Kunz R, 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.CrossRefPubMedCentralPubMedGoogle Scholar
  35. 35.
    Schünemann HJ, Oxman AD, Brozek J, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336(7653):1106–10.CrossRefPubMedCentralPubMedGoogle Scholar
  36. 36.
    Guyatt GH, Oxman AD, Kunz R, et al. Rating quality of evidence and strength of recommendations: incorporating considerations of resources use into grading recommendations. BMJ. 2008;336(7654):1170–3.CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Guyatt GH, Oxman AD, Kunz R, et al. Rating quality of evidence and strength of recommendations: going from evidence to recommendations. BMJ. 2008;336(7652):1049–51.CrossRefPubMedCentralPubMedGoogle Scholar
  38. 38.
    Jaeschke R, Guyatt GH, Dellinger P, et al. Use of GRADE grid to reach decisions on clinical practice guidelines when consensus is elusive. BMJ. 2008;337:a744.CrossRefPubMedGoogle Scholar
  39. 39.
    Dey PK, Sharma HS. Influence of ambient temperature and drug treatments on brain oedema induced by impact injury on skull in rats. Indian J Physiol Pharmacol. 1984;28(3):177–86.PubMedGoogle Scholar
  40. 40.
    Deluga KS, Plotz FB, Betz AL. Effect of indomethacin on edema following single and repetitive cerebral ischemia in the gerbil. Stroke. 1991;22:1259–64.CrossRefPubMedGoogle Scholar
  41. 41.
    Shalk KA, Faraci FM, Heistad DD. Effect of endothelin on production of cerebrospinal fluid in rabbits. Stroke. 1992;23(4):560–3.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Nick Sader
    • 1
  • Frederick A. Zeiler
    • 1
  • Lawrence M. Gillman
    • 2
    • 3
  • Michael West
    • 1
  • Colin J. Kazina
    • 1
  1. 1.Section of Neurosurgery, Department of SurgeryUniversity of ManitobaWinnipegCanada
  2. 2.Section of Critical Care Medicine, Depertment of MedicineUniversity of ManitobaWinnipegCanada
  3. 3.Section of General Surgery, Department of SurgeryUniversity of ManitobaWinnipegCanada

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