e2 interactions at the M3 muscarinic receptor Anesthesiology 2005; 103 1195 1203 76 Zappi L, Song P, Nicosia S, et al Do pipecuronium and rocuronium affect human bronchial smooth muscle? Anesthesiolog[.]
e2 52 Reich DL, Hollinger I, Harrington DJ, Seiden HS, Chakravorti S, Cook DR Comparison of cisatracurium and vecuronium by infusion in neonates and small infants after congenital heart surgery Anesthesiology 2004;101:1122-1127 53 Ornstein E, Matteo RS, Schwartz AE, et al The effect of phenytoin on the magnitude and duration of neuromuscular blockade following atracurium or vecuronium Anesthesiology 1987;67:191-196 54 Robertson EN, Driessen JJ, Booij LH Pharmacokinetics and pharmacodynamics of rocuronium in patients with and without renal failure Eur J Anaesthesiol 2005;22:4-10 55 Robertson EN, Driessen JJ, Vogt M, et al Pharmacokinetics of rocuronium 0.3 mg/kg in adult patients with and without renal failure Eur J Anaesthesiol 2005;22:929-932 56 Cooper RA, Mirakhur RK, Wierda JM, et al Pharmacokinetics of rocuronium bromide in patients with and without renal failure Eur J Anaesthesiol 1995;11:43-44 57 Driessen JJ, Robertson EN, Van Egmond J, et al Time-course of action of rocuronium 0.3 mg/kg in children with and without endstage renal failure Paediatr Anaesth 2002;12:507-510 58 Szenohradszky J, Fisher DM, Segredo V, et al Pharmacokinetics of rocuronium bromide (ORG 9426) in patients with normal renal function or patients undergoing cadaver renal transplantation Anesthesiology 1992;77:899-904 59 Wierda JM, Meretoja OA, Taivainen T, et al Pharmacokinetics and pharmacodynamic modeling of rocuronium in infants and children Br J Anaesth 1997;78:690-695 60 Rapp HJ, Altenmueller CA, Waschke C Neuromuscular recovery following rocuronium bromide single dose in infants Paediatr Anaesth 2004;14:329-335 61 Cooper R, Mirakhur RK, Clarke RSJ, Boulex Z Comparison of intubating conditions after administration of rocuronium and suxamethonium Br J Anaesth 1992;69:269-273 62 Mazurek AJ, Rae B, Hann S, et al Rocuronium versus succinylcholine: are they equally effective during rapid-sequence induction of anesthesia? Anesth Analg 1998;87:1259-1262 63 Scheiber G, Ribeiro FC, Marichal A, et al Intubating conditions and onset of action after rocuronium, vecuronium and atracurium in young children Anesth Analg 1996;83:320-324 64 Baraka AS, Sayyid SS, Assaf BA Thiopental-rocuronium versus ketamine-rocuronium for rapid-sequence intubation in parturients undergoing Cesarean section Anesth Analg 1997;84:1104-1107 65 Munoz R, Gonzalez AG, Dagnino JA, et al The effect of ephedrine on the onset time of rocuronium Anesth Analg 1998;85:437-440 66 Bock M, Haselmann L, Böttiger BW, et al Priming with rocuronium accelerates neuromuscular block in children: a prospective randomized study Can J Anaesth 2007;54:538-543 67 Reynolds LM, Lau M, Brown R, et al Intramuscular rocuronium in infants and children Anesthesiology 1996;85:231-239 68 Park S Prevention of rocuronium injection pain Korean J Anesthesiol 2014;67:371-372 69 Chiarella AB, Jolly DT, Huston CM, et al Comparison of four strategies to reduce the pain associated with intravenous administration of rocuronium Br J Anaesth 2003;90:377-379 70 Soriaon SG, Kaus SJ, Sullivan LJ, et al Onset and duration of action of rocuronium in children receiving chronic anticonvulsant therapy Paediatr Anaesth 2000;10:133-136 71 Tobias JD Continuous infusion of rocuronium in a paediatric intensive care unit Can J Anaesth 1996;43:353-357 72 Rajchert DM, Pasquariello CA, Watcha MF, et al Rapacuronium and the risk of bronchospasm in pediatric patients Anesth Analg 2002;94:488-493 73 Tobias JD, Johnson JO, Sprague K, et al Effects of rapacuronium on respiratory function during general anesthesia Anesthesiology 2001; 95:908-912 74 Jooste E, Klafter F, Hirshman CA, et al A mechanism for rapacuronium induced bronchospasm Anesthesiology 2003;98:906-911 75 Jooste E, Sharma A, Zhang Y, et al Rapacuronium augments acetylcholine-induced bronchoconstriction via positive allosteric interactions at the M3 muscarinic receptor Anesthesiology 2005; 103:1195-1203 76 Zappi L, Song P, Nicosia S, et al Do pipecuronium and rocuronium affect human bronchial smooth muscle? Anesthesiology 1999;91: 1616-1621 77 Yang CI, Fine GF, Jooste EH, et al The effect of cisatracurium and rocuronium on lung function in anesthetized children Anesth Analg 2013;117:1393-1400 78 Brandom BW, Sarner JB, Woelfel SK, et al Mivacurium infusion requirements in pediatric surgical patients during nitrous oxidehalothane and during nitrous oxide narcotic anesthesia Anesth Analg 1990;71:16-22 79 Fox MH, Hunt PCW Prolonged neuromuscular blockade associated with mivacurium Br J Anaesth 1995;74:237-238 80 Petersen RS, Bailey PL, Kalameghan R, et al Prolonged neuromuscular blockade after mivacurium Anesth Analg 1993;76:194-196 81 Goudsouzian NG, Alifimoff JK, Eberly C, et al Neuromuscular and cardiovascular effects of mivacurium in children Anesthesiology 1989; 70:237-242 82 Theroux MC, Brandom BW, Zagnoev MM, et al Combinations of high-dose vecuronium and mivacurium provide similar paralysis and intubation conditions to succinylcholine in paediatric patients Paediatr Anaesth 1996;6:453-458 83 Stevens JB, Shepherd JM, Vories PA, et al A mixture of mivacurium and rocuronium is comparable in clinical onset to succinylcholine J Clin Anesth 1996;8:486-490 84 Schmidt J, Muenster T, Wick S, et al Onset and duration of mivacurium-induced neuromuscular blockade in patients with Duchenne muscular dystrophy Br J Anaesth 2005;95:769-772 85 Tobias JD, Atwood R Mivacurium in children with Duchenne muscular dystrophy Paediatr Anaesth 1994;4:57-60 86 Uslu M, Mellinghoff H, Diefenback C Mivacurium for muscle relaxation in a child with Duchenne’s muscular dystrophy Anesth Analg 1999;89:340-341 87 Goudsouzian NG, Gelb C Histamine release from suxamethonium and atracurium in adolescents Paediatr Anaesth 1991;1:41-45 88 Goudsouzian NG, Young ET, Moss J, et al Histamine release during the administration of atracurium or vecuronium in children Br J Anaesth 1986;58:1229-1233 89 Lawson DH, Plaice GM, Glavin RJ, et al Atracurium—a post marketing surveillance study: UK study and discussion Br J Anaesth 1989;62:596-600 90 Woods L, Morris P, Meakin G Severe bronchospasm following the use of atracurium in children Anaesthesia 1985;40:207-208 91 Brandom BW, Cook DR, Woelfel SK, et al Atracurium infusion requirements in children during halothane, isoflurane, and narcotic anesthesia Anesth Analg 1985;64:471-476 92 Wait CM, Goat VA Atracurium infusion during paediatric craniofacial surgery Closed loop control of neuromuscular blockade Anaesthesia 1989;44:567-570 93 Haraldsted VY, Nielsen JW, Madsen JV, et al Maintenance of constant 95% neuromuscular blockade by adjustable infusion rates of pancuronium and atracurium Br J Anaesth 1988;60:491-494 94 Mann R, Blobner M, Jelen-Esselborn S, et al Preanesthetic train-offour fade predicts the atracurium requirements of myasthenia gravis Anesthesiology 2000;93:346-350 95 Jenkins JA, Facer EK Anesthetic management of a patient with myotonic dystrophy for a Nissen fundoplication and gastrostomy Paediatr Anaesth 2004;14:683-696 96 Playfor SD, Thomas DA, Choonara I Duration of action of atracurium when given by infusion to critically ill children Paediatr Anaesth 2000;10:77-81 97 Chow B, Bowden MI, Ho E, et al Pharmacokinetics and dynamics of atracurium infusions after paediatric orthotopic liver transplantation Br J Anaesth 2000;85:850-855 98 Playfor SD, Thomas DA, Choonara I The effect of induced hypothermia on the duration of action of atracurium when given by continuous infusion to critically ill children Paediatr Anaesth 2000;10:83-88 e3 99 Taivainen T, Meakin GH, Meretoja OA, et al The safety and efficacy of cisatracurium 0.15 mg/kg during nitrous oxide-opioid anaesthesia in infants and children Anaesthesia 2000;55:1047-1051 100 Bluestein LS, Stinson Jr LW, Lennon RL, et al Evaluation of cisatracurium, a new neuromuscular blocking agent for endotracheal intubation Can J Anaesth 1996;43:925-931 101 de Ruiter J, Crawford MW Dose-response relationship and infusion requirements of cisatracurium besylate in infants and children during nitrous oxide-narcotic anesthesia Anesthesiology 2001;94: 790-792 102 Tobias JD A prospective evaluation of the continuous infusion of cis-atracurium for neuromuscular blockade in the pediatric ICU patient: efficacy and dosing requirements Am J Ther 1997;4:287-290 103 Odetola FO, Bhatt-Mehta V, Zahraa J, et al Cisatracurium requirements for neuromuscular blockade in the pediatric intensive care unit: a dose finding study Pediatr Crit Care Med 2002;3: 250-254 104 Reich DL, Hollinger I, Harrington DJ, et al Comparisons of cisatracurium and vecuronium by continuous infusion in neonates and small infants after congenital heart surgery Anesthesiology 2004;101: 1122-1127 105 Koening HM, Edwards TL Cisatracurium-induced neuromuscular blockade in anticonvulsant treated neurosurgical patients J Neurosurg Anesthesiol 2000;12:314-318 106 Tobias JD Changes in cis-atracurium infusion requirements during induced hypothermia to treat increased intracranial pressure in a child J Intensive Care Med 1997;12:261-263 107 deBacker J, Hart N, Fan E Neuromuscular blockade in the 21st century management of the critically ill patient Chest 2017;151: 697-706 108 Murray M, DeBlock H, Erstad B, et al Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient Crit Care Med 2016;44:2079-2103 109 Bevan DR, Donati F, Kopman AF Reversal of neuromuscular blockade Anesthesiology 1992;77:785-805 110 Miller RD, Van Nyhuis LS, Eger EI II, et al Comparative times to peak effect and durations of action of neostigmine and pyridostigmine Anesthesiology 1974;41:27-33 111 Cronelly R, Morris RB, Miller RD Edrophonium: duration of action and atropine requirements in humans during halothane anesthesia Anesthesiology 1982;57:261-266 112 Tobias JD Current evidence for the use of sugammadex in children Paediatr Anaesth 2017;27:118-125 113 Groudine SB, Soto R, Lien C, et al A randomized, dose-finding, phase II study of the selective relaxant binding drug, sugammadex, capable of safely reversing profound rocuronium-induced neuromuscular blockade Anesth Analg 2007;104:555-562 114 Naguib M Suggamadex: another milestone in clinical neuromuscular pharmacology Anesth Analg 2007;104:575-581 115 Lee C, Jahr JS, Candiotti KA, Warriner B, Zornow MH, Naguib M Reversal of profound neuromuscular block by sugammadex administered three minutes after rocuronium: a comparison with spontaneous recovery from succinylcholine Anesthesiology 2009;110:1020-1025 116 Ghoneim AA, El Beltagy MA Comparative study between sugammadex and neostigmine in neurosurgical anesthesia in pediatric patients Saudi J Anaesth 2015;9:247-252 117 Ozgün C, Cakan T, Baltacƒ± B, Ba≈üar H Comparison of reversal and adverse effects of sugammadex and combination of anticholinergicanticholinesterase agents in pediatric patients J Res Med Sci 2014;19: 762-768 118 Kara T, Ozbagriacik O, Turk HS, et al Sugammadex versus neostigmine in pediatric patients: a prospective randomized study Rev Bras Anestesiol 2014;64:400-405 119 Black AE, Flynn PE, Smith HL, Thomas ML, Wilkinson KA, Association of Pediatric Anaesthetists of Great Britain and Ireland Development of a guideline for the management of the unanticipated difficult airway in pediatric practice Paediatr Anaesth 2015;25:346-362 120 Rahe-Meyer N, Fennema H, Schulman S, et al Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients Anesthesiology 2014;121:969-977 121 Tsur A, Kalansky A Hypersensitivity associated with sugammadex administration: a systematic review Anaesthesia 2014;69:1251-1257 122 Mason LJ, Betts EK Leg lift and maximum inspiratory force, clinical signs of neuromuscular blockade reversal in infants and children Anesthesiology 1980;52:441-442 123 Frankel H, Jeng J, Tilly E, et al The impact of implementation of neuromuscular blockade monitoring standards in a surgical intensive care unit Am Surg 1996;62:503-506 124 Tavernier B, Rannou JJ, Vallet B Peripheral nerve stimulation and clinical assessment for dosing of neuromuscular blocking agents Crit Care Med 1998;26:804-805 125 Tobias JD Airway management in the pediatric trauma patient J Intensive Care Med 1998;13:1-14 126 Tobias JD The laryngeal mask airway: a review for the emergency room physician Pediatr Emerg Care 1996;12:370-373 127 Davidson AJ, Huang GH, Czarnecki C, et al Awareness during anesthesia in children: a prospective cohort study Anesth Analg 2005;100:653-661 128 Berkenbosch JW, Fichter CR, Tobias JD The correlation of the bispectral index monitor with clinical sedation scores during mechanical ventilation in the pediatric intensive care unit Anesth Analg 2002;94:506-511 129 Twite MD, Zuk J, Gralla J, et al Correlation of the bispectral index monitor with the COMFORT scale in the pediatric intensive care unit Intensive Care Med 2003;29:2239-2246 130 Grindstaff RJ, Tobias JD Applications of bispectral index monitoring in the pediatric intensive care unit J Intensive Care Med 2004; 19:111-116 131 Segredo V, Caldwell JE, Matthay MA, et al Persistent paralysis in critically ill patients after long term administration of vecuronium N Engl J Med 1992;327:524-528 132 Watling SM, Dasta JF Prolonged paralysis in intensive care unit patients after the use of neuromuscular blocking agents: a review of the literature Crit Care Med 1994;22:884-893 133 Griffiths RD, Hall JB Intensive care unit-acquired weakness Crit Care Med 2010;38:779-787 134 Dhand UK Clinical approach to the weak patient in the intensive care unit Respir Care 2006;51:1024-1040 135 Leatherman J, Fluegel W, David W, et al Muscle weakness in mechanically ventilated patients with severe asthma Am J Respir Crit Care Med 1996;153:1686-1690 136 Sladen RN Neuromuscular blocking agents in the intensive care unit: a two edged sword Crit Care Med 1995;23:423-428 137 Tobias JD Neuromuscular blockade in the pediatric intensive care unit: pancuronium, vecuronium, rocuronium, or atracurium J Intensive Care Med 1997;12:213-217 138 Dodson BA, Kelly BJ, Braswell LM, Cohen NH Changes in acetylcholine receptor number in muscle from critically ill patients receiving muscle relaxants: an investigation of the molecular mechanisms of prolonged paralysis Crit Care Med 1995;23:815-821 e4 Abstract: In the pediatric ICU setting, various clinical circumstances mandate control of movement with the use of neuromuscular blocking agents (NMBAs), commonly including control of intracranial pressure, prevention of shivering with therapeutic hypothermia, and during the early care of patients with acute respiratory distress syndrome Given their adverse effect profile, including the potential for increased nosocomial infections, longer duration of mechanical ventilation, atelectasis with ventilation-perfusion mismatching, and pressure injuries, NMBAs should be used only when absolutely indicated Daily review of their continued need is suggested Because these agents provide no amnestic, analgesic, or sedative properties, co-administration of an amnestic agent (benzodiazepine, ketamine, or propofol) is necessary whenever they are used The term NMBA is preferred because it identifies the mechanism of action of these agents as a competitive antagonist for acetylcholine at the neuromuscular junction This chapter reviews the pharmacology of depolarizing and nondepolarizing NMBAs, along with monitoring principles, adverse effects, and agents for reversal Key words: neuromuscular blocking agent, nondepolarizing agent, train-of-four, acetylcholine receptor, neuromuscular junction, succinylcholine, rocuronium, neostigmine, acetylcholinesterase, sugammadex 132 Sedation and Analgesia CHRISTOPHER M B HEARD, OMAR ALIBRAHIM, AND ALEXANDRE T ROTTA PEARLS • • • • A wide selection of sedation and analgesia options is available in the pediatric intensive care unit No ideal sedative agent exists for all patients Most children well with a combination of opiates (fentanyl or morphine) and supplementation with benzodiazepines either by infusion (midazolam) or on an as-needed basis (lorazepam) to provide adjunct anxiolysis and amnesia Dexmedetomidine is being used increasingly as an adjunct in place of benzodiazepines Postoperatively, patients require adequate analgesia, which may include the use of epidural anesthesia or patient-controlled analgesia Sedation is an integral part of patient management in the pediatric intensive care unit (PICU) It is necessary to minimize the perception of and response to anxiety and pain Children who are not adequately sedated or who experience pain may become tachycardic and hypertensive, among other signs of stress Provision of adequate sedation and analgesia facilitates bedside nursing, rehabilitation, and respiratory care It also prevents dislodging of critical tubes and monitoring devices, such as central venous lines, arterial lines, chest tubes, and endotracheal tubes Optimizing sedation and analgesia has been shown to reduce oxygen consumption in critically ill children and modulate the intensity of stress inflammatory response Conversely, oversedation can cause cardiovascular depression, ileus, interfere with a comprehensive neurologic examination, and prolong the ICU stay In patients requiring prolonged sedation, tolerance and tachyphylaxis develop, which lead to increasing sedative requirements The patient may also be at risk for postsedation-related complications, such as delirium and post-ICU psychological disorders There are different sedative classes available to use in the PICU It is worth noting that the majority of these agents are not approved by the US Food and Drug Administration (FDA) for long-term sedation in children and that most of the experience with these medications comes from short-term use in the operating room Their effectiveness, safety, and adverse effect profiles may not transfer between these two environments The possibility of impaired brain development after anesthesia in young children must also be a concern for the PICU physician • • • When the ability to perform a rapid neurologic examination is necessary, use of short-acting agents—such as remifentanil, propofol, or isoflurane—may be warranted All sedative agents result in tolerance with prolonged use The clinician must be aware that withdrawal may occur with the prolonged use of these agents (i.e., more than 3–5 days) A proactive treatment plan with methadone at the equivalent dose can effectively and safely prevent opiate withdrawal in the patient in the pediatric intensive care unit Patients may recall their stay in the ICU despite adequate sedation Many remember having an endotracheal tube or having their lungs mechanically ventilated Nightmares and hallucinations also have been reported.1 Single-drug therapy or inadequate dosing may be associated with a heightened incidence of recall in the patient receiving neuromuscular blocking agents.2 In adults, delusional memories and underlying anxiety states may predict the development of posttraumatic stress disorders after sedation in the ICU.3 Delusional memories were reported much more frequently than factual memories, and most patients did not remember correctly the events that occurred during their stay in the ICU In pediatric patients, recall of the PICU experience has also been reported.4 More than 66% of pediatric patients remembered their stay in the PICU; 18% had bad memories, 16% remembered mechanical ventilation and anxiety, and 29% remembered pain from a procedure or movement Overall, approximately 15% of the recollections among PICU patients were considered negative.4 Verbal children with normal cognition have had delusional memories, often reported as disturbing visual hallucinations.5 Delusional memories were more common with longer use of opiates and benzodiazepines, which is consistent with the adult literature Children with head injuries are less likely to report factual memories Sleep disturbance and loss of sleep are reported to adversely affect short-term recovery and long-term cognitive function.5 A normal sleep-wake pattern has benefits with respect to immunity, thermoregulation, reducing the risk of delirium, and preventing the development of a catabolic state.6 The sleep that children experience under sedation is not restful, with decreased 1583 1584 S E C T I O N X I V Pediatric Critical Care: Anesthesia Principles in the Pediatric Intensive Care Unit slow-wave and rapid eye movement sleep patterns and loss of circadian rhythm Noise levels in the PICU are often high and can interfere with the child’s ability to rest.7 Monitor alarms and awakening during routine assessments contribute to this distraction The use of earplugs and eye masks may help reduce the disruption and facilitate a more normal sleep pattern Posttraumatic Stress Disorder Posttraumatic stress disorder (PTSD) is a possible complication of a child’s stay in the ICU Several components are required for the diagnosis of PTSD.8 The American Psychiatric Association’s Diagnostic and Statistical Manual, Fifth Edition (DSM-V) requires the following criteria for a diagnosis of PTSD in adults, adolescents, and children older than years: (1) an exposure, (2) one or more intrusion or reexperiencing symptoms, (3) avoidance behavior, and (4) alterations in arousal associated with the traumatic event; in addition, (5) the symptoms should have exceeded month and (6) have a clinically significant effect on the child’s functioning There is no specific test for PTSD, but children often have a low basal cortisol level, with exaggerated cortisol suppression in response to dexamethasone Using slightly modified alternate DSM-V criteria shown to be more appropriate for children (Box 132.1), the incidence of postPICU PTSD was 29% in children aged through 16 years.9 There appeared to be no difference in the incidence with respect to age; however, younger children tended to have more avoidance of thoughts, whereas older children suffered from diminished in• BOX 132.1 Posttraumatic Stress Disorder Alternative Algorithm Criterion A (Event) Experienced event that threatened death or serious injury Criterion B (Reexperiencing) Recurrent distressing memories Recurrent distressing dreams Sense of reliving events Psychologic distress with reminders Physiologic reactivity with reminders terest in activities and difficulty concentrating.9 This is important, as these findings may persist for up to months and affect the daily function of the child and family after discharge Children who are more critically ill or those who require multiple procedures are more likely to report symptoms of PTSD High postICU anxiety scores and delusional memories (rather than factual ones) appear to be related to higher risk of PTSD.10,11 The use of dexmedetomidine has been shown to reduce the risk of delirium; however, it is associated with increased recall along with greater post-ICU anxiety.12 It is important to ensure that children are suitably sedated and receiving appropriate analgesia to reduce the unpleasant memories of painful procedures during their ICU stay Sedation Scoring and Assessment Various scoring systems have been used to guide sedation A recently validated and now often used assessment tool is the Richmond Agitation Sedation Scale (RASS).13 The RASS grades a patient’s level of sedation using a 10-point score (Table 132.1) and appears to be better suited for PICU sedation than the Ramsay score.14 Many units use protocols in which the bedside nurse assesses the patient’s RASS score and then adjusts the sedative medication dosing as necessary to achieve the desired level of sedation, which varies from patient to patient and over time Most clinicians seek to maintain instrumented patients in a sleepy but easily awakened state A RASS score of 22 to 23 seems to be the ideal clinical end point for sedation for most patients Deeper sedation (RASS 24) should be reserved for selected patients who are often younger, are receiving concurrent neuromuscular blockade, or have severe head injury The use of sedation scoring systems has been shown to reduce costs in surgical ICUs It allows patients to be weaned more rapidly from the ventilator through better control of the sedation level, resulting in more ventilatorfree days and shorter ICU stay.15 The COMFORT scale, which is composed of eight variables (each with five categories), has also been validated for use in the PICU to assess sedation level in children However, use of this system is more complicated and time consuming.16 Clinical scoring systems may be affected by some degree of subjectivity and interobserver variability; thus, more objective Criterion C (Avoidance) Avoidance of thoughts, feelings Avoidance of activities Diminished interest in activities Detached from others Restricted affect Sense of foreshortened future TABLE 132.1 Richmond Agitation-Sedation Scale (RASS) 14 Combative Unacceptable; increase sedation 13 Very agitated Unacceptable; increase sedation Criterion D (Hyperarousal) 12 Agitated Unacceptable; increase sedation Difficulty sleeping Irritability/anger Difficulty concentrating Hypervigilance Exaggerated startle response 11 Restless Acceptable; no action necessary Alert and calm Acceptable; no action necessary 21 Drowsy Acceptable; no action necessary 22 Light sedation Acceptable; no action necessary 23 Moderate sedation Acceptable; no action necessary 24 Heavy sedation Unacceptable; monitor respiratory status and sedation level until stable at or 25 Unarousable Unacceptable; monitor respiratory status and sedation level until stable at or Criterion E (Duration) Duration greater than month Criterion F (Effect) The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning ... action of these agents as a competitive antagonist for acetylcholine at the neuromuscular junction This chapter reviews the pharmacology of depolarizing and nondepolarizing NMBAs, along with monitoring... child’s ability to rest.7 Monitor alarms and awakening during routine assessments contribute to this distraction The use of earplugs and eye masks may help reduce the disruption and facilitate... reminders Physiologic reactivity with reminders terest in activities and difficulty concentrating.9 This is important, as these findings may persist for up to months and affect the daily function