Paracetamol research is not cause for concern
“Taking too much paracetamol in pills and cold remedies could kill you,” the Daily Mail has reported.
BBC News said researchers have found that even taking slightly too much paracetamol day after day “can cause overdose”.
People should not be alarmed by this news, which is based on an analysis of over 600 paracetamol users admitted to a Scottish liver transplant unit over a 16-year period. Rather than looking at how often small overdoses caused hospitalisation or death, the research actually looked at the pattern of paracetamol use in those people that ended up needing special liver care after accidental and deliberate paracetamol overdoses.
Crucially, this research does not undermine the fact that paracetamol is a safe and effective painkiller when taken correctly. The research provides valuable information on this specific group of patients, particularly the impact of ‘staggered overdose’, when people take two or more paracetamol doses above the recommended level over a period of more than eight hours. Approximately 6 out of every 10 patients in the staggered overdose group survived for 30 days at the clinic, whereas 7 out of 10 survived in a group that had overdosed at single point in time.
While this research does not undermine the safety of paracetamol, it reminds us to always read the label or leaflet that comes with the medication we take and ensure we do not accidentally exceed the recommended dose, especially when taking different medications for different ailments.
Where did the story come from?
The study was carried out by researchers from the University of Edinburgh. It was unclear how this research was funded as the published article states there was no financial support.
The study was published in the peer-reviewed British Journal of Clinical Pharmacology.
What kind of research was this?
This study used information collected over a period of 16 years from a group (or cohort) of patients who were admitted to a Scottish liver unit with paracetamol-induced severe liver injury.
The authors say that the harms caused from paracetamol overdose are the commonest cause of short-term liver failure in the UK. However, they say that at present there is still relatively little known about the harms of regularly taking slightly too much paracetamol over a prolonged period of time – a so-called staggered overdose pattern – and about the effect of delaying going to hospital following an overdose.
This study used hospital admission data on paracetamol overdoses to investigate whether taking a staggered overdose of paracetamol or delaying hospital treatment after an overdose would impact on the risk of death from liver failure or the need for a liver transplant.
The news coverage that stated that ‘taking too much paracetamol in pills and cold remedies could kill you’ did overemphasise the risk of death as described in this research study. It also quite erroneously suggested that taking paracetamol pills in the instructed way is in itself dangerous. Most coverage failed to reassure the public that sticking to the recommended dose of paracetamol is a safe and effective method of pain relief.
What did the research involve?
The researchers studied 938 patients admitted to the Scottish Liver Transplantation Unit over a 16-year period from 1992 to 2008. They attempted to collect detailed information about that patient’s clinical history and medication use, recorded before and after they were admitted to the unit.
Information on paracetamol use was recorded on admission to the transplantation unit by asking the patients to recall their paracetamol use in the last seven days. This included:
- the number of tablets
- the type
- the timing of any overdose
- any delay to presentation (time between taking an overdose and admission to the transplantation unit)
Paracetamol overdose was defined as the cause of the admission to the transplant unit when there was a clear history of ingesting potentially toxic amounts of paracetamol (greater than 4g/day, the equivalent of eight 500mg tablets) within seven days of being admitted to the unit.
Patients also had to have either a high concentration of paracetamol in their blood (greater than 10mg/L) or elevated levels of enzyme called ALT in the blood without high paracetamol levels. ALT is normally found within the liver cells, and high levels in the blood indicate that it has been released into the bloodstream due to liver cells becoming damaged. Patients with other causes of liver failure, such as viral hepatitis and liver cancer, were excluded from the study.
The researchers then categorised patients by their self-reported paracetamol use. Those who had reported taking taken more than 4g over the course of a single day were labelled as having a ‘single time point overdose’ (that is, 4g is the equivalent of at least eight standard 500mg tablets).
Patients were labelled as having had a staggered overdose if they had taken two or more paracetamol doses above the recommended level over more than eight hours resulting in a cumulative dose of greater than 4g a day. Those who were admitted to hospital more than 24 hours after taking a paracetamol overdose at a single point of time were classified as having a ‘delayed presentation’.
The researchers compared the laboratory blood test results, liver transplant rates and survival of the patients in the different paracetamol groups.
What were the basic results?
Of the 938 patients admitted to the transplant unit, the majority (70.7%) were classified as having paracetamol-induced liver damage. Information on paracetamol use was available for 611 patients; the majority of whom (73.6%) had taken a single point overdose. About one-quarter (26.4%) had taken a staggered overdose. They found that the staggered group had taken significantly less paracetamol than the single point group.
The main finding was that a significantly lower proportion of the staggered overdose group survived 30 days after admittance to the unit (62.7%) when compared to the single overdose group (72.4%). This means that roughly 7 out of 10 survived in the single overdose group survived for 30 days, but only 6 out of every 10 patients in the staggered overdose group.
Compared to single point overdose patients, staggered overdose patients were more likely:
- to be older
- to have a history of alcohol abuse
- to have taken alcohol with their overdose
- to experience worsening brain function due to liver damage while at the transplant unit
- require kidney replacement therapy or mechanical ventilation
The group who did not get to a hospital in less than 24 hours following a single point overdose were more likely to develop worsening brain function due to liver damage during their stay at the transplant unit compared to those who came to hospital earlier.
Information on the reasons for overdose was available for 134 patients. The most common reason given for overdose was for pain relief. Among patients with available data, about one-third (34.3%) of staggered overdoses were taken in deliberate suicide attempts, while accidental overdose was reported in nine cases.
How did the researchers interpret the results?
The authors conclude that patients with staggered paracetamol overdoses had ‘reduced survival compared with single overdoses, despite ingestion of lower total amounts of paracetamol’. The researchers also acknowledged that the patients admitted to the transplant unit represented the more severe cases of paracetamol-induced liver disease. They stated that in a standard hospital emergency department the vast majority of paracetamol overdoses will suffer no long-term disease and will not need to be referred to a specialist liver transplant unit.
This study of 938 patients admitted to a liver transplant clinic in Scotland shows that taking a staggered overdose of paracetamol may have a greater adverse effect on survival compared to patients who experience a single point overdose, even though they have ingested less paracetamol overall.
However, while these are certainly valuable results they do not change the fact that paracetamol is a safe and effective painkiller when taken correctly. Instead, the research provides important insight into the outcomes that might occur when paracetamol is not taken in the correct manner, and how different patterns of overuse can affect the body differently.
The study also highlighted the need for people to ensure they take the correct amount, which is always stated on the drug packaging and in the information leaflet inside. It is important to take medication at the recommended dose, so always read the label and seek medical attention if you believe you have taken an overdose.
There are also a number of important strengths and limitations that must be considered when analysing the study’s results. One principal fact to remember is that the people who went to the liver unit do not necessarily represent all people who have overused or overdosed on paracetamol. Also on their own, the results certainly do not support newspaper suggestions that even a small overdose is likely to kill.
To put the phenomenon into context, these results will have to be considered alongside data quantifying how many people overusing paracetamol actually end up attending hospital for liver problems in the first place. The authors of the research themselves state that the patients at the liver transplant unit represent those most severe cases of paracetamol damage and that “the vast majority of paracetamol overdoses will suffer no long-term physical damage”.
This study is, however, strengthened by the fact that the Scottish transplant clinic serves all patients in Scotland and so the researchers will have picked up the majority of paracetamol-induced liver failure in Scotland in the last 16 years. On this basis, it provides important information on patients who overdose and require hospital assistance, although obviously not all cases of overdose.
One of the main limitations of this study is that it relied on patients recalling their past paracetamol use accurately and reliably. This may be prone to human error, which could influence the results of the study. Similarly, information on paracetamol use was only available for 611 out of 938 patients admitted to the transplant unit. If this missing information had been included, it may have influenced the results.
In terms of the overall relevance for people taking paracetamol for pain relief, it is worth noting that accidental overdose in the staggered group was reported in only nine individuals. Most patients either knew they were taking too much paracetamol for pain relief or took paracetamol deliberately as part of a suicide attempt (one-third of people).
The average amount of paracetamol taken was high at 24g, or 48 tablets, in the staggered overdose group. However, as little as 10g, or 20 tablets, was reported as the lowest taken by one person who developed liver failure. There was a high proportion (almost 50%) of alcohol abuse in the staggered group, suggesting that alcohol use could play a strong part in determining whether people using too much paracetamol will need to attend hospital.
- Craig DGN, Bates CM, Davidson JS et al. Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity. British Journal of Clinical Pharmacology, 2011