Temperatures and Febrile seizures.

[Momtezuma Tuatara]

Temperatures are a source of concern for many parents, and we as parents have been conditioned to reach for the acetaminophen products. However, three are good reasons to re-evaluate that advice, because when you review the literature on it, there is little in the medical literature to suggest it's a good idea, and plenty to suggest that it's counterproductive.

I've attached the fever chapters from both JALP and FOPTA below. If you want to read the chapters below, the JALP chapter sets the scene.

But for some mothers, when their children react to temperature with seizures it can be very scarey.

Here is an interesting article written by a paediatrician (http://www.youandyourchildshealth.org/articles/fever.html): extract

As a parent, one of my first exposures to anthroposophical medicine was when my child had a cold and a fever of 104. He didn't have a sore throat, cough, or any difficulty breathing and his lungs were clear to auscultation. He also didn't have any vomiting, or a stiff neck, so there weren't any signs of meningitis. It was late at night, and I was up in the mountains and at least 30 minutes away from any hospital or urgent care. Well, my son started having auditory hallucinations with his fever. I gave him a lukewarm bath. The bath worked temporarily (for 5-10 minutes), but he would get chilled and shiver and then the fever rose higher than ever. After two more tepid baths which didn't work, I then called a friend who was an anthroposophical physician. I was told to feel my sons feet. If they were warm (and not cold) then I could apply a "Lemon Wrap". If the feet were cold I would need to warm them first using blankets or a covered hot water bottle before applying the lemon wrap.


Now, to make a lemon wrap you take a lemon, squeeze it into a pan and add 1/2 to


1 cup of water and heat it to almost boiling. I was then instructed to soak a pair of my cotton socks in this hot lemon juice (reportedly tepid or warm lemon juice also works), wring the socks out well, and put the hot socks on both of my child's feet (pulling the socks up over his calves). I then placed a pair of my wool socks over the cotton socks so his feet and legs would not get chilled and covered him with a blanket. All I could think of while doing this was the headlines in the morning newspaper- "Son dies of a febrile seizure while mother, who is a pediatrician, applies lemon juice to his calves".


Well, the headlines didn't turn out like that. My son's fever immediatedly came down to 102 and the hallucinations stopped, all in 10 minutes. I left the lemon wrap on his legs for a total of 20 minutes and then removed it. Lemon wraps are usually only needed when a child is restless and uncomfortable with a fever greater than 102 degrees. Usually one would apply no more than three lemon wraps in a 24 hour period while carefully observing the child for any signs of a more serious illness. A lemon wrap does not cause a large drop in temperature but rather it works by pulling the inflammation away from the head.

[Momtezuma Tuatara]

The first thing to be aware of, with babies is that normal temperatures vary. I don't do celcius, so you might need to find a converter.

In Fahrenheit, these are a rough guide to normal temperatures for various ages:

3 mo. 99.4
6 mo. 99.5
1 yr. 99.7
3 yr. 99.0
5 yr. 98.6
7 yr. 98.3
9 yr. 98.1
11 yr 98.0
13 yr 97.8

I used the word "rough" because I don't think everyone fits into a "mould"....
This came from a nurse on Mothering.. she looked it up in a textbook, but I forgot to ask for the reference, and .. um.. well, I can't now, can I?

[Momtezuma Tuatara]

http://www.med.umich.edu/1libr/pa/pa_feverpho_hhg.htm (http://www.med.umich.edu/1libr/pa/pa_feverpho_hhg.htm)

Extract


Myths and Facts about Fever

Misconceptions about the dangers of fever are commonplace. Unwarranted fears about harmful side effects from fever cause lost sleep and unnecessary stress for many parents. Let the following facts help you put fever into perspective:

MYTH: All fevers are bad for children.

FACT: Fevers turn on the body's immune system. Fevers are one of the body's protective mechanisms.

Most fevers are good for children and help the body fight infection. Use the following definitions to help put your child's level of fever into perspective:

100°F to 102°F Low-grade fever: Beneficial. Try (37.8°C to 39°C) to keep the fever in this range.

102°F to 104°F Moderate-grade fever: Beneficial. (39°C to 40°C)

Over 104°F High fever: Causes discomfort, but (40°C) is harmless.

Over 105°F High fever: Higher risk of (40.6°C) bacterial infections.

Over 108°F Serious fever: The fever itself can (42°C) be harmful.

Read on.

[Momtezuma Tuatara]

Official guidelines for Dutch family doctors in case of fever in children:

A realistic notion about fever will make it more easy for parents to deal with children having fever.

In general, fever does not need treatment.

Actively lowering the body temperature is not neccessary. Applying cold compresses and cold sponging of the child is not meaningful.

In principle, no antipyretics are given. Antipyretics do not fight the disease and at best will make the child feel a bit better.

Fever is qualified as a rectal temperature above 38 degrees C.

There are no injurious effects of fever below 41.7 degrees C.

Fever is a useful bodily reaction. If the heat is allowed to drain away, fever will not rise above 41.7 degrees C.

The increase of the body temperature seems to be important in fighting the disease.

If the fever is not treated, this does not mean the temperature will keep rising.

The main reason for taking the temperature is knowing whether or not there is a fever.

There is no use in measuring each change. It is sufficient to take the temperature once a day.

Parents should not wake their child to take the temperature.

Temperature should be measured per rectum. Other ways are not reliable.

Observing the child and registering changes in the childs behaviour are more important than frequently measuring the temperature.

The extent to which the child is sick is far more important than the temperature of the fever.

[Momtezuma Tuatara]

http://www.eurekalert.org/pub_releases/2004-02/nioa-efa020604.php (http://www.eurekalert.org/pub_releases/2004-02/nioa-efa020604.php)

Public release date: 9-Feb-2004
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Contact: Paul Williams
pwilliams@niaid.nih.gov (pwilliams@niaid.nih.gov)
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases (http://www.niaid.nih.gov/)
Early fevers associated with lower allergy risk later in childhood

Infants who experience fevers before their first birthday are less likely to develop allergies by ages six or seven, according to a new study funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).

The study, published today in the Journal of Allergy and Clinical Immunology, lends support to the well-known "hygiene hypothesis," which contends that early exposure to infections might protect children against allergic diseases in later years.


"The prevalence of asthma and allergies has increased dramatically worldwide in recent years," says Anthony S. Fauci, M.D., director of NIAID. "This study provides evidence that diminished exposure to early immunological challenges could be one of the reasons for this trend."

"The hygiene hypothesis is widely recognized but largely unproven," says Kenneth Adams, Ph.D., who oversees asthma research funded by NIAID. "The findings of this study strengthen the hypothesis and, after more research, could lead to preventative therapies for asthma and allergies."

The authors of the study followed the medical records of 835 children from birth to age 1, documenting any fever-related episodes. Fever was defined as a rectal temperature of 101 degrees Fahrenheit or above.

At age 6 to 7 years, more than half of the children were evaluated for their sensitivity to common allergens, such as dust mites, ragweed and cats.

Researchers found that, of the children who did not experience a fever during their first year, 50.0 percent showed allergic sensitivity.

Of those who had one fever, 46.7 percent became allergy-prone.

The children who suffered two or more fevers in their infancy had greater protection, with only 31.3 percent showing allergic sensitivity by ages 6 to 7.

In particular, fever-inducing infections involving the eyes, ears, nose or throat appeared to be associated with a lower risk of developing allergies, compared with similar infections that did not result in fevers.

"We didn't expect fever to relate with such a consistent effect," says Christine C. Johnson, Ph.D, M.P.H., senior research epidemiologist of the Henry Ford Health System in Detroit, MI, and one of the co-authors of the study. "It also was interesting that the more fevers an infant had, the less likely it was that he or she would be sensitive to allergies."

Dr. Johnson says that more research is needed to establish if early fevers have a direct effect on allergic development in children. Additionally, she and the other authors are working to determine if early exposure to pets as well as high levels of bacteria could also lower allergy risk. "If we can uncover which environmental factors affect allergic development and why, it may be possible to immunize children against these conditions," she says.


###

This study also received support from the National Institute of Environmental Health Sciences, another NIH component.
NIAID is a component of the National Institutes of Health (NIH), an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.
Reference:
L Keoki Williams et al. The relationship between early fever and allergic sensitization at age 6 to 7 years. Journal of Allergy and Clinical Immunology 113(2): 291-296 (2004).
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov (http://www.niaid.nih.gov/).

[MinorityView]

Interesting account in the first section.

We are very vulnerable as new mothers. I honestly expected my daughter to die. First of starvation. After she got so fat (on my milk) that she had trouble moving, I gave that one up. Then she got her first fever, at 8 months of age. Luckily my mother was around and managed to convince me that death wasn't imminent and that she would survive. She did.

Oddly, scared as I was, I still didn't vax her.

This is a good thread!

[Momtezuma Tuatara]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9917880 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9917880)

Ann N Y Acad Sci. 1998 Sep 29;856:214-23. Related Articles, (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=pubmed_pubmed&from_uid=9917880)Links (http://javascript<b></b>:PopUpMenu2_Set(Menu9917880,'','','','','');)

Benefits and risks of antipyretic therapy.

Mackowiak PA, Plaisance KI.

VA Maryland Health Care System, Baltimore, Maryland 21201, USA.

Physicians have used various forms of antipyretic therapy since antiquity to lower the temperature of febrile patients. Nevertheless, it has yet to be determined whether the benefits of antipyretic therapy outweigh its risks. It is not known, for example, if core temperatures encountered during the febrile state ever reach levels that are intrinsically noxious (and therefore merit antipyretic intervention) or when, if ever, fever's metabolic costs exceed its physiologic benefits, or if the benefits of symptomatic relief afforded by antipyretic drugs consistently exceed their toxicologic cost. Whereas preliminary experimental and clinical observations suggest that antipyretic therapy has the potential to increase the duration and/or severity of certain infections, such data are as yet too fragmentary to draw firm conclusions regarding their validity. Finally, although clinicians have long suspected that bacteremia and other severe infections might induce fevers that are less responsive to antipyretic therapy than are those associated with self-limited infections, this concept has not held up under scientific scrutiny. Thus, despite over 2.5 millennia of clinical experience, important questions regarding the risks and benefits of antipyretic therapy remain to be answered.

Publication Types:
· Review
· Review, Tutorial

PMID: 9917880 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11113026 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11113026)

Clin Infect Dis. 2000 Oct;31 Suppl 5:S219-23.Related Articles, (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=pubmed_pubmed&from_uid=11113026)Links (http://javascript<b></b>:PopUpMenu2_Set(Menu11113026,'','','','','');)

Toxicities of drugs used in the management of fever.

Plaisance KI.

University of Maryland School of Pharmacy, Baltimore, MD 21201, USA. kplaisan@rx.umaryland.edu (kplaisan@rx.umaryland.edu)

Fever is frequently managed outside the purview of medical professionals, and antipyretic therapy, on the whole, is generally considered safe. However, each of the drugs used in the management of fever has significant toxicities. The purpose of this review is to examine the relative safety of such agents with a focus on the nonsteroidal anti-inflammatory drugs and acetaminophen. Toxicity to the gastrointestinal, renal, and hepatic systems are considered; the comparative safety profile of acetaminophen and ibuprofen as antipyretics are highlighted; and specific recommendations to improve the safe use of these therapies are advanced.

Publication Types:
· Review
· Review, Tutorial

PMID: 11113026 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3090790 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3090790)

Yale J Biol Med. 1986 Mar-Apr;59(2):107-16.

Fever: is it beneficial?

Blatteis CM.

Data obtained in lizards infected with live bacteria suggest that fever may be beneficial to their survival. An adaptive value of fever has also been inferred in mammals, but the results are equivocal. Findings that certain leukocyte functions are enhanced in vitro at high temperatures have provided a possible explanation for the alleged benefits of fever. However, serious questions exist as to whether results from experiments in ectotherms and in vitro can properly be extrapolated to in vivo endothermic conditions. Indeed, various studies have yielded results inconsistent with the survival benefits attributed to fever, and fever is not an obligatory feature of all infections under all conditions. Certainly, the widespread use of antipyretics, without apparent adverse effects on the course of disease, argues against fever having great benefit to the host. In sum, although fever is a cardinal manifestation of infection, conclusive evidence that it has survival value in mammals is still lacking.

PMID: 3090790 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11165933 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11165933)

Microbes Infect. 2000 Dec;2(15):1891-904.

The role of fever in the infected host.

Hasday JD, Fairchild KD, Shanholtz C.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, and the Medicine Services of the Baltimore Veterans Affairs Centre, MD 21201, USA. jhasday@umaryland.edu (jhasday@umaryland.edu)

Sepsis is a highly lethal clinical syndrome characterized by a systemic inflammatory response to infection. Fever, a non-specific acute-phase response, has been associated with improved survival and shortened disease duration in non-life-threatening infections. However, the influence of fever and the effects of antipyresis in patients with sepsis has not been prospectively studied in humans. This paper reviews the state of our knowledge concerning the biological effects of fever in infected hosts and the influence of fever and antipyretic therapy on survival during sepsis in experimental models and in man.

Publication Types:
· Review
· Review, Tutorial

PMID: 11165933 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10695685 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10695685)


Arch Intern Med. 2000 Feb 28;160(4):449-56.

Antipyretic therapy: physiologic rationale, diagnostic implications, and clinical consequences.

Plaisance KI, Mackowiak PA.

University of Maryland School of Pharmacy, Baltimore 21201, USA.

Various treatments have been used to suppress fever since antiquity. Surprisingly, few studies have been performed to ascertain the physiologic consequences of antipyresis and validate the rationale behind such therapy. More importantly, it has not been established conclusively that the benefits of antipyretic therapy outweigh its risks. The present review considers these issues in light of currently available data and formulates guidelines for antipyretic therapy based on these data.

Publication Types:
· Review
· Review, Tutorial

PMID: 10695685 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12015457 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12015457)

Curr Opin Infect Dis. 2002 Jun;15(3):241-5.

Fever: beneficial and detrimental effects of antipyretics.

Greisman LA, Mackowiak PA.

Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.

Although various forms of therapy have been used, since antiquity, to lower the temperature of febrile patients, it is still not known whether the benefits of antipyretic therapy outweigh its risks. Justifications for the use of antipyretic drugs, and the evidence pertaining to these rationales, are examined. Antipyretic therapy in sepsis, and adverse effects of antipyretic medications, are also reviewed.

Publication Types:
· Review
· Review, Tutorial

PMID: 12015457 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8698984 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8698984)

Infect Dis Clin North Am. 1996 Mar;10(1):1-20.

The adaptive value of fever.

Kluger MJ, Kozak W, Conn CA, Leon LR, Soszynski D.

Lovelace Institutes, Albuquerque, New Mexico, USA.

There is overwhelming evidence in favor of fever being an adaptive host response to infection that has persisted throughout the animal kingdom for hundreds of millions of years. As such, it is probable that the use of antipyretic/anti-inflammatory/analgesic drugs, when they lead to suppression of fever, results in increased morbidity and mortality during most infections; this morbidity and mortality may not be apparent to most health care workers because fever is only one of dozens of host defense responses. Furthermore, most infections are not life-threatening and subtle changes in morbidity are not easily detected.

Publication Types:
· Review
· Review, Tutorial

PMID: 8698984 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11113022 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11113022)

Clin Infect Dis. 2000 Oct;31 Suppl 5:S185-9.

Physiological rationale for suppression of fever.

Mackowiak PA.

Medical Care Clinical Center, Veterans Affairs Maryland Health Care System, and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Philip.Mackowiak@med.va.gov (Philip.Mackowiak@med.va.gov)

Two critical assumptions are made when prescribing antipyretic therapy. One is that fever is, at least in part, noxious, and the other is that suppression of fever will reduce, if not eliminate, the noxious effects of fever. At present, neither assumption has been validated experimentally.

Publication Types:
· Review
· Review, Tutorial

PMID: 11113022 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12400525 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12400525)

Nursing. 2002 Oct;32(10):66-70.

Combating infection: should you treat a fever?

Husain MA, Coleman R.

Clinical Medicine, University of Illinois, Chicago, IL, USA.

Publication Types:
· Review
· Review, Tutorial

PMID: 12400525 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11866359 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11866359)

Clin Pediatr (Phila). 2002 Jan-Feb;41(1):11-4.
Comment in:
· Clin Pediatr (Phila). 2002 Jan-Feb;41(1):14-6. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11866360)

Comment on:
· Clin Pediatr (Phila). 2002 Jan-Feb;41(1):9-11. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11866375)

Fever: to treat or not to treat. Counterpoint.

Narang AS.

Department of Pediatrics, Louisiana State University Health Science Center and Children's Hospital, New Orleans, USA.

Publication Types:
· Comment

PMID: 11866359 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11055601 (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11055601)

Pediatr Infect Dis J. 2000 Oct;19(10):983-90.

Household crowding a major risk factor for epidemic meningococcal disease in Auckland children.

Baker M, McNicholas A, Garrett N, Jones N, Stewart J, Koberstein V, Lennon D.

Institute of Environmental Science and Research, Wellington, New Zealand.

BACKGROUND: New Zealand is in its ninth year of a serogroup B meningococcal disease epidemic with annual rates of up to 16.9 cases per 100,000. The highest incidence is in Maori and Pacific Island children in the Auckland region. We conducted a case-control study to identify potentially modifiable risk factors for this disease. METHODS: A case-control study of 202 cases of confirmed and probable meningococcal disease in Auckland children younger than 8 years of age recruited from May, 1997, to March, 1999, was undertaken. Controls (313) were recruited door-to-door by a cluster sampling method based on starting points randomly distributed in the Auckland region. They were frequency matched with the expected distribution of age and ethnicity in the meningococcal disease cases. RESULTS: With the use of a multivariate model and controlling for age, ethnicity, season and socioeconomic factors, risk of disease was strongly associated with overcrowding as measured by the number of adolescent and adult (10 years or older) household members per room [odds ratio (OR), 10.7; 95% confidence interval (CI), 3.9 to 29.5]. This would result in a doubling of risk with the addition of 2 adolescents or adults to a 6-room house. Risk of disease was also associated with analgesic use by the child, which was thought to be a marker of recent illness (OR 2.4, CI 1.5 to 4.0); number of days at substantial social gatherings (10 or more people for > 4 h; OR 1.8, CI 1.2 to 2.6); number of smokers in the household (OR 1.4, CI 1.0 to 1.8); sharing an item of food, drink or a pacifier (OR 1.6, CI 1.0 to 2.7); and preceding symptoms of a respiratory infection (cough, "cold or flu," runny nose, sneezing) in a household member (OR 1.5, CI 1.0 to 2.5). CONCLUSION: Some of these identified risk factors for meningococcal disease are modifiable. Measures to reduce overcrowding could have a marked effect on reducing the incidence of this disease in Auckland children.

PMID: 11055601 [PubMed - indexed for MEDLINE]

[MinorityView]

Babies get fevers from vaccines, right? Why wouldn't a vaccine provoked fever prevent allergies? [playing devil's advocate]

[Momtezuma Tuatara]

http://www.telegraph.co.uk/news/newstopics/politics/health/2977483/Paracetamol-use-found-to-increase-risk-of-asthma-three-fold.html


Paracetamol use found to increase risk of asthma three-fold


Taking paracetamol weekly increases the risk of asthma three-fold, research has found.

By Rebecca Smith, Medical Editor
Last Updated: 12:18AM BST 18 Sep 2008

The same effect was not seen for other painkillers and experts have called for more research into the link as it may suggest a simple way to reduce the numbers of people suffering with asthma.

More to follow

[Momtezuma Tuatara]

Babies get fevers from vaccines, right? Why wouldn't a vaccine provoked fever prevent allergies? [playing devil's advocate]

becuase the mothers pack in tylenol/pamol/paracetamol?

[Momtezuma Tuatara]

http://www.chestjournal.org/cgi/reprint/127/2/604 (http://www.chestjournal.org/cgi/reprint/127/2/604)


Chest. (http://javascript<b></b>:AL_get(this,%20'jour',%20'Chest.');) 2005 Feb;127(2):604-12.
Related Articles (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pubmed&LinkReadableName=Related%20Articles&IdsFromResult=15706003&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Links (http://javascript<b></b>:PopUpMenu2_Set(Menu15706003);)

Comment in:
· Chest. 2005 Feb;127(2):427-9. (http://www.ncbi.nlm.nih.gov/pubmed/15705977?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract)

Acetaminophen and the risk of asthma: the epidemiologic and pathophysiologic evidence.

Eneli I (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Eneli%20I%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Sadri K (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Sadri%20K%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Camargo C Jr (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Camargo%20C%20Jr%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Barr RG (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Barr%20RG%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).

Department of Pediatrics and Human Development, Michigan State University, B220 Clinical Center Bldg, East Lansing, MI 48824-1313, USA. Eneli@msu.edu (Eneli@msu.edu)

The prevalence of asthma has increased worldwide. The reasons for this rise remain unclear. Various studies have reported an association between acetaminophen, a widely used analgesic, and diagnosed asthma. In a prospective cohort study, the rate of newly diagnosed asthma was 63% higher among frequent acetaminophen users than nonusers in multivariate analyses. Studies of patients with asthma suggest that acetaminophen challenge can precipitate a decline in FEV(1) > 15% among sensitive individuals. Plausible mechanisms to explain this association include depletion of pulmonary glutathione and oxidative stress. This article reviews the existing literature and evaluates the epidemiologic and pathophysiologic evidence underlying a possible link between acetaminophen and asthma.

Publication Types:
· Review (http://javascript<b></b>:AL_get(this,%20'ptyp',%20'Review');)

PMID: 15706003 [PubMed - indexed for MEDLINE]


full text free here: http://www.chestjournal.org/content/127/2/604

[Momtezuma Tuatara]

The use of acetaminophen products reduces the effectiveness of Gardasil, and presumably other vaccines?

Full text article here http://www.jimmunol.org/cgi/content/full/177/11/7811

J Immunol. (http://javascript<b></b>:AL_get(this, 'jour', 'J Immunol.');) 2006 Dec 1;177(11):7811-9.
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(http://www.ncbi.nlm.nih.gov/entrez/utils/fref.fcgi?PrId=3051&itool=Abstract-def&uid=17114452&db=pubmed&url=http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=17114452)
Cyclooxygenase-2 inhibition attenuates antibody responses against human papillomavirus-like particles.

Ryan EP (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Ryan%20EP%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Malboeuf CM (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Malboeuf%20CM%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Bernard M (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Bernard%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Rose RC (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Rose%20RC%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Phipps RP (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Phipps%20RP%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).

Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.

Vaccination to generate protective humoral immunity against infectious disease is becoming increasingly important due to emerging strains of virus, poorly immunogenic vaccines, and the threat of bioterrorism. We demonstrate that cyclooxygenase-2 (Cox-2) is crucial for optimal Ab responses to a model vaccine, human papillomavirus type 16 virus-like particles (HPV 16 VLPs). Cox-2-deficient mice produce 70% less IgG, 50% fewer Ab-secreting cells, and 10-fold less neutralizing Ab to HPV 16 VLP vaccination compared with wild-type mice. The reduction in Ab production by Cox-2(-/-) mice was partially due to a decrease in class switching. SC-58125, a structural analog of the Cox-2-selective inhibitor Celebrex reduced by approximately 70% human memory B cell differentiation to HPV 16 VLP IgG-secreting cells. The widespread use of nonsteroidal anti-inflammatory drugs and Cox-2-selective inhibitory drugs may therefore reduce vaccine efficacy, especially when vaccines are poorly immunogenic or the target population is poorly responsive to immunization.


Publication Types:

Research Support, N.I.H., Extramural (http://javascript<b></b>:AL_get(this, 'ptyp', 'Research Support, N.I.H., Extramural');)
PMID: 17114452 [PubMed - indexed for MEDLINE]

[Momtezuma Tuatara]

Remember that acetaminophen nuked the glutathione pathway, which is important:

http://jpet.aspetjournals.org/cgi/content/abstract/187/1/211

http://www.ncbi.nlm.nih.gov/pubmed/8937421?dopt=Citation

In rats, acetaminophen messes with mitochondrial function:http://www.ncbi.nlm.nih.gov/pubmed/8937421
Our findings suggest that acetaminophen administration selectively depletes (within 2 hr) mitochondrial glutathione, and produces local toxicity by altering membrane permeability and decreasing the efficiency of oxidative phosphorylation. This renders mitochondria more susceptible to oxidative damage, especially during increased free radical production, as in the case of enhanced mitochondrial respiration in State 4. The concomitant restoration of mitochondrial respiration, oxidative phosphorylation, membrane permeability, and glutathione levels is consistent with the importance of the mitochondrial glutathione pool for the protection of the mitochondrial membrane against oxidative damage.

what about humans? Interestingly, they haven't even bothered to study that since 1997. As in, "study anything, but not that..."

[Momtezuma Tuatara]

Oh, oh, oh.. I'm wrong. They have studied it... in alcoholics...

full article here: http://dmd.aspetjournals.org/cgi/content/full/30/12/1413

Drug Metab Dispos. (http://javascript<b></b>:AL_get(this, 'jour', 'Drug Metab Dispos.');) 2002 Dec;30(12):1413-7. Links (http://javascript<b></b>:PopUpMenu2_Set(Menu12433812);)

Effects of ethanol dose and ethanol withdrawal on rat liver mitochondrial glutathione: implication of potentiated acetaminophen toxicity in alcoholics.

Zhao P (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Zhao%20P%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus), Slattery JT (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Slattery%20JT%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus).
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington 98195-7631, USA.

Chronic ethanol consumption potentiates acetaminophen (APAP) hepatotoxicity through enhanced NAPQI formation via CYP2E1 induction and selective depletion of mitochondrial glutathione. Because the prevalence of the interaction is extremely low given the use of APAP and the incidence of alcohol abuse, we studied the effects of ethanol dose and ethanol withdrawal on selective mitochondrial glutathione (GSH) depletion and APAP toxicity in liver slices. Rats were fed the Lieber-DeCarli diet containing ethanol (0, 7, 18, 27, and 36% total energy) for 6 weeks. The highest ethanol-containing diet (36% energy as ethanol) was replaced by control diet for 2, 5, 12, and 17 h. Maximal CYP2E1 induction was caused by 36% energy as ethanol diet (2.2-fold, p < 0.05 versus control). The activity and liver protein content returned to the control level 17 h after ethanol withdrawal. The 36% energy as ethanol diet caused maximal mitochondrial GSH depletion (51%, p < 0.05 versus control), which was restored 17 h after ethanol withdrawal (22.0 +/- 4.9 versus 11.7 +/- 1.7 nmol/mg protein of 0 h, p < 0.01). Elevated glutathione S-transferase-alpha release in liver slices (a measure of toxicity) was observed in rats fed 36% energy as ethanol diet (1 mM APAP: 69 +/- 10 versus 3 +/- 1% of control, p < 0.01). Enhanced toxicity disappeared when ethanol dose decreased and when ethanol was removed (7.2% ethanol: 3 +/- 1% and 17 h: 2 +/- 1%, p < 0.01 versus 0 h 36% energy as ethanol). In conclusion, high-dose ethanol potentiated APAP hepatotoxicity via CYP2E1 induction and selective mitochondrial GSH depletion. Mitochondrial GSH depletion quickly reversed when ethanol was withdrawn. The time window for both mechanisms to act in concert is narrow.
PMID: 12433812 [PubMed - indexed for MEDLINE]

[Momtezuma Tuatara]

http://www.ncbi.nlm.nih.gov/pubmed/2721538?dopt=Citation

Eur J Clin Pharmacol. (javascript:AL_get(this, 'jour', 'Eur J Clin Pharmacol.');) 1989;36(2):127-31.
Related Articles (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&DbFrom=pubmed&Cmd=Link&LinkName=pubmed_pubmed&LinkReadableName=Related%20Articles&IdsFromResult=2721538&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVCitation), Links (javascript:PopUpMenu2_Set(Menu2721538);)

Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration.

Burgunder JM (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Burgunder%20JM%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVCitation), Varriale A (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Varriale%20A%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVCitation), Lauterburg BH (http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Search&Term=%22Lauterburg%20BH%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVCitation).

Department of Clinical Pharmacology, University of Berne, Switzerland.

The effect of oral N-acetyl-L-cysteine (NAC) on plasma sulphhydryls has been studied in healthy volunteers. Following NAC 30 mg.kg-1, total NAC in plasma (i.e. free NAC and NAC as disulphides) reached a median peak concentration of 67 nmol.ml-1 within 45 to 60 min, and disappeared with an apparent half-life of 1.3 h. Only a fraction of total NAC (AUC 163 nmol.ml-1.h) was in the form of free NAC (AUC 12 nmol.ml-1.h, peak concentration 9 nmol.ml-1). Free cysteine was markedly increased (peak increment 49 nmol.ml-1; AUC 80 nmol.ml-1.h). Total cysteine and free and total glutathione in plasma were unchanged. Following the administration of 2 g paracetamol plasma cysteine and glutathione decreased (median decrement in AUC over 3 h was 5.1 nmol.ml-1.h and 3.8 nmol.ml-1.h, respectively). In contrast, the administration of 2 g NAC together with paracetamol resulted in an increase in the AUC of cysteine (+29.2 nmol.ml-1.h) and glutathione (+4.6 nmol.ml-1.h). The data show that NAC leads to a marked increase in circulating cysteine, in part by reacting with cystine and thereby forming mixed disulphides with cysteine and releasing free cysteine as shown in vitro. NAC had no effect on plasma glutathione in the absence of increased stress on the glutathione pools. However, NAC supports glutathione synthesis when the demand for glutathione is increased, as during the metabolism of paracetamol.

PMID: 2721538 [PubMed - indexed for MEDLINE]

[Momtezuma Tuatara]

http://www.medscape.com/viewarticle/539154 (http://www.medscape.com/viewarticle/539154)


July 5, 2006 — Acetaminophen at recommended doses can cause elevated alanine aminotransferase (ALT) levels, and these may remain high even when acetaminophen levels become undetectable, according to the results of a randomized study reported in the July 5 issue of JAMA....

"Initiation of recurrent daily intake of 4 g of acetaminophen in healthy adults is associated with ALT elevations and concomitant treatment with opioids does not seem to increase this effect," the authors write. "History of acetaminophen ingestion should be considered in the differential diagnosis of serum aminotransferase elevations, even in the absence of measurable serum acetaminophen concentrations."

[Momtezuma Tuatara]

http://www.medscape.com/viewarticle/510637 (http://www.medscape.com/viewarticle/510637)


August 15, 2005 — The two most commonly used non-narcotic analgesic drugs, acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), increase the risk of hypertension (HTN) in women, according to investigators an article in the Aug. 15 Online First issue of Hypertension. The risk increases by dosage and is present regardless of whether the drugs are taken for headache, the investigators reported.
"We observed that NSAIDs as well as a higher average daily dose of acetaminophen were significantly and independently associated with a higher risk of incident

hypertension," write John P. Forman, MD, from Brigham and Women's Hospital in Boston, Massachusetts, and colleagues. "In those without headache, acetaminophen and NSAIDs remained independently associated with hypertension. Aspirin dose was not significantly associated with hypertension. ...These results confirm and expand on our previous reports that frequency of acetaminophen and NSAID use increases the risk of incident hypertension in women."

[Momtezuma Tuatara]

http://www.australianprescriber.com/magazine/18/2/33/5/

http://www.australianprescriber.com/images/_lib/blue/title_graphic.gif Paracetamol: use in children
Frank Shann, Intensive Care Unit, Royal Children's Hospital, Melbourne

Summary


It is sensible to use paracetamol to reduce the discomfort caused by minor acute infections, surgical procedures and triple antigen. It is also sensible to use paracetamol to reduce fever in patients with cardiac or respiratory failure. However, there is little evidence to support the use of paracetamol to treat fever in patients without heart or lung disease, or to prevent febrile convulsions. Paracetamol may prolong infection and reduce the antibody response in mild disease, and increase morbidity and mortality in severe infection. The dose in children is 10-15 mg/kg 4 hourly, to a maximum of 100mg/kg/day, and no patient should receive more than 4 g/day.
Key words: fever, pain, analgesia, antipyretic

(Aust Prescr 1995;18:33-5)

Despite the widespread use of paracetamol, there is still confusion about when it should be used and the correct dose.1 (http://www.australianprescriber.com/magazine/18/2/33/5/#sha)

Indications for paracetamol

Fever

In patients with cardiac or respiratory failure who are febrile, it can be helpful to give paracetamol to reduce oxygen consumption, carbon dioxide production and cardiac output. However, in patients without heart or lung disease, fever is harmful only at temperatures over 41oC. Such high temperatures are usually caused by heat stroke or brain injury2 (http://www.australianprescriber.com/magazine/18/2/33/5/#sch), and, if so, they do not respond to paracetamol or aspirin.

Febrile convulsions

There is no evidence that antipyretics prevent febrile convulsions; this is probably because the convulsion is caused by the rapid rise in temperature that usually occurs at the beginning of an illness.2 (http://www.australianprescriber.com/magazine/18/2/33/5/#sch)

There are no controlled trials comparing an antipyretic to placebo for febrile convulsions, but one study comparing phenobarbitone plus antipyretic to placebo plus antipyretic found a high risk of febrile convulsions in the placebo plus antipyretic group, suggesting that antipyretic therapy did not protect against convulsions.3 (http://www.australianprescriber.com/magazine/18/2/33/5/#cam)

In a recent controlled trial in children who had had a febrile convulsion4 (http://www.australianprescriber.com/magazine/18/2/33/5/#sch), children given paracetamol 15-20 mg/kg every 4 hours were just as likely to have another convulsion as children given paracetamol only when their rectal temperature exceeded 37.9oC.

Discomfort

It is sensible to give paracetamol to reduce the unpleasant symptoms caused by mild acute infections. However, paracetamol does not have a dramatic effect: a recent controlled trial5 (http://www.australianprescriber.com/magazine/18/2/33/5/#cra)found that paracetamol caused only a modest improvement in activity and alertness in children with acute infection, and that there was no significant improvement in mood, comfort, appet ite or fluid intake. Because many patients with infection have fever and discomfort, it is often assumed that fever causes discomfort but strenuous exercise causes temperatures up to 40oC without causing discomfort.

Triple antigen reactions

Two studies6 (http://www.australianprescriber.com/magazine/18/2/33/5/#ipp),7 (http://www.australianprescriber.com/magazine/18/2/33/5/#lew)have shown that paracetamol reduces fever and abnormal behaviour in children who have had triple antigen injection. A third study8 (http://www.australianprescriber.com/magazine/18/2/33/5/#uha)found that paracetamol had no significant effect, but only one dose of 10 mg/kg of paracetamol was given 4 hours after immunisation. A reduction in adverse reactions to triple antigen is likely to improve immunisation rates.

Postoperative pain

There has been little systematic study of the use of paracetamol for postoperative pain, but controlled trials of nonsteroidal antiinflammatory drugs9 (http://www.australianprescriber.com/magazine/18/2/33/5/#dah)and experience with paracetamol suggest that paracetamol provides adequate analgesia for minor surgery, and allows a reduced dose of opiates after major surgery. Paracetamol should probably be given before surgery, rather than waiting for pain to develop after surgery.9 (http://www.australianprescriber.com/magazine/18/2/33/5/#dah)

The dose of paracetamol

While a single dose of 5 mg/kg of paracetamol results in some reduction in the temperature of febrile children, there is a much larger fall with 10 mg/kg and an even larger and more prolonged fall with 20 mg/kg.10 (http://www.australianprescriber.com/magazine/18/2/33/5/#sha)

The maintenance dose of paracetamol in children is 10-15 mg/kg 4 hourly10 (http://www.australianprescriber.com/magazine/18/2/33/5/#10), to a maximum of 100 mg/kg/day, and no patient should receive more than 4 g/day. An initial dose of 20 mg/kg can be given if it is felt that maximum effect is needed quickly. A dose of 30 mg/kg 8 hourly gives levels in the therapeutic range.10 (http://www.australianprescriber.com/magazine/18/2/33/5/#sha)A single dose of 30 mg/kg of paracetamol at bedtime can increase the amount of sleep for the whole family when a child has mild acute infection, but the danger of repeating this dose has to be emphasised.

In Australia, paracetamol is sold in preparations containing 60mg in 0.6 mL (or 100 mg/mL), 100 mg/mL, 50 mg/mL, 120 mg in 5 mL (or 24 mg/mL) and 240 mg in 5 mL (or 48 mg/mL). It is difficult to calculate a dose of 15 mg/kg from these formulations.

Parents often give a very low dose of paracetamol because they use the infant dropper, designed for 100 mg/mL preparations, to measure a dose of the more dilute preparations designed for use in older children.10 (http://www.australianprescriber.com/magazine/18/2/33/5/#sha)

Cost

Liquid preparations of paracetamol are expensive, with the MIMS price varying from $1.11 to $5.39 per g of paracetamol (mean $2.52 per g). In contrast, the MIMS price of 500 mg tablets of paracetamol is 10c to 45c per g. Tablets are a much cheaper form of paracetamol than liquid preparations, and some brands of paracetamol tablets are very much cheaper than others (the brands listed in the Schedule of Pharmaceutical Benefits tend to be less expensive).


Antipyretics may be harmful

Immunity

Too many parents and health workers think that infection is bad, infection causes fever, and that therefore fever is bad. In fact, fever is often a beneficial host response to infection, and moderate fever improves immunity.11 (http://www.australianprescriber.com/magazine/18/2/33/5/#rob)Therefore, it may not be a good idea to give drugs that reduce temperature to patients with severe infection. I have recently reviewed 1 the results of 9 controlled trials in mammals of the effect of paracetamol or aspirin on mortality or virus excretion. Four trials found that aspirin increased mortality in bacterial or viral infection. Viral shedding was increased by paracetamol or aspirin in 3 studies, possibly increased in one, and not affected in two (one used only pharyngeal washings, and one had only 9 subjects in the aspirin and placebo groups). One study found that antibody production was impaired by both paracetamol and aspirin, but no effect on antibody production was detected in the study with only 9 subjects in the aspirin and placebo groups. This evidence suggests that aspirin and paracetamol increase mortality in severe infection, and that they may prolong the infection and reduce the antibody response in mild disease.


Direct toxicity

Despite the millions of children treated with paracetamol, very little serious toxicity has been recognised (but note that the association between aspirin and Reye's syndrome was not recognised for many years). Penna and Buchanan 12 (http://www.australianprescriber.com/magazine/18/2/33/5/#pen)reviewed reports of 7 deaths and 11 cases of hepatotoxicity associated with paracetamol in children. The children who died had had more than 300 mg/kg/day of paracetamol for 1-6 days, except for one child where the plasma level suggested that the actual dose may have been much higher than the reported dose. The children who had hepatotoxicity but survived had all had 150 mg/kg/day for 2-8 days, except for two children where there was a discrepancy between the low reported doses and the high plasma levels of paracetamol (which was probably due to miscalculation of the dose or deliberate poisoning).

Presumably, other cases of paracetamol toxicity in children have occurred and have gone unrecognised or unreported, but the evidence suggests that toxicity from paracetamol is rare with doses less than 150mg/kg/day. The dose of paracetamol should not exceed 100mg/kg/day in children, and no patient should receive more than 4 g/day.

In acute poisoning from paracetamol, treatment with acetylcysteine should be started within 10 hours if possible. If the delay in starting acetylcysteine is more than 10 hours or if there is established liver failure, a longer course of acetylcysteine should be given.13 (http://www.australianprescriber.com/magazine/18/2/33/5/#smi),14 (http://www.australianprescriber.com/magazine/18/2/33/5/#kea)The best regimen has not been determined; I suggest giving 150 mg/kg of acetylcysteine in 5% dextrose intravenously over 15 minutes; then 12mg/kg/hour (200 microgram/kg/minute) for 4 hours; then 6mg/kg/hour (100 microgram/kg/minute) for at least 16 hours if the delay in starting was less than 10 hours, for at least 28 hours if the delay was 10-16 hours and at least 68 hours if the delay was more than 16 hours. Acetylcysteine should be continued as long as the patient has encephalopathy, abnormal liver function tests or paracetamol detected in the serum.

Conclusion

The antipyretic action of paracetamol is useful in febrile patients with cardiac or respiratory failure.

The analgesic action is useful in minor acute infection, for postoperative pain and after vaccination with triple antigen.

There is little evidence to support the use of paracetamol to treat fever in patients without heart or lung disease, or to prevent febrile convulsions. Indeed, paracetamol may decrease the antibody response to infection, and increase morbidity and mortality in severe infection. It should be explained to parents that fever is usually a helpful response to infection, and that paracetamol should be used to reduce discomfort, but not to treat fever.

Although an initial dose of 20 mg/kg of paracetamol can be given, this is rarely necessary. The maintenance dose in children is 10-15 mg/kg 4 hourly. Hepatotoxicity has been reported with doses of 150 mg/kg/day, and no patient should be given more than 100 mg/kg/day (up to a maximum of 4 g/day).

References
1. Shann F. Paracetamol: when, why and how much [editorial; comment]. J Paediatr Child Health 1993;29:84-5.
2. Schmitt BD. Fever in childhood. Pediatrics 1984;74:929-36.
3. Camfield PR, Camfield CS, Shapiro SH, Cummings C. The first febrile seizureantipyretic instruction plus either phenobarbital or placebo to prevent recurrence. J Pediatr 1980;97:16-21.
4. Schnaiderman D, Lahat E, Sheefer T, Aladjem M. Antipyretic effectiveness of acetaminophen in febrile seizures: ongoing prophylaxis versus sporadic usage. Eur J Pediatr 1993;152:747-9.
5. Kramer MS, Naimark LE, RobertsBrauer R, McDougall A, Leduc DG. Risks and benefits of paracetamol antipyresis in young children with fever of presumed viral origin [see comments]. Lancet 1991;337:591-4. Comments in: Lancet 1991;337:1045,1347-8.
6. Ipp MM, Gold R, Greenberg S, Goldbach M, Kupfert BB, Lloyd DD, et al. Acetaminophen prophylaxis of adverse reactions following vaccination of infants with diphtheriapertussistetanus toxoidspolio vaccine. Pediatr Infect Dis J 1987;6:721-5.
7. Lewis K, Cherry JD, Sachs MH, Woo DB, Hamilton RC, Tarle JM, et al. The effect of prophylactic acetaminophen administration on reactions to DTP vaccination. Am J Dis Child 1988;142:62-5.
8. Uhari M, Hietala J, Viljanen MK. Effect of prophylactic acetaminophen administration on reaction to DTP vaccination. Acta Paediatr Scand 1988;77:747-51.
9. Dahl JB, Kehlet H. Nonsteroidal antiinflammatory drugs: rationale for use in severe postoperative pain [see comments]. Br J Anaesth 1991;66:703-12. Comment in: Br J Anaesth 1992;68:118.
10. Shann F. Paracetamol and fever. Aust Pharm 1991;10:217-20.
11. Roberts NJ Jr. Impact of temperature elevation on immunologic defenses. Rev Infect Dis 1991;13:462-72.
12. Penna A, Buchanan N. Paracetamol poisoning in children and hepatotoxicity. Br J Clin Pharmacol 1991;32:143-9.
13. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral Nacetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985) [see comments]. N Engl J Med 1988;319:1557-62. Comment in: N Engl J Med 1989;320:1417-8.
14. Keays R, Harrison PM, Wendon JA, Forbes A, Gove C, Alexander GJ, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. Br Med J 1991;303:1026-9.

This article has been reprinted (with minor modifications) from the Journal of Paediatrics and Child Health 1993;29:84-5.

[Momtezuma Tuatara]

Download this, and read it in full, and ask yourself why this has never been headline news anywhere.


Bulletin of the World Health Organization 2003, 81 (5)


http://www.scielosp.org/pdf/bwho/v81n5/v81n5a11.pdf




Growing evidence shows the potential for hepatotoxicity in children given multiple therapeutic or subtherapeutic doses of acetaminophen (paracetamol) (8– 10). Product information recommends a maximum daily dose of 60 mg/kg, but it is not uncommon for children to receive 90 mg/kg/day in hospital (11).



Paracetamol and bacterial infections


Limited data exist on the use of paracetamol in sepsis in humans, particularly children. Despite this, antipyretic therapycommonly is administered to patients with bacterial sepsis (15). A mixed retrospective and prospective study of 180 hospitalized children (ages not stated) with uncomplicated proven bacterial infections were assessed for the effect of paracetamol treatment on duration of hospital stay (16). Patients were
divided into six groups of 30 children. Children with pneumococcal pneumonia, staphylococcal cellulitis, or Haemophilus influenzae meningitis who received at least two doses of paracetamol were compared with counterparts who received one or no doses of paracetamol. Three of the children received both aspirin and paracetamol, however, and three received only aspirin. No statistically significant difference was seen in duration of hospital stay between any of the clinical groups who received paracetamol and those who did not after adjustments were made for age, temperature on admission, and the number of doses received (16). This study, however, only described the number of doses of paracetamol received rather than the actual dose received.

Two retrospective (and therefore non-randomized) studies have been published. Administration of paracetamol (dose not stated) at the time of blood culture was an independent predictor of survival in patients with Escherichia coli bacteraemia (17) and Pseudomonas aeruginosa sepsis (18). The use of paracetamol and improvement in survival did not correlate, however, with reductions in core temperature. It should be noted that as these studies are not randomized the effect of paracetamol on survival might only represent a proxy for the ability of the individual to
mount an effective response to infection.

Many studies suggest that fever is a beneficial response to bacterial infection. Fever has been reported to be associated with increased survival in patients with spontaneous bacterial peritonitis (19, 20) and polymicrobial sepsis (21).A prospective study of 748 children with severe pneumonia in Papua New Guinea found mortality rates of 29% in afebrile malnourished children and 12% in febrile malnourished children; no such difference was found in well-nourished children with severe pneumonia (22). In three other prospective studies of sepsis, hypothermia was present in about 10% of adults surveyed and was associated with a greater than two-fold higher mortality than the presence of fever (23, 24). Several retrospective studies confirmed that human survival after serious infection is reduced in patients with hypothermia or in those who fail to generate a fever (23–26).

[Momtezuma Tuatara]

http://www.youandyourchildshealth.org/articles/fever.html (http://www.youandyourchildshealth.org/articles/fever.html)

From a paediatrician:




As a parent, one of my first exposures to anthroposophical medicine was when my child had a cold and a fever of 104.

He didn't have a sore throat, cough, or any difficulty breathing and his lungs were clear to auscultation.

He also didn't have any vomiting, or a stiff neck, so there weren't any signs of meningitis.

It was late at night, and I was up in the mountains and at least 30 minutes away from any hospital or urgent care. Well, my son started having auditory hallucinations with his fever.

I gave him a lukewarm bath. The bath worked temporarily (for 5-10 minutes), but he would get chilled and shiver and then the fever rose higher than ever. After two more tepid baths which didn't work, I then called a friend who was an anthroposophical physician.

I was told to feel my sons feet. If they were warm (and not cold) then I could apply a "Lemon Wrap". If the feet were cold I would need to warm them first using blankets or a covered hot water bottle before applying the lemon wrap.

Now, to make a lemon wrap you take a lemon, squeeze it into a pan and add 1/2 to 1 cup of water and heat it to almost boiling. I was then instructed to soak a pair of my cotton socks in this hot lemon juice (reportedly tepid or warm lemon juice also works), wring the socks out well, and put the hot socks on both of my child's feet (pulling the socks up over his calves). I then placed a pair of my wool socks over the cotton socks so his feet and legs would not get chilled and covered him with a blanket.

All I could think of while doing this was the headlines in the morning newspaper- "Son dies of a febrile seizure while mother, who is a pediatrician, applies lemon juice to his calves".

Well, the headlines didn't turn out like that.

My son's fever immediatedly came down to 102 and the hallucinations stopped, all in 10 minutes.

I left the lemon wrap on his legs for a total of 20 minutes and then removed it. Lemon wraps are usually only needed when a child is restless and uncomfortable with a fever greater than 102 degrees.

Usually one would apply no more than three lemon wraps in a 24 hour period while carefully observing the child for any signs of a more serious illness.

A lemon wrap does not cause a large drop in temperature but rather it works by pulling the inflammation away from the head.

[Epona]

Thankyou so much for this information. I really needed to read this.

My son had a febrile convulsion on sunday night and was unconscious for 45 mins. He is only 21 months old. Still trying to process it. :(

[deesalie]

How is he now PP?

[Epona]

He is much better, thanks for asking. He still has an absent look in his eyes, im not sure whether its because his body is still fighting an infection or that he is trying to process the trauma of going to hospital.
What is hard for me to process is that, THIS happened to my boy. A very healthy, never before been ill, never medicated, unvaccinated, fed organic foods, young man who is usually tough as nails. It just floored me that this happened to him.. when he has barely even contracted a cold in his lifetime.

This was very scary and awful to witness. I dont think i will ever get over it. Ergh.

I am hoping he is better tommorrow.

[Momtezuma Tuatara]

Did the hospital run any tests to see what the infection was?

45 minutes sounds far too long for a febrile seizure....

[cartersmom]

He is much better, thanks for asking. He still has an absent look in his eyes, im not sure whether its because his body is still fighting an infection or that he is trying to process the trauma of going to hospital.
What is hard for me to process is that, THIS happened to my boy. A very healthy, never before been ill, never medicated, unvaccinated, fed organic foods, young man who is usually tough as nails. It just floored me that this happened to him.. when he has barely even contracted a cold in his lifetime.

This was very scary and awful to witness. I dont think i will ever get over it. Ergh.

I am hoping he is better tommorrow.

How horrible and scary for you. Im so sorry! I hope he continues to improve!

[Nirvana]

Oh! Sounds really scary. I pray he's doing much better now. Big hugs to you mamma. :bighug::hug:

[jul511riv]

Yea, the 45 min thing is really bothering me too. This is NOT the normal length of a febrile seisure. Very scary. Does anyone have any thoughts about what this might be?

[Wonder-Full]

Where is perth pony, has she logged in recently? hope all is well.

[Epona]

Did the hospital run any tests to see what the infection was?

45 minutes sounds far too long for a febrile seizure....

I apologise for not logging in recently but yes, they did run blood tests and cultures and all were normal. They assumed he had an infection of some kind but couldnt tell me what.

He was unconscious for 45 minutes, but fitting for 15 of those. He was unresponsive for 5 minutes before he started to fit, then unconscious for a futher 25 minutes when the fit stopped. I had asked the doctor to hold off the midazolam while we were at the hospital as he seemed to be settling. They did give him IV paracetamol though.

He had a fair bit of froth and blood coming from his mouth during the fitting, because of this, they needed to clear his airways and remove the blood. He bit into his tongue quite badly which we thought would require futher care, but have now really started to heal up, (after 5 days of not eating).

He is now very very well and no worse for wear. Cant say the same thing about myself though. I am shit scared of it happening again and have gone from being completely against using panadol for fever.. to having a bottle of the shit in the house "just in case".
He has put the weight he lost back on and his bowels are back to normal.

It seems it was a fucking virus we contracted at a water park.. some moronic mother/father had taken their diseased festering kid there and he/she had shit in the water.. making my whole family ill, including my son.
Fucking idiots.

Interestingly enough.. i had two doctors ask if he was "up to date" with his vaccinations and i said a straight out "NO not vaccinated.. ever. Rather surprisingly they didn't bat an eyelid and kept on with other questions. I was expecting a fight or lecture and it was quite nice not to be harrassed.



Yea, the 45 min thing is really bothering me too. This is NOT the normal length of a febrile seisure. Very scary. Does anyone have any thoughts about what this might be?

FWIW. They dont have any idea why it took him so long to wake up. I presume it was a combination of him being exhausted due to the long fit and blood loss, having not eaten anything during the day, having a soaring temperature and it being past his bed time. He screamed when he woke up until i left ASAP. Poor thing. :(

[jul511riv]

the 45 min thing bothered me when I was under the impression that he was "fitting" or convulsing for the full 45 min.

I would be wary of the pharmamitacol or however you say it (Americans and Israelis have different "brand names" for these things), because there may be an increased risk of complication for a child who is prone to febrile seisures. I would recommend, again, using the foot bath, immediately, when a fever comes on , as it is not the height of the temp that is the problem, its the quickness of the fever rising. An olive oil garlic rub would be great for right after the footbath, but my dear friend has stopped her daughters febrile seisures (knock on wood) completely, buy just doing the foot bath at the onset of the fever.

[ema-adama]

What alternatives are there for comforting pain? Like a miserable flu/cold. In a baby, a young child and an adult?

[Momtezuma Tuatara]

What sort of pain?

[ema-adama]

Sorry, was not specific. Aches from a fever. General misery.

My 7 month old had a fever and would not get in the lukewarm bath with me. And would not sleep. And just was miserable all around. She is fine now, but I want something for next time. My older child just gets hot and sleeps it off and it's all over. She was really miserable. :(

[Momtezuma Tuatara]

You can't use something with fever. And if she's got through it this time, she will get through it better next time. I see no need for "something" for next time. IMO children learn to cope by experience. Skirting the experience, only teaches them avoidance tactics, not coping strategies.