Victor O. Morell

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.

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.

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.

The association of renal dysfunction and the use of aprotinin in patients undergoing congenital cardiac surgery requiring cardiopulmonary bypass.

BACKGROUND: The use of large-dose aprotinin during cardiopulmonary bypass (CPB) in adult patients has been linked to postoperative renal dysfunction, but its effect on the pediatric population undergoing complex congenital cardiac operations is not well defined. METHODS: We used a retrospective cohort analysis to evaluate children undergoing cardiac surgery requiring CPB between July 2004 and July 2006. Demographic data and surgical risk quantified by the Aristotle surgical complexity level were analyzed as covariates. Renal dysfunction was defined according to the RIFLE criteria, an international consensus classification which defines three grades of increasing severity of acute kidney injury: risk (Class R), injury (Class I), and failure (Class F) based on serum creatinine values. A univariate and multivariate logistic regression analysis and a propensity score were used to analyze the data. The propensity score was developed using pretreatment covariates associated with the administration of aprotinin. A multivariate logistic regression was then used with the propensity score and intraoperative measures as covariates. A P value <0.05 was considered statistically significant. RESULTS: Among 395 patients who underwent cardiac surgery, 55% received aprotinin and 45% did not. Thirty-one percent of the cohort had previous cardiac surgery; 17% were neonates. According to the RIFLE criteria, 80 of the patients (20.3%) had acute kidney injury in the postoperative period; 53 (13.4%) had risk of renal dysfunction with 23 (5.8%) having injury and four patients (0.7%) having failure. Those receiving aprotinin had a higher incidence of previous cardiac surgery (54.1% vs 5%), sepsis (6.9% vs.0.0%), heart failure (24.8% vs 12.4%), mechanical ventilation (25.2% vs 2.8%), or mechanical circulatory support (6.0% vs.0.6%). More patients had an Aristotle level of 4 (26.6% vs 2.8%) and were treated with diuretics (63.8% vs 26.6%), angiotensin converting enzyme inhibitors (21.1% vs 7.9%), milrinone (25.7% vs 4.5%), and inotropic support (16.1% vs 2.3%). Although there was a significant difference in the unadjusted risk of renal dysfunction, adjustment with the preoperative propensity score revealed that there was no association between aprotinin and renal dysfunction (OR 1.32; 95% CI 0.55–3.19). The duration of CPB was the only independent variable associated with the development of renal dysfunction (OR 1.0; 95% CI 1.009–1.014). CONCLUSIONS: Patients who receive aprotinin are more likely to present with preoperative risk factors for the development of postoperative renal dysfunction. However, when associated risk factors are properly considered, the use of aprotinin does not seem to be associated with a higher risk of developing renal dysfunction in the immediate postoperative period in children.

Effect of dexmedetomidine on pulmonary artery pressure after congenital cardiac surgery: A pilot study.

Objective: To characterize the effects of dexmedetomidine on the pulmonary artery pressure in patients after congenital cardiac surgery. Design: Prospective observational pilot study. Setting: Pediatric cardiac intensive care unit at a university hospital. Patients: Twenty-two patients who received dexmedetomidine after cardiothoracic surgery. Interventions: None. Measurements and Main Results: An echocardiogram was performed at three time points: 1) baseline (T0); 2) 6 mins after dexmedetomidine loading (T1); and 3) 1 hr after initiation of dexmedetomidine infusion (T2). Transthoracic echocardiography was used to estimate pulmonary artery pressure based on tricuspid regurgitant velocity (4 × Velocity2) plus central venous pressure. Twenty-two patients aged 0.9 yrs old (interquartile range, 7.9) were enrolled at a median of 1 hr (1.5) after surgery. Dexmedetomidine loading, 0.62 &mgr;g/kg (0.5), was given in all patients followed by 0.5 &mgr;g/kg/hr (0.6) at T1 and 0.65 &mgr;g/kg/hr (0.5) at T2. None of the patients had any increase in pulmonary artery pressure. Overall, the pulmonary artery pressure decreased from 30 mm Hg (13) at T0 to 24 mm Hg (10) at T1 and 26 mm Hg (8) at T2 (p < .001). The pulmonary artery pressure/systemic systolic blood pressure ratio decreased from 33% (12) at T0 to 23% (15) at T1 and 25% (13) at T2 (p = .002). There was no difference in the left ventricular function, Fio2, oxygen %, Po2, CO2, and vasoactive agents. Conclusions: Administration of dexmedetomidine after congenital cardiac surgery was not associated with any increase in pulmonary artery pressure.

Activated partial thromboplastin time is a better trending tool in pediatric extracorporeal membrane oxygenation

Objectives: To determine whether activated partial thromboplastin times are a better heparin management tool than activated clotting times in pediatric extracorporeal membrane oxygenation. Design: A single-center retrospective analysis of perfusion and patient records. Setting: Academic pediatric tertiary care center. Patients: Pediatric patients (<21 yrs old) requiring extracorporeal membrane oxygenation support initiated at Children’s Hospital of Pittsburgh. Interventions: None. Measurements and Main Results: Point-of-care activated clotting time and activated partial thromboplastin time values, clinical laboratory activated partial thromboplastin time values, weight-normalized heparin administration (units/kg/hr), and reported outcomes were collected for pediatric patients treated for cardiac and/or respiratory failure with extracorporeal membrane oxygenation. Spearman’s ranked correlations were performed for each coagulation test compared to heparin dosage. The Bland–Altman test was used to determine the validity of the point-of-care activated partial thromboplastin time. Hazard analysis was conducted for outcomes and complications for patients whose heparin management was based on the clinical laboratory activated partial thromboplastin time or the activated clotting time. Only the clinical laboratory activated partial thromboplastin time showed a correlation (&rgr; = 0.40 vs. &rgr; = −0.04 for activated clotting time) with the heparin administration (units/kg/hr). Point-of-care activated partial thromboplastin time and activated partial thromboplastin time values correlated well (&rgr; = 0.76), with <5% of samples showing a difference outside 2 SDs, but differences in their absolute values (&Dgr;activated partial thromboplastin time = 100 secs) preclude them from being interchangeable measures. Furthermore, despite no effective change in the mean activated clotting time, cardiac patients showed a significantly improved correlation to heparin dose for all coagulation tests (e.g., point-of-care activated partial thromboplastin time &rgr; = 0.60). Management of patients with the clinical laboratory activated partial thromboplastin time did not significantly affect patient survival rates but did significantly reduce bleeding complications and significantly increased clotting in the extracorporeal membrane oxygenation circuit. A hazard analysis demonstrated that bleeding complications were associated with an increased risk of mortality, whereas clotting complications in the extracorporeal membrane oxygenation circuit were not. Conclusions: The activated clotting time is not an accurate monitoring tool for heparin management in pediatricextracorporeal membrane oxygenation. The point-of-care activated partial thromboplastin time correlates well with the clinical laboratory activated partial thromboplastin time but cannot be substituted for the clinical laboratory activated partial thromboplastin time values. Management of pediatric extracorporeal membrane oxygenation patients with the clinical laboratory activated partial thromboplastin time reduced bleeding complications which are associated with increases in mortality.

Dexmedetomidine: therapeutic use for the termination of reentrant supraventricular tachycardia.

OBJECTIVES The current drug of choice for reentrant supraventricular tachycardia (SVT) is adenosine followed by verapamil or diltiazem. Although limitations and significant adverse events have been encountered over the years, an alternative effective and safe agent has not been available. Dexmedetomidine has recently been shown to have potential antiarrhythmic effects, and here we describe our experience in the acute termination of reentrant SVT. DESIGN Retrospective case series. SETTING Quaternary University Childrens Hospital, Cardiac Intensive Care Unit. PATIENTS Patients who received dexmedetomidine for SVT in the past 5 years. INTERVENTIONS None. OUTCOME MEASURES SVT episodes terminated with dexmedetomidine were compared with episodes terminated with adenosine. RESULTS Fifteen patients, median age of 10 days (6-16), were given 27 doses of dexmedetomidine, mean dose 0.7 ± 0.3 mcg/kg, for a total of 27 episodes of SVT. Successful termination occurred in 26 episodes (96%) at a median time of 30 seconds (20-35). Duration of sinus pause was 0.6 ± 0.2 seconds, there was one episode of hypotension and no bradycardia and sedation lasted for 34 ± 8 minutes. Five patients received 27 doses of adenosine, with an overall successful cardioversion in 17 patients (63%) (P= .0017). Transient bradycardia and hypotension was seen in three patients (11%), agitation in 16 patients (59%), and broncospasm in one patient. Median sinus pause was 2.5 seconds (2-9) (P < .001). CONCLUSIONS Dexmedetomidine appears to have novel antiarrhythmic properties for the acute termination of reentrant SVT. Although adenosine is very effective, dexmedetomidine may prove to possess a more favorable therapeutic profile with increased effectiveness and fewer side effects.

Polytetrafluoroethylene Bicuspid Pulmonary Valve Implantation: Experience With 126 Patients

This article reports our initial experience in 126 consecutive patients treated with placement of a surgically created polytetrafluoroethylene (PTFE) bicuspid pulmonary valve at The Congenital Heart Institute of Florida (CHIF). A bicuspid pulmonary valve is created with PTFE and sutured into the right ventricular outflow tract. PTFE bicuspid pulmonary valves were placed in 126 patients (age: range, 3.1-64.7 years, mean, 17.9 years; weight: range, 14.2-113.6 kg, mean, 55.4 kg). All patients had pulmonary insufficiency, pulmonary stenosis, or both, most commonly after previous repair of tetralogy of Fallot (71 patients). Follow-up was up to 8.3 years (range, 0-8.3 years, mean, 3.34 years). Operative mortality was 1 patient (0.8%). Late mortality was non–valve-related in 3 patients (2.4%). The initial 84 patents in this series received valves constructed from PTFE with 0.6-mm thickness. The next 42 patients received valves constructed from PTFE with 0.1-mm thickness. Six patients of 126 (4.8%) required replacement of the PTFE bicuspid pulmonary valve because of immobile and calcified leaflets. All 6 who required replacement of the PTFE bicuspid pulmonary valve initially received a valve constructed from porous 0.6-mm PTFE material. We currently use nonporous 0.1-mm PTFE, which does not allow cellular in-growth and thickening. Early echocardiographic follow-up of these valve leaflets made with 0.1-mm PTFE has demonstrated improved leaflet mobility and pliability and lower transvalvar gradients. PTFE bicuspid pulmonary valve implantation is safe and effective and demonstrates acceptable performance for the intermediate term. It is anticipated that using thinner 0.1-mm PTFE will improve valve function and durability. Long-term follow-up is necessary to determine the true value of this technique.