Rotigotine patch prescription in inpatients with Parkinson’s disease: evaluating prescription accuracy, delirium and end-of-life use (2024)

Abstract

Key points

• Acute conversion of oral Parkinson’s medication to trans-dermal Rotigotine patch is poorly done and problematic.

• Standardised methods and validated tools can help clinicians avoid conversion errors.

• Use in inpatients may precipitate new or worsening delirium and this risk should be taken into account.

• Use in inpatients may serve as a proxy marker for poor prognosis and could prompt proactive advance care planning discussions.

• Use at end-of-life has not been well established and requires further study.

Background

Parkinson’s disease (PD) is a common neurodegenerative disorder affecting approximately 145,000 people in the UK [1]. The prevalence increases with age, and 75% of those affected are aged over 70 [1].

Swallowing difficulties are common in later-stage disease and are reflected in high rates of death from pneumonia [2,3]. Choking is recognised as an indicator of poor prognosis [4]. Dysphagia is commonly seen in hospital where inter-current illness, PD medication failure, or missed doses may decompensate underlying swallowing difficulties.

Where oral administration of PD medication is not possible, non-oral routes include nasogastric tube, trans-dermal Rotigotine, or, occasionally, sub-cutaneous apomorphine [5]. Rotigotine patch, a trans-dermal dopamine agonist (DA), can be used (off-label) acutely where oral administration is not feasible [6].

At end-of-life (EoL), continuation of dopaminergic medication is desirable to avoid complications of abrupt medication cessation, including non-motor ‘off’ symptoms. In our experience, it has become common place for Rotigotine to be used in this role at EoL but, to our knowledge, only one case study exists describing this [7].

Concerns regarding Rotigotine use for dopaminergic replacement in hospital include difficulty achieving dopaminergic equivalence and promotion of delirium/hallucinations. Theoretical concerns at EoL, particularly for patients who are DA naïve, include promotion of terminal agitation.

Objectives

Our objectives were to establish: (i) accuracy of Rotigotine prescribing, (ii) rates of delirium/hallucinations and (iii) rates of terminal agitation.

Methods

We retrospectively evaluated Rotigotine use for dopaminergic replacement in an inpatient population at a UK teaching hospital.

Rotigotine prescriptions between January 2018 and July 2019 were identified using the hospital’s pharmacy database. Records were examined using the hospital’s electronic document management system.

Patients were included if they had a formal diagnosis of PD and were prescribed Rotigotine for dopaminergic replacement during their admission; those taking Rotigotine prior to admission or those admitted electively under the neurology service were excluded.

Data were collected regarding admission, background, delirium, demographics, discharge, hallucinations, medication, mortality and survival. Where appropriate, additional data were collected regarding agitation, stiffness and use of sedative anticipatory medication.

The OPTIMAL drug conversion calculators are freely available online tools endorsed by Parkinson’s UK and British Geriatric Society Movement Disorder Section to help clinicians convert a patient’s oral PD medication to more appropriate preparations [8]. Two tools exist: Calculator 1 is designed for patients with poor swallow or assigned nil-by-mouth and converts to dispersible preparations via nasogastric tube. Calculator 2 is designed for patients with gastrointestinal failure or those in whom nasogastric intubation is not appropriate and converts to trans-dermal Rotigotine patch. Notably Calculator 2 recommends a lower dose for patients with dementia/delirium at risk of new/worsening delirium. We determined dopaminergic equivalence using Calculator 2.

Delirium was identified from case notes using a previously validated approach [9] by clinicians trained in geriatric medicine. A second reviewer adjudicated where uncertainty existed.

Terminal agitation was defined as new/worsening delirium/hallucinations in the terminal phase, or by the recurrent (>2) use of sedative anticipatory medications (usually Midazolam) in a 24-hour period. Terminal symptoms, including agitation and stiffness, were identified through case notes including an hourly ‘symptom observation’ chart, which is routinely completed in the hospital during intentional rounding for people in the terminal phase.

Descriptive statistics were utilised throughout. The project was registered with the hospital’s audit and quality improvement office. No ethical approval was required.

Results

A total of 84 patients were included in the evaluation (see Table 1 for patient characteristics and Figure 1 for patient inclusion)

• (i) Accuracy of Rotigotine prescribing

Twenty-five (30%) patients were prescribed the recommended dose of Rotigotine.

Of the 59 (70%) patients where the prescribed dose differed from the recommended dose, 31 (53%) were prescribed a higher dose and 28 (47%) a lower dose.

Fifteen of 41 (37%) patients who had dementia received the standard dose of Rotigotine rather than the lower dose recommended for dementia.

Twenty-two of 49 (45%) patients who had delirium before initiation of Rotigotine received the standard dose of Rotigotine rather than the lower dose recommended for delirium.

• (ii) Rates of delirium/hallucinations

Forty-nine (58%) patients had delirium before initiation of Rotigotine. Twenty (24%) patients developed new/worsening delirium after Rotigotine use, of whom 12 (60%) were prescribed a higher than recommended dose, 4 (20%) were prescribed the recommended dose, 4 (20%) were prescribed a lower than recommended dose and 18 (90%) were DA naïve.

Nine (11%) patients had hallucinations before initiation of Rotigotine. Eight (10%) patients developed new/worsening hallucinations after Rotigotine use.

• (iii) Rates of terminal agitation

Fifty-nine (70%) patients were dead and 25 (30%) were alive at the time of evaluation.

Forty (48%) patients died in hospital. Median survival from initiation of Rotigotine was 5days. All remained on Rotigotine until death. Ten of 40 (25%) demonstrated evidence of terminal agitation, of whom 9 (90%) were DA naïve. Fourteen of 40 (35%) required at least one dose of sedative medication with an average dose of 12.5mg (range 2.5–30mg) in the last 24hours of life. No cases of terminal stiffness were identified in the notes.

Nineteen (23%) patients died in the community. Median survival from initiation of Rotigotine was 75days. No data were available to comment on continuation of Rotigotine and rates of terminal agitation.

Discussion

These results suggest that Rotigotine is being widely used for people with Parkinson’s (PwP) in our institution. The conversion of oral PD medication to a dopa-equivalent dose of Rotigotine was accurate in only 30% of cases suggesting that this process is still not well understood. Conversion errors, where they occurred, tended to overestimate the required dose. This is of particular concern in hospitalised patients, where our findings support the assertion that the risk of developing new/worsening delirium may be greater in those who receive higher than recommended doses and those who are DA naïve. The high proportion of patients who developed new/worsening delirium despite having received recommended or lower than recommended doses (40%) suggests that even careful and considered Rotigotine use is not without risk and that prescription decisions should be made on an individual patient basis. We used OPTIMAL Calculator 2 as a gold standard reference because it has been endorsed by relevant organisations and recommends a lower dose for people at risk of delirium. Other calculators exist, which may account for some of the differences observed.

The rate of in-hospital death in this patient cohort was high, likely reflecting the high aspiration risk in people prescribed Rotigotine for dopaminergic replacement. Of those who were discharged from hospital, almost half had died at the time of evaluation, with a median survival of 75days. These findings suggest that, even in patients reaching discharge, acute Rotigotine use may serve as a proxy marker for poor prognosis and could usefully be considered as a prompt for proactive advance care planning discussions. Future research comparing survival with a group of similar patients with PD, who did not use Rotigotine for dopaminergic replacement, should be considered to examine this assertion.

Delirium at EoL may be as high as 88% in some studies [10], with 10–23% requiring sedation in the terminal phase [11,12]. We identified sedation requirements at the upper end of this estimate, suggesting terminal agitation may have been prominent in people receiving Rotigotine at EoL. These estimates are derived from non-PD specific studies and may not reflect expectations in PwP. Moreover, rates of terminal agitation in PwP not receiving Rotigotine were not available for comparison making it impossible to determine whether acute Rotigotine use was driving terminal agitation. Nonetheless, we feel these findings raise an important point, not least because the efficacy of Rotigotine at EoL, although theoretically grounded, has not been well established. This represents an important area for further study. A case series of these patients is planned to guide future work.

Previous evaluation of hospice patients dying with PD suggested the dying phase may be prolonged [13], and this may support our observations regarding median survival.

This work evaluates the acute use of Rotigotine in a real-world setting. However, the methodological limitations of this retrospective notes analysis should be borne in mind. Omissions or documentation errors could have been carried forwards. Some cases of delirium might have been missed in retrospective assessment, despite steps taken to minimise this. Cause-and-effect relationships cannot be established from this methodology which sought only to describe patterns at our institution. Nonetheless, we believe it highlights important issues around acute Rotigotine use, which would benefit from future study.

Conclusions

Rotigotine is an option for clinicians caring for PwP in hospital where enteral administration of PD medication is temporarily impaired.

It is important for standardised methods to be used when converting oral PD medication to Rotigotine and for delirium risk to be taken into account; our findings suggest this may not currently be the case.

Inpatient Rotigotine use may serve as a proxy marker for poor prognosis and could usefully be considered as a prompt for proactive advance care planning discussions.

Rotigotine use at EoL has not been well established. The best management of PwP at EoL urgently requires further study.

Declaration of Conflicts of Interest

None.

Declaration of Sources of Funding

None.

References

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