AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Sedatives and Analgesics
• Approach to Sedation
• Pediatric Considerations
• Common Sedation Regimens
• Antagonists
• Summary
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Sedatives and Analgesics
• Approach to Sedation
• Pediatric Considerations
• Common Sedation Regimens
• Antagonists
• Summary
• References

One of the most important goals of physicians is patient comfort. When patients present to the emergency department, treating the pain and anxiety that accompany the chief complaint are critical to patient satisfaction and quality of care. Nonetheless, clinicians may underuse sedation, usually from a lack of experience or from unchallenged myths regarding its use.

Sedation is the depression of a patient's awareness to the environment and reduction of his or her responsiveness to external stimulation. This is accomplished along a continuum of sedation levels:

• Minimal sedation is equivalent to anxiolysis, that is, a drug-induced relief of apprehension with minimal effect on sensorium.
• Moderate sedation is a depression of consciousness in which the patient can respond to external stimuli (verbal or tactile). Airway reflexes, spontaneous ventilation, and cardiovascular function are maintained.
• Deep sedation is a depression of consciousness in which the patient cannot be aroused but responds purposefully to repeated or painful stimuli. The patient may not be able to maintain airway reflexes or spontaneous ventilation, but cardiovascular function is preserved.
• General anesthesia is a state of unconsciousness; the autonomic nervous system is unable to respond to surgical or procedural stimuli.
• Dissociation, which could be considered a type of moderate sedation, is seen when using medications in the phencyclidine group (eg, ketamine). They cause a disconnection between the thalamoneocortical system and the limbic systems, preventing higher centers from receiving sensory stimuli. Like moderate sedation, airway reflexes, spontaneous ventilation, and cardiovascular function are all maintained.

Prior to the administration of medications, it is important for physicians to know the level of sedation required for a given procedure and to give the appropriate dose of the pharmacologic agent or agents chosen. This will determine the equipment that one should have readily available prior to starting the procedure.

Individual patient response to medications can vary; therefore, the physician can potentially overshoot the desired level of anesthesia. Clinicians must be prepared for this and should have emergency apparatus available if problems arise.

The medications used during sedation typically have additional beneficial effects, as important as sedation. These actions include the following:

• Anxiolysis - Relief of trepidation or agitation with minimal alteration of sensorium
• Amnesia - Lapse in memory for a period of time
• Analgesia - Relief of pain without an altered sensorium

Sedatives typically have more than one of these actions, although one may predominate. The ideal sedative would exhibit all of the above qualities; most do not. It is common practice to coadminister medications with different qualities to compensate for any shortcomings, for example, midazolam primarily an anxiolytic with some amnestic qualities and fentanyl primarily an analgesic. When drugs are used as adjuncts, decreasing the dose of each respective drug is important, so as to decrease the incidence of side effects.

The medications below are presented according to pharmacologic class. In general, these medications are usually given intravenously when used for procedures in the emergency department (ED), with some exceptions for children. Intravenous medications generally have a quick onset, predictable drug absorption, and are titratable compared with other modes of administration. The intravenous route is emphasized in the discussion below.

SEDATIVES AND ANALGESICS

Section 3 of 9  

• Authors and Editors
• Introduction
• Sedatives and Analgesics
• Approach to Sedation
• Pediatric Considerations
• Common Sedation Regimens
• Antagonists
• Summary
• References

Benzodiazepines

The benzodiazepines act by stimulating specific benzodiazepine receptors in the CNS. Stimulation of this receptor potentiates the inhibitory effects of gamma-aminobutyric acid (GABA) on GABAA receptors. This results in chloride influx, hyperpolarization, and decreased ability of the neuron to reach an action potential, producing sedation and anxiolysis.

In addition, this class of drugs produces amnesia and has anticonvulsant actions. They have no analgesic properties. Their most significant adverse effect is respiratory depression and subsequent hypoxemia. Therefore, one should exercise caution when administering this medication to patients with underlying COPD. Cardiovascular depression, resulting in hypotension with reflex tachycardia, is another adverse effect, but it is not significant at typical doses unless hypovolemia is present or unless it is coadministered with centrally acting analgesics. One should also be cautious when giving a hepatically metabolized benzodiazepine (eg, midazolam) to a patient with cirrhosis.

Benzodiazepines differ by the methods they can be given, time of onset, action duration, mechanism of metabolism, and presence of active metabolites. As mentioned earlier, their mechanism of action is seen clinically as anxiolysis, amnesia, and sedation; if a particular procedure is painful, these drugs must be given with analgesic agents. In nonintubated patients, the desired effect is found by titration until the desired effect is achieved. Caution must be used in children; they may have a paradoxical disinhibition and increased agitation at low doses.

Benzodiazepines include midazolam, lorazepam, and diazepam.

Midazolam

Midazolam is a benzodiazepine with a unique imidazole ring that allows for both lipophilic and hydrophilic properties. When the pH is less than 4, it is water soluble and the chance of pain at the injection site is less. Unlike other benzodiazepines, midazolam becomes lipophilic at a pH greater than 4. Midazolam crosses the blood-brain barrier with ease as a lipophilic molecule, producing sedation in less than 5 minutes. The total dose in adults is 0.02-0.1 mg/kg. The initial pediatric dose is 0.05-0.15 mg/kg IV or IM. The duration of action is about 30 minutes, although sedation may be prolonged in elderly patients. Midazolam is metabolized by the hepatic microsomal system and is not affected by renal failure. (Caution with cirrhosis.) Midazolam is the fastest acting of its class because of its lipophilic abilities, and it is superior to lorazepam and diazepam in its amnestic effects, making it the ideal benzodiazepine for use in short ED procedures.

Lorazepam

Lorazepam is a water-soluble benzodiazepine. The dose range in adults is usually 1-4 mg. The initial pediatric dose is 0.1 mg/kg. It is an intermediate-acting benzodiazepine; its effects begin within 3-5 minutes and peak at 20-30 minutes. Lorazepam generally lasts 1-4 hours. Lorazepam has a few advantages over midazolam: first, metabolism occurs by means of conjugation, which makes it more suitable than other benzodiazepines for use in the presence of renal and/or hepatic failure. Second, lorazepam does not have any active metabolites. Thus, it can be given as a continuous intravenous infusion (0.03-0.1 mg/kg/h) with less concern for side effects than an intravenous midazolam drip. (For this reason, it is the preferred agent for continuous administration.) Lorazepam's utility in the ED could be for longer-term sedation; for example, patients undergoing mechanical ventilation.

Diazepam

Diazepam, a longer-acting benzodiazepine, was the first benzodiazepine developed for intravenous use. It is insoluble in water and is commercially prepared in propylene glycol. The intravenous dose range for adults is 2-10 mg. The onset of action is relatively rapid, but the duration of action is 2-4 hours. It is metabolized almost exclusively in the liver; therefore, this drug should not be used in patients with cirrhosis. When it is broken down, its metabolites are not only active but they possess very long half-lives (ie, 36-90 h). The drug profile of diazepam is not very conducive to ED usage.

Barbiturates

Barbiturates are very potent sedatives. Some of the more common uses include induction for endotracheal intubation and ED sedation. They possess primarily sedative properties and some amnestic effects but no analgesic properties. Like benzodiazepines, they are often used as adjuncts to analgesics for painful procedures. Barbiturates should be given with caution to persons with COPD, as they have been shown in early studies to increase the potential for respiratory suppressive effects.

Drugs in the barbiturates class include methohexital and thiopental.

Methohexital

Methohexital is the shortest acting of the barbiturate sedatives, with a rapid onset of action ( <1 min) and a short duration of action (5-10 min). The dose for induction is 0.75-1 mg/kg. It also can be used as a sedative for brief procedures, in which case, it is titrated to effect. Adverse effects include hypotension (due to vasodilatation and myocardial depression with reflex tachycardia), which can be more evident in hypovolemia. It should be used with caution in hemodynamically unstable patients, starting off at lower doses (0.5 mg/kg) and titrating up slowly to sedation.

Thiopental

Thiopental is another short-acting barbiturate sedative, lasting about 5-20 minutes. Like methohexital, it is used for induction during intubation. The dose is 2-4 mg/kg. The dose should again be lowered for critically ill or elderly patients. It also can be used during brief procedures. The main adverse effects include hypotension, which is potentiated by patients that are hypovolemic or critically ill.

Nonbarbiturate sedatives

Nonbarbiturate sedatives have all of the sedative properties of barbiturates. They include propofol and etomidate.

Propofol

Propofol is an alkyl phenol derivative compound prepared in a 10% lipid emulsion. Originally promoted as an anesthetic induction agent, propofol is also used as a short-acting sedative for bolus administration or continuous infusion. It has a rapid onset of action ( <1 min) and short duration of action (approximately 10 min but is dose dependent). Clearance of the drug is not affected by renal or hepatic dysfunction, as it has no active metabolites.

Propofol is a respiratory and cardiovascular depressant; these effects have limited its use in the ED in the past, but it has become increasingly popular in procedural sedation. Propofol can be used in the ED as a sedative for short-term procedures and is dosed by means of titration to effect in increments of 10-20 mg in adults. This also is a very good agent for sedation in patients receiving mechanical ventilation; under these circumstances, it is administered as a continuous infusion starting at 5-10 mcg/kg/min and then titrated to effect. The total dose given typically ranges from 25-125 mcg/kg/min. It has direct cardiodepressant effects, leading to decreased blood pressure and heart rate.

Blood pressure should be frequently monitored during titration. The suppression of hypoxic respiratory drive is dose dependent. Because of an association with lactic acidosis, prolonged or continuous infusion in pediatric patients is not recommended. Propofol is also contraindicated in patients with allergies to soybean or eggs.

Etomidate

Etomidate is an imidazole derivative compound with sedative properties. Administered intravenously, etomidate has rapid onset of action ( <1 min) and a short but dose-dependent duration of action (5-8 min). A major feature of this agent is that during deep sedation, cardiovascular effects are negligible. It may cause transient neuromuscular twitching that is sometimes confused with seizure activity. Recent studies show that pretreatment with magnesium sulfate may prevent etomidate-induced myoclonus.

Its major application is induction for endotracheal intubation, especially for patients at risk for hemodynamic compromise. The recommended dose for intubation is 0.3 mg/kg in adults and children, although the dose may be reduced to 0.15 mg/kg in critically ill patients. It can be also be used in procedures as a one-time dose. Etomidate has been shown to depress adrenal cortical function, but this is not clinically significant in short-term administration. Because of this effect and because the drug is mixed in propylene glycol, neither titration nor continuous infusion is recommended. In addition, one should exercise caution when giving this medication to a patient with septic shock; it should be given with steroids.

Opioids

Opioids are agents that induce systemic analgesia, some anxiolysis, and mild sedation. They do not induce amnesia of any significance. Opioids are typically coadministered with benzodiazepines for added sedation, anxiolysis, and amnesia. They act by binding to specific opioid receptors in the CNS. They are the class of drugs most commonly used for pain management.

Opioids include morphine, fentanyl, and meperidine.

Morphine

Morphine is the oldest and most established agent for pain management in the ED. In its intravenous form, it has a rapid onset of action. Its duration of action, however, can be as long as 3-4 hours. The dose is 0.1-0.15 mg/kg (5-10 mg initially for adults), with additional doses as needed. The primary adverse effect is hypotension, explained partially by histamine release. Administering the medication slowly can minimize this effect. Respiratory suppression can also occur, and its risk increases with coadministration of sedative agents.

Fentanyl

Fentanyl is a very potent synthetic opioid, and one of the commonly used analgesic adjuncts in the ED. It rapidly crosses the blood-brain barrier and thus has a rapid onset of analgesia (<90 seconds). However, the serum levels rapidly decline due to tissue redistribution, making the duration of action about 30-40 minutes. It has minimal cardiovascular effects such as hypotension. Respiratory depression is uncommon, but it is potentiated when used in combination with benzodiazepines. The intravenous dose is 2-3 mcg/kg (50-200 mcg in adults), titrated in 50 to 100-mcg increments. It is the preferred drug for analgesia in short procedures and in cases of trauma with potential hemodynamic compromise. As an analgesic adjunct to continuous sedation, it can be administered as a continuous infusion in doses of 1-3 mcg/kg/h.

Meperidine

Meperidine's duration of action (2-3 h) is intermediate when compared with fentanyl and morphine. Intravenous dosing is 0.5-1 mg/kg initially (35-100 mg for adults). It has an active metabolite, normeperidine, that can lower the seizure threshold and it becomes problematic in renal failure. It offers no advantage over fentanyl or morphine. Its use has been declining.

Nonopioid analgesics

Ketamine is a dissociative anesthetic and analgesic with a short duration of action. It is unique in that it produces a state in which respiration and airway reflexes are maintained while patients are unaware of their surroundings. At lower doses, patients can respond to simple commands, but they seem to be unaware of painful stimuli. It rarely produces hemodynamic depression.

Ketamine is water soluble and lipophilic. Given intravenously, the onset of action is rapid (causing minimal pain at the injection site), and the duration of action is about 15-30 minutes. The dose is 1-2 mg/kg IV, which typically produces a full dissociative state. The emergence reaction (ie, hallucinations developing during recovery from the dissociative state) is one adverse effect. It is more severe in adults and can be attenuated with the administration of a benzodiazepine, such as midazolam, before recovery.

Laryngospasm is another adverse reaction. Although laryngospasm usually is manageable with conservative techniques, expertise and equipment must be available to manage the airway in this situation. Ketamine also causes inhibition of the reuptake of catecholamines at the neuromuscular junction, which leads to slight increases in the heart rate, blood pressure, and cardiac output. In children, ketamine can cause increased salivary and respiratory tract secretions; it is usually given withatropine (0.01 mg/kg; maximum dose, 0.5 mg).

Ketamine is useful in various situations. For example, it is a good choice in children when analgesia and unconsciousness are required (eg, for the repair of a complex facial laceration or the reduction of an extremity fracture). Because of the emergence phenomenon, much of the data on ketamine come from the pediatric population. However, it is useful in adults as well. Ketamine causes bronchial smooth muscle relaxation, making it the preferred drug for sedation/analgesia in asthmatics. Also, since its cardiovascular effects are minimal, it is another agent to consider for use in hemodynamically unstable patients (eg, induction for intubation). Moreover, it shows promise as a preferred drug in patients with traumatic brain injury.

Ketamine was once thought to increase intracranial pressure (ICP), and its use in patients with traumatic brain injury (TBI) was not recommended. However, newer data suggest that ketamine might actually decrease ICP, potentially making it a drug of choice (with or without a sedative adjunct) in patients with TBI. Its neuroprotective effects require further study.

Inhalation agents

The inhaled anesthetic nitrous oxide, as a 30-50% mixture in oxygen, acts as a sedative and analgesic. It has a rapid onset of action (1-2 min) and a rapid duration of action (5 min). It is thought to act by binding to the opiate receptors in the CNS. Side effects include hypoxia, if not mixed with an adequate oxygen percentage fraction. Its sedative properties are more noticeable clinically than its analgesic properties. Therefore, unless the procedure is a minor one, coadministration with an analgesic is recommended. Since a scavenging system is required for its use, nitrous oxide is not routinely administered in the ED.

APPROACH TO SEDATION

Section 4 of 9  

• Authors and Editors
• Introduction
• Sedatives and Analgesics
• Approach to Sedation
• Pediatric Considerations
• Common Sedation Regimens
• Antagonists
• Summary
• References

The therapeutic goals of sedation in the ED must constantly be considered before, during, and after the process to ensure the necessity and adequacy of anesthesia. The clinician must weigh the potential for pain and discomfort of a given procedure with the risks that might be associated with sedative medications. However, physicians should not withhold needed analgesia or sedation, especially in particularly painful or stressful procedures. Doses can always be adjusted as the clinical situation demands.

Numerous indications exist for sedation: Invasive procedures are highly stressful and should at least prompt consideration of sedation. Even minor procedures routinely performed without sedation, such as lumbar puncture, may be facilitated and performed with more patient comfort when sedatives are administered. Rapid-sequence endotracheal intubation in a patient who is not in arrest is another indication for sedation, often used in conjunction with paralytics. If one decides to use neuromuscular blockers/paralytics, adequate sedation is an absolute requirement. An agitated or confused patient who does not respond to reassurance is another candidate for sedation, particularly if the patient has cardiopulmonary compromise that is affected by physiologic stress.

Considerations before and during sedation

Considerations before and during sedation include periprocedural patient assessment, periprocedural fasting, and monitoring.

Periprocedural patient assessment

A patient's preprocedural health status is an important factor to consider before giving any sedative or analgesic. Not only would it help the physician determine whether to use sedation for a given procedure but also to determine which pharmacologic agent to use.

At the current time, very little outcome-based studies that dictate what clinical parameters to focus on are available. ED physicians depend on a comprehensive medical and surgical history, vital signs, mental status, and airway and cardiopulmonary assessment. At the current time, no preprocedural diagnostic tests are supported by literature.

The American Society of Anesthesiologists (ASA) developed a physical status classification system to risk stratify patients receiving sedation for surgical procedures:

• Class 1 - A normal healthy patient
• Class 2 - A patient with mild disease
• Class 3 - A patient with severe disease
• Class 4 - A patient with severe disease that is a constant threat to life
• Class 5 - A moribund patient who is not expected to survive without the operation

ASA class 3 or more is proven to be an independent risk factor for adverse outcome in patients undergoing general anesthesia. Procedural sedation in the ED has been studied most extensively in the ASA class 1 and 2 patients. These patients are at low risk for periprocedural and postprocedural complications. Many physicians would opt not to give sedation to a patient with ASA class 3 and greater, given a risk of morbidity or mortality. However, there are data to suggest that propofol and etomidate may not result in adverse outcomes in patients ASA class 3 or greater, when compared to those ASA class 1 or 2. Hopefully, further study will be done on this subject to further streamline periprocedural assessment and the applicability of the ASA physical status classification system to the ED.

Periprocedural fasting

Periprocedural fasting has historically been a concern for physicians because of the suspected risk of aspiration. Most of the data are from patients receiving general anesthesia; procedures where airway reflexes are lost and thus aspiration risk is increased. It is known that aspiration most commonly occurs during intubation and extubation. Thus, while depth of sedation should be a concern, the idea of preprocedural fasting for procedural sedation is being challenged. The current recommendation from the anesthesia community, given the most up-to-date literature, is 2 hours for clear liquids and 6 hours for solids. However, in an ED, where the flux of patients is constant and very little control of preprocedural fasting times is possible, these recommendations may not be realistic.

To date, there have been no reports of aspiration involving procedural sedation in the ED. This can be explained by the following: (1) In order to aspirate, one must vomit and lose protective airway reflexes, and with the exception of sedation used in rapid-sequence intubation, this combination is unlikely to happen during procedural sedation. (2) With the exception of nitrous oxide, procedural sedation is not accomplished in the ED using inhalational agents, known emetogens.

Given the lack of solid evidence to support periprocedural fasting times, the academic emergency medicine community does not risk-stratify based on a patient's last meal; instead, they advise physicians to rely on clinical judgment. The procedural sedation guidelines from the American College of Emergency Physicians state that "recent food intake is not a contraindication for administering procedural sedation and analgesia, but should be considered in choosing the timing and target level of sedation."

Monitoring

The physician must use visual observation to assess the patient's level of consciousness (ie, level of sedation). The tools used should include vital signs, oxygen saturation through pulse oximetry, and cardiac rhythm monitoring. However, these are not enough.

An objective observational assessment of sedation depth may also be useful in providing continuity of care and to provide an end point for nursing staff to administer subsequent doses of sedatives. The common measures used are the Observer's Assessment of Alertness/Sedation Scale (OAA/S) and the (modified) Ramsey scale. To date, such tools are used mainly in research and their utility in detecting and preventing adverse respirator outcomes need to be proven.

Exhaled carbon dioxide levels may prove very useful in assessing respiratory suppression. While pulse oximetry is useful in detecting hypoxemia, it is not useful at detecting hypercapnia that often precedes hypoxemia in a patient with respiratory suppression. Hypoxia is a late marker of inadequate ventilation. An increase in exhaled CO₂ might be the only clue one has of respiratory compromise.

This has been examined most recently in a prospective study evaluating whether end-tidal carbon dioxide (ETCO₂) can (1) detect subclinical respiratory suppression and (2) detect the level of sedation as compared to clinical criteria. While the latter was not proven, in a post-hoc analysis, all patients with episodes of respiratory suppression had corresponding ETCO₂ >50, increase >10, or absent waveform, the latter indicating a transiently obstructed airway. ETCO₂ is already a standard assessment tool in the ICU and the OR, but future study will be needed to validate its use in the ED.

The bispectral index (BIS) may also be very useful. BIS was once only used by anesthesiologists. Encephalographic wave patterns are used to determine sedation depth, measured on a 100-point scale, 1 being no brain activity and 100 being full alertness. A BIS score below 60 corresponds with a low probability of response to verbal stimuli.

Studies have been performed to validate BIS as a reliable marker for respiratory suppression. One such observational study showed that BIS scores between 70 and 85 provided adequate amnesia and analgesia while minimizing risk of respiratory depression. A follow-up sought to show that knowledge of the BIS value changed clinician behavior. In this prospective randomized study, the incidence of propofol-induced respiratory suppression was decreased when the BIS was known to the physician. Although the latest recommendations from the American College of Emergency Physicians state that "there is insufficient evidence to advocate [the routine use of BIS] in procedural sedation and analgesia", there will likely be future studies assessing its utility.

Sedation route and frequency

Every patient responds differently to dose and type of sedative, and durations of action vary greatly among patients. One must constantly reassess the patient and repeat administration of drug as needed. To date, however, no guidelines are put forth in the medical literature.

In the ED, the ideal route of administration is intravenous. Oral and intramuscular absorption may be unreliable and can often be delayed. With intravenous administration, the effect can be assessed fully, since time to peak effect can be predicted with reasonable accuracy. This can allow repeated dosing with much less chance of unexpected deterioration due to drug accumulation.

PEDIATRIC CONSIDERATIONS

Section 5 of 9  

• Authors and Editors
• Introduction
• Sedatives and Analgesics
• Approach to Sedation
• Pediatric Considerations
• Common Sedation Regimens
• Antagonists
• Summary
• References

Essentially all the sedatives and analgesics listed above can be used in children. However, it is important for the physician to recognize the differences between children and adults and how that relates to the type of sedation chosen. Differences exist in cognitive abilities and developmental status, respiratory mechanics, airway anatomy, drug metabolism, and toxic dosages. For instance, small children have a higher oxygen consumption and lower alveolar volume relative to their weight, making them more susceptible to desaturation and apnea. Moreover, their tongues are larger and they are at increased risk for airway obstruction during moderate or deep sedation. Body composition changes as the child grows, thus altering the distribution of a given medication. Hepatic enzyme systems, plasma concentration of proteins, and renal dynamics all change as the child grows, and thus a guide should be handy to the physician to accommodate those differences.

Initial dosing and incremental dosing are generally based on weight. Two important considerations are (1) prolonged administration of propofol, which is associated with lactic acidosis (see nonbarbiturate sedatives, propofol in Sedatives and Analgesics); and (2) opiate use in neonates. Opiate clearance is relatively slow in neonates; continuous pulse oximeter monitoring and easy access to airway equipment is strongly recommended, as apnea is a risk. End tidal CO₂ monitoring may be useful as well.

COMMON SEDATION REGIMENS

Section 6 of 9  

• Authors and Editors
• Introduction
• Sedatives and Analgesics
• Approach to Sedation
• Pediatric Considerations
• Common Sedation Regimens
• Antagonists
• Summary
• References

Benzodiazepines and barbiturates (in combination with an analgesic) are proven to be effective sedative agents. The following will focus on the effectiveness of some of the newer agents when compared with other sedatives and analgesics.

The use of propofol in procedural sedation has been gaining increasing popularity since the 1990s. Many studies have proven its utility as an effective agent. Noteworthy studies include two randomized prospective trials. Havel et al proved that the sedation scores and rates of oxygen desaturation between propofol and midazolam were similar, with equal complication rates. In fact, propofol offered a quicker recovery time than midazolam, which means a shorter ED postprocedural stay.

Another study performed by Miner et al randomized patients into a methohexital/morphine or a propofol/morphine group for ED fracture reduction. The two groups were equally efficacious at providing adequate sedation (as measured by the BIS) and had statistically similar rates of respiratory depression. Similar study results were seen in another randomized trial comparing propofol with etomidate and midazolam during cardioversion. Taylor et al had equally good results when comparing propofol to midazolam/fentanyl in patients requiring shoulder reduction, with shorter recovery times in the former group.

Some potential limitations to propofol usage do exist. One recent observational study assessing propofol for deep sedation showed clinically significant hypotension, hypoxemia, and apnea. Taylor et al also expressed concern over respiratory depression. Physicians must exercise caution when administering propofol to patients with cardiovascular or pulmonary disease or when procedures require deep sedation. Under those circumstances, etomidate may be a better alternative.

Etomidate is a safe and efficacious in the ED for procedural sedation. Like propofol, it has a quick onset and short action duration. Burton et al in a prospective, double-blinded trial compared midazolam with etomidate for shoulder reduction and found an equal success rate between the two groups, with no cardiopulmonary complications. These results were seen again in a data analysis of 3 observational studies and 5 prospective randomized trials; onset of sedation and recovery times were rapid, comparable to propofol and thiopental and much faster than midazolam. The most common side effects seen were myoclonus (20-45%), nausea, and vomiting. Hemodynamic and pulmonary complications were minimal, especially when compared with propofol. A study by Hunt produced similar results.

Ketamine, a nonopioid analgesic, has been proven to be the drug of choice for pediatric sedation, superior to both opioids/benzodiazepines and to propofol. One very recent systemic review included two randomized controlled trials that tested efficacy and safety of ketamine. Compared with fentanyl/midazolam and propofol/midazolam, ketamine/midazolam was shown to have less pain and anxiety and equal depth of sedation. The incidence of respiratory suppression/desaturation and apnea were less in the ketamine/fentanyl group. The trade-off was a longer recovery time seen with ketamine.

ANTAGONISTS

Section 7 of 9  

• Authors and Editors
• Introduction
• Sedatives and Analgesics
• Approach to Sedation
• Pediatric Considerations
• Common Sedation Regimens
• Antagonists
• Summary
• References

Flumazenil

Flumazenil is a competitive antagonist of the benzodiazepine class of drugs. The onset of action is within 1-2 minutes after intravenous administration, with peak effects within 10 minutes. The duration of action is dose related, but it is typically shorter than that of longer-acting benzodiazepines. Repeat dosing may be required. The total recommended dose in adults is 1 mg, which will sustain reversal for up to 48 minutes. Flumazenil is generally given in increments of 0.2 mg, titrated to effect. One must exercise caution in patients receiving long-term benzodiazepine therapy because seizures can occur.

Naloxone

Naloxone is a competitive opiate antagonist. The onset of action following intravenous administration is rapid, with effects appearing within 2-3 minutes. The duration of action is dose related. The initial dose in adults is 0.4 mg IV. It can be repeated to a total dosage of 2 mg. This antagonist may have shorter duration of action compared with that of the longer-acting opioids. In that case, the patient may need multiple doses. If the patient is exhibiting signs of respiratory depression before the end of the procedure, one can give 0.1-0.4 mg for partial reversal. Virtually no side effects occur when given naloxone for procedural oversedation.

SUMMARY

Section 8 of 9  

• Authors and Editors
• Introduction
• Sedatives and Analgesics
• Approach to Sedation
• Pediatric Considerations
• Common Sedation Regimens
• Antagonists
• Summary
• References

In summary, the administration of analgesics and sedatives is an important part of the physician practice in the ED. Familiarity with available agents allows their appropriate selection and permits the effective and safe use of these drugs. Further study of each of the medications used and the more commonly used combinations will aid in that endeavor.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Sedatives and Analgesics
• Approach to Sedation
• Pediatric Considerations
• Common Sedation Regimens
• Antagonists
• Summary
• References

• Bassett KE, Anderson JL, Pribble CG, Guenther E. Propofol for procedural sedation in children in the emergency department. Ann Emerg Med. Dec 2003;42(6):773-82. [Medline].
• Bauman BH, McManus JG. Pediatric pain management in the emergency department. Emerg Med Clin North Am. May 2005;23(2):393-414, ix. [Medline].
• Burton JH, Bock AJ, Strout TD, Marcolini EG. Etomidate and midazolam for reduction of anterior shoulder dislocation: a randomized, controlled trial. Ann Emerg Med. Nov 2002;40(5):496-504. [Medline].
• Charney DA, Mihic SJ, Harris RA. In: Hardman JG, Limbird LE, eds. Goodman and Gilman's The Pharmacologic Basis of Therapeutics. 10th ed. New York: McGraw-Hill. 2001:399-427.
• Chudnofsky CR, Lozon MM. Sedation and analgesia for procedures. In: Marx JA, Hockberger RS, Walls RM, eds. Rosen's Emergency Medicine: Concepts and Clinical Practice. 5th ed. St. Louis, MI: Mosby, Inc;2002:2578-90.
• Coll-Vinent B, Sala X, Fernandez C, et al. Sedation for cardioversion in the emergency department: analysis of effectiveness in four protocols. Ann Emerg Med. Dec 2003;42(6):767-72. [Medline].
• Dickinson R, Singer AJ, Carrion W. Etomidate for pediatric sedation prior to fracture reduction. Acad Emerg Med. Jan 2001;8(1):74-7. [Medline].
• Falk J, Zed PJ. Etomidate for procedural sedation in the emergency department. Ann Pharmacother. Jul-Aug 2004;38(7-8):1272-7. [Medline].
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Article Last Updated: Jun 4, 2006