Patient harm

Acute kidney injury, cardiac arrhythmias, seizures and sudden death are associated with Tumour Lysis Syndrome (TLS). Delays in treatment of TLS with rasburicase puts individuals at greater risk of developing these symptoms and associated patient harm.

Delaying rasburicase treatment in patients at risk of developing TLS may result in a subsequent delay of chemotherapy.

Scope

This article provides individuals and organisations with mitigation strategies to minimise harms occurring from delayed access to rasburicase, or failures in communication and operational processes associated with rasburicase therapy.

The clinical decision to treat with rasburicase is complex and covered by British Society of Haematology (BSH) clinical guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies.

High risk scenarios

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

Emergency treatment

The need for therapy with 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 use is predominately in specialist acute oncology clinical settings. There may be the need to treat patients outside of these areas, for example where a patient is an outlier in another clinical speciality setting.  Staff in these areas may lack a familiarity with rasburicase and it’s time critical nature.

Transfers of care

The decision to treat with rasburicase may occur when a patient is in a day care setting. The patient may require a transfer of care to a different clinical setting to administer treatment, following closure of the day care setting.  Failure in communication, or a lack in familiarity with rasburicase and its time critical nature in the new clinical setting may lead to delayed therapy.

Clinical use

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 and cardiac arrhythmias. TLS can develop rapidly and is difficult to treat once established.

The British Society of Haematologists (BSH) have produced clinical guidelines for the management of tumour lysis syndrome in adults and children with haematological malignancies.

Time critical

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

National clinical guidelines do not specify a recommended timeframe from ‘decision to treat’ to administration.

Clinical regimens

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

The decision to treat with rasburicase and dose required is complex. Variation of practice may occur within and between organisations.

The BSH clinical guidelines state that in the absence of contraindications, patients with established TLS should be given rasburicase at a dose of 0·2 mg/kg/day as a 30-min infusion. The duration of treatment should be determined by the clinical response

Some organisations require validation by a senior clinician, independent of the patient’s clinical team, prior to treatment with rasburicase.

G6PD deficiency

Rasburicase may cause haemolytic anaemia or methaemoglobinaemia in at risk patients, such as those with G6PD deficiency.  The G6PD status of the patient may be a clinical consideration affecting the decision to treat.

Prescribing and supply

Where separate oncology prescribing systems are in operation, there may be multiple locations for the prescribing, documentation of supply, and administration of rasburicase.

There are organisations that ensure rasburicase is always prescribed on an in-patient prescribing chart and, prescribing on any other systems such as chemotherapy prescribing systems is only undertaken after a completed and 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

After the decision to treat with rasburicase is made, barriers to timely access should be minimised to prevent potential harm.

Stock locations

Rasburicase is a costly medicine. Until recently, it was excluded from the standard tariff of payment (the Payment by Results (PbR) contract) and often required approval of funding prior to use. Historically barriers to access were intentionally put in place, requiring confirmation of financial approval prior to supply. As a result, stock holding was restricted to central locations, such as pharmacy, rather than clinical areas or emergency supply stock locations.

Rasburicase is no longer a PbR excluded drug, thus negating the need to restrict access for financial restrictions. However, organisations may not have reviewed their stock holding since this change in funding status and may not have expanded access within clinical areas.

Refrigeration

Rasburicase requires storage in a medication fridge.

Available formulations

Rasburicase is available in two presentations – 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 Medicines Supply Tool can be used to identify supply shortages (registration to the SPS website required). During times where one presentation is unavailable, mitigation strategies detailed below should be reviewed to assess local impact.

Stock levels

Dosing may involve using a number of vials of different presentations to make up the required dose. Rasburicase may be needed in an emergency in a patient where therapy was not anticipated. Stock levels should ensure sufficient vials are available.

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 after a decision to treat has been made 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 and may result in the handling of a number of vials and/or a risk of underdosage.

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 and clinical guidelines/protocols regarding the indication and clinical parameters for treatment and, appropriate dosing of rasburicase for prophylaxis and treatment of TLS.  This 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 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/protocol should state that in a clinical situation where there is a lack of clinical clarity on the required dose regimen or validation required, timely actions are taken to ensure therapy with rasburicase is given without delay.

Local policies and clinical guidelines/protocols should clearly outline the location of prescription (type of prescription) and supply/administration documentation for all rasburicase therapy.

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

Supply

Undertake a regular organisational-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 of prescribed doses
• there should be a central location where rasburicase can be obtained in a timely manner, e.g. an out of hours pharmacy service and/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. This may be organisational policy/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.

Considerations

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.

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

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