Procedural sedation and analgesia (PSA) is the administration of a short-acting sedative-hypnotic or dissociative agent, with or without an analgesic, for patients undergoing anxiety-provoking and/or painful procedures.
The goal of PSA is to provide needed sedation and pain relief while minimizing respiratory depression, hypoxia, and hypotension.
PSA should be done only by trained personnel. Many institutions require special instruction and certification for PSA providers, as well as adherence to procedural protocols. A trained observer (who may also be the person giving the PSA drugs) is required to monitor the patient (sedation level, airway, ventilation, vital signs, pulse oximetry and/or capnography) throughout the sedation and recovery periods. Ventilatory and cardiovascular equipment and trained personnel must be immediately available.
If PSA provides inadequate sedation or analgesia, injectable anesthetic (peripheral nerve block or local infiltration) may be added. Sometimes, anesthesia and treatment in the operating room may be necessary.
Indications
Relieve pain and/or anxiety that occurs with therapeutic or diagnostic procedures*
Facilitate a procedure by relaxing the patient and reducing patient motion
Provide amnesia for a procedure, thereby sparing the patient possible psychologic trauma
* Procedures include, but are not limited to, cardioversion, joint or fracture reduction, arthrocentesis, abscess drainage, laceration repair, foreign body removal, lumbar puncture, vascular access and cannulation.
Contraindications
Absolute contraindications
Urgent need for treatment (eg, hemodynamic instability) that cannot await sedation
Hypersensitivity to one of the drugs or to the delivery vehicle*
Particular to ketamine: Age < 3 months (increased risk of airway compromise)
Particular to nitrous oxide: Pneumothorax, pneumomediastinum, bowel obstruction, or intraocular gas bubble (post-vitreoretinal surgery), which are sites of air accumulation into which nitrous oxide can expand
* Allergy to eggs or soy are no longer a contraindication to propofol (the egg/soy allergens are different from the egg/soy moieties in the propofol formulation).
Relative contraindications
Severe cardiopulmonary disease (increased risk of decompensation from respiratory depression)†
Obstructive sleep apnea†
Obesity or anatomic characteristics (eg, micrognathia, macroglossia, short neck, congenital anomalies) that suggest difficult intubation†
Chronic liver or kidney disease: Some drugs will be metabolized slowly, leading to prolonged sedation.
Patients > 60 years of age (increased risk of decompensation): PSA drug doses should often be decreased.
Acute alcohol/sedative drug intoxication (increased risk of respiratory complications): PSA drug doses should be decreased.
Chronic alcohol or substance use disorder: PSA drug doses may need to be increased.
Pre-procedural food or drink: Review institution-specific protocols regarding fasting before PSA‡
† If one of these contraindications is present, consult an anesthesiologist and/or consider use of a drug that does not depress respiration (eg, ketamine).
‡ Although some guidelines recommend delaying elective procedural sedation for a few hours after ingestion of clear liquids and 8 hours after ingestion of solids, no data establish the efficacy or necessity for doing so (1).
Complications
Respiratory depression
Oxygen desaturation
Hypotension (rarely significant in the absence of concurrent serious disease or cardiovascular compromise)
Aspiration (rare)
Particular to etomidate: Myoclonus (minimal and brief, rarely clinically significant); adrenal suppression (usually inconsequential and transient)
Particular to fentanyl: Chest wall rigidity (rigid chest syndrome) due to too-rapid IV push (infrequent at the low dose used for analgesia)
Particular to ketamine: Occasional laryngospasm or apnea (prevented by adhering to slow push [> 30 to 60 seconds]); sympathomimetic effects (hypertension, tachycardia, which pose risk to patients with ischemic heart disease or underlying hypertension); on recovery, vomiting or emergence reactions (anxiety/panic/hallucinatory episode), more frequent in adults than in children
Equipment
Monitoring equipment (pulse oximeter, capnograph [end-tidal CO2 monitor], blood pressure cuff, cardiac monitor)
IV catheters and fluid (eg, 0.9% saline)
Supplemental oxygen (with high-flow capacity)
Suction source and tips
Airway management equipment, especially a bag-valve-mask (BVM)
Cardiopulmonary resuscitation equipment
PSA drugs and reversal agents (see examples below)
Additionally, for nitrous oxide administration: Fail-safe gas administration equipment (built-in lower limit of 30% oxygen delivery); demand valve mask or continuous flow mask; ambient nitrous oxide sensor and gas scavenger apparatus (for removal of exhaled nitrous oxide from room air)
PSA drugs
Sedative-hypnotics (primarily sedative, anxiolytic, and amnestic):
Midazolam IV, IM, intranasal: Short-acting sedation (benzodiazepine); IV onset 1 to 2 minutes, duration 10 to 40 minutes
Propofol IV: Ultra-short-acting, deep sedation; onset 30 seconds, duration 5 minutes
Etomidate IV: Ultra-short-acting, deep sedation; onset 5 to 15 seconds; duration 5 to 15 minutes
The sedative-hypnotics are highly sedating (with accompanying decreased response to pain), but they provide no direct analgesia. They may be given alone when pain control is not required. They may be supplemented with opioid analgesia (eg, fentanyl) or injectable regional or local anesthesia if needed.
Midazolam is often used alone to provide mild sedation (anxiolysis) before painless or mildly painful procedures. It has a potent amnestic effect.
Propofol and etomidate provide rapid-onset, deep sedation useful for quick, painful procedures (eg, cardioversion or joint reduction); their short duration can also help decrease the risk of accumulation that reach toxic drug levels resulting from repeated dosing during longer procedures.
Propofol may be anticipated to cause hypotension that usually is brief and readily managed.
Etomidate neither lowers nor raises blood pressure or pulse. It may be considered in patients with hypotension and in those with cardiovascular disease (ie, those at risk of decompensation from changes in pulse and blood pressure).
Opioids (primarily analgesic):
Fentanyl IV: Short-acting analgesia; onset 2 to 3 minutes, duration 30 to 60 minutes
Opioids produce analgesia but also cause sedation. In PSA, opioid analgesia is typically used as an adjunct to a sedative when analgesia is required, which increases the risk of respiratory depression. Fentanyl is often used with midazolam; a reversal agent (naloxone and flumazenil) is available for each. A longer-acting opioid such as morphine may be chosen if the patient's pain is likely to continue after the procedure (eg, with certain fractures or other persistently painful injuries).
Dissociative agent (primarily analgesic and amnestic):
Ketamine IV, IM, intranasal: Dissociative sedation; IV onset < 1 minute, duration 10 to 20 minutes
Ketamine causes a dissociative state (trance-like mind-body dissociation) that provides analgesia, sedation, and amnesia but does not cause respiratory depression or diminish upper airway tone or protective reflexes and may be a first choice for patients at risk of aspiration. Moreover, ketamine does not cause hypotension but typically increases pulse and blood pressure modestly. Ketamine may be given alone or with a sedative. However, at PSA doses,* ketamine should not be supplemented with another analgesic.
*Low-dose (sub-dissociative) ketamine (eg, 0.1 to 0.2 mg/kg) provides substantial analgesia without causing dissociation; it may be used to supplement opioid analgesia (eg, allowing smaller fentanyl doses).
Nitrous oxide gas (primarily anxiolysis):
Nitrous oxide (30% to 50%) in oxygen: Short-acting anxiolysis; onset and offset < 5 minutes each
Nitrous oxide provides excellent anxiolysis but only mild amnesia and analgesia. It is not typically used alone for analgesia but may be given with (or as an adjunct to) an analgesic, sedative, or nerve block. It is particularly useful for children because it does not require IV catheterization. In children, it may be preferred to midazolam or ketamine. At the low doses used for PSA, it is safe.
Reversal agents:
Flumazenil (0.1 mg/mL—benzodiazepine antagonist)
Naloxone (opioid antagonist)
Additional Considerations
Degrees of sedative-hypnotic sedation are defined as:
Anxiolysis (minimal sedation): Consciousness and interactivity are retained; coordination and cognition may be impaired.
Moderate sedation: Consciousness is depressed; response to verbal requests or touch is retained.
Deep sedation: Consciousness is depressed; arousal is difficult and may require repeated verbal or painful stimuli; airway patency may decrease; spontaneous breathing may slow.
General anesthesia: Patient is unconscious and unresponsive to stimuli; respiratory depression or airway compromise is frequent; cardiovascular compromise may occur. General anesthesia is not expected with PSA; however, PSA providers must be able to reverse general anesthesia and provide cardiopulmonary support as needed.
Dissociative sedation (unique to ketamine; distinct from sedative-hypnotic sedation): analgesia and amnesia, preservation of spontaneous breathing, airway reflexes, and cardiopulmonary function
Capnography is a more sensitive indicator of respiratory depression than oximetry, and, unlike oximetry, remains a reliable indicator when supplemental oxygen is being given.
Respiratory depression occurs most commonly at the beginning of sedation and during the recovery period after the sedation. Bag-valve-mask ventilation usually suffices for temporary ventilatory support. Airway positioning and nasal or oral airways may be needed to maintain airway patency, particularly if patients have no gag reflex.
Hypotension should be anticipated during PSA. IV fluids (eg, 0.9% saline) usually can correct procedural hypotension. In patients with low blood pressure prior to PSA, consider a hemodynamically neutral or supportive alternative (ie, etomidate or ketamine).
Pregnant or possibly pregnant staff members should be excluded from environments in which nitrous oxide is used because nitrous oxide is a teratogen.
Positioning
Position the patient recumbent or supine. The patient's head and shoulders should be exposed (to permit observation of breathing) and readily accessible (to permit immediate ventilatory assistance when needed).
Step-by-Step Description of Procedure
PSA should be done, in accordance with institutional guidelines, by a clinician or service proficient with the procedure and with equipment and trained personnel available to provide emergency airway and ventilatory support.
Preparatory tasks
Select a PSA strategy: A decision to do PSA and the selection of PSA drugs to use (including alternative or additional drugs) must consider factors such as clinical need, patient risk factors for complications and difficult intubation, and adequacy of provider training and familiarity with PSA drugs.
Ensure the availability of reversal agents as well as PSA drugs.
Ensure the availability of a nearby resuscitation cart, airway suction, and rescue airway equipment.
Assemble bag-valve-mask and oxygen line, to be able to provide immediate oxygen support, as needed.
Attach monitoring devices to the patient and verify that they are working correctly.
Establish intravenous access. Consider cannulating a large vein (eg, antecubital vein) if propofol or etomidate are to be used for sedation, to help decrease the pain of those injections.
Recommended: Begin slow IV infusion (eg, 0.9% saline at 30 mL/h) to ensure IV patency and thereby be able to provide immediate blood pressure support, as needed.
Before giving PSA drugs, establish the patient's pre-sedation vital signs, cardiac rate and rhythm, mental status (level of consciousness), and quality of breathing and ventilation.
Patient monitoring
Monitor the patient throughout PSA, to ensure PSA safety (absence of respiratory depression or cardiovascular compromise) and effectiveness (relief of pain and anxiety):
Breathing: Continuously assess the state of spontaneous breathing. Changes in the rate, depth, or noise of breathing may precede other signs of respiratory depression.
End-tidal CO2 (capnography) and O2 saturation (pulse oximetry): Maintain continuous vigilance for hypoventilation. Changes in end-tidal CO2 occur virtually simultaneously with drug-induced hypoventilation and precede hypoxia.
Respiratory depression due to short-acting PSA drugs usually resolves quickly (as the drugs wear off).
If hypoventilation or apnea occurs, provide supplemental oxygen, airway repositioning maneuvers, nasal and oral airways, and bag-valve-mask ventilation as needed. Provide verbal and tactile patient stimulation as needed. If necessary, continue bag-valve-mask ventilation and use appropriate reversal agents. More advanced respiratory support is seldom needed.
Blood pressure, heart rate, heart rhythm: Frequently check hemodynamics. Transient hypotension may occur, but other cardiovascular events are rare.
If procedural hypotension occurs, infuse IV fluid as needed to support blood pressure.
Patient response to verbal and tactile stimuli: Periodically check patient responsiveness, which is used primarily to detect undersedation (insufficient relief of pain and anxiety), not to determine oversedation (which is more efficiently recognized as respiratory depression).
Do not check patient responsiveness too frequently or aggressively, because doing so can unnecessarily disrupt an effective sedation and possibly incur an additional drug titration. If the patient is calm and pain-free, rely on monitoring of breathing, ventilation, oxygenation, and hemodynamics to ensure the patient's safety during PSA.
Continue patient monitoring until the patient has fully recovered from the sedation.
PSA using midazolam
To avoid oversedation, always wait at least 2 minutes after a midazolam dose before giving another dose—of midazolam or any other PSA drug.
IV midazolam: Titrate to patient response (sedation) as follows:
Initial dose: 0.5 to 2 mg IV over ≥ 2 minutes
Subsequent doses (after 2 to 5 minutes): 0.5 to 2 mg IV doses over ≥ 2 minutes
Maximum dose: 2.5 mg/dose and 5 mg cumulative IV dose (1.5 mg and 3.5 mg for patients ≥ 60 years of age)
Intramuscular midazolam:
5 mg IM (0.1 to 0.15 mg/kg in children). Do not rapidly titrate.
Intranasal midazolam:
For children, 0.2 to 0.5 mg/kg intranasally. Do not rapidly titrate.
PSA using midazolam and fentanyl
When used together, use smaller doses of each drug than when used alone and titrate carefully to avoid respiratory depression. Always wait at least 2 minutes after a midazolam dose before giving another PSA drug. Either drug may be given first; one strategy is to give midazolam first for primarily anxiety-provoking procedures and fentanyl first for more painful procedures.
IV midazolam: Titrate to patient response (mild sedation), as follows:
Initial dose: 0.02 to 0.1 mg/kg IV over ≥ 2 minutes
Subsequent doses (after 3 to 5 minutes): 0.005 to 0.025 mg/kg IV over ≥ 2 minutes
Maximum dose: 2.5 mg/dose and 5 mg cumulative dose (1.5 mg and 3.5 mg for patients ≥ 60 years of age).
IV fentanyl: Titrate to patient response (analgesia) as follows:
Initial dose: 50 to 100 mcg (or 1 mcg/kg) IV
Subsequent doses: May repeat 50-mcg IV dose every 3 minutes as needed.
Maximum dose: Use extreme caution if exceeding 0.5 mcg/kg/dose if given with other sedatives (eg, midazolam, propofol) as the combination may cause respiratory depression.
PSA using propofol
Avoid propofol in hypotensive patients.
Give supplemental oxygen (eg, nasal oxygen at 2 to 4 liters per minute).
IV propofol: Titrate doses to patient response (deep sedation), as follows:
Initial dose: 0.5 to 1.0 mg/kg IV (1.0 to 2.0 mg/kg for children)
Subsequent doses (after 1 to 3 minutes): 0.25 to 0.5 mg/kg IV every 1 to 3 minutes
For obese and older patients, start with lower doses. For otherwise healthy adults, start at the higher doses.
PSA using etomidate
IV etomidate: Titrate doses to patient response (deep sedation), as follows:
Initial dose: 0.1 to 0.15 mg/kg IV
Subsequent doses: 0.05 mg/kg IV every 3 to 5 minutes
PSA using ketamine
Before and during the initial ketamine dose, converse with the patient about a happy or joyful topic (eg, a favorite person, place, or activity). This may reduce unpleasant emergence phenomena (confusion, anxiety, panic) following ketamine PSA.
IV ketamine: Give doses over 30 to 60 seconds and titrate to patient response (sedation) as follows:
Initial dose: 1 to 1.5 mg/kg IV (1 to 2 mg/kg for children) over 1 to 2 minutes
Subsequent doses (after 10 minutes): 0.5 to 0.75 mg/kg IV (0.5 to 1 mg/kg for children)
Use lower doses (0.25 to 0.5 mg/kg) depending on the patient's clinical status (eg, older age) or other sedation; however, note that patients may experience partial dissociation and anxiety that is sometimes severe at doses of 0.5 to 1 mg/kg.
Intramuscular ketamine (for children):
Initial dose: 4 to 5 mg/kg IM
Subsequent doses 2 to 2.5 mg IM every 10 minutes
Intranasal ketamine (for children):
2 to 10 mg/kg intranasally. Do not rapidly titrate.
PSA using nitrous oxide inhalation
A trained individual is required to administer or supervise nitrous oxide inhalation.
Assemble gas-delivery and scavenger systems: Select a demand valve mask for a cooperative adult or child >5 years of age or a continuous flow mask for patients 2 to 5 years of age or who are unable to cooperate.
Give 100% oxygen for 2 minutes.
Then switch to a nitrous oxide/oxygen mixture (eg, 40% N2O [N2O 4 L/m and O2 6 L/m]).
Cooperative patient (self-administered N2O): Instruct the patient to hold the demand valve mask over the face (without strapping it on) and to breathe normally. As the patient becomes drowsy, the mask falls away from the face, the patient will breathe room air, and gas flow from the demand valve mask will stop. When the patient is once again awake or experiencing pain, tell him or her to resume breathing through the mask.
Uncooperative patient/child (closely supervised N2O administration): Strap a continuous flow mask over the patient's nose and mouth and observe the patient's respirations and sedation level continuously.
Titrate the gas mixture to provide mild sedation with normal respirations. Prolonged N2O delivery of concentrations > 50% are not typically needed.
When mild sedation is achieved, add an analgesic, sedative, or nerve block as needed for pain control.
When the procedure is concluded, give 100% O2 for 5 minutes or more, to prevent diffusion hypoxia during recovery.
Aftercare
Do not give flumazenil or naloxone to speed recovery from midazolam or fentanyl unless resuscitation is required.
Continue dedicated observation of patients until normal wakefulness has returned.
Do not discharge adult patients until they can walk unaided.
Do not discharge children until they can sit up unaided and speak at an age-appropriate level.
Discharge patients accompanied by an adult who will continue observing the patient for post-sedative complications (eg, nausea and vomiting, dizziness, vertigo).
Do not allow patients to drive themselves home.
Instruct patients to restrict their activity for 12 hours after PSA (eg, no driving, alcohol, or important decision-making; light meals only).
Warnings and Common Errors
Be sure to designate a dedicated observer (eg, appropriately trained nurse, respiratory therapist) whose primary responsibility is to monitor the patient throughout PSA. The operator providing the patient's procedure should not be the dedicated observer.
Ensure bedside availability of airway equipment. A bag-valve-mask (BVM) usually suffices for temporary ventilatory support.
Consider avoiding supplemental oxygen if capnography is not available; supplemental oxygen alleviates hypoxemia during respiratory depression, which impedes detection of respiratory depression by pulse oximetry.
Continue patient monitoring during the recovery period after PSA because respiratory depression, if it occurs, frequently happens soon after the procedure is finished and the pain has ended.
Tricks and Tips
Adhere to established drug-administration rates; too-slow administration of short-acting drugs is common, can delay onset of effective sedation, and risks excessive drug accumulation.
For subsequent dosing of a drug, frequent smaller doses are preferred over less frequent larger doses to maintain a steady state of sedation.
Because combined use of ketamine and propofol ("ketofol") has the same risk of adverse respiratory events requiring intervention as propofol (2) and is more complex to use, ketofol has no advantage over propofol; ketofol is thus no longer recommended for routine use.
References
1. Beach ML, Cohen DM, Gallagher SM, et al: Major adverse events and relationship to nil per os status in pediatric sedation/anesthesia outside the operating room: A report of the pediatric sedation research consortium. Anesthesiology 124(1):80-88, 2016. doi: 10.1097/ALN.0000000000000933
2. Ferguson I, Bell A, Treston G, et al: Propofol or ketofol for procedural sedation and analgesia in emergency medicine—the POKER study: A randomized double-blind clinical trial. Ann Emerg Med 68(5): 574-582, 2016. doi: 10.1016/j.annemergmed.2016.05.024
More Information
The following is an English-language resource that may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Green SM, Roack MG, Krauss BS, et al: Unscheduled procedural sedation: A multidisciplinary consensus practice guideline. Ann Emerg Med 73(5):e51-e65, 2019. doi: 10.1016/j.annemergmed.2019.02.022