utilizing dexmedetomidine during an anterior cervical

University of North DakotaUND Scholarly Commons

Nursing Capstones Department of Nursing

6-15-2017

Utilizing Dexmedetomidine During an AnteriorCervical Discectomy and FusionDanielle L. Kiedrowski

Follow this and additional works at: https://commons.und.edu/nurs-capstones

This Independent Study is brought to you for free and open access by the Department of Nursing at UND Scholarly Commons. It has been accepted forinclusion in Nursing Capstones by an authorized administrator of UND Scholarly Commons. For more information, please [email protected].

Recommended CitationKiedrowski, Danielle L., "Utilizing Dexmedetomidine During an Anterior Cervical Discectomy and Fusion" (2017). NursingCapstones. 185.https://commons.und.edu/nurs-capstones/185

https://commons.und.edu?utm_source=commons.und.edu%2Fnurs-capstones%2F185&utm_medium=PDF&utm_campaign=PDFCoverPages

https://commons.und.edu/nurs-capstones?utm_source=commons.und.edu%2Fnurs-capstones%2F185&utm_medium=PDF&utm_campaign=PDFCoverPages

https://commons.und.edu/nurs?utm_source=commons.und.edu%2Fnurs-capstones%2F185&utm_medium=PDF&utm_campaign=PDFCoverPages

https://commons.und.edu/nurs-capstones?utm_source=commons.und.edu%2Fnurs-capstones%2F185&utm_medium=PDF&utm_campaign=PDFCoverPages

https://commons.und.edu/nurs-capstones/185?utm_source=commons.und.edu%2Fnurs-capstones%2F185&utm_medium=PDF&utm_campaign=PDFCoverPages

mailto:[email protected]

Running head: DEXMEDETOMIDINE AND ANTERIOR CERVICAL DISCECTOMY

Utilizing Dexmedetomidine During an Anterior Cervical Discectomy and Fusion

by

Danielle L. Kiedrowski

Bachelor of Arts in Nursing, Concordia Moorhead, 2010

An Independent Study

Submitted to the Graduate Faculty

of the

University of North Dakota

in partial fulfillment of the requirements

for the degree of

Master of Science

Grand Forks, North Dakota

December

2017

DEXMEDETOMIDINE AND ANTERIOR CERVICAL DISCECTOMY

2

PERMISSION

Title Utilizing Dexmedetomidine During an Anterior Cervical Discectomy and Fusion

Department Nursing

Degree Master of Science

In presenting this independent study in partial fulfillment of the requirements for a graduate

degree from the University of North Dakota, I agree that the College of Nursing and Professional

Disciplines of this University shall make it freely available for inspection. I further agree that

permission for extensive copying or electronic access for scholarly purposes may be granted by

the professor who supervised my independent study work or, in his absence, by the chairperson

of the department or the dean of the School of Graduate Studies. It is understood that any

copying or publication or other use of this independent study or part thereof for financial gain

shall not be allowed without my written permission. It is also understood that due recognition

shall be given to me and to the University of North Dakota in any scholarly use which may be

made of any material in my independent study.

Signature ____________________________

Date _____________________________


3

ABSTRACT

Title: Utilizing Dexmedetomidine During an Anterior Cervical Discectomy and Fusion

Background: Dexmedetomidine, is a highly selective 2-adrenoreceptor agonist containing

sedative, amnesic, analgesic, anxiolytic, and sympatholytic properties. Spine surgery can be very

challenging and specific anesthetic considerations should be applied when planning an anesthetic

plan. Safe neurophysiologic monitoring and pain management are two areas in which

dexmedetomidine can assist to allow for improved patient outcomes.

Purpose: Discover the evidence supporting the use of dexmedetomidine and spine surgery.

Process: The author’s literature search was performed through the University of North Dakota

Health Sciences Library. PubMed was selected as the search engine, as the intended use is for

medical professionals including the author’s profession of nurse anesthesia. PubMed also was

thought to have the most relevant and up-to-date journal articles concerning the wanted literature

search. The search box was selected and the first search term “dexmedetomidine” was placed.

This produced over 3,400 results which convinced the author to decrease the search results with

a filter and utilize the Medical Subject Headings (MeSH) database. The filter applied included

full text, English language, human subjects, and published within last five years. MeSH database

link was selected under the More Resources column. Additional search terms included “spine”

(with the addition of surgery under controlled vocabulary in MeSH), “anterior cervical

discectomy and fusion”, “myelomalacia”, “neurophysiologic monitoring”, “evoked potentials”,

and “opioid”. The most relevant journal articles pertaining to the author’s wanted literature

search included the search terms “dexmedetomidine” and “spine surgery”.

Results: Dexmedetomidine does not affect evoked potentials, it reduces the amount of volatile

and intravenous anesthetic, and minimizes the impedance of anesthetics on neurophysiologic

monitoring. It was also discovered that opioid use was decreased intraoperatively as well as

postoperatively with dexmedetomidine use. Thus, the negative side effects of opioids are

lessened, which may improve patient satisfaction. Adjuncts such as ketamine and lidocaine to

dexmedetomidine also became apparent to assist in additional pain relief intraoperatively.

Implications: The use of dexmedetomidine is beneficial for individuals undergoing spine

surgery, specifically an anterior cervical discectomy and fusion. It may also be helpful among

other surgeries such as minimally invasive spine surgery, laparoscopic cholecystectomies,

uterine artery embolization for fibroid tumors or adenomyosis, as well as for chronic pain and

opioid dependent patient populations (Bakan et al., 2014; Dunn, Durieux, & Nemergut, 2016; C.

H. Kim et al., 2013; K. H. Kim, 2014).

Keywords: Dexmedetomidine, spine surgery, anterior cervical discectomy and fusion,

myelomalacia, neurophysiologic monitoring, and evoked potentials.


4

Utilizing Dexmedetomidine During an Anterior Cervical Discectomy and Fusion

Surgery of the spine is highly invasive which presents challenges to the medication

regimen that is administered to maintain safety with untainted neurophysiologic monitoring

ability, patient comfort, and stable hemodynamics. It is imperative for anesthesia professionals to

have the knowledge regarding anesthetics (intravenous and volatile) and opioid requirement as it

pertains to the surgical procedure. For example, spine surgeries often “require larger doses of

opioids and higher concentration of anesthetic agents to suppress the hypertensive response,

which can interfere with neurophysiological monitoring” (Mariappan, Ashokkumar, &

Kuppuswamy, 2014, p. 192). Both inhaled and intravenous anesthetics can hinder evoked

potentials, displaying as false readings mimicking the appearance of spinal cord compromise

thus requiring an anesthetic plan that provides comfort and safety. Given that, balanced

anesthesia is the goal of anesthesia professionals, it is vital that these concerns are considered

when developing an anesthetic plan of care for these patients.

Case Report

A 47-year-old, 160 cm, 79.8 kg male presented for an anterior cervical discectomy and

fusion of the 4th and 5th cervical vertebrae. His medical history included seizures, anxiety,

hypertension, hydronephrosis, developmentally delayed from neonatal meningitis, impaired

mobility and activities of daily living, gait instability, and dysphagia. Past surgical history

included a ventriculoperitoneal shunt placement with two revisions and recent laminectomies of

the 2nd to 6th cervical vertebrae. The laminectomy surgery was post-operatively complicated with

pneumonia, treated then discharged home. Subsequently, the patient presented with increased

gait instability, left sided weakness, dysphagia, and worsening incontinence following his recent

laminectomies of the 2nd to 6th cervical vertebrae indicating the need for an additional spine


5

surgery. Pre-operative magnetic resonance imaging (MRI) scan of the cervical spine displayed

worsening disc herniation at the 4th and 5th cervical vertebrae and myelomalacia of the spinal

cord at the 5th cervical vertebrae warranting the plan for an anterior cervical discectomy and

fusion of the 4th and 5th cervical vertebrae. His current medication regimen included guaifenesin-

dextromethorphan, miconazole powder, acetaminophen, triamcinolone acetonide, aspirin,

carbamazepine, divalproex sodium, epinephrine pen, lacosamide, lorazepam, magnesium

hydroxide, melatonin, oyster shell calcium + vitamin D, paroxetine, risperidone, and senna-

docusate. Allergies included bee stings, amoxicillin, and augmentin. Given the patient’s medical

history and current health status, he was considered an American Society of Anesthesiologists

physical status level 3.

Pre-operative airway evaluation demonstrated a Mallampati III, with visualization of only

soft palate and uvula base, a thyromental distance less than 6 cm, an inter-incisor distance less

than 4 cm, and limited atlanto-occipital joint mobility suggesting a potential difficult airway. The

anesthesia team planned a modified rapid sequence induction and the use of the GlideScope

(Verathon Inc., Bothell, WA) for intubation to minimize cervical vertebrae movement as well as

the potential for difficult placement of the endotracheal tube. Pre-operative vital signs included a

blood pressure of 148/80 mmHg, heart rate 82 in normal sinus rhythm, oxygen saturation of 98%

on room air, and afebrile with a temperature of 98.7. The patient’s chart was further reviewed

then the patient and guardian were informed of the anesthetic risks and benefits of general

anesthesia and consented.

In the surgical holding room, an 18-gage intravenous (IV) access was established and

Lactated Ringers (LR) fluid was initiated. Upon arrival to the operating room, standard monitors

were applied, midazolam 2 mg IV was given for anxiolysis, and oxygen supplementation at 10


6

liters/minute of flow via facemask for 5 minutes was started. A modified rapid sequence

intravenous induction was utilized. Induction medications included fentanyl 100 mcg, lidocaine

40 mg, rocuronium 5 mg, propofol 150 mg, and succinylcholine 140 mg. Once the patient

achieved unconsciousness and negative eyelid movement with eyelash stimulation, artificial

ointment was applied to bilateral lower conjunctiva then the eyelids were closed and secured

with tape. Next, a GlideScope (Verathon Inc., Bothell, WA) Macintosh size 3 was introduced

into the mouth and placed into oropharynx providing a full grade I view of the vocal cords onto

the video monitor. An 8.0 mm cuffed endotracheal tube with stylet was advanced through the

larynx successfully on first attempt. Placement was confirmed by the presence of end-tidal

carbon dioxide (ETCO2) as well as auscultation of bilateral breath sounds in upper and lower

lung lobes. The endotracheal tube was secured and the patient was placed on synchronized

intermittent mechanical ventilation. General anesthesia was maintained with 1% sevoflurane

inspired concentration in an oxygen and air mixture of 1 L/min each, a propofol infusion at 50

mcg/kg/min, and a dexmedetomidine infusion at 0.5 mcg/kg/hr. No dexmedetomidine loading

dose was given. Slight hypotension was encountered mid-way during the case so the propofol

infusion was decreased to 25 mcg/kg/min.

The surgical procedure was uneventful and neurophysiological monitoring remained

stable throughout the case. Upon conclusion of the case, the patient successfully followed

commands by opening eyes and lifting head, a regular breathing pattern was noted with 600 ml

of tidal volume, and the trachea was extubated. A simple mask with oxygen 6 liters/min was

applied. Hemodynamics remained stable and was transferred to the post-anesthetic recovery unit

without complications. The post-operative evaluation was also stable without anesthetic

complications. The patient was admitted as pre-operatively planned for close monitoring. Post-


7

operative day 1, the patient’s baseline left-sided weakness was still present but improvement was

noted to the patient’s ambulation as compared to preoperatively. The patient’s post-operative

hospital length of stay totaled 8 days. During the hospital course, the patient developed

worsening dysphagia resulting in a failed swallow evaluation. A nasopharyngeal feeding tube

was initially placed but then later required a gastrostomy tube with interventional radiology. The

patient required chest physiotherapy during his hospital stay to assist the prevention of

pneumonia as the patient failed to successfully complete incentive spirometry. Also, the patient

developed intermittent fevers and bowel distension, both of which resolved spontaneously

without treatment. Patient was successfully discharged to a group home with this gastrostomy

tube but had improved left sided-weakness and ambulation. The patient was scheduled to follow

up with speech therapy two weeks following his hospital stay for his dysphagia.

Discussion

Dexmedetomidine

Mechanism of action. Dexmedetomidine, is a highly selective 2-adrenoreceptor

agonist, binding to the 2 and 1 receptors in a 1620:1 ratio (Mariappan et al., 2014). In

comparison, clonidine, another selective 2-adrenoreceptor agonist has selectivity towards 2

receptors in a 200:1 fashioned ratio (Mariappan et al., 2014). Dexmedetomidine produces

sedative, amnesic, analgesic, anxiolytic, and sympatholytic properties without causing

respiratory depression (Sen, Chakraborty, Santra, Mukherjee, & Das, 2013).

Indications. The United States Food and Drug Administration (FDA) approved

dexmedetomidine for sedative infusions for 24 hours or less in the Intensive Care setting when

the patient is intubated and mechanically ventilated (Hospira, 2016). Additionally,


8

dexmedetomidine has been approved for “sedation of non-intubated patients prior to and/or

during surgical and other procedures” (Hospira, 2016, p. 3).

Side effects. The side effects associated with dexmedetomidine include hypotension,

bradycardia, sinus arrest, transient hypertension, and dry mouth (Hospira, 2016).

Dexmedetomidine is also associated with tolerance, tachyphylaxis, acute respiratory distress

syndrome, respiratory failure, and agitation when the infusion exceeds 24 hours (Hospira, 2016).

Dose. A loading dose is recommended as 1 mcg/kg to be given over 10 minutes, then the

initiation of a maintenance dose infusion rate of 0.2 to 0.7 mcg/kg/hour for sedation for the

intensive care setting or 0.2 to 1 mcg/kg/hour for adult procedural sedation and titrated for

desired clinical effect (Hospira, 2016).

Cost. For a 100-ml bottle with the concentration of 4 mcg/ml, the cost is $75.26 (K.

Kern, personal communication, January 4, 2017).

Pharmacokinetics.

Absorption. Currently, dexmedetomidine is only registered for intravenous

administration but further research is being conducted evaluating off-labeled uses of oral,

intramuscular, intranasal, and buccal routes of administration (Weerink et al., 2017). A four-

period, cross-over design, randomized open study was conducted with 12 healthy male subjects

evaluating the bioavailability among extravascular routes of dexmedetomidine (Anttila, Penttilä,

Helminen, Vuorilehto, & Scheinin, 2003). When dexmedetomidine is administered orally, it

undergoes significant first pass effect with approximately 16% bioavailability and complete

bioavailability with intramuscular administration (Anttila et al., 2003). Additionally, intranasal

and buccal route, alternative noninvasive administration techniques were also evaluated, both

illustrating an 82% mean bioavailability, which would be helpful for the uncooperative patient


9

population when intravascular placement is impossible (Anttila et al., 2003; Yoo et al., 2015).

Distribution. Distribution is rapid, it may cross the placenta as well as distribute into

breast milk and has been assigned as a pregnancy category C (Hospira, 2016). The steady-state

volume of distribution is 118 liters with a half-life of 6 minutes. When dexmedetomidine is

administered intravenously for up to 24 hours between the dosages of 0.2-0.7 mcg/kg/hour, it

demonstrates linear pharmacokinetics (Hospira, 2016). Protein binding is approximately 94%

(Hospira, 2016).

Metabolism. Dexmedetomidine is metabolized through hepatic processes via N-

glucoronidation, N-methylation, and cytochrome P2A6 (Hospira, 2016).

Elimination. Terminal elimination half-life of 2 hours and undergoes clearance of

approximately 39 L/h (Hospira, 2016). Excretion of dexmedetomidine occurs 95% through urine

and 4% through feces (Hospira, 2016).

Pharmacodynamics.

Sedative effects. The mechanism is not well understood however the sedative effects are

thought to occur from the stimulation of 2-receptors in the locus coeruleus among central

presynaptic and postsynaptic receptors promoting an endogenous physiologic sleeping pattern

(Weerink et al., 2017).

Analgesic effects. It is believed that the analgesic effects occur from dexmedetomidine

binding to the central and spinal cord 2-receptors resulting in decreased release of substance P

and glutamate thus potentially resulting in opioid-sparing effects (Weerink et al., 2017).

Cardiovascular effects. Dexmedetomidine binds 2-adrenoreceptors found within the

peripheral and central nervous systems in pre-, post-, and extra-synaptic sites reducing the

release of norepinephrine and the plasma norepinephrine concentration (Penney, 2010). There


10

are three 2-adrenoreceptors: 2a, 2b, and 2c. Hemodynamic effects are dose dependent.

Hypertension and bradycardia are commonly seen when high dosages of dexmedetomidine are

administered, especially following the loading dose of 1 mcg/kg over 10 minutes (Weerink et al.,

2017).

This hyperdynamic vasoconstrictive response is thought to be caused by the stimulation

among 2b-receptors within the vascular smooth muscle resulting in increased blood pressure

and a decrease of heart rate from the baroreceptor reflex (Penney, 2010; Weerink et al., 2017).

As the plasma concentration of dexmedetomidine diminishes, for instance once the loading dose

is completed, the 2-receptors within the vascular endothelial cells respond by causing a

vasodilation response resulting in the common side effect of hypotension associated with

dexmedetomidine (Weerink et al., 2017). It is also believed that centrally located 2a and 2c

adrenoreceptors may contribute to the hypotension associated with dexmedetomidine (Penney,

2010). “If necessary, high plasma concentrations can be avoided by decreasing loading dose

sizes or by increasing time over which the loading dose is administered” (Weerink et al., 2017, p.

13). Sympatholytic properties that dexmedetomidine possesses include a decrease in heart rate,

mean arterial blood pressure, cardiac output, and norepinephrine release from binding to 2-

receptors both centrally and peripherally (Jamaliya et al., 2014). Dexmedetomidine has also been

used in conjunction for spine surgery as a hypotensive agent to a decrease in blood loss as well

as improve surgical field visualization (Jamaliya et al., 2014).

Respiratory effects. Dexmedetomidine minimally suppresses respiratory drive in which

the response to carbon dioxide is still present mimicking a natural sleeping pattern (Weerink et

al., 2017).

Spine Pathophysiology and Surgery


11

Myelomalacia. Spinal cord injury resulting in softening of the spinal cord through

compression, ischemia, or hemorrhage is termed myelomalacia (Zhou, Kim, Vo, & Riew, 2015).

Clinical manifestations of this disorder may be displayed as weakness, sensory loss, and poor

coordination or dexterity (Smorgick et al., 2015). The patient discussed in the case report

displayed this abnormality of myelomalacia of the spinal cord at the 5th cervical vertebrae. This

patient’s clinical manifestations that corresponded with myelomalacia includes gait instability

and left sided weakness. Myelomalacia is reversible if interventions are implemented early with

decompression surgery.

According to Potter & Saifuddin (2003), myelomalacia is the most common disorder

among spinal cord injury patients represented by a 55% prevalence. Furthermore, Zhou et. al.

(2015) completed a retrospective study evaluating 23,139 patients undergoing cervical MRI’s,

964 patients were diagnosed with cervical myelomalacia calculating to approximately 4.2% of

this population. In addition, they found that myelomalacia was higher among the male gender at

5.6% (576/10,196) compared to 3.0% (388/12,943) (Zhou et al., 2015). Further, as a person ages,

the prevalence for myelomalacia also increases until 80 years of age. The highest prevalence for

myelomalacia was among individuals between 70 to 79 years of age with a 7.6% prevalence then

interestingly enough decreases after age 80 at 5.1% (Zhou et al., 2015).

Anterior cervical discectomy and fusion. Discectomy is a procedure that is completed

to alleviate compression of the spinal cord or nerve roots by removing herniated disks or

osteophytes (Jaffe, Schmiesing, & Golianu, 2014). Fusions are also commonly completed during

spine surgery by placing a bone graft or prosthesis to support the disc space preventing collapse

of the disc space and deformity as well as restoring the natural curvature of the spine (Jaffe et al.,


12

2014). Most commonly the patient assumes prone position for spine surgeries but if an anterior

approach is determined such as in the cervical vertebrae region the patient assumes supine.

In the case report, the patient’s cervical discectomy and fusion was determined in which

the anterior approach was decided, implicating the supine position. Due to the more predictable

anatomic path of the left recurrent laryngeal nerve, injury risk is reduced when the left side of the

neck is utilized for the anterior approach (Jaffe et al., 2014). Exposure of the anterior cervical

spine is accomplished by dissecting a route between the carotid sheath and the esophagus then

the disc is removed microscopically after fluoroscopic confirmation (Jaffe et al., 2014).

Complications. Complications associated with anterior cervical spine surgery include

venous air embolisms, esophagus perforation, retraction nerve injury, hypotension, airway

obstruction from edema, hematoma, neurologic deficit, and tension pneumothorax (Jaffe et al.,

2014). According to a retrospective cohort study evaluating 183 elective anterior cervical

discectomy and fusion patients by Basques and colleagues, patients with a history of nonspinal

malignancy, pulmonary disease, and corpectomy are at risk for increased length of stay thus

placing these individuals at a higher risk for additional complications (Basques, Bohl,

Golinvaux, Gruskay, & Grauer, 2014). These additional complications include pneumonia,

venous thromboembolisms, and delirium (Basques et al., 2014). In contrast, “[a]ge, elevated

BMI, ASA class, smoking history, diabetes, heart disease, number of levels fused, and the use of

an iliac crest bone graft did not correlate with extended length of stay” (Basques et al., 2014, p.

945). Thus, at lower risk of further complications.

Anesthetic Considerations

Evoked potentials. One major concern during spine surgery is the neurophysiologic

status of the patient. Neurophysiologic monitoring with the use of evoked potentials is


13

commonly used to enhance patient safety during spine surgery (Rozet et al., 2015). Evoked

potentials are frequently used for spine surgery including somatosensory evoked potentials

(SSEPs) and motor evoked potentials (MEPs) (Rozet et al., 2015). SSEPs assess the dorsal

sensory portion and MEPs evaluate the anterior motor portion of the spinal cord. These two

neurophysiologic monitoring modalities evaluate spinal cord compromise by measuring the

amplitude and latency during evoked potentials, thus assessing the intactness of the spinal cord

during surgery (Mahmoud et al., 2010). Amplitude depression, prolonged latency, and decreased

motor response indicates neurologic injury and requires immediate intervention (Mahmoud et al.,

2010). Specifically, in SSEPs, criteria for significant change occurs when a 50% decrease of

amplitude and/or a 10% increase of latency is detected and the cause should be examined (Bithal,

2014). For MEPs, a 50% decrease in amplitude and diminished motor response indicates

significant change also requiring attention (Bithal, 2014). Hence, it is important for the

anesthesia professional to consider evoked potentials when developing an anesthetic plan.

Intravenous and volatile anesthetics suppress evoked potentials by interrupting the quality

and accuracy of neurophysiologic monitoring (Rozet et al., 2015). A common intravenous

anesthetic utilized intraoperatively for spine surgery is propofol, due to its high safety profile and

rapid emergence (Sen et al., 2013). It is believed to enhance the interaction of gamma-

aminobutyric acid (GABA), an inhibitory neurotransmitter, with the GABA receptor, resulting in

sedation by cell membrane hyperpolarization and synaptic inhibition (Mariappan et al., 2014;

Bithal, 2014). Propofol displays a decrease in amplitude of SSEPs as well as suppresses MEPs

when given in high dosages or in bolus doses which may result in complete interruption of

neurophysiologic monitoring (Bithal, 2014). Determining an appropriate intravenous anesthetic

dose is challenging when evoked potentials are included within the surgical plan.


14

Further, according to Bithal (2014), all volatile anesthetics are associated with dose

dependent amplitude depression, prolonged latency, and motor suppression. Isoflurane

suppresses evoked potentials the greatest, however, monitoring of SSEPs may be still possible

when a goal of minimum alveolar concentration (MAC) value of 0.5-1.0 is implemented.

Likewise, sevoflurane and desflurane may be included in the anesthetic plan if the MAC value is

less than 1.5. Moreover, MEPs are deterred at lower MAC values with all halogenated volatile

anesthetics, yet still allows monitoring of MEPs when the MAC value is less than 0.5% (Bithal,

2014).

If volatile anesthetic technique is utilized within an anesthetic plan when EPs are

executed, the anesthesia provider must communicate with the neurophysiology team as to

whether SSEPs and/or MEPs will be applied. As a rule of thumb, a goal MAC value of 0.5

would be safe for either SSEPs or MEPs.

A combination of volatile and intravenous anesthetic plan was utilized for the case report.

As described in the case report, the anesthesia was initiated and maintained with 0.5 MAC of

sevoflurane along with intravenous anesthetic of propofol and adjunct dexmedetomidine

infusions. The propofol infusion was decreased to alleviate hypotension.

Due to intravenous and volatile anesthetic interruption to evoked potentials, it is

recommended that an anesthetic-sparing technique is employed when evoked potentials are

utilized (Rozet et al., 2015). Dexmedetomidine is known to decrease anesthetic dosages without

hindering neurophysiologic monitoring and weakening sedation. According to Rozet et al.,

dexmedetomidine does not prolong latency or decrease amplitude of SSEPs, MEPs, and VEPs

when used at clinical doses (2015). In a double-blind, placebo-controlled trial of 40 adult patients

undergoing elective spine surgery with total intravenous anesthetic with propofol and


15

remifentanil, assessed adjunct dexmedetomidine and evoked potential response (Rozet et al.,

2015). This study discovered that dexmedetomidine did not alter EPs at clinically relevant

dosages and declared its use to be safe during spine surgery when EPs are used (Rozet et al.,

2015). Dexmedetomidine also enhances the hypnotic effect of propofol allowing for reduced

doses of this anesthetic while still allowing accurate neurophysiologic monitoring.

Furthermore, Sen and colleagues (2013) performed a randomized control trial of 70

patients undergoing elective spine surgery evaluating propofol requirements during induction

and maintenance anesthetic phases. Half of the patients received dexmedetomidine with propofol

and the other half omitted dexmedetomidine. This study found a 48.08% decrease in mean

requirement of propofol during induction and a 61.87% decrease during the maintenance phase

of anesthesia when dexmedetomidine was used (Sen et al., 2013). The requirement of volatile

anesthetic is also reduced with the use of a dexmedetomidine infusion.

Similarly, a randomized controlled trial consisting of 48 patients undergoing abdominal

surgery, dexmedetomidine allowed a 39% reduction in sevoflurane based anesthetic (Harsoor et

al., 2015). Alike, Mizrak and colleagues reported a double-blind, placebo-controlled study

assessing dexmedetomidine administration prior to induction and the effects on sevoflurane

MAC concentration during an inhalation induction on 60 adult patients undergoing intubation for

general anesthesia (2013). Induction time was decreased by approximately 75% and significantly

decreased the sevoflurane end-tidal concentration (Mizrak et al., 2013). Also, a 28% reduction of

sevoflurane concentration was noted when a dexmedetomidine infusion was applied within a

randomized, double-blind controlled trial among 40 patients undergoing general anesthesia for

abdominal surgery (Harsoor, Rani, Lathashree, Nethra, & Sudheesh, 2014). In a concise manner,


16

dexmedetomidine, reduces intravenous and inhaled anesthetics preventing anesthetic interference

while promoting the ability to safely monitor and detect negative neurologic outcomes.

Other anesthetic considerations related to neurophysiologic monitoring include avoiding

neuromuscular antagonists if motor evoked potentials are used. Neuromuscular antagonists

disturb and prevent the conduction of motor evoked potentials thus preventing the ability to

neurophysiologically monitor (Jaffe et al., 2014). Also, the neurophysiology team should be

updated if any changes to anesthetic depth, anesthetic medications, blood pressure, PCO2, and

PO2 occur as these may cause false readings of spinal cord compromise (Jaffe et al., 2014).

Pain Management. In addition to the anesthetic-sparing effects, dexmedetomidine also

has opioid-sparing effects (Dunn et al., 2016). Spine surgery is very stimulating and may require

large doses of opioids (Garg et al., 2016). Often, the patient population that presents for spine

surgery frequently suffers from chronic pain and are treated with long-term opioid medication

regimens making pain management perioperatively difficult due to opioid tolerance (Dunn et al.,

2016). Opioids may provide pain relief; however in large dosages, opioids have been found to

cause hyperanalgesia (Mariappan et al., 2014). Hyperanalgesia results in patient tolerance

consequently increasing the requirement of opioids to provide adequate pain control thus

increasing the risk of negative opioid side effects. These side effects include itching, respiratory

depression, nausea/vomiting, and constipation. Interestingly, the patient described in the case

report did not take chronic opioids in which did not fit the typical spine surgical patient and

contrasts with this patient profile.

According to a cross-sectional study evaluating 1,857 adults with a history of spine

related pain and the prevalence of chronic neuropathic pain from spinal cord or nerve root

compression or damage revealed a 53.3% prevalence of neuropathic pain (Yamashita, Takahashi,


17

Yonenobu, & Kikuchi, 2014). Thus, the incidence of chronic pain is high within the spine

surgical patient population and must be considered within the anesthetic plan.

Likewise, a prospective study involving 67 anterior cervical discectomy and fusion

patients were evaluated investigating pain, range of motion, motor function, and sensory function

pre-operatively and post-operatively assessing the influence of these factors on patient

satisfaction (Hessler et al., 2012). It was found that range of motion, motor function, and sensory

function did not significantly impact patient satisfaction. However, improvement of pain

displayed a significant role in patient satisfaction as well as the patient’s perception of success of

the surgery (Hessler et al., 2012). Pain-reducing regimens during and after surgery should be the

aim of anesthesia providers to reach highest patient satisfaction and improve quality of life.

Dexmedetomidine contains analgesic properties therefore reducing opioid requirements

intraoperatively as well as post-operatively. With the reduction of opioids, hyperanalgesia,

tolerance, and side effects that are associated with opioids and can be reduced with the use of

dexmedetomidine. Moreover, Arain, Ruehlow, Uhrich, & Ebert (2004) conducted a randomized

control trial of 34 inpatients scheduled for elective surgery evaluating the use of

dexmedetomidine and morphine requirements post-operatively. Two groups were divided evenly

between patients receiving a dexmedetomidine infusion or a morphine infusion intraoperatively.

A 66% decrease of opioid requirement post-operatively was noted among the dexmedetomidine

group (Arain, Ruehlow, Uhrich, & Ebert, 2004).

Similarly, Garg and colleagues conducted a prospective randomized double-blind placebo

controlled study involving 66 patients undergoing spine surgery and found a 54% decrease in

opioid requirement post-operatively when dexmedetomidine was used (Garg et al., 2016).

Furthermore, Kim and colleagues (2013) performed a prospective randomized study


18

investigating opioid consumption and opioid-related side effects among 50 patients undergoing

uterine artery embolization. The 50 patients were divided into two groups: a dexmedetomidine

infusion was started 30 minutes prior to the procedure and continued 6 hours after, while the

other group received a placebo of matching normal saline volume (Kim et al., 2013). Both

groups were given patient controlled analgesia (PCA) with intravenous fentanyl. A lower pain

score, less rescue analgesics, as well as a decrease of 28% of fentanyl was found when a

dexmedetomidine infusion was utilized (Kim et al., 2013). Multi-modal approaches with

dexmedetomidine infusions also assists in opioid-sparing anesthetic plans improving patient

comfort and pain management (Garg et al., 2016).

Adjuncts. A promising analgesia relieving adjunct to dexmedetomidine is ketamine.

Ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist, may be added as an adjunct to

dexmedetomidine to assist in pain management as well as reduce anesthetic requirements.

Sedation from ketamine is due to the functional dissociation of the thalamo-neocortical system

and limbic system causing depression of the thalamus and cerebral cortex while simultaneously

activating the limbic system resulting in additional anesthetic-sparing capability (Mion &

Villevieille, 2013). Plus, it contains analgesic properties due to binding of opioid receptors,

subsequently providing supplementary opioid-sparing ability (Mion & Villevieille, 2013). “By

blocking the NMDA receptor, ketamine holds obvious promise for attenuating these centrally

mediated pain processes, thereby reducing acute pain and potentially preventing chronic pain”

(Gorlin, Rosenfeld, & Ramakrishna, 2016, p. 162).

Ketamine may be a beneficial adjunct to dexmedetomidine to assist in the opioid tolerant

and chronic pain population. In 2011, a systematic review of 70 studies, evaluated intravenous

ketamine for perioperative analgesia (Laskowski, Stirling, McKay, & Lim, 2011). This


19

systematic review revealed that within placebo groups, 78% experienced more pain even with

increased amounts of opioids than ketamine groups (Laskowski et al., 2011). Additionally,

among the ketamine treated groups, there was a reduction in opioid consumption post-

operatively, improved quality of pain control, as well as delayed time to the first post-operative

analgesic requirement (Laskowski et al., 2011).

Further, in a prospective, double-blinded, and placebo-controlled study of 102 opiate

dependent patients receiving major lumbar spine surgery determined that there was a 37%

reduction of opioids in the acute post-operative phase (Loftus et al., 2010). Also, a decreased

intensity of pain in post-anesthetic care unit and 6 weeks following surgery was discovered,

along with a decreased amount of morphine analgesia needed during the post-operative period up

until the first follow up visit (Loftus et al., 2010).

Concerted dexmedetomidine and ketamine infusions appear to be a novel practice. A case

report by Penney (2010) discussed the combination of dexmedetomidine and ketamine infusions

for a 15 year old female undergoing scoliosis repair surgery. It discussed the potential future for

these two medications in spine surgery in neurophysiologic monitoring. Evoked potentials were

not interrupted and in fact, with the addition of ketamine, motor-evoked potentials were

enhanced (Penney, 2010). Additionally, analgesia properties of both medications presented an

avenue for supplementary pain relieving methods.

Relatedly, Nama, Meenan, & Fritz (2010), examined a case report of a 47 year old female

suffering from complex regional pain syndrome whom was also treated with the combination of

dexmedetomidine and ketamine infusions. This combined infusion was given for 19 hours to

which the patient experienced complete relief of pain due to the synergist analgesic effect while

eliminating the negative side effects of both medications (Nama et al., 2010). All in all, ketamine


20

as an adjunct to dexmedetomidine and spine surgery would assist in providing additional

analgesia coverage especially for those opioid dependent individuals but warrants additional

research.

However, the many positive effects of dexmedetomidine, it is still necessary to

continually assess the patient for negative side effects such as hypotension and bradycardia

(Garg et al., 2016). Ketamine may also be helpful in countering these negative side effects.

Tachycardia, increases in blood pressure, and cardiac output are common with ketamine,

preventing hypotension and bradycardia from dexmedetomidine (K. H. Kim, 2014; Tobias,

2012). Likewise, dexmedetomidine prevents tachycardia, hypertension, and salivation associated

with ketamine (K. H. Kim, 2014; Tobias, 2012).

Similarly, many studies have evaluated dexmedetomidine and ketamine use in procedural

sedation among the pediatric population. For example, Tobias (2012) reviews four large case

series (n >10) and eight small (n <10) or single case series involving dexmedetomidine-ketamine

infusions for procedural sedation with infants and children. It was also found that the

combination of ketamine and dexmedetomidine offset the negative side effects of both

medications.

Bronchodilatory properties are also present with ketamine as well as allows maintenance

of respiratory drive and airway reflexes. To note, ketamine is contraindicated in ischemic heart

disease, hypertension (pulmonary/systemic), elevated intracranial pressure, elevated intraocular

pressure, globe injuries, psychosis, hepatic dysfunction, liver transplant, porphyria,

pheochromocytoma, and seizure patient populations (Gorlin et al., 2016). As previously

discussed, the case report patient did not receive adjunct intravenous ketamine due to the

patient’s history of seizures.


21

Like dexmedetomidine and ketamine, lidocaine may also deliver supplementary pain

relief especially for those individuals whom suffer from chronic pain and opioid use. Lidocaine,

a sodium channel blocker, may also assist in pain management as an adjunct to

dexmedetomidine. When administered intravenously, lidocaine provides anti-inflammatory,

analgesic, and anti-hyperanalgesic properties (Farag et al., 2013). A randomized control trial

consisting of 116 adults undertaking complex spine surgery were evaluated on pain, opioid

consumption, and quality of life following surgery (Farag et al., 2013). One group received

intravenous lidocaine intraoperatively and during the post-anesthetic care unit at a rate of 2

mg/kg/hr or received a placebo (Farag et al., 2013). Those individuals belonging to the lidocaine

group voiced improved pain scores in comparison to the placebo group (Farag et al., 2013).

Likewise, in 2014, a randomized control trial of 80 patients undergoing a laparoscopic

cholecystectomy were placed into two groups: opioid-free anesthesia (dexmedetomidine,

lidocaine, and propofol infusions) and opioid-based anesthesia (remifentanil and propofol

infusions) (Bakan et al.). The authors concluded that opioid-free anesthesia had considerably

lower pain ratings, consumption of rescue analgesics, and less antiemetic use (Bakan et al.,

2014).

Similarly, another study that evaluated lidocaine as an adjunct infusion to total

intravenous anesthesia with propofol-sufentanil was a retrospective review 129 cases whom

underwent spine surgery (Sloan, Mongan, Lyda, & Koht, 2014). It was discovered that sufentanil

and propofol dosages were decreased among groups receiving the lidocaine adjunct, specifically

five 5-ml ampules of sufentanil and one hundred and four 50-ml bottles of propofol (Sloan et al.,

2014).


22

Additionally, 51 lumbar surgical patients were included in a randomized, double-blinded,

placebo-controlled trial evaluating the effect of lidocaine on postoperative pain (K. T. Kim et al.,

2014). With the use of a lidocaine infusion pre- and intraoperatively, for up to 48 hours pain

post-operatively was reduced as well as opioid consumption for 24 hours following surgery (K.

T. Kim et al., 2014). To note, lidocaine should be avoided among individuals that have a

hypersensitivity to amide local anesthetics.

All evidence considered, great possibility is among these adjuncts for additional pain

management medications, however, more research is needed in this topic of adjunct use with

dexmedetomidine.

Evidence Based Recommendations

Practice.

Method of Anesthetic. Propofol is superior over volatile anesthetics as there is less

potential of interruption of SSEPs and MEPs (Rozet et al., 2015). Specifically, MEPs are easily

depressed with volatile anesthetics (Mahmoud et al., 2010). Therefore, it is suggested that

volatile anesthetics are avoided and total intravenous anesthesia is recommended during spine

surgeries when evoked potentials are used (Bithal, 2014; Mahmoud et al., 2010; Rozet et al.,

2015). However, a combination of volatile anesthesia with intravenous anesthesia is still

possible. Approach each case individually and communicate with the neurophysiological team

regarding the goals for monitoring. For example, if only SSEPs are to be conducted, evoked

potentials can generally still be accurately monitored if the minimum alveolar concentration is

less than 1.5 (isoflurane) or less than 1.0 (desflurane or sevoflurane) (Bithal, 2014). Likewise,

when MEPs are implemented, a lower MAC should be maintained at 0.5 or less to avoid

hindrance (Bithal, 2014). Maintaining a MAC of 0.5 or less is would allow either SSEPs or


23

MEPs to be safely monitored. Also, consider induction paralytic for intubation. Again, open

communication with the neurophysiologic team is vital to prevent inaccurate readings. Discuss

when MEPs will be applied and consider duration of action of paralytic during intubation.

Administration of Dexmedetomidine. An infusion of dexmedetomidine is to not exceed

24 hours. It is recommended to administer a dexmedetomidine loading dose of 1 mcg/kg over 10

minutes and prior to starting a continuous infusion of 0.2 mcg/kg/hour to 1 mcg/kg/hour to avoid

significant hypotension and bradycardia (Garg et al., 2016; Hospira, 2016). Most importantly,

incorporating dexmedetomidine into an anesthetic plan should be individualized and not

generalized to all patient populations.

Adjuncts. Intravenous opioids minimally alter SSEPs and MEPs and may be safely used

as continuous infusions during neurophysiologic monitoring (Bithal, 2014). Although more

research is needed, regarding ketamine dosing with the use of dexmedetomidine; sub-anesthetic

of plain ketamine for perioperative analgesia is suggested by Gorlin et al. (2016). Dosing is

based on length of case and if the patient will continue to receive ketamine post-operatively

(Gorlin et al., 2016). If the surgical case is less than 60 minutes, 0.1-0.3 mg/kg IV bolus is

recommended with induction (Gorlin et al., 2016). If the case is longer than 60 minutes and there

is no plan for a postoperative infusion of ketamine, 0.1-0.3 mg/kg IV bolus with induction and

0.1-0.3 mg/kg repeated every 30-60 minutes but avoid re-dosing within 30 minutes of emergence

(Gorlin et al., 2016). If the patient will be receiving a ketamine infusion post-operatively, 0.1-0.3

mg/kg IV bolus with induction then infused continuously at a rate of 0.1-0.2 mg/kg/hr and may

continue infusing for 24-72 hours (Gorlin et al., 2016). Once 24 hours is achieved with the

continuous ketamine infusion, it is suggested to reduce infusion dose to 10 mg/hour or less

(Gorlin et al., 2016). According to numerous studies, lidocaine loading dose during induction is


24

1.5 mg/kg and recommended maintenance continuous infusion dose ranged from 1.5 to 2

mg/kg/hr (Bakan et al., 2014; Farag et al., 2013; Harsoor et al., 2015; K. T. Kim et al., 2014).

Anterior cervical discectomy and fusion. During the pre-operative period, every patient,

but especially individuals undergoing spine surgery should be assessed for pre-operative

neurologic signs and symptoms and the anesthesia provider should document these deficits (Jaffe

et al., 2014). Also assess and document the patient’s neck range of motion, note if there is pain

present with manipulation. Head movement should be limited with airway manipulation and

securement during intubation and intraoperatively (Jaffe et al., 2014). Due to the area of the

surgical field of an anterior cervical discectomy and fusion, edema may be present and it is

recommended to ensure the patient reaches awake extubation criteria (Jaffe et al., 2014).

Methods to assess airway patency prior to extubation include deflating the cuff with the

endotracheal tube remaining in the trachea and assess air movement around the endotracheal

tube or a bougie or placement of an airway exchange device preceding to extubation (Jaffe et al.,

2014). Additionally, the patient’s arms are tucked and limits intravenous access to the anesthesia

provider so ensure the intravenous catheter is infusing adequately following repositioning of the

arms.

Research. There is lack of research regarding the prevalence of myelomalacia. In

addition, the combined use of intravenous dexmedetomidine-ketamine, dexmedetomidine-

lidocaine, and dexmedetomidine-ketamine-lidocaine intraoperatively is lacking and warrants

additional evidence especially amid the adult population. Also, bradycardia is more common

following the loading dose (Blaudszun, Lysakowski, Elia, & Tramèr, 2012). This suggests the

omission of the dexmedetomidine bolus may be advantageous in preventing bradycardia.

However, additional evidence is needed for this finding to be generalizable.


25

Conclusion

In summary, anesthetic (intravenous and volatile) and opioid requirements during spine

surgery are decreased due to the analgesic and synergistic sedative properties that are present

within dexmedetomidine. Dexmedetomidine is a great adjunct to use for spine surgery to

enhance safety intraoperatively and increase patient satisfaction postoperatively. Ketamine and

lidocaine may also assist in further pain control.

Of course, the administration of dexmedetomidine should be evaluated by the anesthesia

professional in an individualized manner and carefully monitored. Further research would be

beneficial in the practice of dexmedetomidine in other procedures or surgeries. Disseminating

the benefits of dexmedetomidine, practice recommendations, and current research will improve

anesthetic practice as well as patient outcomes.


26

References

Anttila, M., Penttilä, J., Helminen, A., Vuorilehto, L., & Scheinin, H. (2003). Bioavailability of

dexmedetomidine after extravascular doses in healthy subjects. British Journal of Clinical

Pharmacology, 56(6), 691–693. http://doi.org/10.1046/j.1365-2125.2003.01944.x

Arain, S. R., Ruehlow, R. M., Uhrich, T. D., & Ebert, T. J. (2004). The efficacy of

dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery.

Anesthesia and Analgesia, 98(1), 153–158.

http://doi.org/10.1213/01.ANE.0000093225.39866.75

Bakan, M., Umutoglu, T., Topuz, U., Uysal, H., Bayram, M., Kadioglu, H., & Salihoglu, Z.

(2014). Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and

lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-

blinded study. Brazilian Journal of Anesthesiology (English Edition), 65(3), 191–9.

http://doi.org/10.1016/j.bjane.2014.05.001

Basques, B. A., Bohl, D. D., Golinvaux, N. S., Gruskay, J. A., & Grauer, J. N. (2014).

Preoperative factors affecting length of stay after elective ACDF with and without

corpectomy: a multivariate analysis of an academic center cohort. Spine, 39(12), 939–946.

http://doi.org/10.1016/j.micinf.2011.07.011.Innate

Bithal, P. (2014). Anaesthetic considerations for evoked potentials monitoring. Journal of

Neuroanaesthesiology and Critical Care, 1(1), 2–12. http://doi.org/10.4103/2348-

0548.124832

Blaudszun, G., Lysakowski, C., Elia, N., & Tramèr, M. R. (2012). Effect of Perioperative

Systemic α2 Agonists on Postoperative Morphine Consumption and Pain Intensity.

Anesthesiology, 116(6), 1312–1322. http://doi.org/10.1097/ALN.0b013e31825681cb


27

Dunn, L. K., Durieux, M. E., & Nemergut, E. C. (2016). Non-opioid analgesics: Novel

approaches to perioperative analgesia for major spine surgery. Best Practice and Research:

Clinical Anaesthesiology, 30(1), 79–89. http://doi.org/10.1016/j.bpa.2015.11.002

Farag, E., Ghobrial, M., Sessler, D. I., Dalton, J. E., Liu, J., Lee, J. H., … Kurz, A. (2013).

Administration on pain, opioid consumption, and quality of life after complex spine

surgery. Anesthesiology, 119(4), 932–940.

Garg, N., Panda, N. B., Gandhi, K. A., Bhagat, H., Batra, Y. K., Grover, V. K., & Chhabra, R.

(2016). Comparison of Small Dose Ketamine and Dexmedetomidine Infusion for

Postoperative Analgesia in Spine Surgery—A Prospective Randomized Double-blind

Placebo Controlled Study. Journal of Neurosurgical Anesthesiology, 28(1), 27–31.

http://doi.org/10.1097/ANA.0000000000000193

Gorlin, A., Rosenfeld, D., & Ramakrishna, H. (2016). Intravenous sub-anesthetic ketamine for

perioperative analgesia. Journal of Anaesthesiology Clinical Pharmacology, 32(2), 160.

http://doi.org/10.4103/0970-9185.182085

Harsoor, S., Devika Rani, D., Roopa, M. N., Lathashree, S., Sudheesh, K., & Nethra, S. S.

(2015). Anesthetic sparing effect of intraoperative lignocaine or dexmedetomidine infusion

on sevoflurane during general anesthesia. Middle East Journal of Anesthesiology, 23(3),

301–307.

Harsoor, S., Rani, D., Lathashree, S., Nethra, S. S., & Sudheesh, K. (2014). Effect of

intraoperative Dexmedetomidine infusion on Sevoflurane requirement and blood glucose

levels during entropy-guided general anesthesia. Journal of Anaesthesiology, Clinical

Pharmacology, 30(1), 25. http://doi.org/10.4103/0970-9185.125693

Hessler, C., Boysen, K., Regelsberger, J., Vettorazzi, E., Winkler, D., & Westphal, M. (2012).


28

Patient satisfaction after anterior cervical discectomy and fusion is primarily driven by

relieving pain. The Clinical Journal of Pain, 28(5), 398–403.

http://doi.org/10.1097/AJP.0b013e318232cddc

Hospira. (2016). Precedex (dexmedetomidine): highlights of prescribing information. Retrieved

from https://www.hospira.com/en/images/EN-4271_tcm81-92504.pdf

Jaffe, R., Schmiesing, C., & Golianu, B. (2014). Anesthesiologist’s Manual of Surgical

Procedures (5th ed.). Philadelphia, PA: Wolters Kluwer.

Jamaliya, R. H., Chinnachamy, R., Maliwad, J., Deshmukh, V. P., Shah, B. J., & Chadha, I. a.

(2014). The efficacy and hemodynamic response to Dexmedetomidine as a hypotensive

agent in posterior fixation surgery following traumatic spine injury. Journal of

Anaesthesiology, Clinical Pharmacology, 30(2), 203–7. http://doi.org/10.4103/0970-

9185.130021

Kim, K. H. (2014). Safe sedation and hypnosis using dexmedetomidine for minimally invasive

spine surgery in a prone position. Korean Journal of Pain, 27(4), 313–320.

http://doi.org/10.3344/kjp.2014.27.4.313

Kim, K. T., Cho, D. C., Sung, J. K., Kim, Y. B., Kang, H., Song, K. S., & Choi, G. J. (2014).

Intraoperative systemic infusion of lidocaine reduces postoperative pain after lumbar

surgery: A double-blinded, randomized, placebo-controlled clinical trial. Spine Journal,

14(8), 1559–1566. http://doi.org/10.1016/j.spinee.2013.09.031

Kim, C. H., Lee, J. S., Kim, Y. J., Kim, M. D., & Han, D. W. (2013). Comparison of the efficacy

of dexmedetomidine plus fentanyl patient-controlled analgesia with fentanyl patient-

controlled analgesia for pain control in uterine artery embolization for symptomatic fibroid

tumors or adenomyosis: A prospective, randomized st. Journal of Vascular and


29

Interventional Radiology, 24(6), 779–786. http://doi.org/10.1016/j.jvir.2013.02.034

Laskowski, K., Stirling, A., McKay, W. P., & Lim, H. J. (2011). A systematic review of

intravenous ketamine for postoperative analgesia. Canadian Journal of Anesthesia, 58(10),

911–923. http://doi.org/10.1007/s12630-011-9560-0

Loftus, R. W., Yeager, M. P., Clark, J. A., Brown, J. R., Abdu, W. A., Sengupta, D. K., & Beach,

M. L. (2010). Intraoperative Ketamine Reduces Perioperative Opiate Consumption in

Opiate-dependent Patients with Chronic Back Pain Undergoing Back Surgery. PAIN

MEDICINE Anesthesiology, 113(3), 639–46.

http://doi.org/10.1097/ALN.0b013e3181e90914

Mahmoud, M., Sadhasivam, S., Salisbury, S., Nick, T. G., Schnell, B., Sestokas, A. K., …

McAuliffe, J. (2010). Susceptibility of transcranial electric motor-evoked potentials to

varying targeted blood levels of dexmedetomidine during spine surgery. Anesthesiology,

112(6), 1364–1373. http://doi.org/10.1097/ALN.0b013e3181d74f55

Mariappan, R., Ashokkumar, H., & Kuppuswamy, B. (2014). Comparing the effects of oral

clonidine premedication with intraoperative dexmedetomidine infusion on anesthetic

requirement and recovery from anesthesia in patients undergoing major spine surgery.

Journal of Neurosurgical Anesthesiology, 26(3), 192–197.

http://doi.org/10.1097/ANA.0b013e3182a2166f

Mion, G., & Villevieille, T. (2013). Ketamine Pharmacology: An Update (Pharmacodynamics

and Molecular Aspects, Recent Findings). CNS Neuroscience and Therapeutics, 19(6), 370–

380. http://doi.org/10.1111/cns.12099

Mizrak, A., Ganidagli, S., Cengiz, M. T., Oner, U., & Saricicek, V. (2013). The effects of DEX

premedication on volatile induction of mask anesthesia (VIMA) and sevoflurane


30

requirements. Journal of Clinical Monitoring and Computing, 27(3), 329–334.

http://doi.org/10.1007/s10877-013-9440-y

Nama, S., Meenan, D. R., & Fritz, W. T. (2010). The use of sub-anesthetic intravenous ketamine

and adjuvant dexmedetomidine when treating acute pain from CRPS. Pain Physician, 13(4),

365–368.

Penney, R. (2010). Use of dexmedetomidine and ketamine infusions during scoliosis repair

surgery with somatosensory and motor-evoked potential monitoring: a case report.

American Association of Nurse Anesthetists, 78(6), 446–450.

Potter, K., & Saifuddin, A. (2003). Pictorial review: MRI of chronic spinal cord injury. The

British Institute of Radiology, 76(905), 347–52. http://doi.org/10.1259?bjr/11881183

Rozet, I., Metzner, J., Brown, M., Treggiari, M. M., Slimp, J. C., Kinney, G., … Vavilala, M. S.

(2015). Dexmedetomidine does not affect evoked potentials during spine surgery.

Anesthesia and Analgesia, 121(2), 492–501.

http://doi.org/10.1213/ANE.0000000000000840

Sen, S., Chakraborty, J., Santra, S., Mukherjee, P., & Das, B. (2013). The effect of

dexmedetomidine infusion on propofol requirement for maintenance of optimum depth of

anaesthesia during elective spine surgery. Indian Journal of Anaesthesia, 57(4), 358–363.

http://doi.org/10.4103/0019-5049.118558

Sloan, T. B., Mongan, P., Lyda, C., & Koht, A. (2014). Lidocaine infusion adjunct to total

intravenous anesthesia reduces the total dose of propofol during intraoperative

neurophysiological monitoring. Journal of Clinical Monitoring and Computing, 28(2), 139–

147. http://doi.org/10.1007/s10877-013-9506-x

Smorgick, Y., Tal, S., Yassin, A., Tamir, E., Mirovsky, Y., & Anekstein, Y. (2015). The relation


31

between location of cervical cord compression and the location of myelomalacia. Skeletal

Radiology, 44(5), 649–652. http://doi.org/10.1007/s00256-014-2074-4

Tobias, J. D. (2012). Dexmedetomidine and ketamine. Pediatric Critical Care Medicine, 13(4),

423–427. http://doi.org/10.1097/PCC.0b013e318238b81c

Weerink, M., Struys, M., Hannivoort, L., Barends, C., Absalom, A., & Colin, P. (2017). Clinical

Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clinical

Pharmacokinetics, 1–17. http://doi.org/10.1007/s40262-017-0507-7

Yamashita, T., Takahashi, K., Yonenobu, K., & Kikuchi, S. (2014). Prevalence of neuropathic

pain in cases with chronic pain related to spinal disorders. Journal of Orthopaedic Science :

Official Journal of the Japanese Orthopaedic Association, 19(1), 15–21.

http://doi.org/10.1007/s00776-013-0496-9

Yoo, H., Iirola, T., Vilo, S., Manner, T., Aantaa, R., Lahtinen, M., … Jusko, W. J. (2015).

Mechanism-based population pharmacokinetic and pharmacodynamic modeling of

intravenous and intranasal dexmedetomidine in healthy subjects. European Journal of

Clinical Pharmacology, 71(10), 1197–1207. http://doi.org/10.1007/s00228-015-1913-0

Zhou, Y., Kim, S. D., Vo, K., & Riew, K. D. (2015). Prevalence of Cervical Myelomalacia in

Adult Patients Requiring a Cervical Magnetic Resonance Imaging. Spine, 40(4), E248–

E252. http://doi.org/10.1097/BRS.0000000000000718


32

Appendix A


33


34


35

utilizing dexmedetomidine during an anterior cervical

Documents