Sedation management in pediatric cardiac critical care is especially challenging due to the heterogenous physiology of congenital heart disease (CHD), complexity of congenital heart surgery, and the wide range of patients' age/size.^1,2 Despite all this, the historical approach to sedation and pain management in children with CHD has been relatively narrow, relying on high-dose opioids as the main agents as well as a short list of additional drugs for sedation during the pre- and postoperative periods for congenital heart surgery.

Although opioid agents offer many excellent pharmacologic properties for sedation, their prolonged use is not devoid of untoward effects, including respiratory depression requiring prolonged mechanical ventilation and a blunted sympathetic response with ensuing hemodynamic instability as well as significant withdrawal symptoms with abrupt cessation.^1-4

On the other side, efforts to decrease these side effects by minimizing sedation can also result in unfavorable cardiopulmonary effects from excessive pain, anxiety, and psychological trauma for both patients and parents.^2,4 Thus, an improved alternative approach may require the use of a wider spectrum of sedative agents, with the goals of facilitating an early extubation of patients, a decreasing incidence of dysrhythmia and inotrope needs, as well as a decreased incidence in opioid dependence and withdrawal.^2,4,5

Several non-opioid agents can be used to supplement sedation and pain management to that effect, including dexmedetomidine, paracetamol, benzodiazepines, and propofol, among others. Their extensive use in the general pediatric population has allowed us to re-evaluate and change our current approach in the cardiac intensive care unit.

Current Practice

The main goal of a sensible sedation strategy for medical and post-operative children with heart disease should be to achieve proper analgesia and sedation without compromising hemodynamic status. Whenever possible, avoiding a prolonged sedative use with the ensuing withdrawal symptoms is a desirable goal as well. A judicious combination of opioids and non-opioids may be helpful in that regard.

Dexmedetomidine was initially approved for short-term use in the adult population. It is a highly selective alpha-2 adrenoceptor agonist with analgesic, sedative, and anxiolytic properties.^6,7 It also has modulating properties on catecholamine release and vagal activity, providing for an overall sympatholytic effect.^7,8 Additional extravascular properties have been postulated, including a protective role in the central nervous system as well as improved glycemic control.^6-9 We first described the use of dexmedetomidine in young children following congenital cardiac repair in 2006.¹⁰ Its use was associated with minimal cardiovascular, respiratory, and gastrointestinal effects while achieving adequate sedation and analgesia following various congenital heart repair procedures.

Since then, many studies have demonstrated its use to be safe in pediatric cardiac patients during the perioperative period. Its minimal effects on respiratory drive not only promote an earlier extubation, but also allow its safe use in non-intubated patients.^8,10,11 It has also been reported that while hemodynamic stability is maintained, dexmedetomidine use in children during the postoperative period of heart surgery resulted in decreased inotrope needs by reducing the stress response following cardiopulmonary bypass, especially when concomitantly used with low-dose opioids or benzodiazepines.^8,12-14

Commonly reported side effects of dexmedetomidine include bradycardia and hypotension, due to its alpha-2 adrenoceptor agonist properties.^6,10

Perioperative use of dexmedetomidine has shown to be associated with a decreased incidence of atrial, supraventricular, junctional, and ventricular tachycardia following congenital heart surgery. Other than slower heart rates, no untoward ECG findings have been reported.^15-17 Additionally, it has been suggested that dexmedetomidine may also have renal protective effects, with a reported decreased incidence of acute kidney injury in patients who received dexmedetomidine following cardiac surgery.¹⁸

Despite its wide use in pediatric cardiac care with a relatively safe profile, prolonged use of dexmedetomidine may lead to dependency and associated withdrawal symptoms including tachycardia, hypertension, and agitation, especially after prolonged infusion and abrupt discontinuation.^14,19 Clonidine is a less selective alpha-2 receptor agonist that is widely used to avoid withdrawal symptoms during dexmedetomidine weaning.²⁰

Paracetamol (intravenous acetaminophen) has been available in the US since 2010.^21,22 It offers both analgesic as well as antipyretic effects. Its use had been somewhat limited due to a higher cost compared with oral acetaminophen, but its rapid action onset and relative safety have contributed to an increasing enthusiasm for its use in the pediatric population.²¹ Following non-cardiac surgeries, paracetamol use decreased opioid requirements and the duration of mechanical ventilation.²³ Unlike NSAIDs, which carry significant risks of bleeding and renal dysfunction, paracetamol offers a relatively safe profile during the peri-operative period, and its concurrent use may offer improved pain and sedation control following pediatric cardiac surgery.^2,22,23

Propofol is a non-opioid intravenous agent with sedative and hypnotic properties.^1,4,24 Its use has been somewhat limited in children due to its potentially serious side effects, including the propofol-infusion syndrome and cardiovascular depression.^1,4,24 However, it has ideal qualities for short-term use during minor procedures, including a rapid onset and short half-life, facilitating faster extubation. When used in conjunction with other agents following cardiac surgery, studies have shown that it is associated with earlier extubation and shorter length of ICU stay, with no significant hemodynamic effects.^4,25 It is often used as a "wash-out" agent in the intensive care unit for patients with a history of prolonged opioid or benzodiazepine use and dependency.²⁶

In addition to the use of novel agents for sedation management, application of regional anesthesia supplementing general anesthesia during the intra- or post-operative period has shown to reduce opioid requirements and duration of mechanical ventilation following cardiac surgery.^27,28

All sedative agents have side effects. Prolonged use of any agent, especially at higher doses, may result in an increased withdrawal risk. Hence, for most cases, a single agent may not be enough during the perioperative period. A carefully titrated approach with selective use of different agents may allow for lower individual dosing, avoidance of undesired side-effects and withdrawal symptoms, as well as a shorter CICU and hospital length of stay.

References

1. Liu H, Ji F, Peng K, Applegate RL, Fleming N. Sedation after cardiac surgery: is one drug better than another? Anesth Analg 2017;124:1061-70.
2. Lucas SS, Nasr VG, Ng AJ, Joe C, Bond M, DiNardo JA. Pediatric Cardiac Intensive Care Society 2014 consensus statement: pharmacotherapies in cardiac critical care: sedation, analgesia and muscle relaxant. Pediatr Crit Care Med 2016;17:S3-15.
3. Tobias JD. Tolerance, withdrawal, and physical dependency after long-term sedation and analgesia of children in the pediatric intensive care unit. Crit Care Medi 2000;28:2122-32.
4. Nasr VG, DiNardo JA. Sedation and analgesia in pediatric cardiac care. Pediatr Crit Care Med 2016;17:S225-31.
5. Naguib AN, Tobias JD, Hall MW, et al. The role of different anesthetic techniques in altering the stress resposne during cardiac surgery in children: a prospective, double-blinded, and randomized study. Pediatr Crit Care Med 2013;14:481-90.
6. Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet 2017;56:893-913.
7. Tobias JD, Gupta P, Naguib A, Yates Ar. Dexmedetomidine: applications for the pediatric patient with congenital heart disease. Pediatr Cardiol 2011;32:1075-87.
8. Su F, Nicolson SC, Zuppa AF. A dose-response study of dexmedetomidine administered as the primary sedative in infants following open heart surgery. Pediatr Crit Care Med 2013;14:499-507.
9. Mantz J, Josserand J, Hamada S. Dexmedetomidine: new insights. Eur J Anaesthesiol 2011;28:3-6.
10. Chrysostomou C, Di Filippo S, Manrique AM, et al. Use of dexmedetomidine in children after cardiac and thoracic surgery. Pediatr Crit Care Med 2006;7:126-31.
11. Achuff BJ, Nicolson SC, Elci OU, Zuppa AF. Intraoperative dexmedetomidine reduces postoperative mechanical ventilation in infants after open heart surgery. Pediatr Crit Care Med 2015;16:440-7.
12. Gupta P, Whiteside W, Sabati A, et al. Safety and efficacy of prolonged dexmedetomidine use in critically ill children with heart disease. Pediatr Crit Care Med 2012;13:660-6.
13. Hasegawa T, Oshima Y, Maruo A, et al. Dexmedetomidine in combination with midazolam after pediatric cardiac surgery. Asian Cardiovasc Thorac Ann 2015;23:802-8.
14. Whalen LD, Di Gennaro JL, Irby GA, Yanay O, Zimmerman JJ. Long-term dexmedetomidine use and safety profile among critically ill children and neonates. Pediatr Crit Care Med 2014;15:706-14.
15. Chrysostomou C, Sanchez-de-Toledo J, Wearden P, et al. Perioperative use of dexmedetomidine is associated with decreased incidence of ventricular and supraventricular tachyarrhythmias after congenital cardiac operations. Ann Thorac Surg 2011;92:964-72.
16. Parent BA, Munoz R, Shiderly D, Chrysostomou C. Use of dexmedetomidine in sustained ventricular tachycardia. Anaesth Intensive Care 2010;38:781.
17. Chrysostomou C, Komarlu R, Lichtenstein S, et al. Electrocardiographic effects of dexmedetomidine in patients with congenital heart disease. Intensive Care Med 2010;36:836-42.
18. Kwiatkowski DM, Axelrod DM, Sutherland SM, Tesoro TM, Krawczeski CD. Dexmedetomidine is associated with lower incidence of acute kidney injury after congenital heart surgery. Pediatr Crit Care Med 2016;17:128-34.
19. Burbano NH, Otero AV, Berry DE, Orr RA, Munoz RA. Discontinuation of prolonged infusions of dexmedetomidine in critically ill children with heart disease. Intensive Care Med 2012;38:300-7.
20. Lardieri AB, Fusco NM, Simone S, Walker LK, Morgan JA, Parbuoni KA. Effects of clonidine on withdrawal from long-term dexmedetomidine in the pediatric patient. J Pediatr Pharmacol Ther 2015;20:45-53.
21. O'Neal JB. The utility of intravenous acetaminophen in the perioperative period. Front Public Health 2013;1:25.
22. White PF. The changing role of non-opioid analgesic techniques in the management of postoperative pain. Anesth Analg 2005;101:S5-22.
23. Ceelie I, de Wildt SN, van Dijk M, et al. Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery: a randomized controlled trial. JAMA 2013;309:149-54.
24. Chidambaran V, Costandi A, D'Mello A. Propofol: a review of its role in pediatric anesthesia and sedation. CNS Drugs 2015;29:543-63.
25. Cray SH, Holtby HM, Kartha VM, Cox PN, Roy WL. Early tracheal extubation after paediatric cardiac surgery: the use of propofol to supplement low-dose opioid anaesthesia. Paediatr Anaesth 2011;11:465-71.
26. Hensel M, Kox WJ. Safety, efficacy, and long-term results of a modified version of rapid opiate detoxification under general anaesthesia: a prospective study in methadone, heroin, codeine and morphine addicts. Acta Anaesthesiol Scand 2000;44:326-33.
27. Hammer GB, Ngo K, Macario A. A retrospective examination of regional plus general anesthesia in children undergoing open heart surgery. Anesth Analg 2000;90:1020-4.
28. Peterson KL, DeCampli WM, Pike NA, Robbins RC, Reitz BA. A report of two hundred twenty cases of regional anesthesia in pediatric cardiac surgery. Anesth Analg 2000;90:1014-9.

Keywords: Child, Hypnotics and Sedatives, Dexmedetomidine, Propofol, Analgesics, Opioid, Acetaminophen, Anti-Anxiety Agents, Antipyretics, Clonidine, Sympatholytics, Pain Management, Benzodiazepines, Airway Extubation, Anti-Inflammatory Agents, Non-Steroidal, Cardiopulmonary Bypass, Bradycardia, Respiration, Artificial, Heart Rate, Hypotension, Acute Kidney Injury, Analgesia, Substance Withdrawal Syndrome, Anesthesia, General, Perioperative Period, Anesthesia, Conduction, Hypertension, Tachycardia, Ventricular, Receptors, Adrenergic, Respiratory Insufficiency, Catecholamines, Electrocardiography, Pediatrics

< Back to Listings