Effects of positive end-expiratory pressure on brain oxygenation, systemic oxygen cascade and metabolism in acute brain injured patients: a pilot physiological cross-sectional study.

Patients with acute brain injury (ABI) often require the application of positive end-expiratory pressure (PEEP) to optimize mechanical ventilation and systemic oxygenation. However, the effect of PEEP on cerebral function and metabolism is unclear. The primary aim of this study was to evaluate the effects of PEEP augmentation test (from 5 to 15 cmH2O) on brain oxygenation, systemic oxygen cascade and metabolism in ABI patients. Secondary aims include to determine whether changes in regional cerebral oxygenation are reflected by changes in oxygenation cascade and metabolism, and to assess the correlation between brain oxygenation and mechanical ventilation settings. Single center, pilot cross-sectional observational study in an Academic Hospital. Inclusion criteria were: adult (> 18 y/o) patients with ABI and stable intracranial pressure, available gas exchange and indirect calorimetry (IC) monitoring. Cerebral oxygenation was monitored with near-infrared spectroscopy (NIRS) and different derived parameters were collected: variation (Δ) in oxy (O2)-hemoglobin (Hb) (ΔO2Hbi), deoxy-Hb(ΔHHbi), total-Hb(ΔcHbi), and total regional oxygenation (ΔrSO2). Oxygen cascade and metabolism were monitored with arterial/venous blood gas analysis [arterial partial pressure of oxygen (PaO2), arterial saturation of oxygen (SaO2), oxygen delivery (DO2), and lactate], and IC [energy expenditure (REE), respiratory quotient (RQ), oxygen consumption (VO2), and carbon dioxide production (VCO2)]. Data were measured at PEEP 5 cmH2O and 15 cmH2O and expressed as delta (Δ) values. Ten patients with ABI [median age 70 (IQR 62-75) years, 6 (60%) were male, median Glasgow Coma Scale at ICU admission 5.5 (IQR 3-8)] were included. PEEP augmentation from 5 to 15 cmH2O did not affect cerebral oxygenation, systemic oxygen cascade parameters, and metabolism. The arterial component of cerebral oxygenation was significantly correlated with DO2 (ΔO2HBi, rho = 0.717, p = 0.037). ΔrSO2 (rho = 0.727, p = 0.032), ΔcHbi (rho = 0.797, p = 0.013), and ΔHHBi (rho = 0.816, p = 0.009) were significantly correlated with SaO2, but not ΔO2Hbi. ΔrSO2 was significantly correlated with VCO2 (rho = 0.681, p = 0.049). No correlation between brain oxygenation and ventilatory parameters was found. PEEP augmentation test did not affect cerebral and systemic oxygenation or metabolism. Changes in cerebral oxygenation significantly correlated with DO2, SaO2, and VCO2. Cerebral oxygen monitoring could be considered for individualization of mechanical ventilation setting in ABI patients without high or instable intracranial pressure.

Positive pressure ventilation in the weaning of preterm newborns.

BACKGROUND: Weaning from invasive mechanical ventilation (IMV) of preterm newborns (PTNB) is one of the critical stages of life support in the Neonatal Intensive Care Unit (NICU). Noninvasive positive pressure ventilation (NPPV) has been used to facilitate weaning from IMV and includes continuous positive airway pressure (CPAP) without or with inspiratory pressure support (bilevel NPPV). Nevertheless, there is little information about their adherence and success rate during weaning process. METHODS: In this retrospective cohort study, weaning data from patients admitted to a NICU from the northeast region of Brazil were analyzed. Sample was composed of PTNB submitted to IMV and divided in two groups according to the weaning strategy adopted: bilevel NPPV or NCPAP. Weaning failure was defined as returning to IMV within less than 48 h after extubation. RESULTS: Fifty-seven PTNB were included. Majority were females, had caesarean delivery, very low weight upon birth (760-1480 g) and neonatal hypoxemia scores (Apgar) <7 in the first minute. Respiratory distress syndrome occurred in 56.7% of PTNB whilst respiratory infections occurred in 35.1% of patients. Bilevel NPPV was the most chosen modality of weaning. No difference in success rate was found between bilevel NPPV and NCPAP (P=0.17). CONCLUSIONS: In this study, the application of noninvasive ventilation in preterm newborns for weaning from IMV was similar success rate between bilevel NPPV and NCPAP.

Brain-heart interaction after acute ischemic stroke.

Early detection of cardiovascular dysfunctions directly caused by acute ischemic stroke (AIS) has become paramount. Researchers now generally agree on the existence of a bidirectional interaction between the brain and the heart. In support of this theory, AIS patients are extremely vulnerable to severe cardiac complications. Sympathetic hyperactivity, hypothalamic-pituitary-adrenal axis, the immune and inflammatory responses, and gut dysbiosis have been identified as the main pathological mechanisms involved in brain-heart axis dysregulation after AIS. Moreover, evidence has confirmed that the main causes of mortality after AIS include heart attack, congestive heart failure, hemodynamic instability, left ventricular systolic dysfunction, diastolic dysfunction, arrhythmias, electrocardiographic anomalies, and cardiac arrest, all of which are more or less associated with poor outcomes and death. Therefore, intensive care unit admission with continuous hemodynamic monitoring has been proposed as the standard of care for AIS patients at high risk for developing cardiovascular complications. Recent trials have also investigated possible therapies to prevent secondary cardiovascular accidents after AIS. Labetalol, nicardipine, and nitroprusside have been recommended for the control of hypertension during AIS, while beta blockers have been suggested both for preventing chronic remodeling and for treating arrhythmias. Additionally, electrolytic imbalances should be considered, and abnormal rhythms must be treated. Nevertheless, therapeutic targets remain challenging, and further investigations might be essential to complete this complex multi-disciplinary puzzle. This review aims to highlight the pathophysiological mechanisms implicated in the interaction between the brain and the heart and their clinical consequences in AIS patients, as well as to provide specific recommendations for cardiovascular management after AIS.

Immunomodulatory effects of anesthetic agents in perioperative medicine.

Anesthetics comprise a heterogeneous group of drugs with multiple functions and mechanisms of action, which are not yet fully elucidated. In the clinical setting, it is difficult to isolate the effects of anesthetic agents from those of surgical stress itself or of other individual covariates. For this reason, several methods involving human immune cells and animal models have been used to study the effects of anesthetic agents on the immune system. The immunomodulation caused by anesthetic agents may lead to distinct consequences: suppression of the immune response, preventing or minimizing further distal organ injury; or suppression of the host immune reaction, which can lead to unacceptably increased risk of opportunistic infections. This review discusses the perioperative inflammatory response and the immunomodulatory properties of the most commonly used anesthetic agents in the perioperative period, addressing both their effects and proposed mechanisms of action on the innate immune system, including: biochemical and cellular defenses; barriers such as the endothelium and epithelium; biological macromolecules; domain proteins; specific cell types; and molecules such as cytokines and chemokines, which coordinate the host defense process. The immunomodulatory consequences of general anesthesia are complex. Immunosuppression can lead to beneficial effects, reducing systemic and local inflammation, or negative effects, which result in increased risk of infection. Anesthesiologists should choose the most appropriate agents based on the immune status of each patient.

Immunomodulation after ischemic stroke: potential mechanisms and implications for therapy.

Brain injuries are often associated with intensive care admissions, and carry high morbidity and mortality rates. Ischemic stroke is one of the most frequent causes of injury to the central nervous system. It is now increasingly clear that human stroke causes multi-organ systemic disease. Brain inflammation may lead to opposing local and systemic effects. Suppression of systemic immunity by the nervous system could protect the brain from additional inflammatory damage; however, it may increase the susceptibility to infection. Pneumonia and urinary tract infection are the most common complications occurring in patients after stroke. The mechanisms involved in lung-brain interactions are still unknown, but some studies have suggested that inhibition of the cholinergic anti-inflammatory pathway and release of glucocorticoids, catecholamines, and damage-associated molecular patterns (DAMPs) are among the pathophysiological mechanisms involved in communication from the ischemic brain to the lungs after stroke. This review describes the modifications in local and systemic immunity that occur after stroke, outlines mechanisms of stroke-induced immunosuppression and their role in pneumonia, and highlights potential therapeutic targets to reduce post-stroke complications. Despite significant advances towards a better understanding of the pathophysiology of ischemic stroke-induced immunosuppression and stroke-associated pneumonia (SAP) in recent years, many unanswered questions remain. The true incidence and outcomes of SAP, especially in intensive care unit settings, have yet to be determined, as has the full extent of stroke-induced immunosuppression and its clinical implications.

Impact of intravascular volume replacement and transfusion on outcome: where are we now?

Intravenous fluid administration is often required to counteract haemodynamic instability during emergency and elective surgeries, as well as in the intensive care unit. However, the best type and the amount of fluid required are controversial. A recent meta-analysis suggested that there is no difference among different types of colloids on outcome. Furthermore, colloids and crystalloids seem to be comparable in terms of efficiency in reverting haemodynamic instability, as well as morbidity and mortality. The interpretation of the results of different randomised controlled trials is somewhat difficult - the context must be always kept in mind. For example, results may differ in septic as compared to non-septic patient populations. Another important aspect concerns the effects on the macro- versus microcirculation. More recent studies emphasise that the microcirculation has to be taken into account when studying and interpreting the interaction between fluid therapy and the underlying disease. Nevertheless, the macrocirculation and clinical parameters have to be considered as well. Given that red blood cells remain the most important oxygen carriers, recent evidence regarding blood age may stimulate new studies according to the actual range for blood storage. Artificial oxygen carriers may play a role in specific situations, where the transfusion is indicated but the access to blood is problematic, but there is doubt that they may replace blood transfusion.