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.

bColistin pharmacokinetics were prospectively studied after intravenous administration of colistin methanesulphonate in critically ill patients without central nervous system infection (controls, n ‫؍‬ 5) and in patients with external ventricular drain-associated ventriculitis after intravenous administration (EVDViv, n ‫؍‬ 3) or combined intravenous/intraventricular administration (EVDVcomb, n ‫؍‬ 4). Cerebrospinal fluid (CSF)/serum colistin concentration ratios were higher in EVDViv than in control patients (11% versus 7%, P < 0.05) and in EVDVcomb compared to all other patients (P < 0.0001). CSF colistin concentrations above the MIC of 0.5 g/ml were achieved only in EVDVcomb patients. Previous studies have suggested that the level of antibiotics in the ventricular cerebrospinal fluid (CSF) is important for the outcome of external ventricular drainage (EVD)-related ventriculitis (1-3). The presence of multiresistant bacteria and the poor penetration of many drugs through the blood-brain barrier have imposed the use of intrathecal therapies (4).Today, colistin, administered as its prodrug colistin methanesulphonate (CMS), is one of the few antibiotics available for treatment of infections by multidrug-resistant Gram-negative organisms. However, intravenous (i.v.) administration is reported to have a relatively poor CSF distribution and clinical outcomes vary (5-7). Data with respect to the efficacy of intraventricular polymyxins, as an add-on therapy, combined with systemic antibiotics are sparse and mainly observational (5, 8).We aimed to determine the effect of intravenous and combined intravenous/intraventricular CMS administration on colistin concentrations in the CSF and serum in critically ill patients with or without central nervous system (CNS) infection.This prospective case-controlled randomized study was conducted in a tertiary hospital, during a 12-month period between 2011 and 2012. Inclusion criteria were as follows: age Ͼ 18 years, diagnosis of EVD-related ventriculitis caused by Gram-negative bacteria, controlled intracranial pressure (Ͻ20 mm Hg) for 24 h prior to the study, no renal failure, and no allergy to colistin. Patients with EVD on i.v. CMS treatment for infections by Gramnegative bacteria other than CNS infections were included in the study as controls. The study was approved by the Hospital Ethics and Research Committee and performed in accordance with good clinical practice guidelines.Control patients received 3,000,000 IU (240 mg) CMS (approximately 90 mg colistin base activity [CBA]) i.v. every 8 h. Patients with EVD-associated ventriculitis caused by Gram-negative bacteria (diagnosed on the basis of clinical grounds plus positive CSF cultures or CSF inflammation, including pleocytosis and a reduced CSF/serum glucose ratio) were randomized to receive the same i.v. dose (EVDViv group), or the i.v. dose combined with 125,000 IU (10 mg) CMS (ϳ3.75 CBA) administered intraventricularly, once daily (EVDVcomb). A 2-ml volume of 0.9% NaCl (volume of catheter lumen) was instilled via the ca...

A complex interrelation between lung and brain in patients with acute lung injury (ALI) has been established by experimental and clinical studies during the last decades. Although, acute brain injury represents one of the most common insufficiencies in patients with ALI and acute respiratory distress syndrome (ARDS), the underlying pathophysiology of the observed crosstalk remains poorly understood due to its complexity. Specifically, it involves numerous pathophysiological parameters such as hypoxemia, neurological adverse events of lung protective ventilation, hypotension, disruption of the BBB, and neuroinflammation in such a manner that the brain of ARDS patients—especially hippocampus—becomes very vulnerable to develop secondary lung-mediated acute brain injury. A protective ventilator strategy could reduce or even minimize further systemic release of inflammatory mediators and thus maintain brain homeostasis. On the other hand, mechanical ventilation with low tidal volumes may lead to self-inflicted lung injury, hypercapnia and subsequent cerebral vasodilatation, increased cerebral blood flow, and intracranial hypertension. Therefore, by describing the pathophysiology of ARDS-associated acute brain injury we aim to highlight and discuss the possible influence of mechanical ventilation on ALI-associated acute brain injury.

In recent years, it has been convincingly demonstrated that acute brain injury may cause severe cardiac complications-such as neurogenic stress cardiomyopathy (NSC), a specific form of takotsubo cardiomyopathy. The pathophysiology of these brain-heart interactions is complex and involves sympathetic hyperactivity, activation of the hypothalamic-pituitary-adrenal axis, as well as immune and inflammatory pathways. There have been great strides in our understanding of the axis from the brain to the heart in patients with isolated acute brain injury and more specifically in patients with stroke. On the other hand, in patients with NSC, research has mainly focused on hemodynamic dysfunction due to arrhythmias, regional wall motion abnormality, or left ventricular hypokinesia that leads to impaired cerebral perfusion pressure. Comparatively little is known about the underlying secondary and delayed cerebral complications. The aim of the present review is to describe the stroke-heart-brain axis and highlight the main pathophysiological mechanisms leading to secondary and delayed cerebral injury in patients with concurrent hemorrhagic or ischemic stroke and NSC as well as to identify further areas of research that could potentially improve outcomes in this specific patient population.

Background This study was conducted to investigate whether high-tidal-volume mechanical ventilation is associated with increased lung inflammation compared with low-tidal-volume mechanical ventilation in critically ill patients with no evidence of lung injury. Methods In this prospective, single-blind, randomized (1:1), parallel-group study, 18 critically ill patients with normal lungs were randomly assigned to receive mechanical ventilation with a tidal volume of either 6 mL/kg (low tidal volume) or 12 mL/kg (high tidal volume) during the first 4 days in the intensive care unit. Results At baseline and at 24, 48, and 96 hours, exhaled breath condensate was collected to measure interleukin 1β, interleukin 10, tumor necrosis factor α, and total nitric oxide metabolites. Interleukin 1β levels in exhaled breath condensate were significantly increased at 24 hours compared with baseline in the high-tidal-volume group but not in the low-tidal-volume group. The interleukin 1β increase in the high-tidal-volume group was transient. Exhaled breath condensate levels of interleukin 1β, interleukin 10, tumor necrosis factor α, and total nitric oxide metabolites did not differ significantly between the high-tidal-volume and low-tidal-volume groups at any time point. Conclusion Short-term mechanical ventilation with a tidal volume of 12 mL/kg may trigger inflammatory responses in the lungs of intensive care unit patients without preexisting lung injury.