Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic.

To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN: Prospective observational study. SETTING: One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS: Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS: None. RESULTS: Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0-81.0 yr) versus 61 years (48.0-72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, -0.84, -1.34, and -0.84; p < 0.001). CONCLUSIONS: Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

Risk Factors for and Outcomes Associated With Peri-Intubation Hypoxemia: A Multicenter Prospective Cohort Study.

BACKGROUND: Little is known about hypoxemia surrounding endotracheal intubation in the critically ill. Thus, we sought to identify risk factors associated with peri-intubation hypoxemia and its effects' on the critically ill. METHODS: Data from a multicenter, prospective, cohort study enrolling 1,033 critically ill adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 were used to identify risk factors associated with peri-intubation hypoxemia and its effects on patient outcomes. We defined hypoxemia as any pulse oximetry ≤ 88% during and up to 30 minutes following endotracheal intubation. RESULTS: In the full analysis (n = 1,033), 123 (11.9%) patients experienced the primary outcome. Five risk factors independently associated with our outcome were identified on multiple logistic regression: cardiac related reason for endotracheal intubation (OR 1.67, [95% CI 1.04, 2.69]); pre-intubation noninvasive ventilation (OR 1.66, [95% CI 1.09, 2.54]); emergency intubation (OR 1.65, [95% CI 1.06, 2.55]); moderate-severe difficult bag-mask ventilation (OR 2.68, [95% CI 1.72, 4.19]); and crystalloid administration within the preceding 24 hours (OR 1.24, [95% CI 1.07, 1.45]; per liter up to 4 liters). Higher baseline SpO2 was found to be protective (OR 0.93, [95% CI 0.91, 0.96]; per percent up to 97%). Consistent results were seen in a separate analysis on only stable patients (n = 921, 93 [10.1%]) (those without baseline hypoxemia ≤ 88%). Peri-intubation hypoxemia was associated with in-hospital mortality (OR 2.40, [95% CI 1.33, 4.31]; stable patients: OR 2.67, [95% CI 1.38, 5.17]) but not ICU length of stay (point estimate 0.9 days, [95% CI -1.0, 2.8 days]; stable patients: point estimate 1.5 days, [95% CI -0.4, 3.4 days]) after adjusting for age, body mass index, illness severity, airway related reason for intubation (i.e., acute respiratory failure), and baseline SPO2. CONCLUSIONS: Patients with pre-existing noninvasive ventilation and volume loading who were intubated emergently in the setting of hemodynamic compromise with bag-mask ventilation described as moderate-severe were at increased risk for peri-intubation hypoxemia. Higher baseline oxygenation was found to be protective against peri-intubation hypoxemia. Peri-intubation hypoxemia was associated with in-hospital mortality but not ICU length of stay. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.

Risk factors for and prediction of post-intubation hypotension in critically ill adults: A multicenter prospective cohort study.

OBJECTIVE: Hypotension following endotracheal intubation in the ICU is associated with poor outcomes. There is no formal prediction tool to help estimate the onset of this hemodynamic compromise. Our objective was to derive and validate a prediction model for immediate hypotension following endotracheal intubation. METHODS: A multicenter, prospective, cohort study enrolling 934 adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 was conducted to derive and validate a prediction model for immediate hypotension following endotracheal intubation. We defined hypotension as: 1) mean arterial pressure <65 mmHg; 2) systolic blood pressure <80 mmHg and/or decrease in systolic blood pressure of 40% from baseline; 3) or the initiation or increase in any vasopressor in the 30 minutes following endotracheal intubation. RESULTS: Post-intubation hypotension developed in 344 (36.8%) patients. In the full cohort, 11 variables were independently associated with hypotension: increasing illness severity; increasing age; sepsis diagnosis; endotracheal intubation in the setting of cardiac arrest, mean arterial pressure <65 mmHg, and acute respiratory failure; diuretic use 24 hours preceding endotracheal intubation; decreasing systolic blood pressure from 130 mmHg; catecholamine and phenylephrine use immediately prior to endotracheal intubation; and use of etomidate during endotracheal intubation. A model excluding unstable patients' pre-intubation (those receiving catecholamine vasopressors and/or who were intubated in the setting of cardiac arrest) was also developed and included the above variables with the exception of sepsis and etomidate. In the full cohort, the 11 variable model had a C-statistic of 0.75 (95% CI 0.72, 0.78). In the stable cohort, the 7 variable model C-statistic was 0.71 (95% CI 0.67, 0.75). In both cohorts, a clinical risk score was developed stratifying patients' risk of hypotension. CONCLUSIONS: A novel multivariable risk score predicted post-intubation hypotension with accuracy in both unstable and stable critically ill patients. STUDY REGISTRATION: Clinicaltrials.gov identifier: NCT02508948 and Registered Report Identifier: RR2-10.2196/11101.

Cardiac Dysfunction in Adult Patients with Traumatic Brain Injury: A Prospective Cohort Study.

BACKGROUND: There are limited data regarding the development of myocardial dysfunction after a traumatic brain injury (TBI). We investigated incidence, risk factors, and prognostic importance of cardiac dysfunction in adult patients admitted to the intensive care unit (ICU) after a moderate to severe TBI. METHODS: Prospective observational study of consecutive patients admitted to neuro-trauma ICU with moderate to severe TBI from August 2014 to June 2015. RESULTS: A total of 46 patients were included. Patients' mean (±SD) age was 44.7 (±20.7) years and mean Glasgow Coma Scale value was 5.6 (±3). Motor vehicle accident was the most common mechanism of TBI, with subdural and subarachnoid hemorrhages as the most common pathologies. Cardiac dysfunction developed in 6 of 46 (13%) patients. Patients with cardiac dysfunction had higher prevalence of diabetes mellitus (50% vs. 10%, P = 0.03) and higher proportion of electrocardiogram abnormalities (83% vs. 27%, P = 0.02) compared to the patients without cardiac dysfunction. Mean Glasgow Coma Scale scores were not significantly different between patients who developed cardiac dysfunction from those who did not (5.5 vs. 5.6, P = 0.95). Requirement for vasopressor support (33.3% vs. 40%, P = 1.0) and median ventilator days (5.2 vs. 4.7, P = 0.9) were similar between patients with and without cardiac dysfunction. There were no significant differences in hospital lengths of stay (12.3 vs. 13.8 days, P = 0.34) and hospital mortality (33% vs. 17.5%, P = 0.58) between the two groups. CONCLUSIONS: Cardiac dysfunction occurs in patients after moderate to severe TBI, with mild to moderate reduction in left ventricular ejection fraction. Patients who developed cardiac dysfunction after TBI had a higher prevalence of diabetes mellitus and higher proportion of abnormalities in electrocardiograms. Development of cardiac dysfunction was not associated with adverse clinical outcomes.

Thrombocytopenia in adult patients with sepsis: incidence, risk factors, and its association with clinical outcome.

BACKGROUND: Sepsis is a major risk factor for the development of thrombocytopenia, but few studies have specifically evaluated prognostic importance of thrombocytopenia in patients with sepsis. We investigated the incidence, risk factors, and prognostic importance of thrombocytopenia in adult patients admitted to the intensive care unit (ICU) with sepsis. METHODS: A retrospective analysis of patients admitted with severe sepsis/septic shock from December 2007 to January 2009 to a 24-bed medical ICU was done. RESULTS: A total of 304 patients were included in the study. The patients' mean (±SD) age was 68.8 (±15.8) years. The majority (93.7%) had septic shock, and pneumonia was the most common infection (38.8%). Thrombocytopenia developed in 145 patients (47.6%): 77 (25.3%) at ICU admission and 68 (22.3%) during their hospital course. The median (IQR) duration of thrombocytopenia was 4.4 (1.9-6.9) days. Patients who developed thrombocytopenia had more episodes of major bleeding (14.4% vs. 3.7%, P < 0.01) and received more transfusions. Patients with thrombocytopenia had a higher incidence of acute kidney injury (44.1% vs. 29.5%, P < 0.01), prolonged vasopressor support (median (IQR): 37 (17-76) vs. 23 (13-46) h, P < 0.01), and longer ICU stay (median (IQR): 3.1 (1.6-7.8) vs. 2.1 (1.2-4.4) days, P < 0.01). The 28-day mortality was similar between patients with and without thrombocytopenia (32.4% vs. 24.5%, P = 0.12). However, while 15 of 86 patients (17.4%) who resolved their thrombocytopenia died, 32 of 59 patients (54.2%) whose thrombocytopenia did not resolve died (P < 0.01). The association between non-resolution of thrombocytopenia and mortality remained significant after adjusting for age, APACHE III score and compliance with a sepsis resuscitation bundle (P < 0.01). CONCLUSIONS: Thrombocytopenia is common in patients who are admitted to the ICU with severe sepsis and septic shock. Patients with thrombocytopenia had more episodes of major bleeding, increased incidence of acute kidney injury, and prolonged ICU stay. Non-resolution of thrombocytopenia, but not thrombocytopenia itself, was associated with increased 28-day mortality.

Eight-year trend of acute respiratory distress syndrome: a population-based study in Olmsted County, Minnesota.

RATIONALE: significant progress has been made in understanding the pathogenesis of acute respiratory distress syndrome (ARDS). Recent advances in hospital practice may have reduced the incidence of this lethal syndrome. OBJECTIVES: to observe incidence trends and associated outcomes of ARDS. METHODS: this population-based cohort study was conducted in Olmsted County, Minnesota. Using a validated screening protocol, investigators identified intensive care patients with acute hypoxemia and bilateral pulmonary infiltrates. The presence of ARDS was independently confirmed according to American-European Consensus Conference criteria. The incidence of ARDS and associated outcomes were compared over the 8-year study period (2001-2008). MEASUREMENTS AND MAIN RESULTS: over the 8-year period, critically ill Olmsted County residents presented with increasing severity of acute illness, a greater number of comorbidities, and a higher prevalence of major predisposing conditions for ARDS. The ARDS incidence decreased significantly from 82.4 to 38.9 per 100,000 person-years during the study period (P < 0.001). A decline in hospital-acquired ARDS (P < 0.001) was responsible for the fall in the incidence density with no change on admission (P = 0.877). Overall, mortality and hospital and intensive care unit lengths of stay decreased over time (P < 0.001), whereas the ARDS case-fatality did not change significantly. CONCLUSIONS: despite an increase in patients' severity of illness, number of comorbidities, and prevalence of major ARDS risk factors, the incidence of ARDS in this suburban community decreased by more than half. Correlation of the observed findings with changes in health care delivery may have important implications for the planning of acute care services in other regions.

Limiting ventilator-induced lung injury through individual electronic medical record surveillance.

BACKGROUND: To improve the safety of ventilator care and decrease the risk of ventilator-induced lung injury, we designed and tested an electronic algorithm that incorporates patient characteristics and ventilator settings, allowing near-real-time notification of bedside providers about potentially injurious ventilator settings. METHODS: Electronic medical records of consecutive patients who received invasive ventilation were screened in three Mayo Clinic Rochester intensive care units. The computer system alerted bedside providers via the text paging notification about potentially injurious ventilator settings. Alert criteria included a Pao2/Fio2 ratio of <300 mm Hg, free text search for the words "edema" or "bilateral + infiltrates" on the chest radiograph report, a tidal volume of >8 mL/kg predicted body weight (based on patient gender and height), a plateau pressure of >30 cm H2O, and a peak airway pressure of >35 cm H2O. Respiratory therapists answered a brief online satisfaction survey. Ventilator-induced lung injury risk was compared before and after the introduction of ventilator-induced lung injury alert. FINDINGS: The prevalence of acute lung injury was 42% (n = 490) among 1,159 patients receiving >24 hrs of invasive ventilation. The system sent 111 alerts for 80 patients, with a positive predictive value of 59%. The exposure to potentially injurious ventilation decreased after the intervention from 40.6 ± 74.6 hrs to 26.9 ± 77.3 hrs (p = .004). INTERPRETATIONS: Electronic medical record surveillance of mechanically ventilated patients accurately detects potentially injurious ventilator settings and is able to influence bedside practice at moderate costs. Its implementation is associated with decreased patient exposure to potentially injurious mechanical ventilation settings.

Hospitalized patients with 2009 H1N1 influenza infection: the Mayo Clinic experience.

OBJECTIVE: To describe the clinical course and outcome of adults hospitalized with the 2009 H1N1 influenza infection. PATIENTS AND METHODS: In this retrospective study, we reviewed the electronic medical records of patients with H1N1 influenza infection treated at Mayo Clinic in Rochester, MN, from May 1, 2009, through December 31, 2009. RESULTS: We identified 1053 patients with H1N1 influenza infection; this study consists of 66 hospitalized adults (6%). Patients' mean +/- SD age was 46.9+/-17.8 years. The 3 most common comorbidities were hypertension in 31 patients (47%), obesity in 29 (44%), and diabetes mellitus in 21 (32%). The most common symptoms were cough in 58 patients (88%), fever or chills in 55 (83%), and dyspnea in 47 (71%). Twenty-nine patients (44%) were admitted to the intensive care unit (ICU). Dyspnea and thrombocytopenia were more common in the ICU patients. The hospital, 28-day, and 90-day mortality rates were 8% (5/66), 11% (7/66), and 14% (9/66), respectively. Among the 29 ICU patients, 23 (79%) received mechanical ventilation, and 16 (55%) developed acute lung injury or acute respiratory distress syndrome. Rescue therapy for refractory respiratory failure was provided for 6 patients (21%). Of the 29 ICU patients, 10 (34%) required vasopressor support, and 4 (14%) required acute renal replacement therapy. CONCLUSION: Hospitalized adults with H1N1 influenza infection are relatively young, and a significant number require treatment in the ICU. Among the patients who require ICU admission, most develop acute lung injury or acute respiratory distress syndrome and require mechanical ventilator support.

Sleep-disordered breathing during pregnancy.

Pregnancy is associated with many physiologic and hormonal changes along with changes in sleep architecture, placing pregnant women at risk for the development of sleep-disordered breathing or worsening of preexisting sleep apnea. Snoring, the most common symptom of sleep-disordered breathing, is markedly increased during pregnancy. The exact prevalence of obstructive sleep apnea in pregnant women is unknown. Because the apneic episodes are commonly associated with oxyhemoglobin desaturations, the combination of obstructive sleep apnea and pregnancy can be potentially harmful to the fetus given the low oxygen reserves during pregnancy. Obstructive sleep apnea has been associated with an increased risk of hypertension among the general population, and this raises the possibility of its association with gestational hypertension and preeclampsia. In this clinical review, we discuss the physiologic changes of pregnancy that predispose pregnant women to the development of obstructive sleep apnea and the effects of sleep-disordered breathing on pregnancy outcomes. We also review the recommendations regarding evaluation for sleep apnea and treatment options during pregnancy and postpartum.