Year 2021 in review – Intensive care
Authors:
J. Beneš 1,2,3; J. Chvojka 1,2,3,4,5; T. Karvunidis 3,4,5; J. Kletečka 1,2; J. Máca 6,7,8; J. Zatloukal 1,2; M. Matějovič 3,4,5
Authors‘ workplace:
Klinika anesteziologie, resuscitace a intenzivní medicíny, Lékařská fakulta v Plzni, Univerzita Karlova
1; Klinika anesteziologie, resuscitace a intenzivní medicíny, Fakultní nemocnice Plzeň
2; Biomedicínské centrum, Lékařská fakulta v Plzni, Univerzita Karlova
3; Jednotka intenzivní péče, I. interní klinika, Lékařská fakulta v Plzni, Univerzita Karlova
4; Jednotka intenzivní péče, I. interní klinika, Fakultní nemocnice Plzeň
5; Klinika anesteziologie, resuscitace a intenzivní medicíny, Fakultní nemocnice Ostrava
6; Ústav fyziologie a patofyziologie, Lékařská fakulta, Ostravská univerzita
7; Katedra intenzivní medicíny, urgentní medicíny a forenzních oborů, Lékařská fakulta, Ostravská univerzita
8
Published in:
Anest. intenziv. Med., 32, 2021, č. 6, s. 271-279
Category:
Review Articles
Overview
The year 2021 took place in the shadow of the ongoing pandemic of the COVID-19. This affected not only the number of pa tients treated, but also the focus of the vast majority of important publications. Nevertheless, several important publications can be identified that relate to the current agenda of the field of Intensive Care Medicine. One of the leading ones is the publication of resuscitation guidelines and guidelines for the treatment of sepsis. In this review article, we bring the readers of the journal a selection of the most important things that have been published this year and should not run away.
Keywords:
intensive care – sepsis – COVID-19 – multiorgan dysfunction
Sources
1. Else H. How a torrent of COVID science changed research publishing – in seven charts. Nature. 2020;588:553.
2. REMAP‑ CAP Trial. https://www.remapcap.org/. Accessed 3 Dec 2021.
3. Welcome — RECOVERY Trial. https://www.recoverytrial.net/. Accessed 3 Dec 2021.
4. Piller C. Many scientists citing two scandalous COVID-19 papers ignore their retractions. Science (80-). 2021. doi: 10.1126/science.abg5806.
5. Reardon S. Flawed ivermectin preprint highlights challenges of COVID drug studies. Nature. 2021;596:173–174. doi: 10.1038/d41586-021-02081-w.
6. Lott C, Truhlář A, Alfonzo A, Barelli A, González‑Salvado V, Hinkelbein J, et al. European Resuscitation Council Guidelines 2021: Cardiac arrest in special circumstances. Resuscitation. 2021;161:152–219. doi: 10.1016/j.resuscitation.2021. 02. 011.
7. Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, et al. European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: Post‑resuscitation care. Resuscitation. 2021;161:220–269. doi: 10.1016/j.resuscitation. 2021. 02. 012.
8. Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, Levin H, Ullén S, et al. Hypothermia versus Normothermia after Out‑of‑Hospital Cardiac Arrest. N Engl J Med. 2021;384: 2283–2294. doi: 10.1056/NEJMOA2100591/SUPPL_FILE/NEJMOA2100591_DATA‑SHARING. PDF.
9. Fernando SM, Di Santo P, Sadeghirad B, Lascarrou JB, Rochwerg B, Mathew R, et al. Targeted temperature management following out‑of‑hospital cardiac arrest: a systematic review and network meta‑analysis of temperature targets. Intensive Care Med. 2021;47:1078–88. doi: 10.1007/S00134-021-06505-Z/TABLES/5.
10. Moseby‑Knappe M, Mattsson‑Carlgren N, Stammet P, Backman S, Blennow K, Dankiewicz J, et al. Serum markers of brain injury can predict good neurological outcome after out‑of‑hospital cardiac arrest. Intensive Care Med. 2021;47:984–94. doi: 10.1007/S00134-021-06481-4/TABLES/5.
11. Aaen AA, Voldby AW, Storm N, Kildsig J, Hansen EG, Zimmermann‑Nielsen E, et al. Goal‑directed fluid therapy in emergency abdominal surgery: a randomised multicentre trial. Br J Anaesth. 2021;127:521–531. doi: 10.1016/J.BJA.2021. 06. 031.
12. de Waal EEC, Frank M, Scheeren TWL, Kaufmann T, de Korte DJD, Cox B, et al. Perioperative goal‑directed therapy in high‑risk abdominal surgery. A multicenter randomized controlled superiority trial. J Clin Anesth. 2021;75:110506.
13. Joosten A, Rinehart J, Van der Linden P, Alexander B, Penna C, De Montblanc J, et al. Computer‑assisted Individualized Hemodynamic Management Reduces Intraoperative Hypotension in Intermediate- and High‑risk Surgery: A Randomized Controlled Trial. Anesthesiology. 2021;135:258–272. doi: 10.1097/ALN.0000000000003807.
14. Wiegers EJA, Lingsma HF, Huijben JA, Cooper DJ, Citerio G, Frisvold S, et al. Fluid balance and outcome in critically ill patients with traumatic brain injury (CENTER‑TBI and OzENTER‑TBI): a prospective, multicentre, comparative effectiveness study. Lancet Neurol. 2021;20:627–638. doi: 10.1016/S1474-4422(21)00162-9.
15. Van Regenmortel N, Moers L, Langer T, Roelant E, De Weerdt T, Caironi P, et al. Fluid‑induced harm in the hospital: look beyond volume and start considering sodium. From physiology towards recommendations for daily practice in hospitalized adults. Ann Intensive Care. 2021;11:1– 12. doi: 10.1186/S13613-021-00851-3/FIGURES/2.
16. Zhu Y, Guo N, Song M, Xia F, Wu Y, Wang X, et al. Balanced crystalloids versus saline in critically ill patients: The PRISMA study of a meta‑analysis. Medicine (Baltimore). 2021;100:e27203. doi: 10.1097/MD.0000000000027203.
17. Zampieri FG, Machado FR, Biondi RS, Freitas FGR, Veiga VC, Figueiredo RC, et al. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA. 2021;326:818–829. doi: 10.1001/JAMA.2021.11684.
18. Zampieri FG, Machado FR, Biondi RS, Freitas FGR, Veiga VC, Figueiredo RC, et al. Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial. JAMA. 2021;326:830–838. doi: 10.1001/JAMA.2021.11444.
19. Kohoutova M, Horak J, Jarkovska D, Martinkova V, Tegl V, Nalos L, et al. Vagus Nerve Stimulation Attenuates Multiple Organ Dysfunction in Resuscitated Porcine Progressive Sepsis. Crit Care Med. 2019;47.
20. Hasegawa D, Sato R, Prasitlumkum N, Nishida K, Takahashi K, Yatabe T, et al. Effect of Ultrashort‑Acting β‑Blockers on Mortality in Patients With Sepsis With Persistent Tachycardia Despite Initial Resuscitation: A Systematic Review and Meta‑analysis of Randomized Controlled Trials. Chest. 2021;159:2289–2300. doi: 10.1016/J.CHEST.2021. 01. 009.
21. Datta PK, Rewari V, Ramachandran R, Singh PM, Ray BR, Aravindan A, et al. Effectiveness of enteral ivabradine for heart rate control in septic shock: A randomised controlled trial. Anaesth Intensive Care. 2021;49:366–378. doi: 10.1177/0310057X211009913.
22. Guinot PG, Martin A, Berthoud V, Voizeux P, Bartamian L, Santangelo E, et al. Vasopressor‑Sparing Strategies in Patients with Shock: A Scoping‑Review and an Evidence‑Based Strategy Proposition. J Clin Med 2021, Vol 10, Page 3164. 2021;10:3164. doi: 10.3390/JCM10143164.
23. Huang H, Wu C, Shen Q, Xu H, Fang Y, Mao W. The effect of early vasopressin use on patients with septic shock: A systematic review and meta‑analysis. Am J Emerg Med. 2021;48:203–208.
24. Mucha SR, Dugar S, McCrae K, Joseph D, Bartholomew J, Sacha GL, et al. Update to coagulopathy in COVID-19: Manifestations and management. Cleve Clin J Med. 2020. doi: 10.3949/ccjm.87a.ccc024-up.
25. Godon A, Tacquard CA, Mansour A, Garrigue D, Nguyen P, Lasne D, et al. Prevention of venous thromboembolism and haemostasis monitoring in patients with COVID-19: Updated proposals (April 2021): From the French working group on perioperative haemostasis (GIHP) and the French study group on thrombosis and haemostasis (GFHT), in collaboration with the French society of anaesthesia and intensive care (SFAR). Anaesth Crit Care Pain Med. 2021;40:100919.
26. Lopes RD, de Barros e Silva PGM, Furtado RHM, Macedo AVS, Bronhara B, Damiani LP, et al. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D‑dimer concentration (ACTION): an open‑ label, multicentre, randomised, controlled trial. Lancet. 2021;397:2253–2263. doi: 10.1016/S0140- 6736(21)01203-4/ATTACHMENT/3789264C-3BC1-48B8-A690-FFAF68CA727C/MMC1.PDF.
27. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med. 2021;385:777–789. doi: 10.1056/NEJMOA2103417/SUPPL_FILE/NEJMOA2103417_ DATA‑SHARING. PDF.
28. Shakur H, Roberts I, Fawole B, Chaudhri R, El‑Sheikh M, Akintan A, et al. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post‑partum haemorrhage (WOMAN): an international, randomised, double‑blind, placebo‑ controlled trial. Lancet. 2017;389:2105–2116. doi: 10.1016/S0140-6736(17)30638- 4/ATTACHMENT/CB18F7B3-136D-41F1-B5DA-893F69B086BF/MMC1.PDF.
29. Sentilhes L, Sénat M V., Le Lous M, Winer N, Rozenberg P, Kayem G, et al. Tranexamic Acid for the Prevention of Blood Loss after Cesarean Delivery. N Engl J Med. 2021;384:1623–1634. doi: 10.1056/NEJMOA2028788/SUPPL_FILE/NEJMOA2028788_DATA‑SHARING. PDF.
30. Bellos I, Pergialiotis V. Tranexamic acid for the prevention of postpartum hemorrhage in women undergoing cesarean delivery: an updated meta‑analysis. Am J Obstet Gynecol. 2021;0. doi: 10.1016/J.AJOG.2021. 09. 025.
31. Al‑Jeabory M, Szarpak L, Attila K, Simpson M, Smereka A, Gasecka A, et al. Efficacy and Safety of Tranexamic Acid in Emergency Trauma: A Systematic Review and Meta‑Analysis. J Clin Med 2021, Vol 10, Page 1030. 2021;10:1030. doi: 10.3390/JCM10051030.
32. Bouillon‑Minois JB, Croizier C, Baker JS, Pereira B, Moustafa F, Outrey J, et al. Tranexamic acid in non‑traumatic intracranial bleeding: a systematic review and meta‑analysis. Sci Reports 2021 111. 2021;11:1–10. doi: 10.1038/s41598-021-94727-y.
33. Taeuber I, Weibel S, Herrmann E, Neef V, Schlesinger T, Kranke P, et al. Association of Intravenous Tranexamic Acid With Thromboembolic Events and Mortality: A Systematic Review, Meta‑analysis, and Meta‑regression. JAMA Surg. 2021;156:e210884–e210884. doi:10.1001/JAMASURG.2021.0884.
34. Ockerman A, Vanassche T, Garip M, Vandenbriele C, Engelen MM, Martens J, et al. Tranexamic acid for the prevention and treatment of bleeding in surgery, trauma and bleeding disorders: a narrative review. Thromb J 2021 191. 2021;19:1–16. doi: 10.1186/S12959- 021-00303-9.
35. Relke N, Chornenki NLJ, Sholzberg M. Tranexamic acid evidence and controversies: An illustrated review. Res Pract Thromb Haemost. 2021;5:e12546. doi: 10.1002/RTH2.12546.
36. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021;384:693–704. doi: 10.1056/NEJMOA2021436/SUPPL_FILE/NEJMOA2021436_DATA‑SHARING. PDF.
37. Abani O, Abbas A, Abbas F, Abbas M, Abbasi S, Abbass H, et al. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open‑label, platform trial. Lancet. 2021;397:1637–1645. doi: 10.1016/S0140-6736(21)00676-0/ ATTACHMENT/7079F7FB‑CB08- 4ACC-87C0-D40759EB5CF0/MMC1.PDF.
38. Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, et al. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet (London, England). 2009;374:1351–63. doi: 10.1016/S0140-6736(09)61069-2.
39. Combes A, Hajage D, Capellier G, Demoule A, Lavoué S, Guervilly C, et al. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome. N Engl J Med. 2018;378:1965–1975.
40. McNamee JJ, Gillies MA, Barrett NA, Perkins GD, Tunnicliffe W, Young D, et al. Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial. JAMA. 2021;326:1013–1023. doi: 10.1001/JAMA.2021.13374.
41. Ramanathan K, Shekar K, Ling RR, Barbaro RP, Wong SN, Tan CS, et al. Extracorporeal membrane oxygenation for COVID-19: a systematic review and meta‑analysis. Crit Care. 2021;25:1–11. doi: 10.1186/S13054-021-03634-1/TABLES/3.
42. Shaefi S, Brenner SK, Gupta S, O’Gara BP, Krajewski ML, Charytan DM, et al. Extracorporeal membrane oxygenation in patients with severe respiratory failure from COVID-19. Intensive Care Med. 2021;47:208–221. doi: 10.1007/S00134-020-06331-9/FIGURES/2.
43. Poon WH, Ramanathan K, Ling RR, Yang IX, Tan CS, Schmidt M, et al. Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta‑analysis. Crit Care. 2021;25:1–9. doi: 10.1186/ S13054-021-03723-1/TABLES/3.
44. Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47:1181–1247.
45. Singer M, Deutschman CS, Seymour CW, Shankar‑Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama. 2016;315:801–10. doi: 10.1001/jama.2016.0287.
46. Stanski NL, Wong HR. Prognostic and predictive enrichment in sepsis. Nat Rev Nephrol. 2020;16:20–31.
47. Shankar‑Hari M, Rubenfeld GD. Population enrichment for critical care trials: phenotypes and differential outcomes. Curr Opin Crit Care. 2019;25.
48. DeMerle KM, Angus DC, Baillie JK, Brant E, Calfee CS, Carcillo J, et al. Sepsis Subclasses: A Framework for Development and Interpretation*. Crit Care Med. 2021;49.
49. Seymour CW, Kennedy JN, Wang S, Chang CCH, Elliott CF, Xu Z, et al. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis. In: JAMA – Journal of the American Medical Association. 2019.
50. Reddy K, Sinha P, O’Kane CM, Gordon AC, Calfee CS, McAuley DF. Subphenotypes in critical care: translation into clinical practice. Lancet Respir Med. 2020;8:631–643.
51. Opal SM, Fisher CJJ, Dhainaut JF, Vincent JL, Brase R, Lowry SF, et al. Confirmatory interleukin- 1 receptor antagonist trial in severe sepsis: a phase III, randomized, double‑blind, placebo‑controlled, multicenter trial. The Interleukin-1 Receptor Antagonist Sepsis Investigator Group. Crit Care Med. 1997;25:1115–1124.
52. Meyer NJ, Reilly JP, Anderson BJ, Palakshappa JA, Jones TK, Dunn TG, et al. Mortality Benefit of Recombinant Human Interleukin-1 Receptor Antagonist for Sepsis Varies by Initial Interleukin-1 Receptor Antagonist Plasma Concentration. Crit Care Med. 2018;46:21–8.
53. Shakoory B, Carcillo JA, Chatham WW, Amdur RL, Zhao H, Dinarello CA, et al. Interleukin- 1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial. Crit Care Med. 2016;44:275–281.
54. Antcliffe DB, Burnham KL, Al‑Beidh F, Santhakumaran S, Brett SJ, Hinds CJ, et al. Transcriptomic Signatures in Sepsis and a Differential Response to Steroids. From the VANISH Randomized Trial. Am J Respir Crit Care Med. 2019;199:980–986.
55. Wong HR, Cvijanovich N, Lin R, Allen GL, Thomas NJ, Willson DF, et al. Identification of pediatric septic shock subclasses based on genome‑wide expression profiling. BMC Med. 2009;7:34.
56. Sweeney TE, Azad TD, Donato M, Haynes WA, Perumal TM, Henao R, et al. Unsupervised Analysis of Transcriptomics in Bacterial Sepsis Across Multiple Datasets Reveals Three Robust Clusters. Crit Care Med. 2018;46.
57. Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC, et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016;4:259–271.
58. Burnham KL, Davenport EE, Radhakrishnan J, Humburg P, Gordon AC, Hutton P, et al. Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia. Am J Respir Crit Care Med. 2017;196:328–339.
59. Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, et al. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016;316:509–518.
60. Wong HR, Hart KW, Lindsell CJ, Sweeney TE. External Corroboration That Corticosteroids May Be Harmful to Septic Shock Endotype A Patients. Crit Care Med. 2021;49:e98–101.
61. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin‑ resistant Staphylococcus aureus infections in adults and children: executive summary. Clin Infect, DiS. 2011;52:285–292. doi: 10.1093/CID/CIR034.
62. Bellos I, Pergialiotis V, Perrea DN. Kidney biopsy findings in vancomycin‑ induced acute kidney injury: a pooled analysis. Int Urol Nephrol. 2021. doi: 10.1007/S11255-021-02831-9.
63. Tantranont N, Luque Y, Hsiao M, Haute C, Gaber L, Barrios R, et al. Vancomycin‑Associated Tubular Casts and Vancomycin Nephrotoxicity. Kidney Int Reports. 2021;6:1912. doi:10.1016/J.EKIR.2021. 04. 035.
64. Blair M, Côté JM, Cotter A, Lynch B, Redahan L, Murray PT. Nephrotoxicity from Vancomycin Combined with Piperacillin‑Tazobactam: A Comprehensive Review. Am J Nephrol. 2021;52:85–97. doi: 10.1159/000513742.
65. Bouchard J, Mehta RL. Timing of Kidney Support Therapy in Acute Kidney Injury: What Are We Waiting For? Am J Kidney, DiS. 2021;0. doi: 10.1053/J.AJKD.2021. 07. 014.
66. Gaudry S, Hajage D, Martin‑Lefevre L, Lebbah S, Louis G, Moschietto S, et al. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open‑ label, randomised, controlled trial. Lancet (London, England). 2021;397:1293–1300. doi: 10.1016/S0140-6736(21)00350-0.
67. Murugan R, Kerti SJ, Chang CCH, Gallagher M, Clermont G, Palevsky PM, et al. Association of Net Ultrafiltration Rate With Mortality Among Critically Ill Adults With Acute Kidney Injury Receiving Continuous Venovenous Hemodiafiltration: A Secondary Analysis of the Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy Trial. JAMA Netw open. 2019;2:e195418. doi: 10.1001/JAMANETWORKOPEN.2019.5418.
68. Lee Y, Okuda Y, Sy J, Kim SR, Obi Y, Kovesdy CP, et al. Ultrafiltration Rate Effects Declines in Residual Kidney Function in Hemodialysis Patients. Am J Nephrol. 2019;50:481–488. doi: 10.1159/000503918.
69. Murugan R, Kerti SJ, Chang CCH, Gallagher M, Neto AS, Clermont G, et al. Association between Net Ultrafiltration Rate and Renal Recovery among Critically Ill Adults with Acute Kidney Injury Receiving Continuous Renal Replacement Therapy: An Observational Cohort Study. Blood Purif. 2021:1–13. doi: 10.1159/000517281.
70. Horák J, Chvojka J, Tégl V, Nalos L, Peltanová M, Beneš J, et al. Hemadsorpční metody u kriticky nemocných - dvojitá sázka naslepo? Anesteziol Intenziv medicína. 2020;31:172–175.
71. Scharf C, Schroeder I, Paal M, Winkels M, Irlbeck M, Zoller M, et al. Can the cytokine adsorber CytoSorb ® help to mitigate cytokine storm and reduce mortality in critically ill patients? A propensity score matching analysis. Ann Intensive Care. 2021;11. doi: 10.1186/ S13613-021-00905-6.
72. Supady A, Weber E, Rieder M, Lother A, Niklaus T, Zahn T, et al. Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open‑ label, randomised, controlled trial. Lancet Respir Med. 2021;9:755–762. doi: 10.1016/S2213-2600(21)00177-6.
73. Garbero E, Livigni S, Ferrari F, Finazzi S, Langer M, Malacarne P, et al. High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial. Intensive Care Med. 2021;47:1303–1311. doi: 10.1007/S00134-021-06501-3.
74. Livigni S, Bertolini G, Rossi C, Ferrari F, Giardino M, Pozzato M, et al. Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: a multicenter randomised controlled clinical trial. BMJ Open. 2014;4. doi: 10.1136/BMJOPEN-2013-003536.
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Anaesthesiology and Intensive Care Medicine
2021 Issue 6
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