Investigating the risk of reintubation by cough force assessment using cough peak expiratory flow: a single-center observational pilot study.

BACKGROUND: No objective indicator exists for evaluating cough strength during extubation of tracheally intubated patients. This study aimed to determine whether cough peak expiratory flow (CPEF) can predict the risk of reintubation due to decreased cough strength. METHODS: This was a retrospective cohort study of patients who were admitted to our Emergency Intensive Care Unit between September 1, 2020 and August 31, 2021 and were under artificial ventilation management for ≥ 24 h. The patients were divided into two groups: successful extubation and reintubation groups, and the relationship between CPEF immediately before extubation and reintubation was investigated. RESULTS: Seventy-six patients were analyzed. In the univariate analysis, CPEF was significantly different between the successful extubation (90.7 ± 25.9 L/min) and reintubation (57.2 ± 6.4 L/min) groups (p < 0.001). In the multivariate analysis with age and duration of artificial ventilation as covariates, CPEF was significantly lower in the reintubation group (p < 0.01). The cutoff value of CPEF for reintubation according to the receiver operating characteristic curve was 60 L/min (area under the curve, 0.897; sensitivity, 78.5%; specificity, 90.9%; p < 0.01). CONCLUSION: CPEF in tracheally intubated patients may be a useful indicator for predicting the risk of reintubation associated with decreased cough strength. The cutoff CPEF value for reintubation due to decreased cough strength was 60 L/min.

A novel method for assessment of airway opening pressure without the need for low-flow insufflation.

BACKGROUND: Airway opening pressure (AOP) detection and measurement are essential for assessing respiratory mechanics and adapting ventilation. We propose a novel approach for AOP assessment during volume assist control ventilation at a usual constant-flow rate of 60 L/min. OBJECTIVES: To validate the conductive pressure (Pcond) method, which compare the Pcond-defined on the airway pressure waveform as the difference between the airway pressure level at which an abrupt change in slope occurs at the beginning of insufflation and PEEP-to resistive pressure for AOP detection and measurement, and to compare its respiratory and hemodynamic tolerance to the standard low-flow insufflation method. METHODS: The proof-of-concept of the Pcond method was assessed on mechanical (lung simulator) and physiological (cadavers) bench models. Its diagnostic performance was evaluated in 213 patients, using the standard low-flow insufflation method as a reference. In 45 patients, the respiratory and hemodynamic tolerance of the Pcond method was compared with the standard low-flow method. MEASUREMENTS AND MAIN RESULTS: Bench assessments validated the Pcond method proof-of-concept. Sensitivity and specificity of the Pcond method for AOP detection were 93% and 91%, respectively. AOP obtained by Pcond and standard low-flow methods strongly correlated (r = 0.84, p < 0.001). Changes in SpO2 were significantly lower during Pcond than during standard method (p < 0.001). CONCLUSION: Determination of Pcond during constant-flow assist control ventilation may permit to easily and safely detect and measure AOP.

Development and assessment of the performance of a shared ventilatory system that uses clinically available components to individualize tidal volumes.

OBJECTIVES: To develop and assess a system for shared ventilation using clinically available components to individualize tidal volumes. DESIGN: Evaluation and in vitro validation study SETTING: Ventilator shortage during the SARS-CoV-2 pandemic. PARTICIPANTS: The team consisted of physicians, bioengineers, computer programmers, and medical technology professionals. METHODS: Using clinically available components, a system of ventilation consisting of two ventilatory limbs was assembled and connected to a ventilator. Monitors for each limb were developed using open-source software. Firstly, the effect of altering ventilator settings on tidal volumes delivered to each limb was determined. Secondly, the impact of altering the compliance and resistance of one limb on the tidal volumes delivered to both limbs was analysed. Experiments were repeated three times to determine system variability. RESULTS: The system permitted accurate and reproducible titration of tidal volumes to each limb over a range of ventilator settings and simulated lung conditions. Alteration of ventilator inspiratory pressures, of respiratory rates, and I:E ratio resulted in very similar tidal volumes delivered to each limb. Alteration of compliance and resistance in one limb resulted in reproducible alterations in tidal volume to that test lung, with little change to tidal volumes in the other lung. All tidal volumes delivered were reproducible. CONCLUSIONS: We demonstrate the reliability of a shared ventilation system assembled using commonly available clinical components that allows titration of individual tidal volumes. This system may be useful as a strategy of last resort for Covid-19, or other mass casualty situations, where the need for ventilators exceeds supply.

Assessment of Comfort during Less Invasive Surfactant Administration in Very Preterm Infants: A Multicenter Study.

INTRODUCTION: This study was set up to investigate if and to what extent non-pharmacological analgesia is able to provide comfort to very preterm infants (VPI) during less invasive surfactant administration (LISA). METHODS: This was a prospective non-randomized multicenter observational study performed in level IV NICUs. Inborn VPI with a gestational age between 220/7 and 316/7 weeks, signs of respiratory distress syndrome, and the need for surfactant replacement were included. Non-pharmacological analgesia was performed in all infants during LISA. In case of failure of the first LISA attempt, additional analgosedation could be administered. COMFORTneo scores during LISA were assessed. RESULTS: 113 VPI with a mean gestational age of 27 weeks (+/- 2.3 weeks) and mean birth weight of 946 g (+/- 33 g) were included. LISA was successful at the first laryngoscopy attempt in 81%. COMFORTneo scores were highest during laryngoscopy. At this time point, non-pharmacological analgesia provided adequate comfort in 61% of the infants. 74.4% of lower gestational aged infants (i.e., 220-266 weeks) were within the comfort zone during laryngoscopy compared to 51.6% of higher gestational aged infants (i.e., 270-320 weeks) (p = 0.016). The time point of surfactant administration did not influence the COMFORTneo scores during the LISA procedure. CONCLUSION: Non-pharmacological analgesia provided comfort in as much as 61% of the included VPI during LISA. Further research is needed to both develop strategies to identify infants who, despite receiving non-pharmacological analgesia, are at high risk for experiencing discomfort during LISA and define patient-tailored dosage and choice of analgosedative drugs.

Assessment of fluid responsiveness in children using respiratory variations in descending aortic flow.

BACKGROUND: The primary aim of the current study was to investigate the ability of respiratory variations in descending aortic flow, measured with two-dimensional echo at the suprasternal notch (ΔVpeak dAo), to predict fluid responsiveness in anesthetized mechanically ventilated children. In addition, variations in peak descending aortic flow measured with apical transthoracic echo (ΔVpeak LVOT) were examined for the same properties. METHODS: Twenty-seven patients under general anesthesia were investigated in this prospective observational study. Cardiac output, ΔVpeak dAo, and ΔVpeak LVOT were measured at stable conditions after anesthesia induction. The measurements were repeated after a 10 mL kg-1 fluid bolus. Patients were classified as responders if stroke volume index increased by >15% after fluid bolus. The ability of each parameter to predict fluid responsiveness was assessed using receiver operating characteristic curves. RESULTS: Twenty-seven patients were analyzed, mean age and weight 43 months and 16 kg, respectively. Twelve responders and 15 non-responders were identified. ΔVpeak dAo was significantly higher in the responder group (14%, 95% confidence interval [CI]: 12%-17%) compared to the non-responder group (11%, 95% CI: 9%-13%) (p = .04) at baseline. Area under the ROC curve for ΔVpeak dAo and ΔVpeak LVOT was 0.73 (95% CI: 0.52-0.89, p = .02) and 0.56 (0.34-0.78, p = .3), respectively. A baseline level of ΔVpeak dAo of >14% predicted fluid responsiveness with a sensitivity of 58% (95% CI: 28%-85%) and specificity of 73% (95% CI: 45%-92%). CONCLUSION: In mechanically ventilated children, ΔVpeak dAo identified fluid responders with moderate diagnostic power in the current study. ΔVpeak LVOT failed to predict fluid responders in the current study.

Assessment of Regional Lung Ventilation with Positron Emission Tomography Using the Radiofluorinated Gas [18F]SF6: Application to an Animal Model of Impaired Ventilation.

PURPOSE: Clinical ventilation studies are primarily performed with computerized tomography (CT) and more often with single-photon emission Computerized tomography (SPECT) using radiolabelled aerosols, both presenting certain limitations. Here, we investigate the use of the radiofluorinated gas [18F]SF6 as a positron emission tomography (PET) ventilation marker in an animal model of impaired lung ventilation. PROCEDURES: Sprague-Dawley rats (n = 15) were randomly assigned to spontaneous ventilation (sham group), endotracheal administration of phosphate-buffered saline (PBS group), or endotracheal administration of lipopolysaccharide (LPS group). PET-[18F]SF6 images (10-min acquisition) were acquired at t = 48 h after LPS or PBS administration under mechanical ventilation. CT images were acquired after each PET session. Volumes of interest were manually delineated in the lungs on CT images, and voxel-by-voxel analysis was carried out on PET images to obtain the corresponding histograms. After the imaging sessions, lungs were harvested to conduct histological analysis. RESULTS: Ventilation studies in sham animals showed uniform distribution of [18F]SF6 and fast elimination of the radioactivity after discontinuation of the administration. For PBS- and LPS-treated rats, ventilation defects were observed on PET images in some animals, identified as regions with low presence of the radiolabelled gas. Hypoventilated areas co-localized with regions with higher x-ray attenuation than healthy lungs on the CT images, suggesting the presence of oedema and, in some cases, atelectasis. Histograms obtained from PET images showed quasi-Gaussian distributions for control animals, while PBS- and LPS-treated animals demonstrated the presence of hypoventilated voxels. Deviation of the histograms from Gaussian distribution correlated with histological score was obtained by ex vivo histological analysis. CONCLUSIONS: [18F]SF6 is an appropriate marker of regional lung ventilation and may find application in the early diagnose of acute lung disease.

Comparative characteristics of some methods for estimating energy expenditure in critically ill mechanically ventilated patients.

AIM: To compare the energy expenditure (EE) assessed by ventilator-derived carbon dioxide production (EE-VCO2-ventilator) and the energy expenditure calculated from six predictive equations with the gold standard energy expenditure measured with indirect calorimetry (IC) in mechanically ventilated patients.

A new method of ventilation inhomogeneity assessment based on a simulation study using clinical data on congenital diaphragmatic hernia cases.

Congenital Diaphragmatic Hernia (CDH) is a diaphragm defect associated with lung hypoplasia and ventilation inhomogeneity (VI). The affected neonates are usually born with respiratory failure and require mechanical ventilation after birth. However, significant interindividual VI differences make ventilation difficult. So far, there are no clinical methods of VI assessment that could be applied to optimize ventilation at the bedside. A new VI index is a ratio of time constants T1/T2 of gas flows in both lungs. Pressure-controlled ventilation simulations were conducted using an infant hybrid (numerical-physical) respiratory simulator connected to a ventilator. The parameters of the respiratory system model and ventilator settings were based on retrospective clinical data taken from three neonates (2, 2.6, 3.6 kg) treated in the Paediatric Teaching Clinical Hospital of the Medical University of Warsaw. We searched for relationships between respiratory system impedance (Z) and ventilation parameters: work of breathing (WOB), peak inspiratory pressure (PIP), and mean airway pressure (MAP). The study showed the increased VI described by the T1/T2 index value highly correlated with elevated Z, WOB, PIP and MAP (0.8-0.9, the Spearman correlation coefficients were significant at P < 0.001). It indicates that the T1/T2 index may help to improve the ventilation therapy of CDH neonates.

Low-cost structured light imaging of regional volume changes for use in assessing mechanical ventilation.

BACKGROUND: Optimal setting of mechanical ventilators is critical for improving outcomes. Accurate, predictive lung mechanics models are effective in optimizing MV settings, but only at a global level as they cannot estimate regional lung volume ventilation to assess the potential of local distension or under-ventilation. This study presents a low-cost structured light system for non-contact high resolution chest motion measurement to estimate regional lung volume changes. METHODS: The system consists of a structured light projector and two cameras. A new pattern is designed to extract motion from sub-regions of the chest surface, and an efficient feature is proposed to provide a fast and accurate correspondence matching between two views. Reconstruction of 3D surface points is based on the matched points and stereo method. Asymmetric distribution of tidal volume into left and right lungs is estimated based on reconstructed regional chest expansion. A proof-of-concept experiment using a dummy model and two test lungs connected to a ventilator to provide differential chest expansion is conducted under tidal volumes of 400 ml, 500 ml and 600 ml, with results compared to the widely-used SURF and ORB methods. RESULTS: Compared to the SURF and ORB methods, the proposed method is more computationally efficient with ∼40% less computational time cost, and higher accuracy for dense point correspondence. Finally, the proposed method estimated the region lung volumes with the maximum error of 8 ml under 600 ml tidal volume, indicating a good accuracy. CONCLUSIONS: Surface reconstruction results in a proof-of-concept experiment with differential chest expansion show good performance for the proposed pattern and method in extracting the key information for regional chest expansion. The proposed method is generalizable, with potential for use in other applications.

Design and Analysis of a Low-Cost Electronically Controlled Mobile Ventilator, Incorporating Mechanized AMBU Bag, for Patients during COVID-19 Pandemic.

The outbreak of novel COVID-19 has severely and unprecedentedly affected millions of people across the globe. The painful respiratory distress caused during this disease calls for external assistance to the victims in the form of ventilation. The most common types of artificial ventilating units available at the healthcare facilities and hospitals are exorbitantly expensive to manufacture, and their number is fairly inadequate even in the so-called developed countries to cater to the burning needs of an ever-increasing number of ailing human subjects. According to available reports, without the provision of ventilation, the novel COVID-19 patients are succumbing to their ailments in a huge number of cases. This colossal problem of the availability of ventilator units can be addressed to a great extent by readily producible and cost-effective ventilating units that can be used on those suffering patients during an acute emergency and in the absence of conventional expensive ventilators at hospitals and medical care units. This paper has made an attempt to design and simulate a simple, yet effective, mechanized ventilator unit, which can be conveniently assembled without a profuse skillset and operated to resuscitate an ailing human patient. The stepper motor-controlled kinematic linkage is designed to deliver the patient with a necessitated discharge of air at optimum oxygen saturation through the AMBU bag connected in a ventilation circuit. With the associated code on MATLAB, the motor control parameters such as angular displacement and speed are deduced according to the input patient conditions (age group, tidal volume, breathing rate, etc.) and thereafter fed to the controller that drives the stepper motor. With a proposed feedback loop, the real-time static and dynamic compliance, airway resistance values can be approximately determined from the pressure variation cycle and fed to the controller unit to adjust the tidal volume as and when necessary. The simplistic yet robust design not only renders easy manufacturability by conventional and rapid prototyping techniques like 3D printing at different scales but also makes the product easily portable with minimal handling difficulty. Keeping the motto of Health for All as envisioned by the WHO, this low-cost indigenously engineered ventilator will definitely help the poor and afflicted towards their right to health and will help the medical professionals buy some time to manage the patient with acute respiratory distress syndrome (ARDS) towards recovery. Moreover, this instrument mostly includes readily available functional units having standard specifications and can be considered as standard bought-out items.

Proportional-assist ventilation with load-adjustable gain factors for mechanical ventilation: a cost-utility analysis.

BACKGROUND: Mechanical ventilation is an important component of patient critical care, but it adds expense to an already high-cost setting. This study evaluates the cost-utility of 2 modes of ventilation: proportional-assist ventilation with load-adjustable gain factors (PAV+ mode) versus pressure-support ventilation (PSV). METHODS: We adapted a published Markov model to the Canadian hospital-payer perspective with a 1-year time horizon. The patient population modelled includes all patients receiving invasive mechanical ventilation who have completed the acute phase of ventilatory support and have entered the recovery phase. Clinical and cost inputs were informed by a structured literature review, with the comparative effectiveness of PAV+ mode estimated via pragmatic meta-analysis. Primary outcomes of interest were costs, quality-adjusted life years (QALYs) and the (incremental) cost per QALY for patients receiving mechanical ventilation. Results were reported in 2017 Canadian dollars. We conducted probabilistic and scenario analyses to assess model uncertainty. RESULTS: Over 1 year, PSV had costs of $50 951 and accrued 0.25 QALYs. Use of PAV+ mode was associated with care costs of $43 309 and 0.29 QALYs. Compared to PSV, PAV+ mode was considered likely to be cost-effective, having lower costs (-$7642) and increased QALYs (+0.04) after 1 year. In cost-effectiveness acceptability analysis, 100% of simulations would be cost-effective at a willingness-to-pay threshold of $50 000 per QALY gained. INTERPRETATION: Use of PAV+ mode is expected to benefit patient care in the intensive care unit (ICU) and be a cost-effective alternative to PSV in the Canadian setting. Canadian hospital payers may therefore consider how best to optimally deliver mechanical ventilation in the ICU as they expand ICU capacity.

Does adherence to a quality indicator regarding early weaning from invasive ventilation improve economic outcome? A single-centre retrospective study.

OBJECTIVES: To measure and assess the economic impact of adherence to a single quality indicator (QI) regarding weaning from invasive ventilation. DESIGN: Retrospective observational single-centre study, based on electronic medical and administrative records. SETTING: Intensive care unit (ICU) of a German university hospital, reference centre for acute respiratory distress syndrome. PARTICIPANTS: Records of 3063 consecutive mechanically ventilated patients admitted to the ICU between 2012 and 2017 were extracted, of whom 583 were eligible adults for further analysis. Patients' weaning protocols were evaluated for daily adherence to quality standards until ICU discharge. Patients with <65% compliance were assigned to the low adherence group (LAG), patients with ≥65% to the high adherence group (HAG). PRIMARY AND SECONDARY OUTCOME MEASURES: Economic healthcare costs, clinical outcomes and patients' characteristics. RESULTS: The LAG consisted of 378 patients with a median negative economic results of -€3969, HAG of 205 (-€1030), respectively (p<0.001). Median duration of ventilation was 476 (248; 769) hours in the LAG and 389 (247; 608) hours in the HAG (p<0.001). Length of stay (LOS) in the LAG on ICU was 21 (12; 35) days and 16 (11; 25) days in the HAG (p<0.001). LOS in the hospital was 36 (22; 61) days in the LAG, and within the HAG, respectively, 26 (18; 48) days (p=0.001). CONCLUSIONS: High adherence to this single QI is associated with better clinical outcome and improved economic returns. Therefore, the results support the adherence to QI. However, the examined QI does not influence economic outcome as the decisive factor.

A contextual needs assessment of families with home invasive mechanical ventilation patients: A qualitative study.

OBJECTIVES: With the advancement of technology the number of patients surviving critical illness has increased. Home mechanical ventilation (HMV) is a growing option for patients requiring long-term mechanical ventilation. Caring for these patients is demanding and challenging. The aim of this study was to explore family caregivers'(carers) needs when providing care to adult patients under HMV from the perspective of nurses, home care attendants, and the caregivers themselves. METHODS: Overall, 15 participants (nine carers, three home nurses, and three home care attendants) were selected by purposive sampling. Data were collected by in-depth semi-structured interviews and structured observation. Finally, data were analyzed through conventional content analysis with MAXQDA software. RESULTS: Three categories of carers'needs were identified, including educational needs (basic and emergencies), psychological needs, and economic needs. In addition, since the needs, feelings, and views of caregivers change over time, the noted needs were divided into three periods: Pre-discharge preparation, initial transition from hospital to home, and appropriate long-term follow-up. CONCLUSION: The study results showed that the families of patients under invasive HMV require a standard discharge plan based on their care needs, financial concerns, and psychological screening before discharge as well as a suitable long-term follow-up plan in collaboration with a multidisciplinary treatment team, insurance providers, and home care services.

Lung ultrasound for the assessment of lung recruitment in neonates with massive pneumothorax during extracorporeal membrane oxygenation: a case report.

Bedside lung ultrasound may be an effective method for the assessment of lung recruitment in newborns with extracorporeal membrane oxygenation (ECMO). We report a case of a neonate who had severe hypoxemia with persistent pulmonary hypertension and massive pneumothorax due to meconium aspiration syndrome and was treated with ECMO. Positive pressure mechanical ventilation resulted in persistent massive air leakage from the disrupted pulmonary tissue. When ECMO was initiated, a "total lung rest" ventilation strategy was used to facilitate healing of the lung rupture and absorption of the pneumothorax. After complete absorption of the pneumothorax, lung recruitment was performed by progressively increasing the positive end-expiratory pressure under the guidance of lung ultrasound. Bedside lung ultrasound was successfully used to assess pneumothorax absorption and improvement of pulmonary inflammation and successfully guided the recruitment of collapsed alveoli and the withdrawal of ECMO.

Real-Time In Vitro Assessment of Aerosol Delivery During Mechanical Ventilation.

Background: A new real-time method for assessing factors determining aerosol delivery is described. Methods: A breath-enhanced jet nebulizer operated in a ventilator/heated humidifier system was tested during bolus and continuous infusion aerosol delivery. 99mTc (technetium)/saline was either injected (3 or 6 mL) or infused over time into the nebulizer. A shielded gamma ratemeter was oriented to count radioaerosol accumulating on an inhaled mass (IM) filter at the airway opening of a test lung. Radioactivity measured at 2-10-minute intervals was expressed as % nebulizer charge (bolus) or % syringe activity per minute infused. All circuit parts were measured and imaged by gamma camera to determine mass balance. Results: Ratemeter activity quantitatively reflected immediate changes in IM: 3 and 6 mL bolus IM% = 16.1 and 18.8% in 6 and 14 minutes, respectively; infusion IM% = 0.64 + 0.13 (run time, min), R2 0.999. Effect of nebulizer priming and system anomalies were readily detected in real time. Mass balance (basis = dose infused in 90 minutes): IM 39.2%, breath-enhanced jet nebulizer residual 35.5%, circuit parts including humidifier 23.4%, and total recovery 98.1%. Visual analysis of circuit component images identified sites of increased deposition. Conclusion: Real-time ratemeter measurement with gamma camera imaging provides operational feedback during in vitro testing procedures and yields a detailed analysis of the parameters influencing drug delivery during mechanical ventilation. This method of analysis facilitates assessment of device function and influence of circuit parameters on drug delivery.

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies.

BACKGROUND: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. METHODS: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. FINDINGS: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42·4% vs 44·2%; absolute difference -1·69 [-9·58 to 6·11] p=0·67; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5-8] vs 6 [5-8] cm H2O; p=0·0011). ICU mortality was higher in MICs than in HICs (30·5% vs 19·9%; p=0·0004; adjusted effect 16·41% [95% CI 9·52-23·52]; p<0·0001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0·80 [95% CI 0·75-0·86]; p<0·0001). INTERPRETATION: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. FUNDING: No funding.

Effect of enterally administered sleep-promoting medication on the intravenous sedative dose and its safety and cost profile in mechanically ventilated patients: A retrospective cohort study.

BACKGROUND: The clinical effect of enteral administration of sleep-promoting medication (SPM) in mechanically ventilated patients remains unclear. This study aimed to investigate the relationship between enteral SPM administration and the intravenous sedative dose and examine the safety and cost of enteral SPM administration. METHODS: This single-center retrospective cohort study was conducted in a Japanese tertiary hospital intensive care unit (ICU). The exposure was enteral SPM administration during mechanical ventilation. The outcome was the average daily propofol dose per body weight administered as a continuous sedative during mechanical ventilation. Patients were divided into three groups based on the timing of SPM administration at ICU admission: "administration within 48 hours (early administration [EA])," "administration after 48 hours (late administration [LA])," and "no administration (NA)." We used multiple linear regression models. RESULTS: Of 123 included patients, 37, 50, and 36 patients were assigned to the EA, LA, and NA groups, respectively. The average daily propofol dose per body weight was significantly lower in the EA group than in the LA and NA groups (ß -5.13 [95% confidence interval (CI) -8.93 to -1.33] and ß -4.51 [95% CI -8.59 to -0.43], respectively). Regarding safety, enteral SPM administration did not increase adverse events, including self-extubation. The total cost of neuroactive drugs tended to be lower in the EA group than in the LA and NA groups. CONCLUSIONS: Early enteral SPM administration reduced the average daily propofol dose per body weight without increasing adverse events.

Uso de infusión continua de bloqueadores neuromusculares en pacientes con COVID-19 en ventilación mecánica invasiva / Use of continuous infusion of neuromuscular blockers in patients with COVID-19 undergoing invasive mechanical ventilation

ANTECEDENTES: El objetivo del presente informe es: Describir el proceso para la elaboración de recomendaciones por el grupo de trabajo designado por el Ministerio de Salud, en adelante denominado grupo de trabajo. Trasladar las Recomendaciones efectuadas por dicho grupo de trabajo en atención al uso de infusión continua de bloqueadores neuromusculares en pacientes con COVID-19 en ventilación mecánica no invasiva, según la pregunta PICO (P: Población, I:Intervención, C:Comparador, O: Outcome o desenlaces) priorizada por el grupo de trabajo. La metodología considerada para arribar a la recomendación fue el Marco de Evidencia a la Decisión/Recomendación (EtD) desarrollado por el Grupo de Trabajo GRADE(1,2). METODOS: Formulación de la pregunta: ¿Debería utilizarse infusión continua de bloqueadores neuromusculares (BNM) versus no hacerlo, en pacientes con COVID-19 en ventilación mecánica invasiva (VMI? ¿Qué medicamento y qué pauta de dosificación debe administrarse? Identificación de la evidencia para la pregunta PICO: Se siguieron las orientaciones establecidas en el documento interno de UNAGESP: Orientaciones para el soporte metodológico otorgado al grupo de trabajo designado por el MINSA. Se describe a continuación los resultados del proceso: Se efectuó la búsqueda de guías de práctica clínica (GPC) que incluyeran recomendaciones respecto al uso de BNM en la población de interés, con fecha de búsqueda 15 de octubre de 2021 en las siguientes plataformas: eCOVID-19 living map of recommendations (eCovid-19 RecMap), Base internacional de Guías GRADE (BIGG) , Guidelines International Network (GIN), COVID-19 Guidelines Dashboard, National Institute for Health and Care Excellence - UK (NICE) y Trip database, identificándose 5 guías de práctica clínica (Ver Anexo 1). En base a criterios como fecha de búsqueda de la evidencia, uso de metodología GRADE para evaluar la certeza de la evidencia, disponibilidad de la tabla Perfil de evidencia o Resumen de hallazgos, disponibilidad de los criterios o Tabla EtD, tipo de recomendación emitida y valoración AGREE II realizada por el equipo de eCovid-19 RecMap, se seleccionó la GPC de Australia titulada "Australian guidelines for the clinical care of people with COVID-19"(5) elaborada por The National COVID-19 Clinical Evidence Taskforce, con fecha de publicación del 15 de octubre de 2021 que utilizó la metodología GRADE para la evaluación de la certeza de la evidencia y el Marco de Evidencia para la decisión (EtD) para esta pregunta PICO, estando disponibles a través de las plataformas magicapp(6) y eCovid RecMap(3). En ésta última plataforma, la evaluación de la calidad metodológica de la GPC mediante la herramienta AGREE II mostró puntajes adecuados en los dominios claves: Alcance y objetivos: 83.3%, Rigor en el desarrollo: 74% e Independencia editorial: 70.8%. La guía no identificó ningún estudio en COVID-19 y la evidencia que informó la recomendación provino de una revisión sistemática y meta-análisis de 5 ensayos clínicos en pacientes con Síndrome de distrés respiratorio agudo (SDRA) por otras causas. Sin embargo, no se identificó la fecha de búsqueda de los estudios ni los métodos realizados para esta revisión sistemática. La recomendación realizada en la GPC de Australia estuvo basada en evidencia con certeza muy baja. Debido a estos resultados, se decidió efectuar una búsqueda de estudios primarios en COVID-19, incorporando parcialmente los términos de búsqueda de la GPC de Australia. La búsqueda se realizó en MEDLINE/ vía Pubmed, plataforma L·OVE de Epistemonikos(7) y en MedRxiv, con fecha 15 de octubre de 2021 (Ver Anexo 1). Los criterios de selección de los estudios fueron: ensayos clínicos aleatorizados, cohortes o casos y control que evaluen la PICO planteada y reportaran al menos uno de los desenlaces de interés. En adición, se efectuó una búsqueda de revisiones sistemáticas de ensayos clínicos, que evaluaran el uso de la infusión continua de BNM en pacientes con SDRA, a fines de obtener evidencia indirecta que complementara los resultados de la búsqueda de estudios primarios en COVID-19. La evaluación de la calidad metodológica de las revisiones sistemáticas se realizó con la herramienta AMSTAR 2(8) y para ensayos clínicos se consideró la evaluación de riesgo de sesgo reportada por la revisión sistemática si esta utilizó la herramienta de Cochrane para ensayos clínicos aleatorios. En caso de estudios observacionales, se empleó la herramienta Risk Of Bias in Non-randomized Studies of Interventions (ROBINS-I)(9). La certeza de la evidencia fue realizada según el enfoque GRADE que toma en cuenta los siguientes criterios: diseño del estudio, riesgo de sesgo, inconsistencia en los resultados, ausencia de evidencia directa, imprecisión, sesgo de publicación, tamaño de efecto, gradiente dosis-respuesta, y efecto de los potenciales factores de confusión residual (los tres últimos aplicables en estudios observacionales)(10,11). Los resultados fueron presentados utilizando la Tablas de Resumen de Hallazgos (SOF, por sus siglas en inglés) construidas a partir del software en línea GRADEpro (https://gradepro.org/)(12). RECOMENDACIÓN: Se sugiere el uso de la infusión continua de bloqueador neuromuscular en pacientes con COVID-19 en ventilación mecánica invasiva con algunas de las siguientes condiciones: Síndrome de distrés respiratorio agudo (SDRA) moderado o grave (PaO2/FiO2 < 150 mmHg) en fase aguda Independientemente del valor de PaO2/FiO2: Asincronía ventilatoria mayor persistente, a pesar de una programación adecuada del ventilador mecánico. Ventilación en posición prona. Necesidad de sedación profunda. Persistencia de presiones plateau altas o PEEP alto. Presencia de barotrauma o riesgo elevado de desarrollarlo. JUSTIFICACIÓN DE LA RECOMENDACIÓN: Se identificó un estudio de cohorte retrospectivo multicéntrico(14) que utilizó la información disponible a través de registros electrónicos de pacientes de 174 centros de investigación en 31 países. El 12% de los centros participantes estaba ubicado en Latinoamérica. El estudio está disponible desde Febrero de 2021 como manuscrito aún no revisado por pares. El estudio incluyó a 2165 pacientes con COVID-19 en VMI, que ingresaron a UCI entre Febrero a Noviembre de 2021, en su mayoría durante la primera ola de la pandemia. El estudio comparó el uso de BNM por 2 o más días, sea uso continuo o intermitente (grupo intervención) versus el uso < 2 días luego del inicio de la VMI (grupo control). En conjunto, la mediana de la duración del BNM fue de 3 días (rango intercuartílico (RIC) 2-6) y en aquellos que usaron el BNM de forma continua, la duración fue de 2 días (RIC 1-5). Sin embargo, el estudio no reportó el BNM utilizado ni la dosis administrada. Asimismo, un 17% de participantes del grupo control llegó a recibir 2 días o más de BNM. La administración de co-intervenciones como pronación, maniobras de reclutamiento y uso de corticoides varió entre los grupos. El estudio realizó emparejamiento por puntaje de propensión en base a características clínicas y sociodemográficas y el análisis multivariado incluyó potenciales factores de confusión como uso de antibióticos, terapia de reemplazo renal continua, ECMO y decúbito prono. Una descripción más detallada del estudio está disponible en el Anexo 2. El estudio reportó un mayor riesgo de mortalidad a los 28 días entre los que habían recibido BNM (HRa: 2.20, IC 95%: 1.67-2.89; 1350 pacientes incluidos en el análisis multivariado). El riesgo de sesgo global fue calificado como Serio, dada la calificación de Serio en los dominios Sesgo debido a confusión, Sesgo en la clasificación de las intervenciones, Sesgo debido a datos perdidos y no información en el dominio Sesgos debido a desviaciones de las intervenciones propuestas, de la herramienta ROBINS-I. La certeza de la evidencia fue calificada como Baja debido a riesgo de sesgo muy serio.

Uso de Remifentanilo en pacientes COVID-19 críticos hospitalizados con ventilación mecánica / Use of Remifentanil in critical COVID-19 patients hospitalized with mechanical ventilation

ANTECEDENTES: El objetivo del presente informe es: Describir el proceso para la elaboración de recomendaciones por el grupo de trabajo designado por el Ministerio de Salud, en adelante denominado grupo de trabajo. Trasladar las Recomendaciones efectuadas por dicho grupo de trabajo en atención al uso de remifentanilo en pacientes COVID-19 críticos hospitalizados con ventilación mecánica, según la pregunta PICO (P: Población, I:Intervención, C:Comparador, O: Outcome o desenlaces) priorizada por el grupo de trabajo. La metodología considerada para arribar a la recomendación fue el Marco de Evidencia a la Decisión/Recomendación (EtD) desarrollado por el Grupo de Trabajo GRADE (1,2). ANALISIS: Formulación de la pregunta: En personas con COVID-19 crítico en ventilación mecánica invasiva ¿Qué analgésico opioide endovenoso debe utilizarse: Remifentanilo vs fentanilo? ¿Cuál es la dosis que debe administrarse? Identificación de la evidencia para la pregunta PICO: Se siguieron las orientaciones establecidas en el documento interno de UNAGESP: Orientaciones para el soporte metodológico otorgado al grupo de trab

Assessment of magnetic flux density properties of electromagnetic noninvasive phrenic nerve stimulations for environmental safety in an ICU environment.

Diaphragm weakness affects up to 60% of ventilated patients leading to muscle atrophy, reduction of muscle fiber force via muscle fiber injuries and prolonged weaning from mechanical ventilation. Electromagnetic stimulation of the phrenic nerve can induce contractions of the diaphragm and potentially prevent and treat loss of muscular function. Recommended safety distance of electromagnetic coils is 1 m. The aim of this study was to investigate the magnetic flux density in a typical intensive care unit (ICU) setting. Simulation of magnetic flux density generated by a butterfly coil was performed in a Berlin ICU training center with testing of potential disturbance and heating of medical equipment. Approximate safety distances to surrounding medical ICU equipment were additionally measured in an ICU training center in Bern. Magnetic flux density declined exponentially with advancing distance from the stimulation coil. Above a coil distance of 300 mm with stimulation of 100% power the signal could not be distinguished from the surrounding magnetic background noise. Electromagnetic stimulation of the phrenic nerve for diaphragm contraction in an intensive care unit setting seems to be safe and feasible from a technical point of view with a distance above 300 mm to ICU equipment from the stimulation coil.