Drugs for Conscious Sedation and Neuromuscular Paralysis: Guidelines and Protoco
January 18, 1998 27 minutes read
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Drugs for Conscious Sedation and Neuromuscular Paralysis: Guidelines and Protocols for Use in the Emergency Department
Author: Raghavan Chari, MD, FACEP, Assistant Director, Department of Emergency Medicine, Washington County Hospital, Hagerstown, MD.
Peer Reviewers: Jonathan A. Edlow, MD, Clinical Director, Emergency Department, Beth Israel Deaconess Medical Center, Boston, MA; Instructor in Medicine, Harvard Medical School, Cambridge, MA.
Sandra M. Schneider, MD, FACEP, Professor and Chair, Department of Emergency Medicine, University of Rochester, Rochester, NY.
Generally speaking, the goal of conscious sedation is to make patients unaware of their surroundings (narcosis) and to relieve pain (analgesia) while still preserving their airway and gag reflexes and maintaining other vital signs. If there is any question of airway compromise, intubation may be required in order to manage the airway and support vital signs.1 At this stage, chemical paralysis (muscle relaxation) can facilitate intubation while allowing evaluation of the patient without risk of reversible depression of organ function and reflexes.
It is important to stress that neuromuscular paralyzing agents are generally used only in patients who are in a low level of consciousness. (See Table 1.) This clinical state may result from either deep chemical sedation, or a serious medical or traumatic insult that places the patient in an impaired state of consciousness. If a patient’s level of consciousness is likely to improve after paralysis and intubation, concomitant use of sedation is imperative prior to paralyzing the patient.
The purpose of this review is to outline indications, actions, side effects, and contraindications of currently available sedating agents. Methods for reversing action of these drugs are also presented. Advantages and disadvantages of these agents in specific clinical situations are also highlighted. Finally, quality improvement and monitoring protocols should always be part of management protocols involving conscious sedation and/or paralysis of patients.
The Editor
Conscious Sedation
The goal of conscious sedation is to provide analgesia and a state of narcosis while maintaining the gag reflex and a patent airway.3,5 In this regard, it is important to distinguish between patients with conscious sedation vs. deep sedation. The latter group requires more vigilant monitoring and airway management, including possible intubation.5 The former group usually requires pulse oximetry, cardiac monitoring, blood pressure monitoring, and close observation since these patients are more easily arousable throughout the whole procedure.5 It is essential that the ED physician be prepared to manage the airway in the event there is an unforeseen response to induction of sedation.
Emergency intervention generally requires adequate suction and availability of intubation equipment (ambu bag, laryngoscopes, ET tubes, stylet, oral and nasal airway adjuncts). Monitoring devices, including a cardiac monitor, pulse oximeter, blood pressure monitor, and, if necessary, a capnometer should be placed on the patient before sedation is begun.
Sedation and analgesia are also being used with greater frequency in children now than they have been in the past.3 Broad policy statements by the American Academy of Pediatrics (AAP) and the American College of Emergency Physicians (ACEP) offer guidelines for drug administration and monitoring in this patient population.3 Of the multiple routes that are available for administration of these drugsinhalation, IV, IM, rectal, oral, and nasalthe last three routes may be especially helpful in children.
It cannot be stressed enough that conscious sedation is optimally accomplished using at least two clinicians, one of whom must be a physician. The other must be a trained clinical provider who is dedicated to monitoring the patient while the physician performs the procedure for which sedation was required. Finally, it is critical to appreciate that when inducing conscious sedation, host response may vary to the dose of medication administered. As a rule, dosages are just recommended guidelines that reflect the patient’s expected response to the drug in question. Patients will vary in degree of response, which underscores the importance of a dedicated observer and a qualified physician to respond to any untoward or exaggerated host response.
Classification of Agents. Many types of medications are available for achieving analgesia, amnesia, anxiety alleviation, and sedation. Inadequate sedation analgesia, which may be due either to physician misperception or severity of the pain produced by the procedure, can cause great discomfort to the patient.4 It is helpful to define some of these terms: analgesia is an altered state of mind in which pain perception is relieved but without necessarily achieving sedation.6 Anxiolytic drugs reduce apprehension without a reduction in awareness;6 hypnotics promote sleep.2 Sedatives (in low doses and dependent on host response) decrease the awareness of pain and a patient’s surroundings. They decrease activity and calm patients while protective airway reflexes are maintained.2,6 Conscious sedation, dissociative sedation, deep sedation, and unconscious sedation define progressive degrees of sedation; the last two states require airway management because of the potential loss of protective airway reflexes.2,6
Some anxiolytic drugs may require the addition of analgesics to alleviate pain, although they can, in appropriate doses, cause sedation.3,6 Patients in whom conscious sedation is accomplished electively in the ED must be chosen carefully.5 The American Society of Anesthesiology’s physical status classification may be a useful tool for selecting patients suited for elective conscious sedation.5 The classification includes the following categories: healthy patients, patients with mild systemic disease, patients with severe systemic disease, patients with severe systemic disease with constant life threat, and surgical candidates whose survival depends upon an operation and who are moribund.5
As a rule, only patients from the first two categories should undergo conscious sedation electively in the ED. Patients in the other categories should either be taken to the operating room if they need elective procedures or have their airway managed either with or without deep sedation in the ED before being sent to the operating room for nonelective procedures.
Agents for Conscious Sedation
Nitrous Oxide. Nitrous oxide offers safe sedation.2,4,7,8 It has some amnestic, hypnotic, and analgesic properties, and can be self-delivered by the patient.4,6,7 It is used in dentistry and many other physician settings, such as orthopedics. During transport to hospitals, paramedics trained in the use of this gas can administer it for painful orthopedic injuries. Nitrous oxide is colorless and diffuses across membranes extremely rapidly.2,4 It is best given at a fixed ratio of 1:1 with 02 (50% concentration), although lower percentages are used in some prehospital protocols and dental offices.4,7 At higher altitudes (greater than 5280 ft.), its effectiveness decreases unless 70% nitrous oxide concentrations are used, which also increases its adverse effects. Usually, patients using the self-administering, demand-valve positive pressure method obtain analgesia in less than 20 seconds and are well-relaxed in 30-60 seconds.2,4,8 Because nitrous oxide is much more soluble than nitrogen, it will exchange for this gas in body tissues. It can diffuse into the lungs and may even displace oxygen, causing alveolar hypoxia.2,4 This is termed "diffusion hypoxia," which is rarely observed in clinical situations.4,8 In one study, using a 40% concentration of nitrous oxide in children with a nasal mask and monitored with pulse oximetry,8 it was concluded that 02 saturation never dropped significantly while using this mixture and returned to 100% post-treatment. No clinically detectable diffusion hypoxia occurred, and although some subjects were given supplemental oxygen and others resumed breathing of room air, no side effects were reported.8
Some of the undesirable effects of nitrous oxide include vomiting and hypoxia, which is usually a problem only with concentrations in excess of 60%.2,4 It is prudent to avoid use of nitrous oxide in patients with significant coronary artery disease, as there is evidence of diminished cardiac output.7 Patients with significant pulmonary disease also should not be sedated with this agent.2 Any patient with a condition characterized by an enclosed gaseous compartment, such as gastrointestinal obstruction or upper respiratory infection with blocked nasal passages or Eustachian tubes, is not suitable for conscious sedation with nitrous oxide. Pregnant women in labor are occasionally candidates for sedation with this inhalation gas.2 Scavenging devices are necessary to avoid exposure of gas to the surrounding health workers, inasmuch as deleterious effects of long-term exposure to nitrous oxide have been reported.7 (See Table 2.)
Haloperidol. This butyrophenone is a neuroleptic agent with sedative properties at higher doses; it is primarily used in critically ill patients to treat delirium and agitation.9 It is an excellent drug since it has little effect on respiratory depression, nor does it potentiate respiratory depression caused by opioids.9 In rare instances it causes hypotension as a side effect.10 Haloperidol can be given intramuscularly, but the IV route is preferred in critical care settings.9,10 (See Table 2.) Continuous infusion of haloperidol is an excellent method for controlling agitation in patients on ventilators and can reduce the need for either benzodiazepines or opioids for sedation.11 Dystonia, extrapyramidal reactions, oculogyric crisis, and neuroleptic malignant syndrome are the principal adverse effects.11
Droperidol. This sedative antiemetic is chemically similar to haloperidol. It does not exhibit significant analgesic effects and, therefore, is used primarily in combination with a narcotic for its antiemetic and anxiolytic properties.58 Doses of 1.25-10.0 mg IV can achieve the desired effect; antiemetic effects are seen at lower doses and sedation/anxiolysis is observed at higher doses. (See Table 2.) When clinically indicated, droperidol can be used in combination with small doses of midazolam or lorazepam.
Chloral Hydrate. Chloral hydrate is used in children only in selected situations in order to achieve sedation for procedures such as a CT scan.12 It is a hypnotic sedative with a delayed onset of action varying from 30 minutes to an hour following administration, and, therefore, it may be better suited for procedures requiring extended duration that are elective in nature.5 The metabolite is the active ingredient, and safe use of chloral hydrate requires intact liver function.5,13 Arrhythmias, cardiovascular effects, and paradoxical effects are common.13
Ketamine. Ketamine, a sedative analgesic, has dissociative properties.4,15 It exhibits minimal toxicity and has only a slight effect on blood pressure, even in patients with depleted volume states.9 Muscle tone is preserved, even accentuated, in this trancelike state. The patient’s pupils become dilated, there is some degree of bronchodilation, and the airway is preserved.5,9 Increased salivation and bronchospasm, which are sometimes associated with this agent, can be minimized with the use of atropine as a pretreatment agent.9
Ketamine is best used in children between the ages of 1-11 years.9,15,14 Emergence reactions are more common in adults than children and present as hallucinations, extremely bizarre dystonic actions, and bad dreams. A small dose of a benzodiazepine can attenuate these reactions in both adults and children.4,9 (See Table 2.) One significant advantage of ketamine is its multiple routes of administration, including IV and IM routes. The latter is effective within five minutes of administration. In addition, oral ketamine, in doses up to 10 mg/kg is also effective for minor procedures.15 Nasal ketamine, 6 mg/kg for children 1-5 years of age also seems to provide adequate sedation.14 Ketamine is effective for sedation in asthmatic/COPD patients needing intubation, with or without paralyzing agents.9 The beneficial effects of ketamine on airway resistance permit its use in status asthmaticus even in the presence of acute myocardial infarction.9,16 It is usually administered in a IV drip form, 20 mg/h, after an initial bolus of 10 mg IV in adults.
Etomidate. This drug is a nonbarbiturate carboxylated imidazole-containing compound with a rapid onset of action. It lacks cardiovascular side effects, making it an excellent sedative drug for intubation.43 It exerts depressant effects primarily on the ascending reticular activating system. Although it does not increase intracranial pressure, it may activate seizure foci.43
Propofol. This sedative hypnotic is not related to other agents available for sedation. Analgesia should be administered in combination if propofol is used for a painful procedure. This agent also has amnesic properties and anticonvulsant activity,17 and can cause hypnosis when administered intravenously. Patients recover quickly and completely from its effects. It can produce cardiovascular depression, lower intracranial pressure, and it is a highly lipophilic compound, most of which is bound to plasma proteins.17 It is available as a thick, white liquid containing glycerol, soy oil, and egg lechitin in a concentration of 10 mg/mL.18 Because of its distribution and high lipid solubility, lean body weight should be used when calculating doses.17,18 Rapid clearance from plasma permits rapid recovery. It should be noted that propofol has limited analgesic properties at sedative doses (1.0-1.3 mg/kg for sedation and 2.0-2.5 mg/kg for deep sedation). Propofol also has some antiemetic properties.5 In children at least 3 years of age, it is used for induction of anesthesia.5,8 (See Table 2.)
Barbiturates. Barbiturates are excellent short-acting hypnotics. It is important to remember that they do not have analgesic properties and, therefore, should be used in combination with pain-reducing drugs or local anesthetics when necessary.2,4 Barbiturates increase neuronal response to GABA and decrease neuronal excitability.4 Ultra-short and short-acting barbiturates are preferred for sedation in the ED. With thiopental and methohexital, emergence is rapid because of high lipid solubility. The initial dose is 3-5 mg/kg of lean body mass. Methohexital has a faster onset and shorter duration of action than thiopental, which has an onset of action of about 30 seconds.4,5 Barbiturates can decrease cardiac output, and, on occasion, cause hypotension and respiratory depression. In addition to their primary role as inducing agents for surgery, methohexital and pentobarbital can also be used for short duration procedures.2,4 In addition to the IV route, both of these short-acting barbiturates are available in rectal suppository form, which makes them useful in children.2,6 However, via the rectal route, the onset of full sedation (30-60 minutes) is unpredictable and recovery time (sometimes more than 2 hours) is also variable. As a result, this method is more useful in radiology for imaging procedures than in the ED.4,19 Intramuscular routes are also unpredictable and produce only slightly more rapid onset of action than the rectal route.4 Rectal methohexital for imaging in pediatric patients 1 month to 14 years of age has been used with excellent results.19 Intravenous use of these barbiturates affords more controlled rapid onset and recovery end points and may be more useful in the ED.4 (See Table 3.)
Benzodiazepines. These are the drugs of choice for treating anxiety, sedating patients, and producing a significant degree of amnesia.2,4,5 These agents also have anticonvulsant properties, cause no change in intracranial pressure; they, for the most part, are metabolized by the liver and excreted by the kidneys.2,20 Although respiratory depression is the primary major side effect of these sedatives, when administered slowly and incrementally, significant adverse effects can be prevented. Midazolam, a short-acting benzodiazepine, has become extremely popular for achieving conscious sedation in a wide range of clinical settings.2 Lorazepam and diazepam are longer-acting benzodiazepines, with the former having a slower onset of action.20 For immediate effects, IV bolus administration of these drugs is the preferred route in the ED. Compared to diazepam, midazolam is less painful at site of injection and produces more rapid onset of sedation.22 Despite potential advantages of midazolam, many ED physicians continue to use diazepam or lorazepam for conscious sedation, either because of established protocols or because they have more experience with those agents.
In children, intranasal, rectal, and oral routes for midazolam have been used.6,23,24,26 Intranasal routes achieve faster sedation in children.23 Midazolam may be used via the rectal or intranasal routes to sedate preschool children in the ED for prolonged laceration repairs.26 In addition to respiratory depression, hypoxia, and emergence delirium have been reported with midazolam in children.25 For purposes of imaging, intranasal midazolam has been shown especially beneficial.24 It should be stressed that midazolam does not have analgesic properties and should be used in conjunction with an analgesic for painful procedures. (See Table 3.)
Opioids. Opioids have analgesic as well as sedative properties. Meperidine, morphine fentanyl, alfentanyl, and sufentanyl are examples of this therapeutic class. IV, IM, and oral routes can be used, but the IV route is the most reliable for both early onset and monitoring the degree of sedation. (See Table 3.) Direct effects on the gastrointestinal tract include decreased motility, constipation, and ileus.27 In the pediatric population, intranasal or oral transmucosal routes for sufentanyl and fentanyl citrate are available.28-30 Oral transmucosal fentanyl ( the "lollipop") has been used with success in children between 2 and 10 years of age in the ED to achieve both analgesia and sedation for laceration repairs. If 10-15 mcg/kg doses are used, safety can be maintained.29,30 In one study, intranasal sufentanyl and midazolam used in children 1-4 years of age was found to be as effective as the old standbya combination of IM meperidine, chlorpromazine, promethazine.28
Combining Sedative Agents. There may be advantages to combining different drugs to achieve the desired level of sedation.21 Some medications achieve sedation without producing analgesia, and therefore require a combination of drugs to achieve both effects. Moreover, a dose-related toxicity caused by a high dose of a single drug can sometimes be prevented with lower doses of two drugs.2,20 The major disadvantage of combining sedatives is additive toxicity and excessive sedation. Cost is another important factor in deciding whether to use sedative singly or in combination.21 Although there are some studies evaluating combined sedative therapy in the ED and ICU, there is still a large gap in information regarding sedative use, especially in the ED.
Reversals. Reversing the effects of sedatives is rarely helpful. Most agents used for reversal are competitive antagonists and can lull one into a false sense of security. Use of reversal agents should be restricted to obtaining information regarding the causative agent of sedation or for reversing life-threatening effects of narcotics or benzodiazepines. Patients should not be reversed for the sake of a more rapid discharge from the ED. Adequate time for natural reversal is mandatory for safe discharge.
Opioid Antagonists. Naloxone is a pure narcotic antagonist,32 a synthetic cogener of oxymorphone. It competitively blocks the sites used by narcotic agents and, therefore, may reverse narcotic effects. Doses of 0.4-10.0 mg have been used in adults without adverse effects.32
Benzodiazepine Antagonists. Flumazenil is a pure benzodiazepine antagonist.2 Seizure activity can be induced by this drug, especially when reversing benzodiazepine administered for seizures. ICP could be raised in patients who have head injury and have been given this reversal agent. Doses ranging from 0.2 mg (2 mL) to 1.0 mg can be administered. Most patients will respond to this dose, although some may require up to 3 mg for reversal.32
Quality Improvement and Monitoring
Monitoring is a requirement for both conscious and deep sedation. Opportunities and equipment for monitoring patients with conscious sedation will vary among EDs. What is clear, however, is the trend toward more vigilant, device-mediated monitoring of patients to whom sedating agents or narcotic analgesics have been administered. The use of pulse oximetry to detect hypoxemia, ECG for cardiac monitoring, and blood pressure monitoring are recommended.33,36 Capnography by nasal cannula for measuring CO2 concentration with the use of an end tidal CO2 monitor appears to be a useful tool in some cases.33 In general anesthesia settings, especially for intubated patients, this is already becoming a standard of care.33 End tidal CO2 monitoring via calorimetric or solid state spectophotometric techniques, has become an adjunct for ED management of conscious sedation, intubated patients, and cardiopulmonary resuscitation.34
Administration of sedatives requires assessment and drug monitoring with impeccable protocols and quality improvement tools.36-41 In hospital units where procedures are conducted (i.e., bronchoscopy, cardiac catheterization lab, endoscopy, and the ED) using conscious sedation and deep sedation, JCAHO requires "leaders to develop and implement mechanisms designed to assure uniform performance of patient care processes throughout the organization."41 (See Table 6.)
In this regard, many scales are available to measure the degree of sedation, including the Ramsey Sedation scale, which ranks from 1-6 (anxious and agitated to no response to loud noise). Sedation guidelines for monitoring infusion of drugs based on this sedation scale are also available.37 These are used primarily in the ICU and are slowly finding their way to the ED with appropriate modifications. Policy development and review in pediatric and adult population should address issues of criteria for the use of sedative agents, staff awareness of the actions and contradictions of each agent, familiarity with all aspects of airway management and monitoring parameters, and institution of continuous quality improvement tools for each patient that undergoes sedation.39,40
These rules are not only applicable to ED physicians but to medical support personnel. Should help be required at any time during the management of the patient, it is prudent to consult an anesthesiologist to help avoid serious injury.40 In this context, JCAHO guidelines suggest approval of credentialing, education, and skill protocols by the department of anesthesia.40 A joint departmental cooperative effort to help formulate protocols, educate, and credential emergency medicine physicians in the use of conscious sedation and deep sedation in the ED seems reasonable. An ongoing monitoring and continuing medical education program for these important skills could be conducted by taking a written examination periodically or by placing requirements for a certain number of sedation to be performed over a given period. Many residency programs have pain control and sedation protocols established for their ED.
Neuromuscular Paralyzing Agents
Neuromuscular paralyzing agents are used as an adjunct to intubation for patients that are either already sedated or have serious head injury, shock, or respiratory distress with mental status changes. Almost without exception, sedation is recommended prior to use of paralyzing agents, which relax striated muscles in order to facilitate intubation and maintain better oxygenation and ventilation, lower ICP, and facilitate safe management of the patient.10 (See Table 6.)
Depolarizing and Non-depolarizing Agents. Although many agents are available, their mode of action is variable. In general, depolarizing agents prolong the refractory period by maintaining a depolarized state at the postjunctional end plate, whereas non-depolarizing agents competitively block the postjunctional receptors and prevent acetylcholine (the natural neurotransmitter of the neuromuscular junction) from depolarizing the end plate.13 Short-, intermediate-, and long-acting agents, with rapid onset and delayed onset of action, are available.43
Depolarizing Agents. Succinylcholine is similar in chemical structure to two acetylcholine molecules and is the only depolarizing agent still in common use. Individuals with inherited pseudocholinesterase metabolize succinylcholine on the motor end plate. Its rapid onset of action and short duration are advantages that explain its popularity.42 Contraindications to use of succinylcholine include elevation of intracranial pressures, hyperkalemia associated with burn or severe crush injuries, bradycardia, and malignant hyperthermia among others.43 Some of these side effects can be avoided by administration of a defasiculating dose of a non-depolarizing agent and administration of atropine prior to the use of succinylcholine; this may be especially useful in infants and children.43,44 The dosage of atropine in children prior to use of succinylcholine is variable, ranging from 10-20 mcg/kg.44-47 Pseudocholinesterase structure is genetically determined, and about 1 in 3000 individuals is homozygous for the atypical variant that causes a severe prolongation in the metabolism of succinylcholine, and, in turn, significantly prolongs paralysis.2,40 In most patients over 2 years who have no major injuries, there is no significant hyperkalemia in response to succinylcholine-assisted intubation.48
Non-depolarizing Agents. Mivacurium and rocuronium are two non-depolarizing agents with a short onset and duration of action. Mivacurium is structurally related to the benzylisoquinolinium compounds and has a short duration of action (15-20 minutes).43,50 Its onset of action is similar to the intermediate-acting agents. By giving the drug slowly, histamine release is avoided, thereby minimizing hypotension and cutaneous flushing.49 Mivacurium undergoes metabolism by plasma cholinesterase and, therefore, patients who are homozygous for the atypical plasma cholinesterase gene will have prolonged paralysis.49,50 Infusion of this drug continuously will maintain paralysis and, upon discontinuation, recovery is relatively rapid (18-20 minutes).50 The duration of action of mivacurium is prolonged in patients with renal and hepatic failure.51
Rocuronium is a monoquaternary amino steroid with a rapid onset of action compared to intermediate-acting agents, although its duration of action is similar.52 With higher doses (0.6-1.2 mg/kg) or with priming (a technique of giving a smaller dose of the drug and then waiting for 2-3 minutes and administering an intubating dose with either mivacurium or rocuronium), the time of onset of action for intubation is diminished. This time approaches the onset of action of succinylcholine.49,53 The priming dose for mivacurium is 0.015 mg/kg and the intubating dose is 0.15 mg/kg, whereas for rocuronium 0.06 mg/kg is priming dose and 0.6 mg/kg is intubating dose.53 With continuous infusion of rocuronium, reversal with neostigmine can easily be achieved.52
Intermediate-acting Non-depolarizing Agents. Vecuronium and atracurium are the most commonly used agents in this category. Vecuronium is an amino steroid structurally related to pancuronium.49 The onset of action is usually about 160 seconds but can be shortened by either giving a larger dose (0.3 mg/kg in contrast to 0.1 mg/kg) or by priming with 0.01 mg/kg and then using the normal intubating dose.43,54,55 Another strategy is the "timing technique," which requires rapid injection of the paralyzing agent and upon observation of weakness, rapid injection of an intubating dose of sedative, hypnotic, or anxiolytic. This approach will shorten the onset of action and prevent prolongation of paralysis. The duration of action will be slightly prolonged with larger intubating doses. As this agent is metabolized in the liver and its metabolites also have paralyzing properties, albeit to a lesser extent if not excreted by the kidneys, these metabolites can accumulate and sustain prolonged paralysis.49 In contrast to atracurium, vecuronium has less cardiovascular effects in asthmatic patients.56 In myasthenia gravis patients, the effects of both intermediate agents are similar, although slightly shorter recovery times occur with vecuronium.57
Atracurium is a bisquaternary ammonium benzyliso-quinilone.49 Hypotension secondary to histamine release occurs with this agent and can be avoided with slow infusion.49 Ester hydrolysis/atracurium is metabolized to non-active metabolites in the bloodstream and, therefore, is independent of end organ function (such as liver or kidney) for excretion of the metabolites.49 As a result, this drug is useful in patients with liver and kidney disease who require paralysis. Laudanosine, a metabolite that may have CNS toxicity, however, accumulates with prolonged use in patients with renal failure.49
Long-acting, Non-depolarizing Agents. Pancuronium and newer long-acting agents such as pipercuronium and doxacurium are long-acting, non-depolarizing agents.49,58 Pancuronium is a synthetic bisquaternary amino steroid with vagolytic effects that can cause hypertension and tachycardia.49 It is also excreted in the kidneys and has active metabolites, so paralysis will last longer in the setting of renal failure.49 Pipercuronium is a steroidal compound like vecuronium and doxacuronium and is a bisbenzylisoquinolinium like atracurium.58 These drugs have no cardiovascular effects and no histamine release is appreciated.58 It must be noted that infusion of intermediate-acting paralyzing agents have been able to sustain paralysis for many hours.
Rapid Sequence Intubation Protocols. Rapid sequence intubation is a technique in which sedation and paralysis are achieved rapidly while avoiding vomiting and aspiration in the patient with a full stomach. Bag-valve ventilation is avoided unless oxygenation drops significantly, and then, only careful, low-volume ventilation is administered in order to avoid filling the stomach with air and increasing the chances of regurgitation. From the time the patient becomes sedated to the time he is intubated, cricoid pressure is maintained.65 The safety and effectiveness of these techniques have been substantiated.63 In the past, the agent of choice has been thiopental for sedation and succinylcholine for paralysis.65 However, newer agents provide alternatives to this time-honored sequence. For example, sedation can be achieved with opioids like fentanyl, alfentanyl, or sufentanyl with or without midazolam.65 Propofol and alfentanyl provide alternatives to thiopental and succinylcholine for rapid sequence intubation.64 A paralyzing agent can be added to the combination of propofol and fentanyl using the timing principle and, thereby, reduce the doses of sedating agents to achieve the same goal. High-dose vecuronium, the priming technique, or timing principles for atracurium or vecuronium are all effective and approach the rapid onset of action times of succinylcholine.60,61,64 Rocuronium, in large doses, is very effective for rapid sequence intubation. Intubation protocols for adults and pediatric patients using different combinations of sedatives and paralyzing agents should be available in the ED.62
The Role of Reversal Agents. Reversal of non-depolarizing agents is usually employed by anesthesiologists in the operating and recovery rooms in order to extubate the patient and to assure full neuromuscular activity. Succinylcholine is a depolarizing agent and cannot be reversed. Generally, in the ED, extubation is not, and should not, be conducted using reversal agents. However, knowledge of using reversal agents is crucial when using paralyzing agents. Reversal agents are generally used only after the patient exhibits spontaneous recovery activity.67,68 With the advent of short- and intermediate-acting agents used as continuous infusions, reversal agents may not be used as regularly.67 However, when necessary and indicated, neostigmine is used in doses of 70-80 mcg/kg for deep block reversals and 40-50 mcg/kg for modest block reversal.68 Side effects of reversal includes bradycardia, nausea and vomiting, bronchospasm, and increased secretions.68 Concomitant use of glycopyrrolate or atropine in doses of 10-20 mcg/kg will attenuate and abolish some of these effects.69
Summary
Conscious sedation is an important tool available to help alleviate pain and discomfort either from the injury or by the procedure or by both. It is fraught with serious problems if knowledge, training, strict adherence to protocols, monitoring parameters, and anticipation of any unforeseen problem (including emergency airway management) are not implemented. It is important for the entire medical staff in the ED (not just the physician) to be proficient in the use of these drugs. A strict review of all cases, using it as a learning tool, should be the rule and not the exception.
Because of the spectrum of agents available for sedation and paralysis, there are no uniformly accepted guidelines for their use, as many choices are left to the physician and local protocols. Although this is an acceptable approach, guidelines are necessary in the current environment of cost containment, quality monitoring, and improvement. Eventually such guidelines will be available for emergency physicians.
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Physician CME Questions
9. All of these agents are sedatives, but not all are analgesics. Which of these agents is a sedative and an analgesic?
A. Propofol
B. Meperidine
C. Thiopental
D. Midazolam
E. Methohexital
10. Nitrous oxide is a safe inhalation agent used for analgesia and sedation. It can be used in all of the following situations except:
A. dentistry.
B. labor.
C. burns.
D. multiple trauma including pneumothorax.
E. shoulder dislocation.
11. The best agent for use in rapid sequence intubation in patient with renal and liver disease is:
A. mivacurium.
B. vecuronium.
C. atracurium.
D. pancuronium.
E. pipecuronium.
12. Neostigmine can reverse the effect of all these agents except:
A. succinylcholine.
B. mivacurium.
C. atracurium.
D. vecuronium.
E. pancuronium.
13. Which of the following drug combinations should not be used to intubate an individual with known pseudocholinesterase deficiency using rapid sequence intubation?
A. Fentanyl, midazolam, succinylcholine
B. Sufentanyl, vecuronium
C. Pentobarbital, atracurium
D. Fentanyl, propofol, rocuronium
E. Morphine, midazolam, vecuronium
14. Which of the following agent is best used for sedation for intubation in status asthmaticus?
A. Meperidine
B. Haloperidol
C. Chloral hydrate
D. Nitrous oxide
E. Ketamine
15. Patients that are undergoing conscious sedation in the ED require all of the following except:
A. pulse oximetry.
B. one-to-one monitoring.
C. IV line.
D. Intubation and oxygen.
E. ECG and BP monitor.
16. Which of the following is not used for sedation in the ED for procedures?
A. phenobarbital
B. pentobarbital
C. methohexital
D. midazolam
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