Paul R. Hickey

Developmental and Neurologic Status of Children after Heart Surgery with Hypothermic Circulatory Arrest or Low-Flow Cardiopulmonary Bypass

Background Deep hypothermia with either total circulatory arrest or low-flow cardiopulmonary bypass is used to support vital organs during heart surgery in infants. We compared the developmental and neurologic sequelae of these two strategies one year after surgery. Methods Infants with D-transposition of the great arteries who underwent an arterial-switch operation were randomly assigned to a method of support consisting predominantly of circulatory arrest or a method consisting predominantly of low-flow bypass. Developmental and neurologic evaluations and magnetic resonance imaging (MRI) were performed at one year of age. Results Of the 171 patients enrolled in the study, 155 were evaluated. After adjustment for the presence or absence of a ventricular septal defect, the infants assigned to circulatory arrest, as compared with those assigned to low-flow bypass, had a lower mean score on the Psychomotor Development Index of the Bayley Scales of Infant Development (a 6.5-point deficit, P = 0.01) and a hig...

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.

Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery

BACKGROUND Extreme hormonal and metabolic responses to stress are associated with increased morbidity and mortality in sick adults. We hypothesized that administering deep opioid anesthesia to critically ill neonates undergoing cardiac surgery would blunt their responses to stress and might improve clinical outcomes. METHODS In a randomized trial, 30 neonates were assigned to receive deep intraoperative anesthesia with high doses of sufentanil and postoperative infusions of opiates for 24 hours; 15 neonates were assigned to receive lighter anesthesia with halothane and morphine followed postoperatively by intermittent morphine and diazepam. Hormonal and metabolic responses to surgery were evaluated by assay of arterial blood samples obtained before, during, and after the operations. RESULTS The neonates who received deep anesthesia (with sufentanil) had significantly reduced responses of beta-endorphin, norepinephrine, epinephrine, glucagon, aldosterone, cortisol, and other steroid hormones; their insulin responses and ratios of insulin to glucagon were greater during the operation. The neonates who received lighter anesthesia (with halothane plus morphine) had more severe hyperglycemia and lactic acidemia during surgery and higher lactate and acetoacetate concentrations postoperatively (P less than 0.025). The group that received deep anesthesia had a decreased incidence of sepsis (P = 0.03), metabolic acidosis (P less than 0.01), and disseminated intravascular coagulation (P = 0.03) and fewer postoperative deaths (none of 30 given sufentanil vs. 4 of 15 given halothane plus morphine, (P less than 0.01). CONCLUSIONS In neonates undergoing cardiac surgery, the physiologic responses to stress are attenuated by deep anesthesia and postoperative analgesia with high doses of opioids. Deep anesthesia continued postoperatively may reduce the vulnerability of these neonates to complications and may reduce mortality.

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...

Developmental and Neurological Status of Children at 4 Years of Age After Heart Surgery With Hypothermic Circulatory Arrest or Low-Flow Cardiopulmonary Bypass

BACKGROUND It is not known whether developmental and neurological outcomes in the preschool period differ depending on whether the predominant vital organ support strategy used in infant heart surgery was total circulatory arrest (CA) or low-flow cardiopulmonary bypass. METHODS AND RESULTS Infants with D-transposition of the great arteries who underwent an arterial-switch operation were randomly assigned to a support method consisting predominantly of CA or low-flow cardiopulmonary bypass. Developmental and neurological status were evaluated blindly at 4 years of age in 158 of 163 eligible children (97%). Neither IQ scores nor overall neurological status were significantly associated with either treatment group or duration of CA. The CA group scored lower on tests of motor function (gross motor, P=0.01; fine motor, P=0.03) and had more severe speech abnormalities (oromotor apraxia, P=0.007). Seizures in the perioperative period, detected either clinically or by continuous electroencephalographic monitoring, were associated with lower mean IQ scores (12.6 and 7.7 points, respectively) and increased risk of neurological abnormalities (odds ratios, 8.4 and 5.6, respectively). The performance of the full cohort was below expectations in several domains, including IQ, expressive language, visual-motor integration, motor function, and oromotor control. CONCLUSIONS Use of CA to support vital organs during open heart surgery in infancy is associated, at the age of 4 years, with worse motor coordination and planning but not with lower IQ or with worse overall neurological status.

Hormonal—Metabolic Stress Responses in Neonates Undergoing Cardiac Surgery

Hormonal and metabolic responses were measured in 15 neonates who underwent repair of complex congenital heart defects during a standardized anesthetic protocol. Four of the 15 neonates died postoperatively in the intensive care unit. Analysis of arterial plasma samples obtained before, during, and 24 h after surgery showed that plasma epinephrine, norepinephrine, cortisol, glucagon, and beta endorphin increased in all patients (P less than 0.05). Insulin levels increased only at the end of surgery but remained elevated for 24 h postoperatively (P less than 0.02). Intraoperative metabolic changes were characterized by hyperglycemia and lactic acidemia that persisted postoperatively. This pattern of neonatal stress responses is distinct from and more extreme than that seen in adult cardiac surgical patients. The four neonates who died postoperatively tended to have higher stress responses intra- and postoperatively despite having been indistinguishable from survivors by the usual clinical and hemodynamic criteria. These preliminary results suggest that neonatal hormonal and metabolic responses to cardiac surgical operations in neonates are extreme and are associated with a high hospital mortality rate.

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.

High dose dexmedetomidine as the sole sedative for pediatric MRI

Objective:  This large‐scale retrospective review evaluates the sedation profile of dexmedetomidine.

Mice Deficient in Mac-1 (CD11b/CD18) Are Less Susceptible to Cerebral Ischemia/Reperfusion Injury

BACKGROUND AND PURPOSE Macrophage-1 antigen (Mac-1) (CD11b/CD18), a leukocyte beta2 integrin, facilitates neutrophil adhesion, transendothelial migration, phagocytosis, and respiratory burst, all of which may mediate reperfusion-induced injury to ischemic brain tissue in conditions such as stroke. To determine the role of Mac-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in mice genetically engineered with a specific deficiency in Mac-1. METHODS Transient focal ischemia/reperfusion was induced by occluding the left middle cerebral artery for 3 hours followed by a 21-hour reperfusion period in Mac-1-deficient (n=12) and wild-type (n=11) mice. Regional cerebral blood flow was determined with a laser-Doppler flowmeter. Brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct volume. Neutrophil accumulation was determined by staining the brain sections with dichloroacetate esterase to identify neutrophils. RESULTS Compared with the wild-type cohort, Mac-1-deficient mice had a 26% reduction in infarction volume (P<0.05). This was associated with a 50%, but statistically insignificant, reduction in the number of extravasated neutrophils in the infarcted areas of the brains in the mutant mice. There were no differences in regional cerebral blood flow between the 2 groups. CONCLUSIONS Mac-1 deficiency reduces neutrophil infiltration and cerebral cell death after transient focal cerebral ischemia. This finding may be related to a reduction in neutrophil extravasation in Mac-1-deficient mice.

Coagulation defects in neonates during cardiopulmonary bypass

We examined components of the coagulation system in 30 neonates (age, 1 to 30 days) undergoing deep hypothermic cardiopulmonary bypass (CPB). A coagulation profile consisting of activated clotting time; prothrombin time; partial thromboplastin time; factors II, V, VII, VIII, IX, X, and I (fibrinogen); antithrombin III; platelet count; and heparin levels was evaluated before bypass, at three intervals during bypass (1 minute after initiation of bypass, stable hypothermic CPB, warm CPB), after weaning from CPB and administration of protamine, and 2 to 3 hours after skin closure. The initiation of CPB resulted in a 50% decrease in circulating coagulation factors and antithrombin III levels. Platelet counts were reduced by 70% with CPB initiation. Neither deep hypothermic temperatures nor prolonged exposure to extracorporeal surfaces had any additional effect on the coagulation profiles. This suggests that the coagulation system of a neonate undergoing CPB is profoundly and globally effected by hemodilution. We believe that treatment of post-CPB coagulopathy in neonates must address these global deficits.