Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy Early Experience and Forecast During an Emergency Respons

Opinion

Critical Care Utilization for the COVID-19 Outbreak VIEWPOINT in Lombardy, Italy Early Experience and Forecast During an Emergency Response

Giacomo Grasselli, MD On February 20, 2020, apatientinhis30sadmitted it would not have been feasible to allocate all critically Department of to the intensive care unit (ICU) in Codogno Hospital ill patients to a single COVID-19 ICU. The decision was to Pathophysiology and (Lodi, Lombardy, Italy) tested positive for a new coro- cohort patients in 15 first-responder hub hospitals, cho- Transplantation, navirus, severe acute respiratory syndrome coronavi- sen because they either had expertise in infectious dis- University of Milan, Italy; and Dipartimento rus 2 (SARS-CoV-2), the virus that causes coronavirus ease or were part of the Venous-Venous ECMO Respi- di Anestesia, disease 2019 (COVID-19). He had a history of atypical ratory Failure Network (RESPIRA).3 Rianimazione ed pneumonia that was not responding to treatment, but The identified hospitals were requested to do the Emergenza-Urgenza, 1 Fondazione IRCCS Ca’ he was not considered at risk for COVID-19 infection. following. Granda Ospedale The positive result was immediately reported to the 1. CreatecohortICUsforCOVID-19patients(areassepa- Maggiore Policlinico, Lombardy health care system and governmental rated from the rest of the ICU beds to minimize risk Milan, Italy. offices. During the next 24 hours, the number of of in-hospital transmission). reported positive cases increased to 36. This situation 2. Organize a triage area where patients could receive Antonio Pesenti, MD Department of was considered a serious development for several rea- mechanical ventilation if necessary in every hospital Pathophysiology and sons: the patient (“patient 1”) was healthy and young; in to support critically ill patients with suspected Transplantation, less than 24 hours, 36 additional cases were identified, COVID-19 infection, pending the final result of diag- University of Milan, without links to patient 1 or previously identified posi- nostic tests. Italy; and Dipartimento di Anestesia, tive cases already in the country; it was not possible to 3. Establishlocalprotocolsfortriageofpatientswithre- Rianimazione ed identify with certainty the source of transmission to spiratory symptoms, to test them rapidly, and, de- Emergenza-Urgenza, patient 1 at the time; and, because patient 1 was in the pending on the diagnosis, to allocate them to the ap- Fondazione IRCCS Ca’ Granda Ospedale ICU and there were already 36 cases by day 2, chances propriate cohort. Maggiore Policlinico, were that a cluster of unknown magnitude was present 4. Ensure that adequate personal protective equip- Milan, Italy. and additional spread was likely. ment (PPE) for health personnel is available, with the OnFebruary21,anemergencytaskforcewasformed organization of adequate supply and distribution Maurizio Cecconi, MD bytheGovernmentofLombardyandlocalhealthauthori- along with adequate training of all personnel at risk Dipartimento Anestesia e Terapie Intensive, ties to lead the response to the outbreak. This Viewpoint of contagion. Humanitas Rozzano, provides a summary of the response of the COVID-19 5. Report every positive or suspected critically ill Milan, Italy. Lombardy ICU network and a forecast of estimated COVID-19 patient to the regional coordinating center. ICU demand over the coming weeks (projected to In addition, to quickly make available ICU beds March 20, 2020). and available personnel, nonurgent procedures were canceled and another 200 ICU beds were made avail- Supplemental Setting the Priorities and the Initial Response able and staffed in the following 10 days. In total, over content In Lombardy, the precrisis total ICU capacity was ap- the first 18 days, the network created 482 ICU beds proximately 720 beds (2.9% of total hospital beds at a ready for patients. total of 74 hospitals); these ICUs usually have 85% to 90% occupancy during the winter months. Containment Measures The mission of the COVID-19 Lombardy ICU Net- Local health authorities established strong containment work was to coordinate the critical care response to the measures in the initial cluster by quarantine of several outbreak. Two top priorities were identified: increasing townsinanattempttoslowvirustransmission.Inthesec- surge ICU capacity and implementing measures for ond week, other clusters emerged. During this time, the containment. ICU network advised the government to put in place every measure, such as reinforcing public health measures Increasing ICU Surge Capacity of quarantine and self-isolation, to contain the virus. The recognition that this outbreak likely occurred via Corresponding community spread suggested that a large number of ICU Admissions Over the First 2 Weeks Author: Antonio COVID-19–positive patients were already present in the There was an immediate sharp increase in ICU admis- Pesenti, MD, region. This prediction proved correct in the following sions from day 1 to day 14. The increase was steady and Fondazione IRCCS Ca’ Granda Ospedale days. Based on the assumption that secondary trans- consistent. Publicly available data indicate that ICU ad- Maggiore Policlinico, mission was already occurring, and even with contain- missions (n = 556) represented 16% of all patients Università degli studi di ment measures that health authorities were establish- (n = 3420)whotestedpositiveforCOVID-19.AsofMarch Milano, Via F. Sforza 35, ing, it was assumed that many new cases of COVID-19 7, the current total number of patients with COVID-19 20122 Milan, Italy (antonio.pesenti@ would occur, possibly in the hundreds or thousands of occupying an ICU bed (n = 359) represents 16% of cur- unimi.it). individuals. Thus, assuming a 5% ICU admission rate,2 rently hospitalized patients with COVID-19 (n = 2217).

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All patients who appeared to have severe illness were admitted for higher than what was reported from China, where only 5% of pa- hypoxic respiratory failure to the COVID-19 dedicated ICUs. tients who tested positive for COVID-19 required ICU admission.2,4 There could be different explanations. It is possible that criteria for Surge ICU Capacity ICU admission were different between the countries, but this seems Within 48 hours, ICU cohorts were formed in 15 hub hospitals to- unlikely. Another explanation is that the Italian population is differ- taling 130 COVID-19 ICU beds. By March 7,the total number of dedi- ent from the Chinese population, with predisposing factors such as cated cohorted COVID-19 ICU beds was 482 (about 60% of the total race, age, and comorbidities.5 preoutbreak ICU bed capacity), distributed among 55 hospitals. As On March 8 and 9, planning for the next response, which in- of March 8, critically ill patients (initially COVID-19–negative pa- cludes defining a new hub and spoke system for time-dependent patients) have been transferred to receptive ICUs outside the region thology,increasingICUcapacityfurther,andreinforcingstrongercon- via a national coordinating emergency office. tainment measurement in the community, has begun, as well as discussions of what could have been done differently. Forecasting ICU Demand Over the Next 2 Weeks First, laboratory capacity to test for SARS-CoV-2 should have been During the first 3 days of the outbreak, starting from February 22, increased immediately.Laboratory capacity reached saturation very the ICU admissions were 11, 15, and 20 in the COVID-19 Lombardy early.Thiscanaddextrastresstoasystemandaffecttheabilitytomake ICU Network. ICU admissions have increased continuously and accurate diagnoses and allocate patients appropriately. exponentially over the first 2 weeks. Based on data to March 7, Second, in parallel to the surge ICU capacity response, a large, when 556 COVID-19–positive ICU patients had been admitted to dedicated COVID-19 facility could have been converted more quickly. hospitals over the previous 15 days, linear and exponential mod- On day 1 of the crisis, it was not possible to predict the speed and els were created to estimate further ICU demand (eFigure in the extent of the contagion. Importantly, the forecasts show that in- Supplement). creasing ICU capacity is simply not enough. More resources should The linear model forecasts that approximately 869 ICU admis- be invested to contain the epidemic. sionscouldoccurbyMarch20,2020,whereastheexponentialmodel As of March 8, Lombardy was quarantined and strict self- growth projects that approximately 14 542 ICU admissions could oc- isolation measures were instituted. This may be the only possible cur by then. Even though these projections are hypothetical and in- waytocontainthespreadofinfectionandallowresourcestobede- volve various assumptions, any substantial increase in the number veloped for the time-dependent disease. of critically ill patients would rapidly exceed total ICU capacity,with- As of March 10, Italy has been quarantined and the govern- out even considering other critical admissions, such as for trauma, ment has instituted stronger containment measures, including strict stroke, and other emergencies. self-isolation measures. These containment measures and indi- In practice, the health care system cannot sustain an uncon- vidual citizen responsibility could slow down virus transmission. trolled outbreak, and stronger containment measures are now the While regional resources are currently at capacity, the central only realistic option to avoid the total collapse of the ICU system. Italian government is providing additional resources, such as trans- For this reason, over the last 2 weeks, clinicians have continuously fersofcriticallyillpatientstootherregions,emergencyfunding,per- advised authorities to augment the containment measures. sonnel, and ICU equipment. The goal is to ensure that an ICU bed is To our knowledge, this is the first report of the consequences available for every patient who requires one. Other health care sys- of the COVID-19 outbreak on critical care capacity outside China. tems should prepare for a massive increase in ICU demand during Despite prompt response of the local and regional ICU network, an uncontained outbreak of COVID-19. This experience would sug- health authorities, and the government to try to contain the initial gest that only an ICU network can provide the initial immediate surge cluster, the surge in patients requiring ICU admission has been over- response to allow every patient in need for an ICU bed to receive one. whelming. The proportion of ICU admissions represents 12% of the Health care systems not organized in collaborative emergency net- total positive cases, and 16% of all hospitalized patients. This rate is works should work toward one now.

ARTICLE INFORMATION Additional Contributions: We acknowledge the influenza A(H1N1) pandemic: preparation for severe Published Online: March 13, 2020. COVID-19 Lombardy ICU Network for their respiratory emergency outbreaks. Intensive Care Med. doi:10.1001/jama.2020.4031 remarkable efforts to provide care for the critically 2011;37(9):1447-1457. ill patients with COVID-19 (listed in the 4. Young BE, Ong SWX, Kalimuddin S, et al. Conflict of Interest Disclosures: Dr Grasselli Supplement). reports receiving payment for lectures and travel Epidemiologic features and clinical course of patients infected with SARS-CoV-2 in Singapore. support for conferences from Getinge, payment for REFERENCES lectures from Draeger Medical, payment for JAMA. Published March 3, 2020. doi:10.1001/jama. lectures and an unrestricted research grant from 1. Bai Y, Yao L, Wei T, et al. Presumed asymptomatic 2020.3204 Fisher & Paykel, payment for lectures from carrier transmission of COVID-19. JAMA. Published 5. Wu Z, McGoogan JM. Characteristics of and Thermofisher, and receiving payment for lectures February 21, 2020. doi:10.1001/jama.2020.2565 important lessons from the coronavirus disease and travel support for conferences from Biotest. Dr 2. Guan WJ, Ni ZY, Hu Y, et al; China Medical 2019 (COVID-19) outbreak in China: summary of a Pesenti reports receiving personal fees from Treatment Expert Group for Covid-19. Clinical report of 72 314 cases from the Chinese Center for Maquet, Novalung/Xenios, Baxter, and Boehringer characteristics of coronavirus disease 2019 in Disease Control and Prevention. JAMA. Published Ingelheim. Dr Cecconi reports consulting for China. N Engl J Med. doi:10.1056/NEJMoa2002032 February 24, 2020. doi:10.1001/jama.2020.2648 Edwards Lifesciences, Directed Systems, and 3. Patroniti N, Zangrillo A, Pappalardo F, et al. The Cheetah Medical. Italian ECMO network experience during the 2009

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Grasselli G, Pesenti A, Cecconi M. Critical care utilization for the COVID-19 outbreak in Lombardy, Italy: early experience and forecast during an emergency response. JAMA. doi:10.1001/jama.2020.4031

eFigure. Linear and Exponential Models Were Fitted to the Number of Occupied ICU Beds Over Time to Predict the Demand for ICU Beds Up to March 20, 2020 Acknowledgment

This supplementary material has been provided by the authors to give readers additional information about their work.

The predicted number of ICU admissions on March 20, 2020, was estimated to be 869 (95%CI: 744-995) with the linear model and was estimated to be 14 542 (95%CI: 8856-23 879) the exponential model. The linear growth rate was estimated to be 36.5 per day (95%CI: 30.0-43.0). The exponential growth rate was estimated to be 0.246 per day (95%CI: 0.221-0.272). Figure courtesy of Stefano Merler, Bruno Kessler Foundation, Trento, Italy, Epilab-JRU, FEM-FBK Joint Research Unit, Province of Trento, Italy.

© 2020 American Medical Association. All rights reserved. Acknowledgment: We acknowledge the COVID-19 Lombardy ICU Network for their remarkable efforts to provide care for the critically ill patients with COVID-19: Alberto Zangrillo, IRCCS Ospedale San Raffaele, Milan (Italy), [email protected]; Alberto Zanella, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy [email protected]; Andrea Lombardo, ASST Lariana - Ospedale Sant'Anna, Como (Italy), [email protected]; Angelo Pezzi, ASST Nord Milano - Ospedale Edoardo Bassini, Cinisello Balsamo (Italy), [email protected]; Antonio Coluccello, ASST Cremona - Ospedale di Cremona, Cremona (Italy), [email protected]; Antonio Pesenti, IRCCS Ca'Granda - Ospedale Maggiore Policlinico, Milan (Italy), [email protected]; Armando Alborghetti, Policlinico San Pietro - Ponte San Pietro (Italy), [email protected]; Benvenuto Antonini, ASST Garda - Ospedale di Manerbio, Manerbio (Italy), [email protected]; Daniel Covello, ASST Valle Olona - Ospedale di Busto Arsizio, Busto Arsizio (Italy), [email protected]; Danilo Radrizzani, ASST Ovest Milanese - Ospedale Nuovo di Legnano, Legnano (Italy), [email protected]; Dario Merlo, ASST Ovest Milanese - Ospedale di Magenta, Magenta (Italy), [email protected]; Davide Chiumello, ASST Santi Paolo e Carlo - Ospedale San Paolo, Milan (Italy), [email protected]; Davide Coppini, ASST Garda - Ospedale Civile di “La Memoria”, Gavardo (Italy), davide.coppini@asst- garda.it; Davide Guzzon, ASST Lecco - Ospedale di Merate, Merate (Italy), [email protected]; Emanuele Catena, ASST Fatebenefratelli - Ospedale Sacco, Milan (Italy), [email protected]; Enrico Beretta, ATS Montagna - Ospedale “Eugenio Morelli” di Sondalo, Sondalo (Italy), [email protected]; Enrico Storti, ASST Lodi - Ospedale Maggiore di Lodi, Lodi (Italy), enrico.storti@asst- lodi.it; Gianluca De Filippi, ASST Rhodense - Presidio ospedaliero G. Salvini, Garbagnate Milanese (Italy), [email protected]; Gianpaolo Castelli, ASST Mantova - Ospedale Carlo Poma, Mantova (Italy), [email protected]; Giorgio Aldegheri, IRCCS Multimedica, Sesto San Giovanni (Italy), [email protected]; Giorgio Gallioli, ASST Vimercate - Ospedale di Vimercate, Vimercate (Italy), [email protected]; Giorgio Iotti, Fondazione IRCCS Policlinico San Matteo, Pavia (Italy), [email protected]; Giovanni Albano, Humanitas Gavazzeni, Bergamo (Italy), [email protected]; Giovanni Landoni IRCCS Ospedale San Raffaele, Milan (Italy), Landoni Giovanni < [email protected]>; Giovanni Marino, ASST Melegnano - Ospedale di Vizzolo Predabissi, Melegnano (Italy), [email protected]; Giovanni Vitale, Policlinico San Marco, Zingonia (Italy), [email protected]; Giuseppe Foti, ASST Monza - Ospedale San Gerardo, Monza (Italy), g.foti@asst- monza.it; Giuseppe Natalini, Fondazione Poliambulanza Istituto Ospedaliero, Brescia (Italy), [email protected]; Guido Merli, ASST Crema - Ospedale Maggiore di Crema, Crema (Italy), [email protected] ; Livio Carnevale, ASST Pavia - Ospedale di Vigevano, Vigevano (Italy), [email protected]; Luca Cabrini, Ospedale di Circolo e Fondazione Macchi, Varese (Italy), [email protected]; Luca Guattieri, Ospedale “Sacra Famiglia” Fatebenefratelli, Erba (Italy),

© 2020 American Medical Association. All rights reserved. [email protected]; Luca Lorini, ASST Papa Giovanni XXIII, Bergamo, (Italy), [email protected]; Marco Dei Poli, IRCCS Policlinico San Donato, Milan (Italy), [email protected]; Mario Riccio, Istituti Ospitalieri di Cremona - C.no Ospedale Oglio Po, Casalmaggiore (Italy), [email protected]; Mario Tavola, ASST Lecco - Ospedale di Lecco, Lecco (Italy), [email protected]; Massimo Borelli, Ospedale Treviglio - Caravaggio, Treviglio (Italy), [email protected]; Maurizio Cecconi, Humanitas Research Hospital, Milan (Italy), [email protected]; Maurizio Raimondi, ASST Pavia - Ospedale Civile di Voghera, Voghera (Italy), [email protected]; Nicola Latronico, ASST Spedali Civili, Brescia (Italy), [email protected]; Nicola Petrucci, ASST Garda - Ospedale di Desenzano d/G, Desenzano del Garda (Italy), [email protected]; Nicolangela Belgiorno, Istituto Clinico San Rocco, Ome (Italy), [email protected]; Paolo Dughi, ASST Franciacorta - Presidio Ospedaliero di Iseo, Iseo (Italy), [email protected]; Paolo Gnesin, ASST Franciacorta - Presidio Ospedaliero Mellino Mellini, Chiari (Italy), [email protected]; Roberto Fumagalli, ASST Grande Ospedale Metropolitano Niguarda, Milan (Italy), [email protected]; Roberto Keim, ASST Bergamo est - Ospedale “Bolognini”, Seriate (Italy), [email protected]; Stefano Bonazzi, ASST Bergamo Est - SS Capitanio e Gerosa, Lovere (Italy), stefano.bonazzi@asst- bergamoest.it; Stefano Greco, ASST Valle Olona - Ospedale di Saronno, Saronno (Italy), [email protected]; Stefano Muttini, ASST Santi Paolo e Carlo - Ospedale San Carlo, Milan (Italy), [email protected].