Comparing

Different Medications used in

General Dentistry Practices for Sedation

Principal Investigator: Cynthia Nichols, DMD

Co-Investigators: James Curtis, DMD, David Hicklin, DMD,
& Matthew Bright
10 Medical Park Rd.
Columbia, SC 29203

Comparing Different Medications used in General Dentistry Practices for Sedation

1) Background / Justification For Study

Benzodiazepines are the most commonly used sedatives in dentistry through the forms of
diazepam, midazolam, lorazepam, and flunitrazepam (Malamed, 2010). Discovered by
Dr. Leo Sternbach in the Chemical Research Department of Hoffmann La Roche,
U.S.A, the compound in particular, Ro#5-0690, was found to have hypnotic and sedative
properties once molecularly rearranged to become a 1:4 benzodiazepine solution (Lader,
1991). First approved by the Food and Drug Administration (FDA) in 1963, diazepams
reported use for sedation in minor oral surgical procedures proved good to excellent
results in 51 of 52 patients treated (ONeil, 1970). In 1970 the previous study was
expanded in which 55 patients underwent a procedure lasting 20-45 minutes. Of the
sample of 55 patients, 49 patients were adequately sedated with the use of
Benzodiazepines, 4 were aroused but able to be treated, and 1 was awake and unable to
be treated (ONeil, 1970). With the creation of this form of effective sedative-hypnotic
drugs, diazepam, the first discovered drug of the Benzodiazepine class, soon became the
most prescribed oral drug in the Western world (Malamed, 2010).
Also a member of the Benzodiazepine class of sedatives, the most widely used dental
sedative of today is midazolam. Midazolam is also a 1:4 benzodiazepine solution that was
synthesized in 1975 by Walser and Fryer at Hoffman-LaRoche (Malamed, 2010). With
the chemical formula of 8-chloro-5(2-fluorophenyl)-1-methyl-4H-imidaze, midazolam
was first approved by the Food and Drug Administration in 1985 (Malamed, 2010).
According to a study completed by P.J. Flynn, the water solubility of midazolam, when
compared to its predecessor diazepam, was virtually free of venous complications and
showed advantages over diazepam in providing a faster onset of action, higher incidence
of amnesia and more rapid recovery (Flynn, 1984). Side effects of midazolam can
include dizziness, yet 92% of participants of a representative study conducted by Conner
et al, stated that they enjoyed their experience produced by the drug midazolam (Conner
et al, 1978).
The second class of sedatives being studied is Opioid Analgesics and Agonists
(narcotics). Most commonly used to alleviate moderate to severe pain, these drug often
cause drowsiness, mood swings, and mental clouding (Malamed, 2010). Opioid agonists
are drugs that interact with opioid receptors. An opioid antagonists are drugs that occupy
a receptor site with no pharmacologic effect. Opioids that are both agonists and
antagonists have properties of both (Malamed, 2010). One common opioid used in
sedative dentistry is a rapid-onset agonist fentanyl. Fentanyl is 100 times more potent
than morphine meaning that 0.1 mg of fentanyl is equivalent to 10 mg of morphine
(Malamed, 2010). It is commonly used as a short term anesthetic that is supplemental to
general anesthesia. Fentanyl has the ability to frequently cause complications with
respiratory depression, apnea, muscular rigidity, and bradycardia if not monitored
closely. Side effects include hypotension, dizziness, nausea, vomiting, and blurry vision
(Malamed, 2010).
Other forms of sedatives used in a dental setting can include histamine blockers such as
promethazine or phenegran. Promethazine can be used as a sedative hypnotic in

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Comparing Different Medications used in General Dentistry Practices for Sedation

conjunction with intravenous sedation (Malamed, 2010). Its clinical use is restrained to 12 hours. Reactions to promethazine can include extrapyramidal reactions including motor
restlessness, protrusion of the tongue, and the development of tremors, rigidity, and
anxiety (Malamed, 2010).
Much is understood about these three classes of intravenous sedatives used in sedative
dentistry by practicing professionals; however patients rarely understand the differences
between different types of sedatives used during dental surgery. This study is aimed at
juxtaposing sedative success and patient perception in order to determine which drug or
combination of drugs provides the highest rate of patient satisfaction through a
retrospective analysis of patient files at the Palmetto Health Dental Center, 10 Medical
Park, Columbia, South Carolina. The results of this study will be compiled for inter office
quality improvement, as well as publication.

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Comparing Different Medications used in General Dentistry Practices for Sedation

2) Objectives / Research Aims

To describe the associations of three classes of sedative agents on the following
outcomes:
i.

Length of recovery

ii.

Observed level of sedation

iii.

Intra-procedural complications

iv.

Paradoxical reactions

v.

Dentist rating of sedation effectiveness

vi.

Patient recall of pleasantness for memory of procedure at follow-up.

3) Setting
This study will be carried out at the Palmetto Health Dental Center, in 10 Medical
Park, Columbia, South Carolina.

4) Resources Available
This study will make use of the Dental Centers Medical Record System, Eaglesoft.
Dr. Curtis, Dr. Hicklin and Dr. Nichols have experience in clinical research. Matthew
Bright will conduct the data collection. Michael Haney will provide a data collection
database. Martin Durkin, MD will conduct the statistical analysis.

5) Study Design
a)

Recruitment Methods

This study is a retrospective medical chart review that involves no patient contact or
recruiting.

b)

Inclusion and Exclusion Criteria

Inclusion Criteria
i) Dental procedure at the Palmetto Health dental center with sedation.
ii) Date of procedure 7/1/12 6/30/15.
iii) Patient age 15 years at the time of the dental procedure.

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Comparing Different Medications used in General Dentistry Practices for Sedation

No exclusions

c)

Local Number of Subjects

It is estimated that approximately 125 patients per year meet the inclusion criteria.
Therefore, a total of approximately 375 patients will meet the inclusion criteria.
We plan to collect data on all patients who meet the inclusion criteria (100%
sample).

d)

Study Timelines

The collection and analysis of data will take approximately 3 months, with another 3
months needed to write the manuscript.

e)

Study Endpoints
i.

Length of recovery as documented in the Patient Procedure Observation

Record. Discharge Time (page 4) - Last Intra-Procedure Monitoring Time
(page 2).

ii.

Observed level of sedation Aw (patient is awake; not sedated or well

sedated) Ar (patient is sedated but arousable) As (patient is over
sedated and not arousable)

iii.

Intra-procedural complications Palmetto Health Richland Dental Center

Quarterly Procedure Audit Tool.

iv.

Paradoxical reactions as described in the electronic record or the Patient

Procedure Observation Record.

v.

Dentist rating of sedation effectiveness (based on patient recollection of

procedure) Ordinal scale ranging from 0 (Very Good Sedation) to 5
(Very Poor Sedation), as the amnesia level recorded in the Continuous
Quality Improvement tool of the General Practice Residency, Palmetto
Health Dental Center Protocol for Monitoring Success of IV Conscious
Sedation. These data are obtained at a post-operative evaluation and
reflect the patients level of amnesia for the procedure.

vi.

Patients level of comfort during sedation for memory of procedure at

follow-up - Ordinal scale ranging from 0 (No Hurt) to 5 (Hurts Worst), as
recorded in the Continuous Quality Improvement tool of the General
Practice Residency, Palmetto Health Dental Center Protocol for
Monitoring Success of IV Conscious Sedation.

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Comparing Different Medications used in General Dentistry Practices for Sedation

f)

Procedures Involved
Data will be collected through the Dental Centers electronic dental record
system, Eaglesoft. Researchers will search provider codes according to the
institutional policy relating to IV sedated surgery. Once records are located, the
information will be collected, and de-identified. Once it is confirmed that the
subjects are greater than or equal to fifteen years of age, the data corresponding to
the record will be entered into a secure study database. Upon the completion of
data gathering, all results will be statistically analyzed and conclusions will be
drawn. The results of this study will be used for inter office quality improvement,
as well as publication.
In addition to the abstracting of study endpoints from the patient dental record, the
following variables will be recorded:
i.

Patient gender

ii.

Patient age in years

iii.

Patient weight and height

iv.

Race

v.

Surgeon type (Faculty member, resident)

vi.

Anesthetist type (Faculty member, resident)

vii.

Procedure type (Extraction, implant, gum surgery, nonsurgical)

viii.

Duration of the procedure

ix.

Sedative agent (benzodiazepine, narcotic, other)

x.

Local anesthetic used (lidocaine, prilocaine, bupivacaine, articaine

g) Statistical Analysis
i) Length of recovery as documented in the dental procedure record.
Kaplan-Meier curves for each of the three sedative types will be constructed.
In addition, a Cox regression model with time to event as the outcome,
sedative type as the major predictor variable and patient gender, age, and race,
as well as surgeon and anesthetist type, procedure type, duration of the
procedure, and local anesthetic used as potential covariates.
ii) Observed level of sedation

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Comparing Different Medications used in General Dentistry Practices for Sedation

Cross-tabulations of observed level of sedation and sedative type will be

made.
iii) Intra-procedural complications
Cross-tabulations of intra-procedural complication type and sedative type will
be made.
iv) Paradoxical reactions
The proportion of patients receiving each of the sedation types who
experience a paradoxical reaction will be calculated. In addition, a logistic
regression model will be built with whether a paradoxical reaction was
experienced as the outcome, sedative type as the major predictor variable and
patient gender, age, and race, as well as surgeon and anesthetist type,
procedure type, duration of the procedure, and local anesthetic used as
potential covariates.
v) Dentist rating of sedation effectiveness Ordinal scale ranging from 1 to 10,
as recorded in the operative record. The median patient recall score will be
determined for each of the three sedative medication groups. In addition, a
linear regression model will be built with patient recall (ordinal, 5 levels) as
the outcome, sedative type as the major predictor variable and patient gender,
age, and race, as well as surgeon and anesthetist type, procedure type, duration
of the procedure, and local anesthetic used as potential covariates.
vi) Patient recall of pleasantness for memory of procedure at follow-up - Ordinal
scale ranging from 1 to 5, as recorded in the record of patient follow-up.
The median patient recall score will be determined for each of the three
sedative medication groups. In addition, a proportional odds logistic
regression model will be built with patient recall (ordinal, 5 levels) as the
outcome, sedative type as the major predictor variable and patient gender, age,
and race, as well as surgeon and anesthetist type, procedure type, duration of
the procedure, and local anesthetic used as potential covariates.

h) Data Management
An excel data sheet will be used to compile information taken from patients
records. This excel data sheet will be kept on four password protected computers
contained within the building of 10 Medical Park, Columbia, South Carolina. The
study team will have access to the compiled data.

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Comparing Different Medications used in General Dentistry Practices for Sedation

Study Key will be made linking a study ID with the respective medical record
number. The data will be de-identified by substituting time intervals for dates and
times, prior to sending to the statistician.

i)

Confidentiality
To protect the confidentiality of the data, all electronic copies of the data will be
stored on a secure network and at Palmetto Health. This computer network
provide secure storage and backup, centralized location for access and processing
of research data. All data will be password protected and accessible to only the
Principal Investigator and members of the study.

6) Risks to Subjects
This study presents no more than minimal risk for the subjects; it is a
retrospective chart review that involves no direct contact with subjects. There
is a slight risk of loss of confidentiality of protected health information (PHI).

7) Potential Benefits to Subjects

There is no direct benefit to the subjects in this study.

8) Provisions to Protect the Privacy Interests of Subjects

The only information about the subjects that the research team will have
access to is data contained in the medical records. We are requesting IRB
approval of a waiver of authorization in order to gain access to PHI without
having to obtain prior authorization from the subjects whose information will
be under review by this study.

9) Consent Process
Due to the retrospective nature of the study, consent will not be obtained. We are
requesting a full waiver of the informed consent requirement.

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Comparing Different Medications used in General Dentistry Practices for Sedation

10)

Bibliographic References
Becker, D.E., Haas, D.A., (2007). Management of Complications During
Moderate and Deep Sedation: Respirator and Cardiovascular
Considerations. Anesthesia Progress, 54, 59-69.
Becker, D.E. (2012). Pharmacodynamic Considerations for Moderate and
Deep Sedation. Anesthesia Progress, 59, 28-42.
Becker, D.E. (2014). Adverse Drug Reactions in Dental Practice.
Anesthesia Progress, 61, 26-34.
Cabrera, L.S., Santana, A.S., Robaina, P.E., & Palacios M.S., (2010).
Paradoxical reaction to midazolam reversed with flumazenil.
Journal of Emergencies, Trauma, and Shock, 3, 307.
Conner, J.T., Katz, R.L., Pagano R.R., & Graham, C.W., (1978). RO 213981 for intravenous surgical premedication and induction of
anesthesia. Anesthesia & Analgesia 2:134.
Dionne, R.A., Gift, H. C., (1988). Drugs used for Parenteral Sedation in
Dental Practice. Anesthesia Progress, 35, 199-205.
Dionne, R.A., (2001). Comparing efficacy and safety of four intravenous
sedation regimens in dental outpatients. Journal of the American
Dental Association, 132, 740-751.

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Comparing Different Medications used in General Dentistry Practices for Sedation

Flynn, P.J., (1984). A comparison of midazolam and diazepam for
intravenous sedation in dentistry. Anaesthesia, 39, 589-593.
Frye-Kryder, S., (1987). Midazolam: A new benzodiazepine. Journal of
the American Association of Nurse Anesthetists, 55, 121-125.
Lader, M., (1991). History of Benzodiazepine Dependence. Journal of
Substance Abuse Treatment, 8, 53-59.
Malamed, S. F., Dr. (2010). Sedation: A Guide to Patient Management
(5th ed.). St. Louis, MI: Mosby Elsevier.
Mohri-Ikuzawa, Y., Inada, H., Takahashi, N., Kohase, H., Jinno S., &
Umino, M. (2006) Delirium During Intravenous Sedation with
Midazolam Alone and with Propofol in Dental Treatment.
Anesthesia Progress 53, 95-97.
Moore, P.A., (1999). Adverse Drug Interactions in Dental Practice:
Interactions Associated with Local Anesthetics, Sedatives, and
Anxiolytics. Journal of the American Dental Association, 130,
541-554.
ONeil R, Verrill P., (1969) Intravenous diazepam in minor surgery,
British. Journal of Oral Surgery, 7, 12-14.

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Comparing Different Medications used in General Dentistry Practices for Sedation

Robin, C., Trieger, N., (2002). Paradoxical Reactions to Benzodiazepines
in Intravenous Sedation: A Report of 2 Cases and Review of
Literature. Anesthesia Progress, 49, 128-132.

11)

Appendices

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