Feasibility of Setting the Tidal Volume Based on End-Expiratory Lung Volume: A Pilot Clinical Study.

OBJECTIVES: To assess the feasibility of setting the tidal volume (TV) as 25% of the actual aerated lung volume (rather than on ideal body weight) in patients with Acute Respiratory Distress Syndrome (ARDS). DESIGN: Physiologic prospective single-center pilot study. SETTING: Medical ICU specialized in the care of patients with ARDS. PATIENTS: Patients with moderate-severe ARDS deeply sedated or paralyzed, undergoing controlled mechanical ventilation with a ventilator able to measure the end-expiratory lung volume (EELV) with a washin, washout technique. INTERVENTIONS: Three-phase study (baseline, strain-selected TV setting, ventilation with strain-selected TV for 24 hr). The TV was calculated as 25% of the measured EELV minus the static strain due to the applied positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: Gas exchanges and respiratory mechanics were measured and compared in each phase. In addition, during the TV setting phase, driving pressure (DP) and lung strain (TV/EELV) were measured at different TVs to assess the correlation between the two measurements. The maintenance of the set strain-selected TV for 24 hours was safe and feasible in 76% of the patients enrolled. Three patients dropped out from the study because of the need to set a respiratory rate higher than 35 breaths per minute to avoid respiratory acidosis. The DP of the respiratory system was a satisfactory surrogate for strain in this population. CONCLUSIONS: In our population of 17 patients with moderate to severe ARDS, setting TV based on the actual lung size was feasible. DP was a reliable surrogate of strain in these patients, and DP less than or equal to 8 cm H2O corresponded to a strain less than 0.25.

Expiratory Muscle Activity Counteracts Positive End-Expiratory Pressure and Is Associated with Fentanyl Dose in Patients with Acute Respiratory Distress Syndrome.

Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

Individual response in patient's effort and driving pressure to variations in assistance during pressure support ventilation.

BACKGROUND: During Pressure Support Ventilation (PSV) an inspiratory hold allows to measure plateau pressure (Pplat), driving pressure (∆P), respiratory system compliance (Crs) and pressure-muscle-index (PMI), an index of inspiratory effort. This study aims [1] to assess systematically how patient's effort (estimated with PMI), ∆P and tidal volume (Vt) change in response to variations in PSV and [2] to confirm the robustness of Crs measurement during PSV. METHODS: 18 patients recovering from acute respiratory failure and ventilated by PSV were cross-randomized to four steps of assistance above (+ 3 and + 6 cmH2O) and below (-3 and -6 cmH2O) clinically set PS. Inspiratory and expiratory holds were performed to measure Pplat, PMI, ∆P, Vt, Crs, P0.1 and occluded inspiratory airway pressure (Pocc). Electromyography of respiratory muscles was monitored noninvasively from body surface (sEMG). RESULTS: As PSV was decreased, Pplat (from 20.5 ± 3.3 cmH2O to 16.7 ± 2.9, P < 0.001) and ∆P (from 12.5 ± 2.3 to 8.6 ± 2.3 cmH2O, P < 0.001) decreased much less than peak airway pressure did (from 21.7 ± 3.8 to 9.7 ± 3.8 cmH2O, P < 0.001), given the progressive increase of patient's effort (PMI from -1.2 ± 2.3 to 6.4 ± 3.2 cmH2O) in line with sEMG of the diaphragm (r = 0.614; P < 0.001). As ∆P increased linearly with Vt, Crs did not change through steps (P = 0.119). CONCLUSION: Patients react to a decrease in PSV by increasing inspiratory effort-as estimated by PMI-keeping Vt and ∆P on a desired value, therefore, limiting the clinician's ability to modulate them. PMI appears a valuable index to assess the point of ventilatory overassistance when patients lose control over Vt like in a pressure-control mode. The measurement of Crs in PSV is constant-likely suggesting reliability-independently from the level of assistance and patient's effort.

Special Considerations in Critical Care of the Congenital Heart Disease Patient.

Outcomes of congenital heart disease have improved markedly over the past 20 years, with survival to adulthood now close to 90%. The mean age of admission to an intensive care unit (ICU) is 40 years. The incidence of hospital and critical care admissions have increased significantly as a consequence of this improved survival. Intensivists are now confronted with the management not only of complex adult congenital heart disease (ACHD) lesions from a cardiac perspective, but also of extracardiac organ consequences of years of abnormal circulation after surgical or palliative correction. Kidney and liver dysfunction and respiratory and hematologic abnormalities are very common in this population. ACHD patients can present to the ICU for a vast number of reasons, classified in this review as medical noncardiac, medical cardiac, and surgical. Community/hospital-acquired infections, cerebrovascular accidents, and respiratory failure, alongside arrhythmias and heart failure, are responsible for medical admissions. Surgical admissions include postoperative management after correction or palliation, but also medical optimisation and work-up for advanced therapies. ICU management of this large heterogeneous group requires a thorough understanding of the pathophysiology in order to apply conventional adult critical care modalities; left ventricular or right ventricular dysfunction, pulmonary hypertension, intracardiac, extracardiac, and palliative surgical shunts can be present and require additional consideration. This review focuses on the pathophysiology, long-term sequelae, and different treatment modalities to supply a framework for the ICU physician caring for these patients. Successful outcome, especially in complex lesions, depends on early involvement of specialised ACHD centres.

A Novel Mask with Selective Ports for Inflow and Outflow Reduces CO2 Rebreathing during Non-Invasive Ventilation: A Physiological Study in Healthy Volunteers.

BACKGROUND: CO2 rebreathing is one of the risks associated with noninvasive ventilation (NIV), possibly contributing to failure. In a bench study, we showed that a novel mask design, with separate limbs for inflow and outflow gases, significantly reduced CO2 rebreathing in different ventilation settings. OBJECTIVES: The study aimed to test whether a new mask design could 1) reduce CO2 rebreathing in healthy volunteers during NIV (phase 1) and 2) reduce minute ventilation (phase 2). MATERIALS AND METHODS: Healthy volunteers were randomly assigned to NIV using two masks in a crossover design: a traditional single-limb mask for inflow and outflow gases and a mask with two separated limbs. In phase 1, six ventilation settings were tested for each mask: CPAP (PEEP 5 cmH2O) and pressure support ventilation (PSV, PS Level 5 cmH2O) using a mechanical ventilator with a bias flow of 8 or 20 L/min; free-flow CPAP (PEEP 5 cmH2O) with 60 or 90 L/min of gas flow. A nasal cannula was inserted in one nostril of the volunteers and connected to a CO2 gas analyzer to measure CO2 during the respiratory cycle. In phase 2, volunteers underwent a prolonged time of ventilation in CPAP 90 L/min and PSV with 20 L/min of bias flow. During free-flow CPAP, electrical impedance tomography was used to record the change in impedance during tidal breathing and then estimate tidal volume. RESULTS: Ten healthy adults were enrolled in phase 1, and 8 volunteers in phase 2. CO2 during inspiration was significantly lower in each setting with the two-limb versus the one-limb mask (p < 0.001). The maximum CO2 reduction was observed in the continuous-flow CPAP settings. EtCO2 was lower with the two-limb mask compared to the one-limb mask (p < 0.001). However, no difference in minute ventilation was observed between the two masks. CONCLUSION: The new mask design with two ports for inhaled and exhaled gases reduced the amount of CO2 rebreathing in all tested ventilation settings. The CO2 rebreathing reduction did not decrease minute ventilation in healthy volunteers.

Low skeletal muscle index and myosteatosis as predictors of mortality in critically ill surgical patients.

OBJECTIVES: After elective surgeries, low muscle mass and other specific body composition indexes, assessed by computed tomography (CT), are associated with adverse outcomes such as an increased risk for postoperative complications and higher mortality. However, limited information is available about the role of these indexes on short- and long-term outcomes in surgical patients admitted to the intensive care unit (ICU). The aim of this study was to assess the association of body composition indexes with 90-d mortality in this specific patient cohort. METHODS: This was a retrospective study including adult surgical patients admitted to the ICU between 2014 and 2018 who underwent a CT scan at the time of admission. Total muscle area (TMA), total fat area (TFA), visceral fat area (VFA), and intramuscular fat area (IMFA) were measured. We then calculated skeletal muscle index (SMI; TMA/m2), myosteatosis (IMFA/TMA), and visceral fat-to-muscle ratio (VFA/TMA). We analyzed the effects of these indexes on mortality. RESULTS: The study included 204 patients. Overall, 90-d mortality was 28%. Log-rank test and Cox multivariate analysis on 90-d mortality showed a significant association of low SMI and myosteatosis with 90-d mortality. Myosteatosis was also significantly associated with prolonged mechanical ventilation and increased ICU length of stay. CONCLUSIONS: Specific body composition indexes may predict mortality in surgical patients admitted to the ICU. Low SMI and myosteatosis were independently associated with increased 90-d mortality.

Reliability of plateau pressure during patient-triggered assisted ventilation. Analysis of a multicentre database.

PURPOSE: An inspiratory hold during patient-triggered assisted ventilation potentially allows to measure driving pressure and inspiratory effort. However, muscular activity can make this measurement unreliable. We aim to define the criteria for inspiratory holds reliability during patient-triggered breaths. MATERIAL AND METHODS: Flow, airway and esophageal pressure recordings during patient-triggered breaths from a multicentre observational study (BEARDS, NCT03447288) were evaluated by six independent raters, to determine plateau pressure readability. Features of "readable" and "unreadable" holds were compared. Muscle pressure estimate from the hold was validated against other measures of inspiratory effort. RESULTS: Ninety-two percent of the recordings were consistently judged as readable or unreadable by at least four raters. Plateau measurement showed a high consistency among raters. A short time from airway peak to plateau pressure and a stable and longer plateau characterized readable holds. Unreadable plateaus were associated with higher indexes of inspiratory effort. Muscular pressure computed from the hold showed a strong correlation with independent indexes of inspiratory effort. CONCLUSION: The definition of objective parameters of plateau reliability during assisted-breath provides the clinician with a tool to target a safer assisted-ventilation and to detect the presence of high inspiratory effort.

Clinical value of electrical impedance tomography (EIT) in the management of patients with acute respiratory failure: a single centre experience.

Objective.We will describe our clinical experience using electrical impedance tomography (EIT) in the management of mechanical ventilation in patients with acute respiratory failure and to determine to which extent EIT-guided positive end-expiratory pressure (PEEP) setting differed from clinically set values.Approach.We conducted a retrospective, observational cohort study performed in a hub centre for the treatment of acute respiratory failure and veno-venous extracorporeal membrane oxygenation (ECMO).Main results.Between January 2017 and December 2019, EIT was performed 54 times in 41 patients, not feasible only in one case because of signal instability. More than 50% was on veno-venous ECMO support. In 16 cases (30%), EIT was used for monitoring mechanical ventilation, i.e. to evaluate recruitability or sigh setting. In 37 cases (70%), EIT was used to set PEEP both with incremental (11 cases in nine patients) and decremental (26 cases, 18 patients) PEEP trial. Clinical PEEP before the decremental PEEP trial (PEEPPRE) was 14.1 ± 3.4 cmH2O and clinical PEEP set by clinicians after the PEEP trial (PEEPPOST) was 13.6 ± 3.1 (p = ns). EIT analyses demonstrated that more hypoxic patients were higher derecruited when compared to less hypoxic patients that were, on the contrary, more overdistended (p < 0.05). No acute effects of PEEP adjustment based on EIT on respiratory mechanics or regional EIT parameters modification were observed.Significance.The variability of EIT findings in our population confirmed the need to provide ventilation settings individually tailored and EIT was confirmed to be an optimal useful clinical bedside noninvasive tool to provide real-time monitoring of the PEEP effect and ventilation distribution.

Occurrence of pendelluft under pressure support ventilation in patients who failed a spontaneous breathing trial: an observational study.

BACKGROUND: Pendelluft, the movement of gas within different lung regions, is present in animal models of assisted mechanical ventilation and associated with lung overstretching. Due to rebreathing of CO2 as compared to fresh gas, pendelluft might reduce ventilatory efficiency possibly exacerbating patient's respiratory workload during weaning. Our aim was to measure pendelluft by electrical impedance tomography (EIT) in patients who failed a spontaneous breathing trial (SBT). METHODS: This is an observational study conducted in a general intensive care unit of a tertiary-level teaching hospital. EIT signal was recorded in 20 patients while pressure support (PS) ventilation was progressively reduced from clinical level (baseline) to 2 cmH2O, as in an SBT; four ventral-to-dorsal lung regions of interest were identified for pendelluft measurement. A regional gas movement (> 6 mL) occurring in a direction opposite to the global EIT signal was considered diagnostic for high pendelluft. RESULTS: Eight patients out of 20 (40%) were classified as high-pendelluft; baseline clinical characteristics did not differ between high- and low-pendelluft patients. At PS reduction, pendelluft and EtCO2 increased more in the high-pendelluft group (p < .001 and .011, respectively). The volume of gas subject to pendelluft moved almost completely from the ventral towards the dorsal lung regions, while the opposite movement was minimal (16.3 [10:32.8] vs. 0 [0:1.8] mL, p = .001). In a subgroup of patients, increased pendelluft volumes positively correlated with markers of respiratory distress such as increased respiratory rate, p0.1, and EtCO2. CONCLUSIONS: Occult pendelluft can be measured by EIT, and is frequently present in patients failing an SBT. When present, pendelluft increases with the reduction of ventilator support and is associated with increased EtCO2, suggesting a reduction of the ability to eliminate CO2.

Assisted mechanical ventilation promotes recovery of diaphragmatic thickness in critically ill patients: a prospective observational study.

BACKGROUND: Diaphragm atrophy and dysfunction are consequences of mechanical ventilation and are determinants of clinical outcomes. We hypothesize that partial preservation of diaphragm function, such as during assisted modes of ventilation, will restore diaphragm thickness. We also aim to correlate the changes in diaphragm thickness and function to outcomes and clinical factors. METHODS: This is a prospective, multicentre, observational study. Patients mechanically ventilated for more than 48 h in controlled mode and eventually switched to assisted ventilation were enrolled. Diaphragm ultrasound and clinical data collection were performed every 48 h until discharge or death. A threshold of 10% was used to define thinning during controlled and recovery of thickness during assisted ventilation. Patients were also classified based on the level of diaphragm activity during assisted ventilation. We evaluated the association between changes in diaphragm thickness and activity and clinical outcomes and data, such as ventilation parameters. RESULTS: Sixty-two patients ventilated in controlled mode and then switched to the assisted mode of ventilation were enrolled. Diaphragm thickness significantly decreased during controlled ventilation (1.84 ± 0.44 to 1.49 ± 0.37 mm, p < 0.001) and was partially restored during assisted ventilation (1.49 ± 0.37 to 1.75 ± 0.43 mm, p < 0.001). A diaphragm thinning of more than 10% was associated with longer duration of controlled ventilation (10 [5, 15] versus 5 [4, 8.5] days, p = 0.004) and higher PEEP levels (12.6 ± 4 versus 10.4 ± 4 cmH2O, p = 0.034). An increase in diaphragm thickness of more than 10% during assisted ventilation was not associated with any clinical outcome but with lower respiratory rate (16.7 ± 3.2 versus 19.2 ± 4 bpm, p = 0.019) and Rapid Shallow Breathing Index (37 ± 11 versus 44 ± 13, p = 0.029) and with higher Pressure Muscle Index (2 [0.5, 3] versus 0.4 [0, 1.9], p = 0.024). Change in diaphragm thickness was not related to diaphragm function expressed as diaphragm thickening fraction. CONCLUSION: Mode of ventilation affects diaphragm thickness, and preservation of diaphragmatic contraction, as during assisted modes, can partially reverse the muscle atrophy process. Avoiding a strenuous inspiratory work, as measured by Rapid Shallow Breathing Index and Pressure Muscle Index, may help diaphragm thickness restoration.

Driving Pressure Is Associated with Outcome during Assisted Ventilation in Acute Respiratory Distress Syndrome.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Higher driving pressure during controlled mechanical ventilation is known to be associated with increased mortality in patients with acute respiratory distress syndrome.Whereas patients with acute respiratory distress syndrome are initially managed with controlled mechanical ventilation, as they improve, they are transitioned to assisted ventilation. Whether higher driving pressure assessed during pressure support (assisted) ventilation can be reliably assessed and whether higher driving pressure is associated with worse outcomes in patients with acute respiratory distress syndrome has not been well studied. WHAT THIS ARTICLE TELLS US THAT IS NEW: This study shows that in the majority of adult patients with acute respiratory distress syndrome, both driving pressure and respiratory system compliance can be reliably measured during pressure support (assisted) ventilation.Higher driving pressure measured during pressure support (assisted) ventilation significantly associates with increased intensive care unit mortality, whereas peak inspiratory pressure does not.Lower respiratory system compliance also significantly associates with increased intensive care unit mortality. BACKGROUND: Driving pressure, the difference between plateau pressure and positive end-expiratory pressure (PEEP), is closely associated with increased mortality in patients with acute respiratory distress syndrome (ARDS). Although this relationship has been demonstrated during controlled mechanical ventilation, plateau pressure is often not measured during spontaneous breathing because of concerns about validity. The objective of the present study is to verify whether driving pressure and respiratory system compliance are independently associated with increased mortality during assisted ventilation (i.e., pressure support ventilation). METHODS: This is a retrospective cohort study conducted on 154 patients with ARDS in whom plateau pressure during the first three days of assisted ventilation was available. Associations between driving pressure, respiratory system compliance, and survival were assessed by univariable and multivariable analysis. In patients who underwent a computed tomography scan (n = 23) during the stage of assisted ventilation, the quantity of aerated lung was compared with respiratory system compliance measured on the same date. RESULTS: In contrast to controlled mechanical ventilation, plateau pressure during assisted ventilation was higher than the sum of PEEP and pressure support (peak pressure). Driving pressure was higher (11 [9-14] vs. 10 [8-11] cm H2O; P = 0.004); compliance was lower (40 [30-50] vs. 51 [42-61] ml · cm H2O; P < 0.001); and peak pressure was similar, in nonsurvivors versus survivors. Lower respiratory system compliance (odds ratio, 0.92 [0.88-0.96]) and higher driving pressure (odds ratio, 1.34 [1.12-1.61]) were each independently associated with increased risk of death. Respiratory system compliance was correlated with the aerated lung volume (n = 23, r = 0.69, P < 0.0001). CONCLUSIONS: In patients with ARDS, plateau pressure, driving pressure, and respiratory system compliance can be measured during assisted ventilation, and both higher driving pressure and lower compliance are associated with increased mortality.

Neurological outcome of postanoxic refractory status epilepticus after aggressive treatment.

Refractory status epilepticus (RSE) occurs in up to 30% of patients following resuscitation after cardiac arrest. The impact of aggressive treatment of postanoxic RSE on long-term neurological outcome remains uncertain. We investigated neurological outcome of cardiac arrest patients with RSE treated with a standardized aggressive protocol with antiepileptic drugs and anesthetics, compared with patients with other electroencephalographic (EEG) patterns. A prospective cohort of 166 consecutive patients with cardiac arrest in coma was stratified according to four independent EEG patterns (benign; RSE; generalized periodic discharges (GPDs); malignant nonepileptiform) and multimodal prognostic indicators. Primary outcomes were survival and cerebral performance category (CPC) at 6 months. Refractory status epilepticus occurred in 36 patients (21.7%) and was treated with an aggressive standardized protocol as long as multimodal prognostic indicators were not unfavorable. Refractory status epilepticus started after 3 ±â€¯2.3 days after cardiac arrest and lasted 4.7 ±â€¯4.3 days. A benign electroencephalographic patterns was recorded in 76 patients (45.8%), a periodic pattern (GPDs) in 13 patients (7.8%), and a malignant nonepileptiform EEG pattern in 41 patients (24.7%). The four EEG patterns were highly associated with different prognostic indicators (low flow time, clinical motor seizures, N20 responses, neuron-specific enolase (NSE), neuroimaging). Survival and good neurological outcome (CPC 1 or 2) at 6 months were 72.4% and 71.1% for benign EEG pattern, 54.3% and 44.4% for RSE, 15.4% and 0% for GPDs, and 2.4% and 0% for malignant nonepileptiform EEG pattern, respectively. Aggressive and prolonged treatment of RSE may be justified in cardiac arrest patients with favorable multimodal prognostic indicators. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Effect of Face Mask Design and Bias Flow on Rebreathing During Noninvasive Ventilation.

BACKGROUND: Noninvasive ventilation (NIV) is used to treat respiratory failure because it reduces the risks of endotracheal intubation and postextubation respiratory failure. A wide range of different interfaces is available, but concerns exist about rebreathing. This study evaluated a total face mask with a 2-limb ventilation circuit and separate access for inflow and outflow gas, which was developed to reduce rebreathing. METHODS: In a bench test, a standard total face mask (with a single connector to the ventilation circuit) and the modified total face mask were applied to a mannequin connected to an active breathing simulator. A known CO2 flow (V̇CO2 ) was delivered to the mannequin's trachea. We tested the following settings: CPAP with the mechanical PEEP valve set at 8 cm H2O (with 60 and 90 L/min continuous flow) and pressure support of 6 and 12 cm H2O (with 2 and 15 L/min bias flow). The settings were tested at simulated breathing frequencies of 15 and 30 breaths/min and with V̇CO2 of 200 and 300 mL/min. The active simulator generated a tidal volume of 500 mL. Airway pressure, air flow, CO2 concentration, and CO2 flow as the product of air flow and CO2 were recorded. RESULTS: The mean volume of CO2 rebreathed and the minimum CO2 inspiratory concentration were significantly lower with the modified mask than with the standard mask. The 15 L/min bias flow significantly decreased rebreathing with the DiMax0 mask, whereas it had no effect with the traditional mask. CONCLUSIONS: A face mask with a two-limb ventilation circuit and separate access for inflow and outflow gas reduces rebreathing during NIV. The addition of bias flow enhances this effect. Further studies are required to verify the clinical relevance.

Identification and Modulation of Microenvironment Is Crucial for Effective Mesenchymal Stromal Cell Therapy in Acute Lung Injury.

Rationale: There are controversial reports on applications of mesenchymal stromal cells (MSCs) in patients with acute respiratory distress syndrome (ARDS). Objectives: We hypothesized that lung microenvironment was the main determinant of beneficial versus detrimental effects of MSCs during ARDS. Methods: Lung proteome was profiled in three models of injury induced by acid instillation and/or mechanical ventilation in mice. Human gene of glutathione peroxidase-1 was delivered before MSC administration; or MSCs carrying human gene of IL-10 or hepatocyte growth factor were administered after lung injury. An inhibitory cocktail against IL-6, fibronectin, and oxidative stress was used in in vitro studies using human small airway epithelial cells and human MSCs after exposure to plasma of patients with ARDS. Measurements and Main Results: Distinct proteomic profiles were observed in three lung injury models. Administration of MSCs protected lung from ventilator-induced injury, whereas it worsened acid-primed lung injuries associated with fibrotic development in lung environment that had high levels of IL-6 and fibronectin along with low antioxidant capacity. Correction of microenvironment with glutathione peroxidase-1, or treatment with MSCs carrying human gene of IL-10 or hepatocyte growth factor after acid-primed injury, reversed the detrimental effects of native MSCs. Proteomic profiles obtained in the mouse models were also similarly observed in human ARDS. Treatment with the inhibitory cocktail in samples of patients with ARDS retained protective effects of MSCs in small airway epithelial cells. Conclusions: MSCs can be beneficial or detrimental depending on microenvironment at the time of administration. Identification of potential beneficiaries seems to be crucial to guide MSC therapy in ARDS.

Neurologic outcome of postanoxic refractory status epilepticus after aggressive treatment.

OBJECTIVE: To investigate neurologic outcome of patients with cardiac arrest with refractory status epilepticus (RSE) treated with a standardized aggressive protocol with antiepileptic drugs and anesthetics compared to patients with other EEG patterns. METHODS: In the prospective cohort study, 166 consecutive patients with cardiac arrest in coma were stratified according to 4 independent EEG patterns (benign, RSE, generalized periodic discharges [GPDs], malignant nonepileptiform) and multimodal prognostic indicators. Primary outcomes were survival and cerebral performance category (CPC) at 6 months. RESULTS: RSE occurred in 36 patients (21.7%) and was treated with an aggressive standardized protocol as long as multimodal prognostic indicators were not unfavorable. RSE started after 3 ± 2.3 days after cardiac arrest and lasted 4.7 ± 4.3 days. A benign EEG pattern was recorded in 76 patients (45.8%); a periodic pattern (GPDs) was seen in 13 patients (7.8%); and a malignant nonepileptiform EEG pattern was recorded in 41 patients (24.7%). The 4 EEG patterns were highly associated with different prognostic indicators (low-flow time, clinical motor seizures, N20 responses, neuron-specific enolase, neuroimaging). Survival and good neurologic outcome (CPC 1 or 2) at 6 months were 72.4% and 71.1% for benign EEG pattern, 54.3% and 44.4% for RSE, 15.4% and 0% for GPDs, and 2.4% and 0% for malignant nonepileptiform EEG pattern, respectively. CONCLUSIONS: Aggressive and prolonged treatment of RSE may be justified in patients with cardiac arrest with favorable multimodal prognostic indicators.