Paracetamol Overdose

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Paracetamol is widely available as a ‘general sales list’ (over the counter) medicine within the United Kingdom (UK) used to

treat pain and raised temperatures in both adults and children. Safe at the recommended dosages of 1 g per 4 hours to a maximum of 4 g per day (Joint Formulary Committee, 2014), paracetamol is known not to be hazardous in pregnancy and is on the World Health Organization’s list of ‘Essential Medicines’—a compendium of medications deemed needed to provide a rudimentary healthcare system (World Health Organization, 2013). Despite the ubiquitous and well-trusted nature of the drug, it is also the most common cause of deliberate self-harm through overdose, constituting some 44% of self-poisoning attempts in England (Carroll et al, 2013) and can be taken in overdoseage accidentally, especially by the very young.

LEARNING OUTCOMESAfter completing this module you will be able to:

l Understand the pharmacology of paracetamol overdose.

l Identify the different categories of overdose.

l Understand the potential pre-hospital treatment options.

l Recognise the role communication plays in the management of a patient who has overdosed.

If you would like to send feedback, please email [email protected]

Continuing Professional Development:Paracetamol overdose

OverviewThis Continuing Professional Development (CPD) module considers paracetamol overdose—both accidental and deliberate—in the pre-hospital setting, and presents an update on current practices that paramedics need to be conversant with in responding to what is a dangerous and potentially fatal situation.CPD

Reflection 1Before you read any of the material below, consider how common you think paracetamol overdose is within the UK in relation to other forms of self-harm. What do you think the demographic details are of the people commonly encountered who have taken an overdose of paracetamol? What are the demographic details of the group whose mortality rate from paracetamol overdose has been noted to have increased very recently? To complete the exercise, click the button.

Paracetamol Overdose

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for easy excretion in the urine—this constitutes up to 90% of paracetamol’s metabolism; a small percentage is excreted entirely unchanged in the urine. Approximately 5%, however, is converted initially by the enzyme cytochrome P450 to a highly reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI) which, unaltered, is toxic to hepatic, renal and other tissues (Galbraith et al, 2007). In health, the liver will further metabolise NAPQI with glutathione, rendering NAPQI inactive and water-soluble for excretion. The issue with paracetamol overdose is simply that the volume of NAPQI that is released will overwhelm the liver’s ability to secrete the glutathione required to safely metabolise it (Walker and Whittlesea, 2007).

It needs to be borne in mind, however, that even in health individuals can vary fiftyfold in their ability to metabolise paracetamol (Richards et al, 2011). Thus, paramedics need to document any amount taken by patients at all, as even small or normally ‘therapeutic’ doses can prove toxic. This is particularly true of very young or very small patients (weighing less than 54 kg), as severe liver damage has been reported in doses as low as 10–15 g (Walker and Whittlesea, 2007). Because paracetamol is contained in a variety of general sales list medications, as well as those available from a pharmacist, the medications history needs to be very thorough.

Overdose can be categorised into three discrete areas (AACE, 2013):

l Accidental l Intentional (self-harm) lNon-accidental.This last categorisation is extremely rare and

would involve deliberate overdosing of vulnerable groups such as the very young or the very elderly. It must remain a consideration by the paramedic, nonetheless, in vague or suspicious presentations. This CPD module focuses on the first two areas.

Accidental overdoseOne group that are especially liable to accidental overdose are children. Because paracetamol is

Reflection 2Consider the questioning and probing techniques that you might need to employ to ascertain how much paracetamol has been administered by a parent or carer. What are the common home-use medications that contain paracetamol but do not state paracetamol overtly on the label? To complete the exercise, click the button.

Paracetamol (actetominophen) is a weak, non-opioid analgesic indicated for mild to moderate pain and pyrexia (Joint Formulary Committee, 2014) and is one of the patient group directive medicines that paramedics are able to administer to patients. Its utility is clear when considering that it can be administered via oral (either as tablets or liquid suspension), intravenous and intra-osseous routes and given across the age span including children as young as six months (Association of Ambulance Chief Executives (AACE), 2013). Additionally, it can be combined with morphine to provide very effective analgesia for stronger pain (AACE, 2013), while helping to minimise the potential unwanted side effects of opiate use such as respiratory depression.

Paracetamol exerts its analgesic effects by inhibiting a cyclo-oxygenase pathway (COX-3) which is specific solely to the central nervous system; this helps to explain the absence of the gastrointestinal side effects noted in many of the non-steroidal anti-inflammatory agents (Barber and Robertson, 2009). However, unlike aspirin and other anti-inflammatory drugs, it does not reduce inflammation (Volans and Wiseman, 2011). It reduces pyrexia by its actions of the heat regulation centre in the hypothalamus causing widespread vasodilation which, in turn, allows heat loss through convection, conduction, radiation and evaporation from the skin (Adams et al, 2008).

PharmacologyParacetamol is absorbed well across the mucous membranes of the gastro-intestinal system and plasma concentrations normally peak within 30 minutes to 1 hour of ingestion, or within 1–2 hours for extended-release preparations (Galbraith et al, 2007). The relevance to paramedic practice here is the time-critical nature of paracetamol overdose—definitive treatment, as discussed below, is limited after a relatively short time span. The liver metabolises the drug predominantly by converting the molecule into inactive metabolites which are made water-soluble


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an active ingredient in a wide variety of easily available medication regimes, there is a risk that parents unwittingly overdose their child by using a number of sources of the drug. Drug concentrations vary in different preparations, potentially confusing an accurate sense of how much has been taken over the course of a day, for instance. It has been acknowledged that some parents or carers do not use measuring devices well or at all (Guyder, 2008), furthering this potential confusion. Although most use of paracetamol in the community to treat a pyrexia, for instance, is done appropriately, there is still a long-identified need for health education for carers administering it as an anti-pyrexial (Mason et al, 2003); paracetamol alleviates the symptom of the pyrexia but not the cause—it is not a treatment per se and repeated doses do not improve the patients actual condition.

As young toddlers become more mobile and ever more curious, it is also possible for them to chance upon household sources of paracetamol and ingest inappropriate amounts. Unfortunately there is a time-lag between ingestion and the more definitive symptoms of paracetamol-induced injury to the liver and kidneys: there can be a delay as late as 36–72 hours in actual organ failure (Lee, 2012).

Intentional overdoseEpidemiologyOverdose features prominently among the most common reasons for young people’s attendance at emergency departments in the United Kingdom (Shanmugavadivel et al, 2014), although it is also acknowledged that a majority of self-harm episodes are not reported to healthcare professionals (Ystgaard et al, 2009), underplaying the scope of the issue. According to the Office of National Statistics (ONS) document Deaths Related to Drug Poisoning in England and Wales, 2013, 2 955 drug poisoning deaths (involving both legal and illegal drugs) were registered in 2013 in England and Wales (2 032 male and 923 female deaths) (ONS, 2013). Male mortality rates significantly increased in relation to paracetamol overdose (as well as that for heroin/morphine and benzodiazepines). Conversely, female mortality rates have remained relatively stable (ONS, 2013).

These findings are in the face of long-term consideration that address the efficacy of UK legislative changes to directly combat paracetamol overdose (Hawton et al, 2013): in 1998 sales of paracetamol were restricted to 32 tablets by pharmacists and 16 tablets for sale by other outlets (Medicines (Sale or Supply) (Miscellaneous Provisions) Amendment (No. 2) Regulations 1997

(SI 1997/2045)). The tablets were also provided in ‘blister’ packaging thought to slow down the access to large quantities of tablets which might slow down what has long understood to be an impulsive act (Hawton et al, 1996). The recent study from Hawton et al (2013) indicates impressive (43%) reduction in deaths due to paracetamol overdose since the introduction of the legislation. However, the continuing trend in paracetamol-related deaths suggests that additional preventive measures are needed.

TreatmentResponses to paracetamol overdose are time-critical; although the patient, who will often be distressed emotionally, will need an environment of calm and a non-judgemental approach to questioning. The history is central—the amount and combination of drugs taken (alcohol is included here) and the timing of the ingestion is of utmost importance. It is appropriate to find ways of repeating the answers given to you back to the patient to ascertain accuracy. Transport to hospital is indicated for ingestion episodes that cover any time period of over an hour, as well as significant discrete overdose. If any impairment to airway, breathing, circulation or neurological function is noted, then these are additional time-critical indicators (AACE, 2013).

Although vomiting must not be induced it is useful to retain a sample of vomit for inspection at hospital (AACE, 2013). In the face of respiratory depression, it may be advised to administer the antagonist agent naloxone. This is because paracetamol is found in combination with either codeine or dextropropoxyphene—both opioid derivatives which can produce respiratory compromise—particularly when combined with alcohol (AACE, 2013).

The antidote to paracetamol poisoning is N-acetylcysteine (NAC) (Medicines and Healthcare Products Regulatory Agency (MHRA), 2012a) and is the definitive treatment for paracetamol overdose. It is administered intravenously on arrival at hospital and is extremely effective, although protectiveness does decline rapidly if its administration commences later than 8 hours after the overdose episode. Acetylcysteine protects the liver and other tissues by maintaining or restoring glutathione levels, or by acting as an alternate substrate for metabolising and thus detoxifying the reactive metabolite NAPQI. Children are treated with the same doses and regimen as adults, although the quantity of intravenous fluid used will be modified to take into account age and weight, with fluid overload being a potential danger (Royal College of Emergency Medicine, 2013).



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overdose is defined as ingestion of paracetamol over a period of 1 hour or more. Again, the precision of the history taking from paramedic staff is crucial here to assess both patient risk and urgency of treatment. However, these guidelines also apply to those patients where there is doubt over the time of paracetamol ingestion (MHRA, 2012b), so a poor history disclosure also indicates the need for transport to definitive care where blood levels of paracetamol can be assessed. All ingestions of over 75 mg/kg are considered significant—the dose at which toxicity can be definitively assumed is 150 mg/kg.

These MHRA revisions were followed by a National Poisoning Information Service (NPIS) response in terms of changing the guidance provided to practitioners on TOXBASE (Pettie and Dow, 2013), access to which is available to paramedics via communication with clinical desks and clinical advisors at the emergency operations centres of individual NHS ambulance services.

Paracetamol overdose can often be accompanied by alcohol use (Hawton et al, 2012) and it is worth highlighting the relationship between the two substances, as alcohol has a paradoxical effect on the liver’s metabolism of paracetamol. Infrequent alcohol consumption will inhibit the activity of cytochrome P450, reducing the metabolism of paracetamol into NAPQI, but chronic drinking will actually amplify the activity of the enzyme, resulting in higher levels of NAPQI produced (McGavock, 2006); chronic alcohol use therefore renders people more vulnerable to smaller doses of paracetamol. Alcohol consumption is thus a very pertinent aspect of the medical history—paramedics need to be very clear about the alcohol consumed with an overdose and also about day-to-day alcohol intake.

Activated charcoal is one alternative for immediate treatment pre-arrival at hospital. It is presented in a viscous liquid format—50 g per bottle—and is used for overdose by ingestion, ideally within an hour of the event itself (AACE, 2013), and is suitable for use in overdose accompanied by alcohol use. It has a very large

Recently, the management of paracetamol poisoning has been revised within the UK following the death of some people having taken an overdose but considered not be at significant risk (MRHA, 2012a). Until 2012, a ‘nomogram’ alongside the application of known risk factors was used to assess risk of paracetamol toxicity (Joint Formulary Committee, 2014), and NAC was administered in accord with the nomogram by ‘plotting’ the patient’s plasma paracetamol levels against the risk factors and elapsed time from ingestion. Following a Commission on Human Medicines review in 2012, this nomogram—the Rumack-Matthew nomogram—was revised and is now presented as a simplified, single treatment line, as illustrated in Figure 1.

The revised guidelines now indicate that any ‘staggered overdose’, regardless of risk factors previously considered for hepatotoxicity should be treated with the administration of NAC, irrespective of the plasma paracetamol concentration (MHRA, 2012b). A staggered

Reflection 3Given that 75 mg/kg is considered significant and that there are 500 mg per paracetamol tablet, how many tablets taken in overdose would give you cause for concern in a 60 kg patient that you have been called to?What are the physical assessment findings that you might encounter in practice that would identify someone as being at increased risk of the toxic effects of paracetamol overdose?To complete the exercise, click the button.

Figure 1. Paracetamol treatment nomogram (MHRA, 2012)

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Reflection 4How would you debrief the communication needs that are required for people having taken an overdose of paracetamol with a student paramedic?What do you feel are the prevalent staff attitudes towards those that have taken a paracetamol overdose?What are the potential consequences for patients and clinicians if these communication strategies are mishandled?To complete the exercise, click the button.

surface area and works by the adsorption, as opposed to absorption, of paracetamol (Richards et al, 2011). Adsorption works by binding the molecules concerned to the surface of the charcoal, which prevents them from entering the bloodstream until the charcoal is excreted from the gastrointestinal system. This differs to absorption of the molecules which would entail the charcoal being permeated by the molecules. Activated charcoal cannot be used for unconscious patients, obviously, nor for those with a poor swallow reflex for risk of aspiration. It is not routinely recommended due to the complications of administration and, again, the possible motion sickness during transport causing vomiting and aspiration (AACE, 2013). However, as it is advised for use within an hour of overdose and overdoses are often reported with some delay (Hawton et al, 2012), activated charcoal is not necessarily a frequently encountered option for paramedics.

Some special groups of patients can be considered to be at increased risk of organ damage from paracetamol, and thus viewed with particular caution in terms of the likelihood of serious consequences of any overdose. These include:

l Those with impaired liver function, e.g. those with chronic alcohol dependency l Those with reduced antioxidant reserve, e.g. the poorly nourished, the anorexic, or those undergoing chemotherapy for cancer or conditions leading to immunodeficiency such as HIV.In tandem with the urgency surrounding

the physiological impact of overdose is the need to address psychosocial factors—it is well documented that paracetamol overdose is often associated with patients feeling embarrassed or ashamed (Farley et al, 2005) and an aspect of the paramedic’s response to an overdose that clearly needs to feature is psychological care. The National Institute for Health and Care Excellence (NICE) Quality Standard for Self Harm (2013) states:

‘All staff ensure that they treat people who have self-harmed with compassion and the same respect and dignity as any service user’ (NICE, 2013: 11).

For those who have self-harmed, staff attitudes are often reported as contributing to poor experiences of care; judgemental or even punitive attitudes can be very upsetting for people who have self-harmed which may in turn lead to further episodes of self-harm or avoidance of seeking medical attention in the future (NICE, 2013).

There is a need to gather the history sensitively, especially with adolescents who may be more concerned with disapproval towards their behaviours or rationales. This may require privacy or, conversely, may require the presence of a supportive friend or ally when recounting the episode. If the patient wishes, these significant others should be included in decision making about treatment and care (NICE, 2011). Communication may be difficult at this time because patients can easily withdraw and wish to be left alone. Actively listening, using open body language, showing concern through tone of voice, and making deliberate efforts to demonstrate empathy are all approaches which encourage a sense of safety for the patient and are likely to gain cooperation in terms of an accurate history of the incident.

Paramedics should bear in mind the gravity of the situation for the patient—not only the acute consequences of organ injury or failure, but the longer terms ramifications for those that self-harm. Self-harm increases the likelihood that the person will commit suicide by between fifty and one hundredfold above the rest of the population in a 12-month period (NICE, 2011), and national data demonstrates that repeat attendance in hospitals for self-harm within a year are common at 17.7% (Hawton et al, 2012). A wide range of psychiatric issues—depression, bipolar disorder, schizophrenia, and drug and alcohol-use disorders—are associated with self-harm



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(NICE, 2011), and the self-poisoning event may be an early indication of complex co-morbidities requiring specialist support. In the immediate short term it is advisable to undertake a suicide risk assessment using, for example, the SAD PERSONS scale (AACE, 2013), which will inform strategies for treatment, appraisal of capacity and handover at hospital.

Referral to specialist services is often challenging for paramedics as there is a noted diurnal pattern to overdose in children and adolescents with most episodes occurring between 22:00 hours and 01:00 hours, with episodes involving alcohol occurring between 01:00 and 05:00 (Hawton et al, 2012), when many established support services may not be immediately available, thus requiring transport to A&E departments. Patients admitted to hospital following an episode of self-harm should be referred to and assessed by the mental health team and although this would be clear to any staff receiving the patient’s handover at hospital, it is still worth underscoring this to them.

Given that a person’s capacity to make informed decisions may change over time, and that sometimes this can happen rapidly in the context of self-harm and suicidal behaviour (NICE, 2011), paramedics need to be able to confidently assess mental capacity, and make decisions about when treatment and care can be given without consent—this is a challenging situation with many potential compromises as the potentially extreme sensitivities involved may result in amplified resentment to any decision to involve the police or to insist that the patient is transported to definitive care, given the potential physical harm an overdose can cause. It is worth emphasising here that, in this light, the NICE (2011) document, ‘Self-harm: longer-term management’ stipulates the following:

l 1.1.12 Health and social care professionals who work with people who self-harm should be trained to: understand and apply the principles of the Mental Capacity Act (2005) and Mental Health Act (1983; amended 1995 and 2007)

l 1.1.16 Understand when and how the Mental Health Act (1983; amended 1995 and 2007) can be used to treat the physical consequences of self-harm l 1.1.17 Health and social care professionals who work with people who self-harm should have easy access to legal advice about issues relating to capacity and consent.These topics in depth are beyond the scope of

this particular CPD module but it does highlight the need to be refreshed on these essential areas of clinical practice whenever possible, even though education programmes will include these areas as standard.

ConclusionsThis CPD module has considered paracetamol overdose both as accidental and intentional events and the paramedic’s role in these instances. Of note, communication plays a significant role: clear, precise history taking in terms of amount and timing of ingestion, possible educational input for parents or carers, and supportive, non-judgemental interaction with those that self-harm with the drug, given the likely co-morbidities that may exist and the need to accept definitive treatment at hospital.

Further self-directed study resourcesTOXlearning is an e-learning site run by the NPIS (www.toxbase.co.uk). It aims to support healthcare professionals in using TOXBASE more efficiently, thus improving their knowledge of poisoning and the proposed best care of patients presenting with poisoning. The self-registration process is free and access to materials is immediate. TOXlearning users can work through individual modules at their own pace and save their work. The results of the assessment can be printed as a ‘certificate of completion’ for continuing professional development purposes.

Useful linksTOXBase: www.toxbase.co.ukNational Poisons Information Service: www.npis.org/

Reflection 5In which ways do you think a patient’s capacity to consent can change—often rapidly—after paracetamol overdose?• Consider physical issues• Consider psychological issuesWhat resources are available to you in terms of making decisions about when treatment and care can be given without consent?To complete the exercise, click the button.



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Kevin Barrett has been course leader for the BSc(Hons) Paramedic Practice course at the University of Brighton since 2009 and is developing approaches to simulation in clinical education.

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