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Procedural sedation in adults outside the operating room

Author: Robert L Frank, MD, FACEP

Section Editor: Allan B Wolfson, MD
Deputy Editor: Jonathan Grayzel, MD, FAAEM

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2017. | This topic last updated: Jun 22, 2017.

INTRODUCTION — The practice of acute care medicine often requires the performance of
procedures that can cause pain and anxiety. Procedural sedation reduces the discomfort,
apprehension, and potential unpleasant memories associated with such procedures and facilitates
performance of the procedure.

The practice of procedural sedation in adults, including monitoring and medications, will be reviewed
here. Procedural sedation in children and the sedation required for lengthier procedures, such as
colonoscopy, are discussed separately. (See "Procedural sedation in children outside of the operating
room" and "Overview of procedural sedation for gastrointestinal endoscopy".)

DEFINITIONS — Procedural sedation involves the use of short-acting analgesic and sedative
medications to enable clinicians to perform procedures effectively, while monitoring the patient closely
for potential adverse effects. This process was previously (and inappropriately) termed "conscious
sedation," but because effective sedation often alters consciousness, the preferred term is now
"procedural sedation and analgesia" (PSA) [1].

The practice of providing sedation, once primarily the domain of anesthesia practitioners, is now
routinely performed by other specialists, such as emergency clinicians, critical care specialists, and
various nurse specialists [2].

Recognizing that PSA exists along a spectrum, the Joint Commission on Accreditation of Healthcare
Organizations in the United States has attempted to define the levels of sedation, which range from
minimal sedation to general anesthesia [3-5]. Common terms include the following:

● Analgesia – Relief of pain without intentionally producing a sedated state. Altered mental status
may occur as a secondary effect of medications administered for analgesia.

● Minimal sedation – The patient responds normally to verbal commands. Cognitive function and
coordination may be impaired, but ventilatory and cardiovascular functions are unaffected.

● Moderate sedation and analgesia – The patient responds purposefully to verbal commands alone
 or when accompanied by light touch. Protective airway reflexes and adequate ventilation are
maintained without intervention. Cardiovascular function remains stable.

● Deep sedation and analgesia – The patient cannot be easily aroused but responds purposefully
to noxious stimulation. Assistance may be needed to ensure the airway is protected and
adequate ventilation maintained. Cardiovascular function is usually stable.

● General anesthesia – The patient cannot be aroused and often requires assistance to protect the
airway and maintain ventilation. Cardiovascular function may be impaired.

● Dissociative sedation – Dissociative sedation is a trance-like cataleptic state in which the patient
experiences profound analgesia and amnesia but retains airway protective reflexes, spontaneous
respirations, and cardiopulmonary stability [6]. Ketamine is the pharmacologic agent used for
procedural sedation that produces this state. (See 'Ketamine' below.)

Sedation exists on a continuum, and it is difficult to divide it into discrete clinical stages, the definitions
above notwithstanding [5]. Moreover, many sedatives can cause rapid changes in the depth of
sedation. Dissociative sedation stands apart from the continuum of sedation due to its unique
characteristics.

INDICATIONS — There are no absolute indications for the performance of procedural sedation and
analgesia (PSA). PSA may be used for any procedure in which a patient's pain or anxiety may be
excessive and may impede performance. PSA is often useful for procedures where deep relaxation
facilitates performance (eg, closed reduction of a dislocated joint). Common procedures in which PSA
may be beneficial include electrical cardioversion, closed joint reduction, complicated laceration repair,
abscess incision and drainage, and lumbar puncture.

CONTRAINDICATIONS AND PRECAUTIONS

General considerations — There are no absolute contraindications to procedural sedation and

analgesia (PSA). Relative contraindications may include: older age, significant medical comorbidities,
and signs of a difficult airway. Whether the patient recently ate should be considered before
performing PSA, although this does not appear to have a major impact on aspiration risk [7,8]. (See
'Aspiration risk' below.)

Several factors must be considered before proceeding with PSA. First, the clinician and the patient
must agree that the potential benefit of PSA outweighs the risks. Risk depends upon the patient and
the procedure.

There is no specific age above which PSA may not be performed. Nevertheless, the elderly have
higher rates of adverse events [9]. This may be due to an increased sensitivity to sedative drugs,
medication interactions, and higher peak serum levels of administered drugs [10-12].

Patients with major comorbid medical conditions are at increased risk for adverse events with PSA.
This correlates with an ASA physical status classification of Class III or greater (table 1) [10,12].
Important comorbidities are those that increase patient susceptibility to the cardiorespiratory
depressant effects of sedatives. They include heart failure, chronic obstructive pulmonary disease,
neuromuscular disease, dehydration, and anemia. Unfortunately, there is no evidence that alternative
approaches (eg, monitored anesthesia care or general anesthesia in the operating room) are safer for
patients at increased risk from PSA.

To reduce the risk of adverse events in the elderly and patients with major comorbid disease, we
suggest a more conservative approach to PSA medications, including:

● Giving a lower starting dose

● Using slower rates of administration
● Repeated dosing of medications at less frequent intervals

PSA is relatively contraindicated in patients who are likely to be difficult to ventilate or oxygenate
should respiratory difficulties arise while the patient is sedated. Alternatives to PSA may be preferable
if signs suggesting a difficult airway are identified. (See "Approach to the difficult airway in adults
outside the operating room".)

No data clearly demonstrate that a longer duration of PSA correlates with an increase in adverse
outcomes. Nevertheless, common sense suggests that it is preferable to sedate patients for the
shortest period necessary to perform the procedure.

Aspiration risk — Aspiration of gastric contents during anesthesia or PSA is a rare, though much
feared complication [7,8]. Patients undergoing emergency procedures requiring sedation are thought
to be at increased risk of aspiration because their stomachs are often full, and the procedure cannot
be delayed. Aspiration frequently does not cause harm. However, aspirated gastric contents above a
critical volume and acidity can cause severe respiratory and systemic consequences [13]. The
importance of fasting for preventing aspiration during PSA remains unclear.

Guidelines to reduce aspiration risk were put forth in a consensus statement by the American Society
of Anesthesiologists (ASA) [3]. These guidelines are based upon expert opinion and to a lesser extent
extrapolated from general anesthesia data, in which aspiration with serious consequences is rare
[3,14]. The ASA guidelines recommend that patients undergoing PSA for "elective procedures" fast
according to the standards used for general anesthesia. This requires that patients not eat or drink for
two hours after drinking clear liquids and six hours after ingesting solid foods or cow's milk [3]. If these
standards cannot be met, the guidelines recommend that the clinician consider delaying the
procedure, reducing the level of sedation, or protecting the airway with endotracheal intubation.

Implementing these guidelines in the emergency department (ED) presents several problems. First, it
is rare that patients requiring emergent PSA meet these fasting criteria. Second, emergent procedures
cannot be delayed. Finally, although fasting to reduce the risk of aspiration during PSA or elective
surgery makes intuitive sense, there is little evidence to support this approach [14-19].

According to one review, patients who fast for two hours have the same gastric volume and pH as
those who fast for longer periods [13]. Furthermore, there is no clear evidence that a relationship
exists among fasting time, gastric volume, gastric pH, depth of sedation, and the likelihood of
aspiration [6,12,16,18,20,21]. Clinically significant aspiration during emergency department PSA
appears to be rare [7]. Furthermore, endotracheal intubation may not protect the patient from
aspiration [14,18,20,22-24]. Aspiration can occur despite the presence of an endotracheal tube, while
the airway manipulation involved in performing intubation appears to increase the risk of aspiration.
In light of the available literature, the American College of Emergency Physicians policy statement on
PSA states: "Recent food intake is not a contraindication for administering procedural sedation and
analgesia but should be considered in choosing the timing and target of sedation" [25]. We concur and
suggest the following approach to reducing aspiration risk:

● Carefully consider the risks and benefits of performing the procedure emergently. Although there
is no proof that longer fasting times reduce aspiration risk, it is reasonable to wait if the patient's
stomach is full and the procedure is not a true emergency [26]. This is particularly true when a
potentially difficult airway or an increased risk for aspiration exists, such as with the following
circumstances [18]:

• Conditions predisposing to esophageal reflux (eg, bowel obstruction, hiatal hernia)

• Extremes of age (<6 months or >70 years old)

• Severe systemic disease (ASA class III or greater)

• Other concerning conditions (eg, depressed mental status)

● Avoid deep sedation. No evidence clearly demonstrates that deeper levels of sedation increase
the risk of aspiration [18]. Nevertheless, lighter sedation may permit the patient to maintain
protective airway reflexes, which reduces risk.

● We do not suggest administration of pre-procedural antacids or motility agents to reduce

aspiration risk. These medications have not been shown to reduce such risk [16].

In some cases it may be best to perform the procedure under general anesthesia in the operating
room, although this approach has not been proven to reduce the risk of aspiration [21,22].

PERFORMING PROCEDURAL SEDATION

Informed consent — Before performing procedural sedation and analgesia (PSA), the clinician must
discuss the risks, benefits, and alternatives of the procedure and the planned sedation with the patient
and answer any questions. A printed informed consent form may be used. Implied consent is
acceptable in some cases where the patient is unable to provide explicit consent due to severe pain or
altered mental status [25].

Prerequisites and personnel — Although previously the domain of anesthesia practitioners, PSA is
performed safely by other clinicians, including emergency and critical care physicians and nurse
specialists [27]. Clinicians providing PSA should have in-depth knowledge of the relevant drugs,
including their mechanism of action, doses, side effects, and reversal agents. Such clinicians must
also be well versed in advanced cardiovascular life support, including airway management. (See
"Advanced cardiac life support (ACLS) in adults".)

The number of clinicians needed to perform PSA and the procedure safely may vary according to the
patient and the procedure. In most cases, one clinician performs the procedure while another (usually
a nurse) administers the sedative agents and monitors and records the patient's vital signs and clinical
status. Whenever possible, we suggest that this minimum standard be met [19].
It remains controversial whether an additional clinician, separate from the clinician performing the
procedure, who is skilled in deep sedation administration and airway management should be present
[12,25]. Guidelines from the American Society of Anesthesiologists (ASA) call for someone with
"advanced life support skills" to be immediately available (within five minutes) for PSA and present in
the procedure room whenever deep sedation is being performed [3]. Large case series of propofol
sedation administered by nurses for ambulatory procedures demonstrate that serious adverse events
can occur [28]. However, one prospective observational study of over 1000 procedural sedations
found that PSA performed by a single emergency clinician (EP) had comparably low complication and
high success rates when compared with PSA performed with both an EP and a nurse present [29].

Equipment — All equipment necessary to perform the procedure and manage the airway should be
available at the bedside during the performance of PSA. Such equipment includes suction to manage
vomiting or oral secretions, airway adjuncts, such as a bag-valve mask and oral and nasal airways,
and equipment to perform endotracheal intubation. Intravenous access should be established.
Resuscitation medications, including advanced cardiac life support medications and reversal agents
(ie, naloxone and flumazenil) should be available. Appropriate monitors should be in place. (See
'Monitoring and preoxygenation' below.)

Monitoring and preoxygenation — Proper monitoring of patients during the performance of PSA is
crucial. The patient's blood pressure, heart rate, and respiratory rate should be measured at frequent,
regular intervals; the oxygen saturation (SpO2), end-tidal carbon dioxide (EtCO2) level, and cardiac
rhythm should be monitored continuously [12].

The patient's response to medications and the procedure must also be closely monitored during PSA.
The patient's level of alertness, depth of respiration, and response to painful stimuli (eg, fracture
reduction) are all important factors in determining subsequent medication doses. Sedation scales,
such as the Richmond Agitation Sedation Scale and the Ramsay Score, have not been adequately
studied in the setting of PSA. They may be more useful in determining the appropriate titration of
sedatives during long-term procedures (eg, mechanical ventilation).

Supplemental oxygen is often recommended during PSA to maintain oxygen reserves and prevent
hypoxemia caused by hypoventilation [3]. However, there is little evidence to show that this is
beneficial and some researchers question the practice.

The best evidence supporting the use of oxygen is a double blind, randomized trial of adults
undergoing PSA with propofol in which episodes of hypoxia (SpO2 <93 percent) lasting longer than 15
seconds occurred significantly more often (41 percent) among the 58 patients given compressed air
by face mask compared to the 59 patients given high flow oxygen (19 percent) using the same
delivery system (difference 23 percent; 95 percent CI 6-38 percent). [30]. However, the clinical
significance of such transient episodes of hypoxia remains debatable.

Several observational studies have found that supplemental oxygen at lower concentrations does not
reliably prevent hypoxemia during PSA [31,32], and delays the detection of respiratory depression in
patients without EtCO2 monitors, since SpO2 levels may not fall until a prolonged period of
hypoventilation or apnea has occurred [33,34]. Nevertheless, we suggest that high flow oxygen by
face mask be given to patients undergoing PSA because it may reduce the likelihood of hypoxic
episodes, particularly with prolonged procedures, is easy to perform, and is highly unlikely to cause
harm.

However, among patients not provided with supplemental oxygen, respiratory difficulty during PSA can
manifest earlier as hypoxia, as detected by pulse oximetry, rather than as hypoventilation, as
determined by EtCO2 monitors, according to a small nested randomized trial [35]. Therefore, close
attention to pulse oximetry readings remains critical when monitoring patients breathing room air
during PSA.

Although evidence is limited, we recommend pulse oximetry and EtCO2 monitoring for all patients
undergoing PSA [36]. EtCO2 measurements correlate closely with arterial CO2 and provide an early
sign of hypoventilation or apnea, especially if supplemental oxygen is used [19,33,37,38]. EtCO2 is
discussed in detail separately. (See "Carbon dioxide monitoring (capnography)".)

While intuitively it makes sense that early detection of hypoxemia and hypoventilation is beneficial,
there is no data to suggest that brief episodes of either have a negative impact on patient outcome,
especially if recognized quickly and treated appropriately [25,39].

Bispectral analysis monitoring (BIS), a technology developed to monitor the level of general
anesthesia, does not appear to be useful for monitoring the depth of procedural sedation [40-42]. BIS
measurements do not appear to correlate well with clinical sedation and have poor reproducibility.

Considerations in pregnancy — Modifications of procedural sedation guidelines recommended for

pregnant women include:

● Pre-procedural administration of medication to improve gastroesophageal sphincter tone and

reduce gastric volume (eg, metoclopramide) and decrease stomach acidity (eg, H2 antagonists,
sodium citrate) may reduce the risk of vomiting and aspiration and is unlikely to cause harm.
Aspiration risk is discussed separately. (See 'Aspiration risk' above.)

● Pre-procedural hydration and left lateral displacement of the uterus (in the late second and the
third trimester) helps to reduce the risk of hypotension, uteroplacental insufficiency, and resultant
fetal hypoxemia. Fetal monitoring is not required but should be considered for women in the third
trimester. (See "Nonstress test and contraction stress test".)

● Oxygen by face-mask is administered because of the risk of sedation-related maternal

desaturation (primarily due to decreased functional residual capacity). (See "Maternal adaptations
to pregnancy: Cardiovascular and hemodynamic changes" and "Maternal adaptations to
pregnancy: Physiologic respiratory changes and dyspnea", section on 'Respiratory changes'.)

COMPLICATIONS — Serious complications attributable to PSA rarely occur [43,44]. According to a

systematic review of 55 studies including 9652 cases of PSA performed in the emergency department,
the rate of severe adverse events requiring an emergency intervention is exceedingly low [44].
Adverse outcomes may include respiratory depression with hypoxia or hypercarbia, cardiovascular
instability, vomiting and aspiration, emergence reactions, and inadequate sedation preventing
completion of the procedure [10]. However, significant respiratory compromise, the most concerning
potential complication, develops in well less than 1 percent of cases. Among the studies included, the
review identified one case of aspiration in 2370 sedations (1.2 per 1000), one case of laryngospasm in
883 sedations (4.2 per 1000), and two intubations in 3636 sedations (1.6 per 1000).
Multiple studies of pediatric patients have found that PSA is safe, with no deaths reported and few
serious consequences [28,45-47]. One observational case series of 640 patients undergoing PSA
reported a 15 percent combined adverse event rate (adverse event and failure to perform procedure)
[9]. In this study, factors associated with adverse events included older age, the presence of multiple
medical conditions (ie, higher ASA class), and the performance of esophagoscopy or cardioversion.

Many complications can be prevented through appropriate selection of patients, proper use of
sedative medication, and careful monitoring of sedation. Particular attention should be paid to patients
in whom oxygenation and ventilation may be difficult, should the need for airway management arise.
Such patients may not be appropriate candidates for PSA. (See 'Contraindications and precautions'
above.)

Nearly all of the sedative agents used for PSA can cause dose-dependent respiratory depression [10].
Therefore, respiratory complications are the most common adverse events. Oxygen desaturation
develops in up to 11 percent of adults who receive PSA with either propofol or etomidate and are
given supplemental oxygen [12]. Rates are slightly higher if supplemental oxygen is not used. Oxygen
desaturation can be minimized by cautious, unhurried medication administration [10].

Hypoventilation and apnea may occur but are usually short-lived due to the brief duration of the drugs
used for PSA. These complications nearly always resolve with patient stimulation, supplemental
oxygen, positioning of the airway, or brief ventilatory support using a bag-valve mask. Treatment with
the reversal agent naloxone or flumazenil may be necessary with more severe or prolonged
respiratory depression during PSA using opioids or benzodiazepines. The use of naloxone and
flumazenil are reviewed separately. (See "Acute opioid intoxication in adults", section on 'Basic
measures and antidotal therapy' and "Benzodiazepine poisoning and withdrawal", section on 'Antidote
(flumazenil)'.)

Significant hypotension and bradycardia seldom occur but may develop in patients with significant
cardiac morbidity and those taking cardiodepressant medications (eg, beta blockers) [10,43,48,49].
The problems are usually transient and resolve without intervention. Hemodynamically neutral
sedatives (eg, etomidate) may be preferable for patients at risk from changes in blood pressure or
heart rate.

Nausea and vomiting occur in about 5 percent of patients undergoing PSA, although rates may be
higher when opioids are used [50-53]. Antiemetics may be used as needed. There is little evidence
about the prophylactic use of antiemetics or which agent is preferable. In one randomized trial
involving PSA with ketamine, 16 of 127 children managed without antiemetics experienced post-
procedural vomiting versus 6 of 128 children pretreated with ondansetron, a 7.9 percent reduction in
absolute risk (95% CI 1.1-14.7) [54].

MEDICATIONS — Procedural sedation and analgesia (PSA) typically involves the intravenous (IV)
administration of sedative or dissociative agents, sometimes in combination with short-acting opioids
(table 2) [25]. Ideal drugs for PSA have a rapid onset and short duration of action, maintain
hemodynamic stability, and do not cause major side effects [2]. Several medications are commonly
used and no single drug is ideal for all situations.

Propofol — Propofol is a phenol derivative that has been shown to provide effective PSA for
emergent procedures [2,55]. Propofol is highly lipophilic and therefore crosses the blood-brain barrier
rapidly. The drug takes effect within approximately 40 seconds, and its duration of action is
approximately six minutes [12,55]. Propofol acts as a sedative and amnestic but provides no
analgesia. In addition to its use for PSA, propofol is used for long-term sedation in critically ill patients,
which is discussed separately. (See "Sedative-analgesic medications in critically ill adults: Properties,
dosage regimens, and adverse effects", section on 'Propofol'.)

Propofol can induce deep sedation rapidly and must be given with careful attention to dosing and
monitoring. For PSA in adults, propofol is given by slow injection in an initial loading dose of 0.5 to 1
mg/kg IV, followed by doses of 0.5 mg/kg IV every three to five minutes as necessary until the
appropriate level of sedation is achieved [12]. One reasonable approach to administration is to give 20
mg every 10 seconds (eg, a 50 mg dose would be given over 25 seconds), although there is no direct
evidence demonstrating improved efficacy or safety using this regimen. (See 'Monitoring and
preoxygenation' above.)

The pharmacokinetics of propofol appear to be unchanged in patients with impaired kidney or liver
function. However, plasma levels appear to be increased in elder patients, which can lead to
prolonged sedation and more pronounced cardiorespiratory depression. Patients over 55 are
particularly sensitive [12]. The manufacturer recommends that doses in elders be reduced by 20
percent and that the drug be given more slowly (over three to five minutes) [56]. Reductions from 20 to
60 percent of the dose used in a healthy young adult are reasonable. (See 'Elderly patients' below.)

The propofol formulation contains egg lecithin and soybean oil, and therefore is contraindicated in
patients with a sensitivity to either of these substances [57].

Potential side effects include hypotension (due to myocardial depression) and respiratory depression.
These side effects generally resolve quickly and uneventfully because of the brief duration of action.
However, hypotension can produce complications in patients with severe medical problems (eg,
sepsis, cardiac dysfunction) or hypovolemia [12].

Respiratory depression usually manifests as a mild oxygen desaturation. Coadministration with other
sedatives or analgesics (eg, fentanyl) can exacerbate respiratory problems. Episodes of hypoxia are
generally uneventful and successfully treated with supplemental oxygen and patient stimulation, and
less commonly require short periods of assisted ventilation with a bag-valve mask. There are no
reports of endotracheal intubation due to propofol-induced respiratory depression during PSA [12].

Propofol provides no analgesia and can cause pain during injection through an intravenous catheter.
According to a systematic review of 177 randomized controlled trials involving 25,260 adult patients,
the following measures are significantly effective at reducing pain caused by propofol injection [58]:

● Injecting into an antecubital vein rather than a hand vein (relative risk [RR] 0.14; 95% CI 0.07-
0.30)

● Lidocaine pretreatment while occluding the vein (RR 0.29; 95% CI 0.22-0.38)

● Pretreatment with lidocaine-propofol admixture (RR 0.40; 95% CI 0.33-0.48)

● Lidocaine pretreatment without vein occlusion (RR 0.47; 95% CI 0.40-0.56)

 ● Opioid pretreatment (RR 0.49; 95% CI 0.41-0.59)

● Ketamine pretreatment (RR 0.52; 95% CI 0.46-0.57)

Pain during injection can also be reduced by using larger catheters placed in larger veins.

Pretreatment with any of several analgesics can reduce the pain caused by propofol. One effective
approach is to place a tourniquet on the arm proximal to the injection site and then give 0.5 mg/kg of
lidocaine IV 30 to 120 seconds before propofol is injected [55].

Another approach is pretreatment with short-acting opioids (eg, fentanyl). Unfortunately, the addition of
opioids increases the likelihood of respiratory complications. As an example, fentanyl at a dose of 1.5
mcg/kg increases the risk of respiratory depression. To reduce this risk, smaller doses of fentanyl
should be used. The best dose to provide adequate analgesia with minimal respiratory risk has yet to
be identified. We suggest that no single dose of fentanyl exceed 0.5 mcg/kg when given with propofol
and that the total amount of fentanyl be kept to the minimum required for effective analgesia.

It may not be necessary to combine propofol with a short-acting opioid if the patient's pain is
adequately treated prior to the procedure. This approach is supported by an unblinded randomized
trial in which patients given PSA consisting of propofol alone had pain levels identical to those treated
with both propofol and alfentanil [59]. For both treatment groups, intravenous morphine was given at
least 20 minutes prior to the procedure to all patients experiencing pain until their symptoms were
adequately relieved. Of note, patients given both alfentanil and propofol required stimulation to induce
respiration more often than those given only propofol.

Another alternative to pretreatment with short-acting opioids is to use sub-dissociative doses of

ketamine (0.3 mg/kg). Ketamine appears to provide comparable analgesia with less risk of respiratory
depression. (See 'Ketamine versus short-acting opioids for analgesia' below.)

In some instances, patients experience little or no pain before or after a procedure (eg, lumbar
puncture, cardioversion) and little if any analgesia may be necessary to supplement propofol. In
addition, some procedures lead to a substantial reduction in pain (eg, dislocation reduction),
decreasing the need for analgesics as part of PSA.

Multiple randomized trials and prospective observational studies have found propofol to be safe and
effective for PSA in the emergency department [12,60,61]. Even in the contentious area of nurse-
administered propofol sedation, where typically the only physician present is performing the procedure
(eg, outpatient endoscopy), there is a large body of evidence documenting the safety and efficacy of
propofol [62,63]. Studies comparing propofol to alternative medications for PSA are limited [64].

Despite the evidence above, not all clinicians who are qualified and wish to administer propofol for
PSA are allowed to do so. Reasons for this are complex and beyond the scope of this discussion but
may include misunderstandings about patient safety as well as political and economic factors [65,66].
The manufacturer's label states: "only those persons trained in the administration of general
anesthesia should administer the drug," and goes on to state: "only those persons not involved in the
conduct of the surgical/diagnostic procedure should administer the drug" [67]. In the United States,
these statements have led some nursing organizations to question whether nurses other than certified
registered nurse anesthetists should administer propofol.
Etomidate — Etomidate, an imidazole derivative, is a sedative that is commonly used for PSA. The
use of etomidate for rapid sequence intubation is discussed elsewhere. (See "Induction agents for
rapid sequence intubation in adults outside the operating room".)

For PSA in adults, etomidate is given IV over 30 to 60 seconds in doses of 0.1 to 0.15 mg/kg, less
than the dose used for rapid sequence intubation. It can be redosed approximately every three to five
minutes as needed. The onset of action of etomidate is almost immediate and its duration of effect is 5
to 15 minutes [68,69].

Etomidate can have more profound and prolonged effects in the elderly and patients with renal or
hepatic dysfunction. In such patients, doses in the lower dosing range should be used. An important
benefit of etomidate is that it maintains cardiovascular stability.

Etomidate has no analgesic properties and often requires the coadministration of a short-acting opioid,
such as fentanyl, which increases the risk of respiratory depression [69]. To reduce this risk, smaller
doses of fentanyl should be used. The best dose to provide adequate analgesia with minimal
respiratory risk has yet to be identified. We suggest that no single dose of fentanyl exceed 0.5 mcg/kg
when given with etomidate and that the total amount of fentanyl be kept to a minimum.

Etomidate causes pain during injection into peripheral veins. Strategies similar to those used for
propofol can be used to reduce such pain. (See 'Propofol' above.)

Several randomized trials and prospective observational studies have found that etomidate is an
effective sedation agent for PSA and does not cause major complications (eg, respiratory depression
requiring endotracheal intubation) [68,70-72]. However, side effects, particularly myoclonus, occur with
regularity and procedure success rates may be lower when compared with propofol or ketamine. (See
'Propofol versus etomidate' below.)

Potential side effects of etomidate include myoclonus, respiratory depression, adrenal suppression,
and nausea and vomiting. Myoclonus is the most frequently reported side effect. It is thought to be
related to subcortical disinhibition and has been reported in up to 80 percent of patients who receive
etomidate for PSA [72-75]. The degree of myoclonus may be dose dependent and ranges from mild
and transient to severe enough to prevent completion of the procedure [68].

Reports of severe myoclonus associated with PSA are rare. In such cases, we suggest immediate
airway support and treatment with midazolam, 1 to 2 mg IV approximately every 60 seconds until
myoclonus abates. Alternative benzodiazepines may be used if midazolam is unavailable.

Strategies to prevent myoclonus vary and there is insufficient evidence to support any one approach:

● According to one small randomized trial, a pretreatment dose of 0.03 to 0.05 mg/kg of etomidate
given 50 seconds before the PSA dose reduces myoclonus [73].

● Another small randomized trial in patients undergoing cardioversion found that a small dose of
midazolam (0.015 mg/kg) given at the same time as etomidate prevents myoclonus [76].

● In another randomized trial, magnesium sulfate administered 90 seconds prior to etomidate was
found to reduce myoclonus [77].
According to a systematic review of etomidate for PSA, respiratory depression occurs in
approximately 10 percent of cases [70]. In this review, respiratory depression was defined as a fall in
oxygen saturation below 90 percent or apnea. No serious complications occurred as a result and
respiratory depression resolved quickly without major interventions in the great majority of cases.
Nevertheless, clinicians must be prepared to support the patient's airway and breathing in the event of
respiratory compromise, as is true whenever PSA is performed.

When given by continuous infusion, etomidate causes adrenal insufficiency. In addition, reductions in
plasma cortisol concentrations have been reported in patients receiving a single induction dose of
etomidate [78,79]. However, the clinical significance of transient reductions in cortisol in patients
undergoing PSA with etomidate remains unclear. Most such patients are relatively healthy and receive
a single sedating dose. In such patients, complications related to adrenal suppression have not been
reported.

Benzodiazepines (midazolam) — Benzodiazepines are commonly used for minimal sedation

(anxiolysis) but less often for deeper sedation due to the superior effectiveness of the ultrashort-acting
agents propofol and etomidate. Benzodiazepines produce anxiolysis and amnesia but have no
analgesic properties.

Midazolam is the benzodiazepine used most often for PSA. Because it is lipophilic, midazolam
penetrates the blood-brain barrier quickly. Midazolam can be used alone for anxiolysis or in
combination with short-acting opioids (eg, fentanyl) for deeper levels of sedation and analgesia. Its
time of onset is two to five minutes, and its duration of action is 30 to 60 minutes [80,81].

Midazolam is usually given IV over one to two minutes in doses of 0.02 to 0.03 mg/kg. Often in adults,
midazolam is given 0.5 or 1 mg at a time and titrated to effect. No single dose should exceed 2.5 mg.
Repeat doses may be given every two to five minutes as necessary.

With repeated doses, midazolam accumulates in adipose tissue, which can significantly prolong
sedation [80]. The elderly, obese, and those with renal or hepatic disease are at greater risk of
prolonged sedation. In such patients, the use of lower doses, longer dosing intervals, and smaller total
amounts reduces risk.

The amount of midazolam necessary for adequate sedation varies based upon many factors,
including patient size and age, medication tolerance, comorbidities, and the duration of the procedure.
In most cases, PSA can be performed using no more than 5 mg of midazolam. For longer procedures
likely to require multiple doses of a sedative, ultrashort-acting agents (eg, propofol) may be preferable.
(See 'Propofol' above.)

Compared with ultrashort-acting agents, midazolam has a longer duration of action that makes it
better suited for anxiolysis than for PSA [74]. Midazolam can cause respiratory depression in high
doses or when given concomitantly with other sedatives or narcotics. For anxiolysis, a single dose of
0.02 mg/kg (approximately 1 to 2 mg) is usually sufficient.

Other benzodiazepines, such as lorazepam and diazepam, are less suited for PSA due to their
relatively prolonged onset and duration of action. They also have more side effects and inferior
amnestic properties compared with midazolam [81,82].
Short-acting opioids — Opioids are often given alone or in combination with sedatives for PSA.
Short-acting agents, such as fentanyl, alfentanil, and remifentanil, are used.

Fentanyl is a synthetic opioid that was frequently used in combination with midazolam to provide
analgesia during PSA before propofol and etomidate became widely available. It has 75 to 125 times
the potency of morphine, a rapid onset of action (two to three minutes), and a short duration of effect
(30 to 60 minutes) but has no amnestic properties [81].

Fentanyl is usually given by slow IV push in doses of 0.5 to 1 mcg/kg every two minutes until an
appropriate level of sedation and analgesia is achieved [81]. The maximum total dose is generally 5
mcg/kg or approximately 250 mcg, but higher doses may be needed in some instances.

Fentanyl rarely causes hypotension and does not stimulate histamine release. Its primary side effect is
respiratory depression, which is potentiated by the coadministration of sedatives. Patients with renal
or hepatic disease and the elderly can experience more prolonged or profound effects. In such
patients, the use of lower doses, longer dosing intervals, and smaller total amounts reduces risk.

Remifentanil and alfentanil are opioids similar in structure to fentanyl with a rapid onset and duration
of action of approximately five minutes, and both are used for PSA [19,83]. The potency of remifentanil
and fentanyl are comparable, but alfentanil is one-fifth to one-tenth as potent. Remifentanil can be
given in combination with propofol for PSA [84-86]. There is no evidence that PSA using remifentanil
and propofol is superior to propofol alone, nor is there evidence that either remifentanil or alfentanil is
superior to fentanyl.

When used in combination with propofol for PSA, remifentanil is given in a dose of 0.5 mcg/kg (and
propofol 0.5 mg/kg) over one minute [85]. Subsequent doses of remifentanil 0.25 mcg/kg and propofol
0.25 mg/kg may be given approximately every one to two minutes. When remifentanil is used ALONE
for PSA, the initial dose is 0.5 to 3 mcg/kg and subsequent doses of 0.25 to 1 mcg/kg may be given
approximately every two minutes as needed [84].

Few studies have assessed alfentanil as a sole agent for PSA and there are no published guidelines
for its use in this manner. In one prospective observational study of 148 adults given alfentanil for
PSA, 58 (39 percent) developed minor respiratory complications requiring intervention (eg, increased
oxygen, brief bag-mask ventilation) despite achieving lighter levels of sedation than typically reached
with propofol [87].

Alfentanil may be used as an adjunct for PSA with propofol and is given in a dose of 2.5 mcg/kg (along
with propofol 0.5 mg/kg). Both may be repeated approximately every two minutes as needed.

Coadministration of midazolam and fentanyl — In settings where ultrashort-acting agents are

unavailable, the combination of midazolam and fentanyl is sometimes used for PSA [25,50,88,89].
Although midazolam alone has not been shown to cause significant respiratory depression, the
combination of midazolam and fentanyl can cause hypoxia and apnea, and increases the need for
airway intervention and medication reversal compared with PSA using ultrashort-acting agents (eg,
propofol) [25,81]. To minimize the risk of respiratory depression, we suggest that midazolam be given
first and fentanyl titrated carefully thereafter, but either order is acceptable. Regardless of drug order,
clinicians must titrate these medications carefully to minimize the risk of oversedation and respiratory
compromise.
One reasonable approach to dosing these medications when they are used together is as follows:

● Give midazolam first: 0.02 mg/kg (maximum 2 mg)

● Wait two minutes and observe patient response; give second dose of midazolam if necessary
● Give fentanyl: 0.5 mcg/kg
● Observe patient; may repeat fentanyl dose every two minutes as necessary; titrate to effect
● Use smaller doses and longer intervals between doses in the elderly and patients with
compromised hepatic or renal function

Ketamine — Ketamine is a phencyclidine derivative that acts as a dissociative sedative. It produces a

trance-like state and provides sedation, analgesia, and amnesia, while preserving upper airway
muscle tone, airway protective reflexes, and spontaneous breathing. Because of its rapid onset,
relatively short duration of action, and excellent sedative and analgesic properties, it is often used for
brief, painful procedures, such as fracture reduction or laceration repair [69,90].

Ketamine is generally given IV to adults, which enables immediate onset, but it can be given
intramuscularly. The duration of effect is 10 to 20 minutes. For PSA in adults, a dose of 1 to 2 mg/kg is
given IV over one to two minutes. Doses of 0.25 to 0.5 mg/kg may be repeated every 5 to 10 minutes
thereafter.

According to a systematic review of 87 studies involving over 70,000 patients, significant adverse
reactions rarely occur when ketamine is used for PSA in adults [91]. The authors emphasize that
ketamine has proven to be an extremely safe drug despite being used frequently in "austere, poorly
monitored settings."

The reported side effects of ketamine include tachycardia, hypertension, laryngospasm, emergence
reactions, nausea and vomiting, increased intracranial and intraocular pressure, and hypersalivation
[69,91-93]. Ketamine can exacerbate schizophrenia and should be avoided in patients with this
condition [94,95]. Tachycardia and hypertension are generally mild and transient, and significant
cardiorespiratory events are rare.

The risk of laryngospasm may be greater in patients with anatomic abnormalities of the upper airway
(eg, tracheal stenosis, tracheomalacia) or those undergoing procedures involving significant or
prolonged stimulation of the oropharynx. Guidelines published by the American College of Emergency
Physicians recommend preventing secretions or blood from accumulating in the posterior oropharynx
and avoiding excessive stimulation of this region with suction devices or other instruments in patients
receiving ketamine for PSA [93].

Emergence reactions are the most commonly reported side effect [91]. These reactions vary in their
intensity and have been described as disorientation, dream-like experiences, or hallucinations that
may be frightening. They occur in up to 20 percent of adults but can be prevented or treated by giving
a small dose of midazolam [2,91,96-99]. For prevention, midazolam, approximately 0.05 mg/kg
(typical adult dose 2 to 4 mg), may be given slowly (over about two minutes) by IV prior to
administering ketamine.

Nausea and vomiting associated with ketamine administration occur in approximately 4 percent of
adults. They usually occur when the patient is awake and alert and do not appear to predispose the
patient to aspiration. Prophylactic treatment with midazolam has met with mixed results in pediatric
populations, but pretreatment with ondansetron or comparable agents may be helpful. (See
"Pharmacologic agents for pediatric procedural sedation outside of the operating room", section on
'Ketamine'.)

Ketamine can lead to hypersalivation, which can be reduced by pretreating with glycopyrrolate or
atropine, although the benefit of such pretreatment is unclear [81].

Barbiturates — Barbiturates suppress the reticular activating center in the brainstem and cerebral
cortex, thereby causing sedation. Methohexital is the most commonly used barbiturate for PSA but
has largely been supplanted by etomidate and propofol.

Methohexital has immediate onset, a duration of action less than 10 minutes, and provides sedation
and amnesia but no analgesia. It is often given in combination with opiates, which can potentiate
respiratory depression. The initial dose of methohexital is 0.75 to 1 mg/kg given intravenously; repeat
doses of 0.5 mg/kg IV can be given every two minutes.

Methohexital causes myocardial depression, which can lead to hypotension and tachycardia. Unlike
other barbiturates, methohexital can precipitate or exacerbate seizures and should be avoided in
patients with a seizure disorder [100]. One small randomized trial found methohexital and propofol to
have comparable safety and efficacy when used for fracture and dislocation reduction [101].

Thiopental is a barbiturate used for induction of general anesthesia, and rarely used in the
performance of PSA. It is similar in efficacy and side effects to methohexital but suppresses seizures.

Ketamine and propofol (ketofol) — "Ketofol" is a combination of ketamine and propofol being
studied for use in PSA. The concept of ketofol is that the benefits of the two medications are
synergistic and allow lower doses of each to be used. Lower doses purportedly reduce the risk for
potential side effects (ie, propofol-induced hypotension and ketamine-induced vomiting and
emergence reactions) [102,103].

According to a systematic review of six randomized trials performed in emergency departments,

patients treated with a ketamine-propofol combination for procedural sedation experienced fewer
adverse respiratory events compared with those treated with propofol alone (29.0 versus 35.4 percent;
RR 0.82, 95% CI 0.68-0.99) [104]. However, many of these adverse events were not clinically
important (eg, brief oxygen desaturation), and the review found no significant difference in the overall
rate of adverse events or in the time required to complete procedures.

Another systematic review of 18 controlled trials comparing combinations of ketamine and propofol (ie,
“ketofol”) to ketamine or propofol alone found that ketofol may cause less respiratory depression
requiring intervention and less bradycardia and hypotension than propofol alone [105]. Although the
interventions required to correct respiratory problems were not described, transient respiratory
depression, bradycardia, or hypotension in patients receiving PSA in the emergency department is
generally not considered clinically significant. If the clinician considers it important to avoid all such
events in a particular patient, the clinician should reconsider whether PSA is appropriate. (See
'Contraindications and precautions' above.)

Some of the better studies of ketofol to date have not shown this combination therapy to be more
efficacious or safer than propofol or ketamine alone when performing PSA in adults [106-111].
Examples include the following:

● A randomized, double-blind, multi-center trial involving 573 patients receiving PSA reported no
clinically significant differences in outcome between those managed with propofol and those
managed with ketofol [112]. Overall, 5 percent of patients in the propofol group and 3 percent in
the ketofol group experienced the primary outcome, a respiratory adverse event (desaturation,
apnea, or hypoventilation) requiring an intervention, an absolute difference of 2 percent (95% CI
-2 to 5%). Patients receiving propofol were more likely to experience hypotension, although this
was not clinically significant, while patients receiving ketofol were more likely to experience
severe emergence delirium.

● A trial performed in the emergency department (ED) of a university teaching hospital reported no
significant difference in the overall incidence of respiratory depression (the primary endpoint)
between patients randomly assigned to treatment with a combination of ketamine and propofol for
PSA (21/97; 22 percent) or propofol alone (27/96; 28 percent) [109]. The authors report that the
group given the combination of ketamine and propofol exhibited fewer episodes of apnea and
oxygen desaturation and more consistent sedation, and required smaller cumulative doses of
propofol. However, these differences did not achieve statistical significance and their clinical
importance remains uncertain.

● A randomized, double-blind trial performed in a community hospital ED, involving 284 patients
requiring PSA, reported no significant difference in adverse respiratory events between patients
treated with a combination of ketamine and propofol (43 events) and those given propofol alone
(46 events) [113]. As with the study above, the ketofol group was reported to experience more
consistent sedation, as determined by sedation scale scores and the need for additional
medication, but there did not appear to be important clinical differences in outcome. Patients
given ketofol had less agitation during the procedure than those given propofol (5 versus 15
patients), while the opposite was true during recovery (10 versus 7 patients).

Nitrous oxide — Nitrous oxide (N2O) is an ultra-short acting agent used for PSA that is inhaled as a
30 to 50 percent mixture, with 30 percent oxygen to avoid hypoxemia. N2O has an immediate onset of
action and provides analgesia, anxiolysis, and sedation. The use of N2O also obviates the need for an
intravenous line. The major disadvantage to N2O is that it must be administered in a well-ventilated
room with a scavenging system to prevent clinician exposure [81].

Few controlled studies about the use of N2O in adults have been published. Studies in children have
generally found it to be safe, but it may not provide adequate analgesia for more painful procedures,
such as fracture reduction [114].

Future medications — New drugs are being developed that may have a future role in PSA.
Fospropofol is a propofol prodrug that may provide more sustained and consistent clinical effects at
lower plasma levels than equivalent doses of propofol. Dexmedetomidine is an alpha 2 agonist similar
to clonidine that has sedative and analgesic effects. Further clinical study of these medications is
needed before recommendations can be made.

MEDICATION SELECTION
Patients without increased risk — Procedural sedation and analgesia (PSA) is generally performed
in relatively healthy patients who are hemodynamically stable. In such patients, we suggest that PSA
be performed using propofol. Etomidate may also be used. The relative advantages and
disadvantages of each drug are discussed immediately below (table 2). However, for well-trained
clinicians experienced in the performance of PSA who are monitoring patients appropriately and
prepared to deal with procedure-related complications, the best sedating medication is often the one
the clinician is most comfortable using.

Propofol versus etomidate — Both propofol and etomidate have gained popularity as
medications for procedural sedation and analgesia (PSA). Both medications are safe and effective in
the performance of PSA, and both possess similar times to onset and recovery [68,115]. Propofol may
result in a higher procedural success rate [68,106].

Factors to consider when choosing between propofol and etomidate include the following:

● Etomidate provides greater hemodynamic stability, as propofol can cause hypotension. The fall in
blood pressure from propofol is generally small and transient, but this difference may be of
importance in patients with hypovolemia or hypotension who undergo PSA [116-118].

● Etomidate can cause myoclonus, which appears to reduce the rate of procedural success
[68,69,119,120].

● Etomidate causes dose-dependent adrenal suppression, which may be harmful in patients with
severe disease (eg, sepsis, multiple trauma). Such patients may not be suitable for PSA. This
effect is unlikely to be important in otherwise healthy patients.

● Respiratory depression occurs at comparable rates during PSA with both drugs, although this
rarely causes harm to the patient.

Few studies have directly compared propofol and etomidate for PSA. In the largest such trial, 214
patients undergoing painful procedures in the emergency department were randomly assigned to
sedation with either medication [68]. Myoclonus was more frequent with etomidate (20 versus less
than 2 percent with propofol). This likely accounts for the lower rate of procedural success in the
etomidate group (89 versus 97 percent). No clinically significant complications (eg, prolonged hypoxia)
occurred in either group.

Propofol versus ketamine — Ketamine is more commonly used to sedate children and few
studies of its role in adult procedural sedation have been performed. One small, unblinded
randomized trial in adults reported higher rates of subclinical respiratory depression (as determined by
changes in end-tidal carbon dioxide [EtCO2] or oxygen saturation), longer median times for return to
baseline mental status (14 versus 5 minutes), and increased agitation during recovery among patients
treated with ketamine for procedural sedation compared to those treated with propofol [121]. The rates
for clinical intervention for respiratory problems, duration of the procedure, and successful completion
of the procedure did not differ between the two groups.

Ketamine plus propofol ("ketofol") — While available evidence suggests that ketofol is a safe
and effective drug combination for procedural sedation, there is no convincing evidence that it
improves clinically significant outcomes or reduces important complications during PSA (which are
rare) compared to propofol.

Patients at increased risk — In some circumstances, clinicians, after carefully considering the
relative risks and benefits, may elect to perform PSA in patients at increased risk of complications.
Suggestions for drug selection in several common scenarios are provided here; contraindications to
PSA are reviewed above (table 2). (See 'Contraindications and precautions' above.)

Patients at risk of hypotension — In patients at risk of hypotension due to recent illness and
dehydration, cardiac disease, or some other condition, we suggest that either etomidate or ketamine
be used for PSA; in contrast, propofol has a greater blood pressure lowering effect [68]. Either agent
will maintain hemodynamic stability. (See 'Etomidate' above and 'Ketamine' above.)

Patient at risk for airway or respiratory complications — In patients who may have a potentially
difficult airway to manage or have compromised respiratory function, we suggest that ketamine be
used for PSA. Ketamine allows the patient to maintain protective airway reflexes and does not cause
respiratory depression.

Elderly patients — Older patients are at increased risk of complications during PSA [9]. As a
result, sedatives administered to older patients for PSA, regardless of the agent, should be given at a
lower starting dose with slower rates of administration and less frequent dosing intervals. In elderly
patients without major comorbidities or hemodynamic instability, it may be best to perform PSA using
an ultrashort-acting sedative, such as propofol. Procedures in elderly patients with major comorbidities
are probably best performed in the operating room. (See 'Propofol' above.)

Ketamine versus short-acting opioids for analgesia — Ultra short-acting opioids (eg, fentanyl)
provide analgesia during PSA but can contribute to respiratory depression. Some researchers
hypothesize that a sub-dissociative dose of ketamine can provide adequate analgesia without the risk
of respiratory depression.

One small randomized trial found that patients given ketamine (0.3 mg/kg IV) and propofol during PSA
achieved similar analgesia but experienced fewer complications compared with patients given fentanyl
(1.5 mcg/kg IV) and propofol, who had five times the risk of experiencing a serious adverse event (eg,
hypoxia) (95% CI 1.9-13.6) [103]. A smaller, nonrandomized trial found that the addition of ketamine
reduced pain and the need for post-procedural analgesics [122]. Further studies are needed to
confirm these preliminary findings.

DISCHARGE CRITERIA — There is little evidence to guide decisions about discharge following
procedural sedation and analgesia (PSA). Some guidelines suggest that patients are ready for
discharge when they have reached their "neuromuscular and cognitive pre-procedure baseline" [123].

Certain conditions should be met before a patient can be considered safe for discharge following PSA:

● The procedure should be of sufficiently low risk that additional monitoring for complications is
unnecessary.

● Symptoms, such as pain, lightheadedness, and nausea should be well-controlled.

● Vital signs and respiratory and cardiac function should be stable.

 ● Mental status and physical function should have returned to a point where the patient can care for
himself or herself with minimal to no assistance.

● A reliable person who can provide support and supervision should be present at the patient's
home for at least a few hours.

Clear written discharge instructions should be given and explained to the patient and to the family
member or friend who will be assisting with the patient's care following PSA. The clinician should
explain what was done, the expected course, potential problems, what to do if problems arise, when
and where to follow up, and when to return to normal activities.

One important issue is to determine a period of observation after which adverse events are sufficiently
unlikely that even a patient who has not entirely returned to baseline (eg, exhibits mild drowsiness)
can be discharged safely. The only study to examine the timing of significant adverse events
associated with PSA was performed in a sample of 1341 children and found that 92 percent of such
events occurred during the procedure, while only 8 percent occurred afterwards [123]. Significant
adverse events rarely occurred more than 25 minutes after the last dose of medication was
administered, provided that no adverse events had occurred up to that point. Rarely, episodes of
hypoxia developed up to 40 minutes after the last medication dose. In all such cases, prior episodes of
hypoxia had occurred.

Based on these data, some clinicians believe that patients can be safely discharged within 30 minutes
of receiving their last dose of sedative provided that no significant adverse events occurred during the
procedure and the patient did not receive a reversal agent (eg, naloxone). Of note, only relatively long
acting agents, such as ketamine, midazolam and fentanyl were used in this study (ie, neither
etomidate nor propofol were used). It is unlikely that a longer period of observation would be
necessary following PSA with ultra-short acting agents [12].

Although serious adverse events, such as hypoxia, rarely occur after discharge, it is not uncommon
for patients to experience mild symptoms, such as nausea, lightheadedness, fatigue, or unsteadiness,
for up to 24 hours [5,124,125]. This should be made clear to the patient.

SUMMARY AND RECOMMENDATIONS

● Procedural sedation and analgesia (PSA) involves the use of short-acting analgesic and sedative
medications to enable clinicians to perform procedures, while monitoring the patient closely for
potential adverse effects. This process was previously (and inappropriately) termed "conscious
sedation." (See 'Definitions' above.)

● PSA may be used for any procedure in which a patient's pain or anxiety may be excessive and
may impede performance. There are no absolute contraindications to PSA. Relative
contraindications include: older age, significant medical comorbidities, and signs of a difficult
airway. Whether the patient recently ate should be considered before performing PSA, although
this may not increase aspiration risk. (See 'Indications' above and 'Contraindications and
precautions' above.)

● The number of clinicians needed to perform PSA and the procedure safely may vary according to
the patient and the procedure. In most cases, one clinician performs the procedure while another
 (usually a nurse) administers the sedative agents and monitors and records the patient's vital
signs and clinical status. Whenever possible, we suggest that this minimum standard be met.
(See 'Prerequisites and personnel' above.)

● Proper monitoring during PSA is crucial. The patient's blood pressure, heart rate, and respiratory
rate should be measured at frequent, regular intervals; oxygen saturation (SpO2), end-tidal
carbon dioxide (EtCO2) level, and cardiac rhythm should be monitored continuously. We suggest
that high flow oxygen (15 L by face mask) be provided to patients receiving PSA. (See 'Monitoring
and preoxygenation' above.)

● Serious complications attributable to PSA rarely occur. Significant respiratory compromise

develops in less than 1 percent of cases. Adverse outcomes may include respiratory depression
with hypoxia or hypercarbia, cardiovascular instability, vomiting and aspiration, and inadequate
sedation preventing completion of the procedure. All equipment and medications necessary for
airway management should be at the bedside during PSA. (See 'Complications' above and
'Equipment' above.)

● Ideal drugs for PSA have a rapid onset and short duration of action, maintain hemodynamic
stability, and do not cause major side effects. Several medications are commonly used and no
single drug is ideal for all situations (table 2). Medications used for PSA are discussed in the text.
(See 'Medications' above.)

● PSA is most often performed in patients without major comorbidities or hemodynamic instability.
In such patients, we suggest that PSA be performed using propofol (Grade 2B). Etomidate may
also be used. The relative advantages and disadvantages of each drug are discussed in the text.
(See 'Patients without increased risk' above.)

● Older patients are at increased risk of complications during PSA. Therefore, sedatives
administered to older patients for PSA, regardless of the agent, should be given using a lower
starting dose, slower rates of administration, and less frequent dosing intervals. (See 'Elderly
patients' above.)

● In some circumstances, clinicians, after carefully considering the relative risks and benefits, may
elect to perform PSA in patients at some increased risk of complications. In patients at risk of
hypotension, we suggest that either etomidate or ketamine be used for PSA (Grade 2C). In
patients who may have a potentially difficult airway or have compromised respiratory function, we
suggest that ketamine be used for PSA (Grade 2C). (See 'Patients at increased risk' above.)

● Criteria for safe discharge following PSA are described in the text. (See 'Discharge criteria'
above.)

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Topic 264 Version 31.0

GRAPHICS

American Society of Anesthesiologists (ASA) Physical Status Classification

System

ASA PS Examples, including, but not

Definition
classification limited to:

ASA I A normal healthy patient. Healthy, non-smoking, no or minimal

alcohol use.

ASA II A patient with mild systemic disease. Mild diseases only without substantive
functional limitations. Current smoker,
social alcohol drinker, pregnancy,
obesity (30<BMI<40), well-controlled
DM/HTN, mild lung disease.

ASA III A patient with severe systemic disease. Substantive functional limitations; one
or more moderate to severe diseases.
Poorly controlled DM or HTN, COPD,
morbid obesity (BMI ≥40), active
hepatitis, alcohol dependence or abuse,
implanted pacemaker, moderate
reduction of ejection fraction, ESRD
undergoing regularly scheduled
dialysis, premature infant PCA<60
weeks, history (>3 months) of MI,
CVA, TIA, or CAD/stents.

ASA IV A patient with severe systemic disease Recent (<3 months) MI, CVA, TIA, or
that is a constant threat to life. CAD/stents, ongoing cardiac ischemia
or severe valve dysfunction, severe
reduction of ejection fraction, sepsis,
DIC, ARDS, or ESRD not undergoing
regularly scheduled dialysis.

ASA V A moribund patient who is not Ruptured abdominal/thoracic

expected to survive without the aneurysm, massive trauma,
operation. intracranial bleed with mass effect,
ischemic bowel in the face of significant
cardiac pathology or multiple
organ/system dysfunction.

ASA VI A declared brain-dead patient whose

organs are being removed for donor
purposes.

The addition of "E" to the numerical status (eg, IE, IIE, etc.) denotes Emergency surgery (an
emergency is defined as existing when delay in treatment of the patient would lead to a significant
increase in the threat to life or body part).

BMI: body mass index; DM: diabetes mellitus; HTN: hypertension; COPD: chronic obstructive pulmonary
disease; ESRD: end-stage renal disease; PCA: post conceptual age; MI: myocardial infarction; CVA:
cerebrovascular accident; TIA: transient ischemic attack; CAD: coronary artery disease; DIC: disseminated
intravascular coagulation; ARDS: acute respiratory distress syndrome.

ASA Physical Status Classification System (Copyright © 2014) is reprinted with permission of the American
Society of Anesthesiologists, 1061 American Lane, Schaumburg, Illinois 60173-4973.
Graphic 87504 Version 8.0
Intravenous procedural sedation medications for adults*

Repeat
Onset Duration
Medication Initial dose dose (as Comments
(minutes) (minutes)
necessary)

Midazolam 0.02 to 0.03 1 to 2.5 10 to 40 May repeat Sedative and

mg/kg over 2 to after 2 to 5 anxiolytic. No
3 minutes; minutes analgesia.
maximum 2.5
Relatively slow
mg (1.5 mg
onset; requires
maximum if more gradual
elderly)
initiation.
Prolonged effect
or delayed
recovery in
elderly, obese, or
impaired hepatic
function.
Use reduced
dose in
combination with
other agents.

Methohexital 0.75 to 1 mg/kg 1 10 0.5 mg/kg Sedative and

every 2 to 5 amnestic. No
minutes analgesia.
Cardiorespiratory
depression,
hypotension,
tachycardia can
occur.
Can precipitate
or worsen
seizures.

Etomidate 0.1 to 0.15 5 to 15 5 to 15 0.05 mg/kg Sedative. No

mg/kg seconds every 3 to 5 analgesia.
minutes
Generally
maintains
cardiorespiratory
stability.
Elderly or
renal/hepatic
insufficiency:
use lower dose
range.
Myoclonus,
injection site
pain,
nausea/vomiting
may occur.
Fentanyl 0.5 to 1 mcg/kg 2 to 3 30 to 60 0.5 mcg/kg Analgesic. No
every 2 amnesia.
minutes Minimal
hypotension and
histamine
release.
Use reduced
dose in
combination with
other agents.

Ketamine 1 to 2 mg/kg 0.5 5 to 20 0.25 to 0.5 Dissociative

over 1 to 2 mg/kg every 5 sedative,
minutes to 10 minutes analgesic, and
amnestic.
Minimal
cardiorespiratory
depression.
Does not inhibit
protective
reflexes.
Sympathetic
stimulation,
tachycardia,
hypertension
may occur
(rare).
Emergence
reactions
common in
adults. Nausea
and vomiting
may occur.
Prolonged effect
in elderly.

Propofol 0.5 to 1 mg/kg 0.5 5 0.5 mg/kg Sedative and

every 3 to 5 amnestic. No
minutes analgesia.
Rapid onset and
neurological
recovery.
Respiratory
depression,
hypotension,
injection site
pain may occur.
Elderly: reduce
dose by 20
percent, slower
administration.
Contains egg
lecithin, soybean
 oil (potential
allergens)

* Elderly patients are at increased risk of adverse events with these agents and dosing should be adjusted
accordingly. See text for details.

Data from: Gan, TJ Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate
sedation. Clin Pharmacokinet 2006;45(9):855-869. Falk, J, Zed, P, Etomidate for procedural sedation in the
emergency department. Ann Pharmacother 2004;38:1272-7.

Graphic 52744 Version 2.0

Contributor Disclosures
Robert L Frank, MD, FACEP Nothing to disclose Allan B Wolfson, MD Nothing to
disclose Jonathan Grayzel, MD, FAAEM Nothing to disclose

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found,
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