Abstract
Objective
We investigated the metabolic, hemodynamic, and inflammatory responses of pharmacological and physical therapies aimed at reducing body temperature in febrile critically ill patients.
Design and setting
Open-label, randomized trial in a surgical ICU in a tertiary university hospital.
Patients
Thirty analgosedated, mechanically ventilated patients with a temperature of 38.5°C or higher were randomized to receive either intravenous metamizol, intravenous propacetamol, or external cooling.
Measurements and results
Body temperature and metabolic and hemodynamic variables were recorded at baseline and during the following 4 h. Cytokine concentrations were assessed before and 4 and 12 h after the initiation of antipyresis. Body temperature decreased significantly in all treatment groups. For a 1°C temperature decrease, the energy expenditure index increased by 5% with external cooling and decreased by 7% and 8% in the metamizol and propacetamol groups, respectively. Metamizol induced a significant decrease in mean arterial pressure and urine output compared to baseline and to the other two groups. C-reactive protein increased over time, but compared to the other groups it was significantly lower in patients receiving metamizol after 4 h. Cytokine concentrations were not different among the three groups or over time, although interleukin 6 tended to decrease over time in the metamizol group.
Conclusions
Metamizol, propacetamol, and external cooling equally reduced temperature. Considering the undesirable hemodynamic effects, metamizol should not be considered the first antipyretic choice in unstable patients. Propacetamol or external cooling should be preferred, although the latter should be avoided in patients unlikely to tolerate the increased metabolic demand induced by external cooling.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Haupt MT, Rackow EC (1983) Adverse effects of febrile state on cardiac performance. Am Heart J 105:763–768
Shimada SG, Otterness IG, Stitt JT (1994) A study of the mechanism of action of the mild analgesic dipyrone. Agents Actions 41:188–192
Boutaud O, Aronoff DM, Richardson JH, Marnett LJ, Oates JA (2002) Determinants of the cellular specificity of acetaminophen as an inhibitor of prostaglandin H (2) synthases. Proc Natl Acad Sci U S A 99:7130–7135
Coimbra C, Boris-Moller F, Drake M, Wieloch T (1996) Diminished neuronal damage in the rat brain by late treatment with the antipyretic drug dipyrone or cooling following cerebral ischemia. Acta Neuropathol (Berl) 92:447–453
Poblete B, Romand JA, Pichard C, Konig P, Suter PM (1997) Metabolic effects of i.v. propacetamol, metamizol or external cooling in critically ill febrile sedated patients. Br J Anaesth 78:123–127
Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 101:1644–1655
Ramsay MA, Savege TM, Simpson BR, Goodwin R (1974) Controlled sedation with alphaxalone-alphadolone. BMJ 2:656–659
Burton P, Gurrin L, Sly P (1998) Extending the simple linear regression model to account for correlated responses: an introduction to generalized estimating equations and multi-level mixed modelling. Stat Med 17:1261–1291
Manthous CA, Hall JB, Olson D, Singh M, Chatila W, Pohlman A, Kushner R, Schmidt GA, Wood LD (1995) Effect of cooling on oxygen consumption in febrile critically ill patients. Am J Respir Crit Care Med 151:10–14
Astrup A, Bulow J, Christensen NJ, Madsen J (1984) Ephedrine-induced thermogenesis in man: no role for interscapular brown adipose tissue. Clin Sci (Colch) 66:179–186
Plattner O, Semsroth M, Sessler DI, Papousek A, Klasen C, Wagner O (1997) Lack of nonshivering thermogenesis in infants anesthetized with fentanyl and propofol. Anesthesiology 86:772–777
Bruder N, Raynal M, Pellissier D, Courtinat C, Francois G (1998) Influence of body temperature, with or without sedation, on energy expenditure in severe head-injured patients. Crit Care Med 26:568–572
Stettler N, Schutz Y, Whitehead R, Jequier E (1992) Effect of malaria and fever on energy metabolism in Gambian children. Pediatr Res 31:102–106
DuBois E (1954) Energy metabolism. Annu Rev Physiol 16:125–134
Pesenti A, Riboni A, Basilico E, Grossi E (1986) Antipyretic therapy in ICU patients: evaluation of low dose diclofenac sodium. Intensive Care Med 12:370–373
Zoppi M, Hoigne R, Keller MF, Streit F, Hess T (1983) [Reducing blood pressure with Dipyron (novaminsulfone sodium)]. Schweiz Med Wochenschr 113:1768–1770
Hoigne R, Zoppi M, Sollberger J, Hess T, Fritschy D (1986) Fall in systolic blood pressure due to metamizol (dipyrone, noramidopyrine, novaminsulfone). Results from the Comprehensive Hospital Drug Monitoring Berne (CHDMB). Agents Actions Suppl 19:189–195
Jansky L, Vybiral S, Pospisilova D, Roth J, Dornand J, Zeisberger E, Kaminkova J (1995) Production of systemic and hypothalamic cytokines during the early phase of endotoxin fever. Neuroendocrinology 62:55–61
Roth J, Conn CA, Kluger MJ, Zeisberger E (1993) Kinetics of systemic and intrahypothalamic IL-6 and tumor necrosis factor during endotoxin fever in guinea pigs. Am J Physiol 265:R653–658
LeMay LG, Vander AJ, Kluger MJ (1990) Role of interleukin 6 in fever in rats. Am J Physiol 258:R798–803
Zampronio AR, Souza GE, Silva CA, Cunha FQ, Ferreira SH (1994) Interleukin-8 induces fever by a prostaglandin-independent mechanism. Am J Physiol 266:R1670–1674
Cartmell T, Luheshi GN, Hopkins SJ, Rothwell NJ, Poole S (2001) Role of endogenous interleukin-1 receptor antagonist in regulating fever induced by localised inflammation in the rat. J Physiol (Lond) 531:171–180
Gabay C, Smith MF, Eidlen D, Arend WP (1997) Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein. J Clin Invest 99:2930–2940
International Agranulocytosis and Aplastic Anemia Study (1986) Risks of agranulocytosis and aplastic anemia. A first report of their relation to drug use with special reference to analgesics. JAMA 256:1749–1757
Hargis JB, La Russa VF, Redmond J, Kessler SW, Wright DG (1989) Agranulocytosis associated with “Mexican aspirin” (dipyrone): evidence for an autoimmune mechanism affecting multipotential hematopoietic progenitors. Am J Hematol 31:213–215
Acknowledgements
We are grateful to Jean-Michel Dayer for his help in designing the study and to Marjan Mohitzadeh and Christine Modoux for their skillful technical assistance.
Author information
Authors and Affiliations
Corresponding author
Additional information
Immunological analyses were supported by the Hans Wilsdof Foundation
Rights and permissions
About this article
Cite this article
Gozzoli, V., Treggiari, M.M., Kleger, GR. et al. Randomized trial of the effect of antipyresis by metamizol, propacetamol or external cooling on metabolism, hemodynamics and inflammatory response. Intensive Care Med 30, 401–407 (2004). https://doi.org/10.1007/s00134-003-2087-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00134-003-2087-2