A continuous infusion of Dexmedetomidine (DEX) will be administered to 80 patients admitted to Critical Care because of signs of Respiratory Insufficiency requiring non-invasive ventilation. Measurements of respiratory performance and quantification of cellular and molecular inflammatory mediators. The primary outcome will be the avoidance of mechanical ventilation with secondary outcomes duration of mechanical ventilation, avoidance of delirium after sedation and association of mediators of inflammation to outcomes. Outcomes will be compared to a matched historical control (no DEX) series
It will be an observational study, with no randomization. To evaluate the influence of
Dexmedetomidine on the time course of ARDS in patients admitted to the ICU unit because of
severe respiratory disease triggered by the SARS-CoV-2 (COVID-19) infection. Patients will be
informed and asked to sign an Informed Consent Form.
Dexmedetomidine will be used as a sedative which is its admitted therapeutic indication in
our country. Dosing will be according to its sedative properties as recommended by the
manufacturer and regulation agencies. The only change is that we will study outcomes that
have nothing to do with sedation but with a possible positive effect on the
hyper-inflammatory state.
The study will be conducted in accordance with the "Orden SAS/3470/2009, of December 16,
2009. Government of Spain
Recruiting and Sample Size calculation We chose mortality as an endpoint to calculate sample
size although our primary outcome is to minimize the requirements of mechanical ventilation.
Mortality of patients admitted to the ICU because of SARS-CoV-2 (COVID-19) induced ARDS is
48%. Assuming a p value<0.05 and a power of 80%, to demonstrate a 10% decrease in mortality
due to the effects of Dexmedetomidine 156 patients should be studied so there will two groups
of 80 patients (cases vs historical controls).
However, due to the specific characteristics and the unknown duration of the pandemic, these
numbers might not be definitive
Inclusion and Exclusion Criteria (see section)
Drug administrations Dexmedetomidine continuous intravenous infusion will be administered at
0.15 mcg/kg/h as a start and titrating according to sedative responses up to 1.5 mcg/kg/h
(max admitted infusion rate)
Other sedatives (usually propofol and remifentanil) may be administered as per ICU protocol
Monitoring
- Ventilation parameters
- Invasive /non-invasive monitoring according to protocols
- The parasympathetic component of HRV will be estimated online by means of the Anesthesia
Nociception Index (ANI, MDoloris Medical Systems, Lille, France).
Patient Management Patient management will be performed according to the clinical protocols
of the Critical Care Units of Hospital CLINIC de Barcelona regarding the management of
patients admitted to ICU because of the consequences of SARS-CoV-2 virus infection
Data Collection Demographic data including age, weight, gender, height, medical conditions,
ICU severity score, SOFA score, medications, hemodynamic support, O2 fraction.
Besides regular protocolized monitoring measures for the purposes of the study it will be
required:
- Routine Acid-Base equilibrium
- Routine hemogram
- Daily Citokine levels IL1b, IL6, TNFa, IL8, IL4, IL10
- Monocyte profiling Patient data will be kept anonymous except for the IP.
Outcomes to be measured are reported in their respective section
Data Analysis Analysis of the data collected includes the comparison of "primary and
secondary outcomes data" acquired to a matched "historical control" with the same severity of
ARDS from another COVID-19 + ICU patient with no administration of Dexmedetomidine. A "p"
value less than 0.05 will be considered significant in the comparisons with the values of the
"historical cohort".
Parametric or non-parametric statistical tests will be used to compare data from the control
and study groups, depending on the distribution of such data.
Analysis of the time course of the mediators of inflammation sampled in the first 25 patients
will be studied as changes from baseline. Mathematical models of the probability of each one
or many of them to be associated with the outcomes of the study will be generated if possible
Drug: Dexmedetomidine Injectable Product
continuous intravenous infusion of dexmedetomidine
Other Name: DEX IV Sedation
Inclusion Criteria:
- Patients with respiratory insufficiency criteria candidates to non-invasive
ventilation techniques (high flow oxygen masks, non-invasive mechanical ventilation)
- SpO2 (at FiO2: 0.21) ≤ 93% equivalent to SaO2/FiO2≤442
- PaO2/ FiO2 < 300
- Bilateral opacities consistent with pulmonary edema must be present and may be
detected on CT or chest radiograph that must not be fully explained by cardiac failure
or fluid overload, in the physician's best estimation using available information
Exclusion Criteria:
- Affected by autoimmune disease
- Under specific therapy with Monoclonal Antibodies targeting inflammatory mediators
Pedro L Gambus, PhD MD
+34687075332
plgambus@clinic.cat
Xavier Borrat, PhD MD
xborrat@clinic.cat