Poisoning

Clinical case scenario

After morning surgery you receive a message asking you to phone the daughter of one of your patients. Mrs McKenzie is a 79-year-old lady who was diagnosed with Alzheimer’s disease 18 months ago. You are aware that she lives alone, but manages well with support from her daughter and uses a dossette box to help with her medication. You see from her notes that she had a consultation about depressive symptoms 2 months ago and was started on citalopram.

Her daughter tells you that this morning her mother appears to have taken all the medication from this week’s dossette box. She has told her daughter that ‘she got in a muddle’ but is being a little more vague than normal. She does not appear unwell. From her notes you confirm that her medication comprises donepezil, atorvastatin, citalopram, amlodipine and aspirin.

Assessment

An accurate history is required to identify patients exposed to potentially harmful substances. If possible, information about precise quantities, doses and timings of substances involved should be gathered. Further targeted history and examination will depend on the substance involved, but in most patients this should include pulse, blood pressure, respiratory rate, oxygen saturations and temperature.

Most patients with suspected poisoning will require referral to an appropriate secondary care setting for full assessment, usually emergency or acute medicine departments. Small accidental drug errors can often be managed safely in the community, but beware of drugs such as lithium with a narrow therapeutic window and drugs with modified release preparations, as initial signs of toxicity may not be apparent.

Accessing information

There are many thousands of substances involved in poisoning, making it impossible for individual clinicians to retain knowledge on the assessment and management of every substance. In the UK, the National Poisons Information Service (NPIS) is commissioned to provide up-to-date information for clinicians. This is primarily available via TOXBASE, an online database that can be accessed freely by all clinicians with departmental or organisation logins. GPs can register their practice for an account for use by all clinical team members. Individual clinicians can access the same information using a mobile app and can create an account using their NHS email addresses. In addition, there is a 24-hour telephone advice service, staffed by advisors and supported by consultant clinical toxicologists.

Table 1 shows the most common products accessed on TOXBASE online and through the NPIS telephone advice line, illustrating the most common agents involved in poisoning in the UK where medical attention is sought (NPIS, 2020).

OPEN IN VIEWER

Table 1.

Most common agents accessed on TOXBASE online and involved in telephone enquiries 2019–20.

TOXBASE online		NPIS telephone enquiries
Agent	No. page views	Agent	No. calls
Paracetamol	145 515	Paracetamol	5077
Ibuprofen	46 993	Ibuprofen	2329
Sertraline	45 596	Co-codamol	1300
Diazepam	29 313	Sertraline	883
Quetiapine	25 313	Multivitamins	673
Codeine	24 564	Mirtazapine	655
Pregabalin	23 572	Naproxen	580
Mirtazapine	22 571	Diazepam	561
Propranolol	21 918	Quetiapine	558
Amitriptyline	21 027	Pregabalin	501

This article aims to cover the principles of assessment and management of some of the more common agents involved in poisoning, and to consider carbon monoxide poisoning, an uncommon but probably under-recognised source of poisoning in the UK.

Paracetamol

In the UK, paracetamol is the most common agent used in attempted deliberate self-harm by poisoning (NPIS, 2020). Paracetamol is also commonly implicated in cases of therapeutic excess, often for painful conditions such as toothache.

Toxic doses of paracetamol cause severe hepatocellular necrosis. Nausea and vomiting, which are the only early clinical features of poisoning, usually settle within 24 hours. Symptoms persisting beyond this, or accompanied by right upper quadrant pain and tenderness, usually indicate hepatic necrosis. Liver damage is maximal 3–4 days after paracetamol overdose, and the absence of symptoms does not confer a lack of need for treatment (Joint Formulary Committee, 2019).

An important step in managing paracetamol poisoning is to establish the type of overdose involved so that appropriate assessment and treatment can commence. Up-to-date information from TOXBASE should be sought when managing any patient with suspected poisoning, and the information below provides an outline of treatment principles only.

Acetylcysteine is the mainstay of treatment in paracetamol poisoning. When paracetamol is taken in large quantities, a toxic metabolite accumulates within the body, which is conjugated by glutathione. When taken in excess, the body's glutathione reserves are not sufficient to deactivate the toxic metabolite damaging liver cells. Acetylcysteine acts to maintain or replenish depleted glutathione reserves in the liver.

Opioid poisoning

Opioids include morphine, codeine, oxycodone, methadone and heroin. Acute opioid poisoning often occurs in the context of opioid dependence, especially at times of reduced tolerance, for example on release from prison. Other scenarios encountered in general practice include patients prescribed high-dose opiates (e.g. in a palliative care setting) where doses may be increased too quickly or accumulation occurs due to a deterioration in renal or liver function.

Clinical features of acute poisoning include drowsiness and coma, pinpoint pupils, apnoea, cyanosis and hypotension. Respiratory depression may cause death within an hour of an opioid overdose, but slow release preparations and methadone, which has a very long half-life of 25–50 hours, should be treated with caution (Wyatt et al., 2011).

When suspected opioid overdose is encountered in the community, naloxone should be administrated whenever possible while awaiting the arrival of the ambulance. In mixed overdoses (for example, also involving benzodiazepines and gabapentinoids) the classic signs of pinpoint pupils may be absent and should not be a reason to withhold treatment (World Health Organisation, 2014). Naloxone is a specific opioid antagonist and will reverse respiratory depression and coma. In hospital settings this is given intravenously, carefully titrated according to effect. In patients with known opioid dependence this may start with as small a dose as 100 micrograms to avoid opiate withdrawal syndrome and to allow safe observation of the patient without fully reversing the action of the opioid (Wyatt et al., 2011).

Naloxone is increasingly available in the community in pre-prepared formulations with training and access available to friends and family of those at risk of overdose, as well as those who are likely to witness an overdose, such as outreach and accommodation workers (World Health Organisation, 2014). Initial doses of 0.4–0.8 mg Intramuscular are normally adequate, with doses above this likely to precipitate withdrawal.

In palliative care settings, the majority of opioid poisoning can be treated by omitting the next dose of opioid and reviewing analgesia requirements. Hydration and oxygenation should be optimised if necessary, and consideration should be given to the patient's current care setting and whether closer observation is required. Use of naloxone is rarely required and over-use may lead to significant pain and suffering for the patient. Scottish guidelines suggest use of naloxone in this setting would be indicated if a patient’s respiration rate dropped below eight per minute or oxygen saturations were below 85%. In this situation low doses of naloxone are recommended with careful titration. Many formulations used in palliative care are long-acting, and therefore repeated doses or infusions may be required (Scottish Palliative Care Guidelines, 2014).

Serotonin syndrome and selective serotonin reuptake inhibitor poisoning

Serotonin syndrome can be caused by any drug or medication that increases the production or reduces the metabolism of serotonin. It can occur in patients who are taking therapeutic doses of these drugs, especially if they have recently started taking them or are taking them in combination with other drugs that affect serotonin metabolism, such as recreational cocaine use (Wyatt et al., 2011).

Symptoms of serotonin syndrome include confusion, agitation, hallucination, tremor, diarrhoea, vomiting and rigidity. Hyperreflexia may be noted, as well as tachycardia, hypertension, and hyperthermia. Severe cases may result in reduced consciousness, seizures, rhabdomyolysis and renal failure (Wyatt et al., 2011).

TOXBASE recommends that all patients who have taken a selective serotonin reuptake inhibitor overdose as an act of deliberate self-harm should be referred for assessment. This would normally include investigations such as serum electrolytes, glucose, LFTs and creatinine kinase, and an electrocardiogram (ECG). A period of monitoring is required if no intervention is necessary. For accidental overdoses, TOXBASE provides guidance on doses which require medical attention. Those who are symptomatic or those who have ingested a potentially toxic dose should be referred for assessment (TOXBASE, 2017).

Carbon monoxide poisoning

Carbon monoxide is an uncommon, but important, cause of poisoning in the UK. It can be extremely difficult to identify, and both acute and chronic cases can be easily misdiagnosed as other common presentations such as influenza, gastroenteritis, tension headache and alcohol toxicity (Ashcroft et al., 2019). Approximately 50 people die from accidental carbon monoxide poisoning in the UK every year (Office for National Statistics, 2020) and it is believed that the morbidity is underestimated (Ashcroft et al., 2019).

Carbon monoxide is a colourless, odourless, tasteless gas produced by incomplete burning of fuels and is highly toxic. Exposure causes tissue hypoxia by binding to haemoglobin and forming carboxyhaemoglobin (COHb). Carbon monoxide has over 200 times the affinity to haemoglobin than oxygen, and therefore, significantly reduces the oxygen-carrying capacity of blood (Ashcroft et al., 2019).

Possible sources of carbon monoxide include appliances such as cookers and boilers that are poorly installed or faulty. It will also cause poisoning if petrol or diesel engine exhaust gases are retained in a small space, or where camping stoves and barbecues are used indoors. Smoke inhaled in building fires is another source of carbon monoxide (Ashcroft et al., 2019)

Children

Accidental exposure of young children to therapeutic drugs and household products is the most common cause of poisoning in paediatric populations. In the UK, and other parts of Northern Europe and North America, single-use laundry detergent pods are the most common toxic substance ingested. There is a secondary peak of poisoning in older teenagers, largely due to deliberate overdose and recreational drug use (Mintegi et al., 2019).

In any case of poisoning in children, whether accidental or deliberate, consideration should be given to child safeguarding issues and information shared with relevant agencies involved in the care of the child where necessary.

Deliberate overdose and assessment of mental health

For patients presenting with self-harm, effective communication skills are needed to make an assessment of current mental state and risk of further self-harm. The underlying intent of the overdose needs to be established. An impulsive overdose, for example after an argument, is very different from one taken with medication stockpiled weeks in advance.

Asking open questions about the preceding events leading up to the overdose will allow an accurate assessment of the context in which it was taken. There are several scoring systems for determining suicidal intent and future suicide risk. Unfortunately, none of these has evidence of reliable predictable ability, and National Institute for Health and Clinical Excellence (NICE) advises against their use. Ongoing suicidal intent should be established along with assessment for mental illness, such as depression. Demographics that increase the risk of suicide completion (e.g. male sex, unemployment and substance misuse) should also be taken into account (NICE, 2011).

Patients who self-harm by poisoning, especially repeatedly, are often vulnerable. In certain groups of patients weekly or daily dispensing of medication can be considered, and although there is no ‘safe limit’ for poisoning, this can reduce the likelihood of a potentially fatal overdose. As with all patients, a non-judgemental and empathetic approach will help with assessment and provision of the required care.

KEY POINTS

All clinicians in the UK have access to up-to-date information on the management of poisoning via the TOXBASE website, app, or helpline on 0344 892 0111