Comparison of effectiveness of two commonly used two-handed mask ventilation techniques on unconscious apnoeic obese adults.

BACKGROUND.: Mask ventilation and tracheal intubation are basic techniques for airway management and mutually inclusive rescue measures to restore ventilation. The aim of this study was to compare the effectiveness of mask ventilation between two commonly used techniques of two-handed mask ventilation in obese unconscious apnoeic adults. METHODS.: Eighty-one obese adults received mask ventilation after induction using C-E clamp and modified V-E clamp techniques in a randomized crossover manner. Mechanical ventilation was provided using a pressure-control mode, at a rate of 10 bpm, with an inspiratory-to-expiratory time ratio of 1:2 and a pre-set plateau airway pressure of 20 cm H 2 O. The primary outcome was expired tidal volume. RESULTS.: The BMI for the subjects was 37 ( sd 4.9) kg m -2 . The failure rates for mask ventilation (tidal volume≤anatomical dead space) were 44% for the C-E technique and 0% for the V-E technique ( P <0.001). Tidal volume was significantly lower for the C-E than the V-E technique [371 ( sd 345) vs 720 (244) ml, P <0.001]. The peak airway pressures were 21 ( sd 1.5) cm H 2 O for the C-E technique and 21 (1.3) cm H 2 O for the V-E technique. CONCLUSIONS.: Mask ventilation using the modified V-E technique is more effective than with the C-E technique in unconscious obese apnoeic adults. Subjects who fail ventilation with the C-E technique can be ventilated effectively with the V-E technique. CLINICAL TRIAL REGISTRATION.: NCT02580526.

Feasibility and accuracy of nasal alar pulse oximetry.

BACKGROUND: The nasal ala is an attractive site for pulse oximetry because of perfusion by branches of the external and internal carotid arteries. We evaluated the accuracy of a novel pulse oximetry sensor custom designed for the nasal ala. METHODS: After IRB approval, healthy non-smoking subjects [n=12; aged 28 (23-41) yr; 6M/6F] breathed hypoxic mixtures of fresh gas by a facemask to achieve oxyhaemoglobin saturations of 70-100% measured by traditional co-oximetry from radial artery samples. Concurrent alar and finger pulse oximetry values were measured using probes designed for these sites. Data were analysed using the Bland-Altman method for multiple observations per subject. RESULTS: Bias, precision, and accuracy root mean square error (ARMS) over a range of 70-100% were significantly better for the alar probe compared with a standard finger probe. The mean bias for the alar and finger probes was 0.73% and 1.90% (P<0.001), respectively, with corresponding precision values of 1.65 and 1.83 (P=0.015) and ARMS values of 1.78% and 2.72% (P=0.047). The coefficients of determination were 0.96 and 0.96 for the alar and finger probes, respectively. The within/between-subject variation for the alar and finger probes were 1.14/1.57% and 1.87/1.47%, respectively. The limits of agreement were 3.96/-2.50% and 5.48/-1.68% for the alar and finger probes, respectively. CONCLUSIONS: Nasal alar pulse oximetry is feasible and demonstrates accurate pulse oximetry values over a range of 70-100%. The alar probe demonstrated greater accuracy compared with a conventional finger pulse oximeter.

Transfusion has no effect on recurrence in hepatitis C after liver transplantation.

BACKGROUND: The literature suggests that blood product transfusions have a negative impact on the survival of liver transplant patients. We investigated the impact of intraoperative blood product usage on the survival of liver transplantation patients being transplanted for hepatitis C-related end-stage liver disease. In addition, we analyzed a potentially more sensitive metric, namely disease recurrence and fibrosis progression, obtained from follow-up liver biopsies. METHODS: We retrospectively studied 194 consecutive patients with hepatitis C virus (HCV) undergoing liver transplantation. To investigate the effect of red blood cell (RBC) or platelet transfusions on post-transplant HCV recurrence, hepatic biopsy data from 4 months and 1 year after transplantation were studied. In addition, survival data were analyzed. RESULTS: There was no effect of intraoperative RBC or platelet transfusion on either 1- or 5-year patient survival following liver transplantation. There was no difference in HCV disease recurrence or progression of hepatic fibrosis at 4 months or 1 year attributable either to RBC or to platelet transfusion. CONCLUSION: This study was not able to confirm an effect on the survival of HCV-infected liver transplant patients related to intraoperative transfusion of RBCs or platelets. In addition, these transfusions had no effect on HCV recurrence or fibrosis progression. This is not to condone a liberal transfusion practice, but rather to reassure that when clinically indicated, transfusion does not have a significant impact on patient survival or disease recurrence in HCV-infected liver transplant patients.

Fetal atrial septal aneurysm: a cause of fetal atrial arrhythmias.

Atrial arrhythmias are commonly found during fetal echocardiography performed during pregnancy to evaluate fetal arrhythmias. An association between atrial arrhythmias and an atrial septal aneurysm has been noted in children and adults. In this study, 105 fetuses were evaluated by fetal echocardiography, 39 (37%) referred to evaluate fetal arrhythmia and 66 (63%) to rule out congenital heart disease. An atrial septal aneurysm was found in 42 (40%) of the fetuses and an atrial arrhythmia in 37 (35%). An atrial septal aneurysm was found in 25 (64%) of the 39 fetuses referred to evaluate a fetal arrhythmia compared with only 17 (26%) of the 66 fetuses referred to rule out congenital heart disease. In this study, the association of an atrial septal aneurysm with an atrial arrhythmia was highly significant (p less than 0.001).

Reversed shunting across the ductus arteriosus or atrial septum in utero heralds severe congenital heart disease.

OBJECTIVES: This study was performed to define the significance of Doppler color flow mapping in demonstrating reversal of the direction of the normal physiologic flow across the atrial septum and ductus arteriosus in the human fetus. BACKGROUND: Reversal of the physiologic shunting across the ductus arteriosus or atrial septum in utero (i.e., left to right) can be readily identified by Doppler color flow mapping, complemented by pulsed and continuous wave Doppler information. METHODS: We reviewed echocardiograms recorded at our three institutions from 1988 to 1993, which displayed reversal of flow by Doppler color flow in 53 fetuses of gestational age 18 weeks to term. The diagnoses were confirmed by postnatal echocardiography, operation or autopsy. Reversal of shunting was consistently associated with severe heart disease. RESULTS: Reversed atrial shunting was found with severe left heart obstructive lesions, including 19 with hypoplastic left heart syndrome, 3 with critical aortic stenosis, 2 with double-outlet right ventricle and 1 each with an interrupted aortic arch, atrioventricular septal defect and severe left ventricular dysfunction due to dilated cardiomyopathy. Reversed ductus arteriosus shunting was found with severe right heart obstructive lesions, including nine fetuses with pulmonary atresia, six with severe obstructive tricuspid valve abnormalities, five with severe tetralogy of Fallot, four with Ebstein's anomaly and two with single ventricle and pulmonary stenosis. Associated cardiac lesions were common in both groups. Only 3 of the 15 infants who were delivered alive from the reverse ductus arteriosus shunt group and 4 of 12 from the reverse atrial shunt group still survive. CONCLUSIONS: The finding of reversed flow by Doppler color flow mapping during fetal life provides a key to subsequent accurate diagnosis and denotes a spectrum of diseases with a very poor prognosis.

In utero pulmonary artery and aortic growth and potential for progression of pulmonary outflow tract obstruction in tetralogy of Fallot.

OBJECTIVES: This study was designed to define patterns of pulmonary artery and aortic growth in fetuses with tetralogy of Fallot and to determine the potential for in utero progression of right ventricular outflow tract obstruction. BACKGROUND: Despite an abundance of reports documenting the prenatal diagnosis of tetralogy of Fallot, there is little information about its course in utero. METHODS: Pulmonary artery and ascending aortic diameters were measured from prenatal and postnatal echocardiograms of 16 fetuses with tetralogy of Fallot, initially studied at 23.6 +/- 6.0 (mean +/- SD) weeks of gestation. Fetuses were classified retrospectively as having mild and severe tetralogy of Fallot according to whether the pulmonary artery circulation was (severe, n = 5) or was not (mild, n = 11) ductus arteriosus dependent at birth. RESULTS: Initial main pulmonary artery diameter was small for gestational age in 9 fetuses, large in 2 and normal in 5 compared with data from 57 gestational age-adjusted normal fetal studies; it was significantly smaller in the group with severe tetralogy of Fallot (p = 0.05). The initial main pulmonary artery/aortic diameter ratio was also smaller for the group with severe tetralogy of Fallot (0.50 +/- 0.15 vs. 0.73 +/- 0.14 in the group with mild tetralogy of Fallot, p = 0.01). Initial aortic and branch pulmonary artery diameters tended to be normal or near normal for age. In eight fetuses serially studied, main and branch pulmonary artery growth was normal or reduced during prenatal follow-up. Pulmonary artery growth was most reduced in two fetuses in the group with severe tetralogy of Fallot, resulting in pulmonary artery hypoplasia at birth. Two fetuses with valvular pulmonary atresia at birth had previously shown anterograde pulmonary outflow in midgestation, suggesting progression of pulmonary outflow obstruction. CONCLUSIONS: The postnatal spectrum of pulmonary artery size in tetralogy of Fallot can be attributed to variable patterns of growth in utero. Main pulmonary artery size, main pulmonary artery/aortic diameter ratio and pattern of pulmonary artery growth may be predictive of the severity of postnatal pulmonary outflow obstruction. Pulmonary atresia can develop in utero in some fetuses with tetralogy of Fallot.

Results of the modified Fontan operation for congenital heart lesions in patients without preoperative sinus rhythm.

Preoperative sinus rhythm has been a criterion for the Fontan operation. However, of 297 patients who underwent the Fontan operation between October 1973 and February 1984, 12 (4%) did not have sinus rhythm. The age at operation ranged from 4 to 34 years (median 15). Nine patients had a univentricular heart, two had tricuspid atresia and one had a complex form of transposition. In all 12 patients, 3 to 8 of the 10 proposed criteria for operability were not met. An atrioventricular (AV) conduction abnormality was present in seven patients, six with complete AV block and one with AV dissociation. The patient with complex transposition had complete AV block and atrial fibrillation. Postoperatively, all seven patients continued to have an AV conduction abnormality, and those with complete AV block had a permanent pacemaker implanted. Six of the 12 study patients had atrial flutter or fibrillation refractory to antiarrhythmic medications. Postoperatively, four of the six patients had sinus rhythm. Two of the six patients had complete AV block (including the patient with complex transposition) and both had a permanent pacemaker implanted. Three of the 12 patients died (mortality rate 25%). The nine survivors were followed up for 6 to 55 months; no late deaths occurred. All had marked clinical improvement. This study demonstrates that 1) complete AV block is not a contraindication to the Fontan operation, 2) some patients may not require AV synchrony postoperatively for survival, and 3) postoperative atrial flutter or fibrillation may cease or be easier to control after the Fontan operation.

Functional single ventricle: cardiorespiratory response to exercise.

The cardiorespiratory response to exercise was measured in 27 children with functional single ventricle. All 27 patients had a significant reduction in exercise time, work performed, maximal exercise heart rate, maximal oxygen uptake and systemic arterial blood oxygen saturation. The reduction in exercise performance increased with increasing age of the patients. All patients ventilated excessively at rest and during exercise. This study documented the precise level of exercise intolerance in patients with functional single ventricle. The progressive deterioration in exercise performance with increasing patient age may lend credence to the concept that operation for physiologic correction of functional single ventricle should be considered during or before adolescence.

Left juxtaposed atrial appendages: diagnostic two-dimensional echocardiographic features.

Left juxtaposition of the atrial appendages is usually associated with cyanotic congenital heart disease. Recognition of this rare anomaly is important before therapeutic or surgical procedures that involve the atrial septum can be undertaken (for example, septostomy, the Mustard or Senning operation and the Fontan anastomosis). The diagnosis of left juxtaposition of the atrial appendages is most commonly an incidental finding at the time of surgery or autopsy. This report describes the two-dimensional echocardiographic visualization of left juxtaposed atrial appendages. The diagnostic echocardiographic features are based on characteristic alterations of the plane of the atrial septum and visualization of the malpositioned right atrial appendage. On the basis of these observations, a noninvasive diagnosis of left juxtaposed atrial appendages is now possible by means of two-dimensional echocardiography.

A novel serine protease inhibition motif involving a multi-centered short hydrogen bonding network at the active site.

We describe a new serine protease inhibition motif in which binding is mediated by a cluster of very short hydrogen bonds (<2.3 A) at the active site. This protease-inhibitor binding paradigm is observed at high resolution in a large set of crystal structures of trypsin, thrombin, and urokinase-type plasminogen activator (uPA) bound with a series of small molecule inhibitors (2-(2-phenol)indoles and 2-(2-phenol)benzimidazoles). In each complex there are eight enzyme-inhibitor or enzyme-water-inhibitor hydrogen bonds at the active site, three of which are very short. These short hydrogen bonds connect a triangle of oxygen atoms comprising O(gamma)(Ser195), a water molecule co-bound in the oxyanion hole (H(2)O(oxy)), and the phenolate oxygen atom of the inhibitor (O6'). Two of the other hydrogen bonds between the inhibitor and active site of the trypsin and uPA complexes become short in the thrombin counterparts, extending the three-centered short hydrogen-bonding array into a tetrahedral array of atoms (three oxygen and one nitrogen) involved in short hydrogen bonds. In the uPA complexes, the extensive hydrogen-bonding interactions at the active site prevent the inhibitor S1 amidine from forming direct hydrogen bonds with Asp189 because the S1 site is deeper in uPA than in trypsin or thrombin. Ionization equilibria at the active site associated with inhibitor binding are probed through determination and comparison of structures over a wide range of pH (3.5 to 11.4) of thrombin complexes and of trypsin complexes in three different crystal forms. The high-pH trypsin-inhibitor structures suggest that His57 is protonated at pH values as high as 9.5. The pH-dependent inhibition of trypsin, thrombin, uPA and factor Xa by 2-(2-phenol)benzimidazole analogs in which the pK(a) of the phenol group is modulated is shown to be consistent with a binding process involving ionization of both the inhibitor and the enzyme. These data further suggest that the pK(a) of His57 of each protease in the unbound state in solution is about the same, approximately 6.8. By comparing inhibition constants (K(i) values), inhibitor solubilities, inhibitor conformational energies and corresponding structures of short and normal hydrogen bond-mediated complexes, we have estimated the contribution of the short hydrogen bond networks to inhibitor affinity ( approximately 1.7 kcal/mol). The structures and K(i) values associated with the short hydrogen-bonding motif are compared with those corresponding to an alternate, Zn(2+)-mediated inhibition motif at the active site. Structural differences among apo-enzymes, enzyme-inhibitor and enzyme-inhibitor-Zn(2+) complexes are discussed in the context of affinity determinants, selectivity development, and structure-based inhibitor design.

New and versatile approaches to the synthesis of CPP-related competitive NMDA antagonists. Preliminary structure-activity relationships and pharmacological evaluation.

Fourteen new CPP analogues have been prepared with methyl 1-(phenylmethyl) (+/-)-1,2-piperazinedicarboxylate 3 as a versatile synthetic intermediate. Derivatives were evaluated as NMDA ligands by their ability to displace [3H]CPP from rat cortical membranes. The binding affinity of various chain lengths at the N4-position of the CPP analogues, 5a, 5b, and 9a mimics the binding affinity observed for the acyclic derivatives AP6, AP8, and AP5. Analogue 9a, with a single methylene group in its phosphonate side chain, exhibited diminished affinity for the NMDA receptor when compared to the structurally similar piperidine compound CGS 19755. Replacement of the phosphonic acid moiety with monoionizable acidic groups such as a carboxylate or a phosphinate resulted in a reduction of binding affinity. An aryl spacer between the N4-nitrogen and the distal acidic group was detrimental to binding as was alkylation at the N1-position. Steric bulk, however, was better tolerated when a phenyl group was positioned alpha to the phosphonate, as seen with analogues 21 and 22.

Combination perfusion-cold storage for optimum cadaver kidney function and utilization.

Dog kidneys were perfused with a newly developed perfusate containing adenosine and PO4 for 48 hr, stored in the same perfusate for an additional 24 hr without perfusion (total preservation time:72 hr), and transplanted with immediate contralateral nephrectomy. Posttransplant renal function and biochemical analysis of the kidneys revealed practically no additional preservation-induced damage during the cold storage period. Serum creatinine levels reached normal between the third and eighth day posttransplant. This preservation method may be the method of choice for patients receiving postoperative cyclosporine therapy--and, in addition, facilitate organ sharing between transplant centers, thus reducing wastage of cadaveric kidneys.

Comparison of echocardiographic acoustic quantification with off-line manual tracing for determining left ventricular volume and ejection fraction in pediatric patients.

Echocardiographic measurement of left ventricular systolic and diastolic volume and ejection fraction in pediatric patients by acoustic quantification using automated border methods compares well with measurements done by manual trace. The time necessary for completion of measurements was similar for the two methods.

Comparison of four Doppler echocardiographic methods for calculating pulmonary-to-systemic shunt flow ratios in patients with ventricular septal defect.

Several methods currently exist for quantifying pulmonary (Qp) and systemic (Qs) shunt flow using Doppler echocardiography, although none is widely utilized. In this study, 39 patients (age 2 months to 12 years, mean 2.1 years) underwent an echocardiographic examination within 1 month of Qp:Qs shunt flow determination by oximetry at catheterization. Qp:Qs was determined by 4 methods that utilized: (1) velocity time integrals and luminal areas to estimate volume flow of the pulmonary artery and aorta; (2) the square of the ratios of pulmonary artery to aorta, multiplied by the ratio of pulmonary to aortic peak flow velocities; (3) inclusion of mitral and tricuspid valve volume flow to pulmonary and aortic volume flow; and (4) ventricular septal defect (VSD) diameter and velocity time integral to calculate left-to-right shunt, which, when added to aortic volume flow (Qs), can be used to estimate Qp. Each of the first 3 methods was statistically correlated to the oximetry Qp:Qs, with r values ranging from 0.54 to 0.66 (p < 0.001). However, the fourth method, based on direct computation of flow across the VSD, had the best correlation to catheterization data (r = 0.82), and further improved when 7 patients with a large VSD (> 9 mm/m2), all of whom had bidirectional shunting, were removed (r = 0.90). Thus, we concluded that this latter method demonstrated the best correlation to catheterization-derived shunt flow data, and because this method is somewhat less labor-intensive than the others, should provide clinically useful data well suited for serial evaluation in infants and children with VSD.

Intraoperative transesophageal echocardiography using high-resolution biplane 7.5 MHz probes with continuous-wave Doppler capability in infants and children with tetralogy of Fallot.

This study reports the role of biplane transesophageal echocardiography in monitoring surgical repairs of tetralogy of Fallot. In our patients, 3 repairs were revised based on transesophageal echocardiography and continuous-wave Doppler results, and intraoperative management was altered in 2 others.

The timing of spontaneous closure of the ductus arteriosus in infants with respiratory distress syndrome.

Previous studies evaluating the incidence of patent ductus arteriosus have not made a distinction between physiologic ductal patency and abnormally persistent ductus arteriosus. However, it has recently been shown that healthy premature infants without respiratory distress syndrome (RDS) undergo spontaneous closure of the ductus arteriosus in the first 4 days of life at times comparable to full-term infants. Thus, ductal patency within this time frame would appear to be physiologic. Although sick premature infants are well recognized to be at risk for ductal shunting, the purpose of this investigation was to evaluate systematically the actual impact that RDS has on duration of ductal shunting by assessing the timing of spontaneous functional closure. The presence of ductal shunting was evaluated using echocardiographic color flow Doppler techniques. Thirty-six premature infants (30 to 37 weeks gestational age) were evaluated. By the fourth day of life, only 4 of 36 (11.1%) of the infants continued to have evidence of ductal patency. The remainder of the infants underwent spontaneous functional closure of the ductus arteriosus at times comparable to healthy infants without RDS. For most infants greater than or equal to 30 weeks gestation, uncomplicated RDS does not alter the usual timing of functional ductal closure.

Relation of atrial size and function to Doppler indexes of diastolic function in normal human fetuses.

Fetal atrial function is compared with diastolic ventricular function indexes. The falloff of hyperfunction in fetal atrial contraction patterns matches sequentially the lessening of A wave dominance in the Doppler filling patterns for both ventricles.

Gestational age- and growth-related alterations in fetal right and left ventricular diastolic filling patterns.

To evaluate the effects of gestational age on left and right ventricular diastolic filling in human fetuses, we retrospectively reviewed the diastolic flow velocity patterns through mitral and tricuspid valves in 307 normal fetuses aged 17 to 39 weeks' gestation. The subjects were divided into 3 age groups; 17 to 24 weeks, 25 to 31 weeks, and 32 to 39 weeks. The variables measured were peak flow velocities of early diastole (peak E wave), of atrial contraction (peak A wave), and the velocity ratio (peak E/A ratio). As a whole, the transmitral peak E wave and peak E/A ratio correlated with age using a second-order polynomial curve fit. The strength of the linear correlation between age and transmitral peak E wave and peak E/A ratio and the slope of the relation were greater in the group aged 32 to 39 weeks than in group aged 25 to 31 weeks. Similar temporal change was observed in the relation between age, transtricuspid peak E wave, and peak E/A ratio. The peak A wave for both atrioventricular valves showed little change with gestational age. Contrary to the accepted concept that fetal peak E wave and peak E/A ratio increases linearly with aging, this study shows that early diastolic filling increases mainly after 25 weeks' gestation. We speculate that the maturational changes in ventricular properties in human fetuses accelerate after midgestation.

Micromultiplane transesophageal echocardiographic probe for intraoperative study of congenital heart disease repair in neonates, infants, children, and adults.

This study reports the development of a micromultiplane 8.2-mm transesophageal echocardiographic probe. The probe is applicable to newborn infants and can deliver diagnostic images in adults.

Evaluation of systolic and diastolic ventricular performance of the right ventricle in fetuses with ductal constriction using the Doppler Tei index.

Fetal ductal constriction (DC) can depress right ventricular (RV) function. However, noninvasive assessment of fetal RV function remains difficult. We evaluated RV and left ventricular (LV) performance in fetuses with DC using the Doppler-derived Tei index. The Tei index measures the ratio of total time spent in isovolumic contraction and relaxation (isovolumic time) to the ejection time. Tricuspid inflow and RV outflow Doppler traces for the derivation of RV Tei indexes and mitral inflow and LV outflow traces for LV Tei indexes were measured in 78 fetuses of pregnant women who received indomethacin and 70 normal fetuses (gestational ages ranging from 20 to 39 weeks). DC occurred in 23 fetuses, defined as pulsatility index <1.9. In fetuses with DC, the RV isovolumic time was prolonged and RV ejection time was shortened, and the RV Tei index was high compared with those in fetuses that received indomethacin without DC and normal fetuses. Also, the RV Tei index clearly separated the fetuses with DC from normal and fetuses that received indomethacin without DC (0.74 +/- 0.14 vs 0.35 +/- 0.07 and 0.37 +/- 0.06, respectively; p <0.0001). The LV Tei index was not affected by DC. Serial study in 7 fetuses with DC showed that the RV Tei index decreased from 0.69 +/- 0.12 to 0.38 +/- 0.04 (p = 0.0002) after discontinuation of indomethacin coincident with ductal relaxation, although it remained elevated in 2 cases at the time of ductal relaxation. Thus, the Tei index is a useful and sensitive indicator for detecting abnormal RV performance in fetuses with DC.