Deep Brain Stimulation for Parkinson’s Disease

Authors: Kiran Jangra (MD, DM)*, Charu Mahajan (MD, DM)**, Hemanshu Prabhakar (MD, PhD)**
*Department of Anesthesia, PGIMER, Chandigarh, India
**Department of Neuroanaesthesiology & Critical Care, AIIMS, New Delhi, India

CASE: A 53 year-old man presents with a history of slowness of activities and asymmetrical tremors for the past 13 years and difficulty in walking with frequent falls. He takes Syndopa (carbidopa + levodopa) but for the last 6 years he suffers with ‘dance like movements’. The disease has now gradually progressed and for the last 3 years, his dyskinesias have also increased. He is now scheduled for surgical implantation of a deep brain stimulator.

Past Medical History: Former smoker, no co-morbidities

Medications: On Syndopa for the past 13 years, and has had a good response He suffers from dopa-induced dyskinesiasfor the past 6 years. Drug modifications were done and amantadine was added. For the last 3 years, his dyskinesias have progressively increased.

Imaging: DBS protocol done

Past Surgical/Anesthetic History: None

Physical Examination: 72 kg, conscious, oriented, no pallor/icterus/cyanosis/clubbing

Neurological Examination: Mini Mental State Examination (MMSE): 30/30, All cranial nerves within normal limits, strength 5/5 bilaterally, tone: rigidity left>right, Deep tendon reflexes (DTR) 2+ bilaterally, plantar bilaterally flexor, sensory system normal, cerebellar signs absent. Unified Parkinson’s Disease rating Scale (UPDRS) motor score 19/108 on Syndopa, 50/108 off syndopa. Total UPDRS on Syndopa 32/176.

Vitals: Pulse 76/min, BP 125/70 mm Hg, RR 19, T 37°C

Labs: Hemoglobin 15 g/dl, Sodium 135 mEq/L, Potassium 4.2mEq/L, urea/creatinine: 25/0.7, PT: 13.5 sec, INR 1.2, ECG – normal, CXR- B/L hilar calcification

KEY QUESTIONS

1. What are the indications for DBS surgery?
2. What is the physiopathology of PD?
3. Are there any disease-specific concerns?
4. What are the pharmacological agents used to treat PD?

Case Continued: The patient is scheduled for an elective DBS procedure. As the patient’s anesthesiologist, you must plan your anesthetic technique and decide if the patient is an appropriate candidate for this procedure.

5. What are the possible anesthetic techniques for the procedure? (general steps, awake and battery placement)
6. Will this protocol hold true for all patients? (indications for electrode placement under GA)
7. What are the contraindications for DBS surgery?

Case Continued: This patient is receiving anti-parkinsonism medications for symptomatic management. He will also be receiving various medications including general anesthetics in the operating room (OR). You must keep in mind the possible drug interactions before administering any medications to this patient.

8. Describe the surgical steps for the placement of electrodes.
9. What interactions do you expect between anti-parkinson medication and other drugs?
10. How will you prepare the patient for the procedure?
11. What is the principle of stereotaxy (frame/frameless)?
12. What special preparation will be required for the intraoperative care of this patient?
13. What monitors would you apply intraoperatively for the procedure?
14. What are the effects of anesthetic drugs on microelectrode recording and macrostimulation testing?

Case Continued: You plan to conduct the procedure in an ‘Asleep – Awake – Asleep’ technique. During the ‘Awake’ part of the procedure, the patient suddenly becomes drowsy and his airway is becoming compromised.

15. If the patient suddenly becomes drowsy and the airway becomes compromised, how will you proceed in your management?
16. What other intraoperative difficulties do you anticipate, and how will you manage them?
17. Describe the anesthetic management for battery placement.

Case Continued: The DBS procedure is now complete and the battery has been placed. The patient has been transported to the ICU for further management.

18. What are the postoperative concerns in this patient?
19. What are the anesthetic concerns a patient with an implanted device presenting for non-neurological surgery?

DISCUSSION

Indications for DBS surgery

• DBS was initially approved by the Food and Drug Administration (FDA) for Parkinson’s disease, but has since been expanded to various other movement disorders such as essential tremors and dystonia.
• There are various other conditions where DBS is being studied but not currently approved by FDA, including Alzheimer disease, spasmodic dysphonia, orthostatic tremor, Meige syndrome, cluster headache, trigeminal neuropathy, trigeminal neuralgia, chronic pain, Tourette’s syndrome, epilepsy, restless legs syndrome obesity/addictions, disorder of consciousness and certain psychiatric illnesses such as aggressive behavior, depression, obsessive-compulsive disorder [1].

Physiopathology of PD

• The basal ganglia include the striatum, globus pallidus, subthalamic nucleus (STN), and the pigmented component of the substantia nigra known as the pars compacta [2]. These brain areas are known to be involved in the control of movements.
• The clinically-important motor circuits originate in the sensorimotor cortex and terminate in the supplementary motor area. There are two outflow tracts from the basal ganglion. One is the direct pathway via the internal part of the pallidum and the other is the indirect pathway via the external globus pallidus, subthalamic nucleus and the internal globus pallidus (GPi).
• The nigrostriatal pathway (from the substantia nigra pars compacta to the striatum) makes the facilitatory synapses via dopaminergic type 1 (D1) receptors upon direct pathway neurons and inhibitory synapses via D2 receptors upon indirect pathway neurons [3].
• Cholinergic internuncial neurons are excitatory and dopamine is inhibitory to projection neurons.
• In PD there is a loss of dopaminergic neurons in the substantia nigra of the basal ganglia. This produces an imbalance in the dopamine:acetylcholine ratio and results in the facilitation of the indirect pathway. This is associated with an increased activity of inhibitory nuclei in the basal ganglia leading to excessive inhibition, and a shutdown of the thalamic and brainstem nuclei [3].
• Thalamic inhibition leads to the suppression of the cortical motor system, which results in akinesia, rigidity and tremor, and inhibition of brainstem locomotor areas that may contribute to abnormalities of posture and gait.

Disease-Specific Concerns in PD

• Neuropsychiatric symptoms of PD include cognitive dysfunction, dementia, behavior and mood changes (depression), delusions, and hallucinations. These symptoms affect some PD patients’ ability to provide an adequate medical history and cooperate during the procedure, and may also affect their emergence after anesthesia.
• Respiratory complications are the leading cause of death in patients with PD [4]. These include both restrictive and obstructive pulmonary disease. An obstructive ventilatory pattern is observed in one-third of patients with PD and appears as a saw tooth appearance on flow volume loops [5]. The chest wall rigidity contributes to the restrictive pattern and predisposes these patients to a high risk of developing pneumonitis.
• Upper airway dysfunction might occur due to uncoordinated involuntary movements of the pharyngeal, glottic and supraglottic structures that results in the retention of secretions, intermittent upper airway obstruction, and aspiration. These patients are also at risk of post-extubation laryngospasm and respiratory failure [6,7]. Sleep apnea has also been described rarely in post-encephalitic Parkinson’s disease [8]. Dysphagia results in poor nutrition and low albumin levels that alter the pharmacokinetics and pharmacodynamics of anesthetic agents.
• Cardiovascular manifestations in patients with PD include cardiac arrhythmias, dependent edema, and orthostatic hypotension [9]. Direct-acting dopamine agonists (bromocriptine and lisuride) and antidepressants (amitriptyline) also aggravate the orthostatic hypotension.
• PD and its drug treatments might lead to autonomic nervous system dysfunction. These patients have difficulty with salivation, micturition and gastrointestinal function. There is a loss of cardiovascular system regulation (exaggerated postural hypotension) and temperature regulation. Seborrhea might also reflect autonomic dysfunction. Patients with autonomic dysfunction are not able to compensate for hypovolemia and vasodilatation, and reflex tachycardia is usually not seen.
• Gastrointestinal manifestations include sialorrhea, dysphagia, abnormalities of esophageal function and constipation. These patients are predisposed to gastric stasis and gastrointestinal reflux and increases the risk of aspiration pneumonitis [10].

Pharmacological Agents Used in the Treatment of PD [11]

• The goals of drug therapy in PD are directed to (a) increase the availability of dopamine or the receptor’s response to dopamine, (b) stimulate the receptor directly with bromocriptine (c) dopaminergic tissue, (d) and decrease cholinergic activity [12].
• Systemic administration of dopamine is not effective in the treatment of PD, as it does not cross the blood brain barrier. A precursor of dopamine, Levodopa, has revolutionized the treatment of PD. It is routinely administered along with a peripheral decarboxylase inhibitor to prevent its peripheral conversion to dopamine. In this way, the side effects such as nausea and vomiting, which are due to the activation of dopamine receptors in the area postrema, can be prevented. Peripheral decarboxylase inhibitors include carbidopa (200–1000 mg levodopa, 2–4 times/day), methyldopa and alpha-Difluoromethyl-DOPA.
• The levodopa therapy is associated with acute dopaminergic side effects such as nausea, vomiting, and orthostatic hypotension. There are fluctuations in motor response and involuntary movements known as dyskinesias. The relatively short half-life (60–90 minutes) is responsible for the “off phenomenon”. High doses of levodopa can lead to purposeless, stereotyped behaviors such as the meaningless assembly and disassembly or collection and sorting of objects known as “punding”.
• Dopamine agonists are another category of drugs that act directly on dopamine receptors. Initial dopamine agonists were ergot derivatives (e.g., bromocriptine, pergolide, cabergoline) and were associated with ergot-related side effects, including cardiac valvular damage. They have largely been replaced by a second generation of non-ergot dopamine agonists [e.g., pramipexole (0.25–1.0 mg tid), ropinirole (6–24 mg/d), rotigotine (6–24 mg/d)]. These are long-acting and while dyskinesia symptoms are improved, hallucinations and cognitive impairments are more common than with levodopa. Acute side effects of dopamine agonists include nausea, vomiting, and orthostatic hypotension. Sedation and episodes of sudden falling asleep while driving a motor vehicle have also been reported.
• Monoamine oxidase type B (MAO-B) inhibitors block the central dopamine metabolism and increase its availability at synaptic sites. Selegiline and rasagiline are relatively selective inhibitors of the MAO-B enzyme. These drugs reduced the “off” time when used as an adjunct to levodopa in patients with motor fluctuations. MAO-B inhibitors are generally safe and well tolerated. MAO-A isoform inhibition might precipitate potentially fatal hypertensive reactions by preventing the metabolism of tyramine in the gut. This is known as the a “cheese effect” as it is precipitated by tyramine-rich products such as some cheeses, aged meats, and red wine. Concomitant use of SSRI antidepressants poses theoretical risks of serotonin reaction.
• Inhibitors of Catechol-O-methyltransferase (COMT) increase the elimination half-life of levodopa and enhance its availability in the brain. Combining levodopa with a COMT inhibitor reduces “off” time and prolongs “on” time. Two COMT inhibitors have been approved by FDA: tolcapone and entacapone.
• Side effects of COMT inhibitors are primarily dopaminergic (nausea, vomiting, increased dyskinesia), severe diarrhea and fatal hepatic toxicity. This problem has not been encountered with entacapone.
• Central-acting anticholinergic drugs such as trihexyphenidyl and benztropine have also been used to treat PD. These agents are more effective on tremor than other symptoms. Their use is limited by a variety of side effects including urinary dysfunction, glaucoma, and particularly cognitive impairment.

Anesthetic Techniques for DBS Placement

• The goals of anesthetic management for DBS insertion are to provide adequate operating conditions, patient comfort, to facilitate intraoperative monitoring including neuro-monitoring for target localization, and to diagnose and treat any complications occurring during surgery.
• The placement of DBS electrodes involves 2 stages. The first stage is the insertion of the electrodes into the target area of the brain, and the second stage is the internalization of the leads and implantation of the programmable pulse generator (IPG).
• As the target nuclei are deep and small in size, a variety of methods are used to increase the accuracy of targeting. These include the use of frame-based imaging, electrophysiologic guidance with microelectrode recording (MER), and macrostimulation testing of an awake patient.
• Both stages may be completed on the same day or the internalization of the electrodes and generator might be planned on a different day, usually 3 days to 2 weeks after the first stage. The reason for delaying of the internalization is the “microlesion” effect due to edema surrounding the freshly implanted electrode. This edema might lead to the improvement in patient’s symptoms without any stimulation, and thus impairs the ability to check for stimulation-induced benefits [13].
• First, a rigid head-frame is applied to the patient’s skull and magnetic resonance imaging (MRI) or computed tomography (CT) is done to visualize the brain structures and to establish references to external coordinates for accurate insertion of the electrode into the target areas.
• Various head frames are available such as Cosman-Roberts-Wells frame and Leksell G [14]. Access to patient’s airway is restricted by both of these frames to varying degrees. There are a few reports of the use of frameless navigation systems also for a DBS electrode insertion [15].
• The stereotactic frame is generally applied after infiltrating with local anesthetic agent at the pin insertion sites. A combination of supraorbital and greater occipital nerve blocks may provide superior analgesia [16]. Some patients (uncooperative or pediatric) may require sedation for frame placement and/or for MRI. The anesthesiologist must be prepared with adequate equipment and support to care for the patient in this potentially “remote” site if conscious sedation or general anesthesia is needed. In an MRI room, all safety issues for anesthesia in an MRI suite must be addressed.
• After imaging, the patient is transported to the operating room where he or she is placed in a supine or semi-sitting position with the stereotactic frame fixed to the operating table.
• Intraoperative brain mapping and macrostimulation for target localization are more reliable if the patient is awake, and is therefore the preferred technique.
• After infiltrating the electrode insertion site on the scalp, a burr hole is made in the cranium. The target areas for stimulation (STN, GPi and Vim) are localized either by obtaining MERs or by macrostimulation.
• To obtain MERs, the electrode is usually inserted 10 to 15mm above the target site and is advanced 0.5 to 1 mm towards the target nuclei and simultaneously the spontaneous discharges of the neurons are recorded. There are specific spontaneous firing rates among the basal ganglia nuclei and the variations observed while advancing the electrode help to identify the target site.
• Macrostimulation is the clinical testing of the patient’s movements and is used to verify that the stimulation of the electrode will improve the symptoms and will not cause any side effects. It is important to psychologically prepare the patient for this period of the procedure as they must be awake and interacting with the neurologist.
• For optimum patient comfort and cooperation; careful positioning, adequate pain control, avoidance of excessive fluid administration, and temperature control are essential intraoperatively. The head and neck should be positioned such that the airway is patent and it is possible to secure the airway in an emergency. In the sitting position the legs should be flexed and compression stockings are used to ensure adequate venous return and to maintain hemodynamic stability. Special treatment modalities have been used to aid in positioning, such as physiotherapy, small doses of levodopa, and intrathecal hydromorphone [17, 18].
• In patients with obstructive sleep apnea, continuous positive airway pressure might be required intraoperatively. The facemask should be fitted prior the head frame application.
• Supplemental oxygen is administered via nasal prongs or face mask. Intermittent communication must be maintained with the patient throughout the surgery.
• Urinary catheterization is usually not necessary and fluid administration should be monitored carefully to avoid hypervolemia and bladder distension.
• Conscious sedation might be used for DBS insertion during the opening and closure of the wound. Various drugs used for conscious sedation are midazolam, propofol, opioids such as fentanyl or remifentanil, and dexmedetomidine.
• Generally, the use of benzodiazepines is discouraged. Propofol has been widely used, most frequently as a continuous infusion, alone, or in combination with remifentanil. However, the use of target-controlled infusion devices might result in over dosage due to the altered pharmacokinetic behavior of propofol in patients with PD.
• Low-dose infusion rates (0.3– 0.6 mg/kg/h) of dexmedetomidine may be a better choice because its non–GABA-mediated mechanism of action does not interfere with MER [19]. Shorter-acting drugs should be used and stopped before the recordings and testing for better results.
• The position of the electrode may be confirmed by imaging prior to the the electrode being secured, and wound closure. If bilateral DBS insertions are planned, a second incision will be made on the other side, and the procedure is repeated.
• The second stage of DBS is performed by tunneling the electrodes and connecting the extension cable through the scalp and subcutaneously on the side of the neck to an infraclavicular area where it is connected to the pulse generator. This is the last step of surgery and is performed under general anesthesia.

Indication for General Anesthesia for DBS Electrode Placement

• General anesthesia may be needed for uncooperative patients or pediatric patients. Patients with chronic pain syndromes, severe “off-medication” movements, an irrational fear of awake surgery, severe dystonia or choreoathetosis, and young pediatric population have DBS electrodes placed under general anesthesia [20].

Contraindications for DBS Surgery

• Contraindications of DBS implantation include factors that increase either the operative risk or risk of device malfunction, and patients in whom the effectiveness of DBS is limited [21].
• Patients carrying an increased operative risk include coagulopathy or uncontrolled hypertension.
• Device malfunction can be caused by MRI using a full body radiofrequency coil, shortwave, microwave, or therapeutic ultrasound diathermy near the implanted device.
• Patients with expected limited benefits include those with psychiatric illnesses, dementia and cognitive deficits, and patients with unsuccessful test stimulation. These patients are associated with a higher incidence of depression and cognitive deficits after STN-DBS.
• Patients with early PD (duration < 5 years) and extremes of age (> 70 years) are considered relative contraindications for DBS.
• DBS is not indicated for dopamine unresponsive symptoms such as walking, talking and thinking problems.

Surgical Steps for The Placement of Electrodes

• The first step in placing DBS electrodes is the placement of the stereotactic frame. This is followed by the localization of target nuclei by MRI (STN and GPi) or computed tomography (if MRI is contraindicated).
• Upon returning to the operating room the patient’s frame is attached to the geometric arc at the calculated angle to identify the target.
• After preparing the scalp, the skin incision is made and a burr hole is drilled, and finally the dura opening is created.
• The DBS electrodes are inserted into the brain until approximately 10–25mm above the target site and thereafter is advanced in 0.5–1mm increments along the planned trajectory. The advancement of electrodes is guided by MERs and macroelectrode stimulation. Various neuronal brain structures are identified based on their unique patterns of spontaneous firing that are viewed on an oscilloscope. These neuronal firings can also be appreciated aurally, and can be played on an audio monitor. The exact location of the electrode is determined by superimposing the MER over the brain atlas [21].
• The final position of the electrodes is confirmed by intraoperative macrostimulation through the deep brain electrode that produces the clinical improvement and side-effects in a conscious patient.

Interactions Between Anti-Parkinson’s Medications and Other Drugs

• The patients with PD are usually taking a variety of drugs, and are at risk of potential interactions. A few such interactions are discussed here.
• Levodopa can precipitate severe nausea and vomiting that along with old age can cause dehydration and hypovolemia. Adequate volume status assessment and replacement is recommended in these patients [22].
• Certain drugs decrease the efficacy of levodopa including anticholinergic, antispasmodics (dicyclomine and hyoscyamine), anti-histamines, antiepileptic (phenytoin), tricyclic antidepressants (amitriptyline) and metoclopramide. Certain drugs increase the effects of levodopa such as medicines containing acetaminophen, antacids containing aluminum, calcium, and magnesium.
• Hypotension is a common side effect in patients with antiparkinson drugs. Levodopa acts through central mechanism while direct acting dopamine agonists by peripheral vasodilation. Levodopa potentiates the effects of antihypertensives resulting in a precipitous fall in blood pressure. A few older antidepressants, such as tricyclic antidepressants and amitriptyline may lead to orthostatic hypotension.
• Monoamine oxidase inhibitors are contraindicated in patients with levodopa. Sympathomimetics (e.g. ketamine, meperidine) should be used with caution in these patients as these can precipitate an acute rise in blood pressure known as serotonin syndrome. This is characterized by autonomic instability, hypertension, tachycardia, hyperthermia, hyperreflexia, confusion, agitation and diaphoresis. Halothane increases the potential for arrhythmias in patients taking levodopa.
• Opioids may lead to muscle rigidity, especially when using a combination of MAOIs and meperidine [23]. It has been shown that the phenylpiperidine series opioids, pethidine (meperidine), tramadol, methadone and dextromethorphan and propoxyphene, appear to be weakserotonin re-uptake inhibitors and have all been involved in serotonin toxicity reactions with MAOIs, including some fatalities. Morphine, codeine, oxycodone and buprenorphine are known not to be Serotonin re-uptake inhibitors, and do not precipitate serotonin toxicity with MAOIs. [24]
• There is a possible risk of hyperkalemia with succinylcholine use in these patients [25].

Preparing the Patient for Surgery

• The preoperative preparation includes careful patient selection and preoperative optimization of comorbidities.
• A multidisciplinary team approach consisting of anesthetists, neurologists, neurosurgeons, neuropsychologists, and nurses should be used to plan the procedure.
• Contraindications which can increase the risk of procedure or limit the effectiveness of DBS must be addressed.
• Medical conditions which can increase the risk of intracranial hemorrhage including poorly controlled hypertension, coagulopathy, magnetic resonance imaging (MRI) evidence of small vessel ischemic disease, or extensive cerebral atrophy should be evaluated [21]. Blood pressure and coagulation parameters should be optimized before taking these patients for surgery. MRI screening of the brain should be obtained before making a final decision to proceed to DBS implantation.
• If awake procedure is planned, the patient’s ability to cooperate during the procedure should be evaluated. Patients with dementia and hallucinations may be unable to tolerate and cooperate during the awake procedures and complicates the adjustment of DBS. In such patients, the electrode placement under general anesthesia can be planned.
• Patients should be screened for metallic implants and other contraindications for MRI if stereotaxy with MRI is planned.
• Parkinson disease-specific concerns include risk of hemodynamic instability, aspiration and laryngospasm, poor cough, and potential drug interactions that must be evaluated.
• Antiplatelet medications should be discontinued if possible before surgery. To facilitate intraoperative monitoring, anti-Parkinsonism medication is withheld to render the patients in an ‘off’ drug state. This can aggravate the patient symptoms. Patients with severe symptoms can be given a reduced dose of anti-Parkinsonian drugs in consultation with the neurosurgical team [20].
• Sedative premedications such as opioids and benzodiazepines can interfere with intraoperative monitoring and may be better avoided. Aspiration prophylaxis may be considered for the patients at increased risk of aspiration. Antihypertensive medications are continued until the day of surgery.
• The intraoperative procedure, risks and potential benefits should be explained to the patients and families.
• A standard preoperative fasting regimen is followed prior to the procedure.

Principles of Stereotaxy

• The aim of stereotaxy is to locate the deep and inaccessible intracerebral structures.
• The first step of frame-based stereotaxy is to enclose the head in a fixed rigid metal frame. This frame should be placed parallel to the anterior commissure–posterior commissure (AC–PC) line, which extends from the lateral canthus/orbital floor to the tragus [26].The head should be centered such that the midline lies within the center point of the head frame system.
• The borders of the frame constitute the Cartesian axes and the cranium supports the frame in which the cerebrum is enclosed. There are fiducials on the frame. In this frame, every point is precisely defined in the space and it is possible to define any intracranial structure with respect of the frame fiducials.
• The patient undergoes brain imaging (Computed tomography, MRI or ventriculography) after application of the frame. These images are superimposed to define the trajectory to the target area.
• There is an instrument holder or guide attached to the frame through which the DBS electrode is passed.
• One such example is the Leksell system where an arc is mounted on the frame with an adjustable instrument holder that can be moved transversely across the circumference of the arc [27]. In this system the center of the arc always coincides with this target point. There is an infinite number of directions of the needle to be pointed at its target as the radius of the arc is centered at the target.
• The frameless system is designed to locate the deeper targets within the brain without the application of a frame. In this system, five small fiducial screws are inserted into the skull at different quadrants in place of the head frame [28].
• The positions of these screw fiducials are registered in space and verified in the navigation system by the surgeon’s hand.
• A brain CT scan is performed 1-3 days prior to the surgery. This system uses an image-guided workstation for image fusion, target selection, and needle insertion trajectory planning.
• The frameless system is more vulnerable to the movements due to more interfaces and transfer of information. There is a larger spread in the deviations using the frameless navigation.
• This system provides larger movements, as the axis of movement is above the level of skull and causes more instability of the electrode.
• The advantage of this system is the absence of a frame that provides an easy access to the airway and good coordination during macrostimulation.
• A conventional stereotactic frame has a better accuracy and causes less dispersion when hitting the deep brain target as compared to the use of frameless stereotactic navigation, but these deviations are very small.

Special Preparation Requirements of the OR

• Options for securing the airway at any stage of the procedure should be considered if awake anesthesia is planned such as laryngeal mask airway (LMA), fiberoptic bronchoscopy, video laryngoscopes and light wands.
• The room temperature should be controlled as these patients are usually elderly and might have associated autonomic neuropathy and both these conditions impair
• Soft padding should be available to aid in positioning.
• Anticonvulsants must be readily available.
• A head frame wrench should be readily available throughout the procedure so that head frame can be removed promptly if need arises.

Intraoperative Monitors

• Standard anesthesia monitors including electrocardiogram, noninvasive arterial blood pressure, oxygen saturation, respiratory rate and end-tidal CO₂ should be routinely used.
• NIBP may not feasible during the awake portion because the patient’s tremor returns. An arterial line would be indicated in that circumstance as well.
• Invasive blood pressure monitoring might be required for the patients with labile blood pressure. Maintaining systolic blood pressure below 140 or less than 20% over the patient’s baseline has been shown to reduce the odds of a clinically significant hemorrhage. For blood pressure control, beta-blockers are avoided as they can mask or complicate intraoperative tremor testing. [29, 30]
• A urinary catheter is not used routinely as it would be uncomfortable to place in the awake patient. Moreover the duration of the procedure is just about 2 hours.
• The patient’s motor systems and level of consciousness should be closely monitored.
• Bispectral Index can also be used to titrate hypnotics and to predict the awakening.

Effects of Anesthetics on Microelectrode Recording and Macrostimulation Testing

• The effect of anesthetic drugs is non-homogeneous at different regions of the brain and varies with the target nuclei and specific disease as well.
• Anesthetics such as benzodiazepines, barbiturates, propofol, etomidate, and volatile agents all potentiate the inhibitory actions of gamma-aminobutyric acid (GABA) within the basal ganglia [31].
• The degree of effect of anesthetic drugs is influenced by the amount of GABA input to the various nuclei. The GPi neurons are known to have higher GABA input than STN. Hence, GPi neurons are more suppressed by anesthetic drugs [32]. The effect of anesthetic drugs on Vim nuclei is unclear.
• The subcortical areas of the brain are extremely sensitive to GABA receptor-mediated medications [20]. This effect can result in loss of MER and tremors. Hence, they should be avoided, especially benzodiazepines.
• Benzodiazepines are direct GABA agonists that can abolish the MER and stimulation testing, and also causes respiratory depression and impairment in consciousness [33]. If needed, a small dose of midazolam can be used prior to starting the procedure.
• Propofol, though it attenuates MER, has been successfully used for MER from GPi, STN and Vim. Its use is associated with abolition of tremors, dyskinesia and occasionally sneezing. The use of opioids such as, fentanyl or remifentanil, can prevent sneezing if given before propofol [34]. Propofol also reduces the firing rates of the GPi nucleus in patients with dystonia and PD, but is more pronounced in PD [35]. Propofol should be stopped at least 15 min prior to the simulation testing.
• Ketamine has little effect on MER and has been used successfully in pediatric patients undergoing DBS [36].
• Less than 1 MAC of Desflurane has been successfully used in DBS surgeries while MAC >1 has been shown to depress GPi discharges in PD [37].
• Dexmedetomidine, due to its non-GABA-mediated mechanisms of action, is considered an ideal sedative agent for DBS surgeries. It produces sedation and anxiolysis, with minimal respiratory depression [38].
• Dexmedetomidine at doses of 0.3–0.6 µg/kg/h does not interfere with MER and assessment of motor functions in PD.
• Calcium channel blockers, such as nicardipine, are recommended for control of blood pressure. Beta-blockers can be utilized if tremor testing is not required [29,30].
• The assessment of clinical benefits (macrostimulation) and adverse effects of DBS is often done but in an awake and cooperative patient. The patients are managed with shorter acting sedative-hypnotic drugs that are stopped prior to simulation testing.
• In uncooperative patients, general anesthesia (GA) is used. GA interferes with clinical testing as well as the assessment of any adverse effects such as paresthesias or abnormal motor activity due to the stimulation of adjacent structures (internal capsule and medial lemniscus).
• In such cases the use of visual evoked potential has been described during GPi stimulation.
• Confirmation of correct electrodes placement is done with MRI in patients who need general anesthesia.

Management for the Drowsy Patient with a Compromised Airway

• This condition arises due to oversedation or intracranial events such as hemorrhage and seizures. If the patient is awake, movement of the head relative to the body can result in airway compromise.
• The management includes communication with the operating surgeons and transient interruption of the procedure.
• Clear any secretions present in the oral cavity.
• As the patient’s head is attached to the frame and fixed on the table, access to the airway is limited. In this situation, conventional techniques to secure the airway with endotracheal intubation (ETI) using direct laryngoscopy is not A more appropriate technique in this situation is the prompt insertion of a laryngeal mask airway [20].
• If patient is at increased risk of aspiration, then endotracheal intubation using fiberoptic bronchoscope is done after initial stabilization of the airway with an LMA.
• The first attempt should be made without removing the frame so that the surgery can proceed. If this fails, then removal of the head frame is advised and the so that the airway can be secured.
• If the cause of airway obstruction results from the patient’s body shifting, leading to acute flexion of the neck, then repositioning should be considered.

Intraoperative Complications

• The insertion of DBS electrodes is associated with various complications involving major organ systems. The reported incidence varies from 6.9% [39] to 16% [40].
• Airway complications are described vide supra. In addition to upper airway obstruction, patients can experience coughing, sneezing, laryngospasm or bronchospasm [20]. Coughing and sneezing can increase patient movements and increase the ICP, which can increase the risk of intracranial hemorrhage. Judicious use of sedation, clearance of upper airway secretions, and administration of aspiration prophylaxis helps prevent these complications. If the airway is compromised, then it should be secured as described in the previous section.
• PD might cause respiratory dysfunction secondary to poor respiratory muscle function, leading to reduced forced vital capacity and reduced baseline arterial oxygen saturation [20]. These complications are aggravated in the absence of anti-Parkinsonian medications. Chest physiotherapy and incentive spirometry can improve the respiratory reserve in these patients. A deeper level of sedation must be avoided in patients with poor preoperative respiratory reserve.
• The most common cardiovascular complication is hypertension, which results from poor preoperative control, intraoperative distress or anxiety, or secondary to other events. Hypertension predisposes the patient to an increased risk of intracerebral hemorrhages [41,42]. Good preoperative control of blood pressure, comfortable positioning and appropriate sedation may decrease the risk of intraoperative hypertension. Pharmacological agents such as dexmedetomidine, labetalol, hydralazine, nitroglycerine, sodium nitroprusside, and esmolol are used to control the blood pressure. However, beta-blockers are best avoided as they may interfere with the testing of tremors. [29]
• PD and the medications used for its treatment can cause orthostatic hypotension. Anesthetic agents and hypovolemia might aggravate the perioperative hypotension. A few patients had also experienced chest pain and tachycardia with ST changes, raised troponins, in the setting of normal coronary arteries during the insertion of DBS electrodes under local anesthesia, which may reflect abnormal vasoactive responses that result in coronary vasospasm [43]. Hypotension is managed with an appropriate assessment of volume status and fluid replacement, slow positioning, raising the legs with a roll below the knees and the use of compression stockings to prevent venous pooling in the sitting position.
• Venous air embolism (VAE) can also be seen in both the supine and in the semi-sitting positions [44,45]. In awake patients, sudden vigorous coughing with associated unexplained hypoxia, tachycardia, tachypnea, chest discomfort, and hypotension indicate the onset of VAE. Coughing, airway obstruction, deep inspiration and hypovolemia can further increase the risk of VAE. Maintaining adequate intravascular volume, meticulous surgical technique, and limited head elevation limits the risk of VAE. Early detection, the use of appropriate monitor such as transthoracic Doppler and unprovoked vigorous coughing, and timely treatment helps prevent major hemodynamic instability.
• Various neurological complications can ensue including seizures, ICH, internal capsule injury (motor deficits), confusion, speech difficulties, agitation, akinetic crisis and tension pneumocephalus [47,48]. Seizures can be controlled with the administration of a low dose of midazolam or propofol [39]. If not controlled, then anticonvulsants are used. ICH is prevented by optimizing the blood pressure and preoperative coagulation status and, once this occurs, more aggressive management is needed.
• A longer duration of surgery, and the need for immobility or the performance of repeated testing, can lead to fatigue in awake patients. Adequate padding of pressure points, intraoperative physiotherapy, massage, and intrathecal hydromorphone [18] helps in relieving the pain and discomfort.
• DBS itself can cause paresthesias, involuntary movements, mood changes and other motor movements due to the stimulation of neighboring intracranial structures, which terminate once the stimulation is stopped [20].

Anesthetic Management for Battery Placement

• Battery placement is a painful procedure that requires subcutaneous tunneling, and is usually performed under general anesthesia. An implantable pulse generator (IPG) or battery can be implanted on the same day as the surgical implantation of the DBS, or after several days.
• Considerations regarding the preoperative evaluation, optimization, and drug interactions are the same as in DBS electrode placement. All medications, including antiparkinsonian medications, are continued until the day of surgery.
• Standard and anesthesia monitoring is used including electrocardiography, non-invasive blood pressure, oxygen saturation and end tidal CO₂.
• The airway is secured either with an endotracheal tube or laryngeal mask airway (LMA). Problems with LMA include an unprotected airway which may predispose to aspiration of gastric contents, and LMA displacement during surgery.
• The patient is positioned supine with the head turned to the opposite side of the intended site of IPG implantation, which can displace the LMA. There are no randomized controlled trials to demonstrate that one airway technique is superior over the other [48].

Postoperative Concerns

• Prior to DBS implantation surgery, patients are usually taken off their medications for at least 12 hours prior to surgery, and the average procedure duration is 4 to 8 hours. This off-drug state can aggravate symptoms of Parkinson’s disease. Patient’s anti-Parkinsonian medications should be restarted as soon as possible.
• DBS placement in the STN might improve the Parkinsonian symptoms immediately after surgery due to a microlesional effect. This effect might act synergistically with the anti-PD medications, and results in severe peak-dose dyskinesias. Close titration of the preoperative anti-PD medications is therefore necessary.
• Neuropsychiatric side effects such as transient confusion are common in the immediate postoperative period following STN-DBS. These symptoms are usually transient and do not need any specific treatment, but may interfere with the neurologic assessment in the postoperative period.
• Postoperative nausea and vomiting are controlled with the drugs that do not have antidopaminergic effects such as ondansetron and dexamethasone. Appropriate analgesics are given for postoperative pain control.
• Patients are usually observed for 24 hours and thereafter are discharged, depending on their neurological and cognitive status.
• Rarely, complications such as tension pneumocephalus and intracerebral hemorrhage may be seen in patients undergoing DBS surgery [49,50].

Anesthetic Concerns in Patients with DBS Presenting for Non-Neurosurgical Procedures

• The preoperative assessment includes the identification of the device and the severity of symptoms when the DBS is deactivated. Oral medications may need to be supplemented if the device needs to be turned off and the symptoms are severe.
• DBS systems may interfere with the functioning of various monitoring and therapeutic devices in the operating room. The DBS may directly produce artifacts in ECG readings that can be minimized by bipolar stimulation of the neurostimulator [51].
• Electrocautery can cause thermal injury to brain, reprogramming, and damage to the DBS [52,53]. The neuro-stimulator may need to be switched off when diathermy is required. The use of bipolar diathermy reduces the risk of thermal injury to the brain tissue or reprogramming of the device. During monopolar diathermy, the grounding pad must be placed as far as possible from the IPG and the lowest diathermic energy in short pulses should be used. DBS system should be re-interrogated after surgery.
• Short wave (microwave and ultrasound) diathermy is contraindicated as it causes significant heating and brain injury in patients with DBS [54].
• Pacemakers and DBS devices can have cross interference. Therefore, the pulse generator and pacemaker should be implanted away from each other and both these devices should be interrogated before and after surgery [55].
• An external defibrillator and intracardiac defibrillator can cause tissue heating around the DBS electrode, and can reprogram or damage the device. The paddles of external defibrillator should be positioned as far as possible from the neurostimulator, and should be kept perpendicular to the lead system [21].
• A peripheral nerve stimulator and electroconvulsive therapy (ECT) do not interfere with DBS system, but ECT electrodes should be placed away from the DBS hardware [56,57].
• Magnetic resonance imaging (MRI) causes heating of the DBS electrode, leading to brain damage and reprogramming of DBS devices. These devices also cause image artifacts. MRI safety guidelines must be followed and MRI exposure should be limited [21].
• When the device is switched off the patients may experience rigidity, and patients may require mechanical ventilation if there is severe rigidity interfering with their ability to breathe. The device should be turned on after completion of the surgery but before awakening.

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