Pulmonary complications associated with veno-arterial extra-corporeal membrane oxygenation: a comprehensive review.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving technology that provides transient respiratory and circulatory support for patients with profound cardiogenic shock or refractory cardiac arrest. Among its potential complications, VA-ECMO may adversely affect lung function through various pathophysiological mechanisms. The interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response which may increase pulmonary vascular permeability and promote the sequestration of polymorphonuclear neutrophils within the lung parenchyma. Also, VA-ECMO increases the afterload of the left ventricle (LV) through reverse flow within the thoracic aorta, resulting in increased LV filling pressure and pulmonary congestion. Furthermore, VA-ECMO may result in long-standing pulmonary hypoxia, due to partial shunting of the pulmonary circulation and to reduced pulsatile blood flow within the bronchial circulation. Ultimately, these different abnormalities may result in a state of persisting lung inflammation and fibrotic changes with concomitant functional impairment, which may compromise weaning from VA-ECMO and could possibly result in long-term lung dysfunction. This review presents the mechanisms of lung damage and dysfunction under VA-ECMO and discusses potential strategies to prevent and treat such alterations

The prognostic value of pulmonary artery compliance in cardiogenic shock.

The aim of this study was to evaluate the pathophysiological role and the prognostic significance of pulmonary artery compliance (C <sub>PA</sub> ), a measure of right ventricular pulsatile afterload, in cardiogenic shock. We retrospectively included 91 consecutive patients with cardiogenic shock due to primary left ventricular failure, monitored with a pulmonary artery catheter within the first 24 h. C <sub>PA</sub> was calculated as the ratio of stroke volume to pulmonary artery pulse pressure, and we determined whether C <sub>PA</sub> predicted mortality and whether it performed better than other pulmonary hemodynamic variables. The overall in-hospital mortality in our cohort was 27%. Survivors and nonsurvivors had comparable left ventricular ejection fraction, systolic, diastolic and mean pulmonary artery pressure, transpulmonary gradient, diastolic pressure gradient, and pulmonary vascular resistance at 24 h. In contrast, C <sub>PA</sub> was the only pulmonary artery variable significantly associated with mortality in univariate and multivariate analyses. Mortality increased from 4.5% at the highest quartile of C <sub>PA</sub> (3.6-6.5 mL/mmHg) to 43.5% at the lowest quartile (0.7-1.7 mL/mmHg). In 64 patients with a PAC inserted immediately upon admission, we calculated the trend of C <sub>PA</sub> between admission and 24 h. This trend was positive in survivors (+0.8 ± 1.3 ml/mmHg) but negative in nonsurvivors (-0.1 ± 1.0 mL/mmHg). The lower C <sub>PA</sub> in nonsurvivors was associated with more severe right ventricular systolic dysfunction. In conclusion, a reduced compliance of the pulmonary artery promotes right ventricular dysfunction and is independently associated with mortality in cardiogenic shock. Future studies should evaluate the impact on pulmonary arterial compliance and right ventricular afterload of therapies used in cardiogenic shock

Disposition of voriconazole during continuous veno-venous haemodiafiltration (CVVHDF) in a single patient

Objectives: To determine whether voriconazole dosage adjustment is required during continuous veno-venous haemodiafiltration (CVVHDF). Methods: Voriconazole pharmacokinetics were studied in a critically ill patient under CVVHDF. The analysis was carried out for 12 h following a 6 mg/kg dose. Voriconazole concentrations were measured by HPLC in blood inlet and outlet lines and in dialysate. Results: The total body clearance of voriconazole was 20.3 L/h, with a terminal half-life of 13.7 h and a distribution volume of 399 L. The estimated sieving coefficient was 0.53 and the filtration-dialysis clearance 1.2 L/h. Conclusions: CVVHDF does not significantly affect voriconazole disposition and requires no dosage adjustmen

Evidence of trace conditioning in comatose patients revealed by the reactivation of EEG responses to alerting sounds.

Trace conditioning refers to a learning process occurring after repeated presentation of a neutral conditioned stimulus (CS+) and a salient unconditioned stimulus (UCS) separated by a temporal gap. Recent studies have reported that trace conditioning can occur in humans in reduced levels of consciousness by showing a transfer of the unconditioned autonomic response to the CS+ in healthy sleeping individuals and in vegetative state patients. However, no previous studies have investigated the neural underpinning of trace conditioning in the absence of consciousness in humans. In the present study, we recorded the EEG activity of 29 post-anoxic comatose patients while presenting a trace conditioning paradigm using neutral tones as CS+ and alerting sounds as UCS. Most patients received therapeutic hypothermia and all were deeply unconscious according to standardized clinical scales. After repeated presentation of the CS+ and UCS couple, learning was assessed by measuring the EEG activity during the period where the UCS is omitted after CS+ presentation. Specifically we assessed the 'reactivation' of the neural response to UCS omission by applying a decoding algorithm derived from the statistical model of the EEG activity in response to the UCS presentation. The same procedure was used in a group of 12 awake healthy controls. We found a reactivation of the UCS response in absence of stimulation in eight patients (five under therapeutic hypothermia) and four healthy controls. Additionally, the reactivation effect was temporally specific within trials since it manifested primarily at the specific latency of UCS presentation and significantly less before or after this period. Our results show for the first time that trace conditioning may manifest as a reactivation of the EEG activity related to the UCS and even in the absence of consciousness

Prediction of awakening from hypothermic post anoxic coma based on auditory discrimination.

OBJECTIVE: Most of the available clinical tests for prognosis of post-anoxic coma are informative of poor outcome. Previous work has shown that an improvement in auditory discrimination over the first days of coma is predictive of awakening. Here, we aimed at evaluating this test on a large cohort of patients undergoing therapeutic hypothermia and at investigating its added value on existing clinical measures. METHODS: We recorded electroencephalography responses to auditory stimuli in 94 comatose patients, under hypothermia and after re-warming to normal temperature. Auditory discrimination was semi-automatically quantified by decoding electroencephalography responses to frequently repeated vs. rare sounds. Outcome prediction was based on the change of decoding performance from hypothermia to normothermia. RESULTS: An increase in auditory discrimination from hypothermia to normothermia was observed for 33 out of 94 patients. Among them, 27 awoke from coma, resulting in a positive predictive value of awakening of 82% (95% confidence interval: 0.65-0.93). Most non-survivors showing an improvement in auditory discrimination had incident status epilepticus. By excluding them, 27 out of 29 patients with improvement in auditory discrimination survived, resulting in a considerable improvement of the predictive value for awakening (93%, with 95% confidence interval: 0.77-0.99). Importantly, this test predicted the awakening of 13 out of 51 patients for which the outcome was uncertain based on current tests. INTERPRETATION: The progression of auditory discrimination from hypothermia to normothermia has a high predictive value for awakening. This quantitative measure provides an added value to existing clinical tests and encourages the maintenance of life support. This article is protected by copyright. All rights reserved

The Sustainable Development Goal on Water and Sanitation

Target 7c of the Millennium Development Goals (MDG 7c) aimed to halve the population that had no sustainable access to water and basic sanitation before 2015. According to the data collected by the Joint Monitoring Programme in charge of measuring progress towards MDG 7c, 2.6 billion people gained access to safe water and 2.3 billion people to basic sanitation. Despite these optimistic figures, many academics have criticised MDG 7c. We provide an overview of this critique by performing a systematic literature review of 61 studies conducted over the MDG implementation period (2002-2015) and shortly after. Our objective is to contribute to the debate on the operationalisation of the Sustainable Development Goal on water and sanitation (SDG 6). The academic debate on MDG 7c mainly focused on the effectiveness of the indicators for safe water and sanitation and on the political dynamics underlying the selection of these indicators. SDG 6 addresses some of the concerns raised on the indicators for safe water and sanitation but fails to acknowledge the politics of indicator setting. We are proposing additional indicators and reflect on the limitations of using only quantitative indicators to measure progress towards SDG 6

Alpha glucocorticoid receptor expression in different experimental rat models of acute lung injury

Background and objectives: Acute respiratory distress syndrome (ARDS) is a frequent form of hypoxiemic respiratory failure caused by the acute development of diffuse lung inflammation. Dysregulated systemic inflammation with persistent elevation of circulating inflammatory cytokines is the pathogenetic mechanism for pulmonary and extrapulmonary organ dysfunction in patients with ARDS. Glucocorticoids (GCs) have a broad range of inhibitory inflammatory effects, including inhibition of cytokines transcription, cellular activation and growth factor production. They inhibit the inflammatory pathways through two specific intracellular glucocorticoid receptors (GRs), named GRα and GRβ. The aim of our study was to evaluate the histologic evidence of inflammatory injury and the GRα uptake of resident and inflammatory cells in different experimental models of acute lung injury (ALI). Methods: We studied four groups of rats: three different experimental rat models of lung injury and a control group. The ALI was caused by barotrauma (due to an overventilation), oleic acid injection and mechanical ventilation. Results were compared to nonventilated rat control group. The duration of mechanical ventilation was of 2.5 h. At the end of each experiment, rats were sacrificed. Lung biopsies were evaluated for morphologic changes. The immunohistochemistry was performed to study GRα expression. Results: Histologic evidence of lung injury (alveolar and interstitial edema, vascular congestion, alveolar haemorrhage, emphysema, number of interstitial cells and neutrophils, and destruction of alveolar attachments) were present in all ventilated groups. Barotrauma lead to an additional inflammatory response. GRα expression significantly increased in the three ventilated groups compared with nonventilated groups. GRα expression was highest in barotrauma group. Conclusions: These data indicate that ALI is associated with diffuse alveolar damage, up-regulation of the inflammatory response and GRα overexpression. Barotrauma is the most effective mechanism inducing acute lung inflammation and GRα overexpression. © 2007 Elsevier Ltd. All rights reserved

Simple equations to predict the effects of veno-venous ECMO in decompensated Eisenmenger syndrome.

Adult patients with uncorrected congenital heart diseases and chronic intracardiac shunt may develop Eisenmenger syndrome (ES) due to progressive increase of pulmonary vascular resistance, with significant morbidity and mortality. Acute decompensation of ES in conditions promoting a further increase of pulmonary vascular resistance, such as pulmonary embolism or pneumonia, can precipitate major arterial hypoxia and death. In such conditions, increasing systemic oxygenation with veno-venous extracorporeal membrane oxygenation (VV-ECMO) could be life-saving, serving as a bridge to treat a potential reversible cause for the decompensation, or to urgent lung transplantation. Anticipating the effects of VV-ECMO in this setting could ease the clinical decision to initiate such therapeutic strategy. Here, we present a series of equations to accurately predict the effects of VV-ECMO on arterial oxygenation in ES and illustrate this point by a case of ES decompensation with refractory hypoxaemia consecutive to an acute respiratory failure due to viral pneumonia