Electronic cigarette vaping with aged coils causes acute lung injury in mice.

Electronic cigarettes (e-cigarettes) have been used widely as an alternative to conventional cigarettes and have become particularly popular among young adults. A growing body of evidence has shown that e-cigarettes are associated with acute lung injury and adverse effects in multiple other organs. Previous studies showed that high emissions of aldehydes (formaldehyde and acetaldehyde) in aerosols were associated with increased usage of the same e-cigarette coils. However, the impact on lung function of using aged coils has not been reported. We investigated the relationship between coil age and acute lung injury in mice exposed to experimental vaping for 1 h (2 puffs/min, 100 ml/puff). The e-liquid contains propylene glycol and vegetable glycerin (50:50, vol) only. The concentrations of formaldehyde and acetaldehyde in the vaping aerosols increased with age of the nichrome coils starting at 1200 puffs. Mice exposed to e-cigarette aerosols produced from 1800, but not 0 or 900, puff-aged coils caused acute lung injury, increased lung wet/dry weight ratio, and induced lung inflammation (IL-6, TNF-α, IL-1ß, MIP-2). Exposure to vaping aerosols from 1800 puff-aged coils decreased heart rate, respiratory rate, and oxygen saturation in mice compared to mice exposed to air or aerosols from new coils. In conclusion, we observed that the concentration of aldehydes (formaldehyde and acetaldehyde) increased with repeated and prolonged usage of e-cigarette coils. Exposure to high levels of aldehyde in vaping aerosol was associated with acute lung injury in mice. These findings show significant risk of lung injury associated with prolonged use of e-cigarette devices.

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial.

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension.Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6).Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7-10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and [Formula: see text]/[Formula: see text] matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13-4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2-0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15-6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the [Formula: see text]/[Formula: see text] ratio.Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT02503241).

The repurposed use of anesthesia machines to ventilate critically ill patients with coronavirus disease 2019 (COVID-19).

BACKGROUND: The surge of critically ill patients due to the coronavirus disease-2019 (COVID-19) overwhelmed critical care capacity in areas of northern Italy. Anesthesia machines have been used as alternatives to traditional ICU mechanical ventilators. However, the outcomes for patients with COVID-19 respiratory failure cared for with Anesthesia Machines is currently unknow. We hypothesized that COVID-19 patients receiving care with Anesthesia Machines would have worse outcomes compared to standard practice. METHODS: We designed a retrospective study of patients admitted with a confirmed COVID-19 diagnosis at a large tertiary urban hospital in northern Italy. Two care units were included: a 27-bed standard ICU and a 15-bed temporary unit emergently opened in an operating room setting. Intubated patients assigned to Anesthesia Machines (AM group) were compared to a control cohort treated with standard mechanical ventilators (ICU-VENT group). Outcomes were assessed at 60-day follow-up. A multivariable Cox regression analysis of risk factors between survivors and non-survivors was conducted to determine the adjusted risk of death for patients assigned to AM group. RESULTS: Complete daily data from 89 mechanically ventilated patients consecutively admitted to the two units were analyzed. Seventeen patients were included in the AM group, whereas 72 were in the ICU-VENT group. Disease severity and intensity of treatment were comparable between the two groups. The 60-day mortality was significantly higher in the AM group compared to the ICU-vent group (12/17 vs. 27/72, 70.6% vs. 37.5%, respectively, p = 0.016). Allocation to AM group was associated with a significantly increased risk of death after adjusting for covariates (HR 4.05, 95% CI: 1.75-9.33, p = 0.001). Several incidents and complications were reported with Anesthesia Machine care, raising safety concerns. CONCLUSIONS: Our results support the hypothesis that care associated with the use of Anesthesia Machines is inadequate to provide long-term critical care to patients with COVID-19. Added safety risks must be considered if no other option is available to treat severely ill patients during the ongoing pandemic. CLINICAL TRIAL NUMBER: Not applicable.

Ideation and assessment of a nitric oxide delivery system for spontaneously breathing subjects.

BACKGROUND: There is an increasing interest in safely delivering high dose of inhaled nitric oxide (NO) as an antimicrobial and antiviral therapeutics for spontaneously breathing patients. A novel NO delivery system is described. METHODS: We developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide. The performance of the system was tested using a mechanical lung, assessing the NO concentration delivered at varying inspiratory flows. Safety was assessed in vitro and in vivo by measuring nitrogen dioxide (NO2) levels in the delivered NO gas. Lastly, we measured the inspired and expired NO and NO2 of this system in 5 healthy subjects during a 15-min administration of high dose NO (160 parts-per-million, ppm) using our delivery system. RESULTS: The system demonstrated stable delivery of prescribed NO levels at various inspiratory flow rates (0-50 L/min). The reservoir bag and a high flow of entering air minimized the oscillation of NO concentrations during inspiration on average 4.6 ppm for each 10 L/min increment in lung inspiratory flow. The calcium hydroxide scavenger reduced the inhaled NO2 concentration on average 0.9 ppm (95% CI -1.58, -0.22; p = .01). We performed 49 NO administrations of 160 ppm in 5 subjects. The average concentration of inspired NO was 164.8±10.74 ppm, with inspired NO2 levels of 0.7±0.13 ppm. The subjects did not experience any adverse events; transcutaneous methemoglobin concentrations increased from 1.05±0.58 to 2.26±0.47%. CONCLUSIONS: The system we developed to administer high-dose NO for inhalation is easy to build, reliable, was well tolerated in healthy subjects.

A lung rescue team improves survival in obesity with acute respiratory distress syndrome.

BACKGROUND: Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m2] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS. METHODS: In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012-2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015-2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring. RESULTS: The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m2), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m2). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13-0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16-0.74). CONCLUSION: Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.

Microbiome, biofilms, and pneumonia in the ICU.

PURPOSE OF REVIEW: Lower respiratory tract infections remain one of the leading causes of death in the world. Recently, the introduction of molecular methods based on DNA sequencing and microarrays for the identification of nonculturable microorganisms and subspecies variations has challenged the previous 'one bug - one disease' paradigm, providing us with a broader view on human microbial communities and their role in the development of infectious diseases. The purpose of this review is to describe recent understanding of the role of microbiome and bacterial biofilm in the development of lung infections, and, at the same time, to present new areas of research opportunities. RECENT FINDINGS: The review describes recent literature in cystic fibrosis patients, chronic obstructive pulmonary disease patients, and literature in mechanically ventilated patients that helped to elucidate the role of microbiome and biofilm formation in the development of pneumonia. SUMMARY: The characterization of the human microbiome and biofilms has changed our understanding of lower respiratory tract infections. More comprehensive, sensitive, and fast methods for bacterial, fungal, and viral detection are warranted to establish the colonization of the lower respiratory tract in healthy individuals and sick patients. Future research might explore the global bacterial, fungal, and viral pulmonary ecosystems and their interdependence to target novel preventive approaches and therapeutic strategies in chronic and acute lung infections.

Autologous transfusion of stored red blood cells increases pulmonary artery pressure.

RATIONALE: Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction. OBJECTIVES: We hypothesized that transfusion of autologous blood stored for 40 days would increase the pulmonary artery pressure in volunteers with endothelial dysfunction (impaired endothelial production of nitric oxide). We also tested whether breathing nitric oxide before and during transfusion could prevent the increase of pulmonary artery pressure. METHODS: Fourteen obese adults with endothelial dysfunction were enrolled in a randomized crossover study of transfusing autologous, leukoreduced blood stored for either 3 or 40 days. Volunteers were transfused with 3-day blood, 40-day blood, and 40-day blood while breathing 80 ppm nitric oxide. MEASUREMENTS AND MAIN RESULTS: The age of volunteers was 41 ± 4 years (mean ± SEM), and their body mass index was 33.4 ± 1.3 kg/m(2). Plasma hemoglobin concentrations increased after transfusion with 40-day and 40-day plus nitric oxide blood but not after transfusing 3-day blood. Mean pulmonary artery pressure, estimated by transthoracic echocardiography, increased after transfusing 40-day blood (18 ± 2 to 23 ± 2 mm Hg; P < 0.05) but did not change after transfusing 3-day blood (17 ± 2 to 18 ± 2 mm Hg; P = 0.5). Breathing nitric oxide decreased pulmonary artery pressure in volunteers transfused with 40-day blood (17 ± 2 to 12 ± 1 mm Hg; P < 0.05). CONCLUSIONS: Transfusion of autologous leukoreduced blood stored for 40 days was associated with increased plasma hemoglobin levels and increased pulmonary artery pressure. Breathing nitric oxide prevents the increase of pulmonary artery pressure produced by transfusing stored blood. Clinical trial registered with www.clinicaltrials.gov (NCT 01529502).

The unexpected epidural: a case report.

BACKGROUND: We report the peculiar case of a patient with a retained large epidural catheter fragment, incidentally found 12 years after its placement. Our primary aim is to emphasize how the breakage and retention of even exceptionally large portions of this device can go undetected. The patient can be completely asymptomatic and, with no clue that such a foreign body exists, the presentation of its potential complications can be subtle and misleading. To our knowledge, this is the first reported case of the incidental discovery of such a large fragment so many years after its placement. No consensus exists about how to handle this complication, therefore our report adds to the amount of available evidence. CASE PRESENTATION: A 53-year-old caucasian female with a history of diverticulitis requiring multiple hospitalizations underwent laparoscopic sigmoidectomy. The early postoperative period was complicated by peritonitis, demanding an urgent "second-look" exploratory laparoscopy. Nine days post-operatively, a filiform metallic object in the upper-quadrant was noted on x-ray. No epidural had been placed for either one of her recent surgeries. Given the patient's history, the object was initially thought to be a retained surgical sponge. Previous studies, however, showed that the same image was already present preoperatively. Upon further questioning, the patient reported an epidural being placed twelve years before, at the time of her pregnancy. No mention of breakage had been made to her at that time, nor a retained foreign body was ever reported afterwards, despite her many imaging exams. She also never experienced any symptoms. A 15 cm fragment of a wire-reinforced catheter was surgically retrieved under local anesthesia and fluoroscopic guidance. CONCLUSION: Breakage of the epidural catheter with fragment retention is a known complication of this device, possibly leading to devastating sequelae. The fragment can go undetected for years. In this case our finding was incidental and the patient was asymptomatic. However, in the event a neurologic complication arose, the identification of the unknowingly retained epidural as the causative agent could have been difficult and delayed, with potential harm to the patient.

Tracheal tube obstruction in mechanically ventilated patients assessed by high-resolution computed tomography.

BACKGROUND: Tracheal intubation compromises mucus clearance and secretions accumulate inside the tracheal tube (TT). The aim of this study was to evaluate with a novel methodology TT luminal obstruction in critically ill patients. METHODS: This was a three-phase study: (1) the authors collected 20 TTs at extubation. High-resolution computed tomography (CT) was performed to determine cross-sectional area (CSA) and mucus distribution within the TT; (2) five TTs partially filled with silicone were used to correlate high-resolution CT results and increased airflow resistance; and (3) 20 chest CT scans of intubated patients were reviewed for detection of secretions in ventilated patients' TT. RESULTS: Postextubation TTs showed a maximum CSA reduction of (mean±SD) 24.9±3.9% (range 3.3 to 71.2%) after a median intubation of 4.5 (interquartile range 2.5 to 6.5) days. CSA progressively decreased from oral to lung end of used TTs. The luminal volume of air was different between used and new TTs for all internal diameters (P<0.01 for new vs. used TTs for all studied internal diameters). The relationship between pressure drop and increasing airflow rates was nonlinear and depended on minimum CSA available to ventilation. Weak correlation was found between TT occlusion and days of intubation (R²=0.352, P=0.006). With standard clinical chest CT scans, 6 of 20 TTs showed measurable secretions with a CSA reduction of 24.0±3.9%. CONCLUSIONS: TT luminal narrowing is a common finding and correlates with increased airflow resistance. The authors propose high-resolution CT as a novel technique to visualize and quantify secretions collected within the TT lumen.

Respiratory therapy device modifications to prevent ventilator-associated pneumonia.

PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is a controversial entity in the field of critical care. After years of research and significant efforts from regulatory agencies and hospitals, this complication is still frequently affecting mechanically ventilated patients, making VAP an active battleground for research. As a result, several preventive measures have recently been tested in experimental and clinical trials. Our interest is focused on those innovations related to the endotracheal tube (ETT). RECENT FINDINGS: Four ETT-related VAP causative mechanisms are reviewed, together with different associated potential solutions. Technologies such as the subglottic secretion drainage and the Mucus Slurper have been studied to eliminate subglottic secretion pooling. Novel designs for the cuff and the management of its pressure may avoid leakage. Antimicrobial coatings can prevent endoluminal biofilm formation, whereas using an ETT cleaning device may also be beneficial. Finally, preserving the tracheal ciliary function will keep our best physiologic protection active. SUMMARY: VAP prevention strategies are a continuously evolving field. Being able to identify the most valuable ideas needs a deep understanding of the disease pathophysiology. The role of the ETT is crucial and there is need for our standards of care to improve. This may soon be possible with newer technologies becoming increasingly available to clinicians.

Role of acupuncture in critically ill patients: A systematic review.

Acupuncture is part of a complex medical approach used in China for about 2000 years, known as Traditional Chinese Medicine, whose central assumption is that health occurs when the patterned energy flow throughout the body is balanced. Within this paradigm, acute illness occurs when a major state of imbalance or disruption arises, and the use of acupuncture may help in correcting these imbalances. While the Chinese hospital system often offers the integration of traditional and western medicine, in Europe and the United States this combined approach is infrequently practiced. However, several investigations have consistently shown the effectiveness of acupuncture for different aspects of critical illness. The aim of this systematic review is to increase the clinician's awareness of the current evidence regarding the use of acupuncture for the management of critically ill patients, both alone or as a complement to western medicine. The effects of acupuncture on critical illness, with a particular focus on respiratory function, pain and delirium treatment and prevention, circulatory function, nutritional support, and recovery after acute illness are explored and summarized, and evidence is provided that acupuncture is an acceptable and feasible option for the management of several aspects of critical illness. In addition, we suggest a practical selection of potentially useful acupuncture points in the critical care setting, with indications for simple localization and the correct puncture method.

Changes in upper airways microbiota in ventilator-associated pneumonia.

BACKGROUND: The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. METHODS: Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). RESULTS: Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value < 0.012). Furthermore, an overall decrease in microbial diversity was observed in both groups at T3 as compared to T0. At T3, a loss of some genera (Prevotella 7, Fusobacterium, Neisseria, Escherichia-Shigella and Haemophilus) was found in VAP patients. In contrast, eight genera belonging to the Bacteroidetes, Firmicutes and Fusobacteria phyla was predominant in this group. However, it is unclear whether VAP caused dysbiosis or dysbiosis caused VAP. CONCLUSIONS: In a small sample size of intubated patients, microbial diversity at intubation was less in patients with VAP compared to patients without VAP.

Effect of Acupuncture on Diaphragm Function in Healthy Volunteers: A Pilot Clinical Study.

Introduction: In western medicine, the diaphragm is the main inspiratory muscle. It is involved in the postural control of the trunk and contributes to balance performance. In traditional Chinese medicine (TCM), the diaphragm represents a gateway between the lower and upper parts of the body, and it regulates the descending and ascending functions of the whole organism. The aim of this study was to assess the effect of acupuncture on diaphragm function. Methods: A proof-of-concept, prospective, controlled, pilot trial in healthy volunteers. Respiratory rate, inspired volume, diaphragm excursion, and thickening were measured during tidal and maximal breathing at baseline and after sham or real acupuncture. Acupuncture was performed on Yanglingquan (GB34), Tai Chong (LV3), Danzhong (CV17), Geshu (BL17), and Geguan (BL46). Results: Ten participants were enrolled (6 males, weight 71 ± 12 kg, height 173 ± 9 cm, BMI 21 ± 1.3 kg/m2). During tidal breathing, tidal volume, diaphragm displacement, and end-expiratory diaphragm thickness did not change with sham or real acupuncture as compared to baseline; thickening ratio was 43.5 ± 16.6 vs. 31.3 ± 14.9 (sham) vs. 30.8 ± 15.3% (baseline), p=0.1066. During breaths at vital capacity, the acupuncture group, as compared to both baseline and sham acupuncture, had a trend toward a larger tidal volume (3840 ± 690 vs. 3110 ± 880 vs. 3230 ± 750 ml, p=0.1247) and showed a significantly higher thickening ratio (270.6 ± 136.4 vs. 172.4 ± 57.4 vs. 188.6 ± 41.7%, p=0.0414). Conclusions: Acupuncture significantly influenced diaphragm function in healthy volunteers, improving its inspiratory thickening fraction during breaths at vital capacity, as compared to no or sham acupuncture.

High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia.

OBJECTIVE: To evaluate whether the use of inhaled nitric oxide (iNO)200 improves respiratory function. METHODS: This retrospective cohort study used data from pregnant patients hospitalized with severe bilateral coronavirus disease 2019 (COVID-19) pneumonia at four teaching hospitals between March 2020 and December 2021. Two cohorts were identified: 1) those receiving standard of care alone (SoC cohort) and 2) those receiving iNO200 for 30 minutes twice daily in addition to standard of care alone (iNO200 cohort). Inhaled nitric oxide, as a novel therapy, was offered only at one hospital. The prespecified primary outcome was days free from any oxygen supplementation at 28 days postadmission. Secondary outcomes were hospital length of stay, rate of intubation, and intensive care unit (ICU) length of stay. The multivariable-adjusted regression analyses accounted for age, body mass index, gestational age, use of steroids, remdesivir, and the study center. RESULTS: Seventy-one pregnant patients were hospitalized for severe bilateral COVID-19 pneumonia: 51 in the SoC cohort and 20 in the iNO200 cohort. Patients receiving iNO200 had more oxygen supplementation-free days (iNO200: median [interquartile range], 24 [23-26] days vs standard of care alone: 22 [14-24] days, P=.01) compared with patients in the SoC cohort. In the multivariable-adjusted analyses, iNO200 was associated with 63.2% (95% CI 36.2-95.4%; P<.001) more days free from oxygen supplementation, 59.7% (95% CI 56.0-63.2%; P<.001) shorter ICU length of stay, and 63.6% (95% CI 55.1-70.8%; P<.001) shorter hospital length of stay. No iNO200-related adverse events were reported. CONCLUSION: In pregnant patients with severe bilateral COVID-19 pneumonia, iNO200 was associated with a reduced need for oxygen supplementation and shorter hospital stay.

The repurposed use of anesthesia machines to ventilate critically ill patients with Coronavirus Disease 2019 (COVID-19).

BackgroundThe surge of critically ill patients due to the coronavirus disease-2019 (COVID-19) overwhelmed critical care capacity in areas of northern Italy. Anesthesia machines have been used as alternatives to traditional ICU mechanical ventilators. However, the outcomes for patients with COVID-19 respiratory failure cared for with Anesthesia Machines is currently unknow. We hypothesized that COVID-19 patients receiving care with Anesthesia Machines would have worse outcomes compared to standard practice.MethodsWe designed a retrospective study of patients admitted with a confirmed COVID-19 diagnosis at a large tertiary urban hospital in northern Italy. Two care units were included: a 27-bed standard ICU and a 15-bed temporary unit emergently opened in an operating room setting. Intubated patients assigned to Anesthesia Machines (AM group) were compared to a control cohort treated with standard mechanical ventilators (ICU-VENT group). Outcomes were assessed at 60-day follow-up. A multivariable Cox regression analysis of risk factors between survivors and non-survivors was conducted to determine the adjusted risk of death for patients assigned to AM group.ResultsComplete daily data from 89 mechanically ventilated patients consecutively admitted to the two units were analyzed. Seventeen patients were included in the AM group, whereas 72 were in the ICU-VENT group. Disease severity and intensity of treatment were comparable between the two groups. The 60-day mortality was significantly higher in the AM group compared to the ICU-vent group (12/17 vs. 27/72, 70.6% vs. 37.5%, respectively, p = 0.016). Allocation to AM group was associated with a significantly increased risk of death after adjusting for covariates (HR 4.05, 95% CI: 1.75-9.33, p = 0.001). Several incidents and complications were reported with Anesthesia Machine care, raising safety concerns.ConclusionsOur results support the hypothesis that care associated with the use of Anesthesia Machines is inadequate to provide long-term critical care to patients with COVID-19. Added safety risks must be considered if no other option is available to treat severely ill patients during the ongoing pandemic.Clinical Trial NumberNot applicable.

Identifying clinical and biochemical phenotypes in acute respiratory distress syndrome secondary to coronavirus disease-2019.

BACKGROUND: Acute respiratory distress syndrome (ARDS) secondary to coronavirus disease-2019 (COVID-19) is characterized by substantial heterogeneity in clinical, biochemical, and physiological characteristics. However, the pathophysiology of severe COVID-19 infection is poorly understood. Previous studies established clinical and biological phenotypes among classical ARDS cohorts, with important therapeutic implications. The phenotypic profile of COVID-19 associated ARDS remains unknown. METHODS: We used latent class modeling via a multivariate mixture model to identify phenotypes from clinical and biochemical data collected from 263 patients admitted to Massachusetts General Hospital intensive care unit with COVID-19-associated ARDS between March 13 and August 2, 2020. FINDINGS: We identified two distinct phenotypes of COVID-19-associated ARDS, with substantial differences in biochemical profiles despite minimal differences in respiratory dynamics. The minority phenotype (class 2, n = 70, 26·6%) demonstrated increased markers of coagulopathy, with mild relative hyper-inflammation and dramatically increased markers of end-organ dysfunction (e.g., creatinine, troponin). The odds of 28-day mortality among the class 2 phenotype was more than double that of the class 1 phenotype (40·0% vs.· 23·3%, OR = 2·2, 95% CI [1·2, 3·9]). INTERPRETATION: We identified distinct phenotypic profiles in COVID-19 associated ARDS, with little variation according to respiratory physiology but with important variation according to systemic and extra-pulmonary markers. Phenotypic identity was highly associated with short-term mortality. The class 2 phenotype exhibited prominent signatures of coagulopathy, suggesting that vascular dysfunction may play an important role in the clinical progression of severe COVID-19-related disease.