- Email: [email protected]
Midazolam as a pediatric premedicant in the ambulatory setting
Midazolam as a Pediatric Premedicant in the Ambulatory Setting BEVERLY M. MOLINE, MS, RN, CPAN REX A. MARLEY, MS, CRNA, RRT In the preoperative setting, the nurse is responsible for the comprehensive evaluation and preparation of the patient. Among these activities, the administration of various premedications to achieve a physiological (eg, raise gastric fluid pH) or psychological (eg, reduce apprehension) effect is commonplace. Midazolam, a benzodiazepine, is one of the more popular medications used preoperatively for its anxiolytic properties. Several stu dies have evaluated the variety of routes by which midazolam can effectively be administered to the pediatric patient. A review of midazolam as a premedication specific to the pediatric population in the ambulatory setting is presented. 9 1997 by American Society of PeriAnesthesia Nurses.
NNUALLY, over 25 million anesthetics are administered in which the perianesthetic nurse is entrusted to provide care. A significant portions of these anesthetics are for children in the ambulatory setting. When a child enters the treatment area, ie, surgical or procedural, two goals are foremost in delineating the patient's care. The first goal is to protect the child and assure a safe therapeutic experience. Secondly, the psychological well-being of the child should be fostered and maintained. The circumstances
A
Beverly M. Moline, MS, RN, CPAN, is the Staff Development Coordinator for Surgical Services, and Rex A. Marley, MS, CRNA, RRT, is a Staff Nurse Anesthetist in the Department of Anesthesia, Poudre Valley Hospital, Fort Collins, CO. Address correspondence to Beverly M. Moline, MS, RN, CPAN, Staff Development Coordinator for Surgical Services, Poudre Valley Hospital, 1024 Lemay Ave, Fort Collins, CO 80524. 9 1997 by American Society of PeriAnesthesia Nurses. 1089-9472/97/1201-0009503.00/0
42
surrounding the child's admission are stressful, not only for the patient but also for the family.1 In an attempt to minimize stress and familiarize the patient and family to the anticipated sequence of events, many institutions offer specialized orientation programs. These preoperative programs are designed to reduce parental and patient trepidation by providing relevant perioperative information (eg, directions, anticipated schedule, instructions for physiological preparation of the child, expected postoperative course, and discharge instructions), offering reassurance, and enhancing coping skills through familiarity. Within these programs, a variety of techniques are incorporated to prepare the child for the operative procedure. Educational tools utilized for these instructional sessions include facility tours, puppet shows, audiovisual programs (eg, slide shows or videotapes), and illustrated pamphlets (eg, coloring or game books). Using either a dress rehearsal or a photographic depiction, children may have an orientation session with the equip-
Journal of PeriAnesthesia Nursing, Vol 12, No 1 (February), 1997: pp 42-47
M I D A Z O L A M FOR PEDIATRIC P R E M E D I C A T I O N Table 1. Commonly Cited Indications for Premedication
Promote amnesia Provide analgesia to the patient in pain Promote antisialagogue (airway drying) effect Decrease patient apprehension (anxiolysis) Cause blunting of autonomic nervous system reflex responses Aid the induction and maintenance of anesthesia Create prophylaxis against: allergic reactions chronic illnesses infections nausea and vomiting pulmonary aspiration of gastric contents vagal stimulation Promote patient cooperation during regional anesthesia Increase pH of gastric fluid Reduce anesthetic requirement Reduce volume of gastric content Sedation
ment that is commonly used in the perioperative setting, eg, blood pressure cuff, thermometer, anesthesia face mask, anesthesia machine, intravenous therapy equipment, and postoperative oxygen therapy devices. Reflective of an effective program will be a well-prepared child who is physiologically and emotionally ready for the treatment experience. The value of such a pro gram is well-accepted in reducing parental and patient stress, and facilitating acceptance and co operation on the child's part. 27 When circumstances prevail so that proper preparation of the child takes place, anxiolytic premedication may not be necessary. When parental separation does not occur, eg, when a parent accompanies the patient into the operating room and participates in the induction of anesthesia, the need for premeditation is reduced, s Unfortunately, although these programs are invaluable, they, along with the support of trusted care givers and skilled health care providers, may not sufficiently allay the child's anxiety from the time of parental separation through the induction of anesthesia. ROLE OF PHARMACOLOGIC PREMEDICATION
Traditional indications for administering premedications vary according to the desired physiological or emotional response (Table 1). The use of premedications (ie, anxiolytics, hypnotics, and sedatives) in children continues to be controversial. 4'9 The concern about giving anxiolytic and sedative premedications relates to their po-
43
tential to delay discharge, thus increasing cost for the ambulatory surgical facility. 1~ Oftentimes, despite intensive educational and emotional preparation of the child, drug administration may be desirable to modify psychological responses before anesthesia. With the contemporary anesthetizing agents and techniques, anxiolytic agents (such as midazolam), are indicated principally for the child's emotional protection and not as a supplement to the anesthesia. 9 The estimate of children who will benefit from anxiolytic premedication approximates 20%. 9 Children come to the preoperative care area in assorted stages of development with unique personalities, a wide variety of past surgical experiences, and different perceptions of health care providers. Some children are curious while others are passive, some are adventurous while others cautious, and some are cooperative while others are challenging. The use of pharmacologic agents in preparing the child for surgery or another procedure should never become routine, rather, it should be determined on an individual need and desired benefit. 5'~3The practitioner must weigh the required effect of the medication (eg, a cahn cooperative child), against potential negative impacls (such as prolonged sedative influence). The perfect anxiolytic agent would be readily accepted by the child, would be absolulely dependable with rapid onset and otTsel, and would not produce excessive sedation or cardiopulmonary depression. 5 To date there is no drug that is considered the ideal premedicant for children and none is expected s o o n . 14 Each anxiolytic premedication (eg, diazepam, flurazepam lorazepam, midazolam, propranolol, temazepam, timolol, triazolam), has its own advantages and disadvantages. The practitioner's choice of premeditation is influenced by the procedure being performed, their familiarity with the drug, the facility's staffing, and the access to proper equipment because some medications and delivery routes require close observation by skilled staff utilizing continuous monitoring capabilities. ANXIOLYSIS
Anxiety is an emotion familiar to all of us at some point in our lives. It is the unpleasant emotional state consisting of psychophysiological responses to anticipation of real or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. 15 Patients of appropriate age will nat-
44
MOLINE AND MARLEY
urally possess a degree of anxiety about the impending operation. The most common reason for premedicating patients is to allay this anxiety. Infants less than 1 year of age do not require anxiolytic premedication. 16'17 As the child matures, anxiolytic medication has been shown to help reduce preoperative anxiety and to minimize posthospitalization behavioral changes. 18 The goal of anxiolysis is to make separation less stressful for the parent and child and to have a calmer, more cooperative child during the induction of anesthesia without prolonging recovery. Several studies have shown midazolam's ability to provide these outcomes.19-25 M I DAZO LAM
Midazolam is a highly lipophilic, short-acting, water-soluble benzodiazepine that acts on selective receptors in the brain, brain stem, and spinal cord. As with other benzodiazepines, the effect of midazolam includes amnestic, anticonvulsant, anxiolytic, hypnotic, muscle-relaxant, and sedative properties. The sedative effects are synergistic when midazolam is coadministered with opioids and other hypnotic agents. The stress response is inhibited by a reduction in the levels of circulating catecholamines. Midazolam is metabolized by the liver and excreted in the urine. For this reason, the dose of midazolam should be reduced in patients who have severe liver disease. When compared with diazepam, midazolam is three to four times as potent, 26 has a more rapid onset of action, and has a shorter duration of effect.
Advantages of Midazolam In addition to providing anxiolysis as a premedicant for general and regional anesthesia, midazolam is appropriately popular as a coinduction agent for general anesthesia. Its acceptance continues for conscious sedation as an adjunct to procedures performed under local anesthesia or for diagnostic purposes. Midazolam offers the most versatile delivery methods and has become widely accepted as a sedative for the pediatric population. 9'27 It produces antegrade and retrograde (however, less predictably if at all 28) amnesia, and therefore limits recall of potentially traumatic events. 27 A rapid onset of action and a 2 to 4 hour elimination half-life make midazolam an ideal outpatient agent 14 that has not been found to increase discharge t i m e s . 19-25
Disadvantages of Midazolam As with any sedative agent, the potential for adverse side effects exists. Midazolam produces relatively mild and infrequent cardiovascular (ie, hypotension) and respiratory (ie, ventilatory depression, hypoxemia, apnea) effects. In the elderly or debilitated patient and in those patients in which careful dosage and titration of the drug has not been followed, severe cardiopulmonary consequences have been observed. Excessive and prolonged sedation may occur in rare patients. Relative overdosage of midazolam may be counteracted with the administration of the only specific benzodiazepine receptor antagonist in clinical use, flumazenil. A useful summation of the perioperative applications for flumazenil can be found in an article by Geller and Halpern. 29 ROUTES OF MIDAZOLAM ADMINISTRATION Methods of midazolam administration are numerous and include intramuscular, intravenous,
nasal, oral, rectal, and sublingual. Each method of drug administration manifests individual advantages and disadvantages. The preferred route of midazolam administration will be dependent on the child's chronological age, maturation level, previous health care experience, expertise of the health care providers, and time until parental separation. A sufficient time interval should be anticipated and allowed for midazolam to exert its desired effect. Administering the drug at the appropriate time in the patient' s preanesthesia care is as important as the drug choice or administration route. See Table 2 for a summary of dosage considerations for the various routes of administration. 5J4,25,3~176
Intramuscular In meeting the pharmacological needs of a child, the intramuscular route is not desirable because of the anxiety and pain associated with
Table 2. Dosage Considerations for Midazolam Route
Dosage
Onset of Effect
Intramuscular Intranasal
0.07 to 0.1 mg/kg TM 0.02 to 0,03 mg/kg 2~
30 to 60 min TM 2.52sto 10 min 14'25
Intravenous Oral
0.05 mg/kg s'3~ 0.5 mg/kg 24'31-33
1 to 2 min 10 to 45 m i n 23'24'31'34'35
Rectal
0.5 to 1 mg/kg 36'37
1037 to 30 rain 39'4~
MIDAZOLAM FOR PEDIATRIC PREMEDICATION the injection. 41 It offers the advantage of being reliable and providing a rapid onset of action. In children with congenital cyanotic heart disease, intramuscular injections administered preoperatively can cause crying and sufficient distress to result in a decrease in oxyhemoglobin saturations (SpO2). 42 This study further noted that orally administered midazolam produced anxiotysis and sedation without a decrease in SpO2.42 Reducing the volume of midazolam injected by using the more concentrated solution, 5 mg/mL, is appropriate to consider in the larger child. The less concentrated midazolam, 1 mg/mL, may be indicated in smaller children to administer a more precise volume of drug. lntranasal The nasal route provides easy and relatively painless access for drug instillation with rapid absorption and onset of action. Medications absorbed in this manner avoid first-pass metabolism through the liver and degradation in the gastrointestinal tract. 43 Nose drops provide better coverage of the walls of the nasal cavity when compared with nasal sprays. 44 Midazolam, 5 mg/mL concentration, can be administered in alternating nares over 30 to 60 seconds. ~ Allhough easily accessible, medications can cause nasal burning q3 and an unpleasant taste. In addition, and the nasal route of drug instillation is often met with resistance in children. 45 In theory, it is possible for intranasally administered midazolam to be carried along neural connections between the nasal mucosa and the central nervous system by way of the olfactory nerves leading to a neurotoxic effect. 46 A comparison of intranasally and orally administered midazolam found both reduced anxiety in 10 minutes without clinically significant side e f f e c t s . 43 Because recreational drugs are often taken intranasally, social concerns have been raised regarding the intranasal administration of drugs in children. 4~ Intravenous Once venous access has been established, this route offers the clear advantage of reliable, rapid onset of effect with or without the cooperation of the child, unlike oral administration that requires patient cooperation. However, establishing venous access before induction can be a challenge and potentially traumatic to the frightened or uncooperative child. In addition, some procedures
4s
(ie, ventilation tubes in the ears of an otherwise healthy child), do not necessitate venous access. Oral The oral route of drug administration is most desirable because it is the least threatening, but it can pose a challenge in the uncooperative child. It also leaves the dosage vulnerable to partial administration should the child decide to spit out an unknown volume of medication. For this reason, it is suggested the child be encouraged to consume as much as possible with the first swallow. 27 An assortment of flavorings, eg, punch, apple juice, cherry or chocolate syrup, chocolatecherry syrup, gelatin, fruit-flavored concentrates, cola, and acetaminophen elixir, have been used to disguise the unpleasant taste of the intravenous form of midazolam. 4'43 Midazolam in the 5 rag/ mL concentration should be diluted with an equal volume of the flavored diluent. Bioavailability of oral midazolam is greatly reduced by the firstpass hepatic effect and therefore prescribed oral doses are considerably greater than that of intravenous doses to achieve the same effect) ~ In a study comparing oral midazolam (0.5 rag/ kg) with oral ketamine (5.0 mg/kg), the level of sedation and anxiolysis was noted to be similar in healthy children at 20 minutes after dosing) ~ However, a difference was noted in discharge readiness between these two groups with the midazolam group being discharged 20 minutes sooner than the ketamine group) ~ When increasing the dosage of midazolam to 0.75 mg/kg or 1.0 mg/kg, there is a likelihood of additional side effects such as increased sedation, 24 loss of balance and head control, blurred vision, and dysphoric reactions) 2 Additionally, these studies tbund no advantage of the higher dosages of midazolam over 0.5 mg/kg. Proper timing of medication administration to produce effective sedation at the moment of separation can be a major challenge in today's fastpaced and unpredictable settings. The minimum time interval between drug administration and parental separation has been found to be acceptable in as little as 10 minutes, 34 yet it may take up to 30 minutes for optimal sedation to occur. 23 It was postulated that the more rapid effect of 10 minutes was secondary to transmucosal absorption of midazolam mixed with a viscous chocolate-cherry syrup that coated the oral mucosa. 34 Sublingual absorption, a popular route for admin-
MOLINE AND MARLEY
46
istering m a n y medications, has been suggested for m i d a z o l a m in a dose a p p r o x i m a t e l y o n e - h a l f o f the n o r m a l oral dose. 46 M i d a z o l a m 0.2 m g / k g administered sublinqually was as effective and better accepted in children than intranasal dosing. 48 H o w e v e r , . with m i d a z o l a m ' s unpleasant taste, it m a y be difficult to gain the cooperation o f children.
Rectal Rectal administration o f m i d a z o l a m offers easy access without requiring cooperation o f the child. A b s o r p t i o n through the rectal route m a y be via the superior h e m o r r h o i d a l veins that drain into the portal circulation and thus expose the drug to first-pass hepatic effect. 49 The appropriateness o f delivering m e d i c a t i o n in this m a n n e r is age related and is appropriate up until the age when cultural influence stresses " b o d y p r i v a c y " and this approach b e c o m e s less acceptable to the patient. It is ideal for the y o u n g infant w h o can r e m a i n in a p a r e n t ' s arms until separation is necessary. Rectal m i d a z o l a m can be instilled with a 14-French lubricated suction catheter 37 placed 3 to 6 c m into the r e c t u m and followed by a 2 m L flush o f air. 14'39 M i d a z o l a m is prepared b y diluting with saline to a concentration o f 2 mg/ m L up to a given v o l u m e o f 10 mL. If the appro-
priate concentration, o f up to 1 mg/kg, requires a larger total v o l u m e then the m i d a z o l a m should be given undiluted (5 m g / m L ) . 37 D o s a g e s o f 0.5 m g / k g and 1.0 m g / k g did not delay e m e r g e n c e or p r o l o n g discharge. 37'38 W h e n c o m p a r i n g rectal m i d a z o l a m (0.35 mg/ kg) and d i a z e p a m (0.70 mg/kg) with placebos, both m e d i c a t i o n groups had significantly better anxiolytic and sedation scores. 4~ The m i d a z o l a m group exhibited better acceptance o f the m a s k with 90% o f the group rated as g o o d acceptance. 4~ SUMMARY
O n c e it has been determined that the administration o f a preoperative sedative w o u l d be beneficial for the pediatric patient, m i d a z o l a m is a p o p u l a r choice and offers several advantages. It has rapid onset, relatively short duration o f effect, and m a y be administered in a variety of routes. Ease o f parental separation is a benefit to the child and parent. A c c e p t a n c e o f the anesthesia face m a s k p r o m o t e s a rapid and s m o o t h inhalation induction. W h e n administered at recomm e n d e d dosages, m i d a z o l a m remains relatively free o f significant side effects and does not lead to p r o l o n g e d patient stay in the a m b u l a t o r y setting.
REFERENCES 1. Zukerberg AL: Perioperative approach to children. Pediatr Clin North Am 41:15-29, 1994 2. Orr R, Lynn A: The combative child. Curr Rev Nurse Anesthetists 14:74-84, 1991 3. Holzman RS: Outpatient anesthesia for children. Curr Rev Nurse Anesthetists 17:125-136, 1994 4. Steward DJ: New thoughts on preparation and premedication of children. Curr Rev Nurse Anesthetists 17:173-180, 1995 5. Cot6 CJ: Changing concepts in preoperative medication and "NPO" status of the pediatric patient. ASA Refresher Courses in Anesthesiology 22:101-116, 1994 6. Maligalig RM: Parents' perceptions of the stressors of pediatric ambulatory surgery. J Post Anesth Nurs 9:278-282, 1994 7. Pauly B: Operation fascination. J Post Anesth Nurs 10:89-93, 1995 8. Larosa-Nash PA, Murphy JM, Wade LA, et al: Implementing a parent-present induction program. AORN J 61:526-531, 1995 9. Hannallah RS, Epstein BS: The pediatric patient, in Wetchler BV (ed): Anesthesia for Ambulatory Surgery (ed 2). Philadelphia, PA, Lippincott, 1991, pp 131-195 10. Booker PD, Chapman DH: Premedication in children
undergoing day care surgery. Br J Anaesth 51:1083-1087, 1979 11. Dawson B, Reed WA: Anaesthesia for adult surgical out-patients. Can Anaesth Soc J 27:409-411, 1980 12. Ogg TW: Use of anaesthesia: Implications of day-case surgery and anaesthesia. BMJ 281:212-214, 1980 13. Marley R: Outpatient anesthesia, in Nagelhout J, Zaglaniczny K (eds): Nurse Anesthesia. Philadelphia, PA, Sannders, 1997, (in press) 14. Bogetz MS: Preoperative preparation, in McGoldrick KE (ed): Ambulatory Anesthesiology: A Problem-Oriented Approach. Baltimore, MD, Williams & Wilkins, 1995, pp 33-55 15. Dorland's Illustrated Medical Dictionary (ed 27): Philadelphia, PA, Saunders, 1988, p 108 16. Stoelting RK, Miller RD: Preoperative medication, in Basics of Anesthesia (ed 3). New York, NY, Churchill Livingstone, 1994, pp 113-125 17. Meakin G: Anaesthesia for infants and children, in Healy TEJ, Cohen PJ (eds): Wylie and Churchill-Davidson's A Practice of Anaesthesia (ed 6). London, United Kingdom, Edward Arnold, 1995, pp 673-689 18. Eckenhoff J: Relationship of anesthesia to postoperative personality changes in children. Am J Dis Childhood 86:587-591, 1953
MIDAZOLAM
FOR PEDIATRIC
PREMEDICATION
19. Raeder JC, Breivik H: Premedication with midazolam in outpatient general anesthesia. A comparison with morphine-scopolamine and placebo. Acta Anaesthesiol Scand 31:509-514, 1987 20. Rita L, Seleny FL, Mazurek A, et al: Intramuscular midazolam for pediatric preanesthetic sedation: A doubleblind controlled study with morphine. Anesthesiology 63:528-531, 1985 21. Vinik HR, Reves JG, Wright D: Premedication with intramuscular midazolam: A prospective randomized doubleblind controlled study. Anesth Analg 61:933-937, 1982 22. Shafer A, White PF, Urquhart ML, et al: Outpatient premedication: Use of midazolam and opioid analgesics. Anesthesiology 71:495-501, 1989 23. Weldon BC, Watcha MF, White PF: Oral midazolam in children: Effect of time and adjunctive therapy. Anesth Analg 75:51-55, 1992 24. Feld LH, Negus JB, White PF: Oral midazolam preanesthetic medication in pediatric outpatients. Anesthesiology 73:831-834, 1990 25. Karl HW, Keifer AT, Rosenberger JL, et al: Comparison of safety and efficacy of intranasal midazolam or sufentanil for preinduction of anesthesia in pediatric patients. Anesthesiology 76:209-215, 1992 26. Physicians' Desk Reference (ed 50). Montvale, NJ, Medical Economics Company, 1996, pp 2170-2173 27. Cot6 CJ: Sedation for the pediatric patient. Pedialr Clin North Am 41:31-58, 1994 28. Twersky RS, Hartung J, Berger BJ, et al: Midazolam enhances auterograde but nut retrograde amnesia in pediatric patients. Anesthesiology 78:51-55, 1993 29. Geller E, Halpern P: Benzodiazcpincs and their anlagonists in anesthesia. IARS Rev Course Lect (Suppl to Anesth Analg) April:136-140. 1993 30. Twcrsky P,S: The pharlnacology of anesthetics used for ambulatory surgery. ASA Refresher Courses in Ancsthcsi ology 21:159-175, 1993 31. Alderson PJ, Lerman L: Oral premeditation for pacdiatric ambulatory anaesthesia: A comparison of midazolam and ketamine. Can J Anaesth 41:221-226, 1994 32. McMillan DO, Spahr-Schopfcr IA, Sikich N, et al: Premedication of children with oral midazolam. Can J Anaesth 39:545-550, 1992 33. Khanderia U, Pandit SK: Use of midazolam hydro chloride in anesthesia. Clin Pharmacol Ther 6:533-547, 1987 34. Levine MF, Spahr Schopfer IA, Hartley E, et al: Oral midazolam premedication in children: The minimum time interval for separation from parents. Can J Anaesth 40:726729, 1993
47
35. Pywell CA, Hung YJ, Nagelhout J: Oral midazolam versus meperidine, atropine, and diazepam: A comparision of premedicants in pediatric outpatients. AANA J 63:124130, 1995 36. Parnis SJ, Foate JA, van der Walt JH, et al: Oral midazolam is an effective premedication for children having day-stay anaesthesia. Anaesth Intensive Care 20:9-14, 1992 37. Spear RM, Yaster M, Berkowitz ID, et al: Preinduction of anesthesia in children with rectally administered midazolam. Anesthesiology 74:670-674, 1991 38. Beebe DS, Belani KG, Chang P-N, et al: Effectiveness of preoperative sedation with rectal midazolam, ketamine, or their combination in young children. Anesth Analg 75:880884, 1992 39. Van Der Bijl P, Roelofse JA, Stander IA: Rectal ketamine and midazolam for premedication in pediatric dentistry. J Oral Maxillofac Surg 49:1050-1054, 1991 40. Roelofse JA, Van Der Bijl P: Comparison of rectal midazolam and diazepain for premedication in pediatric dental patients. J Oral Maxillofac Surg 51:525-529, 1993 41. Steward DJ: Preoperative evaluation and preparation for surgery, in Gregory GA (ed): Pediatric Anesthesia (ed 3). New York, NY, Churchill Livingstone, 1994, pp 179-195 42. Levine MF, Hartley EJ, Macpherson BA, et al: Oral midazolanl premedication for children with congenital cyanotic heart disease undergoing cardiac surgery: A comparative study. Can J Anaesth 40:934-938, 1993 43. Connors K, Terndrup TE: Nasal versus oral midazolain for sedation of anxious children undergoing laceration repair. Ann Emerg Med 24:1074 1079, 1994 44. Zandsberg S, Rosenblum M: Nonconventional drug administration in anesthesia. Anesth Clin N Amer 12:17 38, 1994 45. Rothstein P: Sedation and pain management for chil dren. IARS Rev Course Lect (Suppl to Anesth Analg) March: 33-36, 1995 46. Cot6 CJ: Preoperative preparation of the pediatric pa tient. ASA 1995 Annual Refresher Course Lecture. Philadelphia, PA, Lippincott, 1995, p 131 47. Berry FA: Preoperative assessment of pediatric outpatients, in White PF (ed): Outpatient Anesthesia. New York, NY, Churchill Livingstone, 1990, pp 147-162 48. Karl HW, Rosenberger JL, Larach MG, et al: Transmucosal administration of midazolam for premedication of pediatric patients. Anesthesiology 78:885-891, 1993 49. Saint-Maurice C, Meistehnan C, Rey E, et al: The pharmacokinetics of rectal midazolam for premedication in children. Anesthesiology 65:536-538, 1986
NNUALLY, over 25 million anesthetics are administered in which the perianesthetic nurse is entrusted to provide care. A significant portions of these anesthetics are for children in the ambulatory setting. When a child enters the treatment area, ie, surgical or procedural, two goals are foremost in delineating the patient's care. The first goal is to protect the child and assure a safe therapeutic experience. Secondly, the psychological well-being of the child should be fostered and maintained. The circumstances
A
Beverly M. Moline, MS, RN, CPAN, is the Staff Development Coordinator for Surgical Services, and Rex A. Marley, MS, CRNA, RRT, is a Staff Nurse Anesthetist in the Department of Anesthesia, Poudre Valley Hospital, Fort Collins, CO. Address correspondence to Beverly M. Moline, MS, RN, CPAN, Staff Development Coordinator for Surgical Services, Poudre Valley Hospital, 1024 Lemay Ave, Fort Collins, CO 80524. 9 1997 by American Society of PeriAnesthesia Nurses. 1089-9472/97/1201-0009503.00/0
42
surrounding the child's admission are stressful, not only for the patient but also for the family.1 In an attempt to minimize stress and familiarize the patient and family to the anticipated sequence of events, many institutions offer specialized orientation programs. These preoperative programs are designed to reduce parental and patient trepidation by providing relevant perioperative information (eg, directions, anticipated schedule, instructions for physiological preparation of the child, expected postoperative course, and discharge instructions), offering reassurance, and enhancing coping skills through familiarity. Within these programs, a variety of techniques are incorporated to prepare the child for the operative procedure. Educational tools utilized for these instructional sessions include facility tours, puppet shows, audiovisual programs (eg, slide shows or videotapes), and illustrated pamphlets (eg, coloring or game books). Using either a dress rehearsal or a photographic depiction, children may have an orientation session with the equip-
Journal of PeriAnesthesia Nursing, Vol 12, No 1 (February), 1997: pp 42-47
M I D A Z O L A M FOR PEDIATRIC P R E M E D I C A T I O N Table 1. Commonly Cited Indications for Premedication
Promote amnesia Provide analgesia to the patient in pain Promote antisialagogue (airway drying) effect Decrease patient apprehension (anxiolysis) Cause blunting of autonomic nervous system reflex responses Aid the induction and maintenance of anesthesia Create prophylaxis against: allergic reactions chronic illnesses infections nausea and vomiting pulmonary aspiration of gastric contents vagal stimulation Promote patient cooperation during regional anesthesia Increase pH of gastric fluid Reduce anesthetic requirement Reduce volume of gastric content Sedation
ment that is commonly used in the perioperative setting, eg, blood pressure cuff, thermometer, anesthesia face mask, anesthesia machine, intravenous therapy equipment, and postoperative oxygen therapy devices. Reflective of an effective program will be a well-prepared child who is physiologically and emotionally ready for the treatment experience. The value of such a pro gram is well-accepted in reducing parental and patient stress, and facilitating acceptance and co operation on the child's part. 27 When circumstances prevail so that proper preparation of the child takes place, anxiolytic premedication may not be necessary. When parental separation does not occur, eg, when a parent accompanies the patient into the operating room and participates in the induction of anesthesia, the need for premeditation is reduced, s Unfortunately, although these programs are invaluable, they, along with the support of trusted care givers and skilled health care providers, may not sufficiently allay the child's anxiety from the time of parental separation through the induction of anesthesia. ROLE OF PHARMACOLOGIC PREMEDICATION
Traditional indications for administering premedications vary according to the desired physiological or emotional response (Table 1). The use of premedications (ie, anxiolytics, hypnotics, and sedatives) in children continues to be controversial. 4'9 The concern about giving anxiolytic and sedative premedications relates to their po-
43
tential to delay discharge, thus increasing cost for the ambulatory surgical facility. 1~ Oftentimes, despite intensive educational and emotional preparation of the child, drug administration may be desirable to modify psychological responses before anesthesia. With the contemporary anesthetizing agents and techniques, anxiolytic agents (such as midazolam), are indicated principally for the child's emotional protection and not as a supplement to the anesthesia. 9 The estimate of children who will benefit from anxiolytic premedication approximates 20%. 9 Children come to the preoperative care area in assorted stages of development with unique personalities, a wide variety of past surgical experiences, and different perceptions of health care providers. Some children are curious while others are passive, some are adventurous while others cautious, and some are cooperative while others are challenging. The use of pharmacologic agents in preparing the child for surgery or another procedure should never become routine, rather, it should be determined on an individual need and desired benefit. 5'~3The practitioner must weigh the required effect of the medication (eg, a cahn cooperative child), against potential negative impacls (such as prolonged sedative influence). The perfect anxiolytic agent would be readily accepted by the child, would be absolulely dependable with rapid onset and otTsel, and would not produce excessive sedation or cardiopulmonary depression. 5 To date there is no drug that is considered the ideal premedicant for children and none is expected s o o n . 14 Each anxiolytic premedication (eg, diazepam, flurazepam lorazepam, midazolam, propranolol, temazepam, timolol, triazolam), has its own advantages and disadvantages. The practitioner's choice of premeditation is influenced by the procedure being performed, their familiarity with the drug, the facility's staffing, and the access to proper equipment because some medications and delivery routes require close observation by skilled staff utilizing continuous monitoring capabilities. ANXIOLYSIS
Anxiety is an emotion familiar to all of us at some point in our lives. It is the unpleasant emotional state consisting of psychophysiological responses to anticipation of real or imagined danger, ostensibly resulting from unrecognized intrapsychic conflict. 15 Patients of appropriate age will nat-
44
MOLINE AND MARLEY
urally possess a degree of anxiety about the impending operation. The most common reason for premedicating patients is to allay this anxiety. Infants less than 1 year of age do not require anxiolytic premedication. 16'17 As the child matures, anxiolytic medication has been shown to help reduce preoperative anxiety and to minimize posthospitalization behavioral changes. 18 The goal of anxiolysis is to make separation less stressful for the parent and child and to have a calmer, more cooperative child during the induction of anesthesia without prolonging recovery. Several studies have shown midazolam's ability to provide these outcomes.19-25 M I DAZO LAM
Midazolam is a highly lipophilic, short-acting, water-soluble benzodiazepine that acts on selective receptors in the brain, brain stem, and spinal cord. As with other benzodiazepines, the effect of midazolam includes amnestic, anticonvulsant, anxiolytic, hypnotic, muscle-relaxant, and sedative properties. The sedative effects are synergistic when midazolam is coadministered with opioids and other hypnotic agents. The stress response is inhibited by a reduction in the levels of circulating catecholamines. Midazolam is metabolized by the liver and excreted in the urine. For this reason, the dose of midazolam should be reduced in patients who have severe liver disease. When compared with diazepam, midazolam is three to four times as potent, 26 has a more rapid onset of action, and has a shorter duration of effect.
Advantages of Midazolam In addition to providing anxiolysis as a premedicant for general and regional anesthesia, midazolam is appropriately popular as a coinduction agent for general anesthesia. Its acceptance continues for conscious sedation as an adjunct to procedures performed under local anesthesia or for diagnostic purposes. Midazolam offers the most versatile delivery methods and has become widely accepted as a sedative for the pediatric population. 9'27 It produces antegrade and retrograde (however, less predictably if at all 28) amnesia, and therefore limits recall of potentially traumatic events. 27 A rapid onset of action and a 2 to 4 hour elimination half-life make midazolam an ideal outpatient agent 14 that has not been found to increase discharge t i m e s . 19-25
Disadvantages of Midazolam As with any sedative agent, the potential for adverse side effects exists. Midazolam produces relatively mild and infrequent cardiovascular (ie, hypotension) and respiratory (ie, ventilatory depression, hypoxemia, apnea) effects. In the elderly or debilitated patient and in those patients in which careful dosage and titration of the drug has not been followed, severe cardiopulmonary consequences have been observed. Excessive and prolonged sedation may occur in rare patients. Relative overdosage of midazolam may be counteracted with the administration of the only specific benzodiazepine receptor antagonist in clinical use, flumazenil. A useful summation of the perioperative applications for flumazenil can be found in an article by Geller and Halpern. 29 ROUTES OF MIDAZOLAM ADMINISTRATION Methods of midazolam administration are numerous and include intramuscular, intravenous,
nasal, oral, rectal, and sublingual. Each method of drug administration manifests individual advantages and disadvantages. The preferred route of midazolam administration will be dependent on the child's chronological age, maturation level, previous health care experience, expertise of the health care providers, and time until parental separation. A sufficient time interval should be anticipated and allowed for midazolam to exert its desired effect. Administering the drug at the appropriate time in the patient' s preanesthesia care is as important as the drug choice or administration route. See Table 2 for a summary of dosage considerations for the various routes of administration. 5J4,25,3~176
Intramuscular In meeting the pharmacological needs of a child, the intramuscular route is not desirable because of the anxiety and pain associated with
Table 2. Dosage Considerations for Midazolam Route
Dosage
Onset of Effect
Intramuscular Intranasal
0.07 to 0.1 mg/kg TM 0.02 to 0,03 mg/kg 2~
30 to 60 min TM 2.52sto 10 min 14'25
Intravenous Oral
0.05 mg/kg s'3~ 0.5 mg/kg 24'31-33
1 to 2 min 10 to 45 m i n 23'24'31'34'35
Rectal
0.5 to 1 mg/kg 36'37
1037 to 30 rain 39'4~
MIDAZOLAM FOR PEDIATRIC PREMEDICATION the injection. 41 It offers the advantage of being reliable and providing a rapid onset of action. In children with congenital cyanotic heart disease, intramuscular injections administered preoperatively can cause crying and sufficient distress to result in a decrease in oxyhemoglobin saturations (SpO2). 42 This study further noted that orally administered midazolam produced anxiotysis and sedation without a decrease in SpO2.42 Reducing the volume of midazolam injected by using the more concentrated solution, 5 mg/mL, is appropriate to consider in the larger child. The less concentrated midazolam, 1 mg/mL, may be indicated in smaller children to administer a more precise volume of drug. lntranasal The nasal route provides easy and relatively painless access for drug instillation with rapid absorption and onset of action. Medications absorbed in this manner avoid first-pass metabolism through the liver and degradation in the gastrointestinal tract. 43 Nose drops provide better coverage of the walls of the nasal cavity when compared with nasal sprays. 44 Midazolam, 5 mg/mL concentration, can be administered in alternating nares over 30 to 60 seconds. ~ Allhough easily accessible, medications can cause nasal burning q3 and an unpleasant taste. In addition, and the nasal route of drug instillation is often met with resistance in children. 45 In theory, it is possible for intranasally administered midazolam to be carried along neural connections between the nasal mucosa and the central nervous system by way of the olfactory nerves leading to a neurotoxic effect. 46 A comparison of intranasally and orally administered midazolam found both reduced anxiety in 10 minutes without clinically significant side e f f e c t s . 43 Because recreational drugs are often taken intranasally, social concerns have been raised regarding the intranasal administration of drugs in children. 4~ Intravenous Once venous access has been established, this route offers the clear advantage of reliable, rapid onset of effect with or without the cooperation of the child, unlike oral administration that requires patient cooperation. However, establishing venous access before induction can be a challenge and potentially traumatic to the frightened or uncooperative child. In addition, some procedures
4s
(ie, ventilation tubes in the ears of an otherwise healthy child), do not necessitate venous access. Oral The oral route of drug administration is most desirable because it is the least threatening, but it can pose a challenge in the uncooperative child. It also leaves the dosage vulnerable to partial administration should the child decide to spit out an unknown volume of medication. For this reason, it is suggested the child be encouraged to consume as much as possible with the first swallow. 27 An assortment of flavorings, eg, punch, apple juice, cherry or chocolate syrup, chocolatecherry syrup, gelatin, fruit-flavored concentrates, cola, and acetaminophen elixir, have been used to disguise the unpleasant taste of the intravenous form of midazolam. 4'43 Midazolam in the 5 rag/ mL concentration should be diluted with an equal volume of the flavored diluent. Bioavailability of oral midazolam is greatly reduced by the firstpass hepatic effect and therefore prescribed oral doses are considerably greater than that of intravenous doses to achieve the same effect) ~ In a study comparing oral midazolam (0.5 rag/ kg) with oral ketamine (5.0 mg/kg), the level of sedation and anxiolysis was noted to be similar in healthy children at 20 minutes after dosing) ~ However, a difference was noted in discharge readiness between these two groups with the midazolam group being discharged 20 minutes sooner than the ketamine group) ~ When increasing the dosage of midazolam to 0.75 mg/kg or 1.0 mg/kg, there is a likelihood of additional side effects such as increased sedation, 24 loss of balance and head control, blurred vision, and dysphoric reactions) 2 Additionally, these studies tbund no advantage of the higher dosages of midazolam over 0.5 mg/kg. Proper timing of medication administration to produce effective sedation at the moment of separation can be a major challenge in today's fastpaced and unpredictable settings. The minimum time interval between drug administration and parental separation has been found to be acceptable in as little as 10 minutes, 34 yet it may take up to 30 minutes for optimal sedation to occur. 23 It was postulated that the more rapid effect of 10 minutes was secondary to transmucosal absorption of midazolam mixed with a viscous chocolate-cherry syrup that coated the oral mucosa. 34 Sublingual absorption, a popular route for admin-
MOLINE AND MARLEY
46
istering m a n y medications, has been suggested for m i d a z o l a m in a dose a p p r o x i m a t e l y o n e - h a l f o f the n o r m a l oral dose. 46 M i d a z o l a m 0.2 m g / k g administered sublinqually was as effective and better accepted in children than intranasal dosing. 48 H o w e v e r , . with m i d a z o l a m ' s unpleasant taste, it m a y be difficult to gain the cooperation o f children.
Rectal Rectal administration o f m i d a z o l a m offers easy access without requiring cooperation o f the child. A b s o r p t i o n through the rectal route m a y be via the superior h e m o r r h o i d a l veins that drain into the portal circulation and thus expose the drug to first-pass hepatic effect. 49 The appropriateness o f delivering m e d i c a t i o n in this m a n n e r is age related and is appropriate up until the age when cultural influence stresses " b o d y p r i v a c y " and this approach b e c o m e s less acceptable to the patient. It is ideal for the y o u n g infant w h o can r e m a i n in a p a r e n t ' s arms until separation is necessary. Rectal m i d a z o l a m can be instilled with a 14-French lubricated suction catheter 37 placed 3 to 6 c m into the r e c t u m and followed by a 2 m L flush o f air. 14'39 M i d a z o l a m is prepared b y diluting with saline to a concentration o f 2 mg/ m L up to a given v o l u m e o f 10 mL. If the appro-
priate concentration, o f up to 1 mg/kg, requires a larger total v o l u m e then the m i d a z o l a m should be given undiluted (5 m g / m L ) . 37 D o s a g e s o f 0.5 m g / k g and 1.0 m g / k g did not delay e m e r g e n c e or p r o l o n g discharge. 37'38 W h e n c o m p a r i n g rectal m i d a z o l a m (0.35 mg/ kg) and d i a z e p a m (0.70 mg/kg) with placebos, both m e d i c a t i o n groups had significantly better anxiolytic and sedation scores. 4~ The m i d a z o l a m group exhibited better acceptance o f the m a s k with 90% o f the group rated as g o o d acceptance. 4~ SUMMARY
O n c e it has been determined that the administration o f a preoperative sedative w o u l d be beneficial for the pediatric patient, m i d a z o l a m is a p o p u l a r choice and offers several advantages. It has rapid onset, relatively short duration o f effect, and m a y be administered in a variety of routes. Ease o f parental separation is a benefit to the child and parent. A c c e p t a n c e o f the anesthesia face m a s k p r o m o t e s a rapid and s m o o t h inhalation induction. W h e n administered at recomm e n d e d dosages, m i d a z o l a m remains relatively free o f significant side effects and does not lead to p r o l o n g e d patient stay in the a m b u l a t o r y setting.
REFERENCES 1. Zukerberg AL: Perioperative approach to children. Pediatr Clin North Am 41:15-29, 1994 2. Orr R, Lynn A: The combative child. Curr Rev Nurse Anesthetists 14:74-84, 1991 3. Holzman RS: Outpatient anesthesia for children. Curr Rev Nurse Anesthetists 17:125-136, 1994 4. Steward DJ: New thoughts on preparation and premedication of children. Curr Rev Nurse Anesthetists 17:173-180, 1995 5. Cot6 CJ: Changing concepts in preoperative medication and "NPO" status of the pediatric patient. ASA Refresher Courses in Anesthesiology 22:101-116, 1994 6. Maligalig RM: Parents' perceptions of the stressors of pediatric ambulatory surgery. J Post Anesth Nurs 9:278-282, 1994 7. Pauly B: Operation fascination. J Post Anesth Nurs 10:89-93, 1995 8. Larosa-Nash PA, Murphy JM, Wade LA, et al: Implementing a parent-present induction program. AORN J 61:526-531, 1995 9. Hannallah RS, Epstein BS: The pediatric patient, in Wetchler BV (ed): Anesthesia for Ambulatory Surgery (ed 2). Philadelphia, PA, Lippincott, 1991, pp 131-195 10. Booker PD, Chapman DH: Premedication in children
undergoing day care surgery. Br J Anaesth 51:1083-1087, 1979 11. Dawson B, Reed WA: Anaesthesia for adult surgical out-patients. Can Anaesth Soc J 27:409-411, 1980 12. Ogg TW: Use of anaesthesia: Implications of day-case surgery and anaesthesia. BMJ 281:212-214, 1980 13. Marley R: Outpatient anesthesia, in Nagelhout J, Zaglaniczny K (eds): Nurse Anesthesia. Philadelphia, PA, Sannders, 1997, (in press) 14. Bogetz MS: Preoperative preparation, in McGoldrick KE (ed): Ambulatory Anesthesiology: A Problem-Oriented Approach. Baltimore, MD, Williams & Wilkins, 1995, pp 33-55 15. Dorland's Illustrated Medical Dictionary (ed 27): Philadelphia, PA, Saunders, 1988, p 108 16. Stoelting RK, Miller RD: Preoperative medication, in Basics of Anesthesia (ed 3). New York, NY, Churchill Livingstone, 1994, pp 113-125 17. Meakin G: Anaesthesia for infants and children, in Healy TEJ, Cohen PJ (eds): Wylie and Churchill-Davidson's A Practice of Anaesthesia (ed 6). London, United Kingdom, Edward Arnold, 1995, pp 673-689 18. Eckenhoff J: Relationship of anesthesia to postoperative personality changes in children. Am J Dis Childhood 86:587-591, 1953
MIDAZOLAM
FOR PEDIATRIC
PREMEDICATION
19. Raeder JC, Breivik H: Premedication with midazolam in outpatient general anesthesia. A comparison with morphine-scopolamine and placebo. Acta Anaesthesiol Scand 31:509-514, 1987 20. Rita L, Seleny FL, Mazurek A, et al: Intramuscular midazolam for pediatric preanesthetic sedation: A doubleblind controlled study with morphine. Anesthesiology 63:528-531, 1985 21. Vinik HR, Reves JG, Wright D: Premedication with intramuscular midazolam: A prospective randomized doubleblind controlled study. Anesth Analg 61:933-937, 1982 22. Shafer A, White PF, Urquhart ML, et al: Outpatient premedication: Use of midazolam and opioid analgesics. Anesthesiology 71:495-501, 1989 23. Weldon BC, Watcha MF, White PF: Oral midazolam in children: Effect of time and adjunctive therapy. Anesth Analg 75:51-55, 1992 24. Feld LH, Negus JB, White PF: Oral midazolam preanesthetic medication in pediatric outpatients. Anesthesiology 73:831-834, 1990 25. Karl HW, Keifer AT, Rosenberger JL, et al: Comparison of safety and efficacy of intranasal midazolam or sufentanil for preinduction of anesthesia in pediatric patients. Anesthesiology 76:209-215, 1992 26. Physicians' Desk Reference (ed 50). Montvale, NJ, Medical Economics Company, 1996, pp 2170-2173 27. Cot6 CJ: Sedation for the pediatric patient. Pedialr Clin North Am 41:31-58, 1994 28. Twersky RS, Hartung J, Berger BJ, et al: Midazolam enhances auterograde but nut retrograde amnesia in pediatric patients. Anesthesiology 78:51-55, 1993 29. Geller E, Halpern P: Benzodiazcpincs and their anlagonists in anesthesia. IARS Rev Course Lect (Suppl to Anesth Analg) April:136-140. 1993 30. Twcrsky P,S: The pharlnacology of anesthetics used for ambulatory surgery. ASA Refresher Courses in Ancsthcsi ology 21:159-175, 1993 31. Alderson PJ, Lerman L: Oral premeditation for pacdiatric ambulatory anaesthesia: A comparison of midazolam and ketamine. Can J Anaesth 41:221-226, 1994 32. McMillan DO, Spahr-Schopfcr IA, Sikich N, et al: Premedication of children with oral midazolam. Can J Anaesth 39:545-550, 1992 33. Khanderia U, Pandit SK: Use of midazolam hydro chloride in anesthesia. Clin Pharmacol Ther 6:533-547, 1987 34. Levine MF, Spahr Schopfer IA, Hartley E, et al: Oral midazolam premedication in children: The minimum time interval for separation from parents. Can J Anaesth 40:726729, 1993
47
35. Pywell CA, Hung YJ, Nagelhout J: Oral midazolam versus meperidine, atropine, and diazepam: A comparision of premedicants in pediatric outpatients. AANA J 63:124130, 1995 36. Parnis SJ, Foate JA, van der Walt JH, et al: Oral midazolam is an effective premedication for children having day-stay anaesthesia. Anaesth Intensive Care 20:9-14, 1992 37. Spear RM, Yaster M, Berkowitz ID, et al: Preinduction of anesthesia in children with rectally administered midazolam. Anesthesiology 74:670-674, 1991 38. Beebe DS, Belani KG, Chang P-N, et al: Effectiveness of preoperative sedation with rectal midazolam, ketamine, or their combination in young children. Anesth Analg 75:880884, 1992 39. Van Der Bijl P, Roelofse JA, Stander IA: Rectal ketamine and midazolam for premedication in pediatric dentistry. J Oral Maxillofac Surg 49:1050-1054, 1991 40. Roelofse JA, Van Der Bijl P: Comparison of rectal midazolam and diazepain for premedication in pediatric dental patients. J Oral Maxillofac Surg 51:525-529, 1993 41. Steward DJ: Preoperative evaluation and preparation for surgery, in Gregory GA (ed): Pediatric Anesthesia (ed 3). New York, NY, Churchill Livingstone, 1994, pp 179-195 42. Levine MF, Hartley EJ, Macpherson BA, et al: Oral midazolanl premedication for children with congenital cyanotic heart disease undergoing cardiac surgery: A comparative study. Can J Anaesth 40:934-938, 1993 43. Connors K, Terndrup TE: Nasal versus oral midazolain for sedation of anxious children undergoing laceration repair. Ann Emerg Med 24:1074 1079, 1994 44. Zandsberg S, Rosenblum M: Nonconventional drug administration in anesthesia. Anesth Clin N Amer 12:17 38, 1994 45. Rothstein P: Sedation and pain management for chil dren. IARS Rev Course Lect (Suppl to Anesth Analg) March: 33-36, 1995 46. Cot6 CJ: Preoperative preparation of the pediatric pa tient. ASA 1995 Annual Refresher Course Lecture. Philadelphia, PA, Lippincott, 1995, p 131 47. Berry FA: Preoperative assessment of pediatric outpatients, in White PF (ed): Outpatient Anesthesia. New York, NY, Churchill Livingstone, 1990, pp 147-162 48. Karl HW, Rosenberger JL, Larach MG, et al: Transmucosal administration of midazolam for premedication of pediatric patients. Anesthesiology 78:885-891, 1993 49. Saint-Maurice C, Meistehnan C, Rey E, et al: The pharmacokinetics of rectal midazolam for premedication in children. Anesthesiology 65:536-538, 1986