Tuesday, July 12, 2011

A Feverish Debate




# 5687



Photo Credit –CDC PHIL


A topic I’ve written about several times in the past is back in the news again; the advisability of using antipyretic meds (ibuprofen, acetaminophen or paracetamol, etc) for flu-related fever.


The eye-catching headline and lede in yesterday’s New Zealand Herald reads:


'Don't use paracetamol for fever'

By Martin Johnston

5:30 AM Monday Jul 11, 2011

A respected scientific group has recommended not using paracetamol and several other drugs to reduce flu-related fever, saying they may increase the risk of death.

(Continue . . . )



The respected scientific group referenced in the article above is Wellington based Medical Research Institute of New Zealand. And their advice runs contrary to what we usually hear from our doctors, the CDC, and the World Health Organization.


Constant readers will recall that last May I wrote (see It Gives You Fever) about about a clinical trial this research group was about begin that would examine the merits and risks of taking antipyretics with influenza.


The concern is that when we take fever reducers, we lower the body’s temperature to provide symptomatic relief – but we also create a more favorable environment for the virus to replicate.


Essentially trading comfort for circumventing the body’s natural defense mechanism.


Last year, in A Hot Topic For Further Research I wrote about new research that suggested (but fell short of proving) that we may be better off carrying a bit of a fever – rather than reaching for the pill bottle -  when we have the flu.


And while that isn’t exactly a new idea, the evidence to support it has been limited.


The study – again conducted by the Medical Research Institute of New Zealand -  appeared in the Journal of the Royal Society of Medicine (registration required for access) – and provided a retrospective analysis of previous animal (not human) studies on the outcomes of the treatment of bacterial and viral infections with antipyretics.


The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis

Sally Eyers, Mark Weatherall, Philippa Shirtcliffe, Kyle Perrin, and Richard Beasley

v.103(10); Oct 1, 2010


In a review of the existing literature, researchers at the Medical Research Institute of New Zealand and Capital & Coast District Health Board, identified 8 (non-human animal) studies that met their inclusion criteria.


They found that the risk of mortality increased by roughly 33% when antipyretics were used in influenza infected animals.  This risk was observed with aspirin, paracetamol, and diclofenac.


As I pointed out at the time, there were a lot of limitations to this study, not the least of which is that research on mice, chickens, and ferrets isn’t always applicable to humans.


Hence the need for the clinical trial on humans underway in New Zealand.


From the Medical Research Institute’s website, a description of goals of the clinical trial.

The effect on mortality of antipyretics in the treatment of influenza

Antipyretics are recommended for the symptomatic treatment of influenza infection.  However there is evidence that fever is a protective physiological response, that treating fever secondary to infections may be harmful and that human tropic influenza viruses are variable temperature-sensitive.

In a systematic review and meta-analysis we have identified that in animal models treatment with antipyretics for influenza infection increases the risk of mortality.  There are no randomised controlled placebo-controlled trials of antipyretic use in influenza infection in humans that reported data on mortality and a paucity of clinical data by which to assess their efficacy.

In response to these findings the MRINZ is now undertaking a placebo-controlled randomised trial of paracetamol use in influenza infection. This study is funded by the Health Research Council of New Zealand.


The results of that trial are not yet available, and so while the Medical Research Institute is publicly questioning the value of reducing fevers with influenza, they are not yet calling for health authorities to change their existing stance on the use of antipyretics.


They also state that using these meds as a pain reliever for muscle aches and headaches when you have influenza, is a reasonable practice.


And to round out this debate, the New Zealand Self Medication Industry Association (who have a vested interest in the sale of these products) has weighed in with the following press release.


Tuesday 12 July 2011, 12:13pm

Media release from New Zealand Self-Medication Industry Association

The New Zealand Self-Medication Industry Association (SMI), the industry body representing non-prescription consumer healthcare products, said today it was aware of a recommendation by the Wellington-based Medical Research Institute that antipyretics, such as paracetamol, ibuprofen and aspirin, not be used to reduce flu-related fever.


"We have only just received this information and, as the Institute itself said, there was insufficient evidence for the Ministry of Health to change its current position on these products. It's important people do not overreact and stop using antipyretics altogether.


Paracetamol and ibuprofen, for example, are well recognized for the relief of pain," commented SMI executive director Tim Roper.

"Fever management guidelines highlight that it is important to treat the patient and not the thermometer - SMI and its members endorse this approach. We are confident that if this approach is used, that these medicines can be used safely.

"Nevertheless, our members welcome the opportunity to work with Medsafe to discuss any matters that may arise, after the Ministry has reviewed the new information."



Although the jury is still out on all of this (and I’ve not discarded the Tylenol from my medicine cabinet), the American Academy of Pediatrics (AAP) released a report earlier this year on the use of antipyretics in children, suggesting that we ought not over-treat fevers.


Clinical Report—Fever and Antipyretic Use in Children

Janice E. Sullivan, MD, Henry C. Farrar, MD,




Fever in a child is one of the most common clinical symptoms managed by pediatricians and other health care providers and a frequent cause of parental concern. Many parents administer antipyretics even when there is minimal or no fever, because they are concerned that the child must maintain a “normal” temperature.


Fever, however, is not the primary illness but is a physiologic mechanism that has beneficial effects in fighting infection. There is no evidence that fever itself worsens the course of an illness or that it causes long-term neurologic complications.


Thus, the primary goal of treating the febrile child should be to improve the child's overall comfort rather than focus on the normalization of body temperature.


(Continue . . . .)



And lastly, I would mention that in 2009 I wrote about some of the downsides to taking anti-inflammatory drugs like Aspirin, Tylenol, and Ibuprofen in a blog called  A Few Inflammatory Remarks.


It concerned a Lancet study that suggested giving babies acetaminophen (Tylenol) right before or immediately after getting a vaccination may inhibit or lower their immune response.


It also discussed several studies from the University of Rochester, that indicate the use of NSAIDs could lower the body’s antibody response.


It is axiomatic that there is no such thing as a 100% safe, 100% benign drug – even those you can buy over the counter.  


If there is a health benefit to be had, we must weigh that against the (usually very slight) risks of taking the these meds.


While the overall risks of taking these drugs are likely exceedingly small, hopefully we’ll soon have research that will help quantify the risks and rewards of using these common fever reducing medicines.

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