In this first account of critically ill COVID-19 patients treated in the Canadian epicentre of the pandemic, we have found encouraging outcomes despite facing one of the largest numbers of cases per capita. We observed a high proportion of overweight and obese patients with hypertension and diabetes, as previously described.18 Patients typically presented to the ICU more than a week after symptom onset with lymphopenia, a hyperinflammatory profile, and evidence of coagulation activation. Of concern, nosocomial transmission was responsible for more than a third of cases. Invasive mechanical ventilation was used in 57% of patients. These were characterized by moderately low PaO2:FiO2 and compliance and very elevated estimated dead space fraction and ventilatory ratio. Hospital mortality was 25% overall and 21% in IMV patients. Critically ill patients with limitations of care excluding IMV had a high non-invasive ventilation failure rate (70%) and a high mortality rate (69%). Finally, patients ≥ 80 yr old had an 82% mortality rate.
As of 21 July, 6,268 HCW had been infected in Montreal, representing 22% of COVID-19 cases in the city.4 No official figures on nosocomial transmission have been published by provincial authorities, with scarce data worldwide. Early records from China reported that only 3.8% of COVID-19 patients were HCW,6 while in Italy they represented 12% of total cases19 and 10–20% of hospitalized COVID-19 patients in the UK.20 Inpatients who acquire COVID-19 during hospitalization are already ill and may be more likely to require ICU. Our observations, in conjunction with the strong representation of HCW among COVID-19 cases reported by public health authorities, may suggest that nosocomial transmission acted as a major amplifier in our region despite strict adherence to national guidelines for infection prevention. Documented in-hospital clusters of infection did initially occur in our institution, originating from non-isolated asymptomatic patients in whom COVID-19 was not suspected. In response, we modified our infection control policies to consider all inpatients as suspected COVID-19 cases, and these new measures sharply reduced nosocomial transmission.
With 166 deaths per 100,000 inhabitants, the COVID-19-related mortality in the Montreal metropolitan area is among the highest reported.4 Nevertheless, nursing ratios were preserved throughout the crisis and no triage was needed. A centralized dispatch centre helped distribute cases more evenly between designated hospitals. Importantly, the vast majority of individuals who died were never transferred to hospital wards or ICUs, as 64% of deaths in the province occurred in nursing homes.3 Nursing-home physicians made substantial efforts to discuss GOC at the crisis onset. This spared hospital resources as no nursing-home patient was admitted to our ICU. Avoidance of IMV in group C patients may have prevented lengthy ICU stays. A shared decision-making model21 with prompt recognition of patients with poor prognosis by clinicians and realistic patient and family expectations may have considerably preserved resources. Resources could then be allocated fully to those who would benefit the most, perhaps contributing to the relatively low mortality seen in patients with a full-code status. Nevertheless, caution is warranted in the interpretation of the association between GOC and outcomes as there is a potential self-fulfilling prophecy.
The hospital mortality rate observed in our cohort was similar to that reported in a recent meta-analysis of international cohorts of critically ill patients (26%),22 but higher than in a recent cohort from Vancouver (15%).23 One of the main limitations of these comparisons is that baseline patient characteristics and extrinsic factors may strongly influence the observed mortality rates. While group B patients are cared for in the ICU in most settings, some group A and C patients could be treated in high-dependency units outside of the ICU in some hospitals. In our institution, resources from our high-dependency units were merged with those of our ICU to adapt more easily to sudden increases in demand for negative-pressure rooms. Hospital characteristics and intensity of ICU-bed demand greatly influence the relative composition of patients in a given ICU, with significant impact on overall mortality. Restricting comparisons between cohorts to patients that underwent IMV (group B) may circumvent this limitation.9
Interestingly, the mortality observed in IMV patients (21%) was similar to that described in cohorts from Boston (17%), New York (25%), and Vancouver (20%), and lower than that in Lombardy (35%), Germany (53%), and China (97%).18,23,24,25,26,27 Differential follow-up may explain some of the differences. The mortality may be underestimated in cohorts with a significant number of patients still in the ICU at the time of reporting, which was not the case in our study. As the indications and timing of initiation of IMV may vary significantly,9 we could also compare different patients. Nevertheless, baseline physiologic indices of severity seem to suggest otherwise. PaO2:FiO2 ratios were similar across cohorts: 182 in Boston, 160 in Lombardy, 180 in Vancouver, and 177 in our cohort.23,24,25 Our cohort had a higher CRS (48 mL/cmH2O) than reported in Boston (35 mL/cmH2O) and Vancouver (35 mL/cmH2O).23,24 Nevertheless, CRS was not associated with survival in a recent unadjusted retrospective analysis of a cohort of COVID-19 patients.28 Moreover, we found a higher Vd:Vt (60% vs 45%) and ventilatory ratio (1.74 vs 1.25) than in Boston,24 indicators that have previously been shown to predict worst outcomes in patients with acute respiratory distress syndrome.14,16
We suspect that the high Vd:Vt and ventilatory ratio may be caused by alveolar capillary microthrombi, as seen in autopsy specimens.29 The high rate of VTE we report (19%), despite a high rate of therapeutic anticoagulation (27% to 57%), supports a prothrombotic state. Moreover, signs of widespread capillary angiopathy were recently shown on computed tomography (CT) pulmonary angiography and dual-energy CT in patients with severe COVID-19.30 The increased dead space, in conjunction with the hyperinflammatory profile with repeated febrile episodes, resulted in the persistent need for high minute ventilation in a significant proportion of IMV patients. This manifested as relentless air hunger whenever neuromuscular blockers and sedation were weaned, as illustrated by the relatively high P0.1 despite high opiate doses in patients on IMV for more than a week. When patients were re-sedated, potentially injurious high-intensity IMV (mechanical power >17 J·min−1)31 had to be applied to maintain acid-base balance, even with bicarbonate infusions. The high ventilatory requirement potentially resulted in a vicious cycle of ventilator or self-inflicted lung injury promoting further lung damage, which in turn increased ventilatory intensity. This is nicely illustrated by the slowly increasing plateau and driving pressures and steep increases in mechanical power with decreasing CRS over time. Our group was conservative with ECMO use because of the relatively good response of hypoxemia to prone positioning and inhaled nitric oxide. One wonders, however, if ECMO could have broken this vicious cycle if instituted early in selected patients with high ventilatory intensity, even with easily managed hypoxemia.
Our study has limitations. The single-centre design limited the sample size and prohibited inferential statistics. All cases of morbidity and mortality may not have been captured as only in-hospital outcomes were assessed. Strengths of our study include it being the first subgroup analysis of patients according to their GOC, shedding light on the excellent prognosis of patients with full-code status. Moreover, no patients were still in the ICU upon data extraction, compared with 56% overall in previous cohorts presenting outcomes of critically ill patients.22 This draws a much more accurate picture of clinical outcomes.