Intermediate monocytes exhibit higher levels of TLR2, TLR4 and CD64 early after congenital heart surgery.

INTRODUCTION: Congenital heart surgery with cardiopulmonary bypass (CPB) initiates an immune response which frequently leads to organ dysfunction and a systemic inflammatory response. Complications associated with exacerbated immune responses may severely impact the postoperative recovery. The objective was to describe the characteristics of monocyte subpopulations and neutrophils at the level of pattern recognition receptors (PRR) and the cytokine response after CPB in infants. METHODS: An observational cohort study was conducted between June 2016 and June 2017 of infants < 2 years of age, electively admitted for surgical correction of acyanotic congenital heart defects using CPB. Fourteen blood samples were collected sequentially and processed immediately during and up to 48 h following cardiac surgery for each patient. Flow cytometry analysis comprised monocytic and granulocytic surface expression of CD14, CD16, CD64, TLR2, TLR4 and Dectin-1 (CLEC7A). Monocyte subpopulations were further defined as classical (CD14++/CD16-), intermediate (CD14++/CD16+) and nonclassical (CD14+/CD16++) monocytes. Plasma concentrations of 14 cytokines, including G-CSF, GM-CSF, IL-1ß, IL-1RA, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, TNF-α, IFN-γ, MIP-1ß (CCL4) and TGF-ß1, were measured using multiplex immunoassay for seven points in time. RESULTS: Samples from 21 infants (median age 7.4 months) were analyzed by flow cytometry and from 11 infants, cytokine concentrations were measured. Classical and intermediate monocytes showed first receptor upregulation with an increase in CD64 expression four hours post CPB. CD64-expression on intermediate monocytes almost tripled 48 h post CPB (p < 0.0001). TLR4 was only increased on intermediate monocytes, occurring 12 h post CPB (p = 0.0406) along with elevated TLR2 levels (p = 0.0002). TLR4 expression on intermediate monocytes correlated with vasoactive-inotropic score (rs = 0.642, p = 0.0017), duration of ventilation (rs = 0.485, p = 0.0259), highest serum creatinine (rs = 0.547, p = 0.0102), postsurgical transfusion (total volume per kg bodyweight) (rs = 0.469, p = 0.0321) and lowest mean arterial pressure (rs = -0.530, p = 0.0135). Concentrations of IL-10, MIP-1ß, IL-8, G-CSF and IL-6 increased one hour post CPB. Methylprednisolone administration in six patients had no significant influence on the studied surface receptors but led to lower IL-8 and higher IL-10 plasma concentrations. CONCLUSIONS: Congenital heart surgery with CPB induces a systemic inflammatory process including cytokine response and changes in PRR expression. Intermediate monocytes feature specific inflammatory characteristics in the 48 h after pediatric CPB and TLR4 correlates with poorer clinical course, which might provide a potential diagnostic or even therapeutic target.

Depth of anesthesia by Narcotrend® and postoperative characteristics in children undergoing cardiac surgery under extracorporeal circulation: a retrospective comparison of two anesthetic regimens.

BACKGROUND: Depth of anesthesia may be insufficient in pediatric cardiac anesthesia if a total intravenous anesthetic regimen with opioids and midazolam is used during cardiopulmonary bypass. The advantages of sevoflurane-based balanced anesthesia may be (1) a more graduated regulation of the depth of anesthesia during cardiopulmonary bypass and (2) a reduction in postoperative ventilation time for children in comparison with total intravenous anesthesia. AIM: To evaluate a possibly positive effect of sevoflurane-based balanced anesthesia in children undergoing cardiac surgery we analyzed whether this anesthetic regimen had a significant effect related to (1) depth of anesthesia, (2) the need for opioids during cardiopulmonary bypass as well as on postoperative characteristics such as (3) time of postoperative ventilation, and (4) duration of stay in the intensive care unit in comparison with total intravenous anesthesia. METHODS: In a retrospective analysis, data from heart-lung machine protocols from 2013 to 2016 were compared according to anesthetic regimen (sevoflurane-balanced anesthesia, n = 70 vs. total intravenous anesthesia, n = 65). Children (age: 8 weeks to 14 years) undergoing cardiac surgery with cardiopulmonary bypass were included. As a primary outcome measure, we compared Narcotrend® system-extracted data to detect insufficient phases of anesthetic depth during extracorporeal circulation under moderate hypothermia. Postoperatively, we measured the postoperative ventilation time and the number of days in the intensive care unit. Furthermore, we analyzed patients' specific characteristics such as opioid consumption during cardiopulmonary bypass. Regression analysis relating primary objectives was done using the following variables: anesthetic regimen, age, severity of illness/surgery, and cumulative dosage of opiates during cardiopulmonary bypass. RESULTS: No significant differences were observed in descriptive patient characteristics (age, body weight, height, and body temperature) between the two groups. Further, no significant differences were found in depth of anesthesia by analyzing phases of superficial B1-C2-electroencephalography Narcotrend® data. No marked difference between the groups was observed for the duration of postoperative intensive care unit stay. However, the postoperative ventilation time (median (95% CI, hours)) was significantly lower in the sevoflurane-based balanced anesthesia group (6.0 (2.0-15.0)) than in the total intravenous anesthesia group (13.5 (7.0-25)). A higher dosage of opioids and midazolam was required in the total intravenous anesthesia group to maintain adequate anesthesia during cardiopulmonary bypass. Regression analysis showed an additional, significant impact of the following factors: severity of illness and severity grade of cardiac surgery (according to Aristotle) on the primary endpoint. CONCLUSION: In children undergoing cardiac surgery in our department, the use of sevoflurane-balanced anesthesia during cardiopulmonary bypass showed no superiority of inhalational agents over total intravenous anesthesia with opioids and benzodiazepines preventing phases of superficial anesthesia, but a marked advantage for the postoperative ventilation time compared with total intravenous anesthesia.

Intracardiac Extension of Wilms Tumor: A Case of a 2.5-Year-Old Girl Presenting with Upper Venous Congestion Caused by Tumor Growth into the Right Cardiac Ventricle.

While Wilms tumors (WT) typically present solely with an abdominally palpable mass, rare cases exhibiting vascular tumor growth can also present with circulatory problems. Here, we report the case of a 2.5-year-old girl presenting with upper venous congestion and arterial hypertension as the primary symptoms of intraventricular tumor growth exhibiting remarkable tubular and perfused morphology. Clinical situation stabilized after initiation of neoadjuvant chemotherapy (NAC) with actinomycin D and vincristine, followed by surgical resection via laparotomy and sternotomy supported by cardiopulmonary bypass and deep hypothermia. Our results highlight the previously reported feasibility of this approach, even in primarily unstable patients.

Image quality influences the assessment of left ventricular function: an intraoperative comparison of five 2-dimensional echocardiographic methods with real-time 3-dimensional echocardiography as a reference.

OBJECTIVES: Transesophageal echocardiography has become a standard tool for evaluating left ventricular function during cardiac surgery. However, the image quality varies widely between patients and examinations. The aim of this study was to investigate the influence of the image quality on 5 commonly used 2-dimensional methods. METHODS: Transesophageal real-time 3-dimensional echocardiography (3DE) served as a reference. Left ventricular function was evaluated in 63 patients with sufficient real-time 3DE image quality. The image quality was rated using the ratio of the visualized border divided by the total endocardial border. These ratings were used to generate groups of poor (0%-40%), fair (41%-70%), and good (71%-100%) image quality. The ejection fraction (EF), end-diastolic volume, and end-systolic volume were analyzed by the Simpson method of disks (biplane and monoplane), eyeball method, Teichholz method, and speckle-tracking method. Furthermore, the fractional area change was determined. Each correlation with real-time 3DE was evaluated. RESULTS: Correlations of the EF and volumes, respectively, as determined by long-axis view methods increased with improving image quality: the Simpson biplane method was found to be the most accurate method, with good image quality for the EF (r = 0.946) and volumes (end-diastolic volume, r = 0.962; end-systolic volume, r = 0.989). Correlations of the EF and fractional area change by short-axis view methods decreased with improving image quality, with the Teichholz EF found to be most accurate with poor (r = 0.928) in contrast to good (r = 0.699) image quality. CONCLUSIONS: With good image quality, the Simpson biplane method is the most accurate 2-dimensional method for assessing the left ventricular EF. Short-axis view methods, especially the Teichholz method yield better correlations with poor image quality. The eyeball method was unaffected by image quality.

Massive calcified tricuspid valve endocarditis in a patient with dual lumen tunneled venous catheter.

Infection is the most common cause of death in hemodialysis patients after cardiovascular complications. The long-term use of venous catheters for dialysis elevates the risk. Valvular calcification is of special concern in developing infective endocarditis and is often found in chronic dialysis patients. The right-sided endocarditis is rarely reported in the literature and may be overseen until the development of further complications. In our case tricuspid valve endocarditis, with severe insufficiency and stenosis due to a calcified laminar plate was found in a 57-year-old female patient undergoing dialysis due to end-stage renal disease. The calcification aroused from the tip of the dual lumen tunneled venous catheter used for routine dialysis. We replaced the tricuspid valve with mechanical valve prosthesis and reconstructed the right atrium.

Entanglement of a circular mapping catheter in the mitral valve with persistent iatrogenic atrial septal defect after attempted pulmonary vein isolation: a word of caution.

A 34-year-old man presented with pulmonary vein isolation due to paroxysmal atrial fibrillation. During the standard procedure, the circular mapping catheter became dislocated and was caught in the mitral valve apparatus. Following multiple failed attempts to remove the catheter in the catheterization laboratory, the patient needed an emergency operation using the heart-lung machine.

Reproducibility in echocardiographic two- and three-dimensional mitral valve assessment.

BACKGROUND: Three-dimensional transesophageal echocardiography (3DTEE) has been demonstrated to provide more accurate information than two-dimensional transesophageal echocardiography (2DTEE) in the localization of mitral valve prolapse (MVP). However, most studies have been single-rater studies. Few results were tested for inter-observer variability with a single second rater. This multicenter study aimed to determine reliability of 2D and 3DTEE mitral valve evaluations by calculating inter-observer agreement between various echocardiographers. METHODS: Fifteen observers from 4 institutions in Germany and Switzerland interpreted 2D and 3DTEE images from 6 patients selected to represent a large spectrum of MVP diversity. Surgical findings served as reference. Individual assessments of MVP and ruptured chordae tendineae (ChR) pathology were compared by calculating Randolph's free-marginal multirater kappa coefficient. RESULTS: Accuracy of MVP evaluation with 3DTEE was 83.9%, CI [81.0%; 86.8%] and 78.7% CI [76.6% 80.8%] with 2DTEE. Flail leaflets with chordal ruptures were described correctly in 91.1%, CI [85.8, 96.4] with 3D compared to 71.1%, CI [65.0, 77.2] with 2DTEE. The multirater kappa coefficient of inter-observer agreement among all 15 observers was κ = 0.65/0.58 for 3D/2D evaluation of MVP and κ = 0.70/0.54 for detection of ChR. CONCLUSION: Three-dimensional assessment of MVP was superior to 2DTEE, although the accuracy of both 3DTEE and 2DTEE was found to be lower than previously published. 3D MVP assessment is less operator dependent than 2DTEE evaluation. Although validity has been demonstrated before, we provide evidence that 3DTEE is reproducible among 15 observers and is a reliable method for MVP evaluation.

Experts and beginners benefit from three-dimensional echocardiography: a multicenter study on the assessment of mitral valve prolapse.

BACKGROUND: Three-dimensional (3D) transesophageal echocardiography (TEE) has been claimed to provide more information than two-dimensional (2D) TEE in the localization of mitral valve prolapse (MVP). However, most studies have been performed by experts in echocardiography, without accounting for differences in training or expertise. This multicenter study was designed to assess the differences between experts and inexperienced echocardiographers in localizing MVP and ruptured chordae tendineae using 2D and real-time 3D TEE. METHODS: Thirty-six observers from 10 institutions in Germany and Switzerland interpreted 2D and 3D transesophageal echocardiographic images from six patients selected to represent a large spectrum of MVP diversity. Surgical findings served as a reference. Individual performance in the prediction of pathology was scored. Differences between 15 experts and 21 beginners in TEE were assessed, and the benefits conferred by 3D TEE were compared. RESULTS: Both study groups scored significantly higher when interpreting 3D transesophageal echocardiographic images (P ≤ .001). The experts were superior in 2D MVP localization (14.8%; P ≤ .001), a difference that diminished with 3D TEE (1.4%; P = .41). The benefit of access to 3D information for MVP localization was greater for inexperienced echocardiographers compared with experts (P < .001). CONCLUSIONS: The reported diagnostic advantage of 3D TEE over 2D TEE in MVP assessment for expert echocardiographers can be transferred to inexperienced echocardiographers. Inexperienced echocardiographers benefit from the technology to a greater extent than their expert colleagues.

Assessment of left ventricular size and function during cardiac surgery. An intraoperative evaluation of six two-dimensional echocardiographic methods with real time three-dimensional echocardiography as a reference.

Transesophageal echocardiography is recommended to monitor left ventricular (LV) size and function in various operations. Generally, two-dimensional (2D) methods are applied intraoperatively. The aim of this study was to compare the accuracy and feasibility of 6 commonly used 2D methods to assess LV function during surgery. LV function in 120 consecutive patients was evaluated. Real time three-dimensional transesophageal echocardiograpy (3DTEE) served as reference. End-diastolic and end-systolic volumes and ejection fraction (EF) were analyzed with Simpson's method of discs (monoplane [MP] and biplane [BP]), eyeball method, Teichholz' method, and speckle tracking (ST) methods. Furthermore, fractional area change (FAC) and peak systolic pressure rise (dP/dt) were determined. Each 2D method was evaluated regarding correlation and agreement with 3DE, intra- and interobserver variability and the time required for evaluation. Simpson BP showed the strongest correlation and best agreement with 3DE for EF (limits of agreement 3.7 ± 11.6%) and volumes. Simpson MP showed similar agreement with 3DE compared to ST (2.8 ± 14.5% vs. 2.0 ± 15.3% and 3.8 ± 14.4% vs. 1.9 ± 15.6%, respectively). Both the eyeball method and Teichholz' method showed wide limits of agreement (-1.5 ± 18.2% and 5.2 ± 22.1%, respectively). DP/dt did not correlate with 3DE. FAC and ST FAC showed similar agreement. Application of 3DE (429 ± 108 seconds) took the longest time, and the eyeball method took the shortest time (8 ± 5 seconds) for analysis. Simpson BP is the most accurate intraoperative 2D method to evaluate LV function, followed by long-axis MP evaluations. Short-axis views were less accurate but may be suited for monitoring. We do not recommend using dP/dt.

Real-time three-dimensional transesophageal echocardiography: improvements in intraoperative mitral valve imaging.

BACKGROUND: Successful surgical repair of a regurgitant mitral valve (MV) is dependent on a comprehensive assessment of its complex anatomy. Although there is limited evidence of the feasibility and accuracy of intraoperative real-time 3-dimensional transesophageal echocardiography (RT3DTEE) in MV surgery, its use is increasing worldwide. We designed this prospective observational study of patients with mitral regurgitation to test initial findings on the accuracy of RT3DTEE images in the diagnosis of MV prolapse and chordal rupture relative to 2D imaging and to assess the potential of RT3DTEE for visualizing leaflet clefts. METHODS: TEE-certified anesthesiologists examined 62 consecutive patients undergoing MV surgery by acquiring a full standard set of 2D TEE sections and 3D zoom recordings. Offline, 2D and 3D images were presented independently and in randomized order to 2 expert interpreters. Accuracy was determined using the surgical findings as the "gold standard." RESULTS: Surgical inspection identified 52 cases of MV prolapse (MVP). RT3DTEE correlated stronger with the surgical findings than 2D TEE for detection and localization of MVP (difference in proportions=33.9%, P<0.001) and chordal rupture (difference in proportions=25.8%, P<0.001). The superiority of RT3DTEE was significant for scallops A2, P1, P2 in MVP and A2, P2 in chordal rupture (all P<0.05). In 22 patients, leaflet clefts were also surgically repaired, and RT3DTEE was feasible in accessing them (κ=0.65, confidence interval [0.44, 0.81]). CONCLUSION: Although 2D TEE is currently the standard tool for intraoperative imaging in MV surgery, RT3DTEE improves the visualization of MV pathology and increases the accuracy of interpretation by facilitating spatial orientation. Further investigations, particularly those aimed at establishing its cost effectiveness, are indicated.

Perioperative management of a child with glutaric aciduria type I undergoing cardiac surgery.

Patients with glutaric aciduria type I are at risk for acute striatal injury precipitated by catabolic stress. Here, we report the successful interdisciplinary anesthetic and perioperative management of a child with glutaric aciduria type I undergoing cardiac surgery with extracorporeal circulation. Given the central focus on prevention of acute striatal injury, our anesthetic strategy emphasized avoiding a high protein load, high-dose inotropics, especially epinephrine (associated with impaired glucose utilization), deliberate hyperventilation, and other interventions associated with systemic inflammatory response.

The bound coherent neutron scattering lengths of the oxygen isotopes.

The technique of neutron interferometry was used to measure the bound coherent neutron scattering length b(coh) of the oxygen isotopes (17)O and (18)O. From the measured difference in optical path between two water samples, either H(2)(17)O or H(2)(18)O versus H(2)(nat)O, where nat denotes the natural isotopic composition, we obtain b(coh,(17)O) = 5.867(4) fm and b(coh,(18)O) = 6.009(5) fm, based on the accurately known value of b(coh,(nat)O) = 5.805(4) fm which is equal to b(coh,(16)O) within the experimental uncertainty. Our results for b(coh,(17)O) and b(coh,(18)O) differ appreciably from the standard tabulated values of 5.6(5) fm and 5.84(7) fm, respectively. In particular, our measured scattering-length contrast of 0.204(3) fm between (18)O and (nat)O is nearly a factor of 6 greater than the tabulated value, which renders feasible neutron diffraction experiments using (18)O isotope substitution and thereby offers new possibilities for measuring the partial structure factors of oxygen-containing compounds, such as water.

Comparison of intraoperative three-dimensional Doppler color flow mapping to assess mitral regurgitation.

BACKGROUND: Three-dimensional (3D) transesophageal echocardiography (TEE) enables the determination of the vena contracta area (VCA), which is an approved parameter to quantify mitral regurgitation (MR). The aim of this study was to determine the VCA in the operative setting and to compare it to alternative 3D and standard 2D methods, with respect to different etiologies of MR. METHODS: MR in 56 consecutive patients undergoing cardiac surgery was evaluated using 2D and 3D TEE. VCA, vena contracta (VC), and effective regurgitation orifice area (EROA) by 3D and 2D flow convergence methods were determined. The correlations among the methods and the determined areas were evaluated. RESULTS: EROA determination using 3D flow convergence areas correlated strongly with VCA (r = 0.653), however the resulting areas were considerably smaller. VC measurements in the 3D data set correlated slightly less (r = 0.629). EROA, which was determined using 2D flow convergence areas, showed the strongest correlation among the 2D methods (r = 0.406). 2D VC measurements showed weak to no correlation with VCA. Although a correlation was detected when using the biplane method or the midesophageal long-axis view to measure VC, statistical significance was only reached in functional MR and MR due to simple prolapse. CONCLUSIONS: Intraoperative 3D methods to determine MR were feasible and showed improved correlation with VCA compared to 2D measurements. The agreement of 2D methods with VCA declined from functional MR to MR due to prolapse. We recommend the utilization of 3D color Doppler for intraoperative evaluation of MR, especially in patients with complex mitral valve prolapses.

Right ventricular function during orthotopic liver transplantation: three-dimensional transesophageal echocardiography and thermodilution.

BACKGROUND: Right ventricular (RV) function is an important aspect of anesthesia management during orthotopic liver transplantation (OLT). Because of its geometrical complexity, assessment of RV dimensions with transesophageal echocardiography (TEE) is a difficult task. The aim of this prospective single-site study was to investigate the feasibility of intraoperative assessment of RV parameters based on reconstructive three-dimensional (3D) TEE and to compare the measurements to thermodilution-derived values acquired with a modified pulmonary artery catheter. MATERIAL/METHODS: Measurements were performed at four different time points during 30 OLT with 3D-TEE. At the same time comparative values of RV parameters were acquired with a fast-response thermistor pulmonary artery catheter. RESULTS: 3D reconstruction was feasible in all patients. RV dimensions measured with 3D-TEE averaged 119.4 ml (± 38.5 ml) for enddiastolic and 68.9 ml (± 27.7 ml) for endsystolic volumes. The RV ejection fraction was 42.2% (± 9.3%). The volumes obtained by thermodilution were 263.7 ml (± 64.5 ml) enddiastolic and 159.3 ml (± 47.5 ml) endsystolic, both significantly greater than by 3D-TEE, and the ejection fraction was found to be 39.5% (± 8.4%). No correlation was found between the volumes or the function determined by either method. CONCLUSIONS: Reconstructive 3D-TEE is a viable technique during OLT and leads to plausible RV parameters. However, no correlation was found with simultaneous measurements or parameters performed with thermodilution. However, based on our data cardiac output measurements by thermodilution appear reasonable. Due to both lack of agreement with 3D-TEE and extraordinary high RV volumes the question about the most valuable monitoring technique of RV dimensions and function during OLT can not finally be answered.

Tricuspid valve endocarditis with septic pulmonary emboli in a drug addict.

Presented is a case of a young, polytoxicomaniac male with a history of intravenous drug abuse. He arrived at our department in a septic state with fever and showed signs of right-sided decompensated cardiac insufficiency. The patient tested positive for hepatitis C, and blood cultures were positive for Staphylococcus aureus. A thoracic computed tomographic scan revealed bilateral, multiple septic pulmonary emboli. Transesophageal echocardiography disclosed large mobile vegetations on the tricuspid valve associated with severe regurgitation. The infected tricuspid valve was replaced with a mechanical heart valve, and the patient recovered uneventfully from surgery.

Left ventricular outflow tract: intraoperative measurement and changes caused by mitral valve surgery.

BACKGROUND: The impact of mitral valve surgery on left ventricular outflow tract (LVOT) dimensions is unclear. Real-time three-dimensional transesophageal echocardiography permits excellent visualization of the LVOT and might improve standard two-dimensional measurements. In this study, LVOT area and shape were assessed before and after mitral valve surgery. METHODS: Thirty-five patients undergoing mitral valve repair or replacement were retrospectively included in the study and compared with 15 patients undergoing coronary artery bypass grafting. LVOT area was measured by planimetry. Maximum possible methodologic errors by assuming a circular LVOT and an eccentricity index were calculated. LVOT diameter in a midesophageal long-axis view served to calculate the error for the circular LVOT determined in common intraoperative practice. RESULTS: Common intraoperative two-dimensional measurements underestimated actual LVOT area by 21%. Mitral valve surgery led to a significant reduction of LVOT area by 7%. Although LVOT height remained unchanged, width decreased from 2.72 to 2.53 cm (-7%), resulting in a more circular shape of the LVOT. This effect was more pronounced the smaller the size of the implanted annuloplasty ring or prosthesis. Coronary artery bypass grafting did not affect the LVOT. Left ventricular ejection fraction was significantly correlated with LVOT eccentricity. Impaired ventricular function and higher end-systolic volumes were associated with a rounder shape. CONCLUSIONS: The eccentric LVOT shape leads to a distinct underestimation of its area with two-dimensional measurements. LVOT eccentricity is less distinct in patients with low ejection fractions and higher end-systolic volumes. LVOT width is decreased through annuloplasty rings and prostheses, and the smaller the implanted device, the more profound the reduction.

Oxygen as a site specific probe of the structure of water and oxide materials.

The method of oxygen isotope substitution in neutron diffraction is introduced as a site specific structural probe. It is employed to measure the structure of light versus heavy water, thus circumventing the assumption of isomorphism between H and D as used in more traditional neutron diffraction methods. The intramolecular and intermolecular O-H and O-D pair correlations are in excellent agreement with path integral molecular dynamics simulations, both techniques showing a difference of ≃0.5% between the O-H and O-D intramolecular bond distances. The results support the validity of a competing quantum effects model for water in which its structural and dynamical properties are governed by an offset between intramolecular and intermolecular quantum contributions.

Kochen-Specker theorem studied with neutron interferometer.

The Kochen-Specker theorem shows the incompatibility of noncontextual hidden variable theories with quantum mechanics. Quantum contextuality is a more general concept than quantum non-locality which is quite well tested in experiments using Bell inequalities. Within neutron interferometry we performed an experimental test of the Kochen-Specker theorem with an inequality, which identifies quantum contextuality, by using spin-path entanglement of single neutrons. Here entanglement is achieved not between different particles, but between degrees of freedom of a single neutron, i.e., between spin and path degree of freedom. Appropriate combinations of the spin analysis and the position of the phase shifter allow an experimental verification of the violation of an inequality derived from the Kochen-Specker theorem. The observed violation 2.291±0.008≰1 clearly shows that quantum mechanical predictions cannot be reproduced by noncontextual hidden variable theories.

Comparison of inhaled nitric oxide with aerosolized iloprost for treatment of pulmonary hypertension in children after cardiopulmonary bypass surgery.

OBJECTIVES: Pilot study to compare the effect of inhaled nitric oxide (iNO) and aerosolized iloprost in preventing perioperative pulmonary hypertensive crises (PHTCs). BACKGROUND: Guidelines recommend the use of iNO to treat PHTCs, but treatment with iNO is not an ideal vasodilator. Aerosolized iloprost may be a possible alternative to iNO in this setting. METHODS: Investigator-initiated, open-label, randomized clinical trial in 15 infants (age range 77-257 days) with left-to-right shunt (11 out of 15 with additional trisomy 21), and pulmonary hypertension (i.e. mean pulmonary artery pressure [PAP] >25 mmHg) after weaning from cardiopulmonary bypass. Patients were randomized to treatment with iNO at 10 ppm or aerosolized iloprost at 0.5 µg/kg (every 2 h). The observation period was 72 h after weaning from cardiopulmonary bypass. The primary endpoint was the occurrence of PHTCs; the secondary endpoints were mean PAP, duration of mechanical ventilation, safety of administration, and in-hospital mortality. RESULTS: Seven patients received iNO and eight patients received iloprost. During the observation period, 13 of the 15 patients had at least one major or minor PHTC. There was no difference between the groups with regard to the frequency of PHTCs, mean PAP and duration of mechanical ventilation (p > 0.05). CONCLUSIONS: In this pilot study, aerosolized iloprost had a favorable safety profile. Larger trials are needed to compare its efficacy to iNO for the treatment of perioperative pulmonary hypertension. However, neither treatment alone abolished the occurrence of PHTCs.