A multi-center, randomized, double blinded, placebo-controlled trial of amantadine to stimulate awakening in comatose patients resuscitated from cardiac arrest.

Objectives: We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest. Methods: We performed a prospective, randomized controlled pilot trial, randomizing subjects to amantadine 100mg twice daily or placebo for up to 7 days. The study drug was administered between 72-120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded. Our primary outcome was awakening, defined as following two-step commands, within 28 days of cardiac arrest. Secondary outcomes included length of stay, awakening, time to awakening, and neurologic outcome measured by Cerebral Performance Category (CPC) at hospital discharge. We compared the proportion of subjects awakening and hospital survival using Fisher's exact tests and time to awakening and hospital length of stay using Wilcoxon rank sum tests. Results: After 2 years, we stopped the study due to slow enrollment and lapse of funding. We enrolled 14 subjects (12% of goal enrollment), 7 in the amantadine arm and 7 in the placebo arm. The proportion of patients who awakened within 28 days after cardiac arrest did not differ between amantadine (n=2, 28.57%) and placebo groups (n=3, 42.86%) (p = 1.00). There were no differences in secondary outcomes. Study medication was stopped in three (21%) subjects. Adverse events included a recurrence of seizures (n=2; 14%), both of which occurred in the placebo arm. Conclusion: We could not determine the effect of amantadine on awakening in comatose survivors of cardiac arrest due to small sample size.

Estimated glomerular filtration rate among intensive care unit survivors: From the removal of race coefficient to cystatin C-based equations.

PURPOSE: Black race coefficient used in serum creatinine (sCr)-based estimated glomerular filtration rate (eGFR) calculation may perpetuate racial disparities. Among intensive care unit (ICU) survivors, sCr overestimates kidney function due to sarcopenia. Cystatin C (cysC) is a race- and muscle mass-independent eGFR marker. We investigated the impact of removing the race coefficient from sCr-based eGFR and compared cysC- and sCr-based eGFR in ICU survivors. MATERIALS AND METHODS: Among 30,920 patients from 2 institutions in the Bronx and Boston, eGFR was calculated at hospital discharge using sCr-based equations with and without race coefficient (eGFRsCr2009 and eGFRsCr2021). In a subset with available cysC between ICU admission and 1-year follow-up, sCr- and cysC-based estimates were compared. RESULTS: eGFRsCr2021 was higher than eGFRsCr2009 by a median of 4 ml/min/1.73 m2 among non-Black patients and lower by a median of 8 ml/min/1.73 m2 among Black patients. Removing race coefficient reclassified 12.9% of non-Black subjects and 16.1% of Black subjects to better and worse eGFR category, respectively, and differentially impacted the prevalence of kidney dysfunction between the institutions due to differences in racial composition. Among 51 patients with available cysC (108 measurements), cysC-based estimates were lower than sCr-based estimates (median difference 9 to 16 ml/min/1.73 m2), resulting in reclassification to worse eGFR category in 34% to 53.5% of measurements. CONCLUSIONS: Among ICU survivors, removal of race coefficient leads to lower eGFR in Black patients and may contribute to overestimation of kidney function in non-Black patients. While cysC is rarely used, estimates based on this marker are significantly lower than those based on sCr.

Kidney-specific biomarkers for predicting acute kidney injury following cardiac arrest.

AIM: To evaluate the performance of kidney-specific biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C) in early detection of acute kidney injury (AKI) following cardiac arrest (CA) when compared to serum creatinine. METHODS: Adult CA patients who had kidney-specific biomarkers of AKI collected within 12 h of return of spontaneous circulation (ROSC) were included. The association between renal biomarker levels post-ROSC and the development of KDIGO stage III AKI within 7 days of enrollment were assessed as well as their predictive value of future AKI development, neurological outcomes, and survival to discharge. RESULTS: Of 153 patients, 54 (35%) developed stage III AKI within 7 days, and 98 (64%) died prior to hospital discharge. Patients who developed stage III AKI, compared to those who did not, had higher median levels of creatinine, NGAL, and cystatin-C (p < 0.001 for all). There was no statistically significant difference in KIM-1 between groups. No biomarker outperformed creatinine in the ability to predict stage III AKI, neurological outcomes, or survival outcomes (p > 0.05 for all). However, NGAL, cystatin-C, and creatinine all performed better than KIM-1 in their ability to predict AKI development (p < 0.01 for all). CONCLUSION: In post-CA patients, creatinine, NGAL, and cystatin-C (but not KIM-1) measured shortly after ROSC were higher in patients who subsequently developed AKI. No biomarker was statistically superior to creatinine on its own for predicting the development of post-arrest AKI.

Obesity is Unlikely to be an Impediment to First-Pass Success During the Intubation of Critically Ill Patients.

Background: Obesity has been described as a potential risk factor for difficult intubation among critically ill patients. Our primary aim was to further elucidate the association between obesity and first-pass success. Our secondary aim was to determine whether the use of hyper-angulated video laryngoscopy improves first-pass success compared to direct laryngoscopy when utilized for the intubation of critically ill obese patients. Study Design and Methods: A retrospective cohort study of adult patients undergoing endotracheal intubation outside of the operating room or emergency department between January 30, 2016 and May 1, 2020 at 3 campuses of an academic hospital system in the Bronx, NY. Our primary outcome was first-pass success of intubation. A multivariate logistic analysis was utilized to compare obesity status with first-pass success. Results: We identified 3791 critically ill patients who underwent endotracheal intubation of which 1417 were obese (body mass index [BMI] ≥ 30). The incidence of hyper-angulated video laryngoscopy increased over the study period. A total of 46.6% of obese patients underwent intubation with hyper-angulated video laryngoscopy as compared to 35.1% of the nonobese group. First-pass success was 79.2% among the entire cohort. Obesity status did not appear to be associated with first-pass success (adjusted odds ratio [OR] 1.07, 95% confidence interval [CI]: 090-1.27; P = .47). Hyper-angulated video laryngoscopy did not seem to improve first-pass success among obese patients as compared to nonobese patients (adjusted OR 1.21, 95% CI: 0.85-1.71; P = .29). These findings persisted even after redefining the obesity cutoff as BMI ≥ 40 and excluding patients intubated during cardiac arrests. Conclusion: We did not detect an association between obesity and first-pass success. Hyper-angulated video laryngoscopy did not appear offer additional benefit over direct laryngoscopy during the intubation of critically ill obese patients.

Transpulmonary pressure measurements and lung mechanics in patients with early ARDS and SARS-CoV-2.

PURPOSE: Acute Respiratory Distress Syndrome (ARDS) secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has demonstrated variable oxygenation and respiratory-system mechanics without investigation of transpulmonary and chest-wall mechanics. This study describes lung, chest wall and respiratory-system mechanics in patients with SARS-CoV-2 and ARDS. METHODS: Data was collected from forty patients with confirmed SARS-CoV-2 and ARDS at Beth Israel Deaconess Medical Center in Boston, Massachusetts. Esophageal balloons were placed to estimate pleural and transpulmonary pressures. Clinical characteristics, respiratory-system, transpulmonary, and chest-wall mechanics were measured over the first week. RESULTS: Patients had moderate-severe ARDS (PaO2/FiO2 123[98-149]) and were critically ill (APACHE IV 108 [94-128] and SOFA 12 [11-13]). PaO2/FiO2 improved over the first week (150 mmHg [122.9-182] to 185 mmHg [138-228] (p = 0.035)). Respiratory system (30-35 ml/cm H2O), lung (40-50 ml/cm H2O) and chest wall (120-150 ml/cm H2O) compliance remained similar over the first week. Elevated basal pleural pressures correlated with BMI. Patients required prolonged mechanical ventilation (14.5 days [9.5-19.0]), with a mortality of 32.5%. CONCLUSIONS: Patients displayed normal chest-wall mechanics, with increased basal pleural pressure. Respiratory system and lung mechanics were similar to known existing ARDS cohorts. The wide range of respiratory system mechanics illustrates the inherent heterogeneity that is consistent with typical ARDS.

Performance of the CURB-65 Score in Predicting Critical Care Interventions in Patients Admitted With Community-Acquired Pneumonia.

STUDY OBJECTIVE: Confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older (CURB-65) is a clinical prediction rule intended to stratify patients with pneumonia by expected mortality. We assess the predictive performance of CURB-65 for the proximal endpoint of receipt of critical care intervention in emergency department (ED) patients admitted with community-acquired pneumonia. METHODS: We performed a retrospective analysis of electronic health records from a single tertiary center for ED patients admitted as inpatients with a primary diagnosis of pneumonia from 2010 to 2014. Patients with a history of malignancy, tuberculosis, bronchiectasis, HIV, or readmission within 14 days were excluded. We assessed the predictive accuracy of CURB-65 for receipt of critical care interventions (ie, vasopressors, large-volume intravenous fluids, invasive catheters, assisted ventilation, insulin infusions, or renal replacement therapy) and inhospital mortality. Logistic regression was performed to assess the increase in odds of critical care intervention or inhospital mortality by increasing CURB-65 score. RESULTS: There were 2,322 patients admitted with community-acquired pneumonia in the study cohort; 630 (27.1%) were admitted to the ICU within 48 hours of ED triage and 343 (14.8%) received a critical care intervention. Of patients with a CURB-65 score of 0 to 1, 181 (15.6%) were admitted to the ICU, 74 (6.4%) received a critical care intervention, and 7 (0.6%) died. Of patients with a CURB-65 score of 2, 223 (27.0%) were admitted to the ICU, 127 (15.4%) received a critical care intervention, and 47 (5.7%) died. Among patients with CURB-65 score greater than or equal to 3, 226 (67.0%) were admitted to the ICU, 142 (42.1%) received a critical care intervention, and 43 (12.8%) died. The areas under the receiver operating characteristic for CURB-65 as a predictor of critical care intervention and mortality were 0.73 and 0.77, whereas sensitivity of CURB-65 score greater than or equal to 2 in predicting critical care intervention was 78.4%; for mortality, 92.8%. CONCLUSION: Patients with CURB-65 score less than or equal to 2 were often admitted to the ICU and received critical care interventions. Given this finding and the relatively low sensitivity of CURB-65 for critical care intervention, clinicians should exercise caution when using CURB-65 to guide disposition. Future ED-based clinical prediction rules may benefit from calibration to proximal endpoints.