Lara S. Shekerdemian

Cardiopulmonary Interactions After Fontan Operations Augmentation of Cardiac Output Using Negative Pressure Ventilation

BACKGROUND The low-output state is the chief cause of morbidity and mortality after Fontan operations. An alternative hemodynamic tool would be a welcome addition for these patients, who are typically resistant to conventional therapeutic measures. METHODS AND RESULTS The hemodynamic effects of conversion from conventional intermittent positive pressure ventilation (IPPV) to cuirass negative pressure ventilation (NPV) was investigated in nine acute postoperative Fontan patients on the pediatric intensive care unit and nine anesthetized patients undergoing cardiac catheterization in the convalescent phase after Fontan operations. Pulmonary blood flow was measured using the direct Fick method during IPPV and after a brief period of NPV. In one subgroup of patients, pulmonary blood flow was measured again after reinstitution of IPPV, and in a second subgroup, pulmonary blood flow was measured after an extended period of NPV. A brief period of NPV increased pulmonary blood flow from 2.4 to 3.5 L x min(-1) x /m(-2), with a mean increase of 42%. Pulmonary blood flow continued to improve, with a total increase of 54% after an extended period of NPV. Values fell toward baseline after reinstitution of IPPV. Heart rate was unchanged during NPV, and the improvement in pulmonary blood flow was achieved by an increase in stroke volume from 25 mL/m2 to 37 mL/m2. CONCLUSIONS Through improvement of the stroke volume alone, NPV brought about a marked increase in the pulmonary blood flow and, hence, cardiac output of Fontan patients. An improvement in cardiac output of this order, and by this mechanism, is currently unmatched by any therapeutic alternatives.

Three decades of pediatric intensive care: Who was admitted, what happened in intensive care, and what happened afterward

Objective: To describe the characteristics of children admitted to intensive care in 1982, 1995, and 2005–2006, and their long-term outcome. Setting: Pediatric intensive care unit in a university-affiliated childrens hospital. Design/Methods: Information for 2005–2006 admissions was obtained from pediatric intensive care unit database, and long-term outcome was ascertained through telephone interviews. Results were compared to previous cohorts from 1982 and 1995. Results: A total of 4010 children were admitted on 5250 occasions. Readmissions increased from 11% for 1982 to 31% in 2005 to 2006 (p < .001). In 2005–2006, fewer children were admitted after accidents (p < .001), or with croup (p < .001), or epiglottitis (p = .01), and 8% were treated with noninvasive ventilation compared to none in 1982 (p < .0001). Among children aged ≥1 month, pediatric intensive care unit length of stay remained constant. The risk of death predicted by the Pediatric Index of Mortality (PIM) remained constant (approximately 6%) between 1995 and 2005–2006.The proportion that died in the pediatric intensive care unit fell from 11.0% in 1982 to 4.8% in 2005–2006 (p < .001). Among children aged ≥1 month, proportion admitted with a preexisting moderate or severe disability was similar: 12.0% in 1982 and 14.6% in 2005–2006 (p = .11), but the proportion with a moderate or severe disability at follow-up increased from 8.4% in 1982 to 17.9% in 2005–2006 (p < .001). The proportion of children aged ≥1 month who either died in the pediatric intensive care unit or survived with disability did not improve: it was 19.4% in 1982 and 22.7% in 2005–2006. Conclusion: Over the last three decades, the length of stay in the pediatric intensive care unit and the severity of illness have not changed, but there has been a substantial reduction in pediatric intensive care unit mortality. However, the proportion of survivors with moderate or severe disability increased significantly. Some children who would have been allowed to die in 1982 and 1995 were kept alive in 2005–2006, but survived with disability. This trend has important implications for our patients and their families, and for the community as a whole.

A Systematic Review of Motor and Cognitive Outcomes After Early Surgery for Congenital Heart Disease

CONTEXT: Brain injury is the most common long-term complication of congenital heart disease requiring surgery during infancy. It is clear that the youngest patients undergoing cardiac surgery, primarily neonates and young infants, are at the greatest risk for brain injury. Developmental anomalies sustained early in life have lifelong repercussions. OBJECTIVE: We conducted a systematic review to examine longitudinal studies of cognitive and/or motor outcome after cardiac surgery during early infancy. METHODS: Electronic searches were performed in Medline, the Cumulative Index to Nursing and Allied Health Literature (Cinahl), and Embase (1998–2008). The search strategy yielded 327 articles, of which 65 were reviewed. Eight cohorts provided prospective data regarding the cognitive and/or motor outcome of infants who had undergone surgery for congenital heart disease before 6 months of age. Two authors, Ms Snookes and Dr Gunn, independently extracted data and presented results according to 3 subgroups for age of follow-up: early development (1 to <3 years); preschool age (3–5 years); and school age (>5 to 17 years). Weighted analysis was undertaken to pool the results of studies when appropriate. RESULTS: All of the identified studies reported results of the Bayley Scales of Infant Development for children younger than the age of 3. Outcome data as reported by the Bayley Scales were combined for infants assessed at 1 year of age, revealing a weighted mean Mental Development Index of 90.3 (95% confidence interval: 88.9–91.6) and Psychomotor Development Index of 78.1 (95% confidence interval: 76.4–79.7). Additional analysis was limited by a lack of data at preschool and school age. CONCLUSIONS: With this review we identified a limited number of prospective studies that systematically addressed outcome in patients at the highest risk. These studies consistently revealed cognitive and motor delay in children after cardiac surgery during early infancy. Additional investigation is required to ascertain the consequences of such impairment during later childhood and into adult life.

Neurodevelopmental Outcomes After Cardiac Surgery in Infancy

BACKGROUND: Neurodevelopmental disability is the most common complication for survivors of surgery for congenital heart disease (CHD). METHODS: We analyzed individual participant data from studies of children evaluated with the Bayley Scales of Infant Development, second edition, after cardiac surgery between 1996 and 2009. The primary outcome was Psychomotor Development Index (PDI), and the secondary outcome was Mental Development Index (MDI). RESULTS: Among 1770 subjects from 22 institutions, assessed at age 14.5 ± 3.7 months, PDIs and MDIs (77.6 ± 18.8 and 88.2 ± 16.7, respectively) were lower than normative means (each P < .001). Later calendar year of birth was associated with an increased proportion of high-risk infants (complexity of CHD and prevalence of genetic/extracardiac anomalies). After adjustment for center and type of CHD, later year of birth was not significantly associated with better PDI or MDI. Risk factors for lower PDI were lower birth weight, white race, and presence of a genetic/extracardiac anomaly (all P ≤ .01). After adjustment for these factors, PDIs improved over time (0.39 points/year, 95% confidence interval 0.01 to 0.78; P = .045). Risk factors for lower MDI were lower birth weight, male gender, less maternal education, and presence of a genetic/extracardiac anomaly (all P < .001). After adjustment for these factors, MDIs improved over time (0.38 points/year, 95% confidence interval 0.05 to 0.71; P = .02). CONCLUSIONS: Early neurodevelopmental outcomes for survivors of cardiac surgery in infancy have improved modestly over time, but only after adjustment for innate patient risk factors. As more high-risk CHD infants undergo cardiac surgery and survive, a growing population will require significant societal resources.

Cardiovascular effects of mechanical ventilation

The heart and lungs work closely to meet the tissues’ oxygen demands. If the balance between oxygen demand and supply becomes disturbed in critical illness, tissue hypoxia and cell death can rapidly result. An essential part of critical care is to maintain cardiopulmonary function with the help of pharmacotherapy, fluid management, and respiratory support. Paradoxically, interventions aimed at improving the function of one system can sometimes have undesirable effects on the other and, although the pulmonary consequences of cardiac disease are well recognised, the influences of changes in pulmonary physiology on cardiac function are less well appreciated. Cardiopulmonary interactions (the effects of spontaneous and mechanical ventilation on the circulation) were first documented in 1733, when Stephen Hales showed that the blood pressure of healthy people fell during spontaneous inspiration.1 Over a century later Kussmaul described pulsus paradoxus (the inspiratory absence of the radial pulse) in patients with tuberculous pericarditis.2 Cardiopulmonary interactions are present in health, and can be exaggerated or abnormal in the presence of disease. This article will provide an overview of this broad topic. By emphasising the underlying physiological principles and the influence of disease states upon these, we hope that respiratory support will then be tailored to the individual patient. Spontaneous and mechanical ventilation induce changes in intrapleural or intrathoracic pressure and lung volume, which can independently affect the key determinants of cardiovascular performance: atrial filling or preload; the impedance to ventricular emptying or afterload; heart rate and myocardial contractility. Changes in intrathoracic pressure are transmitted to the intrathoracic structures: namely the heart and pericardium, and the great arteries and veins. Spontaneous inspiration produces a negative pleural pressure, and the reduction in intrathoracic pressure is transmitted to the right atrium. In contrast, intermittent positive pressure ventilation (IPPV) produces inspiratory increases in intrathoracic pressure and therefore …

New White Matter Brain Injury After Infant Heart Surgery Is Associated With Diagnostic Group and the Use of Circulatory Arrest

Background— Abnormalities on magnetic resonance imaging scans are common both before and after surgery for congenital heart disease in early infancy. The aim of this study was to prospectively investigate the nature, timing, and consequences of brain injury on magnetic resonance imaging in a cohort of young infants undergoing surgery for congenital heart disease both with and without cardiopulmonary bypass. Methods and Results— A total of 153 infants undergoing surgery for congenital heart disease at <8 weeks of age underwent serial magnetic resonance imaging scans before and after surgery and at 3 months of age, as well as neurodevelopmental assessment at 2 years of age. White matter injury (WMI) was the commonest type of injury both before and after surgery. It occurred in 20% of infants before surgery and was associated with a less mature brain. New WMI after surgery was present in 44% of infants and at similar rates after surgery with or without cardiopulmonary bypass. The most important association was diagnostic group (P<0.001). In infants having arch reconstruction, the use and duration of circulatory arrest were significantly associated with new WMI. New WMI was also associated with the duration of cardiopulmonary bypass, postoperative lactate level, brain maturity, and WMI before surgery. Brain immaturity but not brain injury was associated with impaired neurodevelopment at 2 years of age. Conclusions— New WMI is common after surgery for congenital heart disease and occurs at the same rate in infants undergoing surgery with and without cardiopulmonary bypass. New WMI is associated with diagnostic group and, in infants undergoing arch surgery, the use of circulatory arrest.

Early experience with Levosimendan in children with ventricular dysfunction

Objective: To describe our preliminary experience with Levosimendan, a new calcium-sensitizing agent in critically unwell infants and children with severe heart failure. Design: Retrospective cohort analysis. Setting: Pediatric intensive care unit. Patients: Fifteen children aged 7 days to 18 yrs (median age 38 months) with severe myocardial dysfunction secondary to end-stage heart failure, or acute heart failure, who were inotrope-dependent (requiring at least one catecholamine). Interventions: A single dose (bolus and intravenous infusion over 24–48 hrs) of Levosimendan was given under continuous hemodynamic monitoring in our intensive care unit. Eleven children received a single dose, three children received two doses, and one child received four doses. Echocardiographic assessments of ventricular function were made before and 3–5 days after Levosimendan infusion. Measurements and Main Results: Heart rate, systolic pressure, diastolic pressure, mean blood pressure, and central venous pressure were unchanged during and after Levosimendan. Levosimendan allowed for discontinuation of catecholamines in ten patients and a dose reduction in three. The dose of dobutamine was reduced from 6.4 &mgr;g/kg/min pre-Levosimendan to 1.8 &mgr;g/kg/min on day 5 (p < .01). Ejection fraction for the group as a whole improved from 29.8% to 40.5% (p = .015); this did not increase significantly in patients with end-stage heart failure but increased by 63% in the children with acute heart failure. Conclusions: Levosimendan can be safely administered to infants and children with severe heart failure. Levosimendan allowed for substantial reduction in catecholamine infusions in children with end-stage or acute heart failure and also produced an objective improvement in myocardial performance in children with acute heart failure.

Pre-operative brain injury in newborn infants with transposition of the great arteries occurs at rates similar to other complex congenital heart disease and is not related to balloon atrial septostomy.

OBJECTIVES The goal of this study was to determine the prevalence and pattern of pre-operative brain injury in infants with transposition of the great arteries (TGA) compared with other complex congenital heart disease (CHD) and to define the risk of balloon atrial septostomy (BAS) for the development of brain injury. BACKGROUND It has recently been suggested that infants with TGA are at increased risk of pre-operative brain injury, in particular, stroke, and that this is strongly associated with having a BAS. METHODS Sixty-four newborn infants with TGA (n = 44), hypoplastic left heart syndrome (n = 13), or pulmonary atresia (n = 7) had magnetic resonance imaging (MRI) scans performed before surgery. RESULTS Thirty-three (75%) of the infants with TGA had a BAS. Brain injury occurred in 19 (30%) infants: white matter injury (WMI) in 17 (27%), and stroke in 3 (5%). There was no difference in the prevalence or pattern of brain injury between diagnostic groups. There was no association between BAS and brain injury in infants with TGA. There was a trend toward increased brain injury in TGA with an intact interventricular septum compared with TGA with a ventricular septal defect (38% vs. 8%, p = 0.075). There was no association between brain injury and any clinical variables. CONCLUSIONS Pre-operative brain injury on MRI scan was present in 30% of infants with CHD. The predominant pattern was WMI. The rates and patterns of pre-operative brain injury are similar in infants with TGA compared with other complex CHD, and BAS does not increase the risk of pre-operative brain injury.

Interaction between Inhaled Nitric Oxide and Intravenous Sildenafil in a Porcine Model of Meconium Aspiration Syndrome

There has been recent interest in the use of the phosphodiesterase-5 inhibitor sildenafil for treating pulmonary hypertension. We examined the interaction between inhaled nitric oxide (iNO) and i.v. sildenafil in 12 piglets with acute pulmonary hypertension and lung injury secondary to meconium aspiration. Six animals (controls) received no intervention after meconium instillation, and six received iNO (20 ppm) from 120 min, with the addition at 240 min of an i.v. sildenafil infusion (2 mg/kg over 2 h). Meconium instillation increased mean pulmonary artery (PA) pressure from 16.0 ± 3.1 to 24.8 ± 4.6 mm Hg (p < 0.01) and pulmonary vascular resistance (PVR) from 0.047 ± 0.008 to 0.089 ± 0.027 mm Hg · ml−1 · min−1 · kg−1 (p < 0.01). Oxygenation index increased from 3 ± 0.8 to 8.3 ± 3.0 (p < 0.01). There were no further changes beyond 120 min in controls. iNO reduced PA pressure and PVR to baseline values, without influencing oxygenation. The addition of sildenafil further reduced PA pressure, tended to increase the cardiac output, and reduced PVR from 0.049 ± 0.02 to 0.028 ± 0.01 mm Hg · ml−1 · min−1 · kg−1 (p < 0.05). Sildenafil lowered the systemic blood pressure and systemic vascular resistance and produced profound arterial hypoxemia, reducing arterial Po2 from 69 ± 23 mm Hg to 49 ± 15 mm Hg, despite substantial increases first in inspired oxygen fraction and subsequently in mean airway pressures. Consequently, the oxygenation index increased by 13.9 ± 4.8 (p = 0.01). When given in addition to iNO, sildenafil at a dose of >0.5 mg/kg produced profound pulmonary vasodilation, but this was coupled with an unacceptable deterioration in oxygenation and systemic vasodilation in this model of pulmonary hypertension with acute parenchymal lung disease.

The prevalence of seizures in comatose children in the pediatric intensive care unit: A prospective video-EEG study

Purpose:  Studies in adult and neonatal intensive care units (ICUs) report a high prevalence of epileptic seizures in comatose patients. The prevalence of seizures in pediatric ICUs is variably reported in a few retrospective studies using different electroencephalography (EEG) methods. We aimed to determine prospectively the prevalence of epileptic seizures (clinical and subclinical) in comatose children in the pediatric ICU using continuous video‐EEG (v‐EEG) monitoring.