The Six Skills of Highly Effective Pediatric Sedation
The Six Skills of Highly Effective Pediatric Sedation
Authors: Jeffrey Proudfoot, DO, FACOEP, Assistant Clinical Professor, Children Emergency Services, CS Mott Children’s Hospital, University of Michigan Medical Center, Ann Arbor, MI.
Emory Petrack, MD, MPH, FAAP, FACEP, Associate Professor of Pediatrics, Director, Pediatric Emergency Medicine, Rainbow Babies and Children’s Hospital, Cleveland, OH.
Peer Reviewer: Steven Green, MD, FACEP, Associate Professor of Emergency Medicine, Loma Linda University School of Medicine, Loma Linda, CA.
While pain and suffering are "frequent flyers" as well as long-time customers of EDs, sedation and aggresively pain control are relatively new visitors. Contributing to the relatively late arrival of more sophisticated pharmacologic interventions has been the significant controversy that has surrounded the use of sedation agents in the ED. A succession of therapeutic misadventures were documented following the early use of many of these agents. Appropriate concerns about the safety of the varied agents were engendered, and as presented by Green and Wittlake,1 different organizations have attempted to establish potentially useful guidelines directing the application of these clinically valuable drugs for sedation and analgesia. In this issue, the authors review six mandatory skills for effective pediatric sedation.
The Editor
Providing sedation and analgesia is an integral part of pediatric medical care in the ED. With pain as one of the most common presenting emergency department complaints, emergency physicians are in the forefront of the development and implementation of new and effective ways to provide comfort and cooperation for pediatric patients. Long neglected as unnecessary, the rational use of sedative and analgesic agents has been hampered by myths and concerns about dangerous side effects, a paucity of scientific documentation regarding effectiveness, and ignorance of options available to the emergency physician.
Over the last decade, there has been a renewed interest in the effective use of pharmacologic pain control and sedation in the emergency department. Recent work suggests that the use of analgesia for procedures in the emergency setting increased significantly from 1988 to 1994.1 Nevertheless, while the increase in analgesic use was seen in all age groups, pediatric patients continue to receive less analgesia for painful procedures than adults.1a
With the ready availability of newer, more potent agents for sedation, emergency physicians are becoming increasingly experienced at providing highly effective and safe analgesia and sedation for pediatric patients. This process has been spurred by documentation in the literature of the safety and efficacy of ED use of these agents by experienced emergency physicians. In fact, many subspecialties now rely on the expertise of the emergency physician to provide the requisite level of sedation to manage therapeutic procedures that in the past would have required an expensive operating room chargea benefit in the managed care environment. Lastly, there is satisfaction of parental expectations that their child will not have to suffer because of lack of experience on the part of the physician.
A review of two key pharmacokinetic and pathophysiologic principles can help explain how these medications exert their effect and interact with the pediatric metabolism. These mechanisms, which govern the clinical response to and recovery from sedative and analgesic medications, are important principles for effective pediatric sedation and analgesia.
CO2 Response Curve. Children normally exhibit a linear, concentration dependent increase in minute ventilation with increasing pCO2. At physiologic pCO2 levels (e.g., 40), minute ventilation is approximately 5 L/min. (See Figure 1, curve A.) Administration of an opiate shifts the curve to the right (i.e., the patient has the same responsive increase in minute ventilation, it simply occurs at a higher pCO2). (See Figure 1, curve B.) Addition of a benzodiazepine to the opiate greatly depresses the response to increasing pCO2, limiting both the rate of increase in minute ventilation and the threshold of pCO2 required to stimulate ventilation. This depression in slope is proportional to both the amount and rate of administration of the drug. Children compromised by poor cardiopulmonary reserve such as those with cystic fibrosis, severe asthma, cardiac defects, etc. mimic the curve shift with a combined opiate/sedative. (See Figure 1, curve C.)
Drug Redistribution. Most sedative and analgesic medications produce their clinical effect by direct passage into the CNS to occupy specific receptor sites in the brain. Termination of effect is brought about by redistribution of drug down the concentration gradient from lipid-rich brain to other body tissues (i.e., muscle, fat, etc.). The same amount of drug remains in the body until metabolized or excreted but is not physiologically active, having relocated to non-neural tissues.
The Six Skills
1. Keep Your End Point and Goal in Mind
Sedation can relieve anxiety, and analgesics can eliminate or control pain during therapeutic or diagnostic maneuvers, thereby improving patient cooperation and satisfaction of parents. The challenge facing emergency physicians is to select an agent that will achieve the desired end point while minimizing the potential adverse effects that every sedative and analgesic medication possesses. Since the benefits are clear, the goal is knowing the medications in intimate detail, matching the patient and the patient’s problem with appropriate technique, controlling the environment, selecting monitoring parameters, and, most importantly, knowing your own limitations. Unfortunately, the ideal medication that is 100% effective, universally safe, with appropriate duration of action, no adverse side effects, and rapid onset and recovery does not yet exist. The medication’s selected for a specific patient should be integrated into the physician’s knowledge of the relative potency of the drug, its effects on vital organ systems, common side effects, duration of action, and factors that affect elimination. An assessment of patient risk is in essence analysis of vital organ reserve (i.e., cardiovascular, respiratory, and neurological systems). Fortunately, most children have large cardiorespiratory reserves with adequate ventilation and oxygenation to withstand the predictable effects of these medications. On the other hand, some patients are not candidates for ED sedation and are best treated in the operating suite with an empty stomach and a general anesthetic. In summary, the physician using these medications must be intimately familiar with their effects, the specifics and nuances of selection, and be knowledgeable with the techniques used. Remembering the classical admonition, "primum non nocere," first do no harm, physicians must be able to manage any untoward consequences of these drugs.
2. Know How To Get To Where You Are Going
After selecting the right patient and drug, a decision must be made on the most appropriate method of administration to get to the planned end point for the task at hand. This may take the form of light (conscious) sedation where the child’s anxiety is alleviated and awareness is blunted. Children under light sedation remain responsive to verbal and physical stimuli and maintain their airway, swallowing reflexes, and vital signs independently. The patient receiving transmucosal agents is unlikely to have any deterioration of airway or cardiovascular function, primarily because variable gastrointestinal absorption with delayed onset and hepatic first pass effect creates a ceiling on response and is not effectively titratable. Transmucosal administration is useful for local anesthetic infiltration, IV starts, lumbar punctures, sexual examinations, or painless procedures requiring limited patient cooperation. Many patients require movement along the sedation continuum from simple anxiety reduction to deeper levels of sedation that have the potential to compromise airway reflexes or cardiorespiratory function. This is particularly true for specific end points such as complete immobilization for computerized tomographic (CT) scanning, which can be difficult or impossible to achieve with light sedation. The newer ultrashort agents are especially advantageous at creating deep sedation with minimum time in a compromised state and allowing rapid recovery. Use of these agents allows titration to desired effect in an incremental fashion (i.e., administer drug and observe central nervous system effect and repeating to quiescence or immobilization). Deep sedation mandates continued physician supervision of the patient from beginning to end, and this supervision cannot be performed at a distance.
The venue in which sedation takes place is crucial to success and has been defined by most institutions via institutional sedation policies. This usually takes the form of limiting procedures and sedation to areas that are adequate to accommodate skilled personnel and all the appropriate monitoring and resuscitation equipmentcommonly a critical care area. It is the responsibility of the emergency physician to know his or her facility’s capabilities and the expertise level of the personnel assisting in the procedure. The controlled chaos present in most pediatric EDs demands a standardized approach to sedation procedures and is prerequisite for minimizing confusion attendant to sudden deterioration or unexpected problems with either patient or procedure. A room setup that has all necessary medications, reversal agents, airway equipment, and suction immediately available within arm’s reach facilitates rapid intervention when necessary.
Monitoring. The American Academy of Pediatrics (AAP) has recommended minimum standards for monitoring of pediatric patients during elective sedation and has defined conscious (light) sedation, deep sedation, and general anesthesia.2 The optimum monitoring situation is a dedicated, experienced, patient observer performing visual confirmation of respiratory effort and patient color, and surveillance of monitoring instruments in place. This is facilitated with appropriate patient exposure, lighting, and positioning of the head to maintain a patent airway and allow visualization of oral mucosa and chest wall excursions. A second provider, in addition to the physician involved, assumes this responsibility, and thus mandates a minimum of two trained personnel when using deep sedation.
Monitor all patients receiving sedation by parenteral routes with a minimum of continuous pulse oximetry. Pulse oximetry monitors detect hypoxia well in advance of its clinical appearance and sequelae.3 Using cardiac monitors or combined EKG/oximeter monitors helps sort out inaccurate oximeter readings due to signal loss from sensors or incomplete correlation with high pulse rates common to pediatric patients. End tidal carbon dioxide monitors using nasal cannula sensors are also available, but efficacy as a monitoring adjunct during sedation remains unproven.3 Children receiving simple or light sedation transmucosally require little in the way of monitoring (pulse oximetry alone should suffice) unless large doses, multiple agents or long-acting agents (e.g., chloral hydrate) are involved. However, infants and children undergoing deep sedation (particularly with multiple agents) require careful monitoring with pulse oximeter, cardiac monitor, and continuous close visual appraisal with interval (usually every 5-10 minutes) documentation of respiratory and pulse rates and blood pressure. The time, route, and dose of medications administered entered on the chart ensure a complete record. Sending a sedated patient to the radiology suite without appropriate monitoring and personnel is a prescription for disaster.
4. Select the Right Drug And Route
The most common clinical error is mismatching a patient with the wrong drug and/or route for the right reason. Administering enough of any sedative can alter the response to painful stimuli but should always be coupled with an analgesic if serious discomfort is anticipated. Likewise, analgesics that cause sedation as a side effect are not the best choice for pure sedation or amnesia. Light (transmucosal route) sedation is a uniquely pediatric phenomenon. It is useful for minor or briefly painful indications yet has an efficacy ceiling due to variability in transmucosal absorption, rapid clearance from first pass hepatic metabolism, and unpredictable duration and response from low drug effect.5 Repeat dosing can increase effectiveness at the cost of delaying the entire procedure. Light (conscious) sedation has the benefit of being minimally invasive, easy to administer, and extremely unlikely to compromise the patient’s cardiorespiratory status. Coupled with topical anesthesia, it is effective for minor lacerations, lumbar punctures, and sexual examinations. Intramuscular (IM) administration of sedative or analgesic agents is to be avoided (the exception being ketamine). Depending on the site of the injection, absorption is erratic and carries the risk of oversedation without benefit of vascular access should complications develop. There is little reason to recommend the antiquated "DPT" or "MPC;" a fixed combination of meperidine (Demerol), promethazine (Phenergan), and chlorpromazine (Thorazine) that produces an unpredictable degree of sedation and significant hypotension in many patients with delayed onset (mean, 27 minutes).5-11
The gold standard for effective and reliable pediatric sedation to a predictable end point is intravenous (IV) administration. Almost all EDs are accomplished at IV access in pediatric patients. Repeat dosing is easy, painless, and can deliver the medication in a controlled, incremental fashion to peak clinical effect. It is the only route suitable for deep sedation, as it provides access for administration of reversal agents and any necessary resuscitation drugs. Deep sedation is facilitated by the IV use of potent, highly lipophilic, and ultrashort-acting agents such as fentanyl or thiopental. Clinicians can administer a small dose, observe the CNS effect within seconds to minutes, and repeat the process until a desired clinical end point is reached. This "individualizes" the process by allowing a combination of medications to be used such as a sedative and an analgesic. It also avoids the "hit or miss" phenomenon where a fixed dose of medication is administered and the patient is observed for the window of effect, as is commonly done with chloral hydrate or "DPT." Additionally, it is anticipated that enough drug will have been given to produce the appropriate duration of sedation required to complete the task at hand. Often the patient requiring and receiving repeat doses is committed to a longer recovery.
As with all procedures, physicians administering sedation to enough patients will eventually experience a complication. It is paramount that emergency clinicians employing sedation be vigilant for potential complications, be able to recognize adverse effects immediately, and be prepared to intervene rapidly and definitively. The worst case scenario of cardiac or respiratory arrest should be uppermost in the mind of the emergency physician managing the sedation. Correct use of therapeutic sedating agents and close adherence to monitoring policies are essential. Physicians who are uncomfortable with active interventional airway management in children are better off seeking supplemental training and relegating sedation to experienced colleagues.
Avoid stacking. One of the most common pitfalls in pediatric sedation is drug "stacking." This process occurs after the physician administers a second or third drug dose before peak clinical effect of the initial administered drug dose. As the first dose is peaking, the subsequent doses that are already delivered literally "stack" up on the initial dose and summate, exaggerating clinical effect and pushing the patient much deeper than was anticipated. Stacking can be prevented by knowing specific pharmacokinetics properties of the medications used. It is much easier to reach a targeted end point with smaller, appropriately timed doses rather than one large dose that has the potential to overshoot the mark. Impatience and an "itchy trigger finger" can lead to an anesthetized and apneic patient.
Beware of the lost stimulus. One of the more common times to experience oversedation is at the completion of a painful procedure, particularly orthopedic reductions. With sudden removal of pain and antagonist stimulation, the patient tends to slide deeper into unopposed sedation and can require stimulation to breathe. Keeping close observation at this point can catch apneic episodes before they lead to desaturation. Providing selected, supplemental noxious stimulation is the easiest way to counteract this (e.g., applying pressure to the painful site).
Minimize crossover titration: Crossover titration occurs when alternating doses of two different classes of medications are used in a sequential fashion (e.g., midazolam then fentanyl, then midazolam then fentanyl, etc.) This practice is risky because the cumulative effect is often unpredictable and much greater than establishing baseline sedation and titrating to an end point with a single analgesic agent. In addition, repeat doses of drugs with differing times to peak effect make it difficult to estimate subsequent doses. Exactly how much to decrease the standard dose for the second or third administration to prevent the rapid shift of the CO2 response curve to the right and into apnea territory is at best a guess given the variability in pediatric metabolism. (See Figure 1, curve C.) Time to recovery is also prolonged with crossover.
Recognize the shifting baseline. Patients who have already received analgesia before their light or deep sedation for procedures such as a fracture reduction represent an increased risk because of their altered baseline. Subsequent administration of sedatives and analgesics must take this into account. Use of the standard doses and techniques can lead to exaggerated effect secondary to interaction with the active drugs already circulating. The same admonition applies to adolescents under the influence of alcohol or drugs of abuse.
Anticipate and avoid cumulation. Repeat administration of any of the analgesic agents (the exception is alfentanil) to extend a procedure beyond the normal duration of action of the drug leads to accumulation of that agent in the body. This obligates the physician to use analgesics or sedatives that will be effective for the duration of the procedure contemplated. Most of the ultrashort medications have predictable termination of their clinical effect via redistribution from lipid-rich brain tissue down a concentration gradient into skeletal and other body fat depots. As the level of active drug present in the brain decreases, the patient demonstrates recovery; however, the great majority of the medication is still present in the body. Cumulation is common to a patient who is sedated for fracture reduction and, after X-ray, undergoes repeat sedation to improve the fracture then gets re-X-rayed, etc. If body tissue depots become saturated, then redistribution is impeded and the patient will experience prolonged sedation. Recovery time is then dependent on hepatic metabolism or renal excretion of the drug involved and not on redistribution. Alfentanil is a notable exception, as it does not cumulate in the body but is rapidly metabolized to terminate its effect.
Ideal emergence from sedation is characterized by a rapid return to presedation levels of consciousness with minimal distress for the child. This ensures safe discharge home without worries of cardiorespiratory compromise, resedation, aspiration of food (commonly given immediately as a reward), or parental anxiety over ongoing abnormal behavior from the medications used. Discharge criteria that list discrete behavioral, motor, or mental status responses and conditions to be met prior to discharge are the best guidelines for determining readiness for discharge. (See Table 1.) Avoid reversal of sedative or analgesic agents with opiate or benzodiazepine antagonists to speed recovery. Sudden reversal of sedation or analgesia, while hastening emergence, also carries with it the return of pain, anxiety, and sympathetic stimulation. Resedation is a possibility, particularly with the longer-acting medications that are metabolized slower than their antagonists. Antagonists are essential adjuncts for the patient who has apnea or respiratory compromise from oversedation. Hopefully, close attention to titration will minimize the duration of apnea or hypotension.
Fentanyl. Fentanyl is a synthetic narcotic. It is 100 times as potent as morphine and 7000 times more lipophilic, with rapid uptake by lipid-rich brain within 30-60 seconds of intravenous injection to peak analgesia in 2-3 minutes.13,14 Because its duration of effect is 20-30 minutes, it is best employed for short, painful procedures.15
The drug has been used extensively with good safety and efficacy in the ED for repair of facial lacerations, orthopedic procedures, incision and drainage, and diagnostic procedures including CT sedation.16,17 The adverse effects of fentanyl relate to either rapid administration or large doses (> 8-10 mcg/kg).18-21 Large doses or too rapid administration of fentanyl can produce rigidity of the chest wall related to stimulation of the spinal cord inspiratory motor neurons and consequently inspiratory muscles leading to sustained inspiration (i.e., "tight chest syndrome").20,22,23 A prominent bradycardia occurs from stimulation of the central vagal nucleus and prolongs both atrio-ventricular node conduction and refractory period; however, fentanyl causes the least hemodynamic changes of any opiate. Additionally, these adverse effects of fentanyl are reportedly reversed by naloxone. Metabolism in infants is prolonged, although children are less likely than adults to suffer respiratory depression,24,25 and patients will maintain awareness even though appearing to be asleep.26 While primarily an analgesic, at higher doses it also has sedative effects. It is highly titratable at a dose of 0.5-1.0 mcg/kg slowly, which can be repeated every 2-3 minutes for effect. The usual total dose is 1-4 mcg/kg.
Alfentanil. Alfentanil is an analog of fentanyl that is one-fifth as potent and has one-third the duration of action.21 As a result of its low pKa, approximately 90% of the drug is non-ionized at physiologic pH, allowing more rapid diffusion across the blood-brain barrier and thus more rapid onset of action than fentanyl.26,28-30 Termination of action is via rapid redistribution. However, unlike fentanyl, alfentanil does not accumulate with repeat dosing due to its smaller volume of distribution and shorter half-life (elimination half-life 70 minutes as compared with 185 minutes for fentanyl).31 Alfentanil has the same adverse effect profile as fentanyl and works best for 20- to 30-minute procedures. The usual dose is 5-20 mcg/kg IV administered slowly.31,32
Midazolam. As a rapid-acting, water soluble benzodiazepine, midazolam has become the most popular ED agent for sedation. It has 3-4 times the potency of diazepam and rapid onset to a peak effect within 2-3 minutes after intravenous administration.33,34 The two minutes delay to peak effect makes it more difficult to titrate for deep sedation and an easy drug to "stack" with repeat doses. It is highly water soluble and non-irritating to veins. This is by virtue of a carbon ring structure which closes at a pH greater than four to become water soluble at physiologic pH and therefore does not require a propylene glycol solubilizing agent as necessitated for diazepam. Because midazolam redistributes rapidly, its duration of action is short.
The drug binds GABA receptors in the CNS to inhibit spinal afferent pathways and produces skeletal muscle relaxation, amnesia, and anxiolysis. Midazolam, while altering the response to pain, like all benzodiazepines, does not reduce pain perception and has a propensity to produce apnea by shifting the CO2 response curve to the right and depressing the slope. (See Figure 1, curve C.) At higher doses, midazolam can produce hypotension, particularly in hypovolemic children.35-37 In low doses, the patient is able to maintain airway reflexes while anxiety is moderated and the patient is calmed. It has the added advantage of providing anterograde and retrograde amnesia.38,39 When used for painful procedures, addition of an analgesic is recommended. Used intravenously or in conjunction with a narcotic, it is a potent sedative-amnestic and requires extreme vigilance to cardiorespiratory function.40-43 The effects of midazolam can be reversed with intravenous flumazenil43 but, as mentioned previously, routine reversal is not recommended. The effectiveness of midazolam in pediatric patients has been well documented.44-53 The initial IV dosing for children 6 months to five years is 0.05-0.1 mg/kg, then titrated to a maximum of 0.6 mg/kg. For children 6-12 years, the initial IVdose is 0.025-0.05 mg/kg, then titrated to a maximum of 0.4 mg/kg.
Thiopental. Thiopental is an ultrashort-acting, potent barbiturate hypnotic that reaches the brain within 30 seconds of intravenous injection. It produces profound hypnosis and sedation that is highly predictable, lasting 10-15 minutes at subanesthetic doses. Because it is a histamine releaser, it must be used with caution in asthmatics. It can cause significant hypotension through venodilation and a depression of the baroreflex mechanism.51-54 Thiopental has the advantage of dose dependent depression of cerebral metabolism, cerebral blood flow, and intracranial pressure.55 It is a highly alkaline solution (pH 10.5) and if extravasated into subcutaneous or dermal sites can cause erythema, edema, and severe tissue necrosis. Sedative dosing is at 1 mg/kg every 1-2 minutes, titrating for effect to a usual total dose of 3-5 mg/kg. Like benzodiazepines, thiopental provides no analgesia and should be combined with an opiate analgesic for painful procedures. Finally, it is active via rectal administration.56
Methohexital. Similar to its lipophilic cousin thiopental methohexital is an oxybarbiturate with faster onset, shorter duration of action,57 and 2-3 times the potency. It has been widely used as an induction agent at doses of 20 mg/kg administered rectally to produce light to deep sedation.58-62 Methohexital has been used intravenously for sedation during painful pediatric oncologic procedures and as sedation for radiologic studies.63,64 The intravenous dose is 0.5-1.0 mg/kg. The drug can cause myoclonic jerking of the musculature and has the potential to induce seizures in patients with temporal lobe epilepsy.65 Respiratory and airway compromise is a concern.66 Coadministration of an analgesic or use of a local anesthetic is recommended for painful procedures.
Propofol. A unique ultrashort agent in the alkylphenol class unrelated to any of the previous agents, propofol is rapidly becoming a favored agent for ED sedation. Formulated as an aqueous emulsion in intralipid (soybean oil, glycerol, and egg phosphatide), it has the advantage of faster onset than thiopental, twice the potency, rapid emergence, and return to baseline with antiemetic, antipruritic, anticonvulsant, anixiolytic effects.67-73 Emergence is so rapid that procedures that last longer than 5-10 minutes require a continuous infusion or repeat bolus injection to maintain effect. Propofol produces hypotension, myocardial depression, and apnea that is directly related to dose and rate of injection. It has not been shown to release histamine but does depress the CO2 response curve by 50%. As many as half of children will experience pain on infusion that can be eliminated by using 0.5 mg/kg lidocaine with the agent, larger veins, or a concomitant analgesic. Unlike thiopental, it is not antianalgesic, yet has no amnestic or analgesic properties and, as such, should be combined with other appropriate agents to maintain amnesia and pain relief. Propofol is administered as intermittent boluses or a continuous infusion at an initial rate of 25-100 mcg/kg/min titrated to effect.74-79 Patients are exquisitely sensitive to rate of injection of propofol, so much so that "time taken over the injection under most clinical circumstances is of greater importance than volume."80 Thus, slow gradual infusion of doses yields the fewest adverse effects. Propofol has been most useful as pediatric sedation for CT or MRI where longer periods of immobilization are required and are easily managed by continuous gravity infusions without pumps or other metallic equipment.81-86 More recently, propofol has been used effectively in the ED setting and the dental suite.87-89 Apnea and hypotension may be more common than with other agents but are also more transient and self limited. This mandates the usual caveat of use by physicians facile with pediatric airway management. The great benefit of propofol is on-off emergence that limits the time the child is at risk from sedation-related events.
Intermediate-/Medium-Duration Agents
Morphine. Morphine is the classic opiate narcotic to which other analgesics are compared. Morphine provides analgesia, sedation, and diminishes anxiety by its agonist activity at mu and kappa opioid brain receptors. It is more effective for continuous, dull pain than for sudden, sharp, painful stimuli. Because of poor lipid solubility, only small amounts of an administered dose enter the CNS, restricting its usefulness as a titratable sedative.12,13,26 It does, however, provide effective analgesia for a 3-4 hour duration, low CNS toxicity, and is preferable for painful procedures longer than 30 minutes.90 Morphine has a relatively slow onset (5 minutes IV, 10-15 minutes IM). It works well when combined with benzodiazepines. Side effects include nausea, hypotension from histamine release, and respiratory depression. Children under 2 months of age are particularly susceptible to respiratory depression. The preferred route is intravenously (at 0.1 mg/kg), but it is absorbed intramuscularly, sublingually, and rectally. The drug causes significant histamine release that can lead to hypotension and, like all narcotics, depresses the medullary response to hypercapnia and hypoxia. It has a prolonged half-life and decreased clearance in infants less than one month of age.91
Meperidine. As the most commonly used narcotic in the ED, the synthetic meperidine has a narrow therapeutic margin (i.e., therapeutic dose close to toxic dose). It is not titratable for deep sedation, as it requires 10-20 minutes to peak clinical effect and has a 2-3 hour duration. Accumulation of its principle active metabolite, normeperidine, has the potential to cause CNS stimulation and seizures.13,26,92,93 Because of this, it is usually administered in conjunction with phenothiazines to potentiate its sedative characteristics. Meperidine is an antiquated favorite of clinicians who shun the newer agents because of its predictable, albeit gradual onset. It offers almost no advantage over morphine and is only one-tenth as potent; it is not recommended routinely for children.
Diazepam. The father of midazolam, diazepam has been the most familiar benzodiazepine to emergency physicians. Solubilized in propylene glycol, diazepam is very irritating to veins on injection and while predictable, has a slower onset to action than midazolam, making it less useful for effective titratation for deep sedation. The side effect profile is similar to midazolam.
Pentobarbital. Pentobarbital is a long-acting barbiturate that induces sedation within five minutes of IV injection. It has a duration of action of 30-60 minutes and requires monitoring for potential hypoxia. Pentobarbital has found most use in sedation for diagnostic studies that are not painful.94-97 Dosing is at 2-5 mg/kg.
Chloral Hydrate. Chloral hydrate is a popular hypnotic/sedative for use in infants, particularly among intensivists and pediatric radiologists.98-101 This agent is active secondary to its hepatic metabolite trichloroethanol and is thus contraindicated in liver failure. Dosages vary from 25-100 mg/kg up to 1000 mg either rectally or orally. In other words, doses higher than recommended by the manufacturer (e.g., 75 mg/kg) are frequently administered. The dose is often repeated if the intended end point is not reached. Chloral hydrate has several disadvantages for the emergency setting. Notably, it has delayed onset up to 60 minutes or more, often resulting in a child who is sedated for several hours with the peak drug effect, minutes to hours beyond the completion of the procedure.101,102 This possibility mandates extended recovery and observation time. Nausea, vomiting, respiratory depression, and death have been reported.103 Additionally, some question has been raised regarding possible carcinogenicity of its metabolite.104
Meperidine, Promethazine, and Chlorpromazine. Also know as the "lytic cocktail," "DPT," or "MPC," this combination of Demerol (meperidine 25 mg/mL), Phenergan (promethazine 6.5 mg/mL), and Thorazine (chlorpromazine 6.5 mg/mL) has been used widely because of its ease of intramuscular administration and reliable sedating effects. It has also been used inappropriately to chemically immobilize children for non-painful procedures.105,106 The combination is not titratable and is well known for complications including seizures, dystonic reactions, hypotension, and even death at the standard (0.1 mL/kg) and lower dosage (0.06 mL/kg).5-11 Combining two phenothiazine class drugs with a long-acting opiate potentiates the respiratory depressant effects of the meperidine and magnifies the toxicity of this combination with duration of action reported as long as 19 hours.107 Current practice recommends against use of this drug combination in the emergency department because of these issues. The Agency for Health Care Policy and Research has stated "the efficacy of this mixture is poor when compared with alternative approaches; it has been associated with a high frequency of adverse effects. It is not recommended for general use and should be used only in exceptional circumstances".108
Dissociative Sedation. Ketamine is a unique medication that is particularly useful in pediatric sedation. It also has a unique profile of advantages and side effects that must be considered before using it safely. A derivative of phencyclidine that creates the trance-like dissociative state characterized by sedation, amnesia, analgesia, and catalepsy, it has been in use since 1970.109 The so-called "kiddie-caine" child appears awake with eyes open with a slow nystagmic gaze, intact corneal and light reflexes but unresponsive to painful and visual stimulioften described as the "lights are on but nobody’s home" phenomenon. A functional dissociation is created between the cortical and limbic systems of the brain that interferes with sensory perception of painful stimuli and memory. This occurs by ketamine binding to the NMDA (N-methyl D aspartate) receptors in the brain. The level of sedation is comparable to deep sedation with other agents, yet the patient independently maintains an airway; as a result, ketamine is enjoying increasing use in the ED.110,111 At low doses ketamine supports cardiovascular function as a positive inotrope that increases blood pressure, heart rate, cardiac output, intracranial pressure (ICP), and shifts the CO2 response curve to the right.109,112,113 It also has a bronchodilatory effect on lungs and maintains airway reflexes. Ketamine can also increase airway secretions, salivation, and rarely causes laryngospasm. At high doses, it is a general anesthetic with the usually attendant cardiopulmonary depressive effects. The drug is highly predictable in onset (1-2 minutes IV, 5 minutes IM) and duration (approximately 45 minutes), even via the intramuscular route. Its safety and efficacy in the ED setting have been extensively documented in more than 11,000 cases.110,111,113,114 Ketamine use mandates several special considerations.
Induction and Administration. Ketamine has been used orally, rectally, and intranasally.115-121 While active via these routes, it is most efficacious and predictable when given IM or slowly IV. Intramuscular administration is used most commonly and the dose is 4 mg/kg. Intravenous loading of ketamine (1-2 mg/kg) should occur over at least 1-2 minutes. Concerns over increased tracheobronchial secretions and salivation have prompted the recommendation that antisialogogues such as atropine (0.01 mg/kg, maximum 0.5 mg) or glycopyrollate (0.005 mg/kg, maximum 0.25 mg) be administered prior to or combined with ketamine.111 Incidence of larygospasm is estimated overall less than 1% to a high of 9% in children with upper respiratory infections.122 Neonates and infants less than 3 months old have a higher incidence of airway complications including apnea and aspiration.111
Emergence. Return from the dissociative process can create an agitated, disoriented, and combative childa process known as "emergence reaction."109,111 Risk factors for emergence reactions are age over 10-15, female gender, a history of vivid dreams, and personality or psychiatric problems. While unusual in children (approx 2%), emergence phenomenon is prevented by coadministration of low-dose midazolam (0.05-0.1 mg/kg) and recovery in a quiet environment. However, use of midazolam may prolong the duration of action. Emesis can occur during recovery but likewise is uncommon (8%). Delayed or long-term effects are almost non-existent.122
Patient selection. Because of its physiologic effects, patient selection is very important. Children with suspected head injury, upper respiratory infections, psychiatric histories, age less than 3 months or greater than 10 years, or those with thyroid or liver diseases are probably not good candidates for dissociative sedation. The nursing staff must be educated to the idiosyncrasies of ketamine. Thorough instructions to the parents regarding persistent nystagmus, ataxia, and behavioral effects of ketamine are necessary to allay parental concerns. Worldwide experience has shown a serious complication rate (apnea, laryngospasm, emergence reaction, aspiration, death) of less than 0.2%.123 Ketamine appears to be among the safest alternatives for sedation in the pediatric population.
Nitrous Oxide. Nitrous oxide is an inhaled sedative analgesic. It is short-acting, rapid in onset, and is easily administered by demand valve face mask in a 50:50 mixture with oxygen to prevent hypoxia. It seems to be most effective in children older than 8 years of age.124,126 It is particularly useful in children who are poorly cooperative (developmental delay, mental retardation), as it is non-invasive, requires minimum expertise and monitoring, and produces light sedation. Because it is highly diffusable, it can accumulate in enclosed body cavities such as the middle ear or bowel and potentially cause perforation, but for short use it is very safe.125-129 When used in conjunction with narcotics or sedatives, it produces deep sedation, and appropriate monitoring is desirable.
Fentanyl "lollipop." Considerable potential was anticipated with the availability of an oral form of fentanyl (Fentanyl Oralet). Fentanyl citrate is impregnated in the matrix of a sweet lozenge on a holder. The child uses it like a "lollipop" with absorption across oral mucosal surface and into systemic circulation without first-pass effect. There are four oralet dosages (100, 200, 300, 400 mcg). The oralet is contraindicated in children less than 10 kg. Randomized studies have shown it to be effective sedation for painful procedures (bone marrow, lumbar puncture), but with as high as 47% of children manifesting nausea and vomiting and a mean time to discharge of 98 minutes.130 It has the same risk of respiratory depression as with parenteral fentanyl.131-137 In addition, some philosophical concern has been raised regarding the use of a medication in "candy" form.
Ketorolac. Ketorolac is the only parenteral nonsteroidal anti-inflammatory analgesic that is currently available for use. Its mechanism of action is inhibition of prostaglandin synthesis.118 Because it is a non-narcotic medication, it offers analgesia without risk of respiratory depression and nausea commonly associated with use of narcotic agents. It has been widely used intravenously without complications.138-147 Adverse reactions reported in the adult population include gastrointestinal bleeding, anaphylaxis, renal insufficiency, and platelet dysfunction.148-155 Pediatric experience is limited due to lack of approval for use in children under 12 years of age and has generated some concern over possible prolongation of bleeding times. Clinical trials have shown ketorolac to be an effective analgesic at doses of 0.5-1.0 mg/kg IM without adverse gastrointestinal or renal effects.156 More commonly, ketorolac has been used post operatively and for renal colic, comparing favorably to morphine or demerol.157 It has also reduced postoperative opioid requirements in children.147
Butorphanol. Recently an intranasal spray of butorphanol tartrate (10 mg/mL) has become available. Butorphanol is an opioid agonist-antagonist analgesic. Its primary agonist activity is at the kappa opioid receptors with some mixed agonist-antagonist function at the mu receptor. While it has the potential of respiratory depression, there is a ceiling on its effects due to the antagonist component. Peak analgesia is within one hour of nasal administration. The recommended dose is one spray in one nostril that delivers approximately 1 mg.158 It has been used successfully for postoperative pain control in outpatient pediatric surgery settings and for migraine headaches.159-161 The reader should be cautioned that its use for children has yet to be clearly identified. Contraindications are sensitivity to butorphanol or the preservative benzethonium chloride and the usual precautions attendant to use of narcotics.
It is clear that there has been significant progress in the provision of pediatric analgesia and sedation in the emergency setting. Over the past several years, new agents have been developed with a more desirable profile for use in this setting. In addition, it appears that the actual use of sedation and analgesia for painful procedures is increasing in the pediatric population. The safe use of these agents remain a central concern to practitioners. It is important that clear, written procedures, with appropriate monitoring, be established to ensure patient safety. Physicians using these agents in children must be adept at advanced airway procedures in this special group of patients. The careful selection of the most appropriate agent(s), combined with appropriate skills in drug administration, will lead to decreased distress and enhanced comfort for children requiring relief from pain and anxiety.
References
1. Green S, Wittlake W. Meeting the guidelines and standards for pediatric sedation and analgesia. Pediatr Emerg Med Rep 1997;2:67-78.
1a. Petrack EM, Christopher NC, Kriwinsky J. Pain management in the emergency department: Patterns of analgesic utilization. Pediatrics 1997;99:711-714
2. American Academy of Pediatrics, Committee on Drugs, Section on Anesthesiology. Guidelines for the elective use of conscious sedation, deep sedation and general anesthesia in pediatric patients. Pediatrics 1985;76:317-321.
3. Wright SW. Conscious sedation in the emergency department: The value of capnography and pulse oximetry. Ann Emer Med 1992; 21:551-55
4. American Academy of Pediatrics, Committee on Drugs. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. Pediatrics 1992;6:1110-1115.
5. Cohen GH, Casta A, Sapire DW, et al. Decorticate posture following "cardiac cocktail." A transient complication of sedation for catheterization. Ped Cardiol 1982;2:251-253.
6. Krippaehne JA, Montgomery MT. Morbidity and mortality from pharmacosedation and general anesthesia in the dental office. J Oral Maxillofac Surg 1992;50:691-698.
7. Mitchell AA, Louik C, Lacouture P, et al. Risks to children from computed tomographic scan premedication. JAMA 1982;247:2385-2388.
8. Nahata MC, Clotz MA, Knogg EA. Adverse effects of meperidine promethazine and chlorpromazine for sedation in pediatric patients. Clin Pediatr 1985;24:558.
9. Ros SP. IM MPC in children: Safe and effective or a poor choice? Ann Emerg Med 1991;20:1274.
10. Snodgrass WR, Dodge WF. Lytic "DPT" cocktail: Time for rational and safe alternatives. Pediatr Clin North Am 1989;36:1285-1291.
11. Sacchetti AD, Schafermeyer RW, Gerardia MJ, et al. Pediatric analgesia and sedation. 1993 Report prepared by the Pediatric Emergency Medicine Committee of the American College of Emergency Physicians, Dallas:1-80.
12. Murphy MR. Opioids. In: Barash PG, Cullen BF, Stoelting KK, eds. Clinical Anesthesia. Philadelphia: Lippincott; 1989:255.
13. Murphy MR, Hug CC Jr, McClain DA. Dose-independent pharmacokinetics of fentanyl. Anesthesiology 1983;59:537-540.
14. Yaster M, Nichols DG, Deshpande JK. Midazolam-fentanyl intravenous sedation in children: Case report of respiratory arrest. Pediatrics 1990;86:463.
15. Billmire DA, Neale HW, Gregory RO. Use of IV fentanyl in the outpatient treatment of pediatric facial trauma. J Trauma 1985;25:1079.
16. Chudnofsky CR, Wright SW, Dronen SC. The safety of fentanyl use in the emergency department. Ann Emerg Med 1989;18:635.
17. Stoeckel H, Hengstmann JH, Schuttler J. Pharmacokinetics of fentanyl as a possible explanation for recurrence of respiratory depression. Br J Anaesth 1979;51:741-745.
18. Streisand JB, Bailey PL, LeMaire L, et al. Fentanyl-induced rigidity and unconsciousness in human volunteers. Anesthesiology 1993;78:4.
19. Tabatabai M, Kitahata LM, Collins JG. Disruption of the rhythmic activity of the medullary inspiratory neurons and phrenic nerve by fentanyl and reversal with nalbuphine. Anesthesiology 1989;70:489.
20. Hubbard AM, Markowitz Rl, Kimmel B, et al. Sedation for pediatric patients undergoing CT and MRI. J Comp Assist Tomog 1992;16:3-6.
21. Scamman FL. Fentanyl-O2-N2O rigidity and pulmonary compliance. Anesth Analg 1983;62:332-334.
22. Koehntop DE, Rodman JH, Brundage DM, et al. Pharmacokinetics of fentanyl in neonates. Anesth Analg 1986;65:227-232.
23. Singleton MA, Rosen Jl, Fisher DM. Plasma concentration of fentanyl in infants, children, and adults. Can J Anesth 1987;34:152-155.
24. Collins VJ. Intravenous anesthesia: Narcotic and neuroleptic narcotic agents. In: Principles of Anesthesiology: General and Regional Anesthesia. 3rd ed. Philadelphia: Lea and Febiger; 1993:712-721.
25. White PF, Coe V, Shafer A, et al. Comparison of alfentanil with fentanyl for outpatient anesthesia. Anesth Analg 1986;64:99.
26. Bailey PL, Stanley TH. Narcotic intravenous anesthetics. In: Miller RD, ed. Anesthesia. 3rd ed. CITY: Churchill Livingstone; 1980:281-365.
27. Goresky GV, Koren G, Sabourin MA. The pharmacokinetics of alfentanil in children. Anesthesiology 1987;67:654.
28. Meistelman C, Saint-Maurice C, Lepaul M, et al. A comparison of alfentanil pharmacokinetics in children and adults. Anesthesiology 1987;66:13.
29. Murphy MR. Clinical pharmacology of alfentanil and sufentanil. Anesthesiology Rev 1984;11:17.
30. Nauata J, deLange S, Koopman D, et al. Anesthetic induction with alfentanil: a new short acting narcotic analgesic. Anesth Analg 1982;61:267-72.
31. Fragen RJ, Avram MJ. Non-Opioids. In: Barash PG, Cullen BF, Stoelting KK, eds. Clinical Anesthesia. Philadelphia, PA: Lippincott; 1989:227-248.
32. Collins VJ. Barbiturate intravenous anesthetic agents. Thiopental. In: Principles of Anesthesiology: General and Regional Anesthesia. 3rd ed. Philadelphia: Lea and Febiger; l993:665-671.
33. Burnett YL. Midazolam preop. effects on sedation, ventilation, and oxygen saturation in higher risk children. Anesth Analg 1993;76:S30.
34. Forster A, Gardaz JP, Suter PM. Respiratory depression by midazolam and diazepam. Anesthesiology 1980;53:494-497.
35. Payne K, Mattheyse FJ, Dawes T. The pharmacokinetics of midazolam in pediatric patients. Eur J Clin Pharmacol 1989;37:267.
36. Twersky RS, Hartung J, Berger BJ. Midazolam enhances anterograde but not retrograde amnesia in pediatric patients. Anesthesiology 1993;78:51.
37. Walters BL. Pain control in the emergency department. In: Reisdorff EJ, Roberts and Weigenstein, eds. Pediatric Emergency Medicine. Philadelphia: WB Saunders; 1993:908-915.
38. Bailey PL, Moll JWB, Pace NL. Respiratory effects of midazolam and fentanyl: Potent interaction producing hypoxemia and apnea. Anesthesiology 1988;169:A813.
39. Forster A, Gardaz JP, Suter PM. Respiratory depression by midazolam and diazepam. Anesthesiology 1980;53:494-497.
40. Wright SW, Chudnofsky CR, Dronen SC, et al. Comparison of midazolam and diazepam for conscious sedation in the emergency department. Ann Emerg Med 1993;22:201-205.
41. Votey SR, Bosse GM, Bayer MJ, et al: Flumazenil: A new benzodiazepine antagonist. Ann Emerg Med 1991;20:181.
42. Anderson BJ, Exarchos H, Lee K, et al. Oral premedication in children: A comparison of chloral hydrate, diazepam, alprazolam, midazolam and placebo for day surgery. Anaesth Intens Care 1990;18:185-193.
43. Diament MJ, Stanley P. The use of midazolam for sedation of infants and children. Am J Roentgenol 1988;150:377.
44. Feld LH, Negus JB, White PF. Oral midazolam preanesthetic medication in pediatric outpatients. Anesthesiology 1990;73:831.
45. Karl HW, Keifer AT, Rosenberger JL, et al. Comparison of the safety and efficacy of intranasal midazolam or sufentanil for preinduction of anesthesia in pediatric patients. Anesthesiology 1992;76:209-215.
46. Karl HW, Rosenberger JL, Larach MG, et al. Transmucosal administration of midazolam for premedication of pediatric patients. Anesthesiology 1993;78:885-891.
47. Lejus C, Renaudin M, Testa S. Midazolam for premediciation in children: Intranasal vs. intrarectal administration. Anesth Analg 1993;76:S217.
48. Theroux MC, West DW, Corddry DH, et al. Efficacy of intranasal midazolam in facilitating suturing of lacerations in preschool children in the emergency department. Pediatrics 1993;91:624-662.
49. Weldon BC, Watcha MF, White PF. Oral midazolam in children: effect of time and adjunctive therapy. Anesth Analg 1992;75:51-55.
50. Wilton NC, Leigh J, Rosen DR, et al. Preanesthetic sedation of preschool children using intranasal midazolam. Anesthesiology 1988;69:972-975.
51. Blouin RT, Conard PF, Gross JB. Time course of ventilatory depression following induction doses of propofol and thiopental. Anesthesiology 1991;75:940-944.
52. Bready R, Spear R, Fisher B, et al. Propofol infusion: Dose response for CT scans in children. Anesth Analg 1992;74:S36.
53. Collins VJ. Barbiturate intrvenous anesthetic agents: Thiopental. In; Principles of Anesthesiology: General and Regional Anesthesia. 3rd ed. Philadelphia: Lea and Febiger; l993:665-671.
54. Fragen RJ, Avram MJ. Barbiturates. In: Miller RD, ed. Anesthesia. 3rd ed. CITY: Churchill Livingstone; 1980:225-243.
55. Collins VJ. Barbiturate intrvenous anesthetic agents: Thiopental. In: Principles of Anesthesiology: General and Regional Anesthesia. 3rd ed. Philadelphia: Lea and Febiger; l993:665-67 1.
56. O’Brien JF, Falk JL, Carey BE, et al. Rectal thiopental compared with intramuscular meperidine, promethazine, and chlorpromazine for pediatric sedation. Ann Emerg Med 1991;20:644-647.
57. Mitchell AA, Louik C, Lacouture P, et al. Risks to children from computed tomographic scan premedication. JAMA 1982;247:2385-2388.
58. Kestin IG, McIlvaine WB,Lockhart CH, et al. Rectal methohexital for induction of anaesthesia in children with and without rectal aspiration after sleep: A pharmaconetic and pharmacodynamic study. Anesth Analg 1988;67:1102-1104.
59. Khalil SN, Nuutinen LS, Rawal N, et al. Sigmoidorectal methohexital as an inducing agent for general anesthesia in children. Anesth Analg 1988;67:S113.
60. Liu LM, Gaudreault P, Friedman PA, et al. Methohexital plasma concentrations in children following rectal administrations. Anesthesiology 1985;62:567-570.
61. Liu LM, Goudsouzian NG, Liu PL. Rectal methohexital premedication in children, a dose comparison study. Anesthesiology 1980;53:343-345.
62. Zink BJ, Darfler K, Salluzo RF, et al. The efficacy and safety of methohexital in the emergency department. Ann Emerg Med 1991;20:1293-1298.
63. Griswold JD, Liu LMP. Rectal methohexital in children undergoing computerized cranial tomography and magnetic resonance imaging scans. Anesthesiology 1987;67:A494.
64. Schwanda AE, Freyer DR, Sanfilippo DJ, et al. Brief unconscious sedation for painful pediatric oncology procedures: Intravenous methohexital with appropriate monitoring is safe and effective. Amer J Ped Hem Onc 1993;15:370-376.
65. Rockoff M, Goudsouzian NG. Seizures induced by methohexital. Anesthesiology 1981;54:333-335.
66. Daniels AL, Cote CJ, Polaner DM. Continuous oxygen saturation monitoring following rectal methohexitone induction in pediatric patients. Can J Anaesth 1992;39:27-30.
67. McNeir DA, Mainous EG, Tieger N. Propofol as an intravenous agent in general anesthesia and conscious sedation. Anesth Prog 1988;35:147-151.
68. Mirakhur RK. Induction characteristics of propofol in children: Comparison with thiopentone. Anesthesiology 1988;43:593-598.
69. White PF. Propofol: Pharmacokinetics and pharmacodynamics. Semin Anesthesia 1988;7:4-20.
70. Borgeat A, Wilder-Smith OHG, Saiah M, et al. Subhypnotic doses of propofol possess direct antiemetic properties. Anesth Analg 1992;74:539-541.
71. Fragen RJ, Avram MJ. Non-Opioids. In: Barash PG, Cullen BF, Stoelting KK eds. Clinical Anesthesia. Philadelphia: Lippincott; 1989:227-248.
72. Hannallah R, Friedfeld S, Verghese P, et al. Comparison of propofol and thiopental for rapid anesthesia induction in infants. Anesth Analg 1992;74:S132.
73. Hannallah RS, Baker SB, Casey W, et al. Propofol. Effective dose and induction characteristics in unpremedicated children. Anesthesiology 1991;74:217-219.
74. Aun CT, Sung RT, O’Meara ME, et al. Cardiovascular effects of IV induction in children: Comparison between propofol and thiopentone. Brit J Anaesthesia 1993;70:647-653.
75. Collins VJ. Intravenous anesthesia: Nonbarbiturates-Non-narcotics In: Principles of Anesthesiology: General and Regional Anesthesia. 3rd. Philadelphia: Lea and Febiger; 1993:768-772.
76. Norreslet J, Wahlgreen C. Propofol infusion for sedation of children. Crit Care Med 1990;18:890-892.
77. Westrin P. The induction dose of propofol in infants 1-6 months of age and in children 10-16 years of age. Anesthesiology 1991:74:455-458.
78. Valtonen M, Lisalo E, Kanto J, et al. Propofol as an induction agent in children: Pain on injection and pharmacokinetics. Acta Anaesthesiol Scand 1989;33:152-155.
79. Patel DK, Keeling PA, Newman GB, et al. Induction dose of propofol in children. Anaesthesia 1988;43:949-952.
80. Goodman NW, Black AM. Rate of injection of propofol for induction of anesthesia. (Letter) Anesth Analg 1992;74:938-39.
81. Bloomfield EL, Masaryk TJ, Schubert A. Pediatric sedation for MRI of the brain and spine: A comparative study of pentobarbital vs. propofol. Anesth Analg 1993;76:S22.
82. Bready R, Spear R, Fisher B, et al. Propofol infusion: Dose response for CT scans in children. Anesth Analg 1992;74:S36.
83. Lefever EB, Potter PS, Seeley NR. Propofol sedation for pediatric MRI. Anesth Analg 1993;76:919-920.
84. Frankville DD, Spear RM, Dyck JB. The dose of propofol required to prevent children from moving during magnetic resonance imaging. Anesthesiology 1993;79:953-958.
85. Kain ZN, Gaal DJ, Kain TS, et al. A first pass cost analysis of propofol versus barbiturates for children undergoing magnetic resonance imaging. Anesth Analg 1994;79:1102-1106.
86. Valtonen M. Anaesthesia for computerised tomography of the brain in children: A comparison of propofol and thiopentone. Acta Anaesthesiol Scand 1989;33:170-173.
87 Ewah B, Carr C. Comparison of propofol and methohexitone for dental chair anaesthesia in children. Anaesthesia 1993;48:260-262.
88. Swanson ER, Seaberg DC, Mathias S. The use of propofol for sedation in the emergency department. Acad Emerg Med 1996;3:234-238.
89. Swanson ER, Seaberg DC, Stypula RW et al. Propofol for conscious sedation: A case series [letter]. Acad Emerg Med 1995.2:661-663.
90. Dahlstrom B, Bolme P, Feychting H, et al. Morphine kinetics in children. Clin Pharmacol Ther 1979;26:354-365.
91. Lynn AM, Slattery JT. Morphine pharmacokinetics in early infancy. Anesthesiology 1988;66:136-139.
92. Dahl SG. Active metabolites of neuroleptic drugs. Possible contribution to therapeutic and toxic effects. Therapeutic Drug Monit 1982;4:33-40.
93. Mather LE, Tucker GT, Pflug AE, et al. Meperidine kinetics in man: Intravenous injection in surgical patients and volunteers. Clin Pharmacol Ther 1975;17:21-30.
94. Cook BA, Bass JW, Nomizu S, et al. Sedation of children for technical procedures current standard of practice. Clin Pediatr 1992;31:137-142.
95. Hubbard AM, Markowitz Rl, Kimmel B, et al. Sedation for pediatric patients undergoing CT and MRI. J Comp Assist Tomog 1992;16:3-6.
96. Keeter S, Benator RM, Weinberg SM, et al. Sedation in pediatric CT: National survey of current practice. Radiology 1990;175:745-752.
97. Strain JD, Campbell JB, Harey LA, et al. IV nembutal: Safe sedation for children undergoing CT. Am J Rad 1988;151:975-979.
98. Binder LS, Leake LA. Chloral Hydrate for Emergent Pediatric Procedural Sedation: A new look at an old drug. Am J Emerg Med 1991;9:530-534.
99. Moody EH Jr, Mourino AP, Campbell RL. The therapeutic effectiveness of nitrous oxide and chloral hydrate administered orally, rectally, and combined with hydroxyzine for pediatric dentistry. Assoc J Dent Child 1986;53:425-429.
100. Greenberg SB,Faerber EN, Aspinall CL, et al. High-dose chloral hydrate sedation for children undergoing CT. J Comput Assist Tom 1991;15:467-9.
101. Reimche LD, Sankaran K, Hindmarsh KW, et al. Chloral hydrate sedation in neonates and infants: Clinical and pharmacologic considerations. Dev Pharmacol Ther 1989;12:57-64.
102. Rumm PD, Takao TR, Fox DJ, et al. Efficacy of sedation of children with chloral hydrate. South Med J 1990;83:1040-1043.
103. Hunt CE, Hazinski TA, Gora P. Experimental effects of chloral hydrate in ventilatory response to hypoxia and hypercarbia. Pediatr Res 1982;16:79-81.
104. Keller DA, Heck HD. Mechanistic studies on chloral toxicity: Relationship to trichloroethylene carcinogenesis. Toxicol Lett 1988;42:183-191.
105. Smith C, Rowe RD, Vlad P. Sedation of children for cardiac catheterization with an ataractic mixture. Can Anaes Soc J 1958;5:35-40.
106. Terndrup TE, Cantor RM, Madden CM. Intramuscular meperidine, promethazine, and chlorpromazine: Analysis of use and complications in 487 pediatric emergency department patients. Ann Emerg Med 1989;18:528.
107. Terndrup TE, Dire DJ, Madden CM, et al. A prospective analysis of intramuscular meperidine, promethazine and chlorpromazine in pediatric emergency department patients. Ann Emerg Med 1991;20:31.
108. U.S. Department of Health and Human Services, Public Health Service: Agency for Health Care Policy and Research. Acute pain management: Operative of medical procedures and trauma. Februrary 1992
109. White PF, Way WL, Trevor AJ. Ketamineits pharmacology and therapeutic uses. Anesthesiology 1982;56:119-136.
110. Green SM, Nakamura R, Johnson NE. Ketamine sedation for pediatric procedures: Part 1, a prospective series. Ann Emerg Med 1990;19:1024-1032.
111. Green SM, Nakamura R, Johnson NE. Ketamine sedation for pediatric procedures: Part 2, review and implications. Ann Emerg Med 1990;19:1033-1046.
112. Hazma J, Ecoffey C, Gross JB. Ventilatory response to CO2 following intravenous ketamine in children. Anesthesiology 1989;70:422-425.
113. Morgan M, Loh L, Singer L. Ketamine as the sole anaesthetic agent for minor surgical procedures. Anaesthesia 1971;26:158-165.
114. Bragg CL, Miller BR. Oral ketamine facilitates induction in a combative mentally retarded patlent. J Can Anesth 1990;2:121-122.
115. Gutstein HB, Iohnson KL, Heard MB, et al. Oral ketamine preanesthetic medication in children. Anesthesiology 1992;76:28-33.
116. Warner DL, Cabaret J, Velling D. Ketamine plus midazolama most effective paediatric oral premedicant. Paediatric Anaesthesia 1995;5:293-295.
117. Alderson PJ, Lerman J. Oral premedication for paediatric ambulatory anaesthesia:A comparison of midazolam and ketamine. Can J Anaesth 1994;41:3:221-226.
118. Roelofse JA, Joubert JJ, Roelofse PG. A double-blind randomized comparison of midazolam alone and midazolam combined with ketamine for sedation of pediatric dental patients. J Oral Maxillofac Surg 1996;54:838-844.
119. Van der Bijl P, Roelofse JA. Rectal ketamine and midazolam for premedication in pediatric dentistry. J Oral Maxillofac Surg 1991;49:1050
120. Louon A, Reddy VG. Nasal midazolam and ketamine for paediatric sedation during computerized tomography. Acta Anaesthesiologica Scandinavica 1994;38:259-26.
121. Aldrete JA, Roman de Jesus JC, Russell LJ. Intranasal ketamine as induction adjunct in children: Preliminary report. Anesthesiology 1987;67:514.
122 Petrack EM, Marx CM, Wright MS. Intramuscular ketamine is superior to meperidine, promethazine and chlorpromazine for pediatric emergency department sedation. Arch Pediatri Adolesc Med 1996;150:676-681.
123. Green SM, CLem KJ, Rothrock SG. Ketamine safety profile in the developing world: Survey of practitioners. Acad Emerg Med 1996;3:598-604.
124. Dula DJ. Nitrous oxide analgesia. In: Roberts JR, Hedges JR, eds. Clinical Procedures in Emergency Medicine. 2nd ed. Philadelphia: WB Saunders Co.; 1991:508-514.
125. Gamis AS, Knapp JF, Glenski JA. Nitrous oxide analgesia in a pediatric emergency department. Ann Emerg Med 1989;8:177-181.
126. McKinnon K. Pre-hospital analgesia with nitrous oxide/oxygen. Can Med Assoc J 1982;125:836-840.
127. Muir JJ, Warner M, Offord K. Role of nitrous oxide and other factors in postoperative nausea and vomiting. Anesthesiology 1987;66:513-518.
128. Evans JK, Buckley SL, Alexander AH, et al. Analgesia for the reduction of fractures in children: A comparison of nitrous oxide with intramuscular sedation. J Ped Orthoped 1995;15:73-77.
129. Hennrikus WL, Shin AY, Klingelberger CE. Self administered nitrous oxide and a hematoma block for analgesia in the outpatient reduction of fractures in children. J Bone and Joint Surg 1995;77A:335-339.
130. Schutzman SA, Burg J, Liebelt E. Oral transmucosal fentanyl citrate for premedication of children undergoing laceration repair. Ann Emerg Med 1994;24:1059-1064.
131. Ashburn MA, Lind GH, Gillie MH, et al. Oral transmucosal fentanyl citrate (OTFC) for the treatment of postoperative pain. Anesth Analg 1993;76:377.
132. Feld LH, Champeau MW, van Steennis CA, et al. Preanesthetic medication in children: A comparison of oral transmucosal fentanyl citrate vs. placebo. Anesthes 1989;71:374.
133. Friesen RH, Lockhart CH. Oral transmucosal fentanyl citrate for preanesthetic medication of pedatric day surgery patients with and without droperidol as a prophylactic anti-emetic. Anesthesiology 1992;76:46-51.
134. Lind GH, Marcus MA, Mears SL. Oral transmucosal fentanyl citrate for analgesia and sedation in the emergency department. Ann Emerg Med 1991;20:1117.
135. Neslon PS, Streisand JB, Mulder SM, et al. Comparison of oral transmucosal fentanyl citrate and an oral solution of meperidine, diazepam, and atropine for premedication in children. Anesthes 1989;70:616.
136. Streisand JB, Stanley TH, Hague B, et al. Oral transmucosal fentanyl citrate premedi cation in children. Anesth Analg 1989;69:28-34.
137. Streisand JB, Varvel JR, Stanski DR, et al. Absorption and bioavailability of oral transmucosal fentanyl citrate. Anesthesiology 1991;75:223.
138. Brocks DR, Jamali F. Clinical pharmacokinetics of ketorolac tromethamine. Clin Pharmacokinet 1992;23:415-427.
139. Maunuksela EL, Kokki H, Bullingham RE. Comparison of intravenous ketorolac with morphine for postoperative pain in children. Clin Pharmacol Ther 1992;52:436-443.
140. Powell H, Smallman JM, Morgan M. Comparison of intramuscular ketorolac and morphine in pain control after laparotomy. Anaesthesia 1990;45:538-542.
141. Sevarino FB, Sinatra RS, Paige D, et al. The efficacy of intramuscular ketorolac in combination with intravenous PCA morphine for postoperative pain relief. J Clin Anesth 1992;4:285-288.
142. Watcha MF, Ramirez-Ruiz M, White PF, et al. Perioperative effects of oral ketorolac and acetaminophen in children undergoing bilateral myringotomy. Can J Anaesth 1992;39:641-642.
143. Yee JP, Koshiver JE, Allbon C, et al. Comparison of intramuscular ketorolac tromethamine and morphine sulfate for analgesia of pain after major surgery. Pharmacotherapy 1986;6:253-261.
144. Buck ML. Clinical experience with ketorolac in children. Ann Pharmacother 1994;28:1009-1013.
145. Sutters KA, Levine JD, Dibble S, et al. Analgesic efficacy and safety of single dose intramuscular ketorolac for postoperative pain management in children following tonsillectomy. Pain 1995;61:145-153.
146. Mendel HG, Guarnieri KM, Sundt LM et al. The effects of ketorolac and fentanyl on postoperative vomiting and analgesic requirements in children undergoing strabismus surgery. Anesth Analg 1995;80:1129-1133.
147. Maunuksela E, Kokki H, Bullingham RES. Comparison of intravenous ketorolac with morphine for postoperative pain in children. Clin Pharmacol Ther 1992;52;436-443.
148. Horswell JL. Bleeding diathesis after perioperative ketorolac. Anesth Analg 1992;74:168-169.
148. Rotenberg FA, Giannini VS. Hyperkalemia associated with ketorolac. Ann Pharmacother 1992;26:778-779.
150. Schoch PH, Ranno A, North DS. Acute renal failure in an elderly woman following intramuscular ketorolac administration. Ann Pharmacother 1992;26:1233-1236.
151. Steinberg RB, Tessier EG. Gastrointestinal bleeding after administration of ketorolac (letter). Anesthiology 1993;5:1146.
152. Zikowski D, Hord AH, Haddox JD, et al. Ketorolac-induced bronchospasm Anesth Analg 1993;76:417-419.
153. Chez MG, Soglin D. Ketorolac tromethamine (Toradol) treatment in children with acute migraine (abstract). Ann Neurol 1991;30:494.
154. Watcha F, Ramirez-Ruiz M, White PF, et al. Perioperative effects of oral ketorolac and acetominophen in children undergoing bilateral myringotomy. Can J Anaesth 1992;39:649-654.
155. Watcha F, Jones B, Lagueruela RG, et al. Comparison of ketorolac and morphine as adjuvants during pediatric surgery. Anesthesiology 1992;76:368-372.
156. Olkkola KT, Maunuksela EL. The pharmacokinetics of postoperative intravenous ketorolac tromethamine in children. Br J Clin Pharmacol 1991;31:182-184.
157. Oosterlinck W, Philp NH, Charig C, et al. A double blind single dose comparison of intramuscular ketorolac tromethamine and pethidine in the treatment of renal colic. J Clin Pharmacol 1990;30:336-341.
158. Schwesinger WH, Reynolds JC, Harshaw DH, et al. Transnasal butorphanol and intramuscular meperidine in the treatment of postoperative pain. Adv in Therapy 1992;9:123-129.
159. Diamond S, Freitag FG, Diamond ML, et al. Transnasal butorphanol in the treatment of migraine headache pain. Headache Quarterly 1992;3:164-171.
160. Wetchler BW, Alexander CD, Uhll MA. Transnasal butorphanol tartrate for pain control following ambulatory surgery. Curr Therap Res 1992;52:571-580.
161. Tobias JD, Rasmussen GE. Transnasal butorphanol for postoperative analgesia following paediatric surgery in a third world country. Paediatric Anaesth 1995;5:63-66.
Physician CME Questions
7. All of the following are complications encountered when administering sedation except:
A. crossover titration.
B. stacking.
C. shifting baseline.
D. cumulation.
E. recovery.
8. Which one of the following medications provides analgesia, amnesia, and sedation?
A. Fentanyl
B. Alfentanil
C. Propofol
D. Ketamine
E. Midazolam
9. Deep sedation is easiest to achieve with which of the following routes of administration?
A. Intranasal
B. Oral
C. Intravenous
D. Rectal
10. Emergence reactions with use of ketamine can be prevented or eliminated by:
A. lowering the dose.
B. IM administration.
C. giving atropine first.
D. giving fentanyl first.
E. giving midazolam.
11. Benzodiazepines affect the CO2 response curve by:
A. shifting the curve to the right.
B. shifting the curve to the right and increasing the slope.
C. shifting the curve to the right and decreasing the slope.
D. shifting the curve to the left.
E. shifting the curve to the left and increasing the slope.
12. All of the following are effects of ketamine except:
A. increased ICP.
B. increased BP.
C. increased sedation.
D. nystagmus.
E. bronchoconstriction.
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