Continuing Education Activity

Procedural sedation permits the safe performance of procedures that a patient cannot tolerate in the fully conscious state. Through this activity, the practitioner will learn how to assess the airway by direct visual examination, tabulate risk factors by analysis of baseline risk, and will be able to properly choose a medication that we will get the patient safely through the proposed procedure.

Objectives:

• Outline the proper medication for procedural sedation based on specific patient risks.
• Describe the equipment, personnel, preparation, and technique in regards to procedural sedation.
• Review the potential complications and clinical significance of procedural sedation.
• Explain interprofessional team strategies for improving care coordination and communication to advance procedural sedation and improve outcomes.

Introduction

Procedural sedation (PS), previously incorrectly referred to as 'conscious sedation,' refers to techniques, medications, and maneuvers performed to help a patient tolerate unpleasant or painful procedures, avoiding potential unwanted memories associated with such procedures.[1] Because the proper use of PS also aims to decrease the patient's perception of pain and is generally obtained through the administration of analgesics combined to a sedative, PS can also serve as procedural sedation analgesia (PSA). Furthermore, PS also increases the likelihood of a successful procedure while decreasing the time required to perform it. Additionally, PS increases safety for the patient and personnel attending the patient. These approaches include medications, psychological techniques, and/or physical maneuvers to achieve the indented effect. According to the American College of Emergency Physicians (ACEP), PS is a 'technique of administering sedatives or dissociative agents with or without analgesics to induce a state that allows the patient to tolerate unpleasant procedures while maintaining cardiorespiratory function. PSA is intended to result in a depressed level of consciousness that allows the patient to maintain oxygenation and airway control independently.'[2]

In various settings, the practice of PS (and PSA) has considerable variability, is practiced with varying degrees of skill, and has been the subject of controversy in the not-so-distant past. The practice of PSA, in fact, is not the exclusive preserve of anesthesia practitioners but is now routinely adopted by other specialists, such as emergency clinicians, critical care specialists, and several nurse specialists. On these bases, this chapter is intended to set out a standard method of practice and address some of the controversies along with providing additional outside resources for the learner’s enrichment. The recommendations herein are not intended to be adopted en bloc but must be customized to the setting where they are used.[3] The matter has been by several scientific societies. In 2018, the American Society of Anesthesiologists (ASA) in conjunction with the American Association of Oral and Maxillofacial Surgeons (AAOMS), the American College of Radiology (ACR), the American Dental Association (ADA), the American Society of Dentist Anesthesiologists (ASDA), and the Society of Interventional Radiology (SIR) organized the task force on Moderate Procedural Sedation and Analgesia, releasing updated practice guidelines.[4] Furthermore, The American Society for Gastrointestinal Endoscopy (ASGE) published guidelines on the use of PSA for gastrointestinal endoscopic procedures.[5] However, there are differences between the proposed guidelines. For example, in contrast to the ASA recommendations, ASGE guidelines do not consider the capnography monitoring useful during PS.[6]

It is essential to understand that sedation, dissociation, and analgesia are separate concepts. Sedation is enabling the patient to lie very still; analgesia is pain relief by central or peripheral interventions, while dissociation is the production of a state of mind-body separation. As a consequence, PS is not general anesthesia or pain control alone, but it is explainable as a tailored approach to the patient, based on anxiety level and pain aimed at achieving optimal sedation and analgesia for performing noninvasive and minimally invasive procedures, conducted primarily in contexts outside of the operating theater such as emergency, dentistry, radiology, and gastrointestinal endoscopy. 

Different evaluation methods have been developed for the degree of sedation, both in the operating theater and in environments outside the theater. The Ramsay scale indicates a straightforward approach described by Ramsey and colleagues in 1974. The tool indicates six categories from patient awake but anxious, agitated, or restless, to patient awake but cooperative, orientated, and tranquil, to patient drowsy but responsive to commands, patient asleep (brisk response to glabella tap or loud auditory stimulus), patient asleep with sluggish response to a stimulus, and finally patients with no response to noxious stimuli. Although this approach continues to be the most widely used scale for the assessment and monitoring of sedation, one major limitation is the non-precise distinction between intentional responses and unintentional ones. Recently, the Ramsey scale has undergone modifications to match the AAP and JCAHO guidelines better. After scoring eight characteristics, a score indicates anxiolysis (2 to 3), moderate sedation (4 to 5), deep sedation (6), and general anesthesia (7 to 8). Another widely used instrument is the Observer's Assessment of Alertness/Sedation (OAA/S) scale. It scores five categories: no response to shaking; response to mild prodding; response to name called loudly; lethargic response to name; and readily responds to name. This tool is an easy-to-use instrument, although it does not well discriminate among deep levels of sedation.[7]

Practically, the most commonly accepted terms for sedation depth are:

• Minimal: also called anxiolysis; the patient remains awake but relaxed, able to interact.
• Moderate: also called conscious sedation, the patient has depressed consciousness but will respond to verbal requests or react to touch. Breathing remains intact, and no support is needed.
• Deep: The patient cannot be easily aroused but will respond to repeated or painful stimuli. Breathing may be impaired and may need to be supported.
• Dissociative: a trance-like state wherein the patient remains awake but unaware of the pain and retains no memory of the event. They can follow commands, and airway reflexes remain intact.

It is generally accepted that, due to patients' varying sensitivities to medications as well as pre-existing co-morbidities, patients may slip into a deeper level than anticipated; the operator must prepare for this event.

Anatomy and Physiology

Because the most severe complication is a respiratory failure from airway obstruction or hypoventilation, intimate knowledge of airway anatomy, its variations, and any history of airway anomalies is mandatory. The most commonly used airway anatomy assessment scale is the Mallampati score.[8] A careful assessment is mandatory for evaluating potential difficulties to ventilate. This assessment should include the presence of any anatomic features that may affect airway management, including dysmorphic or asymmetrical facial features, beard, significant malnutrition or cachexia with sunken cheeks and missing teeth, facial trauma (e.g., lacerations through the cheek or unstable bony injuries). Limited neck extension and mouth opening of less than 4 to 5 cm, which restricts access, requires checking. Finally, obesity can represent an obstacle to ventilation, even in the absence of the previously considered factors.

Indications

PS and PSA are indicated any time the patient requires an intervention that will cause significant discomfort. The level of sedation needed depends on the amount of pain the patient is likely to experience, and the necessity of the patient remaining still during the procedure. For instance, an orthopedic procedure that requires joint reduction, and thus muscle relaxation will require deeper sedation than a less uncomfortable procedure. Decision-making also has to take into account the vital signs of stability of the patient. For example, a patient who cannot tolerate cessation of breathing or a drop in blood pressure may be better handled using a dissociative agent rather than moderate to deep sedation.

Additionally, a review of the patient's history for chronic diseases (e.g., cardiovascular or respiratory diseases) and their stability, drug history, and allergy are mandatory to assess the risk of harm during the proposed sedation and procedure. The most commonly used system for clinical assessment is the ASA Physical Status (Class) scoring:

• ASA Class 1. Normal healthy patient with no organic, physiologic, or psychiatric disturbance: excludes the very young and very old; healthy with acceptable exercise tolerance.
• ASA Class 2. Patients presenting with mild systemic disease: No functional limitations; has a well-controlled disease involving one body system; controlled hypertension or diabetes without systemic effects, cigarette smoking absent chronic obstructive pulmonary disease (COPD); mild obesity, pregnancy.
• ASA Class 3. Patients with severe systemic disease: Some level of functional limitation; has a controlled disease involving more than one body system or one major system; no immediate danger of death; controlled congestive heart failure (CHF), stable angina, prior heart attack, poorly controlled hypertension, morbid obesity, chronic renal failure; a bronchospastic disease with intermittent symptoms.
• ASA Class 4. Patients with severe systemic disease that represents a constant threat to life: Has at least one severe disease not well controlled or at end-stage; possible risk of death; unstable angina, symptomatic COPD, symptomatic CHF, hepatorenal failure.
• ASA Class 5. Moribund patients not expected to survive without the operation: Not expected to survive over 24 hours without surgery; imminent risk of death; multiorgan failure, sepsis syndrome with hemodynamic instability, hypothermia, poorly controlled coagulopathy.
• ASA Class 6. A patient declared brain-dead whose organs are being harvested for donor purposes. 

The addition of “E” to physical status denotes an emergency procedure. The definition of an emergency is as existing when a delay in treatment of the patient would lead to a significant increase in the threat to life or body part.

Contraindications

In certain conditions and contexts, PSA is not appropriate.

• Operator skillset (training). If the person performing the sedation lacks the skillset to secure an unstable airway, from intubation to cricothyrotomy, PSA is not an option.
• Appropriate monitoring and resuscitation equipment are not available.
• Patient needs. If the patient requires any more than a brief painful procedure (e.g., surgery,) general anesthesia in an operating theater may be more appropriate.
• Patient conditions. Patients with a high ASA risk score may be safer with the services of a qualified anesthetist. In particular, PSA is contraindicated in patients with an ASA classification of unstable class II or class IV and above (unless requiring immediate intervention such as for ventricular tachycardia conversion).
• Patient allergies or hypersensitivity to medications used for PSA purposes
• High risk of aspiration (e.g., acute alcohol intoxication). Note: concerning fasting times before procedural sedation, it is possible to refer to guidelines used for general anesthesia that recommend the timing of 2 hours for clear fluids (these liquids must not include alcohol) and 6 hours for everything else. Infants may ingest breast milk for up to 4 hours before the procedure. Additional fasting time (8 or more hours) may be necessary in cases of patient intake of fried foods, fatty foods, or meat.[9]

Equipment

Before starting a PSA, the operator should have available, open, or immediately at hand and checked for operational readiness:

• IV, running or functional saline lock
• Medications and equipment for cardiac resuscitation
• Oxygen administration equipment ranging from the nasal cannula to high-flow oxygen mask (nonrebreather) 
• Suction device
• Airway equipment including bag valve mask, laryngeal mask airway, bougie, direct or video-assisted laryngoscopy with appropriate blades, appropriately sized oral airways, and endotracheal tubes, surgical and needle airways
• Reversal drugs if using drug-reversible agents such as opioids and benzodiazepines. Naloxone and flumazenil effectively terminate the effects of fentanyl (or of other opioids) and midazolam (or of other benzodiazepines), respectively. Of note, personnel should consider that flumazenil use can be associated with status epilepticus, mainly in patients with unidentified benzodiazepine abuse or affected by a seizure disorder.
• Monitoring equipment, usually including cardiac, blood pressure, pulse-oximetry monitors (SaO2), respirations. EtCO2 monitor is highly desirable

Personnel

In the ideal situation, there are two operators. One person will perform the intended procedure, whereas the other person will be dedicated to sedation, patient monitoring, and team coordination. Nevertheless, there are many circumstances where having two operators is not possible, particularly for unplanned procedures. This situation is most common in a rural or resource-constrained setting. If the circumstance is the lone operator, this person must be prepared to abandon the procedure and rescue the patient.

Personnel involved in PSA must have the following training:

• Perform appropriate patient selection
• Acquire advanced airway-management skills (a mandatory prerequisite for performing these techniques)
• Understand and manage medications administered
• Perform patient's' monitoring
• Manages all potential complications

Preparation

Meticulous preparation for PSA is mandatory and best practiced beforehand in a simulation environment.

Standard operative checklist procedures should be followed; the World Health Organization (WHO) template is useful.[10] 

1. Verify identity, procedure, and consent.
2. Mark the site/side.
3. Check that needed medications are available. This may include reversal drugs (e.g., opioids/naloxone, benzodiazepines/flumazenil) and "agents/adjuncts" as some procedural medications lack reversal agents but have reversal adjuncts (e.g., propofol/bag-mask).
4. Check monitoring devices: EKG, SaO2, EtCO2 (preferred if available as it is more sensitive for hypoventilation than SaO2) and review potential errors from devices (e.g., SaO2 may drop during automated blood pressure cuff inflation by occlusion of arterial flow.) Review allergies.
5. Assess for airway difficulties/anomalies (e.g., Mallimpati score).
6. Patients with contact lenses should be removed (especially for nitrous oxide use).
7. Individually confirm team members' roles and preparation.
8. Display the necessary images.

At the conclusion of the procedure, as the patient recovers, confirm each team member's confirmation that their role shows stability before leaving the procedure room.

Technique or Treatment

Medications

The ideal agent for PSA purposes should possess sedative, analgesic, and amnestic properties as well as a rapid onset and short duration of action to allow a safe and quick recovery and discharge. Although PSA is usually the result of combining a short-acting benzodiazepine such as midazolam (sedative, amnestic, and anxiolytic properties but not analgesic effects) with an opioid (e.g., fentanyl), several drugs are also options, alone or in combination.[11] The combination of fentanyl and midazolam is one of the most adopted procedures to carry out PSA, but other combinations (e.g., propofol and fentanyl or propofol and ketamine combination) are also adopted.   

Midazolam 

• Dose. IV: 2 to 2.5 mg initially, with further 1 mg doses repeated after 2 to 5 minutes, titrated to effect. In adults older than 60 and those chronically ill: starting dose 0.5 to 1 mg (and 1 mg over at least 30 seconds). A total dose of more than 5 mg is not usually necessary in a healthy young adult; less than 3.5 mg is the required dose in debilitated and older subjects. In patients 6 months to 5 years: IV initial dose of 0.05 to 0.1 mg/kg (total dose less than 6 mg); in children 6 to 12 years: IV initial dose of 0.025 to 0.05 mg/kg (total dose less than 10 mg); rectal greater than 6 months: 0.3 to 0.5 mg/kg; IM 1 to 15 years: 0.05 to 0.15 mg/kg.
• Onset time. IV: 2 to 3 minutes. Note: the onset of sedation may vary individually depending on the physical status and other factors such as the speed of administration, and dose.
• Duration. IV: the maximum effect occurs in about 5 to 10 minutes. The elimination half-life is 1.5 to 2.5 hours.
• Comments. Midazolam should be prepared as a 1 mg in 1 ml solution, especially in children less than 15 kg of body weight where midazolam solutions with concentrations higher than 1 mg/ml are not recommended. The antidot of midazolam is flumazenil, but care must be taken as this drug may have a shorter duration of action than the sedative agent, resulting in re-sedation. In the elderly, it is necessary to pay attention to the triggering of benzodiazepine-induced neurocognitive alterations.[12][13]

Fentanyl

• Dose. (IV only) Adult and children: 1 to 1.5 mcg/kg initial dose and then titrated 1 mcg/kg every 3 minutes
• Onset time. IV: 1 to 2 minutes
• Duration: IV: 30 to 60 minutes
• Comments. Fentanyl is a synthetic opioid metabolized by the liver. It presents a rapid redistribution from the central nervous system 

Ketamine [14]

• Dose. Adult and children IV: 1 to 3 mg/kg. IM: 5 to 10 mg/kg.
• Onset time. IV: 1 minute (Note: If the family is observing, prepare them for the sudden vacant stare Ketamine induction causes)
• Duration. IV: 5 to 15 minutes, IM: 15 to 30 minutes
• Comments. Adverse effects of ketamine include recovery agitation, transient airway complications such as laryngospasm, and emesis. Administration of a benzodiazepine (e.g., diazepam, lorazepam) at the time of the final dose of ketamine may blunt emergence phenomena (visual hallucinations, occasionally disturbing) and the potential sympathomimetic effects of the drug, especially in children. Avoid this agent in individuals who are predisposed to psychotic behavior.

Etomidate [15]

• Dose. (IV only) Adult and children over ten years old: 0.3 mg/kg. (Not studied in children under ten years old)
• Onset time. 1 to 2 minutes, IM: 3 to 4 minutes (Note: A third of patients may experience myoclonic jerks on induction; this may be important for orthopedic procedures and may be lessened by pretreatment with an opioid agent)
• Duration. 5 to 7 minutes; may be longer in the elderly and patients with decreased renal function.
• Comments. There is controversy about the suppression of the adrenal production of stress hormones; this has not been shown to be meaningful with single bolus use. Additionally, etomidate is a hypnotic only as it has essentially no analgesic properties.

Propofol [16]

• Dose. (IV only) Adult (healthy): 1 to 2 mg/kg. Adult (debilitated): 0.5 to 1 mg/kg. Children: 2 to 3 mg/kg. (Not studied in children under three years old). May be repeated at half doses several times as needed.
• Onset time: 15 to 30 seconds (circulatory time to the brain)
• Duration. 1 to 3 minutes; termination of action of this highly lipophilic drug is through redistribution/equilibration across other bodily tissues. Repeat doses prolong recovery.
• Comments. Some literature contains a verbal confusion, stating Propofol-caused hypoventilation has no reversal agent; the confusion results from conflating "agent" with "drug." Propofol's reversal agent for hypoventilation is a bag-mask. Additionally, orthostatic hypotension may occur; use IV isotonic fluids as a "reversal agent" and resume seated position cautiously. Be aware that this hypotensive effect, likely caused by peripheral vasodilation, may cause cardiac ischemia, further reducing cardiac output.[17] This condition can create a cycle of worsening cardiac ischemia, further decreasing cardiac output.

Dexmedetomidine [18]

• Dose. (IV only) Adult and children IV: 1 mcg/kg.
• Onset time. IV: 3 to 5 minute
• Duration. IV: 15 minutes
• Comments. Dexmedetomidine does not cause respiratory suppression. Research has recently called into question the effectiveness of dexmedetomidine as a sole sedative.[19]

Methohexital [20] 

• Dose. Adult and Children: IV: 1 to 2 mg/kg. IM: 6 to 10 mg/kg. (Note: IM route is rarely used in adults)
• Onset. IV: 15 to 30 seconds, IM: 2 to 10 minutes
• Duration. IV: 4 to 7 minutes, IM: 6 to 15 minutes
• Comments. As a barbiturate, methohexital is contraindicated in patients with acute intermittent porphyria. Methohexital may cause suppression of respiration; bag-mask ventilatory support may be needed. Transient hypotension may occur from vasodilation; administer IV fluids, and/or sit up slowly.

Nitrous oxide

Nitrous oxide (N2O) is an analgesic/anxiolytic gas causing CNS depression and euphoria with little effect on the respiratory function. The onset of action is rapid, and recovery is fast. There is a wide margin of safety. Moreover, nausea and vomiting are uncommon, and reflex integrity is maintained. It is commonly used for PSA in dentistry, especially in the pediatric setting.[21] Gas delivery is with oxygen. Usually, the patient receives 100% oxygen at the beginning of the procedure, and then, oxygen is slowed, and N2O incrementally increased. A flow rate of 5 to 6 L/min is generally acceptable to most patients. Although the therapeutic levels will vary from patient to patient, the concentration of N2O should not routinely exceed 50%.[22] This approach is contraindicated in COPD, severe emotional disturbances or drug-related dependencies, the first trimester of pregnancy, treatment with bleomycin sulfate, recent tympanic membrane graft, and methylenetetrahydrofolate reductase deficiency.[23]

Reversal agents 

Naloxone

• Dose. (IV only) Adults: 0.1 to 2.0 mg 
• Onset time. One minute
• Duration: 15 to 30 minutes
• Comments. Opiate reversal, very safe, but routine use NOT recommended

Flumazenil

• Dose. (IV only). Adults: 0.2 mg per minute. Maximum: 1.0 mg every 20 minutes
• Onset time. One minute
• Duration. 45 minutes
• Comments. Benzodiazepine reversal use is discouraged for potential benzodiazepine withdrawal or status epilepticus.

Complications

A bedrock concept is using the right drug at the correct dose for the correct patient. This concept may mean using a more potent drug that has a shorter duration or a more straightforward intervention in the event of a complication. This counter-intuitive concept is built into modern sedation protocols. For example, using combinations of medications in a high dose with a long duration of action (e.g., fentanyl and lorazepam) may appear safer than using propofol for brief duration procedures. This idea represents a crucial error and demonstrates a misunderstanding of the realities of practice; avoidance of this error is especially incumbent on credentialing and training committees because the creation of artificial, non-evidence based restrictions can lead to workarounds that imperil patient safety. The reason is, if the person doing the procedure or performing the sedation gets into trouble with the sedation portion of the procedure, rescuing from hypopnea from propofol is several orders of magnitude easier and briefer duration than fentanyl/lorazepam.[24]

Clinical Significance

Properly done, PSA is a humane approach to helping patients tolerate brief, painful procedures. Furthermore, it is vital that the procedure takes place in a safe environment with personnel prepared to rescue the patient from adverse effects of the sedation. Special attention is necessary for respiratory suppression, which is mitigated by monitoring, especially EtCO2, and having a low threshold to support respirations, particularly with bag valve mask ventilation. It is also essential that the respiratory support of the patient not be regarded as an adverse outcome but rather a necessary patient intervention.Because hypotension can also represent a complication, it is imperative to have an IV in place and be prepared to support blood pressure with IV fluids. It is also best practice to be cautious in moving the patient from recumbent to sitting position. Again, the operators must have experience in managing other potential complications such as vomiting. 

Enhancing Healthcare Team Outcomes

PS/PSA is one of the areas of medicine that exemplifies medicine as an interprofessional team sport. Ideally, there are two physicians available, one to perform the procedure and one to administer the sedation and monitor the patient. In resource-constrained settings and many emergency departments, a properly trained nurse can monitor the patient and can, under the supervision of a qualified physician, administer these medications. However, the operating physician must be ready to abandon the procedure and support the patient, paying particular attention to the airway. A nurse or another staff dedicated to the monitoring of the patient during the procedure is mandatory. Additionally, the nurse should ensure that all resuscitative equipment and antidotes are in the room before the procedure starts.  Interprofessional team communication is crucial among all interprofessional team members for patient safety and positive outcomes. [Level 5]

Nursing, Allied Health, and Interprofessional Team Interventions

Nurses function as integral team members during procedural sedation. They are tasked with patient assessment by nursing standards, controlling the room with the procedure will be performed, and ensuring the patient has adequate monitoring in place, including IV access. The nurse should also ensure that they seek out training opportunities to be adept at administering and monitoring these medications. Additionally, nurses have a professional obligation to ensure that their professional societies support the nurses' education and function as full team members to the top of their license. This support includes advocating for the elimination of non-evidence-based restrictions on nursing practice.

Nursing, Allied Health, and Interprofessional Team Monitoring

Nurses must be cognizant of errors that can occur because of the interference of monitoring equipment. For instance, a blood pressure cuff inflating can create an artifactual decrease in oxygen saturation because of arterial compression. Additionally, the nurse must feel empowered to bring the attention of the physician and the rest of the team to adverse events, as observed.