Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review.

Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

Differential frontal alpha oscillations and mechanisms underlying loss of consciousness: a comparison between slow and fast propofol infusion rates.

Mechanisms underlying loss of consciousness following propofol administration remain incompletely understood. The objective of this study was to compare frontal lobe electroencephalography activity and brainstem reflexes during intravenous induction of general anaesthesia, in patients receiving a typical bolus dose (fast infusion) of propofol compared with a slower infusion rate. We sought to determine whether brainstem suppression ('bottom-up') predominates over loss of cortical function ('top-down'). Sixteen ASA physical status-1 patients were randomly assigned to either a fast or slow propofol infusion group. Loss of consciousness and brainstem reflexes were assessed every 30 s by a neurologist blinded to treatment allocation. We performed a multitaper spectral analysis of all electroencephalography data obtained from each participant. Brainstem reflexes were present in all eight patients in the slow infusion group, while being absent in all patients in the fast infusion group, at the moment of loss of consciousness (p = 0.010). An increase in alpha band power was observed before loss of consciousness only in participants allocated to the slow infusion group. Alpha band power emerged several minutes after the loss of consciousness in participants allocated to the fast infusion group. Our results show a predominance of 'bottom-up' mechanisms during fast infusion rates and 'top-down' mechanisms during slow infusion rates. The underlying mechanisms by which propofol induces loss of consciousness are potentially influenced by the speed of infusion.

Prevalence of Spasticity and Postural Patterns in the Upper Extremity Post Stroke.

INTRODUCTION: A high number of patients with stroke develop upper extremity spasticity, causing abnormal postures and patterns. These alterations limit the use of arm in functional activities and affect social participation. AIM: To determine the prevalence of spasticity and postural patterns of the upper extremity post stroke. MATERIALS AND METHODS: A cross-sectional descriptive design was used with a prospective follow-up. The sample included 136 patients. The study included 3 measuring times; at 10 days (T1), applying a record with sociodemographic-clinical data, the evaluation of muscle tone in the elbow and wrist and the postural patterns of the UE, and at 3 months (T2) and 12 months (T3) post stroke, re-evaluating tone and patterns. Prevalence was calculated through the one-sample chi-squared (χ2) test followed by inspection of the standardized residuals (z) in each cell. The Kappa coefficient evaluated the degree of agreement in elbow and wrist tone. RESULTS: The prevalence of spasticity in the elbow was 37.5% at T1, 57.4% at T2, and 57.4% at T3. At each time there was a high degree of agreement between elbow and wrist tone. Patients developed increased elbow tone between T1 and T2, with maintained tone between T2 and T3. Postural pattern III was the most prevalent according to Hefter's classification. CONCLUSION: The prevalence of spasticity in the elbow and wrist increases between 10 days and 3 months post stroke, and is maintained between 3 and 12 months. The onset of spasticity occurs in almost half of patients during the first 10 days post stroke. Postural pattern III according to Hefter's classification presented the greatest prevalence in the spastic UE.

[Inherited bleeding disorders in adolescents with excessive menstrual bleeding. Should we evaluate the fibrinolytic pathway?] / Trastornos hereditarios de la coagulación en adolescentes con sangrado menstrual excesivo, ¿debemos evaluar la vía fibrinolítica?

INTRODUCTION: Heavy Menstrual Bleeding (EMB) is a frequent problem in adolescence. The prevalence of inherited bleeding disorders (IBD) as a cause of EMB is not well established and the involvement of fibri nolytic pathway defects has been poorly explored. OBJECTIVE: To determine the prevalence of IBD and fibrinolysis defects in adolescents with EMBs. PATIENTS AND METHOD: 93 adolescents (11 to 18 years old) were included. Personal and family history of bleeding were obtained through a standard ized questionnaire. The following lab tests were performed: prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor quantification, and platelet count and function. Those patients who were not diagnosed with IBD were further evaluated with clot lysis time assay. RESULTS: 41 patients (44%) were diagnosed as IBD (Von Willebrand disease n = 28, platelet func tion defects n=8, mild hemophilia n = 5. Decreased clot lysis time was found in 31 patients. 54% of patients diagnosed with IBD had EMB as the first hemorrhagic manifestation. CONCLUSION: These results support the need to evaluate the coagulation process, including the fibrinolytic pathway in the study of adolescents with EMB.

Neural inertia and differences between loss of and recovery from consciousness during total intravenous anaesthesia: a narrative review.

Most anaesthetists using target-controlled infusion systems will have observed that the calculated effect-site concentration at loss of consciousness is usually higher than the concentration at emergence. Inertia is the ability of biological systems to keep a functional state at rest or in activity and is an active process of resistance to change in state. Hysteresis is a phenomenon whereby the value of a physical property lags behind changes in the effect that is causing it and this is also seen in anaesthesia pharmacology. Recently, a phenomenon called neuronal inertia has been proposed when trying to explain the resistance observed to changes in consciousness induced by general anaesthesia, independent of drug kinetics. This review discusses the existence of this phenomenon and the conceptual and practical impact it may have on induction and recovery from general anaesthesia.

Trends of maxillofacial trauma: An update from the prospective register of a multicenter study in emergency services of Chile.

BACKGROUND: Determine the behavior of the maxillofacial trauma of adults treated in 3 tertiary care centers in the central zone of Chile. MATERIAL AND METHODS: descriptive, cross-sectional, multicenter study, based on the prospective records of maxillofacial trauma cases attended between May 2016 and April 2017 by dental and maxillofacial clinical teams of Adult Emergency Units of hospitals Dr. Sótero del Río (metropolitan region), Carlos Van Buren and Dr. Gustavo Fricke (region V). Age, sex, date of occurrence, type of trauma according to ICD-10, etiology, legal medical prognosis and associated injuries were recorded, stratifying by sex and age. Chi square and unpaired Wilcoxon tests were used to compare by groups. RESULTS: 2.485 cases and 3.285 injuries were investigated. The male: female ratio was 1.7: 1 with age under 30 predominant, followed by older adults. Variability was observed in the yearly, weekly and daily presentation. The highest frequencies were in January and September, weekends and at night. The main etiologies were violence (42.3%), falls (13.1%) and road traffic crashes (12.9%) with differences by age and sex (p <0.05). 31,9% of the injuries occurred in hard tissue, being fractures in nasal bones predominant (S02.2). CONCLUSIONS: the profile of the maxillofacial trauma in Chile seems to be mixed by age, affecting young people and the elderly. The male sex predominates; the main cause, which varies by age group, is violence. Their surveillance is possible from hospital emergency records.

Evidence of hysteresis in propofol pharmacodynamics.

It is commonly assumed that loss of responsiveness and recovery of responsiveness occur at similar concentrations of propofol. However, the 'conscious' and 'anaesthetised' conditions produced by general anaesthetics may behave as two bistable states. We hypothesised that loss of responsiveness and recovery of responsiveness occur at different propofol concentrations. Propofol was administered to 19 healthy volunteers by effect-site target-controlled infusion using increasing and decreasing stable concentration steps of 7 min. Propofol serum concentrations were measured from venous blood samples at the end of each 7-min step. A long step of 14 min was performed at loss of responsiveness. At this step, propofol concentrations were measured at 7 and 14 min. Propofol concentrations measured at loss of responsiveness and recovery of responsiveness were 2.6 (1.2-4.7) µg.ml-1 and 1.6 (0.6-3.3) µg.ml-1 , respectively (p < 0.001). Propofol plasma concentration and the corresponding bispectral index values measured at minute 7 and minute 14 of the long step performed at loss of responsiveness were 2.6 (1.2-4.7) vs. 2.6 (1.3-4.3) at recovery of responsiveness, (p = 0.96) and 61.2 (49.0-77.0) vs. 58.4 (45.0-74.0), (p = 0.058), respectively. Loss of responsiveness and recovery of responsiveness appear to occur at different propofol concentrations. However, it is possible that, if equilibration was not achieved between plasma and effect-sites at the end of each 7-min step, the higher concentrations found at loss of responsiveness compared with those observed during recovery of responsiveness could be explained by a possible bias in estimations of the effect-site concentrations of propofol by the Schnider model, rather than neural inertia.

[Gender differences in health-related quality of life of Chilean adolescent students]. / Diferencias de género en la calidad de vida relacionada con la salud en adolescentes escolarizados chilenos.

BACKGROUND: Health-related quality of life (HRQOL) refers to individuals' perception of their subjective well-being, considering various aspects of their life and the impact on their health. AIM: To analyze gender differences in the HRQOL of adolescent students in Chile, by age, type of school attended, and area of residence. MATERIAL AND METHODS: Analytical cross-sectional study conducted in a population of 5th and 12th grade students attending municipal, subsidized and private schools in 11 regions of the country. HRQOL was assessed with the KIDSCREEN-52, an instrument that has been previously adapted and validated in Chile. The database obtained from that adaption and validation process was analyzed. RESULTS: In total, 7,910 students (median age 14 years, 53% female) completed the questionnaire. Compared to males, females had lower HRQOL scores in most of the KIDSCREEN-52 dimensions. However, males were more likely to have lower scores in the “Peers and Social Support” and “School Environment” dimensions. These differences remained valid when the sample was stratified by age, type of school, and area of residence were analyzed. CONCLUSIONS: This study supports the existence of inequalities in the self-perceived HRQOL of Chilean adolescent students. The existing differences are not only related to gender but are also evident when stratifying by type of school attended.

[Psychometric properties of the quality of life questionnaire health related KIDSCREEN-27 in Chilean adolescents]. / Propiedades psicométricas del cuestionario de calidad de vida relacionada con la salud KIDSCREEN-27 en adolescentes chilenos.

BACKGROUND: KIDSCREEN-52, which assesses health related quality of life in adolescents, has been adapted and validated in Chile showing excellent psychometric properties. There is a shorter version of the instrument, whose psychometric properties must be assessed. AIM: To evaluate the psychometric properties of the instrument KIDSCREEN-27 in Chilean adolescents. MATERIAL AND METHODS: A secondary analysis of the database obtained for the adaptation and validation of KIDSCREEN-52. RESULTS: The reliability, calculated through Cronbach’s alpha, for the entire instrument (five dimensions) was 0.89. For physical well-being, psychological well-being, autonomy and relationship with parents and peer social support dimensions, scores were higher than 0.75 while for school environment, the score was 0.69. The confirmatory factor analysis showed that the indices obtained to assess the goodness of fit in this study were a χ2 (314) = 10521.4, a Root Mean Square Error of Approximation = 0.064 and a Comparative Fit index = 0.96. KIDSCREEN-27 scores were higher among men in the physical well-being, psychological well-being, autonomy and relationship with parents dimensions and among women in social support and peers and school environment dimensions. Scores were higher in younger age groups. CONCLUSIONS: The Chilean version of KIDSCREEN-27 instrument has adequate reliability and validity.

Casein kinase 2 phosphorylates and induces the SALL2 tumor suppressor degradation in colon cancer cells.

Spalt-like proteins are Zinc finger transcription factors from Caenorhabditis elegans to vertebrates, with critical roles in development. In vertebrates, four paralogues have been identified (SALL1-4), and SALL2 is the family's most dissimilar member. SALL2 is required during brain and eye development. It is downregulated in cancer and acts as a tumor suppressor, promoting cell cycle arrest and cell death. Despite its critical functions, information about SALL2 regulation is scarce. Public data indicate that SALL2 is ubiquitinated and phosphorylated in several residues along the protein, but the mechanisms, biological consequences, and enzymes responsible for these modifications remain unknown. Bioinformatic analyses identified several putative phosphorylation sites for Casein Kinase II (CK2) located within a highly conserved C-terminal PEST degradation motif of SALL2. CK2 is a serine/threonine kinase that promotes cell proliferation and survival and is often hyperactivated in cancer. We demonstrated that CK2 phosphorylates SALL2 residues S763, T778, S802, and S806 and promotes SALL2 degradation by the proteasome. Accordingly, pharmacological inhibition of CK2 with Silmitasertib (CX-4945) restored endogenous SALL2 protein levels in SALL2-deficient breast MDA-MB-231, lung H1299, and colon SW480 cancer cells. Silmitasertib induced a methuosis-like phenotype and cell death in SW480 cells. However, the phenotype was significantly attenuated in CRISPr/Cas9-mediated SALL2 knockout SW480 cells. Similarly, Sall2-deficient tumor organoids were more resistant to Silmitasertib-induced cell death, confirming that SALL2 sensitizes cancer cells to CK2 inhibition. We identified a novel CK2-dependent mechanism for SALL2 regulation and provided new insights into the interplay between these two proteins and their role in cell survival and proliferation.

[Histiocytic necrotizing lymphadenitis: report of 3 cases]. / Linfadenitis necrotizante histiocitaria: comunicación de 3 casos.

Histiocytic necrotizing lymphadenitis (also known as Kikuchi-Fujimoto's disease) is an uncommon, benign and self-limiting lymph disease. We report three patients aged 14, 22 and 50 years, who presented with fever and cervical lymphadenopathy, accompanied by skin lesions and joint pain in two of the three cases. One of the patient's sister suffered from histiocytic necrotizing lymphadenitis. Laboratory abnormalities varied and findings included leucopenia, relative neutrophilia, elevated C reactive protein, erythrocyte sedimentation rate and ferritin. Basic laboratory screening tests were performed on all patients to rule out autoimmune and infectious diseases. Lymph node biopsy and subsequent pathological examination were essential to establish the diagnosis. All patients received antibiotics at some point of their hospital stay. Two patients required glucocorticoid treatment, while the remaining case experienced a spontaneous recovery. Its pathogenesis is still unknown, but clinical and histopathological studies suggest a connection with autoimmune diseases. There is no established treatment, but apparently the disease responds to the administration of glucocorticoids.

[Validation of an instrument to measure health-related quality of life in Chilean children and adolescents]. / Adaptación transcultural y validación de un instrumento de calidad de vida relacionada con la salud en adolescentes chilenos.

BACKGROUND: KIDSCREEN-52 is an instrument to assess health related quality of life in children and adolescents. AIM: To culturally adapt and validate the KIDSCREEN-52 questionnaire in Chileans. MATERIAL AND METHODS: Two independent translations from the English Spanish language were conciliated and retranslated to English. The conciliated version was tested during a cognitive interview to adolescents of different socioeconomic levels. The final version was validated in 7,910 school attending adolescents. RESULTS: In the cross-cultural adaptation, 50 of the 52 items presented low or medium levels of difficulty and a high semantic equivalence. Distribution according to gender, grades and types of schools was similar to the sample. Single ages were not affected by sex distribution. The Confirmatory Factor Analyses were: X² (1229) = 20996.7, Root Mean Square Error of Approximation = .045 and Comparative Fit Index = .96. The instrument had a Cronbach's alpha of .93. The domains had scores over 0.70 points, with the exception of the "Selfperception" domain, with a score of 0.62. CONCLUSIONS: The Chilean version of KIDSCREEN-52 is culturally appropriate and semantically equivalent in its English and Spanish versions (from Spain). Its reliability and validity were adequate.

[Reevaluation of the time course of the effect of propofol described with the Schnider pharmacokinetic model]. / Reevaluación del comportamiento del curso temporal del efecto de propofol descrito por el modelo farmacocinético de Schnider.

BACKGROUND: The first order plasma-effect-site equilibration rate constant (k(e0)) links the pharmacokinetics (PK) and pharmacodynamics (PD) of a given drug. This constant, calculated for each specific PK drug model, allowed us to predict the course of the effect in a target controlled infusion (TCI). The PK-PD model of propofol, published by Schnider et al., calculated a k(e0) value of 0.456min(-1) and a corresponding time to peak effect (t peak) of 1.6min. The aim of this study was to reevaluate the k(e0) value for the predicted Schnider model of propofol, with data from a complete effect curve obtained by monitoring the bispectral index (BIS). METHODS: The study included 35 healthy adult patients (18-90 years) scheduled for elective surgery with standard monitoring and using the BIS XP(®) (Aspect), and who received a propofol infusion to reach a plasma target of 12 µg/ml in 4min. The infusion was then stopped, obtaining a complete effect curve when the patient woke up. The Anestfusor™ (University of Chile) software was used to control the infusion pumps, calculate the plasma concentration plotted by Schnider PK model, and to store the BIS data every second. Loss (LOC) and recovery (ROC) of consciousness was assessed and recorded. Using a traditional parametric method using the "k(e0) Objective function" of the PK-PD tools for Excel, the individual and population k(e0) was calculated. Predictive Smith tests (Pk) and Student t test were used for statistical analysis. A P<.05 indicated significance. RESULTS: The evaluation included 21 male and 14 female patients (18 to 90 years). We obtained 1,001 (±182) EEG data and the corresponding calculated plasma concentration for each case. The population k(e0) obtained was 0.144min(-1) (SD±0.048), very different from the original model (P<.001). This value corresponds with a t peak of 2.45min. The predictive performance (Pk) for the new model was 0.9 (SD±0.03), but only 0.78 (SD±0.06) for the original (P<.001). With a baseline BIS of 95.8 (SD±2.34), the BIS at LOC was 77.48 (SD±9.6) and 74.65(SD±6.3) at ROC (P=.027). The calculated Ce in the original model at LOC and ROC were 5.9 (SD±1.35)/1.08 µg/ml (SD±0.32) (P<.001), respectively, and 2.3 (SD±0.63)/2.0 µg/ml (SD±0.65) (NS) for the new model. The values between LOC/ROC were significantly different between the 2 models (P<.001). No differences in k(e0) value were found between males and females, but in the new model the k(e0) was affected by age as a covariable (0.26-[age×0.0022]) (P<.05). CONCLUSIONS: The dynamic relationship between propofol plasma concentrations predicted by Schnider's pharmacokinetic model and its hypnotic effect measured with BIS was better characterized with a smaller k(e0) value (slower t½k(e0)) than that present in the original model, with an age effect also not described before.

[Evaluation of the Aspergillus Galactomannan ag VircliaR Monotest test as an alternative to Platelia™ Aspergillus EIA kit]. / Evaluación de la prueba Aspergillus Galactomannan Ag VircliaR Monotest como alternativa a kit Platelia™ Aspergillus EIA.

BACKGROUND: The Aspergillus Galactomannan Ag Virclia® (GMVClia) test is a monotest and automated galactomannan technique based on chemiluminescent immunoassay (CLIA). AIM: To evaluate the performance of the GM-VClia test in serum and bronchioalveolar lavage (BAL) samples previously processed with the Platelia ™ Aspergillus EIA kit (GM-Plat). METHODS: 56 samples of serum 40 from BAL (some of them with galactomaman determination in both samples), from patients with pulmonary diseases, hematological diseases, SLE, Covid-19 and tumors, among others, were studied. Thirteen patients had invasive aspergillosis (1 proven and 12 probable). RESULTS: The correlation between both methods for serum and BAL was r = 0.8861 p < 0.0001 and r = 0.6368 p < 0.001, respectively. There was a global concordance of 67.7% (65/96), being 85.7% (48/56) in sera and 42.5.0% (14/49) in BAL. By raising the cut-off point in LBA by GM-VClia, the agreement increased to 85.7%. CONCLUSION: A greater correlation and concordance was observed in sera than in BAL. The GM-VClia kit had a higher sensitivity and NPV than the GM-Plat kit. The disadvantages of GM-VClia are the "doubtful" category, which makes interpretation difficult and that with the current cut-off points in LBA the correlation with GM-Plat is lower. The advantages are its greater sensitivity, ease of processing and faster results.

Circulation of zoonotic flaviviruses in wild passerine birds in Western Spain.

We explore the presence of zoonotic flaviviruses (West Nile virus (WNV) and Usutu virus (USUV)) neutralizing antibodies in rarely studied passerine bird species. We report, for the first time in Europe, WNV-specific antibodies in red avadavat and cetti's warbler, and USUV in yellow-crowned bishop. The evidence of WNV and USUV circulating in resident and migratory species has implications for both animal and public health. Future outbreaks in avian reservoir hosts may occur and passerines should be considered as priority target species in flavivirus surveillance programmes.

Performance evaluation of paediatric propofol pharmacokinetic models in healthy young children.

BACKGROUND: The performance of eight currently available paediatric propofol pharmacokinetic models in target-controlled infusions (TCIs) was assessed, in healthy children from 3 to 26 months of age. METHODS: Forty-one, ASA I-II children, aged 3-26 months were studied. After the induction of general anaesthesia with sevoflurane and remifentanil, a propofol bolus dose of 2.5 mg kg(-1) followed by an infusion of 8 mg kg(-1) h(-1) was given. Arterial blood samples were collected at 1, 2, 3, 5, 10, 20, 40, and 60 min post-bolus, at the end of surgery, and at 1, 3, 5, 30, 60, and 120 min after stopping the infusion. Model performance was visually inspected with measured/predicted plots. Median performance error (MDPE) and the median absolute performance error (MDAPE) were calculated to measure bias and accuracy of each model. RESULTS: Performance of the eight models tested differed markedly during the different stages of propofol administration. Most models underestimated propofol concentration 1 min after the bolus dose, suggesting an overestimation of the initial volume of distribution. Six of the eight models tested were within the accepted limits of performance (MDPE<20% and MDAPE<30%). The model derived by Short and colleagues performed best. CONCLUSIONS: Our results suggest that six of the eight models tested perform well in young children. Since most models overestimate the initial volume of distribution, the use for TCI might result in the administration of larger bolus doses than necessary.

Influence of rate of administration on the mechanism behind propofol induced loss of consciousness.

BACKGROUND: Propofol effect-site time course models included in TCI systems have been under discussion. We hypothesized that the rate of administration is a major contributor affecting the construction of a useful effect-site model: yielding different plasmatic concentrations, loss of consciousness may occur by different mechanisms more complex than the pharmacological effect-site. METHODOLOGY: ASA III patients were randomized in two groups: rapid induction (RI) received TCI of propofol effect-site (CeCALC) 5.4 µg/mL (modified Marsh model), and slow induction (SI) propofol infusion of 10 mg/kg/hour. A neurologist, blinded to induction method, performed neurological assessments using the FOUR score until the loss of consciousness (LOC). At LOC, the presence of brain stem reflexes, EEG index (PSI) and infusion time/mass of drug were registered. Fisher's exact test was used to describe differences between brain stem reflexes and respiration components of the FOUR score and CeCALC for 4 propofo models at LOC time. RESULTS: 16 patients divided in two groups were included. All patient in SI had brainstem reflexes free at LOC. In the RI, all patients had brain stem reflexes abolished and 1 patient had B and R of 4 points in the FOUR score (brain stem reflexes unaffected; P < .001). CeCALC at LOC time were contradictory at LOC in both groups and using 4 different Pk/Pd models. CONCLUSIONS: Depending of the infusion rate, propofol CeCALC at LOC calculated by different Pk/Pd models could be the source of confuse data to be used to guide the state of general anesthesia.

Influence of rate of administration on the mechanism behind propofol induced loss of consciousness. / Influencia de la tasa de administración en el mecanismo subyacente a la pérdida de consciencia inducida por propofol.

BACKGROUND: Propofol effect-site time course models included in TCI systems have been under discussion. We hypothesized that the rate of administration is a major contributor affecting the construction of a useful effect-site model: yielding different plasmatic concentrations, loss of consciousness may occur by different mechanisms more complex than the pharmacological effect-site. METHODOLOGY: ASA I-II patients were randomized in two groups: rapid induction (RI) received TCI of propofol effect-site (CeCALC) 5.4µg/mL (modified Marsh model), and slow induction (SI) propofol infusion of 10mg/kg/hour. A neurologist, blinded to induction method, performed neurological assessments using the FOUR score until the loss of consciousness (LOC). At LOC, the presence of brain stem reflexes, EEG index (PSI) and infusion time/mass of drug were registered. Fisher's exact test was used to describe differences between brain stem reflexes and respiration components of the FOUR score and CeCALC for 4 propofol models at LOC time. RESULTS: 16 patients divided in two groups were included. All patient in SI had brainstem reflexes free at LOC. In the RI, all patients had brain stem reflexes abolished and 1 patient had B and R of 4 points in the FOUR score (brain stem reflexes unaffected; P<.001). CeCALC at LOC time were contradictory at LOC in both groups and using 4 different Pk/Pd models. CONCLUSIONS: Depending of the infusion rate, propofol CeCALC at LOC calculated by different Pk/Pd models could be the source of confuse data to be used to guide the state of general anesthesia.