key: cord-0701791-4re4n268
authors: Janz, David R.; Mackey, Scott; Patel, Nirav; Saccoccia, Beau P.; St. Romain, Michelle; Busack, Bethany; Lee, Hayoung; Phan, Lana; Vaughn, Jordan; Feinswog, David; Chan, Ryan; Auerbach, Lauren; Sausen, Nicholas; Grace, Joseph; Sackey, Marian; Das, Anushka; Gordon, Angellica O.; Schwehm, Jennifer; McGoey, Robin; Happel, Kyle I.; Kantrow, Stephen P.
title: Critically Ill Adults with COVID-19 in New Orleans and Care with an Evidence-based Protocol
date: 2020-09-14
journal: Chest
DOI: 10.1016/j.chest.2020.08.2114
sha: 17b861e7fadf472070db61e75b75d34f25b77fcd
doc_id: 701791
cord_uid: 4re4n268

Background Characteristics of critically ill adults with coronavirus disease 2019 (COVID-19) in an academic safety net hospital and the effect of evidence-based practices in these patients are unknown. Research Question What are the outcomes of critically ill adults with COVID-19 admitted to a network of hospitals in New Orleans, LA and is an evidence-based protocol for care associated with improved outcomes? Study Design and Methods: In this multi-center, retrospective, observational cohort study of intensive care units in four hospitals in New Orleans, LA, we collected data on adults admitted to an intensive care unit (ICU) and tested for SARS-CoV-2 between March 9, 2020 and April 14, 2020. The exposure of interest was admission to an ICU which implemented an evidence-based protocol for COVID-19 care. The primary outcome was ventilator-free days. Results The initial 147 patients admitted to any ICU and tested positive for SARS-CoV-2 comprised the cohort for this study. In the entire network, exposure to an evidence-based protocol was associated with more ventilator-free days (25 days, 0 – 28) compared with non-protocolized ICUs (0 days, 0 – 23, p = 0.005), including in adjusted analyses (p = 0.02). Twenty patients (37%) admitted to protocolized ICUs died compared with 51 (56%, p = 0.02) in non-protocolized ICUs. Among 82 patients admitted to the academic safety net hospital’s ICUs, the median number of ventilator-free days was 22 (IQR 0 – 27) and mortality rate was 39%. Interpretation Care of critically ill COVID-19 patients with an evidence-based protocol is associated with increased time alive and free of invasive mechanical ventilation. In-hospital survival occurred in the majority of critically ill adults with COVID-19 admitted to an academic safety net hospital’s ICUs despite a high rate of co-morbidities.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions worldwide and caused coronavirus disease 2019 in hundreds of thousands 1 . COVID-19 is associated with a high rate of critical illness, morbidity, and mortality 2 . Specifically, acute respiratory failure requiring respiratory support, the development of the acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and shock are common in critically ill adults with COVID-19 3, 4 . Outcomes of critically ill adults with COVID-19 admitted to an academic safety net hospital are unknown.

The syndromes caused by COVID-19, specifically acute respiratory failure and ARDS, have evidence-and guideline-based management recommendations. First, there are patient populations where the use of certain respiratory support devices, such as non-invasive positive pressure ventilation (NIPPV), decrease the need for tracheal intubation [5] [6] [7] [8] and is recommended for consideration in patients with COVID-19 9 . Second, if patients do require endotracheal intubation and develop ARDS, the provision of low tidal volume ventilation (LTV) 10 and a conservative fluid management strategy 11 improve the number days alive and free of invasive mechanical ventilation. If ARDS is moderate to severe, treatment with prone positioning 12, 13 and higher amounts of positive end-expiratory pressure (PEEP) 12,14 may improve survival.

When patients with respiratory failure have improved, liberation from sedatives 15 and invasive ventilation by providing support with NIPPV may decrease the need for reintubation 16 .

However, some have argued against using these interventions in critically ill adults with COVID-19 due to unknown effectiveness and potential harm 17, 18 .

We conducted a retrospective, cohort, observational study of critically ill adults with COVID-19 admitted to a network of four hospitals. Some ICUs in this network implemented an evidence-based pilot protocol that provided guidance on the management of the patient with acute respiratory failure and ARDS. We hypothesized that protocol implementation would be associated with increased ventilator-free days in critically ill adults with COVID-19.

We conducted a retrospective cohort study of all initial patients admitted to a group of four hospitals in New Orleans, LA who were critically ill and tested positive for SARS-CoV-2 between March 9, 2020 and April 14, 2020. The study was approved with a waiver of informed consent by the institutional review board at Louisiana State University School of Medicine New Orleans.

The retrospective study was conducted using quality improvement data collected by a network of four hospitals located in New Orleans, Louisiana. The study population consisted of the first 147 critically ill adults who were admitted to any ICU in the network of hospitals and had a positive nasopharyngeal swab for SARS-CoV-2. The current observational study was conducted with data entered into the database at the time of analysis and consisted of patients admitted to any ICU from March 9, 2020 through April 14, 2020. At the time of submission, 28-day hospital vital status or discharge status was known on all patients. Seven patients remain alive J o u r n a l P r e -p r o o f and hospitalized beyond 28 days. Data included demographics, co-morbidities, laboratory values, ventilator parameters, medication administration, and in-hospital clinical outcomes.

As a potential quality improvement initiative and during the observational period, two ICUs located in an academic, safety-net hospital within the network implemented an evidence- 

The primary comparison in this cohort study was between patients admitted to an ICU that implemented the pilot care protocol versus patients admitted to an ICU that did not undergo implementation during the observation period. The primary analysis in this cohort was ventilator-free days, calculated by 28 minus the number of days the patient was tracheally intubated with a value of zero assigned to patients who died in the hospital. Ventilator-free days was chosen as the primary outcome as this is a well-validated, patient-centered outcome commonly chosen in studies of acute respiratory failure 10, 11, 19, 20 . Secondary outcomes included 28-day in-hospital mortality, need for tracheal intubation, and need for renal replacement therapy. We also analyzed the primary outcome of VFDs and processes of care over the course of the observational period to see if this outcome improved over time. Finally, given we only had access to data that were already entered into this database and could not exclude the possibility of patients not yet entered into the database late into the observation period, we performed a sensitivity analysis for the primary outcome of VFDs restricted to patients admitted in the first calendar month since the diagnosis of the index ICU patient.

The majority of data were not normally distributed and, therefore, reported as median values with interquartile range (IQR) for continuous variables and frequencies for categorical variables. Univariate analyses of continuous variables were conducted with Mann-Whitney U tests and Chi-square tests for categorical variables. A linear regression model was also used to analyze the dependent variable of VFDs with the independent variables of pilot protocol implementation, APACHE II score, age, and the ratio of partial pressure of oxygen to the fraction of inspired oxygen (PaO 2 /FiO 2 ) on ICU admission. One-way repeated measures analysis J o u r n a l P r e -p r o o f of variance was used to compare groups regarding repeated measures over time. IBM SPSS Statistics (version 25) was used for statistical analysis. A two-sided significance value of 0.05 was used for statistical significance. The STROBE Guidelines for Reporting Observational Studies were followed in drafting this manuscript 21 .

Of 214 critically ill adults who were admitted to a network ICU and tested for SARS-CoV-2 during the observation period, 147 patients tested positive and comprised the primary cohort for the current analysis (Figure 1) . Regarding patients exposed to protocol implementation or not, there were statistically significant imbalances in location prior to ICU admission, asthma, and end-stage renal disease. Laboratory values on ICU admission were not statistically significantly different other than a lower PaO 2 /FiO 2 ratio in patients not exposed to protocol implementation ( Table 1) .

A total of 14 (25%) patients in the pilot protocol group never required intubation compared with 16 (17%, p = 0.15) patients admitted to ICUs without pilot protocol implementation. In patients never requiring intubation and in pilot protocol ICUs, 57% were supported with noninvasive positive pressure ventilation (Supplemental Digital Content - Table 1 ). In intubated patients, there was no statistically significant difference in tidal volumes provided, FiO 2 to PEEP ratio, or receipt of prone positioning over the first five days of ICU care (Supplemental Digital J o u r n a l P r e -p r o o f Content - Figures 1, 2, 3) . Patients cared for in ICUs undergoing protocol implementation received higher mean daily doses of furosemide over the first five days of ICU care (p = 0.005) (Supplemental Digital Content - Figure 4) . At the time of extubation, 57% of patients were extubated to non-invasive positive pressure ventilation ( Table 2) .

The median number of VFDs in patients exposed to pilot protocol implementation was 25 days (0 -28) compared with 0 days (0 -23, p = 0.005) in patients not exposed to pilot protocol implementation ( Table 3) . Pilot protocol implementation remained associated with increased VFDs after adjustment for APACHE II score alone (p = 0.007, Figure 2 ) and after adjustment for APACHE II score, age, and PaO 2 /FiO 2 on ICU admission (p = 0.02) (Supplemental Digital Content - Table 2 ). In a sensitivity analysis restricted to the first calendar month of ICU admissions for COVID-19, pilot protocol implementation remained associated with increased VFDs (23 days, 0 -27) compared with no pilot protocol implementation (0 days, 0 -22) in both unadjusted (p = 0.03) and adjusted analyses for APACHE II score, age, and PaO 2 /FiO 2 ratio on ICU admission (Beta 5.28, 95% CI 0.1 -10.4, p = 0.04).

Exposure to pilot protocol implementation was associated with a decreased 28-day inhospital mortality for all comers (37% vs 56%, p = 0.02) as well as for those who required invasive mechanical ventilation (47% vs 68%, p = 0.03). Pilot protocol implementation was also J o u r n a l P r e -p r o o f associated with a reduction in need for any type of renal replacement therapy (14% vs 38%, p = 0.002) ( Table 2) .

Regarding the entire cohort of the initial 147 patients admitted to any network ICU, VFD 

A total of 82 patients were admitted to ICUs in the Network's academic safety net hospital.

Patients admitted to this academic safety net hospital had a median age of 61 years (50 -71) with a body mass index of 35 kg/m 2 (30 -43) and 93% were African American. Additionally, patients admitted to this academic safety net hospital had high rates of hypertension (86%) and diabetes mellitus (57%) ( Table 1) . In these 82 patients, the median number of ventilator-free days was 22 (IQR 0 -27) and mortality rate was 39% ( Table 3) .

The majority of critically ill adults with COVID-19 admitted to an academic safety net hospital survived to hospital discharge and 21% never required tracheal intubation. Implementation of a pilot patient care protocol was associated with significantly more ventilator-free days and higher survival. Ventilator-free days increased over the duration of the observation, along with an increase in NIPPV use, higher PEEP, and decreased tracheal intubation rates. To our knowledge, this is the first description of the outcomes of patients with COVID-19 patients in an academic safety net hospital and of the associated treatment effect of evidence-and guidelinebased interventions for patients with ARDS in a population with COVID-19.

Safety net hospitals, defined as those that by obligation or mission provide healthcare to patients regardless of insurance status or ability to pay, are commonly also academic hospitals and frequently care for a patient population with high rates of co-morbidities 22, 23 . We observed these same high rates of co-morbidities in the patient population admitted to the academic safety net hospital during this study. However, the majority of these critically ill patients with COVID-19 had good clinical outcomes such as survival to hospital discharge. The cause of the improved outcomes in this patient population is unknown. Mortality rates from the current study are not directly comparable to reported mortality rates in other studies of COVID-19 as the number of measured and unmeasured differences between geographically separate hospitals are numerous. 

An academic safety net hospital caring for critically ill adults with COVID-19 and high rates of co-morbidities achieved in-hospital survival in a majority of patients. Additionally, a care strategy of using NIPPV to avoid intubation and evidence-based ARDS management strategies applied, if intubated, may be safe for healthcare workers and is associated with improved patient-centered outcomes. Future study is needed to confirm this associated effect is consistent in a larger cohort over time. For every increase in APACHE II score, pilot protocol implementation was always associated with increased ventilator-free days. P-value represents result of a linear regression analysis with the dependent variable as ventilator-free days and the independent variables of pilot protocol implementation (p = 0.007) and APACHE II score. 

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