Acetaminophen for Fever in Critically Ill Patients with Suspected Infection

Young, Paul; Saxena, Manoj; Bellomo, Rinaldo; Freebairn, Ross; Hammond, Naomi; Haren, Frank Van; Holliday, Mark; Henderson, Seton; Mackle, Diane; McArthur, Colin; McGuinness, Shay; Myburgh, John; Weatherall, Mark; Webb, Steve; Beasley, Richard

doi:10.1056/nejmoa1508375

Cited by 183 publications

(149 citation statements)

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“…Acetaminophen (perfalgan) 1 g intravenous every 6 hours or as needed is considered the most common antipyretic therapy used in these settings for this purpose. Acetaminophen showed a significant effect in reducing the mean daily peak body temperature and the mean daily average body temperature as reported previously (4,5). However, its effect onother parameters including ICU length of stay, hospital stay and the survival is still controversial.…”

Section: Introductionsupporting

confidence: 71%

“…(Figure 1) Table 1. Quality of the included studies Randomized controlled trial (7,8)and one prospective observational study (9) were included finally in this review. In all the three studies, the treatment of fever was with acetaminophen in one group and no treatment givento the other placebo group.…”

Section: Resultsmentioning

confidence: 99%

“…One study evaluated non-surgical patients (8)and the others evaluated both surgical and medical patients (7,9). Two studies included patients with fever and infection at time of diagnosis (7,9), whereas the third study included patients with fever due to other reasons (8). Based on the analysis of these three trials,there is no difference in ICU and hospital length of stay between the group treated with acetaminophen and placebo ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…One recent observational study showed that acetaminophen is associated with a reduction in hospital mortality and time to death in ICU patients with fever without an infection (6). However, in a recent randomized controlled trial, acetaminophen did not add any additional benefit comparing to placebo in improving ICU-free days or survival in patients with fever due to infection (5). Therefore, the main objective for this study is to discuss and analyze the main literatures regarding the use of acetaminophen in critically ill patients with fever due to infections or other non-infectious insults.…”

Section: Introductionmentioning

confidence: 99%

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Acetaminophen in critically ill patients with fever

Mahmood¹

2016

IOSRPHR

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Abstract:-Background: Acetaminophen is one of the most treatments used to reduce the temperature in ICU patients. However, it is still unclear whether the use of acetaminophen improves patients' survival and hospital length of stay. This study aims to analyze the main literatures which studied the use of acetaminophen in ICU patients with fever due to infections or other non-infectious insults. Methods:Severaldatabases including Cochrane library database, Academic Search Complete, and PubMed were searched for studies on acetaminophen in ICU patients. The search was limited to randomized controlled trials, cohort studies, adult human critically ill patients, treatment with acetaminophen in one arm and no treatment (placebo) in the other arm. The outcomes assessed were the ICU and hospital length of stay, mortality rate, ICU-free days and changes in temperature. Results:Two randomized control trials and one cohort study covering 32,408 patients were included. There wereno differences in ICU and hospital length of stay between the group treated with acetaminophen and placebo. In addition, the mortality rate did not differ between the two groups in patients with fever due to infection; however, a difference was shown in patients with fever due to non-infectious insults. Finally, there was a significant reduction in temperature in acetaminophen group compared to placebo. Conclusion: The use of acetaminophen for fever in critically ill patients was not associated with better outcome in terms of ICU and hospital length of stay and mortality ratecompared to placebo especially when the fever is due to infections.

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Section: Introductionsupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acetaminophen in critically ill patients with fever

Mahmood¹

2016

IOSRPHR

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“…Six randomized controlled trials (RCTs) were extracted as a result of the systematic review conducted for this CQ 374, 375, 376, 377, 378, 379. All six RCTs assessed mortality rates, one assessed ICU‐free survival days, four examined the length of ICU stay, and two examined the rates of complication from infection.…”

Section: Cq15: Body Temperature Regulationmentioning

confidence: 99%

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

Nishida

Ogura

Egi

et al. 2018

Acute Medicine & Surgery

157

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Background and PurposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two‐thirds (>66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J‐SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta‐analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese‐specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non‐specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

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Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis

Ware,

Files,

Fowler

et al. 2024

JAMA

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ImportanceAcetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates.ObjectiveTo determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo.Design, Setting, and ParticipantsPhase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation.InterventionPatients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days.Main Outcome and MeasuresThe primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL.ResultsOf 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P = .56; difference, 0.6; 95% CI, −1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P = .01; difference, −6.3; 95% CI, −10.8 to −1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen.Conclusions and RelevanceIntravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients.Trial RegistrationClinicalTrials.gov Identifier: NCT04291508

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Acetaminophen for Fever in Critically Ill Patients with Suspected Infection

Abstract: Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days. (Funded by the Health Research Council of New Zealand and others; HEAT Australian New Zealand Clinical Trials Registry number, ACTRN12612000513819.).

Cited by 183 publications

References 18 publications

Acetaminophen in critically ill patients with fever

Acetaminophen in critically ill patients with fever

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis

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