Paracetamol Overdose Update: Accelerated NAC infusions (February 2020)

Why this topic?

As previously discussed, paracetamol overdose is still common
Medical treatment is principally with intravenous N-acetylcysteine (NAC)
This can be a lengthy process associated with significant difficulties with distressed patients
Reducing the length of treatment can be seen as desirable for patients and healthcare professionals alike

Traditional protocol

The authorised dose regimen for acetylcysteine in paracetamol overdose is 3 consecutive intravenous infusions given over a total of 21 hours.

The dosing is based upon weight of the patient with the infusions described within the BNF

1. 150 mg/kg of NAC in 200ml 5% dextrose over 1 hour
2. 50 mg/kg of NAC in 500ml 5% dextrose over 4 hours
3. 100mg/kg of NAC in 1000ml 5% dextrose over 16 hours

Continued treatment (given at the dose and rate as used in the third infusion) may be necessary depending on the clinical evaluation of the individual patient. This is most commonly guided by blood markers including liver function tests (LFTs) and clotting (principally INR).


SNAP protocol

Scottish and Newcastle Anti-emetic Pre-treatment for Paracetamol Poisoning (SNAP) protocol

This protocol was introduced in Edinburgh in 2015, approved as local practice with ongoing collection of patient outcomes data

This protocol provided NAC in the following doses

1. 100mg/kg of NAC over two hours
2. 200mg/kg of NAC over ten hours

Blood tests were completed prior to completion of the NAC infusion, with the following used as criteria for safely stopping the infusions

• INR<1.3 
• ALT <100 and less than double the ALT at presentation
• Paracetamol level <20mg/L

SNAP outcomes

The SNAP research paper published its results in 2019. This included outcomes for patients treated in several centres, including Royal Infirmary Edinburgh, Royal Victoria Infirmary and St Thomas' Hospital

Data suggested that there was no significant increase in adverse outcomes, defined as:

• Evidence of evolving acute liver injury
• Allergic / anaphylactoid reactions

Of note, on trialling this protocol blood tests were also taken at an interval which would be comparable with the timing of the usual protocol - approximately 19-20h after initiation of treatment

Implications for Local Practice

Within the our trust we are looking to explore use of this protocol
Important to be aware that protocol and prescribing may be different for patients treated in this way
Patients are initially likely to still need bloods at usual time intervals after initiation of NAC treatment
This will provide us with stronger evidence that the SNAP protocol is as effective as current practice, whilst also not being associated with any increase in adverse events

This may allow us to make patients medically fit for discharge more quickly, reducing length of stay and potentially pressures associated with hospitalisation for both patients and AMU staff

HIV testing in Community Acquired Pneumonia: a local perspective (January 2020)

Why this topic?

• Community acquired pneumonia (CAP) is a common diagnosis in the AMU
• The World Health Organisation suggests that universal testing is recommended for all medically admitted patients in high risk areas
• In areas with lower risk (<2 in 1000 patients with HIV), it is suggested we opportunistically test for HIV in relation to certain clinical presentations
• CAP is one such presentation

What do we know about HIV?

Human immunodeficiency virus (HIV) can be associated with significant morbidity and mortality, especially in the context of Acquired Immunodeficiency Syndrome (AIDS)
HIV is readily treatable with antiviral drugs

1. Early identification of HIV has a number of benefits
2. Early initiation of treatment to avoid the complications of AIDS
3. Improved morbidity and mortality for the individual
4. Treatment significantly reduces the risk of transmission

Locally our prevalence of HIV in the Southwest of England is relatively low. Data from Public Health England calculated this to be 1.1 in 1000 people
As such, local testing is opportunistic, guided by WHO advice, rather than universal
It is acknowledged that testing rates may be lower than guidance might suggest

Who should be tested for HIV?

In a low prevalence area, we are encouraged to follow guidance available on the EuroTEST website

Facts about HIV screening

Patients do not need to be formally counselled prior testing, but should be advised of plans to undertake the test. This can be as simple as telling them “in patients with your condition, we will routinely undertake a HIV test – is that ok?”

You do not need to undertake a sexual health history – clear risk factors may be a helpful clue to testing but awkwardness associated with discussing sexual health should not preclude testing

HIV treatment is now available for nearly all patients and early treatment is associated with improved long term outcomes and prevention of complications, such as infection.  Treatment is now commenced for most patients irrespective of their CD4 count / viral load

Changing local practice

During a local quality improvement project, the microbiology/antibiotic guidelines for community acquired pneumonia in patients under 65 years of age was updated to include the following statement

Summary

HIV is a treatable condition with many positives associated with early identification and treatment
HIV testing should be considered for all patients diagnosed with community acquired pneumonia
Testing should not be considered taboo and simply seen as part of our usual practice

Getting more out of venous blood gases (December 2019)

Why this topic?

Venous blood gases are commonly undertaken in AMU and the Emergency Department as rapid means of assessing multiple aspects of a patients blood biochemistry.

In recent years, these have commonly been undertaken to quickly obtain a lactate level as part of the infamous Sepsis Six, but it is important we understand how much more there is to be gleaned from these tests and what we might do with this information


Acid-Base Balance

There are multiple mechanisms which contribute to ensuring that the body's pH remains within an acceptable range for optimal functioning of cells and tissues.

Respiratory and metabolic problems can contribute to both acute and/or chronic derangement in blood chemistry

When considering acid-base balance, think about the following:

1. Is the pH normal (7.35-7.45), low (acidaemic), or high (alkalaemic)?
2. Is there a respiratory component, indicated by an abnormal carbon dioxide level (pCO2)?
3. Is there a metabolic component, indicated by an abnormal bicarbonate level (HCO3)?

4. Additionally it is possible to understand that there may also be a compensatory mechanism. For example, a patient with a metabolic acidosis may also have a low carbon dioxide level to try and correct their acidaemia. This might be seen in diabetic ketoacidosis (DKA), for example.


Electrolyte Derangement

Blood gases can often be useful for quickly understanding whether there is any significant abnormality with a patient's electrolytes.  Each machine may check different electrolytes but almost all will rapidly check sodium (Na) and potassium (K) levels

Potassium

• High and low potassium levels can be associated with cardiac rhythm disturbances and should prompt the need for an ECG and consideration of cardiac monitoring
• Low potassium levels can be difficult to correct if magnesium levels are also low so it is worth checking this as well

Sodium

• Low sodium levels can occur for a number of reasons including infection, drugs and heat failure. Early identification of a low sodium can allow us to think about a likely cause and request additional tests if appropriate, such as urine sodium/osmolality and cortisol levels
• High sodium levels are most commonly seen in severe dehydration but can be seen in people with underlying endocrine conditions, such as diabetes insipidus

Glucose

All patients being admitted to hospital should have a blood sugar level checked on arrival, which allows for quick identification of high or low levels.  VBGs are at least as reliable as bedside monitoring of glucose (BMGs, or BMs) and there is no need to do both.

Hypoglycaemia (BM<4), with or without symptoms, should be treated as a medical emergency. This should be treated in accordance with the local guidelines found with the 'hypo boxes'. The medical team should also be informed to allow for a plan for further management to be put in place.

Hyperglycaemia can be seen in the context of poor baseline blood sugar control, in the context of acute illness or as part of a new diagnosis of diabetes


Lactate

Elevated lactate levels can be caused by tissue hypoperfusion (Type A lactataemia) in conditions such as:

• sepsis, 
• heart failure, 
• hypovolaemia 
• and in cardiac arrest.

Alternatively, lactate levels may be elevated in the absence of hypoperfusion (Type B lactataemia) with conditions such as:

• diabetes (and some of its treatments)
• malignancy
• alcohol
• beta-adrenergic agonists (e.g. salbutamol)
• HIV

Haemoglobin 

Low haemoglobin (Hb) levels may be seen in the context of acute bleeding, or in more chronic conditions
If the haemoglobin level is low (particularly Hb<80g/L), consider sending an additional blood sample to the laboratory as a "group and save" sample as this may more readily allow for a blood transfusion to be arranged in a timely manner

Paracetamol Overdose (November 2019)

Why this topic?

Paracetamol is widely available without prescription
As a result is one of the more common overdoses seen in hospital
It is also one of the most common causes of death associated with overdose

Pathophysiology

Paracetamol is normally converted to non-toxic metabolites, with only 5% converted into a toxic NAPQI
In overdose, the normal pathways become overwhelmed and more toxic NAPQI is created with  insufficient amounts of glutathione to bind it and make it non-toxic
High levels of NAPQI cause liver cell damage and necrosis
Acetylcysteine reduces paracetamol toxicity by increasing availability of glutathione

Initial Assessment

Non-staggered ingestion

If all of the paracetamol was taken within an hour this is considered a non-staggered overdose and a paracetamol level after 4 hours can help guide the need for treatment, using the nomogram
If there are adverse features like deranged LFTs or renal impairment at presentation consider treatment despite levels

 Original source: bnf.nice.org.uk

Staggered ingestion

Consider treatment irrespective of blood test results

Toxicity is less concerning if total dose less than 150mg/kg but may still require treatment depending

on presentation and other results

Baseline Investigations

Paracetamol level, renal profile, LFTs, INR, FBC

Consider ECGs and other investigations in cases of mixed overdose

Treatment

Although there are oral options for treatment, in hospital management of paracetamol overdose is almost exclusively with N-acetylcysteine (NAC)

10-20% of patients develop hypersensitivity reactions which can mimic anaphylaxis (itching, rash, swelling, respiratory distress, low blood pressure). These patients should be urgently assessed

Nausea and vomiting are common and can usually be managed symptomatically

Consider steroids and antihistamines who have previously had reactions

Treatment is most commonly administered as per the guidance from the BNF, using 1h, 4h and 16h infusions with N-acetylcysteine dosing based upon patient weight

There is increasing literature to suggest that accelerated administration may be possible without increased risk to patients, for example the SNAP 12h Acetylcysteine Regimen

Assessing response to treatment

Blood tests (LFTs, INR, renal profile) should be repeated before completion of 3rd bag, and prior to completion of subsequent bags if needed

Worrying features include rising ALT and/or INR and this may require further treatment with NAC

Rising lactate, deranged renal function and hypoglycaemia are all associated with adverse outcomes

Note: some analysers significantly underestimate paracetamol levels when taken during NAC infusion and this may therefore not be helpful

Where LFTs and clotting continue to deteriorate despite treatment, NAC should be continued and discussions may need to be had with a specialist liver unit, such as Kings College, London

Acute mental health crises

Although paracetamol overdoses can occur due to excessive therapeutic use or other error, healthcare professionals will most commonly encountner paracetamol toxicity in the context of intentional overdose with intent to self harm or end one's life

It is important to give consideration at to the ongoing risk felt to be associated with this act or other behaviours exhibited during the course of clinical assessment i.e. ongoing suicidal ideations

Ensure that local processes are observed to ensure that an adequate mental health assessment is made

Within the UK, many hospitals with have a psychiatric liaison service 

When a patient attempts to leave prior to such an assessment, risk and capacity should be assessed and it may be felt necessary to put a legal framework in place to detain the individual. In the UK, this would be under the Mental Health Act (often a Section 5(2) when the patient is under the care of a medical team, rather than psychiatric service)

Note that Section 5(2) of the Mental Heath Act does not allow a team to treat a person for their overdose and a concurrent assessment of their capacity should occur to determine whether the patient should be treated under the Mental Capacity Act, and in their best interests

These can be very difficult decisions to make and, as such, seek support from colleagues including the mental health team is encouraged to ensure the right decision is made for any given patient

Learning Points

• Assess need for treatment through history and baseline bloods (paracetamol level, INR, LFTs, renal profile, FBC)
• Ensure treatment is prescribed appropriately based upon weight
• Repeat blood tests should be undertaken before completion of 16h bag
• Treatment should continue until we are satisfied that blood tests are improving
• When LFTs, INR and other measures deteriorate despite treatment, advice should be sought from a specialist liver unit

Additional Resources

British National Formulary bnf.nice.org.uk

Toxbase toxbase.org

The Mental Heath Act 1983 www.mind.org.uk/information-support/legal-rights/mental-health-act-1983