chapter 8 
Rectal Sedation
CHAPTER OUTLINE
ADVANTAGES
DISADVANTAGES
DRUGS
Hydromorphone
Oxymorphone
Promethazine
Chloral Hydrate
I nterest in the rectal route of drug administration has
increased in anesthesiology and, to a lesser extent, in
dentistry in recent years.1–3 Historically the rectal route
of drug administration was used for the administration of
smoke (“fumigation”) for resuscitation4 and the administration
of anesthetics. An ether boiler for rectal application was
developed in 1847 by Pirogoff.1,5 With the advent of more
reliable routes of drug administration (e.g., intravenous [IV]
and inhalation), use of the rectal route decreased.
Certain situations remain in which rectal drug administration
may be valuable. These include the administration of a drug
to a patient who is unwilling or unable to take drugs orally.
In most instances, this is a child or an adult with a disability
requiring sedation either to permit treatment to proceed6–8 or
as a preliminary to the induction of general anesthesia.9–11
Another situation in which rectal drugs are warranted is the
administration of antiemetics to patients with nausea and
vomiting.12 Although parenteral administration is preferred (if
the patient is present in the office where the drug may be
injected), rectal administration can be used if the patient objects
to injection or if the patient is at home. Another indication
for rectal administration of drugs is analgesics for postoperative
control of pain.13
ADVANTAGES
Advantages of the rectal route include a relatively rapid onset
of clinical activity; a decreased incidence and intensity of
drug-related side effects; the lack of a needle, syringe, or other
120
Diazepam
Midazolam
Ketamine
Lytic Cocktail
COMPLICATIONS OF RECTAL
ADMINISTRATION
potentially threatening equipment; the avoidance of an injection;
ease of administration (many children who vehemently object
to the oral route will not object to this route); and its low cost.
In the past, it was thought that rectally administered drugs
were absorbed directly into the systemic circulation via the
vena cava, bypassing the enterohepatic circulation and thereby
eliminating the hepatic first-pass effect that influences the
clinical activity of most drugs administered enterally.14 The
superior rectal vein empties into the inferior mesenteric vein
and then into the portal system. The middle and inferior rectal
veins empty into the internal iliac vein and the inferior vena
cava.15,16 However, it has been demonstrated that hepatic
clearance is the main factor affecting bioavailability of rectally
administered drugs.1 This may be because blood flow occurs
through anastomoses that interconnect the superior, middle,
and inferior rectal venous systems, thereby producing a hepatic
first-pass effect with rectally administered drugs. Other potential
factors, such as adsorption by feces, intraluminal degradation
by microorganisms, metabolism within the mucosal cell, and
lymphatic drainage, do not significantly affect the fate of rectally
administered drugs.
Comparing the oral, nasal, and rectal administration of the
water-soluble benzodiazepine midazolam, Tolksdorf9 found
that children aged 1 to 6 years accepted the oral drug better
than rectal or nasal, but that the rectally administered midazolam
had the most rapid onset of action and fewest side effects in
the postoperative period. In several studies, peak levels of
clinical action were noted rapidly after rectal administration.
Roelofse et al6 noted good anxiolysis, sedation, and cooperation
 CHAPTER 8  Rectal Sedation 121
30 minutes after rectal administration of midazolam, whereas
Kraus et al17 noted peak plasma levels of midazolam at 7.5
minutes.
DISADVANTAGES
Disadvantages of the rectal route include inconvenience to the
administrator and the patient, variable absorption of some
drugs from the large intestine, possible irritation of the intestines
by some drugs, inability to reverse the action of the drug easily,
prolonged recovery with some drugs, and an inability to titrate
precise individual doses.
The primary use of rectal drug administration in both
medicine and dentistry is management of uncooperative patients,
whether children or adults. It is strongly advised that rectally
administered central nervous system (CNS) depressants be
administered in the medical or dental office by the dentist or
a staff person (or parent, if the patient is a child). Signs and
symptoms of sedation develop rapidly with many rectal drugs;
clinical sedation is evident at 15 to 30 minutes.6,17 Because
the possibility of oversedation exists, it would be beneficial
for the patient to be in an environment where oversedation
could be easily recognized and the patient managed (“rescued”).
An automobile en route to the dentist’s office is not a desirable
location.
Because of the lack of control over the clinical actions of
the drug, rectal administration ought not to be used in an
effort to achieve deep sedation unless the dentist has been
well trained in general anesthesia and is able to manage the
airway of an unconscious patient. The recommended use of
rectal sedation is for the induction of minimal-to-moderate
sedation when other, more controllable methods of anxiety
control (IV, inhalation) may be added, if needed, during treat-
ment. Rectally administered drugs may provide a level of patient
management adequate for many procedures, such as root planing
and curettage7 and restoration or extraction of primary teeth,8
but it may prove inadequate for procedures such as radiographs,
which require a patient to remain immobile during exposure,18
though more recent studies do demonstrate considerable success
with rectal sedation for radiologic examination.19,20
The administration of rectal drugs is often considered difficult
for the administrator and uncomfortable for the patient. Of
80 children receiving rectal premedication, deWaal, Huisman,
and Veerman reported that 66 (82.5%) accepted rectal instil-
lation well, 12 (15%) moderately well, and 2 (2.5%) poorly.21
The patient receiving rectal drugs for sedation should receive
supplemental oxygen and be monitored via pulse oximetry
and pretracheal stethoscope. Personnel and equipment for
resuscitation must always be available.
DRUGS
Many drugs have been administered rectally. Ideally a rectally
administered drug will be available as a suppository, although
in several cases (e.g., midazolam), drug formulations designed
for parenteral administration have been successfully employed.
Historically the two major drug groups that have been employed
rectally are the barbiturates and opioids. More recently, the
rectal administration of the benzodiazepine midazolam has
received considerable attention. Because barbiturates are no
longer recommended for clinical use in sedation, the discussion
to follow will focus on nonbarbiturates. Full discussion of the
rectal administration of barbiturates may be found in prior
editions of this textbook.22
1. Opioids
a. Hydromorphone
b. Oxymorphone
2. Promethazine
3. Chloral hydrate
4. Benzodiazepines
a. Diazepam
b. Midazolam
5. Ketamine
Hydromorphone
Hydromorphone is an opioid analgesic whose primary indication
is the relief of pain. One of the advantages of hydromorphone
is a low incidence of nausea and vomiting. Sleep occurring
after its administration is a result of the relief of pain, not
hypnosis.
Hydromorphone administered rectally provides long-
lasting pain relief. The onset of action of the drug
occurs within 30 minutes, and it has a duration of action of
4 to 5 hours.
Dosage
Adults: 3 mg suppository PR (per rectum) every 6 to 8 hours.
Titrate to pain relief.23
Availability
Dilaudid (Knoll): 3-mg suppositories. Hydromorphone is
classified as a Schedule II drug.
Oxymorphone
Oxymorphone is a rapid-acting opioid analgesic used primarily
for the management of pain. It also produces sedation and is
therefore indicated for use in preoperative sedation. Following
oral or rectal administration, the onset of action occurs within
30 minutes; the duration of action is approximately 6 hours.
Dosage
Adults: 5 mg PR every 4 to 6 hours. Doses may be cautiously
increased as needed. Geriatric or debilitated adults may require
lower doses or extended dosing intervals.24 The safe use of
oxymorphone in children younger than 12 years has not been
established.
Availability
Numorphan (DuPont): 5-mg suppositories. Oxymorphone is
classified as a Schedule II drug.
122 CHAPTER 8  Rectal Sedation
Promethazine
The pharmacology of promethazine, a phenothiazine derivative,
has been discussed in the section on oral sedation (see Chapter
7). Promethazine may also be administered rectally for preopera-
tive sedation and in the management of nausea and
vomiting.
Dosage
The usual adult dose is 25 to 50 mg 1 hour before bedtime.
For preoperative sedation of adults, the dose is 50 mg 1 hour
before treatment. For sedation of children ≥2 years, the usual
dose is 12.5 to 25 mg 1 hour before treatment.25
Availability
Phenergan (Wyeth): 12.5-, 25-, and 50-mg suppositories.
Chloral Hydrate
Chloral hydrate, a nonbarbiturate sedative-hypnotic, no longer
available in the United States and the United Kingdom, has
been reviewed in Chapter 7. Chloral hydrate is also used rectally
for preoperative sedation.
Dosage
For adults for preoperative sedation or to aid in falling asleep
the night before dental treatment, the usual dose is 650 to
1300 mg 1 hour before treatment or bedtime. The dosage for
children is discussed in Chapter 35.
Availability
Rectules (Fellows): 650- and 1300-mg suppositories. Chloral
hydrate is classified as a Schedule IV drug. Chloral hydrate is
no longer available in the United States, United Kingdom and
European Union.
Diazepam
Diazepam has been used rectally for two specific purposes in
medicine: management of seizures26 and management of anxiety
in a variety of clinical settings, including in terminal cancer
patients27 and in adults for sedation during oral surgery.28 The
pediatric use of rectal diazepam has been well received.29 Mattila
et al30 stated that the rectal solution of diazepam is a faster
and more effective and reliable alternative to either tablets or
suppositories and to the uncertain intramuscular (IM) injection
of diazepam. Diazepam is not available at this time in the
United States in a rectal formulation; however, it is available
in this form in many countries, where its administration rectally
has been well accepted.
Flaitz, Nowak, and Hicks31 reported on the effective use of
rectally administered diazepam for pediatric sedation in
dentistry. Using the IV formulation of diazepam, a dose of
0.6 mg/kg was administered rectally. Effective levels of both
sedation and anterograde amnesia were found in most patients.
A potential complication of the rectal administration of diazepam
is intestinal irritation, the incidence of which is thought to be
quite low.32
Midazolam
Midazolam, a water-soluble benzodiazepine, has received
considerable attention as a rectally administered drug for
premedication or sedation.6,8,9,11,17,18,21,33–38 Various doses of
rectal midazolam have been used, ranging from 0.2 to 5.0 mg/
kg. It appears that a rectal dose of approximately 0.35 mg/
kg6,17,39 to 0.5 mg/kg9,21 provides a rapid onset of action and
a high level of successful sedation, with minimal intraoperative
or postoperative complications. Roelofse et al6,39 observed that
23% of the 60 patients receiving rectal midazolam exhibited
disinhibition reactions, particularly those receiving a dose of
0.45 mg/kg. Reactions observed included agitation-excitement,
restlessness-irritation, disorientation-confusion, and emotional-
crying responses.
Midazolam is not available in a rectal formulation. The
parenteral formulation of midazolam has been used, with 2 mL
of midazolam diluted with 8 mL of distilled water.21 This volume
is then instilled behind the anal sphincter with a suitable plastic
applicator. Unlike diazepam, midazolam has not been observed
to produce irritation of the rectal mucosa.
Studies in which vital signs and other physiologic parameters
were monitored after the rectal administration of midazolam
show no clinically significant changes in arterial blood pressure,
heart rate, oxyhemoglobin saturation, or end-tidal carbon
dioxide concentrations.11,40
Availability
Midazolam is not available as a rectal formulation, nor is it
recommended for rectal administration in the United States.
Several European countries (e.g., France and Switzerland) have
approved the pediatric use of midazolam via rectal administra-
tion.41 Midazolam is classified as a Schedule IV drug.
Ketamine
Ketamine, a cyclohexane derivative, is classified as a dissociative
anesthetic. First reported in 1969, ketamine produces a surgical-
depth anesthesia by interrupting afferent impulses reaching
the cerebral cortex.42 During dissociative anesthesia, patients
appear to be awake—their eyes may be open, their mouths
moving—yet they are incapable of purposefully reacting to
environmental stimulation with appropriate motor responses.43
The pharmacology of ketamine is discussed in greater detail
in Chapter 31. Although used primarily via the IM and IV
routes, ketamine has also been administered rectally for pre-
medication or sedation.1,35,38 Holm-Knudsen, Sjogren, and
Laub35 used 10 mg/kg ketamine and 0.2 mg/kg midazolam
for induction of general anesthesia in healthy 2- to 10-year-olds
and reported that no cases of rectal irritation or unpleasant
dreams occurred and that postoperative analgesia was good.
Vander Bijl, Roelofse, and Stander38 also administered rectal
ketamine (5 mg/kg) and midazolam (0.3 mg/kg) to patients
2 to 9 years old. They reported that 30 minutes after administra-
tion of the two drugs, good anxiolysis, sedation, and cooperation
were obtained in most patients. The group that received
midazolam alone appeared to have more efficacious results
 CHAPTER 8  Rectal Sedation 123
and fewer adverse effects than the group that received ketamine
alone (but no statistical difference was noted).38
A commonly reported side effect of ketamine via any route
of administration is vivid dreams or hallucinations.42 Such
adverse events are rarely noted in pediatric patients, who
generally tolerate ketamine anesthesia quite well. Ketamine
should not be used by dentists who are not trained in general
anesthesia and in the management of the airway of the uncon-
scious patient.
Lytic Cocktail
The lytic cocktail is a combination of meperidine (Demerol),
promethazine (Phenergan), and chlorpromazine (Thorazine),
also known as DPT.43 Used intramuscularly, DPT was frequently
used in hospitals (especially in the emergency room) during
painful procedures. The efficacy of this mixture is poor,
especially when compared with alternative approaches, and it
has been associated with a high frequency of adverse effects.44,45
It has been used rectally in pediatric patients. A dose of 0.07 mL/
kg was administered to patients ranging in age from 1 to 12
years.46 One milliliter of lytic cocktail contains 28 mg meperi-
dine, 7 mg promethazine, and 7 mg chlorpromazine. Satisfactory
sedation was achieved before operation in most patients, but
following the procedure, rectally premedicated patients were
less sedated than a control group that received IM DPT.
The lytic cocktail has fallen into disfavor, and this is noted
in the U.S. Department of Health and Human Services’ Clinical
Practice Guideline on Acute Pain Management.47 They conclude
that the lytic cocktail “is not recommended for general use
and should be used only in exceptional circumstances.”
COMPLICATIONS OF RECTAL
ADMINISTRATION
Several complications are associated with rectal administration
of drugs. Primary among these is the initiation of a bowel
movement by instillation of a large volume of fluid into the
rectum.14 The incidence of this complication is not documented,
but it is estimated to occur in 5% to 10% of patients receiving
rectal drugs.14
Irritation of rectal mucosa, even to the extent of
ulceration, is possible with certain drugs and with prolonged
rectal administration.48 Long-term rectal administration of
acetylsalicylic acid has produced rectal ulceration. However,
even single-dose rectal instillation has produced rectal
irritation.
The potential for oversedation or the loss of consciousness
(general anesthesia), both with attendant risk of airway obstruc-
tion produced by the relaxed tongue, must be considered
whenever rectally administered drugs are intended to provide
deep sedation. This risk is increased when opioid agonists or
ketamine are used. The occurrence of oversedation, inadvertent
general anesthesia, or airway obstruction is decreased when
rectal benzodiazepines are employed.
SUMMARY
The use of rectally administered drugs has increased in popular-
ity in many countries, especially since the introduction of
midazolam. Clinical trials have demonstrated that drugs
administered rectally are usually well accepted, are well toler-
ated, and provide a relatively rapid onset of action with a
minimum of adverse effects or complications. Rectally admin-
istered drugs provide an alternative to the oral and parenteral
routes, which might prove difficult to employ or be contrain-
dicated in certain populations, such as pediatric patients and
patients with disabilities.
Rectal sedation should be considered only by dentists
who are knowledgeable in the pharmacology of the drug(s)
to be administered and in the potential side effects and com-
plications of the technique and drug(s) and who are adept
in the management of the unconscious patient and airway.
In addition, I strongly recommend that (1) supplemental
oxygen be administered to all patients receiving sedation via
rectal drugs; (2) an IV infusion be maintained throughout
the procedure; and (3) continuous monitoring of the patient,
to include pulse oximetry, capnography (where required by
state or provincial mandate), and a pretracheal stethoscope,
be employed.
When rectal sedation is used, the drug should be admin-
istered in the dental office to ensure proper dosing and monitor-
ing following administration. Whenever possible, the use of
benzodiazepines, midazolam or diazepam, should be considered.
Opioids, ketamine, and especially the barbiturates or lytic
cocktail ought not to be given rectally. Adequately trained
personnel must be available to manage the patient during and
after sedation.
State and provincial regulations for enteral sedation (oral)
govern the use of rectal sedation in most jurisdictions.
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