Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study.

BACKGROUND: Respiratory variation in pulse pressure (ΔPP) is commonly used to predict the fluid responsiveness of critically ill patients. However, some researchers have demonstrated that this measurement has several limitations. The present study was designed to evaluate the proportion of patients satisfying criteria for valid application of ΔPP at a given time-point. METHODS: A 1 day, prospective, observational, point-prevalence study was performed in 26 French intensive care units (ICUs). All patients hospitalized in the ICUs on the day of the study were included. The ΔPP validity criteria were recorded prospectively and defined as follows: (i) mechanical ventilation in the absence of spontaneous respiration; (ii) regular cardiac rhythm; (iii) tidal volume ≥8 ml kg(-1) of ideal body weight; (iv) a heart rate/respiratory rate ratio >3.6; (v) total respiratory system compliance ≥30 ml cm H2O(-1); and (vi) tricuspid annular peak systolic velocity ≥0.15 m s(-1). RESULTS: The study included 311 patients with a Simplified Acute Physiology Score II of 41 (39-43). Overall, only six (2%) patients satisfied all validity criteria. Of the 170 patients with an arterial line in place, only five (3%) satisfied the validity criteria. During the 24 h preceding the study time-point, fluid responsiveness was assessed for 79 patients. ΔPP had been used to assess fluid responsiveness in 15 of these cases (19%). CONCLUSIONS: A very low percentage of patients satisfied all criteria for valid use of ΔPP in the evaluation of fluid responsiveness. Physicians must consider limitations to the validity of ΔPP before using this variable.

NeuroAiD: properties for neuroprotection and neurorepair.

BACKGROUND: Treatments for stroke and other brain injuries are limited. NeuroAiD has been shown to be beneficial in clinical studies. We reviewed the pharmacological effects of NeuroAiD on the normal and ischemic brain and neurons. METHODS: In vivo and in vitro experiments using mouse model of stroke (focal ischemia), rat model of cardiac arrest (global ischemia) and cortical neurons in culture were reviewed and summarized. RESULTS: NeuroAiD improved survival, attenuated infarct size, improved functional recovery in the model of focal ischemia, and protected neurons against glutamate-induced injury. Furthermore, it enhanced cognitive recovery by reducing hippocampal CA1 cell degeneration, DNA fragmentation, Bax expression and ma-londialdehyde release in the model of global ischemia. Activation of the Akt survival pathway and opening of KATP channels may contribute to the neuroprotective properties of NeuroAiD. NeuroAiD increased BDNF expression and induced proliferation of cells which differentiate and mature into neurons. It enhanced rosette formation of human embryonic stem cells. NeuroAiD-treated embryonic cortical neurons developed into neurons with longer neurites, denser outgrowths and networks, and more synaptic release sites. CONCLUSIONS: NeuroAiD demonstrated both neuroprotective and neuroregenerative properties in rodent models of focal and global ischemia and in cortical cell cultures. These properties would be important for developing a treatment strategy in reducing the long-term disability of stroke, cardiac arrest and other brain injuries.

French recommendations for the management of patients with spinal cord injury or at risk of spinal cord injury.

OBJECTIVES: To update the French guidelines on the management of trauma patients with spinal cord injury or suspected spinal cord injury. DESIGN: A consensus committee of 27 experts was formed. A formal conflict-of-interest (COI) policy was developed at the outset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e. pharmaceutical, medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. METHODS: The committee studied twelve questions: (1) What are the indications and arrangements for spinal immobilisation? (2) What are the arrangements for pre-hospital orotracheal intubation? (3) What are the objectives of haemodynamic resuscitation during the lesion assessment, and during the first few days in hospital? (4) What is the best way to manage these patients to improve their long-term prognosis? (5) What is the place of corticosteroid therapy in the initial phase? (6) What are the indications for magnetic resonance imaging in the lesion assessment phase? (7) What is the optimal time for surgical management? (8) What are the best arrangements for orotracheal intubation in the hospital environment? (9) What are the specific conditions for weaning these patients from mechanical ventilation for? (10) What are the procedures for analgesic treatment of these patients? (11) What are the specific arrangements for installing and mobilising these patients? (12) What is the place of early intermittent bladder sampling in these patients? Each question was formulated in a PICO (Patients, Intervention, Comparison, Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE® Methodology. RESULTS: The experts' work synthesis and the application of the GRADE method resulted in 19 recommendations. Among the recommendations formalised, 2 have a high level of evidence (GRADE 1+/-) and 12 have a low level of evidence (GRADE 2+/-). For 5 recommendations, the GRADE method could not be applied, resulting in expert advice. After two rounds of scoring and one amendment, strong agreement was reached on all the recommendations. CONCLUSIONS: There was significant agreement among experts on strong recommendations to improve practices for the management of patients with spinal cord injury.

Botulism and hot-smoked whitefish: a family cluster of type E botulism in France, September 2009.

A family cluster of three cases of type E botulism were identified in south-east France in September 2009. The suspected food source of infection was a vacuum packed hot-smoked whitefish of Canadian origin purchased by the family during a visit to Finland and consumed several weeks later in France on the day prior to symptom onset. No leftover fish was available to confirm this hypothesis. Vacuum packed hot-smoked whitefish has previously been associated with cases of type E botulism in multiple countries, including Finland, Germany, the United States and Israel.

[Activated proteine C]. / La protéine C activée.

Recombinant human activated protein C (APC) might be the first pharmacological intervention which decreases mortality in the course of severe sepsis. Surviving Sepsis Campaign guidelines have recommended the use of APC with grade B level of proof. During sepsis, the APC pathway serves as a major system for controlling thrombosis inhibiting thrombin formation, limiting inflammatory responses, and potentially decreasing endothelial cell apoptosis. APC use was assessed in the course of severe sepsis 24 microg/kg/h for 96 hours with the aim of inhibiting coagulopathy and inflammation. The PROWESS trial included 1,690 patients and demonstrated a significantly decreased mortality in the treated group. Additional publications have clarified the characteristics of the included patients and tried to outline the potential benefits of APC. The results of ENHANCE, a multicenter open trial, have confirmed the trends reported in the PROWESS trial. Evidence supporting the efficacy of APC in the management of severe sepsis is clearly assessed. However, several issues remain unsolved and require to be addressed as the appropriate use of the drug and its place with other adjunctive therapies directed the sepsis process.

[Dynamic left ventricular obstruction associated with a pheochromocytoma reversible after tumor ablation]. / Obstruction dynamique intraventriculaire gauche associée à un phéochromocytome et réversible après son exérèse.

The association of dynamic left ventricular outflow tract obstruction and pheochromocytoma is rare with only about fifteen previously reported cases in the literature. The association may be the result of chronic increased catecholamine secretion which induces intra-ventricular obstruction in a hypertrophied ventricle due to hypertension. The authors report a new case in which the intraventricular gradient on Doppler echocardiography was particularly high at 120 mmHg. The gradient totally regressed after removal of the pheochromocytoma. The finding of a systolic murmur in a patient with pheochromocytoma should lead to the prescription of Doppler echocardiography and diagnosis of left ventricular tract obstruction must lead to the association of betablocker and alphablocker therapy before surgery. The removal of the pheochromocytoma is usually followed by the complete regression of left intraventricular obstruction, as in this case.

[Anesthesia of hypertensive patients]. / Anesthésie du malade hypertendu.

Hypertension is a frequent condition among adults. It is one of the major risk factors of atherosclerotic diseases. Anesthetologists are frequently confronted to the management of treated or untreated hypertensive patients whose major risk during that period concerns the potential association with coronary artery disease. Therefore, the preoperative assessment should be insured of an adequate control of blood pressure, the presence of potential target organ damage and especially the detection an underlying coronary disease and its importance. The risk of cardiovascular complications and consecutively the preoperative check-up depend of the type of surgery scheduled. Preoperative systolic blood pressures (SBP) below 180 mmHg and diastolic blood pressures (DBP) below 110 mmHg are recommended. Due to their efficacy, tolerability and the easiness of their use, dihydropyridins and beta-blockers are the most frequent drugs used in the peri-operative period. Many studies evidenced the benefit of beta-blocking agents in patients with definite or potential coronary artery disease during the immediate period of major surgery, with not only a decrease of serious cardiac complications and post-operative mortality but also an improvement of mid- and longterm prognosis. There is no evidence to privilege any type of anesthesia. A respect of hemodynamic conditions (avoidance of severe hypotension and tachycardia) reduces the incidence of ischemic complications. The hemodynamic stability is obtained with an adapted anesthesia and the use of intravenous vasoconstrictive or vasodilator agents as well as beta-blockers (esmolol). The diagnosis of perioperative myocardial infarction is based on the measurement of seric concentrations of cardiac Troponin isoforms (TnI or TnT).

[A case of association of atypical localisations of Streptococcus pneumoniae]. / Association de localisations atypiques à Streptococcus pneumoniae: à propos d'un cas.

Streptococcus pneumoniae can be responsible for spinal, joints, pulmonary or infrequently cutaneous septic localisations. The association between different septic localisation is extremely rare with this microorganism. We describe the first case of concomitant spinal, joints and cutaneous septic localisations in a critically ill patient with S. pneumoniae septicaemia. This observation illustrates that heterogeneity of clinical features depends on the pathogen characteristic and its interaction with the host.

[Cerebral oedema: new therapeutic ways]. / Œdème cérébral: nouvelles pistes thérapeutiques.

Cerebral oedema (CO) after brain injury can occur from different ways. The vasogenic and cytotoxic oedema are usually described but osmotic and hydrostatic CO, respectively secondary to plasmatic hypotonia or increase in blood pressure, can also be encountered. Addition of these several mechanisms can worsen injuries. Consequences are major, leading quickly to death secondary to intracerebral hypertension and later to neuropsychic sequelae. So therapeutic care to control this phenomenon is essential and osmotherapy is actually the only way. A better understanding of physiopathological disorders, particularly energetic ways (lactate), aquaporine function, inflammation lead to new therapeutic hopes. The promising experimental results need now to be confirmed by clinical data.

MLC901, a Traditional Chinese Medicine induces neuroprotective and neuroregenerative benefits after traumatic brain injury in rats.

Traumatic brain injury (TBI) is a frequent and clinically highly heterogeneous neurological disorder with large socioeconomic consequences. NeuroAid (MLC601 and MLC901), a Traditional Medicine used in China for patients after stroke has been previously reported to induce neuroprotection and neuroplasticity. This study was designed to evaluate the neuroprotective and neuroregenerative effects of MLC901 in a rat model of TBI. TBI was induced by a moderate lateral fluid percussion applied to the right parietal cortex. MLC901 was injected intraperitoneally at 2h post-TBI, and then administered in drinking water at a concentration of 10mg/ml until sacrifice of the animals. The cognitive deficits induced by TBI were followed by using the "what-where-when" task, which allows the measurement of episodic-like memory. MLC901 treatment decreased brain lesions induced by TBI. It prevented the serum increase of S-100 beta (S100B) and neuron-specific enolase (NSE), which may be markers to predict the neurologic outcome in human patients with TBI. MLC901 reduced the infarct volume when injected up to 2h post-TBI, prevented edema formation and assisted its resolution, probably via the regulation of aquaporin 4. These positive MLC901 effects were associated with an upregulation of vascular endothelial growth factor (VEGF) as well as an increase of endogenous hippocampal neurogenesis and gliogenesis around the lesion. Furthermore, MLC901 reduced cognitive deficits induced by TBI. Rats subjected to TBI displayed a suppression of temporal order memory, which was restored by MLC901. This work provides evidence that MLC901 has neuroprotective and neurorestorative actions, which lead to an improvement in the recovery of cognitive functions in a model of traumatic brain injury.

Fluid therapy in neurointensive care patients: ESICM consensus and clinical practice recommendations

Objective To report the ESICM consensus and clinical practice recommendations on fluid therapy in neurointensive care patients. Design A consensus committee comprising 22 international experts met in October 2016 during ESICM LIVES2016. Teleconferences and electronic-based discussions between the members of the committee subsequently served to discuss and develop the consensus process. Methods Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles generated. The consensus focused on three main topics: (1) general fluid resuscitation and maintenance in neurointensive care patients, (2) hyperosmolar fluids for intracranial pressure control, (3) fluid management in delayed cerebral ischemia after subarachnoid haemorrhage. After an extensive literature search, the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were applied to assess the quality of evidence (from high to very low), to formulate treatment recommendations as strong or weak, and to issue best practice statements when applicable. A modified Delphi process based on the integration of evidence provided by the literature and expert opinions­using a sequential approach to avoid biases and misinterpretations­was used to generate the final consensus statement. Results The final consensus comprises a total of 32 statements, including 13 strong recommendations and 17 weak recommendations. No recommendations were provided for two statements. Conclusions We present a consensus statement and clinical practice recommendations on fluid therapy for neurointensive care patients.

[Economic and clinical impact of a controlled sedation procedure in an intensive care unit]. / Impact clinique et économique d'une politique de contrôle de la sédation par protocole dans un service de réanimation médicochirurgicale.

OBJECTIVE: Since the last consensus conducted by Sfar/SRLF, the use of protocol for sedation became the reference in our ICUs. Decrease in length of stay and length of mechanical ventilation with used of these protocols have been already described. We would like to investigate the economic impact associated. STUDY DESIGN: Using the PMSI data, we studied retrospectively, the economic effect, one year before and one year after protocol implementation in our ICU. METHOD: The economic evaluation compared the cost of sedation but also the cost of mechanical ventilation and length of stay in ICU. RESULTS: Characteristic and number of patients were equivalent during the two years. We described a significant decrease in length of mechanical ventilation (8.8 vs. 8.4; p<0.05) but not in length of stay (11.4 vs. 11.7; NS) between the two periods. We described a decrease of sedation cost of 11 412 euros and a decrease of mechanical ventilation cost of 27 360 Euros between the two years. CONCLUSION: We confirm in this study that use of sedation protocol in ICU is associated with a clinical impact but also with an economic effect.

French survey on current use of ultrasound in the critical care unit: ECHOREA.

INTRODUCTION: Over the last ten years, ultrasound became standard procedure in the intensive care unit (ICU). STUDY DESIGN: A national survey to evaluate the use of this technique in French ICUs. METHODS: Three hundred and twenty-seven units were contacted from the listing of the Société de réanimation de langue française (SRLF). A survey containing 20 questions addressing the availability, the training for, and the use of ultrasound was sent to the ICUs. Collection of data took place over a period of three months. RESULTS: We received 132 completed surveys out of the 327 sent out (40%). Seventy-nine percent of the public community and private centers and 94% of the university centers had an available device in the unit. Forty percent of the units carried out five to ten examinations per week. Seventy-two percent had staff trained in echocardiography. Fifty-five percent used association of monitoring techniques for the haemodynamic assessment of patients with shock. Only 73% carried out formalized reports after examination. In more than 80%, the echocardiograph was also used for the evaluation of other organs. CONCLUSION: Ultrasound, and particularly echocardiography, has taken on a more prominent role in the routine assessment of critically ill patients. The availability of equipment and of training has increased over the last ten years, but the demand for training in this area remains strong. This French survey confirms this technique became the "extension of the hand" of the intensivist in ICU.

MLC901, a traditional Chinese medicine protects the brain against global ischemia.

Global ischemia leads to damage in the hippocampal CA1 region and is associated with behavioral deficits. NeuroAid (MLC601 and MLC901), a Traditional Chinese Medicine is used in China for patients after stroke. We have investigated here the effects of MLC901 on brain injury and deficits after global ischemia in the rat. Global ischemia induced by four-vessel occlusion resulted in degeneration of CA1 neurons. MLC901 (0.074 mg/ml) prevented both necrosis and apoptosis of neurons up to 3 h after ischemia. These positive MLC901 effects were associated with a decrease in Bax expression and in levels of the lipid peroxidation product malondialdehyde. Using the PI3-kinase inhibitor LY294002 we also demonstrated the critical role of the Akt pathway in MLC901-mediated neuroprotection. MLC901 enhanced neurogenesis. Furthermore, MLC901 improved functional recovery of rats after global ischemia as assessed by the Morris water maze. In this test MLC901 reduced the increase in escape latency and in swim distance induced by ischemia. MLC901 also improved post-ischemic grip strength. If observations made with rats can be extended to humans, then MLC901 will represent a novel therapeutic strategy after cardiac arrest with a clinically interesting time window of protection.

[Serious pulmonary embolism and thromboaspiration]. / Embolie pulmonaire grave et thrombo-aspiration.

Pulmonary embolism is a common disease with a mortality rate of approximately 3%. Polytraumatised patients are particularly susceptible to thromboembolism because of prolonged immobilisation and inflammatory syndrome, thrombembolic risk also increases significantly during the peripartum period. Rapid diagnosis and intervention are essential for survival. Conventional treatment consists of systemic intravascular thrombolysis, but this procedure is often contraindicated in intensive care patients because of the high risk of haemorrhage. We report two cases of successful treatment using radiological endovascular thrombectomy.

[What is the contribution of Stewart's concept in acid-base disorders analysis?]. / Qu'apporte le modèle de Stewart à l'interprétation des troubles de l'équilibre acide-base?

OBJECTIVES: To explain the different approaches for interpreting acid-base disorders; to develop the Stewart model which offers some advantages for the pathophysiological understanding and the clinical interpretation of acid-base imbalances. DATA SOURCE: Record of french and english references from Medline data base. The keywords were: acid-base balance, hyperchloremic acidosis, metabolic acidosis, strong ion difference, strong ion gap. DATA EXTRACTION: Data were selected including prospective and retrospective studies, reviews, and case reports. DATA SYNTHESIS: Acid-base disorders are commonly analysed by using the traditional Henderson-Hasselbalch approach which attributes the variations in plasma pH to the modifications in plasma bicarbonates or PaCO2. However, this approach seems to be inadequate because bicarbonates and PaCO2 are completely dependent. Moreover, it does not consider the role of weak acids such as albuminate, in the determination of plasma pH value. According to the Stewart concept, plasma pH results from the degree of plasma water dissociation which is determined by 3 independent variables: 1) strong ion difference (SID) which is the difference between all the strong plasma cations and anions; 2) quantity of plasma weak acids; 3) PaCO2. Thus, metabolic acid-base disorders are always induced by a variation in SID (decreased in acidosis) or in weak acids (increased in acidosis), whereas respiratory disorders remains the consequence of a change in PaCO2. These pathophysiological considerations are important to analyse complex acid-base imbalances in critically ill patients. For example, due to a decrease in weak acids, hypoalbuminemia increases SID which may counter-balance a decrease in pH and an elevated anion gap. Thus if using only traditional tools, hypoalbuminemia may mask a metabolic acidosis, because of a normal pH and a normal anion gap. In this case, the association of metabolic acidosis and alkalosis is only expressed by respectively a decreased SID and a decreased weak acids concentration. This concept allows to establish the relationship between hyperchloremic acidosis and infusion of solutes which contain large concentration of chloride such as NaCl 0.9%. Finally, the Stewart concept permits to understand that sodium bicarbonate as well as sodium lactate induces plasma alkalinization. In fact, sodium remains in plasma, whereas anion (lactate or bicarbonate) are metabolized leading to an increase in plasma SID. CONCLUSION: Due to its simplicity, the traditional Henderson-Hasselbalch approach of acid-base disorders, remains commonly used. However, it gives an inadequate pathophysiological analysis which may conduct to a false diagnosis, especially with complex acid-base imbalances. Despite its apparent complexity, the Stewart concept permits to understand precisely the mechanisms of acid-base disorders. It has to become the most appropriate approach to analyse complex acid-base abnormalities.