Use of dexmedetomidine in patients with trisomy 21 after cardiac surgery 使用美托咪啶与21三体心脏手

CASE REPORTUse of Dexmedetomidine in Patients with Trisomy 21After Cardiac SurgeryM.Kalyanaraman ÆJ.L.Costello ÆJ.P.StarrReceived:12October 2006/Accepted:24February 2007ÓSpringer Science+Business Media,LLC 2007Abstract Children with trisomy 21have a high incidenceof congenital heart disease that frequently requires surgicalrepair.These patients often require multiple and higherdosage sedatives during the postoperative period.Dex-medetomidine is an a 2-adrenergic receptor agonist that hassedative,analgesic,and anxiolytic properties.We reportthe successful use of dexmedetomidine in patients withtrisomy 21following surgical repair of congenital heartdisease.Keywords Dexmedetomidine ÁCardiac Surgery ÁPostoperative ÁTrisomy 21ÁSedation ÁAnalgesiaCongenital heart disease is diagnosed in approximately40%of children with trisomy plete atrioventricularseptal defect is the most common cardiac lesion seen in thispopulation,followed by ventricular septal defects,tetral-ogy of Fallot,patent ductus arteriosus,and atrial septaldefects.A majority of these defects will require surgery,and effective sedation and analgesia are necessary duringrecovery from surgery.Children with trisomy 21often posechallenges with respect to attaining and maintainingeffective postoperative sedation and analgesia,oftenrequiring higher medication dosages and multiple agents inorder to reach therapeutic objectives [7].Even when opiate analgesia is effective,there can stillbe significant superimposed anxiety and restlessness thatindependently jeopardize postoperative stability andpatient safety.Sedative–anxiolytics such as benzodiaze-pines are effective in this population but can cause hemo-dynamic instability during bolus administration and over time risk inducing dependency that may require prolonged drug weaning strategies.Hence,there is interest in identi-fying sedative–anxiolytic agents without these unwanted properties.One such agent is dexmedetomidine.Dex-medetomidine is a selective a 2-adrenergic receptor agonist that has sedative,analgesic,and anxiolytic properties.It has both a short distribution and a short terminal half-life.Due to its minimal risk of inducing respiratory depression,it has shown promise as a periprocedural sedative,for sedation during mechanical ventilation,and as a sedative–anxiolytic after cardiac surgery [2,5,11,12,14].We report results after dexmedetomidine infusion in five patients with trisomy 21who underwent surgical repair of congenital heart disease.Our institutional review board granted waiver for publication of information in this case series.Case Reports Case 1A 2-month-old female infant with trisomy 21underwent patch closure of a ventricular septal defect,excision of a nonobstructive left atrial membrane,and partial closure of patent foramen ovale.After surgery,she was mechanically ventilated under conditions of neuromuscular relaxation with cisatracurium infusion and opiate analgesia with fen-tanyl infusion (maximum dose 3l g/kg/hr).In anticipation of weaning assisted ventilation and extubation (postopera-tive day 1),fentanyl and cisatracurium infusions were dis-continued and dexmedetomidine infusion was started at 0.5l g/kg/hr.After successful extubation,dexmedetomi-M.Kalyanaraman (&)ÁJ.L.Costello ÁJ.P.StarrChildren’s Hospital of New Jersey,C-5,201Lyons Avenue,Newark,NJ 07112,USAe-mail:mkalyanaraman@123Pediatr Cardiol (2007)28:396–399DOI 10.1007/s00246-006-0072-6dine was continued at the same dose for an additional24 hours.During the48-hour dexmedetomidine infusion,she received nine‘‘rescue’’interventions(with fentanyl,mor-phine,midazolam,or chloral hydrate)in order to quiet agitation.She incurred no significant bradycardia or hypo-tension,nor did she require escalation of inotropic support.Case2A6-month-old female infant with trisomy21underwent patch closure of a ventricular septal defect.After surgery, she was mechanically ventilated under conditions of neu-romuscular relaxation with cisatracurium infusion,opiate analgesia with fentanyl infusion,and benzodiazepine seda-tion with midazolam infusion.The fentanyl infusion was titrated to a maximum of12l g/kg/hr and the midazolam infusion was titrated to a maximum of0.2mg/kg/hr.On postoperative day2,in anticipation of weaning assisted ventilation and extubation later the same day,cisatracurium, fentanyl,and midazolam infusions were discontinued and dexmedetomidine was started at0.5l g/kg/hr.Rescue ther-apy with fentanyl or midazolam was needed on15occasions, and the dexmedetomidine infusion was gradually increased in increments of0.5l g/kg/hr to afinal dose of2.5l g/kg/hr. Total duration of dexmedetomidine infusion was29hours. She incurred no significant bradycardia or hypotension,nor did she require escalation of inotropic support.Case3A7-month-old female infant with trisomy21underwent patch closure of a ventricular septal defect and repair of pectus excavatum.After surgery,she was mechanically ventilated under conditions of fentanyl(2l g/kg/hr)and midazolam(0.1mg/kg/hr)continuous infusion for analgesia and sedation.Hypotension attributed to initiating midazo-lam infusion was addressed by reducing the infusion rate by half.Dexmedetomidine infusion was started at0.5l g/kg/hr. In advance of extubation,fentanyl and midazolam infusions were discontinued and the dosage of dexmedetomidine was increased to0.8l g/kg/hr.The patient requiredfive bolus doses of morphine during the next24hours.The total duration of the dexmedetomidine infusion was39hours.She incurred no significant bradycardia or hypotension,nor did she require escalation of inotropic support.Case4A4-month-old male infant with trisomy21underwent complete surgical reconstruction of tetralogy of Fallot. After surgery,he was mechanically ventilated under con-ditions of neuromuscular relaxation with cisatracurium infusion,opiate analgesia with fentanyl infusion,and benzodiazepine sedation with midazolam infusion.The fentanyl infusion was titrated to7l g/kg/hr,and the midazolam infusion was subsequently discontinued sec-ondary to hypotension(maximum dose0.02mg/kg/hr).On postoperative day2,dexmedetomidine infusion was started at0.5l g/kg/hr,fentanyl was discontinued,and he was extubated.The dexmedetomidine infusion was subse-quently titrated to0.7l g/kg/hr during the45-hour infusion period.Five rescue interventions with morphine or chloral hydrate were necessary during dexmedetomidine infusion. He incurred no significant bradycardia or hypotension,nor did he require escalation of inotropic support.Case5A3-year-old female with trisomy21underwent patch closure of an ostium primum atrial septal defect and suture closure of cleft anterior mitral valve leaflet.After surgery, she was mechanically ventilated under conditions of neu-romuscular relaxation with cisatracurium infusion and opiate analgesia with fentanyl infusion(maximum dose 2l g/kg/hr).Dexmedetomidine infusion was started at 0.2l g/kg/hr and subsequently increased to a maximum of 0.7l g/kg/hr in response to agitation.Fentanyl infusion was then discontinued.Dexmedetomidine infusion was inter-rupted for30minutes after observing a decrease in heart rate from110to70beats per minute.There was no asso-ciated hypotension.Dexmedetomidine infusion was resumed until she was extubated on postoperative day 2.Following extubation,and with a dexmedetomidine infusion rate of0.3l g/kg/hr,she had a transient episode of bradycardia and hypotension.The infusion was again briefly interrupted,inotropic support was transiently in-creased,and the vital signs normalized.Total duration of dexmedetomidine infusion was40hours,during which time no rescue interventions were required.DiscussionTo our knowledge,this is thefirst reported use of dex-medetomidine in infants and children with trisomy21after cardiac surgery.In this often challenging patient popula-tion,dexmedetomidine was effective in terms of attaining and maintaining sedation,especially after discontinuation of other sedative–analgesic infusions in advance of and after extubation.An ideal sedative agent in patients at risk for cardio-pulmonary instability after cardiac surgery is one that can be titrated to attain adequate sedation,analgesia,and anxiolysis at a low risk of hemodynamic or respiratory compromise.Children with trisomy21frequently require higher sedative–analgesic dosage,increasing the risk of123adverse effects.Our experience(as described in cases3and 4)highlights the common post-cardiac surgery problem of hypotension induced by benzodiazepine infusion.Dexmedetomidine is a highly selective a2-adrenergic receptor agonist with sedative,analgesic,and anxiolytic properties.It has a distribution half-life of approximately8 minutes and terminal half-life of3.5hours.This allows for titration of dexmedetomidine infusion to both achieve adequate sedation and enable prompt reversal of dose-re-lated side effects[3].Dexmedetomidine has been safely used for procedural sedation in children.A bolus dose of1 or2l g/kg followed by a continuous infusion in the range of0.25–0.75l g/kg/hr will generally provide effective sedation[2,11,12].Dexmedetomidine exhibits some similarity with natural sleep and does not cause clinically significant respiratory depression[8].Hemodynamic effects of dexmedetomidine are varied.Rapid bolus administration of dexmedetomidine has been associated with hypotension and bradycardia, especially in patients with cardiac disease.Bolus doses of dexmedetomidine may also cause transient hypertension and reflex bradycardia secondary to stimulation of a2 receptors in the peripheral blood vessels[4,10].In one case report,dexmedetomidine caused significant brady-cardia in an infant with atrial septal defect who was also receiving digoxin.The bradycardia was reversed with discontinuation of dexmedetomidine[1].Dexmedetomi-dine has also been associated with asytole in an adult with myasthenia gravis who was on pyridostigmine.Dexmede-tomidine was discontinued,the period of asytole lasted less than2minutes,and the patient was successfully resusci-tated[9].In both of these patients,a bolus dose of dex-medetomidine was followed by a continuous infusion.Experience with use of dexmedetomidine in children after cardiac surgery is limited.Intraoperative dexmede-tomidine has been shown to have sympatholytic effects with reduction in plasma epinephrine and norepinephrine in pa-tients undergoing cardiopulmonary bypass surgery for congenital heart disease[13].Dexmedetomidine has been used to facilitate opioid and benzodiazepine withdrawal in children after cardiac transplantation[6].Dexmedetomidine infusion between0.2and0.75l g/kg/hr(no bolus dose be-fore infusion)was shown to be effective and well tolerated in children after cardiothoracic surgery,although transient hypotension was reported in15%of these patients[5].Dexmedetomidine dose-related bradycardia and hypo-tension were seen in one of our patients(case5)and im-proved after transient interruption of the infusion.We initiated dexmedetomidine infusion without a loading or bolus dose,and the therapeutically effective dosage range in our patients was0.5–2.5l g/kg/hr.As experience with this drug was gained,our reliance on additional rescue interventions decreased.None of our patients required a tapering or weaning schedule of opiates or benzodiazepines during recovery from heart surgery.In conclusion,dexmedetomidine was effective and generally well tolerated in this series of infants and chil-dren with trisomy21after cardiac surgery.Dexmedetom-idine was especially useful during and after weaning from mechanical ventilation,and it enabled all patients in this series to avoid escalating opiate and benzodiazepine exposure and the potential for inducing drug dependency. The limitations of this study relate to its retrospective nature and the absence of standard pain and anxiety control scales applied to treatment decisions.Further randomized and controlled studies are necessary to establish the safety and efficacy of dexmedetomidine in children after surgery for congenital heart disease.Acknowledgments We thank Dr.Timothy S.Yeh and Dr.Joel T. 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