Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis
Authors: Li Bassi Gianluigi , Gibbons Kristen , Suen Jacky Y. , Dalton Heidi J. , White Nicole , Corley Amanda , Shrapnel Sally , Hinton Samuel , Forsyth Simon , Laffey John G. , Fan Eddy , Fanning Jonathon P. , Panigada Mauro , Bartlett Robert , Brodie Daniel , Burrell Aidan , Chiumello Davide , Elhazmi Alyaa , Esperatti Mariano , Grasselli Giacomo , Hodgson Carol , Ichiba Shingo , Luna Carlos , Marwali Eva , Merson Laura , Murthy Srinivas , Nichol Alistair , Ogino Mark , Pelosi Paolo , Torres Antoni , Ng Pauline Yeung , Fraser John F. ,   The COVID-19 Critical Care Consortium, Al-Dabbous Tala , Alfoudri Huda , Shamsah Mohammed , Elapavaluru Subbarao , Berg Ashley , Horn Christina , Mayasi Yunis , Schroll Stephan , Meyer Dan , Velazco Jorge , Ploskanych Ludmyla , Fikes Wanda , Bagewadi Rohini , Dao Marvin , White Haley , Meyer Dan , Ehlers Ashley , Shalabi-McGuire Maysoon , Witt Trent , Grazioli Lorenzo , Lorini Luca , Grandin E. Wilson , Nunez Jose , Reyes Tiago , OBriain Diarmuid , Hunter Stephanie , Ramanan Mahesh , Affleck Julia , Veerendra Hemanth Hurkadli , Rai Sumeet , Russell-Brown Josie , Nourse Mary , Joseph Mark , Mitchell Brook , Tenzer Martha , Abe Ryuzo , Cho Hwa Jin , Jeong In Seok , Rahman Nadeem , Kakar Vivek , Brozzi Nicolas , Mehkri Omar , Krishnan Sudhir , Duggal Abhijit , Houltham Stuart , Graf Jerónimo , Diaz Roderigo , Orrego Roderigo , Delgado Camila , González Joyce , Sanchez Maria Soledad , Piagnerelli Michael , Sarrazin Josefa Valenzuela , Zabert A./Prof. Gustavo , Espinosa Lucio , Delgado Paulo , Delgado Victoria , Rincón Diego Fernando Bautista , Yanten Angela Maria Marulanda , Duque Melissa Bustamante , Brodie Daniel , Elhazmi Alyaa , Al-Hudaib Abdullah , Callahan Maria , Taufik M. Azhari , Wardoyo Elizabeth Yasmin , Gunawan Margaretha , Trisnaningrum Nurindah S. , Irawany Vera , Rayhan Muhammad , Panigada Mauro , Pesenti Antonia , Zanella Alberto , Leone Michela , Grasselli Giacomo , Coppola Silvia , Colombo Sebastiano , Antonelli Massimo , Carelli Simone , Grieco Domenico L. , Asaki Motohiro , Hoshino Kota , Salazar Leonardo , Duarte Laura , Laffey John , McNicholas Bairbre , Cosgrave David , McCaffrey Joseph , Bone Allison , Hakeem Yusuff , Winearls James , Tallott Mandy , Thomson David , Arnold-Day Christel , Cupido Jerome , Fanie Zainap , Miller Malcom , Seymore Lisa , van Straaten Dawid , Hssain Ali Ait , Aliudin Jeffrey , Alqahtani Al-Reem , Mohamed Khoulod , Mohamed Ahmed , Tan Darwin , Villanueva Joy , Zaqout Ahmed , Kurtzman Ethan , Ademi Arben , Dobrita Ana , El Aoudi Khadija , Segura Juliet , Giwangkancana Gezy , Ohshimo Shinichiro , Hoshino Koji , Hitoshi Saito , Osatnik Javier , Joosten Anne , Torres Antoni , Yang Minlan , Motos Ana , Luna Carlos , Arancibia Francisco , Williams Virginie , Noel Alexandre , Luque Nestor , Trung Trieu Huynh , Yacoub Sophie , Fantini Marina , García Ruth Noemi Jorge , Alvarez Enrique Chicote , Greti Anna , Ceccato Adrian , Sanchez Angel , Vazquez Ana Loza , Roche-Campo Ferran , Franch-Llasat Diego , Tuazon Divina , Amato Marcelo , Cassimiro Luciana , Pola Flavio , Ribeiro Francis , Fonseca Guilherme , Dalton Heidi , Desai Mehul , Osborn Erik , Deeb Hala , Arcadipane Antonio , Martucci Gennaro , Panarello Giovanna , Vitiello Chiara , Bianco Claudia , Occhipinti Giovanna , Rossetti Matteo , Cuffaro Raffaele , Cho Sung-Min , Shimizu Hiroaki , Moriyama Naoki , Kim Jae-Burm , Kitamura Nobuya , Gebauer Johannes , Yokoyama Toshiki , Al-Fares Abdulrahman , Buabbas Sarah , Alamad Esam , Alawadhi Fatma , Alawadi Kalthoum , Tanaka Hiro , Hashimoto Satoru , Yamazaki Masaki , Oh Tak-Hyuck , Epler Mark , Forney Cathleen , Kruse Louise , Feister Jared , Williamson Joelle , Grobengieser Katherine , Gnall Eric , Golden Sasha , Caroline Mara , Shapiro Timothy , Karaj Colleen , Thome Lisa , Sher Lynn , Vanderland Mark , Welch Mary , McDermott Sherry , Brain Matthew , Mineall Sarah , Kimura Dai , Brazzi Luca , Sales Gabriele , Ogston Tawnya , Nagpal Dave , Fischer Karlee , Lorusso Roberto , Rangappa Rajavardhan , Rai Sujin , Appu Argin , Esperatti Mariano , OBriain Diarmuid , Carton Edmund G. , Sen Ayan , Palacios Amanda , Rainey Deborah , Samoukoviv Gordan , Campisi Josie , Durham Lucia , Neumann Emily , Seefeldt Cassandra , Falcucci Octavio , Emmrich Amanda , Guy Jennifer , Johns Carling , Potzner Kelly , Zimmermann Catherine , Espinal Angelia , Buchtele Nina , Schwameis Michael , Stecher Stephanie-Susanne , Singh Delila , Barnikel Michaela , Arenz Lukas , Zaaqoq Akram , Galloway Lan Anh , Merley Caitlin , Nichol Alistair , Csete Marc , Quesada Luisa , Saba Isabela , Kasugai Daisuke , Hiraiwa Hiroaki , Tanaka Taku , Marwali Eva , Purnama Yoel , Dewayanti Santi Rahayu , Ardiyan  , Juzar Dafsah Arifa , Siagian Debby , Chen Yih-Sharng , Ogino Mark , Ratsep Indrek , Oigus Getter , Erikson Kristo , Post Andra-Maris , Enneveer Lauri , Sillaots Piret , Manetta Frank , Mihelis Effe , Sarmiento Iam Claire , Narasimhan Mangala , Varrone Michael , Komats Mamoru , Garcia-Diaz Julia , Harmon Catherine , Satyapriya S. Veena , Bhatt Amar , Mokadam Nahush A. , Uribe Alberto , Gonzalez Alicia , Shi Haixia , McKeown Johnny , Pasek Joshua , Fiorda Juan , Echeverria Marco , Moreno Rita , Zakhary Bishoy , Cavana Marco , Cucino Alberto , Foti Giuseppe , Giani Marco , Russotto Vincenzo , Chiumello Davide , Castagna Valentina , DellAmore Andrea , Navalesi Paolo , Shum Hoi-Ping , Vuysteke Alain , Usman Asad , Acker Andrew , Smood Benjamin , Mergler Blake , Sertic Federico , Subramanian Madhu , Sperry Alexandra , Rizer Nicolas , Burhan Erlina , Rasmin Menaldi , Akmal Ernita , Sitompul Faya , Lolong Navy , Naivedh Bhat , Erickson Simon , Barrett Peter , Dean David , Daugherty Julia , Loforte Antonio , Khan Irfan , Abraar Quraishi Mohammed , DeSantis Olivia , So Dominic , Kandamby Darshana , Mandei Jose M. , Natanael Hans , YudhaLantang Eka , Lantang Anastasia , Wijaya Surya Oto , Jung Anna , Ng George , Ng Wing Yiu , Ng Pauline Yeung , Fang Shu , Tabah Alexis , Ratcliffe Megan , Duroux Maree , Adachi Shingo , Nakao Shota , Blanco Pablo , Prieto Ana , Sánchez Jesús , Nicholson Meghan , Butt Warwick , Serratore Alyssa , Delzoppo Carmel , Janin Pierre , Yarad Elizabeth , Totaro Richard , Coles Jennifer , Pujo Bambang , Balk Robert , Vissing Andy , Kapania Esha , Hays James , Fox Samuel , Yantosh Garrett , Mishin Pavel , Yuliarto Saptadi , Hari Santoso Kohar , Djajalaksana Susanthy , Fatoni Arie Zainul , Fukuda Masahiro , Liu Keibun , Pelosi Paolo , Battaglini Denise , Jiménez Juan Fernando Masa , Bastos Diego , Gaião Sérgio , Rusmawatiningtyas Desy , Buchner Jessica , Cho Young-Jae , Lee Su Hwan , Kawasaki Tatsuya , Munshi Laveena , Sakiyalak Pranya , Nitayavardhana Prompak , Seitz Tamara , Arora Rakesh , Kent David , Marino Daniel , Parwar Swapnil , Cheng Andrew , Miller Jennene , Fujitani Shigeki , Shimizu Naoki , Madhok Jai , Owyang Clark , Buscher Hergen , Reynolds Claire , Maasikas Olavi , Beljantsev Aleksan , Mihnovits Vladislav , Akimoto Takako , Aizawa Mariko , Horibe Kanako , Onodera Ryota , Hodgson Carol , Burrell Aidan , Young Meredith , George Timothy , Shekar Kiran , McGuinness Niki , Irvine Lacey , Flynn Brigid , Endo Tomoyuki , Sugiyama Kazuhiro , Shimizu Keiki , Fan Eddy , Exconde Kathleen , Ichiba Shingo , Lussier Leslie , Lotz Gösta , Malfertheiner Maximilian , Maier Lars , Dreier Esther , Kusumastuti Neurinda Permata , McCloskey Colin , Dabaliz Al-Awwab , Elshazly Tarek B. , Smith Josiah , Szuldrzynski Konstanty S. , Bielański Piotr , Hakeem Yusuff , Wille Keith , Murthy Srinivas , Parhar Ken Kuljit S. , Fiest Kirsten M. , Codan Cassidy , Shahid Anmol , Fayed Mohamed , Evans Timothy , Garcia Rebekah , Gutierrez Ashley , Shimizu Hiroaki , Song Tae , Rose Rebecca , Bennett Suzanne , Richardson Denise , Peek Giles , Arora Lovkesh , Rappapport Kristina , Rudolph Kristina , Sibenaller Zita , Stout Lori , Walter Alicia , Herr Daniel , Vedadi Nazli , Bartlett Robert , Pesenti Antonio , Thompson Shaun , Sindt Lace , Rajnic Sean , Ewald Cale , Hoffman Julie , Ying Xiaonan , Kennedy Ryan , Griffee Matthew , Ciullo Anna , Kida Yuri , Roca Ricard Ferrer , Riera JordI , Contreras Sofia , Alegre Cynthia , Kay Christy , Fischer Irene , Renner Elizabeth , Taniguci Hayato , Fraser John , Bassi Gianluigi Li , Suen Jacky , Barnett Adrian , White Nicole , Gibbons Kristen , Forsyth Simon , Corley Amanda , Pearse India , Hinton Samuel , Abbate Gabriella , Hassan Halah , Heinsar Silver , Karnik Varun A. , Ki Katrina , ONeill Hollier F. , Obonyo Nchafatso , Pimenta Leticia Pretti , Reid Janice D. , Sato Kei , Shekar Kiran , Vuorinen Aapeli , Wildi Karin S. , Wood Emily S. , Yerkovich Stephanie , Lee James , Plotkin Daniel , Citarella Barbara Wanjiru , Merson Laura , Hartley Emma , Lubis Bastian , Ikeyama Takanari , Bhaskar Balu , Jung Jae-Seung , McGuinness Shay , Eastwood Glenn , Marta Sandra Rossi , Guarracino Fabio , Gerle Stacy , Coxon Emily , Claro Bruno , Loverde Daniel , Patil Namrata , Parrini Vieri , McBride Angela , Negaard Kathryn , Ratsch Angela , Abdelaziz Ahmad , Uribe Juan David , Peris Adriano , Sanders Mark , Emerson Dominic , Kamal Muhammad , Povoa Pedro , Francis Roland , Cherif Ali , Joseph Sunimol , Di Nardo Matteo , Heard Micheal , Kyle Kimberly , Blackwell Ray A. , Piagnerelli Michael , Biston Patrick , Jeong Hye Won , Smith Reanna , Prawira Yogi , Montrucchio Giorgia , Garcia Arturo Huerta , Salterain Nahikari , Meyns Bart , Moreno Marsha , Walia Rajat , Mehta Amit , Schweda Annette , Supriatna Moh , Kirakli Cenk , Williams Melissa , Kim Kyung Hoon , Assad Alexandra , Giraldo Estefania , Karolak Wojtek , Balik Martin , Pocock Elizabeth , Gajkowski Evan , Masafumi Kanamoto , Barrett Nicholas , Takeyama Yoshihiro , Park Sunghoon , Amin Faizan , Andriyani Fina Meilyana , Sudakevych Serhii , Ratsch Angela , Vera Magdalena , Cornejo Rodrigo , Schwarz Patrícia , Mardini Ana Carolina , de Paula Thais , Neto Ary Serpa , Villoldo Andrea , Colafranceschi Alexandre Siciliano , Iglesias Alejandro Ubeda , Granjean Juan , Melro Lívia Maria Garcia , Romualdo Giovana Fioravante , Gaia Diego , Souza Helmgton , Galas Filomena , Mendiluce Rafael Máñez , Sosa Alejandra , Martinez Ignacio , Kurosawa Hiroshi , Salgado Juan , Hugi-MayrCharbonneau Beate Eric , Barzilai Vitor Salvatore , Monteiro Veronica , de Souza Rodrigo Ribeiro , Harper Michael , Suzuki Hiroyuki , Adams Celina , Brieva Jorge , Nyale George , Eltatar Faisal Saleem , Fatani Jihan , Baeissa Husam , Masri Ayman AL , Rabie Ahmed , Hui Mok Yee , Yamane Masahiro , Jung Hanna , Margaret Ayorinde Mojisola , Nacpil Newell , Ruck Katja , Bakken Rhonda , Jara Claire , Felton Tim , Berra Lorenzo , Shah Bobby , Chakraborty Arpan , Cardona Monika , Capatos Gerry , Akkanti Bindu , Orija Abiodun , Jain Harsh , Ito Asami , Housni Brahim , Low Sennen , Iihara Koji , Chavez Joselito , Ramanathan Kollengode , Zabert Gustavo , Naidoo Krubin , Seppelt Ian , VanDyk Marlice , MacDonald Sarah , Ichiba Shingo , McGregor Randy , Siebenaler Teka , Flynn Hannah , Lofton Kristi , Aokage Toshiyuki , Shigemitsu Kazuaki , Moscatelli Andrea , Fiorentino Giuseppe , Baumgaertel Matthias , Mba Serge Eddy , Assy Jana , Hutahaean Amelya , Roush Holly , Sichting Kay A. , Alessandri Francesco , Burns Debra , Rabie Ahmed , Salt Gavin , Garabedian Carl P. , Millar Jonathan , Sim Malcolm , Mattke Adrian , McAuley Danny , Tadili Jawad , Frenzel Tim , Bar-Lavie Yaron , Ortiz Aaron Blandino , Stone Jackie , Tabah Alexis , Attokaran Antony , Farquharson Michael , Patel Brij , Gunning Derek , Baillie Kenneth , Watson Pia , Tamai Kenji , Sajinadiyasa Gede Ketut , Kanyawati Dyah , Salgado Marcello , Sassine Assad , Yudo Bhirowo , McCaul Scott , Lee Bongjin , Lee Sang Min , Afek Arnon , Iwashita Yoshiaki , Semedi Bambang Pujo , Kusumastuti Neurinda Permata , Metiva Jack , Van Belle Nicole , Martin-Loeches Ignacio , Ivatt Lenny , Woon Chia Yew , Kang Hyun Mi , Smith Timothy , James Erskine , Al-Rawas Nawar , Iwasaki Yudai , King-Chung Kenny Chan , Gudzenko Vadim , Hugi-Mayr Beate , Taccone Fabio , Perdhana Fajar , Lamarche Yoan , Ribeiro Joao Miguel , Bradic Nikola , Van den Bossche Klaartje , Lansink Oude , Singh Gurmeet , Debeuckelaere Gerdy , Stelfox Henry T. , Yi Cassia , Elia Jennifer , Tribble Thomas , Shankar Shyam , Padmanabhan Raj , Hallinan Bill , Paoletti Luca , Leyva Yolanda , Fykuda Tatuma , Badulak Jenelle , Koch Jillian , Hackman Amy , Janowaik Lisa , Hernandez Deb , Osofsky Jennifer , Donadello Katia , Lawang Aizah , Fine Josh , Davidson Benjamin , Vazquez Andres Oswaldo Razo 
Published: May 2022

Background

The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis.

Methods

We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression.

Results

Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59,p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61,p = 0.729). At 28 days, VFD were 16 (IQR 0–25) and 25 (IQR 7–26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00,p = 0.055). At 90 days, VFD were 77 (IQR 0–87) and 87 (IQR 0–88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07;p = 0.177).

Conclusions

In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.