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Canadian Journal of Anesthesia 51:950-951 (2004)
© Canadian Anesthesiologists' Society, 2004

Correspondence

Continuous low-dose diclofenac infusion for fever control in patients with acute neurological lesions

Anselmo Caricato, MD, Giorgio Conti, MD, Giovanna Mercurio, MD, Aldo Mancino, MD, Federico Santilli, MD, Massimo Antonelli, MD and Rodolfo Proietti, MD

Rome, Italy

To the Editor:

The optimal treatment of fever in acute neurological patients is still a matter of debate. Several methods are reported, but may be unsuccessful or associated with hemodynamic instability.1,2

We examined the effect of a continuous infusion of low doses of diclofenac (DCF) on bladder temperature and cerebral and systemic hemodynamics. After approval from the Institutional Review Board 18 consecutive, febrile patients (bladder temperature ≥ 38.3°C)3 with acute neurological lesions (Glasgow Coma Scale ≤ 7) were studied prospectively.

In the presence of fever lasting more than four hours, a continuous low-dose DCF infusion (0.04 mg·kg·hr–1) was administered for at least 24 hr.4 Initially, 500 mL of sodium chloride 0.9% were infused in four hours. Infusion rate of vasopressors was kept constant.

Results are presented as mean ± standard error. ANOVA for repeated measures and Newman-Keuls test for post-hoc comparisons between groups were used for statistical analysis.

At baseline, temperature was 38.6 ± 0.1°C. In all but two patients, DCF was able to reduce the bladder temperature below 38.3°C; the decrease in temperature was statistically significant at 6 hr, 12 hr and 24 hr (P< 0.0001); (T6 hr 37.1 ± 0.3°C, P < 0.001; T12 hr 36.8 ± 0.3°C, P < 0.001; T24 hr 36.8 ± 0.3°C, P < 0.001). The effects of DCF on mean arterial pressure (MAP), intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are shown (FigureGo). No impairment in liver and renal function, modification in blood cell count or gastrointestinal bleeding was observed.



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  		FIGURE Mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and intracranial pressure (ICP) before, and at 6 hr, 12 hr, 24 hr after the beginning of the infusion. *P < 0.05;
**P < 0.01. Statistically significant differences with baseline are reported. Means ± SEM are shown.

 
DCF was effective in reducing fever in the majority of the cases, without affecting CPP. We observed a high hemodynamic tolerance of DCF, probably due to the low dosage and use of a continuous infusion. Nonetheless, we found a significant reduction of MAP at 6 hr, in association with a decrease of ICP. Although CPP was not reduced, this effect must be kept in mind during the infusion of DCF, and fluid administration may be necessary to maintain hemodynamic stability.

We observed that two patients did not respond to treatment; no infection was apparent in these cases, (positive cultures were found in 14 patients) suggesting that fever caused by a non-infective mechanism might not respond as well to DCF.

In conclusion, we observed that a low-dose DCF infusion was effective in treating fever, without modifications of CPP or systemic side-effects. This treatment may be suggested as an alternative to conventional antipyretic drugs.

Footnotes

Research conducted in the Department of Anesthesia and Intensive Care, Catholic University School of Medicine, Rome

No funding sources supported this work. The authors declare that there is no conflict of interest with any commercial or non-commercial organization.

References

1 Plaisance KI, Mackowiak PA. Antipyretic therapy: physiologic rationale, diagnostic implications, and clinical consequences. Arch Intern Med 2000; 160: 449–56.[Abstract/Free Full Text]

2 Stocchetti N, Rossi S, Zanier ER, Colombo A, Beretta L, Citerio G. Pyrexia in head-injured patients admitted to intensive care. Intensive Care Med 2002; 28: 1555–62.[Medline]

3 O’Grady NP, Barie PS, Bartlett J, et al. Practice parameters for evaluating new fever in critically ill adult patients. Task Force of the American College of Critical Care Medicine of the Society of Critical Care Medicine in collaboration with the Infectious Disease Society of America. Crit Care Med 1998; 26: 392–408.[Medline]

4 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.[Medline]





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