Breast Cancer and Anaesthesia: Genetic Influence.

Breast cancer is the leading cause of mortality in women. It is a heterogeneous disease with a high degree of inter-subject variability even in patients with the same type of tumor, with individualized medicine having acquired significant relevance in this field. The clinical and morphological heterogeneity of the different types of breast tumors has led to a diversity of staging and classification systems. Thus, these tumors show wide variability in genetic expression and prognostic biomarkers. Surgical treatment is essential in the management of these patients. However, the perioperative period has been found to significantly influence survival and cancer recurrence. There is growing interest in the pro-tumoral effect of different anaesthetic and analgesic agents used intraoperatively and their relationship with metastatic progression. There is cumulative evidence of the influence of anaesthetic techniques on the physiopathological mechanisms of survival and growth of the residual neoplastic cells released during surgery. Prospective randomized clinical trials are needed to obtain quality evidence on the relationship between cancer and anaesthesia. This document summarizes the evidence currently available about the effects of the anaesthetic agents and techniques used in primary cancer surgery and long-term oncologic outcomes, and the biomolecular mechanisms involved in their interaction.

Comparative efficacy of ancillary drugs in sevoflurane-related emergence agitation after paediatric adenotonsillectomy: A Bayesian network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: The comparative efficacy of ancillary drugs on sevoflurane-related emergence agitation (EA) in paediatric anaesthesia for adenotonsillectomy remains unclear. The purpose of this Bayesian network meta-analysis was to investigate the efficacy of ancillary drugs on sevoflurane-related EA in paediatric anaesthesia for adenotonsillectomy. METHODS: MEDLINE, Embase, the Cochrane Library and Web of Science databases were electronically searched to identify randomized controlled trials (RCTs) of different ancillary drugs used in adenotonsillectomy from inception to April 2019. Two reviewers independently screened the literature, extracted data and assessed the risk of bias in included studies. Subsequently, a network meta-analysis was performed using the R software and RevMan 5.3 software. RESULTS AND DISCUSSION: We included 25 RCTs, involving 2151 participants. The proportion of patients with sevoflurane-related EA was significantly lower in the dexmedetomidine, ketamine, propofol, fentanyl, midazolam, sufentanil, remifentanil and clonidine groups than in the placebo group (P < .05). Fentanyl was superior to sufentanil (P < .05), whereas dexmedetomidine was superior to fentanyl (P < .05). Among ancillary drugs, dexmedetomidine (90.04%) showed the highest possibility of reducing the risk of EA, followed by fentanyl (87.45%), remifentanil (63.85%), ketamine (52.07%), midazolam (51.27%), clonidine (49.94%), propofol (29.89%), sufentanil (21.38%) and placebo (4.09%). WHAT IS NEW AND CONCLUSION: Evidence suggests that the effects of dexmedetomidine in reducing the risk of sevoflurane-related EA in paediatric anaesthesia for adenotonsillectomy were better than the effects of other drugs. However, large, high-quality RCTs are required to further confirm this.

Differential effects of sevoflurane on the metastatic potential and chemosensitivity of non-small-cell lung adenocarcinoma and renal cell carcinoma in vitro.

BACKGROUND: Increasing evidence suggests that perioperative factors including anaesthetics influence cancer recurrence and metastasis after surgery. This study investigated the influence of sevoflurane on the response of lung and renal cancer cells to cisplatin, with focus on transforming growth factor-beta (TGF-ß) and osteopontin (OPN) that are both closely associated with cancer tumorigenesis and metastasis. METHODS: Non-small cell lung adenocarcinoma (A549) and renal cell carcinoma (RCC4) cells were exposed to 3.6% sevoflurane for two hrs. Malignant potential represented by cell viability, migration, chemosensitivity to cisplatin was evaluated. Expression of OPN, TGF-ß1, TGF-ß receptor type II (TGF-ßRII) and the canonical downstream effector Smad3 was assessed. SiRNA knockdown of TGF-ß1 and OPN and chemical inhibition of TGF-ßRI/II was performed. RESULTS: Sevoflurane reduced cell viability (0.394) versus control (0.459) (P < 0.01), enhanced chemosensitivity but had no effect on migration of A549 cells. It enhanced viability (0.467) versus control (0.347) (P < 0.001), chemoresistance and migration of RCC4. In A549, there was enhanced nuclear Smad3. In RCC4, TGF-ßRII and OPN were upregulated, while TGF-ß1 was over- expressed with reduced nuclear Smad3. TGF-ßRII inhibition and OPN knockdown abolished sevoflurane-mediated viability, and migration, respectively, in RCC4. CONCLUSIONS: Sevoflurane promotes the metastatic potential of renal carcinoma, but not of non-small cell lung cancer. This may be associated with its differential effect on cellular signalling including TGF-ß. Our findings indicate that sevoflurane may have different effects on the metastatic potential and chemosensitivity of different tumour types.

Intelligence quotient scores at the age of 6 years in children anaesthetised before the age of 5 years.

We analysed the association of independent variables with non-verbal cognition at 6 years in children with complete data (3441 from a cohort of 9901), of whom 415 were anaesthetised before the age of 5 years. Using multivariable regression, cognition was reduced by a mean (95% CI) score for children: anaesthetised before the age of 5 years, 2.1 (0.7-3.5), p = 0.004; born prematurely, 9.8 (4.1-15.4), p = 0.001; whose mothers smoked while pregnant, 2.3 (0.8-3.8), p = 0.004; whose mothers had lower IQ scores, 0.3 (0.2-0.3) for each unit reduction in maternal IQ, p < 0.0001. The association of child IQ with exposure to anaesthetic drugs was sensitive to missing data.

Current options in aerosolised drug therapy for children receiving respiratory support.

Inhalation of aerosolised medications are the mainstay of treatment for a number of chronic lung diseases and have several advantages over systemically-administered medications. These include more rapid onset of action for drugs such as ß-adrenergic agonists when compared with oral medication, high luminal doses for inhaled antibiotics when used to treat endobronchial infection, and an improved therapeutic index compared with systemic delivery for these and other classes of drugs such as corticosteroids. The use of aerosolised drugs to treat patients whose tracheas are intubated is less well established, in part because systemic delivery via the intravenous route can be a simpler alternative for many drugs. Consequently, research in this area is largely limited to a number of in vitro studies and very few clinical trials. Unfortunately, a lack of focus in this area has resulted in a number of practices which at best are ineffective, and at worst dangerous for the patient. Although there have been some attempts to re-invigorate research in order to improve delivery systems, current devices are, to a great extent, based on long-standing technology developed more than 50 years ago. In this review, we explore current knowledge and provide guidance as to when and how the inhaled route may be of value when treating patients whose tracheas are intubated, and we set out the challenges facing those attempting to advance the topic. We conclude by reviewing current areas of interest that may lead to more effective and widespread use of aerosols in the treatment of intubated patients.

Topical sevoflurane for chronic venous ulcers infected by multi-drug-resistant organisms.

Several anaesthetic drugs have demonstrated antibacterial properties in vitro. Anaesthetics can primarily affect the cell wall of both susceptible and multi-resistant bacteria. They may also have a synergistic effect with conventional antibiotics through an unknown mechanism. We present three cases of a chronic venous ulcer infected by multi-resistant bacteria refractory to conventional systemic antibiotics, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). Treatment with topical sevoflurane was performed for 1 month without systemic antibiotics. Patients with an MRSA infection showed progressive improvement with negative culture at the end of the treatment. Multi-drug-resistant P. aeruginosa infection persisted at the end of treatment with positive culture. The local adverse events were mild and transient, including heat, pruritus and erythema. Topical sevoflurane may have an antibacterial effect on sensitive and multi-resistant strains. It can allow more complete surgical cleaning, leaving a cleaner wound with less fibrin and necrotic tissue. This decreases the bacterial colonisation and therefore the infectious risk, the bad smell and the exudation. The simultaneous use of conventional antibiotics and topical sevoflurane can have a synergistic antimicrobial effect.

Anaesthetics and time perception: A review.

Consciousness requires subjective experience in the "now." Establishing "now," however, necessitates temporal processing. In the current article, we review one method of altering consciousness, anaesthetic drug administration, and its effects on perceived duration. We searched PubMed, PsycInfo, and ScienceDirect databases, and article reference sections, for combinations of anaesthetic drugs and time perception tasks, finding a total of 36 articles which met our inclusion criteria. We categorised these articles with regard to whether they altered the felt passage of time, short or long interval timing, or were motor timing tasks. We found that various drugs alter the perceived passage of time; ketamine makes time subjectively slow down while GABAergic drugs make time subjectively speed up. At a short interval there is little established evidence of a shift in time perception, though temporal estimates appear more variable. Similarly, when asked to use time to optimise responses (i.e., in motor timing tasks), various anaesthetic agents make timing more variable. Longer durations are estimated as lasting longer than their objective duration, though there is some variation across articles in this regard. We conclude by proposing further experiments to examine time perception under altered states of consciousness and ask whether it is possible to perceive the passage of time of events which do not necessarily reach the level of conscious perception. The variety of methods used raises the need for more systematic investigations of time perception under anaesthesia. We encourage future investigations into the overlap of consciousness and time perception to advance both fields.

What's New in Intravenous Anaesthesia? New Hypnotics, New Models and New Applications.

New anaesthetic drugs and new methods to administer anaesthetic drugs are continually becoming available, and the development of new PK-PD models furthers the possibilities of using arget controlled infusion (TCI) for anaesthesia. Additionally, new applications of existing anaesthetic drugs are being investigated. This review describes the current situation of anaesthetic drug development and methods of administration, and what can be expected in the near future.

Safety of general anaesthetics on the developing brain: are we there yet?

Thirty years ago, neurotoxicity induced by general anaesthetics in the developing brain of rodents was observed. In both laboratory-based and clinical studies, many conflicting results have been published over the years, with initial data confirming both histopathological and neurodevelopmental deleterious effects after exposure to general anaesthetics. In more recent years, animal studies using non-human primates and new human cohorts have identified some specific deleterious effects on neurocognition. A clearer pattern of neurotoxicity seems connected to exposure to repeated general anaesthesia. The biochemistry involved in this neurotoxicity has been explored, showing differential effects of anaesthetic drugs between the developing and developed brains. In this narrative review, we start with a comprehensive description of the initial concerning results that led to recommend that any non-essential surgery should be postponed after the age of 3 yr and that research into this subject should be stepped up. We then focus on the neurophysiology of the developing brain under general anaesthesia, explore the biochemistry of the observed neurotoxicity, before summarising the main scientific and clinical reports investigating this issue. We finally discuss the GAS trial, the importance of its results, and some potential limitations that should not undermine their clinical relevance. We finally suggest some key points that could be shared with parents, and a potential research path to investigate the biochemical effects of general anaesthesia, opening up perspectives to understand the neurocognitive effects of repetitive exposures, especially in at-risk children.

Anaesthetic Drug Choices of Senior Anaesthetists: An Observational Analysis of Medication Habits in a Tertiary Hospital.

OBJECTIVE: Various drugs are available for general anaesthesia, and the anaesthesiologist in charge may choose the one that is considered as the most appropriate for each specific case. When selecting an anaesthetic drug, its specific pharmacokinetic and pharmacodynamics as well as certain non-pharmacological properties have to be considered. This may lead to decisions that may be justified or unjustified according to scientific evidence and local standards. METHODS: In a prospective, single-centre, non-randomised and non-interventional study, 30 attending anaesthetists were interviewed about their drug prescription for general anaesthesia cases scheduled for the next day. The stated reasons for their choices from available alternatives were recorded and analysed for being justified or unjustified. RESULTS: We found 69% of all decisions as justified, while 31% were incorrect, unjustified or random. Female anaesthetists made 83%±15% justified decisions, whereas males achieved a lower performance with 69%±17% justified decisions (p=0.046). CONCLUSION: To a large proportion, convenience, habit and personal preferences influence the decision-making in choosing the anaesthetic medication. A change of paradigm in the postgraduate education and training seems to be necessary.

Chirality and anaesthetic drugs: A review and an update.

Many molecules can exist as right-handed and left-handed forms that are non-superimposable mirror images of each other. They are known as enantiomers or substances of opposite shape. Such compounds are also said to be chiral (Greek chiros meaning 'hand'). Such chiral molecules are of great relevance to anaesthetic theory and practice. This review summarizes the basic concepts, pharmacokinetic and pharmacodynamic aspects of chirality, and some specific examples of their application in anaesthesia, along with recent advances to elucidate the anaesthetic mechanisms. Chirality is relevant to anaesthesia, simply because more than half of the synthetic agents used in anaesthesia practice are chiral drugs. Almost all these synthetic chiral drugs are administered as racemic mixture, rather than as single pure enantiomers. These mixtures are not drug formulations containing two or more therapeutic substances, but combination of isomeric substances, with the therapeutic activity residing mainly in one of the enantiomer. The other enantiomer can have undesirable properties, have different therapeutic activities or be pharmacologically inert. Specific examples of application of chirality in anaesthetic drugs include inhalational general anaesthetics (e.g. isoflurane), intravenous anaesthetics (e.g. etomidate, thiopentone), neuromuscular blocking agents (e.g. cisatracurium), local anaesthetics (e.g. ropivacaine and levobupivacaine) and other agents (e.g. levosimendan, dexmedetomidine, L-cysteine). In the recent advances, chirality study has not only helped new drug development as mentioned above, but has also contributed in a more profound way to the understanding of the mechanism of anaesthesia and anaesthetic drugs.