Catherine K. Allan

The Relationship Between Inflammatory Activation and Clinical Outcome After Infant Cardiopulmonary Bypass

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response. The magnitude and consequences in infants remain unclear. We assessed the relationship between inflammatory state and clinical outcomes in infants undergoing CPB. METHODS: Plasma concentrations of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor &agr;, IL-1&bgr;, and C-reactive protein (CRP) were measured pre-CPB and immediately post-CPB, and at 6, 12, and 24 hours post-CPB in infants ⩽9 months old. Perioperative clinical data were collected prospectively. RESULTS: Diagnoses of 93 patients included transposition of the great arteries (40), tetralogy of Fallot (28), ventricular septal defect (21), truncus arteriosus (2), and complete atrioventricular canal (2). The median age was 37 days (range = 2 to 264). Pre-CPB IL-6 and CRP were higher in younger infants but were not associated with postoperative inflammatory mediator concentrations or measured clinical outcomes. IL-6 increased post-CPB (median 3.2 pg/mL pre-CPB, 24.2 post-CPB, 95.4 at 6 hours, and 90.3 at 24 hours; all P < 0.001). CRP increased post-CPB, peaking at 24 hours (median 27.5 at 24 hours, 0.3 pre-CPB; P < 0.001). IL-10 and IL-8 increased immediately post-CPB. After adjusting for age and diagnosis, postoperative IL-6 and IL-8 correlated with intensive care unit length of stay and postoperative blood product administration and, for IL-8, 24-hour lactate. CONCLUSIONS: Greater preoperative cytokine and CRP production in younger infants did not correlate with postoperative outcomes; correlation between postoperative inflammatory mediator production and clinical course was statistically significant but clinically modest. We conclude that in infants undergoing low-to-moderate-complexity cardiac surgery in a single high-volume center, the contribution of inflammatory mediator production to postoperative morbidity is relatively limited.

Management and Outcomes in Pediatric Patients Presenting with Acute Fulminant Myocarditis

OBJECTIVE To investigate factors associated with mechanical circulatory support and survival in patients with acute fulminant myocarditis (AFM). STUDY DESIGN Retrospective cohort of AFM patients admitted to the cardiac intensive care unit during 1996-2008. AFM was defined as distinct onset of symptoms ≤14 days before admission, rapid-onset cardiogenic shock, and normal left ventricular size. Demographic and physiological variables were compared between patients treated with extracorporeal membrane oxygenation (ECMO) and those who were not and between survivors and nonsurvivors. RESULTS Twenty patients (median age 12.7 years) met inclusion criteria. Seventeen patients (85%) survived to hospital discharge. One underwent heart transplantation. Ten (50%) patients required ECMO, and 7 (70%) of these survived. On admission, patients requiring ECMO had elevated lactate (9 vs 1 mmol/L), creatinine (0.8 vs 0.6 mg/dL), and aspartate aminotransferase (256 vs 35 IU/L) (all P < .05) and a trend towards increased incidence of dysrhythmias (80% vs 30%, P = .07). During hospitalization, non-survivors had higher peak lactate (10 vs 3 mmol/L), creatinine (1.5 vs 0.8 mg/dL), and aspartate aminotransferase (3007 vs 156 IU/L) (all P < .05) compared with survivors. CONCLUSIONS Patients with AFM with end organ dysfunction or arrhythmias on admission may require mechanical circulatory support. The transplant-free survival rate in this critically ill cohort was excellent (80%).

Initial experience with fenoldopam after cardiac surgery in neonates with an insufficient response to conventional diuretics.

Objective: Fenoldopam, a selective dopamine-1 receptor agonist, causes systemic vasodilation and increased renal blood flow and tubular sodium excretion. We hypothesized that urine output would improve when fenoldopam was added to conventional diuretic therapy after neonatal cardiopulmonary bypass. Design: Retrospective cohort study using a time-series design. Setting: Pediatric cardiac intensive care unit. Patients: All neonates who received fenoldopam to promote diuresis after cardiac surgery requiring cardiopulmonary bypass from February 2002 through December 2004. Interventions: Fenoldopam infusion for inadequate urine output despite conventional diuretics. Measurements: Demographics, diagnostic information, and surgical procedures were recorded. Urine output, fluid balance, inotrope scores, diuretic doses, and other clinical variables that may influence diuresis were recorded for the 24-hr period immediately preceding fenoldopam initiation and during the initial 24 hrs of drug administration. Main Results: A total of 25 neonates received fenoldopam to promote diuresis after the modified Norwood (n = 14), arterial switch (n = 4), or other operations (n = 7). Heart rate, conventional diuretic dosing, and fluid intake were similar during the 24-hr periods of conventional therapy and fenoldopam use (p = not significant for all), whereas inotrope scores decreased during the study (p = .021). There was a small but statistically significant increase in blood pressure during the 48-hr study period. Median urine output was 3.6 mL·kg−1·hr−1 (range, 0.2–7.2 mL·kg−1·hr−1) during the 24-hr period of conventional therapy and 5.8 mL·kg−1·hr−1 (range, 1.6–11.7 mL·kg−1·hr−1) during the initial 24 hrs of fenoldopam administration (Wilcoxons signed-rank test, p = .001). Conclusions: Fenoldopam may improve urine output in neonates who are failing to achieve an adequate negative fluid balance despite conventional diuretic therapy after cardiac surgery and cardiopulmonary bypass. This study is limited by its retrospective design and the possibility that urine output improved spontaneously during the treatment period. A randomized, placebo-controlled clinical trial will be required to confirm these findings.

Emergent use of extracorporeal membrane oxygenation during pediatric cardiac catheterization.

Objectives: The goal of this study was to evaluate the utility of extracorporeal membrane oxygenation (ECMO) to resuscitate patients following critical cardiac events in the catheterization laboratory. Design: Retrospective review of medical records. Setting: Cardiac intensive care unit and cardiac catheterization laboratory at a tertiary care children’s hospital. Patients: Pediatric patients cannulated emergently for ECMO in the cardiac catheterization laboratory (n = 22). Interventions: ECMO was initiated emergently in the cardiac catheterization laboratory for progressive hemodynamic deterioration due to low cardiac output syndrome or catheter-induced complications. Measurements and Main Results: Twenty-two patients were cannulated for ECMO in the catheterization laboratory between 1996 and 2004. Median age was 33 months (range 0–192), median weight 14.8 kg (2.4–75), and median duration of ECMO 84 hrs (2–343). Indications included catheter-induced complication (n = 14), severe low cardiac output syndrome (n = 7), and hypoxemia (n = 1). Three patients (14%) were cannulated in the catheterization laboratory before catheterization for low cardiac output or hypoxemia. During cannulation, 19 patients (86%) were receiving chest compressions; median duration of cardiopulmonary resuscitation was 29 mins (20–57). Eighteen patients (82%) survived to discharge (five of whom underwent cardiac transplantation) and four (18%) died. Of 19 patients who received cardiopulmonary resuscitation during cannulation, 15 (79%) survived to discharge and nine (47%) sustained neurologic injury. There was no significant difference between survivors and nonsurvivors in age, weight, duration of cardiopulmonary resuscitation or ECMO support, pH, or lactate levels. Conclusions: ECMO is a technically feasible and highly successful tool in the resuscitation of pediatric patients following critical events in the cardiac catheterization laboratory.

Long-term results of right ventricular outflow tract reconstruction in neonatal cardiac surgery: Options and outcomes

OBJECTIVES Neonatal surgery for tetralogy of Fallot and truncus arteriosus requires reconstruction of the right ventricular outflow tract. Although the method of reconstruction is often dictated by the individual anatomy, choices exist. This review examines the durability and outcomes of right ventricular outflow tract reconstruction in the neonate. METHODS This is a retrospective review of all 278 neonates with the diagnosis of tetralogy of Fallot and truncus arteriosus undergoing right ventricular outflow tract reconstruction at a single center between 1990 and 2007. Diagnostic variants included tetralogy of Fallot/pulmonary stenosis (n = 83), tetralogy of Fallot/pulmonary atresia (n = 81), and tetralogy of Fallot with absent pulmonary valve (n = 17). Truncus arteriosus was present in 97 patients. Patients were analyzed on the basis of diagnosis and the method of right ventricular outflow tract reconstruction: aortic homograft, pulmonary homograft, transannular patch, transannular patch with monocusp pulmonary valve, and nontransannular patch. Freedom from reoperation/reintervention was determined by using the log-rank test. RESULTS The mean age at right ventricular outflow tract reconstruction was 11.8 +/- 8 days, and hospital survival was 95.0% for the tetralogy of Fallot group and 90.7% for the truncus arteriosus group. Overall freedom from reoperation and reintervention was 76.2% +/- 14.8% in the nontransannular patch group and 59.5% +/- 6.8% in the transannular patch group; both were significantly greater than seen in patients receiving either aortic (0%) or pulmonary (6.7% +/- 4.2%) homografts (P < .05). There was no difference between aortic and pulmonary homografts. Among patients with tetralogy of Fallot/pulmonary stenosis, there was no difference in 10-year freedom from reoperation/reintervention between the transannular (70.8% +/- 7.4%) and nontransannular patch methods (76.2% +/- 14.8%, P = .53). At 10 years, the diagnosis of tetralogy of Fallot/pulmonary stenosis was associated with a greater freedom from reoperation/reintervention (68% +/- 6.8%) when compared with tetralogy of Fallot/pulmonary atresia (5.3% +/- 4.3%, P = .0001), tetralogy of Fallot/absent pulmonary valve (0%, P = .00315), or truncus arteriosus (4.2% +/- 2.8%, P = .0001). Eight patients (4 with tetralogy of Fallot/pulmonary stenosis, 3 with tetralogy of Fallot/pulmonary atresia, and 1 with tetralogy of Fallot/absent valve) underwent placement of a transannular patch with monocusp valve. Among this group, freedom from reoperation/reintervention is 41.7% +/- 20.5% at 2.5 years. Monocusp function, as determined by means of echocardiographic analysis obtained at 11.4 +/- 11.7 months (range, 0.3-31 months) showed an average monocusp gradient of 23.5 +/- 26.1 mm Hg, and 3 (37.5%) patients had more than moderate pulmonary regurgitation. CONCLUSIONS The durability of neonatal right ventricular outflow tract reconstruction is diagnosis and method dependent. Anatomy allowing right ventricular outflow tract patching (either transannular or nontransannular) provides a durability advantage compared with that seen with a homograft. There was no difference in performance between aortic and pulmonary homografts, and the monocusp valve has limited durability and effectiveness in neonatal right ventricular outflow tract surgery. The long-term outcomes of transannular and nontransannular patching techniques for neonatal repair of tetralogy of Fallot/pulmonary stenosis are similar.

An extracorporeal membrane oxygenation cannulation curriculum featuring a novel integrated skills trainer leads to improved performance among pediatric cardiac surgery trainees.

Introduction American Heart Association guidelines recommend timely extracorporeal membrane oxygenation (ECMO) cannulation during cardiopulmonary resuscitation for pediatric cardiac arrest refractory to conventional resuscitation. Traditional cannulation training relies on the apprenticeship model. We hypothesized that a simulation-based ECMO cannulation curriculum featuring a novel integrated skills trainer would improve ECMO cannulation during cardiopulmonary resuscitation performance by cardiothoracic surgery trainees. Methods An embedded surgical neck cannulation trainer, designed in collaboration with expert surgeons, formed the focus for a simulation-based cannulation curriculum. The course included a didactic presentation and 2 neck cannulations during cardiopulmonary resuscitation with video-assisted expert feedback with a further cannulation at 3 months. Primary outcome was time to cannulation on the trainer. Secondary outcomes were performance on a validated Global Rating Scale (GRS) of surgical technique and a novel Composite ECMO Cannulation Score (CECS). Results Ten cardiothoracic surgery trainees participated. The trainer was rated as authentic, and sessions was rated as highly useful. Median time to cannulation decreased between cannulation 1 and 2 (15 minutes 24 seconds vs. 12 minutes 15 seconds, P = 0.002). Improvement was sustained at 3 months (13 minutes 36 seconds, P = 0.157 vs. attempt 2). Likewise, GRS increased significantly at attempt 2 versus 1 (77% vs. 62%, P = 0.003) as did CECS (88% vs. 52%, P = 0.002). No deterioration in GRS or CECS was measured at 3 months. Conclusions Cardiothoracic surgery trainees found a contextualized ECMO cannulation during cardiopulmonary resuscitation cannulation curriculum to be highly useful and demonstrated sustained improvement in time to cannulation, CECS, and GRS. Further work will focus on determining the clinical impact of this training and defining the optimal interval and number of training sessions.

Preoperative Extracorporeal Membrane Oxygenation as a Bridge to Cardiac Surgery in Children With Congenital Heart Disease

BACKGROUND The efficacy of extracorporeal membrane oxygenation (ECMO) in bridging children with unrepaired heart defects to a definitive or palliative surgical procedure has been rarely reported. The goal of this study is to report our institutional experience with ECMO used to provide preoperative stabilization after acute cardiac or respiratory failure in patients with congenital heart disease before cardiac surgery. METHODS A retrospective review of the ECMO database at Childrens Hospital Boston was undertaken. Children with unrepaired congenital heart disease supported with ECMO for acute cardiac or respiratory failure as bridge to a definitive or palliative cardiac surgical procedure were identified. Data collection included patient demographics, indication for ECMO, details regarding ECMO course and complications, and survival to hospital discharge. RESULTS Twenty-six patients (18 male, 8 female) with congenital heart disease were bridged to surgical palliation or anatomic repair with ECMO. Median age and weight at ECMO cannulation were, respectively, 0.12 months (range, 0 to 193) and 4 kg (range, 1.8 to 67 kg). Sixteen patients (62%) survived to hospital discharge. Variables associated with mortality included inability to decannulate from ECMO after surgery (p = 0.02) and longer total duration of ECMO (p = 0.02). No difference in outcomes was found between patients with single and biventricular anatomy. CONCLUSIONS Extracorporeal membrane oxygenation, used as a bridge to surgery, represents a useful modality to rescue patients with failing circulation and unrepaired complex heart defects.

Impact of Empiric Nesiritide or Milrinone Infusion on Early Postoperative Recovery After Fontan SurgeryCLINICAL PERSPECTIVE

Background—We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. Methods and Results—In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ⩽5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0–24]; milrinone, 18 [0–23]; placebo, 20 [0–23]; P=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. Conclusions—Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543309.

Intensive Care of the Adult Patient With Congenital Heart Disease

Prevalence of congenital heart disease in the adult population has increased out of proportion to that of the pediatric population as survival has improved, and adult congenital heart disease patients make up a growing percentage of pediatric and adult cardiac intensive care unit admissions. These patients often develop complex multiorgan system disease as a result of long-standing altered cardiac physiology, and many require reoperation during adulthood. Practitioners who care for these patients in the cardiac intensive care unit must have a strong working knowledge of the pathophysiology of complex congenital heart disease, and a full team of specialists must be available to assist in the care of these patients. This chapter will review some of the common multiorgan system effects of long-standing congenital heart disease (eg, renal and hepatic dysfunction, coagulation abnormalities, arrhythmias) as well as some of the unique cardiopulmonary physiology of this patient population.

Impact of empiric nesiritide or milrinone infusion on early postoperative recovery after Fontan surgery: a randomized, double-blind, placebo-controlled trial.

Background—We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. Methods and Results—In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ⩽5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and all were analyzed based on intention to treat. Demographics, patient characteristics, and operative factors were similar among treatment groups. No significant treatment group differences were found for median days alive and out of the hospital within 30 days of surgery (nesiritide, 20 [minimum to maximum, 0–24]; milrinone, 18 [0–23]; placebo, 20 [0–23]; P=0.38). Treatment groups did not significantly differ in cardiac index, arrhythmias, peak lactate, inotropic scores, urine output, duration of mechanical ventilation, intensive care or chest tube drainage, or adverse events. Conclusions—Compared with placebo, empirical perioperative nesiritide or milrinone infusions are not associated with improved early clinical outcomes after Fontan surgery. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543309.