This is one of the largest multicenter studies from India which showed 7 days trend of patients with COVID pneumonia. The parameters which were statistically significant among survivors and non-survivors were CVA, APACHE II score, day1 requirement of invasive ventilator support, minimum PO2, fluid balance and complications such as pneumothorax and arrhythmia as shown by multivariable analysis (Table 4). The ICU mortality observed was higher (60%) as compared to other studies.
The largest study from Italy by Grasselli, et al, which included 1591 patients, with a larger proportion of patients received invasive mechanical ventilation (1150/1591;88%). The population was elderly and required higher PEEP 14 (12-16) and ICU mortality was 26% [4].
The (Pro vent COVID) study which included 553 patients who were mechanically ventilated showed median tidal volume was 6·3 ml/kg of predicted body weight (IQR 5·7–7·1), PEEP was 14 cm H2O (IQR 11·0–15·0), and driving pressure was 14 cm H2O (11·2–16·0) with the ICU mortality of 35% [5].
In our study, tidal volume was 6.24(1.36) ml/kg to 7.45(2.28) ml/kg and maximum PEEP of 10.29(3.5) cm of H2O, dynamic compliance was 17.55(5.18) ml/cm of H2O and static compliance was 24.20(8.57) ml/cm of H2O. The driving pressure was 18.22(6.16) cm of H2O which was higher in our study, correlating with the higher mortality as shown by previous studies of ARDS [9].
The study by Ferrando, et al, of 742 patients requiring invasive ventilation showed all- cause ICU mortality was 32% and mortality seen in severe ARDS patients was 39% [10]. The multicenter study from the US with 2215 patients showed a mortality of 39.5% [11].
As compared to above-mentioned studies, in our study one of the reasons for high mortality was the severity of illness as shown by the mean APACHE II score 29.8(6.11), (27.89 survivors vs 31.05 in non-survivors). Also, the P/F ratio on day 1 of ICU admission was lower with a median PF ratio of 109.31(77.79-187.26) as compared to Italian study 160 (114-220), Pro vent COVID 158·8 (128·6–200·5), Spanish study 120 (83–177) and US study 124 (86-188) as mentioned [4–5, 10–11].
One of the largest multicenter studies of COVID patients, from 138 hospitals, including > 4000 patients showed that 90 days mortality was around 31%. Mortality was higher among older, obese, diabetics and severe ARDS patients. In this study, the PF ratio on day1 was 154 (106–223) which was higher than that observed in our study 109.31(77.79-187.26) [12].
In our study among the ventilator parameters, routine parameters such as tidal volume and plateau pressure (P Plat) were not found significant. Probably due to the practice of low tidal volume and monitoring of P Plat was the established standard in the majority of the ICUs. P Peak and PCO2 were found to be significant parameters, along with minimum PO2. This suggests the possibility of impaired oxygenation as well as ventilation, indicating higher PCO2 levels in non-survivors as compared to survivors (46.15mm of Hg (18.30) vs 39.64mm of Hg (11.36). This also suggests the possibility of intrapulmonary shunt due to micro-thrombi or dead space.
Another peculiar finding in our study was the 7days trend of ventilator parameters. Among the ventilator parameters, change in any of the ventilator parameters over 7 days was not statistically significant, but dynamic compliance was higher on day3 and 4 in survivors (Figure 3). This highlights that pathophysiology of COVID is not only due to impaired static compliance alone but dynamic compliance also plays a role which is a measure of compliance and airway resistance [13]. It also indicates possibility of different phenotypes of ARDS in COVID patients [14].
A retrospective study by Xie, et al, of 733 patients showed a median age of 65 years, and mortality was around 53.8 %. The higher mortality was due to associated organ failure like respiratory failure, shock and acute kidney injury. These findings were similar to our study as indicated by higher APACHE II score and SOFA score in non-survivors [15].
There were two small studies by Bhataraju, et al and Arentz, et al, that showed higher mortality of 50% and 67% respectively [16, 17].
The study by Yang, et al, of 52 critically ill patients showed 28- day mortality of 61.5%, with a lower PF ratio, similar to our study. Surprisingly these patients had a lower incidence of barotrauma of 2 % as against 9.9% in our study, possibly due to timely use of rescue therapy such as ECMO in 17% of patients. In our study, only 1 patient received ECMO [18].
A study looking at the timing of intubation from India showed baseline mortality of 60 % which was similar to our study [8].
The strengths of our study include, the patients who were admitted to the ICU were having severe disease, which is a true representation of the critically ill population. Also as shown in Table S1, echocardiographic parameters suggest, these were the patients, with low LV filling pressure as shown by E/e’ ratio, as a true representation of the ARDS population. This study also describes characteristics of the patients requiring invasive as well as non-invasive ventilator support. The trend of parameters for 7 days for each patient helped in understanding the progress of the disease. Collection of data was a big challenge when healthcare workers were already overburdened by the caseload which was overcome by a volunteered team of research enthusiasts.
There were certain limitations to our study. Although the study was designed as a multicenter project, the actual number of ICUs which could participate was only 4, hence the data cannot represent the practices across various ICUs. The second limitation was depending on the type of hospital and case surge, criteria for admission for each ICU may be variable hence mortality among various ICUs may differ. The third limitation was the enrolment of different centers that happened at variable times during the study, which might have affected the number of patients recruited from each center. In addition to this, there was a difference in the timing of the surge of cases in various states. So during the study period, it was difficult to figure out the approximate number of patients who could be enrolled in the study, which resulted in a total enrolment of 667patients that was higher than the calculated sample size.
This study helped in evaluating the management of patients with COVID across the centers and also helped to check the practice patterns of managing ARDS, especially the use of low tidal volume strategy and prone positioning for which evidence is already established [19]. It also highlights the challenges for healthcare workers while taking care of these sick patients, such as the use of awake proning, prone positioning and managing the complications as mentioned in one of the largest meta-analyses [20].