Reduction In VT Research Articles

Evaluation of a new hyperbaric oxygen ventilator during pressure-controlled ventilation.

The stability of a new hyperbaric ventilator (Shangrila590, Beijing Aeonmed Company, Beijing, China) at different clinically relevant pressures in a hyperbaric chamber during pressure-controlled ventilation (PCV) was investigated. The ventilator was connected to a test lung in the multiplace hyperbaric chamber. The inspiratory pressure (PI) of the ventilator was set to 1.0, 1.5, 2.0, 2.5 and 3.0 kPa (approximately 10, 15, 20, 25 and 30 cmH₂O). The compliance and resistance of the test lung were set to 200 mL·kPa⁻¹ and 2 kPa·L⁻¹·s⁻¹, respectively. Experiments were conducted at 101, 203 and 284 kPa ambient pressure (1.0, 2.0 and 2.8 atmospheres absolute respectively). At each of the 5 PI values, the tidal volume (VT), peak inspiratory pressure (Ppeak) and peak inspiratory flow (Fpeak) displayed by the ventilator and the test lung were recorded for 20 cycles. Test lung data were considered the actual ventilation values. The ventilation data were compared among the three groups to evaluate the stability of the ventilator. At every PI, the Ppeak detected by the ventilator decreased slightly with increasing ambient pressure. The Fpeak values measured by the test lung decreased substantially as the ambient pressure increased. Nevertheless, the reduction in VT at 284 kPa and PI 30 cmH₂O (compared to performance at 101 kPa) was comparatively small (approximately 60 ml). In PCV mode this ventilator provided relatively stable VT across clinically relevant PI values to ambient pressures as high as 284 kPa. However, because Fpeak decreases at higher ambient pressure, some user adjustment might be necessary for precise VT maintenance during clinical use at higher PIs and ambient pressures.

Impact of tracheostomy tube modalities on ventilatory mechanics: a bench study

PurposeTracheostomized patients often present with muscle weakness, altered consciousness, or swallowing difficulties. Hence, the literature is scarce regarding the challenging management of tracheostomy weaning. There is a need to strengthen the understanding of respiratory mechanisms with the different tracheostomy tube modalities that compose this weaning pathway. We aimed to evaluate the impact of these modalities on the work of breathing (WOB), total positive end-expiratory pressure (PEEPtot), and tidal volume (VT).MethodsWith a three-dimensional (3D) printed head mimicking human upper airways, we added a tracheal extension, and pierced to allow insertion of a size 7.0 tracheostomy cannula. The whole was connected to an artificial lung. Three lung mechanics were simulated (normal, obstructive and restrictive). We compared five different tracheostomy tube modalities to a control scenario in which the tube was capped and the cuff was deflated.ResultsA marginal difference was observed on the WOB within conditions with a slight increase + 0.004 [95% CI (0.003–0.004); p < 0.001] when the cuff was inflated in the normal and restrictive models and a slight decrease in the obstructive model. The highest PEEPtot that was reached was + 1 cmH2O [95% CI (1–1.1); p < 0.001] with high-flow therapy (HFT) with the cuff inflated in the obstructive model. We observed a statistically significant reduction in VT [up to − 57 mL 95% CI (− 60 to − 54); p < 0.001] when the cuff was inflated, in both the normal and obstructive models.ConclusionsOur results support the use of conditions that involve cuff deflation. Intermediate modalities with the cuff deflated produced similar results than cannula capping.

Inhalation of Aerosolized Fentanyl Induces Respiratory Disorder and Sudden Death in Anesthetized Rats

In synthetic opioids, fentanyl (FNT) is the deadliest in clinical settings, resulting from respiratory disorder (RD) including ventilatory depression (dVE) and apnea. Rapid intravenous injection of FNT has been reported to cause immediately central and upper airway obstructive apnea that is mediated by vagal afferents in anesthetized rat (Zhuang J et al, 2012 and 2023). Here we asked whether acute inhalation of FNT also induced similar RD. EMGs of the internal and external intercostal muscles and thyroarytenoid muscles (EMGII, EMGEI, and EMGTA), minute ventilation (VE), heart rate and arterial blood pressure were recorded in anesthetized rats exposed to aerosolized FNT for 10 min. Immediately after exposure to FNT at 100 mg/m3, the rats showed apneas and remarkable prolongation of expiratory duration (TE) associated with hypotension and bradycardia. The apneas were characterized by cessation of EMGEI activity (central apnea) with enhanced tonic discharges of EMGTA (vocal closure, i.e., obstructive apnea) and EMGII (expiratory muscle constriction, i.e., chest wall rigidity). After a brief rebound at ~0.5 min exposure when the cardiorespiratory activities almost recovered to the baseline level, the rats presented gradual dVE by reduction of VT and fR, lasting for approximately 10 min. Apneas and ventilatory arrest subsequently occurred, leading to cardiac arrest a few minutes later. In contrast, FNT at 50 mg/m3 initially failed to significantly change VE, but subsequently developed gradual dVE (70% reduction) with significant TE prolongation, bradycardia and hypotension. These cardiorespiratory responses disappeared 30 min later. Our results suggest that acute exposure to a lethal dose of aerosolized FNT initially induces both central and upper airway obstructive apnea followed by dVE and ventilatory arrest, which is responsible for the sudden death in anesthetized rats. Supported by NIH R01 grants HL163512 and DA059063. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Contribution of electrical impedance tomography to personalize positive end-expiratory pressure under ECCO2R

Extracorporeal Carbon Dioxide Removal (ECCO2R) is used in acute respiratory distress syndrome (ARDS) patients to facilitate lung-protective ventilatory strategies. Electrical Impedance Tomography (EIT) allows individual, non-invasive, real-time, bedside, radiation-free imaging of the lungs, providing global and regional dynamic lung analyses. To provide new insights for future ECCO2R research in ARDS, we propose a potential application of EIT to personalize End-Expiratory Pressure (PEEP) following each reduction in tidal volume (VT), as demonstrated in an illustrative case. A 72-year-old male with COVID-19 was admitted to the ICU for moderate ARDS. Monitoring with EIT was started to determine the optimal PEEP value (PEEPEIT), defined as the intersection of the collapse and overdistention curves, after each reduction in VT during ECCO2R. The identified PEEPEIT values were notably low (< 10 cmH2O). The decrease in VT associated with PEEPEIT levels resulted in improved lung compliance, reduced driving pressure and a more uniform ventilation pattern. Despite current Randomized Controlled Trials showing that ultra-protective ventilation with ECCO2R does not improve survival, the applicability of universal ultra-protective ventilation settings for all patients remains a subject of debate. Inappropriately set PEEP levels can lead to alveolar collapse or overdistension, potentially negating the benefits of VT reduction. EIT facilitates real-time monitoring of derecruitment associated with VT reduction, guiding physicians in determining the optimal PEEP value after each decrease in tidal volume. This original description of using EIT under ECCO2R to adjust PEEP at a level compromising between recruitability and overdistention could be a crucial element for future research on ECCO2R.

Effect of Ventilator Settings on Mechanical Power During Simulated Mechanical Ventilation of Patients With ARDS.

In recent years, mechanical power (MP) has emerged as an important concept that can significantly impact outcomes from mechanical ventilation. Several individual components of ventilatory support such as tidal volume (VT), breathing frequency, and PEEP have been shown to contribute to the extent of MP delivered from a mechanical ventilator to patients in respiratory distress/failure. The aim of this study was to identify which common individual setting of mechanical ventilation is more efficient in maintaining safe and protective levels of MP using different modes of ventilation in simulated subjects with ARDS. We used an interactive mathematical model of ventilator output during volume control ventilation (VCV) with either constant inspiratory flow (VCV-CF) or descending ramp inspiratory flow, as well as pressure control ventilation (PCV). MP values were determined for simulated subjects with mild, moderate, and severe ARDS; and whenever MP > 17 J/min, VT, breathing frequency, or PEEP was manipulated independently to bring back MP to ≤ 17 J/min. Finally, the optimum VT-breathing frequency combinations for MP = 17 J/min were determined with all 3 modes of ventilation. VCV-CF always resulted in the lowest MPs while PCV resulted in highest MPs. Reductions in VT were the most efficient for maintaining safer and protective MP. At targeted MPs of 17 J/min and maximized minute ventilation, the optimum VT-breathing frequency combinations were 250-350 mL for VT and 32-35 breaths/min for breathing frequency in mild ARDS, 200-350 mL for VT and 34-40 breaths/min for breathing frequency in moderate ARDS, and 200-300 mL for VT and 37-45 breaths/min for breathing frequency for severe ARDS. VCV-CF resulted in the lowest MP. VT was the most efficient for maintaining safe and protective MP in a mathematical simulation of subjects with ARDS. In the context of maintaining low and safe MPs, ventilatory strategies with lower-than-normal VT and higher-than-normal breathing frequency will need to be implemented in patients with ARDS.

Epi Source-Drain Damage Mitigation During Channel Release of Stacked Nanosheet Gate-All-Around Transistors

Nanosheet (NS) gate-all-around (GAA) devices have demonstrated advantages in device performance and area scaling over finFET devices [1-11]. Enablement and future scaling of GAA devices require robust etch processes for Inner Spacer (IS) and Channel Release (CR) for well-controlled device performance and yield (Fig. 1). CR requires an isotropic, complete etch of the sacrificial SiGe layer with extremely high selectivity to the spacer (Sp0), IS, and Si channels. Furthermore, during CR, the Si channels must be released simultaneously for all sheet widths (WNS) [1], which range from 20nm to 100nm, necessitating significant over-etch (OE) on the narrowest sheets. We demonstrated excellent device performance across all WNS with more than 150 % OE on the widest sheets [1]. However, this extreme OE makes the pFET source/drain (S/D) SiGe:B especially vulnerable to damage. In this paper, we explore several mechanisms that result in SiGe:B S/D damage and demonstrate how to prevent the damage with IS, CR, and S/D epitaxial optimization.The S/D Si:B and Si:P used in our high-performance test devices are not susceptible to damage during CR due to high etch selectivity [2]. Thus, SiGe:B S/D is required to evaluate the mechanisms causing S/D damage. To enable these studies, we developed high-quality S/D SiGe:B, which shows substantial device performance improvement over our baseline S/D Si:B, with 150% increase in peak mobility, 50% reduction in Vt, and 45% reduction in Ron (Fig. 2).The ability to target IS thickness allows tuning of device performance through Cov and Ron and is critical for future device scaling. In addition, the IS plays a critical role as a physical barrier to prevent S/D damage during CR [1,2]; reducing IS thickness below a critical value can result in S/D damage. The optimal IS thickness is determined by balancing maximum device performance for all WNS while maintaining S/D integrity during CR. This process window can be maximized by optimizing the CR etch process, and can be further increased by integrating an Si:B buffer in the S/D epitaxy. We have developed four CR processes with different chemistries and evaluated their process windows.We evaluated S/D damage for two CR processes versus IS thickness. We observed no S/D damage with Process A until 4nm IS thickness at 50% OE (Fig. 3a). Process C showed no damage at 4nm IS thickness, even up to 100% OE. The plan-view TEM in Fig. 3a shows that S/D damage occurs at the corners of the S/D region as well as at the center, indicating several mechanisms for S/D damage (see Fig. 4): CR etch gas permeation through the IS, exposed S/D through pinholes in the IS or at the IS edges due to rounded IS shape, and exposed S/D at the intersection of the Si/SiGe fins and gate.To isolate and characterize permeation of the CR etch gas through the IS, we deposited various thicknesses of IS on SiGe/Si multilayers (Fig. 5a), then exposed the structures to CR Process A. The SiGe layers showed no damage until the IS layer was thinned to <1nm. The difference in critical thickness for etch gas permeation on fully integrated structures compared to these test structures (4nm compared to <1nm) could be attributed to the other mechanisms.S/D damage due to IS permeation can be prevented by a better quality IS; by optimizing the CR chemistry to tune the selectivity between the sacrificial SiGe and the S/D SiGe:B (Fig. 5b); or by integrating a Si:B buffer prior to S/D SiGe:B deposition (Fig. 6). The process window then can be maximized by selecting the best CR process since selectivity to Si:B and permeation through the IS varies with the chemistry. Fig. 7 shows the improvement in the process window with a 2nm Si:B buffer on wafers with no IS for Processes A, B and C.The other S/D damage mechanisms highlighted in Fig. 4 are characterized in Fig. 3b. The S/D damage starts at the corners of the active region and the extent of damage increases with CR OE. These failure modes require changes in integration to improve the Sp0 at the fin-gate corner, reducing the IS rounding, or creating a straighter etch front across the sheet [2].S/D damage during CR is a significant issue in NS architecture. This can be mitigated by optimizing the CR etch process, incorporating an Si:B buffer layer, improving the IS quality or shape, and improved integration. Understanding these mechanisms is critical to ensure robust S/D quality with scaling for future technology nodes. Figure 1

Low Tidal Volume Ventilation Is Poorly Implemented for Patients in North American and United Kingdom ICUs Using Electronic Health Records

Low tidal volume ventilation (LTVV;< 8mL/kg predicted body weight [PBW]) is a well-established standard of care associated with improved outcomes. This study used data collated in multicenter electronic health record ICU databases from the United Kingdom and the United States to analyze the use of LTVV in routine clinical practice. What factors are associated with adherence to LTVV in the United Kingdom and North America? This was a retrospective, multicenter study across the United Kingdom and United States of patients who were mechanically ventilated. Factors associated with adherence to LTVV were assessed in all patients in both databases who were mechanically ventilated for > 48 h. We observed trends over time and investigated whether LTVV was associated with patient outcomes (30-day mortality and duration of ventilation) and identified strategies to improve adherence to LTVV. A total of 5,466 (Critical Care Health Informatics Collaborative [CCHIC]) and 7,384 electronic ICU collaborative research database [eICU-CRD] patients were ventilated for > 48h and had data of suitable quality for analysis. The median tidal volume (VT) values were 7.48mL/kg PBW (CCHIC) and 7.91mL/kg PBW (eICU-CRD). The patients at highest risk of not receiving LTVV were shorter than 160cm (CCHIC) and 165cm (eICU-CRD). Those with BMI > 30kg/m2 (CCHIC OR, 1.9 [95%CI, 1.7-2.13]; eICU-CRD OR, 1.61 [95%CI, 1.49-1.75]) and female patients (CCHIC OR, 2.39 [95%CI, 2.16-2.65]; eICU-CRD OR, 2.29 [95%CI, 2.26-2.31]) were at increased risk of having median VT > 8mL/kg PBW. Patients with median VT< 8mL/kg PBW had decreased 30-day mortality in the CCHIC database (CCHIC cause-specific hazard ratio, 0.86 [95%CI, 0.76-0.97]; eICU-CRD cause-specific hazard ratio, 0.9 [95%CI, 0.86-1.00]). There was a significant reduction in VT over time in the CCHIC database. There has been limited implementation of LTVV in routine clinical practice in the United Kingdom and the United States. VT > 8mL/kg PBW was associated with worse patient outcomes.

Abstract P1-04-08: Independent Validation of a Novel, Non-invasive Approach to Predict Pathologic Complete Response (pCR) in a Blinded, Prospectively-Run Single Center Trial

Abstract Background: As pathologic complete response (pCR) is correlated with higher rates of event free survival, accurately forecasting pCR advances our collective endeavors in precision oncology to discern and translate individual patient-specific data into risk stratification. We developed the TumorScope engine, a software platform that utilizes pretreatment diagnostic data to build a computational tumor model that simulates in vivo tumor characteristics and interactions, incorporating morphology, metabolism, vascularity, and nutrient and drug delivery. This non-invasive approach enables accurate forecasting of a patient’s response to physician-chosen neoadjuvant chemotherapy-based treatment (NAC). Here we validate the prognostic capacity of this technology at a single site cancer center. Methods: A blinded, prospective trial using retrospective data was conducted at UNC. The study cohort included patients aged 18 years or older diagnosed with any subtype of breast cancer who were treated with a NAC regimen and had a pre-treatment T1-weighted dynamic contrast enhanced (DCE) MRI available. Pre-treatment diagnostic and planned treatment data (demographics, drug regimen, receptor status (ER/PR/HER2), DCE MRI, and pathology) were input into the TumorScope engine to simulate predicted final tumor volumes (Vt) for each tumor and predict pCR or residual disease (RD); pCR predictions were compared to post-surgery pathologic assessments defined as ypT0/is/N0. Predicted pCR was set at pre-defined threshold of predicted Vt less than 0.01 cm^3, or at least a 99.9% Vt reduction. Results: One hundred and fifty subjects with 157 tumors were enrolled in the study. After excluding missing data (absent DCE-MRI), a total of 143 cases in 136 patients were included. The majority of patients self-identified as Caucasian (63%) or African American (23%). TumorScope had a pCR overall prediction accuracy of 92.3% (95% CI: 86.7 - 96.1%) with a sensitivity of 90.9 % (95% CI: 75.7 - 98.1 %) and specificity of 92.7% (95% CI: 86.2 – 96.8%). Based on our subgroup analysis, predictive accuracy remained reliable for HR+/HER2- (n=65; 95.4%), HR+/HER2+ (n=20; 85.0%), HR-/HER2+ (n=21; 85.7%) and TNBC (n=37; 94.6%) subtypes. Predictive performance remained stable across ethnic subtypes and tumor grade (see Table 1). Conclusion: The TumorScope noninvasive method that incorporates imaging, pathologic, demographic and planned treatment data appears to accurately predict an individual patient’s probability of pCR across clinical subtypes. Table 1. TumorScope prediction performance. Citation Format: Cherie Kuzmiak, Terry S. Hartman, Thad Benefield, Joseph Peterson, Anuja K. Antony, Tushar Pandey, John A. Cole Jr, Benjaminc C. Calhoun, Lisa Carey. Independent Validation of a Novel, Non-invasive Approach to Predict Pathologic Complete Response (pCR) in a Blinded, Prospectively-Run Single Center Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-04-08.

Very Low Driving-Pressure Ventilation in Patients With COVID-19 Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation: A Physiologic Study

To determine in patients with acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) whether reducing driving pressure (ΔP) would decrease plasma biomarkers of inflammation and lung injury (interleukin-6 [IL-6], IL-8, and the soluble receptor for advanced glycation end-products sRAGE). A single-center prospective physiologic study. At a single university medical center. Adult patients with severe COVID-19 ARDS on VV ECMO. Participants on VV ECMO had the following biomarkers measured: (1) pre-ECMO with low-tidal-volume ventilation (LTVV), (2) post-ECMO with LTVV, (3) during low-driving-pressure ventilation (LDPV), (4) after 2 hours of very low driving-pressure ventilation (V-LDPV, main intervention ΔP=1 cmH2O), and (5) 2 hours after returning to LDPV. Twenty-six participants were enrolled; 21 underwent V-LDPV. There was no significant change in IL-6, IL-8, and sRAGE from LDPV to V-LDPV and from V-LDPV to LDPV. Only participants (9 of 21) with nonspontaneous breaths had significant change (p < 0.001) in their tidal volumes (Vt) (mean ± SD), 1.9 ± 0.5, 0.1 ± 0.2, and 2.0 ± 0.7 mL/kg predicted body weight (PBW). Participants with spontaneous breathing, Vt were unchanged-4.5 ± 3.1, 4.7 ± 3.1, and 5.6 ± 2.9 mL/kg PBW (p=0.481 and p=0.065, respectively). There was no relationship found when accounting for Vt changes and biomarkers. Biomarkers did not significantly change with decreased ΔPs or Vt changes during the first 24 hours post-ECMO. Despite deep sedation, reductions in Vt during V-LDPV were not reliably achieved due to spontaneous breaths. Thus, patients on VV ECMO for ARDS may have higher Vt (ie, transpulmonary pressure) than desired despite low ΔPs or Vt.

Paradoxical response to chest wall loading predicts a favorable mechanical response to reduction in tidal volume or PEEP

BackgroundChest wall loading has been shown to paradoxically improve respiratory system compliance (CRS) in patients with moderate to severe acute respiratory distress syndrome (ARDS). The most likely, albeit unconfirmed, mechanism is relief of end-tidal overdistension in ‘baby lungs’ of low-capacity. The purpose of this study was to define how small changes of tidal volume (VT) and positive end-expiratory pressure (PEEP) affect CRS (and its associated airway pressures) in patients with ARDS who demonstrate a paradoxical response to chest wall loading. We hypothesized that small reductions of VT or PEEP would alleviate overdistension and favorably affect CRS and conversely, that small increases of VT or PEEP would worsen CRS.MethodsProspective, multi-center physiologic study of seventeen patients with moderate to severe ARDS who demonstrated paradoxical responses to chest wall loading. All patients received mechanical ventilation in volume control mode and were passively ventilated. Airway pressures were measured before and after decreasing/increasing VT by 1 ml/kg predicted body weight and decreasing/increasing PEEP by 2.5 cmH2O.ResultsDecreasing either VT or PEEP improved CRS in all patients. Driving pressure (DP) decreased by a mean of 4.9 cmH2O (supine) and by 4.3 cmH2O (prone) after decreasing VT, and by a mean of 2.9 cmH2O (supine) and 2.2 cmH2O (prone) after decreasing PEEP. CRS increased by a mean of 3.1 ml/cmH2O (supine) and by 2.5 ml/cmH2O (prone) after decreasing VT. CRS increased by a mean of 5.2 ml/cmH2O (supine) and 3.6 ml/cmH2O (prone) after decreasing PEEP (P < 0.01 for all). Small increments of either VT or PEEP worsened CRS in the majority of patients.ConclusionPatients with a paradoxical response to chest wall loading demonstrate uniform improvement in both DP and CRS following a reduction in either VT or PEEP, findings in keeping with prior evidence suggesting its presence is a sign of end-tidal overdistension. The presence of ‘paradox’ should prompt re-evaluation of modifiable determinants of end-tidal overdistension, including VT, PEEP, and body position.

Electrical Impedance Tomography to Set Positive End Expiratory Pressure During Pediatric Extracorporeal Membrane Oxygenation for Respiratory Failure... Is it Feasible?

Electrical Impedance Tomography to Set Positive End Expiratory Pressure During Pediatric Extracorporeal Membrane Oxygenation for Respiratory Failure... Is it Feasible?

Respiratory mechanics behavior after heart surgery: an experimental study

Changes in ventilatory mechanics and their consequent pulmonary complications are common after surgical procedures, particularly in cardiac surgery (CS), and may be associated with both preoperative history and surgical circumstances. This study aims to compare ventilatory mechanics in the moments before and after cardiac surgery (CS), describing how pulmonary complications occurred. An experimental, uncontrolled study was conducted, of the before-and-after type, and with a descriptive and analytical character. It was carried out in a private hospital in the city of Salvador, Bahia, Brazil, and involved 30 adult patients subjected to CS. In addition to clinical and epidemiological variables, minute volume (VE), respiratory rate (RR), tidal volume (VT), forced vital capacity (FVC), maximum inspiratory pressure (MIP), and peak expiratory flow (PEF) were also recorded. Data were collected in the following moments: preoperative (PRE-OP) period, immediate postoperative (IPO) period, and 1st postoperative day (1st POD). The sample was aged 48.1 ± 11.8 years old and had a body mass index of 25.5 ± 4.9 kg m-2; 60% of the patients remained on mechanical ventilation for less than 24 hours (17.5 [8.7-22.9] hours). There was a significant reduction in VT, FVC, MIP and PEF when PRE-OP versus IPO, and PRE-OP versus 1st POD were compared (p &lt; 0.05). There were no significant changes between IPO and the 1st POD. The highest incidence of pulmonary complications involved pleural effusion (50% of the patients). This study showed that patients subjected to CS present significant damage to ventilatory parameters after the surgery, especially in the IPO period and on the 1st POD. It is possible that the extension of this ventilatory impairment has led to the onset of postoperative pulmonary complications.

High-dose testosterone treatment reduces monoamine oxidase A levels in the human brain: A preliminary report

The sex hormones testosterone and estradiol influence brain structure and function and are implicated in the pathogenesis, prevalence and disease course of major depression. Recent research employing gender-affirming hormone treatment (GHT) of gender dysphoric individuals and utilizing positron emission tomography (PET) indicates increased serotonin transporter binding upon high-dosages of testosterone treatment. Here, we investigated the effects of GHT on levels of monoamine oxidase A (MAO-A), another key target of antidepressant treatment. Participants underwent PET with the radioligand [11C]harmine to assess cerebral MAO-A distribution volumes (VT) before and four months after initiation of GHT. By the time this study was terminated for technical reasons, 18 transgender individuals undergoing GHT (11 transmen, TM and 7 transwomen, TW) and 17 cis-gender subjects had been assessed. Preliminary analysis of available data revealed statistically significant MAO-A VT reductions in TM under testosterone treatment in six of twelve a priori defined regions of interest (middle frontal cortex (−10%), anterior cingulate cortex (−9%), medial cingulate cortex (−10.5%), insula (−8%), amygdala (−9%) and hippocampus (−8.5%, all p<0.05)). MAO-A VT did not change in TW receiving estrogen treatment. Despite the limited sample size, pronounced MAO-A VT reduction could be observed, pointing towards a potential effect of testosterone. Considering MAO-A’s central role in regulation of serotonergic neurotransmission, changes to MAO-A VT should be further investigated as a possible mechanism by which testosterone mediates risk for, symptomatology of, and treatment response in affective disorders.

Effect of change in tidal volume on left to right shunt across ventricular septal defect in children - A pilot study.

Background :Pulmonary vascular resistance, an important determinant of shunting across ventricular septal defects (VSD), rises at both extremes of lung volume.Aims :We sought to determine the effect of changes in tidal volumes (VT) on pulmonary blood flow (Qp), systemic blood flow (Qs), and shunt (Qp/Qs) in children with VSD.Setting :Single-center teaching hospital.Design :Prospective observational study.Methods :Thirty children with a mean age of 11.8 ± 5 months undergoing surgical closure of VSD were studied. Hemodynamics and shunt-related parameters were assessed using transthoracic echocardiography measured at three different VT i.e. 10, 8, and 6-ml/kg keeping the minute ventilation constant.Results :Reduction in VT from 10 to 8 to 6 ml/kg led to a reduction in gradient across VSD measuring 23.5, 20 and 13 mmHg respectively (P < 0.001). Similarly, right ventricluar outflow tract (RVOT) diameter, RVOT velocity time integral, Qp (57.3 ± 18.1, 50.6 ± 16.9, 39.9 ± 14.7 mL; P < 0.001), Qs (24.1 ± 10.4, 20.0 ± 8.7, 15.3 ± 6.9 mL; P < 0.001) and peak airway pressure (17.2 ± 1.5, 15.8 ± 1.3, 14.5 ± 1.2 cmHg; P < 0.001) showed progressive decline with decreasing VT from 10 to 8 to 6 ml/kg, respectively. However, Qp/Qs (2.4 ± 0.4, 2.6 ± 0.4, 2.6 ± 0.4) demonstrated a minor increasing trend.Conclusion :Lower VT reduces the gradient across VSD, the pulmonary blood flow, and the peak airway pressure. Hence, ventilation with lower VT and higher respiratory rate maintaining adequate minute ventilation might be preferable in children with VSD. Further studies are required to confirm the findings of this pilot study.

Efficacy of amiodarone in the treatment of ventricular arrhythmias in patients with coronary artery disease in Bangladesh

Background: Ventricular arrhythmias (VA) are among the most feared complications of coronary artery disease (CAD) and one of the major contributors of death in CAD patients. Antiarrhythmic drug (AAD) therapy is required for recurrent significant VA in the absence of need for further revascularization. But all AADs do not have the same efficacy against life threatening VA and supraventricular arrhythmias (SVAs).&#x0D; Methodology: All (50) patients admitted in the department of Cardiology, BSMMU with ventricular arrhythmias with CAD fulfilling the inclusion and exclusion criteria were included in the study. Informed written consent was taken from each patient before enrollment. Detailed history was taken and relevant physical examinations were done. Loading dose followed by maintenance dose of amiodarone was given and recorded. Relevant lab investigations were performed and recorded in predesigned semi-structured data collection sheet. Symptomatic improvement was assessed, relevant physical examination was done and lab investigations were performed at 1, 3 and 6 month follow up. After editing data analysis was carried out by using the Statistical Package for Social Science (SPSS) version 23.0 windows software.&#x0D; Results: The mean age was found 57.7±8.0 years with a range of 45 to 78 years. Almost two third (62.0%) patients were male and 19(38.0%) patients were female. Male female ratio was 1.6:1. Almost three fourth (74.0%) patients had chest pain, 15(30.0%) had palpitation and 11(22.0%) had shortness of breath. Two third (66.0%) patients had hypertension, 23(46.0%) had dyslipidemia, 17(34.0%) had smoking and 9(18.0%) had diabetes mellitus. Twenty nine (58.0%) patients had family history of IHD. The difference was statistically significant (p&lt;0.05) when compared to baseline. Regarding arrhythmia, 45(90.0%) patients was found to have PVC in baseline and 3(6.4%) at 6th month. The reduction of PVC and VT at six month were statistically significant (p&lt;0.05) when compared to baseline. Regarding outcome 2(4.1%) patients died, one patient dropped out due to thyroid dysfunction and 47 were alive.&#x0D; Conclusion: In conclusion it was found that different forms of ventricular arrhythmias like PVCs, VT were significantly reduced gradually with amiodarone therapy at 6th month follow up.&#x0D; J Dhaka Medical College, Vol. 29, No.2, October, 2020, Page 158-164

Adaptive mechanical ventilation with automated minimization of mechanical power\u2014a pilot randomized cross-over study

BackgroundAdaptive mechanical ventilation automatically adjusts respiratory rate (RR) and tidal volume (VT) to deliver the clinically desired minute ventilation, selecting RR and VT based on Otis’ equation on least work of breathing. However, the resulting VT may be relatively high, especially in patients with more compliant lungs. Therefore, a new mode of adaptive ventilation (adaptive ventilation mode 2, AVM2) was developed which automatically minimizes inspiratory power with the aim of ensuring lung-protective combinations of VT and RR. The aim of this study was to investigate whether AVM2 reduces VT, mechanical power, and driving pressure (ΔPstat) and provides similar gas exchange when compared to adaptive mechanical ventilation based on Otis’ equation.MethodsA prospective randomized cross-over study was performed in 20 critically ill patients on controlled mechanical ventilation, including 10 patients with acute respiratory distress syndrome (ARDS). Each patient underwent 1 h of mechanical ventilation with AVM2 and 1 h of adaptive mechanical ventilation according to Otis’ equation (adaptive ventilation mode, AVM). At the end of each phase, we collected data on VT, mechanical power, ΔP, PaO2/FiO2 ratio, PaCO2, pH, and hemodynamics.ResultsComparing adaptive mechanical ventilation with AVM2 to the approach based on Otis’ equation (AVM), we found a significant reduction in VT both in the whole study population (7.2 ± 0.9 vs. 8.2 ± 0.6 ml/kg, p < 0.0001) and in the subgroup of patients with ARDS (6.6 ± 0.8 ml/kg with AVM2 vs. 7.9 ± 0.5 ml/kg with AVM, p < 0.0001). Similar reductions were observed for ΔPstat (whole study population: 11.5 ± 1.6 cmH2O with AVM2 vs. 12.6 ± 2.5 cmH2O with AVM, p < 0.0001; patients with ARDS: 11.8 ± 1.7 cmH2O with AVM2 and 13.3 ± 2.7 cmH2O with AVM, p = 0.0044) and total mechanical power (16.8 ± 3.9 J/min with AVM2 vs. 18.6 ± 4.6 J/min with AVM, p = 0.0024; ARDS: 15.6 ± 3.2 J/min with AVM2 vs. 17.5 ± 4.1 J/min with AVM, p = 0.0023). There was a small decrease in PaO2/FiO2 (270 ± 98 vs. 291 ± 102 mmHg with AVM, p = 0.03; ARDS: 194 ± 55 vs. 218 ± 61 with AVM, p = 0.008) and no differences in PaCO2, pH, and hemodynamics.ConclusionsAdaptive mechanical ventilation with automated minimization of inspiratory power may lead to more lung-protective ventilator settings when compared with adaptive mechanical ventilation according to Otis’ equation.Trial registrationThe study was registered at the German Clinical Trials Register (DRKS00013540) on December 1, 2017, before including the first patient.

Determinants of the effect of extracorporeal carbon dioxide removal in the SUPERNOVA trial: implications for trial design.

To describe the variability and determinants of the effect of extracorporeal CO2 removal (ECCO2R) on tidal volume (Vt), driving pressure (ΔP), and mechanical power (PowerRS) and to determine whether highly responsive patients can be identified for the purpose of predictive enrichment in ECCO2R trial design. Using data from the SUPERNOVA trial (95 patients with early moderate acute respiratory distress syndrome), the independent effects of alveolar dead space fraction (ADF), respiratory system compliance (Crs), hypoxemia (PaO2/FiO2), and device performance (higher vs lower CO2 extraction) on the magnitude of reduction in Vt, ΔP, and PowerRS permitted by ECCO2R were assessed by linear regression. Predicted and observed changes in ΔP were compared by Bland-Altman analysis. Hypothetical trials of ECCO2R, incorporating predictive enrichment and different target CO2 removal rates, were simulated in the SUPERNOVA study population. Changes in Vt permitted by ECCO2R were independently associated with ADF and device performance but not PaO2/FiO2. Changes in ΔP and PowerRS were independently associated with ADF, Crs, and device performance but not PaO2/FiO2. The change in ΔP predicted from ADF and Crs was moderately correlated with observed change in ΔP (R2 0.32, p < 0.001); limits of agreement between observed and predicted changes in ΔP were ± 3.9cmH2O. In simulated trials, restricting enrollment to patients with a larger predicted decrease in ΔP enhanced the average reduction in ΔP, increased predicted mortality benefit, and reduced sample size and screening size requirements. The increase in statistical power obtained by restricting enrollment based on predicted ΔP response varied according to device performance as specified by the target CO2 removal rate. The lung-protective benefits of ECCO2R increase with higher alveolar dead space fraction, lower respiratory system compliance, and higher device performance. ADF and Crs, rather than severity of hypoxemia, should be the primary factors determining whether to enroll patients in clinical trials of ECCO2R.

A 2-year multicenter, observational, prospective, cohort study on extracorporeal CO2 removal in a large metropolis area

BackgroundExtracorporeal carbon dioxide removal (ECCO2R) is a promising technique for the management of acute respiratory failure, but with a limited level of evidence to support its use outside clinical trials and/or data collection initiatives. We report a collaborative initiative in a large metropolis.MethodsTo assess on a structural basis the rate of utilization as well as efficacy and safety parameters of 2 ECCO2R devices in 10 intensive care units (ICU) during a 2-year period.ResultsSeventy patients were recruited in 10 voluntary and specifically trained centers. The median utilization rate was 0.19 patient/month/center (min 0.04; max 1.20). ECCO2R was started under invasive mechanical ventilation (IMV) in 59 patients and non-invasive ventilation in 11 patients. The Hemolung Respiratory Assist System (Alung) was used in 53 patients and the iLA Activve iLA kit (Xenios Novalung) in 17 patients. Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median VT was observed in ARDS patients from 5.9 to 4.1 ml/kg (p <0.001). A reduction in PaCO2 values was observed in AE-COPD patients from 67.5 to 51 mmHg (p< 0.001). Median duration of ECCO2R was 5 days (IQR 3–8). Reasons for ECCO2R discontinuation were improvement (n = 33), ECCO2R-related complications (n = 18), limitation of life-sustaining therapies or measures decision (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which being ECCO2R-related.ConclusionsBased on a registry, we report a low rate of ECCO2R device utilization, mainly in severe COPD and ARDS patients. Physiological efficacy was confirmed in these two populations. We confirmed safety concerns such as hemolysis, bleeding, and thrombosis, with different profiles between the devices. Such results could help to design future studies aiming to enhance safety, to demonstrate a still-lacking strong clinical benefit of ECCO2R, and to guide the choice between different devices.Trial registrationClinicalTrials.gov: Identifier: NCT02965079 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02965079

A Modified Method to Assess Tidal Recruitment by Electrical Impedance Tomography.

Avoiding tidal recruitment and collapse during mechanical ventilation should reduce the risk of lung injury. Electrical impedance tomography (EIT) enables detection of tidal recruitment by measuring regional ventilation delay inhomogeneity (RVDI) during a slow inflation breath with a tidal volume (VT) of 12 mL/kg body weight (BW). Clinical applicability might be limited by such high VTs resulting in high end-inspiratory pressures (PEI) during positive end-expiratory pressure (PEEP) titration. We hypothesized that RVDI can be obtained with acceptable accuracy from reduced slow inflation VTs. In seven ventilated pigs with experimental lung injury, tidal recruitment was quantified by computed tomography at PEEP levels changed stepwise between 0 and 25 cmH2O. RVDI was measured by EIT during slow inflation VTs of 12, 9, 7.5, and 6 mL/kg BW. Linear correlation of tidal recruitment and RVDI was excellent for VTs of 12 (R2 = 0.83, p < 0.001) and 9 mL/kg BW (R2 = 0.83, p < 0.001) but decreased for VTs of 7.5 (R2 = 0.76, p < 0.001) and 6 mL/kg BW (R2 = 0.71, p < 0.001). With any reduction in slow inflation VT, PEI decreased at all PEEP levels. Receiver-Operator-Characteristic curve analyses revealed that RVDI-thresholds to predict distinct amounts of tidal recruitment differ when obtained from different slow inflation VTs. In conclusion, tidal recruitment can sufficiently be monitored by EIT-based RVDI-calculation with a slow inflation of 9 mL/kg BW.

The effect of electroconvulsive therapy on cerebral monoamine oxidase A expression in treatment-resistant depression investigated using positron emission tomography

BackgroundElectroconvulsive therapy (ECT) constitutes one of the most effective antidepressant treatment strategies in major depression (MDD). Despite its common use and uncontested efficacy, its mechanism of action is still insufficiently understood. Previously, we showed that ECT is accompanied by a global decrease of serotonin-1A receptors in MDD; however, further studies to investigate the involvement of the serotonergic system in the mechanism of action of ECT are warranted. The monoamine oxidase A (MAO-A) represents an important target for antidepressant treatments and was found to be increased in MDD. Here, we investigated whether ECT impacts on MAO-A levels in treatment-resistant patients (TRD). Methods16 TRD patients (12 female, age 45.94 ± 9.68 years, HAMD 25.12 ± 3.16) with unipolar depression according to DSM-IV were scanned twice before (PET1 and PET2, to assess test-retest variability under constant psychopharmacotherapy) and once after (PET3) completing a minimum of eight unilateral ECT sessions using positron emission tomography and the radioligand [11C]harmine to assess cerebral MAO-A distribution volumes (VT). Age- and sex-matched healthy subjects (HC) were measured once. ResultsResponse rate to ECT was 87.5%. MAO-A VT was found to be significantly reduced after ECT in TRD patients (−3.8%) when assessed in 27 a priori defined ROIs (p < 0.001). Test-retest variability between PET1 and PET2 was 3.1%. MAO-A VT did not significantly differ between TRD patients and HC at baseline. ConclusionsThe small effect size of the significant reduction of MAO-A VT after ECT in the range of test-retest variability does not support the hypothesis of a clinically relevant mechanism of action of ECT based on MAO-A. Furthermore, in contrast to studies reporting elevated MAO-A VT in unmedicated depressed patients, MAO-A levels were found to be similar in TRD patients and HC which might be attributed to the continuous antidepressant pharmacotherapy in the present sample.