In Babies and children, Pain relief

Paracetamol (or acetaminophen) is one of the most widely-used drugs in the world. A study of 20,000 Spanish children showed that more than 87% of them had taken paracetamol in the previous year and in the first year of life only 48% of babies had not been given the drug. Another study showed that 25% of of children under the age of 2 had taken a dose in the previous week and there are estimates that over 75% of children in the Western world are treated with paracetamol during childhood. More than half of all pregnant women in the USA and Europe use the drug too. 1 2

Paracetamol is mainly used to treat pain and fever, and is marketed under various names in different countries (Panado, Panadol, Tylenol, and others). In South Africa, you might also find it as Calpol, Dolorol, Paramed, Grand-Pa, and others. It can also be found in combination with other drugs in some formulations.

How Does Paracetamol Work?

It is not known how Paracetamol works. While it is proposed that it works on the central nervous system, it is important to note that it has a general effect on the whole body. It does cross the protective blood-brain barrier and affects the brain directly where it seems to block signals from the body so messages can’t reach the brain. Pain signals are most affected so the protective mechanism of pain, that helps you be aware of danger and take action, is dulled. 3

Chemicals called prostaglandins in the brain are affected by paracetamol and these are involved in pain and fever. It also seems to affect serotonin pathways in the brain that are not only involved with pain but also mood.

How Safe is Paracetamol?

We’ve seen how widely paracetamol is used and you’ve probably heard that at ’normal’ doses it is safe for use, even in pregnancy, for babies and for children. There are many versions of the drug that are sweetened and marketed explicitly for children and babies. Not all researchers agree that it is as safe as some might think. In this article, we’ll explore why there isn’t scientific consensus.

Liver and Kidneys

Liver and kidney damage are recognised effects of paracetamol toxicity. Long-term exposure and overdose can be very harmful, and even fatal. If used in combination with alcohol and other compounds toxic to the liver, the effects can be magnified.

Glutathione Antioxidant

One of the effects paracetamol is thought to have on the body is deplete levels of glutathione, especially in the lungs. Glutathione is one of the three main antioxidants your body uses to protect itself from damage at a cellular level. With lower levels of glutathione, cells are more susceptible to oxidative damage which creates an immune reaction, including inflammation. Studies have shown that the more paracetamol a person takes, the more glutathione is depleted – this is called a dose-response relationship and is a key element in determining whether something is toxic. 1

If this is the case then we could expect to see detrimental effects in large numbers of people who have been exposed to the drug. It turns out there is a reasonable body of studies who have looked into it and come up with some interesting results.

It’s important to note is that long-term safety studies in babies, children and pregnant women seem to be lacking. Many of the safety studies done on adults generally don’t last longer than a number of weeks and may of the concerns over paracetamol use are around the cumulative effects over longer time frames.

Brain

There have been at least eight studies that have specifically looked into the effects of long-term paracetamol use in children and its effects on brain and neurological developmental disorders, ranging from ADHD to Autism Spectrum Disorders (ASD). Amongst these are two studies that were published in one of the most respected journals, JAMA Pediatrics. All eight studies suggest that paracetamol is neurotoxic to the developing brain. 2  4 5 6

Mood

A few studies have shown that people taking paracetamol have blunted emotional responses, both positive and negative. The researchers speculate that the drug causes neurochemical changes that alter sensitivity to emotional stimuli. 7 8 This seems to make sense when we consider that the drug acts directly on the brain and can affect the serotonin pathways.

Lungs

The lungs need high concentrations of glutathione to develop and function properly. Given the known effects paracetamol has on the lungs some studies discover some very interesting links.

In the study of Spanish children, there was a clear dose-response relationship between exposure to paracetamol and asthma symptoms. A dose of the drug once a month on average resulted in a 400%  increase in the risk developing of asthma symptoms. 1

In 322,959 children aged 13–14 years from 113 centers in 50 countries looking at the impact of recent paracetamol use on asthma symptoms, they found a strong dose-response relationship. 9

These studies come after a systematic review and meta-analysis of 13 cross-sectional, 4 cohort, and 2 case-controlled studies including 425,140 children and babies revealing a 63% increased risk of developing asthma. This link was strong whether the drug use was assessed

  • One year before asthma diagnosis
  • During pregnancy or
  • During the first year of life 10

Children of mothers who used paracetamol when pregnant also raise this risk of their children developing asthma. Another study involving 1,006 babies in Ethiopia studied at ages 1 and 3 years showed that paracetamol use in pregnancy had a strong dose-response relationship with wheezing in the children. 11

Immune System & Fever

Give me the power to produce fever, and I will cure all disease.

—Parmenides, c. 500 BC

One of the primary reasons parents give their children paracetamol is to manage a fever. The idea that fevers have beneficial effects is not new. One researcher called our insistence on interfering with the immune system ‘fever phobia’. The interference with this healing process has been hypothesised to create and imbalance in Th1 and Th2 immune pathways and predispose people to inflammatory issues like asthma and eczema and also to autoimmune diseases.

We have to look at our ideas of how effective paracetamol is in the first place. A randomised, controlled trial of children with fever of presumed viral origin found that paracetamol was not much better than a placebo in lowering fever. 12

If we are interfering with the immune system then there will be consequences with how well the body can deal with pathogens. A randomised, controlled trial showed that preventative use of paracetamol with a vaccine had a negative effect on the immune response. 13

The most common concern with fevers in children is the risk of seizures. The US National Institute of Neurological Disorders and Stroke states the following:

  • The vast majority of febrile seizures are short and do not cause any long-term damage
  • During a seizure, there is a small chance that the child may be injured by falling or may choke on food or saliva in the mouth. Using proper first aid for seizures can help avoid these hazards
  • There is no evidence that short febrile seizures cause brain damage
  • Large studies have found that even children with prolonged febrile seizures have normal school achievement and perform as well on intellectual tests as their siblings who do not have seizures 14

Seizures should certainly not be ignored and children who have seized should be assessed by a medical professional as soon as possible, but the vast majority of seizures are benign and require no additional treatment.

When it comes to medication with seizures a recent research review states, “toxicities associated with these drugs outweigh the relatively minor risk associated with febrile seizures.” 15

Skin

Many of the studies that link asthma to paracetamol have persistent findings of a link with eczema too. This is very interesting as this link refutes the assertion by some people that the paracetamol-asthma link is one of reverse causation (i.e. They are taking paracetamol because they have asthma).

Pain relief

In a randomised controlled trial in over 1,600 people with lower back pain, paracetamol was found to have no effect compared to placebo 16 which was confirmed in previous systematic review and meta-analysis 17. Interestingly this review also found that it only provides minimal short term relief for people with osteoarthritis.

No free lunches

In biology there are no free lunches. By trying to cover over one symptom with a drug there are going to be payoffs that may cause additional problems. These issues may be silent for many years before surfacing and they may also have other factors like nutrition, genetic susceptibility and others involved too.

Taking a pill, lotion, potion or drug to silence symptoms will usually not allow us to address the cause. Headaches and fevers are not caused by a lack of paracetamol!

Pain and fever are processes that are normal in life. In the vast majority of cases, they are safe and the body has the means to deal with them if well-supported. Our view of our body as a machine that is liable to break down and needs to be fixed (see the myths of the sick care system) makes us fear the discomfort of pain and fever. While they can certainly be uncomfortable, the fear of them limits our personal growth.

Personal growth and discomfort go hand in hand. Learning something new can be challenging and it allows us to progress through life. Exercising your body can be uncomfortable and it allows the body to adapt and improve. Avoiding the inconvenience of learning and exercise would not be useful.

Fever = Progress

Most childhood fevers will pass without incident as long as basic requirements of hydration and nutrition are well-covered. If you or your family is eating a biologically appropriate diet and are supplementing smartly in everyday life then there is little need to do anything special when fever occurs.

We’ve noticed with our own children, and the many hundreds that we have cared for, that with a fever there usually comes a developmental leap. The few nights of disturbed sleep and the fews days of giving them more attention are a small price to pay for their optimal development. We’ve noticed, time and again, that that a day or two after a fever, a child will be doing something like using noticeably more words, be walking or be taking stairs better, be more co-ordinated or show improved handwriting.

Pain is an Invitation to Consciousness

Stubbing your toe is an indication that it would be useful to be more mindful of how you are moving your body. The unpleasant sensation cuts through your busy mind to bring full awareness to what you have done and allows you to be more present and make sure you don’t do it again.

The best way to deal with a fire alarm going off is to deal with the fire, not cut the wire to the alarm. If you had to numb your body with potent painkillers and continue to slam your poor little toe against furniture you might break a bone, lacerate the skin and never know it. The wound might get infected, or succumb to gangrene and you would be none the wiser because you numbed the pain. A trifling thing like a stubbed toe could prove fatal! Thank goodness we have intelligent signals in the body to prevent such trivialities killing our species off.

Headaches, back pain, and the like are probably more complex than stubbing your toe and they are very similar. They are invitations from our body to pay more attention to them. Maybe the back pain or the headache is the result of an accumulation of mild physical stressors, like sitting for too many hours in poor positions, and have created painful compensations. Maybe a more severe physical stressor (like a fall or accident) from your past has finally caught up with you, even after many years, and your body can no longer compensate for them without causing pain.

No pill is going to undo the damage that a compromised lifestyle created.

None of these studies can say with certainty that paracetamol causes these issues but they do raise serious questions. When you are reaching for the pill bottle for you or your family, you deserve to have enough of the facts to make an informed decision. Informed consent is a cornerstone of healthcare and without the facts you cannot be informed.

 

References

  1. Gonzalez-Barcala FJ, Pertega S, Perez Castro T, et al. Exposure to paracetamol and asthma symptoms. Eur J Public Health. 2013;23(4):706–710. doi:10.1093/eurpub/cks061.
  2. Stergiakouli E, Thapar A, Davey Smith G. Association of Acetaminophen Use During Pregnancy With Behavioral Problems in Childhood: Evidence Against Confounding. JAMA Pediatr. 2016;170(10):964–970. doi:10.1001/jamapediatrics.2016.1775.
  3. Kumpulainen E, Kokki H, Halonen T, Heikkinen M, Savolainen J, Laisalmi M. Paracetamol (acetaminophen) penetrates readily into the cerebrospinal fluid of children after intravenous administration. Pediatrics. 2007;119(4):766–771. doi:10.1542/peds.2006-3378.
  4. Hoover RM, Hayes VAG, Erramouspe J. Association Between Prenatal Acetaminophen Exposure and Future Risk of Attention Deficit/Hyperactivity Disorder in Children. Ann Pharmacother. 2015;49(12):1357–1361. doi:10.1177/1060028015606469.
  5. Liew Z, Ritz B, Rebordosa C, Lee P-C, Olsen J. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatr. 2014;168(4):313–320. doi:10.1001/jamapediatrics.2013.4914.
  6. Seneff S, Davidson MR, Liu J. Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure. Entropy. 2012;14(11).
  7. Durso GRO, Luttrell A, Way BM. Over-the-Counter Relief From Pains and Pleasures Alike. Psychol Sci. 2015;26(6):750–758. doi:10.1097/PSY.0b013e3181ce6a7d.
  8. DeWall CN, MacDonald G, Webster GD, et al. Acetaminophen Reduces Social Pain. Psychol Sci. 2010;21(7):931–937. doi:10.1037/0022-3514.79.5.748.
  9. Beasley RW, Clayton TO, Crane J, et al. Acetaminophen use and risk of asthma, rhinoconjunctivitis, and eczema in adolescents: International Study of Asthma and Allergies in Childhood Phase Three. Am J Respir Crit Care Med. 2011;183(2):171–178. doi:10.1164/rccm.201005-0757OC.
  10. Etminan M, Sadatsafavi M, Jafari S, Doyle-Waters M, Aminzadeh K, FitzGerald JM. Acetaminophen use and the risk of asthma in children and adults: a systematic review and metaanalysis. Chest. 2009;136(5):1316–1323. doi:10.1378/chest.09-0865.
  11. Amberbir A, Medhin G, Alem A, Britton J, Davey G, Venn A. The role of acetaminophen and geohelminth infection on the incidence of wheeze and eczema: a longitudinal birth-cohort study. Am J Respir Crit Care Med. 2011;183(2):165–170. doi:10.1164/rccm.201006-0989OC.
  12. Kramer MS, Naimark LE, Roberts-Brauer R, McDougall A, Leduc DG. Risks and benefits of paracetamol antipyresis in young children with fever of presumed viral origin. Lancet. 1991;337(8741):591–594.
  13. Shaheen SO. Acetaminophen and childhood asthma: Pill-popping at our peril? Journal of Allergy and Clinical Immunology. 2015;135(2):449–450. doi:10.1016/j.jaci.2014.10.030.
  14. Febrile Seizures Fact Sheet. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Febrile-Seizures-Fact-Sheet. Accessed July 4, 2018.
  15. N S, Schellack G. An overview of the management of fever and its possible complications in infants and toddlers. South African Pharmaceutical Joural. 2018;85(1):26–33. https://journals.co.za/content/journal/10520/EJC-da054fbc8.
  16. Morgan DJ, Dhruva SS, Wright SM, Korenstein D. Update on Medical Practices That Should Be Questioned in 2015. JAMA Intern Med. 2015;175(12):1960–1964. doi:10.1001/jamainternmed.2015.5614.
  17. Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225.
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