Factors relating to the patient Past experience As part of a detailed sedation history prio r to the procedure the previous experiences of the patient should be elicited. For example, a patient who became combative with a dose of oral midazolam would not be well served by r epeating that drug for another proce- dure. Th e sedation provider should also consider the anxiety level of the patient and family. Th e severely anxious patient will oft en need si gnifi cantly more pharmacological sedation where a relaxed patient may only need support or distraction (Mintegi et al., 2008). Child life or play therapists can play an integral rol e in determin- ing the optimal strategy for managing each patient \200\231s emotional and p sychological needs (Brewer et al., 2006, Stevenson et al., 2005). Several sedation monitoring scales are available for use dur- ing sedation activity. Unfort unately most have been designed for sedation depth monitoring in the intensive care unit (I CU) environment and, in order to test the depth of sedation, most of them require stimulati on and documentation of response. Th e University of Michigan Sedation Score (UMSS) (Box 20 .1 ) has been widely used and has undergone testing for validity. It is simple to use (repe atedly) during the course of a sedation activity (Malviya et al., 2002; Mason et al., 2004) Other sedation scores include the Allergies and adverse reactions It is imperative that a drug allergy and adverse reaction h istory be elicited prior to providing sedation. Reports of an allergy to a given SECTION 4 pain in specific populations and diseases 196 medication should be followed up with a history of the nature of the reaction. Drugs that w ere associated with truly allergic symptomatol- ogy (such as rash or wheezing) should be av oided. Families commonly interpret nausea or odd behavior aft er sedation as an allergy. In fact these issues are oft en commonly known reactions to a medication or procedure. Nausea and vomiting are always possible aft er sedation \200\224 particularly with medications s uch as ketamine (Langston et al., 2008). Anticipatory treatment with 5HT3 inhibitors or ste roids may decrease nausea and vomiting eff ects (Gan et al., 2007). Approximately 2% of pat ients will have paradoxical reactions to sedative medications such as midazolam or chloral hydrate (Sakurai et al. 2010). In these cases crying and combative behavior is elicited sho rtly aft er administra- tion rather than the desired sedation. Observational studies sugges t the use of the benzodiazepine reversal agent romazicon can be useful in truncating the be havior (Rodrigo, 1991; Weinbroum et al., 2001). Emergence agitation has been described duri ng the recovery phase aft er sedation (Karaaslan et al., 2006). In these cases, patients ma y be delirious and combative for a period of 10 to 30 min (rarely longer) on awakening from sedation. gastro-oesophageal refl ux disease should be considered a risk fac- tor for pulmonary aspir ation during sedation or anesthesia (ASA Committee on Standards and Practice Parameters, 20 11). General health Th e general health status for each patient who presents for sedation should be assessed. A general physical examination with focus on the airway, cardiovascular, and respiratory systems is critical. Th e ASA status classifi cation system categorizes individuals based on a general health (A SA Committee on Standards and Practice Parameters, 2011) (Table 20.2 ). Rather than focus o n any specifi c disease entity, the ASA status is intended to group patients together based on their health status in order to better assess the risk of anaes- thesia or sedation. Se veral studies have documented that the risk for any complication during sedation (desaturat ion episodes, airway obstruction, hypotension) rises by four- to fi vefold with increasing ASA status (Cravero et al., 2009; Krauss and Green, 2008). Airway issues As part of the pre-sedation evaluation, specifi c abnormalities of the airway should be noted. Th ese issues can be divided into two gen- eral categories: (1) the diffi cult functional airway, and (2) the dif- fi cult anatomical airway (Sims and von Ungern-St ernberg, 2012). NPO status and assessment of aspiration risk Th e ASA and AAP (ASA Task Force on Preoperati ve Fasting, 1999, Cote and Wilson, 2006) guidelines have historically taken the approach th at anyone receiving moderate sedation or deep sedation should be treated similarly to those receiving anesthesia regard- ing the timing of oral intake to prevent aspiration (Table 20 .1 ) Th e authors argue that since sedation depth is variable it is possible that patients will enter a state where they will have impaired airway pro- tective refl exes even when mo derated sedation is targeted. Th e diffi cult functional airway refers to those patients who are expected to have diffi c ulty exchanging air through their natural airway when sedated. Children in this category wo uld include those with severe sleep apnoea, obesity, recurrent croup, mark- edly enlarged t onsils, or those with congenital anomalies that make sleeping supine diffi cult or impossib le (Donnelly et al., 2000). When children in this category are sedated to the point of unco n- sciousness, airway obstruction would be much more common than in healthy children (Adewa le, 2009). In the UK, NICE guidelines recommend nothing by mouth (NPO) intervals of 2 h for clear liqu ids, 4 h for breast milk, and 6 h for solids (NICE, 2010) Fasting is not recommended for in dividu- als who will receive minimal sedation or moderate sedation where verbal contact wil l be monitored and maintained throughout. Table 20.2 Outline of the ASA physical status criteria Recently, two retrospective reviews have questioned the application of these guidelines to the fi eld of pediatric sedation. Th ese studies reviewed the charts of over 2400 emergency department pediatric sedation encounters and found no relationship between NPO dura- tion prior to sedation and adverse outcomes (Agrawal et al., 2003; Roback et al., 2004). In ligh t of this data, the American College of Emergency Physicians has developed its own set of f asting guidelines that diff ers signifi cantly from the ASA (Green et al., 2007). ASA class Description 1 A normal, healthy patient, without organic, physiological, or psychiatric disturbance 2 A patient with controlled medical conditions without signi \201 cant systemic e \200 ects 3 A patient having medical conditions with signi \201 cant systemic e \200 ects intermitten tly associated with signi \201 cant functional compromise In addition to the history of oral intake, the ASA Practice Guidelines for Perioperative Fa sting recommend that a history of 4 A patient with a medical condition that is poorly controlled, associated with signi \201 c ant dysfunction and is a potential threat to life Table 20.1 ASA fasting guidelines for sedation or anesthesia Food Hours of fasting required 5 A patient with a critical medical condition that is associated with little chance of surviv al with or without the surgical procedure Clear liquids 2 Breast milk 4 6 A patient who is brain dead and undergoing anesthesia care for the purposes of organ donati on Formula or light meal (no fat) 6 Full meal 8 E Th is modi \201 er is added to any of the above classes to signify a procedure that is bei ng performed as an emergency and may be associated with a suboptimal opportunity for risk m odi \201 cation Reprinted with permission from Practice Guidelines for Preoperative Fasting and the Use of Pharmacologic Agents to Reduce the Risk of Pulmonary Aspiration: Application to Healthy Pat ients Undergoing Elective Procedures: An Updated Report by the American Society of Anesthes iologists Committee on Standards and Practice Parameters, Anesthesiology , Volume 114, Issu e 3, pp. 495 \200\223511, Copyright 2011 of the American Society of Anesthesiologists. A copy of the full text can be obtained from ASA, 520 N. Northwest Highway, Park Ridge, Illi nois 60068 \200\2232573. Reprinted with permission of the American Society of Anesthesiology, Copyright 2013 of t he American Society of Anesthesiologists. A copy of the full text can be obtained from ASA, 520 N. Northwest Highway, Park Ridge, Illinois 60068 \200\2232573. CHAPTER 20 procedural sedation 197 Th e diffi cult anatomical airway subgroup includes patients in whom the visualization of t he airway with a standard direct laryn- goscopy is expected to be diffi cult. Th e sedation provider must note this issue even if intubation is not planned. Since defi nitive airway management with an endotracheal tube is the ultimate res- cue maneuver for children who are severely compromised during sedation, it is critical to anticipate if this is going to be a diffi cult intervention. A small or malformed mandible or a large tongue is oft en associ ated with diffi cult visualization of the glottis (Sims and von Ungern-Sternberg, 2012). Te eth that are protruding or particu- larly loose should be noted as they may hinder airway v isualization or be knocked free during manipulation. Furthermore any patient who has limite d neck mobility (such as trauma or burn patients) may be diffi cult to position in a manner that makes laryngoscopy possible. Finally any syndrome that results in an unusual facial a ppearance should be carefully noted as they may also be associated with an airway that is d iffi cult to visualize (Candido et al., 2000; Sarvet and Brewer, 2011). complications when they have surgery while experiencing a URTI (Homer et al., 2007). Th ese problems include oxygen desatura- tion, increased secretions, laryngospasm, and coughing. Th e risk period exists not only during the time the child has the URI, but for approximate ly 2 weeks aft er the child is symptomatically improved (von Ungern-Sternberg et al., 2010) . Fortunately, the frequency of severe complications (such as cardiac arrest, unexpected ad mis- sions, neurological injury, or death) have not been determined to be increased for thi s population (Tait and Malviya, 2005). It is prudent for sedation providers to consider the presence of a URTI when evaluating a child for sedation. If the procedure is going to be e xtended and/or if absolute movement control is required, it may be wise to reschedule an el ective intervention even if symptoms are limited to the upper airway. If sedation is provid ed for those with a limited URTI the post-procedural observation may need to be extended (H omer et al., 2007). Elective sedation should be postponed in children who have a fever, or those with a signifi cant cough and sputum production, rales, or wheezing. Developmental issues Th e neurodevelopmental status of the child should be noted prior to p lanning sedation. Requirements for sedation will change greatly for any child who is severe ly delayed and/or autistic (Pasternak, 2002). Furthermore induction of sedation can be very diffi cult in large patients who cannot, or will not, cooperate with starting an intraveno us (IV) line or taking oral medications (Rodrigo, 1995). Input from the family, primary car e givers, and/or Child Life Specialists can be critical in determining the best strategies for accomplishing sedation and the amount of intervention that will be required for a given procedure (Mintegi et al., 2008). Factors relating to the procedure When choosing a sedation medication or technique, the pro - vider should consider the time that the procedure will require to be accomplished. For dr ugs that are given as a single dose orally or nasally it is appropriate to match the durati on of the procedure with the duration of the sedative. For short acting sedatives that are given as infusions \200\224 such as propofol, short or long duration procedures are equall y easily accommodated. (Cravero et al., 2009; Wheeler et al., 2003) An essential aspect of sedation that must be considered is the presence or absence of pain with any given procedure. Many of the sedatives that are commonly used for sedation \200 \224 such as chlo- ral hydrate, benzodiazepines, and even propofol \200\224 have no analge - sic component (Jayabose et al., 2001; White and Romero, 2006). Options such as fentanyl, ketamine, and/or local anesthesia should be considered to complement the eff ects of the pu rely sedative medications in these cases (Singh et al., 2010). It should be noted however, that the addition of opiates to other sedatives will signifi - cantly potentiate the probab ility of apnoea or airway obstruction (Taylor et al., 1986). Cardiac and respiratory systems As already mentioned, the cardiac and pulmonary systems mus t be assessed prior to beginning sedation. In particular, patients with pulmonary hypertens ion may have signifi cantly adverse reac- tions to hypoventilation and increased carbon dio xide (CO 2 ), or hypoxia, which can easily occur with sedation (Carmosino et al., 2007). In children with complex anatomical defects, the degree of left -to-right or right-to-left sh unting may be changed by pulmo- nary or systemic vasodilation which can be a side eff ect o f seda- tion medications. Patients with complex congenital heart disease should be sedated by practitioners who understand their physiol- ogy completely and also understand the physi ological implications of sedation. Th e provider must consider the position that the patient will be in during the procedure. Position can aff ect access to the airway during the procedure. Most children will maintain an open airway in the supine position when deeply sedated as long as the neck can be sligh tly extended and jaw lift ed slightly forward (Shorten et al., 1995). If there is no access to the head, or if the head must be fl exed during a procedure or a scan, obstruction of t he airway will be much more likely (Isono et al., 2004). Care should be taken to avoid deep sedation unless the provider is ready to provide positive pressure ventilation. Airway res istance is actually decreased when a child is placed in the lateral decubitus or prone posi tion (Vialet and Nau, 2009). While defi nitive management of the airway may be more complic ated in these positions, spontaneous ventilation is oft en improved when compared to supine position if all other fac- tors are unchanged. Respiratory illness Although little data exists concerning the risk of sedation for patient s with asthma, data from anesthesia literature indicate that an asthmatic should be in the patient \200\231s best possible condition prior to beginning the procedure (Dones et al., 2 012). Management should include administration of all currently prescribed inhal- ers prior to the sedation and assuring that the child is not actively wheezing at the time of sedati on (Doherty et al., 2005). Th ere is little data to indicate the impact of an upper respiratory tract infection (URTI) on the success or safety of procedural seda- tion. URTIs are extremely common during the w inter months with as many as 20% to 30% of the pediatric population having symp- toms of an upper respiratory infection (Zaman et al., 1997). While it is simply not practical to canc el all procedures in this patient group, several studies have found an increase in airway a nd respiratory Sedation should be considered for procedures that are particu- larly emotionally stressful even if not necessarily painful, but where a brief period of unconsciousness will allow the patient to avoid an emotionally harmful experience. Oft en these procedures involve SECTION 4 pain in specific populations and diseases 198 invasion or examination of the genitalia (such as sexual abuse eval- uations) or voiding cy stourethrograms (Harari and Netzer, 1994). CAPNOGRAM End-tidal CO2 value \200\224 peak CO2 concentration normally at end of exhalation 60 Factors related to the sedation provider When moderate or deep sedation is induced at least one person, in addition to the clinician performing the procedure, should be present to he lp care for the patient (Cote and Wilson, 2006). Th is person \200\231s responsibility is t o monitor parameters such as pulse oxi- metry, heart rate, ventilation, and blood pressure and to assist in any supportive or resuscitation measures, as required. It is strongly enco uraged that this individual at a minimum be trained in paedi- atric basic life support. Cur rent knowledge of the emergency cart access/inventory as well as knowledge of how to activa te back-up systems is critical (ASA Task Force on Sedation and Analgesia by Non-Anesthesiol ogists, 2002; Cote et al., 2006). III 40 2 O C 20p II IV INSPIRATION EXPIRATION Figure 20.1 Key aspects of the capnogram. Components of the normal capnogram: I \200\224 (near zero baseline). Exhalation of CO 2 free gas contained in dead space. Sedation systems and sedation providers must recognize that the skill and training of provi ders of sedation varies greatly. Th e pro- vider should be readily able to rescue that pati ent from the poten- tial side eff ects of unexpected deepening sedation \200\224 which inc ludes loss of airway integrity and spontaneous ventilation. Th ose who provide deep sedatio n for children should be able to rescue a child from the possible eff ects of general anest hesia including defi nitive management of the airway and cardiovascular depression. II \200\224 (rapid sharp rise). Exhalation of mixed dead space and alveolar gas. III \200\224 (alveolar plateau). Exhalation of mostly alveolar gas. IV \200\224 (rapid sharp downstroke). Inhalation. Sedation drugs Hypnotic medications (sedatives) Chloral hydrate Chloral hydrate is a haloge nated hydrocarbon that has been used as a sedative for 90 years. Th e common doses used var y between 20 to 75 mg/kg orally. Most practitioners limit the dose to 100 mg/kg or a total dose of 2 g (Greenberg et al., 1991). Th e pharmacokinet- ics of chloral hydrate are somewh at prolonged. Th e peak eff ect may not be seen for 60 min and the plasma half-life is 4 to 9 h. Th e drug can result in prolonged sedation, particularly in infants, with peak eff ec t occurring well aft er the intended time of desired sedation (Cote, 1994, Malviya et al., 2000). On the other hand, the drug rarely results in respiratory depression (Sanborn et al. , 2005). Th e potential for respiratory compromise does exist however, and is most marked w hen combined with opioids or other sedatives. Deaths have been reported with doses of chlor al hydrate in the recommended range. Th is drug is of limited use for painful procedures si nce it lacks analgesic eff ect. In addition, the prolonged onset time and duration do not m atch well with many pediatric procedures. Emergence can be marked by behavioral disturbance s and agitation. It may still have a niche for use during radiology procedures such as magn etic resonance imaging (MRI) scans or for electroencephalograms. Th e drug is most eff ecti ve in infants and toddlers. Studies of sedation related critical events have shown that severe adverse outcomes are mos t common in venues where a good backup or rescue system is not available (Cote et al., 2000 a, 2000b, 2000c). Furthermore, sedation rescue has been shown to vary greatly between sedat ion providers and sedation settings (Blike et al., 2001). Given this evidence, it is logica l that a protocol for accessing the backup help for sedation critical events (hospital resu scitation team or emer- gency medical systems) should be clearly laid out and tested. Equipment needs for sedation Th e following equipment is necessary for sedation. A bag and mask for positive pressure ventilation, masks of appropriate size for any patient, a second backup source of oxygen, a variety of sizes of oral and nasal suction equipment. Vital signs, including oxygen saturation via pulse oximetry and heart rate, should be docum ented at least every 5 min in a time- based record. While the pulse oximeter measures oxyge nation it does not directly measure ventilation. Depending on the amount of oxygen that the patient is breathing, there can be signifi cant lag time between the onset of apnoea and o xygen desaturation (Langhan et al., 2012; Lightdale et al., 2006). In addition, a patient m ay experience signifi cant hypoventilation but have acceptable oxygen saturation if receivi ng high-fl ow oxygen. In the spring of 2012 the only manufacturer of chloral hydrate in the US ceased production. It is still available in most areas outside of the US including Canada, Europe, and Asia ( FDA, 2012). Th ere are several methods for monitoring ventilation. Th e most basic is direct observatio n of the patient \200\224 noting coordinated chest wall/abdominal wall motion. When observ ation is not possible, other methods such as a precordial stethoscope or capnography should be used. Midazolam Midazolam is a short-acting benzodiazepine that is widely used for anxiolysis and sedation. It has become particularly popular because of its short duration, predictable on set, and lack of active metabo- lites. Prominent eff ects include skeletal muscle relaxatio n, amnesia, and anxiolysis (Kain et al., 2000). Capnography measures and displays CO 2 levels sampled from the breathing interface of the p atient. For patients who are not intu- bated, a side stream detection technique is most oft en employed in which a small amount of gas (50 \200\223100 cc/min) is continuously sam- pl ed from the nasal cannula or inside of the mask on the patient. Apnoea is detected as soon as it occurs since it would result in an immediate loss of the expired CO 2 waveform (Figur e 20.1 ). Although originally formulated for IV use, the same medica- tion used orally has proven ver y successful in producing mini- mal to moderate sedation and amnesia (Malinovsky et al., 19 95; CHAPTER 20 procedural sedation 199 McMillan et al., 1992). Th e recommended oral dose is 0.5 to 0.75 mg/kg, with onset of seda tion in approximately 15 min. Off set occurs approximately 30 min aft er the peak eff ect i s noted. Oral midazolam is excellent for minor invasive procedures such as IV catheter plac ement or minor laceration repair when combined with local anesthesia. and induction of deep sedation/anesthesia may be achieved with 2 to 3 mg/kg in 95% of patie nts within 60 to 90 sec. Sleep may be induced with as little as 1.5 mg/kg and maintenance o f sedation is usually accomplished through the use of an IV infusion at 50 to 200 mcg/kg/mi nute. Recovery from the drug is faster than with any other IV sedative (2 \200\2233 min red istribution time) and the incidence of prolonged sedation or vomiting is extremely low. A d ose-related decrease in blood pressure is noted that is similar to that found with other an esthetics (Hertzog et al., 1999). Midazolam may be given by the intranasal route at doses of 0.2 to 0.4 mg/kg (Harcke et al., 1995). Onset time is intermediate between the oral and IV routes of administration (10 \200\22315 min). Th e eff ective- ness of this route of administration is well established as a premedi- cation for anesthesia and sedation for minor procedures but its use is limite d by signifi cant discomfort on administration. Recent stud- ies have noted that discomfort may be minimized through the use of a mucosal atomizer device for administration and pretr eatment with lidocaine on the nasal mucosa (Chiaretti et al., 2011). To reduce pain associated with injection a small dose of lidocaine (1 mg/kg) can be given t hrough the IV catheter prior to administra- tion or propofol can be given through a fast-fl owing IV line into a large vein. Some hospitals limit propofol use to anesthesia personnel however studies have described th e role of this drug in the ICU and emergency department (Barbi et al., 2003; Bassett et al. , 2003; Guenther et al., 2003). A recent report found excellent eff ectiveness with a low r ate of adverse events among sedation services using propofol for procedural sedation in chi ldren (Cravero et al., 2009). Airway interventions (intubation, bag-mask ventilation, or or al/ nasal airway insertions) were required in approximately one out of 65 sedated patients in this cohort. Th e authors of these and other studies emphasize that safe use of propofol for sedation requires proven competencies in airway management. IV midazolam is titrated to eff ect with fractionated doses of 0.05 to 0.10 mg/kg that may be repeated at intervals of 3 to 4 min to a total dose of 0.5 to 0.7 mg/kg. IV midazolam re aches peak eff ect in 2 to 3 min. Slow IV administration is recommended with close observat ion for respiratory depression. When combined with IV opioids for painful procedures, midaz olam has much more potent sedative and respiratory depressant eff ects when compared to its use as a single agent. Respiratory depression is rare with administration of midazolam in recommended doses regard less of the route of administration. Patients are generally relaxed and drowsy aft er admin istration. One of the most desirable side eff ects is the anterograde amnesia. Th e extent of this eff ect will vary with the age of the patient and the dose employed. Intravenous dexmedetomidine Dexmedetomidine (DEX) has become increasingly popular as a seda tive for radiological tests and procedures. Th is drug produces a sedated state with a smal l component of analgesia and little decrease in respiratory drive. DEX is an 2 agonist w ith a short half-life that is generally given in a bolus (0.5 \200\2231 mcg/kg over 10 min) followed by constant infusion (0.5 \200\2232 mcg/kg/h; Tobias and Berkenbosch, 2002; Tobia s et al., 2003). In order to maximize eff ectiveness, doses two to three times this amount have been reported in patients aged 1 to 8 years (Mason et al., 2008b). Certain underlying conditions or medications may prolong the eff ects of midazolam. Heparin decreases protein binding and increases the free fraction. Hepatic metabolism is inhibited by cimetidine which prolongs the elimination half-life. Patients in renal failure may have three times the free fraction of the drug sec- ondary to decreased protein binding. DEX has been reported for sedation of children on ventila- tors in the pediatric intensive care unit and as a sedative for procedures (Berkenbosch et al., 2005; Tobias and Berkenbosc h, 2002). In one series of over 700 patients given 2 to 3 mcg/kg as a loading dose followed by infusions of 1.5 to 2.0 mcg/kg/h, no respiratory adverse events were reported (Mason et al., 2008c). Caution is warranted as hypertension, hypotension, and brady- cardia have bee n reported side eff ects with DEX (Mason et al., 2008a, 2008b). Pentobarbital Pentobarbital has potent sedative hypnotic properties, but it has no analgesi c properties. Onset of action aft er IV administration is rapid, resulting in moderate \200 \223deep sedation within 3 to 5 min. Th e eff ective dose ranges from 3 to 6 mg/kg for over 98% of patients (Greenberg et al., 2000). Highest success rates are reported when the drug is used for patients under 12 years old and under 50 kg. Th e incidence of respiratory dep ression is less than 1% when pentobarbital is used as a sole agent at the recommended dosag es (Sanborn et al., 2005). Failure to achieve sedation rates have been reported in 1.2% of patients when confi ned to this population. Paradoxical reactions leading to agitation occu r in approximately 1% of patients. Pentobarbital is used in 14% of all sedations from an in ternational collaboration of over 30 institutions (Cravero et al., 2006). Given the collect ed data on this drug reviewed above, pento- barbital is a reasonable choice for patients un dergoing painless radiological procedures. Analgesic medications Fentanyl Fentanyl is a synthetic opioid which is 100 times more poten t than morphine. It has a very high degree of fat solubility that allows for very rapid pen etration of the blood \200\223brain barrier (Cote, 1994). Th e sedation eff ects are relati vely brief as the off set of the drug is dependent on redistribution rather than eliminatio n. Th e IV dose recommendation for fentanyl is 0.5 to 1 mcg/kg/ dose for procedures associated with signifi cant pain such as lum- bar punctures, bone marrow biopsies, bronchoscopies, m inor sur- gical procedures, and central venous catheter placement (Chiaretti et al., 2011). Fentanyl as a sole agent off ers excellent pain relief with mild sedation at these doses. Maximal eff ect occurs within 5 min when administered intravenously. Opioid eff ects last f or 30 Intravenous propofol Propofol is a 2, 6-diisopropylphenol compound that has potent sedative and hypnotic properties. Th e highly lipophilic nature of the drug requires that it be del ivered in a lipid emulsion. It can only be delivered by the IV route. Onset of action is ex tremely rapid SECTION 4 pain in specific populations and diseases 200 to 40 min. More oft en fentanyl is combined with sedatives to pro- vide an analgesic compon ent to sedation. Th ere are reports of its use in combination with benzodiazepines or propo fol for endos- copy (Langhan et al., 2012), hematology/oncology procedures (Langhan, 2011; Langhan et al., 2012), and invasive line placement (Chiaretti et al., 2011). described in 5% to 13% of children receiving ketamine (Bloomfi eld et al., 1993) while agit ation on emergence is noted in 12% to 22% (Kienstra et al., 2004). Respiratory drive is not inhibited by keta- mine and airway refl exes are largely left intact. A pooled analysis of ketamine sedation in over 8000 patients found an airway adverse event rate of less than 4% with the majority of events consisting of oxygen desaturation responsive to minimal interv ention (Green et al., 2009). Chest wall rigidity may occur with IV fentanyl dosing and is particularly problematic when the drug is rapidly administered (Scamman, 1983). Respiratory depression is markedly increa sed when the drug is combined with midazolam or other sedative (Kennedy et al., 1998). Nalo xone should be readily available when Fentanyl is administered. Nitrous oxide Nitrous oxide (N 2 O) was described for use as an analgesic/anaes- thetic ove r 100 years ago. It is a colorless, odorless gas that has analgesic, anxiolytic, and weak s edative eff ects. Th e drug may be delivered alone at concentrations of 30% to 70% for mode rately painful procedures (Zier et al., 2008) or in combination with a mild sedative at low er concentrations for similar eff ect (Litman et al., 1998a). Onset of sedation and analges ia occurs in minutes and is terminated rapidly when the gas is discontinued. N 2 O has mini mal cardiovascular and respiratory eff ects when not combined with a potent sedative or opi oid. It appears to cause a synergistic increase in sedation when used with other sedative o r analgesic medica- tions. (Litman et al., 1998b) Ketamine Ketamine is a phencyclidine derivative. It blocks N-methyl-D- aspartate receptors to produce intense analgesic and sedative quali- ties. Its use has been described for over 40 years as a sedative for painful procedures in children (Green et al., 1990, 2001). A fun c- tional dissociation is created between the cortical and limbic sys- tems of the brain. S pontaneous respirations and airway refl exes are maintained. Patients may exhibit random to nic movements of the extremities that make this drug inappropriate for procedures where the patient must lie perfectly still (i.e. computed tomography and MRI scans). Ketamine genera lly causes an increase in heart rate, blood pressure, cardiac output, and intracranial pres sure. Oral secretions may be mildly increased although a recent meta-anal- ysis of ketamine data suggests an increase in complications when combined with anticholinergics (Green et a l., 2009). Ketamine has bronchodilator qualities making it ideal for use in children with i ssues relating to bronchospasm. Current systems for administering N 2 O include continuous fl ow systems that deliver anywh ere from 0% to 70% N 2 O and older \200\230demand valve \200\231 systems that use a premix ed 50% mixture of N 2 O in oxygen. Demand valve systems require the patient to initiate neg a- tive pressure to open the inspiratory valve of the system (Farrell et al., 2008). Th is can be diffi cult for some toddlers and thus the continuous fl ow systems are preferable fo r the youngest patients. Scavenging systems should be available for N 2 O at any location t hat it is being delivered (Rowland et al., 1995). Recent studies have shown excellent safet y outcomes (no apnoea or airway interven- tions in over 5000 patient encounters) for 70% N 2 O administered by continuous fl ow to pediatric patients (Farrell et al., 2008; Zier and Liu, 2011). Ketamine can be given orally at a dose of 5 to 6 mg/kg. Onset of sedation occurs in 15 to 3 0 min and eff ects may be prolonged with this route \200\224 lasting 3 to 4 h (Rowland et al., 1995; Srinivasan et al., 2012). Intramuscular (IM) ketamine reaches peak blood levels and clinical eff ect in 5 min aft er a 3 to 5 mg/kg IM injection. Recovery from dissociatio n occurs within 15 to 30 min with coherence and purposeful neuromuscular activity returning in 30 to 120 min (Sanderson, 1997). Th ere are two formulations for ketamine \200\224 10 mg/ml and 100 mg/ml. Th e more concentrated formulation of ket- amine is preferred for IM a dministration. IM ketamine has been widely reported in the pediatric emergency medicine lit erature for sedation during painful procedures such as facial laceration repair, fracture r eduction, abscess incision and drainage, and foreign body removal (Bloomfi eld et al., 1993 ; Sanderson, 1997). Ketamine can also be given intramuscularly to uncooperative patients in whom IV or oral administration of ketamine or other sedatives is not pos- sible (Pershad e t al., 2007). Reversal agents Reversal agents should be available when performing sedation with a benzodi azepine or opioid. Flumazenil can be used to reverse the eff ects of benzodiazepines and sh ould be immedi- ately available when using benzodiazepines for sedation. A dose of 0.01 mg/ kg should be administered initially. Although rare, re-sedation may occur and additional do ses of fl umazenil may be required. Naloxone (Narcan ) is an opioid antagonist and can be given intravenously, intramuscularly , or subcutaneously. Th e drug should be given in a slowly titrated manner when possible. T h e standard preparation contains 0.4 mg/cc of naloxone. Th e dose for children is 0.1 mg/k g for children under 20 kg. Th e dose for children over 20 kg is 2 mg (Table 20.3 ). Ketamine may be given in small IV doses of 0.5 to 1 mg/kg to produce rapid and profound sed ation with analgesia. Peak concen- trations occur within 1 min and allow almost immediate i nduction of clinical eff ects and lasts 15 min if no additional doses are given (Clements a nd Nimmo, 1981). Painful procedures are tolerated well following administration of ketamine because of its profound analgesic properties. IV ketamine is ideal for painful procedures such as burn debridement, foreign body removal, abscess incision, and orthopedic procedures with a success rate over 98% (Baculard et al., 2007; Kienstra et al., 2004). Discharge Th e criteria for discharge from a sedated procedure should include stable vital signs; pain under control; a return to the level of con- sciousness that is similar to the baseline for that patient; adequate head control and muscle strength to maintain a patent a irway; nau- sea and/or vomiting should be controlled; and the patient should be adequately hydrated. Adverse events under ketamine sedation are similar regard- less of the route of administrat ion. Nausea and vomiting has been CHAPTER 20 procedural sedation 201 Table 20.3 Sedation regimens Propofol 50 \200\223200 mcg/kg/min IV Non-painful procedures Pentobarbital 3 \200\2236 mg/kg IV or PO Radiology imaging Midazolam 0.5 \200\2230.75 mg/kg PO 0.025 \200\2230.5 mg/kg IV 0.2 mg/kg intranasal Anxiolysis, premedication, procedural sedation along with a topical anesthetic or opioid Chloral hydrate 50 \200\223100 mg/kg PO Imaging, EEG, not commercially available in the US. Prolonged sedation Dexmedetomidine 0.5 \200\2232.0 mcg/kg bolus (over 10 min) followed by 1 \200\2232 mcg/kg/h infusion. For procedural sedation Propofol with fentanyl Fentanyl 1 \200\2232 mcg/kg IV with Propofol.5 \200\2231mg/kg boluses Painful procedures Midazolam with fentanyl Midazolam 0.020mg/kg IV Fentanyl 1 \200\2232mcg/kg IV Painful procedures Ketamine 3 \200\2234 mg/kg IM 1 \200\2232 mg/kg IV Painful procedures Even when these criteria are used children have been found to be discharged with residual s edation eff ects (Malviya et al., 2004). In particular, children who have received a large dose of long-acting sedation medications (such as chloral hydrate) are very prone to re-sed ation aft er vigorous eff orts are made to rouse them. Th ese patients should not be discha rged until they have demonstrated that they can maintain wakefulness for 15 min or more. undergo a large number of procedures and tend to focus on the process over time. Conclusion s: procedures result in fear and anxiety and may involve pain as well in children. Sedation is not always required, but may help eliminate unwanted long-term behavioral and psycholog ical outcomes from invasive procedures. Th e need for pharmacological intervention should b e determined by the developmental status, the level of anxiety, and context of the pro- ced ure. Th e formation of expert teams of providers is critical to optimal outcomes. Case example Presentation : an 8-year-old, 35-kg girl with acute lymphoblastic leukemia presents for a l umbar puncture with intrathecal chem- otherapy administration. Management : the child is he ld in mother \200\231s arms (as is her pref- erence) while an IV infusion begun. She is giv en 0.5 mcg/kg of fentanyl followed by 1 mg/kg of propofol as a slow IV push. As she starts to become sleepy she is placed in a left lateral decubi- tus position with nasal cannula ox ygen equipped with end-tidal CO 2 monitoring. A pulse oximeter and blood pressure cuff are also placed. Aft er 3 min she is deeply sedated as evidenced by no response to voice and mi nimal movement when 2 mg of 2% lidocaine is infi ltrated subcutaneously in the L3 to L4 int erspace. She receives no further sedation and does not move during the lumbar puncture proc edure. Heart rate is steady at 90 and her pulse oximeter remains at 98%. Breathing is parti ally obstructed and is easily improved with minimal jaw thrust \200\224 not required aft e r about 2 min. She wakes up 9 min aft er procedure is com- pleted and eats an ice lolly at that point. Comment : this case is an example of a painful procedure where an analgesic (fe ntanyl) is used in conjunction with the sedative (propofol). Th e combination results in de ep sedation which can (and does in this case) result in partial loss of airway tone requir- ing some airway manipulation. Th e sedation is very eff ective and results in movement con trol that would likely not be possible if analgesic were not added to the propofol. Of note , the providers allowed the child to choose how she would approach induction. Th is is part icularly important for children such as this who will References Adewale, L. (2009). Anatomy and assessment of the pediatric airway . Paediatr Anaesth , 19 (Suppl.1), 1 \200\2238 . Agrawal, D., Manzi, S. F., Gupta, R., and Krauss, B. (2003). Preprocedural fasting state an d adverse events in children undergoing procedural sedation and analgesia in a pediatric em ergency department. Ann Emerg Med , 42 , 636 \200\223646 .