title: Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection.
abstract: No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready-made infusion of paracetamol.
  
  
  
  Eighty patients with a body temperature onset ≥38.5°C in the previous 24 h due to infection were randomized to a single administration of placebo (n = 39) or 1 g paracetamol (n = 41), and their temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for the measurement of APAP and its metabolites. The primary endpoint was defervescence, defined as a core temperature ≤37.1°C.
  
  
  
  During the first 6 h, defervescence was achieved in 15 (38.5%) patients treated with placebo compared with 33 (80.5%) patients treated with paracetamol 1 g (P < 0.0001). The median time to defervescence with paracetamol 1 g was 3 h. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol, respectively (P = 0.007); nine (60.0%) and two (40.0%) of these patients, respectively, experienced defervescence. No further antipyretic medication was needed for patients becoming afebrile with rescue medication. Serum glucuronide-APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No drug-related adverse events were reported.
  
  
  
  The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism.
authors: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors: Thomas
authors: T
authors: Tsaganos
authors: Uni-Pharma S.A., Athens, Greece.
authors: Ioulia K
authors: IK
authors: Tseti
authors: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors: Nikolaos
authors: N
authors: Tziolos
authors: Uni-Pharma S.A., Athens, Greece.
authors: Georgios-Stefanos
authors: GS
authors: Soumelas
authors: 1st Department of Internal Medicine, Thriasio Elefsis General Hospital, Greece.
authors: Marina
authors: M
authors: Koupetori
authors: 2nd Department of Propedeutic Medicine, Aristotle University of Thessaloniki, Medical School, Greece.
authors: Athina
authors: A
authors: Pyrpasopoulou
authors: Department of Internal Medicine, University of Patras, Medical School, Greece.
authors: Karolina
authors: K
authors: Akinosoglou
authors: Department of Internal Medicine, University of Patras, Medical School, Greece.
authors: Charalambos
authors: C
authors: Gogos
authors: Department of Internal Medicine, Chalkida General Hospital, Greece.
authors: Nikolaos
authors: N
authors: Tsokos
authors: 2nd Department of Propedeutic Medicine, Aristotle University of Thessaloniki, Medical School, Greece.
authors: Asterios
authors: A
authors: Karagiannis
authors: 1st Department of Internal Medicine, Thriasio Elefsis General Hospital, Greece.
authors: Styliani
authors: S
authors: Sympardi
authors: 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
authors: Evangelos J
authors: EJ
authors: Giamarellos-Bourboulis
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D058633:Antipyretics / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D005500:Follow-Up Studies; D006760:Hospitalization; D006801:Humans; D007239:Infections / Q000150:complications*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058633:Antipyretics; D000082:Acetaminophen
keywords: fever; hepatic metabolism; paracetamol