Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 1/2021

01-12-2021 | Acute Respiratory Distress-Syndrome | Review

Brain–lung interactions and mechanical ventilation in patients with isolated brain injury

Authors: Mairi Ziaka, Aristomenis Exadaktylos

Published in: Critical Care | Issue 1/2021

Login to get access

Abstract

During the last decade, experimental and clinical studies have demonstrated that isolated acute brain injury (ABI) may cause severe dysfunction of peripheral extracranial organs and systems. Of all potential target organs and systems, the lung appears to be the most vulnerable to damage after brain injury (BI). The pathophysiology of these brain–lung interactions are complex and involve neurogenic pulmonary oedema, inflammation, neurodegeneration, neurotransmitters, immune suppression and dysfunction of the autonomic system. The systemic effects of inflammatory mediators in patients with BI create a systemic inflammatory environment that makes extracranial organs vulnerable to secondary procedures that enhance inflammation, such as mechanical ventilation (MV), surgery and infections. Indeed, previous studies have shown that in the presence of a systemic inflammatory environment, specific neurointensive care interventions—such as MV—may significantly contribute to the development of lung injury, regardless of the underlying mechanisms. Although current knowledge supports protective ventilation in patients with BI, it must be born in mind that ABI-related lung injury has distinct mechanisms that involve complex interactions between the brain and lungs. In this context, the role of extracerebral pathophysiology, especially in the lungs, has often been overlooked, as most physicians focus on intracranial injury and cerebral dysfunction. The present review aims to fill this gap by describing the pathophysiology of complications due to lung injuries in patients with a single ABI, and discusses the possible impact of MV in neurocritical care patients with normal lungs.
Literature
1.
2.
McDonald SJ, et al. Beyond the brain: peripheral interactions after traumatic brain injury. J Neurotrauma. 2020;37(5):770–81.PubMedCrossRef
3.
Brain Trauma F, et al. Guidelines for the management of severe traumatic brain injury. XIV Hyperventilation. J Neurotrauma. 2007;24(Suppl 1):S87-90.
4.
Robba C, et al. Extracranial complications after traumatic brain injury: targeting the brain and the body. Curr Opin Crit Care. 2020;26(2):137–46.PubMed
5.
6.
Das M, Mohapatra S, Mohapatra SS. New perspectives on central and peripheral immune responses to acute traumatic brain injury. J Neuroinflammation. 2012;9:236.PubMedPubMedCentralCrossRef
7.
Mascia L. Acute lung injury in patients with severe brain injury: a double hit model. Neurocrit Care. 2009;11(3):417–26.PubMedCrossRef
8.
9.
10.
Oddo M, Citerio G. ARDS in the brain-injured patient: what’s different? Intensive Care Med. 2016;42(5):790–3.PubMedCrossRef
11.
Battaglini D, et al. Mechanical ventilation in neurocritical care setting: a clinical approach. Best Pract Res Clin Anaesthesiol. 2021;35(2):207–20.PubMedCrossRef
12.
Picetti E, et al. VENTILatOry strategies in patients with severe traumatic brain injury: the VENTILO Survey of the European Society of Intensive Care Medicine (ESICM). Crit Care. 2020;24(1):158.PubMedPubMedCentralCrossRef
13.
Mascia L, et al. High tidal volume is associated with the development of acute lung injury after severe brain injury: an international observational study. Crit Care Med. 2007;35(8):1815–20.PubMedCrossRef
14.
Vaporidi K, et al. Clusters of ineffective efforts during mechanical ventilation: impact on outcome. Intensive Care Med. 2017;43(2):184–91.PubMedCrossRef
15.
Goyal K, et al. Non-neurological complications after traumatic brain injury: a prospective observational study. Indian J Crit Care Med. 2018;22(9):632–8.PubMedPubMedCentralCrossRef
16.
Bronchard R, et al. Early onset pneumonia: risk factors and consequences in head trauma patients. Anesthesiology. 2004;100(2):234–9.PubMedCrossRef
17.
Li Y, et al. Incidence, risk factors, and outcomes of ventilator-associated pneumonia in traumatic brain injury: a meta-analysis. Neurocrit Care. 2020;32(1):272–85.PubMedCrossRef
18.
Zygun DA, et al. Ventilator-associated pneumonia in severe traumatic brain injury. Neurocrit Care. 2006;5(2):108–14.PubMedCrossRef
19.
Sachdeva D, et al. Assessment of surgical risk factors in the development of ventilator-associated pneumonia in neurosurgical intensive care unit patients: Alarming observations. Neurol India. 2017;65(4):779–84.PubMedCrossRef
20.
Esnault P, et al. Early-onset ventilator-associated pneumonia in patients with severe traumatic brain injury: incidence, risk factors, and consequences in cerebral oxygenation and outcome. Neurocrit Care. 2017;27(2):187–98.PubMedCrossRef
21.
Jovanovic B, et al. Risk factors for ventilator-associated pneumonia in patients with severe traumatic brain injury in a Serbian trauma centre. Int J Infect Dis. 2015;38:46–51.PubMedCrossRef
22.
Griffin GD. Stroke, mTBI, infection, antibiotics and beta blockade: connecting the dots. Med Hypotheses. 2015;85(2):224–9.PubMedCrossRef
23.
24.
Ott L, et al. Cytokines and metabolic dysfunction after severe head injury. J Neurotrauma. 1994;11(5):447–72.PubMedCrossRef
25.
Abraham E, et al. p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. Ro 45-2081 Study Group. JAMA. 1997;277(19):1531–8.PubMedCrossRef
26.
Llompart-Pou JA, et al. Acute Hypothalamic-pituitary-adrenal response in traumatic brain injury with and without extracerebral trauma. Neurocrit Care. 2008;9(2):230–6.PubMedCrossRef
27.
Dimopoulou I, et al. Endocrine abnormalities in critical care patients with moderate-to-severe head trauma: incidence, pattern and predisposing factors. Intensive Care Med. 2004;30(6):1051–7.PubMedCrossRef
28.
Hoover L, et al. Systemic inflammatory response syndrome and nosocomial infection in trauma. J Trauma. 2006;61(2):310–6 (discussion 316–7).PubMedCrossRef
29.
Steyerberg EW, et al. Case-mix, care pathways, and outcomes in patients with traumatic brain injury in CENTER-TBI: a European prospective, multicentre, longitudinal, cohort study. Lancet Neurol. 2019;18(10):923–34.PubMedCrossRef
30.
Kasuya Y, et al. Ventilator-associated pneumonia in critically ill stroke patients: frequency, risk factors, and outcomes. J Crit Care. 2011;26(3):273–9.PubMedCrossRef
31.
32.
Rogers FB, et al. Neurogenic pulmonary edema in fatal and nonfatal head injuries. J Trauma. 1995;39(5):860–6 (discussion 866–8).PubMedCrossRef
33.
Fontes RB, et al. Acute neurogenic pulmonary edema: case reports and literature review. J Neurosurg Anesthesiol. 2003;15(2):144–50.PubMedCrossRef
34.
35.
36.
Ell SR. Neurogenic pulmonary edema. A review of the literature and a perspective. Invest Radiol. 1991;26(5):499–506.PubMedCrossRef
37.
Finsterer J. Neurological perspectives of neurogenic pulmonary edema. Eur Neurol. 2019;81(1–2):94–102.PubMedCrossRef
38.
39.
Zhao J, et al. Neurogenic pulmonary edema following acute stroke: the progress and perspective. Biomed Pharmacother. 2020;130:110478.PubMedCrossRef
40.
Sacher DC, Yoo EJ. Recurrent acute neurogenic pulmonary edema after uncontrolled seizures. Case Rep Pulmonol. 2018;2018:3483282.PubMedPubMedCentral
41.
Solenski NJ, et al. Medical complications of aneurysmal subarachnoid hemorrhage: a report of the multicenter, cooperative aneurysm study. Participants of the Multicenter Cooperative Aneurysm Study. Crit Care Med. 1995;23(6):1007–17.PubMedCrossRef
42.
Ochiai H, Yamakawa Y, Kubota E. Deformation of the ventrolateral medulla oblongata by subarachnoid hemorrhage from ruptured vertebral artery aneurysms causes neurogenic pulmonary edema. Neurol Med Chir Tokyo. 2001;41(11):529–34 (discussion 534–5).PubMedCrossRef
43.
Al-Dhahir MA, Joe MD, Sharma S. Neurogenic pulmonary edema. In: StatPearls; 2021. Treasure Island (FL).
44.
Fan E, Brodie D, Slutsky AS. Acute respiratory distress syndrome: advances in diagnosis and treatment. JAMA. 2018;319(7):698–710.CrossRefPubMed
45.
46.
47.
Mrozek S, et al. Crosstalk between brain, lung and heart in critical care. Anaesth Crit Care Pain Med. 2020;39(4):519–30.PubMedCrossRef
48.
Hoesch RE, et al. Acute lung injury in critical neurological illness. Crit Care Med. 2012;40(2):587–93.PubMedCrossRef
49.
Contant CF, et al. Adult respiratory distress syndrome: a complication of induced hypertension after severe head injury. J Neurosurg. 2001;95(4):560–8.PubMedCrossRef
50.
Bratton SL, Davis RL. Acute lung injury in isolated traumatic brain injury. Neurosurgery. 1997;40(4):707–12 (discussion 712).PubMedCrossRef
51.
Mascia L, et al. Extracranial complications in patients with acute brain injury: a post-hoc analysis of the SOAP study. Intensive Care Med. 2008;34(4):720–7.PubMedCrossRef
52.
Kapinos G, Chichra A. Lung-protective ventilation for SAH patients: are these measures truly protective? Neurocrit Care. 2014;21(2):175–7.PubMedCrossRef
53.
54.
Heuer JF, et al. Acute effects of intracranial hypertension and ARDS on pulmonary and neuronal damage: a randomized experimental study in pigs. Intensive Care Med. 2011;37(7):1182–91.PubMedPubMedCentralCrossRef
55.
Veeravagu A, et al. Acute lung injury in patients with subarachnoid hemorrhage: a nationwide inpatient sample study. World Neurosurg. 2014;82(1–2):e235–41.PubMedCrossRef
56.
57.
Masek K, et al. Neuroendocrine immune interactions in health and disease. Int Immunopharmacol. 2003;3(8):1235–46.PubMedCrossRef
58.
Robertson CS, et al. Prevention of secondary ischemic insults after severe head injury. Crit Care Med. 1999;27(10):2086–95.CrossRefPubMed
59.
60.
61.
Smith WS, Matthay MA. Evidence for a hydrostatic mechanism in human neurogenic pulmonary edema. Chest. 1997;111(5):1326–33.PubMedCrossRef
62.
McClellan MD, Dauber IM, Weil JV. Elevated intracranial pressure increases pulmonary vascular permeability to protein. J Appl Physiol (1985). 1989;67(3):1185–91.CrossRef
63.
Avlonitis VS, et al. The hemodynamic mechanisms of lung injury and systemic inflammatory response following brain death in the transplant donor. Am J Transplant. 2005;5(4 Pt 1):684–93.PubMedCrossRef
64.
Khalili H, et al. Beta-blocker therapy in severe traumatic brain injury: a prospective randomized controlled trial. World J Surg. 2020;44(6):1844–53.PubMedCrossRef
65.
Maron MB. Effect of elevated vascular pressure transients on protein permeability in the lung. J Appl Physiol (1985). 1989;67(1):305–10.CrossRef
66.
Keegan MT, Lanier WL. Pulmonary edema after resection of a fourth ventricle tumor: possible evidence for a medulla-mediated mechanism. Mayo Clin Proc. 1999;74(3):264–8.PubMedCrossRef
67.
Avlonitis VS, et al. Pulmonary transplantation: the role of brain death in donor lung injury. Transplantation. 2003;75(12):1928–33.PubMedCrossRef
68.
Peterson BT, Ross JC, Brigham KL. Effect of naloxone on the pulmonary vascular responses to graded levels of intracranial hypertension in anesthetized sheep. Am Rev Respir Dis. 1983;128(6):1024–9.PubMed
69.
McKeating EG, et al. Transcranial cytokine gradients in patients requiring intensive care after acute brain injury. Br J Anaesth. 1997;78(5):520–3.PubMedCrossRef
70.
71.
Nakajima K, Kohsaka S. Microglia: activation and their significance in the central nervous system. J Biochem. 2001;130(2):169–75.PubMedCrossRef
72.
Yenari MA, et al. Microglia potentiate damage to blood-brain barrier constituents: improvement by minocycline in vivo and in vitro. Stroke. 2006;37(4):1087–93.PubMedCrossRef
73.
Pun PB, Lu J, Moochhala S. Involvement of ROS in BBB dysfunction. Free Radic Res. 2009;43(4):348–64.PubMedCrossRef
74.
Habgood MD, et al. Changes in blood-brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci. 2007;25(1):231–8.PubMedCrossRef
75.
Fisher AJ, et al. Enhanced pulmonary inflammation in organ donors following fatal non-traumatic brain injury. Lancet. 1999;353(9162):1412–3.PubMedCrossRef
76.
Fisher AJ, et al. Elevated levels of interleukin-8 in donor lungs is associated with early graft failure after lung transplantation. Am J Respir Crit Care Med. 2001;163(1):259–65.PubMedCrossRef
77.
Kalsotra A, et al. Brain trauma leads to enhanced lung inflammation and injury: evidence for role of P4504Fs in resolution. J Cereb Blood Flow Metab. 2007;27(5):963–74.PubMedCrossRef
78.
Campbell SJ, et al. Central nervous system injury triggers hepatic CC and CXC chemokine expression that is associated with leukocyte mobilization and recruitment to both the central nervous system and the liver. Am J Pathol. 2005;166(5):1487–97.PubMedPubMedCentralCrossRef
79.
Wu S, et al. Enhanced pulmonary inflammation following experimental intracerebral hemorrhage. Exp Neurol. 2006;200(1):245–9.PubMedCrossRef
80.
81.
Offner H, et al. Experimental stroke induces massive, rapid activation of the peripheral immune system. J Cereb Blood Flow Metab. 2006;26(5):654–65.PubMedCrossRef
82.
Chang L, et al. Cocaine-and amphetamine-regulated transcript modulates peripheral immunity and protects against brain injury in experimental stroke. Brain Behav Immun. 2011;25(2):260–9.PubMedCrossRef
83.
84.
Prass K, et al. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med. 2003;198(5):725–36.PubMedPubMedCentralCrossRef
85.
86.
Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med. 1998;157(1):294–323.PubMedCrossRef
87.
Asehnoune K, et al. A multi-faceted strategy to reduce ventilation-associated mortality in brain-injured patients. The BI-VILI project: a nationwide quality improvement project. Intensive Care Med. 2017;43(7):957–70.PubMedCrossRef
88.
Turon M, et al. Mechanisms involved in brain dysfunction in mechanically ventilated critically ill patients: implications and therapeutics. Ann Transl Med. 2018;6(2):30.PubMedPubMedCentralCrossRef
89.
Rowat AM, Dennis MS, Wardlaw JM. Hypoxaemia in acute stroke is frequent and worsens outcome. Cerebrovasc Dis. 2006;21(3):166–72.PubMedCrossRef
90.
Gupta AK, et al. Thresholds for hypoxic cerebral vasodilation in volunteers. Anesth Analg. 1997;85(4):817–20.PubMedCrossRef
91.
Robba C, et al. Mechanical ventilation in patients with acute brain injury: recommendations of the European Society of Intensive Care Medicine consensus. Intensive Care Med. 2020;46(12):2397–410.PubMedCrossRefPubMedCentral
92.
Simonis FD, et al. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS: a randomized clinical trial. JAMA. 2018;320(18):1872–80.PubMedPubMedCentralCrossRef
93.
Teismann IK, et al. Discontinuous versus continuous weaning in stroke patients. Cerebrovasc Dis. 2015;39(5–6):269–77.PubMedCrossRef
94.
Bilotta F, et al. Contrast-enhanced ultrasound imaging in detection of changes in cerebral perfusion. Ultrasound Med Biol. 2016;42(11):2708–16.PubMedCrossRef
95.
Ziaka M, et al. High-tidal-volume mechanical ventilation and lung inflammation in intensive care patients with normal lungs. Am J Crit Care. 2020;29(1):15–21.PubMedCrossRef
96.
Tejerina E, et al. Association between ventilatory settings and development of acute respiratory distress syndrome in mechanically ventilated patients due to brain injury. J Crit Care. 2017;38:341–5.PubMedCrossRef
97.
Hardcastle TC, Muckart DJJ, Maier RV. Ventilation in trauma patients: the first 24 h is different! World J Surg. 2017;41(5):1153–8.PubMedCrossRef
98.
Ranieri VM, et al. Effects of positive end-expiratory pressure on alveolar recruitment and gas exchange in patients with the adult respiratory distress syndrome. Am Rev Respir Dis. 1991;144(3 Pt 1):544–51.PubMedCrossRef
99.
Blanch L, et al. Effect of PEEP on the arterial minus end-tidal carbon dioxide gradient. Chest. 1987;92(3):451–4.PubMedCrossRef
100.
Doblar DD, et al. The effect of positive end-expiratory pressure ventilation (PEEP) on cerebral blood flow and cerebrospinal fluid pressure in goats. Anesthesiology. 1981;55(3):244–50.PubMedCrossRef
101.
Georgiadis D, et al. Influence of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure in patients with acute stroke. Stroke. 2001;32(9):2088–92.PubMedCrossRef
102.
McGuire G, et al. Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure. Crit Care Med. 1997;25(6):1059–62.PubMedCrossRef
103.
Muench E, et al. Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation. Crit Care Med. 2005;33(10):2367–72.PubMedCrossRef
104.
Lawrence T, et al. Traumatic brain injury in England and Wales: prospective audit of epidemiology, complications and standardised mortality. BMJ Open. 2016;6(11):e012197.PubMedPubMedCentralCrossRef
105.
Esteban A, et al. Evolution of mortality over time in patients receiving mechanical ventilation. Am J Respir Crit Care Med. 2013;188(2):220–30.PubMedCrossRef
106.
107.
Opdenakker O, et al. Sedatives in neurocritical care: an update on pharmacological agents and modes of sedation. Curr Opin Crit Care. 2019;25(2):97–104.PubMedCrossRef
108.
Barr J, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263–306.PubMedCrossRef
109.
Devlin JW, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825–73.PubMedCrossRef
110.
Mehta S, et al. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA. 2012;308(19):1985–92.PubMedCrossRef
111.
Strøm T, Martinussen T, Toft P. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet. 2010;375(9713):475–80.PubMedCrossRef
112.
Skoglund K, et al. The neurological wake-up test increases stress hormone levels in patients with severe traumatic brain injury. Crit Care Med. 2012;40(1):216–22.PubMedCrossRef
113.
114.
Burry L, et al. Daily sedation interruption versus no daily sedation interruption for critically ill adult patients requiring invasive mechanical ventilation. Cochrane Database Syst Rev. 2014;7:CD009176.
115.
Frutos-Vivar F, et al. Risk factors for extubation failure in patients following a successful spontaneous breathing trial. Chest. 2006;130(6):1664–71.PubMedCrossRef
116.
Pelosi P, et al. Management and outcome of mechanically ventilated neurologic patients. Crit Care Med. 2011;39(6):1482–92.PubMedCrossRef
117.
Roquilly A, et al. Implementation of an evidence-based extubation readiness bundle in 499 brain-injured patients. A before-after evaluation of a quality improvement project. Am J Respir Crit Care Med. 2013;188(8):958–66.PubMedCrossRef
118.
Jaber S, et al. The intensive care medicine research agenda for airways, invasive and noninvasive mechanical ventilation. Intensive Care Med. 2017;43(9):1352–65.PubMedCrossRef
119.
120.
Wrigge, H., et al., The effects of different ventilatory settings on pulmonary and systemic inflammatory responses during major surgery. Anesth Analg. 2004;98(3):775–81, table of contents.
121.
122.
Aslam, T.N., et al., Spontaneous versus controlled mechanical ventilation in patients with acute respiratory distress syndrome. Curr Anesthesiol Rep, 2021:1–7.
123.
Yoshida T, et al. Fifty years of research in ARDS. Spontaneous breathing during mechanical ventilation. Risks, mechanisms, and management. Am J Respir Crit Care Med. 2017;195(8):985–92.PubMedCrossRef
124.
Yoshida T, et al. Spontaneous effort causes occult pendelluft during mechanical ventilation. Am J Respir Crit Care Med. 2013;188(12):1420–7.PubMedCrossRef
125.
Putensen C, et al. Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury. Am J Respir Crit Care Med. 2001;164(1):43–9.PubMedCrossRef
126.
Vassilakopoulos T, Petrof BJ. Ventilator-induced diaphragmatic dysfunction. Am J Respir Crit Care Med. 2004;169(3):336–41.PubMedCrossRef
127.
Putensen C, et al. Spontaneous breathing during ventilatory support improves ventilation-perfusion distributions in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999;159(4 Pt 1):1241–8.PubMedCrossRef
128.
Yoshida T, et al. Spontaneous effort during mechanical ventilation: maximal injury with less positive end-expiratory pressure. Crit Care Med. 2016;44(8):e678–88.PubMedCrossRef
129.
Pohlman MC, et al. Excessive tidal volume from breath stacking during lung-protective ventilation for acute lung injury. Crit Care Med. 2008;36(11):3019–23.PubMedCrossRef
130.
Zhou Y, et al. Etiology, incidence, and outcomes of patient-ventilator asynchrony in critically-ill patients undergoing invasive mechanical ventilation. Sci Rep. 2021;11(1):12390.PubMedPubMedCentralCrossRef
131.
Chanques G, et al. Impact of ventilator adjustment and sedation-analgesia practices on severe asynchrony in patients ventilated in assist-control mode. Crit Care Med. 2013;41(9):2177–87.PubMedCrossRef
132.
van Haren F, et al. Spontaneous breathing in early acute respiratory distress syndrome: insights from the large observational study to understand the global impact of severe acute respiratory failure study. Crit Care Med. 2019;47(2):229–38.PubMedPubMedCentralCrossRef
Metadata
Title
Brain–lung interactions and mechanical ventilation in patients with isolated brain injury
Authors
Mairi Ziaka
Aristomenis Exadaktylos
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2021
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-021-03778-0

Other articles of this Issue 1/2021

Critical Care 1/2021 Go to the issue

Research

Validation of the Critical-Care Pain Observation Tool-Neuro in brain-injured adults in the intensive care unit: a prospective cohort study

Research

Benefits and risks of noninvasive oxygenation strategy in COVID-19: a multicenter, prospective cohort study (COVID-ICU) in 137 hospitals

Letter

Comparison of culture‑negative and culture‑positive sepsis or septic shock: outcomes are more influenced by the nature of the infectious agent itself than by the samples’ positivity

Research

An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients

Correction

Correction to: Ventilator-associated pneumonia in critically ill patients with COVID-19

Letter

Initial antimicrobial management of sepsis: increased prehospital blood lactate levels for identifying sicker patients who may benefit from prehospital antibiotic therapy initiation