Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health.

Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.

Outcomes of Venovenous Extracorporeal Membrane Oxygenation in Viral Acute Respiratory Distress Syndrome.

Our study assessed the relationship between the duration of venovenous extracorporeal membrane oxygenation (V-V ECMO) and patient outcomes. We studied patients undergoing V-V ECMO support for acute respiratory distress syndrome (ARDS) between 2009 and 2017 who were reported to the Extracorporeal Life Support Organization registry. We evaluated survival, major bleeding, renal failure, pulmonary complications, mechanical complications, neurologic complications, infection, and duration of V-V ECMO support. Multivariable regression modeling assessed risk factors for adverse events. Of the 4,636 patients studied, the mean support duration was 12.2 ± 13.7 days. There was a progressive increase in survival after the initiation of V-VECMO, peaking at a survival rate of 73% at 10 days of support. However, a single-day increase in V-V ECMO duration was associated with increased bleeding events (odds ratio [OR] 1.038; 95% confidence interval [CI]: 1.029-1.047; p < 0.0001), renal failure (OR 1.018; 95% CI: 1.010-1.027; p < 0.0001), mechanical complications (OR 1.065; 95% CI: 1.053-1.076; p < 0.0001), pulmonary complications (OR 1.04; 95% CI: 1.03-1.05; p < 0.0001), and infection (OR 1.04; 95% CI: 1.03-1.05; p < 0.0001). V-V ECMO progressively increases survival for ARDS over the first 10 days of support. Thereafter, rising complications associated with prolonged durations of support result in a progressive decline in survival.

A Target for Increased Mortality Risk in Critically Ill Patients: The Concept of Perpetuity.

BACKGROUND: Emergency medicine is acuity-based and focuses on time-sensitive treatments for life-threatening diseases. Prolonged time in the emergency department, however, is associated with higher mortality in critically ill patients. Thus, we explored management after an acuity-based intervention, which we call perpetuity, as a potential mechanism for increased risk. To explore this concept, we evaluated the impact of each hour above a lung-protective tidal volume on risk of mortality. METHODS: This cohort analysis includes all critically ill, non-trauma, adult patients admitted to two academic EDs between 1 November 2013 and 30 April 2017. Cox models with time-varying covariates were developed with time in perpetuity as a time-varying covariate, defined as hours above 8 mL/kg ideal body weight, adjusted for covariates. The primary outcome was the time to in-hospital death. RESULTS: Our analysis included 2025 patients, 321 (16%) of whom had at least 1 h of perpetuity time. A partial likelihood-ratio test comparing models with and without hours in perpetuity was statistically significant (χ2(3) = 13.83, p = 0.0031). There was an interaction between age and perpetuity (Relative risk (RR) 0.9995; 95% Confidence interval (CI95): 0.9991-0.9998). For example, for each hour above 8 mL/kg ideal body weight, a 20-year-old with 90% oxygen saturation has a relative risk of death of 1.02, but a 40-year-old with 90% oxygen saturation has a relative risk of 1.01. CONCLUSIONS: Perpetuity, illustrated through the lens of mechanical ventilation, may represent a target for improving outcomes in critically ill patients, starting in the emergency department. Research is needed to evaluate the types of patients and interventions in which perpetuity plays a role.

First Pass Success Without Adverse Events Is Reduced Equally with Anatomically Difficult Airways and Physiologically Difficult Airways.

INTRODUCTION: The goal of emergency airway management is first pass success without adverse events (FPS-AE). Anatomically difficult airways are well appreciated to be an obstacle to this goal. However, little is known about the effect of the physiologically difficult airway with regard to FPS-AE. This study evaluates the effects of both anatomically and physiologically difficult airways on FPS-AE in patients undergoing rapid sequence intubation (RSI) in the emergency department (ED). METHODS: We analyzed prospectively recorded intubations in a continuous quality improvement database between July 1, 2014-June 30, 2018. Emergency medicine (EM) or emergency medicine/pediatric (EM-PEDS) residents recorded patient, operator, and procedural characteristics on all consecutive adult RSIs performed using a direct or video laryngoscope. The presence of specific anatomically and physiologically difficult airway characteristics were also documented by the operator. Patients were analyzed in four cohorts: 1) no anatomically or physiologically difficult airway characteristics; 2) one or more anatomically difficult airway characteristics; 3) one or more physiologically difficult airway characteristics; and 4) both anatomically and physiologically difficult airway characteristics. The primary outcome was FPS-AE. We performed a multivariable logistic regression analysis to determine the association between anatomically difficult airways or physiologically difficult airways and FPS-AE. RESULTS: A total of 1513 intubations met inclusion criteria and were analyzed. FPS-AE for patients without any difficult airway characteristics was 92.4%, but reduced to 82.1% (difference = -10.3%, 95% confidence interval (CI), -14.8% to -5.6%) with the presence of one or more anatomically difficult airway characteristics, and 81.7% (difference = -10.7%, 95% CI, -17.3% to -4.0%) with the presence of one or more physiologically difficult airway characteristics. FPS-AE was further reduced to 70.9% (difference = -21.4%, 95% CI, -27.0% to -16.0%) with the presence of both anatomically and physiologically difficult airway characteristics. The adjusted odds ratio (aOR) of FPS-AE was 0.37 [95% CI, 0.21 - 0.66] in patients with anatomically difficult airway characteristics and 0.36 [95% CI, 0.19 - 0.67] for patients with physiologically difficult airway characteristics, compared to patients with no difficult airway characteristics. Patients who had both anatomically and physiologically difficult airway characteristics had a further decreased aOR of FPS-AE of 0.19 [95% CI, 0.11 - 0.33]. CONCLUSION: FPS-AE is reduced to a similar degree in patients with anatomically and physiologically difficult airways. Operators should assess and plan for potential physiologic difficulty as is routinely done for anatomically difficulty airways. Optimization strategies to improve FPS-AE for patients with physiologically difficult airways should be studied in randomized controlled trials.

Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity.

We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection.

Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure.

We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.

Mechanical Ventilation Strategies for the Patient with Severe Obstructive Lung Disease.

Patients with respiratory failure due to obstructive lung disease present a challenge to the emergency physician. These patients have physiologic abnormalities that prevent adequate gas exchange and lung mechanics which render them at increased risk of cardiopulmonary decompensation when managed with invasive mechanical ventilation. This article addresses key principles when managing these challenging patients: patient-ventilator synchrony, air trapping and auto-positive end-expiratory pressure, and airway pressures. This article provides a practical workflow for the emergency physician responsible for managing these patients.

Impact of Point-of-Care Ultrasound in the Emergency Department on Care Processes and Outcomes in Critically Ill Nontraumatic Patients.

Outcomes data on point-of-care ultrasound (POCUS) in critically ill patients are lacking. This study examines the association between POCUS in the emergency department and outcomes in critically ill patients. DESIGN: Retrospective cohort study of critically ill emergency department patients in two academic emergency departments. All emergency department patients admitted to the intensive care unit or that die in the emergency department were entered prospectively into a registry. SETTING: Two academic emergency departments. PATIENTS: All adult (> 18 years old) non-trauma patients with hemodynamic instability [shock index (heart rate/systolic blood pressure) > 0.6] between November 1, 2013-October 31, 2016, were included. INTERVENTIONS: Cohorts were assigned as follows: no POCUS (cohort 1), POCUS prior to a key intervention (cohort 2), and POCUS after a key intervention (cohort 3). A key intervention was either a fluid bolus or vasoactive drug initiation. MEASUREMENTS AND MAIN RESULTS: Multivariable logistic regression was used to evaluate the association between POCUS use and the primary outcome of in-hospital mortality. We conducted several sensitivity analyses including propensity score matching and inverse-probability-weighted regression-adjustment along with multiple imputation to account for non-random assignment of POCUS as well as bias due to missing data. Of the 7,734 eligible patients, 2,293 patients were excluded. The remaining 5,441 patients were included in the analysis: 4165 in Cohort 1, 614 in Cohort 2, and 662 in Cohort 3. Mortality was 22%, 29%, and 26%, respectively (p < 0.001). POCUS prior to an intervention was associated with an adjusted odds ratio for death of 1.41 (95% CI, 1.12-1.76) compared to no POCUS. The sensitivity analyses showed an absolute increased mortality of +0.05 (95% CI, 0.02-0.09) for cohort 2 compared to 1. CONCLUSIONS: POCUS use prior to interventions appears to be associated with care delays and increased in-hospital mortality compared to critically ill patients with no POCUS. Further explorations of the impact of POCUS in the emergency department appear warranted.

Management of Patients with Predicted Difficult Airways in an Academic Emergency Department.

BACKGROUND: Patients with difficult airways are sometimes encountered in the emergency department (ED), however, there is a little data available regarding their management. OBJECTIVES: To determine the incidence, management, and outcomes of patients with predicted difficult airways in the ED. METHODS: Over the 1-year period from July 1, 2015 to June 30, 2016, data were prospectively collected on all patients intubated in an academic ED. After each intubation, the operator completed an airway management data form. Operators performed a pre-intubation difficult airway assessment and classified patients into routine, challenging, or difficult airways. All non-arrest patients were included in the study. RESULTS: There were 456 patients that met inclusion criteria. Fifty (11%) had predicted difficult airways. In these 50 patients, neuromuscular blocking agents (NMBAs) were used in 40 (80%), an awake intubation technique with light sedation was used in 7 (14%), and no medications were used in 3 (6%). In the 40 difficult airway patients who underwent NMBA facilitated intubation, a video laryngoscope (GlideScope 21, Verathon, Bothell, WA and C-MAC 19, Karl Storz, Tuttlingen, Germany) was used in each of these, with a first-pass success of 90%. In the 7 patients who underwent awake intubation, a video laryngoscope was used in 5, and a flexible fiberoptic scope was used in 2. Ketamine was used in 6 of the awake intubations. None of these difficult airway patients required rescue with a surgical airway. CONCLUSIONS: Difficult airways were predicted in 11% of non-arrest patients requiring intubation in the ED, the majority of which were managed using an NMBA and a video laryngoscope with a high first-pass success.

Suspected Heparin-Induced Thrombocytopenia in Patients Receiving Extracorporeal Membrane Oxygenation.

Heparin-induced thrombocytopenia (HIT) is an immune reaction usually secondary to unfractionated heparin. Anticoagulation management is critical in patients while on extracorporeal membrane oxygenation (ECMO) to prevent thromboembolism and for the optimal functioning of the circuit. We identified five patients with respiratory failure at our hospital managed with ECMO in the last 2 years that were treated for HIT. A brief clinical course and their management are discussed. We also briefly review the literature for best evidence for management of such patients.

Failure to achieve first attempt success at intubation using video laryngoscopy is associated with increased complications.

The purpose of this investigation was to investigate the association between first attempt success and intubation-related complications in the Intensive Care Unit after the widespread adoption of video laryngoscopy. We further sought to characterize and identify the predictors of complications that occur despite first attempt success. This was a prospective observational study of consecutive intubations performed with video laryngoscopy at an academic medical Intensive Care Unit. Operator, procedural, and complication data were collected. Multivariable logistic regression was used to examine the relationship between the intubation attempts and the occurrence of one or more complications. A total of 905 patients were intubated using a video laryngoscope. First attempt success occurred in 739 (81.7 %), whereas >1 attempt was needed in 166 (18.3 %). One or more complications occurred in 146 (19.8 %) of those intubated on the first attempt versus 107 (64.5 %, p < 0.001) of those requiring more than one attempt. Logistic regression analysis shows that >1 attempt is associated with 6.4 (95 % CI 4.4-9.3) times the adjusted odds of at least one complication. Pre-intubation predictors of at least one complication despite first attempt success include vomit or edema in the airway as well as the presence of hypoxemia or hypotension. There are increased odds of complications with even a second attempt at intubation in the Intensive Care Unit. Complications occur frequently despite a successful first attempt, and as such, the goal of airway management should not be simply first attempt success, but instead first attempt success without complications.

Difficult Airway Characteristics Associated with First-Attempt Failure at Intubation Using Video Laryngoscopy in the Intensive Care Unit.

RATIONALE: Video laryngoscopy has overcome the need to align the anatomic axes to obtain a view of the glottic opening to place a tracheal tube. However, despite this advantage, a large number of attempts are unsuccessful. There are no existing data on anatomic characteristics in critically ill patients associated with a failed first attempt at laryngoscopy when using video laryngoscopy. OBJECTIVES: To identify characteristics associated with first-attempt failure at intubation when using video laryngoscopy in the intensive care unit (ICU). METHODS: This is an observational study of 906 consecutive patients intubated in the ICU with a video laryngoscope between January 2012 and January 2016 in a single-center academic medical ICU. After each intubation, the operator completed a data collection form, which included information on difficult airway characteristics, device used, and outcome of each attempt. Multivariable regression models were constructed to determine the difficult airway characteristics associated with a failed first attempt at intubation. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in sex, age, reason for intubation, or device used between first-attempt failures and first-attempt successes. First-attempt successes more commonly reported no difficult airway characteristics were present (23.9%; 95% confidence interval [CI], 20.7-27.0% vs. 13.3%; 95% CI, 8.0-18.8%). In logistic regression analysis of the entire 906-patient database, blood in the airway (odds ratio [OR], 2.63; 95% CI, 1.64-4.20), airway edema (OR, 2.85; 95% CI, 1.48-5.45), and obesity (OR, 1.59; 95% CI, 1.08-2.32) were significantly associated with first-attempt failure. Data collection on limited mouth opening and secretions began after the first 133 intubations, and we fit a second logistic model to examine cases in which these additional difficult airway characteristics were collected. In this subset (n = 773), the presence of blood (OR, 2.73; 95% CI, 1.60-4.64), cervical immobility (OR, 3.34; 95% CI, 1.28-8.72), and airway edema (OR, 3.10; 95% CI, 1.42-6.70) were associated with first-attempt failure. CONCLUSIONS: In this single-center study, presence of blood in the airway, airway edema, cervical immobility, and obesity are associated with higher odds of first-attempt failure, when intubation was performed with video laryngoscopy in an ICU.

Video Laryngoscopy Improves Odds of First-Attempt Success at Intubation in the Intensive Care Unit. A Propensity-matched Analysis.

RATIONALE: Urgent tracheal intubation is performed frequently in intensive care units and incurs higher risk than when intubation is performed under more controlled circumstances. Video laryngoscopy may improve the chances of successful tracheal intubation on the first attempt; however, existing comparative data on outcomes are limited. OBJECTIVES: To compare first-attempt success and complication rates during intubation when using video laryngoscopy compared with traditional direct laryngoscopy in a tertiary academic medical intensive care unit. METHODS: We prospectively collected and analyzed data from a continuous quality improvement database of all intubations in one medical intensive care unit between January 1, 2012, and December 31, 2014. Propensity matching and multivariable logistic regression were used to reduce the risk of bias and control for confounding. MEASUREMENTS AND MAIN RESULTS: A total of 809 intubations took place over the study period. Of these, 673 (83.2%) were performed using video laryngoscopy and 136 (16.8%) using direct laryngoscopy. First-attempt success with video laryngoscopy was 80.4% (95% confidence interval [CI], 77.2-83.3%) compared with 65.4% (95% CI, 56.8-73.4%) for intubations performed with direct laryngoscopy (P < 0.001). In a propensity-matched analysis, the odds ratio for first-attempt success with video laryngoscopy versus direct laryngoscopy was 2.81 (95% CI, 2.27-3.59). The rate of arterial oxygen desaturation events during the first intubation attempt was significantly lower for video laryngoscopy than for direct laryngoscopy (18.3% vs. 25.9%; P = 0.04). The rate of esophageal intubation during any attempt was also significantly lower for video laryngoscopy (2.1% vs. 6.6%; P = 0.008). CONCLUSIONS: Video laryngoscopy was associated with significantly improved odds of first-attempt success at tracheal intubation by nonanesthesiologists in a medical intensive care unit. Esophageal intubation and oxygen desaturation occurred less frequently with the use of video laryngoscopy. Randomized clinical trials are needed to confirm these findings.

Extracorporeal membrane oxygenation (ECMO) for critically ill adults in the emergency department: history, current applications, and future directions.

Extracorporeal membrane oxygenation (ECMO) is a mode of extracorporeal life support that augments oxygenation, ventilation and/or cardiac output via cannulae connected to a circuit that pumps blood through an oxygenator and back into the patient. ECMO has been used for decades to support cardiopulmonary disease refractory to conventional therapy. While not robust, there are promising data for the use of ECMO in acute hypoxemic respiratory failure, cardiac arrest, and cardiogenic shock and the potential indications for ECMO continue to increase. This review discusses the existing literature on the potential use of ECMO in critically ill patients within the emergency department.

Ventilator Strategies and Rescue Therapies for Management of Acute Respiratory Failure in the Emergency Department.

Acute respiratory failure is commonly encountered in the emergency department (ED), and early treatment can have effects on long-term outcome. Noninvasive ventilation is commonly used for patients with respiratory failure and has been demonstrated to improve outcomes in acute exacerbations of chronic obstructive lung disease and congestive heart failure, but should be used carefully, if at all, in the management of asthma, pneumonia, and acute respiratory distress syndrome. Lung-protective tidal volumes should be used for all patients receiving mechanical ventilation, and FiO2 should be reduced after intubation to achieve a goal of less than 60%. For refractory hypoxemia, new rescue therapies have emerged to help improve the oxygenation, and in some cases mortality, and should be considered in ED patients when necessary, as deferring until ICU admission may be deleterious. This review article summarizes the pathophysiology of acute respiratory failure, management options, and rescue therapies including airway pressure release ventilation, continuous neuromuscular blockade, inhaled nitric oxide, and extracorporeal membrane oxygenation.

Failed noninvasive positive-pressure ventilation is associated with an increased risk of intubation-related complications.

BACKGROUND: Noninvasive positive-pressure ventilation (NIPPV) use has increased in the treatment of patients with respiratory failure. However, despite decreasing the need for intubation in some patients, there are no data regarding the risk of intubation-related complications associated with delayed intubation in adult patients who fail NIPPV. The objective of this study is to evaluate the odds of a composite complication of intubation following failed NIPPV compared to patients intubated primarily in the medical intensive care unit (ICU). METHODS: This is a single-center retrospective cohort study of 235 patients intubated between 1 January 2012 and 30 June 2013 in a medical ICU of a university medical center. A total of 125 patients were intubated after failing NIPPV, 110 patients were intubated without a trial of NIPPV. Intubation-related data were collected prospectively through a continuous quality improvement (CQI) program and retrospectively extracted from the medical record on all patients intubated on the medical ICU. A propensity adjustment for the factors expected to affect the decision to initially use NIPPV was used, and the adjusted multivariate regression analysis was performed to evaluate the odds of a composite complication (desaturation, hypotension, or aspiration) with intubation following failed NIPPV versus primary intubation. RESULTS: A propensity-adjusted multivariate regression analysis revealed that the odds of a composite complication of intubation in patients who fail NIPPV was 2.20 (CI 1.14 to 4.25), when corrected for the presence of pneumonia or acute respiratory distress syndrome (ARDS), and adjusted for factors known to increase complications of intubation (total attempts and operator experience). When a composite complication occurred, the unadjusted odds of death in the ICU were 1.79 (95% CI 1.03 to 3.12). CONCLUSIONS: After controlling for potential confounders, this propensity-adjusted analysis demonstrates an increased odds of a composite complication with intubation following failed NIPPV. Further, the presence of a composite complication during intubation is associated with an increased odds of death in the ICU.