Risk Factors for Prolonged Invasive Mechanical Ventilation in COVID-19 Acute Respiratory Distress Syndrome

Background

On February 21th 2020, SARS-CoV-2 outbreak erupted in Italy and, in the immediately subsequent period, all the Italian regional Health Systems had to face with an overwhelming increase of COVID-19 admissions requiring isolation, oxygen, ventilation and ICU beds.

The COVID-19 related pneumonia presented as a particular entity in terms of clinical management and different ICUs adopt different clinical strategies, sometimes this is due to the local resources' availability. Mortality rate of the patients admitted to ICU is up to 26%.

To date, it is not clear which clinical, pharmacological and radiologic factors relate to a prolonged duration of mechanical ventilation, mortality and ICU length of stay and it's urgent to understand these aspects in order to develop optimal strategies to allow faster but safe paths for these patients.

Hypothesis and significance

SARS-CoV-2 related pneumonia ICU management is still undefined, in fact this entity seems to have clinical aspects rather different from other forms of interstitial pulmonary syndromes evolving in diffuse alveolar damage and many aspects related to ventilation such pulmonary compliance, driving pressure and response to pronation are very different from what traditionally observed from other forms of ARDS, moreover an abnormal trend towards hypercoagulability has been described in these patients.

Different treatments have been proposed and are under evaluation such as Tocilizumab, corticosteroids, hydroxychloroquine, antivirals, anticoagulants and antiplatelet therapies.

These treatments, together with common ICU practice aspects such as early/late tracheostomy, ventilatory parameters believed adequate in order to start a weaning procedure, fluidic balance, choice of analgesia and sedation regimens, are not standardized in this particular syndrome due to the lack of evidence available and there is need for information about which factors correlate to a lower duration of mechanical ventilation and mortality.

Collected data:

• Demographics and anamnesis: age, sex, weight, height, previous pathologies (Hypertension, Chronic ischemic heart disease, Chronic kidney disease, COPD, Diabetes, Chronic liver disease, active cancer, immunosuppressive therapy), smoker status, therapy with ACE-inhibitors, statins and Angiotensin II Receptor Blockers.
• Conditions at ICU admission: date of symptoms onset (fever and or cough), date of hospital admission, date of ICU admission, SOFA and SAPS II score, high flow nasal oxygen therapy before intubation, NIV/CPAP trial before intubation, duration of the NIV/CPAP trial, PaO2/FiO2 value before intubation, initial tidal volume set, initial PEEP set, Initial pplateau observed.
• Ventilation during the first 5 days: lowest PaO2/FiO2 value, ventilatory strategy (pressure control ventilation vs volume control ventilation and volumes), lowest static respiratory system compliance, highest driving pressure, highest PEEP, highest arterial pCO2 observed, number and duration of pronation cycles, response in terms of oxygenation to the first pronation, need for decapneization, use of nitric oxide, tracheostomy date, need for extracorporeal membrane oxygenation treatment.
• Pharmacologic strategies during the first 5 days: sedative regimen and maximum doses, neuromuscular blocking agents (type of NMBA and duration of continuous infusion).
• COVID specific therapies: antivirals (type, start and end date), chloroquine, tocilizumab (start date and route of administration), intravenous corticosteroids, other specific therapies.
• Other supportive therapies: first line antibacterial regimen, amines (maximum dose), renal replacement therapy, fluidic balance during the first 3 days after ICU admission, anticoagulation, antiaggregation.
• Complications during ICU stay:

• Cardiovascular (myocardial infarction, new onset supraventricular or ventricular arrhythmia, pulmonary embolism, pulmonary edema, haemorragic shock, cardiogenic shock, acute peripheral ischemia, pneumothorax)
• Neurologic (new onset ischemic stroke or cerebral haemorrage, critical illness polyneuropathy / myopathy, new onset seizures)
• Gastroenteric (gastrointestinal bleeding, severe diarrhea, intestinal occlusion, gastrointestinal perforation/ischemia)
• Extrapulmonary infections (documented blood steam, urinary tract, central nervous system, abdominal infection)
• Pulmonary infections after intubation (early onset VAP - < 7 days of mechanical ventilation, late onset VAP - ≥ 7 days of mechanical ventilation)
• Weaning from mechanical ventilation: last day of highest PEEP, first attempt of pressure support ventilation (PSV), P/F at the first attempt of PSV, entity of pressure support at the first attempt of PSV, PEEP at the first attempt of PSV, day of extubation, non-invasive ventilation or high flow oxygen therapy after extubation, first day of spontaneous breathing, need for reintubation and date
• Radiology: first available CT, last CT before ICU admission and intubation, last ICU follow-up CT. First available chest X ray, last chest X ray before ICU admission and intubation, last ICU- follow up chest X ray. 30 days follow-up CT (if available).

Inclusion criteria

• Age ≥ 18 years
• ICU admission because of the need of mechanical ventilation in the context of COVID-19 related pneumonia (swab proven)

Exclusion criteria

• COVID-19 related pneumonia complicating the clinical course of patients admitted to the ICU for another reason (e.g. trauma, stroke)