Download Free Medical Acute Respiratory Distress Syndrome PowerPoint Presentation

Acute Respiratory Distress Syndrome PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical PowerPoint presentation titled "Acute Respiratory Distress Syndrome" by Jon Pickos, DO; Brian Sumner, MD; Michael Franczak, MD; Melissa Villars, MD, MPH; Mina Ghobrial, MD and Sean Hickey, MD.

This medical PowerPoint presentation talks about Acute Respiratory Distress Syndrome (ARDS), a severe lung condition that causes fluid to accumulate in the lungs, making it difficult to breathe. ARDS is often seen in critically ill patients and can be caused by a variety of factors, including pneumonia, sepsis, trauma, and aspiration.

The hallmark of ARDS is the presence of widespread inflammation in the lungs, which can lead to damage of the lung tissue and decreased oxygen exchange. Symptoms of ARDS may include rapid breathing, shortness of breath, low blood oxygen levels, and fatigue.

Tags : Acute Respiratory Distress Syndrome, ARDS, severe lung condition, inflammation in the lungs, critical care medicine, critical care medicine PowerPoint presentation

Published on : Mar 28, 2023 | Views : 979 | Downloads : 1

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

DEEP DIVE SERIES Acute Respiratory Distress Syndrome Acute Respiratory Distress Syndrome (ARDS) is a life-threatening form of respiratory failure characterized by massive inflammation leading to pulmonary edema, decruitment of alveoli, and hypoxemia. Despite its incidence rate and lethality, there are limited direct therapeutic options available for its treatment. This EMRA Critical Care Committee Deep Dive will review the current best available literature on ARDS management and provide insight on how to best treat ARDS patients in the emergency department. By Jon Pickos, DO; Brian Sumner, MD; Michael Franczak, MD; Melissa Villars, MD, MPH; Mina Ghobrial, MD; Sean Hickey, MD
Slide 2-

Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome Acute Respiratory Distress Syndrome Network, et al. N Engl J Med. 2000;342(18):1301-1308. Objective - To compare a lung protective strategy using low tidal volumes to a traditional ventilation strategy in patients with Acute Lung Injury and Acute Respiratory Distress Syndrome Intervention - Patients receiving mechanical ventilation were randomly assigned to either traditional tidal volumes (starting at 12mL/kg and plateau pressure <50cm H2O) or low tidal volumes (starting at 6mL/kg and plateau pressure <30cm H2O) -Monitored for 28 days or until death Methods - Multicenter randomized control trial comparing low tidal volume ventilation with a traditional ventilation strategy - 861 patients who were intubated with ratios of PaO2/FiO2 <300, bilateral pulmonary infiltrates, and no signs of left atrial hypertension or pulmonary-capillary wedge pressures of 18mm Hg or less - Inclusion criteria: >18 year old patients receiving mechanical ventilation with a diagnosis of ALI/ARDS less than 36 hours before enrollment in the trial Primary Outcome: Mortality before discharge or before breathing without assistance; ventilator-free days at 28 days The trial was terminated early as the use of lower tidal volumes was associated with decreased mortality and increased ventilator-free days The second primary outcome may be difficult to interpret as there was a similarity of ventilator-free days among survivors in both groups The Bottom Line A lung-protective ventilation strategy emphasizing lower tidal volume ventilation over acidosis or partial pressure of arterial CO2 reduces mortality in patients with ALI and ARDS DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 3-

Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome Brower RG, Lanken PN, MacIntyre N, et al. N Engl J Med. 2004;351:327-336. Objective - To compare the effects of using either a High or Low Positive End-Expiratory Pressure (PEEP) strategy on clinical outcomes in patients with acute lung injury and acute respiratory distress syndrome Intervention - Patients receiving mechanical ventilation with a PaO2/FiO2 of less than 300, recent bilateral pulmonary infiltrates, and no evidence of left-atrial hypertension were randomly assigned to either a low or high PEEP strategy Methods - Multicenter randomized control trial comparing a low or high PEEP strategy in patients with acute lung injury/ARDS -Two different strategies for adjusting PEEP and FiO2 were developed with a goal SpO2 of 88-95% or PaO2 of 55-80mmHg -Both groups used a 6mL/kg tidal volume goal and a plateau-pressure less than 30cm H2O goal - 549 patients were included in the trial Primary Outcome: Proportion of patients who died prior to discharge home without assisted breathing Secondary Outcomes: Ventilator-free days, ICU-free days, organ failure-free days The Bottom Line In patients with ALI/ARDS, there is no mortality difference between a High versus Low PEEP strategy, further emphasizing the importance of low tidal volumes and low inspiratory pressures DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 4-

Driving Pressure and Survival in the Acute Respiratory Distress Syndrome Amato MB, Meade MO, Slutsky AS, et al. N Engl J Med. 2015;372(8):747-755. Objective - To simplify optimal settings for mechanical ventilation in patients with ARDS by comparing driving pressure (ΔP) as an index for survival, relative to tidal volume (Vt), PEEP, and plateau pressure -Lower tidal volumes, lower plateau pressures, and higher PEEP have been associated with improved mortality metrics in patients with ARDS -The relative importance of each variable is controversial Methods - A mediation analysis of 3652 patients with ARDS from nine previous RCTs - The authors examined driving pressure or ΔP, defined as tidal volume/respiratory system compliance (Vt/Crs) or plateau pressure - PEEP, as an independent variable associated with survival - The authors also evaluated Vt, plateau pressure, and PEEP as variables associated with survival Primary Outcome: Mortality at 60 days Driving Pressure (ΔP) = Tidal Volume / Compliance of Respiratory System = Plateau Pressure - PEEP Higher ΔP predicted higher mortality rates across the analyzed RCTs Higher mortality was found only when higher driving pressures were associated with higher plateau pressures Higher survival rates associated with higher PEEP were found only when the higher PEEP was associated with decreased ΔP Thus survival benefits associated with reduction in tidal volume or increases in PEEP were only present if associated with decreased in ΔP The authors did not find a similar mediating effect with any of the other tested variables Driving pressure thought to be surrogate for cyclic lung strain The Bottom Line A Driving Pressure <15 was found to be the most accurate ventilatory variable in stratify patient risk, noting that decreases in ΔP are associated with increased survival DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 5-

Effect of Lung Recruitment and Titrated PEEP v Low PEEP on Mortality: a multicenter, randomised controlled trial Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial Investigators. JAMA. 2017;318(14):1335-1345. Objective To determine if lung recruitment and PEEP titration decreased 28-day mortality in patients with ARDS compared to a low-PEEP strategy Methods: Multicenter RCT across 120 ICUs in 9 countries over 6 years Intervention Lung recruitment maneuvers: Titrate up PEEP: with 25 cm H2O for 1 minute, then 35 for 1 min, then 45 for 2 minutes and then titrate down PEEP associated with best compliance (minimum of 11) for 24 hours (up-titration later lowered to 25, 30, 35 PEEP) Control ARDSNet or lower PEEP Enrollment Total Patients Intervention Group Control Group 1010 501 509 Primary Outcome: Mortality at 28 days 55.3% of patients in experimental group v 49.3% in control group died (HR 1.20, 95% 1.01-1.42, p = 0.041) Secondary Outcomes: Compared to control group, experimental group had increased 6-mo mortality, decreased number of ventilator free days, and increased risk of pneumothorax and barotrauma The Bottom Line The study concludes that a ventilatory management strategy with lung recruitment and titrated PEEP compared to low PEEP increased 28 day mortality and therefore should not be used. DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 6-

Prone Positioning in Severe Acute Respiratory Distress Syndrome Guérin C, Reignier J, Richard JC, et al. N Engl J Med. 2013;368(23):2159-2168. Objective - To assess if the early application of prone positioning reduces all-cause mortality at 28 days, when compared with supine positioning, in patients with severe acute respiratory distress syndrome Intervention - Patients with severe ARDS underwent proning for a minimum of 16 consecutive hours, daily for at least 28 days Methods - Multicenter, prospective, randomized-controlled trial - 466 patients with severe ARDS were randomized to supine positioning or prone-positioning for at least 16 hours repeated daily for at least 28 days -Patients underwent an initial 12 to 24 hour stabilization period prior to enrollment - Inclusion Criteria: Severe ARDS, defined as a PaO2/FiO2 < 150mm Hg with an FiO2 of at least 0.6, PEEP of at least 5cm H2O, and a tidal volume of about 6mL/kg, and mechanical ventilation for < 36 hours Primary Outcome: Mortality at 28-days The 28-day mortality was 16.0% in the prone group compared to 32.8% in the supine group (p<0.001) The hazard ratio for death at 28-days with prone positioning was 0.39 (95% CI, 0.25-0.63) The mortality benefit was also demonstrated at 90-days, with a hazard ratio of 0.44 (95% CI 0.29-0.67) The Bottom Line In patients with severe ARDS, particularly in patients with severe hypoxemia, the early use of prolonged prone-positioning significantly decreases mortality at 28 and 90 days DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 7-

Comparison of Two Fluid-Management Strategies in Acute Lung Injury National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, et al. N Engl J Med. 2006;354(24):564-2575. Objective - To compare a conservative fluid management strategy with a liberal fluid management strategy in patients with acute lung injury Intervention - Patient were randomized to receive either a conservative fluid management strategy (targeting a CVP <4mm Hg) or a liberal fluid management strategy (targeting a CVP of 10-14mm Hg) Methods - Multicenter, two-by-two factorial, randomized-controlled trial -1000 patients were randomized to either a conservative or liberal fluid management strategy, as well as randomized to receive either a pulmonary-artery catheter (PAC) or a central-venous catheter (CVC) - Eligible patients had to be receiving positive-pressure mechanical ventilation, have a PaO2/FiO2 <300, bilateral infiltrates on chest x-ray, without evidence of left atrial hypertension Primary Outcome: Mortality at 60 days Secondary Outcomes included: Ventilator-free days and organ-failure-free days No difference in 60-day mortality between the conservative versus liberal fluid strategy groups nor the PAC vs CVC groups The conservative strategy had greater ventilator-free days and ICU-free days The Bottom Line There was no difference in mortality at 60 days between a conservative and liberal fluid management strategy. However, a conservative fluid strategy was associated with significantly greater ventilator-free days, improved measures of lung function, and fewer ICU-days, without a significant increase in non-pulmonary organ failures. DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 8-

Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome (ACURASYS) Papazian L, Forel JM, Gacouin A, et al. N Engl J Med. 2010;363(12):1107-1116. Objective This was a multicenter, randomized, placebo-controlled, double-blind trial to determine whether a short period of treatment with the neuromuscular blocking agent cisatracurium besylate early in the course of severe ARDS would improve clinical outcomes. Intervention Patients randomized to cisatracurium besylate (CB) bolus + drip vs placebo. Methods -Patients were eligible if endotracheally intubated for acute hypoxemic respiratory failure for <48 hours and had clinical markers for ARDS w/o signs of ischemic heart disease. - Randomized to CB bolus + 48 hour infusion vs placebo - All patients ventilated to SpO2 88-95% (or PaO2 55-88 mmHg) on volume assist-control mode as per ARMA trial. - Patients monitored for organ-system failure: systolic BP <90 mmHg, platelets <80K/cm^3, total bilirubin >2mg/dl, serum creatinine >2mg/dl Primary Outcome: Proportion of patients who died before hospital discharge [ cisatracurium vs placebo, HR 0.68, 95% CI 0.48-0.98, p=0.04] and within 90 days after study enrollment [31.6% (95% CI, 25.2 to 38.8) vs 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08)] Secondary Outcomes included: 28-day mortality [23.7% vs. 33.3% (RR 0.71; 95% CI 0.51-1.00; P=0.05)], the number of days without organ or system failure between day 1 and day 28 [15.8% vs. 12.2% (P=0.01), number of ventilator-free days [Day 1-28: 10.6% vs. 8.5% (P=0.04); Day 1-90: 53.1% vs. 44.6% (P=0.03)]. The Bottom Line Paralysis with cisatracurium for 48 hours had favorable results on survival to hospital discharge, lower rates of mortality within 90 days, and increased rate of ventilator-free days. DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 9-

Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome (The ROSE Trial) The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network*. N Engl J Med. 2019;380(21):1997-2008. Objective - Can POCUS determine outcomes in cardiac arrest? Intervention - POCUS performed at beginning and end of ACLS efforts Methods - non-randomized prospective observational study Inclusion Criteria - Out of hospital + in-ED non-traumatic cardiac arrest patients w/ asystole or PEA Exclusion Criteria - brief resuscitation efforts (< 5 min), resuscitation efforts not cont’d after initial POCUS, efforts halted for DNR status N=793 N=208 ROSC N=114 Hosp Adm Primary Outcome: survival to hospital admission 114/793 (14.4%, 95%CI 12.1–17.0) Secondary Outcomes: Survival to discharge 13/793 (1.6%, 95%CI 0.9–2.8) ROSC 208/793 = 26.2% (95%CI 23.3–29.4) N=13 Hosp Dis Black = cardiac activity on initial POCUS Grey = no cardiac activity on initial POCUS Pts with cardiac activity demonstrated higher rates of ROSC (51.2%vs 14.3, p < 0.001), survival to hospital admission (29.0% vs 7.2, p < 0.001) and survival to hospital discharge (3.8% vs 0.6, p = 0.04). Objective Multicenter, unblinded, randomized trial to determine the efficacy and safety of early neuromuscular blockade with concomitant heavy sedation Intervention Experimental group received 48 hours continuous neuromuscular blockade + deep sedation Control Group received light-sedation strategy Methods -Patients were eligible if endotracheally intubated for acute hypoxemic respiratory failure for <48 hours and had clinical markers for ARDS w/o signs of ischemic heart disease. - Randomized to CB bolus + 48 hour infusion vs light sedation strategy - All participants were treated with low tidal volume and high PEEP strategy - Light-sedation strategy was to a RAAS score of 0 to -1 - Patients monitored for organ-system failure via SOFA score Primary Outcome: In-hospital death from any cause at 90 days (included if patient transferred to another hospital or while in long-term acute care facilities): 42.5% in intervention group, 42.8 in control (95% CI, −6.4 to 5.9; P = 0.93) Secondary Outcomes included: organ dysfunction, in-hospital death, days not in the ICU, days free of mechanical ventilation, and days not in the hospital at day 28. *At 28 days, there was no between-group difference in hospital mortality, days free of ventilation, days out of the ICU, or days out of the hospital The Bottom Line In a cohort of critically ill patients identified shortly after the diagnosis of moderate-to-severe ARDS, the addition of early continuous neuromuscular blockade with concomitant deep sedation did not result in lower mortality than a usual-care approach to mechanical ventilation that included lighter sedation targets. There were increased rates of adverse cardiovascular events in patients who were in the intervention group. DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 10-

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome Combes A, Hajage D, Capellier G, et al. for the EOLIA Trial Group, REVA, and ECMONet*. N Engl J Med. 2018;378(21):1965-1975. Objective To evaluate if patients with severe ARDS unrelented by traditional therapy benefit from early ECMO Intervention Patients who met inclusion criteria slotted to either ECMO or standard airway management (including nitric oxide, proning, inhaled prostacyclin, IV almitrine) Methods International, randomized trial with patients meeting inclusion criteria allocated to either ECMO or Standard therapy Inclusion criteria: Clinical ARDS, underwent ET intubation for <7 days, met criteria for severe disease (PaO2/FiO2 <50mmg for >3 hrs, < 80mmHg for > 6 hours, arterial pH <7.25 with PaCO2 >60 for more than 6 hours) Exclusion criteria were many: <18, mechanical ventilation for 7 or more days, pregnancy, obesity, respiratory insufficiency[chronic], cardiac failure, HIT, cancer with life expectancy <5 years, moribund patient SAPS score >90, difficult access, irreversible neurologic disease, non-medically induced coma s/p cardiac arrest Patients in standard therapy group were allowed to cross over if they had refractory hypoxemia Primary Outcome: Mortality at 60 days Key Secondary Outcome: Death by day 60 in ECMO group and crossover to ECMO or death patients in the control group. The Bottom Line ECMO did not improve 60-day mortality in patient who were clinically determined to have very severe ARDS. Value of benefit of early ECMO may be underappreciated in this study with a large number of patients who crossed over to ECMO. DEEP DIVE SERIES Acute Respiratory Distress Syndrome Limitations: Stopped per-protocol at 75% maximum sample size; 28% crossover from control group to ECMO group; some patients needed transfer to ECMO centers; underpowered to detect mortality that was 20 percentage points lower in the ECMO group than in the control group
Slide 11-

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial Peek GJ, Mugford M, Tiruvoipati R, et al. Lancet. 2009;374(9698):1351-1363. To evaluate if patients with severe ARDS unrelented by traditional therapy benefit from early ECMO Intervention Patients who met inclusion criteria either slotted to ECMO or standard airway management (including nitric oxide, proning, inhaled prostacyclin, IV almitrine) Methods International, randomized trial with patients meeting inclusion criteria allocated to either ECMO or Standard therapy Inclusion criteria: Clinical ARDS, underwent ET intubation for <7 days, met criteria for severe disease (PaO2/FiO2 <50mmg for >3 hrs, < 80mmHg for > 6 hours, arterial pH <7.25 with PaCO2 >60 for more than 6 hours) Exclusion criteria were many: <18, mechanical ventilation for 7 or more days, pregnancy, obesity, respiratory insufficiency[chronic], cardiac failure, HIT, cancer with life expectancy <5 years, moribun patient SAPS score >90, difficult access, irreversible neurologic disease, non-medically induced coma s/p cardiac arrest Patients in standard therapy group were allowed to cross over if they had refractory hypoxemia Study was also designed to look at health status at 6 months: activities of daily living, quality adjusted life years, respiratory symptoms, cognitive psychological state and lung function. DEEP DIVE SERIES Acute Respiratory Distress Syndrome Primary Outcome: Death or severe disability at 6 months after randomization Key Secondary Outcome: Duration of stay in ICU, Duration of hospital stay The Bottom Line Study authors support ECMO for patients with severe respiratory distress. The results do not show ECMO to be better than conventional therapy, however it shows that transfer to an ECMO capable/ARDS center has improved mortality. Limitations ~25% patients in ECMO group did not receive ECMO; no standard management protocol for patients randomized to conventional therapy; follow up information is largely incomplete.
Slide 12-

Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial Girardis M, Busani S, Damiani E, et al. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA. 2016;316(15):1583–1589. Objective To assess whether a conservative protocol for oxygen supplementation could improve outcomes in patients admitted to intensive care units (ICUs). Intervention Conservative (PaO2 70-100 mm Hg, or SaO2 94-98%) versus Conventional (PaO2 up to 150 mm Hg, or SaO2 97-100%) Methods single-center, open-label, 2-parallel group, randomized clinical trial Inclusion Criteria 18 years or older and admitted to the ICU with an expected length of stay of 72 hours or longer Exclusion Criteria Notable exclusions: COPD exacerbation and severe ARDS (Pa02:Fi02 <150 mm Hg) N=434 N=218, Conventional N=216, Conservative Primary Outcome: ICU mortality (conservative vs conventional) 11.6% versus 20.2% (ARR 0.086, CI 0.017-0.15, p=0.01) Secondary Outcomes: New organ failure after 48 hours in ICU Infection after 48 hours in ICU The Bottom Line Girardis et al found a significant reduction in ICU mortality (11.6% versus 20.2%), hospital mortality (24.2% verses 33.9%), and ventilator-free hours (72 versus 48). However, the study was stopped early due to enrollment difficulties and unforeseen circumstances when the study was short 180 patients from their planned enrollment. Additionally, they excluded patients with severe ARDS so this study cannot be extrapolated to include all ARDS patients. DEEP DIVE SERIES Acute Respiratory Distress Syndrome Probability of survival significantly higher in conservative oxygen group vs conventional (Figure 2: Probability of survival from study inclusion through day 60 in conservative vs conventional group) Enrollment
Slide 13-

Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial Panwar R, Hardie M, Bellomo R, et al. Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial. Am J Respir Crit Care Med. 2016;193(1):43-51. Objective To determine whether a conservative oxygenation strategy is a feasible alternative to a liberal oxygenation strategy among ICU patients requiring invasive mechanical ventilation. Intervention Conservative oxygenation strategy with target oxygen saturation as measured by pulse oximetry (SpO2) of 88–92% or a liberal oxygenation strategy with target SpO2 of greater than or equal to 96% Methods Multicenter, multinational, randomized controlled trial Inclusion Criteria 18 years and older and having received mechanical ventilation (MV) for less than 24 hours and expected to require MV for at least the next 24 hours N = 104 Liberal Group N = 51 Conservative Group N = 53 Primary Outcome: Feasibility of conservative oxygen therapy strategy Secondary Outcomes: Safety of conservative oxygen therapy strategy The Bottom Line This study by Panwar et al determined that a conservative oxygen strategy with a target SpO2 of 88 to 92% was feasible, decreased the exposure of mechanically ventilated patients to hyperoxia, and was not associated with an increase in safety risks. DEEP DIVE SERIES Acute Respiratory Distress Syndrome Enrollment
Slide 14-

Conservative Oxygen Therapy during Mechanical Ventilation in the ICU ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group, et al. Conservative Oxygen Therapy during Mechanical Ventilation in the ICU. N Engl J Med. 2020;382(11):989-998. Objective Hypothesized that conservative oxygen therapy would result in more ventilator free days than usual oxygen therapy in adults who were expected to undergo mechanical ventilation in the ICU beyond the day after recruitment. Intervention The conservative group had an upper limit of SpO2 of 97% with a mandatory alarm. The usual group had no upper limit on SpO2. Both groups had a mandatory minimum of SpO2 of 90%. Methods Multicenter, bi-national ICU-ROX, parallel group, randomized clinical trial Inclusion Criteria All patients > 18 years old expected to receive mechanical ventilation in the ICU beyond the day of enrollment Conservative Oxygen Therapy 484 Patients Usual Oxygen Therapy 481 Patients Primary Outcome: Number of ventilator free days from enrollment to day 28 (conservative vs usual) Mean 21.3 (IQR 0.0 to 26.3) vs 22.1 (IQR 0.0 to 26.2) Between group difference −0.3 (IQR −2.1 to 1.6) Median 15.5 ± 11.8 vs 16.0 ± 11.5 −0.4 (−1.9 to 1.0) Secondary Outcomes: Death from any cause at day 90 166/479 (34.7%) vs 156/480 (32.5%) Unadjusted Odds Ratio 1.10 (0.84 to 1.44) Death from any cause day 180 170/476 (35.7%) vs 164/475 (34.5%) Unadjusted Odds Ratio 1.05 (0.81 to 1.37) Other Secondary Outcomes duration of survival, the proportion of patients in paid employment at baseline who were unemployed at day 180, and cognitive function and health-related quality of life at day 180 The Bottom Line In this study by the ICU-ROX group, they found no significant difference in ventilator free days and no significant different in 90 day or 180 day mortality. These findings are in opposition to prior studies as well as systematic review data. The wide range of the SpO2 (90-97%) for the conservative oxygen group may suggest an lower and/or narrower oxygen supplementation protocol would be better. DEEP DIVE SERIES Acute Respiratory Distress Syndrome DEEP DIVE SERIES Epinephrine in Cardiac Arrest Total Enrollment 1001 Patients
Slide 15-

Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome Barrot L, Asfar P, Mauny F, et al. Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome. N Engl J Med. 2020;382(11):999-1008. Primary Outcome: Death from any cause at 28 days (conservative vs liberal) 34/99 (34.3%, 95%CI 25.0 - 43.7) vs 27/102 (26.5%, 95%CI 17.9-35.0) Secondary Outcomes Death in ICU 36/99, 36.4% (26.9–45.8) vs 27/102, 26.5% (17.9–35.0) Death at day 90 44/99, 44.4% (34.7–54.2) vs 31/102, 30.4% (21.5–39.3) Ventilator-associated pneumonia 17/99, 17.2% (9.7–24.6) vs 22/102, 21.6% (13.6–29.6) Septicemia 11/99, 11.1% (4.9–17.3) vs 19/102, 18.6% (11.1–26.2) Total Enrollment Conservative Liberal 205 99 102 Objective ARDS Clinical Trials Network recommends a target partial pressure of arterial oxygen (Pao2) between 55 and 80 mm Hg. Authors hypothesized that targeting the lower limit of this range would improve outcomes in patients with ARDS. Methods Prospective, multicenter, random ized,open-label trial involving patients with ARDS Intervention Patients with ARDS received either conservative oxygen therapy (target Pao2, 55 to 70 mm Hg; oxygen saturation as measured by pulse oximetry [Spo2], 88 to 92%) or liberal oxygen therapy (target Pao2, 90 to 105 mm Hg; Spo2, ≥96%) for 7 days. The Bottom Line In this study by Barrot, Asfar, Mauny et al, they found no significant difference in death from any cause at day 28. They did find the mean PaO2, SaO2, and FiO2 were significantly lower in the conservative group. Additionally, they found a significant increase in mortality at day 90 in the conservative oxygen group suggest potential harm with lower oxygenation goals. DEEP DIVE SERIES Acute Respiratory Distress Syndrome DEEP DIVE SERIES Epinephrine in Cardiac Arrest
Slide 16-

Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial Villar J, Ferrando C, Martínez D, et al. Lancet Resp Med. 2020;8(3):267-276. Objective To determine if dexamethasone addition to ARDS treatment can decrease systemic and pulmonary inflammation and decrease duration of mechanical ventilation and mortality. Intervention Dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Methods Investigator-initiated, multicentre, randomised controlled trial done in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain Enrollment Total Patients Dexamethasone Control Group 277 139 138 Primary Outcome: Number of Ventilator Free Days Mean 12.3 [SD 9.9] vs 7.5 [9.0] days; between-groups difference 4.8 days [95% CI 2·57–7·03]; p<0·0001 Secondary Outcome: All cause mortality at 60 days 29 (21%) vs 50 (36%), –15.3% (–25.9 to –4.9) 95% CI, p=0.0047 The Bottom Line This study by Villar, Ferrando, Martinez et al suggests an increase in ventilator free days and mortality benefit with dexamethasone addition to ARDS treatment with a number needed to treat of 7. This is the first study to examine dexamethasone specifically in ARDS. DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 17-

Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report The RECOVERY Collaborative Group*, et al. N Engl J Med. 2020;NEJMoa2021436. Online ahead of print. Objective To determine if dexamethasone in patient hospitalized with COVID-19 reduced mortality Intervention Eligible patients assigned in 2:1 ratio to receive usual standard of care alone vs standard of care + PO or IV dexamethasone 6 mg qd for up to 10 days. Methods Controlled, open-label, randomized trial of patients with COVID-19 in 176 National Health Service (NHS) organizations Enrollment Total Patients Dexamethasone Control Group 6425 2104 4321 Primary Outcome: All cause mortality within 28 days Mortality was lower in the dexamathasone group vs usual care group. 482 of 2104 patients (22.9%) and 1110 of 4321 patients (25.7%), respectively (rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001) Secondary Outcomes: Time until hospital discharge: 12 days in dexamethasone group, 13 in usual care group Recipients of invasive mechanical ventilation who were not on said support at time of randomization Lower in dexamethasone group: risk ratio 0.92; 95% CI, 0.84 to 1.01 The Bottom Line In patients with COVID-19 requiring oxygen support, 28 day mortality was lower in the cohort of patient receiving dexamethasone vs usual care. DEEP DIVE SERIES Acute Respiratory Distress Syndrome
Slide 18-

Use of Inhaled Pulmonary Dilators in Acute Respiratory Distress Syndrome: A Systematic Review Dzierba A, Abel E, Buckley MS, Lat I. Pharmacotherapy. 2014;34(3):279-290. Objective To assess the safety and efficacy of inhaled nitric oxide (iNO) and aerosolized epoprostenol (aEPO) for the treatment of acute lung injury and acute respiratory distress syndrome. Methods Systematic review including 9 trials examining iNO and 7 studies examining aEPO. Inclusion Criteria Prospective randomized controlled clinical trials of adult populations with ARDS or ALI receiving iNO. For aEPO, case series and case reports were used. Exclusion Criteria Trails evaluating iNO or aEPO with other drug therapies were excluded. Inhaled Nitric Oxide Efficacy: Measured through improvements in oxygenation and changes in mortality and ventilator free days Of the 9 trials examining iNO, 7 looked at iNO use in ARDS, 2 in ALI. Of these 5 collected data on oxygenation Statistically significant improvements in oxygenation through 24 hrs, though not observed at 72 No change in morbidity or ventilator free days Safety: A significant increased risk of kidney injury (RR 1.59) noted from combined analysis Methemoglobinemia, decreased platelet aggregation leading to bleeding, and free radical accumulation in lungs are theoretical adverse effects, but none were reported in these trails The Bottom Line Dzierba et al found improvement in oxygenation for up to 24 hours with iNO. No significant improvements in clinical outcomes were observed. aEPO did not result in a significant improvement in oxygenation or clinical outcomes across studies, however a definitive conclusion is difficult to reach due to a lack of robust studies. In practice, this review indicates that iNO could be used a rescue therapy in severe refractory hypoxemia to provide time for optimal adjustments in mechanical ventilation. DEEP DIVE SERIES Acute Respiratory Distress Syndrome Aerosolized Epoprostenol Efficacy: 7 case series of patients with ARDS or ALI recieving aEPO showed mixed results: 4 studies showed improvement in oxygenation, 1 showed worsening of oxygenation and 2 had no change Mortality and other markers of disease severity were not studied Safety: No adverse effects were identified, a study of aEPO in piglets reported mild acute tracheitis
Slide 19-

Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome Zhou Y, Jin X, Lv Y, et al.Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med. 2017;43(11):1648-1659. Objective To assess whether early application of airway pressure release ventilation (APRV) would improve oxygenation, respiratory compliance, and reduce duration of mechanical ventilation compared to lung protective ventilation (LTV) Intervention APRV (Phigh=plateau on VCV settings, Plow=5) versus LTV based on ARDSnet protocol Methods Single-center, randomized controlled trial Inclusion Criteria 18 years or older and admitted to the ICU with ARDS based on Berlin definition and <48 since intubation Exclusion Criteria Notable exclusions: severe COPD, expected 6-mo mortality > 50%, patients >85 yo N=138 N=71 APRV N=67 LTV Primary Outcome: Ventilator free days at day 28 (APRV v LTV) 19 days (IQR 8-22) v 2 days (IQR 0-15) (p<0.001) Secondary Outcomes: Oxygenation, respiratory mechanics, clinical outcomes Improved oxygenation and lung compliance, higher rates of successful extubation, fewer tracheostomies, decreased ICU LOS in APRV group No difference in mortality, hospital LOS The Bottom Line Zhou et al found significant increase in the number of ventilator free days (19 days v 2 days) and significant improvement in ventilation, respiratory compliance, extubation success, ICU and hospital LOS with the use of early APRV compared to LTV. While there was no difference in mortality, these results are very promising for the positive impact early APRV (<48 hours from intubation) on clinical outcomes for patients with ARDS. DEEP DIVE SERIES Acute Respiratory Distress Syndrome Kaplan-Meir curve representing the percent of patients breathing without mechanical ventilation in APRV v LTV groups Enrollment