Anesthetic Drugs Research Articles

The effect of the type of anaesthesia on long-term outcomes after cancer resection surgery: a narrative review.

The peri-operative period may create a biological environment conducive to cancer cell survival and dissemination. Microscopic residual tumours (micrometastases) can be dislodged even with excellent surgical technique. At the same time, the stress response from surgery can temporarily impair immune function and activate inflammatory processes, increasing the risk of tumour proliferation. This narrative review investigates how peri-operative anaesthetic and analgesic interventions may influence cancer recurrence and metastasis by exploring evidence from both experimental and clinical studies. A comprehensive review of the literature was conducted to identify relevant preclinical and clinical studies published. While surgery remains the best curative option for many cancers, metastasis remains the leading cause of death. Numerous studies have suggested that different anaesthetic drugs and techniques could impact cancer outcomes including volatile anaesthetic agents; total intravenous anaesthesia with propofol; local anaesthetics; regional anaesthesia; and opioids. This review focuses on these five commonly used anaesthetic approaches and evaluates their potential impact on cancer progression. There is a complex interplay between anaesthetic and analgesic techniques and cancer outcomes. Despite promising data from laboratory experimental models, the balance of available clinical trials indicates an equivalent influence of all evaluated anaesthetic techniques on long-term oncologic outcomes, except, possibly, for peritumoral or intraperitoneal local anaesthetic infiltration.

Taylor Series Approximation for Accurate Generalized Confidence Intervals of Ratios of Log-Normal Standard Deviations for Meta-Analysis Using Means and Standard Deviations in Time Scale.

With contemporary anesthetic drugs, the efficacy of general anesthesia is assured. Health-economic and clinical objectives are related to reductions in the variability in dosing, variability in recovery, etc. Consequently, meta-analyses for anesthesiology research would benefit from quantification of ratios of standard deviations of log-normally distributed variables (e.g., surgical duration). Generalized confidence intervals can be used, once sample means and standard deviations in the raw, time, scale, for each study and group have been used to estimate the mean and standard deviation of the logarithms of the times (i.e., "log-scale"). We examine the matching of the first two moments versus also using higher-order terms, following Higgins etal. 2008 and Friedrich etal. 2012. Monte Carlo simulations revealed that using the first two moments 95% confidence intervals had coverage 92%-95%, with small bias. Use of higher-order moments worsened confidence interval coverage for the log ratios, especially for coefficients of variation in the time scale of 50% and for larger sample sizes per group, resulting in 88% coverage. We recommend that for calculating confidence intervals for ratios of standard deviations based on generalized pivotal quantities and log-normal distributions, when relying on transformation of sample statistics from time to log scale, use the first two moments, not the higher order terms.

Anesthetic Drugs: A Comprehensive Overview for Emergency Medicine

The purpose of this document is to provide a unique white paper on the use of different anesthetic drugs and the key clinical pearls for ensuring patient safety in humans. This paper is designed to be a convenient guide that can be placed in work rooms for residents and medical school trainees to improve their learning and to provide reminders about drug-drug interactions. Finally, it is designed to be a potential living document - the first of its kind within the field. Unlike other white papers, this could be added to and modified based on the current literature and amended as newer drugs are discovered and made available. This document is intended to become a ‘go-to-guide’ for clinical anesthetic drug use on humans that houses an in depth, yet condensed encyclopedia of the most pertinent, necessary information for emergency medicine health professionals.

Pharmacokinetics Based Suggestive Model Predictive Control for Inspired Respiratory Anesthetic Drug Delivery in Patients Undergoing Surgery

Pharmacokinetics Based Suggestive Model Predictive Control for Inspired Respiratory Anesthetic Drug Delivery in Patients Undergoing Surgery

Anesthesia depth monitoring during opioid free anesthesia – a prospective observational study

BackgroundPatients undergoing general anesthesia are more frequently monitored for depth of anesthesia using processed electroencephalography. Opioid-free anesthesia is nowadays an accepted modality for general anesthesia, however it is unclear how to interpret data from processed electroencephalography when using a mixture of non-opioid anesthetic drugs. Our objective was to describe density spectral array patterns and compare processed encephalographic data indices between opioid-free and routine opioid based anesthesia.MethodsThis prospective observational cohort study was conducted on 30 adult patients undergoing laparoscopic surgery in a non-tertiary regional hospital. The patients underwent general anesthesia with three different methods and were monitored for anesthesia depth using processed encephalography and density spectral array. Primary outcome is a group-derived mean difference in patient state index and spectral edge frequency. As a secondary outcome a descriptive comparison of the spectral power, derived from the density spectral array, was done between groups.ResultsThe opioid-free anesthesia group had significantly higher patient state index and spectral edge frequency compared to routine anesthesia. Density spectral array patterns were also different, most notably lacking the high power in alpha frequency spectrum seen in the other routine anesthesia methods.ConclusionsProcessed electroencephalography monitoring can be used in opioid-free anesthesia, however clinicians should expect higher values in monitoring indices. The density spectral array pattern using a common protocol for opioid-free anesthesia, with mainly sevoflurane combined with low doses of dexmedetomidine and esketamine, differs from well described opioid and GABA-ergic anesthesia methods. These findings should be further validated using other protocols for opioid-free anesthesia in order to safely monitor anesthesia depth.Trial registrationClinicaltrials.gov registration number NCT06227143, registration date; 26th of January 2024.

Metal Oxide Nanocatalysts for the Electrochemical Detection of Propofol

Propofol is one of the most widely used intravenous drugs for anaesthesia and sedation and is one of the most commonly used drugs in intensive care units for the sedation of mechanically ventilated patients. The correct dosage of propofol is of high importance, but there is currently a lack of suitable point-of-care techniques for determining blood propofol concentrations. Here, we present a cytochrome P450 2B6/carbon nanotube/graphene oxide/metal oxide nanocomposite sensor for discrete measurement of propofol concentration. Propofol is converted into a quinol/quinone redox couple by the enzyme and the nanocomposite enables sensitive and rapid detection. The metal oxide nanoparticles are synthesised via green synthesis and a variety of metal oxides and mixed metal oxides are investigated to determine the optimal nanocatalyst. Converting propofol into the redox couple allows for the measurement to take place over different potential ranges, enabling interference from common sources such as paracetamol and uric acid to be avoided. It was found that nanocomposites containing copper titanium oxide nanoparticles offered the best overall performance and electrodes functionalised with such nanocomposites demonstrated a limit of detection in bovine serum of 0.5 µg/mL and demonstrated a linear response over the therapeutic range of propofol with a sensitivity of 4.58 nA/μg/mL/mm2.

Guidelines for animal models of endurance and resistance exercise.

This mini-review details the guideline for implementing the most common exercise patterns in small laboratory rodents (mice/rats) and the advantages and disadvantages of each, in ways that are comparable to humans. Also, criteria for targeted selection and control of workload and intensity of activity are proposed in different exercise programs. As an available and low-cost intervention in physiological, biochemical and cellular-molecular assessments, different exercise programs can be effective in the prevention/treatment of many skeletal-structural, behavioral and neurodegenerative disorders. Exercise tolerance/intolerance is an indicator of the complex function of the physiological, metabolic, neuromuscular, cardiovascular and respiratory systems, and in this sense, animal models of exercise are of interest to researchers by creating a controllable and precise environment. Considering the different species of laboratory animals and various exercise paradigms, selecting the type, intensity and duration of the program in an optimal manner is a difficult task, especially in conditions such as old age or illness, and if necessary, existing research tools and protocols should be reviewed. In fact, one of the most attractive applications of exercise models is the discovery of preventive/therapeutic strategies for many disorders, which necessitates more knowledge about exercise protocols. Animal models of endurance/resistance exercise on land/water make it possible to evaluate physiological/pathological conditions. However, to obtain optimal and reproducible results in human samples, the effectiveness of anesthetic drugs, surgical procedures, and the stress caused by exercise tools and equipment must be carefully controlled.

Anesthetic Drug Used by Şerafeddin Sabuncuoğlu in the 15th Century: Murkid

Anesthetic Drug Used by Şerafeddin Sabuncuoğlu in the 15th Century: Murkid

Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?

Ketamine is a racemic compound and medication comprised of (S)-ketamine and (R)-ketamine enantiomers and its metabolites. It has been used for decades as a dissociative anesthetic, analgesic, and recreational drug. More recently, ketamine, its enantiomers, and its metabolites have been used or are being investigated for the treatment of refractory depression, as well as for comorbid disorders such as anxiety, obsessive-compulsive, and opioid use disorders. Despite its complex pharmacology, ketamine is referred to as an N-methyl-d-aspartate (NMDA) receptor antagonist. In this review, the authors argue that ketamine's pharmacology should be redefined to include opioid receptors and the endogenous opioid system. They also highlight a potential mechanism of action of ketamine for depression that is attributed to bifunctional, synergistic interactions involving NMDA and opioid receptors.

Anaesthesia for paediatric radiotherapy: A narrative review.

Radiotherapy is currently used in approximately one-third of children with cancer. Treatments are typically received as weekday outpatient appointments over 3-6 weeks. The treatment is painless but requires a still, co-operative patient who can lie alone in set positions, facilitated by the use of immobilisation devices, for up to 1 h. We conducted a literature search to identify relevant articles relating to radiotherapy treatment. Key search terms included: 'radiotherapy'; 'proton beam'; 'photon'; 'sedation'; 'anaesthesia'; and 'paediatric'. The abstracts of identified articles were assessed for relevance and their references reviewed for further relevant publications. The requirement for anaesthesia is almost exclusively limited to younger children, who are committed to daily anaesthetics over the duration of their treatment course. Centres tend to adopt a primary anaesthetic technique of either general anaesthesia using a supraglottic airway device or deep sedation, with spontaneous ventilation maintained. A full variety of anaesthetic drugs has been used with insufficient evidence to support a standardised primary approach but an apparent global trend towards propofol by infusion for sedation. Children may become acutely unwell during their treatment course and systems for escalation of clinical care in this event are vital. Distance from the patient for staff radiation shielding, patient positioning for treatment delivery and the use of immobilisation devices may provide additional access challenges in the event of an emergency. The requirement for anaesthesia for paediatric radiotherapy is typically confined to younger children. Patients may be unwell, with several specific considerations related to their cancer diagnosis and the impact of various treatments including surgery and chemotherapy, in addition to the radiotherapy. A multidisciplinary team approach to all aspects of care is imperative in this group of high-risk patients.

The global research trends in perioperative cognitive function protection for preventing postoperative delirium: A bibliometric analysis.

This study aims to analyze the global trends and current status of perioperative cognitive function protection for preventing postoperative delirium(PCFP-POD), as well as to predict research hotspots. We conducted a literature search on the Web of Science Core Collection (WoSCC) and selected articles published between January 1, 2014, and December 31, 2023, related to PCFP-POD. The retrieved data were subjected to bibliometric analysis and visualization using CiteSpace 6.2.R4, VOSviewer 1.6.20 software, and the Bibliometrics website. A total of 355 articles published between 2014 and 2023 were retrieved from the online databases. The number of publications on perioperative cognitive function protection for preventing postoperative delirium sharply increased from 2018 onwards. Key themes included drug and non-drug interventions, postoperative cognitive dysfunction in cardiac and hip surgery, and the effects of anesthetic drugs. High-frequency keywords included postoperative delirium, intervention, postoperative cognitive impairment, and cognitive training. The number of research articles on PCFP-POD increased significantly from 2014 to 2023. Future research trends may focus on cognitive function protection related to surgical categories, anesthesia methods, electroencephalogram monitoring, and nursing care.

Sudden Loss of Motor-Evoked Potentials (MEPs) During the Resection of A Nondominant Insular Glioma: Case Report and Management Review.

A 43-year-old man was admitted into the emergency room at our hospital after presenting with a tonic-clonic seizure. MRI showed a right-side operculo-insular tumor. This was treated by performing a craniotomy under general anesthesia with intraoperative monitoring. Tumor resection was started by exploring the temporal and frontal opercula without problems. However, during the resection of the insular compartment, a sudden loss of MEPs was observed. Surgery was stopped immediately, and all the relevant anesthetic parameters, vital signs, anesthetic drugs were reviewed. No retractors had been used at that time, so vasospasm was suspected as the underlying cause of the signal change. An ICG bolus injection confirmed vasospasm in one of the M2 branches running over the insula. A direct vessel massage was performed yet resulted in no apparent improvement in the appearance of the vessel when ICG was injected. Therefore, repeated massage with nimodipine was performed, which resulted in the resolution of the vasospasm. MEPs progressively recovered to base line levels, and surgery could then be finished without further incident. During the postoperative recovery period, no focal deficit was identified, and the postoperative MRI showed a planned subtotal resection without apparent ischemia. The goal of this report is to review the potential causes of such a loss of intraoperative MEPs and its best management in order to prevent postoperative motor deficit and to manage the situation should it occur.

Experiment and modelling focus on interaction and thermodynamic studies of anaesthetic drug and pluronic (F127) mixture

Experiment and modelling focus on interaction and thermodynamic studies of anaesthetic drug and pluronic (F127) mixture

Drug Allergy Testing in a Pediatric Patient with Diffuse Cutaneous Mastocytosis

Mastocytosis represents a group of diseases characterized by excessive accumulation of mast cells in one or more tissues. It can affect only the skin or have systemic involvement. It has a low prevalence and the prognosis in children is benign. Patients with pediatric mastocytosis often require sedation or anesthesia for diagnostic and therapeutic procedures. Here, we report our experience with anesthesia in a pediatric patient with diffuse cutaneous mastocytosis undergoing surgical intervention for circumcision. The aim was to determine the risk of anesthetic drugs to be used for general anesthesia in a patient with diffuse cutaneous mastocytosis. A 5-year-old male patient who was consulted with anesthesia for circumcision operation and diagnosed with diffuse cutaneous mastocytosis by skin biopsy was not operated because of the risk of drug allergy and referred to the pediatric allergy and immunology department. Routine hemogram and biochemistry laboratory results were within normal limits. Occasional elevation of serum tryptase level was observed. Skin prick test with lidocaine did not show any significant change compared to the negative control due to dermatographism. However, intradermal tests with lidocaine 1:1 and 1:10 dilutions were negative. For drug allergy provocation test, increasing doses of lidocaine were administered subcutaneously and no reaction developed. Intradermal tests with midazolam and bupivacaine were also negative. There was no early or late reaction to any of these. In conclusion, it has been presented in the literature which drugs can be used without any problem according to intradermal test results as in our case. However, all precautions should be taken against the possibility of anaphylaxis in these patients. Re-consultation 24 hours before surgery regarding the use of prophylactic drugs is appropriate

Strategies to prevent postoperative delirium: a comprehensive evaluation of anesthesia selection and drug intervention

Postoperative delirium (POD) represents a common neurological complication encountered predominantly among the elderly cohort undergoing surgical intervention for hip fractures. This phenomenon, particularly commonplace in geriatric populations with heightened preoperative risk profiles, pronounced comorbidities, and later stages of lifespan, poses complex clinical challenges. The impact of perioperative pharmacological interventions and anesthetic strategies on POD’s emergence cannot be understated, as it may profoundly affect the length of hospital stays, rehabilitation milestones, and the overall mortality hazard. The pharmacotherapeutic landscape for managing POD remains constrained, underscoring the imperative nature of preventive measures. Prudent preoperative risk stratification, meticulous intraoperative neuromonitoring guided by electroencephalographic studies, and a holistic postoperative patient welfare model are cornerstone recommendations in the quest to mitigate POD’s incidence. Nonetheless, an extensive exploration into the influence of anesthetic approaches and perioperative medications on the emergence of POD is yet to be satisfactorily charted. Our investigation endeavors to dissect the nexus between anesthetic modalities, perioperative pharmacological interventions, and POD incident rates among the elderly with hip fractures. This study spotlights pivotal determinants of POD in the wake of hip fracture surgery by evaluating and synthesizing data from peer-reviewed sources that adhere to rigorous inclusion criteria. Preliminary studies have revealed that certain anesthesia protocols and perioperative medications may increase the potential incidence of POD, such as higher depth of anesthesia or benzodiazepine use, and the incidence of POD in specific populations, such as patients with higher age, prior history of psychosis, and lower intraoperative oxygen saturation The findings from this study are instrumental in refining strategic perioperative plans tailored for the elderly recipients of hip fracture surgery, aimed at not only diminishing the incidence but also the gravity of POD. Despite these forward steps, the clinical uncertainty concerning the efficacy and safety of the specific drugs and surgical techniques in question remains. These lingering questions underscore the exigency for more extensive, empirically grounded research to consolidate the learnings of this investigation.

In vivo changes in zebrafish anesthetic sensitivity in response to the loss of kif5Aa are associated with the alteration of mitochondrial motility.

Anesthetic and sedative drugs are small compounds known to bind to hundreds of proteins. One intriguing binding partner of propofol is the kinesin motor domain, kif5A, a neuronal mitochondrial transport protein. Here, we used zebrafish WT and kif5Aa KO larval behavioral assays to assess anesthetic sensitivity and combined that with zebrafish primary neuronal cell culture to probe for alteration in mitochondrial motility. We found that the loss of kif5Aa increases behavioral sensitivity to propofol and etomidate, with etomidate hypersensitivity greater than propofol. In contrast, kif5Aa KO animals were resistant to the behavioral effects of dexmedetomidine. Finally, WT and kif5Aa KO larvae responded similarly to the behavioral effects of ketamine. Propofol inhibited the anterograde motility of mitochondria in WT zebrafish neurons, while etomidate inhibited mitochondrial motility in both anterograde and retrograde directions; neither drug altered mitochondrial motility in the kif5Aa knockout (KO) neurons. In contrast, dexmedetomidine enhanced retrograde mitochondrial motility in both WT and kif5Aa KO animals. Finally, ketamine had little significant effect on mitochondrial motility in either mutant or WT animals. These data demonstrate that each anesthetic/sedative drug affects the motor protein machinery uniquely and is associated with unique changes in behavior. Understanding how different anesthetic compounds alter neuron motor proteins will be important in defining how anesthetics alter neuronal signaling and energetic dynamics.

Pharmacokinetic-pharmacodynamic Modelling of NH600001 in Healthy Subjects and Patients Undergoing Gastroscopy.

NH600001 is a new general anaesthetic drug with a structure similar to etomidate. The objective of this study was to investigate the relationship between concentrations of NH600001 and sedation efficacy based on data from phase I-II studies and factors influencing the pharmacokinetics and pharmacodynamics of NH600001. The dataset consisted of 2 phase I studies in healthy subjects and 1 phase II study in patients undergoing gastroscopy. Nonlinear mixed effects modeling was used in developing the population pharmacokinetics and pharmacodynamics (PopPK/PD) model of NH600001. Three-compartment model was used to describe the PK profile of NH600001. Parameters were used for allometric scaling on body weight, where the exponents were set to 0.75 for clearance and 1 for volumes. Co-administration of alfentanil hydrochloride influenced the distribution volume of the central compartment and clearance. Effect of patients undergoing gastroscopy (compared with healthy subjects) on clearance, the distribution volume of the superficial peripheral compartment and inter-compartmental clearance for deep peripheral compartment and central compartment was included the final PopPK model. The effect compartment model well characterized the PK/PD relationship of NH600001. Simulation results showed that an initial dose of 0.25mg/kg of NH600001 resulted in rapid sedation, and three additional doses at 5-min intervals could maintain sedation for more than 20min. A PopPK/PD model was successfully constructed for NH600001 in healthy subjects and in patients undergoing gastroscopy that could inform the dosing regimens of the forthcoming phase III study.

Prognostic factors and impact of management strategies for status epilepticus: The STEPPER study in the Emilia-Romagna region, Italy.

The STEPPER (Status Epilepticus in Emilia-Romagna) study aimed to investigate the clinical characteristics, prognostic factors, and treatment approaches of status epilepticus (SE) in adults of the Emilia-Romagna region (ERR), Northern Italy. STEPPER, an observational, prospective, multicentric cohort study, was conducted across neurology units, emergency departments, and intensive care units of the ERR over 24 months (October 2019-October 2021), encompassing incident cases of SE. Patients were followed up for 30 days. A total of 578 cases were recruited (56% female, mean age = 70 years, 32% with previous diagnosis of epilepsy, 43% with in-hospital onset, 35% stuporous/comatose, 46% with nonconvulsive SE). Etiology was known in 87% (acute 43%, remote 24%, progressive 17%, definite epileptic syndrome 3%). The mean pre-SE Rankin Scale score was 2, the Status Epilepticus Severity Score was ≥4 in 33%, the Epidemiology-Based Mortality Score in Status Epilepticus score was ≥64 in 61%, and 34% were refractory. The sequence of treatments followed current clinical practice guidelines in 63%. Benzodiazepines (BDZs) were underused as first-line therapy (71%), especially in in-hospital onset cases; 15% were treated with continuous intravenous anesthetic drugs. Mortality was 24%; 63% of survivors had functional worsening. At the two-step multivariable analysis, incorrect versus correct treatment sequence with correct BDZ dose was the strongest predictor of failure to resolve SE in the in-hospital group (odds ratio [OR] = 4.42, 95% confidence interval [CI] = 1.86-10.5), with a similar trend in the out-of-hospital group (OR = 2.22, 95% CI = .98-5.02). In turn, failure to resolve was the strongest predictor of 30-day mortality (OR = 11.3, 95% CI = 4.16-30.9, out-of-hospital SE; OR = 6.42, 95% CI = 2.79-14.8, in-hospital SE) and functional worsening (OR = 5.83, 95% CI = 2.05-16.6, out-of-hospital SE; OR = 9.30, 95% CI 2.22-32.3, in-hospital SE). The STEPPER study offers insights into real-world SE management, highlighting its significant morbidity and functional decline implications. Although nonmodifiable clinical factors contribute to SE severity, modifiable factors such as optimized first-line therapies and adherence to guidelines can potentially influence prognosis.

Adverse Effects of Chemotherapy and the Interaction With Anesthesia: A Narrative Review.

Many cancer patients have their main tumors surgically removed with the goal of curing them, or as part of palliative care. When a patient receives general anesthesia, the side effects of the administered chemotherapy regimens must be considered, especially those that may have significant repercussions during anesthetic care. The aim of this study is to review the existing literature to identify adverse effects of chemotherapy and known interactions between chemotherapy and anesthetic drugs, analyze the mechanisms underlying these interactions, and discuss relevant clinical implications. This integrative review searched for articles using the search terms: chemotherapy, anesthetic drugs, interaction, adverse effects, and drug combination. Negative perioperative outcomes may be related to the chemotherapy. Regarding the type of oncological surgery, factors such as blood loss, hypothermia, and extended operative time influence the increase in morbimortality. Many anesthetic drugs are related to immunomodulation and interact with chemotherapy, which may get better or worse cancer patients. It is crucial for anesthetists to have a comprehensive understanding of the potential adverse effects of chemotherapy drugs and their interactions with anesthetics.

Postoperative Cognitive Dysfunction: A Review.

Elderly patients are more vulnerable to cognitive dysfunction in the postoperative period. Patients who are apparently well in cognitive functions in the preoperative period after undergoing anesthesia in noncardiac surgery will develop symptoms of cognitive dysfunction. Postoperative cognitive dysfunction (POCD) doesn't continue for a long duration and usually undergoes self-resolution. Proper definitions and congruous tests for diagnosis are absent. Rigorous preoperative assessment of cognitive function and distinguishing risk factors are indispensable for recognizing the range of POCD and its association with surgery and anesthesia. Recent studies haven't revealed any anesthesia technique or drug which can significantly reduce the incidence of POCD. Therefore, giving accurate information to patients can be challenging.