Ensuring time critical use of rasburicase

Patient harm

Tumour Lysis Syndrome (TLS) is a life-threatening complication that arises when rapid breakdown of tumour cells leads to the release of excessive quantities of cellular contents into the bloodstream. This can lead to acute renal failure, cardiac arrhythmias, seizures, and sudden death. TLS can develop rapidly and is difficult to treat once established.

Delays in treatment of TLS with rasburicase puts individuals at greater risk of developing these symptoms and associated harm.

Delaying rasburicase treatment in patients at risk of developing TLS may delay their chemotherapy.

Using this advice

This article provides mitigation strategies to minimise harms caused by delayed access to rasburicase, or failures in communication and operational processes associated with rasburicase therapy.

Safety directive

NHS England’s National Patient Safety Alert outlines actions for all organisations with an Emergency Department (ED) or cancer services. The actions aim to minimise the risk of harm from delayed administration of rasburicase for tumour lysis syndrome.

High risk scenarios

The following scenarios are likely to increase the risk of rasburicase treatment delays.

Emergency treatment

The need for rasburicase may be clinically unexpected, with a treatment schedule not documented in the individual’s care plan. In this scenario the time critical nature of therapy may be even greater.

Clinical outliers

Rasburicase is predominately used in specialist acute oncology clinical settings. Patients may need treatment outside of these areas, for example when an outlier in another clinical speciality setting.  Staff in these areas may be unfamiliar with rasburicase and its time critical nature.

Transfers of care

The decision to treat with rasburicase may occur when a patient is in a day care setting. This may require a transfer of care to a different clinical setting to administer treatment, after the day care setting has closed. Failure in communication, differing prescribing systems or unfamiliarity with rasburicase and its time critical nature in the new clinical setting may lead to delayed therapy.

Clinical use

Rasburicase may be used for both the treatment and prophylaxis of TLS.

The decision to treat with rasburicase and the dose regimen may be complex. Practice may vary within and between organisations.

The British Society of Haematologists (BSH) have produced guidelines for the diagnosis and management of tumour lysis syndrome in adults and children

Time critical

Rasburicase acts immediately, even on already formed urate. It is extremely effective and reduces the plasma levels of uric acid within 4 hours of intravenous administration.

The BSH recommends that rasburicase should be available for administration within 1 hour of prescription.

Clinical validation by a senior clinician, independent of the patient’s clinical team, is required by some organisations prior to treatment with rasburicase. This may lead to a delay in therapy

G6PD deficiency

Rasburicase may cause haemolytic anaemia or methaemoglobinaemia in at risk patients, such as those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The patient’s G6PD status may affect the decision to treat.

Prescribing and supply

Where separate oncology prescribing systems are used, there may be multiple locations for prescribing, documenting supply, and administering rasburicase.

Some organisations ensure rasburicase is prescribed only on an in-patient prescribing chart, with prescribing on other systems, such as chemotherapy prescribing systems, only done after a documented risk assessment.

Risk

Delays in treatment may result from:

• failure by staff to recognise the time critical nature of rasburicase
• failure to communicate and escalate concerns related to treatment delays
• the need for additional validation prior to treatment with rasburicase, especially out-of-hours
• confusion related to the clinical indication and need for treatment, and appropriate dosing of rasburicase
• confusion related to the documentation of prescription, supply validation and administration.

Access

Barriers to timely access should be minimised to prevent potential harm.

Stock locations

Rasburicase is a costly medicine. Restricting stock holding to central non-clinical areas has been an intentional practice intended to prevent unauthorised use within historical commissioning processes.

Rasburicase is not on the current NHS England high-cost drugs commissioning list, however organisations may not have recently reviewed their stock holding and may not have expanded access within clinical areas.

Refrigeration

Rasburicase requires storage in a medication fridge.

Available formulations

Rasburicase is available as a 1.5mg vial and a 7.5mg vial.

Following dilution, the resultant concentration of product with the two presentations is the same. The two different presentations are used to make up the required dose using the minimum number of vials, with an aim of minimising waste and product handling during the preparation process.

Supply disruption

The SPS Medicines Supply Tool can be used to identify supply shortages (registration to the SPS website required). If one presentation is unavailable, mitigation strategies detailed below should be reviewed to assess local impact.

Stock levels

Stock levels should ensure sufficient vials are available, taking into account any potential supply issues and potential unplanned emergency use.

Risk

Failure of healthcare staff to identify rasburicase as an item stored in a fridge may delay access.

A delay in obtaining a supply of rasburicase may occur after a decision to treat, due to inappropriate stock holding locations and levels within the organisation.

During a period of supply disruption, staff may be unfamiliar with the need to use only one of the available presentations to make up the total required dose. This may lead to a delay while trying to locate the alternative presentation. Where the lower dose presentation is solely available to make up the required dose, stock levels would need to be adjusted to account for a higher usage of vials. This may result in handling a number of vials or a risk of underdosage (or both).

Mitigation

Rasburicase therapy should be considered ‘time critical’ and actions should be taken locally to minimise all potential delays to therapy.

The following strategies can help minimise common risks.

Standardise clinical practice

Ensure there is clarity in local policies, clinical guidelines and protocols regarding the indication and clinical parameters for treatment, including appropriate dosing of rasburicase for prophylaxis and treatment of TLS.  Organisational policy for documenting this information within clinical care plans and pathways minimises the need for clinical validation outside of the immediate clinical team.

Ensure the use of rasburicase in non-specialist settings is minimised.

Where rasburicase is used in a non-specialist setting, organisational policy should ensure that risks associated with delayed treatment are highlighted, and additional information and support is provided on each occasion.

Organisational processes should be in place to ensure communication between all healthcare professionals involved in the care of the patient and the supply and administration process of rasburicase is clear, timely and documented.

Awareness and knowledge

Ensure healthcare professionals responsible for the prescribing, supply and administration of rasburicase are aware of the risks associated with delays to treatment and when to escalate concerns.

Prescribing and validation

Local policies and clinical guidelines or protocols should:

• state that in situations where there is a lack of clinical clarity on the dose regimen or validation required, timely actions are taken to ensure therapy with rasburicase is given without delay.
• clearly outline the location of prescription (type of prescription) and supply and administration documentation for all rasburicase therapy.

Utilise electronic functionality and validation opportunities on prescriptions to highlight storage of rasburicase in the fridge.

Supply

Undertake a regular organisation-wide review of rasburicase stockholding to ensure timely access:

• clinical areas where rasburicase is routinely used should hold sufficient level of stock of each strength to enable administration within 1 hour of prescribing
• there should be a central location where rasburicase can be obtained in a timely manner, for example an out of hours pharmacy service or ‘emergency drugs cupboard’
• assurance of organisational systems to ensure stockholding in these areas do not fall below the minimum level without escalation to a clinical lead

Healthcare professionals in all clinical settings across the organisation should have an awareness of and access to information to support timely access to rasburicase (including an awareness of its refrigeration status). This may be organisational policy or systems to support healthcare professionals in obtaining all medications required at the point of care.

At times of supply shortages, organisations should cascade advice to healthcare professionals regarding the appropriate handling of available presentations to minimise delays and risks associated with incorrect preparation.

Local assessment

Standardisation of practice should not remove the need for individualised patient care. When putting any mitigation strategies into practice there are considerations which may be locally unique, which will require local assessment of the impact.

Acknowledgments

Information on prevalent risks associated with delayed use of rasburicase was provided by the Patient Safety Team at NHS England.

An earlier version of this article has also been reviewed by the British Society of Haematology (BSH) TLS clinical guidelines writing group.

Update history