key: cord-0728182-8w3ojgd4
authors: Cavayas, Yiorgos Alexandros; Noël, Alexandre; Brunette, Veronique; Williamson, David; Frenette, Anne Julie; Arsenault, Christine; Bellemare, Patrick; Lagrenade-Verdant, Colin; LeGuillan, Soazig; Levesque, Emilie; Lamarche, Yoan; Giasson, Marc; Rico, Philippe; Beaulieu, Yanick; Marsolais, Pierre; Serri, Karim; Bernard, Francis; Albert, Martin
title: Early experience with critically ill patients with COVID-19 in Montreal
date: 2020-09-15
journal: Can J Anaesth
DOI: 10.1007/s12630-020-01816-z
sha: 65222c4d60bc7807942141274115c6659512eb20
doc_id: 728182
cord_uid: 8w3ojgd4

PURPOSE: Montreal has been the epicentre of the coronavirus disease (COVID-19) pandemic in Canada. Given the regional disparities in incidence and mortality in the general population, we aimed to describe local characteristics, treatments, and outcomes of critically ill COVID-19 patients in Montreal. METHODS: A single-centre retrospective cohort of consecutive adult patients admitted to the intensive care unit (ICU) of Hôpital du Sacré-Coeur de Montréal with confirmed COVID-19 were included. RESULTS: Between 20 March and 13 May 2020, 75 patients were admitted, with a median [interquartile range (IQR)] age of 62 [53–72] yr and high rates of obesity (47%), hypertension (67%), and diabetes (37%). Healthcare-related infections were responsible for 35% of cases. The median [IQR] day 1 sequential organ failure assessment score was 6 [3–7]. Invasive mechanical ventilation (IMV) was used in 57% of patients for a median [IQR] of 11 [5–22] days. Patients receiving IMV were characterized by a moderately decreased median [IQR] partial pressure of oxygen:fraction of inspired oxygen (day 1 PaO(2):F(i)O(2) = 177 [138–276]; day 10 = 173 [147–227]) and compliance (day 1 = 48 [38–58] mL/cmH(2)O; day 10 = 34 [28–42] mL/cmH(2)O) and very elevated estimated dead space fraction (day 1 = 0.60 [0.53–0.67]; day 10 = 0.72 [0.69–0.79]). Overall hospital mortality was 25%, and 21% in the IMV patients. Mortality was 82% in patients ≥ 80 yr old. CONCLUSIONS: Characteristics and outcomes of critically ill patients with COVID-19 in Montreal were similar to those reported in the existing literature. We found an increased physiologic dead space, supporting the hypothesis that pulmonary vascular injury may be central to COVID-19-induced lung damage.

related infections were responsible for 35% of cases. The median [IQR] day 1 sequential organ failure assessment score was 6 [3] [4] [5] [6] [7] . Invasive mechanical ventilation (IMV) was used in 57% of patients for a median [IQR] of 11 [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] days. Patients receiving IMV were characterized by a moderately decreased median [IQR] Overall hospital mortality was 25%, and 21% in the IMV patients. Mortality was 82% in patients C 80 yr old. Conclusions Characteristics and outcomes of critically ill patients with COVID-19 in Montreal were similar to those reported in the existing literature. We found an increased physiologic dead space, supporting the hypothesis that pulmonary vascular injury may be central to COVID-19induced lung damage.

Objectif Montre´al a e´te´l'e´picentre de la pande´mie du coronavirus (COVID-19) au Canada. E´tant donne´les disparite´s re´gionales dans l'incidence et la mortalite´dans la population ge´ne´rale, nous avons tente´de de´crire les caracte´ristiques locales, les traitements et le devenir des patients atteints de la COVID-19 en e´tat critique aM ontre´al. Méthode Notre e´tude de cohorte re´trospective monocentrique a inclus tous les patients adultes admis conse´cutivement a`l'unite´de soins intensifs de l'Hôpital du Sacre´-Coeur de Montre´al avec un diagnostic confirme´de COVID-19. Résultats Soixante-quinze patients ont e´te´admis entre le 20 mars et le 13 mai 2020. Ceux-ci avaient un aˆge me´dian [e´cart interquartile (E´IQ)] de 62 [53-72] ans et pre´sentaient une incidence e´leve´e d'obe´site´(47 %), d'hypertension (67 %) et de diabe`te (37 %). Les transmissions associe´es aux soins de sante´e´taient responsables de 35 % des cas. Au jour 1, le score SOFA (Sequential Organ Failure Assessment -e´valuation se´quentielle de de´faillance des organes) me´dian [E´IQ] e´tait de 6 [3] [4] [5] [6] [7] . La ventilation me´canique invasive (VMI) a e´te´utilise´e chez 57 % des patients, pour une dure´e me´diane [E´IQ] de 11 [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] 2 The catchment area of our hospital has been particularly affected with more than 7,000 confirmed cases of COVID-19. 3 A rate of 3,083 confirmed cases/100,000 population was reached in one of the covered boroughs, 4 the highest reported rate in the country and similar to that reported in New York City. 5 Severe acute respiratory syndrome coronavirus 2 infection can result in a wide range of clinical manifestations, ranging from asymptomatic to critically ill. 6 Exaggerated inflammatory mediator release triggered by the cytopathic viral infection and coagulation dysregulation are thought to be central to the development of severe lung damage. 7 Different distribution of determinants of this host response may significantly impact the expression of the disease in different populations. Older populations with higher rates of hypertension, diabetes, and obesity have a higher risk of more severe disease. 8 Extrinsic factors, including healthcare system characteristics (i.e., number of hospital or ICU beds), may also impact patient management and disease progression towards severe forms. Finally, cultural differences in terms of goals of care and end-of-life decision-making may also affect ICU admission and choice of supportive therapy. 9 Given regional differences in the above-mentioned factors, detailed characterization of critically ill patients is needed to understand how COVID-19 affects our population. Our aim was to describe the demographics, presentation, treatments, and outcomes of a cohort of critically ill adult patients with COVID-19 hospitalized in a large academic ICU in Montreal, Canada.

We conducted a single-centre retrospective observational study of consecutive adult patients with confirmed COVID-19 admitted to the ICU of Hôpital du Sacré-Coeur de Montréal between 20 March and 13 May 2020. Diagnosis was established in all cases by reverse transcriptasepolymerase chain reaction in nasopharyngeal, tracheal aspirate, or bronchoalveolar lavage specimens. The institutional review board approved the study and waived the requirement for informed consent.

Hôpital du Sacré-Coeur de Montréal is a large academic hospital with a pre-pandemic 38-bed capacity mixed medical-surgical ICU and a 1:1.3 nurse to patient ratio. It is a level-1 trauma centre and severe acute respiratory failure centre, with extracorporeal membrane oxygenation (ECMO) capacity. Hôpital du Sacré-Coeur de Montréal was among the first designated COVID-19 centres in the province. An organizational plan was in place to progressively increase the number of ICU beds to [ 100 in a stepwise approach if needed. 10 All COVID-19 cases were managed by boardcertified intensivists supported by a multidisciplinary team according to international treatment guidelines, including lung-protective ventilation, prone position, neuromuscular blockade, and conservative fluid management. 11, 12 Intensive care unit admission criteria for COVID-19 patients included an oxygen requirement of [ 5 LÁmin -1 accompanied with signs of respiratory distress. Patients with pre-established limitations of care excluding invasive mechanical ventilation (IMV) and cardiopulmonary resuscitation (CPR) were only admitted if considered for a trial of highflow oxygen therapy or non-invasive positive-pressure ventilation (NIPPV). These therapies were permitted only in negative-pressure ICU rooms and their use was initially strongly discouraged because of aerosol generation. Some patients admitted from the emergency department (ED) did not have pre-established goals of care (GOC). Such patients were admitted quickly in an effort to liberate ED beds and GOC were discussed in the ICU. In patients with respiratory distress, NIPPV was sometimes started to provide time to discuss GOC. Although GOC were continuously reviewed as per patient evolution and families' wishes, only initial GOC at ICU admission were used for analysis.

An early intubation strategy was initially advocated, with a slightly longer period of observation before intubation as experience was gained. With a few exceptions, no antimalarial, antiviral, or immunomodulating agents were administered outside of clinical trials. Corticosteroids were used at the discretion of 

We recorded baseline characteristics, laboratory parameters, ICU day 1 sequential organ failure assessment (SOFA) score, 13 treatments, and outcomes. Day 1 of IMV arterial blood gas values and IMV parameters were collected (those closest to 6:00 AM). Data were extracted from our ICU database (SEMi CriticareÒ, Montreal, QC, Canada), complemented by retrospective chart review. The ventilatory ratio, estimated dead space fraction (V d :V t ; Weir rearrangement using the Harris-Benedict equation for the resting energy expenditure), and mechanical power (simplified) were calculated according to published formulas. [14] [15] [16] Descriptive statistics were used to summarize clinical data. Categorical variables were presented as counts and percentages and continuous variables as median [interquartile range (IQR)]. In patients missing PaO 2 measurements, we used the SpO 2 :F I O 2 ratio to calculate the respiratory component of the SOFA score. 17 Missing data imputation was not performed. Data were analyzed ACEi = angiotensive coverting enzyme inhibitor; AST = aspartate aminotransferase; ALT = alanine aminotransferase; ARB = angiotensive receptor blockers; AST = aspartate aminotransferase; BMI = body mass index; CKD = chronic kidney disease; COPD = chronic obstructive lung disease; CRP = C-reactive protein; hs = high sensitivity; ICU = intensive care unit; LDH = lactate dehydrogenase; NSAID = non-steroidal antiinflammatory drugs; pulm. dis. = pulmonary disease; SOFA = sequential organ failure assessment; WBC = white blood cell count using IBM SPSS Statistics, Version 25.0 (IBM Corp, Armonk, NY, USA).

Between Non-invasive respiratory support A high-flow nasal cannula was used in only two patients (3%) because of concerns over aerosolization. Noninvasive positive-pressure ventilation was also initially avoided, but as the pandemic evolved, it was used more frequently (16/75; 21%), mainly in patients with respiratory distress who declined IMV (10/16; 63%). Failure of NIPPV was high in that context (seven deaths/ 10; 70%). In the remaining six patients that consented to IMV, NIPPV was used as the initial support modality in two patients likely to have poor outcomes with IMV (advanced chronic pulmonary diseases); intubation was successfully avoided in both. In the other four patients, NIPPV was used post-extubation; it failed in three of those four instances (one patient who declined re-intubation died and two patients were re-intubated).

A total of 43 patients underwent IMV (57% Figure. Only two patients below 60 yr of age died (2/32; 6%). Fifteen of the 19 patients who died (79%) gave do-notresuscitate orders upon ICU admission. The mortality was 67% (8/12) for patients with initial GOC excluding both resuscitation and IMV, 54% (7/13) for patients with initial GOC excluding resuscitation but allowing IMV, and 8% (4/49) for those with initial full-code status. There were no missing data on ICU therapies and outcomes.

Patients were categorized into three groups (Table 5 ). Group A consisted of patients agreeing to IMV but did not receive it (n = 20). This group was younger and had fewer comorbidities. They presented with the lowest rate of lymphopenia, the lowest ferritin, and lowest D-dimers, while having the highest median C-reactive protein levels. All but one patient survived and the ICU LOS was short 632-3,060] ). The majority were treated with NIPPV (10/13; 77%). Mortality in this group was 69%.

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 PaO 2 :F I O 2 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 C 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 cases 19 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 nonisolated 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 model 21 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 highdependency 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. Respiratory rate (breathsÁmin -1 ) 20 [16] [17] [18] [19] [20] [21] [22] 22 [20] [21] [22] [23] [24] [25] [26] [27] [28] 24 [20] [21] [22] [23] [24] [25] [26] [27] [28] 25 [21] [22] [23] [24] [25] [26] [27] [28] 24 [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] Plateau pressure (cmH 2 O)* 21 [19] [20] [21] [22] [23] [24] 26 [24] [25] [26] [27] [28] 25 [22] [23] [24] [25] [26] [27] 26 [20] [21] [22] [23] [24] [25] [26] [27] [28] 30 [28] [29] [30] [31] [32] PEEP (cmH 2 O) 9 [8] [9] [10] 8 [5] [6] [7] [8] [9] [10] 10 [8] [9] [10] [11] [12] 8 [7] [8] [9] [10] [11] 8 [7] [8] [9] [10] Driving pressure (cmH 2 O)* 13 [10] [11] [12] [13] [14] [15] [16] 14 [12] [13] [14] [15] [16] 15 [12] [13] [14] [15] 14 [12] [13] [14] [15] [16] 17 [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] Pressure support (cmH 2 O) 13 [9] [10] [11] [12] [13] 13 [9] [10] [11] [12] [13] [14] [15] 16 [14] [15] [16] [17] [18] [19] [20] 13 [10] [11] [12] [13] [14] [15] [16] [17] 13 [10] [11] [12] [13] [14] [15] 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%). 18,23-27 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. PaO 2 :F I O 2 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 C RS (48 mL/cmH 2 O) than reported in Boston (35 mL/cmH 2 O) and Vancouver (35 mL/ cmH 2 O). 23, 24 Nevertheless, C RS was not associated with survival in a recent unadjusted retrospective analysis of a cohort of COVID-19 patients. 28 Moreover, we found a higher V d :V t (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 V d :V t 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 P 0.1 despite high opiate doses in patients on IMV for more than a week. When patients were re-sedated, potentially injurious highintensity IMV (mechanical power [17 JÁmin -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 selfinflicted 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 C RS 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.

We found that characteristics and outcomes of critically ill patients with COVID-19 in Montreal were similar to those reported in the existing literature. Some findings did stand out. A significant proportion of ICU patients likely acquired the virus in healthcare facilities, highlighting the importance of appropriate infection control policies. Noninvasive positive-pressure ventilation had a high failure rate (70%) when used in critically ill patients with limitations of care excluding IMV. Finally, we found a significantly increased physiologic dead space in patients on IMV, supporting the hypothesis that pulmonary vascular injury may be at the heart of COVID-19-induced lung damage.

HCO 3 = bicarbonate

PBW = predicted body weight; PEEP = positive end expiratory pressure; PaCO 2 = arterial partial pressure of carbon dioxide; PaO 2 :F I O 2 = partial pressure of oxygen:fraction of inspired oxygen

V t = tidal volume; V d :V t = dead space fraction. *Only reported for

A novel coronavirus from patients with pneumonia in China

Données COVID-19 au Québec

Données détaillées COVID-19 -Ensembble des régions du Québec

Test Results Table View. COVID-19 Tracker

Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention

The trinity of COVID-19: immunity, inflammation and intervention

Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19

Mechanical ventilation in COVID-19: interpreting the current epidemiology

Augmentation of hospital critical care capacity after bioterrorist attacks or epidemics: Recommendations of the Working Group on Emergency Mass Critical Care

Surviving Sepsis Campaign: guidelines on the Management of Critically Ill Adults With Coronavirus Disease 2019 (COVID-19)

An official American Thoracic Society/European Society of Intensive Care Medicine/ Society of Critical Care Medicine Clinical Practice guideline: Mechanical ventilation in adult patients with acute respiratory distress syndrome

Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on ''sepsis-related problems'' of the European Society of Intensive Care Medicine

Estimating deadspace fraction for secondary analyses of acute respiratory distress syndrome clinical trials

Ventilator-related causes of lung injury: the mechanical power

Physiologic analysis and clinical performance of the ventilatory ratio in acute respiratory distress syndrome

Derivation and validation of Spo2/Fio2 ratio to impute for Pao2/Fio2 ratio in the respiratory component of the sequential organ failure assessment score

Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area

COVID-19 integrated surveillance: key national data

Covid-19: Doctors sound alarm over hospital transmissions

Challenges in end-of-life care in the ICU

Mortality rates of patients with COVID-19 in the intensive care unit: a systematic review of the emerging literature

Baseline characteristics and outcomes of patients with COVID-19 admitted to intensive care units in Vancouver, Canada: a case series

Respiratory pathophysiology of mechanically ventilated patients with COVID-19: a cohort study

Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region. Italy

Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study

Clinical course and outcomes of 344 intensive care patients with COVID-19

ICU and ventilator mortality among critically ill adults with coronavirus disease 2019

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid

Pulmonary angiopathy in severe COVID-19: physiologic, imaging and hematologic observations

Time-varying intensity of mechanical ventilation and mortality in patients with acute respiratory failure: a registry-based, prospective cohort study

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations

Author contributions Yiorgos Alexandros Cavayas, Alexandre Noe¨l, Ve´ronique Brunette, David Williamson, Karim Serri, Francis Bernard, and Martin Albert contributed to all aspects of this manuscript, including study conception and design; acquisition, analysis, and interpretation of data; and drafting the article. Anne Julie Frenette, Christine Arsenault, Patrick Bellemare, Colin Lagrenade-Verdant, Soazig Le Guillan, E´milie Levesque, Yoan Lamarche, Marc Giasson, Philippe Rico, Yanick Beaulieu, and Pierre Marsolais contributed to interpretation of data and drafting the article.Acknowledgements We would like to thank ICU nurses, respiratory therapists, orderlies, and all the other support staff who are the real heroes behind every life saved. Moreover, we would like to recognize all the difficult work accomplished by our research coordinator, Virginie Williams, without whom no research would have been accomplished during these difficult times.Disclosures None.

Editorial responsibility This submission was handled by Dr. Sangeeta Mehta, Associate Editor, Canadian Journal of Anesthesia.