Changing hemostatic management in post-partum hemorrhage.

Early and fast assessment of hemostasis during postpartum hemorrhage (PPH) is essential to allow early characterization of coagulopathy, estimate bleeding severity and improve outcome. During PPH, fibrinogen decrease occurs earlier than other coagulation factors deficiency and hypofibrinogenemia is an early marker of PPH severity of progression. With good evidence in the context of PPH, point-of-care viscoelastic (VET) hemostatic assays have been shown to provide rapid assessment of hemostatic disorders, low fibrinogen levels, and allow VET-guided fibrinogen replacement. Further studies are needed to define the thresholds for the other coagulation parameters.

Relationship between pre-incision Pupillary Pain Index and post-incision heart rate and pupillary diameter variation in children.

BACKGROUND: The Pupillary Pain Index is a recent pupillometric index designed to assess the level of analgesia under general anesthesia in children and adults. If analgesia is inadequate, acute nociceptive stimuli such as skin incision may induce significant hemodynamic disturbances. AIMS: Our aim was to investigate the potential relationship between pre-incision Pupillary Pain Index and heart rate increase following skin incision in children. METHODS: This was a prospective, non-randomized, registered pilot study. We included children undergoing surgery under general anesthesia. Pupillary Pain Index was assessed 2 min before skin incision. Then, heart rate maximal variation (ΔHR ) and pupillary diameter maximal variation (ΔPD ) in the minute following incision were recorded. Spearman coefficient was calculated to characterize the relationship between Pupillary Pain Index and ΔHR or ΔPD . Using receiver operating characteristic curve analysis, we also studied the predictive value of pre-incision Pupillary Pain Index for heart rate and pupillary diameter reactivity. RESULTS: 53 patients were included (10 ± 4 years, 40 ± 19 kg). There was a modest correlation between pre-incision Pupillary Pain Index and ΔHR (Spearman rs = 0.35 [0.05-0.57], p = .011), and between pre-incision Pupillary Pain Index and ΔPD (Spearman rs = 0.54 [0.33-0.71], p < .001). Regarding the predictive value of Pupillary Pain Index for heart rate or pupillary diameter reactivity, the corresponding areas under the receiver operating characteristic curves were 0.90 [0.82-0.99] and 0.78 [0.65-0.93], respectively. A threshold of Pupillary Pain Index <3 predicted the absence of heart rate reactivity at incision with a good performance (negative predictive value = 1). CONCLUSIONS: In children, pre-incision Pupillary Pain Index was moderately correlated with post-incision nociception. Pre-incision Pupillary Pain Index had good predictive performances for heart rate or pupillary diameter reactivity to skin incision. Pre-incision Pupillary Pain Index <3 might predict the absence of heart rate reaction to incision.

Effect of Different Concentrations of Propofol Used as a Sole Anesthetic on Pupillary Diameter: A Randomized Trial.

BACKGROUND: Pupillometry monitoring under general anesthesia is based on the assumption that pupillary diameter variations reflect the adequacy of the provided analgesia to the intensity of the nociceptive surgical stimulus. The accurate interpretation of pupillometric data requires establishing clearly what the expected baseline unstimulated pupillary diameter at each specific level of hypnosis is. Opioids decrease pupillary diameter in a dose-dependent fashion. In contrast, the effects of hypnotic drugs on pupillary diameter are not well known. Our aim was to describe the potential relationship between propofol predicted effect-site concentrations (Cets) ranging from 1 to 3 µg/mL and pupillary diameter. METHODS: Patients were randomized to receive propofol by target-controlled infusion at a predicted Cet of 1, 2, or 3 µg/mL (groups P1, P2, and P3, respectively). Pupillary diameter measurements were performed after 10 minutes of steady-state propofol infusion at the randomized Cet. No stimulation was performed during the study. Heart rate and bispectral index (BIS) were continuously recorded. RESULTS: Forty patients were included: (13, 14, and 13 in groups P1, P2, and P3, respectively). Mean pupillary diameter was 5.7 mm (1 mm) in group P1, 4.8 mm (1.3 mm) in group P2, and 3.3 mm (0.8 mm) in group P3. Propofol had a dose-dependent effect on pupillary diameter (linear regression R = 0.45, P < .001). Pupillary diameter was positively correlated with the BIS (Spearman r = 0.75 [95% confidence interval (CI), 0.54 to -0.87] P < .001). CONCLUSIONS: From 1 to 3 µg/mL of predicted Cet, propofol has a dose-dependent effect on pupillary diameter. Within this concentrations range, there is a positive correlation between BIS and pupillary diameter. The subcortical effect of propofol on pupillary diameter is correlated to its effect on the cortex. Studies assessing pupillary diameter as a marker of the nociception-antinociception balance should be performed in patients with a standardized depth of hypnosis.

Assessment of Coagulation by Thromboelastography During Ongoing Postpartum Hemorrhage: A Retrospective Cohort Analysis.

BACKGROUND: Rapid assessment of hemostasis during postpartum hemorrhage (PPH) is essential to allow characterization of coagulopathy, to estimate bleeding severity, and to improve outcome. Point of care (POC) coagulation monitors could be of great interest for early diagnosis and treatment of coagulation disorders in PPH. METHODS: Women with ongoing PPH >500 mL who clinically required an assessment of coagulation with thromboelastography (TEG) were included. The primary aim of this retrospective observational cohort study was to assess the predictive accuracy of TEG parameters for the diagnosis of coagulation disorders (hypofibrinogenemia ≤2 g/L, thrombocytopenia ≤80,000/mm, prothrombin ratio ≤50%, or activated partial thromboplastin time ratio ≥1.5) during PPH. The analyzed TEG parameters were Kaolin-maximum amplitude (K-MA), Kaolin-maximum rate of thrombus generation using G (K-MRTGG), functional fibrinogen-maximum amplitude (FF-MA), and functional fibrinogen-maximum rate of thrombus generation using G (FF-MRTGG). Secondary aims of this study were (1) comparison of the time delay between classical parameters and velocity curve-derived parameters (K-MA versus K-MRTGG and FF-MA versus FF-MRTGG) and (2) evaluation of the accuracy of TEG parameters to predict severe hemorrhage estimated by calculated blood losses. RESULTS: Ninety-eight patients were included with 98 simultaneous TEG analyses and laboratory assays. All parameters had an excellent predictive performance. For the Kaolin assay, no significant difference was evidenced between K-MA and K-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm (respective area under the curve [AUC], 0.970 vs 0.981). For the functional fibrinogen assay, no significant difference was evidenced between FF-MA and FF-MRTGG for the predictive performance for hypofibrinogenemia ≤2 g/L (respective AUC, 0.988 vs 0.974). For both assays, the time to obtain results was shorter for the velocity parameters (K-MRTGG: 7.7 minutes [2.4 minutes] versus K-MA: 24.7 minutes [4.2 minutes], P < .001; FF-MRTGG: 2.7 minutes [2.7 minutes] versus FF-MA: 14.0 minutes [4.3 minutes], P < .001). All TEG parameters derived from the Kaolin and functional fibrinogen assays and Clauss fibrinogen were significantly predictive of severe PPH >2500 mL. CONCLUSIONS: During PPH, when coagulation assessment is indicated, TEG provides a rapid and reliable detection of hypofibrinogenemia ≤2 g/L and/or thrombocytopenia ≤80,000/mm. No difference in performance was evidenced between the velocity-derived parameters (K-MRTGG and FF-MRTGG) and the classical parameters (K-MA and FF-MA). However, velocity-derived parameters offer the advantage of a shorter time to obtain results: FF-MRTGG parameter is available within ≤5 minutes. POC assessment of hemostasis during PPH management may help physicians to diagnose clotting disorders and to provide appropriate hemostatic support.

Pupillary Pain Index Changes After a Standardized Bolus of Alfentanil Under Sevoflurane Anesthesia: First Evaluation of a New Pupillometric Index to Assess the Level of Analgesia During General Anesthesia.

BACKGROUND: The pupillary pain index (PPI) is a novel pupillometric index, designed to assess intraoperative analgesia. It is based on the evaluation of the pupillary response to electrical stimuli of increasing intensity. It ranges from 1 (low level of pupillary reactivity, high level of analgesia) to 10 (high level of pupillary reactivity, low level of analgesia). In this first evaluation of the PPI, our objective was to investigate the PPI changes after a bolus of 10 µg·kg(-1) of alfentanil in children under sevoflurane general anesthesia. METHODS: After ethics committee approval and informed consent, 20 healthy children (9 ± 5 years) undergoing elective surgery under general anesthesia were included in this prospective, open, registered pilot study (NCT02646592). Anesthetic induction was standardized with sevoflurane 6% and propofol 1 mg·kg(-1). After tracheal intubation, sevoflurane concentration was maintained at 2% for 10 minutes. A first PPI measurement was performed (PPI-1), and a bolus of 10 µg·kg(-1) was administered. Two minutes after this bolus, a second PPI measurement was performed (PPI-2). Heart rate, blood pressure, and bispectral index were recorded before and after each PPI measurement. Resting pupillary diameter was recorded before each PPI measurement. PPI scores before and after the bolus of alfentanil were compared using a Wilcoxon signed rank test. RESULTS: PPI scores decreased after administration of a bolus of alfentanil (median difference: -3 [95% confidence interval, -4 to -2]). The median (quartiles) of PPI-1 (baseline, before alfentanil) was 6 (4, 7), and the median (quartiles) of PPI-2 (after alfentanil) was 2 (2, 3) (P < .001). No difference was found in resting pupillary diameter before PPI-1 and PPI-2 (2.2 ± 0.2 and 2.2 ± 0.3 mm, respectively; P = .86). There were no significant changes in heart rate or blood pressure after PPI measurements (P = .46 and .49, respectively). Bispectral index was slightly increased after PPI measurements (P = .01; mean bispectral index increase <5%). No withdrawal movements occurred during PPI measurements. CONCLUSIONS: There was a significant decrease in PPI after alfentanil administration. The results of this pilot study suggest that PPI score decreases when the level of analgesia increases. PPI measurement was not associated with a clinical or hemodynamic nociceptive response. This new index might provide useful information to individually adapt opioid administration before nociceptive stimuli under general anesthesia.

EEG profiles during general anesthesia in children: A comparative study between sevoflurane and propofol.

BACKGROUND: In this prospective study, we describe the electroencephalographic (EEG) profiles in children anesthetized with sevoflurane or propofol. METHODS: Seventy-three subjects (11 years, range 5-18) were included and randomly assigned to two groups according to the anesthetic agent. Anesthesia was performed by target-controlled infusion of propofol (group P) or by sevoflurane inhalation (group S). Steady-state periods were performed at a fixed randomized concentration between 2, 3, 4, 5, and 6 µg.ml-1 of propofol in group P and between 1, 2, 3, 4, and 5% of sevoflurane in group S. Remifentanil was continuously administered throughout the study. Clinical data, Bispectral Index (BIS), and raw EEG were continuously recorded. The relationship between BIS and anesthetic concentrations was studied using nonlinear regression. For all steady-state periods, EEG traces were reviewed to assess the presence of epileptoid signs, and spectral analysis of raw EEG was performed. RESULTS: Under propofol, BIS decreased monotonically and EEG slowed down as concentrations increased from 2 to 6 µg.ml-1 . Under sevoflurane, BIS decreased from 0% to 4% and paradoxically rose from 4% to 5% of expired concentration: this increase in BIS was associated with the occurrence of fast oscillations and epileptoid signs on the EEG trace. Propofol was associated with more delta waves and burst suppression periods compared to sevoflurane. CONCLUSION: Under deep anesthesia, the BIS and electroencephalographic profiles differ between propofol and sevoflurane. For high concentrations of sevoflurane, an elevated BIS value may be interpreted as a sign of epileptoid patterns or EEG fast oscillations rather than an insufficient depth of hypnosis.

Influence of Depth of Hypnosis on Pupillary Reactivity to a Standardized Tetanic Stimulus in Patients Under Propofol-Remifentanil Target-Controlled Infusion: A Crossover Randomized Pilot Study.

BACKGROUND: Pupillometry allows the measurement of pupillary diameter variations in response to nociceptive stimuli. This technique has been used to monitor the balance between analgesia and nociception. Under general anesthesia, the amplitude of pupillary dilation is related to the amount of administered opioids. The objective of this study was to determine whether at a constant infusion rate of opioids, the pupillary response was influenced by depth of hypnosis assessed by the bispectral index (BIS). METHODS: Twelve patients (14-20 years) anesthetized for orthopedic surgery were included. Under propofol-remifentanil target-controlled infusion, remifentanil effect site target concentration was fixed at 1 ng/mL. Two measures of pupillary reflex dilation were performed on each patient in a randomized order: one at BIS 55 and one at BIS 25. These levels of BIS were obtained by adjusting propofol target concentration and maintained for 10 minutes before each measure. For each measure, we applied a standardized tetanic stimulation on the patient's forearm (60 mA, 100 Hz, 5 seconds). All measures were performed before the beginning of surgery. RESULTS: Pupillary dilation was significantly greater at BIS 55 than at BIS 25: 32.1% ± 5.3% vs 10.4% ± 2.5% (mean difference estimate [95% confidence interval]: 21.8% [12.9-30.6], P < .001), without carryover effect (P = .30) nor period effect (P = .52). Hemodynamic parameters and BIS were not modified by the stimulation. CONCLUSIONS: In patients receiving a constant infusion of remifentanil at a target concentration of 1 ng/mL, pupillary dilation after a standardized tetanic stimulation was influenced by depth of hypnosis assessed by the BIS.

Pupillary reflex dilation in response to incremental nociceptive stimuli in patients receiving intravenous ketamine.

Pupillometry is a non-invasive monitoring technique, which allows dynamic pupillary diameter measurement by an infrared camera. Pupillary diameter increases in response to nociceptive stimuli. In patients anesthetized with propofol or volatile agents, the magnitude of this pupillary dilation is related to the intensity of the stimulus. Pupillary response to nociceptive stimuli has never been studied under ketamine anesthesia. Our objective was to describe pupillary reflex dilation after calibrated tetanic stimulations in patients receiving intravenous ketamine. After written consent, 24 patients of our pediatric burn care unit were included. They received an oral morphine premedication (0.3 mg kg-1) 1 h before their scheduled daily dressing change. Just before the procedure, they received 1 mg kg-1 of intravenous ketamine. Two minutes after this bolus, tetanic stimulations of incremental intensities were performed on the arm of each patient (5-10-20-30-40-60 mA, 60 s interval between stimulations). Pupillary diameter, heart rate and movements were recorded before and after each stimulation. Tetanic stimulations were associated with changes in pupillary diameter and heart rate. The magnitude of these changes was significantly influenced by the intensity of stimulation (ANOVA for repeated measures, p < 0.001). Movement was associated with a 32% increase in diameter (ROC curves, AUC 0.758) with 65% sensitivity and 77% specificity. In children, pupillary reflex dilation to nociceptive stimuli persists under deep sedation obtained with 1 mg kg-1 of intravenous ketamine combined with a 0.3 mg kg-1 oral morphine premedication, and its magnitude depends on the intensity of the stimulation. Our results confirm that pupillometry could be a relevant way to monitor nociception in anaesthetised subjects, including those receiving ketamine. Trial registration clinicaltrials.gov, NCT 02648412.

Pupillometry-guided Intraoperative Remifentanil Administration versus Standard Practice Influences Opioid Use: A Randomized Study.

BACKGROUND: Pupillometry has shown promising results for assessing nociception in anesthetized patients. However, its benefits in clinical practice are not demonstrated. The aim of this prospective randomized study was to evaluate the impact of intraoperative pupillometry monitoring on perioperative opioid consumption in major gynecologic surgery. METHODS: After receiving ethics committee approval and written consent of patients, American Society of Anesthesiologists status I to II women undergoing gynecologic surgery were included in this single-blinded, prospective, parallel-arm randomized study. General anesthesia was standardized with propofol-remifentanil target-controlled infusion. Patients were randomly assigned into two groups. In the pupillometry group, remifentanil administration was guided by pupillary diameter changes. In the standard group, remifentanil administration was left to the discretion of the anesthesiologist. The primary outcome was intraoperative remifentanil consumption. RESULTS: Fifty-five patients were analyzed. Remifentanil consumption was markedly decreased in the pupillometry group (3.8 [3.4 to 4.8 µg · kg · h] vs. 7.9 µg · kg · h [6.5 to 9.0 µg · kg · h] in the standard group; difference = 4.2 µg · kg · h [95% CI, 3.0 to 5.3 µg · kg · h]; P < 0.001). Cumulative 0- to 12-h morphine consumption was reduced in the pupillometry group (two-way repeated measures ANOVA 0.3 ± 0.1 vs. 0.4 ± 0.2 mg/kg; P = 0.048). A telephone survey 3 months after surgery revealed that 15 of 29 patients in the standard group still experienced procedure-related pain versus 3 of 23 in the pupillometry group (chi-square P = 0.037). No adverse events associated with pupillometry were observed during the study. CONCLUSIONS: The use of pupillometry to guide intraoperative analgesia reduced intraoperative remifentanil consumption and postoperative morphine requirements. The possible consequences of decreasing intraoperative remifentanil in terms of chronic pain require further investigation.

Bispectral index under propofol anesthesia in children: a comparative randomized study between TIVA and TCI.

BACKGROUND: In children, only a few studies have compared different modes of propofol infusion during a total intravenous anesthesia (TIVA) with propofol and remifentanil. The aim of this study was to compare Bispectral Index (BIS) profiles (percentage of time spent at adequate BIS values) between four modes of propofol infusion: titration of the infusion rate on clinical signs (TIVA0 ), titration of the infusion rate on the BIS (TIVABIS ), target controlled infusion (TCI) guided by the BIS either with the Kataria model (TCI KBIS ) or the Schnider model (TCI SBIS ). METHODS: Sixty-six children (aged from 4 to 14 years) were prospectively randomized into one of the four groups. In the TIVA0 group, the anesthesiologist was blinded to the BIS. In each group, the percentage of time with adequate BIS values (45-55), the bias, and imprecision were calculated. RESULTS: The propofol consumption was similar in the four groups. During the maintenance phase, the percentage of time spent in the targeted BIS range was significantly lower in the TIVA0 group compared to the three other groups (TIVA0 : 31% ± 22, TIVABIS : 59% ± 17, TCI KBIS : 53% ± 12, TCI SBIS : 56% ± 17). The bias was not statistically different between the four groups, but the imprecision was larger for the TIVA0 group. Compared to the Kataria model, the Schnider model was associated with shorter time delay to reach the desired BIS, to eyes opening, and to tracheal extubation. CONCLUSIONS: Propofol administration using manual infusion guided by clinical signs was associated with higher risks of over- or underdosage when compared to BIS-guided administrations. When propofol infusion was guided by the BIS, no major difference was found between TIVA and TCI (either with the Kataria or the Schnider model). This study highlights the need of a pharmacodynamic feedback during propofol anesthesia in children.

Nonuniversality in the pinch-off of yield stress fluids: role of nonlocal rheology.

The pinch-off behavior of yield stress fluids is investigated using droplet and liquid-bridge breakup experiments. Contrary to expectations, the neck thinning behavior depends strongly on the way the breakup experiment is carried out. This nonuniversal behavior can be explained through an analysis of the thinning dynamics as well as the shapes of the fluid necks. Recent nonlocal models for the rheology of yield stress fluids are found to be compatible with the results presented.

Pain monitoring in anesthetized children: first assessment of skin conductance and analgesia-nociception index at different infusion rates of remifentanil.

BACKGROUND: Analgesia and nociception can not be specifically monitored during general anesthesia. Movement of the patient or hemodynamic variations are usually considered as symptoms of insufficient analgesia. The measure of skin conductance (SC) allows an assessment of peripheral sympathetic activity. The analgesia-nociception index (ANI) provides an evaluation of the parasympathetic activity based on heart rate variability. These two non-invasive monitors might allow a better assessment of perioperative nociception. OBJECTIVES: Describe the profiles of SC and ANI after a standardized nociceptive stimulation, in anesthetized children, at different infusion rates of remifentanil. MATERIALS/METHODS: For this pilot study, 12 children (8.4 ± 5 years) scheduled for middle-ear surgery were anesthetized with desflurane to maintain a bispectral index at 50. Remifentanil was used for analgesia, at an initial infusion rate of 0.2 µg·kg(-1) ·min(-1) . Remifentanil infusion rate was then decreased: Five steady-state periods of 10 min were obtained at 0.2, 0.16, 0.12, 0.08, and 0.04 µg·kg(-1) ·min(-1) . At the end of each period, a standardized tetanic stimulation was applied to the patient. Variations in heart rate, blood pressure, SC, and ANI were recorded before and after each stimulation. RESULTS: After the stimulation, ANI was significantly decreased compared with prestimulation values for all remifentanil infusion rates. This decrease was greater at 0.04 µg·kg(-1) ·min(-1) than at the other infusion rates. SC, heart rate, and blood pressure were not modified by the stimulations, whatever the dose of remifentanil. CONCLUSION: ANI might provide a more sensitive assessment of nociception in anesthetized children than hemodynamic parameters or skin conductance.

Epileptogenic effect of sevoflurane: determination of the minimal alveolar concentration of sevoflurane associated with major epileptoid signs in children.

BACKGROUND: Sevoflurane has become the gold standard for inhalation induction in children. However in children as in adults, epileptiform electroencephalographic signs have been described under high concentrations of sevoflurane. The aim of this study was to determine the minimal alveolar concentration (MAC) of sevoflurane associated with the occurrence of major epileptiform signs (MES) in 50% children under steady-state conditions. The MAC of MES (MAC MES) was determined in 100% oxygen and with the addition of 50% nitrous oxide or after the injection of alfentanil (ALFENTA). METHODS: Seventy-nine children (3-11 yr), undergoing elective surgery and premedicated with hydroxyzine were included. After induction by inhalation and tracheal intubation, a 10-min period with a stable expired fraction of sevoflurane was obtained. The MES were defined as rhythmic polyspikes or epileptiform discharges. Electroencephalographic recordings were blindly analyzed by two independent experts. The MAC MES were determined by the Dixon method: the concentration of sevoflurane was determined by the result from the previous patient: increase of 0.2% if MES were absent or decrease of 0.2% if MES were present. Three consecutive series were performed: (1) in 100% oxygen (MAC MESO2); (2) in 50% oxygen and 50% nitrous oxide (MAC MESN2O); and (3) in 100% oxygen with a bolus of alfentanil (MAC MESALFENTA). RESULTS: The MAC MESO2 was 4.3±0.1% (mean±SD), the MAC MESN2O and the MAC MESALFENTA were higher, respectively: 4.6±0.2% (P=0.01) and 4.6±0.2% (P=0.02). CONCLUSIONS: In children premedicated with hydroxyzine, the MAC MES of sevoflurane calculated in 100% O2 corresponded to 1.75 surgical MAC. In addition, our results have demonstrated a moderate effect of nitrous oxide and alfentanil in raising the threshold of MES.

Analgesia Nociception Index-Guided Remifentanil versus Standard Care during Propofol Anesthesia: A Randomized Controlled Trial.

The clinical benefits to be expected from intraoperative nociception monitors are currently under investigation. Among these devices, the Analgesia Nociception-Index (ANI) has shown promising results under sevoflurane anesthesia. Our study investigated ANI-guided remifentanil administration under propofol anesthesia. We hypothesized that ANI guidance would result in reduced remifentanil consumption compared with standard management. This prospective, randomized, controlled, single-blinded, bi-centric study included women undergoing elective gynecologic surgery under target-controlled infusion of propofol and remifentanil. Patients were randomly assigned to an ANI or Standard group. In the ANI group, remifentanil target concentration was adjusted by 0.5 ng mL-1 steps every 5 min according to the ANI value. In the Standard group, remifentanil was managed according to standard practice. Our primary objective was to compare remifentanil consumption between the groups. Our secondary objectives were to compare the quality of anesthesia, postoperative analgesia and the incidence of chronic pain. Eighty patients were included. Remifentanil consumption was lower in the ANI group: 4.4 (3.3; 5.7) vs. 5.8 (4.9; 7.1) µg kg-1 h-1 (difference = -1.4 (95% CI, -2.6 to -0.2), p = 0.0026). Propofol consumption was not different between the groups. Postoperative pain scores were low in both groups. There was no difference in morphine consumption 24 h after surgery. The proportion of patients reporting pain 3 months after surgery was 18.8% in the ANI group and 30.8% in the Standard group (difference = -12.0 (95% CI, -32.2 to 9.2)). ANI guidance resulted in lower remifentanil consumption compared with standard practice under propofol anesthesia. There was no difference in short- or long-term postoperative analgesia.

Impact of Lacticaseibacillus rhamnosus GG on the Emulsion Stability of Raw Milk.

Lactic acid bacteria (LAB) have been studied for several decades to understand and determine their mechanism and interaction within the matrix into which they are introduced. This study aimed to determine the spatial distribution of Lacticaseibacillus rhamnosus GG (LGG) in a dairy matrix and to decipher its behaviour towards milk components, especially fat globules. Two strains of this widely studied bacterium with expected probiotic effects were used: LGG WT with pili on the cell surface and its pili-depleted mutant-LGG ΔspaCBA-in order to determine the involvement of these filamentous proteins. In this work, it was shown that LGG ΔspaCBA was able to limit creaming with a greater impact than the wild-type counterpart. Moreover, confocal imaging evidenced a preferential microbial distribution as aggregates for LGG WT, while the pili-depleted strain tended to be homogenously distributed and found as individual chains. The observed differences in creaming are attributed to the indirect implication of SpaCBA pili. Indeed, the bacteria-to-bacteria interaction surpassed the bacteria-to-matrix interaction, reducing the bacterial surface exposed to raw milk. Conversely, LGG ΔspaCBA may form a physical barrier responsible for preventing milk fat globules from rising to the surface.

Management of severe thermal burns in the acute phase in adults and children.

OBJECTIVES: To provide recommendations to facilitate the management of severe thermal burns during the acute phase in adults and children. DESIGN: A committee of 20 experts was asked to produce recommendations in six fields of burn management, namely, (1) assessment, admission to specialised burns centres, and telemedicine; (2) haemodynamic management; (3) airway management and smoke inhalation; (4) anaesthesia and analgesia; (5) burn wound treatments; and (6) other treatments. At the start of the recommendation-formulation process, a formal conflict-of-interest policy was developed and enforced throughout the process. The entire process was conducted independently of any industry funding. The experts drew up a list of questions that were formulated according to the PICO model (Population, Intervention, Comparison, and Outcomes). Two bibliography experts per field analysed the literature published from January 2000 onwards using predefined keywords according to PRISMA recommendations. The quality of data from the selected literature was assessed using GRADE® methodology. Due to the current paucity of sufficiently powered studies regarding hard outcomes (i.e. mortality), the recommendations are based on expert opinion. RESULTS: The SFAR guidelines panel generated 24 statements regarding the management of acute burn injuries in adults and children. After two scoring rounds and one amendment, strong agreement was reached for all recommendations. CONCLUSION: Substantial agreement was reached among a large cohort of experts regarding numerous strong recommendations to optimise the management of acute burn injuries in adults and children.

The relationship between bispectral index and propofol during target-controlled infusion anesthesia: a comparative study between children and young adults.

BACKGROUND: In this prospective study, we compared the relationship between propofol concentrations and bispectral index (BIS) in children versus young adults anesthetized with target-controlled infusion (TCI) of propofol. METHODS: Forty-five prepubertal subjects (children) and 45 postpubertal subjects (adults) were studied. All patients were anesthetized with TCI of propofol, based on the Kataria et al.'s model for children and on the Schnider et al.'s model for adults. All data from the BIS and the TCI system were continuously recorded using Rugloop software. Remifentanil was continuously administered throughout the study (0.25 microg x kg(-1) x min(-1)). In all patients, after the end of surgery, a 12-min period with a stable target plasma concentration (Ct) of propofol, randomly assigned at 2, 3, 4, 5, and 6 microg/mL, was performed. In addition, in most of the patients, another 12-min period was performed during which the BIS was targeted at 50 +/- 5. After each 12-min steady-state period, the Ct and BIS were noted and the plasma concentration of propofol was measured (Cm). The Ct and Cm corresponding to half maximal effect (BIS(50)) was determined by the Hill equation, and by targeting BIS at 50. RESULTS: In children, as in adults, BIS values were highly correlated with the corresponding Ct or Cm of propofol following classical E(max) dose-response curves. The ECt(50) and the ECm(50), derived from the dose-response curves, were higher in children than in adults: ECm(50): 4.0 (3.6-4.5) microg/mL vs 3.3 (3.0-3.7) microg/mL [mean (95% CI)], P < 0.001; as well were the Ct and Cm clinically obtained when BIS was targeted at 50 (Cm(50): 4.3 +/- 1.1 microg/mL vs 3.4 +/- 1.2 microg/mL, (mean +/- SD) P < 0.05, children versus adults). Cm was generally under-estimated by the Ct, and the bias was higher in children than in adults: 2.6 +/- 2.6 microg/mL vs 1.7 +/- 1.6 microg/mL (P = 0.05). CONCLUSIONS: The good relationship between propofol and BIS demonstrated in children as in adults suggested a slightly lower sensitivity to propofol in children. As the predictability of plasma propofol concentrations with the classical pharmacokinetic/pharmacodynamic models is limited in children, a cerebral pharmacodynamic feedback, such as BIS, may be useful in this population.

Comparison of MSC properties in two different hydrogels. Impact of mechanical properties.

Once articular cartilage is damaged, it has poor ability to heal. At present, alginate-based hydrogels have 3D-dimensional physical structures with great potential for applications in carilage tissue engineering. For osteochondral defect, it will be necessary to use stratified scaffold to mimic zonal organization of cartilage. This study aims to compare the characteristics of alginate (Alg)/hyaluronic acid (HA) hydrogels which will mimic cartilage with alginate (Alg)/hydroxyapatite (Hap) hydrogels which will mimic subchondral bone. In this work, we fabricated the 3D-Alg/HA and Alg/Hap hydrogel scaffolds by the original spraying method. From the physical-mechanical properties, we compared mechanical behaviour of Alg/HA and Alg/Hap hydrogel scaffolds, which were examined using indentation testing and viscosity behaviour. This results showed that the Alg/Hap hydrogels exhibited a relative high mechanical strength, as well as the viscosity of Alg/Hap hydrogels is slight slower than Alg/HA hydrogels. However, autoclaving has more deleterious effect on the mechanical and viscosity properties of Alg/HA and Alg/Hap hydrogels. Cytotoxicity was evaluated through the culture of hydrogel beads-laden Wharton's jelly mesenchymal stem cells (WJ-MSC). In addition, the chondrogenic differentiation of WJ-MSC encapsulated into Alg/HA and Alg/Hap hydrogels were performed by histological analyzing during 30 days of culture. From these results, the percentage of living cells for Alg/Hap is significantly higher than Alg/HA, which also is associated with the results of shear viscosity. Both of hydrogels exhibited differentiate into chondrocyte matrix as collagen and proteoglycans. In conclusion, Alg/Hap hydrogels presented better mechanical property, cytocompatibility and differentiation characteristics than Alg/HA hydrogels.