[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.

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.

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.

[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.

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.

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.

[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.

[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.

[Recent therapeutic advances in intensive care: update on severe sepsis/septic shock and on pulmonary embolism]. / Actualités thérapeutiques en soins intensifs: le point sur le sepsis sévère/choc septique et sur l'embolie pulmonaire.

Septic shock and pulmonary embolism remain leading causes of death in intensive care units. Recent therapeutic advances have contributed to decrease the mortality rate of septic shock. Among these, early goal directed hemodynamic therapy, corticoid and activated protein C are the most efficient. However, due to the increased incidence of sepsis, the absolute number of deaths remains unacceptably high. In order to improve the prognosis of septic patients, the "surviving sepsis campaign" started in 2002. Its main objective is to decrease mortality rate of sepsis by 25% in the next five years. The diagnostic strategy of pulmonary embolism has been improved by the use of validated algorithms using clinical probability, d-dimers, angioscan and venous doppler. The growing use of low molecular weight heparin has also improved and facilitated the therapeutic management of pulmonary embolism while indication of fibrinolysis in presence of right ventricular dysfunction, but without shock, remains controversial.

[Beriberi]. / Béribéri.

We discuss the case of a 49 year old man who was admitted to the emergency department with acute heart failure. He suffered from severe alcoholism and malnutrition. His heart failure was of the high output type and the diagnosis beriberi, a disease caused by thiamine (vitamin B1) deficiency. The treatment consisted of intravenous administration of thiamine. The clinical response was spectacular with normalization of cardiac function within a few hours.

Confirmation of high cytokine clearance by hemofiltration with a cellulose triacetate membrane with large pores: an in vivo study.

OBJECTIVE: To confirm in vivo the hypothesis that hemofiltration with a large pore membrane can achieve significant cytokine clearance. METHOD: We used a well-known animal model of endotoxinic shock (0.5 mg/kg of lipopolysaccharide from Escherichia Coli over a period of 30 mins). Six pigs were hemofiltrated for 3 hours with a large pore membrane (78 A pore, 80 kDa cut off) (Sureflux FH 70, Nipro, Osaka, Japan). The ultrafiltration rate was 45 ml/kg/min. Samples were taken from arterial, venous line and in the ultrafiltrate at T120 and T240. We measured concentrations of interleukin 6, interleukin 10 and albumin. RESULTS: At T120 and T240, the IL-6 clearances were 22 +/- 7 and 15 +/- 3 ml/min, respectively. The IL-6 sieving coefficients were 0.97 and 0.7 at T120 and T240, respectively. At T120 and T240, the IL-10 clearances were 14 +/- 4 and 10 +/- 7 ml/min, respectively. The sieving coefficients were 0.63 and 0.45 at T120 and T240, respectively. The concentrations of IL-6 and IL-10 were the same at T0 and T240. At T60 and T240, the plasmatic albumin concentrations were 24 +/- 4 g/L and 23 +/- 4 g/L, respectively (p = 0.13). CONCLUSIONS: In this animal model of endotoxinic shock, we confirm the high cytokine clearance observed when hemofiltration is applied to a large pore membrane. The loss of albumin seems negligible. The impact of such clearances on hemodynamic stability and survival remains to be proved.

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.

Analysis of endotoxin effects on the intact pulmonary circulation.

OBJECTIVE: The mechanism of sustained alterations in pulmonary hemodynamics during endotoxin shock remains unclear. To gain more detailed knowledge we used the four-element windkessel model as a descriptor of the pulmonary circuit. METHODS: Consecutive changes in characteristic resistance (R1), vascular compliance (C), input resistance (R2) and inductance (L) were continuously assessed following injection of endotoxin in 6 anaesthetised pigs, and were compared with the corresponding values measured in a similar group of sham-operated animals. RESULTS: Endotoxin challenge resulted in a biphasic pulmonary artery pressure response. Blood flow decreased progressively from 2.8 +/- 0.2 l/min to 2 +/- 0.2 l/min. Ohmic pulmonary vascular resistance (PVR) increased gradually from 0.2 +/- 0.04 to 0.76 +/- 0.1 mm Hg s ml-1. The early increase in PAP (from 14 +/- 2 to 27 +/- 4 mm Hg) was mediated by changes in both R1 (from 0.04 +/- 0.01 to 0.06 +/- 0.01 mm Hg s ml-1) and R2 (from 0.16 +/- 0.04 to 0.61 +/- 0.2 mm Hg s ml-1). These responses, in turn, altered the proximal vascular compliance. A subsequent increase in PAP (from 27 +/- 2 to 32 +/- 3 mm Hg) paralleled the specific decline in distal pulmonary vasculature compliance from 0.84 +/- 0.1 to 0.65 +/- 0.1 ml/mmHg. Analysis of the time course of PVR did not allow us to distinguish between vasoconstriction and stiffening of the vascular tree as mechanisms accounting for PAP changes. CONCLUSIONS: Endotoxemia leads to pulmonary hypertension, which is a result of constriction of proximal pulmonary arteries during the early phase, whereas the late phase is characterised by a decline in distal pulmonary vasculature compliance.

Pulmonary impedance and right ventricular-vascular coupling in endotoxin shock.

OBJECTIVE: We tested the hypothesis that right heart failure during endotoxin shock may result from altered ventriculovascular coupling responsible for impeding power transfer to the pulmonary circulation. METHODS: The changes in vascular pulmonary input impedance and right ventricular contractility produced by low-dose endotoxin infusion were studied in 6 intact anesthetized dogs. RESULTS: Endotoxin insult resulted in pulmonary hypertension (from 22 +/- 2 to 33 +/- 3 mmHg) associated with significant decreases in stroke volume (from 26.9 +/- 4 to 20.2 +/- 3 ml) and right ventricular ejection fraction (from 41 +/- 3 to 32 +/- 2%). The first minimum of input impedance spectrum and zero phase were shifted towards higher frequencies. Input resistance and characteristic resistance were dramatically increased. The latter change contributed to a significant increase in the pulsatile component of total right ventricular power output from 13 to 21%, indicating a reduction in the hydraulic right ventricle power output delivered into the main pulmonary artery. Overall changes in input pulmonary impedance were indicative of increased afterload facing the right ventricle leading to depressed performance. In contrast, right ventricular systolic elastance was simultaneously increased from 0.56 to 0.93 mmHg/ml indicating an increase in right heart contractility. CONCLUSION: These data suggest that pulmonary hypertension in the setting of experimental endotoxin shock is accompanied by deleterious changes in the pulmonary impedance spectrum, which are responsible for a mismatch of increased contractile state of the right ventricle to the varying hydraulic load ultimately leading to ventricular-vascular uncoupling.

Effects of cold and warm ischemia on the mitochondrial oxidative phosphorylation of swine lung.

BACKGROUND: The aim of the study was to investigate the consequence of warm and cold ischemia on lung mitochondria in order to define bioenergetic limits within lung could be suitable for pulmonary transplantation. METHODS: Twenty-two pigs underwent lung harvesting after lung flush with Euro-Collins solution. Mitochondria were isolated from fresh lungs, from lungs submitted to 24 or 48 hr of cold ischemia, to 30 or 45 min of warm ischemia, and to 30 min of warm ischemia followed by 24 or 48 hr of cold ischemia. Mitochondrial oxidative phosphorylation parameters were determined in isolated mitochondria by in vitro measurement of oxygen consumption. RESULTS: Relative to controls, mitochondria submitted to cold ischemia showed an alteration in the oxidoreductase activities of the respiratory chain but no membrane permeability alteration. After 48 hr of cold ischemia, there was a decrease in the yield of the oxidative phosphorylation. Thirty minutes of warm ischemia did not alter the mitochondrial respiratory parameters. However, lung submitted to 45 min of warm ischemia showed mitochondrial damage as a decrease in the oxidative phosphorylation efficiency and ADP availability but no change in the oxidoreductase activities. Relative to cold ischemia alone, 30 min of warm ischemia preceding cold ischemia promoted no significant change in the respiratory parameters. CONCLUSIONS: On bioenergetic basis, lung submitted to warm ischemia could be suitable for transplantation if the warm ischemia duration does not exceed 30 min. This could be a major concern in lung procurement from non-heart beating donors.