David L. Wessel

Postoperative Course and Hemodynamic Profile After the Arterial Switch Operation in Neonates and Infants A Comparison of Low-Flow Cardiopulmonary Bypass and Circulatory Arrest

BACKGROUND The neurological morbidity associated with prolonged periods of circulatory arrest has led some cardiac surgical teams to promote continuous low-flow cardiopulmonary bypass as an alternative strategy. The nonneurological postoperative effects of both techniques have been previously studied only in a limited fashion. METHODS AND RESULTS We compared the hemodynamic profile (cardiac index and systemic and pulmonary vascular resistances), intraoperative and postoperative fluid balance, and perioperative course after deep hypothermia and support consisting predominantly of total circulatory arrest or low-flow cardiopulmonary bypass in a randomized, single-center trial. Eligibility criteria included a diagnosis of transposition of the great arteries and a planned arterial switch operation before the age of 3 months. Of the 171 patients, 129 (66 assigned to circulatory arrest and 63 to low-flow bypass) had an intact ventricular septum and 42 (21 assigned to circulatory arrest and 21 to low-flow bypass) had an associated ventricular septal defect. There were 3 (1.8%) hospital deaths. Patients assigned to low-flow bypass had significantly greater weight gain and positive fluid balance compared with patients assigned to circulatory arrest. Despite the increased weight gain in the infants assigned to low-flow bypass, the duration of mechanical ventilation, stay in the intensive care unit, and hospital stay were similar in both groups. Hemodynamic measurements were made in 122 patients. During the first postoperative night, the cardiac index decreased (32.1 +/- 15.4%, mean +/- SD), while pulmonary and systemic vascular resistance increased. The measured cardiac index was < 2.0 L.min-1.m-2 in 23.8% of the patients, with the lowest measurement typically occurring 9 to 12 hours after surgery. Perfusion strategy assignment was not associated with postoperative hemodynamics or other nonneurological postoperative events. CONCLUSIONS After heart surgery in neonates and infants, both low-flow bypass and circulatory arrest perfusion strategies have comparable effects on the nonneurological postoperative course and hemodynamic profile.

A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery

Background Hypothermic circulatory arrest is a widely used support technique during heart surgery in infants, but its effects on neurologic outcome have been controversial. An alternative method, low-flow cardiopulmonary bypass, maintains continuous cerebral circulation but may increase exposure to known pump-related sources of brain injury, such as embolism or inadequate cerebral perfusion. Methods We compared the incidence of perioperative brain injury after deep hypothermia and support consisting predominantly of total circulatory arrest with the incidence after deep hypothermia and support consisting predominantly of low-flow cardiopulmonary bypass in a randomized, single-center trial. The criteria for eligibility included a diagnosis of transposition of the great arteries with an intact ventricular septum or a ventricular septal defect and a planned arterial-switch operation before the age of three months. Results Of 171 patients with D-transposition of the great arteries, 129 (66 of whom were assign...

Efficacy and Safety of Milrinone in Preventing Low Cardiac Output Syndrome in Infants and Children After Corrective Surgery for Congenital Heart Disease

Background—Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS. Methods and Results—The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25-&mgr;g/kg bolus over 60 minutes followed by a 0.25-&mgr;g/kg per min infusion for 35 hours; high dose, 75-&mgr;g/kg bolus followed by a 0.75-&mgr;g/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% (P =0.023) in 238 treated patients and 64% (P =0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (P =0.049). Conclusions—The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.

Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass.

BackgroundIncreased pulmonary vascular resistance is common in congenital heart disease and is exacerbated by cardiopulmonary bypass (CPB). We investigated whether CPB is responsible for pulmonary endothelial dysfunction and contributes to postoperative pulmonary hypertension. Methods and ResultsWe infused the endothelium-dependent vasodilator acetylcholine (ACH) into the pulmonary circulation of pulmonary hypertensive children with congenital heart disease either before (n= 12) or after (n=22) surgical repair on CPB. The dose response to ACH (10−1 to 10–6 M) was recorded for all hemodynamic variables. Nine additional postoperative patients were studied with ACH followed by inhalation of 80 ppm nitric oxide, an endothelium-independent smooth muscle relaxant. Plasma levels of cyclic GMP (cGMP) were measured before and after ACH and nitric oxide administration. Pulmonary vasodilation with 10−1 M ACH was seen in all preoperative patients but was markedly attenuated in postoperative patients. Baseline pulmonary vascular resistance (5.6±1.0 U m2) fell 46±5% in preoperative patients but declined only 11±4% from baseline (5.8±0.9 U m2) in postoperative patients (P<.002). However, inhalation of 80 ppm nitric oxide after ACH infusion in postoperative patients lowered pulmonary vascular resistance by 33±4% (P<.0002 compared with postoperative ACH response) with minimal effects on the systemic circulation. This finding suggests that the capacity for smooth muscle relaxation and pulmonary vasodilation was present in postoperative patients but could not be induced by ACH. Plasma levels of cGMP in postoperative patients were unchanged after acetylcholine infusion but rose more than threefold during pulmonary vasodilation with nitric oxide (P<.0001). This finding is consistent with the purported role of cGMP as the second messenger effecting smooth muscle relaxation in this process. ConclusionsCPB may be responsible for postoperative dysfunction of the pulmonary endothelial cell and may contribute to postoperative pulmonary hypertension in children. Inhaled nitric oxide is a potent pulmonary vasodilator after CPB with minimal systemic circulatory effects. It may have important diagnostic and therapeutic applications in patients with congenital heart disease.

Gamma-globulin treatment of acute myocarditis in the pediatric population.

BACKGROUND Myocardial damage in myocarditis is mediated, in part, by immunological mechanisms. High-dose intravenous gamma-globulin (IVIG) is an immunomodulatory agent that is beneficial in myocarditis secondary to Kawasaki disease, as well as in murine myocarditis. Since 1990, the routine management of presumed acute myocarditis at Childrens Hospital, Boston, and Childrens Hospital, Los Angeles, has included administration of high-dose IVIG. METHODS AND RESULTS We treated 21 consecutive children presenting with presumed acute myocarditis with IVIG, 2 g/kg, over 24 hours, in addition to anticongestive therapies. A comparison group comprised 25 recent historical control patients meeting identical eligibility criteria but not receiving IVIG therapy. Left ventricular function was assessed during five time intervals: 0 to 7 days, 1 to 3 weeks, 3 weeks to 3 months, 3 to 6 months, and 6 to 12 months. At presentation, the IVIG and non-IVIG groups had comparable left ventricular enlargement and poor fractional shortening. Compared with the non-IVIG group, those treated with IVIG had a smaller mean adjusted left ventricular end-diastolic dimension and higher fractional shortening in the periods from 3 to 6 months (P = .008 and P = .033, respectively) and 6 to 12 months (P = .072 and P = .029, respectively). When adjusting for age, biopsy status, intravenous inotropic agents, and angiotensin-converting enzyme inhibitors, patients treated with IVIG were more likely to achieve normal left ventricular function during the first year after presentation (P = .03). By 1 year after presentation, the probability of survival tended to be higher among IVIG-treated patients (.84 versus .60, P = .069). We observed no adverse effects of IVIG administration. CONCLUSIONS These data suggest that use of high-dose IVIG for treatment of acute myocarditis is associated with improved recovery of left ventricular function and with a tendency to better survival during the first year after presentation.

Sildenafil Ameliorates Effects of Inhaled Nitric Oxide Withdrawal

and anesthesia in a neonate, especially those aged less than 2 months, may indicate an infectious problem either related or unrelated to the operative and anesthetic techniques. We report the first documented occurrence of aseptic meningitis in an infant after spinal anesthesia. Because of the infant’s underlying status and recent life-threatening illness, it was not possible to definitely prove a causal relationship between the aseptic meningitis and the spinal anesthetic. Although no definitive treatment is necessary, the recognition of aseptic meningitis may avoid the prolonged and indiscriminate use of antibiotics if the fever is attributed to other sources.

Perioperative effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants.

OBJECTIVES In a randomized, single-center trial, we compared perioperative outcomes in infants undergoing cardiac operations after use of the alpha-stat versus pH-stat strategy during deep hypothermic cardiopulmonary bypass. METHODS Admission criteria included reparative cardiac surgery, age less than 9 months, birth weight 2.25 kg or more, and absence of associated congenital or acquired extracardiac disorders. RESULTS Among the 182 infants in the study, diagnoses included D-transposition of the great arteries (n = 92), tetralogy of Fallot (n = 50), tetralogy of Fallot with pulmonary atresia (n = 6), ventricular septal defect (n = 20), truncus arteriosus (n = 8), complete atrioventricular canal (n = 4), and total anomalous pulmonary venous return (n = 2). Ninety patients were assigned to alpha-stat and 92 to pH-stat strategy. Early death occurred in four infants (2%), all in the alpha-stat group (p = 0.058). Postoperative electroencephalographic seizures occurred in five of 57 patients (9%) assigned to alpha-stat and one of 59 patients (2%) assigned to pH-stat strategy (p = 0.11). Clinical seizures occurred in four infants in the alpha-stat group (4%) and two infants in the pH-stat group (2%) (p = 0.44). First electroencephalographic activity returned sooner among infants randomized to pH-stat strategy (p = 0.03). Within the homogeneous D-transposition subgroup, those assigned to pH-stat tended to have a higher cardiac index despite a lower requirement for inotropic agents; less frequent postoperative acidosis (p = 0.02) and hypotension (p = 0.05); and shorter duration of mechanical ventilation (p = 0.01) and intensive care unit stay (p = 0.01). CONCLUSIONS Use of the pH-stat strategy in infants undergoing deep hypothermic cardiopulmonary bypass was associated with lower postoperative morbidity, shorter recovery time to first electroencephalographic activity, and, in patients with D-transposition, shorter duration of intubation and intensive care unit stay. These data challenge the notion that alpha-stat management is a superior strategy for organ protection during reparative operations in infants using deep hypothermic cardiopulmonary bypass.

Mechanical circulatory support in children with cardiac disease

OBJECTIVE To review the experience from a single center that uses both extracorporeal membrane oxygenation and ventricular assist devices for children with cardiac disease requiring mechanical circulatory support. METHODS A retrospective chart review was performed for all pediatric patients with cardiac disease who required support with extracorporeal membrane oxygenation or ventricular assist devices. Statistical analysis of the impact of multiple clinical parameters on survival was performed. RESULTS From 1987 through 1996 we provided mechanical circulatory support for children with a primary cardiac diagnosis using extracorporeal membrane oxygenation (67 patients) and ventricular assist devices (29 patients). Twenty-seven of 67 (40.3%) patients supported with extracorporeal membrane oxygenation and 12 of 29 (41.4%) patients supported with ventricular assist devices survived to hospital discharge. Failure of return of ventricular function within 72 hours of the institution of support was an ominous sign in patients supported with either modality. Univariate analysis revealed the serum pH at 24 hours of support, the serum bicarbonate at 24 hours of support, the urine output over the first 24 hours of support, and the development of renal failure to have a statistically significant association with survival in children supported with extracorporeal membrane oxygenation. None of the clinical parameters evaluated by univariate analysis were significantly associated with survival in the patients supported with ventricular assist devices. CONCLUSIONS Extracorporeal membrane oxygenation and ventricular assist devices represent complementary modalities of mechanical circulatory support that can both be used effectively in children with cardiac disease.

A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of Oral Sildenafil Citrate in Treatment-Naive Children With Pulmonary Arterial Hypertension

Background— Safe, effective therapy is needed for pediatric pulmonary arterial hypertension. Methods and Results— Children (n=235; weight ≥8 kg) were randomized to low-, medium-, or high-dose sildenafil or placebo orally 3 times daily for 16 weeks in the Sildenafil in Treatment-Naive Children, Aged 1–17 Years, With Pulmonary Arterial Hypertension (STARTS-1) study. The primary comparison was percent change from baseline in peak oxygen consumption (PV[Combining Dot Above]O2) for the 3 sildenafil doses combined versus placebo. Exercise testing was performed in 115 children able to exercise reliably; the study was powered for this population. Secondary end points (assessed in all patients) included hemodynamics and functional class. The estimated mean±SE percent change in PV[Combining Dot Above]O2 for the 3 doses combined versus placebo was 7.7±4.0% (95% confidence interval, −0.2% to 15.6%; P=0.056). PV[Combining Dot Above]O2, functional class, and hemodynamics improved with medium and high doses versus placebo; low-dose sildenafil was ineffective. Most adverse events were mild to moderate in severity. STARTS-1 completers could enter the STARTS-2 extension study; patients who received sildenafil in STARTS-1 continued the same dose, whereas placebo-treated patients were randomized to low-, medium-, or high-dose sildenafil. In STARTS-2 (ongoing), increased mortality was observed with higher doses. Conclusions— Sixteen-week sildenafil monotherapy is well tolerated in pediatric pulmonary arterial hypertension. Percent change in PV[Combining Dot Above]O2 for the 3 sildenafil doses combined was only marginally significant; however, PV[Combining Dot Above]O2, functional class, and hemodynamic improvements with medium and high doses suggest efficacy with these doses. Combined with STARTS-2 data, the overall profile favors the medium dose. Further investigation is warranted to determine optimal dosing based on age and weight. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT00159913.

Use of rapid-deployment extracorporeal membrane oxygenation for the resuscitation of pediatric patients with heart disease after cardiac arrest.

INTRODUCTION We have recently used extracorporeal membrane oxygenation as a means of rapidly resuscitating pediatric patients with heart disease after cardiopulmonary arrest, in whom conventional resuscitation measures have failed. METHODS We developed a fully portable extracorporeal membrane oxygenation circuit that is maintained vacuum and carbon dioxide-primed at all times. When needed, the circuit is crystalloid-primed and can be ready for use within 15 minutes. Since February 1996, we have used this rapid-deployment circuit to resuscitate 11 pediatric patients in full cardiopulmonary arrest. RESULTS The median age of the 11 patients was 120 days (2 days to 4.6 years). Nine patients had a cardiac arrest after cardiac surgery. One patient had a cardiac arrest during cardiac catheterization and one patient had a cardiac arrest before cardiac surgery. Median duration of cardiopulmonary resuscitation was 55 minutes (range 20 to 103 minutes), with no difference in the duration of cardiopulmonary resuscitation between survivors and nonsurvivors. Ten of 11 patients (91%) were weaned from extracorporeal membrane oxygenation and seven (64%) survived to hospital discharge. Six patients are long-term survivors, five of whom are in New York Heart Association class I; one survivor is in class II. Seven patients resuscitated with extracorporeal membrane oxygenation before the use of this rapid-deployment circuit had a median duration of cardiopulmonary resuscitation of 90 minutes, with two (28.6%) survivors. CONCLUSIONS The use of rapid-deployment extracorporeal membrane oxygenation results in shorter resuscitation times and improved survival in pediatric patients with heart disease after cardiopulmonary arrest.