Study design and setting
This was a retrospective descriptive study enrolling adult patients admitted to the Emergency Department of the Niguarda Ca’ Granda Hospital of Milan, Italy, from March 18th to April 18th 2020 with acute respiratory failure due COVID-19 pneumonia.
A local protocol was drawn up to standardize a first trial of CPAP, and only patients who strictly respect the protocol were considered.13 STROBE guidelines for reporting observational studies were followed.14
Ethical consideration
The study was approved by the ethical committee of the Niguarda Ca’ Granda Hospital of Milan, whereas informed consent was waived due to the retrospective and descriptive nature of the study according to the Italian law on observational studies.
Participants
Patients admitted to the ED from March 18th to April 18th 2020 with ARF due to COVID-19 pneumonia treated with helmet CPAP according our operational flowchart were included in the study.
Diagnosis of COVID-19 pneumonia was made if typical CT scan patterns were present (ground-glass opacities, crazy-paving pattern, consolidations) and a SARS-CoV2 infection was confirmed by positive real-time reverse transcriptase–polymerase chain reaction assay of nasopharyngeal swab.15
According to the local protocol, the inclusion criteria were age 18 years or older, diagnosis of COVID-19 related pneumonia, a preserved state of consciousness (Kelly Score 1 or 2) and stable hemodynamics, SpO2 level < 94% and a respiratory rate (RR) ≥ 28 despite 5 L/min oxygen administration through nasal googles or face mask.16 All these patients started a trial of helmet CPAP. Exclusion criteria were: the achievement and maintenance of a SpO2 ≥ 94% and FR < 28 with standard O2 support (5 L/min of O2 administered with goggles or facemask); the need for immediate ETI for cardiovascular arrest, impaired and ineffective respiratory mechanics (e.g. agonic breathing and thoracic-abdominal dyskinesia); hemodynamic instability or severe arrhythmias; altered state of consciousness (Kelly score ≥ 3); contraindications to CPAP (severe bleeding of the upper digestive tract, vomiting, inability to protect the airways; recent surgery on the skull or esophagus; trauma and cranio-facial burns; undrained pneumothorax). Patients with symptoms and radiological imaging suggestive for COVID-19 pneumonia but no microbiological confirmation were also excluded.
All the patients enrolled started a trial of helmet CPAP and were followed up to from the day of hospital admission to the day of death or hospital discharge.
CPAP was delivered through helmet and high-flow generating devices as first choice. The CPAP trial lasted 120 minutes. Initial settings were a PEEP of 7,5 cm/H20, a Flow ≥ 60 L/Min and a FiO2 titrated to reach a SpO2 ≥ 94% and a RR ≤ 25 bpm. PEEP was increase by 2.5 cmH2O up to a maximum of 12.5 cmH2O in case of failure to reach the RR established target. Alternatively, in patients with risk of muscular exhaustion (e.g. history of Chronic Obstructive Pulmonary Disease, neuromuscular disease) a trial of Bi-PAP was started with a face mask.
Data collection
Demographics, comorbidities, time from symptoms onset, Arterial Blood Gases (ABG), clinical and laboratory findings on admission were recorded.
SpO2, RR and body temperature were recorded before CPAP trial was started and then every 30 minutes together with PEEP and FiO2 used until the end of the trial (t0 - t30 – t60 – t90 – t120).
ETI was performed according to clinical judgment of ICU specialist. Patients not considered eligible for ETI due to their age and comorbidity and the severity of the disease, received a Do Not Intubate (DNI) order after the evaluation of a ICU specialist in agreement with the emergency physician. Data on time from the beginning of CPAP trial to ETI together with data on duration of NIPPV (intended as cycles of CPAP or Bi-PAP longer than 6 hours for day) or of IMV were collected. Pharmacological treatment was recorded too.
Statistical analysis
No statistical sample size calculation was performed a priori, and sample size was equal to the number of patients treated with helmet CPAP during the study period.
Socio-demographic variables and clinical data were reported as absolute and relative frequencies for categorical variables, while for numerical ones the mean and the corresponding standard deviation (SD) or median and InterQuartile Range (IQR) were reported, as appropriate.
Percentage of subjects who needed invasive mechanical ventilation and died were calculated with their 95% confidence interval (95% CI).
To explore the risk factors associated with ETI, the χ² test or Fisher’s exact test and the student or Mann-Whitney U test were used to compare the socio demographic and clinical variables with the use of IMV.
To better understand the time trend of parameters related to the use of CPAP (Fio2, PEEP, RR, SP02), graphical representations were done using mixed models, which take into account for repeated measures within subjects. The same models, adding as covariate the use of ETI, were also performed to evaluate if significant changes between groups were observed.
Survival curves were plotted using the Kaplan-Meier method and compared between patients with vs without ETI using the log-rank test.
A two-sided α of less than 0.05 was considered statistically significant. Statistical analyses were done using the SAS software (version 9.4).