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The Efficacy of Preemptive Analgesia Using a Non-Opioid Alternative Therapy Regimen on Postoperative Analgesia Following Block Bone Graft Surgery of the Mandible: A Prospective Pilot Study in Pain Management in Response to the Opioid Epidemic Research Article

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Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
026
© 2019 - Medtext Publications. All Rights Reserved.
The Efcacy of Preemptive Analgesia Using a Non-Opioid
Alternative Therapy Regimen on Postoperative Analgesia
Following Block Bone Graft Surgery of the Mandible: A
Prospective Pilot Study in Pain Management in Response to
the Opioid Epidemic
Research Article
Cameron Y.S. Lee, DMD, MD, PHD, MPH1*, and Jon B. Suzuki, DDS, PHD, MBA2
1Private Practice in Oral, Maxillofacial and Reconstructive Surgery, Aiea, Hawaii 96701; Clinical Professor of Periodontology and Oral Implantology; Kornberg
School of Dentistry, Temple University, Philadelphia, PA 19140, USA
2Professor (Emeritus) of Microbiology and Immunology (School of Medicine); Professor (Emeritus) of Periodontology and Oral Implantology (School of Dentistry);
Kornberg School of Dentistry, Temple University, Philadelphia, PA 19140, USA
Citation: Lee CYS, Suzuki JB. The Efcacy of Preemptive Analgesia
Using a Non-Opioid Alternative Therapy Regimen on Postoperative
Analgesia Following Block Bone Graft Surgery of the Mandible: A
Prospective Pilot Study in Pain Management in Response to the Opioid
Epidemic. Clin J Pharmacol Pharmacother. 2019; 1(2): 1006.
Copyright: © 2019 Cameron Y.S. Lee
Publisher Name: Medtext Publications LLC
Manuscript compiled: Feb 13th, 2019
*Corresponding author: Cameron Y.S. Lee, DMD, MD, PHD,
MPH, Oral, Maxillofacial and Reconstructive Surgery, Department
of Periodontology/Oral Implantology, Kornberg School of Dentistry.
Temple University, 98-1247 Kaahumanu Street. Suite 314. Aiea, Hawaii
96701, USA, Tel: 808-484-2288; E-mail: CLee555294@aol.com
Abstract
Purpose: e authors examined whether a novel alternative treatment regimen that is opioid-free administered preemptively 3 days prior to block bone gra
surgery of the mandible has a preemptive analgesic eect on the intensity of pain at the gra harvest site during the 72-hour postoperative period.
Materials and methods: is qualitative prospective pilot study was conducted in a single oce in 2018. irty-four patients were randomly divided into two
groups: Group A (14 patients) were provided the opioid-free regimen three days prior to surgery; Group B (20 patients) were not provided the opioid-free
regimen, but only opioid analgesics. e primary outcome variable was pain intensity measured at the bone gra harvest site by each patient using a 10-point pain
intensity scale (PIS) from 0 (no pain) to 10 (worst pain possible). Secondary outcome variables measured were the total number of opioid rescue analgesics used
over a 72-hour postoperative period and the time interval to initial use of opioid analgesics to relieve the postoperative pain in both cohort groups. A P value less
than .05 was statistically signicant.
Results: Patients in Group A recorded lower pain intensity scores at all time intervals. e median time interval to use of the rst opioid rescue analgesic aer
surgery in Group A was 4.3-hours compared with 1.9 hours for patients in Group B. e average postoperative pain intensity score for Group A patients was
5.6 on the 0 to 10 PIS. e average number of opioid rescue analgesics consumed was 2.3 tablets per day over the 72-hour postoperative period. For Group B
patients, the average postoperative pain intensity score was 7.1 on the PIS and average number of opioid analgesics used was 3.8 tablets per day over the 72-hour
postoperative period.
Conclusions: e results of the study illustrate that postoperative pain intensity was lower in the group of patients with the opioid-free regimen when used
preemptively compared to the group of patients that did not receive the opioid-free regimen. Further, use of this novel treatment alternative in managing
postoperative pain resulted in less consumption of opioid analgesic medication and increased the time interval to rst use of an opioid analgesic. e results of
this pilot study support the need for novel alternative and complementary analgesic strategies.
Introduction
e opioid abuse, addiction, and overdose epidemic in the
United States is at a public health crisis and has caught the attention
of the Food and Drug Administration (FDA), National Institute of
Drug Abuse (NIDA), National Institutes of Health (NIH), Drug
Enforcement Agency (DEA), the Centers for Disease Control (CDC),
and medical and dental organizations such as the American Medical
Association (AMA), American Dental Association (ADA), and the
American Association of Oral and Maxillofacial Surgeons (AAOMS)
[1-5]. On October 26, 2017, President Donald Trump declared the
opioid crisis a national public health emergency under the federal
Public Health Services Act [6].
Opioid analgesics (synthetic variants of opium) have always been
important in the management of acute and chronic pain. But when
used by patients improperly the consequences can be unforgiving.
Aer marijuana, prescription painkillers are the second most abused
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Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
drug [7]. In 2016, greater than 11 million Americans misused
opioid drug prescriptions. Since 1994, deaths from opioid use more
than quadrupled and parallels the increased number of opioid
prescriptions [8-10]. In 2015, there were over 33,00 deaths reported
involving opioids.10 Further, over 2 million citizens are addicted to
opioids, In 2015, greater than 12 million reported misusing opioids.11
Such increased morbidity and mortality can also be attributed to
injudicious prescribing and has increased the spread of HIV and
hepatitis C infections and heroin use [11,12].
While in oce, former President Barrack Obama and his
administration did address the opioid epidemic as millions of dollars
were invested in drug treatment and monitoring programs. As part of
this call to action, the Centers for Disease Control developed guidelines
for clinicians in the prescribing of opioids [13]. However, the opioid
epidemic cannot be solved completely by our federal government.
Clinicians must also be held accountable [14]. In the American
Association of Oral and Maxillofacial Surgeons White Paper on
opioid prescribing for acute and postsurgical management, clinicians
should decrease the number of opioid drug prescriptions to control
the post-operative pain to reduce opioid misuse and abuse [15]. Most
important, clinicians can elect to prescribe non-opioid medications
as a safer alternative to opioid drugs to manage postsurgical pain and
avoid prescribing long-acting and extended release opioids.
Preemptive analgesia has received considerable attention in the
past few years. e goal of preemptive analgesia is to control and
decrease postsurgical pain when it is most intense prior to exposing
the patient to the surgical procedure [15]. is will reduce the reliance
of opioid analgesics to control the postoperative pain, lead to a faster
return to daily life activities and reduce the cost of overall patient
care [16,17]. Several clinical trials established that direct links with
preemptive analgesia decreases postsurgical pain resulting in less
dependence on pain medication and increased patient comfort and
satisfaction [18-23]. Acute pain is due to an inammatory cascade that
occurs in the tissues and results in chemical, mechanical and thermal
nociceptive stimuli from the surgical procedure [18,24]. Preemptive
analgesia attempts to inhibit nociceptive signals from peripheral and
central pain pathways that prevents release of chemical mediators,
such as histamine, substance P, bradykinin and prostaglandins that
results in primary hyperalgesia at the site of tissue injury and may last
for several hours aer tissue injury [15,18,25]. Hyperalgesia during
surgery in the oral cavity is due to peripheral sensitization of periosteal
and mucosal receptors from large amounts of prostaglandin release
that appears one hour aer the surgical procedure. is facilitates
peripheral and central sensitization before tissue trauma and injury
from the surgical procedure [26-28]. A reduction in sensitization
is believed to reduce postsurgical hyperalgesia, allodynia and the
magnitude and duration of postsurgical pain that could inuence the
need for rescue analgesics, post-surgically [18,25,27].
Although controversial regarding its eectiveness in controlling
postsurgical pain, preemptive analgesia has been studied in the surgical
removal of impacted third molars with dierent pharmacologic agents
because of the moderate to severe patient response to pain that occurs
6 to 8 hours, postsurgery [16,17,19-21,23]. However, the severity of
postsurgical pain aer harvesting monocortical blocks of bone from
the posterior mandible and ramus in preparation for placement of
dental implants in the jaws has not b een studied. e painful stimuli of
so tissues due to periosteal and muscle dissection and ultimately, the
osteotomy to harvest the block of bone from the posterior mandible
will cause moderate to severe postoperative pain and swelling.
Interestingly, current research with opioids in preemptive
analgesia has revealed minimal clinical ecacy in controlling
postsurgical pain [25,28]. Because of the opioid epidemic, the authors
evaluated a novel opioid-free alternative treatment regimen during
the preemptive analgesic stage to control postoperative pain at the
bone gra harvest site at the ascending ramus and posterior mandible
in preparation for dental implant surgery. Like removal of impacted
mandibular third molar teeth and orthognathic surgery that requires
advanced surgical skill and can be challenging even for experienced
surgeons, the postoperative recovery observed in the maxillofacial
region from harvesting bone from the mandible is associated with an
acute inammatory response that includes pain, bleeding, so tissue
edema and ecchymosis [29,30]. For the surgical patient who completes
any of these surgical procedures, the rst 24 hours aer surgery
are considered the most excruciating. As an anesthesia strategy,
preemptive analgesia may decrease the pain intensity associated with
block bone gra surgery and decrease the number of opioid analgesics
during the postoperative recovery period.
e VEGA Oral Care Recovery Kit evaluated in this study
is opioid-free and has been shown to accelerate wound healing,
decrease pain, edema and ecchymosis [31]. It consist of 16 active
ingredients that are monographed in the Homeopathic Pharmacopeia
of United States (HPUS) and recognized for their accelerated healing
properties. However, there are no published articles in the peer-
reviewed medical and dental literature as a preemptive analgesic for
controlling postoperative pain. e hypothesis of this study is that
preemptively managing pain before its onset with this non-opioid
alternative regimen may eectively reduce the pain intensity and
number of opioid rescue analgesics consumed in the postoperative
period. Specic goals of this study are to evaluate if the VEGA Oral
Care Recovery Kit administered 3 days prior to block bone gra
surgery of the mandible would produce a preemptive analgesic eect
compared with no treatment with patients who underwent harvesting
of monocortical blocks of bone from the posterior mandible and
ramus with local anesthesia. e primary outcome variable is pain
intensity measured at the bone gra harvest site. Secondary outcome
variables measured are the total number of opioid rescue analgesics
used over the 72-hour postoperative period and the time interval to
use of the rst opioid rescue analgesic.
Materials and Methods
Study Design and Participants
is prospective qualitative pilot study was conducted on a
group of 34 patients in a single oce (CYSL) in 2018. Demographic
characteristics for both groups are summarized in Table 1. Gender
was measured as a binary variable, while race was measured as a
categorical variable. e primary outcome variable was pain intensity
measured at the bone gra harvest site using a 10-point pain intensity
scale (PIS) from 0 (no pain) to 10 (worst pain possible). Secondary
outcome variables measured are the total number of rescue opioid
analgesics used over a 72-hour postoperative period (Table 2 and 3)
and the time interval to initial use of an opioid rescue analgesic (Table
4). A P value less than .05 was statistically signicant.
Patients included in the study were over 18 years of age and
diagnosed with either atrophy in the vertical or horizontal dimension
of the maxilla or mandible and referred for bone gra reconstructive
surgery in preparation for dental implant surgery. All patients were
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Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
identied as either physical status class I or II according to the
American Society of Anesthesiologists for this elective surgical
procedure in an oce-based setting under local anesthesia. Excluded
from this study were patients with a history of opioid or alcohol
misuse, recreational drug abuse, chronic pain and past medical
history of treatment for chronic pain. A total of 42 monocortical
blocks of bone were harvested from the twenty-nine patients from
the ramus and posterior mandible as described by Pikos [32]. Every
patient included in this study was informed of the primary diagnosis,
treatment options, surgical procedure and goals of this prospective
pilot study. Written and verbal informed consent from each patient
and ethical approval was obtained prior to initiation of this study.
Patients were randomly divided into 2 groups. Group A patients
(14 in preemptive treatment group) received the opioid-free regimen
prior to surgery and the instructions on it use. In addition, each
patient was prescribed ve tablets of an opioid rescue analgesic (5mg
hydrocodone/325mg acetaminophen). Group B patients (20 in cont rol
group) only received a prescription of opioid analgesic (total of 15),
5mg hydrocodone/acetaminophen 325mg aer the surgery to control
the postsurgical pain. All patients were prescribed chlorhexidine
gluconate 0.12% mouthwash that was to be used twice per day for a
period of seven days.
Study Protocol
All 34 patients completed bone gra surgery under local
anesthesia with vasoconstrictor. To harvest the monocortical block
gras, local anesthetic consisting of 2% lidocaine with 1:100,000
epinephrine was administered for nerve block of the inferior alveolar
nerve and buccal so tissue inltration at the bone gra harvest site.
e average dose used at the bone gra harvest site was 7.2 ml. At the
recipient bone gra site, the average dose of local anesthesia was 5.4
ml. e operation time was recorded from initial mucosal incision to
placement of the last suture.
Monocortical blocks of bone harvested from the buccal posterior
and ascending ramus of the mandible were used to increase the
vertical and horizontal dimensions of the future implant sites (Figure
1-3). Bone gra average size harvested from the mandible was width
3-4mm; length 10-20mm and height 8-12mm. Of the 14 patients in
Group A, ve patients had two monocortical blocks of bone harvested
from the bilateral posterior mandible to reconstruct implant sites in
the anterior maxilla. Eight patients in Group B had two monocortical
blocks of bone harvested from the bilateral posterior mandible to
reconstruct the anterior or posterior maxilla in preparation for future
implant surgery.
Study Variables
Primary Outcome Variable: To evaluate postoperative pain,
immediately aer the completion of the surgical procedure all
patients began to complete the pain scale as instructed. Patients were
instructed on how to complete the 10-point pain intensity scale (PIS)
regarding postoperative pain intensity that recorded pain from 0 (no
pain) to 10 (worst pain experienced). e primary outcome variable
is the postoperative pain intensity recorded from the results of the
intensity scale (PIS). All participants were instructed to record their
pain intensity scores at 4, 8, 12, 16, 24-time intervals over the next 72
hours aer surgery. An assumption could be made that the recording
of low pain intensity scores correlates with an increased time interval
to use of opioid rescue analgesics and in a reduction in the amount of
rescue analgesic used. Such an assumption is based on the hypothesis
Group 1 (n=14) Group 2 (n=20)
Female 13 16
Male 1 4
Ethnicity 
asian 13 17
white  2
other 1 1
ASA Classication
1 2 4
2 12 16
3  
Table1: Patient Demographics.
Group 1: VEGA Oral Care Kit
Group 2: Control Group
POD 1 POD 2 POD 3
Average Postoperative Pain Intensity 6.3 5.5 5
*Average Number of Opioids 3.5 2 1.5
POD: Postoperative Day
*Average number of opioids used per 24 hours
Table 2: Group 1 Opioid Rescue Analgesics Consumed over 72 Hours.
POD 1 POD 2 POD 3
Average Postoperative Pain Intensity 8.5 7.5 5.5
*Average Number of Opioids 5.5 4 2.5
*Average number of opioids used Per 24 hours.
Table 3: Group 2 Average Opioid Consumption Over 72 Hours.
Group 1 Group 2
Time Interval (hr) 4.3 1.9
Table 4: Time Interval to Use of First Opioid Analgesic.
Group 1: VEGA Oral Care Kit
Group 2: Control Group
Figure 1: Clinical photograph of 42-year old Asian female missing two
anterior maxillary incisor teeth causing psychological embarrassment and
anxiety.
Figure 2: Two monocortical blocks of bone harvested from bilateral posterior
ascending ramus of mandible four months ago rigidly xated to maxilla
using micro screws now successfully incorporated with maxilla and ready for
implant placement. Post-operative pain is most intense at harvest site during
rst 24-48 hours after surgery.
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Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
that the opioid -free alternative regiment has a preemptive analgesic
eect.
Secondary Outcome Variable: Secondary outcome variables
evaluated were the total amount of opioid rescue analgesics consumed
to relieve the postoperative pain over the 72-hour observation period
and the time interval to administration of the rst opioid rescue
analgesic. Time interval is the time from the end of the surgical
procedure to use of the opioid rescue analgesic.
Statistical Analysis
Data collected from this pilot study was entered into a statistical
database and conducted using the Statistical Package for Social
Sciences (SPSS for Windows, version 25; SPSS, Chicago, IL). e level
of signicance for all statistical evaluations was set at P < .05. Data
are presented as a mean +/- standard deviation. Descriptive statistics
were used to describe the data obtained for each clinical outcome.
Unpaired student t test with a 95% condence interval was used to
compare mean postoperative pain intensity scores and use of rescue
opioid analgesics. e Wilcoxon rank sum test was used to evaluate
the time interval to use of opioid analgesics for both groups.
Results
A total of 40 adult patients were initially enrolled in the project.
However, only 34 completed this study as 6 patients were removed f rom
the research group due to lack of instructional compliance. Patients in
Group A (14 in preemptive treatment) reported lower cumulative pain
intensity scores throughout the 72-hour postoperative observation
period compared to patients in Group B (20 in control group) (Table
2 and 3). e average postoperative pain intensity score for patients in
Group A using the PIS was 5.6 over the 72-hour observational period
(range 2 to 8.5). e average rescue opioid analgesic consumption
over the 72-hour observational period was 2.3 tablets per day. For
patients in Group B, the average postoperative pain intensity score
was 7.1 (range 4.0 to 9.5) on the PIS. e average number of opioid
analgesics consumed to relieve postoperative pain over the 72-hour
observational period was 3.8 tablets per day. e median time interval
to use of the rst opioid rescue analgesic was 4.3 hours for patients in
Group A. For patients in Group B, the median time interval to initial
use of opioid pain medication was 1.9 hours.
Discussion
e intensity of postoperative pain is directly correlated with
the type of surgical procedure the patient completes. Harvesting
monocortical blocks of bone is similar to orthopedic and orthognathic
surgery. All three types of surgical procedures commonly involve
sharp dissection of the periosteum and muscles and surgical
osteotomies with a high-speed cutting device such as a saw or ssure
bur that result in moderate to severe postoperative pain and the need
for opioid analgesics to control the pain. In surgery, strategies utilizing
medications have been developed to decrease the postoperative
pain response, including the use of opioids [25,28,33-40]. Opioid
analgesics such as hydrocodone and oxycodone are commonly
prescribed to reduce postoperative pain with or without non-steroidal
anti-inammatory drugs (NSAIDS) to provide pain relief. e dental
profession is the third highest prescribers of opioid analgesics in the
United States [41]. In a study by Denisco and colleagues [42] greater
than 3 million patients each month are exposed to opioid analgesics
from oral and maxillofacial surgeons. Opioids provide excellent
pain relief, but are associated with drug tolerance, abuse and risk of
addiction. is is the driving force for the search for an ecacious
opioid-free alternative treatment regimen in the management of
postoperative pain [43].
In a third molar study by Ong evaluating the ecacy of ketorolac
on postoperative pain, the cohort of patients receiving the pain
medication prior to surgery reported signicantly lower levels of pain
12 hours post-surgery compared to the cohort who received ketorolac
aer surgery. In another study by Ong on rofecoxib, the group of
patients who received the medication prior to surgery also reported
decreased levels of pain over the rst 12 hours post-surgery, compared
to the group of patients who received rofecoxib aer surgery. Studies
by Presser-Lima and Fontanella and Zor also showed that preemptive
analgesia administered to their patients resulted in less pain
postoperatively. However, some studies failed to show the benets of
preemptive analgesia in the post-surgical, but rather a reduction in
the amount of rescue drug used to control the postoperative pain, or
in a delay in the time for the onset of pain experienced by the patient.
Although the mechanism of action is not entirely known, a reduction
or delay in the use of an opioid rescue analgesic may be due to the
preemptive eect of the alternative therapy in our study. Stimulation
of free nerve endings at the bone harvest site causes nociceptive pain.
As the VEGA Oral Care Recovery Kit is provided as an oral
rinse, sublingual spray and topical gel, we hypothesize that all three
Figure 3: (A) Clinical photograph of patient without teeth. (B and C)
Intraoral view of anterior maxilla restored with implants and zirconia teeth.
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Clinical Journal of Pharmacology and Pharmacotherapeutics
2019 | Volume 1 | Article 1006
routes of product administration contribute to the preemptive eects
due to peripheral and possibly, central sensitization by blockade of
nociception when applied three days prior to the date of the surgical
procedure and during the 72-hour postoperative period. e cohort
group that used the opioid-free regimen preemptively experienced
less postoperative pain (average pain intensity of 5.6 over the 72-hour
observation period) than the control group based on the results of
the pain intensity scale (average pain intensity of 7.1 over 72 hours,
postoperatively). is observation was most signicant at the 2 to
4-hour time interval aer surgery when the reported pain was most
severe for patients who were not treated preemptively. When used
preemptively, onset of postoperative pain by a mean time of 4.3 hours
before having to resort to use of any opioid rescue analgesic was
observed. Such a preemptive analgesic aect may be due to inhibition
of peripheral nociceptor input. For the surgical patient, a prolonged
pain-free period from the end of surgery to the rst use of an opioid
analgesic to control the onset of postoperative pain is clinically
signicant. Like third molar surgery where the postoperative pain
is most intense 2 to 4 hours aer surgery, it has been the authors
experience that the postoperative pain from harvesting monocortical
blocks of bone at the osteotomy site is also most intense during this
time interval.
is pilot study did have limitations, such as not being blinded
and its small sample size. Studies that are not blinded can result in
research bias, as both the research investigators and the patient know
which treatment they were assigned to. As the study included only 34
patients, its small sample size may aect statistical power. As clinicians
are well-aware of, postoperative pain is subjective, dicult to measure
and perceived dierently among dierent age groups, races and
cultures. Such self-reporting by patients is another limitation of any
study and could be inuenced by several dierent factors. In both
groups, over 90% of the patients in this qualitative study were Asian,
female and older in age. Many of the participants in both groups
limited their opioid consumption to control the postoperative pain.
With advanced age, there may be a “blunting eect” on peripheral
nociceptive function that decreases pain perception and the need for
less analgesic medication [44,45].
Conclusion
is novel, opioid-free alternative form of therapy administered
preemptively prior to block bone gra surgery resulted in decreased
postoperative pain, less reliance of opioid analgesics and increased
the time interval to use of an opioid analgesic. e authors believe
that there is a denite role in the use of this novel opioid-free
alternative therapy in managing postoperative pain. As the opioid-
abuse epidemic is now at a national public health crisis with no end in
sight, the use of a non-opioid product should be considered by every
clinician who manages postoperative pain in their daily practice.
Because of the paucity of studies in this area of pain management,
long-term randomized clinical studies are needed as alternative
and complementary treatment regimens do have a role in pain
management in oral and maxillofacial surgery and implant dentistry.
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... Recently, a novel, opioid-free VEGA oral care recovery kit has been recognized as an effective treatment to reduce pain owing to its more natural formulation. It consists of 16 active ingredients that are monographed in the Homeopathic Pharmacopeia of United States (HPUS) and recognized for their accelerated healing properties with antimicrobial properties [3]. Lee and Suzuki utilized the VEGA oral care recovery kit to evaluate pain, wound healing, edema, and ecchymosis in two groups-one with opioid use and the other without-in patients who underwent harvesting of monocortical blocks of bone from the posterior mandible and ramus with local anesthesia [3]. ...
... Recently, a novel, opioid-free VEGA oral care recovery kit has been recognized as an effective treatment to reduce pain owing to its more natural formulation. It consists of 16 active ingredients that are monographed in the Homeopathic Pharmacopeia of United States (HPUS) and recognized for their accelerated healing properties with antimicrobial properties [3]. Lee and Suzuki utilized the VEGA oral care recovery kit to evaluate pain, wound healing, edema, and ecchymosis in two groups-one with opioid use and the other without-in patients who underwent harvesting of monocortical blocks of bone from the posterior mandible and ramus with local anesthesia [3]. The authors reported that this novel, opioid-free alternative form of therapy administered preemptively prior to block bone graft surgery resulted in decreased postoperative pain and less reliance of opioid analgesics [3]. ...
... It consists of 16 active ingredients that are monographed in the Homeopathic Pharmacopeia of United States (HPUS) and recognized for their accelerated healing properties with antimicrobial properties [3]. Lee and Suzuki utilized the VEGA oral care recovery kit to evaluate pain, wound healing, edema, and ecchymosis in two groups-one with opioid use and the other without-in patients who underwent harvesting of monocortical blocks of bone from the posterior mandible and ramus with local anesthesia [3]. The authors reported that this novel, opioid-free alternative form of therapy administered preemptively prior to block bone graft surgery resulted in decreased postoperative pain and less reliance of opioid analgesics [3]. Furthermore, a study conducted by Tatch also found a 3-fold reduction in prescribed opioids when the VEGA oral care recovery kit was added to routine private practice procedures over a 3-year period (>1000 patients evaluated-reduction in opioids prescribed from 59% down to 19% of patients) [4]. ...
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Most available antiseptic solutions available today have strong antibacterial effects, however most also possess major cytotoxic effects on human gingival tissues. The VEGA Oral Care Recovery Kit (StellaLife), previously evaluated in clinical studies, consists of 16 active ingredients that are monographed in the Homeopathic Pharmacopeia of United States (HPUS) and recognized for their accelerated healing properties (reduction in post-op pain). The aim of this study was to compare VEGA to chlorhexidine (CHX) in vitro on gingival fibroblast viability, survival at various concentrations, migration assay, proliferation activity, expression of both regenerative growth factors as well as inflammatory markers, and collagen synthesis. A 10-fold dilution of standard CHX (0.02%) led to cell death, whereas cell viability was significantly better in the VEGA group for all tested parameters. Furthermore, VEGA also induced significantly greater fibroblast migration and proliferation. CHX negatively impacted the cellular inflammatory response of gingival fibroblasts, and also led to a reduction in collagen synthesis (50% decrease). Findings from the present study provide support from basic laboratory experiments that validate the previous clinical studies supporting the use of the VEGA oral rinse on its superior biocompatibility and wound healing properties when compared to CHX.
... Ultimately, this selective cytotoxicity could facilitate uncomplicated wound healing and reduce adverse events. In fact, a SLife oral kit that includes the herbal compound extract oral rinse as well as an additional herbal extract compound with analgesic activity delivered as a sublingual spray and gel has demonstrated human efficacy for inflammatory pain management in a prospective study of thirty-four surgical dental patients (Lee and Suzuki, 2019). The authors found that use of the SLife reduced opioid consumption by 1.5 tablets per day on average (Lee and Suzuki, 2019). ...
... In fact, a SLife oral kit that includes the herbal compound extract oral rinse as well as an additional herbal extract compound with analgesic activity delivered as a sublingual spray and gel has demonstrated human efficacy for inflammatory pain management in a prospective study of thirty-four surgical dental patients (Lee and Suzuki, 2019). The authors found that use of the SLife reduced opioid consumption by 1.5 tablets per day on average (Lee and Suzuki, 2019). Thus, this work supports that herbal anti-inflammatory compounds may have a significant clinical effect for the management of post-operative inflammation after oral surgical procedures by supporting cellular responses to surgical trauma and enabling uninterrupted wound healing. ...
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The aim of this study was to evaluate the cytocompatibility of an herbal extract compound oral rinse [StellaLife VEGA (SLife)] against relevant human cellular models of oral surgical wound healing. SL was compared to the gold standard for peri-/post-operative oral surgical use, i.e., Chlorhexidine (CHX) and to a commonly utilized essential-oil (EO) based antiseptic rinse. Fibroblasts and primary oral stem cells of the apical papilla (SCAPs) were employed to assess its comparative cytotoxicity to the active comparator antiseptic rinses and its effects on wound healing in vitro. In cytotoxicity assays, multiple timepoints were tested ranging from clinically relevant of 60-s rinsing to protracted challenge of up to 5 min, to determine dose-dependent toxicity. The SLife group consistently demonstrated minimal cytotoxicity as compared to active comparators across experimental timepoints and different cells lines. At concentrations up to 20% v/v SLife-challenged fibroblasts and SCAPs demonstrated no significant toxicity as compared to unstimulated controls ( p > 0.05). When assessing wound healing, a scratch wound assay revealed significantly accelerated cell migration for SLife as compared to CHX ( p < 0.05). Notably, all active comparator antiseptic rinses affected wound healing responses by significantly reducing total collagen deposition after intermittent “rinsing” intervals that simulated post-surgical oral rinsing. Nonetheless, intermittent as well as continuous challenge of cells with SLife had a positive effect in functional collagen assays. An herbal extract compound-based oral rinse was found to be cytocompatible to cells critical to oral wound healing and to promote fibroblast migration and differentiation, contrary to existing antiseptic rinses that lack selective cytotoxicity.
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The aim of this study was to establish whether the pre-emptive use of lornoxicam (16mg) in third molar surgery ensures successful postoperative analgesia and reduces rescue analgesic intake when compared to postoperative application, and in comparison with placebo. Ninety patients were split randomly into three groups: group A received lornoxicam 60min before surgery and placebo 60min after surgery; group B received placebo 60min before surgery and lornoxicam 60min after surgery; group C received placebo 60min before surgery and placebo 60min after surgery. Postoperative pain was recorded on a visual analogue scale and on a numerical rating scale at 1, 2, 4, 6, 8, 12, and 24h after surgery. The patients recorded total dose of paracetamol intake during the 24h after the procedure. The efficacy of postoperative analgesia was greater in lornoxicam groups when compared to the placebo group; there was no difference between the two lornoxicam groups (A and B). Patients in group C took their first rescue analgesic dose earlier after surgery than patients in the two lornoxicam groups. The average dose of paracetamol taken in group C was 1000mg, while it was500 mg in the lornoxicam groups.
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This guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care. The guideline addresses 1) when to initiate or continue opioids for chronic pain; 2) opioid selection, dosage, duration, follow-up, and discontinuation; and 3) assessing risk and addressing harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation. CDC obtained input from experts, stakeholders, the public, peer reviewers, and a federally chartered advisory committee. It is important that patients receive appropriate pain treatment with careful consideration of the benefits and risks of treatment options. This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death. CDC has provided a checklist for prescribing opioids for chronic pain (http://stacks.cdc.gov/view/cdc/38025) as well as a website (http://www.cdc.gov/drugoverdose/prescribingresources.html) with additional tools to guide clinicians in implementing the recommendations.
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A large fraction of heroin users now report that they formerly used prescription opioids nonmedically, a finding that has led to restrictions on opioid prescribing. Nevertheless, only a small fraction of prescription-opioid users move on to heroin use.
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The purpose of this study was to investigate the effectiveness of preemptive analgesia with nonsteroidal anti-inflammatory drugs (NSAIDs) in third-molar surgery. A PubMed literature search was conducted for articles restricted to the English language using the following terms (DeCS/MeSH) or combinations: analgesia, third molar, and preemptive. From a total of 704 articles, 6 (n = 420 subjects) were selected. All studies presented a low risk of bias (Cochrane criteria) but exhibited high heterogeneity of methods. Two studies were excluded from the meta-analysis because they did not have adequate numeric values (dichotomous data) for the calculations. Preemptive analgesia showed no significant benefit (n = 298, P = .2227, odds ratio: 2.30, 0.60-8.73) in reducing postoperative pain after removal of lower impacted third molars. However, there was a probable direct relationship between the effectiveness of NSAIDs in preemptive analgesia for removal of third molars and its selectivity for the cyclooxygenase-2 (COX-2). Preemptive analgesia did not have a significant effect in reducing postoperative pain after removal of lower impacted third molars. More homogeneous and well-delineated clinical studies are necessary to determine a possible association between NSAIDs' selectivity for COX-2 and treatment effectiveness.
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Purpose: The aim of this study was to compare the clinical efficacies of naproxen sodium-codeine phosphate in combination, benzydamine hydrochloride, and diclofenac potassium for pain, edema, and trismus after lower third molar extraction. Materials and methods: Ninety healthy volunteers in whom impacted third molar extraction was indicated were randomly distributed into 3 groups. One hour before the tooth-extraction process, patients were administered one of the following drugs: naproxen sodium, 550 mg, and codeine phosphate, 30 mg, in a tablet; diclofenac potassium, 50 mg, in a coated pill; or benzydamine hydrochloride, 50 mg, in a coated pill. Pain assessment was conducted via a visual analog scale; edema assessment, by measuring the distances between predetermined facial landmarks; and trismus assessment, by measuring interincisal distance. Regarding rescue analgesics (paracetamol, 500 mg), the number and time of use by patients were recorded. Results: Naproxen sodium-codeine phosphate was more effective for pain, edema, and trismus than diclofenac potassium and benzydamine hydrochloride (P < .05). Benzydamine hydrochloride yielded similar clinical responses to diclofenac potassium (P > .05). No drug-related side effects were observed. Conclusions: Naproxen sodium-codeine phosphate constitutes the drug of choice after the extraction of a patient's impacted lower third molar. Benzydamine hydrochloride has similar efficacy to diclofenac potassium, and it can be used as a nonsteroidal anti-inflammatory analgesic drug.
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We at the Food and Drug Administration (FDA) continue to be deeply concerned about the growing epidemic of opioid abuse, addiction, and overdose - an epidemic directly related to the increasingly widespread misuse of powerful opioid pain medications. As the federal agency charged with ensuring that the drugs used by the U.S. public are both effective and safe, we are committed to working in partnership with other government agencies, health care providers, the medical products industry and, most important, patients and their families to deal proactively with this unfolding public health crisis, which has already profoundly affected individuals, families, and . . .
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What is already known on this topic? The rate for drug overdose deaths has increased approximately 140% since 2000, driven largely by opioid overdose deaths. After increasing since the 1990s, deaths involving the most commonly prescribed opioid pain relievers (i.e., natural and semisynthetic opioids) declined slightly in 2012 and remained steady in 2013, showing some signs of progress. Heroin overdose deaths have been sharply increasing since 2010. What is added by this report? Drug overdose deaths increased significantly from 2013 to 2014. Increases in opioid overdose deaths were the main factor in the increase in drug overdose deaths. The death rate from the most commonly prescribed opioid pain relievers (natural and semisynthetic opioids) increased 9%, the death rate from heroin increased 26%, and the death rate from synthetic opioids, a category that includes illicitly manufactured fentanyl and synthetic opioid pain relievers other than methadone, increased 80%. Nearly every aspect of the opioid overdose death epidemic worsened in 2014. What are the implications for public health practice? Efforts to encourage safer prescribing of opioid pain relievers should be strengthened. Other key prevention strategies include expanding availability and access to naloxone (an antidote for all opioid-related overdoses), increasing access to medication-assisted treatment in combination with behavioral therapies, and increasing access to syringe service programs to prevent the spread of hepatitis C virus infection and human immunodeficiency virus infections. Public health agencies, medical examiners and coroners, and law enforcement agencies can work collaboratively to improve detection of and response to outbreaks associated with drug overdoses related to illicit opioids. © 2016, Department of Health and Human Services. All rights reserved.