Critical Care Pharmacist Attitudes and Perceptions of Neuromuscular Blocker Infusions in ARDS.

BACKGROUND: Current critical care pharmacist (CCP) practices and perceptions related to neuromuscular infusion (NMBI) use for acute respiratory distress syndrome (ARDS) maybe different with the COVID-19 pandemic and the publication of 2020 NMBI practice guidelines. OBJECTIVE: To evaluate CCP practices and perceptions regarding NMBI use for patients with moderate-severe ARDS. METHODS: We developed, tested, and electronically administered a questionnaire (7 parent-, 42 sub-questions) to 409 American College of Clinical Pharmacy (ACCP) Critical Care Practice and Research Network members in 12 geographically diverse states. The questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2<150) whose causes of dyssynchrony were addressed. Two reminders were sent at 10-day intervals. RESULTS: Respondents [131/409 (32%)] primarily worked in a medical intensive care unit (ICU) 102 (78%). Compared to COVID-negative(-) ARDS patients, COVID positive(+) ARDS patients were twice as likely to receive a NMBI (34 ± 18 vs.16 ± 17%; P < 0.01). Respondents somewhat/strongly agreed a NMBI should be reserved until after trials of deep sedation (112, 86%) or proning (92, 81%) and that NMBI reduced barotrauma (88, 67%), dyssynchrony (87, 66%), and plateau pressure (79, 60%). Few respondents somewhat/strongly agreed that a NMBI should be initiated at ARDS onset (23, 18%) or that NMBI reduced 90-day mortality (12, 10%). Only 2/14 potential NMBI risks [paralysis awareness (101, 82%) and prolonged muscle weakness (84, 68%)] were frequently reported to be of high/very high concern. Multiple NMBI titration targets were assessed as very/extremely important including arterial pH (109, 88%), dyssynchrony (107, 86%), and PaO2: FiO2 ratio (82, 66%). Train-of-four (55, 44%) and BIS monitoring (36, 29%) were deemed less important. Preferred NMBI discontinuation criteria included absence of dysschrony (84, 69%) and use ≥48 hour (72, 59%). CONCLUSIONS AND RELEVANCE: Current critical care pharmacists believe NMBI for ARDS patients are best reserved until after trials of deep sedation or proning; unique considerations exist in COVID+ patients. Our results should be considered when ICU NMBI protocols are being developed and bedside decisions regarding NMBI use in ARDS are being formulated.

Physicians' attitudes and perceptions of neuromuscular blocker infusions in ARDS.

PURPOSE: The perceptions and practices of ICU physicians regarding initiating neuromuscular blocker infusions (NMBI) in acute respiratory distress syndrome (ARDS) may not be evidence-based amidst the surge of severe ARDS during the SARS-CoV-2 pandemic and new practice guidelines. We identified ICU physicians' perspectives and practices regarding NMBI use in adults with moderate-severe ARDS. MATERIALS AND METHODS: After extensive development and testing, an electronic survey was distributed to 342 ICU physicians from three geographically-diverse U.S. health systems(n = 12 hospitals). RESULTS: The 173/342 (50.5%) respondents (75% medical) somewhat/strongly agreed a NMBI should be reserved until: after a trial of deep sedation (142, 82%) or proning (59, 34%) and be dose-titrated based on train-of-four monitoring (107, 62%). Of 14 potential NMBI risks, 2 were frequently reported to be of high/very high concern: prolonged muscle weakness with steroid use (135, 79%) and paralysis awareness due to inadequate sedation (114, 67%). Absence of dyssychrony (93, 56%) and use ≥48 h (87, 53%) were preferred NMBI stopping criteria. COVID-19 + ARDS patients were twice as likely to receive a NMBI (56 ± 37 vs. 28 ± 19%, p < 0.01). CONCLUSIONS: Most intensivists agreed NMBI in ARDS should be reserved until after a deep sedation trial. Stopping criteria remain poorly defined. Unique considerations exist regarding the role of paralysis in COVID-19+ ARDS.

Predicting hospitalization of COVID-19 positive patients using clinician-guided machine learning methods.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) is a resource-intensive global pandemic. It is important for healthcare systems to identify high-risk COVID-19-positive patients who need timely health care. This study was conducted to predict the hospitalization of older adults who have tested positive for COVID-19. METHODS: We screened all patients with COVID test records from 11 Mass General Brigham hospitals to identify the study population. A total of 1495 patients with age 65 and above from the outpatient setting were included in the final cohort, among which 459 patients were hospitalized. We conducted a clinician-guided, 3-stage feature selection, and phenotyping process using iterative combinations of literature review, clinician expert opinion, and electronic healthcare record data exploration. A list of 44 features, including temporal features, was generated from this process and used for model training. Four machine learning prediction models were developed, including regularized logistic regression, support vector machine, random forest, and neural network. RESULTS: All 4 models achieved area under the receiver operating characteristic curve (AUC) greater than 0.80. Random forest achieved the best predictive performance (AUC = 0.83). Albumin, an index for nutritional status, was found to have the strongest association with hospitalization among COVID positive older adults. CONCLUSIONS: In this study, we developed 4 machine learning models for predicting general hospitalization among COVID positive older adults. We identified important clinical factors associated with hospitalization and observed temporal patterns in our study cohort. Our modeling pipeline and algorithm could potentially be used to facilitate more accurate and efficient decision support for triaging COVID positive patients.

CRITICAL CARE PHARMACIST ATTITUDES AND PERCEPTIONS OF NEUROMUSCULAR BLOCKER INFUSIONS IN ARDS

B Conclusions: b Most pharmacists agree NMBI infusions in ARDS are best reserved until after trials of deep sedation or proning. For COVID+ ARDS patients, few respondents felt any of the following were very/extremely important reasons for NMBI initiation: reduced self-extubation and COVID aerosolization exposure during reintubation 8(6%) or reduced sedative use during shortages 8(6%). B Introduction: b In the face of the COVID pandemic, and recent evidence and practice guidelines surrounding neuromuscular infusion (NMBI) use during ARDS, the practices/perceptions of ICU pharmacists regarding NMBI use during ARDS may not be evidence-based. [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration: ClinicalTrials.gov: NCT04332991.

Evaluation of the Efficacy and Safety of Inhaled Epoprostenol and Inhaled Nitric Oxide for Refractory Hypoxemia in Patients With Coronavirus Disease 2019.

OBJECTIVES: The objectives of this study were to evaluate the efficacy and safety of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019. DESIGN: Retrospective single-center study. SETTING: ICUs at a large academic medical center in the United States. PATIENTS: Thirty-eight adult critically ill patients with coronavirus disease 2019 and refractory hypoxemia treated with either inhaled epoprostenol or inhaled nitric oxide for at least 1 hour between March 1, 2020, and June 30, 2020. INTERVENTIONS: Electronic chart review. MEASUREMENTS AND MAIN RESULTS: Of 93 patients screened, 38 were included in the analysis, with mild (4, 10.5%), moderate (24, 63.2%), or severe (10, 26.3%), with acute respiratory distress syndrome. All patients were initiated on inhaled epoprostenol as the initial pulmonary vasodilator and the median time from intubation to initiation was 137 hours (68-228 h). The median change in Pao2/Fio2 was 0 (-12.8 to 31.6) immediately following administration of inhaled epoprostenol. Sixteen patients were classified as responders (increase Pao2/Fio2 > 10%) to inhaled epoprostenol, with a median increase in Pao2/Fio2 of 34.1 (24.3-53.9). The mean change in Pao2 and Spo2 was -0.55 ± 41.8 and -0.6 ± 4.7, respectively. Eleven patients transitioned to inhaled nitric oxide with a median change of 11 (3.6-24.8) in Pao2/Fio2. A logistic regression analysis did not identify any differences in outcomes or characteristics between the responders and the nonresponders. Minimal adverse events were seen in patients who received either inhaled epoprostenol or inhaled nitric oxide. CONCLUSIONS: We found that the initiation of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019, on average, did not produce significant increases in oxygenation metrics. However, a group of patients had significant improvement with inhaled epoprostenol and inhaled nitric oxide. Administration of inhaled epoprostenol or inhaled nitric oxide may be considered in patients with severe respiratory failure secondary to coronavirus disease 2019.

Inflammatory Biomarker Trends Predict Respiratory Decline in COVID-19 Patients.

In this single-center, retrospective cohort analysis of hospitalized coronavirus disease 2019 (COVID-19) patients, we investigate whether inflammatory biomarker levels predict respiratory decline in patients who initially present with stable disease. Examination of C-reactive protein (CRP) trends reveals that a rapid rise in CRP levels precedes respiratory deterioration and intubation, although CRP levels plateau in patients who remain stable. Increasing CRP during the first 48 h of hospitalization is a better predictor (with higher sensitivity) of respiratory decline than initial CRP levels or ROX indices (a physiological score of respiratory function). CRP, the proinflammatory cytokine interleukin-6 (IL-6), and physiological measures of hypoxemic respiratory failure are correlated, which suggests a mechanistic link. Our work shows that rising CRP predicts subsequent respiratory deterioration in COVID-19 and may suggest mechanistic insight and a potential role for targeted immunomodulation in a subset of patients early during hospitalization.

Early clinical and sociodemographic experience with patients hospitalized with COVID-19 at a large American healthcare system.

BACKGROUND: Despite over 4 million cases of novel coronavirus disease 2019 (COVID-19) in the United States, limited data exist including socioeconomic background and post-discharge outcomes for patients hospitalized with this disease. METHODS: In this case series, we identified patients with COVID-19 admitted to 3 Partners Healthcare hospitals in Boston, Massachusetts between March 7th, 2020, and March 30th, 2020. Patient characteristics, treatment strategies, and outcomes were determined. FINDINGS: A total of 247 patients hospitalized with COVID-19 were identified; the median age was 61 (interquartile range [IQR]: 50-76 years), 58% were men, 30% of Hispanic ethnicity, 21% enrolled in Medicaid, and 12% dual-enrolled Medicare/Medicaid. The median estimated household income was $66,701 [IQR: $50,336-$86,601]. Most patients were treated with hydroxychloroquine (72%), and statins (76%; newly initiated in 34%). During their admission, 103 patients (42%) required intensive care. At the end of the data collection period (June 24, 2020), 213 patients (86.2%) were discharged alive, 2 patients (0.8%) remain admitted, and 32 patients (13%) have died. Among those discharged alive (n = 213), 70 (32.9%) were discharged to a post-acute facility, 31 (14.6%) newly required supplemental oxygen, 19 (8.9%) newly required tube feeding, and 34 (16%) required new prescriptions for antipsychotics, benzodiazepines, methadone, or opioids. Over a median post-discharge follow-up of 80 days (IQR, 68-84), 22 patients (10.3%) were readmitted. INTERPRETATION: Patients hospitalized with COVID-19 are frequently of vulnerable socioeconomic status and often require intensive care. Patients who survive COVID-19 hospitalization have substantial need for post-acute services.