Anesthesia Medication's Impacts on Inflammatory and Neuroendocrine Immune Response in Patients Undergoing Digestive Endoscopy.

The aim of this study was to explore the impact of anesthetic drugs currently used to perform lower digestive endoscopy on serum concentrations of inflammation markers and catecholamines. We selected 120 patients and divided them into three lots of 40 patients each: L1, in which no anesthetics were used; L2, in which propofol was used; and L3, in which propofol combined with fentanyl was used. All patients had serum concentrations of adrenaline/epinephrine (EPI), noradrenaline/norepinephrine (NE), tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), IL-6, IL-8, and IL-10, taken at three time points: at the beginning of the endoscopic procedure (T0), 15 min after (T1), and 2 h after the end of the endoscopic procedure (T2). The results of the research showed changes in the levels of catecholamines and interleukins (ILs) at T0, with an increased response in L1 above the mean recorded in L2 and L3 (p < 0.001). At T1, increased values were recorded in all lots; values were significantly higher in L1. At T2, the values recorded in L3 were significantly lower than the values in L2 (student T, p < 0.001) and L1, in which the level of these markers continued to increase, reaching double values compared to T0 (student T, p < 0.001). In L2 at T1, the dose of propofol correlated much better with NE, EPI, and well-known cytokines. Our results show that propofol combined with fentanyl can significantly inhibit the activation of systemic immune and neuroendocrine response during painless lower digestive endoscopy.

Effect of intravenous anesthetic drugs on fertilization rate in oocyte retrieval.

BACKGROUND: The purpose of this study was to investigate the effects of intravenous anesthetic drugs on fertilization rate in subjects receiving oocyte retrieval by assisted reproduction technology (ART). METHODS: A retrospective cohort study was designed. The clinical information of subjects who received oocyte retrieval procedure was collected. The subjects were divided into two groups based on the type of anesthesia used: the no-anesthesia group and the intravenous anesthesia group. Propensity score matching (PSM) was performed and multiple linear regression analyses were conducted. Fertilization rate was compared between the two groups before and after PSM. RESULTS: A total of 765 subjects were divided into two groups: the no-anesthesia group (n = 482) and the intravenous anesthesia group (n = 283). According to propensity scores, 258 pairs of subjects were well matched, and the baseline data between the two groups were not significantly different (P > 0.05). Fertilization rate was 77% in the intravenous anesthesia group, and 76% in the no-anesthesia group, without significant between-group difference (P = 0.685). Before matching, Poisson regression analysis showed no effect of intravenous anesthetic drugs on fertilization rate (RR = 0.859, 95%CI: 0.59 to 1.25, P = 0.422). After matching, no difference was found either (RR = 0.935, 95%CI: 0.67 to 1.29, P = 0.618). CONCLUSION: Intravenous anesthetic drugs may exert no effects on fertilization rate in subjects receiving ART.

Sustained effort network for treatment of status epilepticus/European academy of neurology registry on adult refractory status epilepticus (SENSE-II/AROUSE).

BACKGROUND: Status Epilepticus (SE) is a common neurological emergency associated with a high rate of functional decline and mortality. Large randomized trials have addressed the early phases of treatment for convulsive SE. However, evidence regarding third-line anesthetic treatment and the treatment of nonconvulsive status epilepticus (NCSE) is scarce. One trial addressing management of refractory SE with deep general anesthesia was terminated early due to insufficient recruitment. Multicenter prospective registries, including the Sustained Effort Network for treatment of Status Epilepticus (SENSE), have shed some light on these questions, but many answers are still lacking, such as the influence exerted by distinct EEG patterns in NCSE on the outcome. We therefore initiated a new prospective multicenter observational registry to collect clinical and EEG data that combined may further help in clinical decision-making and defining SE. METHODS: Sustained effort network for treatment of status epilepticus/European Academy of Neurology Registry on refractory Status Epilepticus (SENSE-II/AROUSE) is a prospective, multicenter registry for patients treated for SE. The primary objectives are to document patient and SE characteristics, treatment modalities, EEG, neuroimaging data, and outcome of consecutive adults admitted for SE treatment in each of the participating centers and to identify factors associated with outcome and refractoriness. To reach sufficient statistical power for multivariate analysis, a cohort size of 3000 patients is targeted. DISCUSSION: The data collected for the registry will provide both valuable EEG data and information about specific treatment steps in different patient groups with SE. Eventually, the data will support clinical decision-making and may further guide the planning of clinical trials. Finally, it could help to redefine NCSE and its management. TRIAL REGISTRATION: NCT number: NCT05839418.

Defective autophagy contributes to bupivacaine-induced aggravation of painful diabetic neuropathy in db/db mice.

Current evidence suggests that hyperactivated or impaired autophagy can lead to neuronal death. The effect of local anesthetics on painful diabetic neuropathy (PDN) and the role of autophagy in the above pathological process remain unclear, warranting further studies. So, PDN models were established by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in leptin gene-mutation (db/db) mice. Wild type (WT) and PDN mice received intrathecal 0.75% bupivacaine or/with intraperitoneal drug treatment (rapamycin or bafilomycin A1). Subsequently, the PWT and PWL were measured to assess hyperalgesia at 6 h, 24 h, 30 h, and 48 h after intrathecal bupivacaine. Also, sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) were measured before and 48 h after intrathecal bupivacaine treatment. The spinal cord tissue of L4-L6 segments and serum were harvested to evaluate the change of autophagy, oxidative stress, oxidative injury, and apoptosis. We found that bupivacaine induced the activation of autophagy but did not affect the pain threshold, SNCV and MNCV in WT mice at predefined time points. Conversely, bupivacaine lowered autophagosome generation and degradation, slowed SNCV and aggravated spinal dorsal horn neuron oxidative injury and hyperalgesia in PDN mice. The autophagy activator (rapamycin) could decrease spinal dorsal horn neuron oxidative injury, alleviate the alterations in SNCV and hyperalgesia in bupivacaine-treated PDN mice. Meanwhile, the autophagy inhibitor (bafilomycin A1) could exacerbate spinal dorsal horn neuron oxidative injury, the alterations in SNCV and hyperalgesia in bupivacaine-treated PDN mice. Our results showed that bupivacaine could induce defective autophagy, slowed SNCV and aggravate spinal dorsal horn neuron oxidative injury and hyperalgesia in PDN mice. Restoring autophagy may represent a potential therapeutic approach against nerve injury in PDN patients with local anesthesia and analgesia.

Seizure recurrences in generalized convulsive status epilepticus under sedation: What are its predictors and its impact on outcome?

BACKGROUND: Management of status epilepticus (SE) is focused on the early seizure termination. Refractory SE is an indication for sedation in patients with SE, but up to 75% of patients may be ventilated due to a neurological or respiratory failure. In patients requiring sedation, the clinical assessment is not sufficient to assess seizure control. Identifying those at risk of recurrent seizures could be useful to adapt their management. On the other hand, patients with low risk could benefit from an early withdrawal of sedation to avoid the impact of inappropriate sedation on outcome. OBJECTIVE: To determine the prevalence and the predictors of uncontrolled SE and its impact on outcome in patients with generalized convulsive SE (GCSE) requiring mechanical ventilation (MV). METHODS: We retrospectively included patients admitted to the intensive care unit with GCSE requiring MV. Uncontrolled SE was defined as persistent or recurrent seizures during sedation or within 24hours following withdrawal. A multivariable logistic regression model was used to assess the associated factors. RESULTS: Uncontrolled SE occurred in 37 out of 220 patients (17%). Persistent seizures at admission, higher SAPS II and central nervous system infection were associated with a higher risk of uncontrolled SE. Acute toxic or metabolic etiologies were associated with a decreased risk of uncontrolled SE. In a supplementary analysis, decrease of albumin blood levels was associated with uncontrolled SE. Uncontrolled SE was associated with a poor functional outcome and mortality at 90 days. CONCLUSIONS: Seventeen percent of patients with a GCSE requiring MV suffered from uncontrolled SE. Etiology and persistent seizures at admission were the main predictors of uncontrolled SE. Patients with uncontrolled SE had a longer duration of sedation and MV, a poor functional outcome and a higher mortality. Further studies are required to determine the impact of continuous electroencephalogram monitoring on the clinical course.

Bibliometric Analysis of Anesthetic Drugs' Effects on Immune Function- Current Knowledge, Hotspots and Future Perspectives.

Objective: The objective of this study is to conduct a bibliometric analysis of the present status, areas of focus, and upcoming developments in the research of anesthetic drugs and their impact on immune function, along with other related research domains. Methods: From January 1, 2008 to June 9, 2023, A thorough exploration of anesthetic drug-related literature pertaining to immune function was carried out through the utilization of the Web of Science. The bibliometric analysis was predominantly executed by means of CiteSpace, GraphPad Prism 8.0, and the acquisition of data regarding the country, institution, author, journal, and keywords associated with each publication. Results: This study analyzed a comprehensive total of 318 publications, consisting of 228 articles and 90 reviews, to determine the publication output of anesthetic drugs on immune function. Notably, China exhibited the highest publication output with (109, 34.28%) articles. Among the institutions analyzed, Harvard University was found to be the most productive with (12, 3.77%) publications. The study findings indicate that Buggy, Donal J (5, 1.57%) and Yuki, Koichi (5, 1.57%) had the highest publication records. Anesthesiology was the most frequently cited journal with a total of (206) citations. The results also revealed that "surgery" was the most frequently used keyword, appearing (48 times), followed by "general anesthesia" (41 times) and "breast cancer" (37 times). The study has identified several current areas of interest, with a particular emphasis on "metastasis", "inflammation", "recurrence", "anesthesia technique", and "induction". It is anticipated that forthcoming research endeavors will concentrate on exploring the impacts of isoflurane, sevoflurane, and ketamine on immune function. Conclusion: This study provided a thorough analysis of the research trends and developments in investigating the impact of anesthetic drugs on immune function, incorporating pertinent research and collaborative entities such as authors, institutions, and countries.

Antiepileptic and anesthetic drugs in the intensive care unit. Their impact on non-convulsive status epilepticus mortality / Drogas antiepilépticas y anestésicas en la unidad de terapia intensiva. Su impacto en la mortalidad en el estado de mal epiléptico no convulsivo

Abstract Background: Status epilepticus (SE) is a neurological emergency. Non-convulsive status epilepticus (NCSE) can only be diagnosed by electroencephalogram (EEG) because the motor clinical symptoms are usually subtle or absent, with high mortality. The best treatment is still unknown. Objectives: Our aim was to assess anticonvulsive and anesthetic drugs in NCSE and their correlation with Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilepticus Severity Score (STESS) and mortality. Methods: Retrospective, observational, descriptive, cross-sectional study. Ninety patients in intensive care unit over 18 years-old (57 females [63.3%] and 33 males [36.6%], mean age 63.5 years [SD ± 19]) with NCSE, at the Buenos Aires British Hospital. Data was collected between January 2018 and June 2021. An adjusted mul tivariate statistical analysis was performed. Ninety-five (95%) CI, p<0.05 as statistically significant. EMSE and STESS were used in this study. Results: Total mortality rate was 37.8% (34/90), and in patients ≥ 65 years-old (54/90) it was 40.7% (22/54). Patients with 0-2 STESS (11/90) were discharged, while those with STESS ≥ 3 (79/90) had a 43% death rate (34/79). Patients with EMSE < 34 (27/90) had 7.4% (2/27) death rate, while those with EMSE ≥ 34 (63/90) had 50.8% (32/63). No significant differences were found in survival with regard to the number of antiepileptic drugs administered. Pa tients treated with anesthetics presented a 2.6-fold death risk increase (95% CI 1.001-6.83). Discussion: It could be assumed that mortality rate increases 2.6-fold when patients are treated with anes thetic drugs, regardless of the number of antiepileptic drugs previously administered.

Resumen Introducción: El estado de mal epiléptico (SE) es una emergencia neurológica. El SE no convulsivo (SENC) se diagnostica únicamente por electroencefalograma de bido a la ausencia o sutileza de sintomatología clínica motora, con una mortalidad elevada. No se conoce aún el mejor tratamiento. Objetivos: Evaluar drogas anticonvulsivas y anestési cas en el SENC y su correlación con Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilep ticus Severity Score (STESS) y el índice de mortalidad. Métodos: Estudio retrospectivo, observacional, de scriptivo, de corte transversal. Noventa pacientes ≥ 18 años (57 mujeres [63.3%] y 33 hombres [36.6%], media de edad 63.5 años [DS ± 19]) con diagnóstico de SENC, en el Hospital Británico. Estudio realizado entre enero 2018 y junio 2021. Análisis estadístico multivariado ajustado. IC 95% p< 0.05 como estadísticamente significativo. Se utilizaron escalas de EMSE y STESS. Resultados: La mortalidad total fue de 37.8% (34/90). Los pacientes ≥ 65 años (54/90) presentaron una mayor tasa de muerte 40.7% (22/54), todos aquellos con STESS de 0-2 (11/90) egresaron, mientras que entre los que presentaron ≥ 3 (79/90) el 43% (34/79) falleció. De los pacientes con EMSE < 34 (27/90) dos fallecieron (7.4%) y de aquellos con EMSE ≥ 34 (63/90) falleció el 50.8% (32/63). No hallamos diferencias significativas entre cantidad de drogas antiepilépticas utiliza das y supervivencia. Pacientes con anestésicos tuvieron un aumento del riesgo de muerte 2.6 veces (IC 95% 1.001-6.83). Discusión: De acuerdo a esto la mortalidad con drogas anestésicas aumenta, independientemente de la cantidad de drogas anticonvulsivas utilizadas previamente.

[Prehospital emergency anesthesia in adults : Current recommendations for performing prehospital emergency anesthesia based on the recommendations for prehospital emergency anesthesia in adults]. / Präklinische Notfallnarkose beim Erwachsenen : Aktuelle Empfehlungen zur Durchführung einer prähospitalen Notfallnarkose basierend auf den Handlungsempfehlungen zur prähospitalen Notfallnarkose beim Erwachsenen.

The frequency of prehospital emergency anesthesia in Germany is around 2-3% of all emergency medical missions. The Association of the Scientific Medical Societies of Germany (AWMF) has published guidelines for the implementation of a prehospital emergency anesthesia. The purpose of this article is to highlight important aspects from these guidelines and to present the implementation and special features for specific patient groups. A case study is intended to illustrate that the preclinical setting can provide various facets that make a certain amount of experience and expertise indispensable. The article emphasizes that clear standard situations are not always present and that there are some challenges in the preclinical setting. Therefore, mastering the content of prehospital emergency anesthesia and the manual skills of induction of anesthesia are essential and obligatory for the emergency team.

Antiepileptic and anesthetic drugs in the intensive care unit. Their impact on non-convulsive status epilepticus mortality.

BACKGROUND: Status epilepticus (SE) is a neurological emergency. Non-convulsive status epilepticus (NCSE) can only be diagnosed by electroencephalogram (EEG) because the motor clinical symptoms are usually subtle or absent, with high mortality. The best treatment is still unknown. OBJECTIVES: Our aim was to assess anticonvulsive and anesthetic drugs in NCSE and their correlation with Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilepticus Severity Score (STESS) and mortality. METHODS: Retrospective, observational, descriptive, cross-sectional study. Ninety patients in intensive care unit over 18 years-old (57 females [63.3%] and 33 males [36.6%], mean age 63.5 years [SD ± 19]) with NCSE, at the Buenos Aires British Hospital. Data was collected between January 2018 and June 2021. An adjusted multivariate statistical analysis was performed. Ninety-five (95%) CI, p < 0.05 as statistically significant. EMSE and STESS were used in this study. RESULTS: Total mortality rate was 37.8% (34/90), and in patients = 65 years-old (54/90) it was 40.7% (22/54). Patients with 0-2 STESS (11/90) were discharged, while those with STESS = 3 (79/90) had a 43% death rate (34/79). Patients with EMSE < 34 (27/90) had 7.4% (2/27) death rate, while those with EMSE = 34 (63/90) had 50.8% (32/63). No significant differences were found in survival with regard to the number of antiepileptic drugs administered. Patients treated with anesthetics presented a 2.6-fold death risk increase (95% CI 1.001-6.83). DISCUSSION: It could be assumed that mortality rate increases 2.6-fold when patients are treated with anesthetic drugs, regardless of the number of antiepileptic drugs previously administered.

Introducción: El estado de mal epiléptico (SE) es una emergencia neurológica. El SE no convulsivo (SENC) se diagnostica únicamente por electroencefalograma debido a la ausencia o sutileza de sintomatología clínica motora, con una mortalidad elevada. No se conoce aún el mejor tratamiento. Objetivos: Evaluar drogas anticonvulsivas y anestésicas en el SENC y su correlación con Epidemiology-based Mortality Score in Status Epilepticus (EMSE), Status Epilepticus Severity Score (STESS) y el índice de mortalidad. Métodos: Estudio retrospectivo, observacional, descriptivo, de corte transversal. Noventa pacientes = 18 años (57 mujeres [63.3%] y 33 hombres [36.6%], media de edad 63.5 años [DS ± 19]) con diagnóstico de SENC, en el Hospital Británico. Estudio realizado entre enero 2018 y junio 2021. Análisis estadístico multivariado ajustado. IC 95% p < 0.05 como estadísticamente significativo. Se utilizaron escalas de EMSE y STESS. Resultados: La mortalidad total fue de 37.8% (34/90). Los pacientes = 65 años (54/90) presentaron una mayor tasa de muerte 40.7% (22/54), todos aquellos con STESS de 0-2 (11/90) egresaron, mientras que entre los que presentaron = 3 (79/90) el 43% (34/79) falleció. De los pacientes con EMSE < 34 (27/90) dos fallecieron (7.4%) y de aquellos con EMSE = 34 (63/90) falleció el 50.8% (32/63). No hallamos diferencias significativas entre cantidad de drogas antiepilépticas utilizadas y supervivencia. Pacientes con anestésicos tuvieron un aumento del riesgo de muerte 2.6 veces (IC 95% 1.001-6.83). Discusión: De acuerdo a esto la mortalidad con drogas anestésicas aumenta, independientemente de la cantidad de drogas anticonvulsivas utilizadas previamente.

Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs.

Cognitive disorders are mental health disorders that can affect cognitive ability. Surgery and anesthesia have been proposed to increase the incidence of cognitive dysfunction, including declines in memory, learning, attention and executive function. Tau protein is a microtubule-associated protein located in the axons of neurons and is important for microtubule assembly and stability; its biological function is mainly regulated by phosphorylation. Phosphorylated tau protein has been associated with cognitive dysfunction mediated by disrupting the stability of the microtubule structure. There is an increasing consensus that anesthetic drugs can cause cognitive impairment. Herein, we reviewed the latest literature and compared the relationship between tau protein and cognitive impairment caused by different anesthetics. Our results substantiated that tau protein phosphorylation is essential in cognitive dysfunction caused by anesthetic drugs, and the possible mechanism can be summarized as "anesthetic drugs-kinase/phosphatase-p-Tau-cognitive impairment".

Factors Associated with Refractory Status Epilepticus Termination Following Ketamine Initiation: A Multivariable Analysis Model.

BACKGROUND: In this study, we identify factors associated with ketamine success in the treatment of refractory status epilepticus (SE). We also evaluate for adverse events including systemic and cerebral hemodynamic stability and fluid volume overload. METHODS: In this retrospective, large, single-center, observational study over a 10-year period, 879 consecutive patients receiving intravenous (IV) ketamine were reviewed, and 81 patients were identified as receiving IV ketamine for the treatment of SE. Descriptive analysis was done to determine treatment response and adverse events in patients receiving IV ketamine for SE. Multivariable logistic regression analyses were fitted to determine prediction models for seizure cessation. RESULTS: Permanent cessation of SE was achieved in 49 of 81 (60.5%) of patients for whom ketamine was part of the treatment plan. Of those, 36 (44.4%) were attributed to ketamine as the last drug used (ketamine-associated cessation [AC]). Prior history of epilepsy had an odds ratio of 3.19 (confidence interval 0.83-12.67, p = 0.09) associated with efficacious medication response. Increased latency to ketamine was associated with cessation of SE specifically in patients in the AC group (p = 0.077). Longer SE duration (p = 0.04), administration of ketamine loading dose (bolus; p = 0.03), and anoxia (p = 0.007) were negatively associated with AC. Administration of ketamine loading dose (p = 0.02) and anoxia (p = 0.009) were negatively associated with overall SE cessation. There was no significant impact of ketamine on cerebral hemodynamics, but evidence of fluid volume overload was seen (28.4% of patients). CONCLUSIONS: Our cohort is a large observational study showing a high success rate of permanent cessation of SE after the addition of ketamine. Using multivariable analysis, we demonstrate a significant association with seizure cessation in patients with prior history of epilepsy and those with prolonged latency to ketamine initiation. Furthermore, we describe the impact of fluid volume overload as an anticipated complication with ketamine use.

Anesthetic drug shortages in Pakistan: a multicentre nationwide survey.

PURPOSE: There is a paucity of literature on anesthetic drug shortages and their impact on patient safety in lower-middle-income countries. We sought to determine the magnitude of the problem, the effect on patient care and safety, and the adverse patient outcomes witnessed by anesthesiologists in Pakistan METHODS: We conducted a nationwide, multicentre, cross-sectional survey of a representative sample of anesthesiologists in Pakistan (January 2021 to June 2021). The survey questionnaire was adapted from the American Society of Anesthesiologists (ASA) survey on drug shortages and was modified based on the national essential medication list 2018 of Pakistan. It was distributed through Google Forms to anesthesiologists practicing in both the private and government sector. The names of hospitals or the identity of anesthesiologists was not required. The questionnaire consisted of 20 items and focused on the anesthesiologists' experience of drug shortages, the availability of drugs, and the impact of drug shortages on their individual practice. RESULTS: Two hundred and forty-six responses were received. Approximately 50% (122/246) of anesthesia practitioners in Pakistan reported anesthetic drug shortages. Fifty-seven percent of respondents mentioned using an inferior drug that may have significantly affected the delivery of anesthetic care. Four participants mentioned severe morbidity and another four mentioned observing a mortality associated with drug shortage. CONCLUSION: Anesthetic drug shortages are common in anesthetic practice in Pakistan and they appear to affect patient care and outcomes.

RéSUMé: OBJECTIF: Il existe peu de littérature sur les pénuries de médicaments anesthésiques et leur impact sur la sécurité des patients dans les pays à revenu intermédiaire ou faible. Nous avons cherché à déterminer l'ampleur du problème, l'effet sur les soins et la sécurité des patients ainsi que les issues indésirables observées par les anesthésiologistes au Pakistan. MéTHODE: Nous avons mené une enquête transversale multicentrique à l'échelle nationale auprès d'un échantillon représentatif d'anesthésiologistes au Pakistan (janvier 2021 à juin 2021). Le questionnaire de l'enquête a été adapté de l'enquête de l'American Society of Anesthesiologists (ASA) sur les pénuries de médicaments et a été modifié en fonction de la liste nationale des médicaments essentiels 2018 du Pakistan. Il a été distribué via Google Forms aux anesthésiologistes exerçant dans les secteurs privé et gouvernemental. Les noms des hôpitaux et l'identité des anesthésiologistes n'étaient pas demandés. Le questionnaire comprenait 20 éléments et portait sur l'expérience des anesthésiologistes en matière de pénuries de médicaments, la disponibilité des médicaments et l'impact des pénuries de médicaments sur leur pratique individuelle. RéSULTATS: Deux cent quarante-six réponses ont été reçues. Environ 50 % (122/246) des praticiens anesthésistes au Pakistan ont signalé des pénuries de médicaments anesthésiques. Cinquante-sept pour cent des répondants ont mentionné avoir utilisé un médicament de qualité inférieure qui pourrait avoir eu une incidence significative sur la prestation des soins anesthésiques. Quatre participants ont mentionné une morbidité grave et quatre autres ont mentionné avoir observé une mortalité associée à une pénurie de médicaments. CONCLUSION: Les pénuries de médicaments anesthésiques sont courantes dans la pratique anesthésique au Pakistan et semblent affecter les soins aux patients et les devenirs.

Balancing the risks and benefits of anesthetics in status epilepticus.

PURPOSE: According to international guidelines, status epilepticus refractory to first- and second-line antiseizure medication should be treated with anesthetics. Therefore, continuously delivered intravenous midazolam, propofol, or barbiturates are recommended as third-line therapy. While electroencephalographically (EEG)-controlled titration of anesthetics to seizure termination or to the emergence of an EEG burst-suppression pattern makes sense, evidence of the efficacy and tolerability of such third-line treatment is limited and concerns regarding the risks of anesthesia remain. The lack of treatment alternatives and persistent international discord reflecting contradictory results from some studies leave clinicians on their own when deciding to escalate treatment. In this conference-accompanying narrative review, we highlight the challenges of EEG-monitored third-line treatment and discuss recent studies that examined earlier administration of anesthetics. RESULTS: Based on the literature, maintaining continuous burst suppression is difficult despite the constant administration of anesthetics, and the evidence for burst suppression as an adequate surrogate target is limited by methodological shortcomings as acknowledged by international guidelines. In our Swiss cohort including 102 patients with refractory status epilepticus, burst suppression as defined by the American Clinical Neurophysiology Society's Critical Care EEG Terminology 2021 was established in only 21%. Besides case reports suggesting that rapid but short-termed anesthesia can be sufficient to permanently stop seizures, a study including 205 patients revealed that anesthesia as second-line treatment was associated with a shorter median duration of status epilepticus (0.5 versus 12.5 days, p < 0.001), median ICU (2 versus 5.5 days, p < 0.001) and hospital stay (8 versus 17 days, p < 0.001) with equal rates of complications when compared to anesthesia as third-line treatment. CONCLUSIONS: Recent investigations have led to important findings and new insights regarding the use of anesthetics in refractory status epilepticus. However, numerous methodological limitations and remaining questions need to be considered when it comes to the translation into clinical practice, and, in consequence, call for prospective randomized studies. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Association of sedation and anesthesia on cognitive outcomes in very premature infants: a retrospective observational study.

PURPOSE: Cognitive outcomes in preterm infants may be adversely affected by use of sedation and anesthetic agents. We investigated the associations between anesthetics/sedatives and full-scale intelligence quotient (FSIQ) measured at 36 months corrected age (CA) in very preterm infants (born < 29 weeks gestational age). METHODS: This retrospective cohort study included preterm infants born at < 29 weeks of gestation between 1 January 2006 and 31 December 2012, whose cognitive outcomes were assessed at 36 months CA. Imputed and complete case univariable and adjusted multivariable linear regressions were used to investigate the associations between FSIQ [standardized to mean (standard deviation) 100 (15)] and exposure to volatile anesthetics, propofol, benzodiazepines, barbiturates, and ketamine. These agents were the subject of a 2016 warning from regulatory authorities in the USA recommending caution for administration to children and pregnant women. RESULTS: A total of 731 infants met the inclusion criteria. Unadjusted associations were -7 (95% confidence interval [CI], -10 to -4; P < 0.001) and -6 (95% CI, -10 to -3; P < 0.001) FSIQ points with exposure to warned medications using imputed and complete case analyses, respectively. Imputed and complete case adjusted associations between FSIQ and warned medications were -3 (95% CI, -7 to 0; P = 0.045) and -4 (95% CI, -8 to 0; P = 0.071) FSIQ points, respectively. Adjusted associations between volatile anesthetic exposure only and FSIQ were -3 (95% CI, -6 to 0; P = 0.072) and -5 (95% CI, -9 to -2; P = 0.004) FSIQ points using imputed and complete case data sets, respectively. FSIQ was not associated with opioid exposure. CONCLUSION: Exposure of very preterm infants to anesthetics/sedatives on the United States Food and Drug Administration warning list was associated with a decrease in FSIQ points at 36 months CA. There was no association between opioid exposure and FSIQ.

RéSUMé: OBJECTIF : L'utilization d'agents sédatifs et anesthésiques pourrait avoir une incidence défavorable sur l'évolution cognitive des nourrissons prématurés. Nous avons analysé les associations existantes entre les anesthésiques/sédatifs et le quotient d'intelligence global (QIg) mesuré à 36 mois d'âge corrigé (AC) chez des enfants nés grands prématurés (nés < 29 semaines d'âge gestationnel). MéTHODES: Cette étude de cohorte rétrospective a inclus des nourrissons prématurés nés avant 29 semaines d'âge gestationnel entre le 1er janvier 2006 et le 31 décembre 2012 et dont les critères d'évaluation cognitifs ont été évalués à 36 mois d'AC. Des régressions linéaires à une seule variable et multivariables ajustée, sur les cas imputés et sur les cas complets, ont été utilisées pour rechercher les associations entre le QIg (standardisé à la moyenne 100 [± écart-type] [15]) et l'exposition à des anesthésiques volatils, du propofol, des benzodiazépines, des barbituriques et de la kétamine. Ces molécules ont fait l'objet d'une mise en garde en 2016 par les autorités de réglementation aux États-Unis, recommandant la prudence concernant leur administration à des enfants et à des femmes enceintes. RéSULTATS: Un total de 731 nourrissons présentait les critères d'inclusion. Les associations non ajustées ont été de -7 (intervalle de confiance [IC] à 95 % : -10 à -4; P < 0,001) et -6 (IC à 95 % : -10 à -3; P < 0,001) points de QIg avec l'exposition aux médicaments sous avertissement en utilisant, respectivement, des analyses de cas imputés et de cas complets. Les associations ajustées de cas imputés et complets entre le QIg et les médicaments sous avertissement ont été, respectivement, de -3 (IC à 95 % : -7 à 0; P = 0,045) et -4 (IC à 95 % : -8 à 0; P = 0,071) points de QIg. Les associations ajustées entre l'exposition aux anesthésiques volatiles, uniquement, et le QIg ont été de -3 (IC à 95 % : -6 à 0; P = 0,072) et -5 (IC à 95 % : -9 à 2; P = 0,004) points de QIg en utilisant, respectivement, les ensembles de données des cas imputés et des cas complets. Le QIg n'a pas été associé à une exposition aux opioïdes. CONCLUSION: L'exposition des nourrissons grands prématurés aux anesthésiques/sédatifs figurant sur la liste d'avertissement de la Food and Drug Administration des États-Unis a été associée à une diminution des points de QIg à 36 mois d'AC. Il n'y a pas eu d'association entre l'exposition aux opioïdes et le QIg.

Prevalence of preoperative anxiety in patients posted for surgical procedures and its relation to the doses of anesthetic drugs: A cross-sectional study.

Background: In patients undergoing surgical procedures, preoperative period is one of the most worrying periods. There are only few studies which revealed that increased preoperative anxiety is associated with increased requirements of doses of anesthetic agents. Aim: The aim of this study is to assess the prevalence of preoperative anxiety in patients posted for surgical procedures and its relation to the doses of anesthetic drugs. Materials and Methods: This is a cross-sectional, analytical study done between January 2021 and April 2021. A total of 100 patients undergoing surgery have given consent to participate in the study by filling self-designed questionnaire, Amsterdam Preoperative Anxiety and Information Scale (APAIS). Data analysis was done by SPSS version 24 using appropriate statistical tests. Results: Preoperative anxiety was noted in 21% of the patients who were undergoing surgery. The association between preoperative anxiety and need for increase in the doses of anesthetic agents during intraoperative period was found to be statistically significant (P < 0.004). Conclusion: A significant number of patients required increased amounts of anesthetic drugs to reduce anxiety during intraoperative period. Therefore, appropriate methods have to be introduced to address the concerns of patients undergoing surgery and thereby reducing anxiety.

Intravenous dantrolene in hypermetabolic syndromes: a survey of the U.S. Veterans Health Administration database.

BACKGROUND: Intravenous dantrolene is often prescribed for hypermetabolic syndromes other than the approved indication of malignant hyperthermia (MH). To clarify the extent of and indications for dantrolene use in conditions other than MH, we sought to document current practices in the frequency, diagnoses, clinical characteristics and outcomes associated with dantrolene treatment in critical care settings. METHODS: Inpatients receiving intravenous dantrolene from October 1, 2004 to September 30, 2014 were identified retrospectively in the U.S. Veterans Health Administration national database. Extracted data included; diagnoses of hypermetabolic syndromes; triggering drugs; dantrolene dosages; demographics; vital signs; laboratory values; in-hospital mortality; complications; and lengths of stay. Frequency and mortality of patients who did not receive dantrolene were obtained in selected diagnoses for exploratory comparisons. RESULTS: Dantrolene was administered to 304 inpatients. The most frequent diagnoses associated with dantrolene treatment were neuroleptic malignant syndrome (NMS; N = 108, 35.53%) and sepsis (N = 47, 15.46%), with MH accounting for only 13 (4.28%) cases. Over half the patients had psychiatric comorbidities and received psychotropic drugs before dantrolene treatment. Common clinical findings in patients receiving dantrolene included elevated temperature (mean ± SD; 38.7 ± 1.3 °C), pulse (116.33 ± 22.80/bpm), respirations (27.75 ± 9.58/min), creatine kinase levels (2,859.37 ± 6,646.88 IU/L) and low pO2 (74.93 ± 40.16 mmHg). Respiratory, renal or cardiac failure were common complications. Mortality rates in-hospital were 24.01% overall, 7.69% in MH, 20.37% in NMS and 42.55% in sepsis, compared with mortality rates in larger and possibly less severe groups of unmatched patients with MH (5.26%), NMS (6.66%), or sepsis (41.91%) who did not receive dantrolene. CONCLUSIONS: In over 95% of cases, dantrolene administration was associated with diagnoses other than MH in critically-ill patients with hypermetabolic symptoms and medical and psychiatric comorbidities. Exploratory survey data suggested that the efficacy and safety of dantrolene in preventing mortality in hypermetabolic syndromes other than MH remain uncertain. However, randomized and controlled studies using standardized criteria between groups matched for severity are essential to guide practice in using dantrolene.

Determination of Local Anesthetic Drugs in Human Plasma Using Magnetic Solid-Phase Extraction Coupled with High-Performance Liquid Chromatography.

In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl-carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02-5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0-108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5-7.7% and 1.5-8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma.

Lesión hepática inducida por fármacos anestésicos / Liver injury induced by anesthetic drugs

Resumen: El daño hepático por medicamentos no es tan raro, su diagnóstico es por exclusión, en algunos casos puede inducir falla hepática aguda. Se realizó una revisión de la bibliografía de los medicamentos más utilizados en los procedimientos anestésicos y el riesgo que existe en estos medicamentos de desarrollar daño hepático por fármacos; los únicos medicamentos que tienen mayor riesgo de hepatotoxicidad son los inhalados halogenados, particularmente el halotano, ahora en desuso, el resto de los medicamentos son seguros.

Abstract: Liver damage by drugs is not so rare, its diagnosis is by exclusion, in some cases can induce acute liver failure. A review of the literature of the drugs most used in anesthetic procedures and the risk that exists of these drugs in the development of liver damage by drugs was carried out; the only drugs that have a higher risk of hepatotoxicity are halogenated inhaled ones, particularly halothane now in disuse, the rest of the drugs are safe.

Advances in the application of different anesthetic methods and drugs in interventional therapy for hepatocellular carcinoma.

Currently, interventional therapy has been widely used in clinical practice as a treatment method for hepatocellular carcinoma (HCC). The limitations of interventional therapy lie mainly in the intolerable pain felt by the patients during the treatment process. Hence, the selection of the anesthetic methods and drugs, as well as the precise control of the dosages, are particularly crucial before the initiation of the treatment. Moreover, different anesthetic methods and drugs may also affect the patient's recovery differently. To better comprehend the current status of various anesthetic methods and drugs used in interventional therapy for HCC, this study reviewed the advantages and disadvantages of different anesthetic methods and drugs.

[Dispersive solid-phase extraction combined with high-performance liquid chromatography for determination of seven anesthetics in aquatic products].

Nowadays, anesthetics are widely used in fishery production processes, such as fish breeding, surgery, and fresh aquatic product transportation. Because of the widespread application of anesthetic drugs in aquatic products, there is an increasing demand for the rapid and sensitive detection of anesthetic drugs in aquatic products. The complex aquatic product matrix contains a variety of interfering substances, such as proteins, fats, and phospholipids, along with anesthetic drug residues at very low concentrations; therefore, it is necessary to adopt appropriate pretreatment methods for improving the sensitivity of detection. In this study, a dispersive solid-phase extraction (DSPE) method, combined with high-performance liquid chromatography, was established for the simultaneous detection of seven anesthetic drugs in aquatic products, viz. procaine, oxybuprocaine, tricaine, eugenol, methyl eugenol, isoeugenol, and methyl isoeugenol. For the DSPE step, pretreatment conditions, such as extraction solvent, extraction time, adsorbent amount, and DMSO dosage, were optimized. Sample pretreatment is a three-step process. First, in ultrasound-assisted extraction, 2.0 g samples were extracted using 10.0 mL 1.0% formic acid in acetonitrile under ultrasound conditions for 10 min. Then, DSPE was performed with mixed adsorbents: the solvent extracts were cleaned using 20 mg poly(styrene-glycidylmethacrylate) microspheres (PS-GMA), 50 mg primary secondary amines (PSA), and 10 mg C18, followed by separation by centrifugation. Finally, DMSO-assisted concentration was applied: the organic layer was collected and was dried at 40 ℃ in a N2 stream with 100 µL DMSO. Water was added to the residue to obtain a final volume of 1.0 mL for HPLC analysis. The seven anesthetic drugs were separated on a Welch welchrom C18 column (250 mm×4.6 mm, 5 µm) by gradient elution using methanol and 0.05% formic acid in 5 mmol/L ammonium acetate aqueous solution as mobile phases. The detection wavelengths were 235, 260, and 290 nm. Two matrix matching standard curves for fish and shrimp were applied for quantitative analysis. Under optimized conditions, the seven target anesthetics showed good linear relationships in their respective concentration ranges (R2>0.999), with the limit of detection (LOD) ranging from 0.011 to 0.043 mg/kg. In fish samples, the mean recoveries obtained at three concentration levels were between 79.7% and 109%, with relative standard deviations (RSDs) being less than 7.2%. In shrimp samples, mean recoveries were 78.0%-99.9%, with RSDs being less than 8.3%. This simple, rapid, accurate, and sensitive method can be applied to the detection of three kinds of aminobenzoic acid esters and four kinds of eugenol anesthetic drugs in aquatic products.