Fever is your friend

I remember a few years ago in one of the lectures of Dr. Sarah Long, former President of the Pediatric Infectious Diseases Society in the United States, emphasizing that "fever is your friend".

It was a simple message. In a nutshell, fever is the immune system's way of recognizing a foreign invasion on our body. Fever is a reaction from this invasion and is the body's defense on this foreign invasion.

The American Academy of Pediatrics recently published "Clinical Report: Fever and Antipyretic Use in Children", written by Janice E. Sullivan and Henry C. Farrar from the Section on Clinical Pharmacology and Therapeutics, and Committee on Drugs [Pediatrics, published online February 28, 2011]. I have time and again explained to my patients parents and guardians on why they should not unnecessarily panic when their children have fever and when to or not to give antipyretics.

Let me summarize the highlights of this report:

1. Appropriate fluid hydration is still the best treatment for fever. Fever results in insensible water losses. This includes a few electrolytes and water when patients have fever. Simply replacing these insensible water losses will not only help bring down the temperature of the patient but will help rehydrate them as well.

In short, when the patients have fever, it is important to take a lot of fluids.

2. "The desire to improve the overall comfort of the febrile child must be balanced against the desire to simply lower the body temperature." This is the most important factor that triggers the domino effect of panic among parents/guardians regarding fever in children. The psychological terror of "fever phobia" is taken out of context and the disproportionate reaction is more often than not due to myths and misconceptions on fever and its sequelae - seizures, brain damage, and death.

And the doctor is just as culpable in fanning the flames of undue panic by not providing education and being trigger happy in giving a prescription to patients with fever.

"It is argued that by creating undue concern over these presumed risks of fever, for which there is no clearly established relationship, physician are promoting an exaggerated desire in parents to achieve normothermia by aggressively treating fever in their children."

3. "There is NO EVIDENCE that reducing fever reduces morbidity or mortality from febrile illness. Possible exceptions to this could be children with underlying chronic diseases that may result in limited metabolic reserves or children who are critically ill, because these children may not tolerate the increased metabolic demands of fever."

4. "There is NO EVIDENCE that antipyretic therapy decreases the recurrence of febrile seizure."

5. Regarding immunization and fever, many pediatricians recommend either pretreatment with paracetamol or ibuprofen before immunization or immediately after immunization to minimize the discomfort associated with injections and minimize the febrile response. "...results of one recent study suggested the possibility of decreased immune response to vaccines in patients treated early with antipyretics." In addition, fever as an adverse reaction post-immunization accounts for only <10% of reactions. Putting patients at risk for adverse events from drugs being administered for no reason at all makes one wonder whether the benefits will actually outweigh the risks of giving drugs.

6. "Although the available literature is limited on the actual risks of fever and the benefits of antipyretic therapy, it is recognized that improvement in patient comfort is a reasonable therapeutic objective. Furthermore, at this time, there is no evidence that temperature reduction, in and of itself, should be the primary goal of antipyretic therapy."

7. Paracetamol (Acetaminophen) or Ibuprofen?
Once upon a time, salicylates was the drug of choice for fever. After sufficient data emerged associating salicylic acid (aspirin) and Reye syndrome (hepatic encephalopathy after aspirin administration with specific viral illnesses), paracetamol eventually replaced aspirin as the treatment of choice for fever. However, paracetamol is NOT without problems. Contrary to the endorsements of John Llyod Cruz regarding paracetamol being absolutely safe and seemingly taken like M&Ms for even minor aches and pain.

Paracetamol is the number one cause of drug-induced liver toxicity worldwide. Hepatotoxicity is most commonly seen in acute overdoses and the most common scenarios are in children receiving higher doses of paracetamol at intervals of less than 4 hours or around the clock!

"One safety concern is the effect of paracetamol on asthma-related symptoms; although asthma has also been associated with paracetamol use, causality has not been demonstrated."

Ibuprofen has gained popularity as an antipyretic. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID). It has very potent anti-inflammatory effect and is widely used for the treatment of rheumatologic problems. Its increasing use in managing fever is probably due to the longer clinical effect at lower doses than paracetamol.

"There is NO EVIDENCE to indicate that there is a difference in the safety of standard doses of ibuprofen compared to paracetamol in healthy children between 6 months to 12 years old with febrile illnesses". Like all NSAIDs, ibuprofen can cause gastritis, bleeding and ulcers of stomach duodenum and esophagus. Unlike paracetamol, ibuprofen has no evidence linking it to worsening of asthma symptoms.

Concern has been raised over the nephrotoxicity of ibuprofen. Because of the increasing reports of renal insufficiency in children treated with ibuprofen or other NSAIDs for febrile illnesses, caution is encouraged when using this drug in children who have fever with dehydration or with complex medical illnesses.

"Children who are at greatest risk of ibuprofen-related renal toxicity are those with dehydration, cardiovascular disease, preexisting renal disease, or the concomitant use of other nephrotoxic agents. Another potential group of risk is infants younger than 6 months because of the possibility of difference in ibuprofen pharmacokinetics and developmental differences in renal function...Another potential risk associated with the use of ibuprofen is the possible association between ibuprofen and varicella-related invasive group A streptococcal infection."

The management of fever is understanding why the patient is febrile. Parents/guardians must be made to understand that fever in itself is not known to endanger a generally healthy child. As I explained in the beginning, fever in itself may be beneficial to patients as it is an indicator that the body is fighting off a foreign intrusion into the immune system. The goal of antipyretic therapy is not to simply normalize body temperature but to improve the overall comfort and well-being of the patient. Hydration,education of parents/guardians on the use/misuse of antipyretics and diagnosing the actual cause of the fever by focusing on the other signs and symptoms accompanying the fever can help promote appropriate drug prescription in this vulnerable population.

After all, it is our duty as health care providers to FIRST DO NO HARM.

POSTHOC ANALYSIS: Does drinking diet soda increase the risk of stroke and heart attack?

I posted a report which was picked up by media from one of the findings based on a study presented at the annual International Stroke Conference in Los Angeles recently.

While the conference centered on many breakthroughs and landmark findings in the management of stroke, the study done by Hannah Gardner from the University of Miami Miller School of Medicine grabbed the media limelight.

The study, which followed more than 2,500 New Yorkers for nine or more years, found that people who drank diet soda every day had a 61 percent higher risk of vascular events, including stroke and heart attack, than those who completely eschewed the diet drinks. In this study, researchers surveyed 2,564 north Manhattan residents about their eating behaviors, exercise habits, as well as cigarette and alcohol consumption. The study volunteers were also given physical check-ups that included blood pressure measurements and blood tests for cholesterol and other factors that might affect the risk for heart attack and stroke. The increased likelihood of vascular events remained even after Gardener and her colleagues accounted for risk factors, such as smoking, high blood pressure and high cholesterol levels. Pointing the finger more squarely at diet drinks, the researchers found no increased risk among people who drank regular soda.


Obviously, this report sent the beverage companies as well as the US FDA scrambling at the preliminary report that could potentially damage a multitrillion dollar industry.

The question that looms is - Does drinking diet soda daily increase the risk of vascular events?

First of all, a prospective study that is randomized and well-controlled in design using a very large number of subjects would be impossible to do. Not only because of the enrollment criteria for such a study but based on this survey, it would pose ethical risks for conducting such a study that can put people enrolled in the study at risk for a vascular event (stroke or heart attack). Let me put it simply - it's like doing a prospective study on whether smoking causes cancer or not. All the data for smoking causing cancer are based on retrospective data. Which means that the investigators looked at patients with lung cancer and then looked back into their history of smoking and voila! The studies point to the fact that patients who had a smoking history had a higher risk of developing lung cancer (and other forms of cancer) than those who did not smoke. Remember. The key word here is HIGHER RISK. Which means that even if you did not smoke, you still have a chance of getting lung cancer in your lifetime even if you lived in a plastic bubble.

So why not design a prospective study? I mentioned the ethical dilemma here. Patient safety as well as patient risk should never be compromised in the design of a scientific study. The prospective risk studies are unethical to conduct. You cannot randomize one group of subjects to 1 pack a day for 20 years and compare them to another group of subjects who do not smoke and then follow them up for a period of 20 years! This is unacceptable and cannot be conducted in humans.

Hence, we're left with looking at studies designed in the way Gardner and colleagues did their study on diet soda and the risk of vascular diseases.

Second is the fact that while the authors had statistically analyzed the data by removing some other risk factors such as increased cholesterol and hypertension and history of heart disease in their study, a historical data is difficult to verify and can be unreliable particularly when you're doing a survey.

I have taught epidemiology even before epidemiology even was a formal course in the Philippines. So I would know what I am talking about when I say that the difficulty in conducting surveys is the veracity of the response of subjects. Reliability can range from 0-100% and the person conducting the survey (enumerator) would have to be in the cast of "Lie to Me" (the TV series) in order to spot whether the subject being surveyed is truthful or not. However, the considerably large number of subjects in this study would possibly account for outliers. But like all surveys and retrospective studies, we take everything as face value and analyze the data given what we have.

This is how studies on linking smoking and lung cancer, marijuana intake and lung cancer, sun exposure and skin cancer, HPV infection and cervical cancer, hepatitis B and liver cancer were born. No one does a prospective study.

Which goes to the analysis on other factors which MAY have contributed to the higher risk of stroke and heart attack of patients drinking diet soda.

In this diet conscious era, we all like to look like supermodels. Yet want to eat like pigs! (Ouch, did I hurt anyone?) So some beverage company comes us with a slogan that we can go ahead and drink all the soda we want without the guilt feeling of having to consume more calories. But the human mind (and the gastronomic capacity) will always reason out that since we're having a can of Coke Zero then we have saved enough calories to go ahead and devour a chicken and go for the unlimited rice galore at Mang Inasal!

So let's do the math.

A regular coke will contain the following calories depending on the amount you take in:

8 fluid oz. = 105 calories
12 =155 calories
16=200 calories

And I'm talking about the bottled beverage. A can of coke is about 140 calories while coke from the dispenser will vary from each fast food outlet. For example, an 8 oz coke from Wendy's is about 160 calories while 8 oz coke from McDonald's is 250 calories. That's because the dispensers will have varied caramel-sweetener-water mixture.

And while we're busy counting calories from the beverage drink, we forget the food we eat.

Let's do the math again. This time we drop the regular coke and exchange it with Coke Zero (0 calories) and go for the extra rice.

In short-grain white rice there are:
approx 267 calories in 1 cup steamed or boiled

In medium-grain white rice there are:
approx 242 calories in 1 cup steamed or boiled

In long-grain white rice there are:
approx 205 calories in 1 cup steamed or boiled

In medium-grain brown rice there are:
approx 218 cals in 1 cup steamed or boiled

In long-grain brown there are:
approx 216 calories in 1 cup steamed or boiled

In basmati rice there are
approx 190 calories in 1 cup steamed or boiled.

In wild rice there are:
approx 166 calories in 1 cup of steamed or boiled

In Chinese restaurant steamed rice there are:
approx 199 calories in 1 cup (loosely packed).

So you've balanced everything off with the same junk you disposed to the junk you took in. Talk about zeroing it out then adding more!

Put that in the Pinoy's perspective where noodles are served in parties as viand and not as main dish and here's what you get with eating pasta or noodles together with your rice:

Without sauce, butter, or oil, there are:

BY THE OUNCE OR 28g
approx 38 calories in each ounce or 28g of cooked fresh pasta
approx 44 calories in each ounce or 28g of (enriched) cooked pasta
approx 35 calories in 1 each ounce or 28g of (enriched) whole wheat pasta

BY THE SERVING
approx 133 calories in a 3½ oz or 100g serving of cooked fresh pasta
approx 152 calories in a 4 oz or 114g serving of cooked fresh pasta
approx 304 calories in an 8 oz or 227g serving cooked fresh pasta
approx 608 calories in a 1 pound or 454g of cooked fresh pasta

BY THE CUP
approx 175 calories in 1 cup (5 oz) of (enriched) cooked whole wheat spaghetti
approx 182 calories in 1 cup (4.1 oz) of cooked small shells
approx 190 calories in 1 cup (5 oz) of cooked fresh spaghetti
approx 212 calories in 1 cup (4.7 oz) of cooked spiral shaped
approx 221 calories in 1 cup (5 oz) of (enriched) cooked elbow shaped
approx 221 calories in 1 cup (5 oz) of (enriched) cooked spaghetti

And I could go on and on, but the take home message is that while we are gullible enough to believe advertising gimmicks (all the models for diet sodas are reed thin), the studies do not take into consideration the daily dietary practice of people who exchange another serving of food for the zero calories in a beverage drink.

Finally, is the fact that artificial sweeteners and coloring have long been studied to be carcinogenic in mice and laboratory animals.

While it may be a fact that aspartame or food coloring (caramel) will need to be consumed in larger amounts in humans compared to animal studies to probably cause cancer or vascular problems, the same science is true for the amount of nicotine exposure to animals before there is lung damage in humans. But the US FDA will not comment on this issue because undermining the diet soda industry will definitely send the stocks of Coca-Cola tumbling down and mark the end of the era of an American beverage industry that supports American Idol. More so, not at this time when the American economy is still reeling from a financial deluge.

So what do the studies show?

If you plan to go on a diet because of nutritional or health reasons - please count the calories. If you need to take something to drink, don't just go for the zero calories but with artificial sweeteners. There's always water which has zero calories as well. This study may not have enough data to shake the rabid eating and drinking habits of people, but it's a wake-up call that we need to improve the overall dietary habit in order to lead healthier lives.

After all - you are what you eat!

[Calorie facts from righthealth.com and Nutrition Center of the Philippines]