Karine Nouette-Gaulain

Antiproliferative activity of levobupivacaine and aminoimidazole carboxamide ribonucleotide on human cancer cells of variable bioenergetic profile

We assessed the impact of ten mitoactive drugs on the viability and the proliferation of human cancer cells of variable origin and bioenergetics. A validated chemotherapeutic drug, doxorubicin, was used as a gold-standard for comparison. We also looked at the effect of these drugs on Rho(0) cells and on embryonic fibroblasts, both of which rely mainly on glycolysis to generate the vital ATP. The statistical analysis of the area under the curves revealed a cell-type specific response to mitodopant and mitotoxic compounds, in correlation with the contribution of glycolysis to cellular ATP synthesis. These findings indicate that the bioenergetic state of the cell determines in part the impact of mitodopants and mitotoxics on cancer cells viability.

Target‐controlled inhalation induction with sevoflurane in children: a prospective pilot study

Background:u2002 Target‐controlled inhalation induction (TCII) with sevoflurane is becoming possible with new anesthesia platforms. Although TCII has already been performed in adults, it remains to be evaluated in children.

Chronic postsurgical pain in children: prevalence and risk factors. A prospective observational study

BACKGROUNDnChronic postsurgical pain (CPSP) is well known in adults, with prevalence rates ranging from 10 to 50%. Little is known about the epidemiology of CPSP in children. The aim of this prospective observational study was to evaluate the prevalence of CPSP after surgery in children.nnnMETHODSnAfter informed consent, children aged six to18 yr were included. Characteristics and risk factors for CPSP were recorded. Exclusion criteria included ambulatory surgery, refusal, inability to understand and change of address. All eligible children completed a preoperative questionnaire the day before surgery about pain, anxiety and their medical history. All data concerning anaesthetic and surgical procedures, such as acute pain scores (VAS) during the first 24 h were recorded. Three months after surgery all included children were sent a postoperative questionnaire about pain at the surgical site.nnnRESULTSnAltogether, 291 children were enrolled; the mean age was 12 yr, most subjects were male (60%). The most common type of surgery was orthopaedic (63%). In the 258 patients who completed the study, the prevalence of CPSP was 10.9%, most often with a neuropathic origin (64.3%). The two main risk factors were the existence of recent pain before surgery (<1 month) and the severity of acute postoperative pain (VAS >30 mm) in the first 24 h after orthopaedic and thoracic surgeries. Six months after surgery, only five children needed a visit with a chronic pain practitioner.nnnCONCLUSIONSnThese results highlight the necessity of evaluating and treating perioperative pain in order to prevent CPSP in children.

Deux utilisations consécutives de l'Airtraq® néonatal chez un nourrisson d'un mois présentant une intubation difficile prévue

We used successfully Airtraq-combined to a gum-elastic boogie to intubate twice a dysmorphic infant with mucolipidosis, in whom direct laryngoscopy failed. If this result is confirmed by prospective studies, Airtraq could be a first-line device to intubate infants with difficult intubation.

Émulsions lipidiques intraveineuses et toxicité systémique des anesthésiques locaux : mécanismes et limites

OBJECTIVESnIntravenous lipid emulsions (ILE) are recommended today in cases of local anesthetic-induced systemic toxicity (LAST). The objectives of this review consists in describing mechanisms involved in the interaction between ILE and local anesthetic (LA) factors influencing this interaction and the limits associated with the use of ILE.nnnDATA SOURCESnReferences were obtained from Pubmed data bank (http://www.ncbi.nlm.nih.gov/pubmed) using the following keywords: Intralipid(®), local anesthetic, toxicity, intravenous lipid emulsion.nnnDATA SYNTHESISnEffects of the association between ILE-LA are based on droplet formations as well as changes in cell metabolism involving survival cell pathway, on functional properties and on direct hemodynamic parameters. Hypoxia, acidosis and high doses of epinephrine modified the effects of ILE-LA association.nnnCONCLUSIONnPrescription of ILE is recommended by published guidelines on LAST resuscitation. ILE cannot substitute to the standard resuscitation protocol. It should be added to that protocol. Experimental studies as well as a case report registry will allow understanding further the effects induced by the ILE-LA association.

Factor V and VIII combined deficiency: Clinical perioperative management for tonsillectomy in a child ☆

Combined factors V (FV) and VIII (FVIII) deficiency is a rarely seen hereditary coagulation disease. Experience of its management in surgery with a high-risk of bleeding is rare. The interest of this case report is to propose a strategy of perioperative management for such a deficit, but also to recall that a careful preoperative anesthetic evaluation with questioning and physical examination permits to detect unsuspected coagulation disorders and to schedule the preventive treatment. The protocol for the perioperative period consisted of the administration of desmopressin and fresh frozen plasma one hour before surgery. The administration of desmopressin was continued for 48hours. Fresh frozen plasma and tranexamic acid were administered during the first 9 postoperative days. A local bleeding occurred at 8 days (scab coming off) and required systematically a surgical hemostasis and an intensification of the therapeutic protocol. Recombinant plasmatic factor VIII was administered for 7 days together with a daily perfusion of fresh frozen plasma for a total treatment period of 14 days.

Acute and chronic effects of bupivacaine on muscle energetics during contraction in vivo: a modular metabolic control analysis

Bupivacaine is a widely used anaesthetic injected locally in clinical practice for short-term neurotransmission blockade. However, persistent side effects on mitochondrial integrity have been demonstrated in muscle parts surrounding the injection site. We use the precise language of metabolic control analysis in the present study to describe in vivo consequences of bupivacaine injection on muscle energetics during contraction. We define a model system of muscle energy metabolism in rats with a sciatic nerve catheter that consists of two modules of reactions, ATP/PCr (phosphocreatine) supply and ATP/PCr demand, linked by the common intermediate PCr detected in vivo by (31)P-MRS (magnetic resonance spectroscopy). Measured system variables were [PCr] (intermediate) and contraction (flux). We first applied regulation analysis to quantify acute effects of bupivacaine. After bupivacaine injection, contraction decreased by 15.7% and, concomitantly, [PCr] increased by 11.2%. The regulation analysis quantified that demand was in fact directly inhibited by bupivacaine (-21.3%), causing an increase in PCr. This increase in PCr indirectly reduced mitochondrial activity (-22.4%). Globally, the decrease in contractions was almost fully explained by inhibition of demand (-17.0%) without significant effect through energy supply. Finally we applied elasticity analysis to quantify chronic effects of bupivacaine iterative injections. The absence of a difference in elasticities obtained in treated rats when compared with healthy control rats clearly shows the absence of dysfunction in energetic control of muscle contraction energetics. The present study constitutes the first and direct evidence that bupivacaine myotoxicity is compromised by other factors during contraction in vivo, and illustrates the interest of modular approaches to appreciate simple rules governing bioenergetic systems when affected by drugs.

Difficult intubation and extubation in adult anaesthesia

OBJECTIVEnTo provide an update to French guidelines about Difficult intubation and extubation in adult anaesthesia 2006.nnnDESIGNnA consensus committee of 13 experts was convened. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. The authors were advised to follow the principles 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 emphasized. Few recommendations were ungraded.nnnMETHODSnThe panel focused on 6 questions: 1) Why must oxygen desaturation be avoided during intubation and what preoxygenation and oxygenation techniques should be used to prevent it? 2) Should videolaryngoscopes be used instead of standard laryngoscopy with or without a long stylet to achieve a better success rate of intubation after the first attempt during anticipated difficult intubation off fiberoptic intubation? 3) Should TCI or target controlled inhalation anaesthesia (TCIA) be used instead of bolus sedation for airway control in the event of suspected or proven difficulty in a patient spontaneously breathing? 4) What mode of anaesthesia should be performed in patients with difficult intubation criteria and potentially difficult mask ventilation? 5) In surgical patients, what criteria predict difficulties encountered during postoperative tracheal extubation? 6) Should decision trees and algorithms be employed to direct decision-making for the management of difficult intubation, whether foreseen or not? (based on the information from the preceding five issues). Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. The analysis of the literature and the recommendations were then conducted according to the GRADE® methodology.nnnRESULTSnThe SFAR Guideline panel provided 13 statements on difficult intubation and extubation in adult anaesthesia. After two rounds of discussion and various amendments, a strong agreement was reached for 99% of recommendations. Of these recommendations, five have a high level of evidence (Grade 1±), 8 have a low level of evidence (Grade 2±). No recommendation was provided for one question.nnnCONCLUSIONSnSubstantial agreement exists among experts regarding many strong recommendations for the best care of patients with difficult intubation and extubation in adult anaesthesia.

Use of volatile anaesthetic agents in anaesthesia: A survey of practice in France in 2012 ☆

Volatile anaesthetic agents are used in the vast majority of general anaesthesias performed in France. We assessed the degree of understanding of French anaesthetists with regard to the general pharmacology of these products and their understanding of the factors that govern selection of the different agents available for use in adults. A validated 13-item questionnaire was sent electronically in 2012 using files from the Société française danesthésie et de réanimation (Sfar). It covered four categories: general characteristics of the respondent; practical aspects of anaesthesia with volatile agents; pharmacological properties and criteria for choosing a volatile agent; risk of intra-operative awareness. Among the 981 respondents, the anaesthetic technique used by 50% was that of an intravenous induction followed by maintenance with sevoflurane. The concepts relating to the practical use of these products are well known. A fresh gas flow of less than 2xa0L/min is used by 96% of the respondents. However, knowledge levels are often inadequate (rate of correct answers often<50%). This lack of knowledge pertains to current themes (climate pollution), those of debatable clinical significance, e.g. pre-conditioning, hypoxic vasoconstriction and those that concern scientific theory (medullary action). However, a lack of knowledge is also observed with regard to basic pharmacology (respiratory, vascular, neurological or pharmacokinetic effects). There is no significant difference in the mode of practice. The experience of the anaesthetist (measured by number of years post diploma) resulted in a number of differences in response to many aspects of the questionnaire but these were minor. These results suggest the need for an improvement both in the initial and continued training of anaesthetists with respect to volatile anaesthetic agents.

Lysis Timer: a new sensitive tool to diagnose hyperfibrinolysis in liver transplantation

Aims Diagnosis of hyperfibrinolysis in orthotopic liver transplantation (OLT) remains challenging. Euglobulin clot lysis time (ECLT) is not adapted to clinical situations. ROTEM is specific but seldom sensitive to hyperfibrinolysis. The Lysis Timer assesses ‘Global Fibrinolytic Capacity’ in citrated plasma (GFC/LT). GFC/LT associates reagents for in vitro triggering of the clot (thrombin and calcium) and its lysis (tissue-plasminogenactivator (t-PA)), turbidity signal acquisition by the Lysis Timer, and dedicated software converting the digital signal into an optical curve. A visual check of the curves was systematic to ascertain the lysis time values calculated by the software. The primary aim of this prospective observational study was to evaluate the ability of GFC/LT to recognise hyperfibrinolysis during OLT. The secondary aim was to compare its results with ROTEM maximum lysis (EXTEM ML) and with standard laboratory tests. Methods Thirty consecutive adult patients undergoing OLT were included (NCT03012633). Standard laboratory tests, ROTEM, GFC/LT, ECLT and fibrinolysis parameters were assayed at five sample times. Results GFC/LT was correlated with ECLT, plasmin activator inhibitor 1 antigen and activity and t-PA activity (r=0.490, 0.681, 0.643 and –0.359, respectively). Hyperfibrinolysis was defined as ECLT ≤60 min. Receiver operating characteristic curve analysis showed that GFC/LT with a threshold of 31 min detected hyperfibrinolysis with a sensitivity of 0.88 (95% CI 0.73 to 0.96), a specificity of 0.68 (95% CI 0.56 to 0.78) and an area under the curve (AUC) of 0.85 (95% CI 0.74 to 0.94). EXTEM ML >12% did not detect hyperfibrinolysis (sensitivity 0.38 (95% CI 0.24 to 0.55), specificity 0.95 (95% CI 0.86 to 0.99) and AUC 0.60 (95% CI 0.46 to 0.75)). Conclusions GFC/LT recognised hyperfibrinolysis during OLT with a significant agreement with the other tests of fibrinolysis. Trial registration number NCT03012633.