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J. Wahidi and J. R. Zuniga
a
b
c
Fig. 22.3 (a) Class III Injury: 62-year-old female 2.5months with painful neuropathy left IAN
following dental implant #18 site with clinical NST consistent with Class III injury. MRN ndings– Left inferior alveolar neuropathy with mild scar entrapment at the prior dental extraction
site. (b) Diffusion tensor imaging (DTI) of the same injury showing abnormal anisotropy of the left
inferior alveolar nerve. (c) Left inferior alveolar nerve on neuropathy showing abnormal, erythematous changes consistent with class III injury
ab
Fig. 22.4 (a) Class IV Injury: 45-year-old female s/p 2months #17 extraction with severe sensory
impairment, positive trigger, dystrophic ageusia, and burning, consistent with Class IV injury left
lingual nerve. MRN ndings: Sunderland class IV/V injury of the left lingual nerve. Minimal
hyperintensity of the left inferior alveolar nerve is probably reactive granulation tissue at the tooth
extraction site. (b). Left lingual nerve injury showing large neuroma with continuity consistent
with a Class IV injury
22 The Evolution of Magnetic Resonance Neurography in Imaging of the Trigeminal…
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397
ab
Fig. 22.5 (a) Class V Injury: 27-year-old female 1week s/p attempted removal #32 with local,
procedure aborted but complete anesthesia of right tongue reported. Unable to perform NST due
to painful trismus. MRN ndings: Lingual nerve: Abnormally enlarged and hyperintense on the
right without appreciable distal continuity. Sunderland class V injury of the right lingual nerve. (b)
Right lingual nerve exposure showing the proximal and distal ends separated consistent with a
Class V injury
Imaging inDifferent Clinical Scenarios
Future Directions
As described, the application of MR neurography in oral and maxillofacial surgery
can gather noninvasive, qualitative information of the IAN and LN, further augmenting the diagnostic acumen of the surgeon. It was also shown that limitations
currently exist regarding the ability of MRN to provide meaningful quantitative
information with nerve gap size. For surgeons to benet from this newer imaging
modality, further investigations with randomized clinical trials must be completed
to solidify the relationship between MRN ndings and the varying degrees of trigeminal neuropathy in the preinjury, postinjury, and post-repair state. Adjunctive
MRN imaging techniques such as fractional anisotropy and diffusion coefcient
alterations can aid further quantication of trigeminal neuropathy but require future
study. As always, imaging ndings and analysis should be an aid to surgical experience, tempered by experienced clinical judgment.
References
1. Mitchell SW, Morehouse GR, Keen WW.The classic: gunshot wounds and other injuries of
nerves. Clin Orthop Relat Res. 2007;458:35–9.
2. Zuniga JR, Mistry C, Tikhonov I, Dessouky R, Chhabra A.Magnetic resonance neurography
of traumatic and nontraumatic peripheral trigeminal neuropathies. J Oral Maxillofac Surg.
2018;76(4):725–36.
3. Zuniga JR, Meyer RA, Gregg JM, Miloro M, Davis LF.The accuracy of clinical neurosensory
testing for nerve injury diagnosis. J Oral Maxillofac Surg. 1998;56(1):2–8.
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4. Dessouky R, Xi Y, Zuniga J, Chhabra A.Role of MR Neurography for the diagnosis of peripheral trigeminal nerve injuries in patients with prior molar tooth extraction. Am J Neuroradiol.
2017;39(1):162–9.
5. Zuniga JR, AbdelBaky O, Alian A, Thakur U, Pezeshk P, Xi Y, Chhabra A.Does presurgical
magnetic resonance neurography predict surgical gap size in trigeminal class IV and V injuries? J Oral Maxillofac Surg. 2021;79(12):2574–81.
J. Wahidi and J. R. Zuniga
Chapter 23
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Advancements andInnovations inOfce
Anesthesia: Novel Drugs andInfusion
Combinations forOfce-Based
Intravenous Sedation
AlfredoArribas, DominikRudecki, StevenHengen, andIssaHanna
Introduction
In the eld of modern dentistry and oral and maxillofacial surgery, ofce-based
procedural sedation with modern anesthetic medications is utilized to provide
patients and providers with safe and predictable outpatient anesthesia outcomes.
The 2016 American Association of Oral and Maxillofacial Surgeons (AAOMS)
White Paper on Ofce-Based Anesthesia asserts that “fearful patients, who are often
in pain, are effectively, economically, and safely managed in the oral and maxillofacial surgery ofce with the use of deep sedation/general anesthesia that frequently
incorporates agents such as propofol and/or ketamine” [1]. The AAOMS’ 2017
Parameters of Care lists several goals of outpatient anesthesia including satisfactory
experience for the surgeon and patient and full recovery from anesthetic effects
within an appropriate time [2]. Though current day anesthetics and techniques have
provided advances in successfully implementing the goals of outpatient anesthesia
care, the road to present-day successes in ofce-based procedural sedation has been
long. We owe thanks to many pioneering professionals past and present as we continually seek to improve outcomes and experiences for ourselves and our patients.
Arguably the most signicant historical advancement in the management of the
surgical patient has been the discovery and application of anesthesia. Boyle was rst
credited with the experimentation with intravenous injections in 1656 [3].
Sir Christopher Wren would later go on to write in a letter “I Have Injected Wine
and Ale in a living Dog into the Mass of Blood by a Veine, in good Quantities, till I
have made him extremely drunk, but soon after he Pisseth it out” [4].
A. Arribas · D. Rudecki · S. Hengen · I. Hanna (*)
Department of Oral and Maxillofacial Surgery, UTHealth Houston, Houston, TX, USA
e-mail: alfredo.r.arribas@uth.tmc.edu; dominik.a.rudecki@uth.tmc.edu;
steven.l.hengen@uth.tmc.edu; issa.a.hanna@uth.tmc.edu
© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
J. C. Melville et al. (eds.), Advancements and Innovations in OMFS, ENT, and
Facial Plastic Surgery, https://doi.org/10.1007/978-3-031-32099-6_23
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Two centuries later in October 1846, Boston dentist Dr. Morton was looking for
alternatives to the already used nitrous oxide anesthetic. He teamed up with
Massachusetts General Hospital surgeon John Collins Warren to perform the rst
public display of a procedure successfully completed under anesthesia. At which
time history attributes Dr. Warren proclaiming “Gentlemen! this is no humbug” [5].
From the 1920s to the mid-1950s, the primary sedatives/hypnotic drugs were
barbiturates [6]. Fortunately, the subsequent decades brought the anesthesia community short-acting anesthetics that included benzodiazepines like midazolam, narcotics like fentanyl, hypnotic sedatives, namely, propofol, and dissociative
anesthetics, namely, ketamine. These noted agents, in some combination, have
become the basis for most ofce-based anesthetics.
In present-day anesthesia, we now have a full array of volatile and intravenousbased anesthetics that meet specic patient needs providing therapeutic outcomes
with relative safety. This chapter intends to review current anesthetic drugs, as well
as anesthetic drug infusion combinations that can assist the clinician in providing
safe and effective outpatient ofce-based anesthesia.
A. Arribas et al.
Remifentanil
Remifentanil is a relatively new opioid, receiving FDA approval in 1996 for applications in general anesthesia, monitored anesthesia care, and short-term postoperative analgesia in PACU.Remifentanil is a pure (mu) opioid receptor agonist, with
little effect on the other opioid receptors. It is characterized by rapid onset and
ultrashort, predictable duration of action. The onset of clinical effect is typically
60–90s. The context-sensitive half-time of elimination is approximately 3min from
discontinuation, regardless of duration of infusion [7]. Remifentanil displays unique
metabolism among opioids, involving rapid and uniform clearance by nonspecic
blood and tissue esterases [8]. The desirable result is twofold; rst, a rapid recovery,
typically 5–10min. Second, the duration of action of remifentanil does not increase
with increasing duration of administration because of the lack of drug accumulation. These unique properties have made remifentanil an attractive adjunct for inpatient, outpatient, and in-ofce surgical procedures.
Remifentanil is packaged in 1mg, 2mg, and 5mg vials which are reconstituted
and diluted before administration. When used for induction of anesthesia in adult
patients, remifentanil is infused at 0.5–1μg/kg/min along with a hypnotic or gas
anesthetic. For maintenance of anesthesia with propofol, remifentanil is given in a
continuous infusion at a rate of approximately 0.25μg/kg/min (range 0.05–2.0μg/
kg/min). A 1μg/kg supplemental bolus dose can be used during episodes of intense
surgical stress or in response to light anesthesia. When remifentanil is used for analgesia in the immediate postoperative period, a continuous infusion of 0.1μg/kg/min
(range 0.025–0.2μg/kg/min) is appropriate [8].
While typically given in conjunction with other anesthetic agents, remifentanil’s
unique pharmacokinetic properties also make it an effective solo agent when given
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as an infusion for select conscious sedation procedures. In a study of 90 patients
undergoing facial surgery, Ferraro etal. showed that remifentanil as a single agent
was better tolerated, provided superior pain control, and displayed more hemodynamic stability when compared to midazolam or propofol as single agents. Their
protocol included 0.08μg/kg/min of remifentanil before administration of local
anesthesia and either blepharoplasty or otoplasty. Remifentanil did not cause respiratory depression in any patients, likely because this adverse effect is more likely
seen with bolus administration [9].
Remifentanil’s short duration of action has also made it increasingly popular for
use as a single agent in emergency departments for procedures including lumbar
punctures, cardioversion, orthopedic manipulation, incision and drainage, and chest
tube placement [10]. Patients can rapidly undergo these procedures, recover within
10min, and undergo a reliable neurological examination.
Adverse effects of remifentanil are similar to other opioids. Remifentanil has
been shown to cause dose-dependent hypotension and bradycardia up to 2μg/kg
within 3–5min of a bolus or an infusion rate increase. When this response is clinically undesirable, it can be reversed relatively quickly by reduction of rate of infusion. Dose-dependent respiratory depression is an effect common to remifentanil
and other similar opioids and is clinically relevant to the oral and maxillofacial
surgeon. Recovery of respiratory drive after discontinuation of remifentanil is signicantly faster than fentanyl and other opioids. After discontinuation of a 0.25μg/
kg/min infusion of remifentanil, the blood level at which spontaneous respiration
occurs is achieved in 2–4min [11]. When co-administered with other anesthetic
agents such as propofol, the recovery depends on the other agent. As with other
opioids, chest wall rigidity is possible with the administration of remifentanil, particularly when given in boluses.
Remifentanil is an effective and efcient drug in the modern oral and maxillofacial surgeon’s toolbox, most often used with other agents such as midazolam and/or
propofol which will be discussed in subsequent sections.
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Dexmedetomidine
Dexmedetomidine was initially approved by the Food and Drug Administration for
sedation, in 1999, for use as a short-term medication (within 24h) for analgesia and
sedation in intubated and mechanically ventilated patients in an ICU setting. In
2008, the FDA approved a new indication for non-intubated patients requiring sedation before and/or during diagnostic and therapeutic procedures.
Dexmedetomidine is an intravenous α2-adrenergic receptor agonist that provides
anxiolysis, sedation, and analgesia but with a decreased risk of respiratory depression [12]. The α-2 adrenergic receptor agonists were rst used as nasal decongestants and soon after were used for the treatment of hypertension and withdrawal
symptoms. The sedative and amnesic qualities of this drug class motivated interest
in its use as an anesthetic adjuvant [12–14].
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A. Arribas et al.
Dexmedetomidine, the pharmacologically active dextro isomer of medetomidine, has an imidazoline structure and is a potent and selective agonist of the α-2
adrenoceptor. It acts on the α-2 receptors in the locus coeruleus, in contrast to other
sedatives (e.g., midazolam and propofol) which act on GABA receptors/cerebral
cortex. Dexmedetomidine has a context-sensitive half-time similar to that of fentanyl, with distribution and elimination half-lives of 6min and 2h, respectively. It
is bio-transformed in the liver and excreted primarily in urine. It shows eight times
greater selectivity for α-2 than α-1 receptors and is considered a full agonist when
compared to clonidine, the prototypic representative of the α-2 adrenergic receptor
agonists drug class. It has demonstrated dose-dependent sympatholytic, sedative,
anxiolytic, and analgesic properties in human volunteers and when administered in
the perioperative period has been shown to reduce the dose requirements of other
anesthetics and attenuate the sympathetic response to stressful events [15].
Its sedative actions resemble physiologic sleep and have been shown to produce
sedation most similar to natural sleep. That is why stimulation facilitates awakening
even during continuous administration, making dexmedetomidine a popular choice
of sedative agent in the intensive care unit, allowing intubated patients to tolerate
mechanical ventilation yet remain easily roused to cooperate with necessary procedures. The OMS outpatient setting involves treatment with constant stimuli making
the quality of sedation with dexmedetomidine a weak point in treatment. The presence of stimuli in OMS procedures could also be the reason that intravenous sedation with dexmedetomidine alone for dental treatment may show less potent
amnestic effects compared with conventional methods like benzodiazepines [16]
and would explain the difculty to evaluate sedation based on bispectral index (BIS)
monitoring. Fan etal. noted that when a patient happened to doze during the loading
infusion, they were often wakened by their own snoring. During the local anesthetic
injections and dental extractions, however, many patients were stimulated to the
point of being awake and aware, with BIS scores rapidly returning to the 90s [17].
The drug has been shown to have signicant respiratory stability and preserve
respiratory rate and oxygen saturation [12, 14]. Slight respiratory depression, less
intense than that related to propofol, is one of its characteristics. Dexmedetomidine
has proven effective in attenuating airway reex responses and maintaining hemodynamic stability without prolonging recovery [18]. Smiley and Prior state that
patients who are likely to benet from sedation with dexmedetomidine are those
who cannot tolerate respiratory depression and those who need protection from catecholamine release and the resultant tachycardia and hypertension [16].
It has been reported dexmedetomidine causes cardiovascular side effects such as
hypertension and bradycardia. It induces peripheral vasoconstriction due to α-2B
receptor stimulation and increases blood pressure. It has also been reported to
decrease blood pressure and cause bradycardia, via inhibition of the sympathetic
nervous system and activation of the parasympathetic nervous system in the presence of α-2A receptor stimulation. Increases in blood pressure can be seen on initial
loading, during which the blood concentration of this agent rapidly increased.
During maintenance, circulatory depression can be seen frequently. Therefore,
close monitoring is needed [20].
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403
Caution should be taken in patients with low ventricular ejection fraction (≤30%)
and heart block, as an episode of sinus arrest associated with dexmedetomidine use
has been reported [19].
Because dexmedetomidine has no selectivity for α-2A/α-2B receptors, blood
pressure changes are not constant.
The manufacturer-recommended dosage is a 1.0μg/kg infusion over 10min, followed by a loading dose of 0.2–0.7μg/kg/h to maintain the required level of sedation [21]. Studies in OMS have shown multiple variations of these recommendations,
where most of the studies considered the manufacturer recommended dosing, while
some try higher and lower doses. Studies have used dexmedetomidine as a single
agent and in combination with other sedative/analgesics [16, 20, 22, 24]. Intranasal
administration is another possible and effective route that was tried in some studies
but requires more research. A study comparing intranasal dexmedetomidine and
midazolam used a dose of 1.5 μg/kg of dexmedetomidine with satisfactory results
[24]. On sedative techniques and dosage, Smiley and Prior concluded that in the oral
surgery model, in which it is impossible to shield the surgical site from the patient,
the unpredictable sedative response of dexmedetomidine using xed dosages suggests a somewhat less practical approach versus traditional sedative techniques [16].
Dexmedetomidine is difcult to evaluate by bispectral index (BIS) monitoring
because during the preoperative period, patients exhibit stable sedation, but as external stimuli start, variability and overlap scores make precise measurement difcult.
Due to this variability and the fact that dexmedetomidine causes decreased HR and
SBP, some practitioners and studies preferred to use conventional monitoring methods to reach a more precise evaluation [25].
A systematic review by Ter Bruggen etal. showed that of the trials measuring
recovery time, 5 out of 13 studies (38.5%) reported a signicantly prolonged recovery time and one showed a signicantly reduced recovery time with dexmedetomidine. The recovery time is reduced if the infusion is stopped at an earlier moment
during the procedure. However, no differences in procedure duration were
found [26].
Other experiences have shown us that the addition of midazolam to dexmedetomidine in the outpatient setting can increases the total anesthesia time and recovery
time in an average of 15–20min each [16, 22].
A systematic review by Davoudi etal. concluded that most trials in the study
showed a signicantly lower level of pain with dexmedetomidine and a signicantly
higher level of patient satisfaction with dexmedetomidine [25]. When dexmedeto-
midine was compared to midazolam, statistically signicant amnesia and cognitive
impairment were present in the midazolam group when compared to the dexmedetomidine group [23], and the patients receiving dexmedetomidine alone were
more likely to report having remembered “the whole surgery” [16].
There is evidence to support dexmedetomidine as a potential sole or combination
sedative agent in the OMS outpatient setting. The sedative quality of dexmedetomidine and its easy arousability makes it a popular choice for the ICU setting but
might be a weakness in the OMS setting as a single agent. Patients who are likely to
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benet from sedation with dexmedetomidine are those who cannot tolerate respiratory depression and those who need protection from catecholamine release and the
resultant tachycardia and hypertension. For this patients, conventional monitoring is
still recommended. The manufacturer recommended loading dose of 1.0 μg/kg
intravenous infusion over 10min is proven to be effective to avoid any possible side
effects, like SpO2 desaturation or bradycardia [14].
Future research should examine in which procedures dexmedetomidine can be
used as a sole sedative agent in preference to other sedatives [26], and in which
procedures should be used as a part of a balanced sedation technique. The analgesic
and amnesic features of dexmedetomidine are still in some doubt, and more studies
are required to determine its effectiveness. Dexmedetomidine has remarkable sedative properties such as safety, amnesia effects, shorter recovery periods after sedation, and providing both surgeons’ and patients’ satisfaction [25].
A. Arribas et al.
Ketamine-Propofol Combination (Ketofol)
Ketamine and propofol are two sedative agents which are commonly used for procedural outpatient sedation. Both medications are routinely used either individually
or with addition of other medications. More recently, ketamine and propofol
admixes have been combined as “ketofol” and have been studied for their synergistic capacities and desired opposing properties.
Propofol is a sedative hypnotic agent, commonly used for induction in the operating room and as a sedative for procedural sedation or monitored anesthesia care.
It has a rapid onset and short duration of action with a smooth recovery [27]. Like
many general anesthetics, it acts by potentiating GABA-mediated chloride channels
in the brain, increasing the inhibitory neurotransmitter effects. It can be given as a
bolus or infusion or as a combination of the two. It possesses antiemetic and anxiolytic properties, which are very desirable for sedation. However, there are respiratory and hemodynamic compromises if used as a single agent. Due to a vasodilatory
and cardiodepressant properties, propofol can cause hypotension and bradycardia.
Also, it is associated with a dose-dependent respiratory depression, which can lead
to hypoventilation and hypoxia [28].
Ketamine is a nonbarbiturate dissociative anesthetic, acting as a noncompetitive
NMDA and glutamate receptor antagonist, producing profound anesthesia, amnesia, and analgesia. Ketamine is often used as a sole agent in pediatric patients for
short sedation procedures. It has a short onset of action, excellent potency, and rapid
recovery time. Ketamine maintains normal airway reexes, has bronchodilatory
properties, and is useful for patients with asthma or bronchospasm risk. However,
its cardiostimulant properties will increase in heart rate and blood pressure [29].
Ketamine also has some additional adverse effects that are undesirable for procedural sedation. By causing hypersalivation, ketamine can put patients at greater risk
of laryngospasm in an open-airway anesthesia setting. There is also an increase in
emergence phenomena, especially in adults, occurring in an estimated 10–20% of
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sedations. Finally, there is increased incidence of nausea and vomiting with ketamine with an incidence of 5–15% in adults [30].
The mixture of propofol with ketamine has been shown to take advantage of
many properties of both medications with fewer reported complications and
decreased dosage requirements of each drug. Meta-analyses have shown that ketofol reduces respiratory complications, hypotension, and bradycardia [31, 32].
Ketofol has been shown to not cause an increase in nausea/vomiting or psychomimetic complications compared to propofol alone.
Although the optimal proportion of propofol with ketamine has not been determined, studies have looked at various ratios of propofol to ketamine and compared
their side effects to propofol alone. A clinical trial by Cillo etal. demonstrated that
a ratio of 10:1 propofol to ketamine provided the greatest benet for continuous
intravenous general anesthesia with fastest time to recovery, compared to 5:1 and
3:1 ratios [33]. Another clinical trial also demonstrated that 1:1 mixtures had the
greatest number of agitation events during recovery, compared to 4:1 mixtures of
propofol to ketamine [34]. These studies suggest that higher proportion of ketamine
provides no advantage to the sedation and is therefore less desirable in mixture.
Thus, ketofol has shown to provide efcacious procedural sedation at lower
doses of each drug. The combination of the two drugs has been shown to offset each
other’s undesired properties. Ketamine blunts the hemodynamic and respiratory
effects of propofol, whereas propofol attenuates the nausea and sympathomimetic
properties of ketamine [35].
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Remifentanil-Propofol Combination (Remi-Prop)
The combination of the ultrafast-acting opioid remifentanil with the sedativehypnotic propofol has become increasingly popular for operating room and procedural sedation applications. Remifentanil offers sedative and powerful analgesic
effects with the highly desirable properties of fast onset and rapid recovery. Propofol
is a versatile agent, displaying rapid onset and rapid recovery from general anesthesia in addition to its antiemetic and amnestic properties. While there are those who
advocate a “propofol-only” approach to outpatient oral surgery, the most common
methods involve multiple drugs. A remifentanil-propofol combination lends itself to
rapid procedures common to the practice of oral and maxillofacial surgery.
Kramer et al. compared continuous infusions of propofol-remifentanil with
propofol- ketamine for deep sedation of 37 patients undergoing extraction of all 4
third molars. Both groups were given 0.03mg/kg midazolam, and the propofolremifentanil group was given a ratio of 10mg propofol to 5μg remifentanil per
milliliter. The propofol-ketamine group was given a ratio of 10mg propofol to
2.5 mg ketamine per milliliter. After a 500μg/kg bolus of the assigned propofol
combination, both groups were infused with propofol at 100μg/kg/min. Several outcomes were measured including emergence and recovery times, hemodynamic and
respiratory stability, and associated drug costs. Hemodynamic and respiratory
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