Effects of capnometry monitoring during recovery in the post-anaesthesia care unit: a randomized controlled trial in adults (CAPNOSSPI).

PURPOSE: Continuous capnography should be used on patients admitted to post-anaesthesia care units (PACUs) with endotracheal tubes, but this monitoring is not always performed. Optimized ventilation in the PACU could be part of the global standards of practice to maintain the benefits of perioperative ventilation. The main objective was to study the rate of patients with alveolar hypoventilation before tracheal extubation or Laryngeal Mask Airway (LMA) removal upon the measurement of continuous capnography. METHODS: In this prospective, parallel-group, randomized controlled study, we enrolled adult patients admitted to the PACU after general anaesthesia with an endotracheal tube or LMA in place. Patients were randomly assigned to two groups: in the Capno + group, nurses managed the patients with access to the capnometer and end-tidal carbon dioxide pressure (PETCO2) measurements; in the Capno- group, nurses monitored the patients without seeing PETCO2 measurements. The primary outcome was the percentage of patients with PETCO2 measurements above 45 mm Hg during the minute before extubation. Secondary endpoints included the delay in recovering spontaneous breathing, rate of hypoxemia, delay before extubation, and length of stay in the PACU. RESULTS: Forty-eight patients were randomized into the two groups. The percentage of patients with PETCO2 > 45 mm Hg the minute before extubation was significantly decreased in the Capno + group (83.3% versus 54,1% in the Capno- and Capno + groups respectively, p = 0.029). There were no significant differences concerning secondary endpoints. CONCLUSIONS: The use of PETCO2 monitoring improves patient safety by decreasing the incidence of CO2 retention during recovery from general anaesthesia. This study suggests that this monitoring should be integrated in the PACU. The risk of hypoxemia can also be prevented through the early recognition of apnoea. CLINICAL TRIAL REGISTRY: clinicaltrial.gov. identifier: NCT03370081.

Utility of changes in end-tidal carbon dioxide after volume expansion to assess fluid responsiveness in the operating room: a prospective observational study.

BACKGROUND: From a physiological viewpoint, changes in end-tidal carbon dioxide (EtCO2) could be a simple, noninvasive, and inexpensive way to monitor changes in cardiac index. This study aimed to assess the utility of changes in EtCO2 as a marker of fluid responsiveness after volume expansion in the operating room. METHODS: A prospective observational study was conducted in a tertiary university teaching hospital, from August 2018 to February 2019. A total of 109 non-consecutive, mechanically ventilated adults undergoing neurosurgery in the supine position with cardiac output monitors were included. Patients with major respiratory disease, arrhythmia, or heart failure were excluded. Volume expansion with 250 ml of saline 0.9% was performed over 10 min to maximise cardiac output during surgery, according to current guidelines. A positive fluid challenge was defined as an increase in stroke volume index of more than 10% from baseline. Changes in stroke volume index (monitored using pulse contour analysis) and EtCO2 were recorded before and after infusion. RESULTS: A total of 242 fluid challenges in 114 patients were performed, of which 26.9% were positive. Changes in EtCO2 > 1.1% induced by infusions had utility for identifying fluid responsiveness, with a sensitivity of 62.9% (95% confidence interval [CI], 62.5-63.3%) and a specificity of 77.8% (95% CI, 77.6-78.1%). The area under the receiver operating characteristic curve for changes in EtCO2 after volume expansion was 0.683 (95% CI, 0.680-0.686). CONCLUSIONS: Changes in EtCO2 induced by rapid infusion of 250 ml saline 0.9% lacked accuracy for identifying fluid responsiveness in mechanically ventilated patients in the operating room. CLINICAL TRIAL REGISTRATION: NCT03635307.

Do changes in perfusion index reflect changes in stroke volume during preload-modifying manoeuvres?

Changes in stroke volume (deltaSV) induced by a lung recruitment manoeuvre (LRM) have been shown to accurately predict fluid responsiveness during protective mechanical ventilation. Cardiac output monitors are used in a limited number of surgical patients. In contrast, all patients are monitored with a pulse oximeter, that may enable the continuous monitoring of a peripheral perfusion index (PI). We postulated that changes in PI (deltaPI) may reflect deltaSV during brief modifications of cardiac preload. We studied 47 patients undergoing neurosurgery and ventilated with a tidal volume of 6-8 ml/kg. All patients were monitored with a pulse contour system enabling the continuous monitoring of SV and with a pulse oximeter enabling the continuous monitoring of PI. LRMs were performed by increasing airway pressure up to 30 cmH20 for 30 s. Fluid loads (250 ml of saline 0.9% in 10 min) were performed only in patients who experienced a deltaSV > 30% during LRMs (potential fluid responders). LRMs induced a 26% decrease in SV (p < 0.05) and a 27% decrease in PI (p < 0.05). We observed a fair relationship between deltaPI and deltaSV (r2 = 0.34). A deltaPI ≥ 26% predicted a deltaSV > 30% with a sensitivity of 83% and a specificity of 78%  (AUC  =  0.84, 95%CI 0.71-0.93). 24 patients experienced a deltaSV > 30% and subsequently received fluid. Fluid loads induced a 16% increase in SV and a 17% increase in PI, but fluid-induced deltaPI and deltaSV were weakly correlated (r2 = 0.19). In neurosurgical patients, we conclude that deltaPI may be used as a surrogate for deltaSV during LRMs but not during fluid loading.

Increased ß-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study.

BACKGROUND: Augmented renal clearance (ARC) is recognized as a leading cause of ß-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased ß-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP). METHODS: In this single-center, retrospective study, every ARC patient treated by ß-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome. RESULTS: During the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15-0.81), p = 0.014. No antibiotic side effect was reported during the treatment period. CONCLUSIONS: Higher than licensed dosing regimens of ß-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.

End-expiratory occlusion maneuver to predict fluid responsiveness in the intensive care unit: an echocardiographic study.

BACKGROUND: In mechanically ventilated patients, an increase in cardiac index during an end-expiratory-occlusion test predicts fluid responsiveness. To identify this rapid increase in cardiac index, continuous and instantaneous cardiac index monitoring is necessary, decreasing its feasibility at the bedside. Our study was designed to investigate whether changes in velocity time integral and in peak velocity obtained using transthoracic echocardiography during an end-expiratory-occlusion maneuver could predict fluid responsiveness. METHODS: This single-center, prospective study included 50 mechanically ventilated critically ill patients. Velocity time integral and peak velocity were assessed using transthoracic echocardiography before and at the end of a 12-sec end-expiratory-occlusion maneuver. A third set of measurements was performed after volume expansion (500 mL of saline 0.9% given over 15 minutes). Patients were considered as responders if cardiac output increased by 15% or more after volume expansion. RESULTS: Twenty-eight patients were responders. At baseline, heart rate, mean arterial pressure, cardiac output, velocity time integral and peak velocity were similar between responders and non-responders. End-expiratory-occlusion maneuver induced a significant increase in velocity time integral both in responders and non-responders, and a significant increase in peak velocity only in responders. A 9% increase in velocity time integral induced by the end-expiratory-occlusion maneuver predicted fluid responsiveness with sensitivity of 89% (95% CI 72% to 98%) and specificity of 95% (95% CI 77% to 100%). An 8.5% increase in peak velocity induced by the end-expiratory-occlusion maneuver predicted fluid responsiveness with sensitivity of 64% (95% CI 44% to 81%) and specificity of 77% (95% CI 55% to 92%). The area under the receiver operating curve generated for changes in velocity time integral was significantly higher than the one generated for changes in peak velocity (0.96 ± 0.03 versus 0.70 ± 0.07, respectively, P = 0.0004 for both). The gray zone ranged between 6 and 10% (20% of the patients) for changes in velocity time integral and between 1 and 13% (62% of the patients) for changes in peak velocity. CONCLUSIONS: In mechanically ventilated and sedated patients in the neuro Intensive Care Unit, changes in velocity time integral during a 12-sec end-expiratory-occlusion maneuver were able to predict fluid responsiveness and perform better than changes in peak velocity.

Mini-fluid Challenge of 100 ml of Crystalloid Predicts Fluid Responsiveness in the Operating Room.

BACKGROUND: Mini-fluid challenge of 100 ml colloids is thought to predict the effects of larger amounts of fluid (500 ml) in intensive care units. This study sought to determine whether a low quantity of crystalloid (50 and 100 ml) could predict the effects of 250 ml crystalloid in mechanically ventilated patients in the operating room. METHODS: A total of 44 mechanically ventilated patients undergoing neurosurgery were included. Volume expansion (250 ml saline 0.9%) was given to maximize cardiac output during surgery. Stroke volume index (monitored using pulse contour analysis) and pulse pressure variations were recorded before and after 50 ml infusion (given for 1 min), after another 50 ml infusion (given for 1 min), and finally after 150 ml infusion (total = 250 ml). Changes in stroke volume index induced by 50, 100, and 250 ml were recorded. Positive fluid challenges were defined as an increase in stroke volume index of 10% or more from baseline after 250 ml. RESULTS: A total of 88 fluid challenges were performed (32% of positive fluid challenges). Changes in stroke volume index induced by 100 ml greater than 6% (gray zone between 4 and 7%, including 19% of patients) predicted fluid responsiveness with a sensitivity of 93% (95% CI, 77 to 99%) and a specificity of 85% (95% CI, 73 to 93%). The area under the receiver operating curve of changes in stroke volume index induced by 100 ml was 0.95 (95% CI, 0.90 to 0.99) and was higher than those of changes in stroke volume index induced by 50 ml (0.83 [95% CI, 0.75 to 0.92]; P = 0.01) and pulse pressure variations (0.65 [95% CI, 0.53 to 0.78]; P < 0.005). CONCLUSIONS: Changes in stroke volume index induced by rapid infusion of 100 ml crystalloid predicted the effects of 250 ml crystalloid in patients ventilated mechanically in the operating room.

Changes in Stroke Volume Induced by Lung Recruitment Maneuver Predict Fluid Responsiveness in Mechanically Ventilated Patients in the Operating Room.

BACKGROUND: Lung recruitment maneuver induces a decrease in stroke volume, which is more pronounced in hypovolemic patients. The authors hypothesized that the magnitude of stroke volume reduction through lung recruitment maneuver could predict preload responsiveness. METHODS: Twenty-eight mechanically ventilated patients with low tidal volume during general anesthesia were included. Heart rate, mean arterial pressure, stroke volume, and pulse pressure variations were recorded before lung recruitment maneuver (application of continuous positive airway pressure of 30 cm H2O for 30 s), during lung recruitment maneuver when stroke volume reached its minimal value, and before and after volume expansion (250 ml saline, 0.9%, infused during 10 min). Patients were considered as responders to fluid administration if stroke volume increased greater than or equal to 10%. RESULTS: Sixteen patients were responders. Lung recruitment maneuver induced a significant decrease in mean arterial pressure and stroke volume in both responders and nonresponders. Changes in stroke volume induced by lung recruitment maneuver were correlated with those induced by volume expansion (r = 0.56; P < 0.0001). A 30% decrease in stroke volume during lung recruitment maneuver predicted fluid responsiveness with a sensitivity of 88% (95% CI, 62 to 98) and a specificity of 92% (95% CI, 62 to 99). Pulse pressure variations more than 6% before lung recruitment maneuver discriminated responders with a sensitivity of 69% (95% CI, 41 to 89) and a specificity of 75% (95% CI, 42 to 95). The area under receiver operating curves generated for changes in stroke volume induced by lung recruitment maneuver (0.96; 95% CI, 0.81 to 0.99) was significantly higher than that for pulse pressure variations (0.72; 95% CI, 0.52 to 0.88; P < 0.05). CONCLUSIONS: The authors' study suggests that the magnitude of stroke volume decrease during lung recruitment maneuver could predict preload responsiveness in mechanically ventilated patients in the operating room.

End-Expiratory Occlusion Test Predicts Fluid Responsiveness in Patients With Protective Ventilation in the Operating Room.

BACKGROUND: End-expiratory occlusion test (EEOT) has been proposed to predict fluid responsiveness in mechanically ventilated intensive care unit patients. The utility of this test during low-tidal-volume ventilation remains uncertain. This study aimed to determine whether hemodynamic variations induced by EEOT could predict the effect of volume expansion in patients with protective ventilation in the operating room. METHODS: Forty-one patients undergoing neurosurgery were included. Stroke volume and pulse pressure variations were continuously recorded using pulse contour analysis before and immediately after a 30-second EEOT and after volume expansion (250 mL saline 0.9% given over 10 minutes). Patients with an increase in stroke volume ≥ 10% after volume expansion were defined as responders. RESULTS: Twenty patients were responders to fluid administration. EEOT induced a significant increase in stroke volume, which was correlated with the stroke volume changes induced by volume expansion (r = 0.55, P < .0001). A 5% increase in stroke volume during EEOT discriminated responders to volume expansion with a sensitivity of 100% (95% confidence interval [CI], 83%-100%), a specificity of 81% (95% CI, 58%-95%), a positive predictive value of 84% (95% CI, 64%-96%), and a negative predictive value of 100% (95% CI, 80%-100%). The gray zone ranged from 4% to 8%, including 17% of patients. The best pulse pressure variation threshold was 9%, with a sensitivity of 60% (95% CI, 36%-81%) and specificity of 86% (95% CI, 64%-97%). The area under the receiver operating characteristics curve generated for changes in stroke volume induced by EEOT (0.91, 95% CI, 0.81-1.00) was significantly higher than the one obtained for pulse pressure variations (0.75, 95% CI, 0.60-0.90); P < .05. CONCLUSIONS: Changes in stroke volume index induced by EEOT can predict fluid responsiveness in patients with protective ventilation in the operating room. This test may have potential applications.

Frequency and risk factors for malnutrition in children undergoing general anaesthesia in a French university hospital: A cross-sectional observational study.

BACKGROUND: Malnutrition is often underdiagnosed in hospitalised children, although it is associated with postoperative complications, longer hospital lengths of stay and increased healthcare-related costs. OBJECTIVE: We aimed to estimate the frequency of, and identify factors associated with, malnutrition in children undergoing anaesthesia. DESIGN: Cross-sectional observational study. SETTING: Paediatric anaesthesia department at the University Children's Hospital, Bordeaux, France. PARTICIPANTS: A total of 985 patients aged less than 18 years. MAIN OUTCOME MEASURES: Anthropometric measurements, American Society of Anesthesiologists physical status classification score and the Pediatric Nutritional Risk Score (PNRS) recorded at the pre-anaesthesia evaluation. RESULTS: When assessed as a Waterlow index less than 80%, malnutrition was present in 7.6% children. This increased to 8.1% of children assessed by clinical signs and to 11% of children when defined by a BMI less than the third percentile. In a univariate analysis, children with a BMI less than the third percentile were more often born prematurely (22.4 vs 10.4%; P = 0.0008), were small for gestational age at birth (18.4 vs 4.5%; P < 0.0001), were admitted from the emergency department (12.0 vs 5.6%; P = 0.02), had a high American Society of Anesthesiologists score (P < 0.0001), or had a high Pediatric Nutritional Risk Score (P < 0.0001). Presence (P = 0.01) and type (P = 0.002) of chronic disease were also associated with malnutrition. In the multivariate analysis, a premature birth, a lower birth weight and a higher Pediatric Nutritional Risk Score were significantly associated with a higher odds of malnutrition when defined by BMI. CONCLUSION: All children should be screened routinely for malnutrition or the risk of malnutrition at the pre-anaesthesia visit, allowing a programme of preoperative and/or postoperative nutritional support to be initiated. We suggest that as well as weight and height, BMI and a pediatric nutritional risk score such as PNRS should be recorded routinely at the pre-anaesthesia visit.

Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial.

BACKGROUND: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. METHODS: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. RESULTS: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86]). CONCLUSIONS: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916).

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.

Quick Epidural Top-up with Alkalinized Lidocaine for emergent caesarean delivery (QETAL study): protocol for a randomized, controlled, bicentric trial.

BACKGROUND: General anesthesia in pregnant women can be associated with significant maternal and fetal morbidity. Emergency caesarean section can be performed by converting labor epidural analgesia to surgical anesthesia by injecting high-dose short-acting local anesthetics through the epidural catheter. The effectiveness and the delay to obtain surgical anesthesia depends upon the protocol used. Data indicate that alkalinization of local anesthetics may shorten their onset of action and increase their effectiveness. This study investigates whether alkalinization of adrenalized lidocaine could increase the efficacy and decrease the delay of onset of surgical anesthesia via an indwelling epidural catheter, thus decreasing the necessity to resort to general anesthesia for emergency caesarean deliveries. METHODS: This study will be a bicentric, double-blind, randomized, controlled trial with two parallel groups of 66 women who require emergency caesarian deliveries and who have been receiving epidural labor analgesia. The number of subjects in groups will be unbalanced with a 2:1 ratio of experimental:control. In both groups, all eligible patients will have had an epidural catheter placed for labor analgesia with levobupicaine or ropivacaine. Patient randomization will occur when the decision is made by the surgeon that an emergency caesarean delivery is indicated. Surgical anesthesia will be obtained by injecting 20 mL of 2% lidocaine with epinephrine 1:200,000, or 10 mL 2% lidocaine with epinephrine 1:200,000 plus 2 mL sodium bicarbonate 4.2% (total of 12 mL). The primary outcome will be the rate of conversion to general anesthesia for failure of the epidural to provide adequate analgesia. This study will be powered to detect a 50% reduction in the incidence of general anesthesia, from 80 to 40%, with a confidence ratio of 90%. DISCUSSION: Sodium bicarbonate could be used to avoid general anesthesia for emergency caesarean deliveries by providing reliable and effective surgical anesthesia in women with pre-existing labor epidural catheters is promising. This randomized controlled trial seeks to determine the optimal local anesthetic mixture for converting epidural analgesia to surgical anesthesia for emergency caesarean sections. This may decrease the need for general anesthesia for emergency caesarian section, shorten the time to fetal extraction, and improve safety and patient satisfaction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05313256. Registered on 6 April 2022.

AICAR inhibits cancer cell growth and triggers cell-type distinct effects on OXPHOS biogenesis, oxidative stress and Akt activation.

The AMP-activated protein kinase agonist AICAR mimics a low intracellular energy state and inhibits the proliferation of cancer cells by different mechanisms, which may depend on the bioenergetic signature of these cells. AICAR can also stimulate mitochondrial biogenesis in myoblasts, neurons and HeLa cells. Yet, whether the reactivation of oxidative phosphorylation biogenesis by AICAR contributes to the growth arrest of cancer cells remains undetermined. To investigate this possibility, we looked at the impact of 24- and 48-hour treatments with 750 µM AICAR on human cancer cell lines (HeLa, DU145, and HEPG2), non-cancer cells (EM64, FM14, and HLF), embryonic cells (MRC5) and Rho(0) cells. We determined the bioenergetic profile of these cells and assessed the effect of AICAR on oxidative phosphorylation biogeneis, cell viability and cell proliferation, ROS generation, mitochondrial membrane potential and apoptosis induction. We also followed possible changes in metabolic regulators such as Akt and Hif1-α stabilization which might participate to the anti-proliferative effect of AICAR. Our results demonstrated a strong and cancer-specific anti-growth effect of AICAR that may be explained by three different modes according to cell type: the first mode included stimulation of the mitochondrial apoptotic pathway however with compensatory activation of Akt and upregulation of oxidative phosphorylation. In the second mode of action of AICAR Akt phosphorylation was reduced. In the third mode of action, apoptosis was activated by different pathways. The sensitivity to AICAR was higher in cells with a low steady-state ATP content and a high proliferation rate.

Local anesthetic 'in-situ' toxicity during peripheral nerve blocks: update on mechanisms and prevention.

PURPOSE OF REVIEW: Peripheral nerve blocks induce undesired side-effects linked to the toxicity of local anesthetics on neuron and myocytes via different cell targets. The effects of local anesthetics on these targets are now well known and summarized in this review. RECENT FINDINGS: Local anesthetic-induced local cell toxicity involved different pathways leading to cell death, necrosis and different factors closely associated with the clinical practice modulated this toxicity. High concentration and prolonged duration of local anesthetic administration are closely associated with severe lesions. SUMMARY: Phenotypic analyses revealed that local anesthetics could induce histological damage with lesions ranging from local to extreme in skeletal muscle. Metabolic alterations were also described involving sarcoplasmic reticulum and calcium dysregulation, alteration of mitochondrial physiology and of oxidative phosphorylation with associated overproduction of harmful reactive oxygen species, typically leading to apoptosis or necrosis. Biochemical and cell biology investigations now indicate that local anesthetics interact with different molecular targets in mammalian cells as respiratory chain complex I or the prosurvival kinase Akt. Functional dysfunction in both muscle and neuron remains to be investigated with caution in patients, as local anesthetic toxicity remains under-evaluated. Likewise, the use of adapted local anesthetics in patients with particular diseases and neuromuscular disorder could further reduce the risk of undesired effect.We need to improve our practice, and the optimization of our clinical protocol could prevent from these side-effects. Lastly, experimental studies highlight the preventive effects of antioxidant drugs or of recombinant human erythropoietin but the pharmacokinetic feature of such strategies remain to be evaluated.

Hemostatic Effects of Tranexamic Acid in Cesarean Delivery: An Ancillary Study of the TRAAP2 Study.

BACKGROUND: Fibrinolysis activation during delivery contributes to postpartum hemorrhage (PPH). Clot lysis time studied with the global fibrinolytic capacity device (GFC/LT) is a functional test which rapidly assesses fibrinolytic profile. Tranexamic acid (TXA) is an efficient antifibrinolytic therapy. METHODS: We prospectively studied fibrinolysis and coagulation in 33 women included in the TRAAP2 trial, which aimed to assess the impact of TXA in preventing PPH following a cesarean delivery. TXA or placebo was randomly administered after childbirth as part of the TRAAP2 trial's protocol. Fibrinolytic (GFC/LT, plasma concentration of fibrinolysis activators and inhibitors) and hemostatic parameters were assayed at three sample times (TREF [T-reference] after anesthesia, T15 and T120minutes after TXA, or placebo administration). RESULTS: All cesarean deliveries were elective. In the placebo group, the clot lysis time assessed with GFC/LT significantly decreased between TREF and T120, indicating an activated fibrinolysis (44 [interquartile range, IQR: 40-48] vs. 34 [IQR: 30-36] minutes, p<0.001). In both TXA and placebo groups, significant fluctuations of the plasmatic concentrations of fibrinolytic mediators were noticed over time, suggesting fibrinolysis activation. Clot lysis time measured by GFC/LT was significantly increased in women of the TXA group as compared with those in the placebo group at T15 (120 [120-120] vs. 36 [34-41] minutes, p<0.001) and T120minutes (113 [99-120] vs. 34 [30-36] minutes, p<0.001) after drug administration, indicating a decreased in fibrinolysis in those women. CONCLUSION: GFC/LT evidenced fibrinolysis activation during cesarean delivery, linked to a decrease in fibrinolytic inhibitors. GFC/LT revealed a significant antifibrinolytic effect of TXA compared with placebo.

Epidemiology and complications of anaesthesia in the French centres that participated to NECTARINE: A secondary analysis.

INTRODUCTION: Neonatal and infant anaesthesia are associated with a high risk of perioperative complications. The aim of the current study was to describe those risks in France using the French data from the NECTARINE study. MATERIAL AND METHODS: Data from the French centres that participated to the NECTARINE study were analysed. The primary goal of the study was the description of patients' characteristics, procedures and perioperative management and their comparison with the results of the European NECTARINE study. Secondary outcomes were the description of major perioperative complications and death. RESULTS: Overall, 926 procedures collected in 15 centres (all teaching hospitals) were analysed. Comparison between the French and European NECTARINE cohorts found few differences related to patients' characteristics and procedures. The rate of interventions for critical events (respiratory, haemodynamic, and metabolic) was similar between the two cohorts. Near-infrared spectroscopy monitoring was used in 12% of procedures. Nearly none of the thresholds for these interventions met the published standards. By day 30, complications (respiratory, haemodynamic, metabolic, renal, and liver failure) and death were observed in 14.4% [95% CI 11.6-16.4]% and 1.8% [95% CI 1.1-2.9] of cases, respectively. DISCUSSION: Although the health status of the patients in the French cohort was less severe, procedures, management and postoperative complications and mortality rates were similar to the European cohort. However, thresholds for interventions were often inadequate in both cohorts. Efforts should be undertaken to improve the knowledge and use of new monitoring devices in this population.

Chronic hypoxia-induced alterations in mitochondrial energy metabolism are not reversible in rat heart ventricles.

Chronic hypoxia alters mitochondrial energy metabolism. In the heart, oxidative capacity of both ventricles is decreased after 3 weeks of chronic hypoxia. The aim of this study was to evaluate the reversal of these metabolic changes upon normoxia recovery. Rats were exposed to a hypobaric environment for 3 weeks and then subjected to a normoxic environment for 3 weeks (normoxia-recovery group) and compared with rats maintained in a normoxic environment (control group). Mitochondrial energy metabolism was differentially examined in both left and right ventricles. Oxidative capacity (oxygen consumption and ATP synthesis) was measured in saponin-skinned fibers. Activities of mitochondrial respiratory chain complexes and antioxidant enzymes were measured on ventricle homogenates. Morphometric analysis of mitochondria was performed on electron micrographs. In normoxia-recovery rats, oxidative capacities of right ventricles were decreased in the presence of glutamate or palmitoyl carnitine as substrates. In contrast, oxidation of palmitoyl carnitine was maintained in the left ventricle. Enzyme activities of complexes III and IV were significantly decreased in both ventricles. These functional alterations were associated with a decrease in numerical density and an increase in size of mitochondria. Finally, in the normoxia-recovery group, the antioxidant enzyme activities (catalase and glutathione peroxidase) increased. In conclusion, alterations of mitochondrial energy metabolism induced by chronic hypoxia are not totally reversible. Reactive oxygen species could be involved and should be investigated under such conditions, since they may represent a therapeutic target.

Pre-operative peripheral intravenous cannula insertion failure at the first attempt in adults: Development of the VENSCORE predictive scale and identification of risk factors.

STUDY OBJECTIVE: Our objective was to develop a clinical scale (the VENSCORE) to predict pre-operative peripheral intravenous cannula (PIVC) insertion failure at the first attempt in adults. DESIGN: This was a prospective multicenter cohort study that included internal validation with bootstrapping. SETTING: The operating rooms of 14 hospitals in southern France from June 2016 to June 2018. PATIENTS: Consecutive adult patients aged 18 years or older were recruited upon arrival to the operating room, regardless of American Society of Anaesthesiology (ASA) physical status. INTERVENTIONS: PIVC insertion on arrival to the OR. MEASUREMENTS: PIVC insertion failure at the first attempt was the outcome of interest. Data collected included the number of PIVC insertion attempts and potential predictors of the risk of failure (including pre-operative patient characteristics and data relative to the procedure). Uni- and multivariable logistic analyses were performed. Based on these results, the VENSCORE scale was developed to predict the risk of failure of the first PIVC insertion. MAIN RESULTS: In total, 3394 patients were included, and 27 were excluded because of protocol violations. The PIVC insertion failure rate at the first attempt was 20.3%. Based on multivariable analysis, a history of difficult PIVC insertions, high-risk surgery, poor vein visibility, and moderate to poor vein palpability were identified as risk factors for insertion failure at the first attempt. The area under the curve of the predictive model was 0.82 (95% confidence interval: 0.80-0.84). A VENSCORE value of 0 points was associated with a failure rate of 7%, versus 97% for a score of 6. CONCLUSIONS: The four-item VENSCORE scale could be useful for prospectively identifying adults at risk of first PIVC insertion attempt failure.