[Inflammation during COVID-19]. / Inflammation au cours de la COVID-19.

Infection due to SARS-CoV-2 is associated with clinical features of diverse severity. Severe disease includes biological criteria of both inflammation and coagulation activation, and high circulating levels of pro- and anti-inflammatory cytokines. The most critical patients present with acute respiratory distress syndrome and multiple organ failure, resembling bacterial sepsis. Clinical trials have shown that steroids reduce mortality of severe cases, suggesting that inflammation as a mechanism of defense against viral invasion is excessive rather than insufficient. Several molecules targeting more specific pathways than steroids are under evaluation. Those reducing interleukin 6 activity have a certain degree of effectiveness. Anticoagulants and fibrinolytics have moderate impact on the hypercoagulation state. Like for bacterial sepsis, future trials will attempt therapy "individualization" based on biomarkers, but we still lack precision diagnostic tools.

: L'infection par le virus SARS-CoV-2 entraîne des tableaux de gravité variable. La biologie des formes graves comporte des critères d'inflammation et d'activation de la coagulation, ainsi que la circulation des cytokines pro- et anti-inflammatoires en grande quantité. Les formes les plus sévères comportent un syndrome de détresse respiratoire aiguë, voire une défaillance multiviscérale qui ressemble au sepsis d'origine bactérienne. Les essais thérapeutiques effectués dans ces formes graves indiquent que les corticoïdes en réduisent la mortalité, ce qui suggère que l'état hyper-inflammatoire peut être excessif plutôt qu'insuffisant dans notre défense contre l'infection virale. Plusieurs molécules plus sélectives que les corticoïdes sont à l'étude. Celles qui réduisent l'activité de l'interleukine 6 ont une certaine efficacité. L'état hyper-coagulable est peu influencé par les traitements anti-coagulants ou fibrinolytiques. Comme dans le sepsis bactérien, l'évolution se fera vers plus d'individualisation des traitements à partir de certains biomarqueurs, mais cette pratique se heurte encore à un manque de précision dans les outils diagnostiques.

[The first wave of COVID-19 in Intensive care]. / La première vague de la COVID-19 aux Soins intensifs, mars-mai 2020.

In December 2019, in Wuhan, a new human infectious pathology was born, COVID-19, consisting above all in pneumoniae, induced by the coronavirus named SARS-CoV-2 because of the respiratory distress it caused (SARS for severe acute respiratory syndrome, and CoV for Coronavirus). A real health and planetary crisis has appeared, much more substantial than that linked to SARS-CoV-1 in 2002-2004 and to MERS-CoV (Middle East Respiratory Syndrome Coronavirus) in 2012. In addition to respiratory damage that can be dramatic, this pathology is complicated by the frequency of cardiovascular, renal and coagulation diseases. Health care systems have had to adapt urgently, in the absence of hindsight from the pathology, and without effective therapeutic weapons. Through this review of the literature, we detail our local practices for the overall management of patients hospitalized in Intensive care.

En décembre 2019, à Wuhan, une nouvelle pathologie infectieuse humaine est née, le COVID-19, consistant avant tout en une pneumonie, induite par le coronavirus nommé SARS-CoV-2 en lien avec l'intensité de la détresse respiratoire qu'il entraîne (SARS pour syndrome respiratoire aigu sévère, et CoV pour coronavirus). Une véritable crise sanitaire et planétaire est apparue, bien plus conséquente que celle liée au SARS-CoV-1 en 2002-2004 et au MERS-CoV (Middle East Respiratory Syndrome Coronavirus) en 2012. Outre une atteinte respiratoire pouvant être dramatique, cette pathologie est complexifiée par la fréquence des atteintes cardiovasculaires, rénales et de la coagulation. Les systèmes de soins de santé ont dû s'adapter urgemment, en l'absence de recul face à la pathologie, et sans armes thérapeutiques efficaces. Au travers de cette revue de la littérature, nous détaillons nos pratiques locales pour la prise en charge globale des patients hospitalisés aux Soins intensifs.

[Acute respiratory distress syndrome]. / Le syndrome de détresse respiratoire aiguë.

Since its first description in 1967, a lot of progress has been made in understanding the pathophysiology, diagnosis and management of acute respiratory distress syndrome (ARDS). This nosological entity is based on the appearance of a diffuse alveolar damage associating pulmonary epithelial barrier disruption with an alveolar filling, both responsible of profound hypoxemia and important morbi-mortality. Nowadays, ARDS remains a frequent syndrome, associated with various etiologies. Diagnosis is based on the occurrence of acute hypoxic respiratory failure not explained by cardiac insufficiency or volume overload, within 7 days after a recognized risk factor, and in the presence of bilateral pulmonary opacities not fully explained by effusions, atelectasis or nodules on the chest radiography. Survivors present an increased risk of developing cognitive decline, depression, post-traumatic stress, and typical ICU related side-effects such as polyneuropathy and sarcopenia. In this context and not withstanding significant recent progress in the field of mechanical ventilation and extra-corporeal respiratory assistance, early diagnosis remains essential to identify patients with ARDS in order to offer them the most appropriate therapy.

Depuis sa première description en 1967, des progrès majeurs ont été réalisés dans la compréhension de la physiopathologie, le diagnostic et la prise en charge du syndrome de détresse respiratoire aiguë (SDRA). Cette entité nosologique repose sur l'apparition d'un dommage alvéolaire diffus associant une rupture de la barrière épithéliale pulmonaire avec un comblement alvéolaire à l'origine d'une hypoxémie profonde. De nos jours, le SDRA reste un syndrome fréquent, grevé d'une mortalité élevée, et prenant source dans de multiples situations pathologiques. Le diagnostic du SDRA repose sur l'apparition d'une insuffisance respiratoire aiguë hypoxique non expliquée par une insuffisance cardiaque ou une surcharge volémique, dans un délai de 7 jours suivant l'apparition d'un facteur de risque reconnu, en présence d'opacités pulmonaires bilatérales non complètement expliquées par des épanchements, des atélectasies ou des nodules. Les survivants sont à haut risque de développer un déclin cognitif, une dépression, ou un stress post-traumatique en plus des effets secondaires classiques d'une longue hospitalisation en unité de soins intensifs que sont la polyneuropathie ou la sarcopénie. Dans ce contexte, et en dépit de progrès importants dans le domaine de la ventilation mécanique et de l'assistance respiratoire par circulation extra-corporelle, il reste primordial d'identifier précocement les patients souffrant de SDRA afin de leur proposer la thérapeutique la plus appropriée dès les premiers signes cliniques.

[How I treat severe beta-blocker poisoning : pharmacological approaches and ECMO]. / Comment je traite... l'intoxication massive aux bêta-bloquants : approches pharmacologiques et place de l'ECMO.

We report the case of a woman with severe beta-blocker poisoning who, after failure of pharmacological therapy, was supported with an ECMO (ExtraCorporeal Membrane Oxygenation) device. We discuss conventional pharmacological treatments and other approaches that have emerged over the past decade such as high dose insulin therapy and lipid emulsions. Major advance has been achieved in the field of ECMO devices and their management. ECMO is now the first line device for refractory acute cardiac and/or pulmonary failure. Finally, we review the role of veno-arterial ECMO in cardiodepressive drug poisoning.

Nous rapportons un cas d'intoxication sévère aux bêta-bloquants. Après l'échec des traitements pharmacologiques, la patiente a bénéficié d'une assistance circulatoire externe de type ECMO (ExtraCorporeal Membrane Oxygenation ou oxygénation par membrane extracorporelle). Nous discutons des traitements pharmacologiques conventionnels et des traitements qui ont émergé durant cette dernière décennie, comme l'insulinothérapie à haute dose et les émulsions lipidiques. L'ECMO a fait des progrès importants ces dernières années et est devenue, à l'heure actuelle, la méthode d'assistance circulatoire externe de première ligne en cas de défaillance cardiaque et/ou respiratoire. Nous verrons sa place dans la prise en charge de l'intoxication massive aux drogues cardiodépressives.

Importance of metabolism variations in a model of extracorporeal carbon dioxide removal.

Extracorporeal CO2 Removal device is used in clinics when a patient suffers from a pulmonary insufficiency like Acute Respiratory Distress Syndrome and allows to decarboxylate blood externally. In this work, a model of the respiratory system coupled with such a device is proposed to analyze the decrease of CO2 partial pressure in blood. To validate the model, some parameters are estimated thanks to experimental data. Metabolism is a crucial parameter and we show that its time evolution must be taken into account in order to have correct CO2 partial pressure simulations in arteries and in veins.

A comparison between four techniques to measure cardiac output.

Cardiac output is an important variable when monitoring hemodynamic status. In particular, changes in cardiac output represent the goal of several circulatory management therapies. Unfortunately, cardiac output is very difficult to estimate, either in experimental or clinical settings. The goal of this work is to compare four techniques to measure cardiac output: pressure-volume catheter, aortic flow probe, thermodilution, and the PiCCO monitor. These four techniques were simultaneously used during experiments of fluid and endotoxin administration on 7 pigs. Findings show that, first, each individual technique is precise, with a relative coefficient of repeatability lower than 7 %. Second, 1 cardiac output estimate provided by any technique relates poorly to the estimates from the other 3, even if there is only small bias between the techniques. Third, changes in cardiac output detected by one technique are only detected by the others in 62 to 100 % of cases. This study confirms the difficulty of obtaining a reliable clinical cardiac output measurement. Therefore, several measurements using different techniques should be performed, if possible, and all such should be treated with caution.

Veno-venous extracorporeal CO2 removal improves pulmonary hemodynamics in a porcine ARDS model.

BACKGROUND: Protective lung ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) to minimize additional injuries to the lung. However, hypercapnic acidosis resulting from ventilation at lower tidal volume enhances pulmonary hypertension and might induce right ventricular (RV) failure. We investigated if extracorporeal veno-venous CO2 removal therapy could have beneficial effects on pulmonary circulation and RV function. METHODS: This study was performed on an experimental model of ARDS obtained in eight anaesthetized pigs connected to a volume-cycled ventilator. A micromanometer-tipped catheter was inserted into the main pulmonary artery and an admittance micromanometer-tipped catheter was inserted into the right ventricle. RV-arterial coupling was derived from RV pressure-volume loops. ARDS was obtained by repeated bronchoalveolar lavage. Protective ventilation was then achieved, and the pigs were connected to a pump-driven extracorporeal membrane oxygenator (PALP, Maquet, Germany) in order to achieve CO2 removal. RESULTS: ARDS induced severe hypercapnic acidosis. Systolic pulmonary artery pressure significantly increased from 29.6±1.8 to 43.9±2.0 mmHg (P<0.001). After the PALP was started, acidosis was corrected and normocarbia was maintained despite protective ventilation. Pulmonary artery pressure significantly decreased to 31.6±3.2 mmHg (P<0.001) and RV-arterial coupling significantly improved (RV-arterial coupling index=1.03±0.33 vs. 0.55±0.41, P<0.05). CONCLUSION: Veno-venous CO2 removal therapy enabled protective ventilation while maintaining normocarbia during ARDS. CO2 removal decreased pulmonary hypertension and improved RV function. This technique may be an effective lung- and RV-protective adjunct to mechanical ventilation.

End of life care in the operating room for non-heart-beating donors: organization at the University Hospital of Liège.

Non-heart-beating (NHB) organ donation has become an alternative source to increase organ supply for transplantation. A NHB donation program was implemented in our institution in 2002. As in many institutions the end of life care of the NHB donor (NHBD) is terminated in the operating room (OR) to reduce warm ischemia time. Herein we have described the organization of end of life care for these patients in our institution, including the problems addressed, the solution proposed, and the remaining issues. Emphasis is given to our protocol elaborated with the different contributors of the chain of the NHB donation program. This protocol specifies the information mandatory in the medical records, the end of life care procedure, the determination of death, and the issue of organ preservation measures before NHBD death. The persisting malaise associated with NHB donation reported by OR nurses is finally documented using an anonymous questionnaire.

Patient specific identification of the cardiac driver function in a cardiovascular system model.

The cardiac muscle activation or driver function, is a major determinant of cardiovascular dynamics, and is often approximated by the ratio of the left ventricle pressure to the left ventricle volume. In an intensive care unit, the left ventricle pressure is usually never measured, and the left ventricle volume is only measured occasionally by echocardiography, so is not available real-time. This paper develops a method for identifying the driver function based on correlates with geometrical features in the aortic pressure waveform. The method is included in an overall cardiovascular modelling approach, and is clinically validated on a porcine model of pulmonary embolism. For validation a comparison is done between the optimized parameters for a baseline model, which uses the direct measurements of the left ventricle pressure and volume, and the optimized parameters from the approximated driver function. The parameters do not significantly change between the two approaches thus showing that the patient specific approach to identifying the driver function is valid, and has potential clinically.

Contribution of donors after cardiac death to the deceased donor pool: 2002 to 2009 University of Liege experience.

OBJECTIVE: In this study, we have evaluated the organ procurement and transplantation activity from donors after cardiac death (DCD) at our institution over an 8-year period. Our aim was to determine whether this program influenced transplantation programs, or donation after brain death (DBD) activity. METHODS: We prospectively collected our procurement and transplantation statistics in a database for retrospective review. RESULTS: We observed an increasing trend in potential and actual DCD number. The mean conversion rate turning potential into effective donors was 58.1%. DCD accounted for 16.6% of the deceased donor (DD) pool over 8 years. The mean age for effective DCD donors was 53.9 years (range, 3-79). Among the effective donors, 63.3% (n = 31) came from the transplant center and 36.7% (n = 18) were referred from collaborative hospitals. All donors were Maastricht III category. The number of kidney and liver transplants using DCD sources tended to increase. DCD kidney transplants represented 10.8% of the DD kidney pool and DCD liver transplants made up 13.9% of the DD liver pool over 8 years. The DBD program activity increased in the same time period. In 2009, 17 DCD and 33 DBD procurements were performed in a region with a little >1 million inhabitants. CONCLUSION: The establishment of a DCD program in our institution enlarged the donor pool and did not compromise the development of the DBD program. In our experience, DCD are a valuable source for abdominal organ transplantation.

Unique parameter identification for cardiac diagnosis in critical care using minimal data sets.

Lumped parameter approaches for modelling the cardiovascular system typically have many parameters of which a significant percentage are often not identifiable from limited data sets. Hence, significant parts of the model are required to be simulated with little overall effect on the accuracy of data fitting, as well as dramatically increasing the complexity of parameter identification. This separates sub-structures of more complex cardiovascular system models to create uniquely identifiable simplified models that are one to one with the measurements. In addition, a new concept of parameter identification is presented where the changes in the parameters are treated as an actuation force into a feed back control system, and the reference output is taken to be steady state values of measured volume and pressure. The major advantage of the method is that when it converges, it must be at the global minimum so that the solution that best fits the data is always found. By utilizing continuous information from the arterial/pulmonary pressure waveforms and the end-diastolic time, it is shown that potentially, the ventricle volume is not required in the data set, which was a requirement in earlier published work. The simplified models can also act as a bridge to identifying more sophisticated cardiac models, by providing an initial set of patient specific parameters that can reveal trends and interactions in the data over time. The goal is to apply the simplified models to retrospective data on groups of patients to help characterize population trends or un-modelled dynamics within known bounds. These trends can assist in improved prediction of patient responses to cardiac disturbance and therapy intervention with potentially smaller and less invasive data sets. In this way a more complex model that takes into account individual patient variation can be developed, and applied to the improvement of cardiovascular management in critical care.

[Acute exacerbation of asthma: a disease that still remains life-threatening]. / Asthme aigu grave: une affection qui demeure redoutable.

Severe exacerbations of asthma can be life-threatening if not aggressively treated. Despite the publication of therapeutic guidelines developed by experts in this field and people education programs, early recognition and characterization of patients at risk for fatal asthma remain scarce. We report the case of a young lady suffering from acute exacerbation of asthma responsible for intensive care admission with long term mechanical ventilation due to the lack in initial appropriate care.

Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient.

Recent studies on spontaneous fluctuations in the functional MRI blood oxygen level-dependent (BOLD) signal in awake healthy subjects showed the presence of coherent fluctuations among functionally defined neuroanatomical networks. However, the functional significance of these spontaneous BOLD fluctuations remains poorly understood. By means of 3 T functional MRI, we demonstrate absent cortico-thalamic BOLD functional connectivity (i.e. between posterior cingulate/precuneal cortex and medial thalamus), but preserved cortico-cortical connectivity within the default network in a case of vegetative state (VS) studied 2.5 years following cardio-respiratory arrest, as documented by extensive behavioral and paraclinical assessments. In the VS patient, as in age-matched controls, anticorrelations could also be observed between posterior cingulate/precuneus and a previously identified task-positive cortical network. Both correlations and anticorrelations were significantly reduced in VS as compared to controls. A similar approach in a brain dead patient did not show any such long-distance functional connectivity. We conclude that some slow coherent BOLD fluctuations previously identified in healthy awake human brain can be found in alive but unaware patients, and are thus unlikely to be uniquely due to ongoing modifications of conscious thoughts. Future studies are needed to give a full characterization of default network connectivity in the VS patients population.

[Prophylaxis of infective endocarditis: improved dental care and oral health rather than systematic antibiotic prophylaxis?]. / Comment je préviens...l'endocardite infectieuse: une meilleure hygiène bucco-dentaire plutôt qu'une antibioprophylaxie systématique?

Prophylaxis for infective endocarditis has been recommended on the basis of the supposed pathophysiology of the disease, although no randomised clinical trial has confirmed its efficacy. Bacteraemia resulting from daily activities is much more likely to cause infective endocarditis than bacteraemia associated with invasive medical procedures. As a result, recommendations for antibiotic prophylaxis tend now to be severely restricted.

Diagnostic and prognostic use of bispectral index in coma, vegetative state and related disorders.

PRIMARY OBJECTIVE: This study investigates (1) the utility of the bispectral index (BIS) to distinguish levels of consciousness in severely brain damaged patients and, particularly, disentangle vegetative state (VS) from minimally conscious state (MCS), as compared to other EEG parameters; (2) the prognostic value of BIS with regards to recovery after 1 year. RESEARCH DESIGN: Multi-centric prospective study. METHOD AND PROCEDURES: Unsedated patients recovering from coma were followed until death or transferal. Automated electrophysiological and standardized behavioural assessments were carried out twice a week. EEG recordings were categorized according to level of consciousness (coma, VS, MCS and Exit MCS). Outcome was assessed at 1 year post-insult. MAIN OUTCOMES AND RESULTS: One hundred and fifty-six EEG epochs obtained in 43 patients were included in the analyses. BIS showed a higher correlation with behavioural scales as compared to other EEG parameters. Moreover, BIS values differentiated levels of consciousness and distinguished VS from MCS while other EEG parameters did not. Finally, higher BIS values were found in patients who recovered at 1 year post-insult as compared to patients who did not recover. CONCLUSION: EEG-BIS recording is an interesting additional method to help in the diagnosis as well as in the prognosis of severely brain injured patients recovering from coma.

Model-based identification and diagnosis of a porcine model of induced endotoxic shock with hemofiltration.

A previously validated cardiovascular system (CVS) model and parameter identification method for cardiac and circulatory disease states are extended and further validated in a porcine model (N=6) of induced endotoxic shock with hemofiltration. Errors for the identified model are within 10% when the model is re-simulated and compared to the clinical data. All identified parameter trends over time in the experiments match clinically expected changes both individually and over the cohort. This work represents a further clinical validation of these model-based cardiovascular diagnosis and therapy guidance methods for use with monitoring endotoxic disease states.

[Unilateral pleural effusion in ovarian hyperstimulation syndrome]. / Un cas rare d'épanchement pleural unilatéral: le syndrome d'hyperstimulation des ovaires.

Ovarian hyperstimulation syndrome is the most severe iatrogenic complication of fertilization modern methods. This syndrome is characterized by a massive cystic ovarian enlargement associated with an acute body fluid shift. Ascite is the most frequent manifestation of this syndrome. In some rare cases ovarian hyperstimulation syndrome is complicated by massive unilateral pleural effusion without ascite. We describe the case of a 36 year old woman who developed a massive unilateral pleural effusion without ascite. An ovarian hyperstimulation syndrome was diagnosed. Chest tube drainage improved patient parameters and symptoms. We discuss the diagnostic approach of pleural effusions.

[Predicting prognosis in post-anoxic coma]. / Comment prédire l'évolution du coma post-anoxique?

Most patients who remain comatose for a few hours after a period of global cerebral ischemia have a poor prognosis. Early identification of these patients is desirable to reduce uncertainty about treatment and non-treatment decisions, and to improve relationships with the family. The absence of pupillary light response and corneal reflexes, absent or stereotyped extension motor response to noxious stimulation (3 days after insult); myoclonus status epilepticus; absence of cortical N20 response on somatosensory evoked potential studies; generalised suppression or burst-suppression EEG and serum neuron-specific enolase above 33 microg/L (sampled 1-3 days after insult) have been shown to predict poor outcome. We here propose an algorithm to help intensive care physicians' clinical decision making in post-anoxic coma.