Adult Paracetamol Poisoning Clinical Guideline
|Publication: 30/09/2021 --|
|Last review: 01/01/1900|
|Next review: 30/09/2024|
|Approved By: Trust Clinical Guidelines Group|
|Copyright© Leeds Teaching Hospitals NHS Trust 2021|
This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
Leeds Teaching Hospital Trust: Adult Paracetamol Poisoning Clinical Guideline
1.2 Scope of Guidance: Patient Population
1.3 Scope of Guidance: Trust Departments
- INITIAL ASSESSMENT
2.1 Initial Assessment: Clinician Information
2.2 Location of initial assessment
2.3 Assessing need for further investigation
2.4 Initial Assessment and Investigation
2.5 Deciding who to treat
- RISK ASSESSMENT
3.1 Need for risk assessment
3.2 Risk Assessment: Liver Function
3.3 Risk Assessment: Renal Dysfunction
3.4 Psychiatric risk assessment
3.5 Placing high risk patients
3.6 Patients requiring critical care
3.7 Patients without high risk factors
4.1 Treatment Choice
4.2 Exceptions to SNAP Regime
4.3 Prescribing NAC
4.4 Treatment: Patient without high risk factors
4.5 Treatment: Patient with high risk factors
4.6 Common side effects and treatments
- SAFETY TO DISCHARGE
5.1 Elements of safety
5.2 Post treatment bloods:
5.3 Stopping Treatment
5.4 Need for further treatment
5.5 Patients with deteriorating blood tests
5.6 Creatinine Interference
5.7 Patients presenting with self-harm
6.2 With Thanks
7.1 Appendix 1: Initial Assessment
7.2 Appendix 2: Risk Assessment and Treatment
7.3 Appendix 3: Safety to Discharge
Paracetamol poisoning relates to the ingestion or administration through any route of paracetamol doses in excess of the British National Formulary (BNF) safe therapeutic limits. This can be through deliberate self or accidental therapeutic excess. Toxicity from paracetamol exposure is dependent on many variables including the amount of paracetamol ingested, the type of exposure and the time since exposure1. Given the wide ranging clinical scenarios relating to paracetamol poisoning it is not possible to cover every eventuality within a single guideline. As such, the following guideline should be interpreted with guidance from senior clinical decision makers with experience in the management of paracetamol poisoning.
This document outlines an evidence based patient pathway for managing and treating patients presenting with paracetamol poisoning. Reference has been made to national policy from the National Poisons Information Service (NPIS) in addition to the experience of senior clinical staff at LTHT.
This guideline is for adult patients aged 16 or over and weighing greater than or equal to 40kg who present to hospital with paracetamol poisoning. A separate clinical guideline exists for children. For adults weighing less than 40 kg please consult the paediatric guideline and seek information from NPIS at www.toxbase.org.
This guideline is intended to be used in all trust areas assessing and caring for patient with paracetamol poisoning. Some elements of this pathway, notably treatment with the SNAP regime of N-acetylcysteine only relate to certain trust areas. Any deviations from the main pathway will be clearly identified in the relevant section.
This guideline aims to supplement nationally recognized assessment and treatment guidelines produced by the national poisons information service (NPIS)1. As such, it is anticipated that NPIS/ www.toxbase.org will be the primary information source for clinicians assessing and treating paracetamol overdose. This guideline creates a patient pathway analogous with NPIS guidelines and relevant to LTHT.
All new patients presenting with paracetamol poisoning to the trust should be initially assessed in the emergency department. Following initial ED assessment patients should be placed according to established trust protocols including through same day emergency care (SDEC) self-harm protocol and Leeds adult clinical pathways. Trust inpatients newly presenting with paracetamol poisoning should be initially assessed in their current clinical area with reference to NPIS guidelines. Clinical advice is also available from the acute medical registrar on call (Bleep 6357). Should a patient need to move clinical area due to paracetamol poisoning this should be as per Leeds Adult Clinical Pathways and discussed with the relevant specialty registrar or consultant prior to transfer.
Asymptomatic patients who ingest < 75mg/kg of paracetamol in 24 hours and who are asymptomatic may not need treatment1. In case of uncertainty, care decisions should be discussed with a senior clinical decision maker. If the exact amount ingested remains unclear, the clinician should err on the side of caution and proceed to assessment and treatment. Patients presenting with <75mg/kg ingestion as a means of self-harm should still receive appropriate mental health risk assessment and referral despite the lower clinical risk.
The initial assessment of a patient presenting with paracetamol poisoning depends on many variables including their symptoms, the reason for their poisoning, the timing since the overdose and their clinical condition. A full pathway for initial clinical assessment can be found at www.toxbase.org. Key parts of the pathway are summarized in Appendix 1: Phase 1 Initial Assessment.
This guideline recommends that the assessment of patients at LTHT reflects the above guidance from the National Poisons Information Service (NPIS).
In most cases the need for treatment in paracetamol overdose depends on the timing of the overdose, patient symptomology and the availability of blood test results. Again this guideline recommends that decisions to treat are based on NPIS guidelines available at www.toxbase.org. The decision to treat pathway is summarized in appendix 1: Phase 1 Initial Assessment.
Given the variety of possible presentations with paracetamol poisoning it is imperative to identify early patients at risk of medical deterioration or with active high risk psychiatric symptoms. Prompt recognition of such patients allows appropriate nursing and medical intervention at initial assessment. It also allows early patient placement in a suitable care environment.
Some degree of liver injury including coagulopathy is very common following a Paracetamol overdose. The peak injury usually occurs at around 72 hours post overdose and liver function will subsequently recover quickly in most cases.
The following risk factors at presentation suggest a patient is at higher risk of progressive liver injury.
- PT ≥25 or INR ≥2.5
- Any grade of hepatic encephalopathy
- pH <7.35 or lactate >3.0 following fluid resuscitation (or more than 24 hours after admission)
- Significant renal impairment (Creatinine >150 or urine output <30mls/hr) in combination with PT>25
- Requiring glucose support
- Bilirubin >100
Such patients should be discussed with the hepatology registrar (Bleep 4873) and should be reviewed by a minimum of registrar grade by the accepting specialty.
Renal dysfunction is the second most common organ dysfunction following paracetamol overdose. The following patients should be considered high risk of progressive kidney injury.
- AKI stage 1 (increase in Serum Creatinine ≥1.5-1.9 × baseline value)
- Persistent oliguria and/or rising serum creatinine despite supportive therapy (<0.5 mL/kg/hr for >6 consecutive hours)
- Complications refractory to medical treatment
- Hyperkalaemia (K+ >6.0 mmol/L)
- Pulmonary oedema
- Acidosis (pH <7.15
Such patients should be discussed with the renal registrar via the PatientPass system or through direct discussion if clinically urgent.
All patients presenting with paracetamol poisoning should have a history taken to establish their intent. Patients presenting with paracetamol poisoning as a form of self-harm should have an appropriate mental health history and examination documented by the assessing clinician. Patients felt to be very high risk by the admitting clinician can be discussed with the ALPS service for advice prior to subsequent assessment.
When placing high risk patients, reference should be made to Leeds Adult clinical pathways. If patients present to the emergency department with either high risk liver or high risk renal features, patient placement should occur after multidisciplinary discussion at a registrar or ideally consultant level. In cases of clinical uncertainty cases should be discussed the relevant specialty consultant.
Following multi-specialty discussion, if admission to a non-specialist ward is required this should be either under the acute medicine or elderly medicine teams as per Leeds adult clinical pathways.
Patients who present with high risk liver, renal or psychiatric features should not be triaged through an SDEC pathway.
Patients requiring critical care following paracetamol poisoning should be escalated jointly to critical care and hepatology teams within the emergency department. Patients who are admitted in critical care due to severe liver injury would be placed under the care of the hepatology team. For patients where liver injury is not the principal reason for critical care should remain under their correct patient specialty as per Leeds adult clinical pathways. If clinical uncertainty remains regarding appropriate placement, there should again be senior multidisciplinary discussion at a registrar or above level.
Patients who present without high risk liver or renal factors should be placed as per Leeds adult clinical pathways in either elderly medicine or acute medicine. Consideration should also be made to the same day emergency care (SDEC) protocol for self harm. Patients with high risk psychiatric factors may still be placed in the above specialties but early consideration should be made to enhanced patient safety through closer nursing observation and bedside safety measures. The ALPS service can be approached for advice in such patients prior to initial assessment.
Once a decision has been made to initiate treatment for paracetamol poisoning this guideline recommends the 12 hour SNAP regimen2 for N-acetylcysteine (NAC). Following initial treatment with the SNAP protocol there may be a need to modify the NAC regime in certain high risk patients. Exceptions to SNAP treatment are described below and in general these modifications should be reserved for patients under the care of the hepatology team.
Following initial treatment with SNAP, patients managed under the care of hepatologists on a specialist liver unit or within critical care may still receive the standard “Kerr” regime of N-acetylcysteine over 21 hours. In such circumstances, the benefits of a shorter treatment regime are reduced and the safety of the SNAP regime is less well established2.
Patients receiving N-Acetylcesteine for non-paracetamol poisoning will remain on the standard 21 hour “Kerr” regime.
It was felt important to clearly differentiate the new SNAP regime and the older “Kerr” regime of NAC to reduce the risk of prescribing errors. This was felt particularly important as the more limited use of “Kerr” protocol NAC within this guideline is limited to critical care and hepatology areas under specialist guidance.
Subsequently, prescription of SNAP protocol NAC will remain on paper charts whereas the prescription of Kerr protocol will be transferred to e-Meds and labelled clearly for specialist use.
Patients without high risk liver or renal factors should be treated with a standard SNAP protocol. This includes an initial 100mg/kg bag NAC over 2 hours followed by a further 200mg/kg NAC over 10 hours. A summarized treatment pathway is shown in appendix 2: Risk assessment and treatment.
Patients with high risk liver or renal factors should be treated with an extended SNAP regime. This includes an initial 100mg/kg bag NAC over 2 hours followed by a 200mg/kg NAC over 10 hours and again by a further 200mg/kg NAC over 10 hours.
This regime aims to minimize periods without NAC therapy in higher risk patients where the benefits of a shorter treatment regime is not apparent. In this pathway blood tests are checked 1 hour before the end of the first 200mg/kg NAC treatment. A safe pathway to discontinue treatment is described in section 5.
One of the key reasons for choosing the SNAP regime is its lower prevalence of side effects2 when compared to the standard 21 hour Kerr regime. The most common side effects following NAC administration are nausea, vomiting and anaphylactoid reactions. Anaphylactoid reactions can involve itching, hives, wheeze and breathlessness but rarely involve life threatening compromise of airway, breathing or circulation3.
This guideline does not recommend prophylactic antiemetic or antihistamine treatment to asymptomatic patients.
If treatment is required for nausea and vomiting this should be made on an individual patient basis. A 12 lead ECG to assess QT interval is recommended prior to choice of antiemetic. It is also prudent to consider the effects of other medication on QT interval in patients with polydrug overdose. In the presence of a normal QTc ondansetron would be a first choice anti-emetic either orally or intravenously4.
Treatment of anaphylactoid reactions is detailed at www.toxbase.org. Most minor reactions can be managed with anti-histamines and it is seldom necessary to pause or withdraw treatment with NAC. Severe reactions should be discussed with a senior clinical decision maker and a decision to proceed with treatment made on the balance of risks.
Patients who are suitable for discharge should have both a suitably low risk of further medical deterioration and, in the case of self-harm, have received appropriate risk assessment and support.
Blood tests should be obtained 1 hour prior to the end of treatment with the initial 200mg/kg 10 hour treatment with NAC. Obtaining bloods at this point aims to achieve a reasonable representation of the patients biochemistry at the end of treatment and support patient flow trough obtaining timely results.
In the case of repeat treatments with 200mg/kg NAC over 10 hours bloods should be obtained 1 hour before the end of each treatment bag. Higher risk patients should not receive a gap in NAC therapy whilst awaiting results5.
Bloods should be obtained for urea and electrolytes (U+E’s), liver function tests (LFT’s), full blood count (FBC), coagulation screen (Coag) and paracetamol levels. Please note that NAC causes interference in serum creatinine measurements which is described in detail in section 5.6.
A diagram depicting the decision to stop treatment is shown in appendix 3: Safety to discharge. Following completion of the SNAP regime, or subsequent treatments with N-acetylcysteine, medical safety for discharge can be deemed when:
- INR < or = 1.3 AND
- PARACETAMOL < 10
- ALT BELOW UPPER LIMIT OR NORMAL
- LESS THAN DOUBLED SINCE ADMISSION
- AND < TWICE UPPER LIMIT NORMAL
Isolated small rises in INR of <0.5 since admission are common following paracetamol ingestion. If ALT, renal function and paracetamol levels are normal, such rises in INR can be observed and blood tests repeated in 6 hours. NAC need not be continued in such patients unless repeat blood tests are deranged 1. It is important to note that this guidance varies slightly from current NPIS guidance.
If the blood tests identified above are not satisfactory, further NAC treatment should be offered with 200mg/kg NAC over 10 hours. Bloods should again be obtained 1 hour prior to completion of NAC and assessed against the above criteria.
Deteriorating blood tests should trigger senior medical review (registrar or above) and assessment against high risk factors. If blood parameters deteriorate to a level identifying high risk liver or renal factors appropriate advice should be sought from the relevant specialty as in section 3. Subsequent patient assessment and placement should also be as recommended in section 3.
It is important to note that treatment with NAC interferes with serum creatinine measurement falsely lowering serum creatinine values. As such, blood tests obtained during SNAP treatment and/or shortly after cessation of treatment should be interpreted with caution. In cases of clinical uncertainty, results should be discussed with a senior clinician and compared to other markers of renal function such as urine output
Following an initial mental health history and mental state examination by the assessing doctor, all patients presenting with paracetamol poisoning as a means of self-harm should be referred to the ALPS service.
When providing ongoing care for patients with self-harm:
- Always consider the risk of ongoing self-harm and suicide at initial assessment.
- Communicate your assessment with patients, provide reassurance and provide information on further actions
- Communicate patients felt to be highest risk with the multi-disciplinary team including the ALPS service. This should occur prior to medical fitness to asses.
- Involve senior decision makers in patients felt to be high risk or in cases of uncertainty
To promote prompt assessment and patients flow, patients should be referred to the ALPS service when medically fit for assessment instead of at the point of discharge.
Patients are medically fit for ALPS assessment if they are:
- Clinically well without a high NEWS score or distressing physical symptoms.
- Have a conscious level suitable for assessment
- Not be under the influence of drugs/alcohol.
- Be able to ambulate to an appropriate area for assessment.
It is useful to know the case presentation and anticipated length of treatment at point of referral as these will be used to prioritize assessments.
7.1 Appendix 1: Initial Assessment
Adult Paracetamol Poisoning
|Target patient group:|
|Target professional group(s):||Pharmacists
Secondary Care Doctors
- National Poisons Information Service, available on the worldwide web at www.toxbase.org
- Thanacoody HK, Gray A, Dear JW, et al. Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study (SNAP). BMC Pharmacology & Toxicology;14:20.
- Pakravan N, Waring WS, Sharma S, et al. Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in acetaminophen overdose. Clinical Toxicology 2008;46:697-702.
- Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomised controlled trial. Lancet 2014;383:697-704.
- Bailey, George P., et al. "Delays during the administration of acetylcysteine for the treatment of paracetamol overdose." British journal of clinical pharmacology 82.5 (2016): 1358-1363.
8.2 Documents reviewed:
- Protocol for routine clinical use of a modified intravenous acetylcysteine protocol for the treatment of paracetamol poisoning (the Scottish and Newcastle Acetylcysteine Protocol, SNAP), July 2015, National Poisons Information Service
- SNAP Protocol Version 2.0, Newcastle Teaching Hospitals
Trust Clinical Guidelines Group
LHP version 1.0
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