Use of haloperidol infusions to control delirium in critically ill adults.

OBJECTIVE: To describe and discuss the use of continuous intravenous infusions of haloperidol to treat severe delirium and agitation in 3 intensive care unit (ICU) patients. CASE SUMMARIES: Three severely agitated patients in ICU did not respond to conventional therapy with opiates, benzodiazepines, and intermittent intravenous doses of haloperidol. In each case, control was achieved rapidly after initiation and titration of a continuous haloperidol infusion. Two patients had a history of schizophrenia. No adverse effects attributable to therapy were identified. DISCUSSION: Haloperidol is often used in the ICU for control of severe agitation, even in patients without a psychiatric history. It usually is given by bolus intravenous injection, sometimes in high doses (> 5 mg), even though that is not approved by the Food and Drug Administration. Intravenous haloperidol is generally well tolerated, but multiform ventricular tachycardia has been reported. Experience with continuous haloperidol infusions is growing, and it appears to be an effective method for control of severe agitation or delirium. In our experience and in other limited published data, adverse effects are rare, but prolongation of the QT interval has occurred and multiform ventricular tachycardia is likely a risk. CONCLUSIONS: In selected patients, a continuous infusion of haloperidol may be a useful alternative for control of agitation and delirium. Close monitoring for QT prolongation or rhythm disturbances is mandatory.

The microfibrillar proteins of human hair: separation by high-performance liquid chromatography and isolation of some proteins enriched in glycine and tyrosine.

The microfibrillar proteins of human hair have been studied by reversed-phase high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A chromatographic procedure which isolates the microfibrillar proteins from other hair-matrix proteins and separates them into collectable fractions has been introduced. These fibrous proteins fall into two major subgroups which are resolved into six components. The same procedure has also resulted in the identification and simultaneous separation of a group of proteins rich in glycine and tyrosine never before detected in human hair. Comparative electrophoretic studies of the crude microfibrillar proteins reveal five bands with apparent molecular weights of 47,000, 50,000, 53,000, 57,000, and 62,000. The relationship between the electrophoretic bands and the chromatographic fractions is now under investigation.

Experience with heart transplantation in children.

Between March 1981 and March 1986, 200 orthotopic heart transplantations were performed at the University of Pittsburgh. Fourteen of those procedures were carried out in children 2 to 16 years of age. Two children received combined liver and heart transplants; one because of familial hypercholesterolemia with associated ischemic heart disease, and the other because of dilated cardiomyopathy associated with intrahepatic biliary atresia. Eight patients had dilated cardiomyopathy, and two had myocarditis. Two had heart transplantations for congenital heart disease: one had multiple muscular ventricular septal defects repaired in infancy and had an associated cardiomyopathy, and the other developed a cardiomyopathic ventricle from a congenital right coronary artery to right atrial fistula. Chronic immune suppression consisted 0.2 to 0.5 mg/kg/d of prednisone and 5 to 50 mg/kg/d cyclosporine, with the addition of antithymocyte globulin for unresolved moderate or severe acute rejection. There were three early postoperative deaths: one from intracranial bleeding, one from Pseudomonas mediastinitis, and one from ischemic injury to transplanted organs. Early postoperative complications included reversible renal failure, hypertension, and seizures. Late problems were related to allograft rejection and side effects of cyclosporine and corticosteroids. Significant rejection episodes occurred in all patients surviving longer than 2 weeks, with seven requiring antithymocyte globulin. Two patients died 8 months following transplantation of severe acute and chronic rejection; another patient required retransplantation for ischemic cardiomyopathy resulting from chronic rejection but subsequently died of recurring rejection 3 months after the second transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of non-nutritive dietary constituents in carcinogenesis.

Very low levels of a large variety of non-nutritive chemicals occur in the diet. Among those that occur naturally are metabolites of molds (for example, mycotoxins) and bacteria (for example, nitrosamines) and natural constituents of plants (for example, pyrrolizidine alkaloids). Many of these are occasional contaminants, whereas others are normal components of relatively common foods. Some compounds (for example, aflatoxin, nitrosamines, and hydrazones) have been found to be carcinogenic in laboratory animals and mutagenic in bacterial and other systems, thereby posing a potential risk to humans. However, there have been very few definitive epidemiologic studies. Therefore, further investigations are necessary to determine the significance of these experimental findings for humans. It is apparent that many foods naturally contain substances with mutagenic properties and that some substances found in foods can enhance or inhibit the mutagenic activity of other compounds. Furthermore, mutagens can be formed during the cooking or processing of foods. However, caution is needed in the interpretation of these findings. Although mutagens by definition are "suspect" carcinogens, many mutagens detected in foods have not been adequately tested for carcinogenicity, and therefore their significance for human health cannot be fully assessed. With the exception of studies on non-nutritive sweeteners like saccharin and cyclamate, or those on nitrate and nitrite, very few epidemiologic studies have been conducted to examine the effect of food additives on cancer risk. Of the few direct food additives that have been tested and found to be carcinogenic in animals, all except saccharin have been banned from use in the food supply. Minute residues of a few indirect additives that are known either to produce cancer in animals (for example, vinyl chloride and acrylonitrile) or to be carcinogenic in humans (for example, vinyl chloride) are occasionally detected in foods. Thus far, the increasing use of food additives does not seem to have contributed significantly to the overall cancer risk for humans. However, the relatively short duration of use of many of these substances and the inadequacy of the data base preclude definitive conclusions. Very low levels of a large and chemically diverse group of substances--environmental contaminants (for example, residues of pesticides, polycyclic aromatic hydrocarbons, and traces of toxic metals)--may be present in foods.(ABSTRACT TRUNCATED AT 400 WORDS)

Cystine-rich proteins of human hair: characterization and structure as revealed by reversed-phase and size-exclusion high-performance liquid chromatography.

The human hair cystine-rich proteins have been separated through the combined use of reversed-phase and size-exclusion chromatography into more than fifty components. These have been grouped, based on molecular weight, into six families of closely related members. The families range in molecular weight from less than 6500 for the low-molecular-weight components to more than 67 000 for the high-molecular-weight components, with average intermediate values for the other families of 8000, 11 500, 15 500 and 19 000. The results also suggest an organized structure of the hair matrix proteins. The combined use of reversed-phase and size-exclusion high-performance liquid chromatography in these studies presents an example where the quaternary structure of a multi-component protein can be largely deduced from its chromatographic behaviour.

Echocardiographic findings before and after liver transplantation.

Echocardiographic studies were performed in 73 patients with various types of chronic liver disease. They were 0.5 to 19 years old (mean 5). Thirteen patients underwent follow-up echocardiography 1 to 13 months (mean 6) after liver transplantation. Preoperatively 60 patients (82%) showed evidence of high cardiac output (cardiac index greater than 4 liters/min/m2); these patients manifested increased left ventricular (LV) and left atrial dimensions and a thickened LV posterior wall. Transvenous contrast echocardiographic study confirmed the presence of intrapulmonary arteriovenous shunting in 4 patients. Studies after liver transplantation revealed a reduced LV end-diastolic dimension in 12 patients. Cardiac index was reduced a mean of 35% after transplantation (p less than 0.001). This study suggests that liver transplantation improves common hemodynamic abnormalities in chronic liver disease.

Reversed-phase high-performance liquid chromatography of some ultra-heterogeneous and covalently-modified proteins from human hair.

A new procedure for the fractionation of the heterogeneous cystine-rich proteins from human hair, utilizing reversed-phase high-performance liquid chromatography, is described. Of these proteins 27 fractions have been collected and analyzed for amino acid composition. There seems to be little correlation between the elution order and the hydrophobicity of the fraction constituents except for the late-eluting fractions. Based on the elution profiles and amino acid contents, these fractions appear to fall into four families. The effects of alkyl chain length, flow-rate and gradient slope, as well as various additives to the organic modifier on the separation have also been investigated. A low flow-rate (0.4 ml/min) and a shallow gradient were essential for the separation of these proteins as was the use of short alkyl chain (C4) or medium alkyl chain (C8) columns. However, with the C4 column reproducibility and recovery were excellent.

Ventricular septal defect associated with aneurysm of the membranous septum.

The most common variety of ventricular septal defect, a perimembranous defect, is frequently associated with a so-called aneurysm of the membranous septum. Previous studies have suggested that ventricular septal defects associated with an aneurysm of the membranous septum tend to spontaneously decrease in size or close more than defects without such an aneurysm. To better define the natural history of this entity, clinical and catheterization data from 87 patients with ventricular septal defect and aneurysm of the membranous septum were reviewed. The initial evaluation was made at a median age of 0.3 years (range 0.1 to 11), with the final evaluation at a median age of 10 years (range 1.5 to 20) and a median duration of follow-up of 8.6 years (range 1.2 to 18.8). Approximately 75% of the ventricular septal defects had a small or no left to right shunt at last evaluation. Overall, 48 patients (55%) had no significant change in the size of the defect, and 39 (45%) showed improvement during the period of observation. Only four patients (5%) had spontaneous closure of the defect. Of the 49 patients who presented with a large left to right shunt, with or without congestive heart failure, 23 (47%) had persistence of a shunt large enough to warrant surgery. When spontaneous improvement occurred, it did so by 6 years of age in all but one patient. Therefore, a continued tendency for a ventricular septal defect associated with an aneurysm of the membranous septum to spontaneously decrease in size or close after this age may be less likely than previously suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular inversion with normal ventriculoarterial connection and left atrial isomerism: correction by the Mustard operation.

A 2 year old boy with ventricular inversion and normal ventriculoarterial connection is described. Associated cardiac lesions included single atrium, absence of the coronary sinus, bilateral superior venae cavae, absence of the hepatic segment of the inferior vena cava with azygos and hemiazygos continuation, right aortic arch, levocardia and left atrial isomerism. At 5 days of age, the patient underwent a Waterston (aortopulmonary) anastomosis because of suspected pulmonary atresia. The correct diagnosis was established at 2 years of age and the patient had a successful Mustard operation (interatrial baffle procedure) and closure of the Waterston anastomosis. Accurate preoperative diagnosis is difficult in this rare cardiac anomaly and the reported mortality rate is high.

Surgical management of univentricular heart with subaortic obstruction.

In children with a univentricular heart and a rudimentary subaortic chamber, surgical relief of subaortic obstruction caused by a restrictive bulboventricular foramen is associated with high morbidity and mortality. A 6-year-old child with a univentricular heart of the left ventricular type, a rudimentary subaortic chamber, and atresia of the left-sided atrioventricular valve had pulmonary artery banding in infancy. Severe subaortic obstruction subsequently developed. At operation, the pulmonary artery was transected and the stump was anastomosed directly to the posterior aspect of the ascending aorta, diverting left ventricular blood into the aorta through the pulmonary valve. The distal pulmonary artery was anastomosed side-to-side to the ascending aorta to provide pulmonary blood flow. Cardiac catheterization fifteen months after the operation demonstrated an excellent hemodynamic result. When the pulmonary artery is adequate in size, a bypass operation by way of an anastomosis between the ascending aorta and the pulmonary artery is a relatively safe and effective means of relieving the ventricular outflow obstruction caused by a restrictive bulboventricular foramen.

The anatomical heterogeneity of hearts lacking a patent communication between the left atrium and the ventricular mass ('mitral atresia') in presence of a patent aortic valve.

Thirty-five hearts were studied with no patent communication between the left atrium and the ventricular mass ('mitral atresia'). In ten, an imperforate and hypoplastic membrane separated the left atrium from a hypoplastic left ventricle. The imperforate valve ranged from a tiny membrane with no evidence of tension apparatus, through a larger membrane supported by muscular columns in the ventricular inlet portion, to an aneurysmal imperforate sac attached to a single hypoplastic papillary muscle. The ventriculo-arterial connection was concordant in nine of the ten hearts and double outlet from the right ventricle in one. In one further heart, there was double inlet left ventricle with imperforate left atrioventricular valve, a rudimentary right ventricle and ventriculo-arterial discordance. In the other 24 hearts the muscular floor of the left atrium was completely separated by the atrioventricular sulcus from the ventricular mass (absent left atrioventricular connection). In 11 of these hearts, the right atrium was connected to a right ventricle and there was a posterior and left-sided rudimentary left ventricular chamber which had no connection with the atrial chambers. The left ventricle supported the aorta in five of the 11 hearts, but in the other six it was simply a pouch of left ventricular morphology. In ten cases the right atrium was connected to a dominant left ventricle. An anterior rudimentary right ventricle was present in each but had no connection with the atrial chambers. It was to the left of the left ventricle in seven, directly anterior in one and to the right in two cases. The right ventricle supported the aorta in eight cases, the pulmonary trunk in one and neither great artery in the remaining case. Lastly, there were three cases in which a sole ventricular chamber of indeterminate morphology was present and gave rise to both great arteries.

Hemodynamic function after the Mustard operation for transposition of the great arteries.

Pre- and postoperative cardiac catheterization data and cinenangiocardiograms of 82 patients who survived the Mustard operation for transposition of the great arteries (TGA) were reviewed. The post-operative catheterizations were performed 20 days to 10 years after operation (mean 2.5 years). Forty-six patients (56%) had no or insignificant associated cardiac lesions, whereas 36 (44%) had ventricular septal defect, pulmonary stenosis, or both, and required surgical intervention at the time of the Mustard operation. Postoperatively, 11 patients (13%) had significant systemic venous obstruction. Of the 11 patients, 6 required reoperation, and 2 patients had evidence of restenosis or complete obstruction in the superior vena cava after reoperation. In most patients, superior vena caval obstruction was well tolerated even in the presence of high pressure in the superior vena cava. Pulmonary venous obstruction occurred in 5 patients (6%), 3 of whom had no clinical symptoms despite severe pulmonary venous obstruction, although all had radiographic evidence of pulmonary venous congestion. The incidence of obstruction was drastically reduced after the Mustard operation was modified to include routine enlargement of the pulmonary venous atrium. Tricuspid regurgitation was uncommon (10%), but did occur in patients who had transatrial closure of a ventricular septal defect. Preoperatively, left ventricular outflow obstruction occurred in 38%. In 12 patients an attempt was made to relieve the obstruction at surgery. The 6 patients who had localized obstruction had a good result, but patients with more diffuse narrowing of left ventricular outflow had little or no relief of obstruction. Mild to moderate left ventricular outflow gradients regressed spontaneously in most patients after the Mustard operation.

Rest and exercise right and left ventricular function late after the Mustard operation: assessment by radionuclide ventriculography.

To evaluate ventricular function late after atrial repair of transposition of the great arteries (TGA), 26 asymptomatic patients had rest and exercise radionuclide ventriculography performed a mean of 9 years (range 5 to 15) after undergoing the Mustard operation. The mean resting right (systemic) ventricular (RV) ejection fraction (EF) was 0.50 +/- 0.10 (+/- 1 standard deviation); the RVEF was less than 0.45 in 8 patients. With exercise the RVEF increased in 9 patients and either failed to increase or decreased in 15 (including all 8 patients with resting values less than 0.45). The weight-adjusted work load performed was a first predictor of RV exercise response (sensitivity 87%, specificity 92%); patients whose RVEF increased did more work. The mean resting left (pulmonary) ventricular (LV) EF was 0.58 +/- 0.09; the LVEF was less than 0.50 in 3 patients. With exercise the LVEF increased in 14 patients and did not increase in 10 (including all 3 with resting values less than 0.50). The presence of complex ventricular arrhythmia documented on Holter monitoring was a first predictor of failure of the LVEF to increase with exercise (sensitivity 84%, specificity 71%). The patient's age, operative age, postoperative interval, residual arterial desaturation, preoperative large ventricular septal defect or pulmonary stenosis, postoperative pulmonary stenosis or superior vena caval obstruction, or performance of a second open-heart procedure was predictive of the rest or exercise EF of either ventricle.

Exercise studies after the Mustard operation in transposition of the great arteries.

Twenty-one postoperative patients with transposition of the great arteries (TGA) underwent graded exercise testing 4 to 15 years (mean 9) after the Mustard operation. No patient had subjective exercise intolerance before testing, although some had symptomatic resting arrhythmias. Correlations were made between cardiac catheterization data and 24-hour ambulatory monitoring. Exercise tolerance was diminished in nearly half of the patients. No statistically significant differences were found in heart rate or blood pressure responses, but maximal oxygen consumption values were lower than the control values (p less than 0.001) in the larger patients. Arrhythmias were present or provoked in most patients during exercise testing. Only 28% remained in normal sinus rhythm during and after exercise. Multifocal premature contractions were the most serious arrhythmias demonstrated. Some long-term survivors of the Mustard operation may have abnormal exercise dynamics, even though they may be asymptomatic and have normal physical activities and endurance. Mean maximal systolic blood pressure, heart rate, oxygen consumption, and maximal treadmill times were consistently in the low-normal range or were statistically lower than normal.

Arrhythmias in transposition of the great arteries after the Mustard operation.

Disorders of rhythm or conduction in patients with transposition of the great arteries (TGA) after the Mustard operation have been widely reported. This study provides a systematic evaluation of the electrophysiologic function of 87 survivors of the Mustard operation at a single institution. Surface electrocardiograms were reviewed in all 87 patients, Holter monitoring data in 26 patients, exercise electrocardiograms in 21 patients, and invasive electrophysiologic data in 61 patients. Surface electrocardiograms showed normal sinus rhythm in 52%, sinus node dysfunction in 27%, and atrioventricular block in 16%. Holter monitoring was obtained in an unselected subgroup of 26 patients who had a mean age of 12 years and a mean interval from operation of 9 years. Sinus node dysfunction was found in 58%, atrioventricular block in 27% ventricular ectopy in 50%, supraventricular ectopy in 27%, and no abnormalities in only 8%. Intracardiac electrophysiologic evaluation showed a high frequency of abnormal sinus node recovery times and suboptimal response of the atrioventricular-conduction system to rapid atrial pacing. When all modalities used in this study were considered, sinus node dysfunction occurred in 47%, ectopy in 34% and atrioventricular block in 23%. Although only 30% of patients had no evidence of arrhythmia, symptoms of rhythm or conduction disturbances were rare.

Unilateral pulmonary vein atresia: clinical and radiographic spectrum.

Three cases of unilateral pulmonary vein atresia are presented to illustrate part of the clinical and radiographic spectrum of this anomaly. One patient had major associated cardiovascular abnormalities and pulmonary hypertension, one had recurrent hemoptysis, and the other patient was asymptomatic with normal pulmonary artery pressure and no associated abnormalities. In one case, serial catheterizations indicated that the pulmonary vein atresia was acquired. This report stresses the radiographic, hemodynamic, and angiographic findings in patients with unilateral severe pulmonary venous obstruction. The embryology, pathology, and surgical approach are also discussed. The diagnosis should be strongly suspected before cardiac catheterization when typical features are present on the chest radiograph and isotopic ventilation perfusion scan.