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Sedation in the Pediatric Intensive Care Unit: Challenges, Outcomes, and Future Strategies in the United States

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Pediatric Sedation Outside of the Operating Room
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Abstract

Sedation and analgesia are required on a daily basis for infants and children in the pediatric intensive care unit (PICU). Regardless of the patient’s age, cognitive level, underlying medical condition, or comorbid conditions, various factors may result in agitation, anxiety, and pain during the PICU process. One of the challenges of the PICU is the variability that is presented in patient type (age, weight, comorbid conditions, acute illness), procedure type and duration, and location (in the PICU versus off-site). The primary goals are to provide analgesia, anxiolysis, and comfort while promoting early mobility and sleep hygiene and preventing delirium. The pediatric intensivists are now also involved in outpatient procedural sedation outside the PICU due to their expertise in early recognition and management of airway and hemodynamic compromise.

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References

  1. Kudchadkar SR, Yaster M, Punjabi NM. Sedation, sleep promotion, and delirium screening practices in the care of mechanically ventilated children: a wake-up call for the pediatric critical care community*. Crit Care Med. 2014;42(7):1592–600.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Enterlein G, Byhahn C, American Society of Anesthesiologists Task F. Practice guidelines for management of the difficult airway: update by the American Society of Anesthesiologists task force. Anaesthesist. 2013;62(10):832–5.

    Article  CAS  PubMed  Google Scholar 

  3. Vargo JJ, et al. Multisociety sedation curriculum for gastrointestinal endoscopy. Gastrointestinal Endoscopy. 2012;76(1):e1–e25.

    Article  PubMed  Google Scholar 

  4. Mallampati SR, Gatt SP, Gugino LD, et al. A clinical sign to predict difficult tracheal intubation: a prospective study. Can Anaesth Soc J. 1985;32(4):429–34.

    Article  CAS  PubMed  Google Scholar 

  5. Green SM, Roback MG. Is the Mallampati score useful for emergency department airway management or procedural sedation? Ann Emerg Med. 2019;74(2):251–9.

    Article  PubMed  Google Scholar 

  6. American Society of Anesthesiologists Task Force on S, Analgesia by N-A. Practice guidelines for sedation and analgesia by non-anesthesiologists. Anesthesiology. 2002;96(4):1004–17.

    Article  Google Scholar 

  7. Green SM, Leroy PL, Roback MG, et al. An international multidisciplinary consensus statement on fasting before procedural sedation in adults and children. Anaesthesia. 2020;75(3):374–85.

    Article  CAS  PubMed  Google Scholar 

  8. Bhatt M, Johnson DW, Taljaard M, et al. Association of preprocedural fasting with outcomes of emergency department sedation in children. JAMA Pediatr. 2018;172(7):678–85.

    Article  PubMed Central  PubMed  Google Scholar 

  9. Beach ML, Cohen DM, Gallagher SM, Cravero JP. Major adverse events and relationship to nil per os status in pediatric sedation/anesthesia outside the operating room: a report of the pediatric sedation research consortium. Anesthesiology. 2016;124(1):80–8.

    Article  CAS  PubMed  Google Scholar 

  10. Cote CJ, Wilson S, American Academy of Pediatrics, American Academy of Pediatric Dentistry. Guidelines for monitoring and management of pediatric patients before, during, and after sedation for diagnostic and therapeutic procedures. Pediatrics. 2019;143(6):e20191000.

    Article  PubMed  Google Scholar 

  11. Curley MA, Harris SK, Fraser KA, Johnson RA, Arnold JH. State behavioral scale: a sedation assessment instrument for infants and young children supported on mechanical ventilation. Pediatr Crit Care Med. 2006;7(2):107–14.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Vet NJ, Kleiber N, Ista E, de Hoog M, de Wildt SN. Sedation in critically ill children with respiratory failure. Front Pediatr. 2016;4:89.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Malviya S, Voepel-Lewis T, Tait AR, Merkel S, Tremper K, Naughton N. Depth of sedation in children undergoing computed tomography: validity and reliability of the University of Michigan Sedation Scale (UMSS). Br J Anaesth. 2002;88(2):241–5.

    Article  CAS  PubMed  Google Scholar 

  14. Aldrete JA. Post-anesthetic recovery score. J Am Coll Surg. 2007;205(5):e3–4; author reply e4–5.

    Article  PubMed  Google Scholar 

  15. Sebel PS, Lang E, Rampil IJ, et al. A multicenter study of bispectral electroencephalogram analysis for monitoring anesthetic effect. Anesth Analg. 1997;84(4):891–9.

    Article  CAS  PubMed  Google Scholar 

  16. Gill M, Haycock K, Green SM, Krauss B. Can the bispectral index monitor the sedation adequacy of intubated ED adults? Am J Emerg Med. 2004;22(2):76–82.

    Article  PubMed  Google Scholar 

  17. McDermott NB, VanSickle T, Motas D, Friesen RH. Validation of the bispectral index monitor during conscious and deep sedation in children. Anesth Analg. 2003;97(1):39–43, table of contents.

    Article  PubMed  Google Scholar 

  18. Courtman SP, Wardurgh A, Petros AJ. Comparison of the bispectral index monitor with the comfort score in assessing level of sedation of critically ill children. Intensive Care Med. 2003;29(12):2239–46.

    Article  PubMed  Google Scholar 

  19. Aneja R, Heard AM, Fletcher JE, Heard CM. Sedation monitoring of children by the bispectral index in the pediatric intensive care unit. Pediatr Crit Care Med. 2003;4(1):60–4.

    Article  PubMed  Google Scholar 

  20. 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(3):506–11; table of contents.

    Article  PubMed  Google Scholar 

  21. Arbour RB. Using the bispectral index to assess arousal response in a patient with neuromuscular blockade. Am J Crit Care. 2000;9(6):383–7.

    Article  CAS  PubMed  Google Scholar 

  22. Zuppa AF, Conrado DJ, Zane NR, et al. Midazolam dose optimization in critically ill pediatric patients with acute respiratory failure: a population pharmacokinetic-pharmacogenomic study. Crit Care Med. 2019;47(4):e301–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Zuppa AF, Benitez GR, Zane NR, et al. Morphine dose optimization in critically ill pediatric patients with acute respiratory failure: a population pharmacokinetic-pharmacogenomic study. Crit Care Med. 2019;47(6):e485–94.

    Article  CAS  PubMed  Google Scholar 

  24. de Wildt SN, de Hoog M, Vinks AA, van der Giesen E, van den Anker JN. Population pharmacokinetics and metabolism of midazolam in pediatric intensive care patients. Crit Care Med. 2003;31(7):1952–8.

    Article  CAS  PubMed  Google Scholar 

  25. Chua MV, Tsueda K, Doufas AG. Midazolam causes less sedation in volunteers with red hair. Can J Anaesth. 2004;51(1):25–30.

    Article  PubMed  Google Scholar 

  26. Katz R, Kelly HW. Pharmacokinetics of continuous infusions of fentanyl in critically ill children. Crit Care Med. 1993;21(7):995–1000.

    Article  CAS  PubMed  Google Scholar 

  27. Cohen M, Sadhasivam S, Vinks AA. Pharmacogenetics in perioperative medicine. Curr Opin Anaesthesiol. 2012;25(4):419–27.

    Article  CAS  PubMed  Google Scholar 

  28. Verlaat CW, Heesen GP, Vet NJ, et al. Randomized controlled trial of daily interruption of sedatives in critically ill children. Paediatr Anaesth. 2014;24(2):151–6.

    Article  PubMed  Google Scholar 

  29. Ely EW. The ABCDEF bundle: science and philosophy of how ICU liberation serves patients and families. Crit Care Med. 2017;45(2):321–30.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Tsze DS, Mallory MD, Cravero JP. Practice patterns and adverse events of nitrous oxide sedation and analgesia: a report from the pediatric sedation research consortium. J Pediatr. 2016;169:260–5. e262.

    Article  CAS  PubMed  Google Scholar 

  31. Tobias JD. Inhalational anesthesia: basic pharmacology, end organ effects, and applications in the treatment of status asthmaticus. J Intensive Care Med. 2009;24(6):361–71.

    Article  PubMed  Google Scholar 

  32. Mencia S, Palacios A, Garcia M, et al. An exploratory study of sevoflurane as an alternative for difficult sedation in critically ill children. Pediatr Crit Care Med. 2018;19(7):e335–41.

    Article  PubMed  Google Scholar 

  33. Tobias JD. Therapeutic applications and uses of inhalational anesthesia in the pediatric intensive care unit. Pediatr Crit Care Med. 2008;9(2):169–79.

    Article  PubMed  Google Scholar 

  34. Olkkola KT, Ahonen J. Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;182:335–60.

    Article  CAS  Google Scholar 

  35. Cai XF, Zhang FR, Zhang L, Sun JM, Li WB. Efficacy of analgesic and sedative treatments in children with mechanical ventilation in the pediatric intensive care unit. Zhongguo Dang Dai Er Ke Za Zhi. 2017;19(11):1138–44.

    PubMed  Google Scholar 

  36. Barends CRM, Absalom AR, Struys M. Drug selection for ambulatory procedural sedation. Curr Opin Anaesthesiol. 2018;31(6):673–8.

    Article  CAS  PubMed  Google Scholar 

  37. Karl HW, Rosenberger JL, Larach MG, Ruffle JM. Transmucosal administration of midazolam for premedication of pediatric patients. Comparison of the nasal and sublingual routes. Anesthesiology. 1993;78(5):885–91.

    Article  CAS  PubMed  Google Scholar 

  38. Cote CJ, Cohen IT, Suresh S, et al. A comparison of three doses of a commercially prepared oral midazolam syrup in children. Anesth Analg. 2002;94(1):37–43, table of contents.

    CAS  PubMed  Google Scholar 

  39. Ku LC, Simmons C, Smith PB, et al. Intranasal midazolam and fentanyl for procedural sedation and analgesia in infants in the neonatal intensive care unit. J Neonatal Perinatal Med. 2019;12(2):143–8.

    Article  CAS  PubMed  Google Scholar 

  40. Bauer TM, Ritz R, Haberthur C, et al. Prolonged sedation due to accumulation of conjugated metabolites of midazolam. Lancet. 1995;346(8968):145–7.

    Article  CAS  PubMed  Google Scholar 

  41. Benzodiazepines. LiverTox: clinical and research information on drug-induced liver injury. Bethesda: National Institute of Diabetes and Digestive and Kidney Diseases; 2012.

    Google Scholar 

  42. Swart EL, van Schijndel RJ, van Loenen AC, Thijs LG. Continuous infusion of lorazepam versus medazolam in patients in the intensive care unit: sedation with lorazepam is easier to manage and is more cost-effective. Crit Care Med. 1999;27(8):1461–5.

    Article  CAS  PubMed  Google Scholar 

  43. Chauhan M, Garg A, Bharadwaj A. Effect of short-term propofol administration on pancreatic enzymes and lipid biochemistry in children between 1 month and 36 months. Paediatr Anaesth. 2013;23(4):355–9.

    Article  PubMed  Google Scholar 

  44. Sommerfield DL, Lucas M, Schilling A, et al. Propofol use in children with allergies to egg, peanut, soybean or other legumes. Anaesthesia. 2019;74(10):1252–9.

    Article  CAS  PubMed  Google Scholar 

  45. Murphy A, Campbell DE, Baines D, Mehr S. Allergic reactions to propofol in egg-allergic children. Anesth Analg. 2011;113(1):140–4.

    Article  CAS  PubMed  Google Scholar 

  46. Pillai U, Hothi JC, Bhat ZY. Severe propylene glycol toxicity secondary to use of anti-epileptics. Am J Ther. 2014;21(4):e106–9.

    Article  PubMed  Google Scholar 

  47. Warrington SE, Collier HK, Himebauch AS, Wolfe HA. Evaluation of IV to enteral benzodiazepine conversion calculations in a pediatric intensive care setting. Pediatr Crit Care Med. 2018;19(11):e569–75.

    Article  PubMed  Google Scholar 

  48. Reynolds HN, Teiken P, Regan ME, et al. Hyperlactatemia, increased osmolar gap, and renal dysfunction during continuous lorazepam infusion. Crit Care Med. 2000;28(5):1631–4.

    Article  CAS  PubMed  Google Scholar 

  49. Grunwell JR, Travers C, Stormorken AG, et al. Pediatric procedural sedation using the combination of ketamine and propofol outside of the emergency department: a report from the pediatric sedation research consortium. Pediatr Crit Care Med. 2017;18(8):e356–63.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Dumps C, Bolkenius D, Halbeck E. Etomidate for intravenous induction of anaesthesia. Anaesthesist. 2017;66(12):969–80.

    Article  CAS  PubMed  Google Scholar 

  51. Bramwell KJ, Haizlip J, Pribble C, VanDerHeyden TC, Witte M. The effect of etomidate on intracranial pressure and systemic blood pressure in pediatric patients with severe traumatic brain injury. Pediatr Emerg Care. 2006;22(2):90–3.

    Article  PubMed  Google Scholar 

  52. Prakash M, Gnanasekar R, Sakthirajan P, Adole PS. A comparative study of two infusion doses of etomidate for induction vs standard induction dose of etomidate. Eur J Clin Pharmacol. 2019;75(7):889–94.

    Article  CAS  PubMed  Google Scholar 

  53. Wagner RL, White PF, Kan PB, Rosenthal MH, Feldman D. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med. 1984;310(22):1415–21.

    Article  CAS  PubMed  Google Scholar 

  54. Devlin RJ, Kalil D. Etomidate as an induction agent in sepsis. Crit Care Nurs Clin North Am. 2018;30(3):e1–9.

    Article  PubMed  Google Scholar 

  55. Scherzer D, Leder M, Tobias JD. Pro-con debate: etomidate or ketamine for rapid sequence intubation in pediatric patients. J Pediatr Pharmacol Ther. 2012;17(2):142–9.

    PubMed Central  PubMed  Google Scholar 

  56. Thompson Bastin ML, Baker SN, Weant KA. Effects of etomidate on adrenal suppression: a review of intubated septic patients. Hosp Pharm. 2014;49(2):177–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Majesko A, Darby JM. Etomidate and adrenal insufficiency: the controversy continues. Crit Care. 2010;14(6):338.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Sterling SA, Puskarich MA, Jones AE. The effect of etomidate on mortality in sepsis remains unclear. Crit Care Med. 2013;41(6):e95.

    Article  PubMed  Google Scholar 

  59. Fazackerley EJ, Martin AJ, Tolhurst-Cleaver CL, Watkins J. Anaphylactoid reaction following the use of etomidate. Anaesthesia. 1988;43(11):953–4.

    Article  CAS  PubMed  Google Scholar 

  60. Nyman Y, Von Hofsten K, Palm C, Eksborg S, Lonnqvist PA. Etomidate-Lipuro is associated with considerably less injection pain in children compared with propofol with added lidocaine. Br J Anaesth. 2006;97(4):536–9.

    Article  CAS  PubMed  Google Scholar 

  61. Bruder EA, Ball IM, Ridi S, Pickett W, Hohl C. Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients. Cochrane Database Syst Rev. 2015;1:CD010225.

    PubMed  Google Scholar 

  62. Malapero RJ, Zaccagnino MP, Brovman EY, Kaye AD, Urman RD. Etomidate derivatives: novel pharmaceutical agents in anesthesia. J Anaesthesiol Clin Pharmacol. 2017;33(4):429–31.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Davis WD, Davis KA, Hooper K. The use of ketamine for the management of acute pain in the emergency department. Adv Emerg Nurs J. 2019;41(2):111–21.

    Article  PubMed  Google Scholar 

  64. Gabriel RA, Swisher MW, Sztain JF, Furnish TJ, Ilfeld BM, Said ET. State of the art opioid-sparing strategies for post-operative pain in adult surgical patients. Expert Opin Pharmacother. 2019;20(8):949–61.

    Article  CAS  PubMed  Google Scholar 

  65. Himmelseher S, Durieux ME. Ketamine for perioperative pain management. Anesthesiology. 2005;102(1):211–20.

    Article  PubMed  Google Scholar 

  66. Dewhirst E, Frazier WJ, Leder M, Fraser DD, Tobias JD. Cardiac arrest following ketamine administration for rapid sequence intubation. J Intensive Care Med. 2013;28(6):375–9.

    Article  PubMed  Google Scholar 

  67. Friesen RH, Twite MD, Nichols CS, et al. Hemodynamic response to ketamine in children with pulmonary hypertension. Paediatr Anaesth. 2016;26(1):102–8.

    Article  PubMed  Google Scholar 

  68. Loomba RS, Gray SB, Flores S. Hemodynamic effects of ketamine in children with congenital heart disease and/or pulmonary hypertension. Congenit Heart Dis. 2018;13(5):646–54.

    Article  PubMed  Google Scholar 

  69. von Ungern-Sternberg BS, Regli A, Frei FJ, et al. A deeper level of ketamine anesthesia does not affect functional residual capacity and ventilation distribution in healthy preschool children. Paediatr Anaesth. 2007;17(12):1150–5.

    Article  Google Scholar 

  70. Jones BP, Paul A. Management of acute asthma in the pediatric patient: an evidence-based review. Pediatr Emerg Med Pract. 2013;10(5):1–23; quiz 23–24.

    PubMed  Google Scholar 

  71. Bourke DL, Malit LA, Smith TC. Respiratory interactions of ketamine and morphine. Anesthesiology. 1987;66(2):153–6.

    Article  CAS  PubMed  Google Scholar 

  72. Erstad BL, Patanwala AE. Ketamine for analgosedation in critically ill patients. J Crit Care. 2016;35:145–9.

    Article  CAS  PubMed  Google Scholar 

  73. Grunwell JR, Travers C, McCracken CE, et al. Procedural sedation outside of the operating room using ketamine in 22,645 children: a report from the pediatric sedation research consortium. Pediatr Crit Care Med. 2016;17(12):1109–16.

    Article  PubMed Central  PubMed  Google Scholar 

  74. Berkenbosch JW, Graff GR, Stark JM. Safety and efficacy of ketamine sedation for infant flexible fiberoptic bronchoscopy. Chest. 2004;125(3):1132–7.

    Article  CAS  PubMed  Google Scholar 

  75. Green SM, Andolfatto G, Krauss BS. Ketamine and intracranial pressure: no contraindication except hydrocephalus. Ann Emerg Med. 2015;65(1):52–4.

    Article  PubMed  Google Scholar 

  76. Cohen L, Athaide V, Wickham ME, Doyle-Waters MM, Rose NG, Hohl CM. The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review. Ann Emerg Med. 2015;65(1):43–51. e42.

    Article  PubMed  Google Scholar 

  77. Caputo D, Iorio R, Vigevano F, Fusco L. Febrile infection-related epilepsy syndrome (FIRES) with super-refractory status epilepticus revealing autoimmune encephalitis due to GABAAR antibodies. Eur J Paediatr Neurol. 2018;22(1):182–5.

    Article  CAS  PubMed  Google Scholar 

  78. Sheth RD, Gidal BE. Refractory status epilepticus: response to ketamine. Neurology. 1998;51(6):1765–6.

    Article  CAS  PubMed  Google Scholar 

  79. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011;57(5):449–61.

    Article  PubMed  Google Scholar 

  80. Heiberger AL, Ngorsuraches S, Olgun G, et al. Safety and utility of continuous ketamine infusion for sedation in mechanically ventilated pediatric patients. J Pediatr Pharmacol Ther. 2018;23(6):447–54.

    PubMed Central  PubMed  Google Scholar 

  81. Martyn JAJ, Mao J, Bittner EA. Opioid tolerance in critical illness. Reply. N Engl J Med. 2019;380(16):e26.

    Article  PubMed  Google Scholar 

  82. Poonai N, Canton K, Ali S, et al. Intranasal ketamine for procedural sedation and analgesia in children: a systematic review. PLoS ONE. 2017;12(3):e0173253.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  83. Green SM, Andolfatto G. Let’s “take ‘em down” with a ketamine blow dart. Ann Emerg Med. 2016;67(5):588–90.

    Google Scholar 

  84. Chidambaran V, Costandi A, D’Mello A. Propofol: a review of its role in pediatric anesthesia and sedation. CNS Drugs. 2015;29(7):543–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Oddo M, Crippa IA, Mehta S, et al. Optimizing sedation in patients with acute brain injury. Crit Care. 2016;20(1):128.

    Article  PubMed Central  PubMed  Google Scholar 

  86. Grim KJ, Abcejo AJ, Barnes A, et al. Caveolae and propofol effects on airway smooth muscle. Br J Anaesth. 2012;109(3):444–53.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Brown RH, Greenberg RS, Wagner EM. Efficacy of propofol to prevent bronchoconstriction: effects of preservative. Anesthesiology. 2001;94(5):851–5; discussion 856A.

    Article  CAS  PubMed  Google Scholar 

  88. Setty S, Kumar AB. Asystole on anesthesia induction in adults: don’t blame the succinylcholine alone. Minerva Anestesiol. 2012;78(2):258–9.

    CAS  PubMed  Google Scholar 

  89. Egan TD, Brock-Utne JG. Asystole after anesthesia induction with a fentanyl, propofol, and succinylcholine sequence. Anesth Analg. 1991;73(6):818–20.

    Article  CAS  PubMed  Google Scholar 

  90. Trotter C, Serpell MG. Neurological sequelae in children after prolonged propofol infusion. Anaesthesia. 1992;47(4):340–2.

    Article  CAS  PubMed  Google Scholar 

  91. Arayakarnkul P, Chomtho K. Treatment options in pediatric super-refractory status epilepticus. Brain and Development. 2019;41(4):359–66.

    Article  PubMed  Google Scholar 

  92. Zhang Q, Yu Y, Lu Y, Yue H. Systematic review and meta-analysis of propofol versus barbiturates for controlling refractory status epilepticus. BMC Neurol. 2019;19(1):55.

    Article  PubMed Central  PubMed  Google Scholar 

  93. Hemphill S, McMenamin L, Bellamy MC, Hopkins PM. Propofol infusion syndrome: a structured literature review and analysis of published case reports. Br J Anaesth. 2019;122(4):448–59.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Dell’Angela L, Gatti G, Morosin M, Lardieri G. Propofol infusion syndrome: an early and unusual electrocardiographic pattern. J Cardiothorac Vasc Anesth. 2019;34:2004–6.

    Article  PubMed  Google Scholar 

  95. Bray RJ. Propofol-infusion syndrome in children. Lancet. 1999;353(9169):2074–5.

    Article  CAS  PubMed  Google Scholar 

  96. Wolf A, Weir P, Segar P, Stone J, Shield J. Impaired fatty acid oxidation in propofol infusion syndrome. Lancet. 2001;357(9256):606–7.

    Article  CAS  PubMed  Google Scholar 

  97. Bray RJ. The propofol infusion syndrome in infants and children: can we predict the risk? Curr Opin Anaesthesiol. 2002;15(3):339–42.

    Article  PubMed  Google Scholar 

  98. Fudickar A, Bein B. Propofol infusion syndrome: update of clinical manifestation and pathophysiology. Minerva Anestesiol. 2009;75(5):339–44.

    CAS  PubMed  Google Scholar 

  99. Pessach I, Paret G. PICU propofol use, where do we go from here? Pediatr Crit Care Med. 2016;17(3):273–5.

    Article  PubMed  Google Scholar 

  100. Rosenfeld-Yehoshua N, Klin B, Berkovitch M, Abu-Kishk I. Propofol use in Israeli PICUs. Pediatr Crit Care Med. 2016;17(3):e117–20.

    Article  PubMed  Google Scholar 

  101. Svensson ML, Lindberg L. The use of propofol sedation in a paediatric intensive care unit. Nurs Crit Care. 2012;17(4):198–203.

    Article  PubMed  Google Scholar 

  102. Koriyama H, Duff JP, Guerra GG, Chan AW, Sedation W, Analgesia T. Is propofol a friend or a foe of the pediatric intensivist? Description of propofol use in a PICU*. Pediatr Crit Care Med. 2014;15(2):e66–71.

    Article  PubMed  Google Scholar 

  103. Kamat PP, McCracken CE, Gillespie SE, et al. Pediatric critical care physician-administered procedural sedation using propofol: a report from the pediatric sedation research consortium database. Pediatr Crit Care Med. 2015;16(1):11–20.

    Article  PubMed  Google Scholar 

  104. Desousa KA. Pain on propofol injection: causes and remedies. Indian J Pharmacol. 2016;48(6):617–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  105. Zorrilla-Vaca A, Arevalo JJ, Escandon-Vargas K, Soltanifar D, Mirski MA. Infectious disease risk associated with contaminated propofol anesthesia, 1989–2014(1). Emerg Infect Dis. 2016;22(6):981–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  106. Yanay O, Brogan TV, Martin LD. Continuous pentobarbital infusion in children is associated with high rates of complications. J Crit Care. 2004;19(3):174–8.

    Article  CAS  PubMed  Google Scholar 

  107. Tasker RC, Goodkin HP, Sanchez Fernandez I, et al. Refractory status epilepticus in children: intention to treat with continuous infusions of midazolam and pentobarbital. Pediatr Crit Care Med. 2016;17(10):968–75.

    Article  PubMed Central  PubMed  Google Scholar 

  108. Tobias JD, Deshpande JK, Pietsch JB, Wheeler TJ, Gregory DF. Pentobarbital sedation for patients in the pediatric intensive care unit. South Med J. 1995;88(3):290–4.

    Article  CAS  PubMed  Google Scholar 

  109. Rai S, Drislane FW. Treatment of refractory and super-refractory status Epilepticus. Neurotherapeutics. 2018;15(3):697–712.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  110. Mansour N, deSouza RM, Sikorski C, Kahana M, Frim D. Role of barbiturate coma in the management of focally induced, severe cerebral edema in children. J Neurosurg Pediatr. 2013;12(1):37–43.

    Article  PubMed  Google Scholar 

  111. Jones NE, Kelleman MS, Simon HK, et al. Evaluation of methohexital as an alternative to propofol in a high volume outpatient pediatric sedation service. Am J Emerg Med. 2017;35:1101–5.

    Article  PubMed  Google Scholar 

  112. Mallory MD, Baxter AL, Kost SI, Pediatric Sedation Research C. Propofol vs pentobarbital for sedation of children undergoing magnetic resonance imaging: results from the pediatric sedation research consortium. Paediatr Anaesth. 2009;19(6):601–11.

    Article  PubMed  Google Scholar 

  113. Baxter AL, Mallory MD, Spandorfer PR, et al. Etomidate versus pentobarbital for computed tomography sedations: report from the pediatric sedation research consortium. Pediatr Emerg Care. 2007;23(10):690–5.

    Article  PubMed  Google Scholar 

  114. Minardi C, Sahillioglu E, Astuto M, Colombo M, Ingelmo PM. Sedation and analgesia in pediatric intensive care. Curr Drug Targets. 2012;13(7):936–43.

    Article  CAS  PubMed  Google Scholar 

  115. Stein C. Opioid receptors. Annu Rev Med. 2016;67:433–51.

    Article  CAS  PubMed  Google Scholar 

  116. Fentanyl. LiverTox: clinical and research information on drug-induced liver injury. Bethesda: National Institute of Diabetes and Digestive and Kidney Diseases; 2012.

    Google Scholar 

  117. Azzam AAH, McDonald J, Lambert DG. Hot topics in opioid pharmacology: mixed and biased opioids. Br J Anaesth. 2019;122(6):e136–45.

    Article  CAS  PubMed  Google Scholar 

  118. Ziesenitz VC, Vaughns JD, Koch G, Mikus G, van den Anker JN. Pharmacokinetics of fentanyl and its derivatives in children: a comprehensive review. Clin Pharmacokinet. 2018;57(2):125–49.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  119. Hungerford JL, O’Brien N, Moore-Clingenpeel M, et al. Remifentanil for sedation of children with traumatic brain injury. J Intensive Care Med. 2019;34(7):557–62.

    Article  PubMed  Google Scholar 

  120. Reyle-Hahn M, Niggemann B, Max M, Streich R, Rossaint R. Remifentanil and propofol for sedation in children and young adolescents undergoing diagnostic flexible bronchoscopy. Paediatr Anaesth. 2000;10(1):59–63.

    Article  CAS  PubMed  Google Scholar 

  121. Pokela ML, Ryhanen PT, Koivisto ME, Olkkola KT, Saukkonen AL. Alfentanil-induced rigidity in newborn infants. Anesth Analg. 1992;75(2):252–7.

    Article  CAS  PubMed  Google Scholar 

  122. Roan JP, Bajaj N, Davis FA, Kandinata N. Opioids and chest wall rigidity during mechanical ventilation. Ann Intern Med. 2018;168(9):678.

    Article  PubMed  Google Scholar 

  123. Morphine. LiverTox: clinical and research information on drug-induced liver injury. Bethesda: National Institute of Diabetes and Digestive and Kidney Diseases; 2012.

    Google Scholar 

  124. Lynn AM, Opheim KE, Tyler DC. Morphine infusion after pediatric cardiac surgery. Crit Care Med. 1984;12(10):863–6.

    Article  CAS  PubMed  Google Scholar 

  125. Bittner EA, Shank E, Woodson L, Martyn JA. Acute and perioperative care of the burn-injured patient. Anesthesiology. 2015;122(2):448–64.

    Article  PubMed  Google Scholar 

  126. Anand KJ, Willson DF, Berger J, et al. Tolerance and withdrawal from prolonged opioid use in critically ill children. Pediatrics. 2010;125(5):e1208–25.

    Article  PubMed  Google Scholar 

  127. Harvey MA. Managing agitation in critically ill patients. Am J Crit Care. 1996;5(1):7–16; quiz 17–18.

    Article  CAS  PubMed  Google Scholar 

  128. Keating GM. Dexmedetomidine: a review of its use for sedation in the intensive care setting. Drugs. 2015;75(10):1119–30.

    Article  CAS  PubMed  Google Scholar 

  129. de Castro REV, Martins RSO, Prata-Barbosa A, de Magalhaes-Barbosa MC. Clonidine doses for sedation in the PICU. Pediatr Crit Care Med. 2020;21(1):110.

    Article  PubMed  Google Scholar 

  130. Hayden JC, Breatnach C, Doherty DR, et al. Efficacy of alpha2-agonists for sedation in pediatric critical care: a systematic review. Pediatr Crit Care Med. 2016;17(2):e66–75.

    Article  PubMed  Google Scholar 

  131. Correa-Sales C, Rabin BC, Maze M. A hypnotic response to dexmedetomidine, an alpha 2 agonist, is mediated in the locus coeruleus in rats. Anesthesiology. 1992;76(6):948–52.

    Article  CAS  PubMed  Google Scholar 

  132. Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003;98(2):428–36.

    Article  CAS  PubMed  Google Scholar 

  133. Maze M, Tranquilli W. Alpha-2 adrenoceptor agonists: defining the role in clinical anesthesia. Anesthesiology. 1991;74(3):581–605.

    Article  CAS  PubMed  Google Scholar 

  134. Kamat PP, Kudchadkar SR. IV clonidine in the PICU: time for dexmedetomidine to share the limelight? Pediatr Crit Care Med. 2018;19(8):792–4.

    Article  PubMed  Google Scholar 

  135. Kleiber N, van Rosmalen J, Tibboel D, de Wildt SN. Hemodynamic tolerance to IV clonidine infusion in the PICU. Pediatr Crit Care Med. 2018;19(8):e409–16.

    Article  PubMed  Google Scholar 

  136. Sottas CE, Anderson BJ. Dexmedetomidine: the new all-in-one drug in paediatric anaesthesia? Curr Opin Anaesthesiol. 2017;30(4):441–51.

    Article  CAS  PubMed  Google Scholar 

  137. Zub D, Berkenbosch JW, Tobias JD. Preliminary experience with oral dexmedetomidine for procedural and anesthetic premedication. Paediatr Anaesth. 2005;15(11):932–8.

    Article  PubMed  Google Scholar 

  138. Berkenbosch JW, Tobias JD. Development of bradycardia during sedation with dexmedetomidine in an infant concurrently receiving digoxin. Pediatr Crit Care Med. 2003;4(2):203–5.

    Article  PubMed  Google Scholar 

  139. Grant MJ, Schneider JB, Asaro LA, et al. Dexmedetomidine use in critically ill children with acute respiratory failure. Pediatr Crit Care Med. 2016;17(12):1131–41.

    Article  PubMed Central  PubMed  Google Scholar 

  140. Venkatraman R, Hungerford JL, Hall MW, Moore-Clingenpeel M, Tobias JD. Dexmedetomidine for sedation during noninvasive ventilation in pediatric patients. Pediatr Crit Care Med. 2017;18(9):831–7.

    Article  PubMed  Google Scholar 

  141. Shutes BL, Gee SW, Sargel CL, Fink KA, Tobias JD. Dexmedetomidine as single continuous sedative during noninvasive ventilation: typical usage, hemodynamic effects, and withdrawal. Pediatr Crit Care Med. 2018;19(4):287–97.

    Article  PubMed  Google Scholar 

  142. Thompson RZ, Gardner BM, Autry EB, Day SB, Krishna AS. Survey of the current use of dexmedetomidine and management of withdrawal symptoms in critically ill children. J Pediatr Pharmacol Ther. 2019;24(1):16–21.

    PubMed Central  PubMed  Google Scholar 

  143. Koroglu A, Demirbilek S, Teksan H, Sagir O, But AK, Ersoy MO. Sedative, haemodynamic and respiratory effects of dexmedetomidine in children undergoing magnetic resonance imaging examination: preliminary results. Br J Anaesth. 2005;94(6):821–4.

    Article  CAS  PubMed  Google Scholar 

  144. Berkenbosch JW, Wankum PC, Tobias JD. Prospective evaluation of dexmedetomidine for noninvasive procedural sedation in children. Pediatr Crit Care Med. 2005;6(4):435–9; quiz 440.

    Article  PubMed  Google Scholar 

  145. Koroglu A, Teksan H, Sagir O, Yucel A, Toprak HI, Ersoy OM. A comparison of the sedative, hemodynamic, and respiratory effects of dexmedetomidine and propofol in children undergoing magnetic resonance imaging. Anesth Analg. 2006;103(1):63–7, table of contents.

    Article  CAS  PubMed  Google Scholar 

  146. Mason KP, Zgleszewski SE, Dearden JL, et al. Dexmedetomidine for pediatric sedation for computed tomography imaging studies. Anesth Analg. 2006;103(1):57–62, table of contents.

    Article  CAS  PubMed  Google Scholar 

  147. Mason KP, Lubisch NB, Robinson F, Roskos R. Intramuscular dexmedetomidine sedation for pediatric MRI and CT. AJR Am J Roentgenol. 2011;197(3):720–5.

    Article  PubMed  Google Scholar 

  148. Baier NM, Mendez SS, Kimm D, Velazquez AE, Schroeder AR. Intranasal dexmedetomidine: an effective sedative agent for electroencephalogram and auditory brain response testing. Paediatr Anaesth. 2016;26(3):280–5.

    Article  PubMed  Google Scholar 

  149. Mason KP, Lubisch N, Robinson F, Roskos R, Epstein MA. Intramuscular dexmedetomidine: an effective route of sedation preserves background activity for pediatric electroencephalograms. J Pediatr. 2012;161(5):927–32.

    Article  CAS  PubMed  Google Scholar 

  150. Tobias JD. Dexmedetomidine and ketamine: an effective alternative for procedural sedation? Pediatr Crit Care Med. 2012;13(4):423–7.

    Article  PubMed  Google Scholar 

  151. Boriosi JP, Eickhoff JC, Klein KB, Hollman GA. A retrospective comparison of propofol alone to propofol in combination with dexmedetomidine for pediatric 3T MRI sedation. Paediatr Anaesth. 2017;27(1):52–9.

    Article  PubMed  Google Scholar 

  152. Sulton C, McCracken C, Simon HK, et al. Pediatric procedural sedation using dexmedetomidine: a report from the pediatric sedation research consortium. Hosp Pediatr. 2016;6(9):536–44.

    Article  PubMed  Google Scholar 

  153. Sulton C, Kamat P, Mallory M, Reynolds J. The use of intranasal dexmedetomidine and midazolam for sedated magnetic resonance imaging in children: a report from the pediatric sedation research consortium. Pediatr Emerg Care. 2020;36(3):138–42.

    Google Scholar 

  154. Perez-Zoghbi JF, Zhu W, Grafe MR, Brambrink AM. Dexmedetomidine-mediated neuroprotection against sevoflurane-induced neurotoxicity extends to several brain regions in neonatal rats. Br J Anaesth. 2017;119(3):506–16.

    Article  CAS  PubMed  Google Scholar 

  155. Endesfelder S, Makki H, von Haefen C, Spies CD, Buhrer C, Sifringer M. Neuroprotective effects of dexmedetomidine against hyperoxia-induced injury in the developing rat brain. PLoS ONE. 2017;12(2):e0171498.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  156. Kamat PP, Kudchadkar SR, Simon HK. Sedative and anesthetic neurotoxicity in infants and young children: not just an operating room concern. J Pediatr. 2019;204:285–90.

    Article  PubMed  Google Scholar 

  157. Reimche LD, Sankaran K, Hindmarsh KW, Kasian GF, Gorecki DK, Tan L. Chloral hydrate sedation in neonates and infants—clinical and pharmacologic considerations. Dev Pharmacol Ther. 1989;12(2):57–64.

    Article  CAS  PubMed  Google Scholar 

  158. Pershad J, Palmisano P, Nichols M. Chloral hydrate: the good and the bad. Pediatr Emerg Care. 1999;15(6):432–5.

    Article  CAS  PubMed  Google Scholar 

  159. Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children. Anesth Analg. 2007;104(3):509–20.

    Article  CAS  PubMed  Google Scholar 

  160. Vade A, Sukhani R, Dolenga M, Habisohn-Schuck C. Chloral hydrate sedation of children undergoing CT and MR imaging: safety as judged by American Academy of Pediatrics guidelines. AJR Am J Roentgenol. 1995;165(4):905–9.

    Article  CAS  PubMed  Google Scholar 

  161. Rokicki W. Cardiac arrhythmia in a child after the usual dose of chloral hydrate. Pediatr Cardiol. 1996;17(6):419–20.

    Article  CAS  PubMed  Google Scholar 

  162. Reynolds J, Sedillo DJ. The evolving role of intranasal dexmedetomidine for pediatric procedural sedation. Hosp Pediatr. 2018;8:115–7.

    Article  Google Scholar 

  163. Collett BJ. Opioid tolerance: the clinical perspective. Br J Anaesth. 1998;81(1):58–68.

    Article  CAS  PubMed  Google Scholar 

  164. Tobias JD. Dexmedetomidine: are tolerance and withdrawal going to be an issue with long-term infusions? Pediatr Crit Care Med. 2010;11(1):158–60.

    Article  PubMed  Google Scholar 

  165. Martyn JAJ, Mao J, Bittner EA. Opioid tolerance in critical illness. N Engl J Med. 2019;380(4):365–78.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  166. Katz R, Kelly HW, Hsi A. Prospective study on the occurrence of withdrawal in critically ill children who receive fentanyl by continuous infusion. Crit Care Med. 1994;22(5):763–7.

    Article  CAS  PubMed  Google Scholar 

  167. Franck LS, Harris S, Soetenga D, Amling J, Curley M. The withdrawal assessment tool (WAT-1): measuring iatrogenic withdrawal symptoms in pediatric critical care. Pediatr Crit Care Med. 2008;9(6):573–58.

    Article  PubMed Central  PubMed  Google Scholar 

  168. Fisher D, Grap MJ, Younger JB, Ameringer S, Elswick RK. Opioid withdrawal signs and symptoms in children: frequency and determinants. Heart Lung. 2013;42(6):407–13.

    Article  PubMed  Google Scholar 

  169. Franck LS, Scoppettuolo LA, Wypij D, Curley MA. Validity and generalizability of the withdrawal assessment tool-1 (WAT-1) for monitoring iatrogenic withdrawal syndrome in pediatric patients. Pain. 2012;153(1):142–8.

    Article  PubMed  Google Scholar 

  170. Franck LS, Naughton I, Winter I. Opioid and benzodiazepine withdrawal symptoms in paediatric intensive care patients. Intensive Crit Care Nurs. 2004;20(6):344–51.

    Article  PubMed  Google Scholar 

  171. Robertson RC, Darsey E, Fortenberry JD, Pettignano R, Hartley G. Evaluation of an opiate-weaning protocol using methadone in pediatric intensive care unit patients. Pediatr Crit Care Med. 2000;1(2):119–23.

    Article  CAS  PubMed  Google Scholar 

  172. Lugo RA, MacLaren R, Cash J, Pribble CG, Vernon DD. Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU. Pharmacotherapy. 2001;21(12):1566–73.

    Article  CAS  PubMed  Google Scholar 

  173. Berens RJ, Meyer MT, Mikhailov TA, et al. A prospective evaluation of opioid weaning in opioid-dependent pediatric critical care patients. Anesth Analg. 2006;102(4):1045–50.

    Article  CAS  PubMed  Google Scholar 

  174. Galinkin J, Koh JL, Committee on Drugs, Section on Anesthesiology and Pain Medicine, American Academy of Pediatrics. Recognition and management of iatrogenically induced opioid dependence and withdrawal in children. Pediatrics. 2014;133(1):152–5.

    Article  PubMed  Google Scholar 

  175. Tobias JD, Deshpande JK, Gregory DF. Outpatient therapy of iatrogenic drug dependency following prolonged sedation in the pediatric intensive care unit. Intensive Care Med. 1994;20(7):504–7.

    Article  CAS  PubMed  Google Scholar 

  176. Lugo RA, Chester EA, Cash J, Grant MJ, Vernon DD. A cost analysis of enterally administered lorazepam in the pediatric intensive care unit. Crit Care Med. 1999;27(2):417–21.

    Article  CAS  PubMed  Google Scholar 

  177. Siddappa R, Fletcher JE, Heard AM, Kielma D, Cimino M, Heard CM. Methadone dosage for prevention of opioid withdrawal in children. Paediatr Anaesth. 2003;13(9):805–10.

    Article  PubMed  Google Scholar 

  178. Atkinson D, Dunne A, Parker M. Torsades de pointes and self-terminating ventricular fibrillation in a prescription methadone user. Anaesthesia. 2007;62(9):952–5.

    Article  CAS  PubMed  Google Scholar 

  179. Mondardini MC, Sperotto F, Daverio M, et al. Efficacy and safety of dexmedetomidine for prevention of withdrawal syndrome in the pediatric intensive care unit: protocol for an adaptive, multicenter, randomized, double-blind, placebo-controlled, non-profit clinical trial. Trials. 2019;20(1):710.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  180. Capino AC, Miller JL, Johnson PN. Clonidine for sedation and analgesia and withdrawal in critically ill infants and children. Pharmacotherapy. 2016;36(12):1290–9.

    Article  CAS  PubMed  Google Scholar 

  181. Traube C, Silver G, Reeder RW, et al. Delirium in critically ill children: an international point prevalence study. Crit Care Med. 2017;45(4):584–90.

    Article  PubMed Central  PubMed  Google Scholar 

  182. Traube C, Mauer EA, Gerber LM, et al. Cost associated with pediatric delirium in the ICU. Crit Care Med. 2016;44(12):e1175–9.

    Article  PubMed Central  PubMed  Google Scholar 

  183. Hong N, Park JY. The motoric types of delirium and estimated blood loss during perioperative period in orthopedic elderly patients. Biomed Res Int. 2018;2018:9812041.

    PubMed Central  PubMed  Google Scholar 

  184. Traube C, Silver G, Kearney J, et al. Cornell assessment of pediatric delirium: a valid, rapid, observational tool for screening delirium in the PICU*. Crit Care Med. 2014;42(3):656–63.

    Article  PubMed Central  PubMed  Google Scholar 

  185. Maldonado JR. Delirium pathophysiology: an updated hypothesis of the etiology of acute brain failure. Int J Geriatr Psychiatry. 2018;33(11):1428–57.

    Article  PubMed  Google Scholar 

  186. Maldonado JR. Acute brain failure: pathophysiology, diagnosis, management, and sequelae of delirium. Crit Care Clin. 2017;33(3):461–519.

    Article  PubMed  Google Scholar 

  187. Cerejeira J, Lagarto L, Mukaetova-Ladinska EB. The immunology of delirium. Neuroimmunomodulation. 2014;21(2–3):72–8.

    Article  CAS  PubMed  Google Scholar 

  188. Silver G, Traube C. A systematic approach to family engagement: feasibility pilot of a pediatric delirium management and prevention toolkit. Palliat Support Care. 2019;17(1):42–5.

    Article  PubMed  Google Scholar 

  189. Mody K, Kaur S, Mauer EA, et al. Benzodiazepines and development of delirium in critically ill children: estimating the causal effect. Crit Care Med. 2018;46(9):1486–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  190. Joyce C, Witcher R, Herrup E, et al. Evaluation of the safety of quetiapine in treating delirium in critically ill children: a retrospective review. J Child Adolesc Psychopharmacol. 2015;25(9):666–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  191. Campbell CT, Grey E, Munoz-Pareja J, Manasco KB. An evaluation of risperidone dosing for pediatric delirium in children less than or equal to 2 years of age. Ann Pharmacother. 2019;54:464–9.

    Article  PubMed  Google Scholar 

  192. Gurschick L, Mayer DK, Hanson LC. Palliative sedation: an analysis of international guidelines and position statements. Am J Hosp Palliat Care. 2015;32(6):660–71.

    Article  PubMed  Google Scholar 

  193. Lowey SE, Powers BA, Xue Y. Short of breath and dying: state of the science on opioid agents for the palliation of refractory dyspnea in older adults. J Gerontol Nurs. 2013;39(2):43–52.

    Article  PubMed  Google Scholar 

  194. Fielding F, Sanford TM, Davis MP. Achieving effective control in cancer pain: a review of current guidelines. Int J Palliat Nurs. 2013;19(12):584–91.

    Article  PubMed  Google Scholar 

  195. American Academy of Pediatrics. Committee on Bioethics and Committee on Hospital Care. Palliative care for children. Pediatrics. 2000;106(2 Pt 1):351–7.

    Article  Google Scholar 

  196. Salas S, Frasca M, Planchet-Barraud B, et al. Ketamine analgesic effect by continuous intravenous infusion in refractory cancer pain: considerations about the clinical research in palliative care. J Palliat Med. 2012;15(3):287–93.

    Article  PubMed  Google Scholar 

  197. Prommer EE. Ketamine for pain: an update of uses in palliative care. J Palliat Med. 2012;15(4):474–83.

    Article  PubMed  Google Scholar 

  198. Johnstone-Petty M. Ketamine use for complex pain in the palliative care population. J Hosp Palliat Nurs. 2018;20(6):561–7.

    Article  PubMed  Google Scholar 

  199. Jonkman K, van de Donk T, Dahan A. Ketamine for cancer pain: what is the evidence? Curr Opin Support Palliat Care. 2017;11(2):88–92.

    Article  PubMed  Google Scholar 

  200. Okamoto Y, Tsuneto S, Tanimukai H, et al. Can gradual dose titration of ketamine for management of neuropathic pain prevent psychotomimetic effects in patients with advanced cancer? Am J Hosp Palliat Care. 2013;30(5):450–4.

    Article  PubMed  Google Scholar 

  201. Sulistio M, Wojnar R, Michael NG. Propofol for palliative sedation. BMJ Support Palliat Care. 2020;10(1):4–6.

    Article  PubMed  Google Scholar 

  202. Bodnar J. The use of propofol for continuous deep sedation at the end of life: a definitive guide. J Pain Palliat Care Pharmacother. 2019;33(3–4):63–81.

    Article  PubMed  Google Scholar 

  203. Anghelescu DL, Hamilton H, Faughnan LG, Johnson LM, Baker JN. Pediatric palliative sedation therapy with propofol: recommendations based on experience in children with terminal cancer. J Palliat Med. 2012;15(10):1082–90.

    Article  PubMed Central  PubMed  Google Scholar 

  204. Burns J, Jackson K, Sheehy KA, Finkel JC, Quezado ZM. The use of dexmedetomidine in pediatric palliative care: a preliminary study. J Palliat Med. 2017;20(7):779–83.

    Article  PubMed  Google Scholar 

  205. Prommer E. Review article: dexmedetomidine: does it have potential in palliative medicine? Am J Hosp Palliat Care. 2011;28(4):276–83.

    Article  PubMed  Google Scholar 

  206. Mulkey MA, Everhart DE. Sedation selection to reduce delirium risk: Why dexmedetomidine may be a better choice. J Am Assoc Nurse Pract. 2020. https://doi.org/10.1097/JXX.0000000000000364. Epub ahead of print. PMID: 31972787.

  207. Hofherr ML, Abrahm JL, Rickerson E. Dexmedetomidine: A Novel Strategy for Patients with Intractable Pain, Opioid-Induced Hyperalgesia, or Delirium at the End of Life. J Palliat Med. 2020. https://doi.org/10.1089/jpm.2019.0427. Epub ahead of print. PMID: 31944877.

  208. Reznik ME, Slooter AJC. Delirium management in the ICU. Curr Treat Options Neurol. 2019;21(11):59.

    Article  PubMed  Google Scholar 

  209. Riker RR, Shehabi Y, Bokesch PM, et al. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. JAMA. 2009;301(5):489–99.

    Article  CAS  PubMed  Google Scholar 

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Kamat, P., Tobias, J.D. (2021). Sedation in the Pediatric Intensive Care Unit: Challenges, Outcomes, and Future Strategies in the United States. In: Mason, MD, K.P. (eds) Pediatric Sedation Outside of the Operating Room. Springer, Cham. https://doi.org/10.1007/978-3-030-58406-1_19

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