Antipyretic Effect of Clonidine in Intensive Care Unit Patients: A Nested Observational Study

Abstract

Fever in the intensive care unit (ICU) is usually an adaptive response to infection or inflammation. Pharmacological intervention is often required in addition to addressing the underlying causes of fever. Animal studies have examined the antipyretic effect of clonidine; however, to our knowledge there are no clinical data available in humans. The observation of an antipyretic effect of clonidine was made during a single-center randomized control trial that was designed to study the effect of clonidine addition to the commonly used sedative agents in mechanically ventilated ICU patients. Forty patients 18 years or older on mechanical ventilation for 3 days or longer were randomized into 2 groups receiving clonidine and placebo. In addition to the usual sedation/analgesia, patients in the clonidine arm received enteral clonidine in doses of 0.1 mg 3 times a day (TID), which was increased to 0.2 mg TID if the hemodynamics remained stable. Vital signs, laboratory data, all cultures, and daily ICU events were recorded. The odds ratio of temperature higher than 38.3°C was 3.96 times higher in the placebo group, after adjustment for the illness severity and the time of follow-up (P = .049). A lower temperature (0.52°C) was observed in the clonidine group after adjustment for the time of follow-up (P = .006). Our report is the first of its kind in humans that demonstrates possible antipyretic properties of enteral clonidine in the critically ill intensive care unit patient.

Does Interrupting Self-Induced Lung Injury and Respiratory Drive Expedite Early Spontaneous Breathing in the Setting of Early Severe Diffuse Acute Respiratory Distress Syndrome?

“…1) Fever control (20) decreases oxygen consumption (Vo 2 ), eases management (21), and improves mortality in ARDS patients (22). Alpha-2 agonists (dexmedetomidine, clonidine: "cooperative" sedation, i.e., stringent restlessness: -2 < Richmond Agitation Sedation Scale < 0) reduce Vo 2 (23,24) and temperature (25). 2) Agitation control decreases Vo 2 .…”

“…Intubation + CMV + paralysis + low driving pressure converts hypocapnia to hypercapnia. But fever and agitation control limit CO 2 production (22)(23)(24)(25), avoiding very high Paco 2 . Under SB, in contrast to propofol (36), an alpha-2 agonist evokes stage 2 sleep: mild hypercapnia without hyperventilation ( 23) is observed, without ventilator-to-patient dyssynchrony (L. Quintin, unpublished observations, 2008).…”

How should dexmedetomidine and clonidine be prescribed in the critical care setting?

“…( 96 ) Clinically, the patient is quiet and sedated (stage 2 sleep; ( 26 , 97 ) -2 ≤ RASS ≤ 0) but “fairly alert” ( 5 ) or cognitively improved ( 24 ) upon a stimulus. The muscular tremor is abated, ( 98 , 99 ) and the temperature ( 100 ) and oxygen consumption (VO 2 ) ( 101 - 103 ) are lowered. …”

“…The muscular tremor is abated, ( 98 , 99 ) and the temperature ( 100 ) and oxygen consumption (VO 2 ) ( 101 - 103 ) are lowered.…”