This is a retrospective observational study, performed in a dedicated COVID-19 Intermediate Care unit in Coimbra Hospital and University Centre, from December 1st 2020 to February 28th 2021. This 16-bed unit was meant for the treatment of more severe cases of COVID-19 infection and consisted of a fixed team of seven physicians working on rotating shifts. There was also a group of dedicated nurses with a nurse-patient ratio of 1:2 to 1:6. All patients were closely monitored for 24 hours a day via telemetry.
Adult patients with tachypnea (respiratory rate > 30 breaths per minute), respiratory effort, oxygen saturation bellow 90% on room air and haemodynamic instability due to SARS-CoV-2 infection (defined as a positive result on real-time reverse transcriptase–polymerase chain reaction assay of nasal and pharyngeal swab specimens) who required NIPPV and were admitted to a dedicated COVID-19 Intermediate Care unit were included in this study. Patients who were intubated less than 24 hours after NIPPV initiation and who were still hospitalized at the time of data analysis were excluded.
Patients were treated with three different types of NIPPV: CPAP, NIV and HELMET-CPAP. For the first 48 hours, NIPPV support was practically permanent. Small breaks of 15 minutes were only allowed for meals and patients only switched to HFNO or conventional oxygen during those periods. Patients were usually placed in the prone position for as many hours a day as they could tolerate. After the first 48 hours of NIPPV, if a clinical improvement was observed, the breaks from ventilation using HFNO or conventional oxygen were progressively increased. NIPPV withdrawal was determined when clinical stability criteria were met: respiratory rate bellow 20cpm, with no respiratory effort, peripheral oxygen saturation (SpO2) above 96% and tidal volume bellow 7 mL/kg of ideal weight.
CPAP and NIV (V60 Plus®, Philips) were delivered by single circuit and a oronasal non-vented mask, with an anti-bacterial/viral filter between the interface and the exhalation port and another anti-bacterial/viral filter between the ventilator and the circuit. CPAP was started at 8 cmH2O and the continuous positive pressure was progressively increased 1 cmH2O to a maximal level of 15cmH2O, to decrease patient respiratory rate, to reach the target tidal volume and to decrease ventilatory effort. Fraction of inspired oxygen (FiO2) was regulated for a SpO2 above 94%. NIV was used for patients who needed CPAP above 15 cmH2O, who experienced discomfort with CPAP or with hypercapnic respiratory failure or according to physician experience. Pressure support (PS) was regulated to reach a tidal volume of 6-7mL/kg of ideal weight and to correct the hypercapnia. FiO2 was regulated for a peripheral oxygen saturation (SpO2) above 94%. HELMET-CPAP (StarMed Ventukit, Intersurgical) was delivered through a Venturi flow driver. FiO2 was set by regulating oxygen and airflow after connecting the oxygen source with the Venturi flow driver. Anti-bacterial/viral filters were applied to the expiratory port. PEEP and FiO2 were regulated to obtain a SpO2 above 94%.
Several data were collected from medical records: demographic information (age, sex); comorbidities; frailty; respiratory condition at admission (respiratory rate); blood sample exams during hospital stay; blood gas tests at admission, before and after 2–24h of NIPPV initiation; time (days) from the beginning of symptoms to the beginning of NIPPV; ventilatory settings of the NIPPV; drugs administered during hospital stay. The PaO2/FiO2 ratio percentage change was calculated as: ((PaO2/FiO2 ratio during NIPPV - PaO2/FiO2 ratio during Venturi mask or reservoir mask) / PaO2/FiO2 ratio during Venturi mask or reservoir mask) * 100. Patients who died or underwent OTI were recorded. Informed consent was waived due to the retrospective nature of this study.
The primary outcome was NIPPV failure, defined as the occurrence of either OTI or death. Indication for OTI included the presence of the following criteria: inability to protect the airway; coma; life-threatening arrhythmias; severe hemodynamic instability (systolic blood pressure < 90mmHg despite adequate fluid therapy or use of vasoactive agents); intolerance to NIPPV and progressive respiratory distress despite NIPPV optimization (respiratory rate above 30 breaths/minute, tidal volume above 8mL/kg of ideal weight, SpO2 bellow 94% and important respiratory effort). The presence of these criteria did not automatically imply OTI, since this decision was based on a multidisciplinary discussion. A Do-Not-Intubate (DNI) order was determined by the medical team in a case-by-case manner, based on concomitant comorbidities, functional status prior to SARS-CoV-2 infection, poor likelihood of survival and Frailty score. The assessment of factors associated with NIPPV failure was the secondary outcome.
Statistical analyses were performed using SPSS software, version 26.0 (IBM SPSS, Armonk, New York). Baseline characteristics of patients treated with different forms of NIPPV were compared. Descriptive statistics were described using absolute and relative frequencies for qualitative variables and mean, median and standard deviation (SD) for continuous variables. Categorical variables were compared using the Chi-squared test or Fisher’s exact test, as appropriate. Continuous variables were compared with the Mann-Whitney-U and Kruskal–Wallis tests.
Factors associated with NIPPV failure were included in an univariate binary logistic regression analysis. Factors with a univariate significance level of P < 0.001 were selected to enter a multivariate binary logistic regression model and odds ratios (OR) with 95% confidence intervals (CI) were calculated for each factor. A value of P < 0.05 was considered statistically significant.