Time course of electrical activity of the diaphragm (EAdi) in the peri extubation period and its role as predictor of extubation failure in difficult to wean patients.

INTRODUCTION: Weaning patients from mechanical ventilation is crucial in the management of acute respiratory failure (ARF). Spontaneous breathing trials (SBT) are used to assess readiness for extubation, but extubation failure remains a challenge. Diaphragmatic function, measured by electrical activity of the diaphragm (EAdi), may provide insights into weaning outcomes. MATERIALS AND METHODS: This prospective, observational study included difficult-to-wean patients undergoing invasive mechanical ventilation. EAdi was recorded before, during, and after extubation. Patients were categorized into extubation success and failure groups based on reintubation within 48 h. Statistical analysis assessed EAdi patterns and predictive value. RESULTS: Thirty-one patients were analyzed, with six experiencing extubation failure. Overall, EAdi increased significantly between the phases before the SBT, the SBT and post-extubation period, up to 24 h (p < 0.001). EAdi values were higher in the extubation failure group during SBT (p = 0.01). An EAdi > 30 µV during SBT predicted extubation failure with 92% sensitivity and 67% specificity. Multivariable analysis confirmed EAdi as an independent predictor of extubation failure. CONCLUSIONS: In difficult-to-wean patients, EAdi increases significantly between the phases before the SBT, the SBT and post-extubation period and is significantly higher in patients experiencing extubation failure. An EAdi > 30 µV during SBT may enhance extubation failure prediction compared to conventional parameters. Advanced monitoring of diaphragmatic function could improve weaning outcomes in critical care settings.

Dysregulated neutrophil extracellular traps formation in sepsis.

The migration and antimicrobial functions of neutrophils seem to be impaired during sepsis and contribute to the dysregulation of immune responses and disease pathogenesis. However, the role of neutrophil extracellular traps (NETs) remains to be clarified. The study aimed to analyse sequential phenotypic and functional changes of neutrophils during the time following the diagnosis of sepsis. We prospectively enrolled 49 septic and 18 non-septic patients from the intensive care unit (ICU) and emergency room (ER) and 20 healthy volunteers (HV). Baseline blood samples from septic and non-septic patients were collected within 12 h of admission to the hospital. Additional septic samples were drawn at 24, 48 and 72 h after baseline. Neutrophil phenotype and degranulation capacity were assessed by flow cytometry and NET formation was quantified by fluorescence. Neutrophils from septic patients exhibited increased CD66b, CD11b and CD177 expression but displayed reduced NET formation at baseline compared with non-septic patients and HV controls. Neutrophils expressing CD177 interacted less with platelets, were related to reduced NETosis and tended to indicate a worse sepsis outcome. In vitro experiments revealed that neutrophil function is compromised by the origin of sepsis, including the pathogen type and the affected organ. Assessing a decision tree model, our study showed that CD11b expression and NETosis values are useful variables to discriminate septic from non-septic patients. We conclude that sepsis induces changes in neutrophil phenotype and function that may compromise the effective capacity of the host to eliminate pathogens.

High-Flow Versus VenturiMask Oxygen Therapy to Prevent Reintubation in Hypoxemic Patients after Extubation: A Multicenter Randomized Clinical Trial.

Rationale: When compared with VenturiMask after extubation, high-flow nasal oxygen provides physiological advantages. Objectives: To establish whether high-flow oxygen prevents endotracheal reintubation in hypoxemic patients after extubation, compared with VenturiMask. Methods: In this multicenter randomized trial, 494 patients exhibiting PaO2:FiO2 ratio ⩽ 300 mm Hg after extubation were randomly assigned to receive high-flow or VenturiMask oxygen, with the possibility to apply rescue noninvasive ventilation before reintubation. High-flow use in the VenturiMask group was not permitted. Measurements and Main Results: The primary outcome was the rate of reintubation within 72 hours according to predefined criteria, which were validated a posteriori by an independent adjudication committee. Main secondary outcomes included reintubation rate at 28 days and the need for rescue noninvasive ventilation according to predefined criteria. After intubation criteria validation (n = 492 patients), 32 patients (13%) in the high-flow group and 27 patients (11%) in the VenturiMask group required reintubation at 72 hours (unadjusted odds ratio, 1.26 [95% confidence interval (CI), 0.70-2.26]; P = 0.49). At 28 days, the rate of reintubation was 21% in the high-flow group and 23% in the VenturiMask group (adjusted hazard ratio, 0.89 [95% CI, 0.60-1.31]; P = 0.55). The need for rescue noninvasive ventilation was significantly lower in the high-flow group than in the VenturiMask group: at 72 hours, 8% versus 17% (adjusted hazard ratio, 0.39 [95% CI, 0.22-0.71]; P = 0.002) and at 28 days, 12% versus 21% (adjusted hazard ratio, 0.52 [95% CI, 0.32-0.83]; P = 0.007). Conclusions: Reintubation rate did not significantly differ between patients treated with VenturiMask or high-flow oxygen after extubation. High-flow oxygen yielded less frequent use of rescue noninvasive ventilation. Clinical trial registered with www.clinicaltrials.gov (NCT02107183).

Medication errors in prescription and administration in critically ill patients.

AIM: To determine the prevalence and magnitude of medication errors and their association with patients' sociodemographic and clinical characteristics and nurses' work conditions. DESIGN: An observational, analytical, cross-sectional and ambispective study was conducted in critically ill adult patients. METHODS: Data concerning prescription errors were collected retrospectively from medical records and administration errors were identified through direct observation of nurses during drug administration. Those data were collected between April and July 2015. RESULTS: A total of 650 prescription errors were identified for 961 drugs in 90 patients (mean error 7[SD 4.1] per patient) and prevalence of 47.1% (95% CI 44-50). The most frequent error was omission of the prescribed medication. Intensive care unit stay was a risk factor associated with omission error (OR 2.14; 1.46-3.14: p < .01). A total of 294 administration errors were identified for 249 drugs in 52 patients (mean error 6 [SD 6.7] per patient) and prevalence of 73.5% (95% CI 68-79). The most frequent error was interruption during drug administration. Admission to the intensive care unit (OR 0.37; 0.21-0.66: p < .01), nurses' morning shift (OR 2.15; 1.10-4.18: p = .02) and workload perception (OR 3.64; 2.09-6.35: p < .01) were risk factors associated with interruption. CONCLUSIONS: Medication errors in prescription and administration were frequent. Timely detection of errors and promotion of a medication safety culture are necessary to reduce them and ensure the quality of care in critically ill patients. IMPACT: Medication errors occur frequently in the intensive care unit but are not always identified. Due to the vulnerability of seriously ill patients and the specialized care they require, an error can result in serious adverse events. The study shows that medication errors in prescription and administration are recurrent but preventable. These findings contribute to promote awareness in the proper use of medications and guarantee the quality of nursing care.

Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome.

BACKGROUND: Mechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R). METHODS: In fifteen patients with moderate ARDS, VT was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure--(Pplat) between 23 and 25 cmH2O. Low-flow ECCO2R was initiated when respiratory acidosis developed (pH < 7.25, PaCO2 > 60 mmHg). Ventilation parameters (VT, respiratory rate, PEEP), respiratory compliance (CRS), driving pressure (DeltaP = VT/CRS), arterial blood gases, and ECCO2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO2R when PaO2/FiO2 was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO2R were also collected. RESULTS: During the 2 h run in phase, VT reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO2 to within 10 % of baseline values. PEEP values tended to increase at VT of 4 mL/kg from 12.2 to 14.5 cmH2O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH2O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking). CONCLUSIONS: The low-flow ECCO2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS.

Ventilatory strategies in obstructive lung disease.

Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation (EFL) due to progressive airflow obstruction. The various mechanisms that cause EFL are central to understanding the physiopathology of COPD. At the end of expiration, dynamic inflation may occur due to incomplete emptying the lungs. This "extra" volume increases the alveolar pressure at the end of the expiration, resulting in auto-positive end-expiratory pressure (PEEP) or PEEPi. Acute exacerbations of COPD may result in increased airway resistance and inspiratory effort, further leading to dynamic hyperinflation. COPD exacerbations may be triggered by environmental exposures, infections (viral and bacterial), or bronchial inflammation, and may result in worsening respiratory failure requiring mechanical ventilation (MV). Acute exacerbations of COPD need to be distinguished from other events such as cardiac failure or pulmonary emboli. Strategies to treat acute respiratory failure (ARF) in COPD patients include noninvasive ventilation (NIV), pressure support ventilation, and tracheal intubation with MV. In this review, we discuss invasive and noninvasive techniques to address ARF in this patient population. When invasive MV is used, settings should be adjusted in a way that minimizes hyperinflation, while providing reasonable gas exchange, respiratory muscle rest, and proper patient-ventilator interaction. Further, weaning from MV may be difficult in these patients, and factors amenable to pharmacological correction (such as increased bronchial resistance, tracheobronchial infections, and heart failure) are to be systematically searched and treated. In selected patients, early use of NIV may hasten the process of weaning from MV and improve outcomes.

Drug-drug interactions in an intensive care unit and comparison of updates in two databases.

OBJECTIVE: Critically ill patients are at increased risk of drug-drug interactions  but their prevalence and clinical relevance remains unclear. The prevalence of  potential drug-drug interactions in an intensive care unit according to  Micromedex Drug-Reax® and Lexi-Interact® databases was studied and the  concordance between the two databases was assessed. In addition, drug-drug  interactions detected in 2013 were compared with those identified in 2018 to  determine updates between these years. METHOD: Between January and June 2013, 152 critical care patients were  prospectively included. Cardiac patients were excluded. Demographic and  clinical data together with the drugs administered on the first calendar day of  intensive care unit admission were recorded. Potential drug-drug interactions  were searched in both Drug-Reax® and Lexi-Interact ® and their prevalence,  level of severity and evidence were compared considering the same sample in  2013 and 2018. RESULTS: In 2013, 1,025 potential drug-drug interactions were identified, corresponding to 438 unique pairs. Lexi-Interact® identified more  interactions (92.8%) than Drug-Reax® (34.0%). The percentage of agreement between databases was 27.4%. The number of interactions  included in both databases increased after the five years but their level of  evidence   decreased. The most common potential drug-drug interactions involved sedatives and analgesics, intentionally prescribed concomitantly. Only two potential drug-drug interactions were classified as contraindicated by both  databases. None of the potential drug-drug interactions identified had a  noticeable clinical impact. Neither did they imply a prescription change. CONCLUSIONS: This study shows that the prevalence of potential drugdrug interactions in the intensive care unit is high, although their clinical relevance is generally low. Our data also show a lack of concordance between Drug-Reax® and Lexi-Interact®, as well as their  updates.

OBJETIVO: Los pacientes críticos presentan un mayor riesgo de interacciones farmacológicas, aunque su prevalencia y relevancia clínica siguen  sin estar claras. En el presente estudio se analizó la prevalencia de  interacciones farmacológicas potenciales en una unidad de cuidados intensivos  mediante las bases de datos Micromedex Drug-Reax® y Lexi-Interact® y se  evaluó la concordancia entre ambas bases de datos. También se compararon  las interacciones farmacológicas detectadas en 2013 con las identificadas en  2018 para evaluar las actualizaciones realizadas durante este periodo de  tiempo. Método: Entre enero y junio de 2013 se incluyeron de forma prospectiva 152  pacientes críticos. Los pacientes cardiacos fueron excluidos. Se registraron los  datos demográficos y clínicos junto con los fármacos administrados durante el  primer día de ingreso en la unidad de cuidados intensivos. Las interacciones se  buscaron tanto en Micromedex Drug-Reax® como en Lexi-Interact® y se  comparó su prevalencia, el nivel de severidad y la evidencia considerando la  misma muestra en 2013 y 2018. Resultados: En 2013 se identificaron 1.025 interacciones farmacológicas potenciales, correspondientes a 438 pares únicos. Lexi- Interact® identificó más interacciones (92,8%) que Drug-Reax® (34,0%). El  porcentaje de concordancia entre las dos bases de datos fue del 27,4%. El  número de interacciones incluidas en ambas bases de datos aumentó durante  los cinco años, pero su nivel de evidencia disminuyó. Las interacciones  farmacológicas potenciales más comunes incluyeron sedantes y analgésicos,  rescritos intencionadamente de forma concomitante. Sólo dos interacciones farmacológicas potenciales fueron clasificadas como contraindicadas por ambas  bases de datos. Ninguna de las interacciones identificadas tuvo un impacto clínico notable ni supuso un cambio de prescripción. CONCLUSIONES: ste estudio muestra que la prevalencia de interacciones farmacológicas potenciales en las unidades de cuidados intensivos es alta,  aunque su relevancia clínica es generalmente baja. Nuestros datos también  muestran la falta de concordancia entre Drug-Reax® y Lexi- Interact®, así  como sus actualizaciones.

Lung volumes and lung volume recruitment in ARDS: a comparison between supine and prone position.

BACKGROUND: The use of positive end-expiratory pressure (PEEP) and prone position (PP) is common in the management of severe acute respiratory distress syndrome patients (ARDS). We conducted this study to analyze the variation in lung volumes and PEEP-induced lung volume recruitment with the change from supine position (SP) to PP in ARDS patients. METHODS: The investigation was conducted in a multidisciplinary intensive care unit. Patients who met the clinical criteria of the Berlin definition for ARDS were included. The responsible physician set basal PEEP. To avoid hypoxemia, FiO2 was increased to 0.8 1 h before starting the protocol. End-expiratory lung volume (EELV) and functional residual capacity (FRC) were measured using the nitrogen washout/washin technique. After the procedures in SP, the patients were turned to PP and 1 h later the same procedures were made in PP. RESULTS: Twenty-three patients were included in the study, and twenty were analyzed. The change from SP to PP significantly increased FRC (from 965 ± 397 to 1140 ± 490 ml, p = 0.008) and EELV (from 1566 ± 476 to 1832 ± 719 ml, p = 0.008), but PEEP-induced lung volume recruitment did not significantly change (269 ± 186 ml in SP to 324 ± 188 ml in PP, p = 0.263). Dynamic strain at PEEP decreased with the change from SP to PP (0.38 ± 0.14 to 0.33 ± 0.13, p = 0.040). CONCLUSIONS: As compared to supine, prone position increases resting lung volumes and decreases dynamic lung strain.

Heat and moisture exchangers and heated humidifiers in acute lung injury/acute respiratory distress syndrome patients. Effects on respiratory mechanics and gas exchange.

OBJECTIVE: To compare, in acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, the short-term effects of heat and moisture exchangers (HME) and heated humidifiers (HH) on gas exchange, and also on respiratory system mechanics when isocapnic conditions are met. DESIGN: Prospective open clinical study. SETTING: Intensive Care Service. PATIENTS: Seventeen invasively ventilated ALI/ARDS patients. INTERVENTION: The study was performed in three phases: (1) determinations were made during basal ventilatory settings with HME; (2) basal ventilatory settings were maintained and HME was replaced by an HH; (3) using the same HH, tidal volume (Vt) was decreased until basal PaCO2 levels were reached. FiO2, respiratory rate and PEEP were kept unchanged. MEASUREMENTS AND RESULTS: Respiratory mechanics, Vdphys, gas exchange and hemodynamic parameters were obtained at each phase. By using HH instead of HME and without changing Vt, PaCO2 decreased from 46+/-9 to 40+/-8 mmHg (p<0.001) and Vdphys decreased from 352+/-63 to 310+/-74 ml (p<0.001). Comparing the first phase with the third, Vt decreased from 521+/-106 to 440+/-118 ml (p<0.001) without significant changes in PaCO2, Vd/Vt decreased from 0.69+/-0.11 to 0.62+/-0.12 (p<0.001), plateau airway pressure decreased from 25+/-6 to 21+/-6 cmH2O (p<0.001) and respiratory system compliance improved from 35+/-12 to 42+/-15 ml/cmH2O (p<0.001). PaO2 remained unchanged in the three phases. CONCLUSIONS: Reducing dead space with the use of HH decreases PaCO2 and more importantly, if isocapnic conditions are maintained by reducing Vt, this strategy improves respiratory system compliance and reduces plateau airway pressure.

End-inspiratory pause prolongation in acute respiratory distress syndrome patients: effects on gas exchange and mechanics.

BACKGROUND: End-inspiratory pause (EIP) prolongation decreases dead space-to-tidal volume ratio (Vd/Vt) and PaCO2. We do not know the physiological benefits of this approach to improve respiratory system mechanics in acute respiratory distress syndrome (ARDS) patients when mild hypercapnia is of no concern. METHODS: The investigation was conducted in an intensive care unit of a university hospital, and 13 ARDS patients were included. The study was designed in three phases. First phase, baseline measurements were taken. Second phase, the EIP was prolonged until one of the following was achieved: (1) EIP of 0.7 s; (2) intrinsic positive end-expiratory pressure ≥1 cmH2O; or (3) inspiratory-expiratory ratio 1:1. Third phase, the Vt was decreased (30 mL every 30 min) until PaCO2 equal to baseline was reached. FiO2, PEEP, airflow and respiratory rate were kept constant. RESULTS: EIP was prolonged from 0.12 ± 0.04 to 0.7 s in all patients. This decreased the Vd/Vt and PaCO2 (0.70 ± 0.07 to 0.64 ± 0.08, p < 0.001 and 54 ± 9 to 50 ± 8 mmHg, p = 0.001, respectively). In the third phase, the decrease in Vt (from 6.3 ± 0.8 to 5.6 ± 0.8 mL/Kg PBW, p < 0.001) allowed to decrease plateau pressure and driving pressure (24 ± 3 to 22 ± 3 cmH2O, p < 0.001 and 13.4 ± 3.6 to 10.9 ± 3.1 cmH2O, p < 0.001, respectively) and increased respiratory system compliance from 29 ± 9 to 32 ± 11 mL/cmH2O (p = 0.001). PaO2 did not significantly change. CONCLUSIONS: Prolonging EIP allowed a significant decrease in Vt without changes in PaCO2 in passively ventilated ARDS patients. This produced a significant decrease in plateau pressure and driving pressure and significantly increased respiratory system compliance, which suggests less overdistension and less dynamic strain.

Molecular diagnosis of bloodstream infections with a new dual-priming oligonucleotide-based multiplex PCR assay.

Mortality from bloodstream infections (BSIs) correlates with diagnostic delay and the use of inappropriate empirical treatment. Early PCR-based diagnosis could decrease inappropriate treatment, improving patient outcome. The aim of the present study was to assess the clinical utility of this molecular technology to diagnose BSIs. We assessed a new dual-priming oligonucleotide-based multiplex PCR assay, the Magicplex Sepsis Test (MST) (Seegene), along with blood culture (BC). A total of 267 patients from the intensive care unit and haematology and emergency departments were enrolled. Clinical data were also used by physicians to determine the likelihood of infection. Ninety-eight (37 %) specimens were positive: 29 (11 %) by both the MST and BC, 29 (11 %) by the MST only, and 40 (15 %) by BC only. The proportion of agreement between the two methods was 73 % (Cohen's κ: 0.45; 0.28-0.6; indicating fair to moderate agreement). According to clinical assessment, 63 (64 %) positive specimens were considered BSIs: 23 (36 %) were positive by both the MST and BC, 22 (35 %) were positive only by BC, and 18 (29 %) were positive only by the MST. Thirty-eight (14 %) positive specimens by the MST and/or BC were considered as contaminants. Of 101 specimens collected from patients receiving antibiotics, 20 (20 %) were positive by the MST and 32 (32 %) by BC. Sensitivity and specificity were 65 % and 92 %, respectively, for the MST and 71 % and 88 %, respectively for BC. We concluded that the MST shows a high specificity but changes in design are needed to increase bacteraemia detection. For viability in clinical laboratories, technical improvements are also required to further automate the process.

Comparison of the effects of two humidifier systems on endotracheal tube resistance.

PURPOSE: To compare the effects of two humidifier systems on endotracheal tube (ETT) resistance during mechanical ventilation, either an active heated humidifier (HH) or a passive heat and moisture exchanger (HME) was selected using current clinical recommendations. METHODS: This was a prospective clinical cohort study performed in an intensive care unit. Gas conditioning was performed using the HH in 22 patients and the HME in another 22. Patients were matched for endotracheal tube diameter, days of mechanical ventilation, simplified acute physiology score II (SAPS II), and fluid balance. RESULTS: Used-ETT resistance was measured immediately after extubation. Unused-ETT resistance was calculated with an identical, clean ETT. No differences were found between the HH and HME groups in ETT diameter (7.9 ± 0.4 vs. 7.9 ± 0.3 mm; p = 0.98), days of mechanical ventilation (11.3 ± 7.7 vs. 9.5 ± 4.5; p = 0.34), SAPS II (41.0 ± 13.6 vs. 42.0 ± 11.7; p = 0.79), or fluid balance (-2,552 ± 6,268 vs. -2,579 ± 5,422 mL; p = 0.98). ETT resistance increased from intubation to extubation: from 6.8 ± 1.1 to 10.6 ± 4.3 cmH(2)O L(-1) s(-1) in the HH group, (p < 0.001) and from 6.8 ± 1.1 to 10.2 ± 3.8 cmH(2)O L(-1) s(-1) in the HME group (p < 0.001), which is a 53% average increase in resistive load. CONCLUSIONS: We did not find differences between the two types of humidifiers in terms of airflow resistance during prolonged mechanical ventilation when the devices were selected on the basis of individual clinical needs. The increase in resistive load is physiologically relevant.