Morphologic changes induced by dilation of the pulmonary valve anulus with overlarge balloons in normal newborn lambs.

The optimal method for balloon dilation valvuloplasty of congenital pulmonary valve stenosis has not been established. The cardiac damage produced by using a balloon the same size as the pulmonary anulus has not been described. The use of balloons that are larger than the anulus or of a dynamic dilation technique may enhance gradient reduction, but their added risks are not known. The pulmonary valve anuli of 14 normal newborn lambs were dilated with angioplasty balloons 20% smaller to 90% larger than the anulus; in 3 dilations, a dynamic technique was used, consisting of withdrawal of the fully inflated balloon from the anulus into the body of the right ventricle. Twelve lambs were killed immediately after the procedure and 2 were killed later, and detailed gross anatomic and microscopic observations of the heart were made. These observations support the following conclusions: (1) Dilation of the pulmonary valve anulus with overlarge balloons is "clinically" well tolerated in normal newborn lambs. (2) The major damage to the heart from any balloon is not the pulmonary anulus, but to the right ventricular outflow tract and free wall, with mural hemorrhages of varying size. (3) Trauma is minor if the balloon is 30% larger than the anulus, but is considerable when the balloon is 50% larger; (4) Trauma is worst subjacent to the proximal end of the balloon, so that longer balloons may cause greater damage; and (5) Resolution of acute right ventricular hemorrhage occurs with small, patchy areas of fibrosis.

Management of congenital stenosis of a branch pulmonary artery with balloon dilation angioplasty. Report of 52 procedures.

Twenty-four children, aged 4 months to 16 years (nine patients 2 years old or younger), underwent balloon dilation angioplasty of hypoplastic or stenotic branch pulmonary arteries between July, 1981, and April, 1984. Most children had tetralogy of Fallot, with or without pulmonary atresia, or isolated peripheral pulmonary artery stenosis. Fifty-two dilations were attempted, 44 in the catheterization laboratory and eight in the operating room. Of these, 26 (50%) were judged successful; the average vessel diameter on angiogram increased from 4.1 +/- 0.3 to 7.2 +/- 0.3 mm (76%), the gradient across the narrowed segment fell from 60 +/- 10 to 36 +/- 5 mm (40%), pressure in the main pulmonary artery or right ventricle proximal to the obstruction decreased from 83 +/- 10 to 66 +/- 6 mm Hg (20%), and the radionuclide-determined fraction of cardiac output directed to the lung ipsilateral to the dilated pulmonary artery increased from 40 +/- 4 to 51 +/- 4 (28%). All changes were significant at the p less than 0.005 level. Reasons for failure included inadequate technique (balloon too small, inability to position balloon or wire) in 14 and the refractory nature of the lesion itself in 11. Technical failures were age independent. Nondilatable lesions were more common in children more than 2 years old (10/25 versus 1/10) or with isolated peripheral pulmonary artery stenosis (5/7). Five of seven stenoses near previous shunts were nondilatable. One child exsanguinated when the pulmonary artery ruptured during dilation, but other complications were few. Eight dilations, followed up for an average of 6 months after dilation, showed angiographic persistence of improvement; two of four lesions were successfully redilated to a larger size. Balloon dilation angioplasty appears beneficial, both short and long term, for some patients with hypoplastic or stenotic branch pulmonary arteries, especially if performed early in life.

Prophylactic antibiotic use in pediatric cardiovascular surgery: a survey of current practice.

There is little information on prophylactic antibiotic practice in pediatric cardiovascular surgery. A consensus prophylactic antibiotic practice, if identified, might serve as a standard to which alternative prophylactic antibiotic practice could be compared. We surveyed North American academic centers with pediatric cardiovascular surgery programs regarding their standard antimicrobial prophylaxis regimens, duration of prophylaxis and modification of prophylaxis for lesion, patient age or medical device considerations. Forty-three (81%) of 53 centers responded; not all responses were complete. Monotherapy was used by 39 (91%) of 43; 38 (97%) of 39 used a 1st or 2nd generation cephalosporin (cefazolin 24, cefamandole 8, cefuroxime 4, cephapirin 1, unspecified 1) and 1 of 39 used vancomycin. Only 4 (9%) of 43 used 2 antibiotics. Prophylactic antibiotics were started pre- or intraoperatively by 41 of 43 centers and discontinued within 2 days by 25 of 37. Prophylactic antibiotics were often continued while thoracostomy tubes (29 of 43), mediastinal tubes (31 of 43) or transthoracic vascular catheters (22 of 43) were in place, but usually not for endotracheal tubes (6 of 43), arterial (9 of 43) or percutaneous central venous (13 of 43) catheters or temporary pacing wires (6 of 43). Our survey indicates that the consensus prophylactic antibiotic regimen for pediatric cardiovascular surgery is monotherapy with a first or second generation cephalosporin, used for < or = 2 days or until transthoracic medical devices are removed.

Patent ductus arteriosus ligation: are we doing better?

Limitation on health care resource use is stimulating critical evaluation of previous preoperative standards. We retrospectively reviewed the clinical and hospital financial records of all children admitted for patent ductus arteriosus ligation from July 1984 to April 1994 for age, perioperative length of stay, readmissions for postoperative surgical problem, and hospital charges adjusted to 1994 dollars. Patients with an isolated patent ductus arteriosus, greater than 3 months of age, without preoperative or postoperative complications were included in this study and stratified into two groups based on date of operation. Group I had operation before January 1, 1991, and group II had operation on or after January 1, 1991. Comparison of these two groups revealed a significant difference in perioperative length of stay (group I, 3.9 +/- 1.2 days [mean +/- standard deviation]; group II, 2.7 +/- 0.9 days; p < 0.0001) and in hospital charges (group I, $8,700 +/- $2,100; group II, $6,600 +/- $1,000; p < 0.0001). These data support the premise that children older than 3 months undergoing elective ligation of a patent ductus arteriosus have been treated with improved efficiency and less charge without an increase in postdischarge morbidity. Health care policy decisions have forced us to evaluate the standards of perioperative care more critically.

Novel therapies for acute respiratory failure.

Mortality in acute respiratory failure in the non-neonatal pediatric patient has not changed substantially in 20 years, despite advances and refinements in conventional therapeutic strategies and technology. A host of innovative therapies are currently in various stages of investigation, including high frequency ventilation, pressure control ventilation, permissive hypercapnia, extracorporeal membrane oxygenation, exogenous surfactant administration, inhaled nitric oxide, and liquid ventilation. While none of these therapies has yet been prospectively studied in non-neonatal pediatric patients, all show much promise by virtue of their emphasis on either directly addressing pathophysiologic derangements associated with acute respiratory failure or by reducing the complications associated with conventional therapy.

Shock in infants and children.

Physiologic data obtained from infants and children in shock indicate that there is a high frequency of abnormalities that can only be discovered with pulmonary artery catheters. Cardiogenic shock is a low-output, high-resistance condition, and septic shock is a relatively high-output, low-resistance condition. The use of pulmonary artery catheter data demonstrates that optimal therapeutic goals can be estimated and basic pathophysiologic abnormalities can be discovered.

Hemodynamic effects following ingestion of an imidazoline-containing product.

Toxic ingestions constitute a major health problem for infants and young children, with an estimated 500,000 poisonings in 1980, 90% of them in children less than five years old. Mortality and associated expense are considerable. Sympathetic amines, while less commonly involved in pediatric poisonings, deserve special attention because of their potent cardiovascular side effects, eg, tachycardia and hypertension. Tetrahydrozoline, the active ingredient in several nasal and ophthalmologic over-the-counter medications, has previously been implicated in childhood ingestions. We report a case of tetrahydrozoline ingestion in which, paradoxically, lethargy, bradycardia, and hypotension were noted.

Solubilized nuclear "receptors" for thyroid hormones. Physical characteristics and binding properties, evidence for multiple forms.

Tissues regulated by thyroid hormones contain chromatin-localized "receptors" that may be involved in the actions of these hormones. In this report, we describe some properties of these receptors after their solubilization from rat liver nuclei and their separation from nucleic acids and basic proteins. The nuclear extract and partially purified preparations contain a dominant class of binding sites which have a high affinity for triiodothyronine (3,5,3'-triiodo-L-thyronine, Kd approximately 1 nM) and for the biologically potent isopropyl diiodothyronine (3,5-diiodo-3'-isopropyl-L-thyronine, Kd congruent to 1 nM) and also bind thyroxine (3,5,3',5'-tetraiodo-L-thyronine, Kd approximately 5 nM) and reverse triiodothyronine (3,3',5'-triiodo-L-thyronine, Kd approximately nM). This binding activity elutes on Sephadex G-100 in an included peak which has a Stokes radius of 35 A and sediments on glycerol gradients at 3.5 S. From these data a molecular weight ratio of 50,500 and a frictional ratio of 1.4 were calculated, suggesting that the receptor is somewhat asymmetrical. There was a sharp decline in triiodothyronine binding by this component above pH 8.7 (optimum around pH 7.6) where there is marked dissociation of the 4' phenolic hydroxyl of triiodothyronine (pKalpha approximately 8.5). A similar decrease in thyroxine (pKalpha approximately 6.7) binding with pH increases in this range was not observed. Thus, ionization of the phenolic hydroxyl may influence binding. The solubilized preparations can also contain a minor specific-binding component that can be identified by binding analyses, and by G-100 or quaternary aminoethyl Sephadex chromatography. this component has a much lower affinity for triiodothyronine and isopropyl diiodothyronine than for thyroxine as compared to the major component. It probably has a pH optima around 6.0 and demonstrates and apparent tendency to aggregate. The minor component was not always identified by direct Scatchard analysis and may be generated in part from the major component as it was more commonly observed after storage or purification of the nuclear extract. Thus, at least two thyroid hormone-binding components can be present in extracts of purified rat liver nuclei; the minor component may be an altered form or subunit of the major component. The relative binding activities of triiodothyronine, isopropyl diiodothyronine, and thyroxine by the major component, similar to those in intact nuclei, parallel the biological potencies of these compounds, and suggest that the dominant binding is by biologically relevant receptors. Since ionization of the phenolic hydroxyl may influence binding, the lower activity of thyroxine relative to triiodothyronine may in part be due to the fact that at physiological pH, the phenolic hydroxyl of thyroxine is more dissociated than is that of triiodothyronine. The finding that this receptor is somewhat asymmetrical provides an indication of the shape of an intrinsic chromatin protein implicated in specific gene regulation...

Regulation of activity of chromatin receptors for thyroid hormone: possible involvement of histone-like proteins.

Thyroid hormone receptors lose their capability for high-affinity binding of the biologically active triiodothyronine after solubilization and separation from other chromatin proteins. The high-affinity triiodothyronine-binding capacity can be reconstituted by addition of a histone-containing extract of chromatin of purified core histones (H2A, H2B, H3, and H4); a number of other acidic or basic proteins tested were ineffective. The data support a model of the receptor in which a "core" receptor subunit that contains a thyroid hormone-binding site interacts with a regulatory subunit, which is possibly a histone or histone-like species. This interaction with the "core" subunit enables the resulting "holo" receptor to bind biologically active hormones. These data also suggest that histones or related proteins can modulate the activity of nonhistone chromosomal proteins that are involved in regulating the expression of specific genes.

Plastic bronchitis occurring late after the Fontan procedure: treatment with aerosolized urokinase.

OBJECTIVE: To describe the use of aerosolized urokinase in a patient with plastic bronchitis after a Fontan procedure. DESIGN: Case report. SETTING: Pediatric intensive care unit in a university-affiliated children's hospital. PATIENTS: Report of one patient with acute respiratory failure secondary to plastic bronchitis. INTERVENTIONS: Aerosolized urokinase, multiple bronchoscopies, corticosteroids, mucolytics, bronchodilators, and atrial pacing. MEASUREMENTS AND MAIN RESULTS: Airway obstruction secondary to recurring casts improved with the treatments. Histologic analysis of the casts demonstrated less fibrin after treatments with aerosolized urokinase. No adverse events were noted. CONCLUSIONS: The addition of aerosolized urokinase to this patient's treatment regimen helped to resolve life-threatening airway obstruction secondary to fibrin casts.

Prevalence of retinal hemorrhages in pediatric patients after in-hospital cardiopulmonary resuscitation: a prospective study.

OBJECTIVE: Child abuse occurs in 1% of children in the United States every year; 10% of the traumatic injuries suffered by children under 5 years old are nonaccidental, and 5% to 20% of these nonaccidental injuries are lethal. Rapid characterization of the injury as nonaccidental is of considerable benefit to child protection workers and police investigators seeking to safeguard the child care environment and apprehend and prosecute those who have committed the crime of child abuse. Physically abused children present with a variety of well-described injuries that are usually easily identifiable. In some cases, however, particularly those involving children with the shaken baby syndrome, obvious signs of physical injury may not exist. Although external signs of such an injury are infrequent, the rapid acceleration-deceleration forces involved often cause subdural hematomas and retinal hemorrhages, hallmarks of the syndrome. Frequently, retinal hemorrhages may be the only presenting sign that child abuse has occurred. Complicating the interpretation of the finding of retinal hemorrhages is the belief by some physicians that retinal hemorrhages may be the result of chest compressions given during resuscitative efforts. The objective of this study is to determine the prevalence of retinal hemorrhages after inpatient cardiopulmonary resuscitation (CPR) in pediatric patients hospitalized for nontraumatic illnesses in an intensive care unit. DESIGN: Prospective clinical study. SETTING: Pediatric intensive care unit. PATIENTS: Forty-three pediatric patients receiving at least 1 minute of chest compressions as inpatients and surviving long enough for a retinal examination. Patients were excluded if they were admitted with evidence of trauma, documented retinal hemorrhages before the arrest, suspicion of child abuse, or diagnosis of near-drowning or seizures. All of the precipitating events leading to cardiopulmonary arrest occurred in our intensive care unit, eliminating the possibility of physical abuse as an etiology. INTERVENTIONS: None. MEASUREMENTS: Examination of the retina was performed by one of two pediatric ophthalmologists within 96 hours of CPR. The chart was reviewed for pertinent demographic information; the platelet count, prothrombin time, and partial thromboplastin time proximate to the CPR were recorded if they had been determined. RESULTS: A total of 43 pediatric patients hospitalized with nontraumatic illnesses survived 45 episodes of inpatient CPR. The mean age was 23 months (range, 1 month to 15.8 years), and 84% of the patients were under 2 years old. The majority of the patients (44%) were admitted to the intensive care unit after surgery for congenital heart disease, and another 21% were admitted for respiratory failure. The mean duration of chest compressions was 16.4 minutes +/- 17 minutes with 58% lasting between 1 and 10 minutes. Five patients had chest compressions lasting >40 minutes, and two patients had open chest cardiac massage. All patients survived their resuscitative efforts. Ninety-three percent of patients had an elevated prothrombin time and/or partial thromboplastin time while 49% were thrombocytopenic. Sixty-two percent of the patients had low platelet counts and an elevated prothrombin time and/or partial thromboplastin time. Small punctate retinal hemorrhages were found in only one patient. CONCLUSIONS: Retinal hemorrhages are rarely found after chest compressions in pediatric patients with nontraumatic illnesses, and those retinal hemorrhages that are found appear to be different from the hemorrhages found in the shaken baby syndrome. Despite the small number of patients in this prospective study, we believe that these data support the idea that chest compressions do not result in retinal hemorrhages in children with a normal coagulation profile and platelet count. A larger number of patients should be evaluated in a prospective multi-institutional study to achieve statistical significance