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救急部 木村 圭一
Early antipyretic exposure does not increase
mortality in patients with gram-negative severe
sepsis: a retrospective cohort study.
Existing data suggest that antipyretic medications may have deleterious effects on
immune function and may increase mortality in human infection. This study was
designed to evaluate the impact of antipyretic therapy on 28-day in-hospital mortality
when administered early in the course of gram-negative severe sepsis or septic
shock. This study was a single-center retrospective cohort study at a 1,111-bed
academic medical center of all febrile patients with gram-negative bacteremia
hospitalized with severe sepsis or septic shock (n = 278) between Jan 2002 and Feb
2008. Although the raw mortality was lower in the group that received an early
antipyretic medication (22 vs. 35 %, p = 0.01), patients in the early antipyretic group
had higher mean arterial pressure (58.0 vs. 52.7, p = 0.01) and higher 24-h T (max)
(39.3 vs. 39.0, p < 0.01). Early antipyretic therapy was not significantly associated with
28-day in-hospital mortality (adjusted OR 0.55, 0.29-1.03) in a multivariable logistic
regression model controlling for APACHE-II score, hypotension, pneumonia, surgery
during hospitalization, persistent fever, and in-hospital dialysis. In conclusion, early
antipyretic therapy is not associated with increased mortality.
Intern Emerg Med. 2012 Oct;7(5):463-70. Epub 2012 Aug 28.
Prophylactic use of antipyretic agents with
childhood immunizations and antibody response:
reason for concern?
In the pediatric primary care setting, well-child visits constitute over 50% of all encounters, treating
over 24 million children annually. Anticipatory guidance topics vary based on different ages, but
immunizations are a focal point of all well-child visits. This article addresses the prophylactic use of
antipyretic agents with the administration of immunizations as a potential reason of concern.
A literature review of the use of antipyretic agents in conjunction with immunizations and the
effectiveness of treatment was performed.
Based on several studies, the standard recommendation of administering antipyretic agents with
immunization administration was a routine. Twenty years later, the scientific evidence was
questioned. A pivotal study questioned these standards, noting no benefit and potential decreased
Although the prophylactic use of antipyretics has been a standard in pediatrics, the lack of scientific
support in the reduction of adverse effects of the vaccinations and the possibility of decreased
immune response warrants further research.
J Pediatr Health Care. 2012 May-Jun;26(3):200-3. Epub 2011 Feb 26.
Association of body temperature and antipyretic
treatments with mortality of critically ill patients
with and without sepsis: multi-centered
prospective observational study.
Fever 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.
We 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.
We 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 36.5°C to 37.4°C),
MAXICU≥39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P=0.01), but not in non-septic patients (adjusted
odds ratio 0.47, P=0.11).
In 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.
Crit Care. 2012 Feb 28;16(1):R33.
Systematic review and meta-analysis of the effects
of antipyretic medications on mortality in
Streptococcus pneumoniae infections.
To determine whether the use of antipyretic medications in the treatment of Streptococcus pneumoniae infection affects mortality in humans or
A systematic search of Medline, Embase, and The Cochrane Register of Controlled Trials was undertaken to identify in vivo animal experiments
or randomised, controlled trials in humans of antipyretic medication in S pneumoniae infection which reported mortality data. Meta-analysis was
by inverse variance weighted method for odds ratios.
Antipyretics are recommended for the symptomatic treatment of various diseases caused by S pneumoniae. However, there is evidence that
fever is a protective physiological response to infection, that treating fever secondary to infection may be harmful, and that some strains of S
pneumoniae are temperature sensitive.
MAIN OUTCOME MEASURES:
Mortality associated with antipyretic use in S pneumoniae infection.
Four studies from two publications met the inclusion criteria and investigated the use of aspirin in animal models. The pooled estimate of mortality
was an OR with aspirin treatment of 1.97 (95% CI 1.22 to 3.19). There were no suitable human studies identified.
A twofold increased risk of mortality was found with aspirin treatment in animal
models of S pneumoniae infection. No relevant human studies were identified. It is
difficult to generalise from animal models to clinical medicine, but based on these findings and the prevalence and severity of S pneumoniae
infections worldwide, future study of the effects of antipyretic therapy in S pneumoniae infection in humans is recommended.
Postgrad Med J. 2012 Jan;88(1035):21-7. doi: 10.1136/postgradmedj-2011-130217. Epub 2011 Nov 25.