Time to Wake Up! The Ongoing Search for General Anesthetic Reversal Agents.

How general anesthetics work remains a topic of ongoing study. A parallel field of research has sought to identify methods to reverse general anesthesia. Reversal agents could shorten patients' recovery time and potentially reduce the risk of postoperative complications. An incomplete understanding of the mechanisms of general anesthesia has hampered the pursuit for reversal agents. Nevertheless, the search for reversal agents has furthered understanding of the mechanisms underlying general anesthesia. The study of potential reversal agents has highlighted the importance of rigorous criteria to assess recovery from general anesthesia in animal models, and has helped identify key arousal systems (e.g., cholinergic, dopaminergic, and orexinergic systems) relevant to emergence from general anesthesia. Furthermore, the effects of reversal agents have been found to be inconsistent across different general anesthetics, revealing differences in mechanisms among these drugs. The presynapse and glia probably also contribute to general anesthesia recovery alongside postsynaptic receptors. The next stage in the search for reversal agents will have to consider alternate mechanisms encompassing the tripartite synapse.

Supraglottic Airway Devices: Present State and Outlook for 2050.

Correct placement of supraglottic airway devices (SGDs) is crucial for patient safety and of prime concern of anesthesiologists who want to provide effective and efficient airway management to their patients undergoing surgery or procedures requiring anesthesia care. In the majority of cases, blind insertion of SGDs results in less-than-optimal anatomical and functional positioning of the airway devices. Malpositioning can cause clinical malfunction and result in interference with gas exchange, loss-of-airway, gastric inflation, and aspiration of gastric contents. A close match is needed between the shape and profile of SGDs and the laryngeal inlet. An adequate first seal (with the respiratory tract) and a good fit at the second seal of the distal cuff and the gastrointestinal tract are most desirable. Vision-guided insertion techniques are ideal and should be the way forward. This article recommends the use of third-generation vision-incorporated-video SGDs, which allow for direct visualization of the insertion process, corrective maneuvers, and, when necessary, insertion of a nasogastric tube (NGT) and/or endotracheal tube (ETT) intubation. A videoscope embedded within the SGD allows a visual check of the glottis opening and position of the epiglottis. This design affords the benefit of confirming and/or correcting a SGD's position in the midline and rotation in the sagittal plane. The first clinically available video laryngeal mask airways (VLMAs) and multiple prototypes are being tested and used in anesthesia. Existing VLMAs are still not perfect, and further improvements are recommended. Additional modifications in multicamera technology, to obtain a panoramic view of the SGD sitting correctly in the hypopharynx and to prove that correct sizes have been used, are in the process of production. Ultimately, any device inserted orally-SGD, ETT, NGT, temperature probe, transesophageal scope, neural integrity monitor (NIM) tubes-could benefit from correct vision-guided positioning. VLMAs also allow for automatic recording, which can be documented in clinical records of patients, and could be valuable during teaching and research, with potential value in case of legal defence (with an airway incident). If difficulties occur with the airway, documentation in the patient's file may help future anesthesiologists to better understand the real-time problems. Both manufacturers and designers of SGDs may learn from optimally positioned SGDs to improve the design of these airway devices.

Diversity in medical PhD curricula: a call for harmonisation.

BACKGROUND: Globalisation has increased human movements around the world, spurring greater connectiveness and opportunities to collaborate. In an increasingly connected world, quality assurance among professionals is paramount, particularly in medical research where PhD (Doctor of Philosophy) degree holders are expected to be at the peak of their field and play advanced-level research, education and leadership roles. While some regional efforts have been made to ensure comparability in the standards of advanced degree training, no previous study has compared these standards for a PhD in medicine across the globe. AIMS: To explore the structural diversity of medical PhD degrees and identify which aspects benefit from greater harmonisation. METHODS: In 2021, the 10 best-ranked universities from each of the top five Western countries, and the top Asian country, were identified based on Quacquarelli Symonds World University Ranking. Data were collected for each university based on individual website information regarding the level of degree required to gain entry into a PhD programme in medicine and requirements for completion of coursework, journal publication and oral defence. RESULTS: Significant variations exist in the requirements for medical PhDs across the world in terms of prerequisite degree and inclusion of coursework. Oral defence is near universal, but a mandatory requirement for publication is largely absent. CONCLUSIONS: Harmonisation of medical PhD degrees through international standards should be considered to encourage quality improvement and benchmarking between institutions, as well as to facilitate greater ease of movement within the medical research community, improving international collaboration and individual career opportunities accordingly.

Transcutaneous carbon dioxide measurements in anesthetized apneic patients with BMI > 35 kg/m2.

Transcutaneous carbon dioxide measurement (TcCO2) offers the ability to continuously and non-invasively monitor carbon dioxide (CO2) tensions when end-tidal monitoring is not possible. The accuracy of TcCO2 has not been established in anesthetized apneic patients with obesity. In this secondary publication, we present a methods comparison analysis of TcCO2 with the gold standard arterial PCO2, in adult patients with body mass index (BMI) > 35kg/m2 who were randomized to receive high flow or low flow nasal oxygenation during post-induction apnea. Agreement between PaCO2 and TcCO2 at baseline, the start of apnea and the end of apnea were assessed using a non-parametric difference plot. Forty-two participants had a median (IQR) BMI of 52 (40-58.5) kg/m2. The mean (SD) PaCO2 was 33.9 (4.0) mmHg at baseline and 51.4 (7.5) mmHg at the end of apnea. The bias was the greatest at the end of apnea median (95% CI, 95% limits of agreement) 1.90 mmHg (-2.64 to 6.44, -7.10 to 22.90). Findings did not suggest significant systematic differences between the PaCO2 and TcCO2 measures. For a short period of apnea, TcCO2 showed inadequate agreement with PaCO2 in patients with BMI > 35 kg/m2. These techniques require comparison in a larger population, with more frequent sampling and over a longer timeframe, before TcCO2 can be confidently recommended in this setting.

Plasma and Interstitial Fluid Pharmacokinetics of Prophylactic Cefazolin in Elective Bariatric Surgery Patients.

Guidelines for surgical prophylactic dosing of cefazolin in bariatric surgery vary in terms of recommended dose. This study aimed to describe the plasma and interstitial fluid (ISF) cefazolin pharmacokinetics in patients undergoing bariatric surgery and to determine an optimum dosing regimen. Abdominal subcutaneous ISF concentrations (measured using microdialysis) and plasma samples were collected at regular time points after administration of cefazolin 2 g intravenously. Total and unbound cefazolin concentrations were assayed and then modeled using Pmetrics. Monte Carlo dosing simulations (n = 5,000) were used to define cefazolin dosing regimens able to achieve a fractional target attainment (FTA) of >95% in the ISF suitable for the MIC for Staphylococcus aureus in isolates of ≤2 mg · L-1 and for a surgical duration of 4 h. Fourteen patients were included, with a mean (standard deviation [SD]) bodyweight of 148 (35) kg and body mass index (BMI) of 48 kg · m-2. Cefazolin protein binding ranged from 14 to 36% with variable penetration into ISF of 58% ± 56%. Cefazolin was best described as a four-compartment model including nonlinear protein binding. The mean central volume of distribution in the final model was 18.2 (SD 3.31) L, and the mean clearance was 32.4 (SD 20.2) L · h-1. A standard 2-g dose achieved an FTA of >95% for all patients with BMIs ranging from 36 to 69 kg · m-2. A 2-g prophylactic cefazolin dose achieves appropriate unbound plasma and ISF concentrations in obese and morbidly obese bariatric surgery patients.

Oddities in the Evolution of Syringes in Anesthesia.

Many procedures in science and medicine involve the use of a syringe, and its invention is a key milestone in general and regional anesthesia history. The end of the 19th century brought major changes in syringe production. An industry that initially manually crafted syringes to individual physicians' instructions saw the introduction of a large variety of syringes, sometimes with odd and unique modifications. For many of these unique syringes, there was no proven evidence that these modifications were effective or safe to use. This article provides examples of "odd" syringe designs for use in medicine, general anesthesia, and regional anesthesia. Some designs proved functional and have stood the test of time; others quickly disappeared and ended up in dusty collections.

Rotational thromboelastometry (ROTEM® ) in gestational diabetes mellitus and coagulation in healthy term pregnancy: A prospective observational study in Australia.

BACKGROUND: Rotational thromboelastometry (ROTEM® ) is a point-of-care test of coagulation. ROTEM® -defined hypercoagulability has been identified in pregnant women and in non-pregnant patients with diabetes mellitus. Pregnancy is known to be a hypercoagulable state, but the influence of gestational diabetes mellitus (GDM) on coagulation is unknown. AIM: The aim of this study was to assess the combined effect of pregnancy and GDM on coagulation using ROTEM® and to compare this to healthy pregnant women presenting for elective caesarean delivery. MATERIALS AND METHODS: Ethics approval was granted for recruitment of women presenting for elective caesarean delivery. Women with pre-existing conditions affecting coagulation were excluded. Group N included health pregnant women at term and Group G included pregnant women at term with GDM. Data regarding GDM management and glycaemic control were collected. Poor glycaemic control was defined by markers of accelerated fetal growth and elevated fasting or postprandial blood glucose levels. The ROTEM® parameters (extrinsically activated thromboelastometric test (EXTEM) / fibrin polymerisation test (FIBTEM) amplitude at five minutes, coagulation time, maximum clot firmness and clot formation time) were compared between the two groups using Student's t-test. RESULTS: There were 75 women in Group N and 21 women in Group G. Mean age and median body mass index values were comparable for both groups. There were no statistical differences found between the EXTEM and FIBTEM parameters analysed for the two groups. CONCLUSIONS: There was no association between GDM and increased hypercoagulability as demonstrated by ROTEM® parameters in healthy pregnant women presenting for elective caesarean delivery at term.

Features of new vision-incorporated third-generation video laryngeal mask airways.

Numerous studies have shown that blindly inserted supraglottic airway devices (SADs) are sub-optimally placed in 50 to 80% of all cases. Placement under direct vision has been recommended. We describe the very first two new SADs of the third generation that incorporate a videoscope with flexible tip. Both devices are made up of two interlocking components-the SAD and a videoscope. The 3rd generation, direct vision SADs allow vision-guided insertion, corrective manoeuvres, if needed, and correct placement in the hypopharynx and possess additional features which permit insertion of a gastric tube and endotracheal intubation should the need arise. This article describes the two new devices' physical characteristics, features, rationale for use, advantages and limitations in comparison to existing devices. Each of the two new devices-the Video Laryngeal Mask (VLMTM, UE Medical®) and the SafeLM® Video Laryngeal Mask System (SafeLMTM VLMS, Magill Medical Technology®) consist of two parts: (a) a disposable 2nd generation SAD with a silicone cuff and an anatomically curved tube; and (b) a reusable patient-isolated videoscope and monitoring screen, with the flexible scope located into a specially-designed, blind-end channel terminating in the bowl of the SAD, preventing the videoscope from contacting patient body fluids in the SAD bowl. Third generation placement-under-direct-vision supraglottic airway devices possess several theoretical safety and ease of use advantages which now need to be validated in clinical use.

Time to consider supraglottic airway device oropharyngeal leak pressure measurement more objectively.

Oropharyngeal leak pressure (OLP) is considered a measure of successful placement, adequate performance and is a useful comparator between supraglottic airway devices (SADs). OLP measurement is based on the premise that the SAD is sited properly in the hypopharynx after blind placements, but the evidence suggests otherwise. Several limitations and controversies surround OLP. This editorial addresses the uses and pitfalls of OLP, the rationale for and methods of ascertaining OLP, the pros and cons of OLP measurement and newer modalities to improve its accuracy.

The case for a 3rd generation supraglottic airway device facilitating direct vision placement.

Although 1st and 2nd generation supraglottic airway devices (SADs) have many desirable features, they are nevertheless inserted in a similar 'blind' way as their 1st generation predecessors. Clinicians mostly still rely entirely on subjective indirect assessments to estimate correct placement which supposedly ensures a tight seal. Malpositioning and potential airway compromise occurs in more than half of placements. Vision-guided insertion can improve placement. In this article we propose the development of a 3rd generation supraglottic airway device, equipped with cameras and fiberoptic illumination, to visualise insertion of the device, enable immediate manoeuvres to optimise SAD position, verify whether correct 1st and 2nd seals are achieved and check whether size selected is appropriate. We do not provide technical details of such a '3rd generation' device, but rather present a theoretical analysis of its desirable properties, which are essential to overcome the remaining limitations of current 1st and 2nd generation devices. We also recommend that this further milestone improvement, i.e. ability to place the SAD accurately under direct vision, be eligible for the moniker '3rd generation'. Blind insertion of SADs should become the exception and we anticipate, as in other domains such as central venous cannulation and nerve block insertions, vision-guided placement becoming the gold standard.

Prophylactic Cefazolin Dosing in Women With Body Mass Index >35 kg·m-2 Undergoing Cesarean Delivery: A Pharmacokinetic Study of Plasma and Interstitial Fluid.

BACKGROUND: Obesity is a risk factor for surgical site infection after cesarean delivery. There is inadequate pharmacokinetic data available regarding prophylactic cefazolin dosing in obese pregnant women. We aimed to describe the plasma and interstitial fluid (ISF) pharmacokinetics of cefazolin in obese women undergoing elective cesarean delivery and use dosing simulations to predict optimal dosing regimens. METHODS: Eligible women were scheduled for elective cesarean delivery at term, with a body mass index (BMI) of >35 kg·m. Plasma and ISF samples were collected following 2 g of intravenous cefazolin. Concentrations were determined using liquid chromatography-mass spectrometry. Population pharmacokinetic modeling and Monte Carlo dosing simulations were performed using Pmetrics. Total and unbound cefazolin concentrations in plasma and ISF were compared with the minimum inhibitory concentration at which 90% of isolates are inhibited (MIC90) of cefazolin for Staphylococcus aureus, 2 mg·L. The fractional target attainment (FTA) of dosing regimens to achieve a pre-established target of 95% unbound ISF concentrations >2 mg·L throughout a 3-hour duration of the surgery was calculated. RESULTS: The 12 women recruited had a median (interquartile range [IQR]) BMI of 41.5 (39.7-46.6) kg·m and a median (IQR) gestation of 38.7 weeks (37.9-39.0). For each timepoint up to 180 minutes, the median across subjects of total and unbound plasma concentration of cefazolin remained above 2 mg·L. The minimum observed total plasma concentration was 31.7 mg·L and plasma unbound concentration was 7.7 mg·L (observed in the same participant). For each timepoint up to 150 minutes, the median across subjects of unbound ISF concentrations remained above 2 mg·L. The minimum observed unbound ISF concentration was 0.7 mg·L (observed in 1 participant). In 2 participants, the ISF concentration of cefazolin was not maintained above 2 mg·L. The mean (± standard error [SE]) penetration of cefazolin (calculated as area under the concentration-time curve for the unbound fraction of drug [fAUC]tissue/fAUCplasma) into the ISF was 0.884 ± 1.11. Simulations demonstrated that FTA >95% was achieved in patients weighing 90-150 kg by an initial 2 g dose with redosing of 2 g at 2 hours. FTA was improved to >99% when an initial 3 g dose was repeated at 2 hours. CONCLUSIONS: To maintain adequate ISF antibiotic concentrations in obese pregnant women, our results suggest that redosing of cefazolin may be required. When wound closure has not occurred within 2 hours, redosing is suggested, following either a 2 or 3 g initial bolus. These preliminary results require validation in a larger population.

The influence of obesity on coagulation in healthy term pregnancy as assessed by rotational thromboelastometry.

BACKGROUND: Rotational thromboelastometry (ROTEM® ) is a point-of-care coagulation test which has been used to demonstrate hypercoagulability in pregnant populations and obese populations. AIM: The aim of this study was to assess the combined effect of pregnancy and obesity on coagulation using ROTEM® in healthy pregnant women of varying body mass indices (BMIs) presenting for elective caesarean delivery. MATERIALS AND METHODS: Ethics approval was granted for recruitment of women presenting for elective caesarean delivery. Women with any condition affecting coagulation were excluded. The ROTEM® parameters of extrinsically activated thromboelastometric test / fibrin polymerisation test (EXTEM/FIBTEM) amplitude at five minutes (A5), coagulation time (CT), maximum clot firmness (MCF) and clot formation time (CFT) were compared between three different groups: normal weight, overweight and obese women. RESULTS: One hundred and eighty-five women presenting for elective caesarean delivery met inclusion criteria and were divided into three groups; normal weight (BMI < 25 kg/m2 , n = 86), overweight (BMI 25-29.9 kg/m2 , n = 54) and obese (BMI ≥ 30 kg/m2 , n = 45). They had a mean (SD) age of 32.7 ± 5.0 years and the median (interquartile range) BMI of 21.9 kg/m2 (20.5-23.0), 27.0 kg/m2 (26.0-28.5), 36.0 kg/m2 (32.2-41.8) for the normal weight, overweight and obese groups respectively. Forty-one (22.2%) women were nulliparous. Across the three groups for FIBTEM A5 (P = 0.018), FIBTEM MCF (P = 0.032), FIBTEM CFT (P = 0.047) and EXTEM MCF (P = 0.015) there was evidence of increasing coagulability with increasing BMI. However, following Bonferroni correction, this was no longer significant. CONCLUSIONS: There is no association between BMI and ROTEM® parameters in pregnant women presenting for elective caesarean delivery at term.

A prospective randomized comparison of airway seal using the novel vision-guided insertion of LMA-Supreme® and LMA-Protector®.

The laryngeal mask airways supreme (LMA-Supreme™) and protector (LMA-Protector™) are generally placed blindly, often resulting in a less than optimal position and vision-guided placement has been recommended. This prospective, randomized controlled study compared the efficacy of airway seal by measuring the oropharyngeal leak pressure in 100 surgical patients who underwent a variety of non-thoracic surgery under general anaesthesia, suitable with a supraglottic airway device. Patients were allocated to either the LMA-Supreme (n = 50) or LMA-Protector (n = 50) group. All insertions were performed under vision of a videolaryngoscope using an 'insert-detect-correct-as-you-go' technique with standardized corrective measures. Our primary endpoint, mean oropharyngeal leak pressure, was significantly higher in the LMA-Protector (31.7 ± 2.9 cm H2O) compared to the LMA-Supreme (27.7 ± 3.5 cm H2O) group (mean difference 4.0 cm H2O, 95% confidence interval (CI) 2.7-5.3 cm H2O, p < 0.001) after achieving a near-optimal fibreoptic position in the LMA-Protector (94%) and LMA-Supreme (96%) groups. No statistically significant differences were shown for secondary outcomes of alignment, number of insertion attempts and malpositions, and final anatomical position as scored by fibreoptic evaluation. Corrective manoeuvres were required in virtually all patients to obtain a correct anatomically positioned LMA. Position outcomes of the two devices were similar except for the proportion of procedures with folds in the proximal cuff (90% LMA-Supreme vs. 2% LMA-Protector, p < 0.001), the need for intracuff pressure adjustments (80% LMA-Supreme vs. 48% LMA-Protector, p = 0.001) and size correction (18% LMA-Supreme vs. 4% LMA-Protector, p = 0.025). In conclusion, a higher oropharyngeal leak pressure can be achieved with LMA-Protector compared to LMA-Supreme with optimal anatomical position when insertion is vision-guided.

Operating room greening initiatives - the old, the new, and the way forward: A narrative review.

Healthcare waste is a rampant issue in Australian hospitals. The operating room (OR) contributes disproportionately to total hospital waste. There has been considerable research in the literature concentrating on strategies to improve OR and hospital waste accumulation, in an attempt to provide guidance and direction on how to reduce the healthcare ecological footprint. We reviewed the literature for leading greening initiatives currently utilised in the OR in Australia and internationally. This narrative literature review focuses on the trend of OR greening initiatives over the last 25 years, comparing different innovative approaches, the successes and setbacks, and the financial implications of initiatives. A variety of measures that hospital management, surgeons, anaesthetists, nurses and other healthcare personnel can take to reduce the ecological footprint of their healthcare facility are outlined. Greening initiatives include reducing, recycling, reusing, rethinking and researching, as well as novel technology and smarter architectural design. We also evaluated the barriers to improving waste management, which include lack of leadership, misconceptions among staff, and an overall resistance to change. In conclusion, in a world where greenhouse gas emissions cause unprecedented climate change and landfill space is finite, it is incumbent upon hospitals to help reduce the environmental impact of their facility. Reducing pollution and greenhouse gas emissions would moderate the incidence of human disease, save money for the healthcare system and society as a whole, and contribute to a safer and healthier world we all would like to live in.

Macintosh Blade Videolaryngoscopy Combined With Rigid Bonfils Intubation Endoscope Offers a Suitable Alternative for Patients With Difficult Airways.

BACKGROUND: In the armamentarium of an anesthesiologist, videolaryngoscopy is a valuable addition to secure the airway. However, when the videolaryngoscope (VLS) offers no solution, few options remain. Earlier, we presented an intubation technique combining Macintosh blade VLS and Bonfils intubation endoscope (BIE) for a patient with a history of very difficult intubation. In the present study, we evaluated this technique to establish whether it is a valuable alternative. METHODS: In this single-blinded nonrandomized study, 38 patients with a history of difficult intubation or 1 or more predictors of difficult intubation, scoring a Cormack & Lehane (C&L) grade III or IV using Macintosh blade VLS, were included. Patients were intubated combining the VLS with the BIE. The C&L grade was scored 3 times during (1) direct laryngoscopy; (2) indirect videolaryngoscopy; and (3) using the combined technique (VLS + BIE). Afterward, 2 blinded anesthesiologists assessed the C&L grade using the pictures taken during the procedure. RESULTS: Data of 38 patients were analyzed. An improvement of the C&L grade with the combined technique occurred in 33 of 38 patients (86.8%; 95% confidence interval, 71.9%-95.6%). Reviewer 1 reported an improvement of the C&L grade with the combined technique in 37 of 38 patients. Reviewer 2 reported improvement in 33 and deterioration in 2 of the patients. No complications occurred. CONCLUSIONS: The combined use of a VLS with Macintosh blade and BIE gives the anesthesiologist a valuable alternative intubation option in patients with extremely difficult airways.

Intraoperative Valsalva maneuver: a narrative review.

The Valsalva maneuver (VM) involves expiratory effort against a closed mouth and/or glottis in the sitting or supine position with the increased intraoral and intrathoracic pressure raised to 40 mmHg for 15-20 sec after which the pressure is suddenly released and the breathing restored to normal. Complex cardiovascular and other physiologic changes occur during the VM. The VM has been used for diagnostic and therapeutic reasons as well as intraoperatively during specific surgical procedures. Although the VM is usually safe, rare complications have been reported. This review examines the published literature surrounding the VM and explores the physiologic changes that occur during its performance. Attempts have been made to understand its intraoperative uses and complications and how these can be prevented.

Perioperative Anesthesia Care and Tumor Progression.

This narrative review discusses the most recent up-to-date findings focused on the currently available "best clinical practice" regarding perioperative anesthesia care bundle factors and their effect on tumor progression. The main objective is to critically appraise the current literature on local anesthetics, regional outcome studies, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs) and their ability to decrease recurrence in patients undergoing cancer surgery. A brief discussion of additional topical perioperative factors relevant to the anesthesiologist including volatile and intravenous anesthetics, perioperative stress and anxiety, nutrition, and immune stimulation is included. The results of several recently published systematic reviews looking at the association between cancer recurrences and regional anesthesia have yielded inconclusive data and provide insufficient evidence regarding a definitive benefit of regional anesthesia. Basic science data suggests an anti tumor effect induced by local anesthetics. New refined animal models show that opioids can safely be used for perioperative pain management. Preliminary evidence suggests that NSAIDs should be an essential part of multimodal analgesia. Volatile anesthetics have been shown to increase tumor formation, whereas preclinical and emerging clinical data from propofol indicate tumor protective qualities. The perioperative period in the cancer patient represents a unique environment where surgically mediated stress response leads to immune suppression. Regional anesthesia techniques when indicated in combination with multimodal analgesia that include NSAIDs, opioids, and local anesthetics to prevent the pathophysiologic effects of pain and neuroendocrine stress response should be viewed as an essential part of balanced anesthesia.