It is dopey to stop giving dopamine to hospitalized patients with Parkinson’s disease

1. Vignette 1

A 55-year-old right-handed woman with Parkinson’s disease (PD) presented to our clinic as Hoehn and Yahr (HY) stage 1 and was started on rasagiline (Azilect). A few months later, unrelated to her PD, she suffered a slip and fall complicated by a hemorrhage in her thoracic cavity requiring surgical repair. There was no prolonged anoxia or hypotension noted in the operating room. This was followed by a prolonged intensive care unit (ICU) stay with minimal physical therapy (PT) or mobilization efforts. No neurology consultation regarding her PD diagnosis was requested. MRI brain was normal prior to discharge. She started taking carbidopa-levodopa (CD/LD) at some point after hospital discharge. She returned to our clinic 1 year later. At that time, she was found to have generalized fixed dystonia and was completely dependent due to her motor disability. She was cognitively intact. She had hypophonia, which responded to dopamine, but with early wearing off. Our patient progressed from early PD to modified Rankin Scale score of 5 and HY stage 5 in 1 year, following prolonged hospitalization with no evidence of gross anoxic, ischemic, metabolic, or structural CNS pathology.

In our movement disorders clinic, unfortunately, it is not uncommon for a patient with PD to present after a recent hospitalization with marked decline in function. Often it becomes apparent that the patient’s dopaminergic medication regimen, including CD/LD, was altered during the admission or was completely discontinued. This, in conjunction with limited mobilization during hospitalization, can be a devastating combination.

The Sinemet (CD/LD) package insert warns against the abrupt dose reduction or discontinuation of levodopa containing drugs due to the risk of hyperpyrexia and confusion, similar to a neuroleptic malignant syndrome. Albeit a rare occurrence, it is well described in the literature, and is one of the reasons the concept of a ‘drug holiday’ from levodopa has fallen out of fashion [1,2]. Discontinuation of medication has been noted to worsen parkinsonian symptoms, sometimes to the point of severe rigidity requiring parenteral feeding [3]. Outside of the United States, levodopa is often combined with the DOPA decarboxylase inhibitor benserazide (as Madopar). With regard to inpatient management, levodopa-benserazide should be given the same consideration as CD/LD.

A possibly avoidable condition known as post-immobilization dystonia can develop after even brief periods of immobilization in patients with PD [3]. The entity was originally described in PD patients with orthopedic injury requiring limb immobilization or a prolonged, primarily bed-bound, hospital course [3]. Continued mobility throughout a hospitalization, assured by PT and eased by PD medications, should help prevent the disabling, often fixed, postures of post-immobilization dystonia.

2. Vignette 2

A 76-year-old man with PD underwent bilateral deep brain stimulation of the subthalamic nuclei 8 years prior. He continued to take CD/LD in the years following the procedure as his condition deteriorated as expected by its natural history. He was admitted to an inpatient medical service for behavioral disturbances and failure to thrive. Typical and atypical antipsychotics were utilized to quell his psychosis. Three weeks into the admission, CD/LD was completely discontinued. One evening between vital signs checks, the patient suffered an unwitnessed cardiac arrest. After return of spontaneous circulation (approximately 15 min after being found), he was transferred to the ICU, the hospital’s hypothermia protocol was initiated, and after rewarming, neurology consultation was finally requested to assess for retained brainstem reflexes …

Commonly, during medical or surgical hospitalizations, a PD patient’s dopaminergic medication regimen will be inappropriately altered [4–6], anti-dopaminergic medications inappropriately given [4,5], and patients will be dissatisfied with their inpatient PD related management [4]. Recent retrospective studies looked at the effect of medication errors, including incorrect timing or complete omission of dopaminergic drugs (as well as inappropriate antipsychotic, e.g. haloperidol, and antiemetic, e.g. metaclopramide, administration), on inpatients with PD [7,8]. Such errors were associated with increased length of hospitalization [7,8] and a higher mortality rate [7]. In one of these studies, neurologists were consulted in less than one quarter of the inpatient encounters [8]. A prospective study followed PD patients admitted to a hospital for various medical or surgical reasons over the course of 1 year [9]. At discharge, 28% had a decrease of 5 points or more on part 3 of the United Parkinson’s Disease Rating Scale (UPDRS-III) [9]. Medication errors were found to be the most important risk factor for this motor deterioration, followed by the development of a hospital acquired infection, and a patient not being in control of their own PD medications [9]. No patients in this study who were in control of their own PD medications suffered motor deterioration [9]. A large survey study found a similar percentage (21–22%) of patients noting motor deterioration after hospitalization and 26% noted improper PD medication administration [10].

When a patient presents with psychosis deemed associated with PD medications, adjustments in the PD medication regimen may be necessary. It is suggested that anticholinergics are eliminated first, followed by amantadine, monoamine oxidase inhibitors, dopamine agonists, catechol-O-methyltransferase inhibitors, and then finally reducing the amount of levodopa [11]. Alternatively, medications can be added to the regimen to treat psychotic symptoms associated with PD [12]. The second-generation antipsychotics, quetiapine, ziprasidone, and clozapine, have been shown to improve psychotic symptoms without worsening motor performance [12]. The addition of cholinesterase inhibitors such as donepezil and rivastigmine have also been found to be beneficial without worsening UPDRS scores [12].

If a patient can tolerate oral medications, there are few reasons why a patient with PD should be denied his PD medications. Medication-related psychosis and profound hypotension are on this short list. If enteral treatment is not an option, then non-enteral options can provide alternatives that are currently available or are coming to the market in the near future. CD/LD is available in a dissolvable formulation (Parcopa); CD/LD and amantadine can be crushed and administered via percutaneous endoscopic gastrostomy (PEG) or nasogastric (NG) tubing; extended release CD/LD (Rytary) capsules can be opened and their contents administered via PEG or NG; rotigotine (Neupro) offers transdermal absorption; and apomorphine is applied via subcutaneous injections. In development are transcutaneous and inhaled formulation of CD/LD, and, in Europe, an apomorphine pump is available.

Transdermal, intravenous, and NG routes have been reported effective in the perioperative setting in surgical and anesthesia literature [13–15]. Nausea and hypotension from IV levodopa (not readily available) should be expected, but are both preventable by pretreatment with a peripheral decarboxylase inhibitor (like carbidopa) [16]. Intravenous ondansetron or trimethobenzamide are non-dopamine-blocking options that may be effective in preventing levodopa-related nausea. NG administration allows for the combination of CD/LD to be given, preventing nausea, giving the brand Sinemet (‘without emesis’) its namesake. The rotigotine patch (Neupro) could be started non-emergently for scheduled procedures requiring an NPO status. It has been reported that the continued use of rotigotine throughout an operation may reduce postsurgical complications in patients with PD [14], which are numerous, varied, and reported with higher frequency than in patients without PD [5,17].

The modifiable risk factors for post-hospitalization or post-surgical motor deterioration and inpatient complications in PD patients include proper medication management, aspiration and fall precautions, mobilization, and utilization of PT [4]. The Parkinson’s Foundation website (www.Parkinson.org) offers a ‘Parkinson’s Toolkit’ to help guide hospital encounters in the care of patients with PD. Systematically reviewed guidelines for inpatient or perioperative PD management do not exist. A large prospective randomized study of patients in this situation would need to be performed (though should not be for many ethical reasons) in order to provide level 1 evidence of the ramifications of discontinuing or altering a PD medication regimen (and subsequent reduced mobility) during a prolonged hospitalization. The utility of PT and maximizing mobilization in hospitalized patients with PD could also be systematically evaluated.

As we have seen in all neurodegenerative conditions, acute emotional or physical stress (hospitalization, infection, and surgery) can lead to an exacerbation of symptoms. The same should be expected in patients with PD. This decrement may not improve back to the patient’s pre-episode baseline function. It is prudent to continue providing dopaminergic therapy and maximizing mobility throughout such stressful times as to not add insult to injury. If the patient is not NPO and not drastically hypotensive or psychotic, then no changes should be made to the patient’s outpatient PD medication regimen. If NPO status is required, then consider alternative routes of administration. When in doubt, consult your local friendly neurologist, or even better, if available, a movement disorder specialist.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

This paper was not funded.