Individualized Treatment Effects of Oxygen Targets in Mechanically Ventilated Critically Ill Adults.

Importance: Among critically ill adults, randomized trials have not found oxygenation targets to affect outcomes overall. Whether the effects of oxygenation targets differ based on an individual's characteristics is unknown. Objective: To determine whether an individual's characteristics modify the effect of lower vs higher peripheral oxygenation-saturation (Spo2) targets on mortality. Design, Setting, and Participants: A machine learning model to predict the effect of treatment with a lower vs higher Spo2 target on mortality for individual patients was derived in the Pragmatic Investigation of Optimal Oxygen Targets (PILOT) trial and externally validated in the Intensive Care Unit Randomized Trial Comparing Two Approaches to Oxygen Therapy (ICU-ROX) trial. Critically ill adults received invasive mechanical ventilation in an intensive care unit (ICU) in the United States between July 2018 and August 2021 for PILOT (n = 1682) and in 21 ICUs in Australia and New Zealand between September 2015 and May 2018 for ICU-ROX (n = 965). Exposures: Randomization to a lower vs higher Spo2 target group. Main Outcome and Measure: 28-Day mortality. Results: In the ICU-ROX validation cohort, the predicted effect of treatment with a lower vs higher Spo2 target for individual patients ranged from a 27.2% absolute reduction to a 34.4% absolute increase in 28-day mortality. For example, patients predicted to benefit from a lower Spo2 target had a higher prevalence of acute brain injury, whereas patients predicted to benefit from a higher Spo2 target had a higher prevalence of sepsis and abnormally elevated vital signs. Patients predicted to benefit from a lower Spo2 target experienced lower mortality when randomized to the lower Spo2 group, whereas patients predicted to benefit from a higher Spo2 target experienced lower mortality when randomized to the higher Spo2 group (likelihood ratio test for effect modification P = .02). The use of a Spo2 target predicted to be best for each patient, instead of the randomized Spo2 target, would have reduced the absolute overall mortality by 6.4% (95% CI, 1.9%-10.9%). Conclusion and relevance: Oxygenation targets that are individualized using machine learning analyses of randomized trials may reduce mortality for critically ill adults. A prospective trial evaluating the use of individualized oxygenation targets is needed.

Fluid Management in Acute Respiratory Failure.

Fluid management in acute respiratory failure is an area of uncertainty requiring a delicate balance of resuscitation and fluid removal to manage hypoperfusion and avoidance of hypoxemia. Overall, a restrictive fluid strategy (minimizing fluid administration) and careful attention to overall fluid balance may be beneficial after initial resuscitation and does not have major side effects. Further studies are needed to improve our understanding of patients who will benefit from a restrictive or liberal fluid management strategy.

Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial.

Importance: Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial. Objective: To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction. Design, Setting, and Participants: The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022. Interventions: Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam. Main Outcomes and Measures: The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days. Results: There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]). Conclusions and Relevance: Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT05094154.

Protocol and statistical analysis plan for the Mode of Ventilation During Critical IllnEss (MODE) trial.

Introduction: For every critically ill adult receiving invasive mechanical ventilation, clinicians must select a mode of ventilation. The mode of ventilation determines whether the ventilator directly controls the tidal volume or the inspiratory pressure. Newer hybrid modes allow clinicians to set a target tidal volume, for which the ventilator controls and adjusts the inspiratory pressure. A strategy of low tidal volumes and low plateau pressure improves outcomes, but the optimal mode to achieve these targets is not known. Methods and analysis: The Mode of Ventilation During Critical Illness (MODE) trial is a cluster-randomized, multiple-crossover pilot trial being conducted in the medical intensive care unit (ICU) at an academic center. The MODE trial compares the use of volume control, pressure control, and adaptive pressure control. The study ICU is assigned to a single ventilator mode (volume control versus pressure control versus adaptive pressure control) for continuous mandatory ventilation during each 1-month study block. The assigned mode switches every month in a randomly generated sequence. The primary outcome is ventilator-free days (VFDs) to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of mechanical ventilation to 28 days after enrollment. Enrollment began November 1, 2022 and will end on July 31, 2023. Ethics and dissemination: The trial was approved by the Vanderbilt University Medical Center institutional review board (IRB# 220446). Results of this study will be submitted to a peer-reviewed journal and presented at scientific conferences. Trial registration number: The trial was registered with clinicaltrials.gov on October 3, 2022, prior to initiation of patient enrollment on November 1, 2022 (ClinicalTrials.gov identifier: NCT05563779).

Video versus Direct Laryngoscopy for Tracheal Intubation of Critically Ill Adults.

BACKGROUND: Whether video laryngoscopy as compared with direct laryngoscopy increases the likelihood of successful tracheal intubation on the first attempt among critically ill adults is uncertain. METHODS: In a multicenter, randomized trial conducted at 17 emergency departments and intensive care units (ICUs), we randomly assigned critically ill adults undergoing tracheal intubation to the video-laryngoscope group or the direct-laryngoscope group. The primary outcome was successful intubation on the first attempt. The secondary outcome was the occurrence of severe complications during intubation; severe complications were defined as severe hypoxemia, severe hypotension, new or increased vasopressor use, cardiac arrest, or death. RESULTS: The trial was stopped for efficacy at the time of the single preplanned interim analysis. Among 1417 patients who were included in the final analysis (91.5% of whom underwent intubation that was performed by an emergency medicine resident or a critical care fellow), successful intubation on the first attempt occurred in 600 of the 705 patients (85.1%) in the video-laryngoscope group and in 504 of the 712 patients (70.8%) in the direct-laryngoscope group (absolute risk difference, 14.3 percentage points; 95% confidence interval [CI], 9.9 to 18.7; P<0.001). A total of 151 patients (21.4%) in the video-laryngoscope group and 149 patients (20.9%) in the direct-laryngoscope group had a severe complication during intubation (absolute risk difference, 0.5 percentage points; 95% CI, -3.9 to 4.9). Safety outcomes, including esophageal intubation, injury to the teeth, and aspiration, were similar in the two groups. CONCLUSIONS: Among critically ill adults undergoing tracheal intubation in an emergency department or ICU, the use of a video laryngoscope resulted in a higher incidence of successful intubation on the first attempt than the use of a direct laryngoscope. (Funded by the U.S. Department of Defense; DEVICE ClinicalTrials.gov number, NCT05239195.).

Protocol and statistical analysis plan for the PREOXI trial of preoxygenation with noninvasive ventilation vs oxygen mask.

Background: Hypoxemia is a common and life-threatening complication during emergency tracheal intubation of critically ill adults. The administration of supplemental oxygen prior to the procedure ("preoxygenation") decreases the risk of hypoxemia during intubation. Research Question: Whether preoxygenation with noninvasive ventilation prevents hypoxemia during tracheal intubation of critically ill adults, compared to preoxygenation with oxygen mask, remains uncertain. Study Design and Methods: The PRagmatic trial Examining OXygenation prior to Intubation (PREOXI) is a prospective, multicenter, non-blinded randomized comparative effectiveness trial being conducted in 7 emergency departments and 17 intensive care units across the United States. The trial compares preoxygenation with noninvasive ventilation versus oxygen mask among 1300 critically ill adults undergoing emergency tracheal intubation. Eligible patients are randomized in a 1:1 ratio to receive either noninvasive ventilation or an oxygen mask prior to induction. The primary outcome is the incidence of hypoxemia, defined as a peripheral oxygen saturation <85% between induction and 2 minutes after intubation. The secondary outcome is the lowest oxygen saturation between induction and 2 minutes after intubation. Enrollment began on 10 March 2022 and is expected to conclude in 2023. Interpretation: The PREOXI trial will provide important data on the effectiveness of noninvasive ventilation and oxygen mask preoxygenation for the prevention of hypoxemia during emergency tracheal intubation. Specifying the protocol and statistical analysis plan prior to the conclusion of enrollment increases the rigor, reproducibility, and interpretability of the trial. Clinical trial registration number: NCT05267652.

Individualized Treatment Effects of Bougie versus Stylet for Tracheal Intubation in Critical Illness.

Rationale: A recent randomized trial found that using a bougie did not increase the incidence of successful intubation on first attempt in critically ill adults. The average effect of treatment in a trial population, however, may differ from effects for individuals. Objective: We hypothesized that application of a machine learning model to data from a clinical trial could estimate the effect of treatment (bougie vs. stylet) for individual patients based on their baseline characteristics ("individualized treatment effects"). Methods: This was a secondary analysis of the BOUGIE (Bougie or Stylet in Patients Undergoing Intubation Emergently) trial. A causal forest algorithm was used to model differences in outcome probabilities by randomized group assignment (bougie vs. stylet) for each patient in the first half of the trial (training cohort). This model was used to predict individualized treatment effects for each patient in the second half (validation cohort). Measurements and Main Results: Of 1,102 patients in the BOUGIE trial, 558 (50.6%) were the training cohort, and 544 (49.4%) were the validation cohort. In the validation cohort, individualized treatment effects predicted by the model significantly modified the effect of trial group assignment on the primary outcome (P value for interaction = 0.02; adjusted qini coefficient, 2.46). The most important model variables were difficult airway characteristics, body mass index, and Acute Physiology and Chronic Health Evaluation II score. Conclusions: In this hypothesis-generating secondary analysis of a randomized trial with no average treatment effect and no treatment effect in any prespecified subgroups, a causal forest machine learning algorithm identified patients who appeared to benefit from the use of a bougie over a stylet and from the use of a stylet over a bougie using complex interactions between baseline patient and operator characteristics.

Implementation of a Near-Peer Support Program to Improve Trainee Well-Being after Patient Safety Events.

Adverse events can take an emotional toll on physicians, which, left unprocessed, can have negative impacts on well-being, including burnout and depression. Peer support can help mitigate these negative effects. Structured programs train physicians to aid colleagues in processing work-related experiences and emotions such as guilt and self-doubt. Although such programs are common for faculty, peer support for resident physicians has not been adequately addressed, and few programs have been described in the literature. Residency is a vulnerable time of professional identity formation, and providing support has specific challenges. The power dynamics and distance between lived experiences limit the utility of faculty peer support programs. Some institutions have trained residents to provide peer support, but widespread implementation may be difficult because of limited resident time and comfort in providing support. Chief residents (CRs), however, are close to residents in training yet experienced enough to afford perspective and are uniquely situated to provide "near-peer" support. We describe the implementation of a CR near-peer support program in which an established peer support framework was adapted to add elements specific to resident stressors and CR-resident relationships. One faculty member and two outgoing CRs lead a 2-hour workshop that is built into existing CR onboarding to ensure sustainability. The workshop combines large-group didactics and small-group breakouts, using clinical vignettes and simulated near-peer support conversations. To date, 36 CRs have been trained. CR near-peer support can serve as a model for programs in which true resident peer support is not feasible.

Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation.

BACKGROUND: Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen-saturation target that will optimize clinical outcomes in this patient population remains unknown. METHODS: In a pragmatic, cluster-randomized, cluster-crossover trial conducted in the emergency department and medical intensive care unit at an academic center, we assigned adults who were receiving mechanical ventilation to a lower target for oxygen saturation as measured by pulse oximetry (Spo2) (90%; goal range, 88 to 92%), an intermediate target (94%; goal range, 92 to 96%), or a higher target (98%; goal range, 96 to 100%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilator-free days) through day 28. The secondary outcome was death by day 28, with data censored at hospital discharge. RESULTS: A total of 2541 patients were included in the primary analysis. The median number of ventilator-free days was 20 (interquartile range, 0 to 25) in the lower-target group, 21 (interquartile range, 0 to 25) in the intermediate-target group, and 21 (interquartile range, 0 to 26) in the higher-target group (P = 0.81). In-hospital death by day 28 occurred in 281 of the 808 patients (34.8%) in the lower-target group, 292 of the 859 patients (34.0%) in the intermediate-target group, and 290 of the 874 patients (33.2%) in the higher-target group. The incidences of cardiac arrest, arrhythmia, myocardial infarction, stroke, and pneumothorax were similar in the three groups. CONCLUSIONS: Among critically ill adults receiving invasive mechanical ventilation, the number of ventilator-free days did not differ among groups in which a lower, intermediate, or higher Spo2 target was used. (Supported by the National Heart, Lung, and Blood Institute and others; PILOT ClinicalTrials.gov number, NCT03537937.).

Pulse Oximetry and Race in Critically Ill Adults.

For critically ill adults, oxygen saturation is continuously monitored using pulse oximetry (Spo2) as a surrogate for arterial oxygen saturation (Sao2). Skin pigmentation may affect accuracy of Spo2 by introducing error from statistical bias, variance, or both. We evaluated relationships between race, Spo2, Sao2, and hypoxemia (Sao2 < 88%) or hyperoxemia (Pao2 > 150 mm Hg) among adults receiving mechanical ventilation in a medical ICU. DESIGN: Single-center, observational study. SETTING: Medical ICU at an academic medical center. PATIENTS: Critically ill adults receiving mechanical ventilation from July 2018 to February 2021, excluding patients with COVID-19, with race documented as Black or White in the electronic medical record, who had a pair of Spo2 and Sao2 measurements collected within 10 minutes of each other. INTERVENTIONS: None. MEASUREMENTS: We included 1,024 patients with 5,557 paired measurements within 10 minutes, of which 3,885 (70%) were within 1 minute. Of all pairs, 769 (14%) were from Black patients and 4,788 (86%) were from White patients. In analyses using a mixed-effects model, we found that across the range of Spo2 values of 92-98%, the associated Sao2 value was approximately 1% point lower for Black patients compared with White patients. Among patients with a Spo2 value between 92% and 96%, Black patients were more likely to have both hypoxemia (3.5% vs 1.1%; p = 0.002) and hyperoxemia (4.7% vs 2.4%; p = 0.03), compared with White patients. CONCLUSIONS: Among patients with a measured Spo2 of 92-96%, greater variation in Sao2 values at a given Spo2 resulted in a higher occurence rate of both hypoxemia and hyperoxemia for Black patients compared with White patients.

Intravenous fluid therapy in sepsis.

Sepsis is the dysregulated immune response to severe infection that is common and lethal among critically ill patients. Fluid administration is a common treatment for hypotension and shock in early sepsis. Fluid therapy can also cause edema and organ dysfunction. Research on the best treatment strategies for sepsis has provided insights on the optimal timing, dose, and type of fluid to treat patients with sepsis. Initial research on early goal-directed therapy for sepsis included an initial bolus of 30 ml/kg of fluid, but more recent research has supported use of smaller volumes. After initial fluid resuscitation, minimizing additional fluid administration may be beneficial, but no single measure has been established as the best method to guide ongoing fluid management in sepsis. Dynamic measures of "fluid responsiveness" can predict which patients will experience an increase in cardiac output from a fluid bolus. Use of such a measure in clinical care remains limited by applicability to patient populations and uncertainty regarding the effect on clinical outcomes. Recent research informs the effect of fluid composition on outcomes for patients with sepsis. Current data support the use of balanced crystalloids, rather than saline, and the use of crystalloids, rather than semisynthetic colloids. The role for albumin administration in sepsis remains uncertain. Future research should focus on determining the optimal volume of fluid during sepsis resuscitation, the effectiveness of measures of "fluid responsiveness" in improving outcomes, the optimal composition of crystalloid solutions, the role of albumin, and the effects of "deresuscitation" after septic shock.

The Influence of the COVID-19 Pandemic on Intensivists' Well-Being: A Qualitative Study.

BACKGROUND: The COVID-19 pandemic has strained health care systems and has resulted in widespread critical care staffing shortages, negatively impacting the quality of care delivered. RESEARCH QUESTION: How have hospitals' emergency responses to the pandemic influenced the well-being of frontline intensivists, and do any potential strategies exist to improve their well-being and to help preserve the critical care workforce? STUDY DESIGN AND METHODS: We conducted semistructured interviews of intensivists at clusters of tertiary and community hospitals located in six regions across the United States between August and November 2020 using the "four S" framework of acute surge planning (ie, space, staff, stuff, and system) to organize the interview guide. We then used inductive thematic analysis to identify themes describing the influence of hospitals' emergency responses on intensivists' well-being. RESULTS: Thirty-three intensivists from seven tertiary and six community hospitals participated. Intensivists reported experiencing substantial moral distress, particularly because of restricted visitor policies and their perceived negative impacts on patients, families, and staff. Intensivists also frequently reported burnout symptoms as a result of their experiences with patient death, exhaustion over the pandemic's duration, and perceived lack of support from colleagues and hospitals. We identified several potentially modifiable factors perceived to improve morale, including the proactive provision of mental health resources, establishment of formal backup schedules for physicians, and clear actions demonstrating that clinicians are valued by their institutions. INTERPRETATION: Restrictive visitation policies contributed to moral distress as reported by intensivists, highlighting the need to reconsider the risks and benefits of these policies. We also identified several interventions as perceived by intensivists that may help to mitigate moral distress and to improve burnout as part of efforts to preserve the critical care workforce.

Radiographic Findings and Association With Clinical Severity and Outcomes in Critically Ill Patients With COVID-19.

PURPOSE: To describe evolution and severity of radiographic findings and assess association with disease severity and outcomes in critically ill COVID-19 patients. MATERIALS AND METHODS: This retrospective study included 62 COVID-19 patients admitted to the intensive care unit (ICU). Clinical data was obtained from electronic medical records. A total of 270 chest radiographs were reviewed and qualitatively scored (CXR score) using a severity scale of 0-30. Radiographic findings were correlated with clinical severity and outcome. RESULTS: The CXR score increases from a median initial score of 10 at hospital presentation to the median peak CXR score of 18 within a median time of 4 days after hospitalization, and then slowly decreases to a median last CXR score of 15 in a median time of 12 days after hospitalization. The initial and peak CXR score was independently associated with invasive MV after adjusting for age, gender, body mass index, smoking, and comorbidities (Initial, odds ratio [OR]: 2.11 per 5-point increase, confidence interval [CI] 1.35-3.32, P= 0.001; Peak, OR: 2.50 per 5-point increase, CI 1.48-4.22, P= 0.001). Peak CXR scores were also independently associated with vasopressor usage (OR: 2.28 per 5-point increase, CI 1.30-3.98, P= 0.004). Peak CXR scores strongly correlated with the duration of invasive MV (Rho = 0.62, P< 0.001), while the initial CXR score (Rho = 0.26) and the peak CXR score (Rho = 0.27) correlated weakly with the sequential organ failure assessment score. No statistically significant associations were found between radiographic findings and mortality. CONCLUSIONS: Evolution of radiographic features indicates rapid disease progression and correlate with requirement for invasive MV or vasopressors but not mortality, which suggests potential nonpulmonary pathways to death in COVID-19.

Bag-Mask Ventilation Versus Apneic Oxygenation During Tracheal Intubation in Critically Ill Adults: A Secondary Analysis of 2 Randomized Trials.

Background: Hypoxemia is common during tracheal intubation in intensive care units. To prevent hypoxemia during intubation, 2 methods of delivering oxygen between induction and laryngoscopy have been proposed: bag-mask ventilation and supplemental oxygen delivered by nasal cannula without ventilation (apneic oxygenation). Whether one of these approaches is more effective for preventing hypoxemia during intubation of critically ill patients is unknown. Methods: We performed a secondary analysis of data from 138 patients enrolled in 2, consecutive randomized trials of airway management in an academic intensive care unit. A total of 61 patients were randomized to receive bag-mask ventilation in a trial comparing bag-mask ventilation to none, and 77 patients were randomized to receive 100% oxygen at 15 L/min by nasal cannula in a trial comparing apneic oxygenation to none. Using multivariable linear regression accounting for age, body mass index, severity of illness, and oxygen saturation at induction, we compared patients assigned to bag-mask ventilation with those assigned to apneic oxygenation regarding lowest oxygen saturations from induction to 2 min after intubation. Results: Patients assigned to bag-mask ventilation and apneic oxygenation were similar at baseline. The median lowest oxygen saturation was 96% (interquartile range [IQR] 89%-100%) in the bag-mask ventilation group and 92% (IQR 84%-99%) in the apneic oxygenation group. After adjustment for prespecified confounders, bag-mask ventilation was associated with a higher lowest oxygen saturation compared to apneic oxygenation (mean difference, 4.2%; 95% confidence interval, 0.7%-7.8%; P = .02). The incidence of severe hypoxemia (oxygen saturation<80%) was 6.6% in the bag-mask ventilation group and 15.6% in the apneic oxygenation group (adjusted odds ratio, 0.33; P = .09). Conclusions: This secondary analysis of patients assigned to bag-mask ventilation and apneic oxygenation during 2 clinical trials suggests that bag-mask ventilation is associated with higher oxygen saturation during intubation compared to apneic oxygenation.

The Influence of the COVID-19 Pandemic on ICU Organization, Care Processes, and Frontline Clinician Experiences: A Qualitative Study.

BACKGROUND: The COVID-19 pandemic resulted in unprecedented adjustments to ICU organization and care processes globally. RESEARCH QUESTIONS: Did hospital emergency responses to the COVID-19 pandemic differ depending on hospital setting? Which strategies worked well to mitigate strain as perceived by intensivists? STUDY DESIGN AND METHODS: Between August and November 2020, we carried out semistructured interviews of intensivists from tertiary and community hospitals across six regions in the United States that experienced early or large surges of COVID-19 patients, or both. We identified themes of hospital emergency responses using the four S framework of acute surge planning: space, staff, stuff, system. RESULTS: Thirty-three intensivists from seven tertiary and six community hospitals participated. Clinicians across both settings believed that canceling elective surgeries was helpful to increase ICU capabilities and that hospitals should establish clearly defined thresholds at which surgeries are limited during future surge events. ICU staff was the most limited resource; staff shortages were improved by the use of tiered staffing models, just-in-time training for non-ICU clinicians, designated treatment teams, and deployment of trainees. Personal protective equipment (PPE) shortages and reuse were widespread, causing substantial distress among clinicians; hands-on PPE training was helpful to reduce clinicians' anxiety. Transparency and involvement of frontline clinicians as stakeholders were important components of effective emergency responses and helped to maintain trust among staff. INTERPRETATION: We identified several strategies potentially to mitigate strain as perceived by intensivists working in both tertiary and community hospital settings. Our study also demonstrated the importance of trust and transparency between frontline staff and hospital leadership as key components of effective emergency responses during public health crises.

Variation in Initial U.S. Hospital Responses to the Coronavirus Disease 2019 Pandemic.

OBJECTIVES: The coronavirus disease 2019 pandemic has strained many healthcare systems. In response, U.S. hospitals altered their care delivery systems, but there are few data regarding specific structural changes. Understanding these changes is important to guide interpretation of outcomes and inform pandemic preparedness. We sought to characterize emergency responses across hospitals in the United States over time and in the context of local case rates early in the coronavirus disease 2019 pandemic. DESIGN: We surveyed hospitals from a national acute care trials group regarding operational and structural changes made in response to the coronavirus disease 2019 pandemic from January to August 2020. We collected prepandemic characteristics and changes to hospital system, space, staffing, and equipment during the pandemic. We compared the timing of these changes with county-level coronavirus disease 2019 case rates. SETTING AND PARTICIPANTS: U.S. hospitals participating in the Prevention and Early Treatment of Acute Lung Injury Network Coronavirus Disease 2019 Observational study. Site investigators at each hospital collected local data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-five sites participated (94% response rate). System-level changes (incident command activation and elective procedure cancellation) occurred at nearly all sites, preceding rises in local case rates. The peak inpatient census during the pandemic was greater than the prior hospital bed capacity in 57% of sites with notable regional variation. Nearly half (49%) expanded ward capacity, and 63% expanded ICU capacity, with nearly all bed expansion achieved through repurposing of clinical spaces. Two-thirds of sites adapted staffing to care for patients with coronavirus disease 2019, with 48% implementing tiered staffing models, 49% adding temporary physicians, nurses, or respiratory therapists, and 30% changing the ratios of physicians or nurses to patients. CONCLUSIONS: The coronavirus disease 2019 pandemic prompted widespread system-level changes, but front-line clinical care varied widely according to specific hospital needs and infrastructure. Linking operational changes to care delivery processes is a necessary step to understand the impact of the coronavirus disease 2019 pandemic on patient outcomes.

Comparison of Clinical Features and Outcomes in Critically Ill Patients Hospitalized with COVID-19 versus Influenza.

Rationale: No direct comparisons of clinical features, laboratory values, and outcomes between critically ill patients with coronavirus disease (COVID-19) and patients with influenza in the United States have been reported.Objectives: To evaluate the risk of mortality comparing critically ill patients with COVID-19 with patients with seasonal influenza.Methods: We retrospectively identified patients admitted to the intensive care units (ICUs) at two academic medical centers with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza A or B infections between January 1, 2019, and April 15, 2020. The clinical data were obtained by medical record review. All patients except one had follow-up to hospital discharge or death. We used relative risk regression adjusting for age, sex, number of comorbidities, and maximum sequential organ failure scores on Day 1 in the ICU to determine the risk of hospital mortality and organ dysfunction in patients with COVID-19 compared with patients with influenza.Results: We identified 65 critically ill patients with COVID-19 and 74 patients with influenza. The mean (±standard deviation) age in each group was 60.4 ± 15.7 and 56.8 ± 17.6 years, respectively. Patients with COVID-19 were more likely to be male, have a higher body mass index, and have higher rates of chronic kidney disease and diabetes. Of the patients with COVID-19, 37% identified as Hispanic, whereas 10% of the patients with influenza identified as Hispanic. A similar proportion of patients had fevers (∼40%) and lymphopenia (∼80%) on hospital presentation. The rates of acute kidney injury and shock requiring vasopressors were similar between the groups. Although the need for invasive mechanical ventilation was also similar in both groups, patients with COVID-19 had slower improvements in oxygenation, longer durations of mechanical ventilation, and lower rates of extubation than patients with influenza. The hospital mortality was 40% in patients with COVID-19 and 19% in patients with influenza (adjusted relative risk, 2.13; 95% confidence interval, 1.24-3.63; P = 0.006).Conclusions: The need for invasive mechanical ventilation was common in patients in the ICU for COVID-19 and influenza. Compared with those with influenza, patients in the ICU with COVID-19 had worse respiratory outcomes, including longer duration of mechanical ventilation. In addition, patients with COVID-19 were at greater risk for in-hospital mortality, independent of age, sex, comorbidities, and ICU severity of illness.

Fluid management in ARDS: an evaluation of current practice and the association between early diuretic use and hospital mortality.

BACKGROUND: Acute respiratory distress syndrome (ARDS) and volume overload are associated with increased hospital mortality. Evidence supports conservative fluid management in ARDS, but whether current practice reflects the implementation of that evidence has not been described. This study reports the variability in contemporary fluid management for ICU patients with ARDS. We compared routine care to trial protocols and analyzed whether more conservative management with diuretic medications in contemporary, usual care is associated with outcomes. METHODS: We performed a retrospective cohort study in nine ICUs at two academic hospitals during 2016 and 2017. We included 234 adult patients with ARDS in an ICU at least 3 days after meeting moderate-severe ARDS criteria (PaO2:FIO2 ≤ 150). The primary exposure was any diuretic use in 48 to 72 h after meeting ARDS criteria. The primary outcome was hospital mortality. Unadjusted statistical analyses and multivariable logistic regression were used. RESULTS: In 48-72 h after meeting ARDS criteria, 116 patients (50%) received a diuretic. In-hospital mortality was lower in the group that received diuretics than in the group that did not (14% vs 25%; p = 0.025). At ARDS onset, both groups had similar Sequential Organ Failure Assessment scores and ICU fluid balances. During the first 48 h after ARDS, the diuretic group received less crystalloid fluid than the no diuretic group (median [inter-quartile range]: 1.2 L [0.2-2.8] vs 2.4 L [1.2-5.0]; p < 0.001), but both groups received more fluid from medications and nutrition than from crystalloid. At 48 h, the prevalence of volume overload (ICU fluid balance >10% of body weight) in each group was 16% and 25%(p = 0.09), respectively. During 48-72 h after ARDS, the overall prevalence of shock was 44% and similar across both groups. Central venous pressure was recorded in only 18% of patients. Adjusting for confounders, early diuretic use was independently associated with lower hospital mortality (AOR 0.46, 95%CI [0.22, 0.96]). CONCLUSIONS: In this sample of ARDS patients, volume overload was common, and early diuretic use was independently associated with lower hospital mortality. These findings support the importance of fluid management in ARDS and suggest opportunities for further study and implementation of conservative fluid strategies into usual care.