Abstract
This study aimed to evaluate adverse cardiac events using dexmedetomidine in infants with trisomy 21 and those without (controls) and examined potential risk factors in infants after cardiovascular surgery. We conducted a single-center retrospective cohort study. The medical records of 124 consecutive infants who had undergone cardiovascular surgery between April 1, 2013, and October 31, 2015, were enrolled. Clinical characteristics, usage of dexmedetomidine, and perioperative medications were analyzed. Adverse cardiac events were assessed with the Naranjo score and World Health Organization-The Uppsala Monitoring Centre (WHO-UMC) criteria. In total, 124 consecutive infants (30 patients and 94 controls) met the inclusion criteria. Eight of 30 (26.7 %) patients with trisomy 21 and 12 of 94 (12.8 %) controls experienced adverse cardiac events (i.e., hypotension, transient hypertension, and bradycardia) during dexmedetomidine with median Naranjo score of 6, and causality categories of WHO-UMC criteria were “certain” or “probable.” Of those, the incidence of bradycardia occurred at a higher rate in patients with trisomy 21 than in controls (P = 0.011). Multiple logistic regression analysis revealed that the presence of trisomy 21 was an independent risk factor for adverse cardiac events of dexmedetomidine after cardiovascular surgery (odds ratio 4.10, 95 % CI 1.17–11.19, P = 0.006). Dexmedetomidine is associated with an increased incidence of bradycardia in patients with trisomy 21 after surgery for congenital heart disease. Physicians using dexmedetomidine should know a great deal about the characteristics of patients with trisomy 21, and hemodynamic monitoring should be closely observed.
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Abbreviations
- DEX:
-
Dexmedetomidine
- SBS:
-
State Behavioral Scale
- IQR:
-
Interquartile ranges
References
Pierpont ME, Basson CT, Benson DW Jr et al (2007) Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: Endorsed by the American Academy of Pediatrics. Circulation 115:3015–3038
Freeman SB, Taft LF, Dooley KJ et al (1998) Population-based study of congenital heart defects in Down syndrome. Am J Med Genet 80:213–217
Fudge JC Jr, Li S, Jaggers J et al (2010) Congenital heart surgery outcomes in Down syndrome: analysis of a national clinical database. Pediatrics 126:315–322
Mukhtar AM, Obayah EM, Hassona AM (2006) The use of dexmedetomidine in pediatric cardiac surgery. Anesth Analg 103:52–56
Mason KP, Lerman J (2011) Dexmedetomidine in children: current knowledge and future applications. Anesth Analg 113:1129–1142
Jakob SM, Ruokonen E, Grounds RM, Dexmedetomidine for Long-Term Sedation Investigators et al (2012) Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 307:1151–1160
Carney L, Kendrick J, Carr R (2013) Safety and effectiveness of dexmedetomidine in the pediatric intensive care unit (SAD-PICU). Can J Hosp Pharm 66:21–27
Gupta P, Whiteside W, Sabati A et al (2012) Safety and efficacy of prolonged dexmedetomidine use in critically ill children with heart disease. Pediatr Crit Care Med 13:660–666
Chrysostomou C, Komarlu R, Lichtenstein S et al (2010) Electrocardiographic effects of dexmedetomidine in patients with congenital heart disease. Intensive Care Med 36:836–842
Gerlach AT, Dasta JF (2007) Dexmedetomidine: an update review. Ann Pharmacother 41:245–252
Curley MA, Harris SK, Fraser KA et al (2006) State Behavioral Scale: a sedation assessment instrument for infants and young children supported on mechanical ventilation. Pediatr Crit Care Med 7:107–114
Behrman RE, Kliegman R, Jenson HB (eds) (2004) Nelson textbook of pediatrics, 17th edn. Saunders, Philadelphia
Naranjo CA, Busto U, Sellers EM et al (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30:239–245
World Health Organization (WHO)-Uppsala Monitoring Centre. The use of the WHO-UMC system for standardized case causality assessment. http://www.who-umc.org/Graphics/24734.pdf
Chrysostomou C, Di Filippo S, Manrique AM et al (2006) Use of dexmedetomidine in children after cardiac and thoracic surgery. Pediatr Crit Care Med 7:126–131
Hosokawa K, Shime N, Kato Y et al (2010) Dexmedetomidine sedation in children after cardiac surgery. Pediatr Crit Care Med 11:39–43
Buck ML (2010) Dexmedetomidine use in pediatric intensive care and procedural sedation. J Pediatr Pharmacol Ther 15:17–29
Honey BL, Harrison DL, Gormley AK et al (2010) Evaluation of adverse events noted in children receiving continuous infusions of dexmedetomidine in the intensive care unit. J Pediatr Pharmacol Ther 15:30–37
Czaja AS, Zimmerman JJ (2009) The use of dexmedetomidine in critically ill children. Pediatr Crit Care Med 10:381–386
Szumita PM, Baroletti SA, Anger KE et al (2007) Sedation and analgesia in the intensive care unit: evaluating the role of dexmedetomidine. Am J Health Syst Pharm 64:37–44
Lin YY, He B, Chen J et al (2012) Can dexmedetomidine be a safe and efficacious sedative agent in post-cardiac surgery patients? A meta-analysis. Crit Care 16:R169
Bai W, Voepel-Lewis T, Malviya S (2010) Hemodynamic changes in children with Down syndrome during and inhalation induction of anesthesia with sevoflurane. J Clin Anesth 22:592–597
Figueroa A, Collier SR, Baynard T et al (2005) Impaired vagal modulation of heart rate in individuals with Down syndrome. Clin Auton Res 15:45–50
Fernhall B, Otterstetter M (2003) Attenuated response to sympathoexcitation in individuals with Down syndrome. J Appl Physiol 94:2158–2165
Pacifici GM (2014) Clinical pharmacology of midazolam in neonates and children: effect of disease-a review. Int J Pediatr 2014:309342
Shafer A (1998) Complications of sedation with midazolam in the intensive care unit and a comparison with other sedative regimens. Crit Care Med 26:947–956
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All procedures performed in studies involving human participants were in accordance with ethics standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, format consent is not required.
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Ueno, K., Ninomiya, Y., Shiokawa, N. et al. Dexmedetomidine is Associated with an Increased Incidence of Bradycardia in Patients with Trisomy 21 After Surgery for Congenital Heart Disease. Pediatr Cardiol 37, 1228–1234 (2016). https://doi.org/10.1007/s00246-016-1421-8
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DOI: https://doi.org/10.1007/s00246-016-1421-8