Trial reportCritical care (London, England)2012
Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study.
Trial report in Critical care (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 4 registered trials, which are not on this map. Cited by 106 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Fever and Antipyretic in Critically Illness Evaluation Study
Effects of Intravenous Acetaminophen on Body Temperature and Hemodynamic Responses in Febrile Critically Ill Adults: a Randomized Controlled Trial
Prospective Comparative Study of the Efficacy of Common Antipyretic Treatments in Febrile Children
Comparison of the Efficacy of Paracetamol and Ibuprofen in the Management of Fever in Sepsis Patients: A Randomized Double-Blind Controlled Study
Who cites it
106 citing papers in PubMed, 8 syntheses or guidelines pooled it, 249 citations in OpenAlex.
- Guideline for Medication Management of Distressing Symptoms in Older Patients Receiving End-of-Life Palliative Care.Journal of evidence-based medicine · 2026Guideline
- Long-term health effects of antipyretic drug use in the aging population: a systematic review.Journal of medicine and life · 2024Pooled it
- Non-corticosteroid adjuvant therapies for acute bacterial meningitis.The Cochrane database of systematic reviews · 2021Pooled it
- The efficacy of steroids in reducing morbidity and mortality from extreme hyperthermia and heatstroke-A systematic review.Pharmacology research & perspectives · 2020Pooled it
- Surviving sepsis campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children.Intensive care medicine · 2020Guideline
- Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis.Critical care medicine · 2017Pooled it
- Fever Is Associated with Reduced, Hypothermia with Increased Mortality in Septic Patients: A Meta-Analysis of Clinical Trials.PloS one · 2017Pooled it
- Should we treat fever in critically ill patients? A summary of the current evidence from three randomized controlled trials.Einstein (Sao Paulo, Brazil)Pooled it
- Randomized, controlled, multicentre clinical trial of the antipyretic effect of intravenous paracetamol in patients admitted to hospital with infection.British journal of clinical pharmacology · 2017Trial
- Respective impact of lowering body temperature and heart rate on mortality in septic shock: mediation analysis of a randomized trial.Intensive care medicine · 2015Trial
- Body temperature and mortality in patients with acute respiratory distress syndrome.American journal of critical care : an official publication, American Association of Critical-Care Nurses · 2015Trial
- The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis.Critical care (London, England) · 2013Trial
- The association between body temperature parameters and blood culture positivity in the inpatient setting: a retrospective cohort study.BMC infectious diseases · 2026Article
- The poikilothermic hypothesis of sepsis.Critical care (London, England) · 2026Review
- Machine learning prediction of early hypothermia in sepsis patients.Archives of medical science : AMS · 2026Article
- Comparative Impact of NSAIDs Versus Acetaminophen on Mortality in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Retrospective Cohort Study of 2484 Patients From a Nationwide Inpatient Database.The Journal of dermatology · 2026Article
- Respiratory National Early Warning Score for 28-day mortality prediction in suspected sepsis patients in the emergency department.BMC emergency medicine · 2025Article
- Fever in Sepsis Revisited: Is a Little Heat What We Need?Open forum infectious diseases · 2025Review
- Recent advances in diagnostic technologies for postoperative central nervous system infections: a review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Systemic Inflammation Index (SII) as a Predictor of Mortality in Intensive Care Units.Biomedicines · 2025Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
42 authors at 20 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionFever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.
methodsWe designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring >48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAXICU) and the use of antipyretic treatments with 28-day mortality.
resultsWe recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P=0.028, acetaminophen: 2.05, P=0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P=0.15, acetaminophen: 0.58, P=0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAXICU ≥ 39.5°C increased risk of 28-day mortality in non-septic patients (adjusted odds ratio 8.14, P=0.01), but not in septic patients (adjusted odds ratio 0.47, P=0.11) [corrected].
conclusionsIn non-septic patients, high fever (≥39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.
trial registrationClinicalTrials.gov: NCT00940654.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.