PATHOPHYSIOLOGY AND ANESTHETIC MANAGEMENT

OF PARKINSON DISEASEPhilip Hess RN

University of Pennsylvania

Objectives

Review the pathophysiology of Parkinson Disease (PD)

Discuss the perioperative management of patients who suffer from PD

Highlight the anesthetists role in Deep Brain Stimulation surgery

Upper Motor Neurons

Movement is initiated in the motor cortex Planned and sensory guided movement Descend in tracts through the

diencephalon and brainstem Separate to innervate the extrapyramidal

and cranial nerve nuclei Descend through the medulla to the

spinal cord via the lateral corticospinal tract (CST)

Pyramidal Tract

Motor fibers which have not branched off to the cranial nerve nuclei or the extrapyramidal tract descend through the pyramidal tract and corticospinal tract (and you know the rest)

Extrapyramidal Tract

Controls involuntary movement and muscle tone

Spatial feeling, muscles of expression

Includes basal ganglia, subthalamus of diencephalon, and cerebellum (among others)

Upper Motor Neurons Summed Up

Upper motor neurons are the final common pathway between cortical and subcortical structures

Basal ganglia Planning, initiating, sequencing, and

modulation of voluntary movement Cerebellum

balance, posture, coordination

So Why Do We Care?

Disruption of signaling pathways gives rise to the debilitating symptoms seen in PD and other diseases of the nervous system

Basal ganglia structures of interest to us Substantia nigra

Dopamine synthesized here Globus pallidus

Inhibitory action that balances the excitatory action of the cerebellum

Subthalamic nucleus Modulates muscle movement (smooths,

coordinates)

Parkinson Disease

Clinical syndrome that manifests as motor dysfunction and psychiatric disturbance (eventually) Rigidity Bradykinesia Tremor Postural instability Involuntary muscle movement

Causes of PD

Prevalence is 1-2 : 1000 Mostly idiopathic Can result from exposure to toxins

(manganese, pesticides, carbon disulfide) Drugs (methamphetamine, reglan,

compazine, 1st generation anti-psychotics, ect)

Repeated head trauma (Muhammed Ali) Feature of other diseases Genetic

Pathophysiology

Neurotransmission within basal ganglia is a balance between the excitatory effects of acetylcholine and the inhibitory effects of dopamine

Dopamine is synthesized by neurons of the substantia nigra

In PD, degeneration of nigral neurons leads to a loss of dopaminergic inhibition

Thus, a relative excess of cholinergic activity ensues

Manifestation

Jerky, uncoordinated movement Early: loss of arm swing when walking,

absence of head rotation when turning the body

Eventually progresses to pill rolling tremor, diaphragmatic spasm, oculogyric crisis

Mask like facies, dysarthria Dementia (often), aspiration, death

Treatment

Designed to increase dopamine concentrations in the basal ganglia or decrease the neuronal effects of acetylcholine

Sinemet (carbidopa/levodopa) most prescribed Levodopa: dopamine precursor

Crosses the blood brain barrier to be converted to dopamine

Carbidopa: decarboxylase inhibitor Does not cross the blood brain barrier Prevents the conversion of levodopa to dopamine in

the periphery; thus, leaves more in circulation to cross BBB

Side Effects of Levodopa

Dyskinesias Psychiatric disturbances Increased myocardial contraction and

heart rate Orthostatic hypotension Nausea, vomiting

Other Medications

MAOIs inhibit the catabolism of dopamine Concerns with MAOIs?

Selegiline is an MAOI that is not associated with adverse side effects

Some others: Bromocriptine mesylate and pergolide mesylate

Dopamine receptor agonists Benztropine mesylate

Anticholinergic Amantadine

Antiviral – may be useful at initial diagnosis

Deep Brain Stimulation

Surgical electrodes inserted into basal ganglia Ventral intermediate nucleus (VIM)

Cerebellar afferent receiving zone of thalamus Reduces tremor

Subthalamic nucleus (STN) Most common target for DBS

Reduces tremor but reduces bradykinesia, rigidity, and improves gait

Internal segment of globus pallidus (GPi) 2nd most common target for DBS (result similar to

STN) Considered the main output for limb movements

Surgical Procedure

The case begins with the patient under MAC anesthesia Stereotactic frame is placed (held in place with

pins or screws) Patient is taken to MRI for brain mapping Patient is returned to OR

The case continues with the patient under deep MAC sedation (I know, a contradiction in terms..) Patient’s head is placed in Mayfield pins and

image guided navigation system is attached to stereotactic frame

Procedure Cont’d

The scalp is localized and 14 mm burr holes are drilled in the skull (bilateral)

A probe is passed into the deep brain tissue No pain here as the brain tissue has no pain

efferents MAC is discontinued

The patient is allowed to wake up in order to communicate with the surgical team as the electrodes are placed.

Computer guided placement of the electrodes ensues

Procedure Cont’d

The patient performs tasks and answers questions during electrode placement

Tremors are elicited and proper electrode placement is confirmed when they are ablated.

Once the permanent electrode placement takes place, the stereotactic frame is removed and general anesthesia is induced.

Electrode leads are tunneled and the stimulus generator is implanted in the chest.

Anesthetic Considerations

To manage the anesthetic , you must understand the treatment of PD (Stoelting, 2012 )

Elimination 1/2t of Sinemet Requires frequent dosing, so give 20 minutes before

surgery and redose via OGT or NGT Hypertension and dysrhythmias

Treat with butyrophenones (droperidol, haloperidol) Antagonize the effects of dopamine in basal ganglia

Acute dystonia with Alfentanil Ketamine controversial due to SNS response

Has been used successfully

Management Cont’d

Patients told to withhold meds prior to DBS Difficult IV placement due to tremor At electrode placement, GABA agonists

(propofol, benzos) may interfere with electrode recordings

opioids and dexmedetomidine are ok Avoid excessive sedation to prevent

airway compromise Remember.. The head frame is in place..the

bed is turned 90 degrees away.. Uh oh.. What if your patient goes apneic?

More Trouble…

Risk of air embolism HOB is usually at 15 degrees

Risk of hypertension with pinning and airway instrumentation

Risk of seizures Stoelting ( 2012 ) says seizures normally

abate; but if they don’t, push propofol or benzos despite delaying the case

Change in LOC Rarely see with electrode placement but may be

due to hemorrhage

Even More Trouble

Upper airway dysfunction is common in PD PD causes chest wall rigidity Often see chronic obstructive disease

Medications used to treat PD cause increased cardiac irritability Blunt autonomic regulatory response

Aspiration prophylaxis H2 blocker or sodium citrate is ok

Never give Reglan Antidopaminergic and will precipitate EPS

Induction Agents

Succinylcholine is ok but RSI needed only in advanced disease

Avoid Ketamine Sympathomimetic responses may exacerbate

PD symptoms All inhalationals ok except halothane

Sensitizes the myocardium to the effects of catecholamines (instability with PD meds)

Treat hypotension with phenylephrine or epinephrine (direct acting) Why not ephedrine?

Emergence

Opioids ok for pain control but.. May cause chest wall rigidity and..

Alfentanil can cause dystonias (so don’t go there)

NSAIDS are ok, as are local anesthetics Use glycopyrrolate for reversal

Doesn’t cross BBB Anticholinergic effect may prevent dystonia

Extubate normally Watch for hypokinetic chest wall activity PD interferes with all muscles of respiration

Post Op

Give anti- Parkinson meds as soon as possible

Neurological assessment Scopolamine may confound

Increased PONV Ondansetron is good Reglan is bad

Medications to avoid Metroclopramide, droperidol, haldoperidol,

promethazine, compazine, ketamine, alfentanil, meperidine, and halothane

Questions?

References

Doyle, S.R. & Kremer, M.J. (2003). Parkinson disease: Update for nurse anesthetists. AANA Journal. 71, (3).

McPhee, S.J. & Hammer, G.D. (2010). Pathophysiology of disease: An introduction to clinical medicine. Chicago, IL. McGraw-Hill

Macksey, L.F. (2012). Surgical procedures and anesthetic implications. Sudbury, MA. Jones and Bartlett.

Perlmutter, J.S. (2006). Deep brain stimulation. Annual Review of Neuroscience. 29, 229-57.