key: cord-0709875-fhmbbqo4
authors: Taboada, Manuel; Baluja, Aurora; Santos, Laura Dos; González, Irene; Veiras, Sonia; Caruezo, Valentín; Naveira, Alberto; Mirón, Paula; Novoa, Carmen; Doldán, Patricia; Calvo, Andrea; Tubio, Ana; Selas, Salomé; Eiras, María; Martínez, Adrián; Campaña, Olga; Rodríguez, María Teresa; Diaz-Vieito, María; Cariñena, Agustín; Otero, Pablo; Mariño, Gumersindo; Domínguez, María; Muniategui, Ignacio; Aneiros, Francisco; Alvarez, Julián
title: Effectiveness of dexmedetomidine combined with high flow nasal oxygen and long periods of awake prone positioning in moderate or severe COVID-19 pneumonia
date: 2021-03-31
journal: J Clin Anesth
DOI: 10.1016/j.jclinane.2021.110261
sha: 96dec3eed97eab0270cbf11b450038c796a708ce
doc_id: 709875
cord_uid: fhmbbqo4

nan

produced by COVID-19. The objective of present study was to evaluate the effectiveness of dexmedetomidine combined with high flow nasal oxygen and long periods of awake prone positioning in ICU patients with moderate or severe COVID-19 pneumonia. The study protocol was approved by the ethics committee of Galicia (code No. 2020-184) , and all participating subjects provided informed consent.

From September 1, 2020, to February 25, 2021, patients admitted to the Intensive Care Unit (ICU) at Clinical University Hospital Santiago of Compostela with laboratory-confirmed COVID-19 disease were enrolled. Inclusion criteria were moderate (100 mmHg < PaO2/FiO2 ≤ 200) or severe ARDS (PaO2/FiO2 ≤100), 18 years of age or older, and those who was able to be in a PP. Exclusion criteria were inability to collaborate with PP or refusal, unstable hemodynamic status, patients with severe ARDS needing urgent intubation and mechanical ventilation. Patients were monitored with continuous electrocardiogram, oxygen saturation, and invasive arterial blood pressure. The flow rate was initially set a 50-60 L/min, and the fraction of inspired concentration (FiO2) was titrated (0.5-1.0) to maintain the oxygen saturation (SpO2) ≥ 90%. Patients were instructed to remain in PP during periods of 2-5 hours during the day and for long periods of PP at night, as tolerated.

During PP sessions, patients received intravenous infusion of DEX (0.2 mcg-1.2 mcg/kg/h) that was initiated 30-60 min prior to PP. DEX was titrated to maintain a Richmond Agitation Sedation Scale (RASS) score between 0 and -3. Sedation with DEX was also used during ICU admission when patients was anxious or agitated. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whereas failure was defined as a need for intubation or death on HFNO. Per protocol, patients needed intubation when they had signs of respiratory fatigue (respiratory rate > 30, and obvious accessory respiratory muscle use), unstable hemodynamic status, lethargy, or unconsciousness.

The following information was collected in all patients: patient characteristics, comorbidities, inflammatory biomarkers, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, PaO2/FiO2, ICU treatments, number and duration of PP sessions, need of mechanical ventilation, duration of ICU admission and ICU outcomes. Data were presented as mean ± standard deviations or median and interquartile range as appropriate taking into account variable distribution. Chi-square and Wilcoxon rank-sum test were used to test for differences between categorical or numeric variables. Multiple testing was addressed by the Benjamini-Hochberg procedure. All analyses were conducted in Rv.3.6.

Among the 89 patients with moderate or severe ARDS by COVID 19 admitted to the ICU during the study period, sixtythree (70.8%) were treated with DEX, HFNC and long periods of PP sessions, and they were finally included in this study (Supplementary Figure 1) . The characteristics of the study population and clinical ICU course are shown in Table 1 . ICU outcomes, total hours of DEX infusion, HFNC, and PP sessions of each patient are described in table 2. Among 63 patients, 43 (68.3%) were weaned from HFNO (successful treatment), 7 (11.1%) died, and 6 (9.5%) remain in ICU. Prone positioning was applied with a median of 4 (IQR: 2.5-8) sessions per subject. Nineteen (30.2%) patients required intubation. Bradycardia J o u r n a l P r e -p r o o f (<40 lpm) during DEX infusion was observed in 5 patients (7.9%). Forty-nine (77.8%) patients were discharged from the ICU during the study period.

In this prospective observational study, we found that DEX was used satisfactory for COVID-19 patients with moderate or severe ARDS treated with HFNC facilitating the acceptance of long periods of awake PP. The benefits of DEX in these patients could be multifactorial. First. DEX is an anxiolytic and sedative agent that may reduce the anxiety of a patient with respiratory failure, decreasing the respiratory rate and improving oxygenation. Second, this sedative properties of DEX can help awake patients with ARDS stay in PP for long periods of time. In intubated patients, Guerin et al. 4 had shown how long periods of PP may improve oxygenation and survival in patients with ARDS. We might expect a similar benefit with long periods of PP in awake COVID-19 patients with ARDS. Third, recent studies suggest DEX may enhance hypoxic pulmonary vasoconstriction, improve ventilation/perfusion ratio, and consequently improve oxygenation. 8-10 Four, DEX has an antiinflammatory effect that can help the inflammation produced by COVID-19, and it has been proposed as a novel therapeutic strategy to attenuate multi-organ dysfunction of COVID-19 patients. [8] [9] [10] Limitations of our study include that it was performed in a single center, there was no control intervention, and the study sample was small. Regardless, these preliminary results are shared in an effort to inform other clinicians the possibility of the use a combination of DEX, HFNO and long periods of PP to treat patients with moderate or severe ARDS by COVID-19, trying to improve oxygenation and avoiding intubation and mechanical ventilation. 

COVID-19 Lombardy ICU Network. Risk Factors Associated With Mortality Among Patients With COVID-19 in Intensive Care Units in

High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure

High-flow nasal oxygen in patients with COVID-19-associated acute respiratory failure

Prone positioning in severe acute respiratory distress syndrome

Effectiveness of Prone Positioning in Nonintubated Intensive Care Unit Patients With Moderate to Severe Acute Respiratory Distress Syndrome by Coronavirus Disease

High-Flow, Noninvasive Ventilation and Awake (Nonintubation) Proning in Patients With Coronavirus Disease 2019 With Respiratory Failure

Early awake prone position combined with high-flow nasal oxygen therapy in severe COVID-19: a case series

The authors thank all physicians and residents of the Department of Anesthesiology and Intensive Care Medicine, Hospital Clínico Universitario Santiago de Compostela. Spain.

 Table 2 J o u r n a l P r e -p r o o f