A 67-year-old female with moderately advanced Parkinson’s disease (PD) had a mechanical fall in her home, which resulted in a humeral fracture. The fall occurred in the morning before she was able to take her medications and was related to her difficulty in initiating movements.
On her current regimen, her PD symptoms are controlled. She is able to perform daily living activities independently and ambulates without assistance. She also performs more complex tasks (e.g., cooking and managing her finances). She has not exhibited any symptoms consistent with dementia. She occasionally experiences dyspnea on exertion and dysphagia, but she has not been evaluated for these complaints. She takes carbidopa/levodopa (CD/LD) 25 mg/100 mg four times a day, amantadine 100 mg twice daily, and ropinirole 3 mg three times a day.
She is scheduled for open reduction internal fixation of her fracture; the orthopedic surgeon has requested a perioperative risk assessment and recommendations concerning her medications. How should PD be managed perioperatively?
Advances in surgical and anesthetic techniques, in combination with an aging population, have contributed to an increasing number of geriatric patients undergoing surgery. As many as 50% of Americans older than 65 will undergo a surgical procedure; hospitalists will comanage many of these patients in the perioperative period.1
Although cardiopulmonary disorders receive a great deal of attention with regard to perioperative risk assessment, other comorbid conditions also contribute to perioperative risk—namely, disorders specific to the elderly population. Parkinson’s disease is one such condition that deserves attention.
PD is a progressive, neurodegenerative condition associated with loss of dopaminergic neurons and the presence of Lewy bodies within the substantia nigra and other areas of the brain and peripheral autonomic nervous system.2 Cardinal clinical features include rigidity, bradykinesia, and resting tremor. A supportive feature is a consistent response to levodopa. Postural instability, cognitive impairment, and autonomic dysfunction usually occur later in the disease.3,4
As the population ages, Parkinson’s disease is becoming more prevalent, affecting approximately 1% of individuals older than 60.5 These patients pose a specific challenge to the hospitalist, not only because the multiorgan system manifestations of PD can raise surgical risk, but also due to the direct effects of dopaminergic medications used to treat PD, lack of a parenteral route for these medications in NPO patients, and the risks associated with abrupt withdrawal of these medications.
Although surgical risk in PD patients has received intermittent attention in surgical, anesthesia, and neurology literature, there is no broad consensus statement or treatment guideline for the perioperative approach.
A retrospective cohort of 51 PD patients undergoing various types of surgery revealed that PD patients have a longer hospital stay than matched cohorts.6 Pepper et al studied a cohort of 234 PD patients in the Veterans Administration population who were undergoing a variety of surgeries.7 They found that patients with PD had a longer acute hospital stay and had higher in-hospital mortality.7 The multisystem manifestations of PD might account for this global increase in perioperative risk.
The following are reviews of organ-system manifestations of PD and their relevance to the perioperative period.
Motor: The motor symptoms of PD place patients at increased risk for falls and might impair their ability to participate in rehabilitation. Mueller et al demonstrated that there was a significantly increased risk of postoperative falls and a higher need for inpatient rehabilitation due to motor difficulties in the PD cohort.6
Pulmonary: PD patients have increased risk of abnormal pulmonary function secondary to rigidity and akinesia. Increased airway resistance and decreased lung elastic recoil lead to obstructive lung disease.8,9 Rigidity of voluntary chest wall and upper airway muscles leads to a restrictive lung disease pattern.8,10 Furthermore, respiratory dyskinesia is a common side effect of levodopa, which can result in restrictive and dyskinetic ventilation.11 As a consequence of disordered respiratory mechanics (especially in combination with disordered swallow mechanics), PD patients are at increased risk of lower respiratory infections. In fact, pneumonia remains the leading cause of mortality among PD patients.11
Not surprisingly, several cohorts have suggested that PD patients undergoing surgical procedures are at higher risk for atelectasis, pneumonia, and postoperative respiratory failure.7,12 Postoperative VTE rates are not statistically different between PD patients and matched cohorts.
Gastrointestinal: Abnor-malities in muscles of the mouth, pharynx, and esophagus account for the dysphagia commonly noted in PD.13 Barium swallow tests are abnormal in 80% or more of PD patients.14 Dysphagia can lead to aspiration, as well as inadequate oral intake, resulting in pneumonia and malnutrition, respectively.15 Dysfunction of the myenteric plexus (evidenced by Lewy Body deposition) accounts for gastrointestinal dysmotility manifested as gastroparesis, ileus, and slow colonic transit, which results in constipation.16
PD patients in the postoperative period are at risk for swallowing difficulties, which increases the risk of aspiration and might delay initiation of oral medications. Gastroparesis threatens appropriate delivery of oral medications for adequate absorption. In addition, postoperative ileus and constipation can pose challenges.
Cardiovascular: Such cardiac sympathetic abnormalities as orthostatic hypotension, postprandial or exercise-induced hypotension, impaired heart rate variability, and dysrhythmias are common in PD.17 Pepper et al found a trend toward increased risk of hypotension and acute myocardial infarction (MI) in PD patients undergoing surgery.7
Genitourinary: Urinary complaints (e.g., nocturia, frequency, urgency, and urge incontinence) are common in PD patients.18 These clinical complaints correspond to involuntary detrusor contractions (detrusor hyperreflexia).19 Pepper et al found an increased risk of postoperative urinary tract infection in PD patients.7
Cognitive: A recognized feature of advanced PD is cognitive impairment. Studies estimate the prevalence of dementia in cohorts of PD patients is from 28% to 44%. PD with dementia has been associated with shortened survival, impaired quality of life, and increased caregiver distress.20 Pepper et al noted a trend toward increased incidence of postoperative delirium in their cohort of 234 PD patients undergoing surgery.7
Medication: Management of anti-Parkinsonian medications in the perioperative period poses unique challenges. These medications’ prodopaminergic effects can lead to hemodynamic compromise and are potentially arrhythmogenic. At the same time, abrupt withdrawal of these medications can lead to a potentially lethal condition called Parkinsonism-hyperpyrexia syndrome (PHS), which is clinically similar to neuroleptic malignant syndrome.21 PHS is characterized by very high fever, extreme muscle rigidity, autonomic instability, altered consciousness, and multiple severe systemic complications (e.g., acute renal failure, disseminated intravascular coagulation, autonomic failure, aspiration pneumonia, and infections). PHS occurs in up to 4% of PD patients; mortality is reported to be from 4% for treated to 20% for untreated episodes.22-24
As many as 30% of patients who survive a PHS episode have worsening of their PD symptoms and never return to their pre-PHS baseline. PHS prevention in hospitalized patients by uninterrupted administration of PD medications should be the goal. Early recognition and aggressive treatment is key to successful recovery.
Furthermore, even brief interruption of medications can lead to decompensation of Parkinsonian symptoms, which not only delays recovery from surgery, but also increases the risk for multisystem complications as discussed above.25 Traditional anti-Parkinsonian medications can only be delivered orally, presenting significant challenges for NPO patients, especially those undergoing enteric surgery requiring bowel rest.
Case reports describe various approaches to medication management in the perioperative period, but no single consensus statement (or treatment guideline) exists. The most common clinical scenarios are:
- Patient undergoes short surgery and is able to take oral medication immediately after the procedure (e.g., orthopedic, eye);
- Patient undergoes more lengthy surgery and will be able to take enteric medications perioperatively (e.g., longer orthopedic surgeries, genitourinary); and
- Patient undergoes lengthy procedure in which they will be required to adhere to bowel rest (e.g., bowel resection).
Depending on the category, the approach to medication management might differ.
Furuya et al describe a 70-year-old male with PD who had previously experienced perioperative complications associated with his medication management, including postoperative rigidity, dysphagia, and difficulty maintaining respiratory secretions.26 These symptoms were reversed with intravenous levodopa. However, the patient experienced hypotension and premature ventricular contractions as side effects of this therapy. This patient was scheduled to undergo hepatic lobectomy. Given his previous complications, Furuya et al provided enteral administration of CD/LD via nasogastric tube every two hours during the surgery, with placement of a duodenostomy for postoperative administration of CD/LD. The patient maintained hemodynamic stability throughout the perioperative period and emerged from anesthesia smoothly with no muscle rigidity or postoperative complications.26
Fujii et al described three cases of PD patients undergoing gastrointestinal surgery. They suggested that the dose of medication required to control symptoms should be minimized before surgery to avoid withdrawal symptoms. They also described the use of intravenous levodopa immediately, postoperatively, while the patient was unable to tolerate enteric medications, and suggested the use of prokinetics to prevent ileus and maximize drug absorption.27
Gálvez-Jiménez et al discuss the limitations of intravenous levodopa, including hemodynamic compromise, need for escalating doses, frequent adjustments to maintain effect, and large amount of fluids required. They propose the use of subcutaneous apomorphine, which is a potent D1/D2 dopamine agonist in conjunction with rectal domeperidone, a D2 antagonist with poor blood-brain-barrier penetration, to counteract the peripheral dopaminergic side effects. The main limitation to this approach is that domeperidone is not available in the U.S.28
Intravenous antihistamines and anticholinergics are readily available. However, they show limited efficacy in halting Parkinsonian symptoms and carry multiple side effects (e.g., confusion, delay in gastrointestinal recovery, and urinary retention).28
Various anesthesiologists agree with administering anti-PD medications immediately, preoperatively, and restarting medications as soon as possible postoperatively. However, they do not provide uniform treatment guidelines regarding specific medication management.29,30
Deep-brain-stimulation (DBS) management: DBS is an effective treatment for advanced PD. There are more than 60,000 patients around the world who have DBS for various conditions, mostly for PD. Therefore, it is increasingly likely that hospitalists will encounter hospitalized patients with advanced PD who are treated both pharmacologically and with DBS. It is important to recognize that stimulation, just like PD medications, cannot be stopped suddenly. If there is any concern of the DBS system malfunctioning (i.e., fracture of the hardware during a fall), the neurologist or neurosurgeon managing the DBS should be contacted immediately. Certain diagnostic tests (MRI) and treatment procedures (diathermy) are contraindicated, and if done inappropriately, can result in permanent brain damage.31,32,33
During surgeries requiring blood-vessel cauterization, DBS should be temporarily turned off. This can be done with the patient’s handheld device or, preferably, by a trained technician usually available through 24/7 technical support services provided by the manufacturer.
Summary of recommendations: There are no clear treatment guidelines regarding the optimal perioperative management of PD patients. The following measures are based on available data and are extensions of routine perioperative management; however, there is no evidence to demonstrate their efficacy in decreasing complication rates among patients with PD:
- A thorough preoperative history and physical examination should include Parkinsonian signs and symptoms, precise medication regimen with doses and timing of intake, effects of medication withdrawal or missed doses, type of surgery planned, and comorbid conditions;
- Depending on symptoms mentioned in the history, consider further testing for dysphagia (preoperative swallow evaluation) and dyspnea (preoperative pulmonary function tests);
- The major goal of medication management in the perioperative period is to continue administration of dopamine replacement therapy as close to the outpatient regimen as possible.
- Titrate down dose of anti-Parkinsonian medications to lowest possible dose prior to surgery if prolonged NPO status is anticipated;
- Ensure medications are administered immediately prior to surgery;
- For short, nonenteric procedures, resume outpatient medication doses and timing of administration as soon as possible postoperatively. For longer, nonenteric surgeries, consider placement of nasogastric tube for medication delivery during procedure and immediately postoperatively;
- If the major limitation of oral medication intake is dysphagia, the use of orally disintegrated formulation CD/LD (parcopa) is helpful;
- For longer enteric surgeries in which patient must be on bowel rest, recommend consultation with neurologist specialized in movement disorders to guide use of intravenous or subcutaneous agents. Transdermal delivery systems of the dopamine agonist rotigotine are in the process of being approved in the U.S. market and might be helpful for this purpose;
- Initiation of tube feeding, when co-administered with levodopa, might result in sudden changes in medication absorption and potential worsening of PD symptoms; feeding should be started slowly and preferably at night when the body’s dopamine requirements are lower;
- Consider use of promotility agents;
- If apomorphine or intravenous LD are not available, consider trial of intravenous anticholinergics or antihistamines, carefully observing for potential cognitive and behavioral side effects;
- Avoid such dopamine antagonists as droperidol, haloperidol, risperidone, metaclopramide, prochlorperazine, or promethazine, as these medications can worsen Parkinsonian symptoms; and
- If patient was on MAO-B inhibitors (selegiline, rasagiline) before surgery, be aware of multiple potential interactions with various medications that are commonly used in perioperative period, including anesthesia agents and certain analgesics, specifically meperidine. These interactions include serotonin syndrome, and can be life-threatening.34
- Psychiatric considerations: delirium precautions;
- Motor considerations: early PT/OT, early referral to inpatient rehabilitation; fall precautions;
- Pulmonary considerations: institute aggressive incentive spirometry, postural drainage, management of respiratory secretions, and breathing exercises; VTE prophylaxis;
- Gastrointestinal considerations: aspiration precautions and prompt speech therapy to evaluate for aspiration and to teach appropriate swallow techniques (chin tuck); institute aggressive bowel regimen; maximize fluids, electrolytes, and avoid narcotics to prevent precipitating or exacerbating ileus;
- Cardiovascular considerations: monitor orthostatic vital signs; fall precautions to avoid syncopal falls; and
- Genitourinary considerations: early urinary catheter removal; vigilance in monitoring for urinary tract infection.
Back to the Case
The patient underwent repair of her fracture, was extubated, and recovered from general anesthesia without incident. She was evaluated in the postanesthesia care unit, at which time she had a slight tremor and mild rigidity. She was immediately given a dose of her CD/LD, and her evening doses of amantadine and ropinirole were resumed. The patient had no significant flare of her Parkinsonian symptoms and did not exhibit any evidence of PHS.
A postoperative consultation was placed for speech therapy, physical therapy, and occupational therapy. She was given low-molecular-weight heparin for VTE prophylaxis and asked to use incentive spirometry. On postoperative day one, she complained of urinary frequency. A urinalysis was consistent with possible infection. She was discharged home on her previous medication regimen, in addition to antibiotics for cystitis.
If the procedure had not been emergent, the patient might have benefited from a preoperative swallow evaluation, given her dysphagia. Consultation with a speech therapist would have ensured that the patient was educated regarding aspiration precautions. Although this patient did not have difficulty with extubation or experience postoperative respiratory failure, abnormal preoperative pulmonary function tests might have prompted the anesthesiologists to consider alternative low-risk techniques (e.g., a local nerve block).
Perioperative management of patients with Parkinson’s disease requires knowledge of the multisystem disease characteristics that raise perioperative risk and the effects of the medications used to treat PD. To date, no clear treatment guidelines exist for the optimal perioperative management of PD patients.
However, vigilance in detecting possible complications and instituting attentive perioperative care can aid a hospitalist consultant in improving overall care for these patients. TH
Dr. Patel is a medical resident at the University of Colorado Denver. Dr. Stickrath is a hospitalist at the Denver VA Medical Center and instructor of medicine at the University of Colorado Denver. Dr. Anderson is a hospitalist at the Denver VA Medical Center and assistant professor of medicine at the University of Colorado Denver. Dr. Klepitskaya is a neurologist and assistant professor of neurology at the University of Colorado Denver.
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