We enrolled in the study 306 consecutive patients (of the nearly 1500 COVID-19 treated) who failed oxygen mask therapy and underwent helmet CPAP treatment outside the ICU. Nearly 50% of the patients were younger than 65 years old ,PaO2/FiO2 ratio with standard oxygen therapy was lower than 150 in two-thirds of the patients (209/306). The majority of the patients had no (30%) or one (30%) comorbidity; about half of the enrolled patients had hypertension (Table 1).
Helmet CPAP treatment
After failure of standard oxygen therapy, helmet CPAP treatment was started with a median PEEP of 5 [5-10] cmH2O and FiO2 of 50% [50-90]. Helmet CPAP therapy led to a dramatic oxygenation improvement: PaO2/FiO2 ratio doubled from about 100 to 200 mmHg (P<0.001, Table 2). The incidence of severely hypoxic patients was markedly reduced by helmet CPAP (Figure 1a, P<0.001 by Chi-Square); the PaO2/FiO2 ratio improvement was more pronounced among more severely hypoxic patients (Figure 1b, P<0.001 for helmet CPAP effect and for its interaction with hypoxia severity class by RM Anova). A clinically significant reduction of respiratory rate was also present (from 28 [22-32] to 24 [20-29] BPM, P<0.001). After beginning of helmet CPAP, 71% of patients presented ARDS criteria (severe 9%; moderate 35%; mild 27%). Higher levels of C-Reactive Proteins were detected in patients whose hypoxaemia was not reverted by helmet CPAP treatment (P=0.009 by Anova, Figure 2). Considering the entire population, helmet CPAP was maintained for 6 [3-9] days with a median PEEP of 10 [7-10] cmH2O and an FiO2 of 65 [50-90] %. During the first two days after start of CPAP therapy, helmet was maintained in place for an average of 21 hours/day; from days three to five for an average of 19 hours/day. After the initial oxygenation improvement with helmet CPAP therapy, PaO2/FiO2 ratio remained steadily impaired during the first week (202 [128-284] mmHg).
Helmet CPAP failure occurred in 48% of the patients, mostly in patients who had a treatment limitation decision (71% vs. 31% in the full treatment group, P<0.001, Figure 3). CPAP failure was associated with several pre-existing factors, such as advanced age, number of comorbidities, and patient’s frailty (Table 1). CPAP failure was strongly associated with worse gas exchange (Table 2, Figure 4), increased inflammatory markers, higher levels of serum lactate dehydrogenase and worse renal function (Table 1). Successful treatment was associated with a nearly double oxygenation response to helmet CPAP therapy as compared to failure (PaO2/FiO2 increase +96 vs. +53 mmHg, P=0.001); a PaO2/FiO2 increasing above 200 mmHg after positioning helmet CPAP (68% in the successful vs. 32% in the failure groups, P<0.001 by Chi-Square; P<0.001 by Log Rank, Figure 5); and a respiratory rate returning to clinically acceptable levels (22 vs. 28 BPM, P=0.007, Table 2).
A subgroup of patients (n=42) had a second evaluation on the first day of Helmet CPAP therapy. At the Receiving Operator Curve (ROC) curve analysis, the respiratory rate after few hours of helmet CPAP therapy was closely associated with CPAP success (AUC=0.802 [95% CI=0.66-0.94], P=0.001. A respiratory rate below 30 BPM showed 100% sensitivity for CPAP success; a respiratory rate above 24 showed 81% sensitivity and 76% specificity for CPAP failure.
The adoption of prone position sessions during helmet CPAP treatment was frequent (45%).
No major adverse event associated with the use of helmet CPAP (e.g. deaths of full treatment patients before intubation) was recorded by MET during the study period.
Full treatment patients
The majority of full treatment patients (122, 69%) did not require intubation and were successfully treated by helmet CPAP outside the ICU for 6 [4-9] days, with a PEEP of 10 [5-10] cmH2O and a FiO2 of 50 [35-80] %. Such patients were discharged from hospital after 14 [10-19] days. Full treatment patients requiring intubation (55, 31%) showed a higher heart rate on day one (92 [82-102] BPM vs. 80 [72-90], P<0.001). They were transferred to ICU for intubation after 4 [3-7] days of helmet CPAP treatment; in those patients, prone positioning was almost always attempted before intubation.
In the full treatment group, while PaO2/FiO2 ratio during standard oxygen therapy did not differ between the groups (P=0.208), helmet CPAP therapy led to a higher PaO2/FiO2 ratio in the success as compared to the failure group (257 [193-314] vs. 190 [131-259] P<0.001); this corresponded to a more pronounced response in oxygenation (PaO2/FiO2 increase +100 [45-162] mmHg vs. +51 [14-99], P=0.002). Among full treatment patients, a PaO2/FiO2 constantly above 150 mmHg during the first week was associates with a probability of recovery without intubation of 91% (P<0.001 by Fisher’s Exact Test). Hospital mortality among full treatment patients was 13%.
A relevant number of patients (42%) had a treatment limitation decision (DNI). A DNI order was associated with age higher than 75 years old, a higher number of comorbidities and worse oxygenation both before and after helmet CPAP as compared to the full treatment group (P<0.001 for all). DNI order was strongly associated with helmet CPAP failure (which corresponds to mortality; P<0.001). However, a third of DNI patients (29%) had a favorable outcome with helmet CPAP treatment outside the ICU, despite a relevant oxygenation impairment on day one both with standard oxygen and with helmet CPAP therapy (PaO2/FiO2 ratio 104 [81-180] and 224 [151-319], respectively; P<0.001 for difference). Successful treatment was associated with younger age (P=0.025) and lower comorbidities (P=0.035).
Factors included in the model, to predict CPAP failure were: age, sex, number of comorbidities, C-reactive protein (CRP), body temperature on day one, time to oxygen mask failure, PaO2/FiO2 ratio and PaCO2 both during standard oxygen and helmet CPAP therapy. At the backward logistic regression analysis, helmet CPAP failure was independently associated with: CRP, time to oxygen mask failure, age, PaO2/FiO2 ratio collected during helmet CPAP treatment, number of comorbidities (Table 3). The other tested factors (sex, body temperature, PaO2/FiO2 ratio and PaCO2 during standard oxygen treatment, PaCO2 measured during CPAP) did not emerge as independent predictors of failure.
The results of a similar multivariate analysis including the PaO2/FiO2 ratio change in place of the PaO2/FiO2 ratio measured during helmet CPAP are reported in the e-Table 2 of the Additional File 1.