Procedural Sedation in the Emergency Department

Journal of the American Academy of Orthopaedic Surgeons Advance Access, published on February 25, 2015 as doi:10.5435/JAAOS-D-14-00236 The latest version is at http://hwmaint.jaaos.org/cgi/doi/10.5435/JAAOS-D-14-00236

Review Article

Procedural Sedation in the Emergency Department Abstract Craig P. Eberson, MD Raymond Y. Hsu, MD Todd R. Borenstein, MD

Procedural sedation options in the emergency department now allow for more effective and safer care and facilitate the delivery of orthopaedic care that would otherwise require operating room anesthesia. Traditional sedation agents, such as nitrous oxide, midazolam, fentanyl, and ketamine, have a persistent role. Etomidate and propofol are relatively recent additions that are highly effective. Combination regimens, such as ketamine-midazolam and ketaminepropofol, may be superior because they benefit from synergistic traits. Despite these sedation regimens, use of local blocks in adults continues to be effective, and intranasal delivery in children has emerged as a viable option. Orthopaedic surgeons should be aware of the appropriateness of different sedation regimens and other options for specific clinical scenarios.

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From Brown University, Providence, RI. Dr. Eberson or an immediate family member has received royalties from Globus Medical; is a member of a speakers’ bureau or has made paid presentations on behalf of Stryker Spine and Orthofix; serves as a paid consultant to Orthofix; and serves as a board member, owner, officer, or committee member of the Scoliosis Research Society and the Pediatric Orthopaedic Society of North America. Dr. Borenstein or an immediate family member has stock or stock options held in Amlyn and Dyax. Neither Dr. Hsu nor any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article. J Am Acad Orthop Surg 2015;0:1-10 http://dx.doi.org/10.5435/ JAAOS-D-14-00236 Copyright 2015 by the American Academy of Orthopaedic Surgeons.

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nitial management of many orthopaedic injuries requires urgent closed reduction to improve the alignment of fractures, dislocations, and soft tissue. Although the use of local blocks, particularly in adults, has a prominent role, sedation is often necessary to achieve sufficient analgesia and relief of anxiety (ie, anxiolysis) during manipulation of the traumatized extremity. Whether the manipulations are performed as a temporizing measure or are considered definitive management, performing these procedures in the emergency department (ED) rather than in the operating room has the potential to deliver more timely and cost-effective care. In a climate of increased emphasis on maintaining quality and minimizing costs, ED procedural sedation offers significant advantages. For closed reduction and casting of pediatric closed forearm fractures, Betham et al1 demonstrated a tenfold decrease in both time to reduction and length of stay with ED sedation

compared with operating room anesthesia. Similar results are seen with spica casting of pediatric femur fractures; ED sedation demonstrates the same quality of reduction with no increase in complications compared with general anesthesia.2,3 With respect to time and costs, Mansour et al2 showed that the time to placement of a spica cast and the cost of the procedure are both decreased by two thirds and the length of stay is decreased by half. ED sedation is also effective with adults. Reduction of total hip prostheses in the ED decreases the time to reduction by 6 to 8 hours, with no increase in complications compared with the OR.4,5 A traditional sedation in the ED with intravenous (IV) midazolam for dislocated total hip prostheses has a success rate of 62% to 64%; for those total hip prostheses that fail to reduce, there is no delay to accomplishing final reduction in the OR.4,5 However, sedation in the ED with propofol has a success rate of 96% for reduction of total hip

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Copyright © the American Academy of Orthopaedic Surgeons. Unauthorized reproduction of this article is prohibited.

Procedural Sedation in the Emergency Department

prostheses, demonstrating the importance of selecting the ideal sedation agent.5,6 In our experience, the sedation regimen chosen in the ED is more often dependent on the sedation provider on call and is less dependent on the procedure at hand. Factors to consider should include injury pattern, length of the procedure, reductionist experience, and patient comorbidities. Despite the importance of procedural sedation, there is very little formal education in orthopaedics. Whereas the orthopaedic surgeon generally does not provide the sedation, a general understanding of sedation medications facilitates an educated discussion with the sedation provider.

Principles of Sedation The ideal procedural sedation provides anxiolysis, analgesia, and decreased consciousness, including amnesia, without compromising the ability to maintain a patent airway. The American Society of Anesthesiologists defines sedation as a continuum rather than a single state7 (Table 1). Procedural sedation in the ED spans both conscious and deep sedation. During conscious sedation, airway reflexes are still intact. Deep sedation borders on general anesthesia; therefore, patients may routinely need ventilation or brief interventions to assist the airway. Although policies vary by institution, procedural sedation generally requires trained sedation providers, sedation nurses, and appropriate monitoring consisting of telemetry, pulse oximetry, and capnography.8 Many sedation medications fall under the category of sedativehypnotics. A sedative produces anxiolysis, whereas a hypnotic produces drowsiness. Many sedatives, when administered at higher doses, further suppress the central nervous system and have a hypnotic effect.

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Although fracture and joint reductions often require muscle relaxation, no sedation agent directly provides muscle relaxation. The only skeletal muscle relaxants, otherwise referred to as paralytics, are succinylcholine or nondepolarizing relaxants, such as cisatracurium and rocuronium; these medications are routinely used only in intubated patients. The muscle relaxation that occurs during sedation is derived secondarily from anxiolysis, analgesia, and decreased consciousness. The one exception is benzodiazepines; these medications provide spasmolysis by depressing transmission at the spinal cord and at the skeletal neuromuscular junction.9 Another common misconception is the fasting requirement for procedural sedation. A recent policy guideline from the American College of Emergency Physicians recommends not delaying procedural sedation in adults or children based on fasting time.8 In their review of multiple level II studies spanning all types of sedation regimens, the policy group found no reduction in the risk of emesis or aspiration with any duration of preprocedural fasting. Although most orthopaedic surgeons and emergency physicians are used to fasting requirements, those guidelines are extrapolated from general anesthesia in the operating room.

Prototypical Sedation and Analgesia Agents Benzodiazepines (Midazolam and Diazepam) Benzodiazepines, the prototypical sedative-hypnotic, increase the activity of gamma-aminobutyric acid (GABA) receptors, a part of the major central nervous system inhibitory pathway.9 The basis for traditional IV sedations, benzodiazepines provide dose-dependent anterograde

amnesia and spasmolysis but provide no analgesia. This is traditionally addressed by premedication or by combination with an opioid.10-12 IV administration affords rapid onset and ease of titration. Midazolam is most commonly favored for sedation, having the fastest onset, shortest half-life (2 to 4 hours), steepest dose-response curve, and .50% incidence of amnesia.9 Diazepam has a more established track record as a spasmolytic, possibly providing better muscle relaxation; however, its use is less favored for sedations because of its slow onset.9 The primary adverse effect of benzodiazepines is respiratory depression. In healthy patients, sedation doses of midazolam (0.05 to 0.2 mg/kg IV) and diazepam (0.04 to 0.8 mg/kg IV) are rarely an issue. In patients with concurrent causes of respiratory depression, such as use of opioids, therapeutic doses may cause significant respiratory depression.9 Cardiovascular depression is rare except in patients with hypovolemia or heart failure.9 In patients with respiratory or cardiovascular depression, flumazenil (5.0 to 10.0 mg/kg IV) is administered; however, because of its short half-life (0.7 to 1.3 hours), it may need to be redosed.9 Flumazenil should be used with caution, particularly in the setting of tricyclic antidepressants, because seizures or arrhythmias may occur.9

Opioids (Fentanyl and Morphine) Opioids bind as agonists to receptors in the brain and spinal cord, producing analgesia and even euphoria. At higher doses, opioids act as a sedativehypnotic but not as an amnestic.9 In practice, the sedative effects are apparent only when used synergistically with other sedatives. Fentanyl (1.0 to 5.0 mg/kg IV), with a rapid onset and a short duration of action (0.1 to 1.5 hours), is ideal for

Journal of the American Academy of Orthopaedic Surgeons

Craig P. Eberson, MD, et al

Table 1 American Society of Anesthesiologists Continuum of Depth of Sedation7

Factor

Minimal Sedation (Anxiolysis)

Responsiveness Normal response to verbal stimulation

Moderate Sedation/ Analgesia (Conscious Sedation)

Deep Sedation/Analgesia

Airway

Unaffected

Purposeful response to verbal or tactile stimulation No intervention required

Spontaneous ventilation Cardiovascular function

Unaffected

Adequate

Purposeful response following repeated or painful stimulation Intervention may be required May be inadequate

Unaffected

Usually maintained

Usually maintained

General Anesthesia Unarousable even with painful stimulation Intervention often required Frequently inadequate May be impaired

Reproduced with permission from American Society of Anesthesiologists House of Delegates: Continuum of Depth of Sedation: Definition of General Anesthesia and Levels of Sedation/Analgesia. Park Ridge, IL, American Society of Anesthesiologists: Standards, Guidelines and Statement, 2009.

titration during sedation.9 Morphine (0.1 to 0.2 mg/kg IV), the prototypical opioid, has a slower onset and longer duration of action (3 to 4 hours). Whereas morphine is a reliable medication for analgesia, it is difficult to titrate to effect during a procedural sedation. Because of the ubiquity of opioid receptors, the adverse effects of opioids are numerous; the most clinically significant effects for procedural sedation are respiratory depression, cough suppression, and emesis.9 Respiratory depression is dose-related but also is notably antagonized by sensory stimulation. Therefore, respiratory complications may manifest in a delayed manner following the resolution of a painful procedure. An opioid combined with a benzodiazepine significantly accentuates the risk. Roback et al13 demonstrated in a large prospective study that the combination of midazolam and fentanyl was four times as likely to cause a respiratory event compared with use of midazolam alone. Careful monitoring for respiratory depression is crucial, with treatment consisting of support and naloxone (0.4 to 2.0 mg IV); similar to flumazenil, redosing may be required because of the short duration of action (1 to 2 hours).9 Month 2015, Vol 0, No 0

Common Single-agent Sedations Nitrous Oxide Nitrous oxide is one of the most traditional sedation agents (Table 2). The inhaled mixture of 50% nitrous oxide and 50% oxygen continues to be popular in part because of its logistical advantage of not requiring IV access.14,15 The low blood solubility of nitrous oxide causes both rapid equilibration with the brain and rapid clearance back through the respiratory system, allowing for rapid onset and recovery.9 Nitrous oxide provides excellent anxiolysis; however, its analgesia effects are variable. As such, nitrous oxide sedation is particularly synergistic with hematoma blocks. In a randomized controlled trial (RCT), Luhmann et al14 showed this combination to be as effective as a deep sedation combination of ketamine and midazolam for pediatric forearm fracture reduction. Additionally, a retrospective study by McKenna et al15 confirmed that nitrous oxide with supplemental IV morphine allows for adequate reduction and casting of pediatric forearm fractures compared with general anesthesia.

Potential adverse effects of nitrous oxide include nausea, vomiting, and respiratory depression. Despite the risk of vomiting, laryngeal reflexes are believed to remain intact when nitrous oxide is used alone.14 However, when nitrous oxide is used in conjunction with other sedatives or opioids, the additive risks of aspiration and respiratory depression dictate greater caution. A common mechanism used to prevent oversedation is selfadministration by the patient; as the sedation deepens, the patient drops the mask and inhalation stops. Nonetheless, pulse oximetry is generally used throughout the procedure, and recovering patients are often placed on 100% oxygen.

Ketamine Ketamine is a phencyclidine derivative that, unlike sedative-hypnotic agents, produces a unique dissociative anesthetic state.16 Blockade of the excitatory N-methyl-D-aspartate receptor causes dissociation between the sensory limbic system and the higher cortical system of the brain.9 Unlike the dose-response continuum observed with sedative-hypnotic agents, once ketamine’s dosing threshold is reached, additional dosing lengthens but does not deepen the dissociative state.17

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Table 2 Common Sedation Agents Sedation Agent Midazolam (benzodiazepines) Fentanyl (opioids) Nitrous oxide Ketamine

Etomidate Propofol

Dosage 0.05-0.1 mg/kg IV 0.5-2.0 mg/kg IV 50% N2O/50% O2 inhaled 1.0-2.0 mg/kg IV 4.0-5.0 mg/kg IM 0.1-0.2 mg/kg IV 1.0 mg/kg IV initial bolus

Ketamine provides excellent analgesia and amnesia while favorably preserving airway muscle tone, airway reflexes, and spontaneous respiration.10,16,17 Distinct features are open eyes with nystagmus and catalepsy characterized by normal to enhanced muscle tone.17 McCarty et al16 first demonstrated in a prospective study the efficacy of ketamine sedation for pediatric fracture reduction. Despite interest in combination regimens, ketamine-only sedation remains a reliable staple for pediatric orthopaedic injuries.18 IV administration (1 to 2 mg/kg) over 30 to 60 seconds permits fast recovery and avoids transient apnea that can occur with a rapid push. Intramuscular administration (4 to 5 mg/kg) is an effective second option when IV access is difficult; however, there is an increased risk of emesis.17 Ketamine uniquely increases salivary flow. An anticholinergic, such as atropine or glycopyrrolate, has traditionally been given concurrently to decrease oral secretions. More recent literature, however, suggests that routine anticholinergic use is not necessary because it does not decrease adverse airway events.17 The most notorious effect of ketamine is the emergence reaction that may include delirium, agitation, and combativeness. Traditionally,

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Sedation Characteristics

Adverse Effects

Anxiolysis, spasmolysis, no analgesia, variable amnesia Analgesia, variable anxiolysis Anxiolysis, unreliable analgesia

Respiratory depression

Dissociative (analgesia, amnesia)

Emergence, vomiting, increased secretions, hypertension

Anxiolysis, no analgesia Anxiolysis, amnesia, no analgesia

Myoclonus Respiratory depression, transient hypotension

benzodiazepines are given preemptively to minimize this phenomenon. More recently, the routine coadministration of benzodiazepines in children has been called into question; more appropriate administration may consist of titration as needed.17 Historically, the reluctance to use ketamine in adults was because of an increased rate of emergence reactions, but the severity of these reactions may have been overstated. Sener et al19 demonstrated in a double-blinded RCT that ketamine both with and without midazolam provided successful adult procedural sedations, over half of which were for orthopaedic reductions. Although pretreatment with midazolam significantly decreased emergence reactions, the clinical significance of these reactions was unclear. Miner et al,20 in another prospective study, showed that while recovery agitation was noted in 17 of 47 adults (36.2%) receiving ketamine, only 4 patients required treatment with IV midazolam. Beyond its already unique dissociative state and adverse effect profile, ketamine also has distinctive contraindications. Ketamine is a sympathomimetic, inhibiting catecholamine uptake; this effect is advantageous when combined with other sedatives; however, this effect also makes it relatively contraindicated in patients with uncontrolled hypertension or

Respiratory depression, vomiting Vomiting, respiratory depression

cardiovascular disease.9,17 Ketamine is also associated with a 0.3% rate of idiosyncratic laryngospasm and a possible increase in intracranial pressure, dictating caution when using it in patients with existing airway or intracranial disease.17

Etomidate Etomidate was introduced in the ED for rapid sequence intubation in the late 1980s. The mechanism of action is enhanced activity of GABA receptors. Typical sedation administration (0.1 to 0.2 mg/kg IV) is half that of an induction dose (0.3 mg/kg IV).21,22 Its profile of rapid loss of consciousness, short duration of action, and minimal depression of cardiovascular and pulmonary function makes it particularly useful for procedural sedation in elderly or trauma patients. It provides no analgesia, however, and an opiate is generally given prior or concurrently. Although etomidate has been used for procedural sedation since the late 1990s, only recently have a few highquality studies been conducted. In a double-blinded RCT of adolescent and adult orthopaedic sedations, Hunt et al22 demonstrated a higher reduction success rate (100% versus 86% [P = 0.06]) and faster recovery time (15 minutes versus 32 minutes [P , 0.001]) compared with midazolam.



Miner et al,21 in a RCT comparison with propofol for adult sedations, demonstrated a slightly lower efficacy (89.5% versus 97.2% [P , 0.05]) but minimal complications for both. Unique to etomidate is a 15% to 20% rate of myoclonus, which contributes to unsuccessful procedures.21,22 In our experience, its short duration of action (3 to 12 minutes), makes it best suited for rapid procedures, such as total hip reductions.

Propofol Propofol, another GABA receptor potentiator and popular IV anesthetic, has similarly gained popularity for procedural sedation. Similar to etomidate, propofol provides rapid, short duration anxiolysis and amnesia but no analgesia. Whereas etomidate will cause respiratory depression only if given as a rapid push, some degree of respiratory depression is common with propofol, especially at higher doses or with redosing.23 Transient hypotension occurs routinely but is clinically inconsequential except in the setting of underlying disease or hypovolemia.23 Despite initial concerns of respiratory depression, the safety of propofol for ED sedations in both adults and children is well established. In RCTs of propofol for adults, Miner et al20,21 demonstrated that when the drug is administered with an initial 1.0-mg/kg bolus, the rates of subclinical respiratory depression in adults are equivalent to the rates of etomidate and less than the rates associated with ketamine. Bassett et al,24 in a prospective series of 393 pediatric propofol sedations used almost exclusively for orthopaedic procedures, found only 19 patients (5%) had hypoxia, of which 11 patients (3%) required airway repositioning, 3 patients (0.8%) required bag-mask ventilation, and none required intubation. We find that propofol provides the best single-agent sedation and compares favorably to combination Month 2015, Vol 0, No 0

sedations. Miner et al25 showed in a RCT that if appropriate analgesia is provided before the sedation, the routine addition of narcotics during propofol sedation in adults provides no benefit and increases the risks of respiratory depression. For hip prosthesis reductions conducted in the ED, Mathieu et al6 demonstrated that propofol provides a greater rate of success (94 of 98 patients [98%]) compared with previously reported rates for traditional benzodiazepine and narcotic sedations (62%). Uri et al,23 in a RCT of adult orthopaedic trauma injuries, demonstrated that propofol, compared with a midazolam-ketamine combination, expedites patient care by decreasing the total sedation time by more than half (16.2 minutes versus 41.6 minutes [P , 0.001]).

Combination Sedation Regimens Midazolam-Fentanyl Despite the existence of newer regimens, combining midazolam’s effects of anxiolysis and amnesia with fentanyl’s effect of analgesia remains a popular strategy for procedural sedation (Table 3). Cevik et al11 demonstrated in a double-blinded RCT of orthopaedic sedations that this combination performs with a good or excellent physician and patient satisfaction rate of .90%. In a study by Kennedy et al,10-12 this combination provided complete amnesia in up to 85% of patients and also demonstrated low rates of nausea and vomiting (9%) and hypotension (6.2%). Respiratory depression, however, is a major concern with this regimen.10,12,26 Cevik et al11demonstrated a high incidence of hypoxia (23 of 30 patients [76.7%]), with one patient requiring positive-pressure ventilation. In addition, despite generally providing effective sedation, the combination of midazolam-fentanyl yields higher

observed pain, anxiety, and distress scores compared with other commonly used drug combinations.11,12

Etomidate-Fentanyl The regimen of etomidate-fentanyl is chosen for its effectiveness and short duration of action. Di Liddo et al,26 in a RCT of pediatric fracture reductions, found a high procedural success rate (48 of 50 patients [96%]) with the use of this combination. Lee-Jayaram et al,27 in a RCT comparison with ketamine-midazolam in pediatric fracture reductions, found significantly shorter recovery times (24.7 minutes versus 61.4 minutes [P , 0.001]) and total sedation times (49.6 minutes versus 77.6 minutes [P = 0.003]). Adverse effects of etomidate-fentanyl are hypoxia and, uniquely, myoclonus. Reported rates of hypoxia are 10% to 17%, with no patients requiring more than repositioning and supplemental oxygen.26,27 Similar to single-agent etomidate, myoclonus is common (11% to 25%), although it does not appear to affect completion of procedures.26,27 In our experience, the myoclonus is disruptive when holding a reduction before immobilization. Lee-Jayaram et al27 also demonstrated more observed distress, worse patient satisfaction, and lower orthopaedic practitioner satisfaction with this drug combination compared with the ketamine-midazolam combination. Because of the short duration of action and myoclonus, we try to limit use of this combination to injury patterns that are relatively stable after reduction. We would not use this regimen for hip dislocations with large posterior wall fragments or for ankle fracture-dislocations with large posterior malleolus fragments.

Propofol-Fentanyl Theoretically, fentanyl amends propofol’s lack of analgesic properties. However, in a RCT of adult procedural sedations comparing

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Table 3 Combination Sedation Regimens Sedation Agents

Dosage

Sedation Characteristics

Ketaminepropofol

1:1 ratio 0.375-1.5 mg/kg 1 0.375-1.5 mg/kg IV

Ketaminemidazolam

1.0-2.0 mg/kg 1 0.02-0.3 mg/kg IV

Etomidatefentanyl Propofolfentanyl Midazolamfentanyl

0.2 mg/kg 1 1.0 mg/kg IV 1.0 mg/kg 1 1.0-2.0 mg/kg IV 0.04-0.3 mg/kg 1 1.0-3.0 mg/kg IV

propofol-fentanyl with single-agent propofol, Miner et al25 found fentanyl provided no benefit in terms of procedure success or patient satisfaction. As part of their protocol, however, all patients had already received IV morphine for pain control up to within 20 minutes of their sedations. The theoretic synergy of propofol-fentanyl may benefit only patients who have not already received sufficient analgesia. Propofol-fentanyl remains an effective regimen in general. As would be expected from two fast-acting agents, Godambe et al,28 in a RCT of pediatric orthopaedic procedures, demonstrated significantly shorter recovery times and total sedation times compared with ketamine-midazolam (33.4 minutes and 23.2 minutes shorter, respectively [P , 0.0001]). Godambe et al28 also reported that orthopaedic surgeons in their study believed that the propofol-fentanyl regimen supplied superior muscle relaxation, especially for difficult reductions.28 The primary concern with propofolfentanyl is the risk of combining two strong respiratory depressants. Godambe et al28 found a significantly higher rate of transient desaturations

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Adverse Effects

Respiratory depression, vomiting, Analgesia, amnesia, anxiolysis, consistent depth of sedation, short transient bradycardia, emergence induction and recovery times Analgesia, amnesia, anxiolysis, Respiratory depression, vomiting, consistent depth of sedation vertigo, emergence, transient hypertension and tachycardia (adult patients) Anxiolysis, analgesia, short Myoclonus, respiratory induction and recovery times depression, vomiting Analgesia, amnesia, anxiolysis, Respiratory depression, short induction and recovery times hypotension Analgesia, amnesia, anxiolysis, Respiratory depression, transient longer induction and recovery bradycardia, vomiting, vertigo times

compared with ketamine-midazolam (31% versus 7% [P = 0.002]), but no patients required any intervention more invasive than airway repositioning or supplemental oxygen. Similarly, Miner et al25 demonstrated an increased need for stimulation to induce respirations compared with propofol alone (28.2% versus 14.9% [P = 0.05]). They found no statistical difference, however, in the need for bag-mask ventilation, the most invasive respiratory intervention required in either group (16.9% versus 9.5% [P = 0.18]). Transient hypotension is almost always subclinical and resolves with IV fluids.25,28 Overall, propofol-fentanyl is a highly effective and safe sedation regimen when accompanied by vigilant monitoring to initiate necessary interventions.

Ketamine-Midazolam Ketamine and midazolam have traditionally been combined for their opposing but complementary traits. Ketamine’s sympathomimetic properties counter midazolam’s tendency to depress respiration. Multiple prospective studies demonstrate rates of

hypoxia of zero to 6% on room air.12,19,23,27,28 Cevik et al11 reported a rate of 45.2%; however, unlike other studies, the authors delivered the medications concurrently without any pause. Even then, patients required nothing more than supplemental oxygen. Theoretically, midazolam counters ketamine’s emergence phenomenon. Clinically, large RCTs in children have shown that midazolam does not significantly decrease emergence.17 In a RCT by Sener et al,19 the authors demonstrated benefit in adults, who have a higher incidence of emergence phenomenon even with midazolam (3% to 19%), but found no difference with respect to procedural success.11,23 This too is our experience because, by definition, emergence phenomenon occurs after procedure completion. For pediatric reductions, ketaminemidazolam has a proven track record of .98% success in large RCTs.12,28 Kennedy et al12 found statistical significance with less patient distress and greater orthopaedic surgeon satisfaction compared with midazolamfentanyl. For adult orthopaedic sedations, Cevik et al11 demonstrated



Table 4 Intranasal Analgesia and Sedation Intranasal Agents

Dosage

Intranasal fentanyl

1.5-4.0 mg/kg

Pain from fractures

Intranasal ketamine

0.5-9.0 mg/kg

Intranasal midazolam

0.2-0.8 mg/kg

Laceration repair, pain from fractures Laceration repair, nail bed repair, wound incision and drainage, foreign body removal, casting minimally displaced fractures

a procedural success rate of 97% and good or excellent physician satisfaction rates of .90%. Uri et al23 similarly reported a procedural success rate of 100% and high physician satisfaction. The most commonly identified problem with ketamine-midazolam is the increased recovery time and the total sedation time. Although times vary across studies, ketaminemidazolam has been shown to have a significantly longer recovery time and total sedation time compared with propofol-fentanyl, etomidate-fentanyl, and single-agent propofol.12,23,27 We find ketamine-midazolam to be very effective in children, especially for longer procedures. The two major downsides are the emergence reactions, which generally have no procedural effect, and the prolonged recovery, which delays turnover when multiple patients require sedation.

Ketamine-Propofol Ketofol, the combination of ketamine and propofol, is particularly synergistic. Ketamine provides analgesia, which propofol lacks, eliminating the need for opioids. Propofol’s anxiolytic properties theoretically decrease the emergence of ketamine.18 The addition of ketamine to propofol may also avoid hypotension and respiratory depression by increasing sympathetic tone. A RCT by Singh et al29 demonstrated significantly Month 2015, Vol 0, No 0

Uses

fewer instances of respiratory compromise with ketofol (10%) compared with propofol (35% [P , 0.05]). Other studies demonstrate more comparable rates of respiratory events (22% to 30%), but with only 2% requiring more than supplemental oxygen or repositioning.30,31 The antiemetic properties of propofol counter the emesis associated with ketamine. Shah et al18 showed decreased emesis with ketofol (2%) compared with ketamine alone (12% [P , 0.05]). Ketofol yields a deeper sedation with less agitation compared with propofol, and it also has a high procedural success rate of 95%.18,30,32 Given these advantages, it is not surprising that physician satisfaction with ketofol is significantly higher than either single-agent ketamine (87% versus 57% [P , 0.05]) or propofol (95% versus 65% [P , 0.05]).18,31 Additionally, the combination allows for lower doses of each medication; this may further reduce adverse events. We find ketofol to be as effective as single-agent propofol but with fewer complications.

Intranasal Delivery Intranasal medications (Table 4) are an attractive alternative to IV analgesia and sedation for minor orthopaedic procedures in the pediatric emergency department. Placement of

Adverse Effects Very limited adverse effects, abdominal pain, rash Dizziness, bad taste, dysphoria, nausea Variable sedation effect, nasal discomfort, bitter taste

an IV line increases pain and anxiety in children and requires additional resources. In comparison, intranasal medications are often painless and inexpensive and require little training to administer.33 The most commonly used intranasal medications are fentanyl, ketamine, and midazolam. For analgesia, intranasal fentanyl is excellent for pediatric orthopaedic injuries.33,34 Saunders et al33 reported that 87% of children had a clinically significant decrease in pain within 30 minutes of administration; only 9% required further analgesia. In a similar population, Furyk et al34 reported that intranasal fentanyl was as effective as IV morphine. Subdissociative doses of intranasal ketamine may also be effective for pain control for pediatric orthopaedic injuries.35 Yeaman et al35 reported clinically significant pain reduction in .80% of patients at both 30 and 60 minutes. For sedation for minor procedures, such as lacerations and nail bed repairs, Lane et al36 showed that intranasal midazolam was effective; only 10 of 201 patients (5%) required additional IV or IM ketamine. We have similarly found intranasal midazolam to be particularly useful for casting minimally displaced and nondisplaced fractures in agitated young children. We would not recommend the use of intranasal medications for more involved procedures, such as fracture

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Table 5 Regimen Selection Guidelines Patient Population Adult

Common Procedures

Regimens

Notes

Propofol 6 (ketamine or fentanyl) Hip/knee arthroplasty reduction Etomidate-fentanyl Native hip reduction 6 acetabular fracture External fixation of grossly unstable ankle or pilon fractures Reduction/casting of minimally Midazolam-fentanyl displaced tibia fractures Ketamine 6 midazolam

Pediatric

Ankle fracture/dislocation reduction/splinting Shoulder and elbow reduction Distal radius fracture reduction Fracture/joint reduction Joint aspiration/lavage Involved laceration repairs or hand procedures

Pain control Casting without reduction Simple laceration or nail bed repairs

reductions, and there are no studies to support this type of usage.

Intra-articular and Hematoma Blocks Despite advances in procedural sedation, intra-articular and hematoma blocks in adults continue to be effective options for fractures and dislocations. In a RCT comparing the use of IV sedation with the use of intra-articular lidocaine for ankle fracture-dislocations, White et al37 demonstrated similar improvements in pain score (4.6 with intra-articular block, 4.2 with IV sedation [P = 0.64]) and rates of successful closed reduction (100% with intra-articular block, 95% with IV sedation). For glenohumeral reductions, a RCT by Miller et al38 found similar success rates

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Lidocaine or marcaine intraarticular and hematoma blocks (no sedation) Ketamine-midazolam Nitrous oxide 1 hematoma block Propofol regimens Etomidate-fentanyl Single-agent ketamine Intranasal midazolam

comparing intra-articular lidocaine with IV midazolam-fentanyl (87% versus 78% [P = 1.00]). Additionally, the authors found savings with respect to time in the ED (75 minutes versus 185 minutes [P , 0.01]), as well as the cost of the procedures ($0.52 versus $97.64). Monitoring for the sedation accounted for $87.57 of the cost difference.38 A RCT by Cheok et al39 showed a significantly higher rate of failure of shoulder reduction with intra-articular lidocaine compared with IV sedation (19% versus zero [P = 0.024]). This finding was offset by a lower complication rate, a shorter length of stay, and similar pain relief and patient satisfaction with intra-articular injections.39 For distal radius fractures in adults, we find that hematoma blocks without IV sedation are the most efficient. A RCT by Fathi et al40

Author preference Effective for shorter procedures and injury patterns that are immediately stable after reduction (arthroplasty dislocations) High rate of respiratory depression Minimal experience at our institution in adults, newer literature suggests very effective With anxious patients, may need sedation

Author preference, longer recovery time, emergence reaction Effective sedation, fast recovery Minimal experience at our institution in children Fast delivery, monitoring not required

demonstrated no difference in pain scores between hematoma blocks and IV midazolam-fentanyl for reduction of distal radius fractures.

Summary A working knowledge of sedation medications allows orthopaedic surgeons to provide efficient and tailored patient care. In general, combination medication regimens may be more effective and safer secondary to their synergy. For adult procedural sedations, we prefer the effectiveness of propofol with either ketamine or opioid analgesia (Table 5). Literature suggests ketofol may be the safer regimen of the two. For pediatric procedural sedations, we find ketamine-midazolam to be very effective, although recovery times can delay care for waiting



patients. Other centers have found similar excellent results with other pediatric sedations, including nitrous oxide combined with hematoma blocks, single-agent ketamine, and propofol regimens. Intra-articular and hematoma blocks in adults and intranasal medication in children are also viable options when indicated. Overall, the needs of the procedure, the patient comorbidities, the sedation provider preference, and the capabilities of the ED are all crucial factors to consider when selecting a sedation regimen.

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