Neurocritical Care

, Volume 6, Issue 2, pp 82–89 | Cite as

Continuous low dose diclofenac sodium infusion to control fever in neurosurgical critical care

  • Manuela Cormio
  • Giuseppe CiterioEmail author
Original Paper



Aim of this randomized prospective clinical trial is to compare two methods of antipyretics and evaluate their efficacy in controlling fever during the acute phase of brain damage.


Twenty-two febrile comatose patients: 12 severe traumatic brain injury and 10 subarachnoid hemorrhage divided in 2 groups: Diclofenac low-dose infusion (10 patients) and extemporaneous boluses of NSAIDs (CTRL, 12 patients). The primary outcome measure was length of time with temperature >38°C. Secondary outcome measures were: 1) to assess the effects of each antipyretic strategy on intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP) and heart rate; 2) to monitor adverse effects of each antipyretic strategy. The baseline characteristics in the two treatment groups were similar.


Primary findings: percentage of time per patient with temperature >38°C was significantly lower (P < 0.0001) in the DCF group, 4% (0–22%), vs. 34% (8–56%) in CTRL group. In addition, mean T°, max T° were lower in DCF than in CTRL (P < 0.05). Secondary findings: CPP and MAP were significantly higher in DCF group (P < 0.05) while ICP was not different (NS). However, if ICP pre randomization was < 25 mmHg, CTRL suffered a worst ICP (24 ± 11 vs. 16 ± 7 P = 0.01), MAP (89 ± 10 vs. 104 ± 10 P = 0.01) and CPP (75 ± 10 vs. 94 ± 17 P = 0.01) compared to DCF. No differences between the two treatment were recorded when ICP ≥ 25 mmHg before randomization. There was no gastrointestinal or intracranial bleeding.


Low dose DCF infusion is a potential useful strategy for a successful control temperature better than intermittent NSAIDs dosing, minimizing potentially brain-damaging effects of fever.


Fever Antipyretic therapy Diclofenac sodium Cerebral perfusion pressure Intracranial pressure Traumatic brain injury Subarachnoid hemorrhage 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Reith J, et al. Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome. Lancet 1996; 347:422–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Albrecht RF, Wass CT, Lanier WL. Occurrence of potentially detrimental temperature alterations in hospitalized patients at risk for brain injury. Mayo Clin Proc 1998; 73:629–35.PubMedGoogle Scholar
  3. 3.
    Schwarz S, Hafner K, Aschoff A, Schwab S. Incidence and prognostic significance of fever following intracerebral hemorrhage. Neurology 2000; 54:354–61.PubMedGoogle Scholar
  4. 4.
    Wang Y, Lim LL-Y, Levi C, Heller RF, Fisher J. Influence of admission body temperature on stroke mortality. Stroke 2000; 31:404–9.PubMedGoogle Scholar
  5. 5.
    Kilpatrick MM, Lowry DW, Firlik AD, Yonas H, Marion DW. Hyperthermia in the neurosurgical intensive care unit. Neurosurgery 2000; 47:850–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Stocchetti N, et al. Pyrexia in head-injured patients admitted to intensive care. Intensive Care Med 2002; 28:1555–62.PubMedCrossRefGoogle Scholar
  7. 7.
    Klein NC, Cunha BA. Treatment of fever. Infect Dis Clin North Am 1996; 10:211–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Dietrich WD. The importance of brain temperature in cerebral injury. J Neurotrauma 1992; 9(Suppl 2):S475–85.PubMedGoogle Scholar
  9. 9.
    Yu CG, et al. Detrimental Effects of Systemic Hyperthermia on Locomotor Function and Histopathological Outcome after Traumatic Spinal Cord Injury in the Rat. Neurosurgery 2001; 49:152–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Hajat C, Hajat S, Sharma P. Effects of post stroke pyrexia on stroke outcome. A meta-analysis of studies in patients. Stroke 2000; 31:410–4.PubMedGoogle Scholar
  11. 11.
    Rossi S, Zanier ER, Mauri I, Colombo A, Stocchetti N. Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage. J Neurol Neurosurg Psychiatry 2001; 71:448–54.PubMedCrossRefGoogle Scholar
  12. 12.
    Malkinson TJ, Cooper KE, Veale WL. Cerebrospinal fluid pressure in conscious rats during prostaglandin E1 fever. Am J Physiol 1990; 258:R783–7.PubMedGoogle Scholar
  13. 13.
    Castillo J, Davalos A, Noya M. Progression of ischaemic stroke and excitotoxic aminoacids. Lancet 1997; 349:79–83.PubMedCrossRefGoogle Scholar
  14. 14.
    Chatzipanteli K, Alonso OF, Kraydieh S, Dietrich WD. Importance of posttraumatic hypothermia and hyperthermia on the inflammatory response after fluid percussion brain injury: biochemical and immunocytochemical studies. J Cereb Blood Flow Metab 2000; 20:531–42.PubMedCrossRefGoogle Scholar
  15. 15.
    Thornhill J, Corbett D. Therapeutic implications of hypothermic and hyperthermic temperature conditions in stroke patients. Can J Physiol Pharmacol 2001; 79:254–61.PubMedCrossRefGoogle Scholar
  16. 16.
    Wass CT, Lanier WL, Hofer RE, Scheithauer BW, Andrews AG. Temperature changes of > or = 1°C alter functional neurologic outcome and histopathology in a canine model of complete cerebral ischemia. Anesthesiology 1995; 83:325–35.PubMedCrossRefGoogle Scholar
  17. 17.
    Corbett D, Thornhill J. Temperature modulation (hypothermic and hyperthermic conditions) and its influence on histological and behavioral outcomes following cerebral ischemia. Brain Pathol 2000; 10:145–52.PubMedCrossRefGoogle Scholar
  18. 18.
    Oliveira-Filho J, et al. Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome. Neurology 2001; 56:1299–304.PubMedGoogle Scholar
  19. 19.
    Natale JE, Joseph JG, Helfaer MA, Shaffner DH. Early hyperthermia after traumatic brain injury in children: risk factors, influence on length of stay, and effect on short-term neurologic status. Crit Care Med 2000; 28:2608–15.PubMedCrossRefGoogle Scholar
  20. 20.
    Alderson P, Gadkary C, Signorini DF. Therapeutic hypothermia for head injury. Cochrane Database Syst Rev. 2004 Oct 18; (4):CD001048.Google Scholar
  21. 21.
    Zandstra DF, Stoutenbeek CP, Alexander JP. Antipyretic therapy with diclofenac sodium. Observations on effect and serious side effects in critically ill patients. Intensive Care Med 1983; 9:21–3.PubMedCrossRefGoogle Scholar
  22. 22.
    Mackenzie I, Forrest K, Thompson F, Marsh R. Effects of acetaminophen administration to patients in intensive care. Intensive Care Med 2000; 26:1408. PubMedCrossRefGoogle Scholar
  23. 23.
    Boyle M, Hundy S, Torda TA. Paracetamol administration is associated with hypotension in the critically ill. Aust Crit Care 1997; 10:120–2.PubMedGoogle Scholar
  24. 24.
    Brown G. Acetaminophen-induced hypotension. Heart Lung 1996; 25:137–40.PubMedCrossRefGoogle Scholar
  25. 25.
    Mayer S, et al. Clinical trial of an air-circulating cooling blanket for fever control in critically ill neurologic patients. Neurology 2001; 56:292–8.PubMedGoogle Scholar
  26. 26.
    Henker R, et al. Comparison of fever treatments in the critically ill: a pilot study. Am J Crit Care 2001; 10:276–80.PubMedGoogle Scholar
  27. 27.
    Cairns CJ, Andrews PJ. Management of hyperthermia in traumatic brain injury. Curr Opin Crit Care 2002; 8:106–10.PubMedCrossRefGoogle Scholar
  28. 28.
    O’Donnell J, Axelrod P, Fischer C, Lorber B. Use and effectiveness of hypothermia blankets for febrile patients in the intensive care unit. Clin Infect Dis 1997; 24:1208–1213.PubMedGoogle Scholar
  29. 29.
    Lenhardt R, et al. The effects of physical treatment on induced fever in humans. Am J Med 1999; 106:550–5.PubMedCrossRefGoogle Scholar
  30. 30.
    Poblete B, Romand JA, Pichard C, Koning P, Suter PM. Metabolic effects of i.v. propacetamol, metamizol or external cooling in critically ill febrile sedated patients. Br J Anaesth 1997; 78:123–7.PubMedGoogle Scholar
  31. 31.
    Bettini R, Grossi E, Rapazzini P, Giardina G. Diclofenac sodium versus acetylsalicylic acid: a randomized study in febrile patients. J Int Med Res 1986; 14:95–100.PubMedGoogle Scholar
  32. 32.
    Pesenti A, Riboni A, Basilico E, Grossi E. Antipyretic therapy in ICU patients: Evaluation of low dose diclofenac sodium. Intensive Care Med 1986; 12:370–73.PubMedCrossRefGoogle Scholar
  33. 33.
    Cormio M, Citerio G, Spear S, Fumagalli R, Pesenti A. Control of fever by continuous, low-dose diclofenac sodium infusion in acute cerebral damage patients. Intensive Care Med 2000; 26:552–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Maas A, et al. EBIC-Guidelines for management of severe head injury in adults. Acta Neurochir 1997; 139:286–94.CrossRefGoogle Scholar
  35. 35.
    Mayberg MR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1994; 25:2315–28.PubMedGoogle Scholar
  36. 36.
    Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections. In: Olmsted RN, (ed.) APIC Infection Control, Applied Epidemiology: Principles and Practice. St. Louis: Mosby; 1996: pp. A-1–20.Google Scholar
  37. 37.
    Pocock SJ. When to stop a clinical trial. Br Med J 1992; 305:235–40.Google Scholar
  38. 38.
    Lundstam SO, Leissner KH, Wahlander LA, Kral JG. Prostaglandin-synthetase inhibition with diclofenac sodium in treatment of renal colic: Comparison with use of a narcotic analgesic. Lancet 1982; 1:1096–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Hetherington JW, Philp NH. Diclofenac sodium versus pethidine in acute renal colic. Br Med J 1986; 292:237–8.CrossRefGoogle Scholar
  40. 40.
    Oborilova A, Mayer J, Pospisil Z, Koristek Z. Symptomatic Intravenous Antipyretic Therapy: Efficacy of Metamizol, Diclofenac, and Propacetamol. J Pain Symptom Manage 2002; 24:608–15.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  1. 1.Neurorianimazione, Dipartimento di Medicina Perioperatoria e Terapie IntensiveOspedale San GerardoMonzaItaly

Personalised recommendations