Constantinos Chrysostomou

Use of dexmedetomidine in children after cardiac and thoracic surgery.

Objective: In this report, we describe our experience with the use of dexmedetomidine in spontaneously breathing as well as in mechanically ventilated patients, after congenital cardiac and thoracic surgery. Design: Retrospective case series. Setting: University hospital, pediatric cardiac intensive care unit. Patients: Thirty-three spontaneously breathing and five mechanically ventilated patients who received dexmedetomidine after cardiothoracic surgery. Interventions: None. Measurements and Main Results: Thirty-eight patients, age 8 ± 1.1 yrs old and weight 29 ± 3.8 kg, were included. Seven patients (18%) were <1 yr old. Dexmedetomidine was used as a primary sedative and analgesic agent, and when its effect was considered inadequate, despite incremental infusion doses, a rescue agent was administered. The initial dexmedetomidine infusion dose was 0.32 ± 0.15 &mgr;g/kg/hr followed by an average infusion of 0.3 ± 0.05 &mgr;g/kg/hr (range 0.1–0.75 &mgr;g/kg/hr). There was a trend toward higher dexmedetomidine infusion requirement in patients <1 yr old compared with older children, 0.4 ± 0.13 vs. 0.29 ± 0.17 &mgr;g/kg/hr (p = .06). Desired sedation and analgesia were achieved during 93% and 83% of the dexmedetomidine infusion, respectively. According to the intensive care unit sedation scale (score 0–3) and two pain scales (Numeric Visual Analog Scale and Face, Legs, Activity, Cry, and Consolability, score 0–10), the mean sedation score was 1.3 ± 0.6 (mild sedation) and the mean pain score was 1.5 ± 0.9 (mild pain). The most frequently rescue drugs administered were fentanyl, morphine, and midazolam. Overall, 49 rescue doses of sedatives/analgesics were given. Patients <1 yr old required more rescue boluses than older children, 22 boluses (3.19 ± 0.8) vs. 27 boluses (0.8 ± 0.2, p = .003). Throughout the dexmedetomidine infusion there was no significant change in the systolic and diastolic blood pressure trend. Six patients (15%) had documented hypotension. In three, hypotension resolved with decreasing the dexmedetomidine infusion dose whereas in the other three, hypotension resolved after discontinuing the infusion. Although there was a trend toward lower heart rates, this was not clinically significant. One patient had an episode of considerable bradycardia without hypotension, which resolved shortly after discontinuing the dexmedetomidine infusion. No significant changes in the arterial blood gases or respiratory rates were observed. There was no mortality, and the total intensive care unit length of stay was 19 ± 2 hrs. Conclusions: Our data suggest that dexmedetomidine is a well-tolerated and effective agent for both spontaneously breathing and mechanically ventilated patients following congenital cardiac and thoracic surgery.

Dexmedetomidine : A Novel Drug for the Treatment of Atrial and Junctional Tachyarrhythmias During the Perioperative Period for Congenital Cardiac Surgery: A Preliminary Study

BACKGROUND: Atrial and junctional tachyarrhythmias occur frequently during the perioperative period for congenital cardiac surgery and can be a cause of increased morbidity and mortality. These rhythm disturbances that may be well tolerated in a normal heart can cause significant hemodynamic instability in patients with congenital heart defects, particularly during the postcardiopulmonary bypass period. Management of these arrhythmias presents more of a challenge, since currently available antiarrhythmic drugs can be ineffective and poorly tolerated. In this study, we examined the possible effect of dexmedetomidine, a primarily sedative drug, on atrial and junctional tachyarrhythmias. Though some animal data have shown that it can prevent certain types of ventricular tachycardia, its therapeutic role during these types of arrhythmias has not been studied. METHODS: This was a retrospective, nonrandomized, noncontrolled study. Fourteen patients admitted to the cardiac intensive care unit and who received dexmedetomidine for both, sedation/analgesia and for junctional ectopic tachycardia (JET), atrial ectopic tachycardia (AET), reentry type supraventricular tachycardia (Re-SVT), atrial flutter (AF) or junctional accelerated rhythm (JAR) were included. Dexmedetomidine was used as a primary drug or as a rescue if other antiarrhythmics had been used. Our primary end-points were (a) conversion to normal sinus rhythm (NSR) within 3 min for Re-SVT, and 2 h for all other arrhythmias or (b) heart rate (HR) reduction to improve hemodynamics; JET ≤170 bpm, AET ≥20%, AF ≤150 bpm and for JAR prevention of progression to JET. RESULTS: The mean age and weight were 2 ± 3 mo and 4 ± 1.5 kg, respectively. Most of the arrhythmias (79%) occurred during the postoperative period. Dexmedetomidine was used as a primary treatment in nine and as a rescue in five patients. Ten patients (71%) received an initial loading dose of 1.1 ± 0.5 &mgr;g/kg. A continuous infusion, 0.9 ± 0.3 &mgr;g · kg−1 · h−1 was administered in 12 patients. Thirteen patients’ lungs were mechanically ventilated. Adverse effects were seen in four patients (28%). Three had hypotension that responded to fluid administration and one had a possible brief complete atrioventricular (AV) block. Nine of the 14 patients were transiently paced with atrial (seven) or AV sequential (two) pacing to improve AV synchrony. The primary outcome with rhythm and/or HR control was achieved in 13 patients (93%). JET rate decreased from 197 ± 22 to 165 ± 17 bpm within 67 ± 75 min of dexmedetomidine administration. Five of these patients converted to NSR in 39 ± 31 h and one remained in JAR. All four patients with Re-SVT had resolution of their tachyarrhythmia. Three converted to NSR and one to JAR. One patient with AET (220–270 bpm) responded well with decreasing HR to 120 bpm within 35 min and to NSR in 85 min. One patient with AF failed to respond. In two patients with JAR, neither progressed to JET and HR decreased from 158 ± 11 to 129 ± 1 bpm. CONCLUSION: This preliminary, observational report suggests that dexmedetomidine may have a potential therapeutic role in the acute phase of perioperative atrial and junctional tachyarrhythmias for either HR control or conversion to NSR.

Dexmedetomidine: sedation, analgesia and beyond

Background: Dexmedetomidine is an α-2 adrenoreceptor agonist with sedative, analgesic and anxiolytic properties. Since its release in the US market in late 1999, it has gained remarkable attention in the adult, pediatric and geriatric populations, predominantly because of its minimal respiratory depression. However, beyond its well-known properties, dexmedetomidine has recently been investigated for its potential in many other clinical scenarios, including neuroprotection, cardioprotection and renoprotection, with promising results. Objective: This review provides an outline of the current use of dexmedetomidine in adult and pediatric populations in several clinical settings, including operating room, intensive care unit, postsurgical patients and patients who need sedation and/or analgesia for invasive and noninvasive procedures. Our objectives were to examine the most up-to-date clinical evidence, describe the magnitude of effects, and shed some light on potential future applications. Methods: Published, peer-reviewed studies, including preclinical data, were included in this review article. Results/conclusions: Dexmedetomidine is a novel agent with a wide safety margin and excellent sedative and moderate analgesic properties. Though its broadest use is currently in surgical and nonsurgical intensive care unit patients, dexmedetomidine appears to have promising future applications in the areas of neuroprotection, cardioprotection and renoprotection.

Perioperative Use of Dexmedetomidine Is Associated With Decreased Incidence of Ventricular and Supraventricular Tachyarrhythmias After Congenital Cardiac Operations

BACKGROUND Postoperative tachyarrhythmias remain a common complication after congenital cardiac operations. Dexmedetomidine (DEX), an α-2 adrenoreceptor agonist, can have a therapeutic role in supraventricular tachyarrhythmias for cardioversion to sinus rhythm or heart rate control. Whether routine perioperative use of DEX decreases the incidence of supraventricular and ventricular tachyarrhythmias was studied. METHODS In this prospective cohort study, 32 pediatric patients undergoing cardiothoracic operations received DEX and were compared with 20 control patients who did not receive DEX. RESULTS Dexmedetomidine was started after anesthesia induction and continued intraoperatively and postoperatively for 38±4 hours (mean dose, 0.76±0.04 μg/kg/h). Ten control patients and 2 DEX patients sustained 16 episodes of tachyarrhythmias (p=0.001), including a 25% vs 0% (p=0.01) incidence of ventricular tachycardia and 25% vs 6% (p=0.05) of supraventricular arrhythmias in the control and DEX group, respectively. Transient complete heart block occurred in 2 control patients and in 1 DEX patient. Control patients had a higher heart rate (141±5 vs 127±3 beats/min, p=0.03), more sinus tachycardia episodes (40% vs 6%; p=0.008), required more antihypertensive drugs with nitroprusside (20±7 vs 4±1 μg/kg; p=0.004) and nicardipine (13±5 vs 2±1 μg/kg; p=0.02), and required more fentanyl (39±8 vs 19±3 μg/kg; p=0.005). CONCLUSIONS Perioperative use of dexmedetomidine is associated with a significantly decreased incidence of ventricular and supraventricular tachyarrhythmias, without significant adverse effects.

Dexmedetomidine as the primary sedative during invasive procedures in infants and toddlers with congenital heart disease

Objective: In this report, we describe the use of dexmedetomidine as the primary sedative agent while performing invasive procedures in infants and toddlers with congenital heart disease who are breathing spontaneously. Design: Retrospective case review. Setting: University Hospital, pediatric cardiac intensive care unit. Patients: Six spontaneously breathing children, five infants and one toddler, all with congenital heart disease, who received dexmedetomidine as the primary sedative agent while undergoing an invasive procedure. Interventions: None. Measurements and Main Results: Six patients with congenital heart disease, age 3 days–29 months were included. Five of the patients were <6 months of age. Each patient underwent an invasive procedure including central venous line placement, chest tube insertion, fiberoptic bronchoscopy, and femoral cut-down for Broviac placement. All patients were breathing spontaneously throughout their procedure. Dexmedetomidine was used as the primary sedative agent during the procedure with additional sedation provided with low dose ketamine for patient movement in three of the six patients. The average dexmedetomidine dose used was 1.5 &mgr;g/kg (1–3 &mgr;g/kg). An additional low dose of ketamine, 0.7 mg/kg (0.3–1.5 mg/kg), was used in 50% of the patients. All patients breathed spontaneously without significant desaturation throughout the procedure, and although there was a trend toward lower blood pressure and heart rate, all patients remained warm and well perfused. Each of the six procedures was successfully completed without any associated complications. Conclusions: Our experience suggests that invasive procedures can be successfully performed in spontaneously breathing infants and toddlers with congenital heart disease using dexmedetomidine alone or in combination with low dose ketamine.

Dexmedetomidine use in a pediatric cardiac intensive care unit: can we use it in infants after cardiac surgery?

Objective: To assess clinical response of dexmedetomidine alone or in combination with conventional sedatives/analgesics after cardiac surgery. Design: Retrospective study. Setting: Pediatric cardiac intensive care unit. Patients: Infants and neonates after cardiac surgery. Measurements and Main Results: We identified 80 patients including 14 neonates, at mean age and weight of 4.1 ± 3.1 months and 5.5 ± 2 kg, respectively, who received dexmedetomidine for 25 ± 13 hours at an average dose of 0.66 ± 0.26 &mgr;g·kg−1·hr−1. Overall normal sleep to moderate sedation was documented 94% of the time and no pain to mild pain for 90%. Systolic blood pressure (SBP) decreased from 89 ± 15 mm Hg to 85 ± 11 mm Hg (p = .05), heart rate (HR) from 149 ± 22 bpm to 129 ± 16 bpm (p < .001), and respiratory rate (RR) remained unchanged. When baseline arterial blood gases were compared with the most abnormal values, pH decreased from 7.4 ± 0.07 to 7.37 ± 0.05 (p = .006), Po2 from 91 ± 67 mm Hg to 66 ± 29 mm Hg (p = .005), and CO2 increased from 45 ± 8 mm Hg to 50 ± 12 mm Hg (p = .001). At the beginning of the study, 37 patients (46%) were mechanically ventilated; and at 48 hours, 13 patients (16%) were still intubated and five patients failed extubation. Three groups of patients were identified: A, dexmedetomidine only (n = 20); B, dexmedetomidine with sedatives/analgesics (n = 38); and C, dexmedetomidine with both sedatives/analgesics and fentanyl infusion (n = 22). The doses of dexmedetomidine and rescue sedatives/analgesics were not significantly different among the three groups but duration of dexmedetomidine was longer in group C vs. A (p = .03) and C vs. B (p = .002). Pain, sedation, SBP, RR, and arterial blood gases were similar. HR was higher in group C vs. B (p = .01). Comparison between neonates and infants showed that infants required higher dexmedetomidine doses, 0.69 ± 25 &mgr;g·kg−1·hr−1, and vs. 0.47 ± 21 &mgr;g·kg−1·hr−1 (p = .003) and had lower HR (p = .01), and RR (p = .009), and higher SBP (p < .001). Conclusions: Dexmedetomidine use in infants and neonates after cardiac surgery was well tolerated in both intubated and nonintubated patients. It provides an adequate level of sedation/analgesia either alone or in combination with low-dose conventional agents.

A Phase II/III, Multicenter, Safety, Efficacy, and Pharmacokinetic Study of Dexmedetomidine in Preterm and Term Neonates

OBJECTIVE To investigate the safety, efficacy, and pharmacokinetic profile of dexmedetomidine in preterm and full-term neonates ≥ 28 to ≤ 44 weeks gestational age. STUDY DESIGN Forty-two intubated, mechanically ventilated patients (n = 42) were grouped by gestational age into group I (n = 18), ≥ 28 to <36 weeks, and group II (n = 24), ≥ 36 to ≤ 44 weeks. Within each age group, there were 3 escalating dose levels, including a loading dose (LD, μg/kg) followed by a maintenance dose (MD, μg · kg(-1) · h(-1)) for 6-24 hours: level 1, 0.05 LD/MD; level 2, 0.1 LD/MD; and level 3, 0.2 LD/MD. The primary endpoint was the number of patients requiring sedation as determined by the Neonatal Pain, Agitation, Sedation Scale. RESULTS During dexmedetomidine infusion, 5% of Neonatal Pain, Agitation, Sedation Scale scores were >3, indicating agitation/pain, with 4 patients (10%) requiring more sedation and 17 (40%) requiring more analgesia. Though there was significant variability in pharmacokinetic variables, group I appeared to have lower weight-adjusted plasma clearance (0.3 vs 0.9 L · h(-1) · kg(-1)) and increased elimination half-life (7.6 vs 3.2 hours) compared with group II. Fifty-six adverse events (AEs) were reported in 26 patients (62%); only 3 AEs (5%) were related to dexmedetomidine. There were no serious AEs and no AEs or hemodynamic changes requiring dexmedetomidine discontinuation. CONCLUSION Dexmedetomidine is effective for sedating preterm and full-term neonates and is well-tolerated without significant AEs. Preterm neonates had decreased plasma clearance and longer elimination half-life.

Magnesium supplementation during cardiopulmonary bypass to prevent junctional ectopic tachycardia after pediatric cardiac surgery: A randomized controlled study

OBJECTIVES We analyzed the role of magnesium sulfate (MgSO(4)) supplementation during cardiopulmonary bypass in pediatric patients undergoing cardiac surgery, assessing the incidence of hypomagnesemia and the incidence of junctional ectopic tachycardia. METHODS We performed a randomized, double-blind, controlled trial in 99 children. MgSO(4) or placebo was administered during the rewarming phase of cardiopulmonary bypass: group 1, placebo group (29 patients); group 2, 25 mg/kg of MgSO(4) (30 patients); and group 3, 50 mg/kg of MgSO(4) (40 patients). RESULTS At the time of admission to the cardiac intensive care unit, groups receiving MgSO(4) had significantly greater levels of ionized magnesium (group 1, 0.51 + or - 0.07; group 2, 0.57 + or - 0.09; group 3, 0.59 + or - 0.09). Hypomagnesemia before bypass was common (75%-86.2%) and not significantly different among the groups. The proportion of hypomagnesemia decreased significantly at admission to the cardiac intensive care unit in groups receiving MgSO(4) (group 1, 77.8%; group 2, 63%; group 3, 47.4%). Patients receiving placebo (group 1) had a significantly greater occurrence of junctional ectopic tachycardia than groups receiving MgSO(4) (group 1, n = 5 [17.9%]; group 2, n = 2 [6.7%]; group 3, n = 0 [0%]). Age (<1 month), Aristotle score (>4), and history of cardiac failure were associated with junctional ectopic tachycardia. None of the patients with those characteristics in group 3 had junctional ectopic tachycardia. No association was found between study groups and the Pediatric Risk of Mortality score or length of stay in the cardiac intensive care unit. CONCLUSIONS Supplementation with MgSO(4) during cardiopulmonary bypass seems to reduce the incidence of hypomagnesemia and junctional ectopic tachycardia at admission to the cardiac intensive care unit. This effect seems to be dose related.

Short- and intermediate-term survival after extracorporeal membrane oxygenation in children with cardiac disease

OBJECTIVES In children with cardiac disease, common indications for extracorporeal membrane oxygenation (ECMO) include refractory cardiopulmonary resuscitation (E-CPR), failure to separate from cardiopulmonary bypass (OR-ECMO), and low cardiac output syndrome (LCOS-ECMO). Despite established acceptance, ECMO outcomes are suboptimal with a survival between 38% and 55%. We evaluated factors associated with significantly increased survival in cardiac patients requiring ECMO. METHODS We conducted a retrospective investigation of consecutive patients undergoing ECMO between 2006 and 2010. Demographic, pre-ECMO, ECMO, and post-ECMO parameters were analyzed. Neurologic outcomes were assessed with the pediatric overall performance category scale at the latest follow-up. RESULTS There were 3524 admissions, 95 (3%) of which necessitated ECMO; 40 (42%) E-CPR, 31 (33%) OR-ECMO, and 24 (25%) LCOS-ECMO. The overall hospital survival was 73%. The within-groups hospital survival was 75% in E-CPR, 77% OR-ECMO and 62% LCOS-ECMO. In the multivariable logistic regression analysis, chromosomal anomalies (odds ratio [OR], 8; 95% confidence interval [CI], 2-35), single ventricle (OR ,6; 95% CI, 3-33), multiple ECMO runs (OR, 15; 95% CI, 4-42), higher 24-hour ECMO flows (OR, 8; 95% CI, 4-22), decreased lung compliance (OR, 5; 95% CI, 2-16), and need for plasma exchange (OR, 5; 95% CI, 3-18) were all significant factors associated with mortality. From the univariate analysis, a common parameter associated with mortality within all groups was intracranial hemorrhage. At 1.9 years (0.9, 2.9) of follow-up, 66% were still alive, and 89% of survivors had normal function or only mild neurodevelopmental disability. CONCLUSIONS ECMO was successfully used in children with cardiac disease with 73% and 66% short- and intermediate-term survival, respectively. The majority of the survivors had normal function or only a minimal neurodevelopmental deficit.

Acute Hemodynamic Changes After Rapid Intravenous Bolus Dosing of Dexmedetomidine in Pediatric Heart Transplant Patients Undergoing Routine Cardiac Catheterization

BACKGROUND: Dexmedetomidine is a highly selective &agr;2-adrenoceptor agonist with sedative, anxiolytic, and analgesic properties that has minimal effects on respiratory drive. Its sedative and hypotensive effects are mediated via central &agr;2A and imidazoline type 1 receptors while activation of peripheral &agr;2B-adrenoceptors result in an increase in arterial blood pressure and systemic vascular resistance. In this randomized, prospective, clinical study, we attempted to quantify the short-term hemodynamic effects resulting from a rapid IV bolus administration of dexmedetomidine in pediatric cardiac transplant patients. METHODS: Twelve patients, aged 10 years or younger, weighing ⩽40 kg, presenting for routine surveillance of right and left heart cardiac catheterization after cardiac transplantation were enrolled. After an inhaled or IV induction, the tracheas were intubated and anesthesia was maintained with 1 minimum alveolar concentration of isoflurane in room air, fentanyl (1 &mgr;g/kg), and rocuronium (1 mg/kg). At the completion of the planned cardiac catheterization, 100% oxygen was administered. After recording a set of baseline values that included heart rate (HR), systolic blood pressure, diastolic blood pressure, central venous pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and thermodilution-based cardiac output, a rapid IV dexmedetomidine bolus of either 0.25 or 0.5 &mgr;g/kg was administered over 5 seconds. The hemodynamic measurements were repeated at 1 minute and 5 minutes. RESULTS: There were 6 patients in each group. Investigation suggested that systolic blood pressure, diastolic blood pressure, systolic pulmonary artery pressure, diastolic pulmonary artery pressure, pulmonary artery wedge pressure, and systemic vascular resistance all increased at 1 minute after rapid IV bolus for both doses and decreased significantly to near baseline for both doses by 5 minutes. The transient increase in pressures was more pronounced in the systemic system than in the pulmonary system. In the systemic system, there was a larger percent increase in the diastolic pressures than the systolic pressures. Cardiac output, central venous pressure, and pulmonary vascular resistance did not change significantly. HR decreased at 1 minute for both doses and was, within the 0.5 &mgr;g/kg group, the only hemodynamic variable still changed from baseline at the 5-minute time point. CONCLUSION: Rapid IV bolus administration of dexmedetomidine in this small sample of children having undergone heart transplants was clinically well tolerated, although it resulted in a transient but significant increase in systemic and pulmonary pressure and a decrease in HR. In the systemic system, there is a larger percent increase in the diastolic pressures than the systolic pressures and, furthermore, these transient increases in pressures were more pronounced in the systemic system than in the pulmonary system.