Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection

Τσαγανός, Θωμάς; Tseti, Ioulia; Tziolos, Nikolaos; Soumelas, Georgios‐Stefanos; Koupetori, Marina; Pyrpasopoulou, Athina; Akinosoglou, Karolina; Gogos, Charalambos; Tsokos, Nikolaos; Karagiannis, Asterios; Sympardi, Styliani; Giamarellos‐Bourboulis, Evangelos J.

doi:10.1111/bcp.13173

Cited by 8 publications

(7 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…APAP is a widely used and effective antipyretic and analgesic drug. − Unfortunately, APAP overdose is the leading cause of acute liver injury or even liver failure . Thus, the treatment for APAP-induced hepatotoxicity is highly desired.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Eriodictyol, Not Its Glucuronide Metabolites, Attenuates Acetaminophen-Induced Hepatotoxicity

et al. 2017

View full text Add to dashboard Cite

Acetaminophen (APAP) is one of the most commonly used oral analgesics and antipyretics, but hepatotoxicity including liver failure may occur after overdose. The therapeutic options for treating APAP hepatotoxicity are limited. Eriodictyol, a dietary flavonoid with anti-inflammatory and antioxidant properties, was used here to determine its protective effects against APAP-induced hepatotoxicity in mice. Various administration routes and pharmacokinetics-pharmacodynamics (PK-PD) analyses were used to determine these effects. Protective effects were observed in intravenously and intraperitoneally but not in intragastrically administered eriodictyol. LC-MS/MS analysis revealed two monoglucuronide metabolites of eriodictyol in liver and intestine microsomes. Recombinant human uridine-5'-diphospho -glucuronosyltransferase (UGT) isoforms and chemical inhibition studies demonstrated that UGT1As (mainly UGT1A1, UGT1A9, UGT1A10) and UGT2B7 were likely the main contributors to eriodictyol glucuronidation. Intragastric administration of eriodictyol, which displayed lower parent and higher metabolite concentrations in the plasma, did not elicit protective effects against APAP hepatotoxicity, when compared to the intraperitoneal injection of eriodictyol. The relative bioavailability of eriodictyol was increased to 216.84% with the coadministration of glycyrrhetinic acid (GA), an inhibitor of UGT1As. Intragastric administration of eriodictyol in combination with GA also induced protective effects against APAP hepatotoxicity. Furthermore, intragastric administration of eriodictyol attenuated APAP hepatotoxicity in heterozygous Ugt1 (Ugt1) mice but not in its wild-type littermates. Thus, UGT1A-mediated metabolic inactivation reduced the protective effect of eriodictyol. Eriodictyol attenuated APAP hepatotoxicity via inhibition of hepatic cytochrome P450 (cyp) 2e1 and cyp3a11 activities; reserve of glutathione (GSH) by improvement of glutathione peroxidase (GSH-Px), glutathione reductase (GR), and glutathione S-transferase (GST) activities; elevation of superoxide dismutase (SOD) activity; and reduction of malondialdehyde (MDA) level. Our findings indicate that parenterally administered eriodictyol may be used to treat APAP-induced hepatotoxicity, and its efficacy can be enhanced by UGT1As down-regulation.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Acetaminophen ( N -acetyl- p -aminophenol, APAP), a widespread and effective analgesic and antipyretic drug, − can cause severe liver injury or even acute liver failure when it is used with acute or cumulative overdose . In the United States, around 30000 people every year are subjected to APAP hepatotoxicity .…”

Section: Introductionmentioning

confidence: 99%

Eriodictyol, Not Its Glucuronide Metabolites, Attenuates Acetaminophen-Induced Hepatotoxicity

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Sixteen trials (19 comparisons) with a total of 2415 participants reported on serious adverse events. The included trials assessed the effects of five different fever therapy interventions: ibuprofen versus placebo (three trials), 47 48 49 paracetamol versus placebo (six trials), 50 51 52 53 54 55 physical cooling versus no intervention (three trials), 56 57 58 antipyretics plus physical cooling versus no intervention (two trials), 18 59 and physical cooling plus antipyretics versus antipyretics (two trials). 60 61 All 2415 participants were admitted to hospital; 2050 were critically ill, and 251 were non-critically ill (supplementary table S1).…”

Section: Resultsmentioning

confidence: 99%

Fever therapy in febrile adults: systematic review with meta-analyses and trial sequential analyses

Holgersson

Ceric

Sethi

et al. 2022

BMJ

View full text Add to dashboard Cite

ObjectiveTo investigate the effects of fever therapy compared with no fever therapy in a wide population of febrile adults.DesignSystematic review with meta-analyses and trial sequential analyses of randomised clinical trials.Data sourcesCENTRAL, BIOSIS, CINAHL, MEDLINE, Embase, LILACS, Scopus, and Web of Science Core Collection, searched from their inception to 2 July 2021.Eligibility criteriaRandomised clinical trials in adults diagnosed as having fever of any origin. Included experimental interventions were any fever therapy, and the control intervention had to be no fever therapy (with or without placebo/sham).Data extraction and synthesisTwo authors independently selected studies, extracted data, and assessed the risk of bias. Primary outcomes were all cause mortality and serious adverse events. Secondary outcomes were quality of life and non-serious adverse events. Aggregate data were synthesised with meta-analyses, subgroup analyses, and trial sequential analyses, and the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.ResultsForty two trials assessing 5140 participants were included. Twenty three trials assessed 11 different antipyretic drugs, 11 trials assessed physical cooling, and eight trials assessed a combination of antipyretic drugs and physical cooling. Of the participants, 3007 were critically ill, 1892 were non-critically ill, 3277 had infectious fever, and 1139 had non-infectious fever. All trials were assessed as being at high risk of bias. Meta-analysis and trial sequential analysis showed that the hypothesis that fever therapy reduces the risk of death (risk ratio 1.04, 95% confidence interval 0.90 to 1.19; I2=0%; P=0.62; 16 trials; high certainty evidence) and the risk of serious adverse events (risk ratio 1.02, 0.89 to 1.17; I2=0%; P=0.78; 16 trials; high certainty evidence) could be rejected. One trial assessing quality of life was included, showing no difference between fever therapy and control. Meta-analysis and trial sequential analysis showed that the hypothesis that fever therapy reduces the risk of non-serious adverse events could be neither confirmed nor rejected (risk ratio 0.92, 0.67 to 1.25; I2=66.5%; P=0.58; four trials; very low certainty evidence).ConclusionsFever therapy does not seem to affect the risk of death and serious adverse events.Systematic review registrationPROSPERO CRD42019134006

show abstract

“…We collected data of patient demographics, LOS, medical history, and comorbidities including history of drug resistance, surgical history, and current infection information including culture results, CURB-65 (confusion of new onset, blood urea nitrogen greater than 7 mmol/L or 19 mg/dL, respiratory rate of 30 breaths per minute or greater, systolic blood pressure less than 90 mmHg or diastolic blood pressure 60 mmHg or less, and age of 65 or older) score, antibiotics used including macrolides, chronic intake of statins, current medication intake, CRP level, erythrocyte sedimentation rate, white blood cell differentials, liver function tests when available, and temperature. Temperature normalization was recorded, defined as temperature 37.1 C. 11…”

Section: Data Collection Processmentioning

confidence: 99%

Effects of statins on clinical outcomes in hospitalized patients with community-acquired pneumonia

et al. 2020

View full text Add to dashboard Cite

Objective We evaluated the effect of chronic use of statins based on C-reactive protein (CRP) levels and hospital length of stay (LOS) in patients admitted with community-acquired pneumonia (CAP). Methods We conducted a retrospective study over 12 months at a teaching hospital in Lebanon comparing patients with CAP taking chronic statins with patients not taking statins. Included patients with CAP were older than age 18 years and had two CRP level measures during hospitalization. CURB-65 criteria were used to assess the severity of pneumonia. A decrease in CRP levels on days 1 and 3, LOS, and normalization of fever were used to assess the response to antibiotics. Results Sixty-one patients were taking statins and 90 patients were not taking statins. Patients on statins had significantly more comorbid conditions; both groups had comparable CURB-65 scores. In both groups, no statistically significant difference was seen for the decrease in CRP level on days 1 and 3 and LOS. No difference in days to normalization of fever was detected in either group. Conclusion No association was found between the chronic use of statins and CRP levels, LOS, or days to fever normalization in patients with CAP.

show abstract

Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection

Cited by 8 publications

References 29 publications

Eriodictyol, Not Its Glucuronide Metabolites, Attenuates Acetaminophen-Induced Hepatotoxicity

Eriodictyol, Not Its Glucuronide Metabolites, Attenuates Acetaminophen-Induced Hepatotoxicity

Fever therapy in febrile adults: systematic review with meta-analyses and trial sequential analyses

Effects of statins on clinical outcomes in hospitalized patients with community-acquired pneumonia

Contact Info

Product

Resources

About