Sedation and analgesia in pediatric patients for procedures outside the operating room

Richard F. Kaplan

and Charles I. Yang

ABSTRACT
Sedation and analgesia in pediatric patients for procedures outside the operating room are becoming more frequent as health care is being driven to be more cost effective and efficient. Although anesthesiologists may not be directly involved in sedation or analgesia outside of the operating room, there is a high likelihood that they will be asked by their institutions to be integrally involved in creating and supervising sedation policy given that the American Society of Anesthesiologists and the Joint Commission on Accreditation of Healthcare Organizations consider sedation and analgesia as part of a continuum ranging from minimal sedation to moderate sedation and analgesia, deep sedation and analgesia, and, finally, general anesthesia. Further, anesthesiologists will be asked to define, teach, and credential nonanesthesiology practitioners who perform deep sedation because these practitioners are now required to be qualified to rescue from general anesthesia.

Article outline Abstract RISKS OF SEDATION DEFINITIONS OF SEDATION REWRITING HOSPITAL POLICIES TO ASSURE COMPLIANCE WITH NEW DEFINITION AND STANDARDS SPECIFIC SEDATION TECHNIQUES ACKNOWLEDGMENT References Copyright Sedation and analgesia in pediatric patients for procedures outside the operating room are becoming more frequent as health care is being driven to be more cost effective and efficient. As an example, sedation for procedures at the Children's National Medical Center (CNMC) in Washington, DC, occurs in the emergency department (fractures, lacerations, 1500/year; diagnostic imaging area (CT scanning, MR imaging, barium studies; 2500/year; gastrointestinal (endoscopy, 1000/year); pulmonary (bronchoscopy; 100/year); cardiology (echocardiography, catheterization, 750/year; burn unit (dressing change); and in other areas (chest tube removal, bone marrow aspirations, etc.). Anesthesiologists may not be directly involved in most of these procedures; however, these procedures require various depths of sedation and analgesia. Some procedures, by nature (i.e., upper esophagoscopy, bronchoscopy) are associated with loss of airway reflexes and are at increased risks for complications. Although anesthesiologists may not be directly involved in sedation or analgesia outside of the operating room, there is a high likelihood that they will be asked by their institutions to be integrally involved in creating and supervising sedation policies, because the American Society of Anesthesiologists (ASA)6 and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO)19, 25 consider sedation and analgesia parts of a continuum ranging from minimal sedation to moderate sedation and analgesia, deep sedation and analgesia, and, finally, general anesthesia. Furthermore, anesthesiologists will be asked to define, teach, and credential nonanesthesiology practitioners who perform deep sedation, because these

practitioners must be qualified to rescue from general anesthesia (JCAHO).19 RISKS OF SEDATION The goals of pediatric sedation28 are to: (1) guard the patient's safety and welfare; (2) minimize physical discomfort; (3) minimize negative psychological responses to treatment by providing analgesia and anxiolysis and maximizing the potential for amnesia; (4) control behavior; and (5) return the child to a state in which safe discharge is possible. The foremost goal is to optimize patient safety by minimizing complications. There are numerous reports describing pediatric sedation complications,7, 16, 24, 32, 34 but few hard data on the frequency of adverse events compared with the total number of sedations. Further confounding factors in quantitating risks include variations in the age of the patient, underlying disease, level of sedation, type of drug, monitors, personnel, guidelines used for sedation, severity of event, and the experience and type of health care practitioner. A recent study reviewed contributing factors associated with adverse sedation events.11 Event information was derived from the US Food and Drug Administration (FDA) adverse drug event self-reporting system,15 the US Pharmacopoeia Reports of Adverse Events, and a survey of more than 1000 pediatric specialists (pediatric anesthesiologists, intensivists, and emergency physicians). Ninety-five incidents from hospital and non-hospital settings were reviewed. Outcomes included death (n=51), neurologic injury (n=9), prolonged hospital stay (n=21), and no harm (n=14). The majority (80%) of initial adverse events were respiratory in both hospital and nonhospital settings. Other causes of adverse sedation events included drug-drug interactions, inadequate monitoring, inadequate initial medical evaluation, lack of an independent observer, and inadequate management of resuscitation. Surprisingly, children who had adverse events in non-hospital settings were older and healthier than children who had adverse events in the hospital. There were more cardiac arrests, neurologic injuries, and deaths in the non-hospital settings compared with hospitals. In both hospital and non-hospital settings, successful outcome was related to the use of pulse oximetry compared with patients without any monitoring. Seventy-eight percent of adverse outcomes in patients who were not monitored resulted in death or neurologic injury, whereas 24% of patients who were monitored with pulse oximetry died or had neurologic injury. Most of the complications reported in this study were preventable. It can be concluded from the aforementioned anecdotal reports and studies on the risks of pediatric sedation that: All classes of drugs (sedatives, barbiturates, benzodiazepines, and narcotics) have caused problems, even when administered in the recommended doses. All areas using sedation have reported adverse events. Children 1 to 5 years of age are at most risk. Most had no severe underlying disease. Respiratory depression, obstruction, and apnea are the most fre quent causes of adverse events. Adverse events involved multiple drugs (especially three or more sedating medications). 6. Drug errors or overdoses, inadequate evaluation, inadequate monitoring, inadequate practitioner skills, and premature discharge were involved in adverse effects. 7. Most complications from sedation were avoidable.

It is clear that a dramatic decrease in risk has recently occurred and that progress in the areas just listed must continue. In particular, rigid application of sedation definitions and policies, combined with advanced airway and resuscitation skills, will improve outcomes of adverse sedation-related events.

DEFINITIONS OF SEDATION The new JCAHO definitions and standards on sedation are based on recommendations by the ASA.6 The JCAHO standards were updated January 1, 2001. The revised standards include new language pertaining to the definition of the continuum of sedation and anesthesia. The definitions of the four levels of sedation and analgesia are:19 Minimal sedation (anxiolysis) A drug-induced state during which patients respond normally to verbal commands. Though cognitive function and coordination may be impaired, ventilatory and cardiovascular functions are unaffected. In the authors' opinion, this level of sedation frequently is inadequate for completion of diagnostic or therapeutic procedures in children. Moderate sedation or analgesia (conscious sedation) A drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. No interventions are required to maintain a patent airway, and spontaneous ventilation is adequate. Cardiovascular function is usually maintained. Deep sedation and analgesia A drug-induced depression of consciousness during which patients cannot be easily aroused but respond purposefully following repeated or painful stimulation. The ability to independently maintain ventilatory function may be impaired. Patients may require assistance in maintaining a patent airway and spontaneous ventilation may be inadequate. Cardiovascular function is usually maintained. Anesthesia General anesthesia is a drug-induced loss of consciousness during which patients are not arousable, even by painful stimulation. The ability to independently maintain ventilatory function is often impaired. Patients often require assistance in maintaining a patent airway, and positive-pressure ventilation may be required because of depressed spontaneous ventilation or drug-induced depression of neuromuscular function. Cardiovascular function may be impaired (Fig. 1).

Figure 1. The American Society of Anesthesiologists (ASA) and Joint Commission on Accreditation of Healthcare Organizations (JCAHO) definition of sedation (effective 01/01/01).

REWRITING HOSPITAL POLICIES TO ASSURE COMPLIANCE WITH NEW DEFINITION AND STANDARDS Many professional societies have established practice guidelines for the care of children and adults being sedated for diagnostic or therapeutic procedures outside the operating room. These organizations include the ASA,5 the American Academy of Pediatric Dentistry,1 the American College of Emergency Physicians,4 the American College of Radiologists,30 and the American Academy of Pediatrics (AAP).3 The guidelines vary in their definitions, monitoring, and personnel requirements. In 1992, the Committee on Drugs of the AAP updated its Guidelines for Monitoring and Management of Pediatric Patients During and After Sedation for Diagnostic and Therapeutic Procedures.3 The guidelines are directed to nonanesthesiologists who provide sedation outside the operating room. The AAP guidelines were established with the consultation of the Committee on Standards, the Committee on Pediatric Anesthesiology of the ASA, and the Society for Pediatric Anesthesia. The AAP definitions and guidelines were the first sedation guidelines developed and endorsed by all the subspecialty committees of the AAP and are the most widely used sedation guidelines. Most hospital sedation policies are based on the AAP definitions and guidelines. The new JCAHO definitions and standards on sedation will require significant changes in these and most other hospital sedation and analgesia policies. The new JCAHO definition of deep sedation19 is different from the 1992 AAP definition.3 The AAP definition states that deep sedation includes the inability ... to respond purposefully to physical stimulation. The state and risks of deep sedation may be indistinguishable from general anesthesia. The new JCAHO and ASA guidelines6, 19, 25 clearly separate deep sedation (responds purposefully to repeated or painful stimuli) from general anesthesia (not arousable to painful stimuli). This clearer separation of deep sedation from general anesthesia allows anesthesiologists to more appropriately write guidelines and criteria for the practice of pediatric sedation. The general theme of the JCAHO standards19 is that moderate and deep sedation should meet standards similar to those for anesthesia (qualified personnel, preoperative evaluation, consent, monitoring, and recovery). Without giving specific details, the standards require appropriate credentials so the practitioner of moderate sedation can rescue patients from deep sedation and the practitioner of deep sedation can rescue patients from general anesthesia. It should be stated that JCAHO regulations must be followed in hospitals as well as surgicenters and all areas under the regulations of a hospital. These regulations do not necessarily apply when sedation is practiced outside the sphere of JCAHO (i.e., independent offices). The left side of Table 1 below contains all the changes to the JCAHO standards19 effective January 1, 2001. The right side of the table contains changes in the authors' (CNMC) policy that attempt to conform to these standards. Figure 2 shows CNMC's revised hospital sedation flow sheet which incorporates the new standards. Though a JCAHO consultant has reviewed and approved these changes, they have not been formally reviewed and the authors therefore do not know whether the new, amended hospital policy and revised sedation flow sheet satisfy the new standards.

Table 1. CHANGES IN STANDARDS AND IN HOSPITAL POLICY TO MEET THE NEW STANDARDS JCAHO Standards Assessment of Patients PE 1.8.1 Pre-sedation assessment for moderate/deep sedation Hospital Policy

1. Policy clearly states new definitions of sedation

2. Pre-sedation assessment clearly stated in hospital policy 3. Sedation flow sheet has area with pre-assessment evaluation PE 1.8.2 Patient is an appropriate candidate for planned anesthesia (moderate/deep sedation) 1. Policy refers to Physical Status (PS) classification ASA-PSI and II appropriate for sedation. ASA-PS III must have consult 2. Sedation flow sheet has ASA-PS documented PE 1.8.3 Immediate re1. Re-assessment, including vital signs, evaluation before anesthesia documented immediately before sedation induction (moderate/deep on sedation flow sheet. Signature verifies sedation) assessment PE 1.8.4 Recovery area admission and discharge assessment Care of Patients TX. 2 Moderate or deep sedation provided by 1. Qualified individuals include MD or Nurse Practitioner with privileges stated 1. Sedation flow sheet has area for admission vital signs and check boxes for discharge criteria

qualified individuals Training:

in policy

1. Administer agents appropriately

1. Practitioners and assistants must attend 2-hour educational course every 2 years given by anesthesia, pharmacy, and nursing staff. Course given every 6 months and available on videotape with handout through hospital library. Course describes monitoring, personnel, regulations, drugs, and techniques involved in pediatric sedation. Postcourse quiz given (> 80% correct for competency). Attendance records kept by nursing and hospital staff office (prerequisite for staff privileges in sedation)

2. Monitor level of sedation Qualifications: 2. Basic Life Support (BLS) certification for moderate sedation Pediatric Advance 1. Competency-based Life Support (PALS) certification when education, training, the goal is deep sedation (practitioners in experience in: Evaluation of cardiac catheterization, gastrointestinal patients Performing endoscopy, bronchoscopy, and sedation Qualified to rescue anesthesiology sedation service) . Policy Moderate Deep sedation states that BLS training should allow Deep General anesthesia for rescue from deep sedation . PALS should allow for rescue from general anesthesia TX. 2.1.1 Moderate or deep 1. Pre-assessment needs identified on sedation is planned and sedation flow sheet (allows for communicated among communication). Deep sedation is providers. Sedation care planned (per hospital policy) for all needs communicated patients undergoing cardiac catheterization, endoscopy,

bronchoscopy, and anesthesiology sedation service. Moderate conscious sedation is planned in all other areas TX. 2.2 Patient understands 1. Informed consent is required, is the options and risks. Education same form used for general anesthesia, is part of process and has a section specifically on sedation 1. Hospital policy states and sedation records clearly show vital signs (moderate sedation every 15 minutes; deep sedation every 5 minutes) and follow ASA Guidelines ( AAP Guidelines)

TX. 2.3 Patient's physiologic status is monitored

TX. 2.4 Post-procedure and 1. Sedation flow sheet has specific post-discharge statuses discharge criteria. Licensed independent assessed practitioner assesses patient TX. 2 Outcomes are 1. Q/A committee reviews sedation flow collected to improve patient sheet for compliance and complications care 2. Pilot project using prospective analysis of complications to improve system 3. Post-sedation telephone calls regarding complications and satisfaction

Figure 2. Children's National Medical Center (CNMC) sedation flow sheet, which attempts to address and comply with new JCAHO regulations. (From Children's National Medical Center, Washington, DC; with permission.)

SPECIFIC SEDATION TECHNIQUES A sedation treatment plan analyzing the requirements for analgesics, anxiolytics, or both, is necessary for each patient and will vary depending on the procedure and anxiety of the patient and family. Psychological techniques to allay anxiety (cuddling, parental support, warm blankets, a gentle reassuring voice, hypnosis) are extraordinarily useful adjuncts to the sedation plan. Despite recent improvements, many drugs used for sedation and analgesia (fentanyl 2 years, morphine 12 years, bupivacaine 12 years, propofol 3 years) are not approved by the FDA for use in young children (Physicians Desk Reference, 2001). The FDA Modernization Act of 1997 extended a company's patent by 6 months if they studied drug effects on children. This financial incentive only partially corrected the problem. As of December 2000, the FDA's pediatric rule24 stated that all new drugs must contain assessments of pediatrics patients (birth to 16 years) unless specifically exempt. Under this rule, the FDA can also require pediatric studies on presently marketed nongeneric drugs if used in more than 50,000 pediatric patients a year. These efforts should allow physicians to more safely care for patients. Local anesthetics play critical roles in analgesia for painful procedures and greatly reduce requirements for systemic narcotics. Application of local anesthetics to skin and mucosal membranes as well as local and regional blocks (including Bier blocks) are easily done. Maximum doses (lidocaine, 5 mg/kg to 7 mg/kg with epinephrine; tracheal lidocaine, 2 mg/kg; bupivacaine 2 mg/kg to 3 mg/kg with EPI; cocaine, 3 mg/kg; tetracaine, 1.5 mg/kg)20 should be calculated and not exceeded to avoid toxicity. The toxic effects of local anesthetics are additive. The total toxic dose must not be exceeded when used in combination. EMLA cream9 (Eutectic Mixture of Local Anestheticslidocaine 2.5% plus prilocaine 2.5%) is particularly useful for starting intravenous access, for lumbar punctures, and in facilitating skin infiltration. Mucosal administration must be avoided because systemic absorption can cause methemoglobinemia. TAC (tetracaine 0.9%; adrenalin 1:200,000; cocaine 4%7%) has been used in emergency rooms to repair skin lacerations. The cocaine component can cause arrhythmias and cardiovascular collapse if administered mucosally.13 Other combinations without cocaine (prilocaine-phenylephrine, bupivacainephenylephrine) have been shown to be as effective.28 Chloral Hydrate is one of the most commonly used sedatives in infants and young (<3 years) children.12, 20 Doses range between 25 and 100 mg/kg with a limit of 1 g per dose (2 g/day). It can be given orally or rectally. The main disadvantages are its onset of 30 to 60 minutes and prolonged duration (half-life, 10 hours in toddlers). Though it is said to have minimal respiratory effects, it can cause severe airway obstruction in children with obstructive sleep apnea.8 Chloral hydrate caused the death of a healthy infant who was given the drug at home prior to an office

procedure. The child died while being transported in a car seat. Apparently, the child became deeply sedated and was unable to maintain a patent airway.20 Proper supervision for all sedative drugs is mandatory. Possible toxic metabolites are not an issue when a single dose is administered.23 Pentobarbital20 is a long-acting barbiturate that causes minimal respiratory depression when used alone. Typical doses are 2 to 5 mg/kg intravenously. This drug is frequently used for nonpainful procedures (e.g., MR imaging). Though it has a long track record of safety, a major disadvantage is prolonged duration (46 hours) and slow wake up, which is associated with agitation. Midazolam's amnesic effect,33 short duration (half-life, 100 minutes), and ease of administration and reversibility (flumazenil, 0.1 mg/kg intravenously) make it particularly useful. The dose and onset times of midazolam are20: oral, 0.50.75 mg/kg, 1030 minutes; nasal 0.10.3 mg/kg, 10 minutes; rectal, 0.30.5 mg/kg, 20 30 minutes; intravenous doses start at 0.05 to 0.1 mg/kg. Sedative doses cause mild depression of the hypoxic ventilatory response. Severe respiratory depression can occur when narcotics and midazolam are used together.22 DPT [demerol (2 mg/kg), phenergan (1 mg/kg), thorazine (1 mg/kg)]12, 20 has been popular because it creates an immobile patient for painful and nonpainful procedures. It usually causes deep sedation and may cause loss of airway reflexes. It has a prolonged effect (48 hours) and severe side effects from the narcotic (hypoventilation) and phenothiazine (seizures, extrapyramidal effects).2, 29 This drug combination should be abandoned. Fentanyl is an example of a potent opioid (100 times morphine) with rapid onset, intermediate duration (3045 minutes), and reversibility (naloxone 0.010.1 mg/kg intramuscular or intravenously). It is very useful for short, painful procedures.20 The respiratory-depressant effect is much longer (4 hours) than its analgesic effect. It, as well as all narcotics, can cause apnea and chest wall rigidity when administered rapidly. Doses starting at 0.5 to 1 g/kg should be titrated to effect or a maximum of 5 g/kg. Respiratory depression can be severe in infants less than 3 months of age. Oralet (oral transmucosal fentanyl citrate) in doses of 5 to 10 g/kg is an effective sedative and useful preoperatively.26, 27 Oralet is now available in 100, 200, 300, and 400 g lozenges. The smallest child recommended for Oralet use is older than 2 years of age and heavier than 10 kg. The onset is usually 15 minutes. It is associated with nausea and vomiting. The authors find this useful as a premedication in painful procedures (burn dressing changes) in patients without intravenous access but not helpful in most nonpainful procedures. Nitrous oxide used alone in concentrations less than 50% is a useful conscious sedative agent, which causes analgesia.20 Verbal contact must be maintained with the patient.3 Appropriate monitoring and guidelines must be in place when nitrous oxide is used in conjunction with other sedatives. Ketamine12 is an excellent analgesic and amnesic that can be given intravenously (0.250.5 mg/kg), orally or rectally (610 mg/kg), or intramuscularly (2 mg/kg). It increases heart rate, blood pressure, and intracranial pressure. It can cause copious secretions and lead to laryngospasm. Ketamine in large doses can cause an incompetent gag reflex, deep sedation, or general anesthesia.10 To avoid complications, it is recommended that intraveuous ketamine be administered in acute care areas only and that the dose be limited to 0.25 to 0.5 mg/kg boluses intravenously with a maximum of 2 mg/kg over 20 minutes. An anesthe siologist should be consulted if higher doses are required.

Propofol's20 sedative and hypnotic effects, fast onset, and extremely short duration have made it useful for sedation in the operating room. Patient controlled sedation using infusions of 25 to 100 g/kg/minute is becoming popular in adults.18, 21 Propofol administered by anesthesiologists as a continuous infusion of 50 to 200 g/kg/minute intravenously is extremely useful in nonpainful pediatric procedures (e.g., MR imaging) when a quick wake-up is desirable. Its anti-emetic effect makes it particularly useful for outpatient procedures. Clinical experience shows that propofol sedation in children can lead to deep sedation and airway obstruction. Prolonged use of propofol in children has been associated with fatal metabolic acidosis31 and rhabdomyolysis.17 These problems have not occurred when used for short periods. There is a desire for clinicians other than anesthesiologists (e.g., intensivists, pulmonologists, etc.) to use propofol for sedation in pediatric patients.22 It must be appreciated that: (1) Propofol can unpredictably cause loss of airway reflexes even in sedative doses; (2) the 2001 Physicians' Desk Reference states that only intubated adult patients should receive propofol for sedation; and (3) the 2001 Physicians' Desk Reference does not recommend the use of propofol for sedation of pediatric patients in the intensive care unit. It also must be appreciated, however, that many drugs used in children are not recommended for such use in the Physicians' Desk Reference and that propofol may be the drug of choice for sedation in some circumstances. Until further studies on safety are published, the authors, therefore, recommend that propofol sedation be considered deep sedation or general anesthesia. Its use by nonanesthesiologists should be restricted to short procedures in intensive care units in intubated children only. Monitors, equipment, and personnel skilled in airway resuscitation and deep sedation must be immediately available.

ACKNOWLEDGMENT The authors thank Deirdre Savoy for her technical assistance. References 1. American Academy of Pediatric Dentistry. Policy statement on the use of deep sedation and general anesthesia in the pediatric dental office. May 1999www.aapd.org/memberinfo 2. American Academy of Pediatrics, Committee on Drugs. Reappraisal of lytic cocktail/demerol, phenergan, and thorazine (DPT) for the sedation of children. Pediatrics. 1995;95:598-602 MEDLINE 3. American Academy of Pediatrics. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. Pediatrics. 1992;89:1110-1115 MEDLINE 4. American College of Emergency Physicians. Clinical policy for procedural sedation and analgesia in the emergency department. Annals Emerg Med. 1998;31:663-677 5. American Society of Anesthesiologists. Practice guidelines for sedation and

analgesia by non-anesthesiologists. Anesthesiology. 1996;84:459-471 MEDLINE 6. ASA Committee on Quality Management and Departmental Administration (approved by the House of Delegates, Oct 1999, p 479): Directory of Members. Dallas, 2000 7. Aubuchon RW. Sedation liabilities in pedodontics. Pediatr Dent. 1982;4:171-180 8. Biban P, Baraldi E, Pettennazzo A, et al. Adverse effect of chloral hydrate in two young children with obstructive sleep apnea. Pediatrics. 1993;92:461-463 MEDLINE 9. Bjerring P, Arendt-Neilsen L. Depth and duration of skin analgesia to needle insertion after topical application of EMLA cream. Br J Anaesth. 1990;64:173-177 MEDLINE 10. Carson IW, Moore J, Balmer JP, et al. Laryngeal competence with ketamine and other drugs. Anesthesiology. 1973;38:128-133 MEDLINE 11. Cot CJ, Notterman DA, Karl HW, et al. Adverse sedation events in pediatrics: A critical incident analysis of contributing factors. Pediatrics. 2000;105:864-865 MEDLINE 12. Cot CJ, Strafford MA. The principles of pediatric sedation. Continuing Medical Educations. Boston, MA: Tufts University School of Medicine 1998 13. Dailey RH. Fatality secondary to misuse of TAC solution. Ann Emerg Med. 1988;17:159-160 MEDLINE 15. Food and Drug Administration, Subcommittee of the Anesthetic and Life Support Drugs Advisory Committee on Pediatric Sedation: Risk experience reported to FDA March 1994 16. Gilger MA, Jeiven SD, Barrish JO, et al. Oxygen desaturation and cardiac arrhythmias in children during esophagogastroduodenoscopy using conscious sedation. Gastroin-test Endosc. 1993;39:392-395 17. Hanna JP, Ramundo ML. Rhabdomyolysis and hypoxia associated with prolonged propofol infusion in children. Neurology. 1998;50:301-303 MEDLINE 18. Holas A, Krafft P, Marcovic M, et al. Remifentanil, propofol or both for conscious sedation during eye surgery under regional anaesthesia. Eur J Anaesthesiol. 1999;16:741-748 MEDLINE 19. JCAHO. Revisions to anesthesia care standards. Comprehensive Accreditation Manual for Ambulatory Care. January 1, 2001http://www.jcaho/standard/anesamb.html 20. Kaplan RF, Yaster M, Strafford M, et al. Pediatric sedation for diagnostic and therapeutic procedures outside of the operating room. In: Cot C, Todres D, Goudsouzian N, eds. A Practice Anesthesia for Infants and Children. (ed. 3)

Philadelphia: WB Saunders 2001 21. Li S, Coloma M, White PF. Comparison of the costs and recovery profiles of three anesthetic techniques for ambulatory anorectal surgery. Anesthesiology. 2000;93:1225-1230 MEDLINE 22. Lowrie UA, Weiss AH, Lacombe C. The pediatric sedation unit: A mechanism for pediatric sedation. Pediatrics [Electronic Journal]. 1998;V102: 23. Mayers DJ, Hindmarsh KW, Sankaran K, et al. Chloral hydrate disposition following single-dose administration to critically ill neonates and children. Developmental Pharmacologic Therapeutics. 1991;16:71-77 24. McCarver-May DG, Kang J, Aouthmany M, et al. Comparison of chloral hydrate and midazolam for sedation of neonates for neuro-imaging studies. J Pediatr. 1996;128:573-576 MEDLINE 25. Poe S, Nolan MT, Dang D, et al. Practice guidelines. Ensuring safety of patients receiving sedation for procedures: Evaluation of clinical practice guidelines. Jt Comm J Qual Improv. January 2001:28-41 26. Schutzman SA, Burg J, Liebelt E, et al. Oral transmucosal fentanyl citrate for premedication of children undergoing laceration repair. Ann Emerg Med. 1994;24:1059-1064 MEDLINE 27. Sharar SR, Bratton SL, Carrougher GJ, et al. A comparison of oral transmucosal fentanyl citrate and oral hydromorphone for inpatient pediatric burn wound care analgesia. J Burn Care Rehabil. 1998;19:516-521 MEDLINE 28. Smith GA, Strausbaugh SD, Harbeck-Weber C, et al. Prilocaine-phenylephrine and bupivacaine-phenylephrine topical anesthetics compared with tetracaineadrenaline-cocaine during repair of lacerations. Am J Emerg Med. 1998;16:121-124 MEDLINE 29. Snodgrass WR, Dodge WF. Lytic/DPT cocktail: Time for rational and safe alternatives. Pediatr Clin North Am. 1989;36:1285-1291 MEDLINE 30. Society of Nuclear Medicine Procedure Guidelines (version 2). www.guidelines.gov, February 15, 1999 31. Strickland RA, Murray MJ. Fatal metabolic acidosis in a pediatric patient receiving an infusion of propofol in the intensive care unit: Is there a relationship?. Crit Care Med. 1995;23:405-409 MEDLINE 32. 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;18:528-533 MEDLINE 33. Twersky RS, Hartung J, Berger BJ, et al. Midazolam enhances anterograde but

not retrograde amnesia in pediatric patients. Anesthesiology. 1993;78:51-55 MEDLINE 34. Vade A, Sukhani R, Dolenga M, et al. Chloral hydrate sedation in children undergoing CT and MR imaging: Safety as judged by American Academy of Pediatrics (AAP) Guidelines. AJR Am J Roentgenol. 1995;165:905-909 MEDLINE 35. Yaster M. Midazolam-fentanyl sedation in children: Case report of respiratory arrest. Pediatrics. 1990;86:463-467 MEDLINE