Skip to main content

Advertisement

SpringerLink
Log in

Intravenous paracetamol for fever control in acute brain injury patients: cerebral and hemodynamic effects

  • Clinical Article - Brain Injury
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

Fever occurs frequently in acute brain injury patients, and its occurrence is associated with poorer outcomes. Paracetamol, an antipyretic frequently employed in patients with cerebral damage, may cause hypotension. We evaluated the cerebral and hemodynamic effects of intravenous (IV) paracetamol for the control of fever in Neuro-Intensive Care Unit (NICU) patients.

Methods

This is a prospective observational study in which we enrolled 32 NICU patients: Subarachnoid Hemorrhage (SAH, n = 18), Traumatic Brain Injury (TBI, n = 10), Intracerebral Hemorrhage (ICH, n = 2) and Acute Ischemic Stroke (AIS, n = 2).

Results

The administration of paracetamol resulted in a decrease of core body temperature (Tc) (p = 0,0001), mean arterial pressure (MAP) (p = 0,0006), cerebral perfusion pressure (CPP) (p = 0,0033), and jugular venous oxygen saturation (SjVO2) (p = 0.0193), and in an increase of arteriojugular venous differences of oxygen (AVDO2) (p = 0.0012). The proportion of patients who had an infusion of norepinephrine increased from 47 % to 75 % (p = 0.0039 McNemar Test). When intracranial pressure (ICP) at the start of paracetamol infusion (t-0) was compared with the measurement of ICP after 2 h, a significant correlation was observed (r = 0.669, p = 0.0002). This marked and significant correlation can be explained by the fact that for the higher levels of ICP assessed at t-0 (greater than 15 mmHg), we observed a marked reduction of ICP concomitant with the decrease of Tc. No problems related to norepinephrine administration and/or increase in dosage were observed.

Conclusion

Paracetamol administration is effective but exposes patients to hypotensive episodes that must be recognized and treated expeditiously to prevent further damage to the injured brain.

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. Boyle M, Hundy S, Torda TA (1997) Paracetamol administration is associated with hypotension in the critically ill. Aust Crit Care 10(4):120–122

    Article  PubMed  CAS  Google Scholar 

  2. Brown G (1996) Acetaminophen-induced hypotension. Heart Lung 25(2):137–140

    Article  PubMed  CAS  Google Scholar 

  3. Cormio M, Citerio G, Spear S, Fumagalli R, Pesenti A (2000) Control of fever by continuous, low-dose diclofenac sodium infusion in acute cerebral damage patients. Intensive Care Med 26:552–557

    Article  PubMed  CAS  Google Scholar 

  4. de Maat MM, Tijssen TA, Bruggemann RJ, Ponssen HH (2010) Paracetamol for intravenous use in medium- and intensive care patients: pharmacokinetics and tolerance. Eur J Clin Pharmacol 66:713–719

    Article  PubMed  CAS  Google Scholar 

  5. den Hertog HM, van der Worp HB, van Gemert HM, Algra A, Kappelle LJ, van Gijn J, Koudstaal PJ, Dippel DW, PAIS investigators (2009) The Paracetamol (Acetaminophen) In Stroke (PAIS) trial: a multicentre, randomised, placebo-controlled, phase III trial. Lancet Neurol 8:434–440

    Article  Google Scholar 

  6. den Hertog HM, van der Worp HB, van Gemert HMA, van Gijn J, Koudstaal PJ, Dippel DW (2012) Effects of high-dose paracetamol on blood pressure in stroke. Acta Neurol Scand 125(4):265–271

    Article  Google Scholar 

  7. Dietrich WD, Bramlett HM (2007) Hyperthermia and central nervous system injury. Prog Brain Res 162:201–217

    Article  PubMed  CAS  Google Scholar 

  8. Dippel DW, van Breda EJ, van Gemert HM, van der Worp HB, Meijer RJ, Kappelle LJ, Koudstaal PJ (2001) Effect of paracetamol (acetaminophen) on body temperature in acute ischemic stroke: a double-blind, randomized phase II clinical trial. Stroke 32:1607–1612

    Article  PubMed  CAS  Google Scholar 

  9. Duggan ST, Scott LJ (2009) Intravenous Paracetamol. Drugs 69(1):101–113

    Article  PubMed  CAS  Google Scholar 

  10. European Stroke Organisation (ESO), Executive Committee, ESO Writing Committee (2008) Guidelines for the management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 25(5):457–507

    Article  Google Scholar 

  11. Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF (2013) The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology 21(3):201–32

    Article  PubMed  CAS  Google Scholar 

  12. Greer DM, Funk SE, Reaven NL, Ouzounelli M, Uman GC (2008) Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive metaanalysis. Stroke 39:3029–3035

    Article  PubMed  Google Scholar 

  13. Hersch M, Raveh D, Izbicki G (2008) Effect of intravenous propacetamol on blood pressure in febrile critically ill patients. Pharmacotherapy 28(10):1205–1210

    Article  PubMed  CAS  Google Scholar 

  14. Johnston NJ, King AT, Protheroe R, Childs C (2006) Body temperature management after severe traumatic brain injury: methods and protocols used in the United Kingdom and Ireland. Resuscitation 70:254–262

    Article  PubMed  Google Scholar 

  15. Kasner SE, Wein T, Piriyawat P, Villar-Cordova CE, Chalela JA, Krieger DW, Morgenstern LB, Kimmel SE, Grotta JC (2002) Acetaminophen for altering body temperature in acute stroke: a randomized clinical trial. Stroke 33:130–134

    Article  PubMed  CAS  Google Scholar 

  16. Kilpatrick MM, Lowry DW, Firlik AD, Yonas H, Marion DW (2000) Hyperthermia in the neurosurgical intensive care unit. Neurosurgery 47:850–855

    Article  PubMed  CAS  Google Scholar 

  17. Koennecke H-C, Leistner S (2001) Prophylactic antipyretic treatment with acetaminophenin acute ischemic stroke: A pilot study. Neurology 57:2301–2303

    Article  PubMed  CAS  Google Scholar 

  18. Mackenzie I, Forrest K, Thompson F, Marsh R (2000) Effects of acetaminophen administration to patients in intensive care. Intensive Care Med 26:1408

    Article  PubMed  CAS  Google Scholar 

  19. Marmarou A, Anderson RL, Ward JD, Choi SC, Young HF (1991) Impact of ICP instability and hypotension on outcome in patients with severe head trauma. J Neurosurg 75:S59–S66

    Google Scholar 

  20. Middleton S, McElduff P, Ward J, Grimshaw JM, Dale S, D’Este C, Drury P, Griffiths R, Cheung NW, Quinn C, Evans M, Cadilhac D, Levi C; QASC Trialists Group (2011) Implementation of evidence-based treatment protocols to manage fever, hyperglycaemia, and swallowing dysfunction in acute stroke (QASC): a cluster randomized controlled trial. Lancet 378:1699–1706

    Article  Google Scholar 

  21. Mrozek S, Constantin JM, Futier E, Zenut M, Ghardes G, Cayot-Constantin S, Bonnard M, Ait-Bensaid N, Eschalier A, Bazin JE (2009) Acetaminophen-induced hypotension in intensive care unit: a prospective study. Ann Fr Anesth Reanim 28(5):448–453

    Article  PubMed  CAS  Google Scholar 

  22. Peacock WF, Breitmeyer JB, Pan C, Smith WB, Royal MA (2011) A randomized study of the efficacy and safety of intravenous acetaminophen compared to oral acetaminophen for the treatment of fever. Acad Emerg Med 18:360–366

    Article  PubMed  Google Scholar 

  23. Rossi S, Roncati Zanier E, Mauri I, Colombo A, Stocchetti N (2001) Brain temperature, body core temperature, and intracranial pressure in acute cerebral damage. J Neurol Neurosurg Psychiatry 71:448–454

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  24. Stocchetti N, Protti A, Lattuada M, Magnoni S, Longhi L, Ghisoni L, Egidi M, Zanier ER (2005) Impact of pyrexia on neurochemistry and cerebral oxygenation after acute brain injury. J Neurol Neurosurg Psychiatry 76(8):1135–9

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Stocchetti N, Rossi S, Zanier ER, Colombo A, Beretta L, Citerio G (2002) Pyrexia in head-injured patients admitted to intensive care. Intensive Care Med 28(11):1555–62

    Article  PubMed  Google Scholar 

  26. Thompson HJ, Tkacs NJ, Saatman KE, Raghupathi R, McIntosh TK (2003) Hyperthermia following traumatic brain injury: a critical evaluation. Neurobiol Dis 12:163–173

    Article  PubMed  Google Scholar 

  27. Tu Y-K, Gilthorpe MS (2007) Revisiting the relation between change and initial value: A review and evaluation. Statist Med 26:443–457

    Article  Google Scholar 

  28. Tu Y-K, Bælum V, Gilthorpe MS (2005) The relationship between baseline value and its change: problems in categorization and the proposal of a new method. Eur J Oral Sci 113:279–288

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Mario Mergoni MD and Tracy K. McIntosh PhD for their valuable suggestions.

This study would not have been possible without the exceptional commitment and contribution of the Nurses of our ICU.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. I Servizio Anestesia e Rianimazione, Azienda Ospedaliero-Universitaria di Parma, Via Gramsci 14, 43100, Parma, Italy

    Edoardo Picetti, Marta Velia Antonini, Ilaria Rossi & Maria Luisa Caspani

  2. Scuola di Specializzazione in Anestesia e Rianimazione, Universita degli Studi di Parma, Parma, Italy

    Antonino De Angelis & Fabio Villani

  3. Neurochirurgia e Neurotraumatologia, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

    Franco Servadei

Authors
  1. Edoardo Picetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonino De Angelis
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fabio Villani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marta Velia Antonini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ilaria Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Franco Servadei
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maria Luisa Caspani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edoardo Picetti.

Additional information

Comment

We have read with interest this article regarding the cerebral and hemodynamic effects of paracetamol utilized as antipyretic in patients with acute brain injuries. Fever is an important secondary insult for the injured brain; its occurrence is associated with poorer outcomes in NICU patients. Nevertheless, the utilization of antipyretics, as observed in daily clinical practice, may be associated with arterial hypotension. With this work the Authors demonstrate the effectiveness of paracetamol in the control of fever but also the occurrence of hypotensive episodes requiring rapid diagnosis and treatment to prevent further damage to the injured brain.

Domenico d'Avella

Marina Munari

Padova, Italy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Picetti, E., De Angelis, A., Villani, F. et al. Intravenous paracetamol for fever control in acute brain injury patients: cerebral and hemodynamic effects. Acta Neurochir 156, 1953–1959 (2014). https://doi.org/10.1007/s00701-014-2129-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00701-014-2129-2

Keywords

Search

Navigation