Myocardial function reclassification: Echocardiographic strain patterns in patients with chronic Chagas cardiomyopathy and intraventricular dyssynchrony.

BACKGROUND: We aimed to identify, among Chronic Chagas Cardiomyopathy (CCC) patients with left ventricular dysfunction (LVD) and non-left bundle branch block (non-LBBB), subgroups with different functional and mechanical patterns of global longitudinal strain (GLS) and intraventricular dyssynchrony (IVD) at rest and after exercise stress test, and reclassify them using a new echocardiographic approach. METHODOLOGY: In this single-center cross-sectional study, 40 patients with CCC, left ventricular ejection fraction (LVEF) ≤ 35% and non-LBBB underwent rest echocardiography and then treadmill exercise stress echocardiography with GLS and IVD analysis. The sample was divided into four groups, based on GLS and IVD significant variation between rest and exercise: GLS + IVD+ (9 patients); GLS + IVD- (9 patients); GLS-IVD+ (10 patients); GLS-IVD- (10 patients). RESULTS: At rest, median LVEF was 28% (21.3%-33%) and GLS (-7% (-5%/-9.3%), were not different among groups. The average response of GLS was an increase of 0.74% over rest values, and the average response of IVD was a decrease of 6.9 ms. Group GLS-IVD+ presented more dyssynchrony at rest (p = 0.01). Left atrial (LA) volume (higher in GLS-IVD-) (p = 0.022) and TAPSE (higher in GLS + IVD+) (p = 0.015) were also different among groups at baseline. Of the 40 patients evaluated, 27 (67.5%) had very severe LVD (GLS < -8%). In addition, among these patients, 11 patients had contractile reserve after undergoing stress echocardiography. CONCLUSIONS: In patients with CCC, severe LVD and non-LBBB, the evaluation of GLS and IVD between rest and exercise was able to reclassify myocardial function and to identify subgroups with contractile reserve and significant dyssynchronopathy.

Sonothrombolysis Improves Myocardial Dynamics and Microvascular Obstruction Preventing Left Ventricular Remodeling in Patients With ST Elevation Myocardial Infarction.

BACKGROUND: It has recently been demonstrated that high-energy diagnostic transthoracic ultrasound and intravenous microbubbles dissolve thrombi (sonothrombolysis) and increase angiographic recanalization rates in patients with ST-segment-elevation myocardial infarction. We aimed to study the effect of sonothrombolysis on the myocardial dynamics and infarct size obtained by real-time myocardial perfusion echocardiography and their value in preventing left ventricular remodeling. METHODS: One hundred patients with ST-segment-elevation myocardial infarction were randomized to therapy (50 patients treated with sonothrombolysis and percutaneous coronary intervention) or control (50 patients treated with percutaneous coronary intervention only). Left ventricular volumes, ejection fraction, risk area (before treatment), myocardial perfusion defect over time (infarct size), and global longitudinal strain were determined by quantitative real-time myocardial perfusion echocardiography and speckle tracking echocardiography imaging. RESULTS: Risk area was similar in the control and therapy groups (19.2±10.1% versus 20.7±8.9%; P=0.56) before treatment. The therapy group presented a behavior significantly different than control group over time (P<0.001). The perfusion defect was smaller in the therapy at 48 to 72 hours even in the subgroup of patients with no recanalization at first angiography (12.9±6.5% therapy versus 18.8±9.9% control; P=0.015). The left ventricular global longitudinal strain was higher in the therapy than control immediately after percutaneous coronary intervention (14.1±4.1% versus 12.0±3.3%; P=0.012), and this difference was maintained until 6 months (17.1±3.5% versus 13.6±3.6%; P<0.001). The only predictor of left ventricular remodeling was treatment with sonothrombolysis: the control group was more likely to exhibit left ventricular remodeling with an odds ratio of 2.79 ([95% CI, 0.13-6.86]; P=0.026). CONCLUSIONS: Sonothrombolysis reduces microvascular obstruction and improves myocardial dynamics in patients with ST-segment-elevation myocardial infarction and is an independent predictor of left ventricular remodeling over time.

Simulation-based assessment in anesthesia: an international multicentre validation study.

PURPOSE: Simulated clinical events provide a means to evaluate a practitioner's performance in a standardized manner for all candidates that are tested. We sought to provide evidence for the validity of simulation-based assessment tools in simulated pediatric anesthesia emergencies. METHODS: Nine centres in two countries recruited subjects to participate in simulated operating room events. Participants ranged in anesthesia experience from junior residents to staff anesthesiologists. Performances were video recorded for review and scored by specially trained, blinded, expert raters. The rating tools consisted of scenario-specific checklists and a global rating scale that allowed the rater to make a judgement about the subject's performance, and by extension, preparedness for independent practice. The reliability of the tools was classified as "substantial" (intraclass correlation coefficients ranged from 0.84 to 0.96 for the checklists and from 0.85 to 0.94 for the global rating scale). RESULTS: Three-hundred and ninety-one simulation encounters were analysed. Senior trainees and staff significantly out-performed junior trainees (P = 0.04 and P < 0.001 respectively). The effect size of grade (junior vs senior trainee vs staff) on performance was classified as "medium" (partial η2 = 0.06). Performance deficits were observed across all grades of anesthesiologist, particularly in two of the scenarios. CONCLUSIONS: This study supports the validity of our simulation-based anesthesiologist assessment tools in several domains of validity. We also describe some residual challenges regarding the validity of our tools, some notes of caution in terms of the intended consequences of their use, and identify opportunities for further research.

Sonothrombolysis in ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention.

BACKGROUND: Preclinical studies have demonstrated that high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion (sonothrombolysis) can restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: This study tested the clinical effectiveness of sonothrombolysis in patients with STEMI. METHODS: Patients with their first STEMI were prospectively randomized to either diagnostic ultrasound-guided high MI impulses during an intravenous Definity (Lantheus Medical Imaging, North Billerica, Massachusetts) infusion before, and following, emergent percutaneous coronary intervention (PCI), or to a control group that received PCI only (n = 50 in each group). A reference first STEMI group (n = 203) who arrived outside the randomization window was also analyzed. Angiographic recanalization before PCI, ST-segment resolution, infarct size by magnetic resonance imaging, and systolic function (LVEF) at 6 months were compared. RESULTS: ST-segment resolution occurred in 16 (32%) high MI PCI versus 2 (4%) PCI-only patients before PCI, and angiographic recanalization was 48% in high MI/PCI versus 20% in PCI only and 21% in the reference group (p < 0.001). Infarct size was reduced (29 ± 22 g high MI/PCI vs. 40 ± 20 g PCI only; p = 0.026). LVEF was not different between groups before treatment (44 ± 11% vs. 43 ± 10%), but increased immediately after PCI in the high MI/PCI group (p = 0.03), and remained higher at 6 months (p = 0.015). Need for implantable defibrillator (LVEF ≤30%) was reduced in the high MI/PCI group (5% vs. 18% PCI only; p = 0.045). CONCLUSIONS: Sonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in systolic function after STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330).

Unusual presentation of postdural puncture headache requiring repeat epidural blood patch in a 4-year-old child.

We present the case of a 4-year-old child who required two epidural blood patches (EBPs) to treat a delayed onset postdural puncture headache (PDPH) caused by lumbar cerebrospinal fluid drain. The first EBP was unsuccessful with 0.41 ml·kg(-1) of blood injected. A second EBP with 0.76 ml·kg(-1) of blood was performed 2 days later with the complete resolution of symptoms. The volume of blood necessary for effective treatment for symptomatic cerebrospinal fluid leaks in children remains controversial, and a repeat EBP may be required for resolution of symptoms.

Comparative bioavailability of two oral formulations of clozapine in steady state administered in schizophrenic volunteers under individualized dose regime.

In the present study, a novel, fast, sensitive and robust method to quantify clozapine in human plasma using quetiapine as the internal standard (IS) is described. The analyte and the IS were extracted from plasma using a single protein precipitation extraction technique with methanol and analyzed by high performance liquid chromatography coupled to the electrospray ionization tandem mass spectrometric (HPLC-ESI-MS/MS). The method was linear over the range 20 to 1500 ng.mL-1. The intra-assay precisions ranged from 3.8 to 5.9%, while inter-assay precisions ranged from 4.2 to 6.0%. The intra-assay accuracies ranged from 99.3 to 107.5%, while the inter-assay accuracies ranged from 98.9 to 101.7%. This method agrees with the requirements proposed by the US Food and Drug Administration of high sensitivity, specificity and high sample throughput and was used to evaluate the pharmacokinetic profiles and bioequivalence of the two clozapine formulations in twenty six schizophrenic patients affected by refractory schizophrenia under steady-state conditions. During the hospitalization period the patients received the 100 mg clozapine formulation tablets corresponding to the same dose they were using 14 days before hospitalization. The clozapine pharmacokinetic did not differ significantly after administration of both test and the reference formulations. The Tmax and T1/2 for the test formulation were 2.26 and 10.92 h, respectively. In addition, the Tmax and T1/2 for the reference formulation were 2.44 and 11.08 h, respectively. The 90% confidence interval of the mean ratio of lnAUC0-t was within 0.80-1.25 range which indicates that the test formulation was bioequivalent to the reference formulation when orally administered to schizophrenic patients regarding both the rate and extent of absorption.

High-fidelity simulation demonstrates the influence of anesthesiologists' age and years from residency on emergency cricothyroidotomy skills.

BACKGROUND: Age-related deterioration in both cognitive function and the capacity to control fine motor movements has been demonstrated in numerous studies. However, this decline has not been described with respect to complex clinical anesthesia skills. Cricothyroidotomy is an example of a complex, lifesaving procedure that requires competency in the domains of both cognitive processing and fine motor control. Proficiency in this skill is vital to minimize time to reestablish oxygenation during a "cannot intubate, cannot ventilate" scenario. In this prospective, controlled, single-blinded study, we tested the hypothesis that age affects the learning and performance of emergency percutaneous cricothyroidotomy in a high-fidelity simulated cannot intubate/cannot ventilate scenario. METHODS: Thirty-six staff anesthesiologists (19 aged younger than 45 years and 17 older than 45 years) managed a high-fidelity cannot intubate/cannot ventilate scenario in a high-fidelity simulator before and after a 1-hour standardized training session. The group division cutoff age of 45 years was based on the median age of our sample subject population before enrollment. The scenarios required the insertion of an emergency percutaneous cricothyroidotomy. We compared cricothyroidotomy skills in the older group with those in the younger group using procedural time, 5-point task-specific checklist score, and global rating scale score. Correlation based on age, years from residency, weekly clinical hours worked, previous continuing medical education in airway management, and previous simulation experience was also performed. RESULTS: In both prestandardization and poststandardization, age and years from residency correlated with procedural time, checklist scores, and global rating scores. Baseline, prestandardization variables were all better for the younger group, with a mean age of 37 years, compared with the older group, with a mean age of 58 years. Procedural time was 100 (72-128) seconds versus 152 (120-261) seconds. Checklist scores were 7.0 (6.1-8.0) versus 6.0 (4.8-8.0). Global rating scale scores were 22.0 (17.8-29.8) versus 17.5 (10.4-20.6). After the 1-hour standardized training session, the younger group continued to perform better than the older group with procedural time of 75 (66-91) seconds versus 87 (78-123) seconds, checklist scores of 10.0 (9.1-10.0) versus 9.0 (8.0-10.0), and global rating scale scores of 35.0 (32.1-35.0) versus 32.0 (29.0-33.8). Regression analysis was performed on the poststandardization data. Both age and years from residency independently affected procedural time, checklist scores, and global rating scale scores (all P < 0.05). CONCLUSIONS: Baseline proficiency with simulated emergency cricothyroidotomy is associated with age and years from residency. Despite standardized training, operator age and years from residency were associated with decreased proficiency. Further research should explore the potential of using age and years from residency as factors for implementing periodic continuing medical education.

Incomplete adherence to the ASA difficult airway algorithm is unchanged after a high-fidelity simulation session.

PURPOSE: Although guidelines for difficult airway management have been published, the extent to which consultant anesthesiologists follow these guidelines has not been determined. The purpose of this study is to observe how consultant anesthesiologists manage a "cannot intubate, cannot ventilate" (CICV) scenario in a high-fidelity simulator and to evaluate whether a simulation teaching session improves their adherence to the American Society of Anesthesiologists (ASA) difficult airway algorithm. METHODS: With Ethics Board approval and informed consent, all staff anesthesiologists in a single tertiary care institution were invited to enrol in this study where they managed a simulated unanticipated CICV scenario in a high-fidelity simulator. The scenario involved a patient with a difficult airway whose trachea could not be intubated and where it was impossible to ventilate the patient's lungs. Airway management options, including laryngeal mask airway, a fibreoptic bronchoscope, and a Glidescope were available for use but scripted to fail. A percutaneous cricothyroidotomy was required to re-establish adequate ventilation. Following the scenario, there was a personalized one-hour video-assisted expert debriefing focusing on the ASA difficult airway guidelines and "hands-on" cricothyroidotomy teaching. The second scenario followed immediately with an identical CICV scenario. The content to either scenario was not revealed beforehand. Outcome measures included: 1) major deviations from the ASA difficult airway guidelines; 2) time to start cricothyroidotomy; and 3) time to achieve ventilation. RESULTS: Thirty-eight anesthesiologists agreed to participate. The number of major deviations from the ASA algorithm was similar in the first and second sessions. These deviations included: multiple laryngoscopies (0 vs 2 pre-post; P = 0.49), use of fibreoptic bronchoscope (8 vs 7 pre-post; P = 1.0), bypass of laryngeal mask airway attempt (7 vs 13 pre-post; P = 0.19), and failure to call for anesthetic help (12 vs 8 pre-post; P = 0.43). However, more participants failed to call for surgical help in the second session (7 vs 16; P = 0.04). The times to start cricothyroidotomy and the times to achieve ventilation were significantly shorter in the second session (205.5 +/- 61.3 sec vs 179.7 +/- 65.1 sec; P = 0.01 and 356.9 +/- 117.2 sec vs 269.4 +/- 77.43 sec; P = 0.0002, respectively). CONCLUSION: No substantial changes in airway management in a CICV scenario were observed after an intense one-hour personalized video-assisted airway-focused simulation debriefing session with an expert. It appears that multiple factors other than airway algorithms come into play in emergency airway decision-making processes, including one's personal clinical experience with the many available airway devices.

Sonoanatomy of the lumbar spine of pregnant women at term.

BACKGROUND AND OBJECTIVES: Spinal ultrasound offers valuable information to facilitate the placement of lumbar neuraxial anesthesia. Lumbar spine sonograms are unique, and aspects may appear atypical at times, particularly the ligamentum flavum (LF). The objective of this study was to describe the sonoanatomy of the lumbar spine and to determine the frequency of atypical images of the LF in pregnant women at term. METHODS: Using a 2-5 MHz curvilinear transducer, we imaged all the lumbar interspaces in the left and right paramedian longitudinal and transverse planes. The images were categorized as typical, atypical or inconclusive. The primary outcome was the presence of an atypical image of the LF in the transverse plane. The distance from the skin to the epidural space, and the dural sac width, were also measured. RESULTS: One hundred subjects were studied. All the images in the longitudinal planes were conclusive and typical, whereas the number of inconclusive images in the transverse plane increased from L1-L2 to L5-S1 (1, 0, 4, 9, and 34, respectively). The incidence of atypical LF images in the transverse plane was 2.0% at L1-L2, 1.0% at L2-L3, 3.1% at L3-L4, 19.8% at L4-L5, and 28.8% at L5-S1. CONCLUSIONS: The paramedian longitudinal sonograms of the lumbar spine are of superior quality to those obtained in the transverse plane. When using the transverse approach, a high incidence of inconclusive sonograms should be expected in the lower segments. The incidence of atypical LF images, especially in the upper lumbar segments, warrants further investigation because it can have implications for the epidural technique.

Simultaneous determination of losartan and hydrochlorothiazide in human plasma by LC/MS/MS with electrospray ionization and its application to pharmacokinetics.

A method based on a simple liquid-liquid extraction (LLE) followed by high-performance liquid chromatography with negative ion electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) detection was developed for the simultaneous determination of losartan (LOS) and hydrochlorothiazide (HCTZ) in human plasma, using valsartan (VAL) and chlorthalidone (CHTD) as an internal standard, respectively. The acquisition was performed in multiple reactions monitoring (MRM) and the limit of quantification was 4 ng/mL for both LOS and HCTZ. The method was linear in the studied range (4-800 ng/mL for LOS and 4-500 ng/mL for HCTZ). The intra-assay precisions ranged from 2.6-11.9% for LOS and 1.4-8.2% for HCTZ, while the inter-assay precisions ranged from 1.0-8.0% for LOS and 2.5-7.7% for HCTZ. The intra-assay accuracies ranged from 91.3 to 107.6% for LOS and 91.5 to 105.8% for HCTZ, while the inter-assay accuracies ranged from 99.9 to 106.4% for LOS and 97.4 to 101.4% for HCTZ. The analytical method was applied to a bioequivalence study, in which 28 healthy adult volunteers (14 men) received single oral doses (100 mg LOS + 25 mg HCTZ) of reference and test formulations, in an open, two-period, balanced randomized, crossover protocol. Based on the 90% confidence interval of the individual ratios for Cmax and AUC0-inf, it was concluded that the test formulation is bioequivalent to the reference Hyzaar formulation with respect to the rate and extent of absorption of both LOS and HCTZ.