Randomized controlled trial of propranolol on social communication and anxiety in children and young adults with autism spectrum disorder.

RATIONALE: Autism spectrum disorder (ASD) is characterized by impaired social communication and is also frequently characterized by co-occurring anxiety. Propranolol is widely utilized to treat performance and public speaking anxiety. Single-dose psychopharmacological challenge studies suggested benefits using propranolol for verbal tasks and social interaction. OBJECTIVE: We conducted a double-blinded, placebo-controlled trial of the ß-adrenergic antagonist propranolol in ASD for social interaction, anxiety, and language. METHODS: Seventy-four participants with ASD, age 7-24 years, were enrolled and randomized to a 12-week course of propranolol or placebo, with blinded assessments at baseline, 6 weeks, and 12 weeks. The primary outcome was the General Social Outcome Measure-2 (GSOM-2) for social interaction, and secondary outcomes were the Clinician Global Clinical Impression-Improvement (CGI-I) ratings independently conducted for social interaction, anxiety, and language at 6 weeks and 12 weeks. RESULTS: Sixty-nine participants completed the 12-week visit. No significant effect of drug was found for the GSOM-2 or the CGI-I for social interaction or language. CGI-I for anxiety showed greater improvement with propranolol at the 12-week time point (p = 0.045, odds ratio = 2.58 (95% CI = 1.02-6.52). Expected decreases in heart rate and blood pressure were observed with propranolol, and side effects were uncommon. CONCLUSIONS: Propranolol did not impact social interaction measures or language, but there were indications of a beneficial effect for anxiety. This will need confirmation in a larger multicenter trial, monitoring markers or characteristics to identify those participants most likely to respond to propranolol for anxiety, and determine whether there is a subset of participants that are responsive for other previously reported outcomes.

Interventricular Septal Pseudoaneurysm After Blunt Chest Trauma in a 6 Year Old: An Illustrative Case and Review.

Motor vehicle accident is the most common cause of blunt cardiac injury (BCI) in children (85.3%) due to the height of the child in relation to proper restraints and the compliant pediatric rib cage (J Trauma. 1996;40:200-202). Trauma to the chest wall may lead to injury of the myocardium, resulting in myocardial contusion, ventricular septal defect (VSD), ventricular free wall rupture, or valve compromise (J Trauma. 1996;40; 200-202; Heart Lung. 2012;41:200-202; J Inj Violence Res. 2012;4:98-100). There are several proposed mechanisms for the formation of VSD after blunt chest trauma including rupture of ischemic myocardium related to the initial trauma and reopening of a spontaneously closed congenital VSD. Also, chest trauma during isovolumetric contraction of the ventricles may generate enough intraventricular force to cause myocardial rupture (J Trauma. 1996;40:200-202; J Inj Violence Res. 2012;4:98-100; Korean J Pediatr. 2011;54:86-89; Ann Thorac Surg. 2012;94:1714-1716; J Emerg Trauma Shock. 2012;5:184-187). Previous case reports highlight the formation of a true VSD after BCI and the requirement of emergent repair (J Emerg Trauma Shock. 2012;5:184-187; Am Heart J. 1996;131:1039-1041; Korean Circ J. 2011;41:625-628; Ann Thorac Surg 2013;96:297-298; Kardiol Pol. 2013;71:992; Chin Med J. 2013;126:1592-1593). Reported is a case of a 6-year-old girl who developed an interventricular septal pseudoaneurysm after a motor vehicle accident of pedestrian versus car. On the day of presentation, she developed bradycardia after emergent surgical repair for abdominal trauma that required cardiopulmonary resuscitation including 5 minutes of chest compressions. At the time of resuscitation, an emergent transthoracic echocardiogram noted an interventricular pseudoaneurysm. She has been followed with serial transthoracic echocardiograms and has not required surgical intervention. We discuss the risk factors, prevalence, and diagnostic studies and recommended treatment options for structural heart disease after BCI.

The role of α-adrenergic receptors in mediating beat-by-beat sympathetic vascular transduction in the forearm of resting man.

Sympathetic vascular transduction is commonly understood to act as a basic relay mechanism, but under basal conditions, competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC) and the contribution of local α-adrenergic receptor-mediated pathways to the observed FVC responses. In 19 young men, MSNA (microneurography), arterial blood pressure and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during supine rest. These measures were also recorded in seven men during intra-arterial infusions of normal saline, phentolamine (PHEN) and PHEN with angiotensin II (PHEN+ANG). The latter was used to control for increases in resting blood flow with α-adrenergic blockade. Spike-triggered averaging was used to characterize beat-by-beat changes in FVC for 15 cardiac cycles following each MSNA burst and a peak response was calculated. Following MSNA bursts, FVC initially increased by +3.3 ± 0.3% (P = 0.016) and then robustly decreased to a nadir of -5.8 ± 1.6% (P < 0.001). The magnitude of vasoconstriction appeared graded with the number of consecutive MSNA bursts; while individual burst size only had a mild influence. Neither PHEN nor PHEN+ANG infusions affected the initial rise in FVC, but both infusions significantly attenuated the subsequent decrease in FVC (-2.1 ± 0.7% and -0.7 ± 0.8%, respectively; P < 0.001 vs. normal saline). These findings indicate that spontaneous MSNA bursts evoke robust beat-by-beat decreases in FVC that are exclusively mediated via α-adrenergic receptors.

Caregiver anxiety upon discharge for neonates with congenital heart disease.

INTRODUCTION: Parents of children with congenital heart disease (CHD) have been shown to be at an increased risk of having psychosocial morbidities including anxiety, depression, and somatization. Little is known about the anxiety level of these parents during the initial hospital course. The goal of this study was to evaluate the anxiety level of the parents at the time of hospital discharge and to determine if certain characteristics predict higher anxiety levels. METHODS: Caregivers of neonates admitted with CHD within the first 30 days of life were recruited. Anxiety levels were measured by using the Spielberger State-Trait Anxiety Scale just prior to discharge. Spearman correlations were performed between state and trait scales vs. clinical variables. RESULTS: Fifty-nine questionnaires were completed for 38 neonates. Based on state score measure of anxiety, 81% of parents denied anxiety, 14% reported borderline anxiety, and 5% reported significant anxiety. Trait scores of anxiety reflected 93% of parents who denied anxiety, 2% who reported borderline anxiety, and 5% who reported significant anxiety. There was a significant positive correlation between state score and level of education (ρ= 0.30, P < .05) and the trait score and level of education (ρ= 0.23, P < .10). Number of medications was also significantly negatively associated with standard trait score (ρ=-0.37, P < .05). CONCLUSION: In general, anxiety trait scores were low for caregivers of neonates with CHD; however, there was a higher proportion of caregivers that reported anxiety in the state anxiety score. Higher education was associated with a higher level of anxiety. Future studies are needed to determine how to minimize anxiety levels during this stressful time period.

Mild Tessier No. 7 cleft with PHACE syndrome: the case for pulmonary vascular steal.

We describe an unusual case of PHACE syndrome that provides a demonstration of the role of vascular anomalies in the causation of external ear and facial anomalies. The child in our case was characterized by a small segmental hemangioma of the face, tetralogy of Fallot, and anomalous origin of left common carotid artery from pulmonary artery with retrograde blood flow. This presumably resulted in hypoperfusion of the left side of the face resulting in a Tessier number 7 cleft and left ear anomaly explained by pulmonary vascular steal phenomenon. The absence of posterior fossa anomalies may reflect normal perfusion via the Circle of Willis.

Acute dilated cardiomyopathy in a patient with deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase.

Deficiency of long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase (LCHADD) is a rare inborn error of metabolism. It is associated with hypertrophic cardiomyopathy and less frequently with dilated cardiomyopathy. The incidence and pathophysiology of cardiac involvement in LCHADD is poorly understood. This report describes the acute decompensation of a 3-year-old girl who had LCHADD with rapidly developing dilated cardiomyopathy. A review of the literature and possible causes of cardiomyopathy in LCHADD are explored.

Management of adults with congenital heart disease with cardiovascular computed tomography.

OBJECTIVE: The purpose of this study was to evaluate the role of cardiac computed tomography (CT) in the care of adults with congenital heart disease (CHD). METHODS: A retrospective analysis of adult patients with CHD who underwent cardiac CT from April 2005 to May 2006 was performed. Data collected included diagnosis, presence or absence of cardiac symptoms, presence or absence of a pacemaker or defibrillator, anatomic and functional abnormalities, and the need for subsequent surgical or transcatheter intervention based on cardiac CT findings. RESULTS: Eighty-seven adult patients with CHD underwent cardiac CT during this period. Fifty-four subjects had cardiac CT findings that warranted possible transcatheter or surgical interventions or both. Of these, 30 patients went on to transcatheter or surgical intervention based on cardiac CT results. Twenty (37%) subjects of the study population had either pacemaker or implantable cardioverter defibrillator. CONCLUSIONS: Cardiac CT provides important volumetric imaging information to guide management in adult patients with CHD.

Increased calcium supplementation is associated with morbidity and mortality in the infant postoperative cardiac patient.

OBJECTIVE: The purpose of this study was to assess the association of calcium replacement therapy with morbidity and mortality in infants after cardiac surgery involving cardiopulmonary bypass. DESIGN: Retrospective chart review. SETTING: The cardiac intensive care unit at a tertiary care children's hospital. PATIENTS: Infants undergoing cardiac surgery involving cardiopulmonary bypass between October 2002 and August 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Total calcium replacement (mg/kg calcium chloride given) for the first 72 postoperative hours was measured. Morbidity and mortality data were collected. The total volume of blood products given during the first 72 hrs was recorded. Infants with confirmed chromosomal deletions at the 22q11 locus were noted. Correlation and logistic regression analyses were used to generate odds ratios and 95% confidence intervals, with p < .05 being significant. One hundred seventy-one infants met inclusion criteria. Age was 4 +/- 3 months and weight was 4.9 +/- 1.7 kg at surgery. Six infants had deletions of chromosome 22q11. Infants who weighed less required more calcium replacement (r = -.28, p < .001). Greater calcium replacement correlated with a longer intensive care unit length of stay (r = .27, p < .001) and a longer total hospital length of stay (r = .23, p = .002). Greater calcium replacement was significantly associated with morbidity (liver dysfunction [odds ratio, 3.9; confidence interval, 2.1-7.3; p < .001], central nervous system complication [odds ratio, 1.8; confidence interval, 1.1-3.0; p = .02], infection [odds ratio, 1.5; confidence interval, 1.0-2.2; p < .04], extracorporeal membrane oxygenation [odds ratio, 5.0; confidence interval, 2.3-10.6; p < .001]) and mortality (odds ratio, 5.8; confidence interval, 5.8-5.9; p < .001). Greater calcium replacement was not associated with renal insufficiency (odds ratio, 1.5; confidence interval, 0.9-2.3; p = .07). Infants with >1 sd above the mean of total calcium replacement received on average fewer blood products than the total study population. CONCLUSIONS: Greater calcium replacement is associated with increasing morbidity and mortality. Further investigation of the etiology and therapy of hypocalcemia in this population is warranted.

Hyperglycemia is a marker for poor outcome in the postoperative pediatric cardiac patient.

OBJECTIVE: Hyperglycemia in critical care populations has been shown to be a risk factor for increased morbidity and mortality. Minimal data exist in postoperative pediatric cardiac patients. The goal of this study was to determine whether hyperglycemia in the postoperative period was associated with increased morbidity or mortality. DESIGN: Retrospective chart review. SETTING: Tertiary care, free-standing pediatric medical center with a dedicated cardiac intensive care unit. PATIENTS: We included 184 patients <1 yr of age who underwent cardiac surgery requiring cardiopulmonary bypass from October 2002 to August 2004. Patients with a weight <2 kg, a preoperative diagnosis of diabetes, preoperative extracorporeal membrane oxygenation support, solid organ transplant recipients, and preoperative renal or liver insufficiency were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Age was 4.3 +/- 3.2 months and weight was 4.9 +/- 1.7 kg at surgery. Duration of hyperglycemia was significantly longer in patients with renal insufficiency (p = .029), liver insufficiency (p = .006), infection (p < .002), central nervous system event (p = .038), extracorporeal membrane oxygenation use (p < .001), and death (p < .002). Duration of hyperglycemia was also significantly associated with increased intensive care (p < .001) and hospital (p < .001) stay and longer ventilator use (p < .001). Peak glucose levels were significantly different in patients with renal insufficiency (p < .001), infection (p = .002), central nervous system event (p = .01), and mortality (p < .001). CONCLUSIONS: Hyperglycemia in the postoperative period was associated with increased morbidity and mortality in postoperative pediatric cardiac patient. Strict glycemic control may improve outcomes in this patient population.

Argatroban for anticoagulation during cardiopulmonary bypass in an infant.

Heparin induced thrombocytopenia (HIT) is a rare, but potentially life-threatening complication of heparin therapy. In patients with HIT, alternative means of anticoagulation are necessary. The authors present an infant with HIT who required anticoagulation during cardiopulmonary bypass for tricuspid valve excision in the treatment of bacterial endocarditis. The direct thrombin inhibitor, argatroban, was successfully used. Previous reports regarding the use of argatroban and other nonheparin anticoagulants for anticoagulation are reviewed and suggestions regarding argatroban dosing in infants are presented.

Vasopressin: applications in clinical practice.

Arginine vasopressin is a peptide produced in the posterior pituitary whose primary physiologic role is fluid homeostasis. Recent investigations have demonstrated a therapeutic role for arginine vasopressin in adult cardiac arrest as well as adult and pediatric vasodilatory shock. We review the physiology of arginine vasopressin and examine the supporting data behind the developing clinical applications of this naturally produced peptide.